Incidence of ventricular arrhythmias related to COVID infection and vaccination in patients with Brugada syndrome: Insights from a large Italian multicenter registry based on continuous rhythm monitoring.

INTRODUCTION: Brugada syndrome (BrS) has a dynamic ECG pattern that might be revealed by certain conditions such as fever. We evaluated the incidence and management of ventricular arrhythmias (VAs) related to COVID-19 infection and vaccination among BrS patients carriers of an implantable loop recorder (ILR) or implantable cardioverter-defibrillator (ICD) and followed by remote monitoring. METHODS: This was a multicenter retrospective study. Patients were carriers of devices with remote monitoring follow-up. We recorded VAs 6 months before COVID-19 infection or vaccination, during infection, at each vaccination, and up to 6-month post-COVID-19 or 1 month after the last vaccination. In ICD carriers, we documented any device intervention. RESULTS: We included 326 patients, 202 with an ICD and 124 with an ILR. One hundred and nine patients (33.4%) had COVID-19, 55% of whom developed fever. Hospitalization rate due to COVID-19 infection was 2.76%. After infection, we recorded only two ventricular tachycardias (VTs). After the first, second, and third vaccines, the incidence of non-sustained ventricular tachycardia (NSVT) was 1.5%, 2%, and 1%, respectively. The incidence of VT was 1% after the second dose. Six-month post-COVID-19 healing or 1 month after the last vaccine, we documented NSVT in 3.4%, VT in 0.5%, and ventricular fibrillation in 0.5% of patients. Overall, one patient received anti-tachycardia pacing and one a shock. ILR carriers had no VAs. No differences were found in VT before and after infection and before and after each vaccination. CONCLUSIONS: From this large multicenter study conducted in BrS patients, followed by remote monitoring, the overall incidence of sustained VAs after COVID-19 infection and vaccination is relatively low.

Management of macro-reentrant right atrial tachycardia around multiple leads aided by high-density mapping.

BACKGROUND: A 61-year-old male with Steinert Dystrophy and prior history of cardiac implantable device complained of highly symptomatic right atrial tachycardia. Unresponsive to pharmacological therapy. METHODS: The patient underwent catheter ablation procedure aided by high-density mapping. RESULTS: Ablation procedure was succesful. CONCLUSIONS: This unique case report highlights the role of high-density mapping in the identification of critical isthmus and management of macro-reentrant tachycardia in complex situations such as the presence of multiple leads in the chamber.

Leadless pacemaker implantation in superobese patient.

Background: A 70 years-old superobese man (weighted 230 kg) was referred to our hospital for recurrent syncope due to asystole alternating to atrial fibrillation. Convectional pacing was highly challenging; therefore, it was decided to implant a leadless pacemaker in a multidisciplinary intervention with surgical management of the femoral venous access. Methods: In a fully equipped operating room with bariatric table and appropriately dimensioned fluoroscope, a vascular surgeon performed surgical isolation of the right common femoral vein. After that, we proceeded to insert sheaths via the femoral vein, and through that a steerable transcatheter delivery system for the device. Results: The implant was successful without complication. Conclusions: Leadless pacemaker implantation can be effectively and safely performed even in superobese patients. Vascular access, fluoroscopic guidance and electronic interrogation could be easily managed and do not constitute a limit.

Antibiotic prophylaxis based on individual infective risk stratification in cardiac implantable electronic device: the PRACTICE study.

AIMS: In patients undergoing cardiac implantable electronic device (CIED) intervention, routine pre-procedure antibiotic prophylaxis is recommended. A more powerful antibiotic protocol has been suggested in patients at high risk of infection. Stratification of individual infective risk could guide the prophylaxis before CIED procedure. METHODS AND RESULTS: Patients undergoing CIED surgery were stratified according to the Shariff score in low and high infective risk. Patients in the 'low-risk' group were treated with only two antibiotic administrations while patients in the 'high-risk' group were treated with a prolonged 9-day protocol, according to renal function and allergies. We followed-up patients for 250 days with clinical outpatient visit and electronic control of the CIED. As primary endpoint, we evaluated CIED-related infections. A total of 937 consecutive patients were enrolled, of whom 735 were stratified in the 'low-risk' group and 202 in the 'high-risk' group. Despite different risk profiles, CIED-related infection rate at 250 days was similar in the two groups (8/735 in 'low risk' vs. 4/202 in 'high risk', P = 0.32). At multivariate analysis, active neoplasia, haematoma, and reintervention were independently associated with CIED-related infection (HR 5.54, 10.77, and 12.15, respectively). CONCLUSION: In a large cohort of patients undergoing CIED procedure, an antibiotic prophylaxis based on individual stratification of infective risk resulted in similar rate of infection between groups at high and low risk of CIED-related infection.

