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  • Dyspnea on exertion and at rest, orthopnea, paroxysmal nocturnal dyspnea, and fatigue.

  • Elevated jugular venous pressure, crackles throughout both lung fields with wheezing, cardiomegaly, S3 gallop, hepatomegaly, and bilateral peripheral pitting edema.

  • Dilated left ventricle with a reduced ejection fraction on transthoracic echocardiography.

  • Elevated left ventricular filling pressures on cardiac catheterization.


Heart failure (HF) is a complex clinical syndrome resulting from any structural or functional myocardial dysfunction that leads to an impaired ability to circulate blood at a rate sufficient to maintain the metabolic needs of internal organs and peripheral tissues. The myocardial dysfunction is often the consequence of long-standing ischemia due to coronary artery disease or loss of myocardial mass due to prior infarction, long-standing myocardial stress due to suboptimally treated hypertension or valvular disease, or direct long-term toxin exposure (alcohol abuse, illicit substance use, or chemotherapeutic agents); rarely, fulminant infections (especially viral) can lead to autoimmune myocardial damage, and in some cases, there is no apparent cause (idiopathic cardiomyopathy, usually related to inherited or spontaneous gene mutations).

The cardinal manifestations of HF are dyspnea and fatigue (which may limit exercise tolerance) and fluid retention (which may lead to pulmonary/hepatic/splanchnic congestion and peripheral edema). Both abnormalities impair the functional capacity and quality of life of affected patients, but they may not necessarily dominate the clinical picture at the same time.

Globally, the prevalence of HF is highest in Central Europe, North Africa, and the Middle East. The lowest rates are observed in Southeast Asia and Eastern Europe. Various HF risk factors predominate in certain geographic regions, with ischemic heart disease being the highest in Europe and North America, valvular heart disease in Asia, and hypertension in Latin America, the Caribbean, and Eastern Europe.

The prevalence of HF in the United States is around 6 million patients, with projections showing a 46% increase from 2012 to 2030 resulting in more than 8 million people with HF. Approximately 50% of those hospitalized with HF have reduced ejection fraction (HFrEF)/systolic dysfunction. Recent data from the Framingham Heart Study have demonstrated that 60% of the middle-aged and older adults had evidence of preclinical HF (AHA/ACC Stage A or B), suggesting a potentially high burden of early HF in the community. There are an estimated one million new HF cases annually in the United States.

In the past 25 years, the residual lifetime risk of developing HF in middle-aged adults increased by about 20% in women and 30% in men. This is likely primarily driven by an increase in both life expectancy and risk factor prevalence (obesity, hypertension, and diabetes). At age 40, the lifetime risk for HF is as high in women as in men and is approximately one in five. Men however have a higher lifetime risk for HFrEF at age 50 compared to women. Although more ...

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