General B2 stuff Flashcards
3 mechanisms of arrhythmias
1)Increased automaticity (inappropriately excitable cells)
2)Triggered automaticity (normal action potential is interrupted or followed by an abnormal depolarization; afterdepolarizations)
3) Reentry (abnormal impulse conduction)
increased automaticity (as seen in membrane potential of SA node)
1) slop of phase 4 is increased
2) threshold potential (TP) is more negative
3) maximum diastolic potential (MDP) is more positive
Triggered automaticity (2 types/ descriptions)
1) EAD (early afterdepolarization): Interrupt repolarization
- Exacerbated by slow rate-long QT syndrome
- Torsades de Pointes results
2) DAD (Delayed (late) afterdepolarization): Occur after repolarization
1) Exacerbated by fast rates, high intracellular Ca2+
2) Digitalis toxicity and catechol-amines (NE, EPI), Ischemia
Four Ways by Which Antiarrhythmic Drugs Reduce Spontaneous Discharge in Autonomic Tissues
1) decreased phase 4 slope
2) increase threshold
3) increase maximum diastolic potential
4) increase AP duration (issues)
4 traditional Anti-arrhythmic drugs
Class I: Sodium channel blockers
Class II: Beta-blockers
Class III: Potassium channel blockers
Class IV: Calcium channel blockers
CHA2DS2VASc
C Congestive Heart Failure 1 point H Hypertension 1 point A2 Age ≥ 75 y 2 points D Diabetes 1 point S2 Stroke 2 points V Vascular disease 1 point (prior myocardial infarct or peripheral vascular disease) A Age≥65y 1point Sc Sex category, female 1 point
Maximum total score = 9 points.
ESC 2010 Anticoagulation Recommendations: Score = 0 no therapy or aspirin (no therapy preferred). Score = 1 aspirin or oral anticoagulation. Score greater than or equal to 2 oral anticoagulation (coumadin INR 2-3, Dabigatran, Apixaban, Rivaroxaban,Edoxaban) .
Requirements for Reentry:
- Two Distinct Paths for Propagation (Called α and β here)
- Slowed Conduction in at Least One Path (Either α or β)
- Unidirectional Block: Tissue capable of conduction in one but not the opposite direction. Such block is often Functional.
Physiology of Valsalva Effect
- Valsalva: forceful expiration against closed glottis
- Increases intrathoracic pressure as thoracic organs are compressed by contracting rib cage, producing increased external pressure on heart and thoracic vessels
- Venous and right atrial compression impedes venous return and preload, initially dropping cardiac output.
- Thoracic aorta compression initially increases aortic pressures, triggering medullary feedback loop that stimulates vagal efferents and slows heart.
- Changes in heart rate are reciprocal to aortic pressures due to baroreceptor reflex.
Management of VT
• Sustained VT is potentially life-threatening and may degenerate to ventricular fibrillation or be associated with hemodynamic collapse.
• Acute therapy in unstable patient: electrical cardioversion.
• Acute therapy stable patient: antiarrhythmic drugs
(amiodarone, lidocaine) or sedate/cardiovert.
• After sinus rhythm restored look for structural heart disease and correct aggravating factors.
• Long term consider need for implantable cardioverter defibrillator (ICD) for secondary prevention and potentially need for antiarrhythmic drugs or VT ablation.
-other drugs??? beta blockers???
BNP
-brain natriuretic peptide
- BNP is synthesized and released in response to ventricular stress and is typically used when diagnosis of heart failure as prime cause of patient symptoms is
in question (e.g. heart failure vs pulmonary disease)
-BNp indicates HF
Amiodarone lung SE
- Amiodarone is an amphiphilic compound (possessing both hydrophilic and lipophilic properties) which can result in long elimination half life of approximately 30-108 days with a volume of distribution close to 5 liters.
- The active principal metabolite, desethylamiodarone, penetrates tissues and accumulates therein, thus providing a sustained source of release.
