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NT-proBNP level may identify patients with non-ischemic systolic HF who might benefit from ICDs

Reuters Health - 08/03/2022 - Patients with non-ischemic systolic cardiomyopathies who received implantable cardiac defibrillators (ICD) in a randomized trial were most likely to have a reduced risk of sudden death (SD) if their baseline level of N-terminal pro-brain natriuretic peptide (NT-proBNP) was below the median, a new analysis revealed.

The findings were drawn from an extended follow-up of 1,116 participants in the DANISH Trial, in which patients with non-ischemic cardiomyopathy and ejection fraction (EF) no higher than 35% were randomly assigned to receive an ICD along with optimal medical therapy or optimal medical therapy alone.

Higher NT-proBNP at baseline was associated with increased age, reduced kidney dysfunction, permanent atrial fibrillation, lower ejection fraction, worse NYHA functional class and previous hospitalization for heart failure (HF).

With the median follow-up now 10 years, patients with baseline NT pro-BNP below the median value of 1,777 pg/mL who were randomized to ICD implantation had a lower risk of sudden cardiovascular (CV) death (hazard ratio, 0.37) compared to medical therapy alone.

In contrast, in the presumably sicker patients with increased NT-pro-BNP over 1,777, ICD implantation had minimal benefit (HR, 0.86), according to a report by Dr. Jawad Butt from Copenhagen University Hospital in Denmark and colleagues in the Journal of the American College of Cardiology. The pattern held true even if NT-proBNP tertile were used for analysis

While there was a trend toward a reduction in CV deaths with ICDs in patients with lower NT pro-BNP (HR 0.69), there were no statistically significant benefits based on NT-pro-BNP level in the risks of non-sudden CV death (HR, 0.94) and non-CV death (HR, 0.92), which suggests that the underlying cardiac dysfunction, pump failure, and other high risk factors explain the results.

The authors acknowledge the limitation of this study for patients presenting in 2022, noting, "Sacubitril-valsartan and sodium-glucose cotransporter-2 inhibitors, both of which are now established therapies in heart failure with reduced ejection fraction (HFrEF), reduce the risk of CV and SCD in patients with HFrEF." These medications were not prescribed to any extent in the DANISH cohort; rather, beta-blockers and angiotension-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) were used at baseline more than 90% of the time, with mineralocorticoid receptor antagonist (MRA) use above 50%.

This study was also performed in a fairly homogeneous Danish population (71-73% males). Median ages in the groups with NT pro-BNP levels below and above the median were 61 and 65, respectively. The group with NT pro-BNP levels above the median had a wider median QRS interval but lower median systolic BP and lower median LVEF (21%, vs 26% in the group with lower median NT pro-BNP).

Among the limitations of the study is that use of cardiac resynchronization therapy pacemakers (CRT-P) was not randomized. Among patients with low NT-proBNP, those randomized to receive an ICD were more likely to have a CRT implanted compared to those randomized to the control group (60% versus 48%), whereas patients with higher NT-proBNP were less likely to have a CRT implanted in the ICD group.

Other limitations include the lack of information on NT-proBNP levels over time, and on hospitalization rates.

Dr. Butt did not respond to a request for comment.

"When there are greater competing risks of death, protection from sudden arrhythmic death with a primary prevent ICD may offer lesser benefits," Dr. Emily Zeiter of Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire and Dr. G. Michael Felker of Duke University School of Medicine in Durham, North Carolina noted in an accompanying editorial.

Neither the authors of the current paper nor the editorialists are convinced that this study answers the question of which patients with non-ischemic cardiomyopathies may benefit from ICDs.

More than a decade ago, the COMPANION study questioned the value of cardiac resynchronization therapy defibrillators (CRT-D) versus CRT-P in patients with both ischemic and non-ischemic cardiomyopathy.

A separate recently published paper in the Journal of the American College of Cardiology suggested that patients with systolic cardiomyopathy could be safely treated without an ICD in the absence of myocardial scar. (https://bit.ly/3t6Y5NS) But whether scarring seen on cardiac magnetic resonance imaging will become a relative contraindication to ICD placement (with or without CRT) in patients with nonischmic cardiomyopathy remains unclear.

SOURCE: https://bit.ly/3HHiVsd and https://bit.ly/35UVNZW Journal of the American College of Cardiology, online February 14, 2022.

By Austin Kutscher MD FACC

© 2023 The Author(s). Published by Medicom Medical Publishers.
User license: Creative Commons Attribution – NonCommercial (CC BY-NC 4.0)

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