Survivors Of Sudden Cardiac Death Research Articles

Cardiac autonomic dysfunction in adult congenital heart disease

PurposeDue to recent advances in diagnosis and treatment, the number of adults with congenital heart disease (ACHD) has substantially increased. This achievement is mitigated by rhythm disorders. Here, we sought to determine alterations in heart rate variability (HRV) and their prognostic value in ACHD.MethodsNinety seven ACHD patients (39.2 ± 14.1 years, 51.5% female) and 19 controls (39.7 ± 15.0 years, 47.4% female) underwent 24-h Holter monitoring.ResultsAs compared to controls, ACHD patients offered a significantly higher burden of premature ventricular contractions (p = 0.02) and decreased HRV indices (natural logarithmic transformation of very low frequency (lnVLF): 7.46 ± 0.76 ms2 vs. 7.91 ± 0.92ms2, p = 0.03; natural logarithmic transformation of low frequency (lnLF): 6.39 ± 0.95ms2 vs. 7.01 ± 1.07ms2, p = 0.01; natural logarithmic transformation of the ratio of low to high frequency spectra (lnLF/HF): 0.81 ± 0.74 vs. 1.17 ± 0.51, p = 0.04). No differences in HRV measures were observed across ACHD lesion groups. NT-proBNP levels were significantly related to both time and frequency domain indices (natural logarithmic transformation of the standard deviation of NN intervals (lnSDNN): Spearman´s rho = -0.32, p = 0.001; natural logarithmic transformation of the standard deviation of the average NN intervals for each 5-min segment of a 24-h Holter monitoring (lnSDANN): Spearman´s rho: -0.33, p = 0.001; natural logarithmic transformation of the total power (lnTP): Spearman´s rho: -0.25, p = 0.01; lnVLF: Spearman´s rho: -0.33, p = 0.001; lnLF: Spearman´s rho: -0.35, p < 0.001; lnLF/HF: Spearman´s rho: -0.34, p = 0.001).After a mean follow-up of 3.9 ± 0.7 years, 8 patients died and 3 patients survived sudden cardiac death (SCD). Several HRV parameters were significantly higher in event-free ACHD patients than in those who died or survived SCD (natural logarithmic transformation of the average of the standard deviations of NN intervals for each 5-min segment of a 24-h Holter monitoring (lnASDNN): p = 0.04; lnPNN30: p = 0.04; lnVFL: p = 0.03; lnLF: p < 0.01). On univariate Cox regression analysis, the time domain indices lnSDNN, lnASDNN and lnPNN30, as well as the frequency domain parameters lnTP, lnVLF and lnLF were associated with death and survived cardiac arrest.ConclusionACHD is accompanied by HRV impairment that carries prognostic implications on ACHD mortality and survived SCD.

Role of localized repolarization and conduction heterogeneities in ventricular arrhythmias and sudden cardiac death

Recent clinical studies have indicated the presence of localized tissue abnormalities in sudden cardiac death (SCD) survivors without apparent structural heart disease, including idiopathic ventricular fibrillation (VF) and J-wave Syndromes. The origin of these abnormalities, showing distinct electrical features on contact mapping, and mechanisms of associated arrhythmias are still a matter of debate. To determine the respective role of localized repolarization and conduction heterogeneities in vulnerability to arrhythmias and SCD, and to characterize their specific electrical signatures. Optical mapping was performed on porcine right ventricular models of either local (i) repolarization shortening, (ii) conduction slowing, or (iii) micro-structural heterogeneity which were created by locally perfusing (i) pinacidil (20 μM n = 13) or (ii) flecainide (2 μM n = 13) via an epicardial catheter (branch of right coronary artery), or (iii) by local epicardial tissue destruction through radiofrequency application (9 micro lesions 30W 1 sec n = 13). Pseudo-ECG were assessed and the number of induced and spontaneous arrhythmias were quantified and mapped in each preparation. An HD grid mapping catheter was used to record bipolar electrograms (n = 5 in each group). Electrograms were normal in model (i), but showed local fragmentation in 40% of preparations in model (ii) with greater effects observed at high pacing frequencies (3 Hz). In model (iii), the structural substrate alone increased the width and number of peaks in the electrograms, and addition of flecainide (2 μM) in this model induced pronounced fragmentation (≥ 3 peaks and ≥ 70ms duration) in 100% of the cases. Arrhythmogenicity was significantly increased in models (i) and (ii) which presented 82% and 45% more spontaneous arrhythmias (P < 0.0001 and 0.05 vs. baseline) and a reduced pacing frequency threshold to induce arrhythmias (−69% and −50%, P < 0.001 vs. baseline). In these models, the frequency of spontaneous activity was increased (+411% P < 0.01 and +181% P < 0.05 vs. baseline) and originated near the heterogeneous area. Microstructural substrates have the most pronounced impact on electrograms, especially when combined with sodium channel blockers, while repolarization heterogeneities do not lead to electrogram fragmentation but are associated with the highest prevalence of spontaneous arrhythmias. Both heterogeneities show increased ectopic activity.

