Rates of pulmonary vein reconnection at repeat ablation for recurrent atrial fibrillation and its impact on outcomes among females and males.

BACKGROUND: Several studies have demonstrated that females have a higher risk of arrhythmia recurrence after pulmonary vein (PV) isolation for atrial fibrillation (AF). There are limited data on sex-based differences in PV reconnection rates at repeat ablation. We aimed to investigate sex-based differences in electrophysiological findings and atrial arrhythmia recurrence after repeat AF ablation METHODS: We conducted a retrospective study of 161 consecutive patients (32% female, age 65 ± 10 years) who underwent repeat AF ablation after index PV isolation between 2010 and 2022. Demographics, procedural characteristics and follow-up data were collected. Recurrent atrial tachycardia (AT)/AF was defined as any atrial arrhythmia ≥30 s in duration. RESULTS: Compared to males, females tended to be older and had a significantly higher prevalence of prior valve surgery (10 vs. 2%; P = .03). At repeat ablation, PV reconnection was found in 119 (74%) patients. Males were more likely to have PV reconnection at repeat ablation compared to females (81 vs. 59%; P = .004). Excluding repeat PV isolation, there were no significant differences in adjunctive ablation strategies performed at repeat ablation between females and males. During follow-up, there were no significant differences in freedom from AT/AF recurrence between females and males after repeat ablation (63 vs. 59% at 2 years, respectively; P = .48). CONCLUSIONS: After initial PV isolation, significantly fewer females have evidence of PV reconnection at the time of repeat ablation for recurrent AF. Despite this difference, long-term freedom from AT/AF was similar between females and males after repeat ablation.

Impact of Advanced Therapy Centers on Characteristics and Outcomes of Heart Failure Admissions.

BACKGROUND: Although much attention has been paid to admission and transfer patterns for cardiogenic shock, contemporary data are lacking on decompensated heart failure (HF) admissions and transfers and the impact of advanced therapy centers (ATCs) on outcomes. METHODS: HF hospitalizations were obtained from the Nationwide Readmissions Database 2016 to 2019. Centers performing at least 1 heart transplant or left ventricular assist device were classified as ATCs. Patient characteristics, outcomes, and procedural volume were compared among 3 cohorts: admissions to non-ATCs, admissions to ATCs, and transfers to ATCs. A secondary analysis evaluated outcomes for severe HF hospitalizations (cardiogenic shock, cardiac arrest, and mechanical ventilation). Multivariable logistic regression was performed to adjust for the presence of HF decompensations and significant clinical variables during univariate analysis. RESULTS: A total of 2 331 690 hospitalizations (81.2%) were admissions to non-ATCs (94.5% of centers), 525 037 (18.3%) were admissions to ATCs (5.5% of centers), and 15 541 (0.5%) were transferred to ATCs. Patients treated at ATCs (especially those transferred) had higher rates of HF decompensations, procedural frequency, lengths of stay, and costs. Unadjusted mortality was 2.6% at non-ATCs and was higher at ATCs, both for directly admitted (2.9%, P<0.001) and transferred (11.2%, P<0.001) patients. However, multivariable-adjusted mortality was significantly lower at ATCs, both for directly admitted (odds ratio, 0.82 [95% CI, 0.78-0.87]; P<0.001) and transferred (odds ratio, 0.66 [95% CI, 0.57-0.78]; P<0.001) patients. For severe HF admissions, unadjusted mortality was 37.2% at non-ATCs and was lower at ATCs, both for directly admitted (25.3%, P<0.001) and transferred (25.2%, P<0.001) patients, with similarly lower multivariable-adjusted mortality. CONCLUSIONS: Patients with HF treated at ATCs were sicker but associated with higher procedural volume and lower adjusted mortality.

Implantable cardiac monitors: artificial intelligence and signal processing reduce remote ECG review workload and preserve arrhythmia detection sensitivity.

