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A 53-year-old man with a subcutaneous implantable cardioverter-defibrillator (S-ICD) presented with inappropriate shocks. He underwent device extraction, and the lead was freed using a rotating mechanical dilator sheath. As patients with S-ICDs get older, extractions will become more complicated and more common. We have described a novel method of S-ICD lead extraction. (Level of Difficulty: Advanced.), Central Illustration

Background: Lead dislodgement (LD) has been one of the most common early complications after cardiovascular implantable electronic device implant. However, limited data are available on the clinical characteristics and long-term outcomes of LD events. The aim of this study was to examine the risk factors, clinical significance, and management strategies of LD events after cardiovascular implantable electronic device implant. Methods: This study was a retrospective cohort analysis of 20 683 patients who underwent cardiovascular implantable electronic device implant between January 1, 2010 and January 31, 2020 in Medtronic’s Product Surveillance Registry, with a mean follow-up time of 3.3±2.5 SD years. The study population was divided into 2 groups: group A with LD events (N=350) and group B without LD events (N=20 333). Results: During this period, 350 patients (1.69%) had LD events involving 371 leads (0.95%), among a total of 39 060 leads implanted. Passive fixation type (right atrium pacing lead, P =0.041), lower sensing amplitude (right ventricle defibrillating lead, P =0.020), and lower lead impedance at implant (right atrium pacing lead, P =0.009) were associated with increased LD risk. Multivariate analysis showed female sex (hazard ratio, 1.520, P =0.008) and higher body mass index (hazard ratio, 1.012, P =0.001) were independently associated with increased risk of LD events. LD events were not associated with significant changes in the long-term risks of cardiac and overall mortality. In group A, repositioning the dislodged leads increased the risk of a second LD event compared with implanting new leads ( P =0.012). Conclusions: Female sex and higher body mass index were associated with higher risk of LD events in the Product Surveillance Registry. Among patients with dislodged leads, implanting new leads was associated with lower risk of future LD events. Further studies on how to reduce LD risk and to improve management of these events are needed. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01524276.

Objectives A prospective, multicenter study was performed to assess the safety and efficacy of the Durata and Optisure HV leads and the Ellipse VR implantable cardioverter-defibrillator (ICD) (St. Jude Medical, Sylmar, California) in a 1.5-T magnetic resonance imaging (MRI) environment. The primary safety objective was >90% freedom from MRI scan-related complications. The primary efficacy objectives were absence of change in capture threshold and absence of decrease of sensing amplitude from pre-MRI examination to 1 month after MRI. Background MRI scanning of patients has been shown to be safe in patients with magnetic resonance-conditional implantable cardioverter-defibrillators (ICD) systems. Methods Patients with a previously implanted magnetic resonance-conditional system underwent a nondiagnostic MRI scan. After the scan, a questionnaire was given to investigators and patients who returned for 1-month follow-up examination. A subset of patients underwent ventricular tachyarrhythmia or ventricular fibrillation (VT/VF) induction testing after the MRI to evaluate defibrillation function. Results There were 220 patients (81% male; 62.1 ± 11.2 years of age) enrolled who received an MRI scans from 29 centers. All primary safety and efficacy endpoints were met (p Conclusions The MRI Ready MRI-conditional ICD system is safe, and electrical performance was not affected in patients receiving a 1.5-T whole-body MRI scan. Investigators reported favorable collaboration between cardiologists and radiologists in the MRI Ready IDE clinical trial. (A Clinical Evaluation of the Durata or Optisure High Voltage Leads and Ellipse VR ICD Undergoing MRI, an IDE Study [MRI Ready IDE]; NCT02787291)

Introduction: The most common complication of alcohol septal ablation (ASA) is periprocedural high grade AV block (HGAVB). No long-term follow-up of cardiovascular implantable electronic device (CIED) utilization after ASA has been reported. Hypothesis: Pacemaker dependence on long-term follow up can be predicted by ECG or procedural characteristics. Methods: We analyzed all patients with hypertrophic cardiomyopathy who underwent ASA from December 1998 to December 2019 at our institution and received their first CIED within 30 days after ASA for HGAVB. All available follow-up interrogations were reviewed. CIED dependence was defined as ventricular pacing of ≥5%. CIED programming was determined by the patients’ cardiologists' discretion. Results: A total of 103 patients with hypertrophic cardiomyopathy underwent ASA. The average follow up duration was 10.1 years. Within 30 days after ASA, a total 25 patients received a CIED for HGAVB. On long term follow-up 16 patients (64%) were found to be CIED-dependent. Baseline characteristics, including pre and post-ASA ECG, were not significantly different between dependent and non-dependent patients (Table). The only predictor for CIED dependence was >1 ml of alcohol injected during ASA (OR 6.0, p Conclusions: CIED implantation after ASA is common. Almost two thirds of patients who received CIED for postprocedural HGAVB were CIED-dependent on long term follow up. CIED dependence can be predicted by amount of injected alcohol >1 ml during ASA.

Background In an era of “big data,” computationally efficient and privacy-aware solutions for large-scale machine learning problems become crucial, especially in the healthcare domain, where large amounts of data are stored in different locations and owned by different entities. Past research has been focused on centralized algorithms, which assume the existence of a central data repository (database) which stores and can process the data from all participants. Such an architecture, however, can be impractical when data are not centrally located, it does not scale well to very large datasets, and introduces single-point of failure risks which could compromise the integrity and privacy of the data. Given scores of data widely spread across hospitals/individuals, a decentralized computationally scalable methodology is very much in need. Objective We aim at solving a binary supervised classification problem to predict hospitalizations for cardiac events using a distributed algorithm. We seek to develop a general decentralized optimization framework enabling multiple data holders to collaborate and converge to a common predictive model, without explicitly exchanging raw data. Methods We focus on the soft-margin l1-regularized sparse Support Vector Machine (sSVM) classifier. We develop an iterative cluster Primal Dual Splitting (cPDS) algorithm for solving the large-scale sSVM problem in a decentralized fashion. Such a distributed learning scheme is relevant for multi-institutional collaborations or peer-to-peer applications, allowing the data holders to collaborate, while keeping every participant's data private. Results We test cPDS on the problem of predicting hospitalizations due to heart diseases within a calendar year based on information in the patients Electronic Health Records prior to that year. cPDS converges faster than centralized methods at the cost of some communication between agents. It also converges faster and with less communication overhead compared to an alternative distributed algorithm. In both cases, it achieves similar prediction accuracy measured by the Area Under the Receiver Operating Characteristic Curve (AUC) of the classifier. We extract important features discovered by the algorithm that are predictive of future hospitalizations, thus providing a way to interpret the classification results and inform prevention efforts.

