Cardio Flashcards
Prevalence of PAD
4% of people 40 years and older
15-20% of those 65+
Greater in men than women
Greater in black patients
Prognosis for PAD
risk of death from cardiovascular causes increases 2.5-6x and their annual mortality rate is 4.3-4.9%
50% 10-year mortality
What percent of people with PAD are asymptomatic
50%
15% have classic claudication
33% have atypical leg pain (functionally limited)
1-2% present with critical limb ischemia
Clinical manifestations of PAD
intermittent claudication (discomfort, ache, cramping in leg with exercise–resolves with rest), functional impairment (slow walking speed, gait disorder), rest pain (pain or paresthesias in foot or toes, worsened by leg elevation and improved by dependence), ischemic ulceration and gangrene
Associated arterial occlusion sites with the related claudication areas for patients with PAD
Aortic/iliac occlusion–gluteal and thigh claudication
Femoral occlusion–calf claudication
Popliteal/tibial occlusion–calf claudication or foot pain
Distinct Syndromes that PAD patients present with
Critical Limb Ischemia: ischemic rest pain, non-healing wounds, or gangrene and symptoms for more than 2 weeks
Acute Limb Ischemia: 5Ps defined by the clinical symptoms and signs for less than two weeks (pain, pulselessness, pallor, parasthesias, paralysis)
Differential Diagnoses for exertional leg pain
Lumbosacral radiculopathy: may see reduced DTR but normal pedal pulses
Describe pseudoclaudication vs claudication
Pseudoclaudication: cramping, tightness, aching, and fatigue with tingling, burning and numbess, location of buttock, hip, thigh, calf, or foot, may or may not be exercise-induced, pain occurs with standing, they sit/lean forward/change position to feel relief, and relief from symptoms occurs in less than 30 minutes
Claudication: cramping, tightness, aching, fatigue in the buttock, hip, thigh, calf, or food, pain is exercise-induced and the distance one must walk for symptoms to begin is consistent, pain does not occur with standing, patients stand or stop walking for symptoms relief, and symptoms improve within 5 minutes
Physical exam for PAD
Do complete CV exam with palpation of all pulses and auscultation of accessible arteries for bruits
Pulse abnormalities and bruits increase the likelihood of PAD
Decreased or absent pulse provides insight into the location of arterial stenoses
Physical findings in PAD physical exam
Arterial ulcers: pale base with irregular borders, usually involve tips of toes or heel of foot, develop at pressure sites
Diagnostic tests for PAD
Ankle- brachial index, PVR, segmental pressures, treadmill test, duplex US, CTA, MRA, angiography
Ankle-brachial index
Ankle systolic pressure/brachial systolic pressure
Normal: 1.00-1.40
Borderline: 0.91-0.99
PAD: less than or equal to 0.9
Pain/ulceration: less than or equal to 0.4
Non-compressible: more than or equal to 1.40
Limits to ABI testing
Calcified vessels can give falsely elevated pressure
Don’t know where stenotic arteries are
Solution: segmental pressures, waveform analysis
Goals for PAD treatment
Reduction in cardiovascular morbidity and mortality (discontinue tobacco use, SUPERVISED walking program, control BP to goal, high-dose statin therapy, antiplatelet therapy)
improve quality of life
maintain limb viability (good foot care, revascularization, cilostazol)
Factors of exercise that gives the best results for PAD patients
Duration of more than 30 minutes per session
at least 3 sessions per week for more than 6 months
walking used as the mode of exercise
Reach maximal claudication pain endpoint each session
When is revascularization considered?
If the patient has lifestyle-limiting claudication with an inadequate response to GDMT (guideline directed medical therapy)
Percutaneous transluminal angioplasty and stents
Peripheral catheter-based interventions are indicated for
- lifestyle limiting claudication despite trial of exercise rehab or pharm therapy
- symptomatic patients and clinical evidence of inflow disease as manifested by buttock or thigh claudication and diminished femoral pulses
- critical limb ischemia whose anatomy is amenable to catheter based therapy
What is the most frequent operation for patients with aortoiliac disease
Aorta-bifemoral bypass
What is the operative mortality rate for extra-anatomic bypass procedures
2-5%
*reflects in part the serious comorbid conditions and advanced atherosclerosis of many of the patients who undergo these procedures
Compare open and endovascular approaches for aortoiliac occlusive disease
Open surgical: excellent long-term patency rate, 85-90% for 5 years, requires general anesthesia, 1-3% mortality rate
Endovascular: high procedural success rates (90%), excellent long-term patency (more than 80-90% at 5 years), less morbidity/mortality
Endovascular procedures are done first in Type A and Type B lesions
Surgery may be considered first in Type D lesions
When do you treat a patient that presents with critical leg ischemia
ASAP ASAP ASAP
localize the lesion and then do revascularization as soon as possible to prevent loss of the limb
What is Dressler Syndrome
Pericarditis that occurs after an MI
What can occur 5-7 days after an MI
Cardiac tamponade (most likely time for the heart to rupture)
cor pulmonale
lung problems causing right heart failure
what are heart failure cells
alveolar macrophages filled with hemosideran
What body systems does Chagas disease affect?
esophagus, colon, heart
Describe Pericardial effusion types
Serous (transudate): low protein and no cells
Purulent (exudate): infectious, high protein, many WBCs
Malignant: metastatic disease
What are the causes of hemopericardium
Ruptured myocardium (from MI or trauma)
Aortic Dissection (hypertension or Marfan)
What is a severe hemopericardium and what can be the consequence?
more than 500 mL of blood
can cause tamponade, leading to sudden death
Causes of pericarditis
infectious agents (viruses, pyogenic bacteria, tuberculosis, fungi, parasites), immunological mediated (Rh fever, SLE, scleroderma, postcardiotomy, Dressler syndrome, drug hypersensitivity reaction), miscellaneous (uremia, trauma, radiation, etc)
** viral, TB, fibrinous, and SLE/scleroderma
Acute Serous Pericarditis
causes: infectious, usually autoimmune diseases, malignancy
Morphology: volume 50-200mL, scant inflammatory cells
3 causes of fibrinous pericarditis
post MI (dressler), uremia, rheumatic fever
causes of hemorrhagic pericarditis
malignancy, bacterial infections, following cardiac surgery
Chronic pericarditis
disabling because of adhesive scar formation
Adhesive Mediastino pericarditis
type of chronic pericarditis
follows suppurative inflammation or TB
sac obliterated and adhered to adjacent structures
increased strain on heart–>hypertrophy and/or dilation
Constrictive pericarditis
type of chronic pericarditis
results from suppurative or hemorrhagic pericarditis (staph or TB)
pericardial space obliterated by scar and/or calcification*
severe cardiac dysfunction (tamponade)
heart encased in dense fibrocalcific scar that limits diastolic expansion
HEART SOUNDS ARE DISTANT AND MUFFLED
ONLY TYPE OF PERICARDITIS ASSOCIATED WITH CALCIFICATION
what are telangiectasis
dilated capillaries that create small focal red lesions usually in skin and mucous membranes of body
Spider telangiectasis: associated with hyperestrogenism (pregnancy, live cirrhosis)
Hemangiomas
benign neoplasm of capillary or cavernous (can be in brain, very problematic if this ruptures)
usually in skin, can occur in liver, spleen, and kidney
usually occur early in life and fade
Glomus tumors
Painful, modified smooth muscle cell tumors on distal digits (ex/ under nails)
arises from glomus body
Painful but benign
Hemangiosarcoma
malignant atypical endothelial cells
associated with known carcinogens (polyvinyl chloride)
Kaposi Sarcoma
Types: classic or European(chronic)–not HIV associated; Immunosuppression or transplant-associated–AIDS-associated
Associated with HHV8–causes proliferation of blood vessels and angiogenesis
can occur in heart, lung, brain, skin, stomach, etc..
Carney syndrome
AD myxomas of skin and hyperpigmentation cardiac myxomas endocrinopathies mutation of some tumor suppressor gene
Myxoma
benign tumor of the atria (usually left)–blocks blood flow out of mitral (or tricuspid) valve (ball valve effect)
Dx: Echocardiography
rhabdomyoma
associated with tuberous sclerosis (hamartomas in CNS, skin, heart, and kidney)
benign
Angiosarcoma
Malignant tumor
where do metastatic tumors of the heart usually originate?
breast or lung
Cardiac transplantation complications
Rejections: cellular (t cells), or humoral (antibodies)
Infections: CMV, toxoplasmosis
Lymphoproliferative disease post-transplant: EBV mediated
Clinical presentation of acute pericarditis
flu-like sx or GI sx (viral prodome is common)
sharp, pleuritic chest pain precipitated by lying flat dt inflammation being placed on posteriorly located nerves, relieved by leaning forward, pain radiates to shoulder
EKG changes (diffuse ST elevations)
Friction rub best heard over left sternal border
pericardial effusion
EKG changes with pericarditis?
diffuse ST elevations and PR segment changes
What will a chest xray look like in most cases of acute pericarditis?
Normal
Diagnosis of acute pericarditis
at least two of the following:
- Characteristic chest discomfort (persistent, pleuritic, and positional)
- Suggestive ECG changes (diffuse ST elevation)
- Pericardial Friction Rub
- New or worsening pericardial effusion
Treatment of Acute Pericarditis
NSAIDs/Salicylates
Colchicine (3 months)
AVOID: glucocorticoids and pericardiectomy
Most cases of pericarditis can be treated outpatient. When is hospitalization (inpatient) required?
High fever (>38) Subacute onset large pericardial effusion trauma evidence of myocarditis immunosupressed pt concominant use of anticoags evidence of cardiac tamponade
Goals of pericarditis treatment
symptom relief, decrease inflammation
Pericardial Effusion
usually serous effusion
if Hemorrhagic: malignant, surgery/procedure complication, post-pericardiotomy syndrome, complications of MI, idiopathic, aortic dissection, infection (TB)
Biggest risk factor for pericardial tamponade
rate of fluid accumulation
*fluid causes compression of all cardiac chambers due to increased pericardial pressure
pericardium has a degree of elasticity but once that limit is reached–>potential for tamponade
Symptoms and PE of cardiac tamponade
symptoms: dyspnea, chest discomfort/fullness, peripheral edema, fatigability
PE: sinus tach, JVD, pulsus paradoxus
what is electrical alternans
beat-to-beat alteration in QRS appearance (best seen in leads V2 to V4)
What is electical alternans suggestive of
Strongly suggestive of pericardial effusion (usually with cardiac tamonade)
the alternating ECG pattern in electrical alternans is related to what?
the back-and-forth swinging motion of the heart in the pericardial fluid
Clinical presentation of tamponade
hypotension with pulsus paradoxus (more than 10 mmHg fall with inspiration)
elevated venous pressure with blunted or absent y descent
distant heart sounds
clear lung fields
Causes of pulsus paradoxus
respiratory: severe bronchial asthma, tension pneumothorax, COPD
Cardiac: cardiac tamponade, constrictive pericarditis, pericardial effusion, restrictive cardiomyopathy
Others: anaphylactic shock, obesity
Treatment for cardiac tamponade
URGENT PERICARDIOCENTESIS (only definitive therapy for cardiac tamponade) usually done percutaneously IV fluids may improve cardiac output (esp in hypotensive pt)
DO NOT GIVE DIURETICS
Constritive pericarditis
thickened, rigid pericardium
Which types of pericarditis are most likely to advance into constrictive pericarditis
TB pericarditis and purulent pericarditis
Clinical presentation of constrictive pericarditis
symptoms related to fluid overload (peripheral edema to anasarca)
symptoms related to diminished cardiac output in response to exertion (fatigability and dyspnea on extertion)
PE findings with constrictive pericarditis
JVP, pulsus paradoxus, Kussmaul’s sign (lack of inspiratory decline in JVP), pericardial knock (accentuated heart sound occurring slightly earlier than S3)
Echo/Doppler results with constrictive pericarditis
accentuated respirophasic effects on transvalvular velocities; septal bounce (ventricular interdependence), pericardial thickening
What is the anatomic imaging modality of choice in constrictive pericarditis?
CT/MR
tx for constrictive pericarditis
diurectics
surgery: results are often limited
* pericardiectomy
* surgical risk factors: age, NYHA class, organ failure, XRT, other cardiac disease
Effusive-Constrictive disease
clinical and hemodynamic manifestations of tamponade on presentation
After pericardiocentesis, residual clinical and hemodynamic manifestations of constriction
(High RAP despite reduction of pericardial pressure to as low as 0)
Cardiac arrest
the abrupt cessation of heart functiong
Causes of sudden cardiac death?
over 35: Coronary artery disease
Under 35: congenital and acquired abnormalities
Hypertrophic obstructive cardiomyopathy
Autosomal Dominant
ECG: QRS waves are very tall
Echo: hypertrophy is in the septum (not symmetrical like in hypertension)
Beta blockers help treat the SYMPTOMS (doesnt prevent SCD)
What is the most common coronary artery anomalous origin in HOCM
the origin of the right coronary artery from the left sinus of Valsalva
Marfan’s Syndrome signs
Wrist sign and thumb sign
Myopic with lens subluxation
Symmetric pectus excavatus
What is a concerning health risk in Marfan’s Syndrome?
Risk of aortic tear or aneurysm
Dysarrythmias that can cause SCD
Long QT syndrome (more than 440 mms)
Brugada’s Syndrome
Wolff-Parkinson White
Commotio Cortis
Vfib and SCD that is triggered by a blunt, non-penetrating, innocent-appearing blow to the chest during ventricular repolarization without any damage to the chest wall or heart
*most common in male baseball players
Pacemaker vein placement
placed in subclavian vein usually (specialists can do axillary or cephalic)
How does a pacemaker work
battery generates electricity and insulated wire has an extendable/retractable corkscrew tip (actively penetrates into myocardium) or a tyne tip (causes reaction at endocardial level)
pacing pulses are delivered to myocardium via the lead
What kind of battery does a pacemaker have?
lithium iodide battery that lasts about 15 years
What arrhythmia requires just a ventricular lead?
Afib
Function of pacemakers
Pace and sense the myocardium
Inhibits when pacing not needed
Algorithm to increase heart rate with activity
How is a lead inserted into the left ventricle
via the coronary sinus
What is a standard lead
goes to atria and right ventricle
corkscrew tip that extends 1.8 mm
How does a HIS bundle lead work?
does not directly stimulate the myocardium
gets the electrical activity to travel down the HIS bundle
How can pacemakers increase heart rate with activity?
Most use an accelerometer to identify postural changes and body movements related to physical activity (only enabled as needed)
Some use Minute Ventilation sensory to drive the pacing rate–measures resistance between an electrode on cardiac pacing lead and the metal housing of the device (changes with respiratory rate and chest excursion)–more natural heart rate response to exercise
DDD tracking mode
pacing and sensing in atrium and ventricle
inhibited by intrinsic P wave and QRS
In DDD mode, the pacemaker can truly adapt to what the heart is doing and mimics normal conduction as closely as possible
what is VOO mode
Pacing in ventricle, sensing is off, response to sensing is off
*paces at a programmed rate regardless of intrinsic activity
What is VVI mode
Pacing in ventricle, sensing in ventricle, inhibit
Pacemaker is capable of sensing the heart’s intrinsic activity and inhibiting pacing when it is unnecessary
When would you use VOO mode?
in surgery that uses cauterization (mimics heart’s electrical activity) or meds that might affect blood pressure
Defibrillation
pulseless VT or VF can be converted to sinus rhythm but delivering sudden electrical massive depolariation–>causes all myocardium to depolarize, then after phase 3 the pacemaker signal gets through the AV node depolarizing the ventricles and sinus rhythm is restored
what is an ICD
implantable cardiovertor defibrillator
electricity delivered to endocardium
Which device does not have pacing programming?
