Week 4: Cardiology (2) (cardiac physiology and pathology) Flashcards
What is BP?
- Driving force to perfuse organs with blood (force per. Unit area acting on vessels)
- Not uniform throughout body
- Reported as systolic (SBP) and diastolic (DBP)
- Cyclical with the cardiac cycle
- Physiologically regulated variable- it changes
calculating Mean arterial pressure
Mean arterial pressure = CO x TPR (total perisperhal resistance)
- CO= SV and HR
MAP= SBP + (2xDPB)/3 (this is how we actually calculate)
blood pressure regulation
- Autonomic sympathetic activity
- RAAS
- Local action by autacoids e.g. bradykinin and NO- action of endothelium on vascular smooth muscle
Resistance and increased mean arterial pressure
Radius decreases and resistance increase
- Smooth muscle tone changes TPR
- Vasoconstriction increase peripheral resistance, requiring higher BP to drive blood through the systemic circulation
RAAS: renin release
Renin Release
The first stage of the RAAS is the release of the enzyme renin. Renin released from granular cells of the renal juxtaglomerular apparatus (JGA) in response to one of three factors:
- Reduced sodium delivery to the distal convoluted tubule detected by macula densa cells.
- Reduced perfusion pressure in the kidney detected by baroreceptors in the afferent arteriole.
- Sympathetic stimulation of the JGA via β1 adrenoreceptors.
The release of renin is inhibited by atrial natriuretic peptide (ANP), which is released by stretched atria in response to increases in blood pressure.
RAAS: Angiotensin I
Production of Angiotensin II
Angiotensinogen is a precursor protein produced in the liver and cleaved by renin to form angiotensin I.
Angiotensin I is then converted to angiotensin II by angiotensin converting enzyme (ACE). This conversion occurs mainly in the lungs where ACE is produced by vascular endothelial cells, although ACE is also generated in smaller quantities within the renal endothelium.
RAAS: angiotensin II binding
Angiotensin II exerts its action by binding to various receptors throughout the body. It binds to one of two G-protein coupled receptors, the AT1 and AT2 receptors. Most actions occur via the AT1 receptor.
The table below outlines its effect at different points. These will be discussed in more detail below.
BNP
Brain-type natriuretic peptide (BNP) is a hormone secreted primarily by the ventricular myocardium in response to wall stress such as volume expansion and pressure overload. BNP is a marker for congestive heart failure
→ secreted in response to ventricular wall stress, therefore reduces BP by increasing natureisis (reducing preload and afterload)
hypertension and types
NICE: 140/90 mmHg= hypertension
- 90% essential/primary/idiopathic hypertension
- Second hypertension (due to other pathology)
- Pre hypertension
- Isolated systolic/diastolic hypertension
- White coat/clinic
Risk factors of hypertension
- Smoking.
- Being overweight or obese.
- Lack of physical activity.
- Too much salt in the diet.
- Too much alcohol consumption (more than 1 to 2 drinks per day)
- Stress.
- Older age.
- Genetics.
signs and symptoms of hypertension
- Usually presents asymptomatically—manage BP to reduce risk of stroke
Diagnosis of hypertension
- Screening those at risk
- Increasing public awareness of risk factors
- Appropriate lifestyle changes to limit risk- no immediate gain presence a challenge
- Reliable measurements based on clinical guidelines
- Regular monitoring and refinement of medication
- Hypertension is a silent killers
Clinical diagnosis (best practice) of hypertension
- Sitting, relaxed and arm is supported
- Both arms, >15 mmHg difference repeat measurement and use arm with higher reading
- Measurements over period of visit +/- ABPM/HBPM
- Emergency treatment required? (>180 SBP or 120 DBP + clinical signs)
- CVD risk and end organ damage should be assessed whilst waiting for hypertension confirmation
Pathophysiology of hypertension
- Elevated BP (essential/primary/idiopathic)- still not completely understood
- Leads to vascular changes
- Remodelling
- Thickening
- Hypertrophy
- Increases vasoactive substances inc ET-1, NAd, angII
- Vascular remodelling also occurs as a direct result of local salt sensitivity
- Hyperinsulinemia and hyperglycaemia lead to endothelial dysfunction and increased reactive oxygen species- NO signalling reduced.
