Cardiac Dysfunction and Noncardiac Dysfunction as Precursors of Heart Failure With Reduced and Preserved Ejection Fraction in the Community

Study Questions:

What is the impact of cardiac and noncardiac organ dysfunction on the clinical manifestation of heart failure (HF)?


Participants (n = 1,038) from the original Framingham Heart Study comprised the cohort. Patients with overt organ dysfunction were excluded, including those with a serum creatinine >2.0 mg/dl. Cardiac systolic and diastolic function were assessed using transthoracic echocardiography. Noncardiac organs studied included the kidneys (serum creatinine), liver (serum albumin), lungs (ratio of forced expiratory volume in 1 second to forced vital capacity FEV1/FVC), and hematologic systems (hemoglobin and white count). HF was defined per Framingham major/minor criteria and then subcategorized into HF with reduced ejection fraction (HFREF = left ventricular [LV] EF ≤45%) and HF with preserved ejection fraction (HFPEF = LVEF >45%). The risk of HF development was assessed using Cox proportional hazard ratios (HRs [95% confidence interval]).


The mean ± standard deviation participant (n = 1,038) age was 75 ± 5 years and 39% were male. Diabetes was present in 5%, treated hypertension in 53%, and 9% had had a prior myocardial infarction. Antecedent asymptomatic LV systolic dysfunction was present in 5% of patients at baseline and was associated with an adjusted HR 2.33 [1.4-3.8] increased risk of HF development. Antecedent asymptomatic diastolic dysfunction was noted in 36% of patients and conferred an adjusted HR 1.3 [1.01-1.7] increased risk of HF development. After controlling for asymptomatic cardiac dysfunction, patients with antecedent higher serum creatinine (HR, 1.2 [1.01-1.45]), lower FEV1/FVC ratios (1.2 [1.02-1.43]), and lower hemoglobins (1.2 [1.1-1.4]) had greater risk of HF development. Overall, the presence of noncardiac organ dysfunction increased subsequent risk of HF development by 30% (HR, 1.3 [1.1-1.6]).


The authors concluded that risk of developing clinical HF is increased in patients with antecedent cardiac and noncardiac organ dysfunction.


This is an interesting and statistically well analyzed population study from a well-known cohort of patients. Not surprisingly, patients with pre-existing ‘asymptomatic’ LV systolic or diastolic abnormalities on echo go on to develop symptoms or signs of HF. Baseline medical therapies prescribed to these patients with asymptomatic disease were not presented nor do we know the true definition of ‘asymptomatic,’ but the information gleaned is important and supports the need for aggressive medical management according to American College of Cardiology Foundation/American Heart Association guidelines. The Framingham HF criteria are biased against identifying class I-II HF patients. Framingham criteria include exam signs like rales, jugular venous distention, paroxysmal nocturnal dyspnea, and tachycardia >120 bpm, which are associated with marked HF decompensation. Thus, this study actually suggests ‘asymptomatic’ dysfunction predisposes to the development of advanced clinical HF. The authors also demonstrated that the presence of other medical comorbidities is associated with increased risk for HF development. In the chronic obstructive pulmonary disease (COPD) patient, one could argue that it may be hard to tease out diagnoses (COPD vs. HF) using some of the Framingham exam criteria (e.g., dyspnea on exertion, nocturnal cough, decreased vital capacity). Statistically, the authors controlled for potential confounders (such as diabetes, prior myocardial infarction, and hypertension) that may be present in greater burden in the COPD or renal failure patient. Further studies, however, are needed establish causality and explain the ‘link.’

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Noninvasive Imaging, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Echocardiography/Ultrasound

Keywords: Myocardial Infarction, Diastole, United States, Echocardiography, Tachycardia, Vital Capacity

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