BACKGROUND:Vagal nerve stimulation (VNS) may reverse autonomic dysfunction in heart failure (HF). This paper describes results from a pivotal trial, while addressing challenges investigators face following premature trial termination. OBJECTIVES:We report VNS actions in patients with HF with reduced ejection fraction and investigators response to early discontinuation. METHODS:Randomization was 2:1 to VNS or control. Entry required NYHA functional class II or III, left ventricular ejection fraction (LVEF) ≤35%, and N-terminal pro-B-type natriuretic peptide ≥800 pg/mL. Primary efficacy endpoint was time to cardiovascular death or HF hospitalization. Secondary endpoints included LVEF, 6-minute walk distance, and Kansas City Cardiomyopathy Questionnaire. Adaptive sample sizing targeted ≤1,000 patients. P values are 1-sided. RESULTS:After randomizing 532 patients, the sponsor terminated enrollment, unrelated to futility or efficacy. The primary efficacy endpoint was not met (HR: 0.84; 95% CI: 0.62-1.12; P = 0.115). The primary safety endpoint achieved 96.7% freedom from procedure- or device-related serious adverse events. Autonomic engagement persisted long-term. Findings were favorable, although inconclusive, for the primary endpoint, HF hospitalization, Kansas City Cardiomyopathy Questionnaire, NYHA functional class, and 6-minute walk distance. LVEF was unchanged. The still-blinded investigators, seeking to extend data reporting while maintaining scientific integrity, had prespecified a single exploratory outcomes-symptoms win ratio. Results were favorable although merely hypothesis-generating, given primary endpoint neutrality, multiplicity, subjective bias, and marginal statistical significance. CONCLUSIONS:Early termination outside Data Monitoring Committee processes challenged investigators to maintain scientific and ethical integrity and transparency, while optimizing data reporting. The underpowered primary endpoint was neutral. Data documented feasibility, safety, and autonomic engagement. Trends favoring outcomes, symptoms, and function were inconclusive although hypothesis-generating. Importantly, we provide guidance for investigators facing trial discontinuation. (ANTHEM-HFrEF Pivotal Study [Autonomic Regulation Therapy to Enhance Myocardial Function and Reduce Progression of Heart Failure with Reduced Ejection Fraction]; NCT03425422).

Zusammenfassung Ein erster Bericht über eine DC-Katheterablation bei 5 Patienten zur Unterbrechung einer schnellen AV-Überleitung bei Vorhofflimmern und anschließender Pacemaker-Implantation erschien 1982 von Scheinmann et al. (San Francisco, CA, USA). In Deutschland berichteten 1984 Seipel, Breithardt und Borggrefe (Düsseldorf) und 1985 Manz und Lüderitz (Bonn) über erste Erfahrungen mit der DC-Katheterablation. Ein erstes internationales DC-Ablationsregister, an dem auch vier deutsche Zentren beteiligt waren, berichtete 1984 über 127 Patienten aus 24 Zentren. Ein kompletter AV-Block wurde bei 71 % der Patienten erreicht. Die Hannover Gruppe (Trappe, Klein und Huang) berichtete 1992 über Ergebnisse der DC-Katheterablation der AV-Leitung zwischen 1983 und 1990 bei 100 Patienten (86 % Vorhofflimmern, 14 % AV-Reentry Tachykardien). Eine erste erfolgreiche DC-Katheterablation bei einem WPW-Syndrom berichtete Morady (San Francisco, CA) 1985. Borggrefe et al. haben 1987 erstmals über einen Wechsel von der DC-Katheterablation auf ein HF-Katheterverfahren bei einem WPW-Syndrom berichtet. Erste DC-Katheterablationen bei Kammertachykardien beschreibt Hartzler (Kansas City, MO, USA) 1983 bei 3 Patienten. Borggrefe et al. berichten 1989 über 24 Patienten, bei denen eine DC-Katheterablation wegen Kammertachykardien durchgeführt wurde; 17 Patienten hatten nach 14 Monaten keine VT-Rezidive. Die Hannover Gruppe (Trappe, Klein) berichtete 1994 über die Langzeitergebnisse der DC-Katheterablation bei Kammertachykardien nach 5 Jahren bei 51 Patienten. Die VT-Rezidivrate (57 %) und auch die Gesamtmortalität (16 %) waren hoch. Einen Vergleich von DC-Ablation mit der HF-Ablation bei Kammertachykardien berichtete Gonska (Göttingen) 1994. Die Erfolgsraten nach 2 Jahren waren nicht wesentlich unterschiedlich.

