No beneficial use of the wearable cardioverter defibrillator among patients suffering from inherited and congenital heart disease: data from a European multicenter registry.

Background: Data on the use of the wearable cardioverter defibrillator in patients suffering from inherited and congenital heart disease are limited. Consequently, evidence for guideline recommendations in this patient population is lacking. Methods: In total 1,675 patients were included in a multicenter registry of eight European centers. In the present cohort, we included 18 patients suffering from congenital and inherited heart disease. Results: Nine patients (50%) were male with a mean age of 41.3 ± 16.4 years. Four patients suffered from hypertrophic cardiomyopathy (HCM), four patients suffered from non-compaction cardiomyopathy (NCCM), two patients were diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC) and one patient suffered from muscular dystrophy of the limb-girdle type with cardiac involvement, secondary cardiomyopathy. Three patients presented with Brugada syndrome (BrS). One patient suffered from long-QT syndrome type 1 (LQTS1). Furthermore, two patients had congenital heart defects and one patient suffered from cardiac sarcoidosis (CS). There were no appropriate/inappropriate shocks with the WCD in this cohort. One patient had recurrent self-limiting sustained ventricular tachycardia during the wear time, but actively inhibited a shock and was hospitalized. The compliance rate in this cohort was 77.8% with a mean wear time of 45.3 ± 26.9 days with a mean follow-up time of 570 ± 734 days. 55.6% (10/18) of the patients received an ICD after WCD wear time. Conclusions: This retrospective study of patients with inherited and congenital heart disease shows that WCD use is not beneficial in the majority of patients with inherited and congenital heart disease.

Predictors of ventricular tachyarrhythmia in patients with a wearable cardioverter defibrillator: an international multicenter registry.

BACKGROUND AND AIMS: Wearable cardioverter defibrillator (WCD) can protect patients from sudden cardiac death due to ventricular tachyarrhythmias and serve as a bridge to decision of definite defibrillator implantation. The aim of this analysis from an international, multicenter WCD registry was to identify predictors of sustained ventricular tachycardia (VT) and/or ventricular fibrillation (VF) in this population. METHODS: One thousand six hundred seventy-five patients with WCD were included in a multicenter registry from 9 European centers, with a median follow-up of 440 days (IQR 120-893). The primary study end point was the occurrence of sustained VT/VF. RESULTS: Sustained VT was detected by WCD in 5.4% and VF in 0.9% of all patients. Of the 30.3% of patients receiving ICD implantation during follow-up, sustained VT was recorded in 9.3% and VF in 2.6%. Non-ischemic cardiomyopathy (HR 0.5, p < 0.001), and medication with angiotensin-converting enzyme inhibitors (HR 0.7, p = 0.027) and aldosterone antagonists (HR 0.7, p = 0.005) were associated with a significantly lower risk of VT/VF. CONCLUSIONS: Patients who received WCD due to a transient increased risk of sudden cardiac death have a comparatively lower risk of VT/VF in the presence of non-ischemic cardiomyopathy. Of note, optimal medical treatment for heart failure not only results in an improvement in left ventricular ejection fraction but also in a reduction in the risk for VT/VF.

Stereotactic arrhythmia radioablation and its implications for modern cardiac electrophysiology: results of an EHRA survey.

