Long-Term Prognosis of Febrile Individuals with Right Precordial Coved-Type ST-Segment Elevation Brugada Pattern: A 10-Year Prospective Follow-Up Study

A febrile state may provoke a Brugada electrocardiogram (ECG) pattern and trigger ventricular tachyarrhythmias in susceptible individuals. However, the prognostic value of fever-induced Brugada ECG pattern remains unclear. We analyzed the clinical and extended long-term follow-up data of consecutive febrile patients with a type 1 Brugada ECG presented to the emergency department. A total of 21 individuals (18 males; mean age, 43.7 ± 18.6 years at diagnosis) were divided into symptomatic (resuscitated cardiac arrest in one, syncope in two) and asymptomatic (18, 86%) groups. Sustained polymorphic ventricular tachycardias were inducible in two patients with previous syncope. All 18 asymptomatic patients had no spontaneous type 1 Brugada ECG recorded at second intercostal space and no family history of sudden death. Among asymptomatic individuals, 4 had a total 12 of repeated non-arrhythmogenic febrile episodes all with recurrent type 1 Brugada ECGs, and none had a ventricular arrhythmic event during 116 ± 19 months of follow-up. In the symptomatic group, two had defibrillator shocks for a new arrhythmic event at 31- and 49 months follow-up, respectively, and one without defibrillator therapy died suddenly at 8 months follow-up. A previous history of aborted sudden death or syncope was significantly associated with adverse outcomes in symptomatic compared with asymptomatic individuals (log-rank p < 0.0001). In conclusion, clinical presentation or history of syncope is the most important parameter in the risk stratification of febrile patients with type 1 Brugada ECG. Asymptomatic individuals with a negative family history of sudden death and without spontaneous type 1 Brugada ECG, have an exceptionally low future risk of arrhythmic events. Careful follow-up with timely and aggressive control of fever is an appropriate management option.

Genotype-Phenotype Correlation of SCN5A Genotype in Patients With Brugada Syndrome and Arrhythmic Events: Insights From the SABRUS in 392 Probands

Background: Brugada syndrome (BrS) is associated with mutations in the cardiac sodium channel gene, SCN5A. However, genetic studies of patients with BrS with arrhythmic events have been limited. We sought to compare various clinical, ECG, and electrophysiological parameters according to SCN5A genotype in a large cohort of BrS probands with first arrhythmic event. Methods: Survey on Arrhythmic Events in Brugada Syndrome is a survey of 10 Western and 4 Asian countries, gathering 678 patients with BrS with first arrhythmic event. Only probands were included, and SCN5A genotype adjudicated. Patients without appropriate genetic data were excluded. Associations of genotype with clinical features were analyzed. Results: The study group comprised 392 probands: 92 (23.5%) SCN5A+ (44 pathogenic/likely pathogenic [P/LP] and 48 variants of unknown significance) and 300 (76.5%) SCN5A−. SCN5A missense variants and the patients hosting them were similar regardless of adjudication. A higher proportion of patients with P/LP were pediatric (<16 years) compared with SCN5A− (11.4% versus 3%, P =0.023). The proportion of females was higher among patients with P/LP compared with SCN5A − (18.2% versus 6.3%, P =0.013). P/LP probands were more likely to have a family history of sudden cardiac death compared with SCN5A − (41.9% versus 16.8%, P <0.001). A higher proportion of patients with P/LP were White compared with SCN5A− (87.5% versus 47%, P <0.001). Ethnicity (odds ratio, 5.41 [2.8–11.19], P <0.001) and family history of sudden cardiac death (odds ratio, 2.73 [1.28–5.82], P =0.009) were independent variables associated with P/LP genotype following logistic regression. Conclusions: The genetic basis of BrS has a complex relationship with gender, ethnicity, and age. Probands hosting a P/LP variant tended to experience their first arrhythmic event at a younger age and to have events triggered by fever compared with patients with SCN5A− . In addition, they were more likely to be White and to have family history of sudden cardiac death. Among females, a P/LP variant suggests an increased risk of being symptomatic. This association should be further studied on an ethnically specific basis in large prospectively collected international cohorts.

The role of the electrocardiographic phenotype in risk stratification for sudden cardiac death in childhood hypertrophic cardiomyopathy

Aims The 12-lead electrocardiogram (ECG) is routinely performed in children with hypertrophic cardiomyopathy (HCM). An ECG risk score has been suggested as a useful tool for risk stratification, but this has not been independently validated. This aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events. Methods and results Data from 356 childhood HCM patients with a mean age of 10.1 years (±4.5) were collected from a retrospective, multi-centre international cohort. Three hundred and forty-seven (97.5%) patients had ECG abnormalities at baseline, most commonly repolarization abnormalities (n = 277, 77.8%); left ventricular hypertrophy (n = 240, 67.7%); abnormal QRS axis (n = 126, 35.4%); or QT prolongation (n = 131, 36.8%). Over a median follow-up of 3.9 years (interquartile range 2.0–7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93–2.04). No ECG variables were associated with 5-year arrhythmic event on univariable or multivariable analysis. The ECG risk score threshold of &gt;5 had modest discriminatory ability [C-index 0.60 (95% CI 0.484–0.715)], with corresponding negative and positive predictive values of 96.7% and 6.7% Conclusion In a large, international, multi-centre cohort of childhood HCM, ECG abnormalities were common and varied. No ECG characteristic, either in isolation or combined in the previously described ECG risk score, was associated with 5-year sudden cardiac death risk. This suggests that the role of baseline ECG phenotype in improving risk stratification in childhood HCM is limited.