Subcutaneous ICD
How does subq ICD minimize infection risk?
Avoids transvenous access
How effective are ICDs
97-98% effective
One of the most successful treatments in medicine today
Why is drug therapy still indicated after ICD implantation
to suppress ventricular arrhythmias, minimize the frequency of ICD shocks, improve patients’ tolerance, and decrease energy use
*multiple shocks associated with shorter life
Chlorthalidone
thiazide diuretic (preferred for black patients with isolated hypertension) Side Effects: hyperglycemia, hypercalcemia, hypokalemia
What causes ischemic heart disease?
due to reduced blood flow due to obstructive atherosclerosis of the coronary arteries (CAD)
Clinical manifestations of ischemic heart disease
- myocardial infarction
- angina pectoris (ischemia is not severe enough to cause infarction)
- chronic ischemic heart disease with heart failure
- sudden cardiac death
what are some causes of ischemic heart disease
reduced coronary flow
increased myocardial demand (hypertrophy)
reduced availability of O2 in the blood
What inflammatory marker predicts the risk of coronary heart disease
C reactive protein
Pathogenesis of ischemic heart disease
Acute plaque change
Inflammation
Thrombosis
vasoconstriction
Describe unstable angina
plaque disruption causes thrombosis and vasoconstriction, leads to a severe but transient reduction in blood flow
Describe sudden cardiac death
regional myocardial ischemia that leads to a fatal ventricular arrhythmia
Stable angina
caused by chronic coronary stenosis of an atheroscleroting coronary artery
pain on exertion
Prinzmetal angina
caused by coronary artery spasm
effect is pain at REST
Where is the most common place for ischemic heart disease?
anterior septum resulting from occlusion of the LAD (45% of all cases)
Transmural infarction
necrosis of full thickness of ventricular wall, perfused by a single coronary artery–>coronary atherosclerosis–>plaque disruption–>thrombus
Subendocardial infarction
necrosis of 1/3 to 1/2 of the ventricular wall–>perfused by more than one coronary artery–>shock, hypertension or transient thrombus
What changes are present in the heart after MI? 0-4 hr 4-12 hr 12-24 hr 1-3 days 3-7 days 7-10 days 10-14 days 2-8 weeks more than 2 months
0-4: no changes
4-12: dark mottling, early coag necrosis, edema, hemorrhage
12-24 hr: dark mottling, ongoing coag necrosis, myocyte hypereosinophilia, early neutrophilic infiltrate
1-3 days: mottling with yellow-tan infarct center, coag necrosis, interstitial infiltrate of neutrophils
3-7 days: hyperemic border, central yellow-tan softening, macrophages at infarct border
7-10 days: yellow-tan with depressed red-tan margins, granulation tissue at margins
10-14 days: red-gray depressed infarct borders, well-established granulation tissue with new blood vessels and collagen deposition
2-8 weeks: gray-white scar with increased collagen deposition and decreased cellularity
more than 2 months:dense collagenous scar
What is the earliest histological change seen in acute MI
contraction band necrosis
myocardial fibers lose cross striations and the nuclei are not clearly visible
many irregular darker pink wavy contraction bands extending across the fibers
What molecules can be used as biomarkers for acute MI?
troponin I (best option, elevates 4-6 hours after MI, lasts 7-10 days)
CK-MB (peaks at 12 hours, back to baseline by 72 hours post-MI)
myoglobin (increased at 2-4 hours, peaks 9-12 hours, back to baseline by 24-36 hours)
Which markers is cardiac specific
troponin-i (99.4% specific)
will not show elevation in trauma or other disease states
What troponin range indicates MI
anything more than 0.5
When is a rupture of the myocardium most likely to occur?
3-5 days post-MI (this is when the myocardium is the softest)
What is chronic ischemic heart disease?
(aka ischemic cardiomyopathy) a condition of elderly who develop progressive heart failure as a result of ischemic myocardial
predisposing factors: post-infarction, severe atherosclerosis without infarction but myocardial dysfunction is present
What can cause sudden cardiac death
acute MI, congenital anomalies, aortic stenosis, mitral prolapse, myocarditis, myopathies, hypertensive heart, cocaine
What are common infectious causes of myocarditis?
coxsackie, lyme, chagas
Common immune-mediated reactions that cause myocarditis
poststreptococcal (rheumatic fever), transplant rejection
Clinical presentation of myocarditis
asymptomatic
fever, malaise, pericardial pain
sudden onset of acute heart failure
Gross findings in myocarditis
dilated ventricles, flabby heart, minute hemorrhages, mural thrombi may be present
What chemotherapeutic agent can cause myocardial disease
doxorubicin (causes lipid peroxidation in myocytes)–>dilated cardiomyopathy
What other drugs can cause myocardial disease
anthracyclin, lithium, chloroquine
Describe the morphology of myocarditis with drug toxicity
myofibers swelling, cytoplasmic vacuolization, fatty change
Name some causes of myocarditis
drug toxicity, amyloidosis (transthyretin), hemochromatosis, hyper/hypothyroidism
Congestive Heart Failure
mechanical failure of the heart to maintain systemic perfusion commensurate with the requirements of metabolizing tissues
what is forward heart failure?
decreased cardiac output
what is backward heart failure
damming back of blood in the venous system
Left-sided heart failure causes
ischemic heart diseases, hypertension, aortic/mitral valve diseases, myocardial diseases
Clinical presentation of left sided heart failure
dyspnea, orthopnea, paroxysmal nocturnal dyspnea
What are heart failure cells and when are they found?
alveolar nuclei with hemosideran inside of them
found in LEFT sided heart failure
What happens to the kidneys in left sided heart failure? the brain?
decreased renal perfusion (activation of RAAS–>retention of salt and water–>increased blood volume)
Brain: hypoxic encephalopathy
what can systolic heart failure cause?
ischemic diseases, valvular diseases
what can diastolic heart failure cause?
defective filling causes amyloidosis, fibrosis, severe hypertrophy
What is the most common cause of right-sided heart failure
left sided heart failure
Signs of right sided heart failure
liver congestion (may cause cardiac cirrhosis)(elevated LDH5, necrosis of hepatocytes around the central vein) congestive splenomegaly pleural effusion ascites peripheral edema brain congestion and edema JVD
What does elevated BNP indicate
values more than 100 indicate congestive heart failure
Where does ANP come from? BNP?
ANP comes from the atria
BNP comes from the ventricles
both increase in response to stretching of atria/ventricles
How are cardiomyopathies diagnosed
cardiac biopsy
Causes of dilated cardiomyopathy
alcohol (may be direct toxicity or thiamine deficiency), peripartum, genetic (dystrophin gene mutation, other sarcomere mutations), myocarditis (coxsackie virus), adriamycin toxicity
What mutations are associated with genetic hypertrophic cardiomyopathy
Cardiac troponin T
Myosin binding protein C
beta myosin heavy chain
what is disproportionately thickened in HCM
the septum
Is dilated cardiomyopathy systolic or diastolic dysfunction?
systolic
Is hypertrophic cardiomyopathy systolic or diastolic dysfunction?
diastolic
Describe the microscopic appearance of HCM
hypertrophy, disarray, fibrosis
What kind of murmur is associated with HCM
harsh systolic ejection murmur
Causes of restrictive/infiltrative CMP?
amyloidosis, hemochromatosis, hyper/hypothyroidism
what protein is associated with cardiac amyloidosis
transerythin
What is cor pulmonale
right ventricular enlargement resulting from structural or functional lung disorders (ex/ PE,, COPD)
explain the pathogenesis of hypertrophy in long-standing hypertension
increase BP–>accelerated aortic stenosis–>decreased large vessel compliance–>thickening of small arteries and arterioles–>increased peripheral resistance–>hypertrophy–>increased O2 demand and decreased heart compliance
What is the goal during adaption to insult to the heart?
maintain perfusion
Wall stress
Frank-Starling (initially helpful)
Hypertrophy (eventually maladaptive)
Molecular, cellular, structural changes=ventricular remodeling (maladaptive)
Activation of neuro-hormonal systems
What is the problem hypertrophy?
increases metabolic demands of the heart, but no increase in capillary volume–>supply and demand mismatch that increases the risk of ischemia
What happens in ventricular remodeling
shift of gene expression to upregulation of early response and fetal genes (in absence of DNA synthesis)
what does a non compressible vein indicate
DVT
Afib EKG findings
absent P waves and irregularly irregular RR interval
what drug is most effective for lowering triglycerides?
Fibrates
How do fibrates work?
activate PPAR-alpha and increase lipoprotein lipase activity–>lowers LDL and SIGNIFICANTLY lowers triglycerides, increases HDL
Side effect of fibrates
increased risk of cholesterol gallstones bc they inhibit CYP450; also hepatotoxicity and myopathy
What murmur is heard in mitral stenosis
diastolic murmur best heard at apex
opening snap after S2
**shorter interval between S2 and opening snap indicates more severe disease
What valve defect is often seen in Marfan syndrome?
Mitral valve prolapse
Describe mitral valve prolapse murmur
late systolic crescendo murmur with a midsystolic click
What is Beck Triad
Muffled heart sounds, distended neck veins, hypotension
describe electrical alternans
low voltage QRS complex with fluctuating R wave amplitude
what happens to the stroke volume is diastolic heart failure
narrow stroke volume
What happens to aortic stenosis murmur with maneuvers that increase the afterload (Ex/ handgrip)
decrease intensity of the murmur
test of choice for diagnosing DVT
compression ultrasonography
which holosystolic murmur increases with inspiration
tricuspid regurgitation
what is amplodipine
dihydropyridine calcium channel blocker
causes vasodilation and decreases BP
Common side effects: peripheral edema, headaches, dizziness, flushing, reflex tachycardia
Antidote for norepinephrine extravasation
phentolamine
Most common congenital cardiac anomaly in down syndrome
Atrioventricular septal defects (aka endocardial cushion defects)
Prinzmetal angina
symptoms occur at rest
triggers include stress, smoking, alcohol, drugs, triptan use
anterior ST elevations
What is the effect of PDGF from platelets and macrophages in atherosclerotic plaques?
intimal migration of smooth muscle cells, which mediates the transformation of fibroblasts into myofibroblasts (necessary for fibrous cap formation)
Infants born to diabetic mothers are at increased risk for which congenital heart defect?
transposition of the great vessels
What medication inhibits cholesterol absorption in the intestines and what is a side effect of this medication
Ezetimibe, elevated liver function tests (hepatotoxicity)
Pressure and volume overload occurs when frank-starling mechanisms fail…this leads to what?
concentric hypertrophy in response to pressure overload
eccentric hypertrophy in response to volume overload
overall, increase in size and mass of the heart
What happens to myocardial metabolism in heart failure?
begins to use glucose (like is a fetal heart) with downregulation of FA metabolism machinery
What causes interstitial fibrosis in heart failure
oxidative stress of cardiac fibroblasts (decrease collagen synthesis and activate fibroblast degradation) and NOX2 (activates fibroblast degradation)
Which adrenergic receptor does NE selectively bind?
beta 1 (more than beta 2 or alpha 1)
What happens in response to decreased cardiac output?
increased RAAS
Increased ADH
Increased SNS activity (increase contractility and HR)
Harmful effects of adrenergic receptors in human heart
cardiac myocyte growth, fibroblast hyperplasia, myocyte damage/myopathy, fetal gene induction, myocyte apoptosis, proarrhythmia, vasoconstriction
Compare the beta receptors in normal hearts and hearts in heart failure
Normal: 70-80% are beta1 agonist receptors
Heart failure: downregulation of beta1 so beta1:beta2 ratio is 60% to 40%
What drug can be used in heart failure
beta blockers
block effects of NE beta1 stimulation to re-establish normal autonomic nervous system homeostasis, also upregulates beta1 receptors slightly (improve exercise tolerance)
What is the effect of natriuretic peptides
vasodilation (also natriuresis and diuresis, antihypertrophy, antifibrosis, inhibition of SNS)
What secretes CNP
vascular endothelial cells, in response to inflammatory mediators
What is sacubitril (entresto)
inhibits neprilysin (normally cleaves ANP, BNP, CNP)
Factors associated with lower than expected BNP or NT-proBNP
obesity, flash pulmonary edema, heart failure causes upstream from left ventricle, cardiac tamponade, pericardial constriction
Factors associated with elevated BNP
left ventricular dysfunction, previous heart failure, arrhythmia, acute coronary syndromes, cardiotoxic drugs, significant pulmonary disease, advanced age, renal dysfunction, anemia, critical illness, high output states (sepsis, cirrhosis, hyperthyroidism)
what type of dysfunction is seen in HFrEF
Systolic dysfunction
what type of dysfunction is seen in HFpEF
diastolic dysfunction (abnormal relaxation)
List some causes of systolic dysfunction
coronary artery disease (MI), chronic volume overload (mitral or aortic regurg), dilated cardiomyopathies, advanced aortic stenosis, uncontrolled severe hypertension
List some causes of diastolic dysfunction
left ventricular hypertrophy, restrictive cardiomyopathy, myocardial fibrosis, transient MI, pericardial constriction or tamponade
describe the PV loop in HFpEF
LV pressure will be higher for any given volume
ESV will be lower due to stiffness
What worses diastolic dysfunction
exercise
Use exercise echo to evaluate diastolic dysfunction
Causes of acute HF
nonadherence with medication regimen, recent addition of negative inotropic drugs, initiation of drugs that increase salt retention, excessive alcohol or illicit drug use, endocrine abnormalities, concurrent infections
When do you administer ACEI/ARB or HF beta blockers to patients who were not previously on these drugs?
wait until after the IV heart failure meds (diuretics and vasopressors) are given
Describe the dose of IV loop diuretics given for acute HF. What if the patient does not respond?
usually about 2X the home dose, either bolus or infusion
no response=increase loop diuretic dose or add metolazone
What are some signs of low perfusion
cool extremities, low urine output, altered mental status, inadequate response to IV diuretic, prerenal azotemia
What are some signs of congestion
increase JVD, peripheral edema, S3, DOE/SOA, orthopnea/PND, rales, recent weight gain
treatments for patients with HFrEF that are
wet and warm
dry and cold
wet and cold
WW: watch for decreased perfusion, BP, mental status changes, decreased urine/kidney function with diuretics
DC: give inotropes to improve perfusion
WC: diuretics and inotropes
what increases risk for in-hospital mortality in acute HF presentation?
Hypotension (SBP less 115 mmHg)
BUN>43
Creatinine >2.75 mg/dL
What treatment is given for HFrEF patient with decreased perfusion
inotropes (beta 1 agonists)
What is milrinone
a PDE3 inhibitor that increases cAMP to cause vasodilation
can be used in acute decompensated HF
What is a common medication used in chronic HFrEF
digoxin (usually oral)
What drug is added for patient with HFrEF if beta blocker therapy is not sufficient
ivabradine (inhibits funny current in SA node)–>reduced persistently elevated HR and does not affect contractility
What are treatment options for ventricular arrhythmias in stage C HFrEF
muscle scar is arrhythmogenic for ventricular arrhythmias
tx=amidarone or sotalol
*mexilitine if they are resistant to the others
What happens to the SVR in cardiogenic shock
SVR is increased to compensate for loss of CO
Describe changes in preload, afterload, and cardiac output in different types of shock
Distributive: preload decreased, afterload decreased, CO increased
Hypovolemic: preload decreased, afterload increased, CO decreased
Cardiogenic: preload increased, afterload increased, CO decreased
Obstructive pulmonary: preload increased in RV and decreased in LV, afterload increased, CO decreased
Obstructive mechanical: preload decreased, afterload increased, CO decreased
Treatment for cardiogenic shock?