Infections after placement of cardiac implantable electronic devices (CIEDs) are associated with substantial morbidity and mortality. There is limited evidence on prophylactic strategies, other than the use of preoperative antibiotics, to prevent such infections.We conducted a randomized, controlled clinical trial to assess the safety and efficacy of an absorbable, antibiotic-eluting envelope in reducing the incidence of infection associated with CIED implantations. Patients who were undergoing a CIED pocket revision, generator replacement, or system upgrade or an initial implantation of a cardiac resynchronization therapy defibrillator were randomly assigned, in a 1:1 ratio, to receive the envelope or not. Standard-of-care strategies to prevent infection were used in all patients. The primary end point was infection resulting in system extraction or revision, long-term antibiotic therapy with infection recurrence, or death, within 12 months after the CIED implantation procedure. The secondary end point for safety was procedure-related or system-related complications within 12 months.A total of 6983 patients underwent randomization: 3495 to the envelope group and 3488 to the control group. The primary end point occurred in 25 patients in the envelope group and 42 patients in the control group (12-month Kaplan-Meier estimated event rate, 0.7% and 1.2%, respectively; hazard ratio, 0.60; 95% confidence interval [CI], 0.36 to 0.98; P = 0.04). The safety end point occurred in 201 patients in the envelope group and 236 patients in the control group (12-month Kaplan-Meier estimated event rate, 6.0% and 6.9%, respectively; hazard ratio, 0.87; 95% CI, 0.72 to 1.06; P0.001 for noninferiority). The mean (±SD) duration of follow-up was 20.7±8.5 months. Major CIED-related infections through the entire follow-up period occurred in 32 patients in the envelope group and 51 patients in the control group (hazard ratio, 0.63; 95% CI, 0.40 to 0.98).Adjunctive use of an antibacterial envelope resulted in a significantly lower incidence of major CIED infections than standard-of-care infection-prevention strategies alone, without a higher incidence of complications. (Funded by Medtronic; WRAP-IT ClinicalTrials.gov number, NCT02277990.).

Aims Lead perforation is a rare, well-known complication of cardiac implantable electronic device (CIED) implants, whose management is mostly not evidence-based. Main management strategies include conservative approach based on clinical and lead function follow-up vs. routine invasive lead revision approach. This study compared the complications of both strategies by composite endpoint, including recurrent perforation-related symptoms, recurrent pericardial effusion (PEf), lead dysfunction, and device infection during 12 month follow-up. Methods and results Multicentre retrospective analysis, inquiring data from imaging studies, device interrogation, pericardiocentesis, and clinical charts of patients with suspected perforating leads between 2007 and 2014 in five hospitals. All cases were reviewed by electrophysiologist and defined as definite perforations by suggestive symptoms along with lead perforation on imaging, bloody PEf on pericardiocentesis shortly after implant, or right ventricular (RV) lead non-capture along with diaphragmatic stimulation upon bipolar pacing. Clinical outcomes associated with both management approaches were compared, with respect to the composite endpoint. The study included 48 definitive perforation cases: 22 managed conservatively and 26 via lead revision. Conservative management was associated with an increased composite endpoint compared with lead revision (8/22 vs. 1/26; P = 0.007). The dominant complication among the conservative cohort was appearance of cardiac tamponade during follow-up; 5/6 occurring in cases which presented with no or only mild PEf and were treated by antiplatelets/coagulants during or shortly after CIED implantation. Conclusion A conservative management of CIED lead perforation is associated with increased complications compared with early lead revision. Lead revision may be the preferred management particularly in patients receiving antiplatelets/coagulants.

A prospective, multicenter study was performed to assess the safety and efficacy of the Durata and Optisure HV leads and the Ellipse VR implantable cardioverter-defibrillator (ICD) (St. Jude Medical, Sylmar, California) in a 1.5-T magnetic resonance imaging (MRI) environment. The primary safety objective was90% freedom from MRI scan-related complications. The primary efficacy objectives were absence of change in capture threshold and absence of decrease of sensing amplitude from pre-MRI examination to 1 month after MRI.MRI scanning of patients has been shown to be safe in patients with magnetic resonance-conditional implantable cardioverter-defibrillators (ICD) systems.Patients with a previously implanted magnetic resonance-conditional system underwent a nondiagnostic MRI scan. After the scan, a questionnaire was given to investigators and patients who returned for 1-month follow-up examination. A subset of patients underwent ventricular tachyarrhythmia or ventricular fibrillation (VT/VF) induction testing after the MRI to evaluate defibrillation function.There were 220 patients (81% male; 62.1 ± 11.2 years of age) enrolled who received an MRI scans from 29 centers. All primary safety and efficacy endpoints were met (p 0.0001). No significant detection delays were found in 34 patients who had VT/VF episodes after the MRI scan was performed. Most physicians reported easy and acceptable programming and ease of MRI scheduling.The MRI Ready MRI-conditional ICD system is safe, and electrical performance was not affected in patients receiving a 1.5-T whole-body MRI scan. Investigators reported favorable collaboration between cardiologists and radiologists in the MRI Ready IDE clinical trial. (A Clinical Evaluation of the Durata or Optisure High Voltage Leads and Ellipse VR ICD Undergoing MRI, an IDE Study [MRI Ready IDE]; NCT02787291).