Cardiac Magnetic Resonance as an Etiological Diagnosis Tool in Recovered Sudden Cardiac Death or Unstable Ventricular Arrhythmia Patients.

Cardiac magnetic resonance (CMR) has an increasing diagnostic relevance in survivors of sudden cardiac death (SCD) or unstable ventricular arrhythmia (UVA) in developed countries. To evaluate retrospectively the additional role of CMR in a developing country where few resources are available, and should be used more effectively. The study included SCD or UVA survivors admitted between 2009 and 2019 at a tertiary academic institution referred to CMR. Demographic, clinical, and laboratory data were collected from the medical records. CMR images and reports were reviewed and their impact on the final etiological diagnosis was determined. A descriptive analysis was performed and p<0.05 established as significant. Sixty-four patients, 54.9±15.4 years old, and 42 (71.9%) males. Most events (81.3%) were out of the hospital and ventricular tachycardia was the most common rhythm. Cardiovascular medications were previously used by 55 patients, and beta-blockers were the most used medications (37.5%). Electrocardiogram had electrical inactive areas in 21.9% and all of them had fibrosis at CMR. Mean left ventricular ejection fraction (LVEF) was 44±14%, with 60.9% ≤50% and only 29.7% ≤35%. Late gadolinium enhancement was identified in 71.9%, with a transmural pattern in 43.8%. Chagas cardiomyopathy was the most common etiology (28.1%), followed by ischemic cardiomyopathy (17.2%). Among 26 without a previously identified etiology, CMR could define it (15 patients - 57%). In accordance with previous studies in developed countries, CMR was capable of increasing etiological diagnosis and identifying the arrhythmogenic substrate, allowing better care in half of the underdiagnosed patients.

Meta-Analysis on Early Versus Delayed Coronary Angiography for Patients With Out-of-Hospital Cardiac Arrest Without ST-Elevation Myocardial Infarction

An estimated 424, 000 patients experience out-of-hospital cardiac arrest (OHCA) annually across the United States, and only ∼10% of patients survive to hospital discharge.12 Coronary artery disease (CAD) is the most common cause of OHCA, with a prevalence as high as 70% to 80%.3–5 Although CAD is the leading cause of OHCA, there has been a dramatic increase in OHCA due to drug overdose.6 Current guidelines recommend emergent coronary angiography among survivors of sudden cardiac death with ST-elevation myocardial infarction (STEMI) and no obvious noncardiac cause of cardiac arrest.

Late ventricular potential for risk prediction of sudden cardiac death risk: a valuable tool or an unnecessary step?

