Hypertensive Cardiomyopathy

Hypertensive cardiomyopathy (hypertensive heart disease) is structural and functional myocardial disease caused by sustained arterial hypertension. Left ventricular hypertrophy is defined by left ventricular mass index over 115 g/m2 in men and over 95 g/m2 in women, with wall thickness of 12 mm or more.

Concentric remodelling and hypertrophy (relative wall thickness over 0.42) lead to diastolic dysfunction and heart failure with preserved ejection fraction, followed in some patients by dilatation and heart failure with reduced ejection fraction.

Left ventricular hypertrophy is present in 15 to 20% of hypertensive adults (more in severe or untreated disease), and increases the risk of heart failure, atrial fibrillation, stroke, coronary events and sudden death.

Hypertension is the leading single cause of heart failure in sub-Saharan Africa (about 40% in registries), where patients present younger, with severe hypertension, late diagnosis and low rates of control. Black patients have more severe and earlier left ventricular hypertrophy.

Pathophysiology. Pressure overload, neurohumoral activation (renin-angiotensin-aldosterone and sympathetic systems) and metabolic factors cause myocyte hypertrophy and interstitial fibrosis. Coronary microvascular dysfunction and capillary rarefaction reduce flow reserve and cause subendocardial ischaemia.

A stiff ventricle with impaired relaxation raises filling pressure, enlarges the left atrium and promotes atrial fibrillation. In late disease, myocyte loss and fibrosis cause systolic dysfunction and dilatation.

• Exertional dyspnoea, orthopnoea, fatigue, oedema, palpitations, angina with normal coronary arteries.
• Elevated blood pressure, forceful non-displaced apex early, a fourth heart sound, then a displaced apex and third heart sound.
• Atrial fibrillation, ventricular ectopy, syncope.
• Target organ damage: retinopathy, proteinuria, reduced eGFR, cerebrovascular disease, peripheral artery disease.
• Acute presentation: pulmonary oedema with severe hypertension (flash pulmonary oedema).

Red flags.

• Blood pressure of 180/110 mm Hg or more with acute pulmonary oedema, chest pain, neurological signs or visual change
• Atrial fibrillation with rapid rates
• Syncope or ventricular arrhythmia
• Ejection fraction under 40%
• Rapid fall in eGFR, bilateral renal artery bruits or flash pulmonary oedema (renovascular disease)
• Young patient with severe hypertension (secondary causes)

• Blood pressure. Confirm with office measurement on two or more visits, home monitoring (hypertension at 135/85 mm Hg or more) or 24-hour ambulatory monitoring (130/80 mm Hg or more over 24 hours, 135/85 mm Hg or more by day).
• ECG. Sokolow-Lyon voltage (S in V1 plus R in V5 or V6 over 35 mm), Cornell voltage (R in aVL plus S in V3 over 28 mm in men and over 20 mm in women), strain pattern, left atrial enlargement, atrial fibrillation.
• Echocardiography. Left ventricular mass index, relative wall thickness, ejection fraction, strain, E/e' ratio (over 14 suggests raised filling pressure), left atrial volume index (over 34 mL/m2), and aortic root.
• Cardiac MRI for mass, fibrosis and exclusion of other causes.
• Natriuretic peptide. Raised in heart failure and often in left ventricular hypertrophy.
• Target organ and cause assessment. Creatinine and eGFR, electrolytes, urinary albumin to creatinine ratio, glucose or HbA1c, lipids, thyroid function, fundoscopy. Secondary hypertension screening in young patients or with resistant disease: aldosterone to renin ratio, plasma or urinary metanephrines, renal artery imaging, cortisol, sleep studies.
• Coronary assessment when angina, risk factors or regional wall motion abnormalities are present.

Differential diagnosis.

• Hypertrophic cardiomyopathy (asymmetric septal thickness of 15 mm or more, family history, late gadolinium enhancement at the insertion points)
• Cardiac amyloidosis (low voltage with thick walls, apical sparing)
• Fabry disease and other storage disease
• Aortic stenosis and coarctation
• Athlete's heart
• Ischaemic and dilated cardiomyopathy
• Diabetic and obesity related cardiomyopathy
• Renal disease and acromegaly
• Primary valve disease

Blood pressure control reduces left ventricular mass, heart failure, stroke and death.