This editorial refers to ‘Early performance of a miniaturized leadless cardiac pacemaker: the Micra Transcatheter Pacing Study’, by P. Ritter et al ., doi:10.1093/eurheartj/ehv214. If at first the idea is not absurd, then there will be no hope for it.A. Einstein Since the first permanent pacemaker implant, almost 60 years ago, there has been continued progress and evolution of these devices. The technology has advanced on many fronts, with longer battery lives, smaller sized generators, with an intelligent ‘adaptive functionality’ closely mimicking the human physiology. However, contemporary implant technology has been disadvantaged by the need for a subcutaneous implantable device (with a risk for infection or erosion) and an attached pacing electrode system within the cardiac vasculature that itself is at risk for fracture and infection. The additional hazard of extracting malfunctioning or infected leads poses further challenges. Notably, almost 10% of the ∼700 000 pacemakers implanted annually worldwide are associated with lead-related problems.1,2 This, in turn, has created the need for a leadless pacemaker system. Although Spickler et al . first reported the theory of a totally self-contained leadless intracardiac pacemaker in 1970,3 it is only through recent technological advancements in battery energy, endocardial fixation, and delivery systems that this concept has become a reality. The leadless device not only has improved the aesthetics of an implant through eliminating the visible lump and scar of a conventional pectoral pacemaker implant but also has potentially reduced the risk of complications, related to infections and lead …

Background— T-wave alternans (TWA) has been implicated in the pathogenesis of ventricular arrhythmias and sudden cardiac death. However, to estimate and suppress TWA effectively, the phase of TWA must be accurately determined. Methods and Results— We developed a method that computes the beat-by-beat integral of the T-wave morphology, over time points within the T-wave with positive alternans. Then, we estimated the signed derivative of the T-wave integral sequence, which allows the classification of each beat to a binary phase index. In animal studies, we found that this method was able to accurately identify the T-wave phase in artificially induced alternans ( P P P P score ), to suppress TWA. Finally, we demonstrated that using the phase of TWA we can suppress spontaneous TWA during acute ischemia; 77.6% for alternans voltage ( P score ( P Conclusions— We developed a method to quantify the temporal variability of the TWA phase. This method is expected to enhance the utility of TWA in predicting ventricular arrhythmias and sudden cardiac death and raises the possibility of using upstream therapies to abort a ventricular tachyarrhythmia before its onset.

The incidence of spontaneous coronary artery dissection (SCAD), defined as nontraumatic, noniatrogenic, and nonatherosclerotic separation of the coronary artery wall, is rising with increasing awareness and advances in diagnostics. Optimal management of SCAD patients remains unclear because

Background— Electric alternans is a pattern of variation in the shape of ECG waveform that occurs every other beat. In humans, alternation in ventricular repolarization, known as repolarization alternans (RA), has been associated with increased vulnerability to ventricular tachycardia/fibrillation and sudden cardiac death. Methods and Results— This study investigates the spatio-temporal variability of intracardiac RA and its relationship to body surface RA in an acute myocardial ischemia model in swine. We developed a real-time multichannel repolarization signal acquisition, display, and analysis system to record ECG signals from catheters in the right ventricle, coronary sinus, left ventricle, and epicardial surface before and after circumflex coronary artery balloon occlusion. We found that RA is detectable within 4 minutes after the onset ischemia and is most prominently seen during the first half of the repolarization interval. Ischemia-induced RA was detectable on unipolar and bipolar leads (both in near- and far-field configurations) and on body surface leads. Far-field bipolar intracardiac leads were more sensitive for RA detection than body surface leads, with the probability of body surface RA detection increasing as the number of intracardiac leads detecting RA increased, approaching 100% when at least three intracardiac leads detected RA. We developed a novel, clinically applicable intracardiac lead system based on a triangular arrangement of leads spanning the right ventricular and coronary sinus catheters, which provided the highest sensitivity for intracardiac RA detection when compared with any other far-field bipolar sensing configurations. Conclusions— In conclusion, intracardiac alternans, a complex spatio-temporal phenomenon associated with arrhythmia susceptibility and sudden cardiac death, can be reliably detected through a novel triangular right ventricular–coronary sinus lead configuration.

Indications for catheter ablation of atrial fibrillation (AF) have expanded to include increasingly complex cases, such as long-standing persistent AF and structural heart disease. Although pulmonary vein isolation remains essential for most ablation procedures, the role of substrate modification has taken on increasing importance. Despite the various ablation strategies available, single-procedure efficacy remains suboptimal among patients with structural heart disease or long-standing persistent AF, where recurrence rates may exceed 50% after a single procedure. These high rates of AF recurrence support the notion that currently available procedural end points are ineffective in identifying which patients are most likely to benefit from substrate modification and defining when that substrate has been sufficiently modified such that additional ablation is unnecessary. In order to improve outcomes, the next generation of procedural end points should seek to define specific properties of the underlying atrial electrical substrate and characterize the impact of catheter ablation on those electrophysiologic properties. The use of substrate-driven end points would be a major step in the process of moving from empiric ablation lesions to a customized ablation strategy based on atrial physiology. In this article, we review current approaches to catheter ablation of AF and discuss specific procedural end points as they pertain to each ablation strategy. We also provide a paradigm for the future development of novel substrate-driven procedural end points.

Background— It is common practice to empirically limit the radiofrequency (RF) power when ablating the posterior left atrium during atrial fibrillation ablation to avoid thermal injury to the esophagus. The objective of this study was to determine whether RF energy delivery limited by luminal esophageal temperature (LET) monitoring is associated with a reduction in esophageal injury compared with a strategy of RF power limitation alone. Methods and Results— Eighty-one consecutive patients who underwent atrial fibrillation ablation followed by esophageal endoscopy were included in this observational study. All patients underwent extraostial electric pulmonary vein isolation by using an electroanatomic mapping system and irrigated RF ablation. All RF applications on the posterior left atrium were limited to 35 W. A commercially available, single-thermocouple esophageal probe was used to monitor LET in a subset of patients (n=67). In these cases, applications were promptly interrupted when LET was ≥38.5�C; further applications were performed at reduced power to obtain a LET P Conclusions— These data suggest that LET monitoring may be associated with a reduction in esophageal injury compared with power limitation alone.

