Uday N. Kumar

Reduced ventricular volumes and improved systolic function with cardiac resynchronization therapy : A randomized trial comparing simultaneous biventricular pacing, sequential biventricular pacing, and left ventricular pacing

Background— Cardiac resynchronization therapy has emerged as an important therapy for advanced systolic heart failure. Among available cardiac resynchronization therapy pacing modes that restore ventricular synchrony, it is uncertain whether simultaneous biventricular (BiV), sequential BiV, or left ventricular (LV) pacing is superior. The Device Evaluation of CONTAK RENEWAL 2 and EASYTRAK 2: Assessment of Safety and Effectiveness in Heart Failure (DECREASE-HF) trial is the first randomized trial comparing these 3 cardiac resynchronization therapy modalities. Methods and Results— The DECREASE-HF Trial is a multicenter trial in which 306 patients with New York Heart Association class III or IV heart failure, an LV ejection fraction ≤35%, and a QRS duration ≥150 ms were randomized to simultaneous BiV, sequential BiV, or LV pacing. LV volumes and systolic and diastolic function were assessed with echocardiography at baseline, 3 months, and 6 months. All groups had a significant reduction in LV end-systolic and end-diastolic dimensions (P<0.001). The simultaneous BiV pacing group had the greatest reduction in LV end-systolic dimension (P=0.007). Stroke volume (P<0.001) and LV ejection fraction (P<0.001) improved in all groups with no difference across groups. Conclusions— Compared with LV pacing, simultaneous BiV pacing was associated with a trend toward greater improvement in LV size. There is little difference between simultaneous BiV pacing and sequential BiV pacing as programmed in this trial.

Diagnostic Utility of a Novel Leadless Arrhythmia Monitoring Device

Although extending the duration of ambulatory electrocardiographic monitoring beyond 24 to 48 hours can improve the detection of arrhythmias, lead-based (Holter) monitors might be limited by patient compliance and other factors. We, therefore, evaluated compliance, analyzable signal time, interval to arrhythmia detection, and diagnostic yield of the Zio Patch, a novel leadless, electrocardiographic monitoring device in 26,751 consecutive patients. The mean wear time was 7.6 ± 3.6 days, and the median analyzable time was 99% of the total wear time. Among the patients with detected arrhythmias (60.3% of all patients), 29.9% had their first arrhythmia and 51.1% had their first symptom-triggered arrhythmia occur after the initial 48-hour period. Compared with the first 48 hours of monitoring, the overall diagnostic yield was greater when data from the entire Zio Patch wear duration were included for any arrhythmia (62.2% vs 43.9%, p <0.0001) and for any symptomatic arrhythmia (9.7% vs 4.4%, p <0.0001). For paroxysmal atrial fibrillation (AF), the mean interval to the first detection of AF was inversely proportional to the total AF burden, with an increasing proportion occurring after 48 hours (11.2%, 10.5%, 20.8%, and 38.0% for an AF burden of 51% to 75%, 26% to 50%, 1% to 25%, and <1%, respectively). In conclusion, extended monitoring with the Zio Patch for ≤14 days is feasible, with high patient compliance, a high analyzable signal time, and an incremental diagnostic yield beyond 48 hours for all arrhythmia types. These findings could have significant implications for device selection, monitoring duration, and care pathways for arrhythmia evaluation and AF surveillance.

