Ventricular Tachycardia/ventricular Fibrillation Research Articles

N-Terminal Pro-B-Type Natriuretic Peptide in Risk Stratification of Heart Failure Patients With Implantable Cardioverter-Defibrillator.

BackgroundThe prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) is well-established. However, whether it could facilitate the risk stratification of HF patients with implantable cardioverter-defibrillator (ICD) is still unclear.ObjectiveTo determine the associations between baseline NT-proBNP and outcomes of all-cause mortality and first appropriate shock due to sustained ventricular tachycardia/ventricular fibrillation (VT/VF) in ICD recipients.Methods and resultsN-terminal pro-B-type natriuretic peptide was measured before ICD implant in 500 patients (mean age 60.2 ± 12.0 years; 415 (83.0%) men; 231 (46.2%) Non-ischemic dilated cardiomyopathy (DCM); 136 (27.2%) primary prevention). The median NT-proBNP was 854.3 pg/ml (interquartile range [IQR]: 402.0 to 1,817.8 pg/ml). We categorized NT-proBNP levels into quartiles and used a restricted cubic spline to evaluate its nonlinear association with outcomes. The incidence rates of mortality and first appropriate shock were 5.6 and 9.1%, respectively. After adjusting for confounding factors, multivariable Cox regression showed a rise in NT-proBNP was associated with an increased risk of all-cause mortality. Compared with the lowest quartile, the hazard ratios (HRs) with 95% CI across increasing quartiles were 1.77 (0.71, 4.43), 3.98 (1.71, 9.25), and 5.90 (2.43, 14.30) for NT-proBNP (p for trend < 0.001). A restricted cubic spline demonstrated a similar pattern with an inflection point found at 3,231.4 pg/ml, beyond which the increase in NT-proBNP was not associated with increased mortality (p for nonlinearity < 0.001). Fine-Gray regression was used to evaluate the association between NT-proBNP and first appropriate shock accounting for the competing risk of death. In the unadjusted, partial, and fully adjusted analysis, however, no significant association could be found regardless of NT-proBNP as a categorical variable or log-transformed continuous variable (all p > 0.05). No nonlinearity was found, either (p = 0.666). Interactions between NT-proBNP and predefined factors were not found (all p > 0.1).ConclusionIn HF patients with ICD, the rise in NT-proBNP is independently associated with increased mortality until it reaches the inflection point. However, its association with the first appropriate shock was not found. Patients with higher NT-proBNP levels might derive less benefit from ICD implant.

A wearable cardioverter defibrillator with a low false alarm rate.

IntroductionA wearable cardioverter defibrillator (WCD) is indicated in appropriate patients to reduce the risk for sudden cardiac death. Challenges for patients wearing a WCD have been frequent false shock alarms primarily due to electrocardiogram noise and wear discomfort. The objective of this study was to test a contemporary WCD designed for reduced false shock alarms and improved comfort.MethodsOne hundred and thirty patients with left ventricular ejection fraction ≤40% and an active implantable cardioverter defibrillator (ICD) were fitted with the ASSURE WCD (Kestra Medical Technologies) and followed for 30 days. WCD detection was enabled and shock alarm markers recorded, but shocks and shock alarms were disabled. All WCD episodes and ICD ventricular tachycardia/ventricular fibrillation (VT/VF) episodes were adjudicated. The primary endpoint was the false‐positive shock alarm rate with a performance goal of 1 every 3.4 days (0.29 per patient‐day).ResultsOf 163 WCD episodes, 4 were VT/VF and 159 non‐VT/VF (121 rhythms with noise, 32 uncertain with noise, 6 atrial flutter without noise). Only three false‐positive shock alarm markers were recorded; one false‐positive shock alarm every 1333 patient‐days (0.00075 per patient‐day, 95% confidence interval: 0.00015–0.00361; p < .001). No ICD recorded VT/VF episodes meeting WCD detection criteria (≥170 bpm for ≥20 s) were missed by the WCD during 3501 patient‐days of use. Median wear was 31.0 days (interquartile range [IQR] 2.0) and median daily use 23.0 h (IQR 1.7). Adverse events were mostly mild: skin irritation (19.4%) and musculoskeletal discomfort (8.5%).ConclusionThe ASSURE WCD demonstrated a low false‐positive shock alarm rate, low patient‐reported discomfort, and no serious adverse events.

Rotors anchored by refractory islands drive torsades de pointes in an experimental model of electrical storm.

