Pulsed Field Energy in Atrial Fibrillation Ablation: From Physical Principles to Clinical Applications.

Atrial fibrillation, representing the most prevalent sustained cardiac arrhythmia, significantly impacts stroke risk and cardiovascular mortality. Historically managed with antiarrhythmic drugs with limited efficacy, and more recently, catheter ablation, the interventional approach field is still evolving with technological advances. This review highlights pulsed field ablation (PFA), a revolutionary technique gaining prominence in interventional electrophysiology because of its efficacy and safety. PFA employs non-thermal electric fields to create irreversible electroporation, disrupting cell membranes selectively within myocardial tissue, thus preventing the non-selective damage associated with traditional thermal ablation methods like radiofrequency or cryoablation. Clinical studies have consistently shown PFA's ability to achieve pulmonary vein isolation-a cornerstone of AF treatment-rapidly and with minimal complications. Notably, PFA reduces procedure times and has shown a lower incidence of esophageal and phrenic nerve damage, two common concerns with thermal techniques. Emerging from oncological applications, the principles of electroporation provide a unique tissue-selective ablation method that minimizes collateral damage. This review synthesizes findings from foundational animal studies through to recent clinical trials, such as the MANIFEST-PF and ADVENT trials, demonstrating PFA's effectiveness and safety. Future perspectives point towards expanding indications and refinement of techniques that promise to improve AF management outcomes further. PFA represents a paradigm shift in AF ablation, offering a safer, faster, and equally effective alternative to conventional methods. This synthesis of its development and clinical application outlines its potential to become the new standard in AF treatment protocols.

Protection against Ischemic Heart Disease: A Joint Role for eNOS and the KATP Channel.

Genetic susceptibility may influence ischemic heart disease (IHD) predisposition and affect coronary blood flow (CBF) regulation mechanisms. The aim of this study was to investigate the association among single nucleotide polymorphisms (SNPs) of genes encoding for proteins involved in CBF regulation and IHD. A total of 468 consecutive patients were enrolled and divided into three groups according to coronary angiography and intracoronary functional tests results: G1, patients with coronary artery disease (CAD); G2, patients with coronary microvascular dysfunction (CMD); and G3, patients with angiographic and functionally normal coronary arteries. A genetic analysis of the SNPs rs5215 of the potassium inwardly rectifying channel subfamily J member 11 (KCNJ11) gene and rs1799983 of the nitric oxide synthase 3 (NOS3) gene, respectively encoding for the Kir6.2 subunit of ATP sensitive potassium (KATP) channels and nitric oxide synthase (eNOS), was performed on peripheral whole blood samples. A significant association of rs5215_G/G of KCNJ11 and rs1799983_T/T of NOS3 genes was detected in healthy controls compared with CAD and CMD patients. Based on univariable and multivariable analyses, the co-presence of rs5215_G/G of KCNJ11 and rs1799983_T/T of NOS3 may represent an independent protective factor against IHD, regardless of cardiovascular risk factors. This study supports the hypothesis that SNP association may influence the crosstalk between eNOS and the KATP channel that provides a potential protective effect against IHD.

[2020 Catheter Ablation Registry of the Italian Association of Arrhythmology and Cardiac Pacing]. / Registro Italiano Ablazioni 2020. Associazione Italiana di Aritmologia e Cardiostimolazione.