Introduction: Implantable cardiac monitors (ICMs) provide long-term arrhythmia monitoring, but high rates of false detections increase the review burden. The new "SmartECG" algorithm filters false detections. Using large real-world data sets, we aimed to quantify the reduction in workload and any loss in sensitivity from this new algorithm. Methods: Patients with a BioMonitor IIIm and any device indication were included from three clinical projects. All subcutaneous ECGs (sECGs) transmitted via remote monitoring were classified by the algorithm as "true" or "false." We quantified the relative reduction in workload assuming "false" sECGs were ignored. The remote monitoring workload from five hospitals with established remote monitoring routines was evaluated. Loss in sensitivity was estimated by testing a sample of 2000 sECGs against a clinical board of three physicians. Results: Of our population of 368 patients, 42% had an indication for syncope or pre-syncope and 31% for cryptogenic stroke. Within 418.5 patient-years of follow-up, 143,096 remote monitoring transmissions contained 61,517 sECGs. SmartECG filtered 42.8% of all sECGs as "false," reducing the number per patient-year from 147 to 84. In five hospitals, nine trained reviewers inspected on average 105 sECGs per working hour. This results in an annual working time per patient of 83 min without SmartECG, and 48 min with SmartECG. The loss of sensitivity is estimated as 2.6%. In the majority of cases where true arrhythmias were rejected, SmartECG classified the same type of arrhythmia as "true" before or within 3 days of the falsely rejected sECG. Conclusion: SmartECG increases efficiency in long-term arrhythmia monitoring using ICMs. The reduction of workload by SmartECG is meaningful and the risk of missing a relevant arrhythmia due to incorrect filtering by the algorithm is limited.

Impella Versus Intra-Aortic Balloon Pump in Patients With Cardiogenic Shock Treated With Venoarterial Extracorporeal Membrane Oxygenation: An Observational Study.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used for patients with cardiogenic shock. Although Impella or intra-aortic balloon pump (IABP) is frequently used for left ventricular unloading (LVU) during VA-ECMO treatment, there are limited data on comparative outcomes. We compared outcomes of Impella and IABP for LVU during VA-ECMO. METHODS AND RESULTS: Using the Nationwide Readmissions Database between 2016 and 2020, we analyzed outcomes in 3 groups of patients with cardiogenic shock requiring VA-ECMO based on LVU strategies: extracorporeal membrane oxygenation (ECMO) only, ECMO with IABP, and ECMO with Impella. Of 15 980 patients on VA-ECMO, IABP and Impella were used in 19.4% and 16.4%, respectively. The proportion of patients receiving Impella significantly increased from 2016 to 2020 (6.5% versus 25.8%; P-trend<0.001). In-hospital mortality was higher with ECMO with Impella (54.8%) compared with ECMO only (50.4%) and ECMO with IABP (48.4%). After adjustment, ECMO with IABP versus ECMO only was associated with lower in-hospital mortality (adjusted odds ratio [aOR], 0.83; P=0.02). ECMO with Impella versus ECMO only had similar in-hospital mortality (aOR, 1.09; P=0.695) but was associated with more bleeding (aOR, 1.21; P=0.007) and more acute kidney injury requiring hemodialysis (aOR, 1.42; P<0.001). ECMO with Impella versus ECMO with IABP was associated with greater risk of acute kidney injury requiring hemodialysis (aOR, 1.49; P=0.002), higher in-hospital mortality (aOR, 1.32; P=0.001), and higher 40-day mortality (hazard ratio, 1.25; P<0.001). CONCLUSIONS: In patients with cardiogenic shock on VA-ECMO, LVU with Impella, particularly with 2.5/CP, was not associated with improved survival at 40 days but was associated with increased adverse events compared with IABP. More data are needed to assess Impella platform-specific comparative outcomes of LVU.

Antithrombotic Therapy for Patients Undergoing Cardiac Electrophysiological and Interventional Procedures: JACC State-of-the-Art Review.