Stereotactic arrhythmia radioablation (STAR) is a treatment option for recurrent ventricular tachycardia/fibrillation (VT/VF) in patients with structural heart disease (SHD). The current and future role of STAR as viewed by cardiologists is unknown. The study aimed to assess the current role, barriers to application, and expected future role of STAR. An online survey consisting of 20 questions on baseline demographics, awareness/access, current use, and the future role of STAR was conducted. A total of 129 international participants completed the survey [mean age 43 ± 11 years, 25 (16.4%) female]. Ninety-one (59.9%) participants were electrophysiologists. Nine participants (7%) were unaware of STAR as a therapeutic option. Sixty-four (49.6%) had access to STAR, while 62 (48.1%) had treated/referred a patient for treatment. Common primary indications for STAR were recurrent VT/VF in SHD (45%), recurrent VT/VF without SHD (7.8%), or premature ventricular contraction (3.9%). Reported main advantages of STAR were efficacy in the treatment of arrhythmias not amenable to conventional treatment (49%) and non-invasive treatment approach with overall low expected acute and short-term procedural risk (23%). Most respondents have foreseen a future clinical role of STAR in the treatment of VT/VF with or without underlying SHD (72% and 75%, respectively), although only a minority expected a first-line indication for it (7% and 5%, respectively). Stereotactic arrhythmia radioablation as a novel treatment option of recurrent VT appears to gain acceptance within the cardiology community. Further trials are critical to further define efficacy, patient populations, as well as the appropriate clinical use for the treatment of VT.

Ventricular arrhythmias in patients with bicuspid aortic valves.

INTRODUCTION: Bicuspid aortic valves (BAV) are the most common congenital heart defects and the extent of ventricular arrhythmias (VA) in patients with BAV is unclear. The objective of this study is to describe VAs and late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) in patients with BAV. METHODS: A total of 19 patients with BAV (18 males, age: 58 ± 13 years) were referred for VA ablation procedures. Ten patients had BAVs at the time of ablation, nine patients had prior aortic valve replacement for a BAV. All but one patient had LGE-CMR and all patients underwent programmed ventricular stimulation at the time of the ablation. RESULTS: Frequent PVCs were the targeted VAs in 17/19 patients and VT in 2/19 patients. Monomorphic ventricular tachycardia (VT) was inducible in 6 patients. A total of 15 VTs were inducible (2.5 ± 1.0 VTs per patient with a mean cycle length of 322 ± 83 msec). LGE was present in 13 patients. Patients with inducible VT had larger borderzone and core scar compared to non-inducible patients (7.8 ± 2.1 cm3 vs. 2.5 ± 3.1 cm3 and 5.1 ± 2.6 cm3 vs. 1.9 ± 3.0 cm3, p-value < .05 for both). PVCs and VTs were mapped to the periaortic valve area in 12 patients and 4 patients, respectively. The PVC burden was reduced from 27 ± 13 to 3 ± 6 (p < .001) and the ejection fraction improved from 49 ± 13% to 55 ± 9% (p = .005). CONCLUSIONS: VAs in patients with BAV often originate from the perivalvular area and patients often have LGE and inducible VT. LGE may be due to ventricular remodeling secondary to the presence of BAV and harbors the arrhythmogenic substrate for VT.

Pleomorphism of premature ventricular complexes originating from papillary muscles and their myocardial connections.

BACKGROUND: Patients with arrhythmias originating from papillary muscles (PAPs) often have pleomorphic ventricular arrhythmias (PVAs) that can result in failed ablations. The mechanism of PVAs is unknown. OBJECTIVE: The purpose of this study was to assess the prevalence and mechanisms of PVAs and the impact on outcomes in patients with focal left ventricular PAP ventricular arrhythmias (VAs). METHODS: The sites of origin (SOOs) of VAs in 43 consecutive patients referred for ablation of focal left ventricular PAP VAs were determined by activation and pacemapping. SOOs were classified as (1) unifocal generating a single VA morphology; (2) unifocal from a deeper-seated origin generating multiple VA morphologies; (3) unifocal located on a PAP branching site; (4) multifocal from a single or multiple PAPs generating multiple VA morphologies; and (5) multifocal from a PAP and a different anatomic source. RESULTS: Most patients had multiple morphologies (n = 34 [79%]) and multiple mechanisms (79%) generating the different VA morphologies. Most of the patients with PVAs had multiple SOOs from a single or different PAPs (n = 23 [68%]), followed by patients with SOOs from PAP and non-PAP sites (n = 19 [56%]). In 13 patients (38%), single SOOs accounted for the observed PVAs. The frequent observation (n = 20) of changing QRS morphologies after radiofrequency energy delivery targeting a single VA suggests the presence of a deeper focus with changing sites of preferential conduction. CONCLUSION: VA pleomorphism in patients with PAP arrhythmias is most often due to premature ventricular complexes originating from different SOOs. The second most common cause is preferential conduction from a single SOO via PAP branching sites.