Functional Characterization of Two Novel Mutations in SCN5A Associated with Brugada Syndrome Identified in Italian Patients.

BACKGROUND: Brugada syndrome (BrS) is an autosomal dominantly inherited cardiac disease characterized by "coved type" ST-segment elevation in the right precordial leads, high susceptibility to ventricular arrhythmia and a family history of sudden cardiac death. The SCN5A gene, encoding for the cardiac voltage-gated sodium channel Nav1.5, accounts for ~20-30% of BrS cases and is considered clinically relevant. METHODS: Here, we describe the clinical findings of two Italian families affected by BrS and provide the functional characterization of two novel SCN5A mutations, the missense variant Pro1310Leu and the in-frame insertion Gly1687_Ile1688insGlyArg. RESULTS: Despite being clinically different, both patients have a family history of sudden cardiac death and had history of arrhythmic events. The Pro1310Leu mutation significantly reduced peak sodium current density without affecting channel membrane localization. Changes in the gating properties of expressed Pro1310Leu channel likely account for the loss-of-function phenotype. On the other hand, Gly1687_Ile1688insGlyArg channel, identified in a female patient, yielded a nearly undetectable sodium current. Following mexiletine incubation, the Gly1687_Ile1688insGlyArg channel showed detectable, albeit very small, currents and biophysical properties similar to those of the Nav1.5 wild-type channel. CONCLUSIONS: Overall, our results suggest that the degree of loss-of-function shown by the two Nav1.5 mutant channels correlates with the aggressive clinical phenotype of the two probands. This genotype-phenotype correlation is fundamental to set out appropriate therapeutical intervention.

Stroke and mortality risk after atrial fibrillation ablation: lesson from the CABANA trial.

The CABANA trial is a randomized controlled study comparing catheter ablation vs. conventional medical therapy in atrial fibrillation (AF) patients. The results of the study showed that catheter ablation did not have a significant reduction of strokes, deaths, serious bleeding, or cardiac arrest compared to medical therapy. However, a significant improvement in AF recurrences, quality of life, and symptom relief has been shown after catheter ablation compared to drug therapy. The mixed results of the study emphasized an active controversy in the cardiology community on the interpretation of the data and their use in current clinical practice. In this review, we summarized the principal controversy points of the trial describing the strengths and weaknesses of the study design and analysis.

Atrial fibrillation ablation in heart failure.

Atrial fibrillation (AF) and heart failure (HF) commonly coexist in the same patient and either condition predisposes to the other. Several mechanisms promote the pathophysiological relationship between AF and HF, reducing quality of life, increasing the risk of stroke, and worsening HF progression. Although restoration and maintenance of sinus rhythm would be ideal for those patients, several trials comparing rhythm and rate control failed to show a benefit of rhythm control strategy, achieved with pharmacological therapy, in terms of hospitalization for HF or death. Catheter ablation is a well-established option for symptomatic AF patients, resistant to drug therapy, with normal cardiac function. Several recent studies have shown an improvement in clinical outcomes after AF ablation in HF patients highlighting the emerging role of the invasive approach in this subset of patients. However, several concerns regarding patients' selection and standardization of the procedure still remain to be addressed.

When to choose cardiac resynchronization therapy in chronic heart failure: type and duration of the conduction delay.

Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure (HF), impaired left ventricular (LV) function, and wide QRS complex. The initial randomized clinical trials, which led to the widespread use of CRT, selected patients on the basis of QRS duration, not focusing on QRS morphology. However, recent evidences emphasized the role of left bundle branch block morphology in patients that underwent CRT in order to predict better response to therapy. Moreover, conventional right ventricular apical pacing might have long-term detrimental effects on cardiac structure and LV function, possibly leading to the development of HF. Therefore, current guidelines recommend upgrade from conventional pacemaker or implantable cardioverter-defibrillator to CRT or de novo CRT in patients with high (or expected high) percentage of ventricular pacing and reduced EF. We reviewed current knowledge on candidates' selection for CRT based on conduction delays that lead to electrical and mechanical dyssynchrony of the left ventricle.

Angina and left ventricular dysfunction: can we 'reduce' it?