BACKGROUND: This report describes the findings of the 2020 Italian Catheter Ablation Registry of the Italian Association of Arrhythmology and Cardiac Pacing (AIAC). METHODS: Data collection was retrospective. A standardized questionnaire was completed by each of the participating centers. RESULTS: A total of 10 378 ablation procedures were performed by 66 institutions. Most centers (70%) have an electrophysiology laboratory, and 23% a hybrid cardiac surgery laboratory. All centers have a 3D mapping system. The median number of electrophysiologists and nurses involved in the electrophysiology laboratory was 3.5 and 3, respectively. An electrophysiology technician was involved in 35% of all centers. In 88.2% of cases, catheter ablation was performed for supraventricular arrhythmias; the most frequently treated arrhythmia was atrial fibrillation (39.4%), followed by atrioventricular nodal reentrant tachycardia (18.6%), and common atrial flutter (10.6%). In 72.9% of patients, catheter ablation was performed using a 3D mapping system, with a "near-zero" fluoroscopic approach in 37.7% of all patients. CONCLUSIONS: The 2020 Italian Catheter Ablation Registry confirmed that the electrophysiology activity was markedly affected by the COVID-19 pandemic; atrial fibrillation is the most frequently treated arrhythmia with an increasing number of procedures performed with a 3D mapping system and a "near-zero" approach.

The need for a subsequent transvenous system in patients implanted with subcutaneous implantable cardioverter-defibrillator.

BACKGROUND: The absence of pacing capabilities may reduce the appeal of subcutaneous implantable cardioverter-defibrillator (S-ICD) devices for patients at risk for conduction disorders or with antitachycardia pacing (ATP)/cardiac resynchronization (CRT) requirements. Reports of rates of S-ICD to transvenous implantable cardioverter-defibrillator (TV-ICD) system switch in real-world scenarios are limited. OBJECTIVE: The purpose of this study was to investigate the need for a subsequent transvenous (TV) device in patients implanted with an S-ICD and its predictors. METHODS: All patients implanted with an S-ICD were enrolled from the multicenter, real-world iSUSI (International SUbcutaneouS Implantable cardioverter defibrillator) Registry. The need for a TV device and its clinical reason, and appropriate and inappropriate device therapies were assessed. Logistic regression with Firth penalization was used to assess the association between baseline and procedural characteristics and the overall need for a subsequent TV device. RESULTS: A total of 1509 patients were enrolled (age 50.8 ± 15.8 years; 76.9% male; 32.0% ischemic; left ventricular ejection fraction 38% [30%-60%]). Over 26.5 [13.4-42.9] months, 155 (10.3%) and 144 (9.3%) patients experienced appropriate and inappropriate device therapies, respectively. Forty-one patients (2.7%) required a TV device (13 bradycardia; 10 need for CRT; 10 inappropriate shocks). Body mass index (BMI) >30 kg/m2 and chronic kidney disease (CKD) were associated with need for a TV device (odds ratio [OR] 2.57 [1.37-4.81], P = .003; and OR 2.67 [1.29-5.54], P = .008, respectively). CONCLUSION: A low rate (2.7%) of conversion from S-ICD to a TV device was observed at follow-up, with need for antibradycardia pacing, ATP, or CRT being the main reasons. BMI >30 kg/m2 and CKD predicted all-cause need for a TV device.

Hypersensitivity Myocarditis after COVID-19 mRNA Vaccination.

BACKGROUND: Myocarditis, even in a severe and lethal form, may occur after COVID-19 mRNA (BNT162b2) vaccination. However, its pathway, morphomolecular characterization and treatment are still unknown. METHODS: Routine hematochemical screening, ECG, Holter monitoring, 2D echocardiogram cardiac magnetic resonance (CMR) and invasive cardiac studies (cardiac catheterization, selective coronary angiography, left ventriculography and left ventricular endomyocardial biopsy) are reported from three patients (39F-pt1, 78M-pt2, 52M-pt3) with severe compromise of conduction tissue (junctional rhythm and syncope, pt1) or cardiac function compromise (LVEF ≤ 35%, pt2 and pt3) after COVID-19 mRNA (BNT162b2). RESULTS: Hematochemical data and coronary angiography were normal in the patients studied. Histology showed in all three patients extensive myocardial infiltration of degranulated eosinophils and elevation of serum cationic protein directly responsible for cardiomyocyte damage. These findings demonstrate myocarditis hypersensitivity to some component of the vaccine (spike protein?) acting as a hapten to some macromolecules of cardiomyocytes. Steroid administration (prednisone, 1 mg/kg die for 3 days, followed by 0.33 mg/kg for 4 weeks) was followed by complete recovery of cardiac contractility in pt2 and pt3. CONCLUSIONS: Eosinophilic myocarditis is a possible adverse reaction to the mRNA COVID-19 vaccine. Its pathway is mediated by release of cationic protein and responds to short courses of steroid administration.