- Despite Amiodarone’s intended myocardial target, Amiodarone concentrations measured in unfractionated pulmonary parenchyma significantly exceed that of the heart
Inherited arrhythmias
- Long QT syndrome (LQTS)
- Brugada syndrome (BrS)
- Catecholaminergic polymorphic ventricular tachycardia (CPVT)
- Short QT syndrome (SQTS)
- Early Repolarization
- Sudden unexplained death syndrome
- Idiopathic ventricular fibrillation
Risk Factors for SCD in Young People
- Structural congenital heart disease
- Congenital anomalies of coronaries
- Myocarditis
- Hypertrophic and other cardiomyopathies
- Wolff-Parkinson-White syndrome
- Inherited arrhythmias
Ion Channels: alpha units
Alpha units are pore-forming and mediate currents
Ion Channels: beta units
Beta units are regulatory
Long QT syndrome (LQTS)
• Prevalence: 1:3,000 – 7,000
• Clinically identified by prolonged QT interval and T wave
abnormalities on EKG and torsade de pointes (TdP)
Presents with syncope and SCD due to ventricular tachyarrhythmias (VT), typically TdP
• TdP also may cause seizures
• Syncopal episodes usually occur during exercise or high emotions, not as
often during rest or sleep
• Syncope on exertion in young patients concerning for malignant cause
• Family history of “seizures,” SCD/SCA, syncope
- QT interval corrects for heart rate
- Bazett: QTc=QT/square root of the RR
* inverserelation - Abnormal QTc
* males >470 ms
* females > 480 ms
* Borderline 450-470 ms - Average QTc for someone with the LQTS is 490 ms
- QT interval changes regularly in an individual
- Long QT patients can have normal/borderline QTc
Causes of Long QT
Acquired
• Primary myocardial problems: myocardial infarction, myocarditis, cardiomyopathy
• Electrolyte abnormalities: hypokalemia, hypomagnesemia, hypocalcemia
• Autonomic influences
• Drug effects
• Hypothermia
Congenital
• Romano-Ward syndrome (RWS) (autosomal dominant LQTS)
• Jervell and Lange-Nielson syndrome (recessive)
LQTS: Genetics
• Primary electrophysiologic disorder due to ion channel abnormalities
• Sometimes called Romano-Ward syndrome (RWS)
• Autosomal dominant disorder
• Reduced penetrance: 50% of individuals with a
disease-causing mutation will not show symptoms
• Genetic heterogeneity: 13 genes known to be associated with RWS
Jervell and Lange-Nielson Syndrome
• Congenital, profound, bilateral sensorineural DEAFNESS and QT prolongation often >500 ms
• increased risk for SIDS
• >50% of untreated children with JLNS die prior to age 15
• Autosomal recessive inheritance
• 2 genes known to be associated with JLNS
• The most common genes include:
• KCNQ1 (LQTS Type 1) 90%
• KCNE1 (LQTS Type 5) 10%
Treatment of LQT3 SCN5A gain of function Na channel
- Class I antiarrhythmics ex. Mexilitine, Flecainide
* Can lead to Brugada type EKG
Treatment and Management for LQTS
Left cardiac sympathetic denervation (LCSD)
• Breakthroughs on beta blockers, ICD
• Left supraclavicular incision, retropleural approach
• Ablation of the left stellate ganglion
• Thoracic ganglia T2-T4
• mean number of cardiac events per patient dropped by 91% after LCSD
Surgical left stellate ganglionectomy
• may be useful in infants with the severe Jervell-Lange and Nielsen form of LQTS as complimentary therapy with beta blockers and pacemakers if there is profound bradycardia
LQTS: Who Should be Treated?