Frequency of Atrial Flutter After Adult Lung Transplantation

Lung transplantation, which involves an anastomosis of the graft to the native left atrium, may increase the risk of left-side atrial flutter (AFL). Our aim was to evaluate the incidence, predisposing conditions, and course of AFL after lung transplantation in adults. Two hundred sixty-nine consecutive patients who underwent lung transplantation were studied retrospectively. All patients received a preoperative echocardiogram and postoperative electrocardiographic monitoring. All 12-lead electrocardiograms were reviewed. Typical or atypical AFL was diagnosed by 2 independent reviewers based on accepted criteria. Predictors of AFL were investigated separately using univariate and multivariate logistic regression analyses. AFL occurred in 35 of 269 patients (13%) over a mean of 12 days after transplantation. All patients who developed AFL had no previous atrial arrhythmia. Of these 35 patients, 24 (68.6%) had atypical AFL by electrocardiographic criteria. In multivariate logistic regression analysis, patients with idiopathic pulmonary fibrosis (IPF) were 2.9 times more likely to have AFL than those patients with lung transplant without IPF (p = 0.009). Other independent risk factors for AFL were advanced age and preoperative left atrial enlargement. Only 3 of 35 patients (8.6%) with AFL had persistent atrial arrhythmia and needed electrophysiologic study and ablation. In conclusion, AFL is common soon after lung transplantation. Those with IPF, advanced age, or left atrial enlargement are at increased risk. In most cases, AFL is a self-limited arrhythmia that resolves spontaneously with no need for ablation.

Needs-Based Innovation in Cardiovascular Medicine: The Stanford Biodesign Process

Summary More than a decade ago, a formalized fellowship training program in medical device innovation, the first of its kind, was created at Stanford University. Now in its 15th year, the Stanford Biodesign Fellowship Program is a 10-month program whereby postgraduate students with a prior background in medicine, engineering, and/or business form interdisciplinary teams for an experiential process of identifying unmet clinical needs, inventing new solutions, and implementing these ideas (the 3 “I’s”). A key component of this structured process is focused attention on needs finding and characterization, which differs from the traditional “tech-push” model (i.e., technologies looking for problems to solve). Although the Stanford Biodesign process can be applied to a wide variety of clinical areas, cardiovascular medicine is particularly well suited, given the breadth of clinical presentations it touches and its history of innovation to solve important clinical problems. Physicians play a vital role in the process, especially for needs identification and characterization. This paper outlines the Stanford Biodesign process and presents an argument for its repeat applicability, discusses its relevance to physicians and to cardiologists in particular, and provides a case study of the process that resulted in a currently available cardiovascular medical technology that came directly from the Fellowship Program.

Proceedings from Heart Rhythm Society's emerging technologies forum, Boston, MA, May 12, 2015

Physicians are in an excellent position to significantly contribute to medical device innovation, but the process of bringing an idea to the bedside is complex. To begin to address these perceived barriers, the Heart Rhythm Society convened a forum of stakeholders in medical device innovation in conjunction with the 2015 Heart Rhythm Society Annual Scientific Sessions. The forum facilitated open discussion on medical device innovation, including obstacles to physician involvement and possible solutions. This report is based on the themes that emerged. First, physician innovators must take an organized approach to identifying unmet clinical needs and potential solutions. Second, extensive funds, usually secured through solicitation for investment, are often required to achieve meaningful progress, developing an idea into a device. Third, planning for regulatory requirements of the US Food and Drug Administration and Centers for Medicare & Medicaid Services is essential. In addition to these issues, intellectual property and overall trends in health care, including international markets, are critically relevant considerations for the physician innovator. Importantly, there are a number of ways in which professional societies can assist physician innovators to navigate the complex medical device innovation landscape, bring clinically meaningful devices to market more quickly, and ultimately improve patient care. These efforts include facilitating interaction between potential collaborators through scientific meetings and other gatherings; collecting, evaluating, and disseminating state-of-the-art scientific information; and representing the interests of members in interactions with regulators and policymakers.

Response to Letter Regarding Article, “Reduced Ventricular Volumes and Improved Systolic Function With Cardiac Resynchronization Therapy: A Randomized Trial Comparing Simultaneous Biventricular Pacing, Sequential Biventricular Pacing, and Left Ventricular Pacing”

We thank Drs Hamilton and Filardo for their interest in our work.1 In a prospective randomized trial in which the same patient is subjected to repeated measurements over time, missing data and repeated measures are known statistical problems for which it is difficult to account. As suggested by Drs Hamilton and Filardo, a longitudinal analysis is …

259 NOVEL SCINTIGRAPHIC PARAMETERS TO ASSESS LEFT VENTRICULAR DYSSYNCHRONY IN PATIENTS REQUIRING CARDIAC RESYNCHRONIZATION THERAPY.

