Supporting Evidence for a Common Practice: BUDAPEST CRT

John M. Mandrola, MD


August 27, 2023

It's dangerous in medicine to make decisions based solely on what makes intuitive sense. At the European Society of Cardiology (ESC) Congress 2023, we learned from the BUDAPEST CRT trial that the common practice of upgrading patients with pacing-induced heart failure to cardiac resynchronization therapy (CRT) works quite well. We got lucky.

As I age, I've come to love the purity and elegance of pacemakers. A pacemaker completely reverses a life-ending disease—in a 45-minute procedure, done mostly with local anesthetic. Think Lazarus.

But. While a right-ventricular paced beat is better than no beat, a standard pacing lead activates the right ventricle (RV) first, then the left ventricle (LV). The delay in RV-LV contraction creates a mechanical dyssynchrony, which can lead to severe cardiomyopathy in 10% to 20% of cases. Essentially, standard RV pacing causes a left bundle-branch–type contraction pattern, and that can lead to typical heart failure with reduced ejection fraction (HFrEF).

BUDAPEST CRT investigators set out to study the benefits and risks of upgrading these patients to a CRT-defibrillator (CRT-D). The idea here is twofold: CRT is electrical therapy for the RV-LV dyssynchrony, and the defibrillator is prevention against death from ventricular arrhythmia.

Strong evidence supports the use of CRT-D in de novo implants, but there was little support for CRT-D during upgrades. Benefit was not a given because these are likely older patients (with more competing risks) and an upgrade procedure is more complex than a new implant.


BUDAPEST CRT investigators have been exemplary in their communication, publishing a rationale/design and baseline characteristics paper as well as a full report.

Over a 7-year period, they randomly assigned 360 patients who had symptomatic HFrEF and a pacemaker or implantable cardioverter-defibrillator (ICD) that paced the RV more than 20% of the time to either a CRT-D upgrade or an ICD. Atrial fibrillation was present in most patients in both groups; this is different from the seminal trials, which studied CRT use mostly during sinus rhythm.

The operative procedures varied and depended both on the assigned strategy and underlying hardware. For instance, a CRT-D upgrade could be as simple as adding a single LV lead if the original device was a dual-chamber ICD, or as complicated as adding three new leads (right atrium, RV, and LV leads) plus extraction of the existing RV lead if the original device was a single-chamber pacemaker.

The average age of enrolled patients was 73 years, 86% of patients were male, and the median LV ejection fraction was 25%. Baseline medical therapy was excellent, and the actual percentage RV pacing was quite high at 85%.

The primary endpoint was a composite of all-cause death, hospitalizations due to heart failure, and a less than 15% decrease in LV end-systolic volume. Authors based this mixed clinical and echocardiographic endpoint on the BLOCK HF trial.

The Results

For every three patients randomly assigned to CRT-D, two were assigned to ICD. After 1 year of follow-up, a primary outcome occurred in 32% of patients in the CRT-D arm vs 79% in the ICD arm (odds ratio, 0.11; 95% CI, 0.06 - 0.19; P < .001).

The key secondary outcome of all-cause mortality and hospitalization for heart failure occurred in 10% of the CRT-D arm vs 32% in the ICD arm (HR, 0.27; 95% CI, 0.16 - 0.47; P < .001).

In the CRT-D arm, 3.4% of patients died without a previous hospitalization for heart failure vs 4.7% in the ICD arm (HR, 0.52; 95% CI, 0.23 - 1.16; P = .110).

Overall death occurred in 5.6% vs 11% of the CRT-D vs ICD arms.

Procedure- or device-related complications occurred in 12.3% of the CRT-D arm vs 7.8% of the ICD arm. Previous leads were extracted in 15% vs 11% of the CRT-D and ICD arms, respectively.

The rate of serious ventricular arrhythmia was much lower in the CRT-D arm (0.5% vs 14.5% for ICD).


An 89% lower odds of a primary endpoint qualifies as a huge effect size. That should always induce concern.

In this case, however, I do not find it worrisome. BUDAPEST CRT enrolled extremely ill patients with symptomatic HFrEF, low ejection fraction, and an entirely correctable substrate. CRT therapy has very rapid effects on cardiac function. These benefits would be expected to improve echo parameters and reduce hospitalization for heart failure.

That said, this trial comes with limitations. It took 7 years to complete enrollment, suggesting that these are highly selected patients. That is important for translation. I would not apply these results to patients with mild or asymptomatic LV dysfunction due to RV pacing. What's more, the BUDAPEST CRT patients were well managed medically, so I would not consider upgrade to CRT a substitute for proper medical therapy for HFrEF.

Another weakness involved the choice to upgrade to a CRT device with a defibrillator vs a CRT with a pacemaker (CRT-P) alone. The authors made this reasonable choice because guidelines favor defibrillator implant for patients with symptomatic heart failure.

I would argue that a CRT-P arm may have performed equally well, perhaps with fewer complications.

I see pacing-induced cardiomyopathy as a correctable form of heart failure. Once you resynchronize the ventricles with biventricular pacing, systolic function not only improves, it often normalizes. Now the patient no longer has heart failure and thus no longer has an indication for an ICD. Supporting this view is the authors' observation that only one patient in the CRT-D arm had a ventricular arrhythmia. Another advantage of a CRT-P arm would be a major simplification of the upgrade procedure—because ICD upgrades require a specific defibrillator lead.

Another hope I have is that pacing-induced cardiomyopathy will become increasingly rare. Conduction system pacing, which I do in nearly all standard pacemaker implantation procedures, promises to pace the RV and LV without dyssynchrony. I purposely chose the words hope and promises because we need more empirical evidence with conduction system pacing.

In sum, the BUDAPEST CRT trial gives us strong evidence for correcting pacing-induced cardiomyopathy. It is reassuring to have evidentiary support for a common practice.

The authors have shown the field of electrophysiology a way forward. We need more studies like this. Next up should be a BUDAPEST-type study of ICD generator changes.

John Mandrola practices cardiac electrophysiology in Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. 

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