Symptomatic patients
Asymptomatic patients (controversial)
• Beta blocker therapy for asymptomatic individuals
High risk
• congenital deafness
• neonates/infants (risk SCD high first months of life)
• affected siblings of children who died suddenly
• T wave alternans
• long QTc (greater than 470 ms)
• two or more pathogenic mutations
Brugada Syndrome (BrS)
- Prevalence: 1:5,000 Western populations 1:2000 southeast asia
- Cardiac conduction abnormalities, ST-segment elevation in the right precordial leads (V1-V3)
High risk for ventricular arrhythmias that can result in SCD
• For every 10 patients with BrS presenting with syncope, 8 will only be diagnosed after a cardiac arrest
Presents as chest pain, palpitations, laboured breathing during sleep, syncope, VT, SIDS or sudden unexpected nocturnal death syndrome (SUNDS)
• average age of sudden death is 40 (reported in ages up to 84)
• Common cause of sudden death in South Asian individuals under the ageof 50
8-10 times more prevalent in males
• Higher Ito epicardial outflow tract concentration in males (testosterone)
Dx criteria:
Type 1 EKG: coved ST segment elevation >2 mm, followed by negative T wave
+
AND at least 1 of the following: • Documented VF/PMVT • family h/o premature SCD • coved type EKG in family members • inducible VT at EPS • Syncope from arrhythmia cause • nocturnal agonal respiration
Brugada-like EKG Patterns – Drug Induced
- AAD- class IC, class IA, Ca channel blockers, Beta blockers
- Antianginal drugs- Ca channel blockers, nitrates
- Psychotropic drugs- tricyclics, phenothiazines, serotonin reuptake inhibitors
- Cocaine
- Alcohol intoxication
- While these drugs may produce Brugada-like ST segment elevation, it is not clear whether genetic predisposition is involved.
Brugada-like EKG Patterns – Differential Diagnosis
- Atypical right bundle branch block (RBBB)
- Left ventricular hypertrophy
- Early repolarization (upsloping rather than downsloping ST elevation)
- Pericarditis
- Acute myocardial ischemia
- Pulmonary embolism
- Prinzmetal angina
- Dissecting aortic aneurysm
- Duchenne muscular dystrophy
- Arrhythmic right ventricular dysplasia (ARVD)
- Hyperkalemia
- Hypercalcemia
- Hypothermia
BrS: Genetics
Autosomal dominant disorder
• Reduced penetrance
• Genetic heterogeneity: 16 genes known to be associated with BrS
Current detection rate: 25-30%
• Majority: alpha subunit of the cardiac voltage-gated Na+ channel (SCN5A) gene
• Other genes (
Sodium Channelopathy
Pleiotropy: pathogenic variants in SCN5A can cause both LQTS3 and BrS, among others
• Gain of function: LQTS3
• Loss of function: BrS
- Genetic modifiers, environmental factors (fever, medication) can affect phenotypic manifestations
- Evidence from families with SCN5A mutations associated with both diseases in same family
BrS: Diagnosis
• Change lead position (Brugada leads)
Provocative drug testing to unmask EKG changes typical to Brugada syndrome
• Sodium channel blocker: flecainide, pilsicainide, ajmaline, or procainamide
• Consider 80% of individuals show the characteristic changes when challenged with a sodium channel blocker (ajmaline)
• Fevers can lead to Brugada-like EKG pattern and arrhythmias
Difficult to diagnose (Raju et al., 2011)
• 49 families with confirmed sudden arrhythmic death and diagnosis of Brugada, 50 probands
• Mean age of death probands 29.1 years
• 41 (82%) males
• 68% of probands would not have fulfilled current criteria for ICD implantation
• Current markers for sudden death in Brugada Syndrome are insensitive making risk stratification challenging
BrS: SCD Risk Factors
- Prior aborted SCD, highest risk for recurrence (69%)
- Prior aborted SCD, highest risk for recurrence (69%)
- Syncope and spontaneous type I EKG (19%)
- Asymptomatic patients with spontaneous type I EKG (8%)
- Risk associated with asymptomatic pt with type I EKG only after provocation with Na channel blocker appears low
- Inducibility of VT/VF at EPS (controversial)
- Male gender
BrS: Who should be treated?
• Implantable Cardiac Defibrillators (ICD)
Symptomatic patients with:
• aborted SCD and spontaneous or drug-induced (Na channel blocker) type I EKG
• syncopal patients with type I EKG either spontaneous or drug-induced
Asymptomatic patients with:
• type I spontaneous EKG and positive EP study for induction of VT
• drug-induced type I EKG and family h/o SCD and positive EPS
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
• Prevalence 1:10,000
• Triggered by exercise or acute emotion (adrenergic stimulation) in an
individual with structurally normal heart
• Bidirectional or polymorphic ventricular tachycardia that can spontaneously resolve or degenerate into VF and sudden death
• Mean onset of symptoms between 7-12 years
• High penetrance
Cumulative survival before 30 years of age is 50-70%
• Associated with high risk sudden death if untreated: 30% of affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal episodes
CPVT: Diagnosis
• Resting EKG is often normal
Exercise stress test
• onset of arrhythmias during exercise occurs at a heart rate threshold of 100-120 beats per minute
• increase in workload, catecholamines -more adrenergic loads….