IV positive inotropes (dobutamine)
what is the number one cause of SCD in athletes
HYPERTROPHIC CARDIOMYOPATHY
Mutations coding for what can be the cause of genetic heart disease?
sarcomeres (more than 1400 mutations have been identified)
Common sequelae of HCM
LV outflow tract obstruction, diastolic dysfunction, myocardial ischemia, mitral regurg, systolic dysfunction
what are the 3 broad symtom categories of HCM
heart failure, chest pain, arrhythmias
what percentage of px with HCM present with a murmur
53%
What is the most common symptom of HCM in px less than 1 year old
murmur
mortality is high for infants with HCM, what is the cause of death
heart failure (as opposed to arrhythmia)
What causes LV outflow tract obstruction
combo of septal hypertrophy and systolic anterior motion of mitral valve–>this causes a murmur
Describe the murmur in HCM
loudest at apex/LLSB, may radiate to axilla, murmur increases with valsalva and standing (decreased preload), murmur decreases with handgrip and squatting (increased afterload)
Name some causes of restrictive cardiomyopathy
hemochromatosis, sarcoidosis, amyloidosis
What kind of heart failure does restrictive cardiomyopathy cause?
diastolic heart failure (HFpEF)
Causes of dilated cardiomyopathy
selenium deficiency, viral myocarditis, alcoholic cardiomyopathy, doxorubicin therapy
Formula for ejection fraction
stroke volume/end diastolic volume
mutations in titin protein will cause what?
dilated cardiomyopathy
describe the pathophysiology of ACS
vulnerable vessel–>acute plaque rupture or erosion–>vascular spasm and in situ thrombosis–>luminal compromise
Signs and symptoms of NSTEMI
chest pain/other ischemic symptoms with abnormal EKG changes (ST depression or T-wave inversions) and elevated troponin levels
How is the unstable angina clinically differentiated from NSTEMI
troponin is negative in unstable angina
Why is ST depression seen in NSTEMI
subendocardial ischemia causes ST vector to be directed toward the inner layer of the affected ventricle and ventricular cavity so the overlying leads record this as ST depression bc the electrical current is traveling away from the leads
Why is ST elevation seen in STEMI
with transmural or epicardial injury, the ST vector is directed outward and toward the overlying leads, so these leads record it as ST elevation (can get reciprocal ST depression in contralateral leads)
How long does it take after an MI to have complete necrosis of the cardiac muscle?
24 hours (wavefront phenomenon)
What biomarker is the gold standard for an MI/ACS
troponin (released from cardiomyocytes when these cells die)
What often causes cardiac arrest in a STEMI
Ventricular fibrillation
Describe treatment for a STEMI
aspirin 325 mg X 1 STAT
Heparin 5000 U bolus
activate STEMI team to fix occluded artery within 90 minutes
Emergency percutaneous coronary intervention
Dual antiplatelet therapy (aspirin plus P2Y12 antagonist)
NSTEMI initial treatment
aspirin and heparin drip, statin and beta blocker, nitroglycerin to receive chest pain, cardiac cath within 2-48 hours, DAPT
Describe EKG changes in an untreated STEMI
Acute: ST elevation
Hours: ST elevation, decreased R wave, Q wave begins
Days 1-2: T wave inversion, Q wave deeper
Days later: ST normalizes, T wave is inverted
Weeks later: ST and T normal, Q wave persists
differentiation between ischemia and infarction
Ischemia: reduced coronary perfusion resulting in myocardium with inadequate oxygen delivery
Infarction: death of cardiomyocytes, usually due to acute coronary syndromes
What is the underlying substrate of ACS
large lipid plaques
list the 3 main platelet activation pathways and the drugs associated with them
COX/thromboxane: aspirin
P2Y12 receptor agonists (ADP agonist): clopidogrel, ticagrelor, prasugrel
GPIIb/IIIa inhibitors: tirofiban, eptifibatide, abciximab
How does heparin work
catalyst for anti-thrombin III–>inhibits thrombin=anticoagulation
When is an ACEI used in ACS patients?
EF less than 40%, Diabetes mellitus, HTN
When are aldosterone blockers used for patients post MI? when are they contraindicated?
if ejection fraction is less than 40%
significant renal disease or hyperkalemia
describe use of anticoag/antiplatelet therapy in ACS
anticoagulation with unfractionated heparin from ER presentation until cardiac cath
STOP anticoag therapy after PCI
DAPT are continued after PCI
Biomarker for acute pulmonary embolism
D-dimer (if positive, then CTA chest PE protocol and V/Q scan)
Treament for PE (esp is patient is not a candidate for t-PA)
surgical embolectomy!
Describe the pain is acute pericarditis
pleuritic chest pain: sharp, worse with deep inspiration
EKG changes seen in acute pericarditis
Diffuse ST elevations, PR segment depression in lead II, PR segment elevation in lead aVR
How is acute pericarditis treated?
NSAIDs or colchicine
common cause of acute pericarditis?
viral
Typical medication treatment for STEMI after PCI
aspirin 81 mg daily, P2Y12 antagonist (clopidogrel or ticagrelor), atorvastatin/rosuvastatin, metoprolol, lisinopril, smoking cessation and therapy, medical therapy for HTN and diabetes as needed
Risk factors for CAD
age, HTN, hyperlipidemia, cigarette smoking, diabetes
What is the major site of resting resistance in the coronary circulation
arterioles
What substance causes max vasodilation of the arterioles which leads to hyperemic blood flow
Adenosine
At what percentage of stenosis do patients experience a drop in coronary flow during exercise (angina symptoms)? at rest?
70% stenosis is when symptoms appear during exertion, 90% stenosis causes symptoms at rest
What is normal resting coronary blood flow?
225 ml/min
When does the coronary blood flow occur?
during diastole (d/t compression during systole)
what should be the effect of exercise on coronary blood flow normally?
about a 4 fold increase in coronary blood flow to match the demand for oxygen
Stable angina
chest pain or tightness + possible dyspnea on exertion and fatigure/exercise intolerance, relieved with rest
Describe primary prevention
prevention of a disease or disease event in a person with no known evidence of this disease
Describe secondary prevention
Prevention of a disease/disease event in a person who has been diagnosed with a disease and/or had a symptomatic event due to disease
What is coronary CTA. what is a requirement to be a candidate for coronary CTA
newer alternative to stress testing to assess patients with chest pain. MUST have creatinine less than 1.5 so they can safely receive IV contrast
Stable angina therapy has two main goals. What are they and what medicines are used to achieve them?
reduce risk of MI and death: aspirin 81 mg daily, high intensity statin therapy
Reduce symptom burden: beta-blockers, long acting nitrates, calcium channel blocker, ranolazine
What are the two methods of revascularization
PCI (stent) and CABG
What are the three options for bypass conduit in CABG
saphenous vein graft, radial artery, or LIMA
Simplistic breakdown of which patients receive which revascularization
Severe, symptomatic CAD with triple vessel CAD or left main disease are treated with CABG; severe, symptomatic CAD with all other CAD anatomy (single vessel, double vessel) are typically treated with PCI
What is the most common method for assessing severity of coronary artery stenosis
visual estimation on coronary angiogram (can have inter-observer variability, over/under estimation of true severity)
What is FFR/intracoronary physiology.
Formula?
a method to determine severity of coronary artery stenosis.
FFR=distal coronary pressure/proximal coronary pressure *measured during maximum hyperemia
what is the FFR cutpoint for significant ischemia
FFR less than or equal to 0.8
what is iFR (instantaneous wave free ratio)
similar to FFR but does not require hyperemia–it is a resting physiologic index
Cutpoint for iFR
less than or equal to 0.89
optimal medical therapy for CAD
antiplatelet therapy (aspirin)
high intensity statin
beta blocker
second anti-anginal med (ex/ nitrate, ranolazine, CCB)
Which medication indicated for CAD is associated with a reduction in the risk for mortality?
Atorvastatin (and aspirin)
What can cause dilated cardiomyopathy?
idiopathic, familial (sarcomere mutations), inflammatory causes (infectious or peripartum) toxic (alcohol, cocaine, chemo), thyrotoxicosis, hypothyroidism, chronic hypocalcemia, tachycardia (afib), myotonic dystrophy
common mutations that cause DCM?
desmin, dystrophin, myosin binding protein C, titin, beta-myosin heavy chain, troponin, lamin A/C (many of these proteins are also mutated in HCM)
pathophysiology of DCM
decreased contractility, decreased stroke volume–>increased ventricular filling pressures (pulmonary and systemic congestion results), LV dilation leads to mitral regurg, decreased foward cardiac output (manifests as fatigue and weakness)
what heart sound is heard with DCM
S3 (also a mitral regurg murmur due to left ventrical dilation)
What happens to the PMI in dilated cardiomyopathy
lateral displacement (bc cardiomegaly)
How do you treat peripartum DCM
during pregnany: avoid nonselective beta blockers, use b1 selective (metoprolol succinate at low doses), NO acei, use hydralazine/nitrate combo
If LVEF is less than 25% or LV dysfunction persists for more than 6 months post partum, what are your recommendations
no subsequent pregnancies anticoagulation therapy (high incidence of LV thrombus if LVEF is less than 35%)
Does heparin cross the placenta
no
Other names for stress cardiomyopathy
broken heart syndrome, apical ballooning syndrome
What is stress cardiomyopathy
transient regional systolic dysfunction of LV apex with sparing of the base, presents like an acute MI, cardiac cath shows normal coronaries
Who gets stress cardiomyopathy
females more than males, common in japan, postmenopausal is common, often preceded by a stressor
Pathophysiology of stress cardiomyopathy
excess catecholamines, microvascular disease (NOT classic epicardial CAD)
Stress cardiomyopathy ECG and cardiac biomarkers
ECG: ST elevation in about 45% of patients, ST depression in 7%, QT prolongation is common
Cardiac biomarkers: troponin is positive in most patients, BNP is positive
Treatment for stress cardiomyopathy
Beta-blockers, ACEI/ARB, diuretics
Prognosis is great (most recover in months), recurrences are possible
describe restrictive cardiomyopathy
impaired diastole (active process) due to loss of compliance, fibrosis or scaring of endomyocardial tissue, infiltration of a noncontractile complex/material into myocardium normal ejection fraction until end stage
Examples of restrictive cardiomyopathy
scleroderma, amyloidosis, sarcoidosis, hemochromatosis, glycogen storage diseases (fabry, pompe), hypereosinophilic syndrome (Loefflers), metastatic tumors, radiation therapy
Pathophysiology in restrictive cardiomyopathies
reduced LV filling, normal ejection fraction, reduced cardiac output, increased diastolic pressures, smaller ventricular chambers (decreased cardiac output and higher heart rates)
Symptoms of restrictive cardiomyopathy
DOE, venous congestion, usual heart failure signs and symptoms, exercise intolerance
Increased diastolic ventricular pressure in restrictive cardiomyopathy can cause what?
atrial fibrillation
Physical exam findings for restrictive cardiomyopathy
tachycardia, JVD, Kussmaul sign (inspiratory increase in JVP as stiff RV cannot accommodate more volumes), pulm congestion with rales, irregularly irregular rhythm if Afib is present, TR murmur, ascites, peripheral edema
ECG findings in restrictive cardiomyopathy
nonspecific ST and T wave changes (can be afib rhythm), amyloid heart has low voltage and Q waves, sarcoid has conduction blocks
Echo findings with restrictive cardiomyopathy
dilated atria, left ventricles have normal to small chamber size, left ventricle EF is normal (until end stage), in infiltrative types there is a speckled appearance of LV
How do you differentiate between restrictive CM versus constrictive pericarditis
echo, invasive heart cath (hemodynamic study), CT chest or MRI (thick pericardium), EM biopsy can be helpful too (normal in constriction)
What kind of medical management is appropriate for restrictive cardiomyopathy
overall poor prognosis
Hemochromatosis: iron chelation plus phlebotomy
Primary amyloid AL: chemo plus stem cell transplant
TTR Amyloid: new treatments available
Arrhythmogenic right ventricular dysplasia
Genetic disorder with incomplete penetrance and incomplete expressivity
Genes that code for desmosomes (loss of intercalated discs) replacement of mainly RV free wall by fibrofatty tissues
diagnosis of ARVC
ECG: epsilon waves, RV arrhythmias
Echo is not very helpful, neither is cardiac biopsy (too many false positives)
Cardiac MRI
Genetic testing when a family member is diagnosed
Signs and symptoms of ARVC
family history positive for syncope or SCD, RV arrhythmias (palpitations, syncope, SCD)
Treatment for ARVC
ICD to prevent SCD
Left ventricular noncompaction
prominent trabeculae, deep recesses, contraction abnormalities and relaxation abnormalities that lead to heart failure, conduction abnormality leads to arrhythmias, thrombotic risk
inheritance of left ventricular noncompaction
AD, AR, or X-linked recessive, sarcomere mutation
Treatment for left ventricular noncompaction
anticoagulation and ICD
ultimately transplant is needed
Why is mitral regurg present in HCM
due to abnormal mitral valve, abnormal chordae tendinae, poor coaptation
Other cardiac findings in HCM
S3 or S4, paradoxic splitting of S2 (with severe LVOTO), brisk and bifid arterial pulses, diffuse LV apical impulse on palpation, parasternal lift, signs of CHF
Describe the murmur in HCM
harsh ejection murmur loudest at apex/LLSB due to combo of septal hypertrophy and systolic anterior motion of mitral valve
May radiate to axilla and base (rarely to the neck)
When would you use a cardiac MRI for HCM
if echo diagnosis is undetermined, to evaluate for fibrosis
ECG for HCM
most sensitive but not specific (5% had a normal ECG)
prominent Q waves in inferior and lateral leads, enlarged P waves in lead II suggesting atrial enlargement (byproduct of diastolic dysfunction), left axis deviation, inverted T-waves in lateral leads
Echo is HCM
can determine LV hypertrophy, systolic anterior motion of the mitral valve, and LVOT obstruction
what is considered gray zone for LV thickness?