These factors result in:
- Permanent and maintained medial hypertrophy of vasculature increasing TPR and decreasing compliance of the vessel
- End organs specifically at risk
- Renal
- Peripheral vascular disease
- Aneurysm
- Vascular dementia
- Retinal disease
- Also causes hypertensive disease- left ventricular heart failure- dilated cardiac failure
- Increased morbidity and mortality
Prehypertension
- Slippery slope (>120/60 <140/90 mmHg
- Aim (to reduce CVD risk)
- Promotion of regular exercise
- Modified diet
- Reduction in stress and increased relaxation
- Limit alcohol intake
- Discourage excessive caffeine consumption
- Smoking cessation
- Reduced dietary sodium
- These should be promoted in all patient groups
staging of hypertension
Non-pharmacological treatment of hypertension
- Weight reduction
- Moderate salt intake
- Aerobic exercise
- Smoking cessation
primary hypertension therapeutic agents
- Angiotensin converting enzyme inhibitors (ACEi)
- Angiotensin (AT1) receptor blockers (ARBs)
- Calcium channel blockers (CCBs)
- Diuretics- thiazide and thiazide-like
- Other. Agents for resistant hypertension
Physical assessment for hypertension
Look for secondary causes: Cushing’s syndrome, enlarged kidneys (PCK disease), renal bruits, radio-femoral delay (coarctation).
investigations for hypertensives
- Test for the presence of protein in the urine by sending a urine sample for estimation of the albumin: creatinine ratio and test for haematuria using a reagent strip.
- Blood sample to measure plasma glucose, electrolytes, creatinine, estimated glomerular filtration rate, serum total cholesterol and HDL cholesterol.
- Bloods may suggest secondary cause (low potassium, high Na: hyperaldosteronism
- Examine the fundi for the presence of hypertensive retinopathy.
- Arrange for a 12-lead electrocardiograph to be performed.
- Consider echocardiography if suggestion of LVH, valve disease or LVSD or diastolic dysfunction.
Hypertensive emergencies
- Crisis in an increase in BIP
- If sustained over few hour will lead to irreversible end organ damage
- Encephalopathy
- LV failure
- Aortic dissection
- Unstable angina
- Renal failure
Symptoms and signs of hypertensive emergency
- Severe chest pain
- Headache
- Nausea and vomiting
- Severe anxiety
- Seizures
Presentations of hypertensive crisis
*
- Emergency: high BP associated with a critical event: encephalopathy, pulmonary oedema, acute kidney injury, myocardial ischaemi
- Urgency: high BP without a critical illness, but may include ‘malignant hypertension’: associated with grade 3/4 hypertensive retinopathy
aim of therapy in hypertensive crisis
Aim of therapy: reduce BP to 110mmHg in 3-12 hours (emergency) or 24 hours (urgecy).
treatment of hypertensive crisis
Treatment
- Sodium nitroprusside- breaks down in circulation to release nitric oxide (NO)
- Labetalol
- GTN (1 - 10 mg/hr)
- Esmolol acts within 60 seconds, with a duration of action of 10 - 20 minutes. Typically, the drug is given as a 0·5 - 1 mg/kg loading dose over 1 minute, followed by an infusion starting at 50 μg/kg/min and increasing up to 300 μg/kg/min as necessary.
Hypertensive urgency
- Severe blood pressure elevation that will cause damage within days.
-
Diastolic is usually > 130 mmHg and retinal changes will be apparent
- Flame haemorrhage
- AIM: reduce BP gradually to a diastolic of 100 mmHg over 48 - 72 hours using an oral regime.
- For oral treatment, any of the following drugs may be used: amlodipine 5 - 10 mg OD, diltiazem 120 - 300 mg daily, lisinopril 5 mg OD, etc.
- A combination of a ACEI and calcium antagonist is effective and well tolerated.