Abstract Background/Introduction Signal-averaged electrocardiography (SA-ECG) is a high-resolution electrocardiography that can detect late ventricular potential, which known to be a noninvasive tool for risk stratification of sudden cardiac death (SCD) by predicting reentrant ventricular tachyarrhythmia. There is a paucity of data with SA-ECG on SCD survivors without structural heart disease, whereas majority of previous studies had been focused on post myocardial infarction survivors. Purpose This study assessed the clinical utility of SA-ECG as a risk stratification modality for lethal arrhythmic event in patients at risk of SCD without definite structural heart disease. Methods Total 629 patients who experienced or had potential risk of SCD were studied with SA-ECG. Among them, 48 patients who were found to have significant structural heart disease were excluded, except arrhythmogenic right ventricular cardiomyopathy. Major arrhythmic event (MAE) was defined as composite of all-cause death, aborted SCD, and sustained VT during any time either before visit of clinic or during follow up period. Syncope and non-sustained VT was defined as non-major arrhythmic event. SA-ECG was defined positive when fulfilling three or more criterion: (1) unfiltered QRS duration ≥114ms, (2) filtered QRS duration ≥114ms, (3) duration of terminal QRS &amp;lt;40uV exceeding 40ms, and (4) root mean square voltage in the terminal 40ms of ≤20ms. Results Among total 581 patients, 145 patients with positive SA-ECG showed higher incidence of MAE compared to patients with negative SA-ECG (21.4% vs. 6.7%, OR 3.816 [95% CI 2.208–6.597], p&amp;lt;0.001, Table). As the number of positive SA-ECG criteria increases, incidence of MAE tended to increase sequentially, which was markedly noted from 2 positive to 3 positive criteria (10.7% to 20.8%, p&amp;lt;0.001, Figure). In particular, patient with inherited arrhythmia showed higher rate of positive late potential compared to those with non-inherited arrhythmia (51.0% vs. 19.3%, p&amp;lt;0.001). Conclusion This study showed that at least 3 out of 4 diagnostic criteria in SA-ECG can independently predict lethal arrhythmic events and the positive late potential was associated with lethal arrhythmic event that leads to SCD, suggesting risk prediction for SCD using SA-ECG in patients even without structural heart disease including inherited arrhythmias. Funding Acknowledgement Type of funding sources: None.

Implantable cardioverter-defibrillator therapy in the very young - Patient characteristics procedural outcome and one-year follow-up - A subgroup analysis of the german DEVICE registry

Abstract Funding Acknowledgements Type of funding sources: None. Background The implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRT-D) are well-established and essential therapeutic pillars for patients with heart failure and survivors of sudden cardiac death. The number of young patients receiving ICD or CRT-D has been increasing in the last decades. Understanding the key differences between the typically older ICD population and younger patients is paramount to optimized patient care. Methods The DEVICE registry prospectively enrolled patients undergoing ICD/CRT implantation or revision from 50 German centers between 2007–2014. Data on patient characteristics, procedural outcome, adverse events and mortality during the initial stay and follow-up was collected. All patients under the age of 45 years were identified and included into a comparative analysis with the remaining population. Results A total number of 4181 patients were enrolled into the registry, of which 236 patients (5.6%) were under the age of 45 years. Median age was 38.0 [31.0; 42.0] vs. 69.0 [60.0; 75.0] years, p&amp;lt;0.001), compared to older patients. Young patients were more likely to receive an ICD (91.5 vs. 69.4%, p&amp;lt;0.001), than CRT device and were less likely to suffer from non-cardiac comorbidities (20.3 vs. 67.4%, p&amp;lt;0.001). Coronary artery disease was less common in young patients (15.7 vs. 63.6%, p&amp;lt;0.001), whereas hypertrophic cardiomyopathy (11.0 vs. 2.5%, p&amp;lt;0.001) and primary cardiac electrical diseases (14.0 vs. 1.6%, p&amp;lt; 0.001) were encountered more often. Mean left-ventricular ejection fractions were 42.4±18.5 vs. 31.5±11.8%, respectively (p&amp;lt;0.001) with less young patients in NYHA functional class III/IV (19.5 vs. 45.3%, p&amp;lt;0.001). Primary symptom at presentation was chronic heart failure for older patients (19.5 vs. 34.8%, p&amp;lt;0.001) and survived sudden cardiac death (30.9 vs. 15.6%, p&amp;lt;0.001) for young patients. Thus, ICD for secondary prevention was more common in young patients (53.8 vs. 43.2%, p&amp;lt;0.001). There were no detectable differences in postoperative complications (3.0 vs. 4.1%, p=0.500) or in-hospital mortality (0.0 vs. 0.3%, p=1.000). Median follow-up time was 514 [398; 669] vs. 458 [391; 563] days (p=0.006). Device-associated complications requiring revision were more common in young patients (16.3 vs. 8.2%, p&amp;lt;0.001) and all-cause 1-year-mortality after implantation was lower (3.1 vs. 7.3%, p=0.029; HR 0.42, 95%CI: 0.19-0.94). Even though there was no difference in rates of rehospitalization between groups (32.1 vs. 32.4%, p=0.93), young patients were re-admitted more often for "cardiac" reasons (82.7 vs. 58.9%, p&amp;lt;0.001). Conclusion Rates for procedural complications and in-hospital mortality were very low and without differences between both age groups. However younger patients experienced a higher rate of postoperative complications requiring revision and had higher readmission rates for cardiac reasons, potentially due to a more active lifestyle.