Age-related differences and associated mid-term outcomes of subcutaneous implantable cardioverter-defibrillators: A propensity-matched analysis from a multicenter European registry.

BACKGROUND: A few limited case series have shown that the subcutaneous implantable cardioverter-defibrillator (S-ICD) system is safe for teenagers and young adults, but a large-scale analysis currently is lacking. OBJECTIVES: The purpose of this study was to compare mid-term device-associated outcomes in a large real-world cohort of S-ICD patients, stratified by age at implantation. METHODS: Two propensity-matched cohorts of teenagers + young adults (≤30 years old) and adults (>30 years old) were retrieved from the ELISIR Registry. The primary outcome was the comparison of inappropriate shock rate. Complications, freedom from sustained ventricular arrhythmias, and overall and cardiovascular mortality were deemed secondary outcomes. RESULTS: Teenagers + young adults represented 11.0% of the entire cohort. Two propensity-matched groups of 161 patients each were used for the analysis. Median follow-up was 23.1 (13.2-40.5) months. In total, 15.2% patients experienced inappropriate shocks, and 9.3% device-related complications were observed, with no age-related differences in inappropriate shocks (16.1% vs 14.3%; P = .642) and complication rates (9.9% vs 8.7%; P = .701). At univariate analysis, young age was not associated with increased rates of inappropriate shocks (hazard ratio [HR] 1.204 [0.675-2.148]: P = .529). At multivariate analysis, use of the SMART Pass algorithm was associated with a strong reduction in inappropriate shocks (adjusted HR 0.292 [0.161-0.525]; P <.001), whereas arrhythmogenic right ventricular cardiomyopathy (ARVC) was associated with higher rates of inappropriate shocks (adjusted HR 2.380 [1.205-4.697]; P = .012). CONCLUSION: In a large multicenter registry of propensity-matched patients, use of the S-ICD in teenagers/young adults was safe and effective. The rates of inappropriate shocks and complications between cohorts were not significantly different. The only predictor of increased inappropriate shocks was a diagnosis of ARVC.

New evidence of direct oral anticoagulation therapy on cardiac valve calcifications, renal preservation and inflammatory modulation.

BACKGROUND: Rivaroxaban is a direct inhibitor of activated Factor X (FXa), an anti-inflammatory protein exerting a protective effect on the cardiac valve and vascular endothelium. We compare the effect of Warfarin and Rivaroxaban on inflammation biomarkers and their contribution to heart valve calcification progression and renal preservation in a population of atrial fibrillation (AF) patients with chronic kidney disease (CKD) stage 3b - 4. METHODS: This was an observational, multicenter, prospective study enrolling 347 consecutive CKD stage 3b - 4 patients newly diagnosed with AF: 247 were treated with Rivaroxaban and 100 with Warfarin. Every 12 months, we measured creatinine levels and cardiac valve calcification via standard trans-thoracic echocardiogram, while plasma levels of inflammatory mediators were quantified by ELISA at baseline and after 24 months. RESULTS: Over a follow-up of 24 months, long-term treatment with Rivaroxaban was associated with a significative reduction of cytokines. Patients treated with Rivaroxaban experienced a more frequent stabilization/regression of valve calcifications comparing with patients treated with Warfarin. Rivaroxaban use was related with an improvement in kidney function in 87.4% of patients, while in those treated with Warfarin was reported a worsening of renal clearance in 98% of cases. Patients taking Rivaroxaban experienced lower adverse events (3.2% vs 49%, p-value <0.001). CONCLUSIONS: Our findings suggest that Rivaroxaban compared to Warfarin is associated with lower levels of serum markers of inflammation. The inhibition of FXa may exert an anti-inflammatory effect contributing to reduce the risk of cardiac valve calcification progression and worsening of renal function.