Dose escalation for stereotactic arrhythmia radioablation of recurrent ventricular tachyarrhythmia - a phase II clinical trial.

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) is delivered with a planning target volume (PTV) prescription dose of 25 Gy, mostly to the surrounding 75-85% isodose line. This means that the average and maximum dose received by the target is less than 35 Gy, which is the minimum threshold required to create a homogenous transmural fibrosis. Similar to catheter ablation, the primary objective of STAR should be transmural fibrosis to prevent heterogenous intracardiac conduction velocities and the occurrence of sustained ventricular arrhythmias (sVA) caused by reentry. We hypothesize that the current dose prescription used in STAR is inadequate for the long-term prevention of sVA and that a significant increase in dose is necessary to induce transmural scar formation. OBJECTIVE: A single arm, multi-center, phase II, dose escalation prospective clinical trial employing the i3 + 3 design is being conducted to examine the safety of a radiation dose-escalation strategy aimed at inducing transmural scar formation. The ultimate objective of this trial is to decrease the likelihood of sVA recurrence in patients at risk. METHODS: Patients with ischemic or non-ischemic cardiomyopathy and recurrent sVA, with an ICD and history of ≥ 1 catheter ablation for sVA will be included. This is a prospective, multicenter, one-arm, dose-escalation trial utilizing the i3 + 3 design, a modified 3 + 3 specifically created to overcome limitations in traditional dose-finding studies. A total of 15 patients will be recruited. The trial aims to escalate the ITV dose from 27.0 Gy to an ITV prescription dose-equivalent level of maximum 35.1 Gy by keeping the PTV prescription dose constant at 25 Gy while increasing the dose to the target (i.e. the VT substrate without PTV margin) by step-wise reduction of the prescribing isodose line (85% down to 65%). The primary outcome of this trial is safety measured by registered radiation associated adverse events (AE) up to 90 days after study intervention including radiation associated serious adverse events graded as at least 4 or 5 according to CTCAE v5, radiation pneumonitis or pericarditis requiring hospitalization and decrease in LVEF ≥ 10% as assessed by echocardiography or cardiac MRI at 90 days after STAR. The sample size was determined assuming an acceptable primary outcome event rate of 20%. Secondary outcomes include sVA burden at 6 months after STAR, time to first sVA recurrence, reduction in appropriate ICD therapies, the need for escalation of antiarrhythmic drugs, non-radiation associated safety and patient reported outcome measures such as SF-36 and EQ5D. DISCUSSION: DEFT-STAR is an innovative prospective phase II trial that aims to evaluate the optimal radiation dose for STAR in patients with therapy-refractory sVA. The trial has obtained IRB approval and focuses on determining the safe and effective radiation dose to be employed in the STAR procedure. TRIAL REGISTRATION: NCT05594368.

Dosimetric analysis of 17 cardiac Sub-structures, Toxicity, and survival in ultra central lung tumor patients treated with SBRT.

•Data on cardiac toxicity after SBRT for ultra-central lung tumors remains limited.•We analyzed the dose to 18 cardiac sub-structures and cardiovascular toxicity.•A SBRT regimen of 45 Gy in 8-10 fractions yields good local control and low toxicity.•The highest cardiac doses were observed in the pulmonary artery and left atrium.•Higher doses to the base of the heart seem to be associated with non-cancer deaths.

Use of the Wearable Cardioverter-Defibrillator Among Patients With Myocarditis and Reduced Ejection Fraction or Ventricular Tachyarrhythmia: Data From a Multicenter Registry.

