High-Output Heart Failure

Study Questions:

What are the causes, pathophysiology, clinical and hemodynamic characteristics, and outcomes of high-output heart failure (HF) in the modern era?


The study authors performed a retrospective analysis of all consecutive patients referred to the Mayo Clinic catheterization laboratory for hemodynamic assessment between 2000 and 2014. They compared subjects with definite HF, as defined by the Framingham criteria and elevated cardiac index (≥4 L/min/m2), to controls of similar age and gender. They categorized patients as having left-sided HF if an elevation in pulmonary capillary wedge pressure was identified at the time of catheterization (≥15 mm Hg). Patients with clinical HF, elevated mean pulmonary artery pressure (≥25 mm Hg), but normal pulmonary wedge pressure (<15 mm Hg) were defined as having right-sided HF. They excluded those with alternative causes of high cardiac output, either physiological (pregnancy, fever, infection), congenital, or iatrogenic (pulmonary vasodilators, inotropes). Also excluded were patients with severe anemia (hemoglobin <8 mg/dl), thyrotoxicosis, valvular heart disease (> mild stenosis, > moderate regurgitation), constrictive pericarditis, left ventricular systolic dysfunction (ejection fraction [EF] <45%), cardiomyopathies, and heart transplantation.


The study cohort was comprised of 525 HF patients that showed an elevated cardiac index, of whom 120 cases had definite high-output HF. Most of the high-output patients presented with left-sided HF (n = 91, 76%), and the remaining presented with right heart failure. The study authors found that most common etiologies of high-output HF (n = 120) were obesity (31%), liver disease (23%), arteriovenous shunts (23%), lung disease (16%), and myeloproliferative disorders (8%). When compared to controls (n = 24), patients with high-output HF displayed eccentric left ventricular remodeling, greater natriuretic peptide activation, higher filling pressures, pulmonary hypertension, and increased cardiac output, despite similar EF. Elevated cardiac output in high-output HF patients was related to both lower arterial afterload (decreased systemic vascular resistance) and higher metabolic rate. Mortality was increased in high-output HF as compared with controls (38% vs. 0%; hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.6-7.6; p = 0.002). Hemodynamics and outcomes were poorest amongst patients with the lowest systemic vascular resistance—(bottom quartile, <1,030 dyne-m2/s/cm-5) displayed increased mortality compared to the remainder of patients with mildly depressed or normal systemic vascular resistance (61% vs. 36%; HR, 2.5; 95% CI, 1.2-5.1; p = 0.01). Also, most patients with high-output HF also displayed an elevated Doppler-estimated right ventricular systolic pressure (≥42 mm Hg; 92% sensitivity; 100% specificity [area under the curve, 0.97; p < 0.0001]).


The authors concluded that given the high mortality and increasing prevalence of these comorbidities in Western countries, high-outpatient HF should be considered in the differential diagnosis of patients presenting with shortness of breath, congestion, and normal EF.


This is an important study because it characterizes the natural history of high-output HF in the modern era. There findings suggest that it is important that such patients are excluded from multicenter trials attempting to determine definitive therapies for diastolic HF. Examination of other similar databases should add value to the important findings reported by these authors.

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