• Targets. Under 140/90 mm Hg at the first step and then under 130/80 mm Hg in most adults, with systolic 120 to 129 mm Hg when tolerated. Adults 65 years or over: 130 to 139 systolic where 120 to 129 is not tolerated, and avoid orthostatic hypotension.
• Lifestyle. Sodium under 2 g daily (salt under 5 g), alcohol limitation, potassium rich diet (unless kidney impairment), weight loss, exercise 150 minutes weekly, smoking cessation.
• Drug therapy. Combination therapy in a single pill is started early when blood pressure is 150/90 mm Hg or more. Drugs that reduce left ventricular hypertrophy (ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, thiazide like diuretics) are preferred. Avoid hydralazine and minoxidil as sole therapy, because they promote hypertrophy.
  • Ramipril 2.5 mg orally once daily, increased every 2 to 4 weeks to 10 mg once daily (maximum 10 mg daily, and 5 mg daily at creatinine clearance under 30 mL/min). Check potassium and creatinine 1 to 2 weeks after each change. Contraindicated in pregnancy and bilateral renal artery stenosis. Alternatively telmisartan 40 mg orally once daily, increased to 80 mg once daily (maximum 80 mg daily), contraindicated in pregnancy and bilateral renal artery stenosis, with potassium and creatinine checked 1 to 2 weeks after each change.
  • Amlodipine 5 mg orally once daily, increased to 10 mg once daily (maximum 10 mg daily; start 2.5 mg in older adults and liver impairment). Ankle oedema is dose related.
  • Indapamide modified release 1.5 mg orally once daily (maximum 1.5 mg daily), or chlortalidone 12.5 mg orally once daily, increased to 25 mg (maximum 50 mg daily). Check sodium, potassium and creatinine at 2 weeks and 3 months. Avoid indapamide at eGFR under 30 mL/min/1.73 m2.
  • In Black patients, start with a calcium channel blocker plus an ACE inhibitor or angiotensin receptor blocker, or with a thiazide like diuretic, since ACE inhibitor monotherapy is less effective.
  • Resistant hypertension (uncontrolled on three drugs including a diuretic): spironolactone 25 mg orally once daily, increased to 50 mg (maximum 50 mg daily in this setting), with potassium and creatinine at 1 week and 4 weeks. Withhold at potassium over 5.5 mmol/L and avoid at eGFR under 30 mL/min/1.73 m2.
  • Beta blockers are not first line unless angina, atrial fibrillation or heart failure with reduced ejection fraction is present.
• Heart failure with preserved ejection fraction. Diuretics for congestion (furosemide 40 mg orally once daily in the morning, increased to 80 to 120 mg daily as needed, higher doses in renal impairment under specialist care, with sodium, potassium and creatinine monitoring), plus dapagliflozin 10 mg orally once daily (start at eGFR 25 mL/min/1.73 m2 or more; contraindicated in type 1 diabetes; withhold during acute illness with poor oral intake) and spironolactone 25 mg once daily (12.5 mg at eGFR 30 to 49 mL/min/1.73 m2, with potassium monitoring).
• Heart failure with reduced ejection fraction. Add sacubitril/valsartan 49/51 mg orally twice daily, doubled at 2 to 4 weeks to the target 97/103 mg twice daily (maximum 194/206 mg daily; start 24/26 mg twice daily if not on an ACE inhibitor or angiotensin receptor blocker, on low doses, with eGFR under 30 mL/min/1.73 m2, or with moderate liver impairment; stop any ACE inhibitor 36 hours before; contraindicated with previous angio oedema, severe liver impairment and pregnancy), and bisoprolol 1.25 mg orally once daily, increased every 1 to 4 weeks to the target 10 mg once daily (maximum 10 mg daily in heart failure; contraindicated in cardiogenic shock, high grade AV block without a pacemaker, sick sinus syndrome and severe asthma), with spironolactone 25 mg orally once daily (12.5 mg at eGFR 30 to 49 mL/min/1.73 m2, up to 50 mg daily) and dapagliflozin 10 mg orally once daily. Stop the ACE inhibitor when sacubitril/valsartan starts.
• Atrial fibrillation: apixaban 5 mg orally twice daily, reduced to 2.5 mg twice daily when at least two of age 80 years or over, weight 60 kg or under and serum creatinine 133 micromol/L or over are present. Also 2.5 mg twice daily at creatinine clearance 15 to 29 mL/min, and avoided under 15 mL/min. Maximum 10 mg daily. Long term.
• Hypertensive emergency with acute pulmonary oedema. Sit the patient upright, give oxygen to a saturation of 94 to 98%, and start non-invasive ventilation for hypoxaemia. Glyceryl trinitrate 10 to 20 microgram/min intravenously, increased by 5 to 10 microgram/min every 5 to 10 minutes, usual maximum 200 microgram/min (contraindicated with phosphodiesterase type 5 inhibitors and in hypotension), plus furosemide 40 to 80 mg intravenously, doubled after 1 to 2 hours if the response is inadequate (maximum single dose 200 mg). Aim for a systolic pressure under 140 mm Hg within the first hour. In other emergencies, reduce mean arterial pressure by no more than 25% in the first hour, then to 160/100 mm Hg over 2 to 6 hours and to normal over 24 to 48 hours.
• Statin and antiplatelet therapy by cardiovascular risk (aspirin only for established vascular disease).

Special groups.

• Pregnancy: use labetalol, nifedipine modified release or methyldopa. Stop ACE inhibitors, angiotensin receptor blockers, sacubitril/valsartan, spironolactone and statins before conception.
• Kidney impairment: limit ramipril to 5 mg daily at creatinine clearance under 30 mL/min, give spironolactone 12.5 mg at eGFR 30 to 49 mL/min/1.73 m2 and avoid it under 30 mL/min/1.73 m2, avoid indapamide at eGFR under 30 mL/min/1.73 m2, avoid dual renin angiotensin blockade, and monitor potassium closely.
• Sub-Saharan Africa: favour fixed dose combinations, once daily drugs and community follow up to improve adherence.

Monitoring. Blood pressure monthly until at target, then every 3 to 6 months. Potassium and creatinine 1 to 2 weeks after each change of ramipril or telmisartan and at 1 week and 4 weeks after starting spironolactone, then every 3 to 6 months. Echocardiography at 6 to 12 months to assess regression of left ventricular mass, and then every 1 to 2 years. ECG yearly. Urinary albumin to creatinine ratio yearly.

Referral and escalation. Refer to cardiology for heart failure, arrhythmia or doubt over the cause, and to a hypertension specialist for resistant or secondary hypertension. Urgent for hypertensive emergency, acute pulmonary oedema or syncope.