The purpose of this study was to analyze the potential usefulness and clinical relevance of adding left atrial (LA) strain to left atrial volume index (LAVI) in the detection of left ventricular ...diastolic dysfunction (LVDD) in patients with preserved left ventricular ejection fraction (LVEF).
Recent studies have suggested that LA strain could be of use in the evaluation of LVDD. However, the potential utility and clinical significance of adding LA strain to LAVI in the detection of LVDD remains uncertain.
Using 2-dimensional speckle-tracking echocardiography, we analyzed a population of 517 patients in sinus rhythm at risk for LVDD such as those with arterial hypertension, diabetes mellitus, or history of coronary artery disease and preserved LVEF.
In patients with LV diastolic alterations and estimated elevated LV filling pressures, the rate of abnormal LA strain was significantly higher than an abnormal LAVI (62.4% vs. 33.6%, p < 0.01). In line with this, in patients with normal LAVI, high rates of LV diastolic alterations and abnormal LA strain were present (rates 80% and 29.4%, respectively). In agreement with these findings, adding LA strain to LAVI in the current evaluation of LVDD increased significantly the rate of detection of LVDD (relative and absolute increase 73.3% and 9.9%; rate of detection of LVDD: from 13.5% to 23.4%; p < 0.01). Regarding the clinical relevance of these findings, an abnormal LA strain (i.e., <23%) was significantly associated with worse New York Heart Association functional class, even when LAVI was normal. Moreover, in a retrospective post hoc analysis an abnormal LA strain had a significant association with the risk of heart failure hospitalization at 2 years (odds ratio: 6.6 95% confidence interval: 2.6 to 16.6) even adjusting this analysis for age and sex and in patients with normal LAVI.
The findings from this study provide important insights regarding the potential usefulness and clinical relevance of adding LA strain to LAVI in the detection of LVDD in patients with preserved LVEF.
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Introduction
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by adrenergically stimulated ventricular tachycardia. The most common form ...of CPVT is due to autosomal dominant variants in the cardiac ryanodine‐receptor gene (RYR2). However, trans‐2,3‐enoyl‐CoA reductase‐like (TECRL) was recently suggested to be a novel candidate gene for life‐threatening inherited arrhythmias. Patients previously reported with pathogenic changes in TECRL showed a special mixed phenotype of CPVT and long‐QT‐syndrome (LQTS) termed CPVT type 3 (CPVT3), an autosomal recessive disorder.
Methods and Results
We implemented TECRL into our NGS panel diagnostics for CPVT and LQTS in April 2017. By December 2018, 631 index patients with suspected CPVT or LQTS had been referred to our laboratory for genetic testing. Molecular analysis identified four Caucasian families carrying novel variants in TECRL. One patient was homozygous for Gln139* resulting in a premature stop codon and loss‐of‐function of the TECRL protein. Another patient was homozygous for Pro290His, probably leading to an altered folding of the 3‐oxo‐5‐alpha steroid 4‐dehydrogenase domain of the TECRL protein. The LOF‐variant Ser309* and the missense‐variant Val298Ala have been shown to be compound heterozygous in another individual. NGS‐based copy number variation analysis and quantitative PCR revealed a quadruplication of TECRL in the last individual, which is likely to be a homozygous duplication.
Conclusion
The data from our patient collective indicate that CPVT3 occurs much more frequently than previously expected. Variants in TECRL may be causative in up to 5% of all CPVT cases. According to these findings, the default analysis of this gene is recommended if CPVT is suspected.
DETECT AF Study Results
Introduction
Reliable detection and monitoring of atrial fibrillation (AF) is essential for accurate clinical decision making, which can now be done continuously with the ...introduction of implantable cardiac monitors (ICM) The DETECT AF study evaluated the performance of the Confirm DM2102 ICM (St. Jude Medical, St. Paul, MN, USA) to accurately detect and monitor AF.