Electrophysiological and interventional procedures have been increasingly used to reduce morbidity and mortality in patients experiencing cardiovascular diseases. Although antithrombotic therapies are critical to reduce the risk of stroke or other thromboembolic events, they can nonetheless increase the bleeding hazard. This is even more true in an aging population undergoing cardiac procedures in which the combination of oral anticoagulants and antiplatelet therapies would further increase the hemorrhagic risk. Hence, the timing, dose, and combination of antithrombotic therapies should be carefully chosen in each case. However, the maze of society guidelines and consensus documents published so far have progressively led to a hazier scenario in this setting. Aim of this review is to provide-in a single document-a quick, evidenced-based practical summary of the antithrombotic approaches used in different cardiac electrophysiology and interventional procedures to guide the busy clinician and the cardiac proceduralist in their everyday practice.

Localized Re-Entry Is a Frequent Mechanism of De Novo Atypical Flutter.

BACKGROUND: Limited data exist about the origins and mechanisms of atypical atrial flutter that occurs in the absence of prior ablation or surgery. OBJECTIVES: The aims of this study were to report a large cohort of patients who presented for catheter ablation of de novo atypical flutters, to identify the most common locations and mechanisms of arrhythmia, and to describe outcomes after ablation. METHODS: Demographic, electrophysiological, and outcome data were collected for patients who underwent ablation of de novo atypical flutter. RESULTS: The mechanisms of 85 atypical flutters were identified in 62 patients and localized to the left atrium (LA) in 58 and right atrium (RA) in 27. In the LA, mechanisms were classified as macro-re-entry in 29 (50%) and localized re-entry in 29 (50%), whereas in the RA, mechanisms were macro-re-entry in 8 (30%) and localized re-entry in 19 (70%) (proportion of localized re-entry in the LA vs. RA, P = 0.08). Nine patients had both localized and macro-re-entrant atypical flutters. In the LA, localized re-entry was commonly found in the anterior LA, followed by the pulmonary veins and septum. In the RA, localized re-entry was found at various sites, including the lateral or posterior RA, septum, and coronary sinus ostium. During 39.4 months (Q1-Q3: 18.2-65.8 months) of follow-up, atrial arrhythmias occurred in 66% of patients after a single ablation and in 50% after >1 ablation. Among patients who underwent repeat ablation, compared with the index arrhythmia, different tachycardia circuits or arrhythmias were documented in 13 of 18 cases (72%). CONCLUSIONS: Atypical atrial flutters in patients without prior surgery or complex ablation are often due to localized re-entry (approximately 50% in the LA and a higher frequency in the RA). Other atrial tachycardias commonly occur during long-term follow-up following ablation, suggesting progressive atrial myopathy in these patients.

Ventricular Tachycardia Due to Triggered Activity: Role of Early and Delayed Afterdepolarizations.

Most forms of sustained ventricular tachycardia (VT) are caused by re-entry, resulting from altered myocardial conduction and refractoriness secondary to underlying structural heart disease. In contrast, VT caused by triggered activity (TA) is unrelated to an abnormal structural substrate and is often caused by molecular defects affecting ion channel function or regulation of intracellular calcium cycling. This review summarizes the cellular and molecular bases underlying TA and exemplifies their clinical relevance with selective representative scenarios. The underlying basis of TA caused by delayed afterdepolarizations is related to sarcoplasmic reticulum calcium overload, calcium waves, and diastolic sarcoplasmic reticulum calcium leak. Clinical examples of TA caused by delayed afterdepolarizations include sustained right and left ventricular outflow tract tachycardia and catecholaminergic polymorphic VT. The other form of afterpotentials, early afterdepolarizations, are systolic events and inscribe early afterdepolarizations during phase 2 or phase 3 of the action potential. The fundamental defect is a decrease in repolarization reserve with associated increases in late plateau inward currents. Malignant ventricular arrhythmias in the long QT syndromes are initiated by early afterdepolarization-mediated TA. An understanding of the molecular and cellular bases of these arrhythmias has resulted in generally effective pharmacologic-based therapies, but these are nonspecific agents that have off-target effects. Therapeutic efficacy may need to be augmented with an implantable defibrillator. Next-generation therapies will include novel agents that rescue arrhythmogenic abnormalities in cellular signaling pathways and gene therapy approaches that transfer or edit pathogenic gene variants or silence mutant messenger ribonucleic acid.

