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INTRODUCTION

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Heart failure is responsible for more than half a million deaths annually in the U.S. Its prevalence is increasing worldwide, likely due to improved survival of those who have had an acute myocardial infarction and an aging population. Median survival rates after the first hospitalization associated with heart failure are worse than those of 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 trend was associated with a 2- to 3-fold higher prescription rate of ACEIs and ARBs, β receptor antagonists (β blockers), and MRAs, suggesting that improved drug therapy has contributed to enhanced survival of heart failure.

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ABBREVIATIONS

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Abbreviations

ACC: American College of Cardiology

ACE: angiotensin-converting enzyme

ACEI: angiotensin-converting enzyme inhibitor

ACh: acetylcholine

ADH: antidiuretic hormone (vasopressin)

ADR: adverse drug reaction

AF: atrial fibrillation

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

BB: β blocker

BNP: brain-type natriuretic peptide

CAD: coronary artery disease

CCB: calcium channel blocker

CG: cardiac glycoside

CHF: congestive heart failure

CM: cardiomyopathy

CNP: C-type natriuretic peptide

COX: cyclooxygenase

CPT1: Carnitine palmitoyltransferase 1

CRT: cardiac resynchronization therapy

CYP: cytochrome P450

DCM: dilated cardiomyopathy

DM: diabetes mellitus

ECG: electrocardiogram

EF: ejection fraction

EMA: European Medicines Agency

eNOS: endothelial nitric oxide synthase

EPI: epinephrine

ESC: European Society of Cardiology

ET: endothelin

FDA: Food and Drug Administration

GC: guanylyl cyclase

GDMT: guideline-directed medical therapy

GFR: glomerular filtration rate

GI: gastrointestinal

GPCR: G protein–coupled receptor

GTN: glycerol trinitrate

HCM: hypertrophic cardiomyopathy

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

HF: heart failure

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

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

HMG CoA: 3-hydroxy-3-methylglutaryl coenzyme A

HRQOL: health-related quality of life

HTN: hypertension

ICD: implantable cardioverter-defibrillator

ISDN: isosorbide 2,5′-dinitrate

ISMN: isosorbide 5′-mononitrate

LV: left ventricular

LVH: left ventricular hypertrophy

MCS: mechanical circulatory support

MI: myocardial infarction

MRA: mineralocorticoid receptor antagonist

NCX: Na+/Ca2+ exchanger

NE: norepinephrine

NO: nitric oxide

NSAID: nonsteroidal anti-inflammatory drug

NYHA: New York Heart Association

PD: pharmacodynamic

PDE: cyclic nucleotide phosphodiesterase

PKA: protein kinase A

PLB: phospholamban

PLM: phospholemman

RAAS: renin-angiotensin-aldosterone system

ROS: reactive oxygen species

RyR: ryanodine receptor

SERCA: sarco/endoplasmic reticulum Ca2+ ATPase

sGC: soluble guanylyl cyclase

SL: sarcolemma

SNS: sympathetic nervous system

SR: sarcoplasmic reticulum

TnC: troponin C

TNF: tumor necrosis factor

TnI: inhibitory subunit of troponin

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PATHOPHYSIOLOGY OF HEART FAILURE

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Definitions

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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, ...

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