Continued LV reverse remodeling in de novo HFrEF with GDMT optimization beyond 90 days

11/07/2024

In the HF-OPT study, continuous optimization of guideline-directed medical therapy (GDMT) resulted in 68% of the patients with newly diagnosed HFrEF reaching LVEF >35% at 180 days. Achievement of GDMT target doses was associated with LVEF >35%.

This summary is based on the publication of Veltmann C, Duncker D, Doering M, et al. - Therapy duration and improvement of ventricular function in de novo heart failure: the Heart Failure Optimization study. Eur Heart J. 2024 Jun 12:ehae334 [Online ahead of print]. doi: 10.1093/eurheartj/ehae334

Introduction and methods

Background

Many patients with HFrEF do not receive the target doses of guideline-directed medical therapies (GDMTs) in the first months post-diagnosis [1-4]. This implies LV reverse remodeling is probably not completed within the first 90 days. In fact, the PROLONG (Prolongation of Reverse remOdelling period to avoid untimely ICD impLantation in newly diagnOsed heart failure usiNG the wearable cardioverter/defibrillator) study on optimization of HF therapy in patients with newly diagnosed low LVEF demonstrated that 33% of the patients with nonimproved LVEF at 90 days showed LVEF improvement to >35% by continuing GDMT optimization [5]. As primary preventive ICD therapy is generally recommended only if LVEF ≤35% despite established optimal GDMT for a minimum of 90 days, knowledge of continued LVEF improvement is important [6,7].

Aim of the study

The authors evaluated continued LV reverse remodeling beyond 90 days in patients with de novo HFrEF wearing a cardioverter-defibrillator who underwent GDMT titration.

Methods

In the multicenter, prospective, observational HF-OPT (Heart Failure Optimization) study, 1300 patients hospitalized for de novo HFrEF (LVEF ≤35%) were enrolled at 68 sites in the USA, Germany, France, and Austria between March 2017 and May 2022. The study consisted of 2 phases: (1) registry phase, during which a wearable cardioverter-defibrillator was prescribed and GDMT was started (90 days; n=1266); (2) study phase, during which GDMT was further optimized (up to 1 year; n=598). During the study phase, medical and device therapy was left to the discretion of the physician.

Outcomes

The primary endpoints were: (1) the proportion of patients with LVEF improvement to >35% between 90 and 180 days following GDMT initiation; and (2) the percentage of target dose reached at 90 and 180 days. Secondary endpoints included mortality and wearable cardioverter-defibrillator–specific results, such as wear-time, compliance, brady- and tachyarrhythmias, and treatments, during the registry and study phase.

Main results

LVEF improvement to >35%

  • In the study phase population with data at 0, 90, and 180 days (n=487), median LVEF increased from 23% (IQR: 18%–28%) at baseline to 34% (IQR: 28%–43%) at 90 days and 40% (IQR: 33%–48%) at 180 days (P<0.001).
  • At 90 days, 222 study phase patients (46%; 95%CI: 41%–50%) had LVEF >35%.
  • Of the remaining 265 study phase patients with persistently low LVEF at 90 days, 122 (46%; 95%CI: 40%–52%) had LVEF >35% by day 180, increasing the total proportion of patients with LVEF >35% to 68% (95%CI: 63%–72%).
  • Multivariable analysis demonstrated that higher systolic blood pressure at baseline, higher index LVEF, and AF in the previous year were associated with LVEF >35% at 180 days (all P≤0.01), whereas history of sudden cardiac arrest was associated with not reaching LVEF >35% by day 180 (P=0.002).
  • Among the 392 patients followed for 360 days, LVEF >35% was observed in 77% (95%CI: 72%–81%).

