Pharmacology  ·  Cardiovascular

HFpEF, Device Therapy, and Special Populations

Why preserved ejection fraction resists standard therapy, and how context changes prescribing

• Heart failure with preserved ejection fraction is driven by systemic inflammation from obesity, hypertension, and diabetes rather than by the neurohormonal activation that drives heart failure with reduced ejection fraction — this different underlying process explains why RAAS blockers and beta-blockers, pillars of reduced ejection fraction therapy, have repeatedly failed to show survival benefit in preserved ejection fraction.
• SGLT2 inhibitors are the exception: the first drug class proven to reduce outcomes across the full ejection fraction spectrum, including preserved ejection fraction, and they now represent the central pharmacological intervention for this population alongside loop diuretics for symptomatic relief.
• Device therapy (defibrillators, cardiac resynchronization) provides benefit independent of and additive to drug therapy — devices do not replace guideline-directed medical therapy, and optimized drug therapy continues in full after device implantation.
• Amiodarone raises digoxin blood levels significantly — when amiodarone is started in a patient already taking digoxin, the digoxin dose must be reduced and levels rechecked; failure to do so is a common and avoidable cause of digoxin toxicity.
• Most heart failure drugs require caution rather than avoidance in chronic kidney disease, and RAAS blockers and mineralocorticoid antagonists are absolutely contraindicated in pregnancy; peripartum cardiomyopathy is managed with beta-blockers, hydralazine, and digoxin as safer alternatives during gestation.