Wait no more – HFrEF patients with high RV pacing burden from pacemakers or defibrillators should be promptly upgraded to CRT devices: insights from the BUDAPEST-CRT Upgrade Study

By Enrico Ferro on

Key Points:

  • A high burden of right ventricular pacing among patients with heart failure patients with reduced ejection fraction is known to cause left ventricular dyssynchrony and progressive dysfunction, yet definitive evidence has been lacking to inform the timing of upgrade to CRT devices.
  • The BUDAPEST-CRT Upgrade Study randomized 360 patients with LVEF ≤ 35%, NYHA functional classes II–IVa, paced QRS ≥ 150 ms, and RV pacing burden ≥ 20% to either CRT-D (n=215) or traditional ICD (n=145). The primary endpoint was a composite of all-cause mortality, a first HHF event, or <15% reduction in LVESV at 12 months.
  • This trial showed a significant reduction in the primary composite endpoint (32.4% in the CRT-D arm versus 78.9% in the ICD arm, aOR = 0.11, 95% CI 0.06-0.19, p-value <0.001), as well as in several individual secondary endpoints. Taken together, these findings support the clinical practice to promptly pursue CRT upgrade among HFrEF patients with intermittent or permanent RV pacing.


Over 30% of patients who receive dual chamber pacemakers or defibrillators may develop left ventricular dysfunction due to high-burden right ventricular pacing and resulting dyssynchrony, which in turn fuels a vicious cycle of heart failure hospitalizations and other adverse clinical outcomes. Over the last 10 years, there have been multiple changes in US and EU guidelines on the value of CRT upgrade in this patient population, due to the lack of definitive evidence from randomized clinical trial that can inform clinical practice.

During the 2023 European Society of Cardiology Conference in Amsterdam, Dr. Bela Merkely presented the results of the  BUDAPEST-CRT Upgrade Study (NCT02270840). This was a prospective, randomized, investigator-sponsored clinical trial that randomized (in a 3:2 ratio) a total of 360 patients from 17 sites in 7 countries to either CRT-D (n=215) or traditional ICD (n=145). The key inclusion criteria were: patients with LVEF ≤ 35%, NYHA functional classes II–IVa, paced QRS ≥ 150 ms, and RV pacing burden ≥ 20%. The primary study outcome was a composite of all-cause mortality, a first HHF event, or <15% reduction in LVESV at 12 months.

The mean age of the study population was 72.8 years, with 11.1% patients of female sex. During a median follow-up time of , the primary outcome occurred in 32.4% of patients in the CRT-D arm, and 78.9% of patients in the ICD arm, generating an aOR of 0.11 with 95% CI 0.06-0.19, p-value <0.001. The benefit of upgrade to CRT-D was found to be homogeneous across all pre-specified subgroups, including patients with ischemic cardiomyopathy, CKD and, most notably, patients with atrial fibrillation – for whom the benefit of CRT therapy has been questioned in the past. The secondary endpoint (composite of mortality and HHF) was also found to be significantly reduced in the CRT-D arm (aOR 0.28, p<0.001), as well as left ventricular remodeling as evidenced by significant improvement in both LVESV and LVEDV, as well as a 10% increase in LVEF, in the CRT-D arm. Notably, the incidence of ventricular arrythmias was also significantly lower in the CRT-D arm (0.5%) compared to the ICD arm (14.5% ), perhaps due to the aforementioned ventricular remodeling. While there was no significant reduction in all-cause mortality in the CRT-D arm, this study was not powered to investigate this specific endpoint.

As commented by Dr. Merkely during the presentation of the trial results, “HFrEF patients with a pacemaker or ICD should be carefully followed in clinical practice, because in the subset of patients who develop significant RV pacing requirements, a CRT-D upgrade should be performed immediately to reduce the risk of left ventricular remodeling and heart failure hospitalizations.”