Phaeochromocytoma
Pheochromocytoma is a type of neuroendocrine tumor that grows from cells called chromaffin cells. These cells produce hormones needed for the body and are found in the adrenal glands.
symptoms and signs of phaechromocytoma
Symptoms (sympathetic triad)
- Episodic headache
- Sweating
- Tachycardia
Signs
- Sustained or paroxysmal hypertension
diagnosis of phaeochromocytoma
- Urinary and plasma fractionated metanephros’s and catecholamines (24 hour urine collection)
- CT or MRI abdomen and pelvis may detect adrenal tumours
treatment of phaechromocytoma
Treatment
- Resection of phaeochromocytoma
- Before surgery: (1) alpha and (2) beta-adrenergic blockade e.g. phenoxybenzamine
- After adequate alpha-adrenergic blockade has been achieve, beta-adrenergic blockage is initiated two to three days prior to surgery
- Beta blocker should never be started first
Cushing ’s syndrome
Usually apparent from the typical physical appearance. Bloods may reveal hyperglycaemia. A 24 hour urine cortisol excretion will be elevated (three times normal). Confirmation can be made with a low-dose dexamethasone suppression test. Adrenal CT is indicated.
Primary Aldosteronism
Suspect if low serum potassium and high/normal sodium. In up to 50% however the potassium is normal. It should certainly be considered in patients with hypokalaemia and in patients with resistant hypertension or in those with a family history of premature hypertension.
An aldosterone: renin ratio should be measured in the morning. Plasma renin activity is typically very low or undetectable in patients with primary aldosteronism, and the plasma aldosterone concentration high. The ratio is typically > 20-30 but the laboratory will define that. Generally speaking patients with suspected primary aldosteronism should be investigated by hypertension specialists or endocrinologists as confirmatory testing will be required. Adrenal CT is indicated.
Acute coronary syndromes
Made up of unstable angina, NSTEMI and STEMI. Stable angina is not a coronary syndrome.
unstable angina
- Cardiac-sounding chest pain
- ECG
- May show ST depression
- T wave inversion
- May be normal
- Hs-TnL will be normal
NON-STEMI
Sub occlusive
- Cardiac sounding chest pain
- ECG
- May show ST depression
- T wave inversion
- May be normal
- Hs-TnL >100 ng/L
STEMI
Occlusive- total occlusion of CA= transmural ischaemia
- Cardiac sounding chest pain
- ECG
- Persistent ST segment elevation (or new LBBB)
- ST elevation should be > 1 mm in limb leads and 2 mm in chest leads.
- Leads to Q waves
- High- sensitivity troponin I (Hs-Tnl) will frequently be above 100ng/L (and CK >400)
ACS history
History
- Cardiac sounding?
- DULL?
- Central?
- Radiating?
- Relieved with GTN? How long did it take to work?
- How long have you had the pain?
- Is the pain getting worse?
- Cardiac dissection
- Pain worse on inspiration? Pleuritic?
ACS RF
Risk factors:
- Smoker
- Family history
- High cholesterol
- Hypertension
- Thrombophilia
- Stress
ACS exam
- BP (if systolic <90mmHg- cardiac shock)
- Tachy or bradycardia?
- Jugular venous pressure
- Lungs- crackles? Pulmonary oedema?
- Heart sounds- missing a murmur could be costly
- Cool peripheries
Investigations ACS
- ECG first
- Troponin I and T
- CK
- CXR
- pneumothorax
- pleural effusion
- Echocardiogram
- LV function
- Valvular disease
- Coronary angiography help determine whether there is a blockage or narrowing in the coronary arteries
- uses contrast – need good enough renal function
Myocardial infarction
Acute myocardial infarction (MI) defines cardiomyocyte necrosis in a clinical setting consistent with acute myocardial ischaemia. A combination of criteria is required to meet the diagnosis of acute MI:
- increase and/or decrease of a cardiac biomarker (troponin)
- Symptoms of ischaemia.
- New or presumed new significant ST-T wave changes or left bundle branch block on 12-lead ECG.
- Imaging evidence of new or presumed new loss of viable myocardium or regional wall motion abnormality.
- Intracoronary thrombus detected on angiography or autopsy.
Troponin and ACS
Should be taken on admission and again at 1 hour to achieve quick diagnosis (only 1 test required if onset of symptoms >3hrs).
- TnI levels begin to rise 3 to 4 hours after myocardial damage and stay elevated for up to two weeks.
- CK should also be measured in STEMI patients.
- Males: hs-TnI levels greater than 34 ng/L for men suggests a high likelihood of myocardial necrosis.