Electrical storm (ES) is a life-threatening emergency in patients at high risk of ventricular tachycardia/ventricular fibrillation (VF), but the pathophysiology and molecular basis are poorly understood. The purpose of this study was to explore the electrophysiological substrate for experimental ES. A model was created by inducing chronic complete atrioventricular block in defibrillator-implanted rabbits, which recapitulates QT prolongation, torsades des pointes (TdP), and VF episodes. Optical mapping revealed island-like regions with action potential duration (APD) prolongation in the left ventricle, leading to increased spatial APD dispersion, in rabbits with ES (defined as ≥3 VF episodes/24 h). The maximum APD and its dispersion correlated with the total number of VF episodes invivo. TdP was initiated by an ectopic beat that failed to enter the island and formed a reentrant wave and perpetuated by rotors whose centers swirled in the periphery of the island. Epinephrine exacerbated the island by prolonging APD and enhancing APD dispersion, which was less evident after late Na+ current blockade with 10 μM ranolazine. Nonsustained ventricular tachycardia in a non-ES rabbit heart with homogeneous APD prolongation resulted from multiple foci with an electrocardiographic morphology different from TdP driven by drifting rotors in ES rabbit hearts. The neuronal Na+-channel subunit NaV1.8 was upregulated in ES rabbit left ventricular tissues and expressed within the myocardium corresponding to the island location in optically mapped ES rabbit hearts. The NaV1.8 blocker A-803467 (10 mg/kg, intravenously) attenuated QT prolongation and suppressed epinephrine-evoked TdP. A tissue island with enhanced refractoriness contributes to the generation of drifting rotors that underlies ES in this model. NaV1.8-mediated late Na+ current merits further investigation as a contributor to the substrate for ES.

Clinical Characteristics, Outcomes, and Genetic Findings of Patients with Catecholaminergic Polymorphic Ventricular Tachycardia in Hong Kong

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare cardiac ion channelopathy. This was the first systematic review of published works on the clinical characteristics, outcomes, and genetic findings of patients with CPVT from Hong Kong. PubMed and Embase were searched electronically from their inception until February 2022. The Joanna Briggs Institute Critical Appraisal Checklist was used to critically appraise included studies. Studies written in English describing at least one patient with CPVT were included. Studies describing overlapping CPVT patients from previous reports were excluded. Two studies describing 17 patients with CPVT were included. All included studies were rated of acceptable quality. The largest case series evaluated 16 CPVT patients with a mean presentation age of 11 ± 4 years. Of these, 15 patients (93.8%) were symptomatic at initial presentation. Ten patients presented with both premature ventricular complexes (PVCs) and ventricular tachycardia/ventricular fibrillation (VT/VF), whereas one had PVCs without VT/VF. Among the 14 patients (87.5%) who underwent genetic testing, eight (57.1%) tested positive for the ryanodine receptor 2 (RyR2) gene. Over a mean follow-up duration of 116 ± 36 months, six patients (37.5%) had incident VT/VF. In a 5-year review of autopsy data retrieved from public mortuaries for 289 sudden cardiac death patients, one CPVT patient (0.03%) was identified. All patients with CPVT in Hong Kong presented at or below 19 years old, of whom a majority were initially symptomatic or had incident VT/VF events. Novel genetic variants in the RyR2 gene not reported beyond our locality were identified.

Short-Term Results of Ivabradine versus Metoprolol: The Effects on Atrial Fibrillation in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting.

Classic coronary artery bypass grafting (CABG) surgery involves diastolic cardiac arrest under cardiopulmonary bypass, while off-pump CABG (OPCABG) has become widespread in recent years. 174 patients who underwent OPCABG were included in the study. Patients were divided into two groups. Group I (n=90) received ivabradine and Group M (n=84) received metoprolol before surgery until postoperative day 10. Intraoperative arrhythmias and hypotension were recorded. Postoperative atrial fibrillation (AF) and arrhythmia, mortality and morbidity rates were assessed based on the 30-day postoperative follow-up. There were no significant differences in the intraoperative amount of inotropic support and red blood cell transfusion between groups (P=0.87 and P=0.31). However, the rates of intraoperative arrhythmias and hypotension were not significantly higher in Group M (P=0.317 and P=0.47). Ventricular tachycardia/ventricular fibrillation (VT/VF) was observed in 2 patients in both groups. Postoperative AF occurred in 7 patients (7.7%) in Group I and in 10 patients (11.9%) in Group M. Although there was a trend towards a higher prevalence of AF in Group M patients, this did not reach statistical significance. In addition, mortality and morbidity rates were comparable between groups.