Despite the evolution in pharmacology and devices, recurrent and persistent angina still represent a frequent issue in clinical practice. A 69-year-old Caucasian female patient has history of surgical aortic valve replacement with a bioprosthesis for severe aortic stenosis with subsequent transcatheter valve-in-valve implantation for bioprosthesis degeneration and single coronary artery bypass graft with left internal mammary artery on left anterior descending (LAD). After transcatheter aortic valve implantation, she started to complain angina [Canadian Cardiovascular Society (CCS) Class III], effectively treated with bisoprolol uptitration and ivabradine 5 b.i.d. addition. After 6 months, she had a non-ST segment elevated myocardial infarction with evidence of left main occlusion and good functioning aortic bioprosthesis. A retrograde drug-eluting balloon percutaneous coronary intervention (PCI) on LAD (in-stent restenosis) was performed. However, the patient continued to complain angina (CCS Class II-III), even after further ivabradine increase to 7.5 mg b.i.d. After 4 months, the patient underwent Reducer implantation. After 2 months, angina started to improve and the patient is currently angina free. In the last decades, PCI materials and stents greatly improved. Medical therapy (such as ß-blockers) has been shown not only to improve symptoms but also to add a prognostic benefit in patients with reduced ejection fraction (EF). Ivabradine showed additional benefits in patients with angina and reduced EF. However, still a relevant portion of patients complain refractory angina. The COSIRA trial showed that a coronary sinus Reducer was associated with greater angina relief than the sham procedure and could be a further step in angina treatment.

Right Ventricle Function in Patients with Acute Coronary Syndrome and Concomitant Undiagnosed Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is frequently undiagnosed in patients with ischemic heart disease. Nowadays, it is still unknown whether undiagnosed concomitant COPD is related to early structural changes of the heart, as detectable by trans-thoracic echocardiography (TTE). Starting from the study population of the Screening for COPD in ACS Patients (SCAP) trial, we sought to investigate potential differences in echocardiographic parameters in patients with acute coronary syndromes (ACS), with or without undiagnosed concomitant COPD. Overall, 137 patients were included. Undiagnosed COPD was detected by spirometry in 39 (29%) patients. TTE was performed at inclusion (before hospital discharge) and after six months. Several echocardiographic parameters including fractional area change (FAC) and RV strain (RVS), were measured. Patients with undiagnosed COPD, as compared to those without COPD, showed lower FAC and reduced RVS both at inclusion (37 ± 6% vs. 44 ± 9%, p < 0.001; -15 ± -4 vs. -20 ± -5, p < 0.001, respectively) and after six months (38 ± 7% vs. 45 ± 9%, p < 0.001; -16 ± -4 vs. -20 ± -5, p < 0.001, respectively). After multivariate analysis undiagnosed COPD was independently associated with lower FAC and reduced RVS at baseline and at TTE after six months. Early impairment of RV function can be detected in ACS patients with concomitant undiagnosed COPD. If these alterations may be changed by an early diagnosis and an early treatment, should be evaluated in future studies. Clinical trial registration: NCT02324660.

Treatment of Angina: Where Are We?

Ischaemic heart disease is a major cause of death and disability worldwide, while angina represents its most common symptom. It is estimated that approximately 9 million patients in the USA suffer from angina and its treatment is challenging, thus the strategy to improve the management of chronic stable angina is a priority. Angina might be the result of different pathologies, ranging from the "classical" obstruction of a large coronary artery to alteration of the microcirculation or coronary artery spasm. Current clinical guidelines recommend antianginal therapy to control symptoms, before considering coronary artery revascularization. In the current guidelines, drugs are classified as being first-choice (beta-blockers, calcium channel blockers, and short-acting nitrates) or second-choice (ivabradine, nicorandil, ranolazine, trimetazidine) treatment, with the recommendation to reserve second-line modifications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. However, such a categorical approach is currently questioned. In addition, current guidelines provide few suggestions to guide the choice of drugs more suitable according to the underlying pathology or the patient comorbidities. Several other questions have recently emerged, such as: is there evidence-based data between first- and second-line treatments in terms of prognosis or symptom relief? Actually, it seems that newer antianginal drugs, which are classified as second choice, have more evidence-based clinical data that are more contemporary to support their use than what is available for the first-choice drugs. It follows that actual guidelines are based more on tradition than on evidence and there is a need for new algorithms that are more individualized to patients, their comorbidities, and pathophysiological mechanism of chronic stable angina.

Reperfusion Damage　- A Story of Success, Failure, and Hope.

