The association between GJB2 gene (producing Cx26 protein) and the ventricular storm: A case report.

BACKGROUND: A structural heart disease or functional electrical abnormalities can cause an electrical storm. CASE PRESENTATION: We present a young boy with an electrical storm who had no cardiac risk factors and a positive family history of sudden cardiac death. The stepwise diagnostic approach was ineffective in determining previously known causes as the origin of the electrical storm. However, whole-exome sequencing (with Next Generation Illumina Sequencing) revealed a mutation in the GJB2 (NM_004004:exon2:c.G71A:p.W24X) gene. CONCLUSION: A mutation in the GJB2 gene, which forms the connexin 26 protein, a crucial component of the myocytes' intercalated disc of gap junction complex between the myocytes, results in an abnormal electrical cell-by-cell conductance, and, eventually, ventricular storm. General anesthesia was used to control the storm, and intracardiac pacing was fruitful in ceasing the subsequent VT storms.

Cardiovascular Autonomic Modulation in Chronic Coronary Syndrome Following Percutaneous Coronary Intervention.

Introduction The risk of sudden death in patients with chronic coronary syndrome (CCS) is increased by unbalanced cardiovascular autonomic function. Since myocardial ischemia appears to be the cause of this condition of autonomic dysregulation, treating this condition should improve and correct the autonomic functions. Improving myocardial perfusion by PCI might have beneficial effects on the recovery of autonomic balance in ischemia-triggered autonomic dysregulation. Objective In the present study, autonomic modulation in patients with CCS was evaluated before and after percutaneous coronary intervention (PCI) using cardiovascular reflex tests. Methods A total of 30 CCS patients were recruited from the cardiology outpatient department. The patients were tested with cardiovascular reflex tests (lying to standing, 30:15 ratio, Valsalva ratio, isometric handgrip test, and deep breathing test) before and after PCI. The licensed statistical software SPSS version 21.0 was used to compile and analyse the data. Results Out of 30 patients, parasympathetic reactivity tests conducted post-PCI were significantly higher as compared to pre-PCI patients: (1) lying to standing - 30:15 ratio (1.17± 0.102 versus 1.03± 0.064, p=0.000); (2) Valsalva ratio (1.42±0.276 versus 1.02±0.133, p=0.000), (3) delta heart rate in deep breathing test (17.23± 3.004 bpm versus 7.85± 4.076 bpm, p=0.000), and (4) expiration to inspiration (E:I) ratio (1.25± 0.050 versus 1.11± 0.064, p=0.000. Among sympathetic reactivity tests, lying to standing test for fall in systolic blood pressure was significantly higher in the pre-PCI state than post-PCI (-20.73± 10.29 versus -2.33± 7.67, p=0.000). The rise in DBP of the isometric handgrip test was significantly higher in post-PCI compared to pre-PCI patients (36.73±8.39 mm Hg versus 16.63±8.47 mm Hg, p=0.000). Conclusion Resting autonomic tone as determined by cardiovascular reflex testing reveals an increase in both parasympathetic and sympathetic reactivity following PCI in CCS, according to the findings of this preliminary study. As a result, we propose that noninvasive procedures like cardiovascular reflex tests be used to stratify the likelihood of illness development in the future.

Coronary artery anomalies: what are they? when to suspect? how to treat?-a narrative review.

Background and Objective: In the literature have been widely discussed different classification criteria for coronary artery anomalies (CAAs), some authors have tried to categorize them only as "major" or "hemodynamically significant" anomalies versus "minor" or "not hemodynamically significant" ones. However, the most recent literature has concluded that all possible coronary anatomy should be taken into consideration in a comprehensive classification of CAAs. The aim of the article is to review the most recent literature regarding CAAs to provide a comprehensive overview of this challenging topic. Methods: We propose a narrative overview of the most impactful and recent literature, synthetizing and re-elaborating the most important articles concerning CAAs. Key Content and Findings: The important gap of knowledge on the specific characteristics of CAAs has led to a progressively increased interest of the current research in this field. Albeit their nature is still unclear, an increased awareness of their fatality is spreading among clinicians and the general population, mostly associated with their clinical relevance among young patients and athletes. On the other side, we do believe that clinical and hemodynamic repercussions are of crucial importance and should always be integrated to understand the true nature of this important pathology. Conclusions: In the field of pediatric cardiology, CAAs are one of the most fascinating and studied subject. We propose a state-of-the art review to provide a comprehensive and systematic description and subsequently an approach to the epidemiological, pathophysiological, and clinical aspects of the most important CAAs in the pediatric population.