Myocardial Tissue Characterization in Heart Failure with Preserved Ejection Fraction: From Histopathology and Cardiac Magnetic Resonance Findings to Therapeutic Targets.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome responsible for high mortality and morbidity rates. It has an ever growing social and economic impact and a deeper knowledge of molecular and pathophysiological basis is essential for the ideal management of HFpEF patients. The association between HFpEF and traditional cardiovascular risk factors is known. However, myocardial alterations, as well as pathophysiological mechanisms involved are not completely defined. Under the definition of HFpEF there is a wide spectrum of different myocardial structural alterations. Myocardial hypertrophy and fibrosis, coronary microvascular dysfunction, oxidative stress and inflammation are only some of the main pathological detectable processes. Furthermore, there is a lack of effective pharmacological targets to improve HFpEF patients' outcomes and risk factors control is the primary and unique approach to treat those patients. Myocardial tissue characterization, through invasive and non-invasive techniques, such as endomyocardial biopsy and cardiac magnetic resonance respectively, may represent the starting point to understand the genetic, molecular and pathophysiological mechanisms underlying this complex syndrome. The correlation between histopathological findings and imaging aspects may be the future challenge for the earlier and large-scale HFpEF diagnosis, in order to plan a specific and effective treatment able to modify the disease's natural course.

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established. OBJECTIVE: We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF. METHODS: An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users. RESULTS: The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52-0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74-0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52-0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50-0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47-0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78-1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78-1.06; p 0.24). CONCLUSIONS: In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

Clinical and economic impact of multipoint left ventricular pacing: A comparative analysis from the Italian registry on multipoint pacing in cardiac resynchronization therapy (IRON-MPP).

INTRODUCTION: Early evidence suggests that multipoint left ventricular pacing (MPP) may improve response to cardiac resynchronization therapy (CRT). It is unknown whether this benefit is sustained and cost-effective. We used real-world data to evaluate long-term impact of MPP-ON clinical status, heart failure hospitalizations (HFH) and costs. METHODS: The Italian registry on multipoint left ventricular pacing is a prospective, multicenter registry of patients implanted with MPP-enabled CRT devices. For this analysis, clinical and echocardiographic data were collected through 24 months and compared between patients with (MPP-ON) or without (MPP-OFF) early MPP activation at implant. The total cost of each HFH was estimated with national Italian reimbursement rates. RESULTS: The study included 190 MPP-OFF and 128 MPP-ON patients with similar baseline characteristics. At 1 and 2 years, the MPP-ON group had lower rates of HFH vs MPP-OFF (1-year hazard ratio [HR]: 0.14, P = .0014; 2-year HR: 0.38, P = .009). The finding persisted in a subgroup of patients with consistent MPP activation through follow-up (1-year HR: 0.19; P = .0061; 2-year HR: 0.39, P = .022). Total HFH per-patient costs were lower in the MPP-ON vs the MPP-OFF group at 1 year (€101 ± 50 vs €698 ± 195, P < .001) and 2 years (€366 ± 149 vs €801 ± 203, P = .038). More MPP-ON patients had ≥5% improvement in ejection fraction (76.8% vs 65.4%, P = .025) and clinical composite score (66.7% vs 47.5%, P = .01). CONCLUSIONS: In this multicenter clinical study, early MPP activation was associated with a significant reduction in cumulative HFH and related costs after 1 and 2 years of follow-up.

Impact of multipoint pacing on projected battery longevity in cardiac resynchronization therapy. An IRON-MPP study sub-analysis.