Target dose reached

  • From baseline to 180 days, increases in of beta-blocker, RAASi, and MRA doses were observed (all P<0.001).
  • Patients who were prescribed the ACEi/ARB/ARNI target dose at 90 days were more likely to have LVEF >35% at 180 days than those not on target dose at 90 days (53% vs. 42%; P=0.02). The same was true for patients reaching the MRA target dose at 90 days compared with those who did not (52% vs. 41%; P=0.02) but not for patients who did or did not achieve the beta-blocker target dose (52% vs. 44%; P=0.14).
  • For all 3 drug classes, achievement of target dose at 180 days was associated with LVEF >35% at that same time point (all P<0.05).
  • Of the 45 patients treated with the target doses of all drug classes at 180 days, 40 (89%) had LVEF >35%, compared with 96 of the 160 patients (60%) who were not on target dose for any of the 3 drug classes.

Wearable cardioverter-defibrillator–specific results

  • During the registry phase (first 90 days), 24 of the 1300 patients with a wearable cardioverter-defibrillator (1.8%) experienced a total of 34 sustained ventricular tachycardia/fibrillation events (15.5 events per 100 patient-years). • Between 90 and 180 days, 1 nonsustained ventricular tachycardia occurred in carriers of the wearable cardioverter-defibrillator but no sustained ventricular tachyarrhythmia.

Mortality

  • In the study population (n=598), cumulative survival was 99.2%, 98.5%, and 97.7% at 180, 270, and 360 days, respectively.
  • During the entire study period, 28 deaths occurred, 14 of which (50%) were adjudicated as CV deaths. In the registry phase, 11 patients (1.8%) died, whereas 17 (2.8%) died after day 90.

Conclusion

In the prospective, observational HF-OPT study among patients with de novo HFrEF (LVEF ≤35%) wearing a cardioverter-defibrillator, continuous optimization of GDMT resulted in more patients reaching LVEF >35% (46% at 90 days, 68% at 180 days, and 77% at 360 days). Achievement of GDMT target doses at 180 days was associated with LVEF >35%. Ventricular tachyarrhythmias occurred mainly in the first 90 days after diagnosis.

The authors conclude that the decision to implant an ICD should “be taken if the patient is medically optimized and LVEF is stable with no further improvement under optimized GDMT, which may take more time than 90 or even 180 days.”

Find this article online at Eur Heart J.

References

1. Greene SJ, Ezekowitz JA, Anstrom KJ, Demyanenko V, Givertz MM, Piña IL, et al. Medical therapy during hospitalization for heart failure with reduced ejection fraction: the VICTORIA registry. J Card Fail 2022;28:1063–77. https://doi.org/10.1016/j.cardfail. 2022.02.011

2. Greene SJ, Fonarow GC, DeVore AD, Sharma PP, Vaduganathan M, Albert NM, et al. Titration of medical therapy for heart failure with reduced ejection fraction. J Am Coll Cardiol 2019;73:2365–83. https://doi.org/10.1016/j.jacc.2019.02.015

3. Brunner-La Rocca H-P, Linssen GC, Smeele FJ, van Drimmelen AA, Schaafsma HJ, Westendorp PH, et al. Contemporary drug treatment of chronic heart failure with reduced ejection fraction. JACC Heart Fail 2019;7:13–21. https://doi.org/10.1016/j.jchf. 2018.10.010

4. DeFilippis EM, Butler J, Vaduganathan M. Waiting period before implantable cardioverter-defibrillator implantation in newly diagnosed heart failure with reduced ejection fraction: a window of opportunity. Circ Heart Fail 2017;10:e004478. https://doi.org/10.1161/CIRCHEARTFAILURE.117.004478

5. Duncker D, König T, Hohmann S, Bauersachs J, Veltmann C. Avoiding untimely implantable cardioverter/defibrillator implantation by intensified heart failure therapy optimization supported by the wearable cardioverter/defibrillator—the PROLONG study. J Am Heart Assoc 2017;6:e004512. https://doi.org/10.1161/JAHA. 116.004512

6. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42:3599–726. https://doi.org/10.1093/eurheartj/ehab368

7. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. 2022 AHA/ ACC/HFSA guideline for the management of heart failure: executive summary. J Am Coll Cardiol 2022;79:1757–80. https://doi.org/10.1016/j.jacc.2021.12.011

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