The data from the PAVE study indicates potential benefits of cardiac resynchronization therapy (CRT) in non-heart failure patient populations, while the data from the DINAMIT study showed no overall mortality benefit of implantable cardioverter defibrillator (ICD) therapy in patients following a recent acute myocardial infarction (heart attack).
PAVE is the first large-scale, prospectively randomized study to evaluate Biventricular (BV) pacing vs. standard Right Ventricular (RV)-only pacing in patients undergoing ablate and pace therapy for atrial fibrillation (AF). The study found that:
- In patients with chronic AF treated with AV nodal ablation (targeted destruction of the AV node, the heart tissue that conducts the electrical impulse from the atria to the ventricles), biventricular pacing produced a statistically significant improvement in cardiac function over standard right-ventricular pacing as measured by the six minute walk test.
- In these same patients, biventricular pacing also produced a statistically significant improvement in functional capacity over standard right-ventricular pacing as measured by peak VO2 and exercise duration.
- BV-paced patients experienced fewer deaths during the trial than RV-paced patients.
Based on these results, the PAVE study suggests that BV pacing should be the preferred mode of pacing therapy in patients with chronic AF undergoing AV nodal ablation.
"The objective of the PAVE trial was to prospectively compare the effect of BV pacing versus RV pacing in patients undergoing ablate and pace therapy," said Rahul Doshi, M.D., Cardiovascular Consultants of Nevada, Las Vegas, Nevada, the leading enroller of patients in the study. "Our results show a significant benefit of BV pacing over RV pacing in exercise and functional capacity for patients with chronic AF and AV nodal ablation."
A previous St. Jude Medical-sponsored trial, DAVID (Dual Chamber And VVI Implantable Defibrillator), demonstrated the potential detrimental effects of active RV pacing in patients with low ejection fractions who received ICD therapy. The PAVE study looked at the potential benefits of pacemaker-based CRT therapy in a patient population required to receive ventricular pacing, and reinforces the conclusions from DAVID that RV pacing in patients with left-ventricular dysfunction may be detrimental.
"Presentation of the PAVE results is yet another milestone in St. Jude Medical's longstanding effort to surround the atrial fibrillation comorbidity with innovative and effective device solutions," said Eric N. Falkenberg, Senior Vice President of Research & Emerging Indications of St. Jude Medical's Cardiac Rhythm Management business.
Data from the PAVE study have been submitted to the U.S. Food and Drug Administration (FDA) in support of a pre-market approval (PMA) application for the St. Jude Medical Frontier™CRT system in post-AV nodal ablation cases. St. Jude Medical reaffirms its previous guidance that it expects FDA approval of this system by the May 2004 NASPE/Heart Rhythm Society meeting.
There were about 37,000 ablate and pace procedures for AF in the United States in 2003. Health Research International predicts an annual growth rate of 18%, with an estimated 63,000 procedures annually by 2006.
DINAMIT was a prospective randomized trial to assess ICD therapy for prevention of death in high-risk patients early after acute myocardial infarction (AMI). Inclusion criteria for the study included a heart attack within six to 40 days, a left ventricular ejection fraction (LVEF) of =35%, and signs of impaired cardiac autonomic modulation (i.e. depressed standard deviation of sinus RR intervals {=70 ms} or elevated heart rate {mean RR interval =750 ms}), and an age range of 18-80 years.
The DINAMIT study found that, in this patient population:
- ICD therapy did not decrease all-cause mortality.
- ICD therapy did significantly decrease arrhythmic mortality.
The study concluded, based on these findings, that ICD therapy is not beneficial in patients with a recent myocardial infarction, even if they have risk factors for arrhythmic death. Other therapeutic strategies need to be identified and investigated to reduce non-arrhythmic mortality in this patient cohort.
"The DINAMIT study showed that ICD therapy can significantly reduce the risk of sudden death in patients with a recent myocardial infarction who are at high risk of arrhythmic death due to extensive myocardial scarring and autonomic imbalance, but that this does not result in reduction in total mortality," said Stefan H. Hohnloser, M.D., Professor of Medicine, J.W. Goethe University, Frankfurt, Germany, one of the study's principal investigators.
"ICD therapy did not prove to be beneficial in patients early after acute myocardial infarction," said Stuart J. Connolly, M.D., Professor of Medicine, McMaster University, Hamilton, Ontario, Canada, also a principal investigator in the study. "This is most likely because their burden of myocardial ischemia puts them at risk of cardiac-related mortality from causes other than sudden cardiac death."
Previous large-scale clinical trials of patients with ischemic heart disease, low ejection fractions and a history of AMI demonstrated that this patient group will experience decreased mortality when ICD therapy is utilized. These clinical trials have generally focused on patients whose AMI event occurred greater than 6 months prior to their ICD implant. The DINAMIT results demonstrate that the overall mortality benefits of ICD therapy in a post-AMI patient population do not extend to those who receive an ICD shortly after their AMI event, as other causes of death offset the observed decrease in arrhythmic mortality.
Further analysis of the data from these studies will attempt to find evidence of other factors which lead to the differences in non-arrhythmic deaths.
ICDs are medical devices implanted under the skin that are designed to deliver a range of electrical therapies, from mild stimulation to more powerful shocks, to treat patients with ventricular tachycardia (VT) and ventricular fibrillation (VF). These potentially lethal heart rhythms commonly contribute to sudden cardiac death (SCD), a condition that kills over 400,000 Americans each year.
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