Person: Singh, Jagmeet
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Singh
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Jagmeet
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Singh, Jagmeet
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Publication Characteristics of Responders to Cardiac Resynchronization Therapy: The Impact of Echocardiographic Left Ventricular Volume(Wiley-Blackwell, 2012) Park, Mi Young; Altman, Robert K.; Orencole, Mary; Kumar, Prabhat; Parks, Kimberly; Heist, Kevin E.; Singh, Jagmeet; Picard, MichaelBackground: One third of patients who receive cardiac resynchronization therapy (CRT) are classified as nonresponders. Characteristics of responders to CRT have been studied in multiple clinical trials. Hypothesis: We aimed to examine characteristics of CRT responders in a routine clinical practice. Method: One hundred and twenty five patients were examined retrospectively from a multidisciplinary CRT clinic program. Echocardiographic CRT response was defined as a decrease in left ventricular (LV) end systolic volume (ESV) of ≥ 15% and/or absolute increase of 5% in LV ejection fraction (EF) at 6 month visit. Results: There were 81 responders and 44 nonresponders. By univariate analyses, female gender, nonischemic cardiomyopathy etiology, baseline QRS duration, the presence of left bundle branch block (LBBB) and left ventricular end-diastolic volume (LVEDV) index predicted CRT response. However, multivariate analysis demonstrated only QRS duration, LBBB and LVEDV index were independent predictors (QRS width: Odd ratio [OR] 1.027, 95% CI 1.004 – 1.050, p = 0.023; LBBB: OR 3.568, 95% CI 1.284 – 9.910, p=0.015; LV EDV index: OR 0.970, 95% CI 0.953 – 0.987, p= 0.001). While female gender and nonischemic etiology were associated with an improved CRT response on univariate analyses, after adjusting for LV volumes, they were not independent predictors. Conclusion: QRS width, LBBB and LVEDV index are independent predictors for echocardiographic CRT response. Previously reported differences in CRT response for gender and cardiomyopathy etiology are associated with differences in baseline LV volumes in our clinical practice.Publication A Novel Method to Capture the Onset of Dynamic Electrocardiographic Ischemic Changes and its Implications to Arrhythmia Susceptibility(Blackwell Publishing Ltd, 2014) Sayadi, Omid; Puppala, Dheeraj; Ishaque, Nosheen; Doddamani, Rajiv; Merchant, Faisal M.; Barrett, Conor; Singh, Jagmeet; Heist, E. Kevin; Mela, Theofanie; Martínez, Juan Pablo; Laguna, Pablo; Armoundas, AntonisBackground: This study investigates the hypothesis that morphologic analysis of intracardiac electrograms provides a sensitive approach to detect acute myocardial infarction or myocardial infarction‐induced arrhythmia susceptibility. Large proportions of irreversible myocardial injury and fatal ventricular tachyarrhythmias occur in the first hour after coronary occlusion; therefore, early detection of acute myocardial infarction may improve clinical outcomes. Methods and Results: We developed a method that uses the wavelet transform to delineate electrocardiographic signals, and we have devised an index to quantify the ischemia‐induced changes in these signals. We recorded body‐surface and intracardiac electrograms at baseline and following myocardial infarction in 24 swine. Statistically significant ischemia‐induced changes after the initiation of occlusion compared with baseline were detectable within 30 seconds in intracardiac left ventricle (P<0.0016) and right ventricle–coronary sinus (P<0.0011) leads, 60 seconds in coronary sinus leads (P<0.0002), 90 seconds in right ventricle leads (P<0.0020), and 360 seconds in body‐surface electrocardiographic signals (P<0.0022). Intracardiac leads exhibited a higher probability of detecting ischemia‐induced changes than body‐surface leads (P<0.0381), and the right ventricle–coronary sinus configuration provided the highest sensitivity (96%). The 24‐hour ECG recordings showed that the ischemic index is statistically