BACKGROUND: Multipoint pacing (MPP) may improve clinical outcomes in patients with cardiac resynchronization therapy defibrillators (CRT-D), but its impact on battery longevity in a real-world population has not been investigated in large trials. OBJECTIVE: Compare projected battery longevity in CRT-D patients with and without MPP during long-term follow-up. METHODS: The Italian registry on multipoint left ventricular pacing (IRON-MPP) is a prospective, multicenter registry of patients implanted with MPP-capable CRT-D devices. Projected battery longevity during follow-up was compared for patients with MPP (MPP ON) vs single-site (MPP OFF) left ventricular pacing at CRT-D implantation. A sub-analysis excluded crossover patients with MPP activation or deactivation occurring after implantation. A second sub-analysis excluded patients with a right or left ventricular pacing amplitude >2.5 V. RESULTS: Out of 237 CRT-D patients (71 ± 9 years, 81% male) followed for 1.9 ± 0.8 years, 102 (43%) had MPP ON at implantation. Programmed atrial and ventricular outputs and percentage of pacing were similar between groups. MPP was associated with a 0.44 years reduction in projected battery longevity (P = .03) during long-term follow-up. Results were similar for the first and second sub-analyses, with a 0.57 years (P < .001) and 0.71 years (P < .001) reduction in projected longevity, respectively. CONCLUSION: In this long-term real-world registry, early MPP activation is associated with less than a 1-year reduction in projected battery life compared to single-site biventricular pacing.

Impact of shale gas development on water resources: a case study in northern poland.

Shale gas is currently being explored in Europe as an alternative energy source to conventional oil and gas. There is, however, increasing concern about the potential environmental impacts of shale gas extraction by hydraulic fracturing (fracking). In this study, we focussed on the potential impacts on regional water resources within the Baltic Basin in Poland, both in terms of quantity and quality. The future development of the shale play was modeled for the time period 2015-2030 using the LUISA modeling framework. We formulated two scenarios which took into account the large range in technology and resource requirements, as well as two additional scenarios based on the current legislation and the potential restrictions which could be put in place. According to these scenarios, between 0.03 and 0.86% of the total water withdrawals for all sectors could be attributed to shale gas exploitation within the study area. A screening-level assessment of the potential impact of the chemicals commonly used in fracking was carried out and showed that due to their wide range of physicochemical properties, these chemicals may pose additional pressure on freshwater ecosystems. The legislation put in place also influenced the resulting environmental impacts of shale gas extraction. Especially important are the protection of vulnerable ground and surface water resources and the promotion of more water-efficient technologies.

Intracardiac echocardiography and electroanatomic mapping in diagnosis of arrhythmogenic right ventricular dysplasia.

A 48-year-old man with an episode of syncope and family history of sudden cardiac death was evaluated. The ECG showed negative T waves from V1 to V3 with evidence of epsilon-wave. Magnetic resonance imaging showed replacement with fibrofatty tissue in midapical regions of free wall of the right ventricle with dyskinesia. Transthoracic echocardiography revealed only mild enlargement of the middle right ventricular cavity. A programmed ventricular stimulation induced only an unsustained monomorphic ventricular tachycardia. Intracardiac echocardiography showed mild right ventricular enlargement and outflow dilatation (26 mm), microaneurysms with systolic bulging along the apical segment of the right ventricle. Bipolar voltage mapping, performed by the Carto system, detected a circumscribed low potential (<1.5 mV) area at the same level of the right ventricular apex. Cardiovascular imaging improves the detection of abnormal myocardial areas. Further studies are warranted to support this hypothesis.

Beneficial effects of C1 esterase inhibitor in ST-elevation myocardial infarction in patients who underwent surgical reperfusion: a randomised double-blind study.