Insights from coronial recommendations for preventing natural deaths in sport and recreation in Québec, Canada.

Introduction: This descriptive retrospective study analyzed coronial recommendations for natural deaths in sport and recreation from January 2006 to December 2019 using data from the Bureau du coroner du Québec. Methods: Reports with recommendations were analyzed by sex, age group, cause of death, context, and activity. The nature of recommendations was assessed using a public health-based model. Thematic analysis was conducted following a four-phase approach in which themes developed were emphasized and further connected with existing literature. Results: Reports involving individuals aged 18-24 and reports related to ice hockey were significantly more likely to contain recommendations. Reports related to individuals ≥45 years old, or related to cycling or hunting had higher death frequencies, but relatively low recommendation rates. Most recommendations aligned with the public health-based model but specifying implementation time frames was rare (11.7%). Nearly 60% of coroner's recommendations focused on automated external defibrillator implementation, delivery and training. Discussion: Mitigation of sudden cardiac arrest risk for individuals ≥45 years old, timely treatment of life-threatening arrhythmias especially for activity practiced in remote regions and specifying implementation time frames were identified as improvement areas. The multi-faceted approach to enhancing public access defibrillation developed by the International Liaison Committee on Resuscitation in 2022 addresses recurrent themes covered by coroners and holds the potential to inform evidence-based decision making.

Arrhythmogenic Mitral Valve Prolapse: Can We Risk Stratify and Prevent Sudden Cardiac Death?

Ventricular arrhythmias associated with mitral valve prolapse (MVP) and the capacity to cause sudden cardiac death (SCD), referred to as 'malignant MVP', are an increasingly recognised, albeit rare, phenomenon. SCD can occur without significant mitral regurgitation, implying an interaction between mechanical derangements affecting the mitral valve apparatus and left ventricle. Risk stratification of these arrhythmias is an important clinical and public health issue to provide precise and targeted management. Evaluation requires patient and family history, physical examination and electrophysiological and imaging-based modalities. We provide a review of arrhythmogenic MVP, exploring its epidemiology, demographics, clinical presentation, mechanisms linking MVP to SCD, markers of disease severity, testing modalities and management, and discuss the importance of risk stratification. Even with recently improved understanding, it remains challenging how best to weight the prognostic importance of clinical, imaging and electrophysiological data to determine a clear high-risk arrhythmogenic profile in which an ICD should be used for the primary prevention of SCD.

A predictable electrocardiogram.

An electrocardiogram of an uncommon congenital heart disease is presented to highlight the unique findings in diagnosis with its clinical implications and predictive value.

Genetic testing for Inherited Arrhythmia Syndromes and Cardiomyopathies: results of the European Heart Rhythm Association Survey.

