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Congestion on Physical Exam in HFrEF Patients
Study Questions:
What is the association between physical signs of congestion at baseline and during study follow-up with quality of life (QoL) and clinical outcomes, and what are the effects of sacubitril/valsartan therapy on congestion in patients with heart failure and reduced ejection fraction (HFrEF)?
Methods:
The study authors analyzed participants from the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in HF) trial with an available physical examination at baseline. They examined the association of the number of signs of congestion (jugular venous distention, S3, rales, and edema) with the primary outcome (cardiovascular death or HF hospitalization), its individual components, and all-cause mortality using time-updated, multivariable-adjusted Cox regression. They also evaluated whether sacubitril/valsartan reduced congestion during follow-up, and whether improvement in congestion is related to changes in clinical outcomes and QoL, assessed by Kansas City Cardiomyopathy Questionnaire clinical summary scores (KCCQ-OSS).
Results:
The study cohort was comprised of 8,380 participants, of whom, 0, 1, 2, and 3+ signs of congestion were present in 70%, 21%, 7%, and 2%. The hazard ratios for the primary endpoint for 1, 2, 3, and 4 signs of congestion (vs. 0 signs) were 1.48, 1.74, 2.35, and 5.96, respectively after these multivariable adjustments (p < 0.001 for all sign groups vs. no congestion). Neither obesity nor body mass index modified the relationship between the number of signs with the primary outcome in fully adjusted models (p for interaction > 0.40 for both comparisons). The study authors found that patients with baseline congestion were older, more often female, and had higher MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) risk scores and lower KCCQOSS (p < 0.05). In a subanalysis of 2,066 individuals with complete natriuretic peptide data available, after adjusting for baseline natriuretic peptides, time-updated MAGGIC score, and time-updated New York Heart Association (NYHA) class, increasing time-updated congestion was associated with all outcomes (p < 0.001). Sacubitril/valsartan reduced the risk of the primary outcome irrespective of clinical signs of congestion at baseline (p = 0.16 for interaction), and treatment with the drug improved congestion to a greater extent than enalapril (p = 0.011). Each 1-sign reduction was independently associated with a 5.1 (95% confidence interval, 4.7-5.5) point improvement in KCCQ-OSS. Change in congestion strongly predicted outcomes even after adjusting for baseline congestion (p < 0.001).
Conclusions:
The authors concluded that in HFrEF patients, the physical exam continues to provide significant, independent prognostic value even beyond symptoms, natriuretic peptides, and MAGGIC risk score. Sacubitril/valsartan improved congestion to a greater extent than enalapril. Reducing congestion in the outpatient setting is independently associated with improved QoL and reduced cardiovascular events, including mortality.
Perspective:
Clinicians have been long aware that improving congestion in flash pulmonary edema is life saving. This is an important study because it demonstrates that clinical signs of congestion (despite interobserver variability) provide prognostic value beyond NYHA class and N-terminal B-type natriuretic peptide. This study also substantiates what any practicing clinical physician by now knows that sacubitril/valsartan improves congestion. Like all good studies, it raises an important question, that is whether physicians managing HF should strive for euvolemia/‘dry weight’ with each HF hospitalization before discharge.
Clinical Topics: Geriatric Cardiology, Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Aminobutyrates, Angiotensin-Converting Enzyme Inhibitors, Edema, Enalapril, Geriatrics, Heart Failure, Natriuretic Peptide, Brain, Neprilysin, Outpatients, Physical Examination, Pulmonary Edema, Quality of Life, Receptors, Angiotensin, Stroke Volume
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