Background— Atrial tachycardia (AT) that develops after ablation of atrial fibrillation often poses a more difficult clinical situation than the index arrhythmia. This study details the use of an impedance-based electroanatomic mapping system (Ensite NavX) in concert with a specialized multielectrode mapping catheter for rapid, high-density atrial mapping. In this study, this activation mapping was combined with entrainment mapping to eliminate ATs developing late after atrial fibrillation ablation. Methods and Results— All study patients developed AT after ablation for atrial fibrillation. The approach to AT ablation consisted of 4 steps: use of a 20-pole penta-array catheter to map the chamber rapidly during the rhythm of interest, analysis of the patterns of atrial activation to identify wave fronts of electric propagation, targeted entrainment at putative channels, and catheter ablation at these “isthmuses.” All ablations were performed with irrigated radiofrequency ablation catheters. Forty-one ATs were identified in 17 patients (2.4�1.6 ATs per patient). Using the multielectrode catheter in conjunction with the Ensite NavX system, we created activation maps of 33 of 41 ATs (81%) (mean cycle length, 284�71 seconds) with a mean of 365�108 points per map and an average mapping time of 8�3 minutes. Of the 33 mapped ATs, 7 terminated either spontaneously or during entrainment maneuvers. Radiofrequency energy was used to attempt ablation of 26 ATs; 25 of 26 of the ATs (96%) were terminated successfully by ablation or catheter pressure. Conclusions— This study demonstrates a strategy for rapidly defining and eliminating the scar-related ATs typically encountered after ablation of atrial fibrillation.

Background— The present study examines the safety and feasibility of using a remote magnetic navigation system to perform endocardial and epicardial substrate-based mapping and radiofrequency ablation in patients with scar-related ventricular tachycardia (VT). Methods and Results— Using the magnetic navigation system, we performed 27 procedures on 24 consecutive patients with a history of VT related to myocardial infarction, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, or sarcoidosis. Electroanatomic mapping of the left ventricular, right ventricular, and ventricular epicardial surfaces was constructed in 24, 10, and 12 patients, respectively. Complete-chamber VT activation maps were created in 4 patients. A total of 77 VTs were inducible, of which 21 were targeted during VT with the remotely navigated radiofrequency ablation catheter alone. With a combination of entrainment and activation mapping, 17 of 21 VTs (81%) were successfully terminated in a mean of 8.4±8.2 seconds; for the remainder, irrigated radiofrequency ablation was necessary. The mean fluoroscopy times for endocardial and epicardial mapping were 27±23 seconds (range, 0 to 105 seconds) and 18±18 seconds (range, 0 to 49 seconds), respectively. In concert with a manually navigated irrigated ablation catheter, 75 of 77 VTs (97%) were ultimately ablated. Four patients underwent a second procedure for recurrent VT, 3 with the magnetic navigation system. After 1.2 procedures per patient, VT did not recur during a mean follow-up of 7±3 months (range, 2 to 12 months). Conclusions— The present study demonstrates the safety and feasibility of remote catheter navigation to perform substrate mapping of scar-related VT in a wide range of disease states with a minimal amount of fluoroscopy exposure.

Aims Permanent cardiac pacing is the only effective treatment for symptomatic bradycardia, but complications associated with conventional transvenous pacing systems are commonly related to the pacing lead and pocket. We describe the early performance of a novel self-contained miniaturized pacemaker. Methods and results Patients having Class I or II indication for VVI pacing underwent implantation of a Micra transcatheter pacing system, from the femoral vein and fixated in the right ventricle using four protractible nitinol tines. Prespecified objectives were >85% freedom from unanticipated serious adverse device events (safety) and

The ProMRI Study is a multicenter prospective, single arm, non-randomized study to evaluate the clinical safety of the Biotronik ProMRI Pacemaker System in patients (Pts) undergoing cardiac or thoracic spine 1.5T MRI scanning. Pts with an Entovis (DR-T or SR-T) and Setrox 53cm or 60cm lead(s) were

International audience; AIMS: For patients undergoing cardiac resynchronization therapy (CRT) with implantable cardioverter-defibrillator (ICD; CRT-D), the effect of an improvement in left ventricular ejection fraction (LVEF) on appropriate ICD therapy may have significant implications regarding management at the time of ICD generator replacement. METHODS AND RESULTS: We conducted a meta-analysis to determine the effect of LVEF recovery following CRT on the incidence of appropriate ICD therapy. A search of multiple electronic databases identified 709 reports, of which 6 retrospective cohort studies were included (n = 1740). In patients with post-CRT LVEF ≥35% (study n = 4), the pooled estimated rate of ICD therapy (5.5/100 person-years) was significantly lower than patients with post-CRT LVEF \textless35% [incidence rate difference (IRD): -6.5/100 person-years, 95% confidence interval (95% CI): -8.8 to -4.2, P \textless 0.001]. Similarly, patients with post-CRT LVEF ≥45% (study n = 4) demonstrated lower estimated rates of ICD therapy (2.3/100 person-years) compared with patients without such recovery (IRD: -5.8/100 person-years, 95% CI: -7.6 to -4.0, P \textless 0.001). Restricting analysis to studies discounting ICD therapies during LVEF recovery (study n = 3), patients with LVEF recovery (≥35 or ≥45%) had significantly lower rates of ICD therapy compared with patients without such recovery (P for both \textless0.001). Patients with primary prevention indication for ICD, regardless of LVEF recovery definition, had very low rates of ICD therapy (0.4 to 0.8/100-person years). CONCLUSION: Recovery of LVEF post-CRT is associated with significantly reduced appropriate ICD therapy. Patients with improvement of LVEF ≥45% and those with primary prevention indication for ICD appear to be at lowest risk

OBJECTIVES We sought to explore the relative contributions of ventricular remodeling and myocardial dysfunction to heart failure in pressure overload hypertrophy (POH). BACKGROUND The mechanism that underlies heart failure in POH is adverse left ventricular (LV) chamber remodeling or decreased myocardial function, or a combination of these. METHODS Twenty weeks after suprarenal aortic banding in rats, animals with POH were classified as those with heart failure (POH-HF) or those with no heart failure (POH-NHF). The LV chamber and myocardial systolic and diastolic functions were determined from in vivo and ex vivo experiments. RESULTS The LV mass was similar in both POH groups. Chamber remodeling in the POH-HF group was characterized by marked LV enlargement with a normal relative wall thickness (eccentric remodeling), whereas remodeling in the POH-NHF group was characterized by a normal chamber size and increased relative wall thickness (concentric remodeling). The LV systolic function, as determined in vivo from the end-systolic pressure-diameter relationship and ex vivo from the pressure-volume relationship, was lower in the POH-HF group than in the POH-NHF and sham-operated control groups. In contrast, myocardial function was similar in both POH groups, as determined in vivo from the stress-midwall fractional shortening relationship and myocardial systolic stiffness, and ex vivo from the slope of the LV systolic stress-strain relationship. The diastolic chamber stiffness constant was lower in the POH-HF group than in the POH-NHF group, but the myocardial stiffness constant was similar in the two POH groups. CONCLUSIONS The two POH groups differed primarily in their remodeling process, which led to a chronically compensated state in one group and to heart failure in the other. Hence, heart failure in POH is more closely related to deleterious LV remodeling than to depressed myocardial function.