- Females: hs-TnI levels greater than 16 ng/L for women suggests a high likelihood of myocardial necrosis.
troponin and false positives
- In patients with renal failure, large PE, CHF and myocarditis, aortic dissection, aortic stenosis, hypertrophic cardiomyopathy, malignancy, stroke, severe sepsis
- May remain positive for a few weeks so should be taken into consideration
ECG and STEMI
STEMI
ST elevation in 2 or more leads from the same zone (ie leads II, III or AVF as inferior leads) or presence of LBBB (left bundle branch block).
ST depression confined to leads V1 to V4 may have
true posterior myocardial infarction and should be treated in the same manner as STEMI.
All ACS patients should routinely have
POSTERIOR (V7 - V9 below) and RIGHT VENTRICULAR LEADS recorded ON OR SOON AFTER ADMISSION, especially those with inferior STEMI, as diagnostic changes may be transient. ST elevation in RV4 is highly sensitive for right ventricular infarction.
diagnose
Figure 2: ECG with anterior St depression but posterior leads V7-9 show ST elevation and therefore posterior STEMI.
ECG in unstable angina and NSTEMI
May manifest as
- Transient segment depression or elevation
- T wave inversion or flattening
- T wave pseudo-normalisation (or even no change at all)
Previously established ECG changes such as old MI, LV hypertrophy and digoxin effect need to be considered.
STEMI mimics on ECG
- Early repolarisation causes up-sloping ST elevation, particularly in leads V1 and V2 (and sometimes V3). It is seen more commonly in younger, especially athletic patients. It is also seen in some Afro-Caribbean’s.
- There may be concave ST elevation in pericarditis and the ST changes may be very widespread.
- Brugada syndrome may also be misdiagnosed as anterior STEMI.
- Takotsubo cardiomyopathy (stress reaction mostly middle aged females) can also mimic STEMI and NSTEMI.
NSTEMI/unstable angina management
- Pain relief (as above)
- Aspirin 300 mg loading and 75 mg od
- Low molecular weight heparin (Enoxaparin for 48 hrs based on weight and creatinine).
- Repeat ECG
- Risk assessment of patient with elevated hs-TnI.
- Ticagrelor if risk > 3% (medium) 180mg loading and 90mg BD.
- Whilst waiting for inpatient angiography consider anti-anginals: nitrates, ranolazine, calcium channel blockers.
STEMI management
If STEMI–?catheter lab
- MONA
- Should not be delayed ‘ time is heart’ by performing more ECGs unless doubt in diagnosis
- Bedside echo looking for regional wall abnormalities can help decisions
Pneumonic for management
- Simple: MONA
- Morphine
- Oxygen
- Nitrates
- Aspirin
- Complicated: BROMANCE
- B B-blockers
- R reassure
- O Oxygen
- M morphine
- A aspirin
- N nitrate (GTN- be careful because will cause vasodilation and decrease BP more)
- C clopidogrel
- E Enoxaparin
- (S) Statins
Full management plan for STEMI
- IV Access
- Pain relief (morphine and anti-emetic)
- Oxygenation (only if hypoxic and aim Sats > 94%)
- Aspirin (300mg loading followed by 75mg od for life)
- Prasugrel (thienopyridine inhibits ADP receptors 60 mg loading and 10 mg daily for up to 12 months, use is restricted to patients undergoing primary percutaneous coronary intervention (PPCI) for STEMI who are under the age of 75 and who weigh more than 60kg and who have not had a prior TIA or stroke.
- Clopidogrel (inhibits ADP receptors, loading dose 600 mg followed by 75mg od for up to 12 months for patients who do not fulfil criteria above for Prasugrel).
- Ticagrelor (non thienopyridine loading dose 180mg followed by 90mg bd for up to 12 months, used in patients who cannot have Prasugrel or as first choice NSTEMI)
- PPCI (Primary angioplasty is defined as PCI (percutaneous coronary intervention) performed as the primary (without thrombolysis) therapeutic measure in patients presenting with myocardial infarction. Restoration of normal flow in the culprit artery is achieved in over 95% in most studies with significant long-term benefits.
- All patients should have a full biochemical screen on admission including lipid profile, random glucose and an HbA1c assay performed. A full blood count is mandatory.
