Dementia risk reduction between DOACs and VKAs in AF: A systematic review and meta-analysis.

Introduction: Direct oral anticoagulants (DOACs) become the recommended treatment over vitamin K antagonists (VKA) in patients with non-valvular atrial fibrillation (AF). However, their effectiveness in reducing cognitive impairment and dementia compared to VKA remains unclear. Methods: A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Database. Randomized controlled trials, cohort, or case-control study that assessed incident dementia between AF patients who received DOAC compared to VKA were selected. Relevant study characteristics and the number of incident dementia diagnosis or hazard ratios (HRs) for incident dementia and each dementia subtypes were extracted. Random-effects model was used to perform meta-analysis. Standardized mean differences (SMDs) were used to estimate effect sizes for continuous data. Results: Twelve cohort studies comprising 1 451 069 individuals were included. The incidence of dementia was lower in AF patients prescribed DOACs compared to VKA (HR 0.88, 95% CI 0.83-0.93, I 2 = 61.2%). A lower incident dementia in DOACs group relative to VKA was significantly observed in those less than 75 years of age (< 65 years, HR 0.83 (95% CI 0.72-0.97, I 2 = 0%); 65-74 years, HR 0.86 (95% CI 0.81-0.92, I 2 = 55.4%); and ≥ 75 years, HR 1.07 (95% CI 0.74-1.55, I 2 = 92.5%)) and for the subgroup of patients with vascular dementia (HR 0.91, 95% CI 0.824-0.997, I 2 = 0%). Conclusions: This meta-analysis reveals a reduction in incidence of dementia in AF patients prescribed DOACs compared to VKA, particularly in those less than 75 years old and in the vascular dementia subtype.

The burden of alcohol-related cardiovascular complications in young and middle-aged adults: rising burden of atrial fibrillation and hypertensive heart disease.

BACKGROUND AND AIMS: The burden of alcohol-related complications is high and rising. However, there are notable deficiencies in comprehensive epidemiological study focusing on cardiovascular complications from alcohol, especially among young and middle-aged adults. We thus aimed to determine the burden of these conditions in young and middle-aged adults globally. METHODS AND RESULTS: We used data from the Global Burden of Disease Study 2019 and analysed the mortality and disability-adjusted life years of alcohol-associated cardiovascular complications in young and middle-aged adults. The findings were classified by sex, region, country, and Sociodemographic Index (SDI). The highest age-standardized death rates (ASDR) were observed in stroke 0.84 (95% UI 0.60-1.09), followed by alcoholic cardiomyopathy 0.57 (95% UI 0.47-0.66) per 100,000 population. The overall burden of alcohol-associated cardiovascular complications decreased globally but increased in atrial fibrillation and hypertensive heart disease. Regionally, most regions underwent a decrease in ASDR, but an increase was observed in Southeast Asia (+2.82%), Western Pacific (+1.48%), low-middle (+1.81%), and middle SDI (+0.75%) countries. Nevertheless, the ASDR and ASDALYs were highest in Europe. CONCLUSIONS: The impact of alcohol-associated atrial fibrillation and hypertensive heart disease has increased over the last decades. Regarding region, the burden in Europe and the rising burden in Asia, require immediate public health policy to lessen these cardiovascular complications from alcohol in young and middle-aged adults.

Premature Ventricular Contraction-Induced Cardiomyopathy: Contemporary Evidence from Risk Stratification, Pathophysiology, and Management.

Premature ventricular complexes (PVCs) are commonly encountered problems in clinical settings. The range of symptoms can be from asymptomatic to palpitations, fatigue, or heart failure symptoms. A higher burden of PVCs is a risk factor for development of PVC-induced cardiomyopathy (PIC). Rhythm evaluation by 12-lead ECG and an ambulatory monitoring device are essential. Currently, several imaging modalities, such as echocardiography and cardiac magnetic resonance imaging, are utilized to evaluate the underlying structure that may be related to PIC. Beta blockers and antiarrhythmic drugs are typically part of the initial management strategy. If these fail, catheter ablation of PVCs is typically the next step. The purpose of this article is to summarize the current evidence/knowledge about PIC.