Summary Background The importance of risk stratification for sudden cardiac death (SCD) after septal myectomy for hypertrophic obstructive cardiomyopathy (HOCM) has not been emphasized previously. Methods and results We report 2 patients with SCD or ventricular tachycardia (VT) after septal myectomy for HOCM in whom risk factors for SCD were identified following surgical myectomy. One received an implantable cardioverter-defibrillator (ICD), which subsequently provided appropriate discharges for VT. The other delayed ICD implantation and suffered SCD. Conclusion These cases emphasize the importance of risk stratification for SCD after septal myectomy for HOCM.

Background In 2008, the United States spent $2.2 trillion for healthcare, which was 15.5% of its GDP. 31% of this expenditure is attributed to hospital care. Evidently, even modest reductions in hospital care costs matter. A 2009 study showed that nearly $30.8 billion in hospital care cost during 2006 was potentially preventable, with heart diseases being responsible for about 31% of that amount. Methods Our goal is to accurately and efficiently predict heart-related hospitalizations based on the available patient-specific medical history. To the best of our knowledge, the approaches we introduce are novel for this problem. The prediction of hospitalization is formulated as a supervised classification problem. We use de-identified Electronic Health Record ( EHR ) data from a large urban hospital in Boston to identify patients with heart diseases. Patients are labeled and randomly partitioned into a training and a test set. We apply five machine learning algorithms, namely Support Vector Machines (SVM), AdaBoost using trees as the weak learner, logistic regression, a naive Bayes event classifier, and a variation of a Likelihood Ratio Test adapted to the specific problem. Each model is trained on the training set and then tested on the test set. Results All five models show consistent results, which could, to some extent, indicate the limit of the achievable prediction accuracy. Our results show that with under 30% false alarm rate, the detection rate could be as high as 82%. These accuracy rates translate to a considerable amount of potential savings, if used in practice.

Background 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 P P P P P ECG recordings showed that the ischemic index is statistically significantly increased compared with baseline in lead I, aVR, and all precordial leads ( P P 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.

Background— Identifying factors predictive of mortality may be important to decrease risk associated with cardiac implantable electrical device (CIED) replacement procedures. This study aimed to determine whether clinical factors and complications independently associate with death and to develop a mortality risk prediction tool after CIED replacement. Methods and Results— The prospective REPLACE Registry determined 6-month complication and mortality rates after CIED replacement with or without planned lead addition or revision. Vital status was collected. Kaplan-Meier survival and multivariable Cox proportional hazards regression analyses were performed to identify patient, procedural, or complication variables predictive of death. The REPLACE DARE (Death After Replacement Evaluation) Score was constructed using hazard ratios, reflecting relative risk contributions of each variable, combined into an additive mortality risk score equation. At 6 months, 70 of 1744 (4.0%) patients had died. Cox regression analysis found no significant association between major complications and death. However, recent heart failure admission, New York Heart Association class III/IV, antiarrhythmic drug use, cerebrovascular disease, and chronic kidney disease stage were independently associated with 6-month mortality. The REPLACE DARE Score was 2.0±1.4 in survivors versus 3.5±1.8 in nonsurvivors ( P P Conclusions— Comorbidities, but not complications, were significantly associated with mortality after CIED replacement. The REPLACE DARE Score is a novel tool that can identify patients with substantial mortality risk. Such patients should have the relative risk and benefit of their procedure considered carefully. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00395447.

This editorial refers to ‘Worldwide experience with a totally subcutaneous ICD: early results from the EFFORTLESS S-ICD registry’[†][1], by P.D. Lambiase et al. , on page 1657 While the clinical significance of the implantable cardioverter defibrillator (ICD) in the reduction of sudden cardiac arrest remains unequivocal, the quest for the best implantable system continues. The first successful, yet experimental ICD system involved two electrodes between the pectoralis muscle and the rib cage, two sensing electrodes in the chest wall musculature, with a pulse generator and capacitor implanted intra-abdominally in animals.1 The first ICD implanted in a human in 1980 consisted of epicardial patches and sensing leads.2 Subsequently, the advent of transvenous ICD leads significantly reduced the morbidity of the procedure and complication rates, while improving clinical outcomes. The transvenous leads, however, came with the cost of a spectrum of vascular complications as well as design faults. Therefore, the quest for a better implantable system has continued. The totally subcutaneous ICD (S-ICD), an innovative strategy obviating the need for vascular access, has come on as a contender to fill this void.3 Evidence favouring the clinical use of the S-ICD came from the feasibility studies and European registries that preceded the Food and Drug Administation (FDA) approval of the device.3–5 Most of these studies have comprised smaller numbers with limited follow-up, calling into question the applicability of these results in real-world practice. The study now presented by Lambiase et al. ,6 reporting on early data from the multicentre EFFORTLESS S-ICD registry, provides valuable information on system performance and inappropriate shock rates. This registry is a laudable effort and comprises an observational, non-randomized, standard of care evaluation of S-ICD in countries outside the USA. The term ‘worldwide experience’ in the title, however, may be a misnomer, as … [1]: #fn-2

Background —The transition from compensated left ventricular hypertrophy (LVH) to heart failure is associated with alterations in the myocardial interstitium. We hypothesized that LV dilatation is associated with modifications in collagen cross-linking. Methods and Results —We studied 2 rat models of LV dilatation: (1) pressure-overload hypertrophy with heart failure (POH-F) induced by suprarenal abdominal aortic banding and (2) LVH induced by 7 months of isoproterenol (ISO, 0.04 mg · kg −1 · d −1 ) administration. In POH-F rats and in rats receiving ISO, LV dilatation and a reduced systolic chamber performance were noted. Myocardial hydroxyproline concentrations ([HPRO]) were increased in the POH-F rats, whereas in rats receiving ISO, [HPRO] was decreased. In POH-F rats, the ratio of myocardial collagen type I to type III was increased, but in rats receiving ISO, myocardial collagen I/III was unchanged. In contrast to the diverse changes in myocardial collagen concentrations and phenotypes observed in the 2 models of LV dilatation, the ratio of myocardial insoluble to soluble (relationship between cross-linked and non–cross-linked) collagen was decreased in both the POH-F and ISO groups. Moreover, administration of captopril (0.22 mmol · kg −1 · d −1 ), which inhibited the ISO-induced reduction in myocardial insoluble/soluble collagen but not the reduction in [HPRO], prevented the ISO-induced alterations in LV dimensions and performance. Conclusions —Because decreases in the ratio of myocardial insoluble to soluble collagen parallel LV dilatation in rats, reductions in myocardial collagen cross-linking may be an important mechanism contributing to LV dilatation in heart disease.