• Increase in complexity of arrhythmias premature ventricular contractions to VT
Consider personal history of:
• Syncope occurring with physical activity, acute emotion
• VF during acute stress
• exercise or emotion-related palpitations or dizziness
• Sudden cardiac arrest triggered by acute emotional stress or exercise (personal and/or family history)
CPVT: Genetics
Mutations of genes encoding proteins involved in intracellular calcium and the release of calcium from the SR result in: • inappropriate calcium leakage • cytosolic calcium overload • delayed after-depolarizations • triggered activity • ventricular arrhythmias
Autosomal dominant disorder
• RYR2 (ryanodine receptor 2): 50-55%
• CALM1 (calmodulin):
CPVT: Acute Treatment for Ventricular Tachycardia Storm
• Most critical step in acute management of VT or VF in CPVT patient is to correct inciting factors and avoid standard epinephrine infusion in resuscitation setting (can propagate arrythmias and make it worse…)
IV Beta blocker is first choice therapy

General anesthesia and sedation should be considered if beta blocker ineffective
• Diminishes the adrenergic stimulation
CPVT: Chronic Therapy
- Avoid competitive sports, strenuous activity, stressful environments
- Avoid sympathomimetic agents, eg pseudoephedrine
Beta-blockers
• Effective for 60% of individuals with CPVT
• Inhibit adrenergic –dependent triggered activity by reducing heart rate and release of calcium release from SR
Flecainide
• RYR2 blocking properties, may directly target the molecular defect in CPVT, evidence for acute arrhythmia suppression but unresolved are long-term efficacy and whether may serve as first-line therapy
Ca channel blockers: may have role in patients with CASQ2 mutation
ICD therapy
• Individuals who survive cardiac arrest
• individuals with syncope or sustained VT despite beta blocker therapy
• Caution in shocks leading to excited state -> epinephrine release -> VT
Left cardiac sympathetic denervation (LCSD)
• favorable preliminary data
• Individuals who experience recurrent syncope, polymorphic/bidirectional VT, or several appropriate ICD shocks while on beta-blocking agents and in those who are intolerant of or with contraindication to beta-blocker therapy
CPVT: Who should be treated?
• All phenotypically or genotypically diagnosed CPVT patients should receive treatment
Unable to identify “low risk” patients
• Meta analysis of 354 patients on beta blockers showed 6.4% fatal events, 37.2% arrhythmic event
• Another study reported that of 10 patients presenting with late-onset CPVT (age > 21) were often female (80%), less likely to have RYR2 mutations and fatal events not observed during f/u (mean 4.1 years)
Currently first line therapy beta blocker
Infectious Endocarditis
• uniformly fatal if untreated
the most common etiological agents are members of normal microbiota
• Staphylococcus aureus – anterior nares
• Coagulase-negative staphylococci (e.g. S. epidermidis) – skin
• viridans streptococci (e.g. S. sanguis, S. mutans, S. mitis) – oral
cavity
• enterococci (E. faecalis, E. faecium) – GI tract
- Access to endocardium provided by transient bacteremia
- More rare agents: HACEK organisms (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingellla) – Gram-negative bacteria, influences choice of Abx
Risk factors of IE
- Common denominators: abnormal heart valves and risk of bacteremia
- Aberrant flow results in platelet-fibrin thrombus on injured endothelium
- Bacteria enter bloodstream through skin or mucosal surfaces and adhere to thrombus
- Once inside growing thrombus, bacteria are resistant to host defenses
Predisposing heart conditions of IE
- Prosthetic valves (mechanical or bio-)
- Mitral valve prolapse with regurgitation or thickened leaflets
- Rheumatic heart disease
- Complex congenital heart disease
- Mitral regurgitation, aortic stenosis, aortic regurgitation, ventricular septal defect
Clinical presentation of IE
- Acute or subacute onset
- Fever 80-95%
- Heart murmur 80-85% (new/worse 10-40%)
- Chills, sweats 40-75%