13-15 mm–hard to distinguish between HCM and athletes heart
Why do we care about thickness of LV in HCM
increasing risk of SCD with increasing wall thickness
Conditions associated with HCM
Fabry disease, noonan syndrome (male version of Turner syndrome), pompe disease, fatty acid oxidation deficiency, mitochondrial
Who should be screened for HCM
all 1st degree relatives of a HCM patient with genetic mutation–should be screened every 12-18 months by eacho and every 5 years after 21
Which arrhythmias are seen in HCM
atrial and ventricular arrhythmias; nonsustained VT associated with significant increase risk of SCD; SVT observed in up to 40% of patients
which type of arrhythmia is rare except for patients with fabry disease
bradyarrhythmias
What is the goal of pharmacologic treatment in HCM
symptoms and improve functional capacity, slow disease progression (NOT prevention of arrhythmias)
What are some factors that are proposed to lead to arrhythmias
myocardiac hypertrophy, disarray, fibrosis, ischemia, and autonomic disturbance
How is myocardial fibrosis detected
late gadolinium enhancement on cardiac MRI
Risk factors for SCD in HCM patients
family history of SCD, unexplained syncope, NSVT (more than 3 beats at a rate of 120), massive left ventricular hypertrophy (more than 33 mm), abnormal blood pressure response to exercise (failure to increase SBP by at least 20 mmHg or fall more than 20 mmHg from peak exercise BP to ongoing exercise)
how many high-risk factors must a HCM patient have to have a drastically increased risk of SCD
at least 3 high-risk factors
Cause of death in young (5-15 years old) HCM patients compared to older HCM patients
younger patients usually die from SCD, older patients have increased chance of dying from heart failure (or stroke)
When is an ICD used in HCM patients
two or more high risk factors (may consider for 1 high risk factor), sudden cardiac arrest, end stage HCM (LVEF less than 50%), or LV apical aneurysm
Side effects of ICD in HCM
25% experience inappropriate ICD discharge, some have lead complications, 4-5% with device infection, 2-3% experience bleeding or thrombosis
What is the goal of treatment for HCM
treat symptoms (if a patient is asymptomatic, treatment is unnecessary)
Common medications given in HCM
beta blockers (reduce LVOTO), calcium channel blockers (usually verapamil), disopyramide, ranolazine, careful use of diuretics (because HCM patients are extremely preload dependent)
How do beta blockers reduce angina symptoms
decrease myocardial oxygen demand
How do CCB reduce angina symptoms
improve microvascular function
Nonpharmacologic treatment of left ventricular outflow tract obstruction
used in pharm fails (heart failure symptoms persist despite max medical therapy or LVOT gradient more than 50 mmHg)
Options include surgical myectomy or alcohol ablation
What is a septal myectomy
direct removal of septal muscle (may also address abnormal mitral valve leaflets at the same time)
Complications associated with septal myectomy
excess septal tissue removed causing a ventricular septal defect; LBBB; CHB
What is alcohol ablation? what is one drawback?
creates localized infarction in basal septum (performed through coronary artery. Alcohol ablation does not offer the ability to address mitral valve issues
Compare septal myectomy and alcohol ablations
no difference in long term mortality or rates of aborted sudden cardiac death
Need for pacemaker is much higher in alcohol ablation
Compare sports restrictions in europe and america
Europe allows recreational activities (no competitive sports), American does not allow any sports
Name two drugs that we learned in cardio that result in tachyphylaxis (rapid diminished response to a drug due to depletion of endogenous receptors)
nitroglycerine, phenylephrine
describe the effects of calcium channel blockers (verapamil)
negative inotropic, negative dromotropic, negative chronotropic, vasodilation
what is the underlying mechanism for mitral valve prolapse?
myxomatous degeneration
what is a prominent side effect of amiodarone?
pulmonary fibrosis (may see blue-grey skin discoloration too but this isnt dangerous)
An increase in which metabolites can lead to local vasodilation in exercising muscle
adenosine, lactate, H+, K+, CO2
Indications for cardiac stress testing
diagnosis of coronary artery disease, prognosis of coronary artery disease, efficacy of treatment of CAD; chest pain; angina in CAD pt; post MI; exercise prescription for cardiac rehab; pre op eval for noncardiac surg; new cardiomyopathy
Contraindications of stress testing
acute MI; 100% pacing or patient with chronotropic incompetence with a pacemaker; unstable angina; uncontrolled cardiac arrhythmias causing sx or hemodynamic compromise; symptomatic severe aortic stenosis; uncontrolled symptomatic heart failure; acute PE or pulm infection; acute myocarditis or pericarditis; acute aortic dissection
Relative contraindications to stress testing
left main coronary stenosis, moderate stenotic valvular heart disease, electrolyte abnormalities, severe arterial hypertension, tachy or bradyarrhythmias, HCM/outflow tract obstruction, mental or physical impairment leading to inability to exercise, high-degree AV block, LVH with repolarization changes
Compare development of CAD in men and women
women are delayed in developing CAD by about 1 decade compared to men
ECG treadmill stress test goals
HR=(220-age)*0.85
BRUCE protocol
treadmill starts flat x 3min
Q3 min treadmill increases speed and angle
Naughton slower and lower treadmill angle for CHF px and modified BRUCE for less conditioned patients
ECG criteria for positive stress test
measure ST depression 80ms from the J point
- 2mm horizontal or downsloping ST depression in anterior or lateral leads=ischemia
- 1mm horizontal or downsloping ST depression in inferior leads=ischemia
What is myocardial perfusion imaging
images of tissue perfusion of isotope after exercise compared to rest images (imaging can occur up to 4-6 hours after injection)
How do we do stress testing in patients unable to do treadmill
nuclear/echo/PET imaging ONLY (ecg not helpful bc there is no target heart rate)
How is regadenosine used in nuclear stress testing
it is a coronary vasodilator–>blocked artery wont be able to vasodilate to caliber of normal artery and will not change with readenosine administration (already max vasodilated due to endogenous vasodilators)–>evaluate for lack of tissue perfusion to identify ischemic areas
Dosage of regadenosine is stress testing
LOW DOSE (bc higher doses can also block the AV node)
what can you do if patient is unable to reach target HR with treadmill test
add regadenosine dose to treatmill test patient and then do usual post stress imaging
Why do we add echo to stress tests?
to determine wall motion abnormalities and determine culprit coronary artery
what is the advantage to using echo over MPI
evaluates for CAD and/or valve function, pulmonary pressures, and LV outflow tract obstruction during exercise
when is dobutamine stress echo indicated
nonCAD dyspnea, diastolic dysfunction, mitral valve disease, aortic valve disease, prosthetic valve eval
Dobutamine protocol
start infusion at 2.5 micrograms/kg/min and increase at 3 minute intervals
What does a biphasic response (improvement then worsening) in a dobutamine stress test indicate?
ischemia
What patient population is likely to receive a dobutamine stress test?
severe COPD patients
*cannot walk on treadmill and cannot tolerate regadenosine
Indications for Holter monitor
symptoms occur daily (monitor duration is 24-72 hours)
indications for event recorder
symptoms occur less than daily, more than 1-2 events per month, Afib burden (monitor duration 2 weeks to 4 weeks)
indications for internal loop recorder
symptoms less than monthly, cryptogenic stroke, AF burden (monitor duration is 3 years)
Chest radiography findings in congestive heart failure
cephalization of vessels, interstitial edema, alveolar edema, pleural effusions
Chest radiography findings in pulmonic valve stenosis
poststenotic dilation of pulmonary artery
Chest radiography findings in aortic valve stenosis
poststenotic dilation of ascending aorta
Chest radiography findings in aortic regurg
left ventricular dilation, dilated aorta
Chest radiography findings in mitral stenosis
left atrial dilation, signs of pulm venous congestion
Chest radiography findings in mitral regurg
left atrial dilation, left ventricular dilation, signs of pulm venous congestion in acute MR
special indications for echo
masses, tumors, myxomas, embolic source for stroke or TIA, endocarditis, congenital heart disease, cardiac device eval, screening of first degree relative for inherited cardiomyopathy
formula for the pressure gradient across a valve
4v^2
v=velocity
Continuity equation in closed flow system
A1V1=A2V2
Indications for TEE
further assess valves (esp mitral valve), embolic source for cause of stroke or TIA (rule out LAA thrombus prior to cardioversion in Afib), further assess PFO, ASD, VSD, endocarditis, prior to Afib ablation procedure
What is considered high risk stress testing that should be referred to a cardiologist
chronotropic incompetence, exercise induced arrhythmias or syncope, prior to AAD, positive CTA with high burden Ca or high Ca score, new cardiomyopathy (LV ejection fraction about 40%), non cardiac transplant eval
Ankle-brachial index results and their meanings
- 99-130: normal vessels of LE
- 91-0.99: borderline for PAD, may have claudication
- 41-0.90: signficant PAD, may cause claudication
- 00-0.41: severe PAD, claudication
Why should you be cautious using an ABI in a patient with diabetes mellitus
their vessels are calcified and uncompressible
What are the two groups of infective endocarditis?
native valve endocarditis and prosthetic valve endocarditis
Four steps required for IE
Injury to endocardial surface–>platelet-fibrin-thrombus formation at the site of injury–>bacteremia–>bacterial adherence to the platelet-fibrin-thrombus complex with bacterial growth and host response
What can cause disruption of the endocardial surface
turbulent blood flow or direct injury to the surface or inflammation
If normal tooth brushing released bacteria into the bloodstream, why do most people not get infective endocarditis?
because the normal cardiac endothelium is highly resistant to bacterial adhesion
What is the one bacteria that can easily infect uninjured endocardial tissue
staph aureus (because extra cellular dextran makes them stickier)
Why are gram positive organisms more likely to cause endocarditis
they are resistant to complement killing
How can bacteria enter the bloodstream?
direct inoculation (tooth brushing, catheter placement into a vein like PWID, hemodialysis, IV line) Indirect entery (bacteria breach local defenses and anatomic barriers like in cellulitis with bacteremia)
75% of IE cases are seen in patients with known structural heart disease…what is the exception?
50% of cases with S. aureus occur in absence of heart disease, especially in PWID
Why are macrophages not able to kill the bacteria in the bacteria/platelet/fibrin interaction?
fibrin matrix inhibits macrophages killing bacteria
describe how the Venturi effect is relevant in IE
IE lesions are seen on the low pressure side of the valve
Risk factors for IE
age over 60 yo (due to decrease in rheumatic heart disease and increase in age associated valvular degeneration), Male, PWID, dialysis, poor dentition, structural heart disease, prosthetic valve/implanted material
What are HACEK organisms
organisms previously associated with culture negative endocarditis (fastidious gram negative rods)
Haemophilus aphrophilus, actinobaccilus actinomycetemcomitans, cardiobacterium hominis, Eikenella corrodens, Kingella kingae
Where is a common place to see IE in PWID
tricuspid valve–this is because they inject directly into a vein, which is returned to the right side of the heart
What causes IE in PWID
usually S. aureus (may also be drug contaminants like pseudomonas, fungi, oral flora)
What is the most common bacteria seen in early prosthetic valve endocarditis
S. aureus and coag neg staph
- usually less than 2 months post-op and due to IO contaminant or hematogenous spread in post op period
- 2-12 months post-op coag neg staph is most common
What is the most common bacteria seen in late prosthetic valve endocarditis
more than 12 months post-op, microbiology and pathophys is usually similar to native valve endocarditis
what is an immunologic phenomenon of IE
immune complex deposition in kidneys (glomerulonephritix)
What are the most common murmurs for IE? (not including PWID)
aortic or mitral regurg (tricuspid regurg in PWID)
What is a Roth spot?
total embolic occlusion of retinal artery that can lead to blindness. Seen with IE
What is one of the most important things to remember when trying to make a diagnosis of IE?
take blood cultures BEFORE giving antibiotics
how is diagnosis of IE definitively made?
3 sets of blood cultures drawn from separate venipuncture sites in patients who have not received antibiotics (consistent, persistent bacteremia is the hallmark of IE)
What imaging is done for all suspected IE cases?
transthoracic echocardiogram (higher sensitivity for abscess around the valve ring, smaller lesions, leaflet perforations
what type of antibiotics must be used in IE (general)
Bacteriocidal–must kill the bacteria
what can infection at the site of surgical attachment of valve to heart tissue lead to?
ring abscess–usually requires surgery for treatment
Is IE usually monomicrobic or polymicrobic?
mono—polymicrobic IE is very rare
What is usually necessary for fungal IE
valve replacement
What are the major Jones criteria?
pancarditis, arthritis, sydenham’s chorea, E. marginatum, S. nodules (on the extensor tendons of hands and feet)
What are the minor Jones criteria
fever, arthralgia, increased ESR, increased PR, leukocytosis
How many major and minor symptoms are needed to make an RF diagnosis
2 major or 1major/2minor
Where is the erythema marginatum rash seen?
usually over the trunk..NEVER on the face
describe the erythema marginatum rash
pink evanescent rash with clear center and red margins on trunk, nonpruritic, migratory, nonindurated, and blanches on pressure
What is the best standardized test for diagnosing RF
Antistreptolysin O test
single titer
250 Todd units in adult and 333 Todd units in children is considered elevated
*20% of patients with RF have low titer
Pathognomonic lesion in RF
Aschoff bodies (giant cells with owl-eye nucleus) 3 phases found in heart *Early (necrosis) *Intermediate (proliferative) *late (healed)
What are anitschkow cells
cells with a caterpillar nucleus seen in RF
What diseases will have fibrinous pericarditis?
rheumatic fever, uremia, post-MI
What kind of endocarditis is seen in rheumatic fever?
verrucous (warty) at the closure of valves on the side of blood flow (atrial surface for AV valves and ventricular surface for semilunar valves)
How is the mitral valve appearance described in RF
fish mouth mitral valve
What is a McCallum patch
Map-like thickening of left atrial endocardium
what percentage of RF cases are recovered by 6 weeks? 12 weeks?
75% by 6 weeks and 90% by 12 weeks
5% persist past 6 months
what percentage RF cases have carditis
70% (frequency of recurrence depends on the frequency and severity of strept infection)
Describe acute IE
usually occurs on normal valve, highly virulent microbes, destructive and rapidly progressive course, death within days to weeks in spite of aggressive therapy
Describe subacute IE
usually occurs on abnormal valves, less virulent organisms, indolent course (over weeks to months), full recovery with treatment
What will you see microscopically in IE?
fibrin, inflammatory cells, bacteria, and granulation tissue (in the subacute)
What are some manifestations of microemboli in IE
petechiae, splinter hemorrhages, janeway lesions, subcutaenous osler nodes, roth spots
Non-infective endocarditis (marantic endocarditis)
STERILE thrombus along the lines of closure of the valves, usually occurs in people with a hypercoagulable state (Trousseau’s syndrome) or very ill patients (ex/ Alzheimers)
Libman-Sacks Endocarditis
SLE endocarditis, SMALL VEGETATIONS ON BOTH SIDES OF VALVES, fibrinoid necrosis and hematoxylin bodies
Carcinoid Heart Disease
thick plaques on the right side of the heart–>acid mucopolysaccharides with matrix
What is the trio of symptoms seen with carcinoid syndrome
flushing, diarrhea, bronchoconstriction (due to increased serotonin)
Mitral valve prolapse (myxomatous degeneration) murmur
mid systolic click
Mitral regurgitation murmur
holosystolic murmur that increases with squatting
Why can mitral regurg happen after an MI
rupture of papillary muscles
Murmur of mitral stenosis
opening snap followed by diastolic rumble
Murmur of aortic stenosis
late systolic ejection murmur with weakened and delayed upstroke of carotid artery pulsations
When will the aortic valve calcify
bicuspid aortic valve (calcification seen in younger px)
Aging
What is a common complication of aortic stenosis
concentric left ventricular hypertrophy–>CHF
microangiopathic hemolytic anemia
What can lead to aortic regurg
syphilis (aortic aneurysm) or infective endocarditis
Murmur of aortic regurg?
early blowing diastolic murmur
What happens to pulse pressure in aortic regurg
increases with aortic regurgitation (diastolic pressure decreases due to regurg and systolic pressure increases due to increased stroke volume)
What are some signs of aortic regurg
bounding water hammer pulse, pulsating nail bed (Quincke pulse), head bobbing
common side effect of amiodarone (a very lipophilic antiarrhythmic)
hyper/hypothyroidism
What is the most common cause of mitral stenosis
rheumatic heart disease
Peripheral blood flow is under dual regulations
CNS and local
Which organs have strong autoregulation? weak autoregulation? little or none?
