Cardiac resynchronisation therapy upgrade is less favourable than de novo implantations

Mate Vamos

Results from a large multicentre observational study have shown that patients undergoing cardiac resynchronisation therapy (CRT) upgrade had worse clinical response and long-term survival compared with de novo implantations.

“The number of upgrade procedures from single- or dual-chamber devices to CRT is increasing. However, there is only weak scientific evidence about the outcomes of patients undergoing upgrade procedures compared with de novo CRT implantations,” argue Mate Vamos (J.W. Goethe University, Frankfurt, Germany) and others in their multicentre study recently published in Circulation: Arrhythmia and Electrophysiology.

In the latest European pacemaker and CRT guidelines (2013), upgrade procedures from conventional pacemakers or ICDs to CRT are given a class I, level of evidence B, for heart failure patients with a New York Heart Association (NYHA) functional class of III to ambulatory IV, left ventricular ejection fraction (LVEF) ≤35%, and a high percentage of ventricular pacing. Additionally, the European heart failure guidelines (2016) restrict the indication for upgrade to CRT as a class IIb, level of evidence B, and do not indicate upgrade for patients with stable heart failure or with a QRS duration of <130ms.

Given the lack of evidence, Vamos et al set out to evaluate clinical response and long-term survival in a large cohort of consecutive patients receiving either de novo (n=375 patients) or upgrade to CRT-D (n=177 patients) at three implant centres in Germany and Hungary.

De novo CRT implantation was considered for patients on optimised medical treatment with heart failure of NYHA functional class from II to IV, LVEF of ≤35%, and QRS width of >120ms. Patients in the upgrade group were more often implanted for secondary prevention, suffered more often from atrial fibrillation, chronic kidney disease with a lower estimated glomerular filtration rate, diabetes mellitus, dyslipidaemia and had more often a non-LBBB wide QRS complex and a lower LVEF.

The authors defined clinical response as an improvement by at least one NYHA functional class. After six-month follow-up, data were available in 96% of patients. Vamos et al found that 57% of patients in the upgrade group responded to CRT by improving their NYHA functional status by at least one class compared with 69% of patients in the de novo group (p=0.008). This lower response rate among upgrade patients, note the authors, remained statistically significant in a multivariate logistic regression analysis (p=0.021). Additionally, the improvement of LVEF and the decrease of left ventricular end-diastolic diameter (LVEDD) at six months were higher in the de novo group compared to the upgrade patients (∆EF 6.7±9.4 vs. 2.9±9, p<0.001; ∆LVEDD -3.5±6.7 vs. 0.0±12.2, p=0.003).

Regarding mortality, the authors found that during a mean follow-up of 37 months, survival was significantly worse among patients undergoing upgrade CRT-D procedures compared with de novo implantations (hazard ratio [HR] 1.65; 95% confidence interval [CI], 1.22‒2.24). After adjustment for important baseline variables with multivariate Cox regression analysis and propensity score matching, the researchers noted that all-cause mortality continued to be higher in the upgrade group (adjusted HR, 1.68; 95% CI, 1.20‒2.34; propensity-adjusted HR, 1.79; 95% CI, 1.08–2.95).

“To the best of our knowledge, this is one of the largest observational studies demonstrating worse outcomes in patients undergoing a CRT upgrade compared to de novo CRT-D implantation,” write Vamos et al. “In our series, patients in the upgrade group had more advanced heart disease and more comorbidities, which could explain the observed worse outcome,” the authors note. However, to account for these differences they explain they carefully adjusted the data for these baseline differences, including propensity score matching and the adjusted findings were consistent with the initial results.

Other factors include, according to Vamos et al, that resynchronisation therapy “may have been initiated too late” in patients who were upgraded from conventional pacemaker/ICD systems. “It is conceivable that these patients were further advanced in their disease process and hence CRT had less chance to modify the risk for bad outcomes,” they argue. Moreover, the authors comment that CRT upgrade procedures may be associated with greater surgical risk than de novo procedures.

“These findings warrant confirmation in prospective randomised trials, such as the ongoing BUDAPEST-CRT Upgrade Study,” ( number, NCT02270840) suggest the authors. “Until these results become available, our observations need to be considered when counselling individual patients on the need for a CRT upgrade.”