- Anorexia, malaise, weight loss 25-50%
- Noncardiac manifestations 5-50%
- Lab abnormalities
Noncardiac manifestations of IE
• Embolic events (20-50% of patients)
• CNS (up to 40%), extremities, spleen, kidneys, bowel
• Splenomegaly 15-50%
• Clubbing 10-20%
• Petechiae 10-40%
• Other peripheral manifestations up to 15%
• splinters (nails)
-Osler’s (Tender, violaceous, subcutaneous, in finger or toe pads Inflammatory/immune complex)
-Janeway’s (Nontender, erythematous or hemorrhagic, macules or papules, in fingertips, palms or soles…..Due to septic emboli)
-Roth’s (Retinal lesions— hemorrhagic with white central spot…Immunologic)
Lab abnormalities of IE
- Anemia 70-90%
- Leukocytosis 20-30%
- Microscopic hematuria 30-50%
- Elevated sed rate and C-reactive protein
Microbiology of IE
• Organisms likely to adhere to thrombus
• Depends on native vs. prosthetic, and how long prosthetic valve has
been in
• Most common organisms are Strep species, Staphylococcus aureus (especially for acute), coagulase-negative Staph (especially for prosthetic valves), and Enterococcus sp. (especially in the elderly)
Streptococci in endocarditis
- Viridans group of streptococci
- Strep sanguis, mutans, mitis
- Strep bovis–assoc. with colonic lesions
- Strep pyogenes and Strep pneumoniae less common as cause of endocarditis
- NVS–Abiotrophia
Unusual causes of endocarditis
- Gram negative rods (Salmonella, Pseudomonas)
- Fungi, especially Candida
- Both are more likely in nosocomial or prosthetic valve (especially early) or in infection drug users
- “Culture-negative”
- Non-infectious causes
- IDU— S aureus, Candida parapsilosis, Pseudomonas
“Culture-negative” endocarditis
- Preceding antibiotics
- HACEK group–fastidious GNR
- Nutritionally variant strep (Abiotrophia)
- Coxiella burnetti (Q fever), psittacosis, typhus
- Bartonella (homeless, EtOH)
- Brucella
- Tropheryma whipplei (Whipple’s dz)
HACEK group
- Haemophilus aphrophilus, paraphrophilus
- Actinobacillus actinomycetemcomitans
- Cardiobacterium hominis
- Eikenella corrodens
- Kingella kingae
Echocardiography
- transthoracic rapid and noninvasive, but transesophageal much more sensitive
- Echo has specificity of 98%
- TTE sensitivity less than 70%
- TEE sensitivity up to 95%
- TEE also better for evaluating prosthetic valves, perivalvular extension, myocardial abscess, fistulas, and valve perforations
Diagnosis of IE
- Based on clinical, lab and echo criteria
- Modified Duke criteria–major and minor
Definite case:
• two major criteria
• one major plus three minor criteria
• five minor criteria
Possible case:
• one major and one minor criteria
• three minor criteria
Modified Duke criteria–Major
Microbiologic
• typical organism from 2 separate blood cxs
• organism from persistently pos. blood cxs
• positive serology for C. burnetti
Evidence of endocardial involvement
• new valvular regurgitation
• positive echocardiogram
Modified Duke criteria–Minor
- Predisposition to infective endocarditis
* cardiac abnormalities (see Prevention section) or injection drug use - Fever
- Vascular phenomena
* excluding petechiae, splinter hemorrhages - Immunologic phenomena
* rheumatoid factor, glomerulonephritis, Osler’s nodes, Roth spots - Microbiologic–not meeting major criterion
Possible indications for surgery in IE
- congestive heart failure (mortality benefit)
- prosthetic valve endocarditis
- valve perforation or rupture
- new heart block
- multiple embolic events
- uncontrolled infection on appropriate Rx
- certain pathogens poorly treated with medical therapy alone (e.g. fungi)
Prolonged fever in IE
- Half of patients afebrile within 3 days of starting treatment, 75% within one week
- More likely in IE due to S aureus, GNR, fungi
- Associated with complications
Complications of endocarditis
Cardiac
• congestive heart failure, heart block, valve failure, abscess or fistula
Neurologic
• embolic stroke, mycotic aneurysm, meningitis
Systemic
• septic emboli, abscesses
Mycotic aneurysms (IE)
Usually silent until bleed. Most common peripheral MCA, at bifurcations.