significantly increased compared with baseline in lead I, aVR, and all precordial leads (P<0.0388). Finally, we showed that the ischemic index in intracardiac electrograms is significantly increased preceding ventricular tachyarrhythmic events (P<0.0360). Conclusions: We present a novel method that is capable of detecting ischemia‐induced changes in intracardiac electrograms as early as 30 seconds following myocardial infarction or as early as 12 minutes preceding tachyarrhythmic events.Publication Usefulness of Hemoglobin A1c to Predict Outcome After Cardiac Resynchronization Therapy in Patients With Diabetes Mellitus and Heart Failure(Elsevier BV, 2012) Shah, Ravi; Altman, Robert K.; Park, Mi Young; Zilinski, Jodi; Leyton-Mange, Jordan Stewart; Orencole, Mary; Picard, Michael; Barrett, Conor D.; Heist, Edwin; Upadhyay, Gaurav; Das, Ranendra; Singh, Jagmeet; Das, SaumyaPatients with diabetes and heart failure (HF) have worse clinical outcomes compared to patients with HF without diabetes after cardiac resynchronization therapy (CRT). Patients with HF and diabetes represent a growing population at high risk for cardiovascular events and are increasingly treated with CRT. Although patients with diabetes and HF appear to benefit from CRT, their clinical outcomes are worse than those of patients without diabetes after CRT. The aim of this study was to identify clinical predictors that explain the differential hazard in patients with diabetes. We studied 442 patients (169 with diabetes) with systolic HF referred to the Massachusetts General Hospital CRT clinic from 2003 to 2010 to identify predictors of outcomes after CRT in patients with HF and diabetes. Patients with diabetes were more likely to have ischemic causes of HF than those without diabetes, but there was no difference in the left ventricular ejection fraction or HF classification at implantation. Patients with diabetes had poorer event-free survival (death or HF hospitalization) compared to those without diabetes (log-rank p = 0.04). The presence of diabetes was the most important independent predictor of differential outcomes in the entire population (hazard ratio 1.65, 95% confidence interval 1.10 to 2.51). Patients with diabetes receiving insulin therapy had poorer survival, whereas those not receiving insulin therapy had similar survival to patients without diabetes. Patients with peri-implantation glycosylated hemoglobin >7% had worse outcomes, whereas patients with glycosylated hemoglobin ≤7% had improved survival (hazard ratio 0.36, 95% confidence interval 0.15 to 0.86) equivalent to that of patients without diabetes. In conclusion, although the presence of diabetes, independent of other variables, increases the hazard of worse outcomes after CRT, there is additional risk conferred by insulin use and suboptimal peri-implantation glycemic control.Publication Mechanism of Decrease in Mitral Regurgitation After Cardiac Resynchronization Therapy: Optimization of the Force-Balance Relationship(Ovid Technologies (Wolters Kluwer Health), 2009) Solis, J.; McCarty, D.; Levine, Robert; Handschumacher, M. D.; Fernandez-Friera, L.; Chen-Tournoux, A.; Mont, L.; Vidal, Barbara; Singh, Jagmeet; Brugada, J.; Picard, Michael; Sitges, M.; Hung, JudyBackground: Cardiac resynchronization therapy (CRT) has been shown to reduce functional mitral regurgitation (MR). It has been proposed that the mechanism of MR reduction relates to geometric change or, alternatively, changes in left ventricular (LV) contractile function. Normal mitral valve (MV) function relies on a balance between tethering and closing forces on the MV leaflets. Functional MR results from a derangement of this force–balance relationship, and CRT may be an important modulator of MV function by its ability to enhance the force–balance relationship on the MV. We hypothesized that CRT improves the comprehensive force balance acting on the valve, including favorable changes in both geometry and LV contractile function. Methods and Results: We examined the effect of CRT on 34 patients