Methods
Ninety patients previously implanted with the ICM and with either suspected or known paroxysmal AF were enrolled at 12 centers in Germany and The Netherlands. At least 2 weeks after ICM implant, patients wore a Holter monitor for 4 days, while the ICM monitored for AF episodes lasting at least 2 minutes. Holter monitor data was analyzed by a blinded, independent core laboratory and compared to the ICM AF detections. Patient and episode sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive (NPV) were calculated using standard analysis and a generalized estimation equation method where appropriate.
Results
A total of 79/90 subjects (61% male, 65.7 ± 9.6 years old) were included in the analysis, totaling 6,894 hours of Holter monitoring. Using a per patient analysis SE was 100%, PPV was 64.0%, SP was 85.7%, and NPV was 100%. Using a per episode analysis, SE was 94.0% and PPV was 64.0%. With an AF duration analysis, the SE was 83.9%, PPV was 97.3%, SP was 99.4% with an NPV of 98.5%.
Conclusion
The SJM Confirm DM2102 can accurately and repeatedly detect paroxysmal AF episodes of at least 2 minutes in length.
Introduction
Radiofrequency (RF) ablation is a commonly used tool in the invasive electrophysiology laboratory to treat a variety of rhythm disorders. Reliable creation of transmural ablation lesions ...is crucial for long‐term success. Lesion size index (LSI) is a multiparametric index that incorporates time, power, contact force (CF), and impedance data recorded during RF ablation in a weighted formula and has been shown to predict the extent of myocardial tissue lesions. Whether the force stability of contact influences lesion size in LSI‐guided ablations is unknown.
Objectives
The aim of this study was to analyze the influence of the force stability of contact on lesion size during LSI‐guided ablations in an ex‐vivo model.
Methods and Results
A total of 267 RF lesions (n = 6 hearts) were created on porcine myocardial slabs by using an open‐tip irrigated ablation catheter with the following settings: 35 W with either intermittent (varied between 0 and up to 20 g), variable (10 to 20 g), or constant tissue contact (15 g) in a perpendicular or parallel fashion (applied manually) up to a target LSI of either 5 or 6. Subsequently, lesion width and depth were determined. Lesion width was mainly influenced by catheter tip orientation and LSI, whereas lesion depth was mainly influenced by LSI alone. The force stability of catheter contact had no relevant impact on lesion width or depth.
Conclusion
The force stability of catheter contact has only little effect on lesion depth or width in LSI‐guided catheter ablation while the catheter orientation primarily affects lesion width.
Background
Single-session high-dose stereotactic radiotherapy (radiosurgery) is a new treatment option for otherwise untreatable patients suffering from refractory ventricular tachycardia (VT). In ...the initial single-center case studies and feasibility trials, cardiac radiosurgery has led to significant reductions of VT burden with limited toxicities. However, the full safety profile remains largely unknown.
Methods/design
In this multi-center, multi-platform clinical feasibility trial which we plan is to assess the initial safety profile of radiosurgery for ventricular tachycardia (RAVENTA). High-precision image-guided single-session radiosurgery with 25 Gy will be delivered to the VT substrate determined by high-definition endocardial electrophysiological mapping. The primary endpoint is safety in terms of successful dose delivery without severe treatment-related side effects in the first 30 days after radiosurgery. Secondary endpoints are the assessment of VT burden, reduction of implantable cardioverter defibrillator (ICD) interventions shock, anti-tachycardia pacing (ATP), mid-term side effects and quality-of-life (QoL) in the first year after radiosurgery. The planned sample size is 20 patients with the goal of demonstrating safety and feasibility of cardiac radiosurgery in ≥ 70% of the patients. Quality assurance is provided by initial contouring and planning benchmark studies, joint multi-center treatment decisions, sequential patient safety evaluations, interim analyses, independent monitoring, and a dedicated data and safety monitoring board.
Discussion
RAVENTA will be the first study to provide the initial robust multi-center multi-platform prospective data on the therapeutic value of cardiac radiosurgery for ventricular tachycardia.