Background Data on the use of the wearable cardioverter-defibrillator (WCD) among patients with myocarditis remain sparse. Consequently, evidence for guideline recommendations in this patient population is lacking. Methods and Results In total, 1596 consecutive patients were included in a multicenter registry from 8 European centers, with 124 patients (8%) having received the WCD due to myocarditis and reduced left ventricular ejection fraction or prior ventricular tachyarrhythmia. The mean age was 51.6±16.3 years, with 74% being male. Patients were discharged after index hospitalization on heart failure medication: Angiotensin-converting enzyme inhibitors (62.5%), angiotensin-receptor-neprilysin inhibitor (22.9%), aldosterone-antagonists (51%), or beta blockers (91.4%). The initial median left ventricular ejection fraction was 30% (22%-45%) and increased to 48% (39%-55%) over long-term follow-up (P<0.001). The median BNP (brain natriuretic peptide) level at baseline was 1702 pg/mL (565-3748) and decreased to 188 pg/mL (26-348) over long-term follow-up (P=0.022). The mean wear time was 79.7±52.1 days and 21.0±4.9 hours per day. Arrhythmic event rates documented by the WCD were 9.7% for nonsustained ventricular tachycardia, 6.5% for sustained ventricular tachycardia, and 0% for ventricular fibrillation. Subsequently, 2.4% of patients experienced an appropriate WCD shock. The rate of inappropriate WCD shocks was 0.8%. All 3 patients with appropriate WCD shock had experienced ventricular tachycardia/ventricular fibrillation before WCD prescription, with only 1 patient showing a left ventricular ejection fraction <35%. Conclusions Patients with myocarditis and risk for occurrence of ventricular tachyarrhythmia may benefit from WCD use. Prior ventricular arrhythmia might appear as a better risk predictor than a reduced left ventricular ejection fraction <35% in this population.

Recurrences of ventricular tachycardia after stereotactic arrhythmia radioablation arise outside the treated volume: analysis of the Swiss cohort.

AIMS: Stereotactic arrhythmia radioablation (STAR) has been recently introduced for the management of therapy-refractory ventricular tachycardia (VT). VT recurrences have been reported after STAR but the mechanisms remain largely unknown. We analysed recurrences in our patients after STAR. METHODS AND RESULTS: From 09.2017 to 01.2020, 20 patients (68 ± 8 y, LVEF 37 ± 15%) suffering from refractory VT were enrolled, 16/20 with a history of at least one electrical storm. Before STAR, an invasive electroanatomical mapping (Carto3) of the VT substrate was performed. A mean dose of 23 ± 2 Gy was delivered to the planning target volume (PTV). The median ablation volume was 26 mL (range 14-115) and involved the interventricular septum in 75% of patients. During the first 6 months after STAR, VT burden decreased by 92% (median value, from 108 to 10 VT/semester). After a median follow-up of 25 months, 12/20 (60%) developed a recurrence and underwent a redo ablation. VT recurrence was located in the proximity of the treated substrate in nine cases, remote from the PTV in three cases and involved a larger substrate over ≥3 LV segments in two cases. No recurrences occurred inside the PTV. Voltage measurements showed a significant decrease in both bipolar and unipolar signal amplitude after STAR. CONCLUSION: STAR is a new tool available for the treatment of VT, allowing for a significant reduction of VT burden. VT recurrences are common during follow-up, but no recurrences were observed inside the PTV. Local efficacy was supported by a significant decrease in both bipolar and unipolar signal amplitude.

Value of genotyping and scar-phenotyping for VT ablation procedures in patients with nonischemic left ventricular cardiomyopathies.