The Impact of Obesity on Sudden Cardiac Death Risk.

We aimed to describe the epidemiology of sudden cardiac death (SCD) in the obese, elaborating on the potential pathophysiological mechanisms linking obesity, SCD, and the outcomes in SCD survivors, as well as looking into the intriguing "obesity paradox" in these patients. Several studies show increased mortality in patients with BMI > 30kg/m2 admitted to the hospital following SCD. At the same time, other studies have implied that the "obesity paradox," described in various cardiovascular conditions, applies to patients admitted after SCD, showing lower mortality in the obese compared to normal weight and underweight patients. We found a significant body of evidence to support that while obesity increases the risk for SCD, the outcomes of obese patients post SCD are better. These findings should not be interpreted as supporting weight gain, as it is always better to prevent the "disaster" from happening than to improve your chances of surviving it. Obesity is shown to be significantly associated with increased risk for SCD; however, there is a growing body of evidence, supporting the "obesity paradox" in the survival of SCD victims. Prospectively, well-designed studies are needed to confirm these findings.

The role of cardiovascular magnetic resonance imaging with T1 and T2 mapping in sudden cardiac death survivors

Abstract Background Sudden cardiac death (SCD) in the adult population is poorly studied, although determining its etiology is crucial for management and prognosis [1]. Cardiovascular magnetic resonance imaging (CMR) is being increasingly utilized in SCD survivors [1,2]. The role of late gadolinium enhancement (LGE) imaging in patients with recent SCD and no significant coronary artery disease (CAD) is well established, but there is no data on the additive role of T1 and T2 mapping [1–3]. Purpose This is a retrospective study to assess the role of CMR including T1 and T2 mapping in SCD survivors. Methods Between 01/2016 and 12/2019, we retrospectively analyzed patients who underwent CMR on a Siemens Magnetom Avanto 1.5 T scanner within 4 weeks of SCD. CMR protocol included cine imaging, T1 and T2 mapping, and LGE imaging. Native and post-contrast myocardial T1 values were measured within the septum on the mid short axis (SAX) and extracellular volume fraction was calculated using the standard formula. T2 values were measured in six mid segments on the mid SAX map. Additional measurements were performed if long axis T2 maps were available. Clinical data, electrocardiography (ECG), transthoracic echocardiography (TTE), coronary computed tomography angiography (CCTA), and left heart catheterization (LHC) were reviewed from the electronic health record. An ischemic evaluation was performed in 33 (94%) of patients. Results A total of 35 patients who underwent CMR for SCD were included for analysis (mean age 46.9±14.1 years; 20 (57%) male). SCD etiology was established based on clinical data, ECG, TTE, CCTA, and LHC in 9 (26%) patients. CMR provided the most probable SCD etiology in an additional 20 (57%) patients with T1 and T2 mapping abnormalities seen in 18 (51%) patients. Diagnoses determined by CMR included myocarditis (35%), hypertrophic cardiomyopathy (CMP) (20%), left ventricular non-compaction CMP (15%), dilated CMP (10%), takotsubo CMP (5%), and myocardial infarction with non-obstructive CAD (15%) (Table, Figure). Elevated native T1 was seen in 15 (43%) (mean T1 1069±60 ms; site specific normal &amp;lt;1080 ms), elevated ECV in 16 (46%) (30±7%; site specific normal &amp;lt;29%), and elevated native T2 in 22 (63%) patients (65±10 ms; site specific normal &amp;lt;60 ms). LGE was present in 31 (89%) patients. The etiology of SCD remained unknown in 6 (17%) patients despite extensive testing including CMR. Conclusions CMR has significant diagnostic and prognostic value in assessing SCD etiology compared to non-CMR based evaluation. Myocarditis is a common underdiagnosed cause of SCD in adult patients well seen in a CMR protocol with T1 and T2 mapping. Myocardial inflammation monitoring in SCD survivors with serial CMRs using T1 and T2 mapping could influence clinical decision making by justifying pharmacotherapy modification and timing of ICD implantation. To conclude, CMR with T1 and T2 mapping provides high diagnostic yield in the investigation of SCD etiology. Funding Acknowledgement Type of funding sources: None.