The prognostic value of 123I-mIBG SPECT cardiac imaging in heart failure patients: a systematic review

This systematic review aimed to evaluate the prognostic value of Iodine123 Metaiodobenzylguanidine (123I-mIBG) SPECT myocardial imaging in patients with heart failure (HF) and to assess whether semi-quantitative SPECT scores can be useful for accurate risk stratification concerning arrhythmic event (AE) and sudden cardiac death (SCD) in this cohort. A systematic literature search of studies published until November 2020 regarding the application of 123I-mIBG SPECT in HF patients was performed, in Pubmed, Scopus, Medline, Central (Cochrane Library) and Web Of Science databases, including the words “MIBG”, “metaiodobenzylguanidine”, “heart”, “spect”, and “tomographic”. The included studies had to correlate 123I-mIBG SPECT scores with endpoints such as overall survival and prevention of AE and SCD in HF patients. According to the sixteen studies included, the analysis showed that 123I-mIBG SPECT scores, such as summed defect score (SDS), regional wash-out (rWO), and regional myocardial tracer uptake, could have a reliable prognostic value in patients with HF. An increased SDS or rWO, as well as a reduced 123I-mIBG myocardial uptake, have proven to be effective in predicting AE- and SCD-specific risk in HF patients. Despite achieved results being promising, a more reproducible standardized method for semi-quantitative analysis and further studies with larger cohort are needed for 123I-mIBG SPECT myocardial imaging to be as reliable and, thus, accepted as the conventional 123I-mIBG planar myocardial imaging.

Sex differences in disease progression and arrhythmic risk in patients with arrhythmogenic cardiomyopathy

Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Area Network on Cardiovascular Diseases (ERA-CVD) Background Arrhythmogenic cardiomyopathy (AC) is an inheritable heart disease characterized by high risk of life-threatening ventricular arrhythmia. Male sex has been reported as a risk factor of high disease penetrance and arrhythmia, but data on sex-specific phenotype in AC are sparse. Purpose To assess sex-specific disease progression in AC patients and structural cardiac changes at time of arrhythmic event. Methods We included consecutive AC patients in a longitudinal cohort study. We performed echocardiography at baseline according to Task Force Criteria of 2010 with additional parameters including strain. Patients were followed with repeated echocardiographic examinations. Ventricular arrhythmia was defined as aborted cardiac arrest, sustained ventricular tachycardia or appropriate therapy by an implantable cardioverter-defibrillator. In patients with documented first time ventricular arrhythmias, echocardiographic findings obtained ±30 days around the event was noted separately. Results We included 191 AC patients (46% female, 51% probands, age 41 ± 17 years) of which 88% had ≥2 echocardiographic examinations during 6.9 (IQR 4.7-9.8) years of follow up. Females and males had similar progression rate of right ventricular dimensions and left ventricular function, but right ventricular function decreased more in females (Figure). Arrhythmic events occurred in 85 (45%) patients and 39 patients had an echocardiographic examination at the time of their first event. There was no difference in right ventricular diameters or right or left ventricular function between females and males at the time of first arrhythmic event (right ventricular outflow tract diameter: 35 ± 7 mm vs. 39 ± 7 mm, p = 0.16, right ventricular fractional area change: 34 ± 9 % vs. 29 ± 11 %, p = 0.26, left ventricular global longitudinal strain: -18.8 ± 3.0 % vs. 17.2 ± 2.2 %, p = 0.12, respectively). Conclusion Disease progression was similar in male and female AC patients indicating no accelerated disease progression in males. First arrhythmic event occurred at similar cardiac dysfunction and diameters in both sexes indicating no lower risk in females. Abstract Figure.

Importance of electrocardiographic markers in predicting cardiac events in children

ECG is a common diagnostic tool in medical practice. Sudden cardiac death (SCD) is a rare but devastating event. The most common cause of SCD in the young is a primary arrhythmic event, which is often produced by malignant ventricular arrhythmia. Several electrocardiographic markers for ventricular repolarization and depolarization have been proposed to predict this arrhythmic risk and SCD in children. Although many of these parameters can easily be used in clinical practice, some of them need specific techniques for interpretation. In this review, we summarized the current knowledge regarding the clinical importance and the ability of these ECG parameters to predict adverse cardiac events in the pediatric population.

