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A 55-year-old man with hypertension, diabetes mellitus and recent drug eluting stent placement to left anterior descending (LAD) artery after suffering a myocardial infarction comes to your clinic after being discharged from the hospital. He is able to carry out daily activities with ease but reports getting short of breath on climbing 2 sets of stairs. An echocardiogram done during the hospitalization revealed an left ventricular ejection fraction (LVEF) of 35%-39% with wall motion abnormalities in LAD territory. He mentions compliance with his regimen of Aspirin 81 mg once daily, Clopidogrel 75 mg once daily, Amlodipine 5 mg, Atorvastatin 80 mg and Furosemide 20 mg once daily. On examination his blood pressure is 147/87 and heart rate 76 beats per minute, he appears in no acute distress, JVP is 7 cm H2O, lungs are clear, heart sounds are regular with no murmurs and no lower extremity edema is noted. He asks about additional therapies to help recover improve his heart function and quality of life.


Understanding the pathophysiological role of the neurohormonal axis in heart failure (HF) has been a key driver of the paradigm shift of the management of HF from one of only symptom management to that involving strategies aimed at modulating pathologic left ventricular (LV) remodeling and HF-related mortality.


A reduction in myocardial function, stemming from any insult, leads to a decrease in cardiac output and blood pressure and, via activation of baroreceptors, leads to activation of the sympathetic nervous system (SNS) and renal hypoperfusion. The SNS primarily mediates its effects via catecholamines.1 Via stimulation from the SNS as well as intrinsic renal mechanisms, the renin angiotensin and subsequently aldosterone system are activated, collectively referred to as the renin-angiotensin-aldosterone system (RAAS). The combined effect of the 2 systems leads to increased inotropy, chronotropy, sodium and water retention (leading to an increase in preload), and vasoconstriction (causing an increase in afterload). Over the short term, the above compensation helps maintain cardiac output (CO) and blood pressure (BP); however, chronic activation of the same compensatory mechanisms leads to pathologic remodeling of the ventricular myocardium (Figure 28-1).2 Although described more extensively in patients with HF with reduced ejection fraction (HFrEF), regardless of the etiology, similar mechanisms may play a role in HF with preserved ejection fraction (HFpEF).

Figure 28-1

Short-term adaptive and long-term pathologic responses to cardiac injury.


Therapies aimed at blocking various steps in the RAAS pathway help to mitigate the effect of the chronically overactivated system, and have demonstrated definitive beneficial effects on morbidity and mortality in HFrEF.


Angiotensin-converting enzyme (ACE) inhibitors ...

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