Strong: kidney, brain, coronary
Weak: skeletal muscle, splanchnic circulation
Little or none: cutaneous
What is active hyperemia?
increased metabolic tissue activity (skeletal muscle, heart during contraction, neuronal, GI tract)–mediated by SNS control
What is reactive hyperemia
increased flow in response to prior decrease–due to metabolite control
What are some natural vasodilators
NO, CO2, H+, K, lactic acid (via pH effect), ANP/BNP, prostacyclin-1
Natural vasoconstrictors
angiotensin II, vasopressin, endothelin-1
What are the high pressure baroreceptors
arterial Aortic sinus (vagus nerve) and carotid sinus (glossopharyngeal nerve)
What are the low pressure baroreceptors
in right atria/ventricle –>ANP/BNP
pulmonary artery/vein–>vagus nerve
What are the chemoreceptors
Aortic body and carotid body–>sense O2, CO2, pH
Central (medulla oblongata)–>CO2, pH
Hypoventilation or diffusional problems lower pO2 and raise pCO2 causing?
reflex vasoconstriction and bradycardia
What is the bainbridge reflex
intravenous infusion–>increased right atrial pressure–>atrial receptors stimulated–>increases heart rate
When does the bainbridge reflex predominate over baroreceptor reflex
when blood volume rises
when does baroreceptor reflex prevail over bainbridge reflex
when blood volume diminishes
What receptor does the SNS act on to cause vasoconstriction? vasodilation?
constriction: alpha-1 receptors (norepi)
dilation: beta-2 receptors (epi)
What is the true long term regulator of arterial pressure
Extracellular fluid
What happens to contractility, TPR, and CO during intense physical exercise?
increased cardiac contractility, reduced TPR, increased CO
What happens to contractility and CO during heart failure?
cardiac contractility is decreased, CO is decreased
end up getting Na retention to increase blood volume–>higher right atrial pressure
What is the Cushing triad
presence of hypertension, bradycardia, and irregular respirations
*Helps save brain tissues during periods of poor perfusion
Formula for cerebral perfusion pressure
MAP-intracranial pressure
normally 5-15 mmHg
What does hypoxia-induced stimulation of aortic bodies cause?
tachycardia and vasoconstriction
Reduced arterial oxygen directly relaxes vascular smooth muscle in all circulations except…?
the lung
Integrated response to hypoxia
increased heart rate, cardiac output, and systolic BP while mean and diastolic arterial pressures remain constant or fall slightly
What is primary (essential) hypertension
hypertension without an identifiable cause–most common disease in US medical practice
What percentage of HTN cases are primary?
90% (more than 75 million americans affected)
What is secondary hypertension
specific cause of HTN is identified
White coat hypertension
BP measured in office is high but BP measured at home or other settings is normal
Define normal, elevated, stage 1 HTN, and stage 2 HTN
normal: less than 120 mmHg and less than 80 mmHg
Elevated: 120-129 mmHg and less than 80 mmHg
Stage 1 HTN: 130-139 mmHg or 80-89 mmHg
Stage 2 HTN: more than 140 mmHg or more than 90 mmHg
Elevations in what 3 things can cause increased BP?
heart rate, increased stroke volume, increased SVR
Where does renin come from
juxtaglomerular cells in kidney
SNS nerve fibers in aortic arch relax with low BP to stimulate JGC, also JGC act as baroreceptors, and chemoreceptors in macula densa cells sense NaCl in loop and released prostaglandins to stimulate renin
Effects of angiotensin II
increase BP, vasoconstriction of afferent and efferent arterioles in kidney, stimulates thirst centers in hypothalamus, increases ADH to increase H2O absorption in kidney, causes adrenal gland to release aldosterone
Best nonpharm interventions for prevention and treatment of hypertension
Weight loss, healthy diet (DASH diet), reduced intake of dietary sodium, enahnced intake of dietary potassium,, increase physical activity, moderation in alcohol intake
Recommended BP goal for patients with hypertension
130/80
Causes of secondary HTN
obstructive sleep apnea, renal artery stenosis, pheochromocytoma, CKD, meds/drugs, hyperaldosteronism, hypercortisolism, thyroid dysfunction, coarctation of aorta
How does obstructive sleep apnea cause HTN
pharyngeal muscles collapse during sleep–>hypoxia and hypercapnia–>stimulates SNS to vasoconstrict–>increased BP
tx=CPAP
How does renal artery stenosis cause HTN
decreases blood flow to kidneys causing renin secretion and activation of RAAS
*may have a renal bruit
*dx with ultrasound, MRA, or captopril nuclear medicine scan
tx with renal angioplasty with stent
What can happen if ACE inhibitors are given and RAS is bilateral
can cause increased Cr due to decreased filtration of kidneys (GFR)
Meds/drugs that cause secondary hypertension
oral contraceptives, NSAIDs, pseudoephedrine, corticosteroids, antidepressants, amphetamines, cocaine
how does pheochromocytoma cause HTN
adrenal tumor that secretes catecholamines–>vasoconstriction
- sweating, tachycardia, anxiety, headaches with high BP
- tx=surgical removal
how does hyperaldosteronism cause HTN
aldosterone producing adrenal adenoma or idiopathic bilateral adrenal hyperplasia–>sodium reabsorption and water reabsorption and potassium secretion in urine
- symptoms are usually related to low potassium (muscle cramps, weakness, arrhythmias)
- tx=surgical or medical
how does hypercortisolism cause HTN
Cushing syndrome (exogenous steroids, adrenal tumor, adrenal hyperplasia, or Cushing's disease)-->increased BP by increasing Na+ retention and stimulating angiotensin II receptors to vasoconstrict, and produce NO *signs: moon face, stria, buffalo hump
how does thyroid dysfunction cause HTN
hypo or hyper thyroidism
hyper: increased T3 stimulates beta-2 receptors of vascular smooth muscle–>decreases vascular resistance and overstimulates the heart increasing cardiac output
How does chronic kidney disease cause HTN
causes salt and water retention and dysregulation of RAAS
- dx by increased creatinine levels or protein in urine
- tx is to treat condition causing CKD along with BP management
Who to test/screen for secondary hypertension
severe or resistant HTN (HTN despite adequate doses of 3 antiHTN meds), an acute rise in BP in previously stable pt, age less than 30 years in nonobese and nonblack pt with negative fam history and no other risk factors, malignant or accelerated HTN, proven age of onset before puberty
Complications of HTN
left ventricular hypertrophy, thickening of arteries and arterioles leading to fibrosis and sclerosis in kidney, narrowing of cerebral arteries that can lead to stroke and other vascular conditions, vessels in eyes become brittle and weak and can hemorrhage into eye causing retinopathy
What is hypertensive urgency
BP is very high but not assocaited with end organ damage, not symptomatic, treatment is outpatient
What is hypertensive emergency
BP high enough to cause immediate complication (BP more than 180 or 120), usually symptomatic and treated in hospital
what are the three classes of drugs commonly used for initial hypertension therapy
thiazide-type diurectis, ACEI/ARBs, calcium channel blockers
MOA of thiazide diuretics (hydrochlorothiazide, chlorthalidone)
not the strongest diuretic, long acting and first-line treatment
selectively inhibits the Na+/Cl- co transporter on luminal side of DCT, also has mild vasodilatory effects
Side effects of thiazide diuretics
increased blood sugar and cholesterol/LDL, hypercalcemia and hyperuricemia (gout), K+ wasting (requires monitoring for hypokalemia)
MOA of loop diuretics (furosemide)
inhibit luminal Na+/K+/2Cl-transporter in thick ascending loop of Henle, induces synthesis of renal prostaglandins that inhibit salt transport in the TAL
Side effects of loop diuretics
increased loss of Ca2+, Mg+, H+ in urine, hyperuricemia, allergic reactions (sulfonamide structure), ototoxicity (reversible, dose related)
K+ sparing diuretics/aldosterone antagonists (spironolactone, eplerenone) MOA
steroid derivatives that are antagonists at aldosterone receptors in collecting tubule, reduce expression of ENaC sodium channels and ATP-dependent K+ pumps
Side effects of K+ sparing diuretics/aldosterone antagonists
hyperkalemia, gynecomastia and antiandrogenic effects (spironolactone only)
What is the main use of K+ sparing diuretics in HTN
weak diuretic effect so its usually added to other diuretics to reduce K+ wasting
What is the net effect of RAAS activation
increasing blood volume and systemic vascular resistance, which increase CO and arterial pressure
MOA of ACE inhibitors (lisinopril, enalapril)
prodrugs–require metabolism to be active
inhibit ACE to prevent production of ATII and increases levels of bradykinin
Side effects of ACEI
initial hypotension, acute renal failure (RARE), hyperkalemia, dry cough and angioedema, teratogenic effects
MOA of ARBs (angiotensin II receptor blockers)–end in -sartan
selective angiotensin II receptor antagonist
Side effects of ARBs
initial hypotension, hyperkalemia, teratogenesis, NO COUGH/ANGIOEDEMA
MOA of direct renin inhibitors (aliskerin)
renin antagonist (binds at renin’s active site)
Side effects of direct renin inhibitors
generally mild headache and diarrhea, contraindicated in pregnancy (not teratogenic in animal models but similar MOA to ACEI/ARBs so best to avoid)
MOA of dihydropyridine CCBs (nifedipine, amlodipine)
block L-type calcium channels, more selective for arterial vascular smooth muscle
*reduce systemic vascular resistance and arterial pressure
Side effects of dihydropyridine CCB
flushing, headache, excessive hypotension, edema, and reflex tachycardia, gingival hyperplasia
MOA of non-dihydropyridine CCB (verapamil, diltiazem)
bind non-selectively to L-type calcium channels on vascular smooth muscle, cardiac myocytes, and cardiac nodal tissues (more cardioselective than DHP CCBs)
*arterial effects predominate
Side effects of NDHP CCB
excessive bradycardia, impaired electrical conduction (AV node block), and depressed contractility, constipation, hyperprolactinemia
Which CCB is the most cardioselective?
verapamil (better antiarrhythmic)
diltiazem is less cardioselective (better antihypertensive)
MOA of nitrate vasodilators (nitroglycerin, sodium nitroprusside)
exogenous source of NO–>activate guanylyl cyclase–>increase cGMP–>activate protein kinase G–>activates myosin light chain phosphatase–>dephosphorylates myosin light chain–>vasodilation
NO also activates K+ channels–>hyperpolarization, relaxation
Side effects of nitrates
headache, flushing, reflex tachycardia, cyanide toxicity (nitroprusside only)
Which nitrate works more on arterials? which works better on veins?
arterioles: nitroprusside
veins: nitroglycerin
Examples of other vasodilatorys
hydralazine, minoxidil, fenoldopam
Hydralazine MOA
releases NO, dilates arterioles
Minoxidil MOA
opens K+ channels in smooth muscle, polarizing effect reduces likelihood of contraction, dilates arterioles
*treats HTN and hair loss
Fenoldopam MOA
D1 agonist, short-term use in severe hypertension
main effect of alpha-1 block?
orthostatic hypotension
main uses of alpha-1 selective blockers
BPH and HTN
treatment for HTN with angina
beta blockers, CCBs
treatment for HTN with Afib/Aflutter
Beta blockers. non-DHP CCBs
treatment for HTN with HF/postMI
ACEI/ARBs, beta blockers, non-DHP CCBs
What can you not give to px with HTN with asthma/COPD
DO NOT give beta blockers or ACEI
What can you give for HTN in pregnancy? what can you not give?
give labetalol, nifedipine, hydralazine, methyldopa
DO NOT give ACEI/ARBs/DRIs
HTN with black patients
give CCBs, thiazide diuretics
do not give beta blockers, ACEI
HTN with diabetic px
gives ACEI/ARBs
do not give beta blockers (can mask hypoglycemia)
How should antihypertensive meds be given to px in hypertensive emergency
IV formulation–>dont need to wait for absorption into blood
What is a side effect of hydralazine, minoxidil, fenoldopam? what can be treat this side effect?
Reflex tachycardia
treat with beta blockers
What is a side effect of vasodilators and SNS-targeted drugs? what can treat this?
fluid retention
treat with diuretics or ACEI
what kind of dysfunction is seen in HCM
diastolic dysfunction
what kind of dysfunction is seen in dilated CM
systolic dysfunction
what heart sound is seen in HCM
s4
diseases associated with HCM
Fabry, noonans, pompe, fatty acid ox definiciency, mitochondrial disease
Levine sign
leaning forward relieves the pain of pericarditis
Concern with myocarditis?
arrhythmias–>ventricular tachycardia
myocarditis clinical manifestations
chest pain, resp distress, GI sx, hepatomegaly, gallop rhythm, poor perfusion/diminished pulses, tachypneic, viral prodome, decreased voltages on ECG
Holosystolic murmurs
at tricuspid area: tricuspid regurg, VSD
at mitral area: mitral regurg
Most common congenital heart disease. (most common sympomatic)
VSD
Acyanotic congenital heart disease
VSD, ASD, AVSD, PDA, COA, valve issues
Congential heart defects with too much pulmonary flow
ASD, VSD, PDA
What. is used to treat pulmonary vascular congestion (like in VSD)
furosemide! (loop diuretic)
What is a consequence of long-standing unrepaired VSD
eisenmenger syndrome
When do you stop hearing a VSD murmur
when right ventricular pressure equalizes with left ventricular pressure
CATCH-22 with digeoge
22q11
cardiac abnormality, abnormal facies, thymic aplasia, cleft palate, hypercalcemia
ASD exam
systolic ejection murmur, fixed split S2 (very loud shunts may cause a diastolic murmur, may heard an S4)
What does ASD lead to
right atrial and right ventricular enlargement
AVSD association
endocardial cushion defect, Down Syndrome
cyanosis
What keeps a PDA open
PGE2 (prostaglandin)
What do you give to close a PDA
indomethacin
PDA signs
continuous machine like murmur and bounding pulses (Due to wide pulse pressure)
What causing bounding pulses
aortic regurg, AV fistula, aortic dissection, LV-aorta tunnel
What causes a narrow pulse pressure
coarctation of aorta
Coarctation of Aorta
Associated with turner syndrome and berry aneurysms
associated with 3 sign and rib notching on x ray
heavily associated with bicuspid aortic valve (50%)
preductal is worse than postductal
MUST KEEP PDA OPEN
What is the most common congenital heart disease in the world
bicuspid aortic valve
Pulm stenosis
SEM at LUSB, hepatosplenomegaly, associated with ToF
Tricuspid regurg
S1 coincident murmur at LLSB, seen with ebsteins anomaly (due to mom taking lithium during pregnancy) or possible IE from IV drug use
murmur associated with RF
mitral regurg (holosystolic murmur at apex)
Where do you see electric alternans
cardiac tamponade and pericarditis
Kussmauls sign
lack of inspiratory decline in JVP
Pericardial knock
accentuated heart sound occurring slightly earlier than S3 (in constrictive pericarditis)
WPW
short PR interval, wide QRS complex (bc ventricular depolarization does not start at bundle of HIS), slurred upstroke of QRS complex
What kills WPW px
atrial fibrillation
pulm stenosis murmur (associated with ToF)
SEM at LUSB
Tetralogy of Fallot
overriding aorta, pulm stenosis, RVH, VSD
truncus arteriosis
single s2
transposition of great vessels
diabetic mother, loud S2
TAPVR
figure 8/snowman on chest xray
3rd degree heart block
very low heart rate, regular escape rhythm, cocaine use?