Indications and clinical impact of genetic testing for cardiac diseases have increased significantly over the past years. The aim of this physician-based EHRA survey was to assess current clinical practice and access to genetic testing for cardiac diseases across ESC countries and to evaluate adherence to the 2022 EHRA/HRS/APHRS/LAHRS Expert Consensus Statement on genetic testing. An online questionnaire composed of 28 questions was submitted to the EHRA Research Network and European Reference Network GUARD-Heart healthcare partners and promoted via dedicated social media channels. There were 357 respondents from 69 countries, 40% working in a hospital setting with a cardiac genetic service and/or a dedicated clinic focusing on inherited cardiac diseases and 27% with an onsite genetic laboratory. No genetic testing or low annual rate (<10/y) was declared by 39% of respondents. The majority of respondents (78%) declared issues or limitations to genetic testing access in their clinical practice. The main reasons for not providing or limited access to genetic testing were no availability of dedicated unit or genetic laboratory (35%) or reimbursement issues (25%). The most frequently reported indication for genetic testing was diagnostic purpose (55%). Most respondents (92%) declared offering genetic testing preceded by genetic counselling and 42% regular multidisciplinary evaluations for patients with cardiac genetic diseases. The perceived value of genetic testing in the diagnostic, prognostic, and therapeutic assessment was variable (67%, 39%, and 29%, respectively) and primarily based on the specific inherited disease. The majority of respondents recommended cascade genetic testing for the first-degree family members in case of pathogenic/likely pathogenic (P/LP) variant in the proband. This survey highlights a significant heterogeneity of genetic testing access and provision and issues attributable to the availability of dedicated unit/genetic laboratory and reimbursement. However, adequate adherence to indications in the current recommendations for genetic testing in patients with cardiac diseases was observed.

Changing landscape of liver transplant in the United States-time for a new innovative way to define and utilize the "non-standard liver allograft"-a proposal.

Since the first liver transplant was performed over six decades ago, the landscape of liver transplantation in the US has seen dramatic evolution. Numerous advancements in perioperative and operative techniques have resulted in major improvements in graft and patient survival rates. Despite the increase in transplants performed over the years, the waitlist mortality rate continues to remain high. The obesity epidemic and the resultant metabolic sequelae continue to result in more marginal donors and challenging recipients. In this review, we aim to highlight the changing characteristics of liver transplant recipients and liver allograft donors. We focus on issues relevant in successfully transplanting a high model for end stage liver disease recipient. We provide insights into the current use of terms and definitions utilized to discuss marginal allografts, discuss the need to look into more consistent ways to describe these organs and propose two new concepts we coin as "Liver Allograft Variables" (LAV) and "Liver Allograft Composite Score" (LACS) for this. We discuss the development of spectrum of risk indexes as a dynamic tool to characterize an allograft in real time. We believe that this concept has the potential to optimize the way we allocate, utilize and transplant livers across the US.

Excellent Outcomes After First-Line Ablation in Post-MI Patients With Tolerated VT and LVEF >35.

BACKGROUND: Post-myocardial infarction (MI) patients with ventricular tachycardia (VT) are considered at risk for VT recurrence and sudden cardiac death (SCD). Recent guidelines indicate that in selected patients catheter ablation should be considered instead of an implantable cardioverter-defibrillator (ICD). OBJECTIVES: This study aimed to analyze outcomes of patients referred for VT ablation according to left ventricular ejection fraction (LVEF), tolerance of VT, and acute ablation outcome. METHODS: Post-MI patients without prior ICD undergoing VT ablation at a single center between 2009 and 2022 were included. Patients who presented with tolerated VT and who had an LVEF >35% were offered catheter ablation as first-line therapy. ICD implantation was offered to all patients but was subject to shared decision according to clinical presentation, LVEF, and ablation outcome. RESULTS: Eighty-six patients (mean age 69 ± 9 years, 84% male, mean LVEF 41 ± 9%) underwent VT ablation. In 66 patients, LVEF was >35%, of whom 51 had tolerated VT. Of these 51 patients, 37 (73%) were rendered noninducible. In 5 of 37 noninducible and in 11 of 14 inducible patients, an ICD was implanted. During a median follow-up of 40 months (Q1-Q3: 24-70 months), 10 of 86 patients had VT recurrence. The overall mortality was 27%, and 1 patient with ICD died suddenly. Among the 37 patients (none on antiarrhythmic drugs) with LVEF >35%, tolerated VT, and noninducibility, no SCD or VT recurrence occurred. Among the 14 patients with LVEF >35%, tolerated VT, and inducibility after ablation, no SCD occurred, but VT recurred in 29%. CONCLUSIONS: Post-MI patients with LVEF >35%, tolerated VT, and noninducibility after ablation have an excellent prognosis. Deferring ICD implantation seems to be safe in these patients.