A Multicenter External Validation of a Score Model to Predict Risk of Events in Patients With Brugada Syndrome

A multivariate risk score model was proposed by Sieira et al in 2017 for sudden death in Brugada syndrome; their validation in 150 patients was highly encouraging, with a C-index of 0.81; however, this score is yet to be validated by an independent group. A total of 192 records of patients with Brugada syndrome were collected from 2 centers in the United Kingdom and retrospectively scored according to a score model by Sieira et al. Data were compiled summatively over follow-up to mimic regular risk re-evaluation as per current guidelines. Sudden cardiac death survivor data were considered perievent to ascertain the utility of the score before cardiac arrest. Scores were compared with actual outcomes. Sensitivity in our cohort was 22.7%, specificity was 57.6%, and C-index was 0.58. In conclusion, up to 75% of cardiac arrest survivors in this cohort would not have been offered a defibrillator if evaluated before their event. This casts doubt on the utility of the score model for primary prevention of sudden death. Inherent issues with modern risk scoring strategies decrease the likelihood of success even in robustly designed tools such as the Sieira score model.

Unique clinical features and long term follow up of survivors of sudden cardiac death in an Asian multicenter study

There has been no long-term clinical follow-up data of survivors or victims of sudden cardiac death (SCD). The Taiwan multi-center sudden arrhythmia death syndrome follow-up and clinical study (TFS-SADS) is a collaborative multi-center study with median follow-up time 43 months. In this cohort, the clinical characteristics of these SADS patients were compared with those with ischemic heart disease (IHD). In this SCD cohort, around half (42%) were patients with IHD, which was different from Caucasian SCD cohorts. Among those with normal heart, most had Brugada syndrome (BrS). Compared to those with SADS, patients with IHD were older, more males and more comorbidities, more arrhythmic death, and lower left ventricular ejection fraction. In the long-term follow-up, patients with SADS had a better survival than those with IHD (p < 0.001). In the Cox regression analysis to identify the independent predictors of mortality, older age, lower LVEF, prior myocardial infarction and history of out-of-hospital cardiac arrest were associated with higher mortality and beta blocker use and idiopathic ventricular fibrillation or tachycardia (IVF/IVT) with a better survival during follow-up. History of prior MI was associated with more arrhythmic death. Several distinct features of SCD were found in the Asia–Pacific region, such as higher proportion of SADS, poorer prognosis of LQTS and better prognosis of IVF/IVT. Patients with SADS had a better survival than those with IHD. For those with SADS, patients with channelopathy had a better survival than those with cardiomyopathy.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Obstructive Sleep Apnea and Cardiovascular Disease: A Scientific Statement From the American Heart Association.

Obstructive sleep apnea (OSA) is characterized by recurrent complete and partial upper airway obstructive events, resulting in intermittent hypoxemia, autonomic fluctuation, and sleep fragmentation. Approximately 34% and 17% of middle-aged men and women, respectively, meet the diagnostic criteria for OSA. Sleep disturbances are common and underdiagnosed among middle-aged and older adults, and the prevalence varies by race/ethnicity, sex, and obesity status. OSA prevalence is as high as 40% to 80% in patients with hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, and stroke. Despite its high prevalence in patients with heart disease and the vulnerability of cardiac patients to OSA-related stressors and adverse cardiovascular outcomes, OSA is often underrecognized and undertreated in cardiovascular practice. We recommend screening for OSA in patients with resistant/poorly controlled hypertension, pulmonary hypertension, and recurrent atrial fibrillation after either cardioversion or ablation. In patients with New York Heart Association class II to IV heart failure and suspicion of sleep-disordered breathing or excessive daytime sleepiness, a formal sleep assessment is reasonable. In patients with tachy-brady syndrome or ventricular tachycardia or survivors of sudden cardiac death in whom sleep apnea is suspected after a comprehensive sleep assessment, evaluation for sleep apnea should be considered. After stroke, clinical equipoise exists with respect to screening and treatment. Patients with nocturnally occurring angina, myocardial infarction, arrhythmias, or appropriate shocks from implanted cardioverter-defibrillators may be especially likely to have comorbid sleep apnea. All patients with OSA should be considered for treatment, including behavioral modifications and weight loss as indicated. Continuous positive airway pressure should be offered to patients with severe OSA, whereas oral appliances can be considered for those with mild to moderate OSA or for continuous positive airway pressure-intolerant patients. Follow-up sleep testing should be performed to assess the effectiveness of treatment.

