Brugada syndrome genetics is associated with phenotype severity.

AIMS: Brugada syndrome (BrS) is associated with an increased risk of sudden cardiac death due to ventricular tachycardia/fibrillation (VT/VF) in young, otherwise healthy individuals. Despite SCN5A being the most commonly known mutated gene to date, the genotype-phenotype relationship is poorly understood and remains uncertain. This study aimed to elucidate the genotype-phenotype correlation in BrS. METHODS AND RESULTS: Brugada syndrome probands deemed at high risk of future arrhythmic events underwent genetic testing and phenotype characterization by the means of epicardial arrhythmogenic substrate (AS) mapping, and were divided into two groups according to the presence or absence of SCN5A mutation. Two-hundred probands (160 males, 80%; mean age 42.6 ± 12.2 years) were included in this study. Patients harbouring SCN5A mutations exhibited a spontaneous type 1 pattern and experienced aborted cardiac arrest or spontaneous VT/VF more frequently than the other subjects. SCN5A-positive patients exhibited a larger epicardial AS area, more prolonged electrograms and more frequently observed non-invasive late potentials. The presence of an SCN5A mutation explained >26% of the variation in the epicardial AS area and was the strongest predictor of a large epicardial area. CONCLUSION: In BrS, the genetic background is the main determinant for the extent of the electrophysiological abnormalities. SCN5A mutation carriers exhibit more pronounced epicardial electrical abnormalities and a more aggressive clinical presentation. These results contribute to the understanding of the genetic determinants of the BrS phenotypic expression and provide possible explanations for the varying degrees of disease expression.

Failure in evoking the trigeminal cardiac reflex by mandibular stretching in healthy volunteers.

Stimulation of trigeminal sensory afferences has been reported to evoke hypotension and bradycardia, a phenomenon known as the trigeminal cardiac reflex. We attempted to evoke such a reflex through cycles of alternate mandibular stretching in healthy volunteers, as previously reported, for its possible therapeutic exploitation. In Phase 1 of the study, 10 healthy volunteers [5 male, 5 female, age (mean ± SD) 27±2 years)] underwent 2 randomized sessions of automated monitoring, every 6 minutes, of systolic blood pressure (SBP), diastolic (D) BP, and heart rate (HR), with a one-week interval, either with mandibular stretching (12 minutes with a spring device fitted in the mouth), or nothing (control). Observation was prolonged for 180 minute after the end of the stretching. In Phase 2, 7 other volunteers (4 male and 3 female, age 24±1.3 years) repeated the protocol with a sampling interval of 2 minutes until the end of stretching. Baseline levels of SBP, DBP and HR were similar in the test and control sessions. There was a progressive fall of BP and HR as a function of time during the test session. With stretching: SBP changed from 119.2±10.1 to 118.1±10.1 to 115.8±10.5 mmHg, at baseline, end of stretching and 180 minutes after, respectively, p<0.001 at ANOVA for time effect). However, similar changes occurred in the control group: from 120.7±12.0 to 120.8±12.0 to 115.4±3.6 mmHg at the same times, P=0.822 for group effect). In Phase 2, again we observed no significant changes for any of the parameters investigated as a function of treatment. Despite attempts at maximum standardization of study condition and the use of operator-independent BP and HR measurements, we could not detect significant BP or HR effects of repeated mandibular stretching.

Mechanical Cardiopulmonary Resuscitation Devices: Evidence Synthesis with an Umbrella Review.

AIM: Sudden cardiac arrest is a significant cause of death worldwide. Good quality cardiopulmonary resuscitation increases patients' survival. Manual cardiopulmonary resuscitation is often ineffective as rescuers may experience physical and mental fatigue. Mechanical cardiopulmonary resuscitation devices are designed to address this issue, providing an automated approach for high-quality resuscitation. In the present comprehensive umbrella review we summarize current evidence on mechanical devices. METHODS: We searched systematic reviews on mechanical devices in MEDLINE/PubMed. Effect estimates were obtained from original reports, including 95% confidence intervals and p values, when applicable and available, focusing on return of spontaneous circulation, survival to discharge or 30 days, survival with good neurological outcome, and resuscitation-related injuries. RESULTS: From 21 potentially pertinent publications, we shortlisted 10 reviews, each including between 5 and 22 studies. AutoPulse, LUCAS, and LUCAS-2 were among the investigated devices. Most reviews concluded toward mechanical devices being similar or better than manual resuscitation for return of spontaneous circulation and 30-days survival. Regarding survival with good neurological function, some reviews lacked data, while the remaining ones reported similar results or worse outcomes in patients undergoing mechanical resuscitation. Focusing on resuscitation-related injuries, data were limited or conflicting with one review reporting higher rates of injuries with mechanical devices, and two others suggesting similar outcomes. CONCLUSIONS: Manual and mechanical cardiopulmonary resuscitation appear to be similar in terms of return of spontaneous circulation and short-term survival. Mechanical devices appear to be associated with higher resuscitation-related injuries, while there are conflicting data in terms of survival with good neurological outcomes. A comprehensive and large dedicated randomized trial is urgently needed.