How does dopamine affect the heart
increases contractility (positive inotrope)
skin side effect of amiodarone
greyish skin appearance
tests to run for amiodarone toxicity
LFT, TFT, PFT
milranone
PDEIII inhibitor, preventing inactivation of of ccAMP and cGMP
tx for Kawasaki disease
IVIG and aspirin
what can Kawasaki disease cause
coronary aneurysms
Why do lipids need lipoproteins
lipids are hydrophobic and have low solubility so lipoproteins help transport lipids in the blood
General structure of plasma lipoproteins
surface layer of amphipathic lipids (phospholipids and cholesterol), core of nonpolar lipids (TAG and cholesterol ester), apolipoprotein
what determines the density of plasma lipoprotein
lipid/protein ratio
What are the functions are apolipoproteins
part of structure of lipoprotein, co-factors/activators for enzymes, inhibitors for enzymes, ligands for lipoprotein receptors
Apoprotein for chylomicrons?
ApoB48
Function of chylomicrones
deliver dietary triacylglycerol from intestine to adipose tissue (and liver and other tissues), deliver dietary cholesterol from intestine to liver
Very low density lipoproteins (VLDL) function
deliver hepatic triacylglycerol to adipose and other tissues, precursor of LDL
Low density lipoproteins (LDL) function
deliver cholesterol from liver to peripheral tissues
High density lipoproteins (HDL) function
deliver cholesterol from peripheral tissues to liver
How does HDL contribute to the metabolism of chylomicrons
Apo C-II and apoE are transferred from HDL to the nascent chylomicron
What is familial lipoprotein lipase deficiency
rare AR disorder, absence of LPL activity and massive accumulation of chylomicrons in plasma and a corresponding increase of plasma triglyceride concentration
What makes up HDL
AI, AII, E, Cs, cholesteryl ester
What makes up LDL
B100, cholesteryl ester
What makes up VLDL
B100, Cs, E, triacylglycerol
what makes up chylomicrons
B45, Cs, E, AI, AII, triacylglycerol
rank the major lipoproteins from largest to smallest
chylomicron>VLDL>LDL>HDL
How are ApoB100 and ApoB48 related
come from same premRNA
ApoB100 (VLDL and LDL) is the full mRNA transcript while ApoB48 (chylomicrons) is a truncated version due to RNA editing
What is the important apolipoprotein in HDL
AI because it plays a major role in cholesterol transport
What catalyzes esterification of cholesterol
LCAT
what transfers cholestol ester to serum albumin
lysolecithin
Major functions of HDL
reverse cholesterol transport, transfer ApoCs and ApoE to chlomicrons and VLDL in plasma
What form of cholesterol is used for storage and transport in the interior of lipoproteins
cholesterol ester (makes them much more hydrophobic)
Functions of cholesterol
important component of cell membranes, precursor for synthesis of steroid hormones, precursor for synthesis of bile acids, biosynthetic pathways contains branch points that lead to other important isoprene products
What is the main regulatory step for cholesterol synthesis
HMG-CoA reductase rxn (3-HMG CoA–>mevalonate)
what is SREBP
steroid response element binding protein: SREBP activates genes with sterol response elements (like LDL receptor, HMG-CoA reductase)
SREBP increases production of LDL receptors and HMG-CoA reductase in response to increased intracellular cholesterol levels
What does the cholesterol released from degraded LDL do
inhibits synthesis of cholesterol and LDL-R
What happens to most bile acids
reabsorbed in ileum and reutilized (5% eliminated in feces)
Major pathways for elimination of cholesterol
excretion of bile acids
PCSK9 mutatuion
lower LDL-C–>reduced risk of cardiovascular disease
Serum lipid levels in metabolic syndrome
decreased HDL-C, increased TG, elevated small dense LDL
Best evidence of lipid hypothesis
statin decrease cholesterol, LDL-C, and cardiovascular disease
Why does reducing cholesterol help decrease LDL
reduced cholesterol increases LDL-receptor synthesis so more LDL-D is cleared from circulation
What is the therapeutic effect of statins
reducing number of LDL particles (not reducing the cholesterol itself)
What is familial hypercholesterolemia (heterozygous or homozygous)
deficit in LDL receptors, causes very high levels of LDL in blood
Friedewald formula
LDL-C=total cholesterol-HDL-C-(TG/5)
Conditions for lipid panel blood draw
fast for 12-14 hours prior to blood draw
When is the friedewald calculation of LDL-C not valid
if triglycerides are over 400 mg/dl
What is considered high for LDL-C, total cholesterol, and HDL-C
LDL-C: over 190 is very high
Total: over 240 is high
HDL-C: over 60 is high
What cholesterol measurement best predicts coronary disease?
triglycerides/HDL-C (LDL-C levels have little effect on risk)
What is the major cholesterol target fo reducing CVD risk
LDL-C
What ratio could be a marker for metabolic syndrome/type II diabetes
high TG/HDL-C
What is associated with markedly elevated levels (more than 500 mg/dL) of triglycerides
pancreatitis
Describe the exogenous pathway of lipid metabolism
chylomicrones are formed within the intestine from dietary fat and are rich in triglycerides–>these particles undergo hydrolysis by lipoprotein lipase in the muscle and adipose tissue to form chylomicron remnants–>liver then clears chylomicron remnants using the LDL receptor
What are the three apolipoproteins that chylomicrons have
ApoB48, ApoC, ApoE
Why are apoC and apoE important for chylomicron metabolism
ApoC is a required cofactor for metabolism by lipoprotein lipase and ApoE is a ligand for the LDL receptor
Describe the endogenous pathway of lipid metabolism
VLDL produced by the liver and is also triglyceride rich–>undergo hydrolysis by lipoprotein lipase in the muscle and adipose tissue to form IDL–>IDL undergoes further metabolism to form LDL particles
What apolipoprotein is needed for the assembly and secretion of VLDL, IDL, and LDL
ApoB100
Which lipoprotein accounts for 70% of the total plasma cholesterol
LDL
Major mechanisms for LDL removal
uptake by LDL receptor on hepatocytes
Where is HDL secreted from and what takes up HDL?
HDL secreted by liver and intestine and accepts cholesterol from macrophages and other peripheral cells..then taken up by liver
Which particles contain ApoB100
LDL, IDL, VLDL
Hyperlipoproteinemias type I and V
genetic defects in lipoprotein lipase–>accumulation of unhydrolyzed chylomicrons and VLDL–>severely elevated triglyceride levels
Hyperlipoporteinemias Type IIa and IIb
genetic defects in LDL receptor (IIb also associated with increased VLDL secretion)–>severely elevated LDL and VLDL
*can be heterozygous or homozygous
Hyperproteinemia type III
defective or nonfunction apoE protein–>chylomicron remnant accumulation and IDL (cant be taken up by hepatocytes)–>elevations in triglycerides ONLY
Hyperproteinemia type IV
increase in VLDL production–>elevated circulating levels of VLDL and elevated triglycerides
What is used to diagnose dyslipidemias
fasting lipid profile (indicated in all px more than 35 years old or those 20 years or older with CAD risk factors and repeated every 5 years, or earlier if levels are elevated)
Symptomatic presentation of dyslipidemia is rare but what are some possible clinical findings
severe hypertriglyceridemia: acute pancreatitis
hypercholesterolemia: cutaneous manifestation (Xanthoma and xanthelasma, corneal arcus)
What is a common manifestation of type V dyslipidemia
pancreatitis
What is the most common site for tendon xanthomata
achilles tendons or dorsum of hands (present in type IIA dyslipidemia)
Palmar dyslipidemias are painful and on the palms (usually in type III dyslipidemia)
What is first line recommendation for dyslipidemia
lifestyle changes (smoking cessation, healthy diet, weight loss, regular exercise)
MOA of statins
HMG-CoA reductase competitive inhibitors–>increases numbers of LDL receptors on liver–>more LDL is taken up by liver and this lowers serum LDL levels, also decreased VLDL synthesis in liver
who gets high-intensity statin? who gets medium or low intensity statin?
High CAD risk gets high intensity
px with intermediate to low risk for CAD are given medium or low intensity statins
What is considered high intensity statin
atorvastatin 40-80mg daily or Rosuvastatin 20-40 mg daily
Side effect of statins
myopathy (in 10-20% of patients), rarely leads to rhabdomylosis
may also see asymptomatic elevation in liver function tests
When are non-statin therapies used
those who do not tolerate statin or when risk reduction or LDL-C reduction is not adequate on statin therapy
PCSK9 inhibitor MOA (evolocumab, alirocumab)
monoclonal Ab that inhibits PCSK9 (which normally targets LDL receptors for degradation)–>more LDL receptors–>more LDL clearance and less LDL in serum
How much is LDL decreased with PCSK9 inhibitors
50-60%
MOA of ezetimibe
cholesterol absorption inhibitor at small intestine (competitively inhibits Niemann-Pick-like 1 protein)–>reduced chylomicrone production and less cholesterol delivery to liver–>increased in liver LDL receptors–>increased clearance of LDL particles
Most common side effect of ezetimibe
diarrhea
MOA of bile acid binding resins (cholestyramine, colestipol, colesevelam)
bind bile acids in intestine and prevent normal reabsorption to liver thru enterohepatic circulation–>hepatic cholesterol converted into newly produced bile acids–>increased production of LDL receptors–>decreased LDL-C, also greater VLDL production and increased TG levels
MOA of fibrates/niacin. what are they used for? (gemfibrozil and fenofibrate)
used to reduced TG levels (if TG levels are over 500 mg/dL) to lower risk of pancreatitis
MOA: activate LPL
Side effects of fibrates
cholesterol gallstones
gemfibrozil: increase in myopathy when combined with statin therapy
outcomes of fibrate?
reduce cardiovascular events in patients with hypercholesterolemia but NOT mortality rate
When do we use icosapent ethyl (EPA)
highly purified omega-3 fatty acid. indicated for secondary prevention in patients with TG>150 mg/dL (on max tolerated statin) and also for primary prevention in patients with multiple risk factors
Normal artery make up
endothelial cells, smooth muscle cells, extracellular matrix (elastin, collagen, and GAGs)
What is the vascular wall response to injury?
intimal thickening
What marker is associated with risk of MI, stroke, sudden cardiac death
high sensitivity CRP
What percentage of cardiovascular event occurs without risk factors (hypertension, smoking, hyperlipidemia, diabetes)
20%
what is present in all stages of atherosclerosis
inflammation (assessment of systemic inflammation has become an important factor in risk stratification)
What does CRP do after it is secreted from cells within the intima
activates local endothelial cells, induces a prothrombotic state, increases adhesiveness of endothelium to leukocytes
Hyperhomocystinemia
elevated homocystein (caused by low folate or B12 or genetics)
What is metabolic syndrome
obesity, diabetes, hypertension, hyperlipidemia
What is lipoprotein A
altered form of LDL; increased levels of lipoprotein a is associated with increased risk of coronary artery diseases and CVD
How does diabetes lead to atherosclerosis
induces hypercholesterolemia
Endothelium injury leads to
increased adhesion molecule VCAM1–>monocytes adhere and migrate to intima and then transform into macrophages and foam cells
Formation of foam cells leads to what?
smooth muscle recruitment from media or circulating precursors–>smooth muscle proliferation and ECM production
Transformation of monocytes to macrophages in atherosclerosis
initially protective via phagocytosis–>generate chemokines (monocyte chemotactic protein)–>produce growth factor to lead to smooth muscle proliferation–>produces toxic oxygen species leading to oxidation of LDL in the lesions
What is the basic lesion in atherosclerosis
atheroma/fibrofatty plaque in intima that consists of macrophages, core of cholesterol, and fibrous cap of ECM like collagen and elastic fibers
What does smooth muscle do to fatty streaks? what initiates this process?
after migrating from media to intima, smooth muscle proliferates and deposits ECM components to convert fatty streaks to mature fibrofatty atheromas (initiated by PDGF released from platelets taht adhered to EC)
Evoluation of atheromas
early intimal plaque foam cells of macrophages and SMC origin–>advaned atheroma modified by SMCs synthesized collagen producing a fibrous cap–>disruption of fibrous cap with superimposed thrombus–>serious clinical events
What is the foundation of atherosclerosis
inflammation
What is the initial lesion in atherosclerosis
foam cells (then fatty streak, then fibrous cap)
What is a fibroatheroma
atheroma with fibrotic core and calcification (mechanism: accelerated smooth muscle and collagen increase)
Brief description of each antiarrhythmic class
class I: membrane stabilizers Class II: beta blockers class III: K+ channel modifiers (prolongs AP) Class IV: Ca2+ channel blockers
what can caused a delayed after depolarization
digoxin toxicity, myocardial ischemia or adrenergic stress, or heart failure
*ca2+ overload
what can cause early after depolarization
interruption of phase 3 repolarization
*slow heart rate, hypokalemia, drugs prolonging QT interval (quinidine, sotalol, procainamide)
Torsades de points
due to marked prolongation of APD
What causes most tachyarrhythmias
re-entry
Class 1A antiarrhythmics MOA and examples
slows conduction velocity and prolongs AP
ex/ disopyramide, procainamide, quinidine
Class IB antiarrhythmics MOA and examples
No effect on conduction velocity, may shorten APD
ex/ lidocaine, mexiletine, phenytoin
Class IC antiarrhythmics MOA and examples
slow conduction and may prolong APD
ex/ flecainide, propafenone
What happens when Na channel is blocked
decreased conduction velocity (dromotropy), manifests as widening of QRS duration; increased AP threshold (decreased automaticity/pacing threshold), slight decrease in AP duration (QT interval), negative inotropy (less contractility bc less Na+ in cell so more Na/Ca exchange)
rank Ia, Ib, and Ic antiarrhythmics on ability to block Na+ channels, ERP duration, and QT prolongation
na+ blockade: Ic>Ia>Ib
ERP duration: Ia>Ic>Ib
prolong QT: only Ia
Which class I antiarrhythmic is good for treating ischemic/depolarized tissue
class Ib (lidocain, mexiletine)
Side effects of class Ia drugs
Proarrhythmics (TdP), negative inotropic, cinchonism (HA, tinnitus, blurry vision), procainamide can cause SLE-like syndrome, disopyramide has anticholinergic side effects (hypotension, dry eyes, dry mouth, urinary retention)
Side effects of Ib
seizures with lidocaine, GI upset with mexilitine
Side effects with Ic
pro-arrhythmic, propafenone causes metallic taste in mouth
MOA of beta blockers as antiarrhythmic
decrease SA node automaticity and prolong refractoriness of AV node, block adrenergic activation of Ca channels to decrease force of contraction
Which currents do beta blockers work on
funny current and inward calcium current
Drug of choice in exercise-induced arrhythmias and in patients with long QT syndrome
beta blockers
how do beta blockers affect heart rate, force of contraction, and oxygen demand
decrease HR, decrease force of contraction, decrease oxygen demand
Uses for beta-blockers has antiarrhythmics
afib/aflutter, atrial tachycardia, PACs/PVCs, recent MI, adjunct to NSVT and VT
Side effects of bet blockers
sinus bradycardia and SA node pauses, AV node blocks or pauses, heart failure, fatigue, sedation, sleep disturbance, sexual dysfunction, dyspnea and bronchospasm (only beta 2 receptors), hypoglycemia unawareness (blocks symptoms of low BG)
When are beta blockers contraindicated
pheochromocytoma and cocaine toxicity (due to unopposed alpha receptor stimulation–severe hypertension, aortic dissection, coronary spasm, MI)
nonselective beta blockers are contraindicated in asthma/COPD
Antidote for beta blocker OD
fluid, atropine, glucagon (increases Ca2+, increases chronotropy and inotropy)
How do class III antiarrhythmics work
block K+ channel to increase APD and prolong refractory period–>longer QT
What kind of effect do many K+ch blockers have
reverse use dependent effects (binds to resting channels)–>AP prolongation is greater at slower rather than faster rates, this leads to an increased risk of triggered activity and therefore proarrhythmias
What drugs are mixed class III? which are pure class III?
mixed: amiodarone, dronedarone, sotalol
Pure: ibutilide, dofetilide
How does amiodarone work
mixed class III prolongs AP duration in both atrial and ventricular myocytes and prolongs the refractory period of AP of atrial and ventricular myocytes *noncompetitive inhibition of alpha and beta adrengergic receptor *reduced automaticity of automatic cells
ECG changes and hemodynamic changes seen with amiodarone
ECG: reduction of sinus rate by 15-20%, increased PR and QT duration, U waves and nonspecific T wave changes
Hemodynamics: vascular smooth muscle relaxation
When is amiodarone used?
atrial flutter and afib, ventricular arrhthmias
Treatment for stable vtach
IV amiodarone, cardioversion, post ECG, expert consult
side effects of amiodarone
acute pulmonary toxicity (hypersensitivity pneumonitis), long term toxicity (interstitial/alveolar pneumonitis), abnormal thyroid function tests to thyrotoxicosis (bc amiodarone has iodine in its structure)
abnormal liver function tests to hepatitis, optic neuritis or corneal microdeposits, photosensitivity (blue/gray discoloration of sun exposed skin), avoid grapefruit juice, caution with digoxin
Loading dose of amiodarone? Ventricular arrhythmia maintenance dose?