Abstract 9774: Shockable Rhythms Are Common First Rhythms in Cardiac Arrests Involving Patient with Heart Failure with Preserved Ejection Fraction

Introduction: Sudden cardiac death (SCD) is responsible from 25% of the total mortality in patients with heart failure with preserved ejection fraction (HFpEF). Whether SCD in HFpEF is due to shockable or unshockable rhythms is unknown. Hypothesis: Cardiac arrests in HFpEF are due to ventricular tachycardia/ventricular fibrillation (VT/VF). Methods: We determined the initial rhythm in 286 consecutive in-hospital cardiac arrests at the Minneapolis VA Health Care system from 2011 through 2020. Clinical and survival information were obtained from electronic health records. According to their heart failure history, we categorized the patients as HFpEF, heart failure with reduced ejection fraction (HFrEF) or no heart failure (NoHF). Results: Of the 286 patients (mean age 70.2±9.0 years old and 97.5% male), 51 (17.8%) had HFpEF, 77 (26.9%) had HFrEF and 158 (55.2%) had NoHF. The initial rhythm was VT/VF in 47.1%, 39.0% and 22.2% of patients with HFpEF, HFrEF and NoHF respectively (p&lt;0.001) (Figure). Return of spontaneous circulation (ROSC) after VT/VF arrest was similar amongst the three groups (66.7%, 73.3% and 74.3%, respectively; p=0.8) but the 30-day survival trended higher in HFpEF (54.2%) and NoHF (48.6%) when compared with HFrEF (26.7%) (p=0.08)(Figure). Among patients with HFpEF, 30-day survival was lower after cardiac arrests due to PEA/Asystole when compared to those due to VT/VF (18.5% vs. 54.2%, respectively, p=0.03). Conclusion: VT/VF was the initial rhythm in 47% of patients with HFpEF who had in-hospital cardiac arrest. The proportion of VT/VF and ROSC after in-hospital cardiac arrest was similar in HFpEF and HFrEF. These data provide one more piece of evidence that SCD could be a therapeutic target in HFpEF.

Abstract 13998: Predicting Atrial and Ventricular Tachyarrhythmias by Monitoring Intra-Thoracic Impedance, an Updated Meta-Analysis

Background: Many cardiac implantable devices have the capability of monitoring the volume status in patients with heart failure by tracking the intra-thoracic impedance changes over time measured by OptiVol fluid index. Objective: The aim of this study is to evaluate the association between the intra-thoracic impedance measured by OptiVol fluid index and the onset of tachyarrhythmias. Methods: We searched Medline and EMBASE databases through January 2021 looking for studies evaluating intra-thoracic impedance measured by OptiVol with either ventricular tachycardia/ventricular fibrillation (VT/VF) or atrial tachycardia/atrial fibrillation (AT/AF). After extracting the data from each study, we calculated the odds ratio with 95% confidence intervals using RevMan 5 software. Results: Ten studies met our inclusion criteria with a total of 118,504 patients were included in our analysis. Seven studies measured VT/VF included 94,816 patients and 5 studies measured AT/AF included 23,688 patients. Two studies measured both AT/AF and VT/VF. The odds ratio for developing VT/VF with OptiVol fluid index crossing a threshold of 60 Ω-days was 1.55 (95% CI 1.35, 1.78) (P&lt;0.00001) and for developing AT/AF was 1.79 (95% CI 1.43, 2.24) (P&lt;0.00001) {Figure1} Conclusion: The decrease in intra-thoracic impedance measured by OptiVol fluid index threshold crossing of 60 Ω-days is associated with higher risk for developing new onset AT/AF and VT/VF. Key Words: intra-thoracic impedance; OptiVol; tachyarrhythmia Figure1: Forest Plot for risk of developing VT/VF Figure: Forest Plot for risk of developing AT/AF

Association of a simple SACAF score with bystander witnessed sudden death due to ventricular tachyarrhythmias in a multicenter cohort

Out-of-hospital cardiac arrest (OHCA) remains a major threat to public health worldwide. OHCA patients presenting initial shockable ventricular tachycardia/ventricular fibrillation (VT/VF) rhythm have a better survival rate. We sought to develop a simple SACAF score to discriminate VT/VF from non-VT/VF OHCAs based on the Taiwan multicenter hospital-based registry database. We analyzed the in- and pre-hospital data, including demographics, baseline comorbidities, response times, automated external defibrillator information, and the 12-lead ECG recording closest to the OHCA event in bystander-witnessed OHCA patients. Among the 461 study patients, male sex (OR 2.54, 95% CI = 1.32–4.88, P = 0.005), age ≤ 65 years (OR 2.78, 95% CI = 1.64–4.70, P < 0.001), cardiovascular diseases (OR 2.97, 95% CI = 1.73–5.11, P < 0.001), and atrial fibrillation (AF) (OR 2.36, 95% CI = 1.17–4.76, P = 0.017) were independent risk factors for VT/VF OHCA (n = 81) compared with non-VT/VF OHCA (n = 380). A composite SACAF score was developed (male Sex, Age ≤ 65 years, Cardiovascular diseases, and AF) and compared with the performance of a modified CHA2DS2-VASc score (Cardiovascular diseases, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke, Vascular disease, Age 65–74 years, female Sex category). The area under the receiver operating characteristic curve (AUC) of the SACAF was 0.739 (95% CI = 0.681–0.797, P < 0.001), whereas the AUC of the modified CHA2DS2-VASc was 0.474 (95% CI = 0.408–0.541, P = 0.464). A SACAF score of ≥ 2 was useful in discriminating VT/VF from non-VT/VF OHCAs with a sensitivity of 0.75 and a specificity of 0.60. In conclusion, the simple SACAF score appears to be useful in discriminating VT/VF from non-VT/VF bystander-witnessed OHCAs and the findings may also shed light on future mechanistic evaluation.