Introduction: Wearable Cardioverter Defibrillator (WCD) is utilized in patients with assumed but not yet confirmed risk for sudden cardiac death (SCD). Many of these patients also present with atrial fibrillation (AF). However, the rate of WCD-detected ventricular or atrial arrhythmia events in this specific high-risk cohort is not well understood. Methods: In WEARIT-II, the cumulative probability of any sustained or non-sustained VT/VF (WCD-treated and non-treated), and atrial/supraventricular arrhythmias during WCD use was assessed using the Kaplan-Meier method by prior AF, with comparisons by the log-rank test. The incidence of ventricular and atrial arrhythmia events were expressed as events per 100 patient-years, and were analyzed by prior AF using negative binomial regression. Results: WEARIT-II enrolled 2000 patients, 557 (28%) of whom had AF prior to enrollment. Cumulative probability of any sustained or non-sustained WCD-detected VT/VF during WCD use was significantly higher among patients with a history of AF than without AF (6% vs. 3%, p=0.001). Similarly, the recurrent rate of any sustained or non-sustained VT/VF was significantly higher in patients with prior AF vs. no prior AF (131.5 events per 100 patient-years vs. 22.7 events per 100 patient-years, p=0.001). Patients with prior AF also had a significantly higher burden of any WCD-detected atrial arrhythmias/SVT/inappropriate therapy (183.2 events per 100 patient-years vs. 74.8 events per 100 patient-years, p<0.001). Conclusion: Our results demonstrate that patients with a history of AF wearing the WCD for risk assessment have a higher incidence of ventricular arrhythmias that may facilitate the decision making for ICD implantation.

Zusammenfassung Der implantierbare Kardioverter-Defibrillator (ICD) war ein Durchbruch in der Prävention des plötzlichen Herztodes. Nach jahrelanger technischer Entwicklung durch Michel Mirowski erfolgten trotz vieler Widerstände in den USA 1980 erste Implantationen. Es konnte gezeigt werden, dass Kammerflimmern zuverlässig durch den ICD automatisch erkannt und defibrilliert wurde. Knapp 4 Jahre nach den USA begannen mehrere Zentren, in Deutschland ICDs zu implantieren. Bald wurden außerhalb der USA in Deutschland die meisten Patienten versorgt. Die absolute Zahl der Implantationen war weiterhin klein, solange nur Implantationen mittels Thorakotomie und epikardialen Defibrillationselektroden möglich waren. Anfang der 1990er Jahre konnte ein ICD pektoral, wie ein Schrittmacher, in Kombination mit einer transvenösen Defibrillationselektrode implantiert werden. Die Implantationszahlen stiegen sprunghaft an. Die klinische Forschung in Deutschland begleitete die technischen Fortentwicklungen und hier erfolgten viele First-in-human-Studien. In den USA und Deutschland wurden 1991 erste Leitlinien zur Indikation herausgegeben. Randomisierte Studien zur Mortalität, zumeist unter amerikanischer Leitung mit deutscher Beteiligung, aber auch unter deutscher Leitung (CASH, CAT, DINAMIT, IRIS), wurden zwischen 1996 und 2009 publiziert. Die Ergebnisse dieser lang zurückliegenden Studien wurden 2016 in Frage gestellt, als die DANISH-Studie keine signifikante Verbesserung der Mortalität ergab. Die Implantationszahlen sind seitdem rückläufig. Derzeit wird daran geforscht, genau die Patienten zu versorgen, die trotz optimaler Therapie vor dem plötzlichen Herztod geschützt werden müssen. Risikoscores unter Einbeziehung myokardialer Narben in der Magnetresonanztomographie (MRT) und genetischer Information sollen hierzu beitragen.