It's a long way to the top! Congenital venous anomalies and left isomerism limiting atrial fibrillation transcatheter ablation.

BACKGROUND: Atrial fibrillation is the most common sustained cardiac arrhythmia in adults and it is associated with a high burden of mortality and morbidity worldwide. Catheter ablation is increasingly used to improve symptoms and prognosis in selected patients. Lower limb venous access with subsequent transseptal approach to the left atrium is the standard procedure for atrial fibrillation catheter ablation. CASE PRESENTATION: We report an unusual case of complex venous anomaly with a left-sided inferior vena cava with hemiazygos continuation to a persistent left superior vena cava draining in an enlarged coronary sinus in a patient with persistent atrial fibrillation scheduled for transcatheter ablation. DISCUSSION: Lower limb venous anomalies may limit a standard transseptal approach to the left atrium thus precluding an effective catheter ablation procedure for atrial fibrillation. Alternative interventions, such as unconventional percutaneous access, thoracoscopic approach and "ablate and pace" procedures, may be necessary in patients with symptomatic atrial fibrillation and complex venous anomalies.

Multivessel coronary spasm triggered by ganglionated plexi stimulation during atrial fibrillation radiofrequency catheter ablation: a case report.

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in adults, and it is associated with a high burden of mortality and morbidity worldwide. AF can be managed with rate-control or rhythm-control strategies. The latter is increasingly used to improve symptoms and prognosis in selected patients, especially after the development of catheter ablation. Although this technique is generally considered safe, it is not free from rare but life-threatening procedure-related adverse events. Among these, coronary artery spasm (CAS) is an uncommon but potentially fatal complication that requires immediate diagnosis and treatment. Case summary: We report a case of severe multivessel CAS triggered by ganglionated plexi stimulation during pulmonary vein isolation with radiofrequency catheter ablation in a patient with persistent AF, promptly resolved after intracoronary nitrate administration. Discussion: Although rare, CAS is a serious complication of AF catheter ablation. Immediate invasive coronary angiography is key for both diagnosis confirmation and treatment of such dangerous condition. As the number of invasive procedures increases, it is important that both interventional and general cardiologists are aware of possible procedure-related adverse events.

Case report: An unusual case of phrenic nerve stimulation in a patient with single chamber implantable cardioverter defibrillator.

Background: Phrenic nerve stimulation is a well-recognized complication related to cardiac implantable electronic devices, in particular with left ventricular coronary sinus pacing leads for cardiac resynchronization therapy. Case presentation: We report an unusual case of symptomatic phrenic nerve stimulation due to inadvertent placement of a right ventricular defibrillation lead in coronary sinus posterior branch in a patient with heart failure with reduced ejection fraction with a recently implanted single-chamber cardioverter defibrillator. Discussion: Phrenic nerve stimulation is a relatively common complication of left ventricular pacing. Inadvertent placement of a right ventricular lead in a coronary sinus branch is a rare but possible cause of phrenic nerve stimulation. Careful evaluation of intraprocedural fluoroscopic and electrocardiographic appearance of pacing and defibrillation leads during implantation may prevent inadvertent placement of a right ventricular lead in the coronary sinus.

Increase of Epicardial Adipose Tissue (EAT) With Fat Infiltration of Right Ventricular Myocardium: Is it Always a High-Risk Stigmata or a Worrisome Feature?

Incidental epicardial adipose tissue (EAT) and subepicardial fat infiltration on CT scans are not uncommon and the differential diagnosis can be a challenge. Considering the vastness of the possible disorders, it is important to differentiate physiologic age-related condition from pathologic disease. We present a case of an asymptomatic 81-year-old woman in which according to ECG and CMR findings we considered as possible differential diagnoses arrhythmogenic cardiomyopathy (ACM) dominant-right variant, lipomatosis and physiological growth of epicardial fat. We focus on patient characteristics, location of the fat replacement, heart morphovolumetry, wall motion of the ventricles and absence of late gadolinium enhancement to diagnose pericardial fat hypertrophy and physiological fatty infiltration. The role of EAT is unclear and it could play a part in the development of atherosclerosis and atrial fibrillation. Therefore, the clinicians should not underestimate this condition even if it would be an incidental finding in asymptomatic patients.

Exercise-induced myocardial edema in master triathletes: Insights from cardiovascular magnetic resonance imaging.