We were pleased to see the results of the validation work done by Barra et al1 in examining the performance of the REPLACE (Death After Replacement Evaluation) DARE score2 in their patient population. The DARE score results in their implantable cardioverter-defibrillator (ICD) replacement group of 228 patients yielded findings that were consistent, and, for some metrics, nearly identical, to those found in the REPLACE population of 1744 patients, despite a longer follow-up period (33 months versus 6 months in REPLACE). We also appreciated the additional efforts by Barra et al1 to compare the DARE score performance to the predictive model proposed by Bilchick et al,3 which was developed on a larger population of Medicare patients (n=17 991) receiving de novo ICD implantation for primary prevention. Although the final risk model of Bilchick et al3 was based on 7 predictor variables in a related but somewhat different patient population with a longer average follow-up (4.4 years), the concordance with 5 of the 6 predictor variables used …

Aims Several studies have reported a poor outcome with cardiac resynchronization therapy (CRT) in non-left bundle branch block (LBBB) patients. Although the left ventricular (LV) lead location is an important determinant of the clinical outcome, there is scant information regarding its role in non-LBBB patients. This study sought to examine the impact of electrical and anatomical location of the LV lead in relation to baseline QRS morphology on the CRT outcome. Methods and results A left ventricular lead electrical delay (LVLED) was measured intra-procedurally as an interval between QRS onset on the surface electrocardiogram (ECG) to the peak of sensed electrogram on LV lead and corrected for QRS width. The impact of the LVLED on time to first heart failure hospitalization (HFH), and composite outcome of all-cause mortality, HFH, LVAD implantation, and cardiac transplantation at 3 years was assessed. Among 144 patients (age 67 ± 12 years, QRS duration 156 ± 28 ms, non-LBBB 43%), HFH was higher in non-LBBB compared with LBBB (43.5 vs. 24%, P = 0.015). Within LBBB, patients with the long LVLED (≥50%) had 17% HFH vs. 53% in the short LVLED (

Background Pulmonary vein isolation (PVI) is recognized as a potentially curative treatment for atrial fibrillation (AF). Ablation of complex fractionated atrial electrograms (CFAEs) in addition to PVI has been advocated as a means to improve procedural outcomes, but the benefit remains unclear. Objective This study sought t synthesize the available data testing the incremental benefit of adding CFAE ablation to PVI. Methods We performed a meta-analysis of controlled studies comparing the effect of PVI with CFAE ablation vs. PVI alone in patients with paroxysmal and nonparoxysmal AF. Results Of the 481 reports identified, 8 studies met our inclusion criteria. There was a statistically significant increase in freedom from atrial tachyarrhythmia (AT) with the addition of CFAE ablation (relative risk [RR] 1.15, P = .03). In the 5 reports of nonparoxysmal AF (3 randomized controlled trials, 1 controlled clinical trial, and 1 trial using matched historical controls), addition of CFAE ablation resulted in a statistically significant increase in freedom from AT (n = 112 of 181 [62%] for PVI+CFAE vs. n=84 of 179 [47%] for PVI alone; RR 1.32, P = .02). In trials of paroxysmal AF (3 randomized controlled trials and 1 trial using matched historical controls), addition of CFAE ablation did not result in a statistically significant increase in freedom from AT (n = 131 of 166 [79%] for PVI+CFAE vs. n=122 of 164 [74%] for PVI alone; RR 1.04, P = .52). Conclusion In these studies of patients with nonparoxysmal AF, addition of CFAE ablation to PVI results in greater improvement in freedom from AF. No additional benefit of this combined approach was observed in patients with paroxysmal AF.

Background— Prospective studies defining the risk associated with pacemaker or implantable cardioverter-defibrillator replacement surgeries do not exist. These procedures are generally considered low risk despite results from recent retrospective series reporting higher rates. Methods and Results— We prospectively assessed predefined procedure-related complication rates associated with elective pacemaker or implantable cardioverter-defibrillator generator replacements over 6 months of follow-up. Two groups were studied: those without (cohort 1) and those with (cohort 2) a planned transvenous lead addition for replacement or upgrade to a device capable of additional therapies. Complications were adjudicated by an independent events committee. Seventy-two US academic and private practice centers participated. Major complications occurred in 4.0% (95% confidence interval, 2.9 to 5.4) of 1031 cohort 1 patients and 15.3% (95% confidence interval, 12.7 to 18.1) of 713 cohort 2 patients. In both cohorts, major complications were higher with implantable cardioverter-defibrillator compared with pacemaker generator replacements. Complications were highest in patients who had an upgrade to or a revised cardiac resynchronization therapy device (18.7%; 95% confidence interval, 15.1 to 22.6). No periprocedural deaths occurred in either cohort, although 8 later procedure-related deaths occurred in cohort 2. The 6-month infection rates were 1.4% (95% confidence interval, 0.7 to 2.3) and 1.1% (95% confidence interval, 0.5 to 2.2) for cohorts 1 and 2, respectively. Conclusions— Pacemaker and implantable cardioverter-defibrillator generator replacements are associated with a notable complication risk, particularly those with lead additions. These data support careful decision making before device replacement, when managing device advisories, and when considering upgrades to more complex systems. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00395447.

