The Valley Hospital Enters into a Historic International Collaboration

Over the past two decades, The Valley Hospital, a 451-bed tertiary-care hospital located in Ridgewood, has gradually evolved into the leading provider of electrophysiology services in the state of New Jersey. Today, care is delivered in three electrophysiology laboratories that are fully equipped with the latest technology. In fact, Valley was the first facility in New Jersey to take possession of the Stereotaxis remote magnetic navigation system.

The group, which consists of six electrophysiologists, is the main provider of electrophysiology at Valley (Figure 1). Members of our group include Dr. Jonathan S. Steinberg (Director of the Arrhythmia Institute; Professor of Medicine at Columbia University), Dr. Suneet Mittal (Director of the Electrophysiology Laboratory; Associate Professor of Clinical Medicine at Columbia University), Dr. Mark Preminger (Director of the Implantable Devices Clinic; Clinical Associate Professor of Medicine at Columbia University), Dr. Aysha Arshad (Director of the Lead Extraction Program; Assistant Professor of Medicine at Columbia University), Dr. Dan Musat (Assistant Professor of Medicine at Columbia University), and Dr. Tina Sichrovsky (Assistant Professor of Medicine at Columbia University). The facility has become the “go-to” center for complex procedures such as atrial fibrillation and ventricular tachycardia ablation, epicardial ablation, and lead extraction of abandoned, dysfunctional, or infected leads in the region.

In September 2011, the Arrhythmia Institute was formally created at Valley. This reflected the recognition of the group’s national and international reputation in electrophysiology that has resulted in numerous presentations, original publications, and commitment to education (as reflected by leadership of several annual educational conferences and publication of multiple important texts in the electrophysiology field). It also reflects the long-term commitment on the part of the Valley Health System to evolve from a state-of-the-art clinical enterprise to one that also fosters cutting-edge research.

Shortly thereafter, in March 2012, the Valley EP group was invited by the Russian leadership of The State Research Institute of Circulation Pathology in Novosibirsk, Russia to develop a research collaborative agreement such that the Valley Arrhythmia Institute would help design clinical trials and analyze clinical trial data to facilitate scientific presentations at top international meetings and publication in the most competitive cardiovascular journals. This historic agreement, signed by Dr. Jonathan S. Steinberg on behalf of the Arrhythmia Institute at Valley and Dr. Evgeny Pokushalov (Deputy Director, Head of Arrhythmia Department and Electrophysiology Laboratory, State Research Institute of Circulation Pathology in Siberia), was poised to generate a robust and productive collaboration between leading arrhythmia centers that would have a meaningful impact on the diagnosis and treatment of a variety of arrhythmic disorders (Figure 2).

The Russian Institute is the largest cardiovascular institution in Europe. It is located in Novosibirsk, Russia’s third largest city and the cultural and industrial center of Siberia. It is an extremely modern and sophisticated health care facility at the cutting edge of clinical care and cardiovascular research. It receives the largest funding of all Russian hospitals and performs all varieties of cardiovascular services. Notably, it performs more than 4,000 cardiac surgeries and over 2,500 electrophysiology procedures per year.

Clinical Research

An initial result of our collaborative efforts has been the impending publication of a manuscript comparing pulmonary vein isolation (PVI) with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension in the Journal of the American College of Cardiology. It is well recognized that hypertension is an important risk factor for the development and maintenance of atrial fibrillation. Recently, renal artery denervation has been reported to significantly decrease blood pressure; furthermore, the effect appears to be sustained over at least the first three years. Thus, this study sought to assess the impact of renal artery denervation in patients with a history of antiarrhythmic drug-refractory atrial fibrillation and drug-resistant hypertension (systolic blood pressure >160 mmHg despite triple drug therapy) who were referred for PVI for definitive management of symptomatic atrial fibrillation. Patients were randomized to PVI only (n=14) or PVI with renal artery denervation (n=13). All patients were followed ≥1 year to assess maintenance of sinus rhythm and to impact on blood pressure.

Not surprisingly, no change in blood pressure was observed in those patients who underwent PVI alone. These patients showed a poor response to PVI in that only 4 of the 14 patients (29%) were free of atrial fibrillation at a year post ablation. In contrast, significant reduction in both systolic (from 181 ± 7 to 156 ± 5, p<0.001) and diastolic (from 97 ± 6 to 87 ± 4, p<0.001) blood pressure was observed in patients who underwent renal artery denervation. Importantly, 9 of these 13 patients (69%) remained free of atrial fibrillation at a year post ablation (p=0.033). These novel results, which will need to be confirmed in a larger study, may forever change the paradigm for the interventional management of patients with hypertension and atrial fibrillation.

Another important investigative collaboration is about to be launched. It is a study entitled, “Randomized Comparison of Catheter Ablation Versus Antiarrhythmic Drug Therapy in Patients with Recently Diagnosed Paroxysmal Atrial Fibrillation; Assessment by Continuous Implantable Monitor.” PVI has been used for more than a decade for the treatment of atrial fibrillation, and it has evolved to become the mainstay of interventional therapy for the elimination of atrial fibrillation. Both the Russian Institute and the Valley Arrhythmia Institute have been leading practitioners of this technique and have published extensively. The Russian Institute, indeed, has the world’s largest experience in implantable loop recording following catheter ablation of atrial fibrillation.

Atrial fibrillation treatment by catheter ablation has traditionally been reserved for patients who have failed antiarrhythmic drug therapy, and this is reflected in current guidelines. Catheter ablation is successful at eliminating all atrial fibrillation without the need for medical therapy in approximately 80% of patients, according to Valley’s published data. The novelty of this new clinical trial is the targeted patient population. Patients in this study will have recently diagnosed paroxysmal atrial fibrillation who are eligible to receive specific rhythm control therapy because of symptom burden but who are naive to antiarrhythmic drug treatment. Patients must have at least two AF episodes lasting more than one hour in duration over the four months proceeding enrollment, with ECG documentation of at least one episode. Patients will be randomized in a 2:1 fashion to catheter ablation or antiarrhythmic drug therapy. Those in the catheter ablation group will undergo standard PVI and those who are scheduled to receive antiarrhythmic drug therapy will have a suitable drug selected. The patients will be followed over approximately 18 months; their arrhythmia burden will be tracked by an implantable loop recorder (ILR). Complete absence of atrial fibrillation will be defined as an atrial fibrillation burden less than 0.5% as measured by the ILR. Anticipated enrollment is approximately 120 patients. This randomized multicenter clinical trial was reviewed enthusiastically and will be sponsored by Biosense Webster and Johnson & Johnson, both in the United States and in Russia.

Summary

The fruits of this unique international collaboration are already being experienced at both sites and in their respective electrophysiology communities. Remarkably, this collaboration has 16 projects that are about to be launched or in preparation. The groups will concentrate on a diverse range of investigations including atrial fibrillation ablation, follow up of ablation for atrial flutter, postoperative atrial fibrillation, and robotic epicardial left ventricular lead implantation for cardiac resynchronization therapy. The success of this relationship rests on the spirit of cooperation that all physician members have expressed, the commitment of their respective institutions, and the extreme zeal that these investigators have for serious and impactful clinical research.