A Rare Case of Symptomatic Anomalous Origin of the Right Coronary Artery With a High Interarterial Course Between the Pulmonary Artery and the Aorta.

The congenital anomalous origin of the right coronary artery (AORCA) with an incongruous course is a rare malformation that can manifest as exertional chest pain, syncope, arrhythmias, heart failure, and sudden cardiac death. We present a case of a 42-year-old male with a history of hypercholesterolemia who presented with chest pain and dizziness upon exertion for two weeks. The physical examination was unremarkable, and the patient was hemodynamically stable. Initial blood tests were normal. Electrocardiogram (ECG) showed sinus bradycardia at 56 bpm without ST or T wave changes. A cardiac stress test indicated antero-apical inducible ischemia with a moderate probability of stress-induced ischemia. Computed tomography angiography (CTA) revealed an AORCA with a high interarterial course between the pulmonary artery and the aorta. Subsequent left heart catheterization confirmed the anomalous origin and revealed atherosclerotic disease. This anomaly was identified as the cause of the patient's symptoms due to the compression of the right coronary artery (RCA). The patient was treated with aspirin and statin and underwent successful internal mammary artery-RCA bypass grafting. Postoperatively, the patient's symptoms resolved, and there were no further episodes of chest pain.

Case report: arrhythmic mitral valve prolapse syndrome-are risk factors underdiagnosed?

Background: Arrhythmic mitral valve prolapse syndrome (ARMV) is a recognized but underdiagnosed disease pattern. Risk factors for ARMV are established but not very well known, and the association of the structural abnormality with ventricular arrhythmias is incompletely understood. Case summary: Here, we present the case of a young man who presented at our hospital for radiofrequency catheter ablation and mitral valve surgery after two episodes of survived sudden cardiac arrest. We discuss the diagnostic and therapeutic strategies that were used. We shine light on the risk factors for ARMV and why early identification is crucial. We address the topic of primary prevention and its limitations. Finally, we discuss different treatment modalities for patients with ARMV. Discussion: More awareness for ARMV is crucial. A consensus statement on clinical management exists, but scientific gaps in prospective data for primary prevention need to be filled and there is a need for a better understanding of the pathogenesis of ARMV.

Age, sex, and pre-arrest comorbidities shape the risk trajectory of sudden cardiac death- Patterns highlighted by population data in Taiwan.

OBJECTIVES: Few reports have indicated the secular trend in the sudden cardiac death (SCD) incidence and pre-arrest comorbidities. This study aimed to comprehensively analyze the trend of SCD incidence and its association with pre-arrest comorbidities. METHODS: This population-based cohort study analyzed Taiwan's National Health Insurance (NHI) research database and identified SCD incidents by inspecting data from all emergency department visits from 2011 to 2018. The inclusion criteria were ICD-9:427.5 or 427.41, or ICD-10:I46.9, I46.8, or I46.2. Pre-existing comorbidities were confirmed based on medication use. Multivariable logistic regression was adopted with covariates age, sex, and pre-existing comorbidities. RESULTS: This study reviewed a total of 184,164,969 person-year records, and identified 92,138 SCD incidents. From 2011 to 2018, the SCD incidence rate increased from 36.3 to 55.4 per 100,000 enrollees in Taiwan. The top five pre-arrest comorbidities were stable, while the prevalence of chronic kidney disease rose significantly. Compared to those aged 20-29, enrollees aged >65 years had significantly higher odds of SCD (aOR:27.30, 95% CI:26.05-28.61). Higher odds of SCD were noted in the enrollees who had a seizure (aOR:2.24, 95% CI:2.12-2.38), parkinsonism (aOR:1.81, 95% CI:1.73-1.89), psychological disorders (aOR:1.59, 95% CI:1.56-1.62), diabetes mellitus (aOR:1.44, 95% CI:1.41-1.46), heart diseases (aOR:1.41, 95% CI:1.38-1.44). CONCLUSIONS: The incidence of SCD steadily increased in Taiwan from 2011 to 2018. Hypertension, diabetes mellitus, heart disease, psychological disorders, and arthritis were major pre-arrest comorbidities. Age is the most important risk factor for SCD. Further large-scaled population-based study that investigated in diverse ethnicities from countries in addition to Asians would be warranted.