with functional MR before and after CRT (209±81 days). MR regurgitant volume, closing forces on MV (derived from Doppler transmitral pressure gradients), including dP/dt and a factor (closing pressure ratio) expressing how long the peak closing gradient is maintained over systole (closing pressure ratio=velocity time integral/MR peak velocity×mitral regurgitation time), and dyssynchrony by tissue Doppler were measured. End-diastolic volume, end-systolic volume, mitral valve annular area (MAA) and contraction (percent change in MAA from end-diastole to midsystole), leaflet closing area (leaflet area during valve closure), and tenting volume (volume under leaflets to annular plane) were measured by 3D echocardiography. After CRT, end-diastolic volume (253±111 versus 221±110 mL, P<0.001) and end-systolic volume (206±97 versus 167±91 mL, P<0.001) decreased and ejection fraction (19±6 versus 27±9%, P<0.001) increased. MR regurgitant volume decreased from 35±17 to 23±14 mL (P<0.001), MAA from 11.6±3.5 to 10.5±3.1 cm2 (P<0.001), leaflet closing area from 15.4±5 to 13.7±3.8 cm2 (P<0.001), and tenting volume from 5.7±2.6 to 4.6±2.2 mL (P<0.001). Peak velocity (and therefore transmitral closing pressure) was more sustained throughout systole, as reflected by the increase in the closing pressure ratio (0.77±0.1 versus 0.84±0.1 before CRT versus after CRT, P=0.01); dP/dt also improved after CRT. There was no change in dyssynchrony or MAA contraction. Conclusions: Reduction in MR after CRT is associated with favorable changes in MV geometry and closing forces on the MV. It does so by favorably affecting the force balance acting on the MV in 2 ways: reducing tethering through reversal of LV remodeling and increasing the systolic duration of peak transmitral closing pressures.Publication Predictors of Sustained Ventricular Arrhythmias in Cardiac Resynchronization Therapy(Ovid Technologies (Wolters Kluwer Health), 2012) Friedman, D. J.; Altman, R. K.; Orencole, M.; Picard, Michael; Ruskin, Jeremy; Singh, Jagmeet; Heist, EdwinBackground: Patients undergoing cardiac resynchronization therapy (CRT) are at high risk for ventricular arrhythmias and risk stratification in this population remains poor. Methods and Results: This study followed 269 patients (LVEF < 35%, QRS > 120ms, NYHA III/IV) undergoing CRT with defibrillator (CRT-D) for 553±464 days after CRT-D implantation to assess for independent predictors of appropriate device therapy for ventricular arrhythmias (VAs). Baseline medication use, medical comorbidities, and echocardiographic parameters were considered. The 4-year incidence of appropriate device therapy was 36%. A Cox proportional hazard model identified left ventricular end systolic diameter (LVESD) > 61mm as an independent predictor in the entire population (HR 2.66, p = 0.001). Those with LVESD > 61mm had a 51% 3-year incidence of VA compared to a 26% incidence among those with a less dilated ventricle (p = 0.001). Among patients with LVESD ≤61mm, multivariate predictors of appropriate therapy were absence of beta-blocker therapy (HR 6.34, p<0.001, LVEF < 20% (HR 4.22, p <0.001), and history of sustained VA (2.97, p = 0.013). Early (<180d after implant) shock therapy was found to be a robust predictor of heart failure hospitalization (HR 3.41, p < 0.004) and mortality (HR 5.16 p < 0.001.) Conclusions: Among CRT-D patients, LVESD > 61mm is powerful predictor of ventricular arrhythmias and further risk stratification of those with less dilated ventricles can be achieved based on assessment of EF, history of sustained VA, and absence of beta-blocker therapy.Publication Contractility sensor-guided optimization of cardiac resynchronization therapy: results from the RESPOND-CRT trial(Oxford University Press, 2016) Brugada, Josep; Delnoy, Peter Paul; Brachmann, Johannes; Reynolds, Dwight; Padeletti, Luigi; Noelker, Georg; Kantipudi, Charan; Rubin Lopez, José Manuel; Dichtl, Wolfgang; Borri-Brunetto, Alberto; Verhees, Luc; Ritter, Philippe; Singh, JagmeetAims Although cardiac resynchronization