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INTRODUCTION

Heart failure is responsible for more than half a million deaths annually in the U.S. Its prevalence is stable in developed countries but increasing worldwide, mainly due to an adoption of western lifestyle and an aging population. Median survival rates after the first hospitalization associated with heart failure are worse than in most cancers but have improved over the past 30 years (1.3 to 2.3 years in men and 1.3 to 1.7 years in women) (Jhund et al., 2009). This positive survival trend was associated with a 2- to 3-fold higher prescription rate of angiotensin-converting enzyme (ACE) inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), β receptor antagonists (β blockers), and mineralocorticoid receptor antagonists (MRAs), suggesting that improved drug therapy has contributed to enhanced survival of patients with heart failure. However, a more complex picture evolved over the past decade with an increasing incidence in people younger than 55 years of age, a decrease in heart failure with reduced ejection fraction (HFrEF); and an increase in heart failure with preserved ejection fraction (HFpEF; Chan et al., 2021; Tsao et al., 2018).

ABBREVIATIONS

Abbreviations

ACC: American College of Cardiology

ACE: angiotensin-converting enzyme

ACEI: angiotensin-converting enzyme inhibitor

ADR: adverse drug reaction

AHA: American Heart Association

AngII: angiotensin II

ANP: atrial natriuretic peptide

ARB: AT1 angiotensin receptor antagonist (blocker)

ARNI: angiotensin receptor–neprilysin inhibitor

AV: atrioventricular

AVP: arginine vasopressin

BNP: brain-type natriuretic peptide

CG: cardiac glycoside

CHF: congestive heart failure

CNP: C-type natriuretic peptide

CYP: cytochrome P450

DA: dopamine

ECG: electrocardiogram

EF: ejection fraction

eNOS: endothelial nitric oxide synthase

EPI: epinephrine

ESC: European Society of Cardiology

ET: endothelin

GC: guanylyl cyclase

GFR: glomerular filtration rate

GI: gastrointestinal

GPCR: G protein-coupled receptor

HCN: hyperpolarization-activated, cyclic nucleotide–gated cation channel

HFpEF: heart failure with preserved ejection fraction (diastolic heart failure)

HFrEF: heart failure with reduced ejection fraction (systolic heart failure)

iNOS: inducible nitric oxide synthase

ISDN: isosorbide 2,5′-dinitrate

ISMN: isosorbide 5′-mononitrate

MRA: mineralocorticoid receptor antagonist

NCX: Na+/Ca2+ exchanger

NE: norepinephrine

NO: nitric oxide

NOS: nitric oxide synthase

NSAID: nonsteroidal anti-inflammatory drug

NYHA: New York Heart Association

PDE: cyclic nucleotide phosphodiesterase

PKA: protein kinase A

RAAS: renin-angiotensin-aldosterone system

RAS: renin-angiotensin system

ROS: reactive oxygen species

SERCA: sarco/endoplasmic reticulum Ca2+ ATPase

sGC: soluble guanylyl cyclase

SGLT2: sodium glucose co-transporter 2

SNS: sympathetic nervous system

SR: sarcoplasmic reticulum

TnC: troponin C

TNF: tumor necrosis factor

PATHOPHYSIOLOGY OF HEART FAILURE

Definitions

Heart failure is a state in which the heart is unable to pump blood at a rate commensurate with the requirements of the body’s tissues or can do so only at elevated filling pressure. This leads to symptoms that define the heart failure syndrome clinically. Low output (forward failure) causes fatigue, dizziness, muscle weakness, and shortness of breath, which is aggravated by physical exercise. Increased filling pressure leads to congestion of the ...

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