Tissue salvage of severely ischemic myocardium requires timely reperfusion by thrombolysis, angioplasty, or bypass. However, recovery of left ventricular function is rare. It may be absent or, even worse, reperfusion can induce further damage. Laboratory studies have shown convincingly that reperfusion can increase injury over and above that attributable to the pre-existing ischemia, precipitating arrhythmias, suppressing the recovery of contractile function ("stunning") and possibly even causing cell death in potentially salvable ischemic tissue. The mechanisms of reperfusion injury have been widely studied and, in the laboratory, it can be attenuated or prevented. Disappointingly, this is not the case in the clinic, particularly after thrombolysis or primary angioplasty. In contrast, excellent results have been achieved by surgeons by means of cardioplegia and hypothermia. For the interventionist, the issue is more complex as, contrary to cardiac surgery where the cardioplegia can be applied before ischemia and the heart can be stopped, during an angioplasty the heart still has to beat to support the circulation. We analyze in detail all these issues.

The frailty in elderly patients receiving cardiac interventional procedures (FRASER) program: rational and design of a multicenter prospective study.

BACKGROUND: Frailty has become a high-priority issue in cardiovascular medicine because of the aging of cardiovascular patients. Simple and reproducible tools to assess frailty in elderly patients are clearly on demand. Their application may help physicians in the selection of invasive and medical treatments and in the timing and modality of the follow-up. The frailty in elderly patients receiving cardiac interventional procedures (FRASER) program is designed with the aim to validate the use of the short physical performance battery (SPPB) as prognostic tools in patients admitted to hospital for acute coronary syndrome (ACS). METHODS: The FRASER program is a multicenter prospective study involving 4 Italian cardiology units. The FRASER program enrolls only patients aged ≥70 years. The core of the FRASER program includes patients admitted to hospital for ACS. The aims are (1) to describe SPPB distribution before hospital discharge and (2) to investigate the prognostic role of SPPB score. The primary outcome is a composite of 1-year all-cause mortality and hospital readmission for any cause. Ancillary analyses will be focused on different study populations (patients hospitalized for arrhythmias or acute heart failure or symptomatic severe aortic stenosis) and on different tools to assess frailty (multidimensional prognostic index, clinical frailty score, grip strength). DISCUSSION: The FRASER program will fill critical gaps in the knowledge regarding the link between frailty, cardiovascular disease, interventional procedures and outcome and will help physicians in the generation of a more personalized risk assessment and in the identification of potential targets for interventions.

P-wave duration in lead aVR and the risk of atrial fibrillation in hypertension.

BACKGROUND: Hypertension entails atrial remodeling that affect P-wave (PW) duration on electrocardiogram (ECG). PW indices (e.g., variance, dispersion, and terminal force) are associated with a higher risk for atrial fibrillation (AF), but their calculation requires multiple measurements of PW duration, limiting their use in clinical practice. We evaluated whether PW duration in specific ECG leads may identify patients with increased susceptibility to AF in a population of hypertensive patients. METHODS: In a case-control study, AF and control subjects were matched for age, sex, and left atrial (LA) dimensions. PW duration was measured from digitally stored ECGs. Logistic regression was used to assess the association of PW duration and indices with AF. RESULTS: We enrolled 44 hypertensive AF patients (16 paroxysmal and 28 persistent) and 44 hypertensive controls. AF and control subjects were matched for sex (males, n = 27), age (67 ± 8 years), LA diameter (40 ± 5 mm), and were comparable for left ventricular mass (45 ± 11 g/m(2.7) vs 48 ± 12 g/m(2.7) , P = 0.19), ejection fraction (58 ± 7% in both groups), and prevalence of mild valvular heart disease (7% vs 5%; P = 0.64). PW duration in lead aVR was significantly higher in AF patients as compared with controls (115 ± 18 ms vs 101 ± 14 ms; P < 0.0001) and was the best independent predictor of AF in multivariable logistic regression (PW ≥ 100 ms: RR = 3.7; 95% CI: 1.3-10.3; P = 0.02). CONCLUSIONS: Simple measurement of PW duration in lead aVR allows effective identification of AF patients in a population of hypertensives. Confirmation of this finding in a larger population would provide a simple and effective risk marker of AF in hypertensive patients.

Osteopontin and galectin-3 predict the risk of ventricular tachycardia and fibrillation in heart failure patients with implantable defibrillators.