Seven day continuous ambulatory electrocardiographic telemetric study with pocket electrocardiographic recording device for detecting hydroxychloroquin induced arrhythmias

BACKGROUND & AIMSThe use of hydroxycholoroquin for COVID 19 treatment and prophylaxis raised issues concerning its cardiac safety owing to possibility of QT prolongation and arrhythmias.1 There was no study on long term electrocardiographic telemetry monitoring of patients taking hydroxychloroquin and we planned a continuous electrocardiographic holter telemetry of these patients for a period of seven days.MethodsHealthcare workers taking hydroxycholoroquin as pre exposure prophylaxis, patients taking hydroxychloroquin were monitored by holter electrocardiographic telemetry with continuous beat to beat analysis for seven days with capacity to report any arrhythmic event or significant QT prolongation instantly to medical faculty.Results25 participants with mean age 42.4 ± 14.1 years, 40% females. 20% patients needed to stop HCQ. Four patients developed QT prolongation > 500 ms and needed to stop HCQ, one patient had accelerated idioventricular rhythm and stopped treatment. one had short episodes of atrial fibrillation. No malignant arrhythmia or ventricular arrhythmia or torsades were noted. No episode of significant conduction disturbance and arrhythmic death noted. Baseline mean QTc was 423.96 ± 32.18 ms, mean QTc corrected at 24 hours 438.93 ± 37.95, mean QTc 451.879 ± 37.99 at 48 hours, change in baseline mean QTc to max QTc was 30.74 ± 21.75 ms at 48 hours. All those develop QTc prolongation > 500 ms were greater than 50 years of age.ConclusionAmbulatory telemetry ECG monitoring seems to detect early QT prolongation and stopping drug timely prevented malignant arrhythmias. HCQ seems to have less risk of QT prolongation in young healthy individuals.

Robustness and relevance of predictive score in sudden cardiac death for patients with Brugada syndrome

Aims Risk stratification of sudden cardiac arrest (SCA) in Brugada syndrome (Brs) remains the main challenge for physicians. Several scores have been suggested to improve risk stratification but never replicated. We aim to investigate the accuracy of the Brs risk scores. Methods and results A total of 1613 patients [mean age 45 ± 15 years, 69% male, 323 (20%) symptomatic] were prospectively enrolled from 1993 to 2016 in a multicentric database. All data described in the risk score were double reviewed for the study. Among them, all patients were evaluated with Shanghai score and 461 (29%) with Sieira score. After a mean follow-up of 6.5 ± 4.7 years, an arrhythmic event occurred in 75 (5%) patients including 16 SCA, 11 symptomatic ventricular arrhythmia, and 48 appropriate therapies. Predictive capacity of the Shanghai score (n = 1613) and the Sieira (n = 461) score was, respectively, estimated by an area under the curve of 0.73 (0.67–0.79) and 0.71 (0.61–0.81). Considering Sieira score, the event rate at 10 years was significantly higher with a score of 5 (26.4%) than with a score of 0 (0.9%) or 1 (1.1%) (P &lt; 0.01). No statistical difference was found in intermediate-risk patients (score 2–4). The Shanghai score does not allow to better stratify the risk of SCA. Conclusions In the largest cohort of Brs patient ever described, risk scores do not allow stratifying the risk of arrhythmic event in intermediate-risk patient.

Clinical Presentation of Sustained Monomorphic Ventricular Tachycardia Without Cardiac Arrest

Background “Palpitations” are one of the most common complaints prompting medical attention. Textbooks of medicine and cardiology as well as guideline documents and position papers describe palpitations as a common symptom of ventricular tachycardia (VT). However, data to support this description are lacking. The aim of our study was to evaluate the symptomatology of sustained monomorphic VT with emphasis on the prevalence of palpitations. Methods and Results Consecutive patients presenting to our center with a first event of a regular sustained monomorphic VT (n=59) or a regular supraventricular tachycardia (SVT; n=109) between January 2012 and September 2019 were interviewed regarding their symptoms during the arrhythmic event. We included only patients with a first arrhythmic event to avoid the influence of previous medical encounters on our patients’ terminology. As expected, patients with VT were older (age 68.8±13.6 versus 52.6±16.8 years; P <0.001), more often of male sex (94.9% versus 37.6%; P <0.001), had lower left ventricular ejection fraction (37±11% versus 59±2%, P <0.001) and more comorbidities (87.6% versus 40.5%; P <0.001) compared with patients with SVT. Importantly, even though the heart rate upon presentation did not differ between the 2 groups (165±26 beats/min during VT versus 171±32 beats/min during SVT; P =0.16), symptomatology differed significantly; specifically, palpitations were reported in only 8.8% of VT patients, compared with 90.7% of SVT patients ( P <0.001). Common symptoms in the VT group included chest pain (64%), dyspnea (21%), and dizziness (26%). Conclusions Despite similar heart rate, patients with VT rarely report having palpitations, whereas patients with SVT do so commonly. This finding may assist with decision making in patients reporting palpitations in whom an ECG tracing is not available.