Zusammenfassung Die Geschichte der Behandlung ventrikulärer Tachykardien durch chirurgische Verfahren ist kurz; sie dauerte nicht länger als 15 Jahre von etwa 1978 bis 1993. Grundsätzlich sind zwei chirurgische Verfahren zu unterscheiden. Die indirekten Verfahren mit Resektion einer Infarktnarbe ohne elektrophysiologische Untersuchung und die direkten Verfahren mit gezielter Endokardinzision („encircling endocardial ventriculotomy“). In Deutschland haben Ostermeyer, Breithardt und Seipel (Düsseldorf) 1979 erstmals über intraoperatives, elektrophysiologisches Mapping bei ventrikulären Tachykardien (VT) berichtet; 1981 hat dann die Gruppe in Hannover (Frank, Klein) über erste Ergebnisse bei der chirurgischen Therapie von Kammertachykardien berichtet. 1984 konnten Ostermeyer, Breithardt und Borggrefe zeigen, dass eine nur partielle Endokardinzision deutlich günstiger und weniger Ventrikel schädigend (8 % vs. 46 %) ist als eine komplette zirkuläre Inzision. 1987 berichtete die Düsseldorfer Gruppe über Behandlungsergebnisse von 93 Patienten. Nach 5 Jahren waren 77 % der Patienten ohne VT-Rezidiv, die Gesamtmortalität nach einem Jahr war 11 %, nach 5 Jahren 30 %. Die Hannover Gruppe berichtete 1992 über 147 Patienten, die mit endokardialem Resektionsverfahren behandelt wurden; die Gesamtmortalität nach 3 Jahren war 27 %, VT-Rezidive traten bei 18 % der Überlebenden auf. Die Geschichte der chirurgischen Verfahren bei supraventrikulären Tachykardien (SVT), insbesondere dem Wolff-Parkinson-White(WPW)-Syndrom ist noch kürzer als die der Chirurgie für VT. Bereits 1969 berichteten Sealy, Gallagher und Cox über die ersten Fälle einer chirurgischen Intervention beim WPW-Syndrom über einen endokardialen Zugang bei kardioplegischem Herzstillstand. 1984 berichteten Guiraudon und Klein über ein neues Verfahren mit epikardialem Zugang zum akzessorischen Bündel ohne Kardioplegie bei lateral lokalisierten Leitungsbahnen. Auch in Deutschland führten seit 1980 die Gruppen in Düsseldorf (Ostermeyer, Seipel, Breithardt, Borggrefe) und seit 1981 die Hannover Gruppe (Frank, Klein und Kallfelz) operative Verfahren bei WPW-Syndrom durch. Borggrefe berichtete 1987 über 18 operierte Patienten mit WPW-Syndrom und Vorhofflimmern. Nach 2 Jahren blieben 14 von 18 Patienten ohne Tachykardie Rezidive; 1989 berichteten Frank, Klein und Kallfelz (Hannover) über 10 operierte Kinder (2−14 Jahre) unter Anwendung der Kryoablationstechnik. Zwischen 1984 und 1992 wurden in Hannover insgesamt 120 Patienten mit SVT, meist WPW-Syndrom, operiert; nach 42 Monaten hatten 12 Patienten ein SVT-Rezidiv. Bei der Reoperation verstarben 2 Patienten.