Cardiac Arrhythmias in Survivors of Sudden Cardiac Death Requiring Impella Assist Device Therapy.

In this retrospective single-center trial, we analyze 109 consecutive patients (female: 27.5%, median age: 69 years, median left ventricular ejection fraction: 20%) who survived sudden cardiac death (SCD) and needed hemodynamic support from an Impella assist device between 2008 and 2018. Rhythm monitoring is investigated in this population and associations with hospital survival are analyzed. Hospital mortality is high, at 83.5%. Diverse cardiac arrhythmias are frequently registered during Impella treatment. These include atrial fibrillation (AF, 21.1%) and ventricular tachycardia (VT, 18.3%), as well as AV block II°/III° (AVB, 7.3%), while intermittent asystole (ASY) is the most frequently observed arrhythmia (42.2%). Nevertheless, neither ventricular nor supraventricular tachycardias are associated with patients’ survival. In patients who experience intermittent asystole, a trend towards a fatal outcome is noted (p = 0.06). Conclusions: Mortality is high in these severely sick patients. While cardiac arrhythmias were frequent, they did not predict hospital mortality in this population. The hemodynamic support of the pump seems to counterbalance the adverse effects of these events.

Non-invasive detection of exercise-induced cardiac conduction abnormalities in sudden cardiac death survivors in the inherited cardiac conditions.

Rate adaptation of the action potential ensures spatial heterogeneities in conduction across the myocardium are minimized at different heart rates providing a protective mechanism against ventricular fibrillation (VF) and sudden cardiac death (SCD), which can be quantified by the ventricular conduction stability (V-CoS) test previously described. We tested the hypothesis that patients with a history of aborted SCD due to an underlying channelopathy or cardiomyopathy have a reduced capacity to maintain uniform activation following exercise. Sixty individuals, with (n = 28) and without (n = 32) previous aborted-SCD event underwent electro-cardiographic imaging recordings following exercise treadmill test. These included 25 Brugada syndrome, 13 hypertrophic cardiomyopathy, 12 idiopathic VF, and 10 healthy controls. Data were inputted into the V-CoS programme to calculate a V-CoS score that indicate the percentage of ventricle that showed no significant change in ventricular activation, with a lower score indicating the development of greater conduction heterogeneity. The SCD group, compared to those without, had a lower median (interquartile range) V-CoS score at peak exertion [92.8% (89.8-96.3%) vs. 97.3% (94.9-99.1%); P < 0.01] and 2 min into recovery [95.2% (91.1-97.2%) vs. 98.9% (96.9-99.5%); P < 0.01]. No significant difference was observable later into recovery at 5 or 10 min. Using the lowest median V-CoS scores obtained during the entire recovery period post-exertion, SCD survivors had a significantly lower score than those without for each of the different underlying aetiologies. Data from this pilot study demonstrate the potential use of this technique in risk stratification for the inherited cardiac conditions.

Secondary prevention of sudden cardiac death.

The prevention and treatment of sudden cardiac death (SCD) remains a significant public health challenge. For patients with a history of sudden death attributable to ventricular arrhythmia, implantable cardioverter-defibrillator (ICD) therapy is a mainstay of treatment, although these patients remain at high risk for recurrent ventricular arrhythmia and defibrillator therapies. In this review, we summarize landmark clinical trials evaluating the efficacy of ICD therapy in secondary prevention patients, review clinical outcomes including mode of death in survivors of SCD, and highlight the role for systematic diagnostic evaluation. We additionally discuss the invasive electrophysiological management of these patients, including ICD selection and programming as well as the role and timing of antiarrhythmic drug therapy and catheter ablation. Finally, we frame future challenges and needs to advance the care for secondary prevention patients.