Personalized medicine in the dish to prevent calcium leak associated with short-coupled polymorphic ventricular tachycardia in patient-derived cardiomyocytes.

BACKGROUND: Polymorphic ventricular tachycardia (PMVT) is a rare genetic disease associated with structurally normal hearts which in 8% of cases can lead to sudden cardiac death, typically exercise-induced. We previously showed a link between the RyR2-H29D mutation and a clinical phenotype of short-coupled PMVT at rest using patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs). In the present study, we evaluated the effects of clinical and experimental anti-arrhythmic drugs on the intracellular Ca2+ handling, contractile and molecular properties in PMVT hiPSC-CMs in order to model a personalized medicine approach in vitro. METHODS: Previously, a blood sample from a patient carrying the RyR2-H29D mutation was collected and reprogrammed into several clones of RyR2-H29D hiPSCs, and in addition we generated an isogenic control by reverting the RyR2-H29D mutation using CRIPSR/Cas9 technology. Here, we tested 4 drugs with anti-arrhythmic properties: propranolol, verapamil, flecainide, and the Rycal S107. We performed fluorescence confocal microscopy, video-image-based analyses and biochemical analyses to investigate the impact of these drugs on the functional and molecular features of the PMVT RyR2-H29D hiPSC-CMs. RESULTS: The voltage-dependent Ca2+ channel inhibitor verapamil did not prevent the aberrant release of sarcoplasmic reticulum (SR) Ca2+ in the RyR2-H29D hiPSC-CMs, whereas it was prevented by S107, flecainide or propranolol. Cardiac tissue comprised of RyR2-H29D hiPSC-CMs exhibited aberrant contractile properties that were largely prevented by S107, flecainide and propranolol. These 3 drugs also recovered synchronous contraction in RyR2-H29D cardiac tissue, while verapamil did not. At the biochemical level, S107 was the only drug able to restore calstabin2 binding to RyR2 as observed in the isogenic control. CONCLUSIONS: By testing 4 drugs on patient-specific PMVT hiPSC-CMs, we concluded that S107 and flecainide are the most potent molecules in terms of preventing the abnormal SR Ca2+ release and contractile properties in RyR2-H29D hiPSC-CMs, whereas the effect of propranolol is partial, and verapamil appears ineffective. In contrast with the 3 other drugs, S107 was able to prevent a major post-translational modification of RyR2-H29D mutant channels, the loss of calstabin2 binding to RyR2. Using patient-specific hiPSC and CRISPR/Cas9 technologies, we showed that S107 is the most efficient in vitro candidate for treating the short-coupled PMVT at rest.

Trends in the Incidence of Cardiogenic Shock, and Utilization of Mechanical Circulatory Support in Myocarditis: Insights from the National Inpatient Sample 2016 to 2019.

A subset of patients with myocarditis present with cardiogenic shock. There is a lack of contemporary data assessing the use of mechanical circulatory support (MCS) in these patients. Myocarditis hospitalizations were analyzed using the National Inpatient Sample between 2016 and 2019. Characteristics of patients with and without cardiogenic shock were assessed. Trends in mortality, MCS, right-sided cardiac catheterization (RHC) and endomyocardial biopsy were evaluated. The impact of RHC on consequent MCS and mortality was studied. A total of 38,300 hospitalizations for myocarditis were included in the study, of which 3,490 hospitalizations (9.1%) had cardiogenic shock. Patients with cardiogenic shock were older (p <0.001) and had more chronic kidney disease and atrial fibrillation. Between 2016 and 2019, there was an increase in myocarditis admissions but no difference in rates of cardiogenic shock and mortality and the use of extracorporeal membrane oxygenation, percutaneous ventricular assist devices, intra-aortic balloon pumps, left ventricular assist devices, and cardiac transplant. The most common form of MCS used in myocarditis was extracorporeal membrane oxygenation. The rates of RHC (p = 0.02) and endomyocardial biopsy (p = 0.03) increased over time. Patients who underwent RHC were more likely to receive mechanical support, and in patients with shock, RHC was associated with lower mortality (adjusted odds ratio 0.34, p <0.01). Myocarditis admissions increased over time but with no increase in the rates of cardiogenic shock and MCS. In patients with cardiogenic shock, RHC resulted in lower mortality.