Loading (about 10grams over 2-3 weeks)
V. arrhythmia maintenance dose=400mg daily
MOA of class IV antiarrhythmics
Calcium channel blockers
(cause a use-dependent selective depression of calcium current in tissues that requires the participation of L-type calcium channels
decrease AV conduction velocity and effective refractory period is increased, PR interval is increased
Effects of CCB
inhibit SA and AV nodes and tissues with abnormal automaticity dependent on Ca2+ channels
- generally little effect on APD
- stops triggered activity (EAD, DAD)
- slows heart rate, decreases contractility
What causes EADs and DADs
EAD: due to oscillatory depolarization due to waves of Ca2+ channel reactivation
DAD: results from ca2+ overload of cell
Uses for CCB
SVT, afib, certain ventricular arrhythmias
Side effects of CCB
AV block, heart failure
Adenosine MOA
IV rapid and short acting drug, blocks Ca2+ entry and K+ channels at AV node (hyperpolarizes cells)
- used in SVTs
- can diagnose atrial arrhythmias
- side effects: flushing, hypotension, dyspnea, chest pain
Digoxin MOA
Parasympathetic vagal nerve effects
- decrease HR at SA and AV nodes
- increase contractility
Digoxin toxicity
NARROW THERAPEUTIC WINDOW
toxicity: atrial tachy with AV node block, bidirectional VT
Antidote: digibind, magnesium
What is the resting membrane potential in cardiac myocytes
-90 mV
What is the bundle that goes from the right atrium to the left atrium
Bachmann’s bundle
What improves AV node conduction? what worsens it?
Exercise, catcholamines, and atropine improve AV node conduction
Carotid massage worsens AV node conduction
Bundle of HIS is silent on surface ECG…Where can it be seen? what does bundle of HIS do?
on intracardiac ECG (catheter tip with electrode)
bundle of HIS conducts impulses to bundle branches
Blood supply of SA node, AV node, HIS bundle, left and right bundle braches, and posterior and anterior fascicle
SA: 60% RCA, 40% LCX
AV: 90% RCA, 10% LCX
HIS: mostly RCA, some contribution from septal branches of LAD
LBB: LAD
RBB: septal branches of LAD, collateral from RCA/LCX depending on which one is dominant
Posterior fascicle: RCA and sometimes LAD septal branches
Anterior fascicle: Septal branches of LAD, very sensitive to ischemia
Directions of ventricular depolarization
left to right across septum, inferiorly to apex, superiorly thru ventricles
In what direction is repolarization directed?
epicardium to endocardium (epicardial cells repolarize first)
Why is T wave longer than the QRS complex
Repolarization of the ventricles takes longer than depolarization
axes on ECG
y-axis: voltage
X-axis: time
on ECG what is positive and what is negative?
depolarization is positive, repolarization is negative
What is wilson’s central terminal?
negative pole for the 6 precordial leads
the average measurement from the electrodes placed on RA, LA, and LL indicating the average potential across the body
How long should a normal QRS be?
0.8-.12 sec duration
How much voltage is a small box on y axis?
how much time is a small box on x axis?
small box on y axis= 1 mV
small box on x axis=40 msec (5 big boxes=1 second)
where should a sinus P wave appear + and where should it appear -
+ in lead I, II
- in lead V1
How does adenosine affect AV node
temporarily stops AV conduction
how does atropine and exercise affect AV node
increases AVN conduction and prolongs subAVN conduction
How does vagal maneuver (carotid massage) affect AV node
prolongs AVN conduction and increases subAVN conduction
Describe 3rd degree heart block. how can you determine where the escape rhythm is?
more Ps than QRSs, AV dissociation
QRS less than 120 ms: escape in HIS bundle
QRS 120-150ms: escape is in fascicles below HIS
QRS more than 150 ms: escape can be anywhere beyond purkinje fibers
what is supraventricular tachycardia
circuit within the AV node or a circuit involving the node and an abnormal connection between the atria and ventircle (bypass tract)
Normal axis
-30 to +90 degrees
Name the leads to correspond to a certain area: anterior, septal, high left lateral, inferior, right ventricle
anterior: V2, V3, V4
septal: V1 and V2
High (left) lateral: I, aVL, V5, V6
Inferior: II, III, aVF
Right ventricle: aVR
What does ST elevation indicate
severe coronary artery occlusion (supply «_space;demand)
Loss of Na+/K+ ATPase pump that normally keeps cell hyperpolarized–>K+ ATP channels open with more loss IC K+–>depolarization
Can ST elevation be arrhythmogenic
yes
what is QTc
allows comparison of QT interval at any HR (tells you what the QT interval would be at 60 bpm)
QTc=QT/square root of RR
What axis deviation is associated with Left Anterior Fascicular Block? Left Posterior Fascicular block?
Left axis deviation with LAFB
Right axis deviation with LPFB
What are some times you may see a RBBB
damage to RBBB, chronic hypertension, MI, cardiomyopathy, congenital heart disease, pulmonary embolism, cor pulmonale, Lev’s disease
When will you see LAFB
chronic HTN, dilated cardiomyopathy, aging, degenerative fibrotic disease, aortic stenosis, aortic root dilation, acute MI, electrical conduction abnormality, lung disease
When will you see LBBB
chronic HTN, ischemic heart disease, anterior MI (new or old), dilated cardiomyopathy, fibrosis of LBB, hyperkalemia, digoxin toxicity, aortic stenosis
what is ST depression associated with?
subendocardial ischemia
What does T wave inversion indicate
lack of oxygen relative to demands and subendocardial is the most susceptible to ischemia where myocardium cant sustain normal activation/depolarization so repolarization occurs earlier in this section and force is opposite to ischemia area
what is happening in phase 4 of cardiomyocyte action potential
resting phase (electrical diastole), at -90mV, K+ inward rectifier channels allow outward leak of K+
what is happening in phase 0 of cardiomyocyte action potential
depolarization
AP from atrial fibers or purkinje fibers and fast Na+ channel open and Na+ leaks into cell until TMP rises to -70mV (threshold), then a large Na+ current into cell and rapid rise of TMP to 0mV or above, then fast Na+ channels close
what is happening in phase 1 of cardiomyocyte AP
TMP just above 0 mV, transient K+ channels open and K+ efflux out of cell so TMP reaches 0mV
what is happening in phase 2 of cardiomyocyte AP
L-type calcium channel remain open and Ca2+ influx, (needed for contraction of cellular myofibrils)
K+ delayed rectifier channel open and K+ efflux
electrical balance causes a plateau in TMP
What is happening in phase 3 of cardiomyocyte AP
Ca2+ channel begin to close but delayed rectifier K+ channel remain open, allows more K+ efflux and TMP re-approaches -90 mV
Na+ ATPase and Ca2+ ATPase carry Na+ and Ca2+ out of cell and SR Na+Ca2+ exchanger carries Ca2+ into SR (relaxation)
What kind of cell junctions are seen in cardiac myocytes
gap junctions (electrical path from cell to cell)
Why are long refractory periods needed in cardiac myocytes
to allow refilling of chambers
Degree of refractoriness=the number of fast Na+ channels to a resting state
Do atria or ventricles have shorter refractory periods
atria (therefore atria are more sensitive to parasympathetic stimulation than ventricles)
What is the negative voltage max in pacemaker cells
-60 mV
describe phase 4 of pacemaker AP
diastolic phase between depolarization
channels for funny current are open at -60 mV and allow Na+ influx–causes slow depolarization and activate voltage gated T-type ca2+ channels
phase 4 is slowly upward until it reaches -40 mV then depolarization occurs
this phase is due to automaticity
describe phase 0 in pacemaker AP
slow long-lasting Ca2+ influx
Describe phase 3 in pacemaker AP
Ca2+ channels are inactivated and K+ channels are activated so there is K+ efflux and therefore repolarization
What part of the heart is most sensitive to parasympathetic stimulation
AV and SA nodes
Describe conduction through the AV node
small diameter fibers conduct slowly and cause a delay–allows for atrial contraction emptying completely before ventricles depolarize and contraction–>excitation contraction coupling
How is ca2+ involved in muscle contraction
Ca2+ attaches to troponin and tropomyosin-troponin complex configuration changes so cross bridges can attach to actin
What connects cardiac muscle cells end to end
intercalated discs
Is ATP needed for relaxation or contraction?
both (ATP binding needed for relaxation, ATP hydrolysis needed for active complex of actin-myosin formation)
How is calcium provided for muscle contraction
influx of ca2+ from interstitial fluid during excitation–>binds ryanodine receptos and allows Ca2+ release from SR–>free cytosolic ca2+ activates contraction of myofilaments (systole), diastole occurs as result of uptake of Ca2+ by SR by extrusion of intracellular ca2+ by the 3Na+1Ca2+ antiporter and by Ca2+ATPase pump
How long is cardiac myocyte refractory period
250 ms
What molecule couples excitation and contraction
Ca2+
What channel actively removes Ca2+ into SR during diastole
SERCA
How does SNS activation affect cardiac contraction
increases intracellular calcium via opening of L-type Ca2+ channels and therefore released more Ca2+ from SR, phosphorylation of PLB increases Ca2+ uptake and stimulates relaxation, PKA-dependent troponin I phosphorylation reduced myofilament sensitivity for Ca and therefore hastens relaxation and diastolic filling
What drugs are effective against early afterdepolarization? how about delayed afterdepolarization?
EAD: treated with lidocaine (decreases AP duration)
DAD (due to increased cytosolic Ca2+ released after repolarization like in digoxin toxicity): treated with ?
Is the heart ever on the descending limb of the LT curve
no, not even in heart failure
What term quantifies affinity of a drug for its receptor?
Kd-dissociation constant (higher affinity=low Kd)
Phenylephrine
alpha 1 agonist
treats rhinitis, eye redness and irritation, dialates eyes, can treat hypotension resulting from vasodilation associated with septic shock or anesthesia
Midodrine
alpha 1 agonist
treats orthostatic hypotension
SE: urine retention, goose bumps, bradycardia
Why do alpha 1 agonist cause bradycardia
reflex bradycardia due to baroreceptor response from vasoconstriction
clonidine
alpha 2 agonist
adjunct treatment for hypertension, can be epidural, or tx for ADHD, tic disorders
rapid discontinuation causes rebound hypertension
SE: dry mouth, sedation
Tizanidine
alpha 2 agonist
muscle relaxant
SE: sedation, hypotension, dry mouth
Dobutamine
beta 1 agonist (some beta 2)
inotropic support in decompensated CHF, stress echo in px that cant exercise
*minimal beta 2 effects allow increase in cardiac output with less reflex tachycardia
administered via continuous IV infusion due to short half life
Albuterol
beta 2 agonist
treats acute bronchospasm in asthma or copd
Salmeterol
beta 2 agonist
prophylaxis against bronchospasm
Terbutaline
treats asthma
tocolytic in premature labor
*SE: tremor, tachycardia, metabolic effects, arrhythmias
Where are D1 receptors found
in periphery (D2 found in brain)
Functions of D1 receptor (Gs)
dilation of vascular smooth muscle, increases renal blood flow
Fenoldopam
D1 agonist
treats severe hypertension
SE: dose related tachycardia (baroreceptor reflex), hypokalemia, increased IOP in glaucoma
Bromocriptine
D2 agonist
treats parkinsons’ disease with levodopa (works on nigrostriatal path) or treats hyperprolactinemia (tuberoinfundibular path), tx for T2D
What enzyme metabolizes catecholamines
COMT
Metabolic effects of endogenous catecholamines
put glucose into circulation, regulates hormone secretion (insulin, renin), CNS effects at very high doses, potent CV effects so very useful in treatment of shock and heart failure
Epinephrine
treatment for anaphylactic shock and IgE mediated reactions, hypotension in shock, mydriatic for intraocular surgery, prolongs effect and reduces toxicity of local anesthetics (via vasoconstriction in skin to reduce diffusion of anesthetics)
*relieves bronchospasm (b2), mucous membrane congestion (a1), and hypotension (a and b1)
How dose dosage of epi change its effects
low dose works more on beta 2 receptors, high doses work more on alpha receptors
Low dose epi effects
increase in pulse rate and systolic pressure, decrease in diastolic pressure, unchanges MAP, small decrease in TPR, increased CO
Norepi
increases contractility and heart rate, vasoconstricts, increases BP and coronary blood flow
*alpha effects are greater than beta effects
Used in cardiogenic and septic shock
SE: bradycardia, arrhythmia, anxiety, headache
If extravastion occurs at IV site, treat with phentolamine to dilate vessels and restore blood supply
CV effects of norepi
decreased pulse rate (compensatory baroreceptor bradycardia), increases MAP (systolic and diastolic increase), increased TPR
Describe how dosage of dopamine determines its effects
low: D1 activation (increasd cAMP mediates vasodilation. inrenal, splanchnic, coronary, cerebral vessels, promotes natriuresis and increases urine output_
Med: beta 1 receptor activity also activated (peripheral resistance may decrease)
High: alpha receptors activated (vasoconstriction, increased BP)
What may result from abrupt discontinuation of dopamine
hypotension
What are some reuptake inhibitors
Cocaine (da reuptake inhibitor), atomoxetine (NE and Da reuptake inhibitor), duloxetine (SNRI)
Selegiline
inhibits MAO-B (tx for parkinsons and depression)
Entacapone
COMT inhibitors (treats parkinson)
Amphetamines
inhibit VMAT and competitively inhibit reuptake of DA, NE, and serotonin), causes uptake transporters to reverse direction (used in ADHD, narcolepsy, obesity)
Ephedrine, pseudoephedrine, phenylephrine
enter neurons via NET and displace stored NE, alpha and beta agonist (except phenylephrine is only alpha), enters CNS
SE: vasoconstriction, reflex bradycardia, cardiac stimulation, inhibiton of urination, bronchodilation, CNS stimulation
OD: agitation, HTN, cardiac arrhythmias
What does alpha 2 activation do?