Paediatric/young versus adult patients with congenital long QT syndrome or catecholaminergic polymorphic ventricular tachycardia

Abstract Introduction Congenital long QT syndrome (LQTS) and catecholaminergic ventricular tachycardia (CPVT) are less prevalent cardiac ion channelopathies than Brugada syndrome in Asia. The present study compared paediatric/young and adult patients with these conditions. Method This was a territory-wide retrospective cohort study of consecutive patients diagnosed with congenital LQTS and CPVT attending public hospitals in Hong Kong. The primary outcome was spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF). Results A total of 142 congenital LQTS (mean onset age= 27±23 years old) and 16 CPVT (mean presentation age=11±4 years old) patients were included. For congenital LQTS, arrhythmias other than VT/VF (HR=4.67, 95% confidence interval = [1.53–14.3], p=0.007), initial VT/VF (HR=3.25 [1.29–8.16], p=0.012) and Schwartz score (HR=1.90 [1.11–3.26], p=0.020) were predictive of the primary outcome for the overall cohort, whilst arrhythmias other than VT/VF (HR=5.41 [1.36–21.4], p=0.016) and Schwartz score (HR=4.67 [1.48–14.7], p=0.009) were predictive for the adult subgroup (&amp;gt;25 years old; n=58). All CPVT patients presented before the age of 25 but no significant predictors of VT/VF were identified. A random survival forest model identified initial VT/VF, Schwartz score, initial QTc interval, family history of LQTS, initially asymptomatic, and arrhythmias other than VT/VF as the most important variables for risk prediction in LQTS, and initial VT/VF/sudden cardiac death, palpitations, QTc, initially symptomatic and heart rate in CPVT. Conclusion Clinical and ECG presentation vary between the pediatric/young and adult congenital LQTS population. All CPVT patients presented before the age of 25. Machine learning models achieved more accurate VT/VF prediction. Funding Acknowledgement Type of funding sources: None. Kaplan-Meier survival curve for LQTSKaplan-Meier survival curve for CPVT

A territory-wide study of arrhythmogenic right ventricular cardiomyopathy patients from Hong Kong

Abstract Background Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a hereditary disease characterised by fibrofatty infiltration of the right ventricular myocardium that predisposes affected patients to malignant ventricular arrhythmias, dual-chamber cardiac failure and sudden cardiac death (SCD). Methods This was a territory-wide retrospective cohort study of patients diagnosed with ARVC/D between 1997 and 2019. The primary outcome was incident ventricular tachycardia/ventricular fibrillation (VT/VF). The secondary outcomes were new-onset heart failure with reduced ejection fraction (HFrEF) and all-cause mortality. Results This study consisted of 115 ARVC/D patients (median age: 60 [44.1–70.2] years; 58% male). Of these, 51 and 24 patients developed incident VT/VF and new-onset HFrEF, respectively. Five patients underwent cardiac transplantation, and 14 died during follow-up. Multivariate Cox regression identified prolonged QRS duration as a predictor of VT/VF (P&amp;lt;0.05). Female gender, prolonged QTc duration, the presence of epsilon waves and T-wave inversion (TWI) in any lead except aVR/V1 predicted new-onset HFrEF (P&amp;lt;0.05). Female gender, prolonged QTc duration and the presence of epsilon waves, in addition to the parameters of older age at diagnosis of ARVC/D, prolonged QRS duration and worsening ejection fraction predicted all-cause mortality (p&amp;lt;0.05). Clinical scores were also developed to predict new-onset HFrEF (Table 1a-c) and all-cause mortality (Table 2a-c). This was followed by the application of a non-parametric machine learning survival analysis models for outcome prediction. These machine learning algorithms better capture nonlinear and interactive patterns within survival data compared to traditionally used Cox regression models, which assume the existence of a hazard function between survival data and censored outcomes. The present study introduced weighted random survival forests models for the prediction of incident VT/VF, HFrEF and all-cause mortality. Findings indicate that these machine learning wRSF models performed the best in the prediction of all three aforementioned outcomes compared to other analytical methods. Conclusion Clinical and electrocardiographic parameters are important for assessing prognosis in ARVC/D patients. Machine learning algorithms appear to be the most optimal tools for event prediction, and as such should potentially be used to aid risk stratification and decision-making in the clinical setting. Funding Acknowledgement Type of funding sources: None.