More common with viridans strep—10-15% at autopsy.
May be due to direct embolization/infection of wall or immune complex deposition.
Rationale for prophylaxis recommendations in IE
- Bacteremia and IE much more likely to result from daily activities than from a procedure (154,000 times more likely)
- Prophylaxis prevents few, if any IE cases
- Risk of antibiotic-associated AEs exceeds this benefit
- Maintenance of optimal oral health/hygiene more important than prophylaxis
Recommendations for endocarditis prophylaxis
• Not at all for any GI/GU procedures
• For manipulation of gingiva or periapical teeth, or
perforation of oral mucosa
Highest risk cardiac conditions only: • Prosthetic valve • Previous IE • Cardiac transplant with valvulopathy • Congenital heart disease—unrepaired cyanotic, for 6 months after repair with prosthetic, or repaired prosthetic with residual defect
Valvular Diseases: Major Causes
- Congenital causes
- Bicuspid aortic valve (most common)
- Acquired causes
- Aortic valve
- Stenosis: senile calcific aortic stenosis
- Insufficiency: dilation of ascending aorta related to hypertension and aging
- Mitral valve
- Stenosis: Rheumatic heart disease*****
- Insufficiency: Myxomatous degeneration
- Aortic valve
- Stenoses are more frequent than insufficiencies
Myxomatous Mitral Valve: Clinical Features & Complications
Asymptomatic
• Incidental finding: mid systolic click on
auscultation
When regurgitation occurs
• Late systolic/holosystolic murmur****
Complications: uncommon
• Infective endocarditis
• Mitral insufficiency
• Thrombi on atrial surfaces lead to stroke or other systemic infarcts due to emboli
• Arrhythmias lead to sudden death
• Most often seen with advanced mitral insufficiency
Jones Criteria Major Manifestations
- Migratory polyarthritis (large joints) (knee…to elbow….immune complexes go to different joints)
- Carditis – pericardial friction rub, weak heart sounds, tachycardia, arrhythmia
- Subcutaneous nodules - rare (extensor surfaces of joints)
- Erythema marginatum of skin – rare (trunk)
- Sydenham chorea (involuntary purposeless, rapid movements)
Jones Criteria Minor Manifestations
Non-specific signs and symptoms
• Fever
• Arthralgia
• Elevated acute-phase reactants
Clinical Features and Course of Acute/Chronic Rheumatic Fever
Acute rheumatic fever:
• 1-4 weeks after group A (β-hemolytic) streptococcal
pharyngitis (only in 3%)
• Children between 5 and 15 years
• ASO titers and antibodies to DNAase B
• ASO= anti-Streptolysin O
• Streptolysin O and DNAase are protein produced by Group A Strep
• Prognosis: good for primary attack; increased vulnerability to reactivation (reinfection or provocation of these ab’s leads to chronic disease….)
Chronic Rheumatic Carditis:
• Years or decades after initial episode
• Valvular disease (valvulitis)
• Prognosis: surgical repair of valves improves outlook
Infective Endocarditis: causative organisms (from second lecture)
- Strep viridans is the organism in 50-60% of cases of infected deformed valves
- Staph aureus is the organism in 10-20% of cases of infective endocarditis (overall)
* Staph aureus: most common organism in IVDA - Other organisms: commensal organisms of mouth, Staph epidermidis in prosthetic valves
Non-infective Vegetations:
1. Nonbacterial thrombotic endocarditis
Depositions of small masses of fibrin, platelets and other blood products on leaflets
• Often in debilitated patients, e.g., cancer, sepsis (marantic)
• May result in emboli and infarcts
Pathogenesis and Etiology
• Hypercoagulable states )cancer patients……)
• Associated with mucin producing adenocarcinomas (DVTs & Trousseau syndrome)
• Endocardial trauma - Swan-Ganz catheter
Non-infective Vegetations: 2. Libman-Sacks Endocarditis
Systemic lupus erythematosus:
• Mitral & tricuspid valves involved
• Antiphospholipid antibodies present (complexes affecting everything….)

