Diastolic dysfunction — clinical presentation, diagnosis and treatment options

Definition and mechanism. Diastolic dysfunction is retarded left ventricular filling with a higher left ventricular diastolic pressure, present both at rest and during exercise in older persons. It arises from impaired active relaxation and increased passive chamber stiffness, caused by myocardial hypertrophy, interstitial fibrosis, arterial stiffening with increased afterload, and impaired calcium handling. The result is that a small increase in volume produces a large rise in filling pressure, causing pulmonary congestion at a normal ejection fraction. When symptomatic it is called heart failure with preserved ejection fraction (HFpEF).

Why it dominates in old age. Diastolic dysfunction, not systolic dysfunction, is the primary cause of heart failure in older patients, and is associated with marked increases in all-cause mortality. Age-related hypertrophy and stiffening mean that older people depend more on atrial contraction than on ventricular relaxation for left ventricular filling; consequently they are far more likely to develop heart failure if atrial fibrillation ensues, since the atrial kick is lost and diastole is shortened. Heart failure may therefore occur in the absence of systolic dysfunction or valvular disease.

Causes and associations. Hypertension with left ventricular hypertrophy is the commonest. Others: coronary artery disease and ischaemia, aortic stenosis, diabetes mellitus, obesity, chronic kidney disease, atrial fibrillation, obstructive sleep apnoea, hypertrophic cardiomyopathy and infiltrative disease — especially wild-type transthyretin cardiac amyloidosis, which is a commonly missed cause in the very old. Constrictive pericarditis is an important mimic.

Clinical presentation. Symptoms are indistinguishable from systolic failure — exertional dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, fatigue and reduced exercise tolerance, with raised JVP, basal crackles and peripheral oedema. Distinguishing features: a fourth heart sound (S4) rather than a third, a sustained apex beat, a predominance in elderly women with hypertension and obesity, and flash pulmonary oedema precipitated by hypertensive surges, tachycardia, atrial fibrillation, fluid or salt loading, or NSAIDs. The patient is exquisitely preload-dependent and decompensates in both directions — congestion with a little too much fluid, and hypotension with a little too much diuretic.

Diagnosis. There are three requirements: symptoms and signs of heart failure, a preserved ejection fraction (≥ 50%), and objective evidence of raised filling pressures or diastolic dysfunction. Echocardiography is the key test — look for left ventricular hypertrophy with normal chamber size, left atrial enlargement (a marker of chronically raised filling pressure), a raised E/e′ ratio, reduced e′ tissue Doppler velocity, and an elevated tricuspid regurgitant velocity. Support with raised natriuretic peptides, remembering that BNP rises with age and renal impairment and is lowered by obesity — so a normal level in an obese patient does not exclude HFpEF. Use the H FPEF or HFA-PEFF score where the diagnosis is uncertain, and exercise (diastolic) stress 2 echocardiography for exertional symptoms with a normal resting study. Always exclude constrictive pericarditis and cardiac amyloidosis.

Treatment. The textbook position is that few large randomised controlled trials of drug treatment in diastolic heart failure have been designed, and trials of digoxin and ARBs have shown minimal benefit (CHARM-Preserved, I-PRESERVE, PEP-CHF and the ancillary DIG trial were all essentially neutral). Therefore: (i) treat the comorbidities that drive it — hypertension, coronary artery disease, atrial fibrillation and diabetes mellitus; (ii) use diuretics to treat pulmonary congestion or peripheral oedema, cautiously, since over-diuresis causes hypotension and renal impairment; (iii) use beta-blockers to control heart rate and lengthen diastolic filling time, and restore or control rate in atrial fibrillation; (iv) control blood pressure aggressively as the single most effective preventive measure; (v) encourage weight loss, salt restriction and supervised exercise training, which reliably improve exercise capacity and quality of life.

HFpEF is no longer an untreatable condition. SGLT2 inhibitors are now the first drug class with proven outcome benefit — EMPEROR-Preserved and DELIVER showed that empagliflozin and dapagliflozin reduce cardiovascular death and heart failure hospitalisation across the preserved and mildly reduced ejection fraction range, and they are recommended for all such patients in the 2023 ESC focused update. Building on this, FINEARTS-HF (NEJM 2024) showed that finerenone reduces worsening heart failure events and cardiovascular death in HFmrEF and HFpEF, and STEP-HFpEF (NEJM 2023) showed that semaglutide produces large improvements in symptoms and exercise capacity in obesity-related HFpEF. The examinable line is that the textbook statement "no proven drug therapy for diastolic heart failure" is now out of date.