The history of surgical treatment of ventricular tachycardias (VT) is short, lasting from 1978 until 1993. "Indirect procedures" with infarct scar resection were performed without electrophysiologic studies, whereas "direct procedures" consisted of either complete endocardial incisions ("encircling endocardial ventriculotomy") or large endocardial resections ("endocardial peel-off" technique) after precise epicardial and endocardial mapping procedures. In Germany, the first to report on intra-operative electrophysiologic mapping for VT treatment were Ostermeyer, Breithardt and Seipel in 1979. In 1981, the Hannover group (Frank, Klein) published their first results of surgical treatment of VT. In 1984, Ostermeyer et al. demonstrated that a partial endocardial incision resulted in more beneficial results with less myocardial damage (8% versus 46%) than applying a complete encircling incision. In 1987, the Düsseldorf group reported treatment results of 93 patients. After 5 years, 77% had no VT recurrence, while total mortality after 1 year was 11% and after 5 years 30%. In 1992, the Hannover group reported results of 147 patients after endocardial resection for VT. Total mortality after 3 years was 27%; recurrence of VT events occurred in 18% of the surviving cohort.The history of surgical procedures for supraventricular tachycardia (SVT), in particular Wolff-Parkinson-White (WPW) syndrome, is even shorter than that of surgery for VT. As early as 1969, Sealy, Gallagher and Cox reported the first cases of surgical intervention for WPW syndrome via endocardial access in cardioplegic arrest. In 1984, Guiraudon and Klein reported on a new procedure with epicardial access to the accessory bundle without cardioplegia in laterally localised conduction pathways. In Germany, too, the groups in Düsseldorf (Ostermeyer, Seipel, Breithardt, Borggrefe) from 1980 and the Hannover group (Frank, Klein and Kallfelz) from 1981 performed surgical procedures for WPW syndrome. In 1987, Borggrefe reported on 18 patients with WPW syndrome and atrial fibrillation who had undergone surgery. After 2 years, 14 of 18 patients had no recurrences of tachycardia; in 1989, Frank, Klein and Kallfelz (Hannover) reported on 10 children (2-14 years) operated on using the cryoablation technique. Between 1984 and 1992, a total of 120 patients with SVT, mostly WPW syndrome, were operated on in Hannover; after 42 months, 12 patients had a recurrence of SVT. Two patients died during the reoperation.

Abstract Background and Aims De novo implanted cardiac resynchronization therapy with defibrillator (CRT-D) reduces the risk of morbidity and mortality in patients with left bundle branch block, heart failure and reduced ejection fraction (HFrEF). However, among HFrEF patients with right ventricular pacing (RVP), the efficacy of CRT-D upgrade is uncertain. Methods In this multicentre, randomized, controlled trial, 360 symptomatic (New York Heart Association Classes II–IVa) HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD), high RVP burden ≥ 20%, and a wide paced QRS complex duration ≥ 150 ms were randomly assigned to receive CRT-D upgrade (n = 215) or ICD (n = 145) in a 3:2 ratio. The primary outcome was the composite of all-cause mortality, heart failure hospitalization, or <15% reduction of left ventricular end-systolic volume assessed at 12 months. Secondary outcomes included all-cause mortality or heart failure hospitalization. Results Over a median follow-up of 12.4 months, the primary outcome occurred in 58/179 (32.4%) in the CRT-D arm vs. 101/128 (78.9%) in the ICD arm (odds ratio 0.11; 95% confidence interval 0.06–0.19; P < .001). All-cause mortality or heart failure hospitalization occurred in 22/215 (10%) in the CRT-D arm vs. 46/145 (32%) in the ICD arm (hazard ratio 0.27; 95% confidence interval 0.16–0.47; P < .001). The incidence of procedure- or device-related complications was similar between the two arms [CRT-D group 25/211 (12.3%) vs. ICD group 11/142 (7.8%)]. Conclusions In pacemaker or ICD patients with significant RVP burden and reduced ejection fraction, upgrade to CRT-D compared with ICD therapy reduced the combined risk of all-cause mortality, heart failure hospitalization, or absence of reverse remodelling.

