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
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
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
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 organs upstream of the ...