Trial registration number
NCT03867747 (clinicaltrials.gov). Registered March 8, 2019. The study was initiated on November 18th, 2019, and is currently recruiting patients.
Graphic abstract
...in selected patients, electro‐anatomical mapping allows the quantification and localization of low‐voltage areas to assess an additional local functional parameter of atrial remodelling. LA ...emptying fraction and LA strain are also reduced in HF with preserved ejection fraction (HFpEF) in clinical studies and randomized controlled trials e.g. Effect of Phosphodiesterase‐5 Inhibition on Exercise Capacity and Clinical Status in Heart Failure with Preserved Ejection Fraction (RELAX trial) substudy and Candesartan in Heart failure ‐ Assessment of moRtality and Morbidity (CHARM trial)‐preserved. Clinical impact of atrial remodelling and relevance in heart failure with preserved ejection fraction Atrial remodelling as risk biomarker Left atrial volume index is strongly associated with cardiovascular disease and a predictor of new HF irrespective of systolic left ventricular (LV) function. Melenovsky et al. have shown that preserved LA function was significantly associated with lower mortality in HFpEF. ...in HFpEF, impaired LA conduit function is associated with exercise intolerance, independent of LV stiffness and relaxation.
Ventricular tachycardia (VT) is a potentially lethal complication of structural heart disease. Despite optimal management, a subgroup of patients continue to suffer from recurrent VT. Recently, ...cardiac stereotactic body radiotherapy (CSBRT) has been introduced as a treatment option in patients with VT refractory to antiarrhythmic drugs and catheter ablation.
The purpose of this study was to establish an expert consensus regarding the conduct and use of CSBRT for refractory VT.
We conducted a modified Delphi process. Thirteen experts from institutions from Germany and Switzerland participated in the modified Delphi process. Statements regarding the following topics were generated: treatment setting, institutional expertise and technical requirements, patient selection, target volume definition, and monitoring during and after CSBRT. Agreement was rated on a 5-point Likert scale. The strength of agreement was classified as strong agreement (≥80%), moderate agreement (≥66%) or no agreement (<66%).
There was strong agreement regarding the experimental status of the procedure and the preference for treatment in clinical trials. CSBRT should be conducted at specialized centers with a strong expertise in the management of patients with ventricular arrhythmias and in stereotactic body radiotherapy for moving targets. CSBRT should be restricted to patients with refractory VT with optimal antiarrhythmic medication who underwent prior catheter ablation or have contraindications. Target volume delineation for CSBRT is complex. Therefore, interdisciplinary processes that should include cardiology/electrophysiology and radiation oncology as well as medical physics, radiology, and nuclear medicine are needed. Optimal follow-up is required.
Prospective trials and pooled registries are needed to gain further insight into this promising treatment option for patients with refractory VT.
Background
Implantable cardioverter defibrillators use low‐voltage shock impedance measurements to monitor the lead integrity. However, previous case reports suggest that low‐voltage shock impedance ...measurements may fail to detect insulation breaches that can cause life‐threatening electrical short circuits.
Methods and results
We report six cases of insulation breaches in transvenous defibrillation leads that were not obvious during standard interrogations and testing of the lead beforehand. In two cases, an electrical short circuit during commanded shock delivery for internal electrical cardioversion resulted in a total damage of the ICD generator. In one of these cases, commanded shock delivery induced ventricular fibrillation, which required external defibrillation. In two cases, a shock due to ventricular tachycardia was aborted as the shock impedance was less than 20 Ω. However, in both cases the tiny residual shock energy terminated the ventricular tachycardia. In contrast, in one case the residual energy of the aborted shock did not end ventricular fibrillation induced at defibrillator threshold testing. In one case, the ICD indicated an error code for a short circuit condition detected during an adequate shock delivery.
Conclusions
This case series illustrates that low‐voltage shock impedance measurements can fail to detect insulation breaches. These data suggest that in patients without a contraindication, traditional defibrillator threshold testing or high voltage synchronized shock at the time of device replacement should be considered.