Opioid Use and the Risk of Ventricular Arrhythmias: A Systematic Review and Meta-Analysis.

BACKGROUND: The association between opioid use and the risk of ventricular arrhythmias (VA) is poorly understood. AIMS: The objective of this study was to synthesize the evidence on the risk of VA associated with opioid use. MATERIALS & METHODS: We systematically searched the Cochrane Library, Embase, MEDLINE, and CINAHL databases in July 2022. Risk of bias was assessed using the Cochrane risk for bias tool for randomized controlled trials (RCTs) and ROBINS-I for observational studies. Certainty of evidence was assessed using GRADE. RESULTS: We included 15 studies (12 observational, 2 post hoc analyses of RCTs, 1 RCT). Most studies focused on opioid use for maintenance therapy (n = 9), comparing methadone to buprenorphine (n = 13), and reported QTc prolongation (n = 13). Six observational studies had a critical risk of bias, and one RCT was at high risk of bias. Two studies could not be included in the meta-analysis as they reported a different outcome and studied an opioid antagonist. Meta-analysis of 13 studies indicated that the use of methadone was associated with an increased risk of VA compared to the use of buprenorphine, morphine, placebo, or levacetylmethadol (risk ratio [RR], 2.39; 95% CI, 1.31-4.35; I2 = 60%). The pooled estimate varied greatly between observational studies (RR, 2.12; 95% CI, 1.15-3.91; I2 = 62%) and RCTs (RR, 14.09; 95% CI, 1.52-130.61; I2 = 0%), but both indicated an increased risk. CONCLUSION: In this systematic review and meta-analysis, we found that methadone use is associated with more than twice the risk of VA compared to comparators. However, our findings should be interpreted cautiously given the limited quality of the available evidence.

Prognostic value of non-invasive programmed ventricular stimulation after VT ablation to predict VT recurrences.

BACKGROUND: The prognostic value of (non)-invasive programmed ventricular stimulation (NIPS) to predict recurrences of ventricular tachycardia (VT) is under discussion. Optimal endpoints of VT ablation are not well defined, and optimal timepoint of NIPS is unknown. The goal of this study was to evaluate the ability of programmed ventricular stimulation at the end of the VT ablation procedure (PVS) and NIPS after VT ablation to identify patients at high risk for VT recurrence. METHODS: Between January 2016 and February 2022, consecutive patients with VT and structural heart disease undergoing first VT ablation and consecutive NIPS were included. In total, 138 patients were included. All patients underwent NIPS through their implanted ICDs after a median of 3 (1-5) days after ablation (at least 2 drive cycle lengths (500 and 400 ms) and up to four right ventricular extrastimuli until refractoriness). Clinical VT was defined by comparison with 12-lead electrocardiograms and stored ICD electrograms from spontaneous VT episodes. Patients were followed for a median of 37 (13-61) months. RESULTS: Of the 138 patients, 104 were non-inducible (75%), 27 were inducible for non-clinical VTs (20%), and 7 for clinical VT (5%). In 107 patients (78%), concordant results of PVS and NIPS were observed. After 37 ± 20 months, the recurrence rate for any ventricular arrhythmia was 40% (normal NIPS 29% vs. inducible VT during NIPS 66%; log-rank p = 0.001) and for clinical VT was 3% (normal NIPS 1% vs. inducible VT during NIPS 9%; log-rank p = 0.045). Positive predictive value (PPV) and negative predictive value (NPV) of NIPS were higher compared to PVS (PPV: 65% vs. 46% and NPV: 68% vs. 61%). NIPS revealed the highest NPV among patients with ICM and LVEF > 35%. Patients with inducible VT during NIPS had the highest VT recurrences and overall mortality. Patients with both negative PVS and NIPS had the lowest any VT recurrence rates with 32%. Early re-ablation of patients with recurrent VTs during index hospitalization was feasible but did not reveal better long-term VT-free survival. CONCLUSIONS: In patients after VT ablation and structural heart disease, NIPS is superior to post-ablation PVS to stratify the risk of VT recurrences. The PPV and NPV of NIPS at day 3 were superior compared to PVS at the end of the procedure to predict recurrent VT, especially in patients with ICM.

