CRT-D Upgrade Suits Patients With Pacing-Related Heart Failure

AMSTERDAM — A cardiac resynchronization therapy (CRT) upgrade produced solid clinical benefit for patients with pacing-induced heart failure with reduced ejection fraction (HFrEF), the small BUDAPEST CRT Upgrade randomized trial found.

In those with an existing implantable cardioverter-defibrillator (ICD) with intermittent or permanent right ventricular (RV) pacing, getting an extra left ventricular (LV) lead implanted to the coronary sinus side branch resulted in lower 12-month heart failure (HF) hospitalization, all-cause mortality, or absence of reverse remodeling (32.4% vs 78.9%, adjusted OR 0.11, 95% CI 0.06-0.19).

This was consistent across prespecified subgroups by age, baseline ejection fraction, atrial fibrillation (Afib), history of ischemic events, diabetes, New York Heart Association (NYHA) class, and BMI — and linked to a number needed to treat of just 2.2, reported Béla Merkely, MD, PhD, of Semmelweis University in Budapest, Hungary, at the European Society of Cardiology (ESC) conference. The findings — the first major trial on CRT upgrade in this setting — were published simultaneously in the European Heart Journal.

“Overall, HFrEF patients with a pacemaker or ICD should be strictly followed in clinical practice, and in those with intermittent or permanent RV pacing, a CRT upgrade should be performed immediately without postponing the procedure to a later date to avoid or reduce the risk of further adverse events such as mortality, heart failure hospitalization, or LV remodelling,” Merkely told the audience.

He reported CRT upgrade’s safety in terms of favorable rates of successful procedures (98.0% with CRT-D vs 100.0% with ICD alone), procedure- or device-related serious adverse events (12.3% vs 7.8%), and low ventricular tachycardia or ventricular fibrillation (0.5% vs 14.%).

Merkely also highlighted “marked significant benefit” based on combined HF hospitalization and all-cause mortality (10.2% vs 34.7%, adjusted HR 0.27, 95% CI 0.16-0.47), a secondary endpoint associated with a number needed to treat of 4.7.

Post hoc analysis suggested benefits were driven by reductions in HF hospitalization — not all-cause mortality — and significant reverse remodeling.

ESC session study discussant Cecilia Linde, MD, of Karolinska Institutet in Stockholm, said these “highly convincing outcome results in favor of CRT-D” from BUDAPEST CRT Upgrade will probably affect guideline recommendations on cardiac pacing for HF.

Approximately one in five RV-paced patients develop HF over 4 years, with an especially greater risk in patients with pre-existing LV dysfunction, Linde noted in a separate editorial.

“Until now upgrading to CRT has been postponed or not considered suitable. Such delay for whatever reason is associated with risk of unnecessary aggravation of the HF condition. The results of the BUDAPEST-CRT Upgrade study call for careful monitoring of LV function, percent RV pacing and HF symptoms to identify patients in need for upgrading to CRT,” Linde wrote.

Currently, ESC guidelines give upgrading to CRT in this setting a class II-B endorsement, whereas the strategy holds a stronger class I-B recommendation from the Heart Rhythm Society, Asia Pacific Heart Rhythm Society, and Latin American Heart Rhythm Society since 2023.

BUDAPEST CRT Upgrade was a randomized trial conducted in 17 centers in six countries that recruited HFrEF patients with a previously implanted pacemaker or ICD with at least 20% RV pacing and a paced QRS complex of at least 150 ms.

Investigators had 360 people randomized to CRT-D (n=215) or no upgrade (n=145). Average age was 73, and approximately 90% were men. Mean LVEF was 25% and symptoms were largely NYHA class II or III. Under 60% had an ischemic etiology, while over 50% had Afib.

Merkely emphasized the amount of Afib patients in the study. “There was always a question mark that CRT is working in atrial fibrillation or not, and this study is really nice and [demonstrates] that patients with chronic atrial fibrillation could have a benefit,” he said.

He nevertheless acknowledged that the trial studied CRT upgrades in high-volume, experienced centers providing optimal medical therapy, which may be of limited generalizability to other settings.

Linde also cautioned that the unblinded study had a long inclusion time over 7 years due to the COVID-19 pandemic and included too few women. There were also substantial crossovers and the loss of echocardiographic data typical of CRT studies, she said.

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