P1107First results of molecular autopsy examinations in sudden cardiac death drawn from nationwide multidisciplinary and multicentric collaboration in the Czech Republic

Abstract Funding Acknowledgements Supported by Ministry of Health of the Czech Republic, grant nr. NV18-02-00237. All rights reserved." Introduction "Molecular autopsy" in sudden cardiac death (SCD) is an important diagnostic tool for primary prevention of cardiac arrest in victim´s relatives and requires multicentric and multidisciplinary collaboration. Purpose To establish a national network for SCD diagnostics, to assess the acceptance of genetic testing in at risk relatives and to elucidate the genetic etiology of SCD in a representative Czech cohort aged below 45 years. Patients and Methods Between 2016 and 2019 we ascertained 70 SCD (50 M / 20 F), with positive family history for cardiac arrest in 8/70 cases. Only one family did not agree with molecular autopsy. Genetic counselling and cardiological screening examination was carried out in first degree relatives of SCD survivors accompanied by custom-made targeted panel massively parallel DNA sequencing comprising 100 cardiac conditions-related genes. Presence of pathogenic variants was validated by Sanger DNA sequencing and through family segregation analyses. Results According to post-mortem diagnosis most victims died of HCM (17/70), ACM (16/70), no structural heart disease was found in 15/70 cases, DCM/LVNC in 9/70, 6/70 were SIDS cases, other rare diagnoses comprised aortic dissection, or myocarditis. Most of victims died at sleep, only 9/70 victims died during strenuous activities. About 50% of SCD victims did not have cardiac complaints before death. Very likely or certain molecular etiology (i.e. based on presence of ACMG.net Class 4 to 5 variants) was disclosed in 12/70 (17%) in RYR2, FLNC, TTN, KCNH2 and KCNQ1 genes, whilst potentially causative DNA variants (Classes 3-4) were observed in 13/70 (18%) cases. In SIDS we did not find any pathogenic variants. Interestingly, the KCNE1 p.Asp85Asn (LQT 5 lite) variant, was detected in 3/70 cases as a recognized risk factor for ventricular arrhythmias. Conclusion The multidisciplinary cooperation in Czech Republic has been established, family survivors are willing to receive genetic and cardiological care, while centralised molecular genetic analysis enables reliable results which are in accordance with other multicentric studies. The molecular autopsy should, especially in SIDS, be expanded to whole exome sequencing.

Cardiac devices in the pediatric population: an overview of the indications and complications

Pacemakers, implantable cardioverter-defibrillators, and biventricular pacemakers have similar uses in the pediatric population as they do in the adult population. Pacemaker indications are similar in adults and children: sinus node dysfunction and second or third degree atrioventricular blocks. Pacemaker candidacy in pediatrics, however, must take into account the patient’s symptom burden rather than absolute heart rate cutoffs. Normal ranges for heart rates in children are also different than adults and vary depending on a child’s age. The guidelines for implantable cardioverter-defibrillators likewise are similar to those for adults, being indicated as secondary prevention for sudden cardiac death survivors and as primary prevention in select patients who experience ventricular tachycardia. However, there are currently no specific recommendations for these devices in children with congenital heart defects. Likewise, though there is new promising research, there are currently no specific indications for biventricular pacing in children. The potential complications of pediatric cardiac devices relate to the different heart rate requirements children have compared to adults and the general procedural risks associated with cardiac implants (infection, bleeding, device failure). Despite the recent growth in the use of cardiac devices in children, there is still much room for continued research into the potential indications for and complications from these tools in the pediatric population. Unfortunately, the lack of evidence holds true not only for South America but worldwide. Research studies conducted in South America would give a better understanding about the demographic differences in terms of outcomes.

Comparison of Long-Term Survival Following Sudden Cardiac Arrest in Men Versus Women