Gender related differences in brugada syndrome

Abstract Background Brugada syndrome (BS) is a heritable channelopathy with male predominance. Males (M) seem to have a higher risk of arrhythmic events, although, there is limited data regarding gender differences in BS. Aim To compare the differences between genders in a Portuguese sample of BS patients (pts). Methods Single-center retrospective study of BS pts followed by the Arrhythmology Department. Pts were divided according to gender and compared regarding baseline characteristics and electrocardiographic (ECG) parameters that possibly predict the arrhythmic risk (significative S wave in DI, R wave sign, Tpeak-Tend interval and fragmented QRS). The events during follow-up were syncope of probable arrhythmic origin, ventricular tachycardia/ventricular fibrillation (VT/VF) and sudden cardiac death (SCD). Results A total of 165 pts were included; 64 (39%) were female (F) and the mean age at diagnosis was 47±15 years. The diagnosis was made by family screening (FS) in 72 (44%) pts. Sixty-seven pts (41%) had spontaneous type 1 pattern, 59 (36%) had history of syncope and 5 (3%) had history of aborted SCD. A positive genetic test was identified in 41 (25%) pts. Sixty-three (38%) pts were referred for an electrophysiological study (EEF) which was positive in 17 (27%) pts. A cardioverter-defibrillator was implanted in 45 (27%) pts. Females were more often diagnosed by FS (64% vs 31%, p &amp;lt;.001), had less type 1 spontaneous pattern (22% vs 53%, p&amp;lt;.001) and had no atrial fibrillation (0% vs 7%, p=.043). They performed EEF less frequently (22% vs 49%, p&amp;lt;.001) and had less spontaneous pattern during treadmill stress test (8% vs 33%, p=.004). Regarding ECG parameters, females had shorter QRS interval (104±12 vs 115±18 ms, p&amp;lt;0.001), less frequent aVR sign (3% vs 27%, p&amp;lt;0.001), less significative S wave in DI (31% vs 55%, p=0.004), and a tendency for a shorter Tp-Te interval (80 vs 100 ms, p=0.051). Corrected QT interval was longer in females (396 vs 392ms, p=0.044). During a median follow-up of 28 (IQR 16–41) months, 7 pts had VT/VF (2F, 5M) and 3 had syncope (3M), with no differences between gender (p=0.287). There were no cardiovascular deaths. Conclusion In BS, female pts are more often diagnosed by FS and have less spontaneous type 1 pattern. Gender appears to affect basal ECG characteristics in BS, namely in parameters that may predict arrhythmic risk. Further studies are important to clarify the role of gender in prognosis and risk stratification of BS pts. Funding Acknowledgement Type of funding sources: None.

Family screening in brugada syndrome patients

Abstract Background Brugada syndrome (BS) is a rare inherited channelopathy associated with sudden cardiac death (SCD) and family screening (FS) of index patients (pts) is recommended. However, data about pts identified through FS is lacking. Aim To compare index pts to non-index pts identified through systematic FS. Methods Single-center retrospective study of BS pts followed by the Arrhythmology Department. FS was offered to 1st degree relatives of all index pts through primary care services and a once-weekly voluntary open appointment. Genetic counselling was performed when indicated. Index and non-index pts were compared regarding baseline characteristics and events during the follow-up (syncope of probable arrhythmic origin, ventricular tachycardia/ventricular fibrillation (VT/VF) and SCD). Results We included 165 pts (61% males, mean age 47±15 years) and 72 (44%) were identified through FS. Non-index pts were diagnosed at a younger age (42±14 vs 51±14 years, p &amp;lt;.001), were more often female (57% vs 25%, p&amp;lt;.001), were diagnosed predominantly through provocative test with ajmaline/flecainide (88% vs 47%, p&amp;lt;.001) and had less documented spontaneous type 1 ECG pattern (17% vs 59%, p&amp;lt;.001). A type 2 pattern was identified in 18 (25%) non-index pts. Genetic testing was performed in 38 (53%) non-index pts: 6 had a pathogenic SCN5A mutation, 18 a likely pathogenic SCN5A mutation and 12 a mutation of uncertain significance. At diagnosis, 24 (33%) non-index pts had history of syncope, 3 (4%) had nocturnal agonal respiration and 11 (15%) had palpitations with no differences between both groups (p=.119). Non-index pts were less likely to implant a cardioverterdefibrillator (14% vs 38%, p=.001). During a median follow-up of 28 (IQR 16–41) months, 10 (6%) pts had an event - 2 (3%) in the non-index group (2 syncope) and 8 (9%) in the index group (1 syncope; 7 VT/VF) - with no significative differences between groups (p=.432). There were nocardiovascular deaths. Conclusions FS identified a considerable proportion of BS pts. Non-index pts were younger at the time of the diagnosis and had less spontaneous type 1 pattern. No differences were found in events between index and non-index pts, however, the event rate was low. Systematic FS can identify individuals at risk of SCD earlier, allowing close monitoring and, when indicated, appropriate treatment. Funding Acknowledgement Type of funding sources: None.

