Failed Trial PRomPTs Questions About Role of Peri-Infarct Pacing for Remodeling of Large MIs


LONDON, England—In what could signal the death knell for peri-infarct zone pacing as a way to attenuate further remodeling in patients with large MIs, data from the PRomPT trial indicates that pacing—whether biventricular or LV only—is ineffective. The study was presented August 30, 2015, at the European Society of Cardiology Congress and simultaneously published online ahead of print in the European Heart Journal.

The Debate: Failed Trial PRomPTs Questions About Role of Peri-Infarct Pacing for Remodeling of Large MIsGregg W. Stone, MD, of Columbia University Medical Center (New York, NY), and colleagues examined the ability of peri-infarct pacing via a cardiac resynchronization therapy-defibrillator device to prevent adverse post-MI remodeling in the multicenter PRomPT trial. Principal inclusion criteria included a first STEMI within 10 days of onset and peak creatine phosphokinase > 3,000 U/L (or peak troponin T >10 mcg/L, if peak creatine phosphokinase value was not available).

Between December 2010 and October 2013, 126 patients from 27 centers in Europe, the Middle East and the United States were randomized to 1 of 3 arms:

  • Biventricular pacing (LV and RV; n = 41)
  • Single-site pacing (LV only; n = 40)
  • Control (no pacing; n = 45)

Baseline features were well matched between groups with the exception that control patients were slightly younger than those assigned to pacing. Most patients (96.7%) underwent PCI, but procedures were performed relatively late (mean, 8.1 ± 10.2 hours after symptom onset).

Patients were followed up at 1, 3, 6, 12, and 18 months and assessed by a variety of measures including NYHA classification, Minnesota Living with HF and European Quality of Life-5 Dimensions questionnaires, transthoracic echocardiography, and 6-minute walk test.

No Support for Pacing

At 18 months, change in LV end-diastolic volume from baseline (primary endpoint) was similar between the control and pooled pacing groups (133.9 mL vs 122.8 mL; P = .92). Changes in LV end-systolic volume and ejection fraction over time also were similar, with no differences between the single and dual pacing groups or between each individual pacing group and controls. 

Additionally, there were no differences in QoL between the pacing and control groups at 18 months. While pacing patients walked slightly longer on the 6-minute walk test than did control subjects, the difference was not significant (P = 0.45). NYHA class improved slightly in both groups, but with no substantial difference between groups (P = .67).

Rates of death or hospitalization for heart failure were fairly high, with freedom from death or hospitalization of 82.6% in the pooled pacing groups and 78.3% in the control group (P = .59). 

No Smoking Gun

Dr. Stone noted that the study was not powered to assess most secondary endpoints or to compare outcomes between the individual pacing groups. However, despite referring to the results of PRomPT as “neutral,” Dr. Stone said it would be premature to “exclude a possible benefit in some subgroups for which the trial was underpowered to detect.”

But discussant Frank Ruschitzka, MD, of University Hospital Zurich (Zurich, Switzerland), called the idea of pacing infarct tissue “quirky, crazy.” History of this type of therapy in heart failure patients is fraught with poor outcomes, he said. The EchoCRT trial, for example, showed an excess of mortality in the device group.  

“We do need this… quirky ‘outside the box’ thinking,” Dr. Ruschitzka said. But while signals from pilot studies are often worth pursuing, the MENDMI trial had already shown prior to PRomPT that there was no “smoking gun” for pacing in remodeling. Further, he dismissed the idea of benefit in PRomPT subgroups considering that it was underpowered. “[T]his will be the end of peri-infarct pacing,” Dr. Ruschitzka predicted, although he said there is still an unmet need for a means of preventing remodeling.

Replying to the critiques, Dr. Stone said that MENDMI “did have trends in patients with large infarcts” and showed improvement in regional wall motion. PRomPT, he noted, was an attempt to overcome some limitations of MENDMI; the more recent trial changed where the leads were placed, for instance.

Dr. Stone agreed, however, that the lack of a signal in PRomPT, “pretty much puts this concept to rest.”  

Note: Dr. Stone is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.



Source: 
Stone GW, Chung ES, Stancak B, et al. Peri-infarct zone pacing to prevent adverse left ventricular remodelling in patients with large myocardial infarction. Eur Heart J. 2015;Epub ahead of print.

Disclosures:

  • Dr. Stone reports receiving personal fees from AstraZeneca ,Atrium, Boston Scientific, Eli Lilly-Daiichi Sankyo partnership, InspireMD, Miracor, Osprey, TherOx, and Velomedix.

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