Primary antiphospholipid syndrome (hypercoagulable…)
Morphology
• Either or both sides of leaflets; may also be on endocardium • 1 – 4 mm verrucae with fibrinous material
• May have intense inflammation
Carcinoid Heart Disease
Carcinoid tumors produce serotonin, kallikrein, bradykinin, histamine, prostaglandins, and tachykinins
•Carcinoid syndrome: flushing, cramps, nausea, vomiting, diarrhea
•Serotonin and bradykinin inactivated by MAO in pulmonary vasculature AND also inactivated by passage through functioning liver
• Cardiac manifestation of the systemic syndrome caused by carcinoid tumors
In 50% of patients with carcinoid syndrome - plaque- like fibrosis of right-heart endocardium and valves
• Usually occurs on right side of heart (not left) because of inactivation of mediators by MAO in lung
• Exact cause is unknown; believed to be related to endothelial injury caused by vasoactive agents
VALVULAR DISEASE: Pathophysiology General Principle of Aortic Stenosis
- pressure overload of chamber proximal to lesion.
- Increased LV afterload (systolic pressure) from the high outflow resistance of the narrowed valve causes concentric LVH.
- Initially LV volume increases and contractility increases (Frank-Starling)
- With progressive remodeling, diastolic dysfunction precedes systolic dysfunction
Aortic stenosis: work-up
- EKG
- Echocardiogram (gold standard)
- Cardiac catheterization – for severity of AS ONLY if echo inconclusive, and to define coronary artery status pro-op
- CT/MR – to evaluate thoracic aorta for aneurysm/dissection if aorta incompletely seen by echo
- CXR
Aortic stenosis: etiologies
- Calcific degenerative disease of trileaflet valve (most common)
- Congenitally abnormal valve (i.e. unicuspid or bicuspid)
- Rheumatic valve disease (rare)
The pathobiology of calcific AS is characterized by atherosclerotic- like changes of lipid accumulation, inflammation and calcification.
Aortic stenosis: Symptoms
Classic triad of severe AS:
Angina
Syncope
Heart failure
More common symptoms:
- DOE – from diastolic dysfunction and limited ability to increase cardiac output across severely narrowed AV
- Exertional dizziness – fixed LV stroke volume reduces cardiac output
- Exertional angina – subendocardial ischemia. Only 50% of pts have obstructive CAD
Aortic stenosis: angina
In symptomatic AS:
Myocardial oxygen demand increases from hypertrophied muscle, and from increased wall stress caused by the increase in systolic ventricular pressure.
Myocardial oxygen supply is reduced because elevated LV diastolic pressure reduces coronary perfusion pressure gradient between the aorta and the myocardium.
Aortic stenosis: chf
In symptomatic AS:
Early in AS, elevated LA pressures are primarily at end diastole, and are compensated by the contracting LA. As the AS worsens, LV end diastolic pressure climbs. LA and pulmonary vein pressures also rise, inciting pulmonary alveolar congestion and symptomatic CHF.
VALVULAR DISEASE: Pathophysiology Aortic Regurgitation
- -Abnormal regurgitation of blood from the aorta occurs during diastole.
- -With each contraction, the LV must pump that regurgitant volume plus the normal amount of blood entering in thru the LA. (early on…contractility increases and heart is able to handle…)
- -Hemodynamic compensation relies on the Frank- Starling mechanism to augment stroke volume.
• Increased end-diastolic volume (pre-load) leads to increased contractility (Frank -Starling) and stroke volume.
• Increased LV diastolic volume leads to LV chamber dilation
• If LV diastolic pressure rises too fast (ACUTE AR), then
blood backs up into the LA and pulmonary veins with resulting increase in pulmonary capillary wedge pressure and pulmonary edema
• If it occurs slowly (chronic AR), then pressure and volume excess results in LV dilation (eccentric hypertrophy) and increased wall thickness (concentric hypertrophy)
- Increased stroke volume increases aortic systolic pressure. Aortic diastolic pressure decreases because blood more rapidly leaves the aorta due to regurgitation. High stroke volume (high systolic pressure) and reduced aortic diastolic pressure result in a widened pulse pressure (systolic – diastolic pressure)
- Reduced diastolic pressure = decreased coronary perfusion pressure = reduced myocardial oxygen supply
VALVULAR DISEASE: Causes (regurgitation)
- Abnormal leaflets (ie bicuspid, calcific)
- Ascending aorta pathology
- Subvalvular abnormalities
- Aortic dissection
- Infective endocarditis • Trauma
AORTIC REGURGITATION: Symptoms in Chronic AR
• DOE
• Fatigue
• Decreased exercise tolerance
• Uncomfortable sensation of forceful heartbeat
• Angina, syncope or LV systolic dysfunction (EF50 mm, and systolic function
MITRAL STENOSIS: Pathophysiology
• High LA pressure is passively transmitted back into the pulmonary circulation, causing elevated pulmonary artery pressures and pulmonary edema.