Severe dilated cardiomyopathy and ventricular arrhythmia in a patient with Emery‐Dreifuss muscular dystrophy harboring a novel frameshift mutation in EMD

AbstractWe report a case of a 55‐year‐old man with dilated cardiomyopathy and ventricular tachycardia/ventricular fibrillation (VT/VF). He had contracture of neck and ankle flexion from infancy and was found to have dilated cardiomyopathy at the age of 24 years. Intensive cardiac treatment including medication and the use of a defibrillator failed to improve his cardiac function, and heart transplantation was indicated at the age of 55 years. Joint contractures and proximal dominant muscle atrophy with mild weakness suggested Emery‐Dreifuss muscular dystrophy (EDMD). The diagnosis of EDMD1 was made based on genetic analysis of EMD and muscle biopsy showing the absence of emerin. The patient was listed as a candidate for heart transplantation, but he died 3 months later due to sustained VT/VF. The present case emphasizes the necessity of considering timely heart transplantation even when a defibrillator is implanted in patients with EDMD.

Paediatric/young versus adult patients with long QT syndrome

IntroductionLong QT syndrome (LQTS) is a less prevalent cardiac ion channelopathy than Brugada syndrome in Asia. The present study compared the outcomes between paediatric/young and adult LQTS patients.MethodsThis was a...

Genetic Variant Score and Arrhythmogenic Right Ventricular Cardiomyopathy Phenotype in Plakophilin-2 Mutation Carriers

Introduction: Whether detailed genetic information contributes to risk stratification of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains uncertain. Pathogenic genetic variants in some genes seem to carry a higher risk for arrhythmia and earlier disease onset than others, but comparisons between variants in the same gene have not been done. Combined Annotation Dependent Depletion (CADD) score is a bioinformatics tool that measures the pathogenicity of each genetic variant. We hypothesized that a higher CADD score is associated with arrhythmic events and earlier age at ARVC manifestations in individuals carrying pathogenic or likely pathogenic genetic variants in plakophilin-2 (PKP2). Methods: CADD scores were calculated using the data from pooled Scandinavian and North American ARVC cohorts, and their association with cardiac events defined as ventricular tachycardia/ventricular fibrillation (VT/VF) or syncope and age at definite ARVC diagnosis were assessed. Results: In total, 33 unique genetic variants were reported in 179 patients (90 males, 71 probands, 96 with definite ARVC diagnosis at a median age of 35 years). Cardiac events were reported in 76 individuals (43%), of whom 53 had sustained VT/VF (35%). The CADD score was neither associated with age at cardiac events (HR 1.002, 95% CI: 0.953–1.054, p = 0.933) nor with age at definite ARVC diagnosis (HR 0.992, 95% CI: 0.947–1.039, p = 0.731). Conclusion: No correlation was found between CADD scores and clinical manifestations of ARVC, indicating that the score has no additional risk stratification value among carriers of pathogenic or likely pathogenic PKP2 genetic variants.

Trends, Predictors and Outcomes of Ischemic Stroke Among Patients Hospitalized with Takotsubo Cardiomyopathy

ObjectivesThis study assessed the temporal trends in the incidence of ischemic stroke among patients hospitalized with takotsubo cardiomyopathy (TCM) stratified by the subtypes of ischemic stroke (cardioembolic versus thrombotic). Predictors of each stroke subtype, the association with atrial fibrillation (AF), the occurrence of ventricular fibrillation/ventricular tachycardia (VF/VT), cardiogenic shock (CS), in-hospital mortality, length of stay (LOS), and total healthcare cost were also assessed. BackgroundIschemic stroke in TCM is thought to be primarily cardioembolic from left ventricular mural thromboembolism. Limited data are available on the incidence of thrombotic ischemic stroke in TCM. Materials and MethodsWe identified 27,970 patients hospitalized with the primary diagnosis of TCM from the 2008 to 2017 National Inpatient Sample, of which 751 (3%) developed ischemic stroke. Of those with ischemic stroke, 571 (76%) had thrombotic stroke while 180 (24%) had cardioembolic stroke. Cochrane armitage test was used to assess the incidence of thrombotic and cardioembolic strokes and multivariate regression was used to identify risk factors associated with each stroke subtype. We compared the incidence of AF, VF/VT, CS, LOS, in-hospital mortality and total cost between hospitalized patients with TCM alone to those with cardioembolic and thrombotic strokes. ResultsFrom 2008 – 2017, the incidence of thrombotic stroke (4.7%–9.5% (p< 0.0001) increased while it was unchanged for cardioembolic stroke (0.5%–0.7% P=0.5). In the multivariate regression, peripheral artery disease, prior history of stroke, and hyperlipidemia were significantly associated with thrombotic stroke, while CS, AF, and Asian race (compared to White race) were associated with cardioembolic stroke. Both cardioembolic and thrombotic strokes were associated with higher odds of IHM, AF, CS, longer LOS and increased cost. Trends in in-hospital mortality and the utilization of thrombolysis, cerebral angiography, and mechanical thrombectomy among patients with TCM and ischemic stroke were unchanged from 2008 to 2017. ConclusionAmong patients with TCM and ischemic stroke, thrombotic stroke was more common compared to cardioembolic stroke. Ischemic stroke was associated with poorer outcomes, including higher in-hospital mortality and increased healthcare resource utilization in TCM.