INTRODUCTION: Variants of cardiomyopathy genes in patients with nonischemic cardiomyopathy (NICM) generate various phenotypes of cardiac scar and delayed enhancement cardiac magnetic resonance (DE-CMR) imaging which may impact ventricular tachycardia (VT) management. METHODS: The objective was to compare the findings of cardiomyopathy genetic testing on DE-CMR imaging and long-term outcomes among patients with NICM undergoing VT ablation procedures. Image phenotyping and genotyping were performed in a consecutive series of patients referred for VT ablation and correlated to survival free of VT. Scar depth index (SDI) (% of scar at 0-3 mm, 3-5 mm and >5 mm projected on the closest endocardial surface) was determined. RESULTS: Forty-three patients were included (11 women, 55 ± 14 years, ejection fraction (EF) 45 ± 16%) and were followed for 3.4 ± 2.9 years. Pathogenic variants (PV) were identified in 16 patients (37%) in the following genes: LMNA (n = 5), TTN (n = 5), DSP (n = 2), AMLS1 (n = 1), MYBPC3 (n = 1), PLN (n = 1), and SCN5A (n = 1). A ring-like septal scar (RLSS) pattern was more often seen in patients with pathogenic variants (66% vs 15%, p = .001). RLSS was associated with deeper seated scars (SDI >5 mm 30.6 ± 22.6% vs 12.4 ± 16.2%, p = .005), and increased VT recurrence (HR 5.7 95% CI[1.8-18.4], p = .003). After adjustment for age, sex, EF, and total scar burden, the presence of a PV remained independently associated with worse outcomes (HR 4.7 95% CI[1.22-18.0], p = .02). CONCLUSIONS: Preprocedural genotyping and scar phenotyping is beneficial to identify patients with a favorable procedural outcome. Some PVs are associated with an intramural, deeper seated scar phenotype and have an increase of VT recurrence after ablation.

Age differences of patients treated with wearable cardioverter defibrillator: Data from a multicentre registry.

BACKGROUND: Wearable cardioverter defibrillators (WCD) are used as a 'bridging' technology in patients, who are temporarily at high risk for sudden cardiac death (SCD). Several factors should be taken into consideration, for example patient selection, compliance and optimal drug treatment, when WCD is prescribed. We aimed to present real-world data from seven centres from Germany and Switzerland according to age differences regarding the outcome, prognosis, WCD data and compliance. MATERIALS AND METHODS: Between 04/2012 and 03/2021, 1105 patients were included in this registry. Outcome data according to age differences (old ≥45 years compared to young <45 years) were analysed. At young age, WCDs were more often prescribed due to congenital heart disease and myocarditis. On the other hand, ischaemic cardiomyopathy (ICM) was more present in older patients. Wear days of WCD were similar between both groups (p = .115). In addition, during the WCD use, documented arrhythmic life-threatening events were comparable [sustained ventricular tachycardia: 5.8% vs. 7.7%, ventricular fibrillation (VF) .5% vs. .6%] and consequently the rate of appropriate shocks was similar between both groups. Left ventricular ejection fraction improvement was documented over follow-up with a better improvement in younger patients as compared to older patients (77% vs. 63%, p = .002). In addition, at baseline, the rate of atrial fibrillation was significantly higher in the older age group (23% vs. 8%; p = .001). The rate of permanent cardiac implantable electronic device implantation (CiED) was lower in the younger group (25% vs. 36%, p = .05). The compliance rate defined as wearing WCD at least 20 h per day was significantly lower in young patients compared to old patients (68.9% vs. 80.9%, p < .001). During the follow-up, no significant difference regarding all-cause mortality or arrhythmic death was documented in both groups. A low compliance rate of wearing WCD is predicted by young patients and patients suffering from non-ischaemic cardiomyopathies. CONCLUSION: Although the compliance rate in different age groups is high, the average wear hours tended to be lower in young patients compared to older patients. The clinical events were similar in younger patients compared to older patients.

Quality assurance process within the RAdiosurgery for VENtricular TAchycardia (RAVENTA) trial for the fusion of electroanatomical mapping and radiotherapy planning imaging data in cardiac radioablation.