opposes SNS effects (BC its a Gi receptor)
What is the role of CNS DA antagonist?
antipsychotics
CV effects of alpha 1 blockade
vasodilation (reduced PVR and MAP, headaches, nasal congestion), orthostatic hypotension, reflex tachycardia
CV effects of alpha 2 blockade
more reflex SNS release of NE, further stimulating beta 1 receptors (increases tachycardia)
Phentolamine
nonselective alpha blocker
used to be used to test for PCC, reverses accidental extravasation with vasopressor infusions, revereses local anesthetic effects
phentolamine and phenoxybenzamine
nonselective alpha blockers
phenoxybenzamine is more alpha 1 blockers
tx for hypertension in preoperative PCC
phenoxybenzamine is preferred for PCC bc it is an irreversible blockade!!–>this cannot be overcome by the large amounts of catecholamines coming from the tumor
Antidotes for hypertensive crisis (like with MAOI+aged cheese)
prazosin
alpha 1 blocker
treats hypertension and PTSD related insomnia
*first dose hypotension
*less reflex tachy than nonselective alpha blockers bc of little a2 blockade
terazosin
alpha 1 blockers
treats hypertension and BPH sx
*first dose hypotension
*less reflex tachy than nonselective alpha blockers bc of little a2 blockade
tamsulosin
alpha1A blocker (alpha 1A found mainly in prostate) tx for BPH with minimal BP effects (less risk of hypotension)
cardioselective beta blockers
atenolol, metoprolol, esmolol, acebutolol, bisoprolol, nevbivolol
Effects of beta 1 blockade
decreased HR and contractility and decreased renin release
Effects of beta 2 blockade
reduced dilation of blood vessels in skeletal muscle–>rise in peripheral resistance
bronchoconstriction ,decreased aqueous humor production, decreased glycogenolysis in liver
Effects of beta blockers on peripheral resistance
acutely beta blockers increase peripheral resistance (baroreceptor response) but with chronic administration they reduce peripheral resistance
When are partial beta agonists useful
for patients who develop symptomatic bradycardia or bronchoconstriction with pure beta blockers
beta blockers may have membrane stabilizing ability..when should we avoid these?
in topical applications to the eye bc they can interact with Na+ channels
clinical uses for beta blockers
chronic stable angina, after acute MI, supraventrtricular and ventricular arrhythmia, hypertension, heart failure, glaucoma, hyperthyroidism, migraine, tremor
treatments for open angle glaucoma
prostaglandins are first tier but beta blockers are also common
what ans drugs may exacerbate glaucoma
beta agonist, alpha antagonists, anticholinergics
Propranolol
nonselective beta blocker (crosses BBB)
tx for migraine, thyroid storm, reducing tremor, anxiety, angina, HTN, arrhythmias, MI
SE: bradycardia, worsened astma, fatigue, vivid dreams, cold hands
*black box warning: cardiac ischemia after abrupt discontinuation
Stalol
nonsel beta blocker
used only in arrhythmia (also acts as ion channel blocker)
*black box: life threatening VTach associated with QT prolongation
timolol
nonsel betablocker
tx for open angle glaucoma, systemically used for HTN, migraine prophylaxis, MCI
Nadolol
nonselective beta blocker
long duration of acts, spectrum of action similar to timolol
Pindolol
partial beta agonist activity, nonselective beta blocker
HTN, adjunct for depression tx
*less likely to cause bradycardia and altered plasma lipids
Atenolol, metoprolol, bisprolol
beta 1 selective beta blockers
HTN, Arrhythmias, MI
Nevbivolol
beta 1 selective beta blocker
HTN only
SE: vasodilates via NO production in endothelial cells
which beta blockers may be better for patients with diabetes or PVD
beta 1 selective drugs
Esmolol
beta 1 selective
very short duration of action so its used in acutely ill patients in HTN emergency, thyroid storm, ventricular tach
Acebutolol
partial beta agonist activity, beta 1 selective blocker
local anesthetic effects
less likely to cause bradycardia and altered plasma lipids
effects for hypertension, agina, and thyrotoxicosis
Labetalol
alpha 1 blocker and beta blocker
Used in acute aortic dissection (decreases aortic pressure and shear stress), BP management in acute ischemic stroke, acute severe HTN, HTN emergency, eclampsia, subarachnoid hemorrhage
Produces hypotension but less tachycardia than phentolamine and other alpha blockers
carvedilol
blocks alpha1 and beta receptors (more potent beta blocker than labetalol)
Prevent LDL oxidation bc of antioxidant effects
CYP2D6 related interactions (poor metabolizer have 10X high blood concentrations)
Adverse effects of beta blockers
bradycardia and hypotension, fatigue, sexual dysfunction
Black box warnings regarding precipitation or worsening of CHF and significant negative chronotropy
Abrupt withdrawal can exacerbate ischemic sx so must taper the dose (chronic beta blockers use increases receptor density…abrupt stopping of beta blockers causes transient supersensitivity to catecholamines–more likely with shorter acting drugs like propranolol that wear off before receptors can down-regulate back to normal)
Avoid in asthma or COPD
can exacerbate peripheral artery disease
can mask hypoglycemia in diabetic px
stages of cardiogenesis
bilateral heart primordia–>primitive heart tube–>heart looping–>artrial and ventricular septation–>outflow tract septation
When is heart most vulnerable to teratogens
weeks 3-6ish (heart is developing up until week 8)
cells from ? give rise to the precardiogenic mesoderm (becomes heart)
anterior lateral plate mesoderm
splanchnic mesoderm
the heart is derived from splanchnic mesoderm as bilateral tubular primordia located ventrolateral to the early pharynx
cardiogenic plate
area of splanchnic mesoderm anterior to the head process of early mammalian embryo that subsequently gives rise to heart
what is cardiac jelly
acellular gelatinous matrix secreted by myocardium which separates it from the endocardium in early heart development
*permits shape changes needed for twisting and folding
cardiac jelly will dimish as heart tube matures so that myocardium is adjacent to endocardium
What does the bulbus cordis become
smooth part of right and left venticles
what does the primitive ventricles become
expand to becom ethe left ventricle
what does the primitive atria become
fuses together to form the common atrium (trabeculated part of right and left atria)
what does the sinus venosus become
right horn: smooth part of right atrium
left horn: coronary sinus
what does the common cardinal vein and right anterior cardinal vein become
superior vena cava
what do the posterior, subcardinal, and supracardinal veins become
IVC
what does the primitive pulmonary vein become
smooth part of left atrium
what does the truncus arteriosis become
ascending aorta and pulmonary trunk
Looping o the heart begins and ends at
looping of heart begins at 23 days and ends at 35 days
splanchnic mesoderm proliferates to form the
myocardial primordium
cardiac jelly layer gives rise to..
subendocardial tissue
Early partitioning of the heart
formation of AV canal, formation of endocardial cushions, separation of atrium from ventricles
Late partitioing of the heart
partitioning of the atria, repositioning of the sinus venosus, partitioning of the ventricles, partitioning of the outflow tract
Cushion cells and tissue in the outflow tract (conotruncal region) are formed from
endothelial-derived cells and neural crest cells
each horn of the sinus venosus receives venous blood from which 3 vessels
vitelline vein, umbilical vein, common cardinal vein
Where does the interventricular septum first emerge from
the floor of the ventricle near the apex
Role of neural crest cells in cardiac development
begin to produce elastic fibers in the outflow tract before and during the partitioning process which provides the resiliency required of the aorta and pulm vessels
what happens to the conducting system in very early heart development
location of pacemaker shifts from caudalmost end of the left tube of the unfused heart to the sinus venosus where it is then incorporated into the right atrium, the pacemaker (SA node), then becomes situated high in the right atrium
what causes closure of the ductus arteriosis
low O2 and decreased prostaglandings (can give indomethacin to close)
vasculogenesis
fusion of locally formed endothelial vesicles
angiogensis
Outgrowth or branching of preformed vessels
anterior cardinal veins(superior)
bring blood from head region via the left and right common cardinal vein
Posterior cardinal veins (inferor)
drain blood from lower half of body into two common cardinal veins
umbilical veins
bring nutrient and O2 rich blood from placental villi via the umbilical cord to the embryo
umbilical veins become included in developing liver
Vitelline veins (omphalomesentertic system)
closely associated with development of duodenum, liver, and drain the blood of the umbilical vesicle
Pumonary veins
not assigned to any of the three systems–they develop independetly
derivatives of first aortic arch
regress and form part of maxillary a.
derivatives of second aortic arch
regress and form part of stapedial artery
derivatives of third aortic arch
common and internal carotid arteries
derivatives of fourth aortic arch
right: proximal right subclavian a.
left: arch of aorta
derivatives of sixth aortic arch
right: part of right pulm a.
left: part of left pulm a. and ductus arteriosus
Right 7th segmental A
part of the right subclavian
left 7th segmental artery
entire left subclavian a
right dorsal aorta
regress and middle of the right subclavian artery
left dorsal aorta
descending throacic aorta
aortic sac
ascending aorta and brachiocephalic artery
recurrent laryngela nerve
wraps around aortic arch on left side and wraps around subclavian a on right side
Right aortic arch
developmental obliteration of left fourth branchial arch artery and regression of the left dorsal aorta
aortic arch is constructed from equivalent vessels on the right side and ductus arteriosus traverses midline (may produce constriction of esophagus)
double aortic arch
anomaly of the arch resuting in two arches that surround the esophagus and trachea in the superior mediastinum to form a vascular ring–>dysphagia and respiratory distress
failure of regression of the section of the right dorsal aorta between the 7th intersegmental artery and junction with the left dorsal aorta
interrupted aortic arch
cause by obliteration of left fourth branchial arch artery
proximal part of aortic arch artery divides to form the brachiocephalic trunk and left common carotid arteries but no continuity of the arch beyond these branches
ductus arteriosus is patent and greatly dilated to support life
Right subclavian artery anomaly
right subclavian artery arises from aortic arch distal to the left subclavian artery (passes behind the esophagus and trachea to reach right side
results from regresion of the right fourth branchial arch artery
Abbott classification groups of congenital heart defects
acyanotic, cynaotic, cyanose tardive
Shunt classification
initial left to right, right to left shunt, no shunt
Types of VSDs
membranous (most common)
muscular (less common)
ASD
caused by excessive resorption around the foramen secundum or hypoplastic growth of septum secundum
most common site of ASD
midportion of the interatrial septum in region of the fossa ovale (ostium secundum ASD)
what infection is PDA associated with
maternal rubella infection during early pregnancy
Coarctation of Aorta
pathologic narrowing of aortic lumen (pre or post ductal)
Preductal coarctation
intracardiac anomaly during fetal life decreased blood flow thru the left side of the heart and aortic isthmus resulting in hypoplastic development of aorta
*CHF shortly after birth
Differential cyanosis if the ductus arteriosus remains open (upper half of the body is perfused but lower half is cyanotic–>hypertension in upper extremities and pressure reduced in lower extremities)
Postductal coarctation
develops postnatally, usually the result of muscular ductal tissue extending into the aorta during fetal life
when ductal tissue constricts following birth, the ectopic tissue within the aorta also constricts and creates a napkin ring-like obstruction
usually obstruction is not severe and kid is ok
if severe, newborn can develop CHF
first weeks of life, infant presents with tachypnea, dyspnea, tachycardia, hepatomegaly
Tetralogy of Fallot
abnormal anterosuperior and rightward displacement of infundibular septum–>unequal division of the bulbus cordis into pulmonary and aortic outflow tracts
*VSD, subvalvular pulm stenosis, overriding aorta, right ventricular hypertrophy
systolic murmur heard best at left upper sternal border
Transposition of great arteries
aorta originates from right ventricles and pulmonary artery originates from left ventricle
failure of spiraling in development or abnormal growth and absorption of the subpulm and subaortic infundibuli during division of truncus arteriosus
persistant truncus arteriosus
result of absent or incomplete partitioning of the truncus arteriosus by the spiral septum (neural crest cell failure)
type 1 is most common variant–>single trunk that gives rise to a common pulm artery and ascending aorta
does SNS or PNS display predominant tone in most organs
PNS is dominant tone in most organs (sweat glands and blood vessels have predominant SNS)
how do M agonists treat glaucoma
close iris (miosis)to icnrease fluid drainage
M2 receptor activation effect on heart rate?
decreases rate of AP generation in SA node and rate of AP transmission in AV node to decrease the heart rate
does the PSNS directly innervate cardiomyocytes
NO
Does PSNS directly innervate vascular smooth muscle cells
no but M3 activation on endothelial cells releases nitric oxide, which can lead to vasodilation
what receptor in kidney cells leads to renin release
beta 1
what kind of receptor are nicotinic receptors
ion channels
cholingeric side effects
miosis, decreased HR, bronchial constriction and increased secretions, increased motility in GI tract and relaxation of sphincters, relaxation of sphincters and bladder wall contraction, increased secretions from glands
Choline esters have what kind of amine group
quaternary, hydrophilic, cant penetrate CNS
are tertiary or quaternary amines better absorbed into CNS
tertiary because they are uncharged and lipophilic
how are cholinomimetic alkaloids excreted
renally
bathanechol
choline ester that activates M1-3 receptors in all peripheral tissues
treats ileus and urinary retention by increasing bowel and bladder tone
Carbachol
choline ester, nonselective M and N agonist, treats open angle claucoma by increasing fluid outflow
pilocarpine
tertiary amine alkaloid, M3 agonist, treats glaucoma by increasing fluid outflow and treats xerostomia in sjogren syndrome
Varenicline
partial agonist at specific N subtype and blocks nicotine activation of CNS reward paths–>smoking cessation aid
Edrophonium
alcohol, increases ACh concentrations
was used to diagnose myasthenia gravis
Pyridostigmine
quat carbamate, increses ACh concentrations
treats MG
cholinergic side effects can be dose limiting and treated with antimuscarinics
Neostigmine
quat carbamate, increases ACh concentrations, treats MG, ileus, and urinary retention, reversal of NMJ blockade post-op
Physostigmine
tertiary carbamate, crosses BBB
antidote for anticholinergic toxicity
Rivastigmine
tertiary carbamate, increases ACh concentrations by inhibiting AChE and BuChE isoforms in memory regions of brain
treats alzheimers
Carbaryl, parathion, malathion, and sarin, and VX
irreversible AChE inhibitors–organophosphates
Anticholinesterase poisoning
too much muscarinic activity–>DUMBBELSS
Antidotes: atropine (crosses BBB), 2-PAM (reverses N and M effects, does not cross BBB)
What do you give someone with OP poisoning
atropine
what plant has antimuscarinic effects
deadly nightshade (atropa belladonna)
Anticholinergic poisoning
hot as a hare, dry as a bone, red as a beet, mad as a hatter, full as a flask, blind as a bat, fast as a …
scopolamine
antimuscarinic used to treat motion sickness
benztropine
antimuscarinic used to relieve acute dystonia in parkinsons
tropicamide
antimuscarinic used to produce mydriasis and cycloplegia for eye exams or surgery
dicyclomine
antimuscarinic used for irritable bowel syndrome
oxybutyinin
antimuscarinic used for bladder spasm and overactive bladder
ipratropium
antimuscarinic used to treat asthma and COPD (they bronchodilate)
glycopyrrolate
antimuscarinic that reduces glandular secretions for axillary hyperhidrosis and focal hyperhidrosis
*antidoite for AChE inhibitor OD
Antidotes for AChE inhibitor OD
glycopyrrolate, atropine, pralidoxeme