Risk of Arrhythmic Death in Patients With Nonischemic Cardiomyopathy: JACC Review Topic of the Week.

Nonischemic cardiomyopathy (NICM) is common and patients are at significant risk for early mortality secondary to ventricular arrhythmias. Current guidelines recommend implantable cardioverter-defibrillator (ICD) therapy to decrease sudden cardiac death (SCD) in patients with heart failure and reduced left ventricular ejection fraction. However, in randomized clinical trials comprised solely of patients with NICM, primary prevention ICDs did not confer significant mortality benefit. Moreover, left ventricular ejection fraction has limited sensitivity and specificity for predicting SCD. Therefore, precise risk stratification algorithms are needed to define those at the highest risk of SCD. This review examines mechanisms of sudden arrhythmic death in patients with NICM, discusses the role of ICD therapy and treatment of heart failure for prevention of SCD in patients with NICM, examines the role of cardiac magnetic resonance imaging and computational modeling for SCD risk stratification, and proposes new strategies to guide future clinical trials on SCD risk assessment in patients with NICM.

A mimicker of constriction: a case report of a rare case of cardiac angiosarcoma.

Background: Cardiac angiosarcoma is an exceptionally rare primary malignant tumour with an aggressive course and typically poor prognosis. Diagnosis is difficult, and patients often present with metastatic disease. We report the rare case of a patient with cardiac angiosarcoma who presents with constrictive physiology due to tumour encasement. Case summary: A 65-year-old female with a past medical history of Hodgkin's lymphoma and limited scleroderma presented with progressive dyspnoea on exertion. Multimodality imaging and haemodynamics with echocardiography, cardiac magnetic resonance imaging (MRI), and cardiac catheterization showed findings of constrictive physiology. Cardiac MRI showed areas of pericardial enhancement, so she was initially started on colchicine, prednisone, and mycophenolate mofetil to treat pericardial inflammation. However, her symptoms progressed, and she underwent pericardiectomy with cardiac surgery. Pericardium was noted to be thickened and a mass-like substance was densely adherent and potentially invading the heart itself and could not be dissected free. Surgical pathology showed features consistent with epithelioid angiosarcoma. Patient had rapid progression of her disease and was started on chemotherapy. Her course, however, was complicated by acute gastrointestinal bleeding, atrial fibrillation with rapid rates, and persistent volume overload. She elected for comfort measures and passed away shortly after her diagnosis. Discussion: Our case shows an extremely rare diagnosis, cardiac angiosarcoma, presenting with typical findings of constrictive physiology. The case shows the typical features of constrictive physiology using multimodality imaging and haemodynamics and emphasizes the need to always think broadly in creating a differential diagnosis for constriction to ensure that rare diseases are considered.

Low Utilization of Lead Extraction Among Patients With Infective Endocarditis and Implanted Cardiac Electronic Devices.

BACKGROUND: Cardiac implantable electronic device (CIED)-associated infections are associated with substantial morbidity, mortality, and costs. Guidelines have cited endocarditis as a Class I indication for transvenous lead removal/extraction (TLE) among patients with CIEDs. OBJECTIVES: The authors sought to study utilization of TLE among hospital admissions with infective endocarditis using a nationally representative database. METHODS: Using the Nationwide Readmissions Database (NRD), 25,303 admissions for patients with CIEDs and endocarditis between 2016 and 2019 were evaluated on the basis of International Classification of Diseases-10th Revision, Clinical-Modification (ICD-10-CM) codes. RESULTS: Among admissions for patients with CIEDs and endocarditis, 11.5% were managed with TLE. The proportion undergoing TLE increased significantly from 2016 to 2019 (7.6% vs 14.9%; P trend < 0.001). Procedural complications were identified in 2.7%. Index mortality was significantly lower among patients managed with TLE (6.0% vs 9.5%; P < 0.001). Presence of Staphylococcus aureus infection, implantable cardioverter-defibrillator, and large hospital size were independently associated with TLE management. TLE management was less likely with older age, female sex, dementia, and kidney disease. After adjustment for comorbidities, TLE was independently associated with significantly lower odds of mortality (adjusted OR: 0.47; 95% CI: 0.37-0.60 by multivariable logistic regression, and adjusted OR: 0.51; 95% CI: 0.40-0.66 by propensity score matching). CONCLUSIONS: Utilization of lead extraction among patients with CIEDs and endocarditis is low, even in the presence of low rates of procedural complications. Lead extraction management is associated with significantly lower mortality, and its use has trended upward between 2016 and 2019. Barriers to TLE for patients with CIEDs and endocarditis require investigation.