IMPORTANCE Current guidelines for primary implantable cardioverter-defibrillator (ICD)therapy do not account for sex differences in arrhythmic risk in ICD candidates. OBJECTIVE To evaluate the association between sex and risk of ventricular tachyarrhythmia (VTA) and mortality. DESIGN, SETTING, AND PARTICIPANTS This cohort study compared differences in the risk of VTA and mortality between 4506 men and women enrolled in the 4 Multicenter Automatic Defibrillator Implantation Trials (MADIT) between July 1, 1997, and December 31, 2011. Data from prospective randomized controlled multicenter studies were analyzed retrospectively. Men and women with an ICD or cardiac resynchronization therapy defibrillator who were enrolled in all MADIT studies were included. Data were analyzed between January 10 and June 10, 2021. EXPOSURES ICD implant. MAIN OUTCOMES AND MEASURES The primary end point was sustained VTA, defined as ICD-recorded, treated or monitored VTA at least 170/min or ventricular fibrillation. Secondary VTA end points included VTA at least 200/min, appropriate ICD shocks, and appropriate antitachycardia pacing. All end points were included in a first and recurrent event analysis. RESULTS Of the 4506 study participants, 3431 were men (76%). Mean (SD) age of the cohort was 64 (12) years. For women vs men, the mean (SD) age (64 [12] years vs 64 [11] years) and left ventricular ejection fraction (24% vs 25%) were similar, but women exhibited a higher frequency of nonischemic cardiomyopathy (454 of 1075 women [42%) vs 2535 of 3431 men [74%]). Women had significantly lower 3-year cumulative probability of sustained VTA (16% vs 26%), fast VTA (9% vs 17%), and appropriate ICD shocks (7% vs 15%) compared with men (P < .001for all). Multivariable analysis showed that female sex was independently associated with at least 40% lower risk of all first and recurrent VTA end points (P < .001for all), including the primary end point (first event, H R = 60 [95% CI, 50-73], P < .001; recurrent event, HR = 49 [95% CI, 43-55], P < .001), after accounting for the competing risk of all-cause mortality and nonarrhythmic mortality. The lower VTA risk associated with female sex was consistent in risk subsets but was significantly more pronounced in patients with nonischemic cardiomyopathy (female vs male in the ischemic group: hazard ratio, 0.73 [95% CI, 0.56-0.95], P = .02; nonischemic group: hazard ratio, 0.50 [95% Cl. 0.38-0.66], P < .001; P = .03 for interaction between female sex and cardiomyopathy). CONCLUSIONS AND RELEVANCE Findings suggest that women display a significantly lower risk of first and recurrent life-threatening VTA events than men, and that it is more pronounced in patients with nonischemic cardiomyopathy, suggesting a need for sex-specific risk assessment for primary prevention ICD therapy.

Current guidelines do not account for possible sex differences in the risk of ventricular tachyarrhythmia (VTA). We sought to identify specific factors associated with increased risk for VTA in women implanted with a primary prevention implantable cardioverter-defibrillator (ICD). Our study cohort consisted of 4,506 patients with an ICD or cardiac resynchronization therapy-defibrillator who were enrolled in the 4 landmark MADIT studies - MADIT-II, MADIT-RISK, MADIT-CRT and MADIT-RIT (1,075 women [24%]). Fine and Gray regression models were used to identify female-specific risk factors for the primary end point of VTA, defined as ICD-recorded, treated, or monitored, sustained ventricular tachycardia ≥170 beats per minute or ventricular fibrillation. At 3.5 years of follow-up, the cumulative incidence of VTA was significantly lower in women than men (17% vs 26%, respectively; p <0.001 for the entire follow-up). Use of amiodarone at enrollment, Black race, and history of previous myocardial infarction without previous revascularization was found to be independent risk factors of VTA in women. Of these factors, only Black race was associated with a statistically significant risk increase in men. At 3.5 years, the cumulative incidence of VTA in women with one or more of these risk factors was 27% compared with 14% in women with none of the risk factors (hazard ratio [confidence interval] = 2.08 [1.49 to 2.91]). In conclusion, our study, comprising 4 landmark ICD clinical trials, shows that sex and race have the potential to be used for improved risk stratification of patients who are candidates for primary prevention ICD.

When we watch a theatre play, we like it and enjoyed the performance of the actors, we applaud the actors we have seen in front of the curtain. However, we rarely see the people, staff, and theater members behind the curtain who shape and arrange the whole play, assist the actors, or are responsible for the whole play. The introduction of the implantable defibrillator (ICD) into modern medicine was a landmark event and is undeniable linked with the name of Dr. Michel Mirowski. However, another outstanding personality, physician and scientist, Dr. Morton M. Mower helped Dr. Mirowski make his dream come true having an effective weapon against sudden arrhythmic death. Being not only Dr. Mirowski’s most important collaborator during the time of ICD development, Dr. Morton M. Mower (Figure 1) continued to improve modern medicine with new ideas, therapies, and engineering skills until today. On Monday, 25 April 2022, Dr. Morton Maimon Mower passed away shortly after his 89th birthday in Denver, Colorado, USA.