Ventricular Tachyarrhythmia Risk in Paediatric/Young vs. Adult Brugada Syndrome Patients: A Territory-Wide Study.

Introduction: Brugada syndrome (BrS) is a cardiac ion channelopathy with a higher prevalence in Asia compared to the Western populations. The present study compared the differences in clinical and electrocardiographic (ECG) presentation between paediatric/young (≤25 years old) and adult (>25 years) BrS patients.Method: This was a territory-wide retrospective cohort study of consecutive BrS patients presenting to public hospitals in Hong Kong. The primary outcome was spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF).Results: The cohort consists of 550 consecutive patients (median age of initial presentation = 51 ± 23 years; female = 7.3%; follow-up period = 83 ± 80 months), divided into adult (n = 505, mean age of initial presentation = 52 ± 19 years; female = 6.7%; mean follow-up period = 83 ± 80 months) and paediatric/young subgroups (n = 45, mean age of initial presentation = 21 ± 5 years, female = 13.3%, mean follow-up period = 73 ± 83 months). The mean annual VT/VF incidence rate were 17 and 25 cases per 1,000 patient-year, respectively. Multivariate analysis showed that initial presentation of type 1 pattern (HR = 1.80, 95% CI = [1.02, 3.15], p = 0.041), initial asymptomatic presentation (HR = 0.26, 95% CI = [0.07, 0.94], p = 0.040) and increased P-wave axis (HR = 0.98, 95% CI = [0.96, 1.00], p = 0.036) were significant predictors of VT/VF for the adult subgroup. Only initial presentation of VT/VF was predictive (HR = 29.30, 95% CI = [1.75, 492.00], p = 0.019) in the paediatric/young subgroup.Conclusion: Clinical and ECG presentation of BrS vary between the paediatric/young and adult population in BrS. Risk stratification and management strategies for younger patients should take into consideration and adopt an individualised approach.

Sulfonylurea antidiabetics are associated with lower risk of out-of-hospital cardiac arrest: Real-world data from a population-based study.

AimsOut‐of‐hospital cardiac arrest (OHCA) mostly results from ventricular tachycardia/ventricular fibrillation (VT/VF), often triggered by acute myocardial infarction (AMI). Sulfonylurea (SU) antidiabetics can block myocardial ATP‐regulated K+ channels (KATP channels), activated during AMI, thereby modulating action potential duration (APD). We studied whether SU drugs impact on OHCA risk, and whether these effects are related to APD changes.MethodsWe conducted a population‐based case–control study in 219 VT/VF‐documented OHCA cases with diabetes and 697 non‐OHCA controls with diabetes. We studied the association of SU drugs (alone or in combination with metformin) with OHCA risk compared to metformin monotherapy, and of individual SU drugs compared to glimepiride, using multivariable logistic regression analysis. We studied the effects of these drugs on APD during simulated ischaemia using patch‐clamp studies in human induced pluripotent stem cell‐derived cardiomyocytes.ResultsCompared to metformin, use of SU drugs alone or in combination with metformin was associated with reduced OHCA risk (ORSUdrugs‐alone 0.6 [95% CI 0.4–0.9], ORSUdrugs + metformin 0.6 [95% CI 0.4–0.9]). We found no differences in OHCA risk between SU drug users who suffered OHCA inside or outside the context of AMI. Reduction of OHCA risk compared to glimepiride was found with gliclazide (ORadj 0.5 [95% CI 0.3–0.9]), but not glibenclamide (ORadj 1.3 [95% CI 0.6–2.7]); for tolbutamide, the association with reduced OHCA risk just failed to reach statistical significance (ORadj 0.6 [95% CI 0.3–1.002]). Glibenclamide attenuated simulated ischaemia‐induced APD shortening, while the other SU drugs had no effect.ConclusionsSU drugs were associated with reduced OHCA risk compared to metformin monotherapy, with gliclazide having a lower risk than glimepiride. The differential effects of SU drugs are not explained by differential effects on APD.