Reduction of left ventricular global longitudinal strain in patients with permanent pacemakers as a predictor of heart failure and mortality outcomes.

INTRODUCTION: Frequent right ventricular (RV) pacing is associated with cardiomyopathy. The impact of RV pacing on left ventricular (LV) global longitudinal strain (GLS) and clinical outcomes is unclear. METHODS: We analyzed GLS via two-dimensional speckle tracking and LV ejection fraction (EF) on pre- and post-implantation transthoracic echocardiograms of patients undergoing dual chamber pacemaker implantation. We collected long-term data on strain, LVEF, and clinical outcomes. RESULTS: One hundred and ten patients (mean age 76 ± 12 years; 59 [54%] female) were followed for mean 23 ± 17 months. Mean baseline LVEF was 58 ± 11% and mean GLS was -17 ± 4%. Twenty-four (22%) patients had an absolute decrease in LVEF > 10% and 43 (39%) patients had a relative reduction of GLS > 15%. Among patients with a reduction of GLS, a larger proportion of patients had RV pacing burden ≥20% (67% vs. 46%; p = .048). Compared to patients without GLS reduction, more patients with a reduction in GLS reached a composite endpoint of HF hospitalization, CRT upgrade or death (47% vs. 16%; p = .001). CONCLUSION: Reduction in LV GLS was seen in nearly four in 10 patients undergoing pacemaker implantation and was significantly associated with increased RV pacing burden. LV GLS reduction was associated with increased risk of adverse outcomes. LV GLS may have utility in predicting outcomes among patients with RV pacing.

Early Stroke and Mortality After Percutaneous Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation.

BACKGROUND: Percutaneous endocardial left atrial appendage occlusion (LAAO) is an alternative therapy for stroke prevention in patients with atrial fibrillation who are poor candidates for oral anticoagulants. Oral anticoagulation is generally discontinued 45 days following successful LAAO. Real-world data on early stroke and mortality following LAAO are lacking. METHODS: Using International Classification of Diseases, Tenth Revision, Clinical-Modification codes, we performed a retrospective observational registry analysis to examine the rates and predictors of stroke, mortality, and procedural complications during index hospitalization and 90-day readmission among 42 114 admissions in the Nationwide Readmissions Database for LAAO between 2016 and 2019. Early stroke and mortality were defined as events occurring during index admission or 90-day readmission. Data on timing of early strokes post-LAAO were collected. Multivariable logistic regression modeling was used to ascertain predictors of early stroke and major adverse events. RESULTS: LAAO was associated with low rates of early stroke (0.63%), early mortality (0.53%), and procedural complications (2.59%). Among patients who had readmissions with strokes after LAAO, the median time from implant to readmission was 35 days (interquartile range, 9-57 days); 67% of readmissions with strokes occurred <45 days postimplant. Between 2016 and 2019, the rates of early stroke after LAAO significantly decreased (0.64% versus 0.46% P-for-trend <0.001), while early mortality and major adverse event rates were unchanged. Peripheral vascular disease and a history of prior stroke were independently associated with early stroke after LAAO. Early post-LAAO stroke rates were similar between low, medium, and high LAAO volume tertile centers. CONCLUSIONS: In this contemporary real-world analysis, the early stroke rate after LAAO was low, with the majority occurring within 45 days of device implantation. Despite an increase in LAAO procedures between 2016 and 2019, there with a significant decline in early strokes after LAAO during that period.