- Medications: Bisoprolol (beta-blocker, reduce heart rate, avoid in shock or hypotension, starting dose 1.25mg od). Ace inhibitors (prevent muscle over- damage). Ramipril starting dose 2.5 mg od with checking of renal function) OR Angiotensin receptor blockers (losartan 25mg od starting dose and check renal function). Uptitrate to maximally tolerated dose. Statin (such as atorvastatin 80 mg od, target is to reduce LDL-C < 1·8 mmol/L or a 40% reduction in non-HDL-C. Total cholesterol target should ideally be < 4·0 mmol/L). Consider rosuvastatin 5mg if sensitive to atorvastatin. Ezetemibe if all statins caused side effects.
- Control of diabetes: May require insulin infusions. HbA1c Target for Type 1 diabetes is < 7% and type 2 diabetes 6·5 - 7·5%. Metformin should be introduced with caution if LV dysfunction post MI suspected.
- Control of hypertension
- Smoking cessation
- Triple therapy: some patients with AF may be taking anticoagulation (different from anti-platelets such as asprin). This may require them to be on 3 medications which increase the risk of bleeding. Therefore limit time on all 3 drugs and give a proton pump inhibitor.
- Be aware of complications: Heart failure treat with diuretics, shock (low BP may require inotropes and balloon pump), valve damage or septal defect consider surgery.
Stable angina
- Usually reflects coronary artery disease
- Pain on exercise or emotion only
- Radiated symptoms such as isolated throat tightness or arm heaviness.
- When severe may get fear, sweating and nausea.
- Difficult to distinguish between GORD, MSK and pulmonary disease
- GTN will relieve. Due to poor blood flow through the vessels of the heart.
Differentials of stable angina
- Aortic stenosis
- Hypertensive heart disease
- Hypertrophic cardiomyopathy
Risk factors for stable angina
- Smoking
- Hypertension
- DM
- Hypercholesterolaemia
- Family history of premature coronary artery disease
Investigations for stable angina
- ECG and troponin to rule out MI
- Full nblood count, glucose/hbA1c
- Full lipid profile
- If angina suspected should be given further investigation in order to establish likelihood and extent of underlying coronary disease
- Associated conditions such as valvular and hypertensive disease should also be investigated
assessment of stable angina
Assessment
- Good history Angina is unlikely if the pain is continuous or very prolonged, unrelated to activity, brought on by breathing or associated with other symptoms such as dizziness and dysphagia.
stable angina examination
- weight and height (to allow calculation of BMI) or waist / hip ratio
- blood pressure
- presence of murmurs, especially that of aortic stenosis
- evidence of hyperlipidaemia
- evidence of peripheral vascular disease and carotid bruits (especially in diabetes).
Drug treatment : stable angina
- Aspirin 75mg OD (or clopidogrel)
- GTN spray
- Symptom control: B blockers for symptoms control
- Rate limitation
- B blocker sand non- dihydropyridine calcium channel blockers (diltiazem or verapamil) or…
- Ivabradine (sinus node blocker) can be used alternatively to. Blocker if not tolerated
- Ranolazine (adjunct) for patients inadequaltey controlled (contra if GFR <30)
- Long acting nitrates (isosorbide mononitrate and potassium channel opening drugs
- Statins
- ACEi
Testing for angina likelihood
Check for Hi = High risk = diabetes, smoking and hyperlipidaemia (total cholesterol > 6·47 mmol/l). Lo = Low risk = none of these three.
- If the estimated likelihood of CAD is 61 - 90%, offer invasive coronary angiography
- If the estimated likelihood of CAD is 30 - 60%, offer functional imaging as the first- line diagnostic investigation (stress MRI, echo or myoview)
- If the estimated likelihood of CAD is 10 - 29%, offer CT calcium scoring as the first- line diagnostic investigation (Ct scan measures calcium level) if the score is zero there is very minimal likelihood there is significant coronary disease. If the score is 1 - 400 consideration should be given to CTCA or stress perfusion imaging. Above 400, coronary angiography should be seriously considered if appropriate
- Do not use exercise ECG to diagnose or exclude stable angina for people without known CAD
- For men older than 70 with atypical or typical symptoms, assume an estimate > 90%. For women older than 70, assume an estimate of 61 - 90% EXCEPT women at high risk AND with typical symptoms where a risk of > 90% should be assumed.