Background: Strenuous exercise has been associated with functional and structural cardiac changes due to local and systemic inflammatory responses, reflecting oxidative, metabolic, hormonal, and thermal stress, even in healthy individuals. We aimed to assess changes in myocardial structure and function using cardiovascular magnetic resonance (CMR) imaging in master triathletes early after a full-distance Ironman Triathlon race. Materials and methods: Ten master triathletes (age 45 ± 8 years) underwent CMR within 3 h after a full-distance Ironman Triathlon race (3.8 km swimming, 180 km cycling, and 42.2 km running) completed with a mean time of 12 ± 1 h. All the triathletes had a 30-day follow-up CMR. Cine balanced steady-state free precession, T2-short tau inversion recovery (STIR), tagging, and late gadolinium enhancement (LGE) imaging sequences were performed on a 1.5-T MR scanner. Myocardial edema was defined as a region with increased T2 signal intensity (SI) of at least two SDs above the mean of the normal myocardium. The extent of myocardial edema was expressed as the percentage of left ventricular (LV) mass. Analysis of LV strain and torsion by tissue tagging included the assessment of radial, longitudinal, and circumferential peak systolic strain, rotation, and twist. Results: Compared with postrace, biventricular volumes, ejection fraction, and LV mass index remained unchanged at 30-day follow-up. Global T2 SI was significantly higher in the postrace CMR (postrace 10.5 ± 6% vs. follow-up 3.9 ± 3.8%, P = 0.004) and presented with a relative apical sparing distribution (P < 0.001) matched by reduction of radial peak systolic strain of basal segments (P = 0.003). Apical rotation and twist were significantly higher immediately after the competition compared with follow-up (P < 0.05). Conclusion: Strenuous exercise in master triathletes is associated with a reversible regional increase in myocardial edema and reduction of radial peak systolic strain, both presenting with a relative apical sparing pattern.

Urine alkalinisation to prevent contrast-induced acute kidney injury: the prospective, randomised, controlled, open-label TEATE trial.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is prognostically relevant in invasive cardiological and radiological procedures. The administration of sodium bicarbonate has controversial effects. It has been hypothesised that bicarbonate is ineffective when unable to achieve adequate urine alkalinisation. AIMS: We tested the hypothesis that alkaline urine status with oral or intravenous (i.v.) bicarbonate on top of hydration alone prevents CI-AKI. METHODS: In a prospective, randomised, parallel-group, open-label trial, we compared 1) saline hydration alone (n=81); 2) i.v. bicarbonate (n=82); and 3) oral bicarbonate (n=78), in patients with chronic kidney disease (CKD) scheduled for the intra-arterial administration of contrast medium. The primary endpoint was the incidence of CI-AKI according to alkaline urine status achieved immediately before angiography. Secondary endpoints were the mean change of urine pH up to the time of angiography and the incidence of CI-AKI in the three groups. RESULTS: The incidence of CI-AKI was not significantly different in the three treatment arms (20% in the hydration group, 21% in the oral bicarbonate group and 22% in the i.v. bicarbonate group; p=0.94). Patients achieving a pH >6 before angiography (n=145) had a significantly lower incidence of CI-AKI compared with the others (n=96; odds ratio [OR] 0.48, 95% confidence interval [CI]: 0.25-0.90; p=0.023, primary study hypothesis). The proportion of patients achieving a pH >6 was higher in the i.v. and oral bicarbonate groups compared with hydration alone. CONCLUSIONS: Urinary pH before administration of contrast medium is an inverse correlate of CI-AKI incidence, and bicarbonate is superior to hydration alone in achieving urinary alkalinisation. Since, however, bicarbonate did not reduce the incidence of CI-AKI, we conclude that urinary pH is a marker and not a mediator of CI-AKI (ClinicalTrials.gov: NCT02980003).

Assessing QT interval in COVID-19 patients:safety of hydroxychloroquine-azithromycin combination regimen.

BACKGROUND: Hydroxychloroquine (HCQ) and azithromycin (AZT) have been proposed for COVID-19 treatment. Data available in the literature reported a potential increased risk of fatal arrhythmias under these therapies. The aim of this study was to assess the effects of these drugs on QT interval and outcome in a COVID-19 population. METHOD: A total of 112 consecutive COVID-19 patients were included in this analysis and were divided in 3 groups according to the receiving therapeutic regimens: 19 (17%) patients in Group 1 (no treatment), 40 (36%) in Group 2 (HCQ only), 53 (47%) in Group 3 (HCQ/AZT). RESULTS: A prolonged QTc interval was found in 61% of patients treated with HCQ alone or in combination with AZT, but only 4 (4%) patients showed a QTc > 500 ms. HCQ/AZT combination determined a greater increase of QTc duration compared to the other two strategies (Group 3 452 ± 26.4 vs Group 2 436.3 ± 28.4 vs Group 1 424.4 ± 24.3 ms, respectively; p < 0.001). Multivariate analysis demonstrated that HCQ/AZT combination (OR 9.02, p = 0.001) and older age (OR 1.04, p = 0.031) were independent predictors of QTc prolongation. The risk increased with age (incremental utility analysis p = 0.02). Twenty patients (18%) died, and no cardiac arrest neither arrhythmic fatalities were documented. CONCLUSIONS: The HCQ/AZT combination therapy causes a significantly increase of QT interval compared to HCQ alone. Older patients under such regimen are at higher risk of experiencing QT prolongation. The use of such drugs may be considered as safe relating to arrhythmic risk in the treatment of COVID-19 patients as no arrhythmic fatalities occurred.