The ANTHEM-HF, INOVATE-HF, and NECTAR-HF clinical studies of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) systems have collectively provided dose-ranging information enabling the development of several working hypotheses on how stimulation frequency can be utilized during VNS for tolerability and improving cardiovascular outcomes in patients living with heart failure (HF) and reduced ejection fraction (HFrEF). Changes in heart rate dynamics, comprising reduced heart rate (HR) and increased HR variability, are a biomarker of autonomic nerve system engagement and cardiac control, and appear to be sensitive to VNS that is delivered using a stimulation frequency that is similar to the natural operating frequency of the vagus nerve. Among prior studies, the ANTHEM-HF Pilot Study has provided the clearest evidence of autonomic engagement with VNS that was delivered using a stimulation frequency that was within the operating range of the vagus nerve. Achieving autonomic engagement was accompanied by improvement from baseline in six-minute walk duration (6MWD), health-related quality of life, and left ventricular EF (LVEF), over and above those achieved by concomitant guideline-directed medical therapy (GDMT) administered to counteract harmful neurohormonal activation, with relative freedom from deleterious effects. Autonomic engagement and positive directional changes have persisted over time, and an exploratory analysis suggests that improvement in autonomic tone, symptoms, and physical capacity may be independent of baseline NT-proBNP values. Based upon these encouraging observations, prospective, randomized controlled trials examining the effects on symptoms and cardiac function as well as natural history have been warranted. A multi-national, large-scale, randomized, controlled trial is well underway to determine the outcomes associated with ART using autonomic nervous system engagement as a guide for VNS delivery.

BACKGROUND There are conflicting data on the impact of implantable cardioverter-defibrillator (ICD) shocks on subsequent mortality. OBJECTIVES The aim of this study was to determine whether the arrhythmic substrate leading to ICD therapy or the therapy itself increases mortality. METHODS The study cohort included 5,516 ICD recipients who were enrolled in 5 landmark ICD trials (MADIT-II, MADITRISK, MADIT-CRT, MADIT-RIT, RAID). The authors evaluated the association of device therapy with subsequent mortality in 4 separate time-dependent models: model I, type of ICD therapy; model II, type of arrhythmia for which ICD therapy was delivered; model III, combined assessment of all arrhythmia and therapy types during follow-up; and model IV, incremental risk associated with repeated ICD shocks. RESULTS When analyzed by the type of ICD therapy (model I), a first appropriate ICD shock was associated with increased risk of subsequent mortality with or without concomitant occurrence of inappropriate shock during follow-up (hazard ratio [HR]: 2.78 and 2.31; p < 0.001 and p = 0.12), whereas inappropriate shock alone was not associated with mortality risk (HR: 1.23; p = 0.42). Similarly, ICD therapy for ventricular tachycardia (VT) $200 beats/min or ventricular fibrillation (VF) (model II) was associated with increased risk of death with or without concomitant therapy for VT <200 beats/min (HRs: 2.25 and 2.62; both p < 0.001), whereas appropriate therapy for VT <200 beats/min or inappropriate therapy (regardless of etiology) did not reach statistical significance (all p > 0.10). Combined assessment of all therapy and arrhythmia types during follow-up (model III) showed that appropriate ICD shocks for VF, shocks for fast VT ($200 beats/min) without prior antitachycardia pacing (ATP), as well as shocks for fast VT delivered after failed ATP, were associated with the highest risk of subsequent death (HR: all >2.8; p < 0.001). Finally, 2 or more ICD appropriate shocks were not associated with incremental risk to the first appropriate ICD shock (model IV). CONCLUSION The combined data from 5 landmark ICD trials suggest that the underlying arrhythmic substrate rather than the ICD therapy is the more important determinant of mortality in ICD recipients. (J Am Coll Cardiol 2021;77:2453-62) (c) 2021 by the American College of Cardiology Foundation.