therapy (CRT) is effective in patients with systolic heart failure (HF) and a wide QRS interval, a substantial proportion of patients remain non-responsive. The SonR contractility sensor embedded in the right atrial lead enables individualized automatic optimization of the atrioventricular (AV) and interventricular (VV) timings. The RESPOND-CRT study investigated the safety and efficacy of the contractility sensor system in HF patients undergoing CRT. Methods and results RESPOND-CRT was a prospective, randomized, double-blinded, multicentre, non-inferiority trial. Patients were randomized (2:1, respectively) to receive weekly, automatic CRT optimization with SonR vs. an Echo-guided optimization of AV and VV timings. The primary efficacy endpoint was the rate of clinical responders (patients alive, without adjudicated HF-related events, with improvement in New York Heart Association class or quality of life), at 12 months. The study randomized 998 patients. Responder rates were 75.0% in the SonR arm and 70.4% in the Echo arm (mean difference, 4.6%; 95% CI, −1.4% to 10.6%; P < 0.001 for non-inferiority margin −10.0%) (Table 2). At an overall mean follow-up of 548 ± 190 days SonR was associated with a 35% risk reduction in HF hospitalization (hazard ratio, 0.65; 95% CI, 0.46–0.92; log-rank P = 0.01). Conclusion: Automatic AV and VV optimization using the contractility sensor was safe and as effective as Echo-guided AV and VV optimization in increasing response to CRT. ClinicalTrials.gov number NCT01534234Publication Erratum to ‘2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing’ [Journal of Arrhythmia 32/1 (2016) 1–28](Elsevier, 2016) Wilkoff, Bruce L.; Fauchier, Laurent; Stiles, Martin K.; Morillo, Carlos A.; Al-Khatib, Sana M.; Almendral, Jesœs; Aguinaga, Luis; Berger, Ronald D.; Cuesta, Alejandro; Daubert, James P.; Dubner, Sergio; Ellenbogen, Kenneth A.; Mark Estes, N.A.; Fenelon, Guilherme; Garcia, Fermin C.; Gasparini, Maurizio; Haines, David E.; Healey, Jeff S.; Hurtwitz, Jodie L.; Keegan, Roberto; Kolb, Christof; Kuck, Karl-Heinz; Marinskis, Germanas; Martinelli, Martino; McGuire, Mark; Molina, Luis G.; Okumura, Ken; Proclemer, Alessandro; Russo, Andrea M.; Singh, Jagmeet; Swerdlow, Charles D.; Teo, Wee Siong; Uribe, William; Viskin, Sami; Wang, Chun-Chieh; Zhang, ShuPublication 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing☆☆☆(Elsevier, 2016) Wilkoff, Bruce L.; Fauchier, Laurent; Stiles, Martin K.; Morillo, Carlos A.; Al-Khatib, Sana M.; Almendral, Jesœs; Aguinaga, Luis; Berger, Ronald D.; Cuesta, Alejandro; Daubert, James P.; Dubner, Sergio; Ellenbogen, Kenneth A.; Estes, N.A. Mark; Fenelon, Guilherme; Garcia, Fermin C.; Gasparini, Maurizio; Haines, David E.; Healey, Jeff S.; Hurtwitz, Jodie L.; Keegan, Roberto; Kolb, Christof; Kuck, Karl-Heinz; Marinskis, Germanas; Martinelli, Martino; McGuire, Mark; Molina, Luis G.; Okumura, Ken; Proclemer, Alessandro; Russo, Andrea M.; Singh, Jagmeet; Swerdlow, Charles D.; Teo, Wee Siong; Uribe, William; Viskin, Sami; Wang, Chun-Chieh; Zhang, ShuPublication Recent Trends in Imaging for Atrial Fibrillation Ablation(Indian Heart Rhythm Society, 2010) Kabra, Rajesh; Singh, JagmeetCatheter ablation provides an important treatment option for patients with both paroxysmal and persistent atrial fibrillation. It mainly involves pulmonary vein isolation and additional ablations in the left atrium in persistent cases. There have been significant advancements in this procedure to enhance the safety and effectiveness. One of them is the evolution of various imaging modalities to facilitate better visualization of the complex left atrial anatomy and the pulmonary veins in order to deliver the lesions accurately. In this article, we review the electroanatomic mapping systems including the magnetic-based and impedence-based systems. Each of these mapping systems has its own advantages and disadvantages. In addition, we also discuss the role of intracardiac echocardiography and three dimensional rotational angiography in atrial fibrillation ablation.