The efficacy and safety of cryoballoon atrial fibrillation ablation in patients with heart failure: A systematic review and meta-analysis.

INTRODUCTION: While atrial fibrillation (AF) ablation has proven beneficial for heart failure (HF) patients, most reports were performed with radiofrequency ablation. We aimed to evaluate the efficacy and safety of cryoballoon AF ablation in patients with HFrEF. METHOD: We comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane database from inception to December 2022. Studies that reported the outcomes of freedom from atrial arrhythmia, complications, NYHA functional class (NYHA FC), and left ventricular ejection fraction (LVEF) after Cryoballoon AF ablation in HF patients were included. Data from each study were combined with a random-effects model. RESULT: A total of 9 studies observational studies with 1414 HF patients were included. Five studies had only HF with reduced ejection fraction (HFrEF), 1 study with HF with preserved ejection fraction (HFpEF), and others with mixed HF types. Freedom from AA in HFrEF at 12 months was 64% (95% CI 56-71%, I2 58%). There was a significant improvement of LVEF in these patients with a standard mean difference of 13% (95% CI 8.6-17.5%, I2 99% P < 0.001. The complication rate in HFrEF group was 6% (95% CI 4-10%, I2 0%). The risk of recurrence of atrial arrhythmia was not significantly different between HF and no HF patients (RR 1.34, 95% CI 0.8-2.23, I2 76%). CONCLUSION: Cryoballoon AF ablation is effective in HFrEF patients comparable to radiofrequency ablation. The complication rate was low.

Atrial fibrillation catheter ablation in endurance athletes: systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) management in endurance athletes (EA) is challenging due to the paucity of data, especially on the efficacy and safety of catheter ablation (CA). The hypothesis is that the efficacy and safety of AF CA in EA are comparable to the non-EA. METHODS: Databases from EMBASE, Medline, PubMed, and Cochrane were searched from inception through February 2023. Studies with available information on efficacy and safety profiles were included. Effect estimates from the individual studies were extracted and combined using random effect and generic inverse variance method of DerSimonian and Laird. RESULTS: Nine observational studies with a total of 1129 participants were identified, of whom 51% were EA. Our analysis found that rate of atrial arrhythmia (AA) recurrences following AF CA was not statistically different between EA and non-EA (RR 1.04, I2 = 57.6%, p = 0.54). The AA survival rates after a single ablation in EA was 60.2%, which improved up to 77% after multiple ablations during the follow-up period. Infrequent complication rates ranging from 0 to 7.6% were observed, with no mortality. CONCLUSIONS: Our meta-analysis suggests that AF CA is as effective and safe in EA as in non-EA. In the future, AF CA should be considered as a first-line therapeutic choice in this patient group.

Outcomes of cardiac resynchronization therapy in congenital heart disease: A meta-analysis and systematic review.

INTRODUCTION: Cardiac resynchronization therapy (CRT) is a standard treatment for patients with heart failure with reduced ejection fraction. However, there is still a gap of evidence in congenital heart disease (CHD) patients regarding resynchronization therapy. METHODS: We performed a meta-analysis and systematic review of CHD patients who received CRT implantation. We comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane database from inception to June 2023. Studies that reported response rate to CRT, total mortality rate, change in QRS duration, change in left ventricular ejection fraction, and change in New York Heart Association functional class were included. RESULTS: A total of 14 studies were included in the study. There were 10 studies that reported response rates after implantation. The overall response rate to CRT in CHD patients was 68% (95% confidence interval [CI] 61%-75%, I2 32%). The response rates in patients with systemic right ventricle (RV), systemic left ventricle (LV), and single ventricle were 58% (95% CI 46%-70%, I2 0%), 80% (95% CI 74%-86% I2 14%), and 67% (95% CI 49%-80% I2 0%). Response to CRT in systemic RV was inferior to systemic LV with an odds ratio of 0.38 (95% CI 0.15-0.95, I2 38%). The total mortality rate from seven studies was 12% (95% CI 8%-18%, I2 55%). The parameters which represented ventricular dyssynchrony improved after CRT implantation. CONCLUSION: The overall response rate to CRT in CHD was 68%. Patients with systemic RV had a lower response rate to CRT when compared to patients with systemic LV. The total mortality rate after CRT implantation was 12%.