Background The equilibrium radionuclide angiogram (ERNA) is an imaging method that can be used to assess left ventricular (LV) function and synchrony. Each pixel of an ERNA is defined by its phase (ø) and amplitude (Amp), which together define its vector; the Amp gives the vectors length. The vector sum of all Amps, based on the angular distribution of ø, divided by the scalar sum of the length of all the vectors defines a new parameter, synchrony (S). The degree of randomness or disorder in the LV based on the Shannon information measure normalized for the number of ø in the LV region defines another new parameter, entropy (E). With complete synchrony, S = 1 and E = 0; with complete dyssynchrony, S = 0 and E = 1. We evaluated S and E in patients requiring cardiac resynchronization therapy (CRT) to determine if these measures can be correlated with a clinical benefit from CRT. Methods We studied 14 patients (9 males, mean age 66 ± 15 years) with advanced congestive heart failure, LV ejection fraction (EF) ≤ 35% and QRS ≥ 120 ms. ERNA was performed before and within 10 weeks after CRT. Assessment of clinical status was made based on NYHA classification assessed before and within 10 weeks of CRT. Patients were graded 2 (n = 5), 1 (n = 5) or 0 (n = 4) if they improved 2, 1, or 0 NYHA classes, respectively. This was then correlated to changes in LVEF, SD ø, S, and E after CRT using a Pearson correlation. Results The patients classified 2 showed large improvements in S and E, less in SD of ø, and least in LVEF. S and E were best correlated with outcome and were strongest when combined (multiple R = .87). One patient classified 2 had improved S and E but not LVEF or SD ø. Most patients without clinical improvement, nonetheless, had an improved LVEF. Changes in LVEF or SD of ø could not differentiate among clinical groups. Conclusions S and E seem to measure different functional characteristics than LVEF. They show promise to be the best and most reproducibly correlated with functional status after CRT.

258 UTILITY OF EQUILIBRIUM RADIONUCLIDE ANGIOGRAMS TO GUIDE CORONARY SINUS LEAD PLACEMENT IN HEART FAILURE PATIENTS REQUIRING CARDIAC RESYNCHRONIZATION THERAPY.

Background In heart failure patients requiring cardiac resynchronization therapy (CRT), there is no reliable method to determine the optimal site to place the coronary sinus (CS) lead. The equilibrium radionuclide angiogram (ERNA) provides an assessment of left ventricular function and the location of dyssynchrony. We compared using the findings from ERNA to guide CS lead placement with the traditional method of placing the CS lead in a lateral CS branch to determine whether ERNA-guided placement improved response to CRT. Methods We obtained ERNA studies on 14 patients with NYHA Class III and IV heart failure referred for CRT device implantation or upgrade from a right-ventricular device. Each pixel of an ERNA is defined by its phase (ø) and amplitude (Amp), which together define its vector; the Amp gives the vectors length. The vector sum of all Amps, based on the angular distribution of ø, divided by the scalar sum of the length of all the vectors defines a new parameter, synchrony (S). With complete synchrony, S = 1, and with complete dyssynchrony, S = 0. Using ERNA studies obtained before and after CRT, we evaluated S, ejection fraction (EF), and NYHA Class at both times. Results 3 out of 6 patients who underwent traditional CS lead placement did not show any improvement in NYHA class (50%). 7 of the 8 patients who had ERNA-guided CS lead placement had an improvement in NYHA class (88%). More patients in the ERNA-guided group had clinical improvement as compared to the traditional group (p = .02 by chi-square analysis). One patient in the ERNA-guided group did not benefit since the location where the CS lead had been placed showed nonviable tissue by a subsequent PET scan. The degree of change in S also significantly predicted the clinical response to CRT. Conclusions In heart failure patients requiring CRT, ERNA is a novel method that can be used to assess dyssynchrony and guide CS lead placement. The use of this method resulted in significant improvements in NYHA class and S but not in EF. Given these findings, this is a novel technique that warrants further study.