Indications for catheter ablation of atrial fibrillation (AF) have expanded to include increasingly complex cases, such as long-standing persistent AF and structural heart disease. Although pulmonary vein isolation remains essential for most ablation procedures, the role of substrate modification has taken on increasing importance. Despite the various ablation strategies available, single-procedure efficacy remains suboptimal among patients with structural heart disease or long-standing persistent AF, where recurrence rates may exceed 50% after a single procedure. These high rates of AF recurrence support the notion that currently available procedural end points are ineffective in identifying which patients are most likely to benefit from substrate modification and defining when that substrate has been sufficiently modified such that additional ablation is unnecessary. In order to improve outcomes, the next generation of procedural end points should seek to define specific properties of the underlying atrial electrical substrate and characterize the impact of catheter ablation on those electrophysiologic properties. The use of substrate-driven end points would be a major step in the process of moving from empiric ablation lesions to a customized ablation strategy based on atrial physiology. In this article, we review current approaches to catheter ablation of AF and discuss specific procedural end points as they pertain to each ablation strategy. We also provide a paradigm for the future development of novel substrate-driven procedural end points.

It is common practice to empirically limit the radiofrequency (RF) power when ablating the posterior left atrium during atrial fibrillation ablation to avoid thermal injury to the esophagus. The objective of this study was to determine whether RF energy delivery limited by luminal esophageal temperature (LET) monitoring is associated with a reduction in esophageal injury compared with a strategy of RF power limitation alone.Eighty-one consecutive patients who underwent atrial fibrillation ablation followed by esophageal endoscopy were included in this observational study. All patients underwent extraostial electric pulmonary vein isolation by using an electroanatomic mapping system and irrigated RF ablation. All RF applications on the posterior left atrium were limited to 35 W. A commercially available, single-thermocouple esophageal probe was used to monitor LET in a subset of patients (n=67). In these cases, applications were promptly interrupted when LET wasor =38.5 degrees C; further applications were performed at reduced power to obtain a LET38.5 degrees C. Esophageal endoscopy was performed 1 to 3 days after the procedure. Ablation-related esophageal ulcerations were identified in 9 of 81 (11%) patients. All patients were asymptomatic. Of these 81 patients, LET monitoring during ablation occurred in 67 (83%) of patients. Esophageal injury was observed more frequently (36% versus 6%, P0.006) in the group without LET monitoring.These data suggest that LET monitoring may be associated with a reduction in esophageal injury compared with power limitation alone.

Alcohol septal ablation (ASA) is a non-surgical alternative to septal myectomy for treatment of symptomatic, drug refractory hypertrophic obstructive cardiomyopathy (HOCM). The effect of ASA on the risk of ventricular arrhythmia (VA) is unknown. There is a theoretic concern for pro-arrhythmia at the site of myocardial injury. We examined the rates of sudden cardiac death (SCD) and VA (defined as VA requiring ICD therapy or documented VT/VF) among all 88 patients treated with ASA at Massachusetts General Hospital between 1998 and 2004. Of these patients, 37 had either an ICD or a permanent pacemaker in situ that enabled surveillance for VA events. Patients were classified as either high-risk (one of the following: VA or positive EP study, syncope due to suspected VA, family history of SCD, septal thickness ≥30mm by echocardiography, or failure to augment sBP >20mmHg on stress testing), or low-risk (no high-risk features). There was no mortality attributable to sudden cardiac death (mean follow up 35±21mo). The event rate for VA in low-risk patients was 3.0% per year (2/18 patients), and 6.3% annually among high-risk patients (4/16 patients). Device data were not available on three patients. In a stepwise Cox proportional hazards multivariate analysis that included pre-ASA arrhythmia, peri-ASA arrhythmia, pre-ASA gradient, change in gradient after ASA, peak CK-MB, and post-ASA gradient, only post-ASA gradient predicted future VA (HR 1.06, 95% CI 1.03–1.10, p

Background: Intracardiac echocardiography (ICE) can be integrated with pre-procedural CT or MR imaging to direct catheter ablation of atrial fibrillation (AF). Prior work has described ICE imaging of the left atrium (LA) with the ICE probe in the RA, but it is feasible to image the LA from an ICE probe placed directly into the LA via a trans-septal puncture performed for the mapping/ablation procedure. The purpose of this study was to determine whether direct LA imaging with ICE results in improved image integration during AF ablation compared with LA imaging indirectly from the RA. Methods: Twenty-five consecutive patients undergoing an AF ablation procedure with the CARTO-Sound system were studied. A 10 French phased array catheter with an embedded CARTO navigation sensor was employed to provide 2D echocardiogram images of the LA - 13 patients underwent imaging from the RA alone and 12 patients from the LA. The accuracy of the image integration was assessed by the average integration error after surface registration and the requirement to take supplementary electroanatomic mapping points to obtain acceptable image integration. Results: Twenty-five patients (56% paroxysmal AF, average LA size = 42±8 mm, average EF = 63±10 %) were examined. There was no difference in the time or number of ultrasound contours required to create a LA anatomic map with ICE imaging from the RA versus the LA (24±17min vs. 24±25min, P=1.0, 24±16 contours vs. 29±18 contours, P=0.5). The average integration error for all patients was 2.19±0.59mm. Direct LA imaging was associated with improved integration error compared to indirect LA imaging from the RA (1.85±0.33mm versus 2.51±0.62mm, P=0.004). Image integration using RA acquired LA images had a tendency to be less accurate resulting in the primary operator acquiring additional registration points to supplement the registration process (patients requiring additional registration points for registration: 3/12 for LA imaging versus 9/13 for RA imaging of the LA, P=0.05). Conclusion: Direct ICE imaging from within the LA is feasible and associated with improved accuracy of image integration during AF ablation.