RR interval analysis based on a newly developed PC program as a predictor of interventions in implantable cardioverter-defibrillator patients.

Prediction of sudden cardiac death remains a significant challenge. There is some evidence that ventricular ectopic activity could be regarded as a predictive marker. We carried out an analysis to explore whether premature ventricular complexes (PVCs) are a risk factor in implantable cardioverter-defibrillator (ICD) interventions. The study method was a RR interval series analysis (n = 184) of arrhythmic events and controls from the ICD. Study group consisted of patients with a mean age of 55 ±27 years; 74% of them were male, 85% were secondary prevention patients, 62% had coronary artery disease (CAD), 15% hypertropic cardiomyopathy (HCM), 15% dilated cardiomyopathy (DCM), and 8% diseases of other etiology. The mean follow-up time was 64 months (range: 3-126 months). The study population was divide into patients with at least 1 appropriate intervention ventricular tachycardia/ventricular fibrillation (VT/VF) (group A, n = 101) and controls without interventions (group B, n = 83). The number of PVC/4000 RR cycles, the shortest coupling intervals between a PVC and preceding R as well as the number of PVCs of very short (180-220 ms), short (220-280 ms) and different cycle lengths (CL) as well as the incidence of short-long-short (SLS) sequences were compared. The number of PVCs/4000 RR cycles was significantly higher in group A (263 ±32 compared to 43 ±17, p < 0.0001). The mean shortest PVC CL was significantly shorter in group A (320 ±13 compared to 400 ±38, p = 0.029). The number of PVCs with a very short CL was 1 ±0.4 compared to 0.1 ±0.1 (p = 0.028). The number of PVCs with a short CL was 5 ±1.2 compared to 0.6 ±0.4 (p = 0.0007) in groups A and B, respectively. The incidence of SLS sequences was significantly higher in group A than in group B (67 (94% of patients) and 4 (33% of patients) respectively (p < 0.0001)). Significant differences were found in the characteristics of PVCs and SLS sequences between patients with appropriate ICD interventions and controls. A newly developed basic computer program called PCRR was applied for RR interval analysis. This simple method could be a predictor of PVC burden and life-threatening arrhythmias in different populations.

Identification of patients at risk of sudden cardiac death in congenital heart disease: The PRospEctiVE study on implaNTable cardIOverter defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease (PREVENTION-ACHD)

Sudden cardiac death (SCD) is the main preventable cause of death in patients with adult congenital heart disease (ACHD). Since robust risk stratification methods are lacking, we developed a risk score model to predict SCD in patients with ACHD: the PRospEctiVE study on implaNTable cardIOverter defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease (PREVENTION-ACHD) risk score model. The purpose of this study was to prospectively study predicted SCD risk using the PREVENTION-ACHD risk score model and actual SCD and sustained ventricular tachycardia/ventricular fibrillation (VT/VF) rates in patients with ACHD. The PREVENTION-ACHD risk score model assigns 1 point each to coronary artery disease, New York Heart Association class II/III heart failure, supraventricular tachycardia, systemic ejection fraction < 40%, subpulmonary ejection fraction < 40%, QRS duration ≥ 120 ms, and QT dispersion ≥ 70 ms. SCD risk was calculated for each patient. An annual predicted risk of ≥3% constituted high risk. The primary outcome was SCD or VT/VF after 2 years. The secondary outcome was SCD. The study included 783 consecutive patients with ACHD (n=239 (31%) left-sided lesions; n=138 (18%) tetralogy of Fallot; n=108 (14%) closed atrial septal defect; median age 36 years; interquartile range 28-47 years; n=401 (51%) men). The PREVENTION-ACHD risk score model identified 58 high-risk patients. Eight patients (4 at high risk) experienced the primary outcome. The Kaplan-Meier estimates were 7% (95% confidence interval [CI] 0.1%-13.3%) in the high-risk group and 0.6% (95% CI 0.0%-1.1%) in the low-risk group (hazard ratio 12.5; 95% CI 3.1-50.9; P < .001). The risk score model's sensitivity was 0.5 and specificity 0.93, resulting in a C-statistic of 0.75 (95% CI 0.57-0.90). The hazard ratio for SCD was 12.4 (95% CI 1.8-88.1) (P = .01); the sensitivity and specificity were 0.5 and 0.92, and the C-statistic was 0.81 (95% CI 0.67-0.95). The PREVENTION-ACHD risk score model provides greater accuracy in SCD or VT/VF risk stratification as compared with current guideline indications and identifies patients with ACHD who may benefit from preventive implantable cardioverter-defibrillator implantation.