Implantable cardioverter defibrillator explantation upon patient request: Clinical and ethical considerations.

BACKGROUND: Implantable Cardioverter Defibrillator (ICD) implantation has significantly modified the natural history of patients at high risk of sudden cardiac death (SCD) in various types of heart diseases. However there is a high rate of psychological distress and reduced quality of life in patients with an ICD, more evident in younger individuals. The ICD removal upon patient request is a very rare event and causes many clinical and ethical issues. METHODS: The article discusses the case of a young patient affected by hypertrophic obstructive cardiomyopathy, who underwent implantable cardioverter defibrillator (ICD) implantation as a primary prevention of sudden cardiac death (SCD). Two years after the implantation, the patient repeatedly requested removal of the ICD due to of a significant and untreatable psychological device intolerance. RESULTS: Intervention became possible only after extensive psychological evaluation, which excluded specific pathology, and the ratification of Italian law 219/2017 on informed consent and advance directives, which guarantees the patient's independent decisions on current and future medical treatment. The explantation was performed 7 years after the implant. The patient is alive and in good health. CONCLUSIONS: The paper debates the issues related to establishing a patient-physician relationship based on respect for the patient's autonomy and experience of illness, in reference to principles such as beneficence and non-maleficence, and the conflicts that sometimes arise between them. If a paternalistic approach in the patient-physician relationship evolves into a patient-centered model, it is more certain that the patient's choice is realistically known and shared, and that it is consistent with the patient's values and life goals. The shared decision making (SDM) process and the use of pathology-specific decision aids are able to transform the informed consent tool, usually related to medical-legal issues, into an aid for true partnership between the patient and the medical care team.

Decision-making regarding subcutaneous implantable cardioverter defibrillator as primary prevention in patients with low ejection fraction.

BACKGROUND: Conventional transvenous implantable cardioverter-defibrillator (TV-ICD) is the standard device used for primary prevention of sudden cardiac death (SCD) in patients with reduced left ventricular ejection fraction (LVEF). Nonetheless its use is associated with lead-related complications including infection and malfunction. A subcutaneous implantable cardioverter-defibrillator (S-ICD) offers an alternative option without the need for a transvenous lead but has limitations. The decision to implant a TV-ICD or S-ICD in patients with impaired LVEF for primary prevention of SCD is controversial. Several randomised controlled trials and large observational studies have confirmed similar safety and efficacy of S-ICDs and TV-ICDs in such population. METHODS: A literature review was conducted to compare the outcomes of subcutaneous (S-ICD) versus transvenous (TV-ICD) implantable cardioverter-defibrillators. Databases including PubMed, MEDLINE, and Cochrane were searched for relevant peer-reviewed articles. Studies were selected based on relevance and quality. Key outcomes like complication rates, efficacy, and patient survival were summarized in a comparative table. RESULTS: Different factors that influence the choice between an TV-ICD and S-ICD for primary prevention of SCD in patients with LVEF are highlighted to guide selection of the appropriate device in different patient populations. Moreover, future perspective on the combination of SICD with leadless pacemaker, and the latest development of the extravascular implantable cardioverter defibrillator are also discussed. CONCLUSIONS: S-ICD offers a safe and efficacious option to primary prevention in reduced ejection fraction. Future development including incorporation of leadless pacemaker will add to the arsenal of choice to protect patients from sudden cardiac death.