Background : Patients who are anti-coagulated following pulse generator implantation have a 20% risk of hematoma development in the pre-pectoral pocket. In general, hematomas are correlated with patient discomfort & pain, lead to increased risk of infections, & may require surgical drainage leading to longer hospitalization. Objectives : This investigation was conducted to evaluate safety & effectiveness associated with use of D-Stat ® Flowable Hemostat following implantation of a pulse generator compared to standard of care. Safety endpoint evaluated the incidence of major study-related adverse events & effectiveness endpoint evaluated the incidence rate of clinically significant hematomas. Clinically relevant hematoma was defined as alteration in the standard of care. Methods : Two hundred sixty nine anticoagulated patients were enrolled at ten sites & followed through 8 weeks post-procedure. Patients undergoing implantation were randomized to either D-Stat Flowable Hemostat or standard of care. Results : No statistical differences were observed in the baseline demographics between treatment groups. The D-Stat Flowable group presented with 65.4% males compared to 71.4% in the control group. Mean age was 73.3 years in the D-Stat Flowable group vs 72.2 years in the control group. Pulse generator distribution between the study groups was 54.4% pacemakers & 45.5% ICDs in the D-Stat Flowable group vs 54.9% pacemakers & 45.1% ICDs in the control group. The safety of the D-Stat Flowable was successfully demonstrated as the incidence rate of major complications experienced in both groups (D-Stat Flowable: 21.3%; Control: 27.8%) was equivalent (p value 0.0008). The effectiveness of D-Stat Flowable was successfully demonstrated as the overall rate of clinically relevant hematomas experienced in the D-Stat Flowable group (11.8%) was significantly less than that of the control group (22.6%) (p-value 0.0231). Conclusions : The findings from this investigation demonstrate the use of D-Stat Flowable within the pre-pectoral pocket in anti-coagulated patient population undergoing placement of a pulse generator is safe and effective. Use of D-Stat Flowable resulted in a 48% reduction in the rate of clinically relevant hematomas in the target population.

Background: Alcohol septal ablation (ASA) is a promising treatment option for patients with hypertrophic obstructive cardiomyopathy (HOCM), but the creation of myocardial infarct during the procedure has raised concern about the proarrhythmic risk of ASA. We analyzed the incidence of clinically significant ventricular tachycardia (VT) and sudden cardiac death (SCD) following ASA at our center. Methods: A total of 97 ASAs in 88 patients were performed between 1998 and 2007 at MGH. 34 of these patients had an implantable cardiac defibrillator (ICD) or pacemaker (PPM) implanted prior to or immediately following ASA. 8 of 34 patients had prior ICD implants for either secondary (n=4) or primary (n=4) prevention for SCD. 8 patients had prior PPMs. 3 patients had implantation of ICD post-ASA and 15 patients had PPM implanted following ASA due to atrioventricular block (AVB). Clinical records as well as device data were analyzed to determine incidence of VT or SCD following ASA. Results: There were no deaths attributable to SCD in our cohort of 88 patients (mean follow-up 35 +/− 21 months, range 4 to 70 months). 1 patient with a previous ICD for primary prevention had VT storm 6 days following ASA. 1 patient who had a cardiac arrest 11 days following the ASA (thought to be a bradycardic arrest, since he had intermittent high grade AVB post-ASA) received an ICD. Neither of these patients had subsequent detections or therapies for VT. 1 patient was upgraded to an ICD following ASA due to NSVT, and 2 patients had ICD implants for NSVT or high risk of SCD. The former had subsequent detection of NSVT 24 months after implant, and therapy for VT 3 years later. 2 patients had upgrades of their PPM to an ICD > 12 months after ASA (for positive electrophysiology studies at other centers), but had no detection or therapies during the follow-up period. No other patients had therapies for tachyrrhythmias. Conclusion: In our experience of 97 procedures, we observed 1 episode of VT storm in the first week following ASA, 1 cardiac arrest, likely bradycardic, in the first 2 weeks after ASA, and only 1 patient with clinically significant VT years after ASA. Our data suggest that close follow-up is warranted in the 2 weeks after ASA, but that ASA does not seem to have a long-term proarrhythmic effect in patients with HOCM.

Aims Although acute haemodynamic improvement in response to cardiac resynchronization therapy (CRT) is reflective of a favourable cardiac contractile response, there is limited information regarding not only its ability to predict long-term clinical outcome but also cardiac-substrate-specific differences in the prognostic value of this measure. Methods and results Fifty-three heart failure patients (69 ± 11 years) with low left ventricle ejection fraction (LVEF) (22 ± 6%), wide QRS (169 ± 31 ms), and indications for CRT were included. There were no significant differences in age, New York Heart Association (NYHA) class, medications, QRS width, or LVEF between ischaemic ( n = 37) and non-ischaemic ( n = 16) groups. Echocardiograms were performed within 24 h of implantation with device OFF and ON. Acute haemodynamic response was measured as LV d P /d t derived from the CW Doppler of mitral regurgitation. Percentage change in d P /d t was used to classify patients: high- (HR: Δd P /d t > 25%) or poor-responders (PR: Δd P /d t ≤ 25%). Clinical response to CRT was defined by a combined endpoint of hospitalizations and all-cause mortality at 12 months. HR group had a significantly better outcome compared to the PR group ( P -value = 0.004) irrespective of the aetiology of the cardiomyopathy. Conclusion Echocardiographic assessment of the acute haemodynamic response to CRT predicts long-term clinical outcome in both ischaemic and non-ischaemic cardiomyopathy.

A 41-year-old man with history of paroxysmal atrial fibrillation underwent routine Holter monitoring for symptoms of palpitations at night. The Holter recording from a person with a regular heart rate is shown in the Figure …

Device diagnostics provide objective assessment of physical activity over prolonged periods of time. The purpose of this study was to investigate the prognostic value of device-measured physical activity data as compared to six-minute walk test (6MWT) in predicting clinical response to CRT. Methods: This was a single-center observational cohort study in which patients undergoing CRT for standard indications were retrospectively reviewed. Daily physical activity was evaluated post-implant at 1-, 3- and 6-months. Manufacturer specific measures of average activity of the last week were converted to common units of minutes/day (m/d). The primary end-point was a composite of heart failure (HF) hospitalization, transplant, LVAD, and all-cause death at 3 years. Secondary endpoint was echocardiographic response, as defined as a >10% improvement in LV ejection fraction (LVEF), after CRT. Results: 165 patients were included: average age was 67.5±12.8 years, 76% were male, baseline LVEF was 25±7%. At 1 month, median device-measured activity and 6MWT were 138 min/day and 315 m, respectively. Kaplan Meier curves (see below) show that both 6MWT and device measured physical activity are predictors of clinical outcome. Multivariate modeling adjusting for covariates demonstrated both physical activity (HR 0.57 [95% CI 0.29-1.11], p=0.003) and 6MWT (HR 0.39 [95% CI 0.23-0.68], p=0.001) as independent predictors of improved clinical outcome. Patients with higher levels of device-measured physical activity at the 3-month mark had a significantly higher rate of echocardiographic response (p