The major trials that established cardiac resynchronization therapy (CRT) as a treatment for heart failure (HF) with reduced ejection fraction (HFrEF) tended not to include patients who already had pacemakers, so evidence supporting their upgrade to CRT is fairly thin.
Now, a new randomized trial suggests clinical and reverse-remodeling benefits after upgrade to a defibrillating CRT device (CRT-D) in a select group of HFrEF patients with non-CRT pacemakers or dedicated defibrillator (ICD) devices.
The international BUDAPEST-CRT study entered 360 such patients with wide QRS complexes and a considerable burden, at least 20%, of right ventricular (RV) pacing.
Their HF was thought to be caused or exacerbated by a high burden of RV pacing, long known to promote ventricular dyssynchrony and worsen left ventricular (LV) function.
The patients were upgraded to a CRT-D device with the CRT function turned either on (full CRT-D function) or off (ICD capability without biventricular pacing).
A year later, the 215 assigned to CRT-D, compared to the 145 in the ICD group, showed an 89% drop (P < .001) in risk for the trial's primary endpoint, an eclectic composite all-cause mortality, HF hospitalization, or less than a 15% decline in LV end-systolic volume.
Risk for death from any cause or HF-related hospitalization in the CRT-D group fell by a significant 73%.
The findings suggest that in practice, patients with HFrEF and a pacing device should be followed closely, and those with "intermittent or permanent" RV pacing should be offered a CRT-D upgrade "without postponing the procedure to a later date to avoid or reduce the risk of further adverse events," said BUDAPEST-CRT principal investigator Béla Merkely, MD, in a presentation August 26 at the European Society of Cardiology (ESC) Congress 2023, held in Amsterdam, the Netherlands.
Merkely, of Semmelweis University Hearth and Vascular Center, Budapest, Hungary, is also lead author of the same-day publication in the European Heart Journal.
"Highly Convincing"
More than half the trial's patients had atrial fibrillation (AF), Merkely observed, and were among a range of prospectively defined subgroups that appeared to benefit from CRT-D about as much as the overall study population.
The finding is noteworthy because "whether CRT works in atrial fibrillation was always a question mark," he noted. The major trials mostly excluded patients with AF, which was thought to cut into the potential benefit from device therapy.
"In my opinion, we have highly convincing outcome results in favor of CRT in the BUDAPEST-CRT upgrade study," Cecilia Linde MD, PhD, Karolinska Institutet, Stockholm, Sweden, said as invited discussant following Merkely's presentation.
"The impressive results of the BUDAPEST-CRT upgrade study are likely to influence future guidelines and clinical practice," Linde states in an editorial accompanying the trial's publication.
"The study clearly shows that upgrading to CRT is associated with improved outcome," she writes. "The results have implications for the organization of pacemaker and ICD follow-up to detect LV deterioration before HF develops and enable upgrading to CRT." Patients who show deterioration in LV function "should be upgraded to CRT without postponement."
"Home Run"
In practice, potential benefits of CRT-D upgrade must be weighed against its risks, not the least of which is the possibility of causing infection when switching in the new device and implanting leads. Its pronounced benefit in BUDAPEST-CRT and the trial's entry requirement of at least 20% RV pacing may alter the risk-benefit equation for some patients.
Even with the 20% or more RV pacing, "mortality and heart failure hospitalizations were independently reduced. That's a home run," Roderick Tung, MD, University of Arizona College of Medicine, Phoenix, who was not involved in the trial, told theheart.org | Medscape Cardiology. "I'm actually surprised by how robust it was."
Practice has varied on how much RV pacing is considered a significant risk for ventricular dyssynchrony, observed Tung, an electrophysiologist and director of cardiovascular clinical research at his center.
A burden of 40% or higher, for example, has sometimes been taken as the critical threshold, based in large part on the DAVID trial, which was published 21 years ago. Heart failure patients with less than 40% RV pacing, he noted, had been thought less vulnerable.
But one lesson from BUDAPEST-CRT, Tung said, may be that "we need to be reducing the threshold, based on historical data, from 40% to 20%."
Wide QRS Intervals Required
Entry criteria, beyond HFrEF and RV pacing, included an LV ejection fraction 35% or lower, prior implantation with a non-CRT pacemaker or ICD, and a paced QRS interval of at least 150 ms — all on optimal HF medical therapy.
The trial randomly assigned 360 such patients in a 3 to 2 ratio to CRT-D upgrade or to receive or be maintained on an ICD. Those in the latter group who already had an ICD either kept their device without having a procedure or were given a CRT-D device with the CRT function deactivated, the report notes.
All patients who received a CRT-D device, regardless of their randomization, received a full complement of leads. Ultimately, about 19% of patients in the ICD group crossed over to CRT-D, accomplished by activation of their device's CRT function.
By intention-to-treat, however, 32.4% and 78.9% of the CRT-D and ICD groups, respectively, met the primary outcome over a median of 12.4 months, for an odds ratio (OR) of 0.11 (95% CI, 0.06 – 0.19; P < .001).
Rates for death from any cause or HF hospitalization were 10% for CRT-D and 32% for ICD, for a hazard ratio (HR) 0.27 (95% CI, 0.16 – 0.47; P < .001). The difference appeared to be driven by HF hospitalizations, HR 0.24 (95% CI, 0.13 – 0.43; P < .001).
Mean LV end-diastolic volume at 12 months was 39 mL lower in the CRT-D compared to ICD group, and their mean LV ejection fraction was almost 10 percentage points higher (P < .001 for both differences).
Only one patient in the CRT-D group, that is 0.5%, developed a major ventricular arrhythmia, compared to 14.5% of the ICD group, Merkely reported.
"This is a population that has not gotten a lot of attention," Tung said about HF patients with substantial RV pacing. One of the study's contributions is its demonstration that pacing-induced or pacing-exacerbated cardiomyopathy "is very real. That's an important message to the community. "
Merkely discloses holding research contracts with Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, CSL Behring, Daiichi-Sankyo, Duke Clinical Research Institute, Eli Lilly, Medtronic, Novartis, Terumo, and Vifor Pharma; and consulting, receiving royalties from, or holding ownership or equity interest in Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, CSL Behring, Daiichi-Sankyo, Duke Clinical Research Institute, Medtronic, and Novartis. Linde discloses receiving honoraria for speaking from AstraZeneca, Bayer, Novartis, Vifor, Medtronic, Abbott, Boehringer Ingelheim, and Impulse Dynamics. Tung has previously disclosed receiving fees for speaking or serving on an advisory board for Abbott, Biotronik, Boston Scientific, and Medtronic; and receiving research grant support from Abbott.
European Society of Cardiology (ESC) Congress 2023: Hot Line 2. Presented August 26, 2023.
Eur Heart J. Published online August 26, 2023. Full text, Editorial
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Cite this: Impact of RV Pacing in Heart Failure, CRT Benefit Shown in BUDAPEST-CRT - Medscape - Aug 31, 2023.
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