BACKGROUND:Physiotherapy prior to open-heart surgery lowers the rate of pneumonia and length of the hospital stay. Pneumonia is a major contributor to short-term mortality following transcatheter aortic valve replacement (TAVR). Hence, we hypothesized that pre- and intensified postprocedural physiotherapy in patients undergoing TAVR might impact the net functional and clinical outcome.METHODS AND RESULTS:The 4P-TAVR study was a prospective, monocentric, randomized trial. The study was designed to compare the efficacy and safety of intensified periprocedural physiotherapy including inspiratory muscle training versus standard postprocedural physiotherapy. Patients were randomized in a 1 : 1 fashion. 108 patients were included and followed up for 90 days after TAVR. While patients in group A (control group: 50 patients, age: 81.7 ± 5.0 years, 52% male) did not receive physiotherapy prior to TAVR, group B (intervention group: 58 patients, age: 82.2 ± 5.82 years, 47% male) participated in intensive physiotherapy. Compared to the control group, patients in the interventional group showed a lower incidence of postinterventional pneumonia (10 [20.0%] vs. 3 [5.1%], p=0.016) and had a 3-day shorter mean hospital stay (13.5 ± 6.1 days vs. 10.1 ± 4.7 days, p=0.02). The primary composite endpoint of mortality and rehospitalization was not different between the groups.CONCLUSION:Intensified physiotherapy is safe and has positive effects on clinical outcomes up to 90 days after TAVR but has no impact on the primary combined endpoint of mortality and rehospitalization. Longer follow-up, a multicenter design, and a higher number of subjects are needed to confirm these preliminary results. This trial is registered with DRKS00017239.

AIMS The benefit of prophylactic implantable cardioverter-defibrillator (ICD) is not uniform due to differences in the risk of life-threatening ventricular tachycardia (VT)/ventricular fibrillation (VF) and non-arrhythmic mortality. We aimed to develop an ICD benefit prediction score that integrates the competing risks. METHODS AND RESULTS The study population comprised all 4531 patients enrolled in the MADIT trials. Best-subsets Fine and Gray regression analysis was used to develop prognostic models for VT (≥200 b.p.m.)/VF vs. non-arrhythmic mortality (defined as death without prior sustained VT/VF). Eight predictors of VT/VF (male, age < 75 years, prior non-sustained VT, heart rate > 75 b.p.m., systolic blood pressure < 140 mmHg, ejection fraction ≤ 25%, myocardial infarction, and atrialarrhythmia) and 7 predictors of non-arrhythmic mortality (age ≥ 75 years, diabetes mellitus, body mass index < 23 kg/m2, ejection fraction ≤ 25%, New York Heart Association ≥II, ICD vs. cardiac resynchronization therapy with defibrillator, and atrial arrhythmia) were identified. The two scores were combined to create three MADIT-ICD benefit groups. In the highest benefit group, the 3-year predicted risk of VT/VF was three-fold higher than the risk of non-arrhythmic mortality (20% vs. 7%, P < 0.001). In the intermediate benefit group, the difference in the corresponding predicted risks was attenuated (15% vs. 9%, P < 0.01). In the lowest benefit group, the 3-year predicted risk of VT/VF was similar to the risk of non-arrhythmic mortality (11% vs. 12%, P = 0.41). A personalized ICD benefit score was developed based on the distribution of the two competing risks scores in the study population (https://is.gd/madit). Internal and external validation confirmed model stability. CONCLUSIONS We propose the novel MADIT-ICD benefit score that predicts the likelihood of prophylactic ICD benefit through personalized assessment of the risk of VT/VF weighed against the risk of non-arrhythmic mortality.

Cardiac resynchronization therapy (CRT) became the standard of care for heart failure patients with broad QRS complex (≥130 ms) and reduced left ventricular function (LVEF≤35%). However, it is not easy to decide which patients will need defibrillator back-up with CRT (CRT-D) or should just receive a biventricular pacing device without ICD (CRT-P). [ [1] Normand C. Linde C. Singh J. Dickstein K. Indications for cardiac resynchronization therapy: a comparison of the major international guidelines. JACC Heart Fail. 2018; 6: 308-316 Google Scholar , [2] Normand C. Linde C. Nigussie B. Blomström-Lundquist C. Auricchio A. Stellbrink C. et al. Cardiac resynchronization therapy pacemaker or cardiac resynchronization defibrillator: what determines the choice? Findings from the ESC CRT Survey II. Europace. 2019; 21: 918-927 Google Scholar ] Application of the heart failure meta-score to predict prognosis in patients with cardiac resynchronization defibrillatorsInternational Journal of CardiologyVol. 330PreviewThe Heart Failure (HF) Meta-score may be useful in predicting prognosis in patients with primary prevention cardiac resynchronization defibrillators (CRT-D) considering the competing risk of appropriate defibrillator shock versus mortality. Full-Text PDF Open Access