A novel quality assurance process for electroanatomical mapping (EAM)-to-radiotherapy planning imaging (RTPI) target transport was assessed within the multi-center multi-platform framework of the RAdiosurgery for VENtricular TAchycardia (RAVENTA) trial. A stand-alone software (CARDIO-RT) was developed to enable platform independent registration of EAM and RTPI of the left ventricle (LV), based on pre-generated radiotherapy contours (RTC). LV-RTC were automatically segmented into the American-Heart-Association 17-segment-model and a manual 3D-3D method based on EAM 3D-geometry data and a semi-automated 2D-3D method based on EAM screenshot projections were developed. The quality of substrate transfer was evaluated in five clinical cases and the structural analyses showed substantial differences between manual target transfer and target transport using CARDIO-RT.

Medical therapy with flecainide and propafenone in atrial fibrillation: Long-term clinical experience in the tertiary care setting.

BACKGROUND: Flecainide and propafenone are Class Ic antiarrhythmic drugs that block the cardiac fast inwards Na+ current and are used for rhythm control in patients with atrial fibrillation (AF). However, data on long-term clinical efficacy and safety of these drugs in a real-world setting are scarce. METHODS: Patients with AF who received chronic flecainide or propafenone therapy were retrospectively studied from the database of a tertiary care center. The primary outcome of the study was clinical efficacy of Class Ic antiarrhythmics, which was assessed based on the improvement of arrhythmia-related symptoms at the time of last follow-up. RESULTS: Among the 361 patients (261 males, 72.3%) with a mean age of 56 ± 12 years, 287 (79.5%) were using long-term flecainide, and 74 (20.5%) patients propafenone. The majority of the patients had paroxysmal AF (n = 331, 91.7%) and had an atrioventricular-nodal blocking co-medication (n = 287, 79.5%). A total of 117 (32%) patients discontinued therapy after a median of 210 days (interquartile range 62-855 days). Clinical efficacy was observed in 188 (52%) patients. The most common reason for therapy discontinuation was adverse drug effects, particularly proarrhythmic effects (48% for flecainide and 33% for propafenone). Patients who did not clinically benefit from Class Ic antiarrhythmics more often underwent pulmonary vein isolation (p = 0.02). CONCLUSIONS: Long-term therapy with Class Ic antiarrhythmics showed clinical efficacy in approximately half of the patients with paroxysmal or persistent AF. However, these drugs were also associated with a relatively high rate of adverse events, and in particular proarrhythmic effects, which often resulted in therapy discontinuation rendering appropriate patient selection and therapy surveillance essential.

Sex differences and adherence of patients treated with wearable cardioverter-defibrillator: Insights from an international multicenter register.

AIMS: Treatment with the wearable cardioverter defibrillator (WCD) may protect against sudden cardiac death (SCD) as a bridging therapy until a cardioverter-defibrillator may be implanted. We analyzed in a multicenter setting a consecutive patient cohort wearing WCD to explore sex differences. METHODS AND RESULTS: We analyzed 708 consecutive patients, 579 (81.8%) from whom were males and 129 (18.2%) females (age, 60.5 ± 14 vs. 61.6 ± 17 years old; p = .44). While the rate of ischemic cardiomyopathy (ICM) as a cause of prescription of WCD was significantly higher in males as compared to females (42.7% vs. 26.4%; p = .001), females received it more frequently due to nonischemic cardiomyopathy (NICM) (55.8% vs. 42.7%); p = .009). The wear time of WCD was equivalent in both groups (21.1 ± 4.3 h/days in males vs. 21.5 ± 4.4 h/days in females; p = .27; and 62.6 ± 44.3 days in males vs. 56.5 ± 39 days in females; p = .15). Mortality was comparable in both groups at 2-year-follow-up (6.8% in males vs. 9.7% in females; p = .55). Appropriate WCD shocks and the incidence of ICD implantations were similar in both groups (2.4% in males vs. 3.9% in females; p = .07) (35.1% in males vs. 31.8% in females; p = .37), respectively. In age tertile analysis, compliance was observed more in 73-91 years old group as compared with 14-51 years old group (87.8% vs. 68.3%; p < .001). CONCLUSION: Compliance for wearing WCD was excellent regardless of sex. Furthermore, mortality and the incidence of ICD implantations were comparable in both sexes. Appropriate WCD shocks were similar in both sexes.