Background
Implantable loop recorders (ILR) are valuable tools for the investigation of patients with suspected arrhythmias. The BioMonitor 2‐AF is a novel insertable ILR with enhanced atrial ...fibrillation (AF) detection algorithm and remote monitoring capability.
Objective
The objective of this first‐in‐human study with the BioMonitor 2‐AF was to analyze course of P‐wave sensing performance and R‐wave amplitude, prevalence of false and correctly sensed and classified episodes, and effectiveness of remote monitoring.
Methods
All 19 patients who underwent ILR insertion were included in the BIOTRONIK Home Monitoring® system (BIOTRONIK GmbH, Berlin, Germany). Daily changes in P‐wave and R‐wave sensing were analyzed over 6 weeks. A breathing test (in‐ and expiration) was performed in two different body positions at baseline and during a 6‐week in‐house follow‐up to investigate alterations of P‐wave and R‐wave sensing.
Results
R‐wave amplitude and the high P‐wave visibility (94.4%) remained unchanged during the follow‐up period. In most patients both an increase and decrease of R‐wave amplitude, and in some cases a complete R‐wave vector change (31.6%), was documented during the “breathing test.” Change of body position did not alter R‐wave sensing amplitude mostly. “Breathing test” and change of body position had no effect on P‐wave sensing performance. In 15.8% of the patients, misclassification of episodes as AF or high ventricular rates due to P‐wave oversensing occurred. No ILR‐related complication occurred. Automatic transmission via BIOTRONIK Home Monitoring® was successful 100% of the time.
Conclusion
This study demonstrates that the BioMonitor 2‐AF is a safe and effective tool for continuous cardiac monitoring.
Background Cardiac injury associated with cytokine release frequently occurs in SARS-CoV-2 mediated coronavirus disease (COVID19) and mortality is particularly high in these patients. The mechanistic ...role of the COVID19 associated cytokine-storm for the concomitant cardiac dysfunction and associated arrhythmias is unclear. Moreover, the role of anti-inflammatory therapy to mitigate cardiac dysfunction remains elusive. Aims and methods We investigated the effects of COVID19-associated inflammatory response on cardiac cellular function as well as its cardiac arrhythmogenic potential in rat and induced pluripotent stem cell derived cardiomyocytes (iPS-CM). In addition, we evaluated the therapeutic potential of the IL-1beta antagonist Canakinumab using state of the art in-vitro confocal and ratiometric high-throughput microscopy. Results Isolated rat ventricular cardiomyocytes were exposed to control or COVID19 serum from intensive care unit (ICU) patients with severe ARDS and impaired cardiac function (LVEF 41±5%; 1/3 of patients on veno-venous extracorporeal membrane oxygenation; CK 154±43 U/l). Rat cardiomyocytes showed an early increase of myofilament sensitivity, a decrease of Ca.sup.2+ transient amplitudes and altered baseline Ca.sup.2+ upon exposure to patient serum. In addition, we used iPS-CM to explore the long-term effect of patient serum on cardiac electrical and mechanical function. In iPS-CM, spontaneous Ca.sup.2+ release events were more likely to occur upon incubation with COVID19 serum and nuclear as well as cytosolic Ca.sup.2+ release were altered. Co-incubation with Canakinumab had no effect on pro-arrhythmogenic Ca.sup.2+ release or Ca.sup.2+ signaling during excitation-contraction coupling, nor significantly influenced cellular automaticity. Conclusion Serum derived from COVID19 patients exerts acute cardio-depressant and chronic pro-arrhythmogenic effects in rat and iPS-derived cardiomyocytes. Canakinumab had no beneficial effect on cellular Ca.sup.2+ signaling during excitation-contraction coupling. The presented method utilizing iPS-CM and in-vitro Ca.sup.2+ imaging might serve as a novel tool for precision medicine. It allows to investigate cytokine related cardiac dysfunction and pharmacological approaches useful therein.
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