• Inability of LA to empty causes progressive dilation and
remodeling leading to atrial fibrillation and
increased blood stasis causing intra-cardiac
thrombus formation. (LA remodeling is bad….*****hallmark of a-fib.)
• Reduced cardiac output occurs due to reduced LV preload, and increased systemic afterload from vasoconstriction and neurohormonal activation
• Prolonged pulmonary hypertension results in RV hypertrophy, dilation and right heart failure.
Why did our patient cough up blood?
• Elevated pulmonary venous pressures may lead to collaterals with bronchial veins, resulting on hemoptysis if they rupture.
Why were her legs edematous?
• Elevated right heart pressures (pulmonary hypertension)
MITRAL STENOSIS: Etiologies
- Rheumatic (especially women in their 40’s and 50’s) – most common
- Calcific
- Congenital
- Rheumatoid arthritis
- SLE
- Other – meds, radiation, etc.
MITRAL STENOSIS: Clinical Presentation
- Dyspnea
- Orthopnea, PND
- Fatigue
- Atrial fibrillation
- Systemic emboli
- Hemoptysis
- Chest pain
- During high flow states beware pulmonary edema (ie pregnancy)
MITRAL STENOSIS: Exam
- Loud S1 when leaflets pliable (MV closure)
- Opening snap (OS) caused by sudden tensing of valve leaflets (shorter S2- OS = more severe MS because higher LA pressure = earlier valve opening
- Mid-diastolic rumble (more severe = longer duration because LA empting takes longer
MITRAL STENOSIS: Associated Findings
- Mitral regurgitation (MR)
- Left atrial enlargement (LAE)
- Left atrial thrombus
- Elevated right ventricular systolic pressures (RVSP)
Other causes of MS aside from RF
- radiation
- medicine
MITRAL REGURGITATION: Two Types
Organic MR: caused primarily by lesions to the valve leaflets and/or chordae tendineae
(i.e. collagen vascular, endocarditis,
rheumatic, MVP)
-torn…wear/tear…anything that damages it… -require surgery
Functional MR: caused primarily by ventricular dysfunction usually with accompanied annular dilatation (i.e. dilated cardiomyopathy or ischemic heart disease)
MITRAL REGURGITATION: Presentation- ACUTE
ACUTE
-Sudden increase in LV preload which
increased stroke volume (Frank-Starling). A
large percent of stroke volume goes backward,
so cardiac output is reduced. Increased LVEDP
causes increased LA and pulmonary artery
pressure and pulmonary edema.
(surgical emergency…)
• Symptoms include: Acute CHF, tachypnea, tachycardia, variable murmur, relative hypotension (these patients are sick and need emergency treatment)
MITRAL REGURGITATION: Presentation- CHRONIC
CHRONIC
-Slowly over time LV dilates and walls stay thin and compliant. LA progressively dilates and remodels until atrial fibrillation develops.
• Symptoms do to: Low cardiac output. Expect DOE and fatigue, especially with exertion. As LV dilates and weakens, we expect orthopnea, PND and right-sided heart failure
Pericardial Anatomy
Stabilized by ligamentous attachments
• Diaphragm
• Sternum
• Spine
Major Functions of the Pericardium
- Maintains heart position
- Lubrication of visceral and parietal layers
- Barrier to infection
Prostaglandin secretion
• Modulation of coronary vascular tone
Restraining effect on cardiac volume
• Mechanical properties of pericardial tissue
• Small reserve volume
• Tensile strength similar to rubber
Normal cardiac volume
• More elastic leads to stretches easily
Increase cardiac volumes
• Pericardial tissue becomes stiff leads to resistant to further stretch