Sudden cardiac death (SCA) is a major cause of mortality with estimates of 450,000 deaths annually in the United States. The incidence of SCA differs between the sexes. Data regarding survival of women compared with men after SCA are, however, conflicting. We, therefore, examined the long-term survival of women versus men after SCA. A total of 1,433 (41% women; 44% out-of-hospital) survivors of SCA at our institution between 2002 and 2012 were followed to the primary end point of death through February 20, 2017. Women in our cohort were older (p = 0.02), were less likely to be white (p = 0.01), or to have suffered an acute myocardial infarction at the time of SCA (p < 0.001). They also had significantly shorter PR (p < 0.001) and QRS (p < 0.001) durations on their surface electrocardiogram, were more likely to present with an initial ventricular rhythm other than ventricular tachycardia or ventricular fibrillation (29% vs 22%, p = 0.001) and less likely to receive an implantable cardioverter defibrillator (22% vs 31%, p < 0.001). Over a median follow-up of 3.6 years, 674 (45%) patients died (53% women vs 43% men, p < 0.001). After adjusting for unbalanced baseline covariates, the sex difference in survival disappeared (hazard ratio 1.05; 95% confidence interval 0.85 to 1.29, p = 0.66). In conclusion, our results demonstrate comparable long-term mortality after SCA for men and women. Differences in unadjusted mortality are mainly due to older age, different risk profiles at the time of index event, and differential treatment with implantable cardioverter defibrillator.

Ventricular conduction stability test: a method to identify and quantify changes in whole heart activation patterns during physiological stress.

Abnormal rate adaptation of the action potential is proarrhythmic but is difficult to measure with current electro-anatomical mapping techniques. We developed a method to rapidly quantify spatial discordance in whole heart activation in response to rate cycle length changes. We test the hypothesis that patients with underlying channelopathies or history of aborted sudden cardiac death (SCD) have a reduced capacity to maintain uniform activation following exercise. Electrocardiographical imaging (ECGI) reconstructs >1200 electrograms (EGMs) over the ventricles from a single beat, providing epicardial whole heart activation maps. Thirty-one individuals [11 SCD survivors; 10 Brugada syndrome (BrS) without SCD; and 10 controls] with structurally normal hearts underwent ECGI vest recordings following exercise treadmill. For each patient, we calculated the relative change in EGM local activation times (LATs) between a baseline and post-exertion phase using custom written software. A ventricular conduction stability (V-CoS) score calculated to indicate the percentage of ventricle that showed no significant change in relative LAT (<10 ms). A lower score reflected greater conduction heterogeneity. Mean variability (standard deviation) of V-CoS score over 10 consecutive beats was small (0.9 ± 0.5%), with good inter-operator reproducibility of V-CoS scores. Sudden cardiac death survivors, compared to BrS and controls, had the lowest V-CoS scores post-exertion (P = 0.011) but were no different at baseline (P = 0.50). We present a method to rapidly quantify changes in global activation which provides a measure of conduction heterogeneity and proof of concept by demonstrating SCD survivors have a reduced capacity to maintain uniform activation following exercise.

Prevalence of early repolarization syndrome and long-term clinical outcome in patients with the diagnosis of idiopathic ventricular fibrillation

Idiopathic ventricular fibrillation (IVF) is diagnosed in up to 14% of sudden cardiac death (SCD) survivors. Early repolarization syndrome (ERS) in patients with ventricular tachyarrhythmia is characterized by an elevated J-point in inferior and/or antero-lateral leads. Our objectives were to determine the prevalence of ERS in IVF patients, and to evaluate potential differences in clinical outcome. Out of 3,552 implantable cardioverter defibrillator (ICD) carriers, 758 SCD survivors were retrospectively identified from the databases of the Medical Universities of Vienna and Innsbruck within the last three decades. Early repolarization pattern (ERP) was classified either as "notching" or "slurring". Endpoints were defined as appropriate ICD therapies for ventricular tachyarrhythmia, either anti-tachycardia pacing or shock, and all-cause mortality. After exclusion of recognized reasons for SCD, 50 patients were assigned to the diagnosis of IVF (6.6%). An ERP was identified in 10 patients, most of them with notching (n = 8). After a mean follow-up of 11.2 ± 6.7 years (539.3 patient years), appropriate ICD therapies were found in 50% of ERS and 43% of IVF patients without ERP (p = 0.732). In ERS patients, all ICD therapies were found in patients with notching pattern. Similarly, incidence of inappropriate ICD therapies, and all-cause mortality was comparable (30% vs. 23%, p = 0.707; 10% vs. 5%, p = 0.496, respectively). In 758 SCD survivors, we found a low prevalence of IVF and ERS. Similar event rates were reported concerning all-cause mortality and ICD therapies for ventricular tachyarrhythmia after long-term follow-up in this cohort.