Treatment Planning for Cardiac Radioablation: Multicenter Multiplatform Benchmarking for the RAdiosurgery for VENtricular TAchycardia (RAVENTA) Trial.

PURPOSE: Cardiac radioablation is a novel treatment option for patients with refractory ventricular tachycardia unsuitable for catheter ablation. The quality of treatment planning depends on dose specifications, platform capabilities, and experience of the treating staff. To harmonize the treatment planning, benchmarking of this process is necessary for multicenter clinical studies such as the RAdiosurgery for VENtricular TAchycardia trial. METHODS AND MATERIALS: Planning computed tomography data and consensus structures from 3 patients were sent to 5 academic centers for independent plan development using a variety of platforms and techniques with the RAdiosurgery for VENtricular TAchycardia study protocol serving as guideline. Three-dimensional dose distributions and treatment plan details were collected and analyzed. In addition, an objective relative plan quality ranking system for ventricular tachycardia treatments was established. RESULTS: For each case, 3 coplanar volumetric modulated arc (VMAT) plans for C-arm linear accelerators (LINAC) and 3 noncoplanar treatment plans for robotic arm LINAC were generated. All plans were suitable for clinical applications with minor deviations from study guidelines in most centers. Eleven of 18 treatment plans showed maximal one minor deviation each for target and cardiac substructures. However, dose-volume histograms showed substantial differences: in one case, the planning target volume ≥30 Gy ranged from 0.0% to 79.9% and the ramus interventricularis anterior V14Gy ranged from 4.0% to 45.4%. Overall, the VMAT plans had steeper dose gradients in the high-dose region, while the plans for the robotic arm LINAC had smaller low-dose regions. Thereby, VMAT plans required only about half as many monitor units, resulting in shorter delivery times, possibly an important factor in treatment outcome. CONCLUSIONS: Cardiac radioablation is feasible with robotic arm and C-arm LINAC systems with comparable plan quality. Although cross-center training and best practice guidelines have been provided, further recommendations, especially for cardiac substructures, and ranking of dose guidelines will be helpful to optimize cardiac radioablation outcomes.

Benefits and outcomes of a new multidisciplinary approach for the management and financing of sudden unexplained death cases in a forensic setting in Switzerland.

Sudden cardiac death (SCD) is an important public health issue. In young persons aged between 1 and 40 years, most SCDs are caused by potentially inherited cardiac diseases, often not detectable during conventional medico-legal investigations and therefore termed as sudden unexplained deaths (SUD). In this study, we describe the implementation, feasibility and importance of a standardized procedure to investigate SUD cases within the forensic framework at the Zurich Institute of Forensic Medicine in Switzerland. This new approach involves a multidisciplinary collaboration including forensic autopsy, second pathology expert opinion, post-mortem molecular genetic testing, cardiac counselling of relatives, and a tentative financing. This procedure is in line with the published Swiss and European recommendations on the management of SCDs. During a two-year pilot project, 39 sudden and unexpected death cases were collected, whereof 10 deceased remained without any identifiable cause of death after medico-legal investigation and second expert evaluation. Molecular autopsy, including 393 genes involved in cardio-vascular and metabolic diseases, identified eight pathogenic or likely pathogenic genetic variants in five out of the 10 deceased (50%). Cardio-genetic follow-up investigations in the families of the 10 deceased revealed phenotype-positive relatives in four families and required specific therapies, including an implantable cardioverter defibrillator (ICD) for primary prevention. Multidisciplinary collaboration is crucial for an optimal management of sudden unexplained death cases, to identify additional relatives at risk, and to prevent other tragic deaths within a family.