BACKGROUND: Myocardial extracellular matrix remodelling provides electrical heterogeneity entailing ventricular tachycardia/fibrillation (VT/VF) in heart failure (HF) patients. Osteopontin (OPN) and Galectin-3 (Gal-3) are fibrosis markers and may reflect the extension of the arrhythmogenic substrate. We assessed whether plasma OPN and Gal-3 predict the risk of sustained VT/VF in a cohort of HF patients with implantable cardioverter-defibrillator (ICD). METHODS: A total of 75 HF patients underwent pre-ICD implantation clinical evaluation and assessment of plasma OPN and Gal-3. The primary endpoint was the time to the occurrence of the first sustained VT/VF. Hazard ratios (HR) were derived from Cox proportional-hazards analysis. RESULTS: Patients with coronary artery disease (CAD) had higher plasma OPN (79.8 ± 44.0 ng/mL vs. 66.0 ± 31.8 ng/mL; P = 0.04). Both Gal-3 (r = -0.38; P = 0.01) and OPN (r = -0.27; p = 0.01) were negatively related to estimated glomerular filtration rate. After 29 ± 17 months, 20 patients (27%) reached the primary endpoint. Patients with VT/VF had higher plasma OPN and Gal-3 (97.4 ± 51.7 ng/mL vs. 65.9 ± 31.3 ng/mL; P = 0.002 and 19.7 ± 8.5 ng/mL vs. 16.2 ± 6.2 ng/mL; P = 0.05). In univariate analysis, OPN (log-OPN, HR: 32.4; 95%CI: 3.9-264.7; P = 0.001) and Gal-3 (HR: 1.05; 95%CI: 1.00-1.11; P = 0.04) predicted sustained VT/VF. In multivariable analysis, both OPN (HR: 41.4; 95%CI: 3.8-441.9; P = 0.002) and Gal-3 (HR: 1.06; 95%CI: 1.00-1.12; P = 0.03) retained their prognostic power after correction for age, sex, history of MI, EF, NYHA class, eGFR, use of ACE-I, and amiodarone. CONCLUSIONS: Plasma OPN and Gal-3 predict sustained VT/VF in HF patients at high risk for SCD. Larger prospective studies should outline the role of these biomarkers in predicting SCD on top of conventional risk stratification.

Trends in atrial fibrillation-related mortality in Europe, 2008-2019.

AIMS: Update data regarding the atrial fibrillation (AF)-related mortality trend in Europe remain scant. We assess the age- and sex-specific trends in AF-related mortality in the European states between the years 2008 and 2019. METHODS AND RESULTS: Data on cause-specific deaths and population numbers by sex for European countries were retrieved through the publicly available World Health Organization mortality dataset for the years 2008-2019. Atrial fibrillation-related deaths were ascertained when the International Classification of Diseases, 10th Revision code I48 was listed as the underlying cause of death in the medical death certificate. To calculate annual trends, we assessed the average annual % change (AAPC) with relative 95% confidence intervals (CIs) using Joinpoint regression. During the study period, 773 750 AF-related deaths (202 552 males and 571 198 females) occurred in Europe. The age-adjusted mortality rate (AAMR) linearly increased from 12.3 (95% CI: 11.2-12.9) per 100 000 population in 2008 to 15.3 (95% CI: 14.7-15.7) per 100 000 population in 2019 [AAPC: +2.0% (95% CI: 1.6-3.5), P < 0.001] with a more pronounced increase among men [AAPC: +2.7% (95% CI: 1.9-3.5), P < 0.001] compared with women [AAPC: +1.7% (95% CI: 1.1-2.3), P < 0.001] (P for parallelism 0.01). Higher AAMR increases were observed in some Eastern European countries such as Latvia, Lithuania, and Poland, while the lower increases were mainly clustered in Central Europe. CONCLUSION: Over the last decade, the age-adjusted AF-related mortality has increased in Europe, especially among males. Disparities still exist between Western and Eastern European countries.

Prognostic Electrocardiographic Signs in Arrhythmogenic Cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is a rare cardiac disease, characterized by the progressive replacement of myocardial tissue with fibrous and fatty deposits. It can involve both the right and left ventricles. It is associated with the development of life-threatening arrhythmias and culminates in sudden cardiac death. Electrocardiography (ECG) has emerged as a pivotal tool, offering diagnostic insights and prognostic information. The specific ECG abnormalities observed in ACM not only contribute to early detection but also hold the key to the prediction of the likelihood of severe complications. The recognition of these nuanced ECG manifestations has become imperative for clinicians as it guides them in the formulation of tailored therapeutic strategies that address both the present symptoms and the potential future risks.