BACKGROUND: The inflammatory cascade has been hypothesized to be an important mechanism of post-ischaemic myocardial reperfusion injury and several studies demonstrated that C1 esterase inhibitor (C1-INH) is effective in post-ischaemia myocardial protection. Therefore, we aimed to investigate prospectively in a randomised double-blind study the cardioprotective effects of C1-INH in ST segment elevation myocardial infarction (STEMI) in patients who underwent emergent reperfusion with coronary artery bypass grafting (CABG). METHODS: In this study, we enrolled 80 patients affected with STEMI who underwent emergent CABG. Patients were assigned in two groups (C1-INH group: receive 1000 UI of C1-INH; and placebo group: receive a saline solution). The effects of C1-INH on complement inhibition, myocardial cell injury extension and clinical outcome were studied. Haemodynamic data and myocardial function were monitored. C1-INH, C3a, C4a complement activation fragments and cardiac troponin I (cTnI) serum levels were measured before, during and after surgery. RESULTS: Patient characteristics were not different between the two groups. The overall in-hospital mortality rate was 6.2%. No statistical significant difference was observed between the two groups with regard to early mortality (p=0.36). Statistical significant difference between the two groups was showed for cardiopulmonary bypass support (p=0.04), administration of high dose of inotropes drugs (p=0.001), time of intubation (p=0.03), intensive care unit (ICU) stay (p=0.04) and in-hospital stay (p=0.03). A significant improvement in mean arterial pressure (p=0.03), cardiac index (p=0.02) and stroke volume (p=0.03) was showed in C1-INH group versus placebo group. The serum cTnI levels were significantly low in the C1-INH group versus placebo group after reperfusion, during the observation period. Plasma levels of C3a and C4a complement fragments were reduced significantly in C1-INH group. No drugs-related adverse effects were observed. CONCLUSIONS: The inhibition of the classic complement pathway by C1-INH appears to be an effective mean of preserving ischaemic myocardium from reperfusion injury as demonstrated by low serum cTnI levels in C1-INH group. Therefore, the use of C1-INH during CABG as a rescue therapy in STEMI patients is probably an effective treatment to inhibit complement activity and to improve cardiac function and haemodynamic performance without impacting early mortality. Large randomised study should be performed to support our results.

Treatment of pulmonary hypertension in patients undergoing cardiac surgery with cardiopulmonary bypass: a randomized, prospective, double-blind study.

OBJECTIVE: Pulmonary hypertension can already be present in patients undergoing cardiac surgery or can be exacerbated by cardiopulmonary bypass. Postoperative treatment is still a challenge for physicians. The aim of this study was to evaluate the effects of inhaled prostacyclin (iPGI2) and nitric oxide (iNO) compared with those of intravenous vasodilators. METHODS: This prospective, randomized, double-blind study included 58 patients affected by severe mitral valve stenosis and pulmonary hypertension with high pulmonary vascular resistance (> 250 dynes x s x cm(-5)) and a mean pulmonary artery pressure > 25 mmHg. All patients were monitored by central venous, radial arterial and Swan-Ganz catheters. Data were recorded at six different time points, before induction of anaesthesia, during and after surgery. Prostacyclin and nitric oxide were administered by inhalation 5 min before weaning from cardiopulmonary bypass and continued in the intensive care unit. Right ventricular function was evaluated by transoesophageal echocardiography. RESULTS: Hospital mortality was 3.4%. After drug administration, the mean pulmonary artery pressure and pulmonary vascular resistance were significantly decreased in the iNO and iPGI2 groups with respect to the baseline values (P < 0.05) and such a decrease was maintained throughout the study; this was not observed in the control group. In the iNO and iPGI2 groups we demonstrated a significant increase in cardiac indices and right ventricular ejection fraction after drug administration with respect to baseline. Furthermore, patients in the inhaled drug groups were weaned easily from cardiopulmonary bypass (P = 0.04) and had a shorter intubation time (P = 0.03) and intensive care unit stay (P = 0.02) than the control group. CONCLUSIONS: Our data suggest that both iNO and iPGI2 are effective in the treatment of pulmonary hypertension. iPGI2 has a number of advantages over iNO, including its easy administration and lower cost. Intravenous vasodilator treatment, on the other hand, is effective in terms of mortality but has a higher morbidity rate.