Mortality benefit with AF ablation: Impact of normal sinus rhythm seen in CABANA and EAST AFnet.

Atrial fibrillation (AF) is significantly associated with morbidity and mortality and erodes the quality and quantity of life. It is standard of care to treat patients with AF and an increased risk of stroke with oral anticoagulation therapy, but the more daunting question many clinicians face is whether to pursue a "rate-only" or "rhythm" control strategy. Historical studies over the years have sought to answer this question but have found no significant difference in major clinical outcomes between the two strategies. There are opportunities based on new data to improve the natural history of the disease. The EAST AFnet trial for the first time revealed a significant morbidity and mortality advantage to rhythm control therapy when performed early in the disease process of AF and in the setting of comprehensive medical management that was maintained. The CABANA trial clearly demonstrated that catheter ablation was a more effective long-term treatment of AF in general and significantly lowers risk of AF progression compared to medical therapy. Like multiple prior trials of rhythm management strategies, when rhythm control was effective in these trials, independent of therapy assignment, there was a significantly lower risk of adverse outcomes and death. These contemporary data provide optimism that the pervasive mortality risk in patients with AF observed over the past 50 years may be improved by the timing, use, and efficacy of use of therapeutic interventions.

Periodontal disease and risk of atrial fibrillation or atrial flutter: A systematic review and meta-analysis.

Background: We conducted a study to evaluate the risk of atrial fibrillation (AF) and atrial flutter (AFL) in periodontal disease (PD) patients. Methods: Cohort studies that evaluate the risk of AF or AFL in PD patients were included. The risk was expressed in the pooled odd ratio (OR) with 95% confidence interval (CI). Results: A total of four cohort studies were included. We found that patients with PD have a significantly higher risk of AF/AFL compared to those without PD with the pooled OR of 1.33 (95% CI 1.29-1.38; p = 0.357, I 2 = 3.0%). Conclusions: PD increases the risk of AF and AFL.

High sensitivity C reactive protein levels and atrial fibrillation recurrence after catheter ablation for atrial fibrillation: A systematic review and meta-analysis.

Background: Atrial fibrillation (AF) recurrence after AF ablation is not uncommon. High sensitivity C reactive protein (hs-CRP) is a widely used inflammatory marker with a potential property to predict AF recurrence. We conducted a systematic review and a meta-analysis to find an association between hs-CRP levels and AF recurrence after ablation. Methods: We searched PubMed, Embase, and Wiley-Cochrane Library from inception to January 2022 for studies that reported hs-CRP levels in patients who underwent AF ablation. Weighted mean difference (WMD) was used to evaluate the difference between hs-CRP levels in post-ablation AF recurrent and non-recurrent group. Also, the difference between hs-CRP levels in pre- and post-ablation was determined. Results: We identified 10 studies, and a total of 789 patients were included (299 recurrent vs. 490 non-recurrent patients). The mean age was 57.7 years (76.4% male). There was no difference in baseline hs-CRP levels between AF recurrent and non-recurrent group (WMD = 0.05, 95% CI = -0.04 to 0.15, p = 0.045). However, higher hs-CRP levels post-ablation were found in AF recurrent group (WMD = 0.09, 95% CI = 0.03-0.15, p < 0.001). Conclusion: There is no significant difference in baseline hs-CRP levels between AF recurrent and non-recurrent patients after AF ablation. However, higher post-ablation hs-CRP level was found in AF recurrent group. High Sensitivity C reactive protein may play a role as a predictor of AF recurrence.

Impact of type of anticoagulant on clinical outcomes in cancer patients who had atrial fibrillation.

To date, evidence on optimal anticoagulant options in patients with AF who concurrently have active cancer remains elusive. To describe anticoagulant patterns and clinical outcomes among patients with a concomitant diagnosis of AF and cancer. Data were obtained from the University of Utah and Huntsman Cancer Institute (HCI) Hospitals. Patients were included if they had diagnosis of AF and cancer. Outcome was type and pattern of anticoagulant. Clinical outcomes were stroke, bleeding and all-cause mortality. From October 1999 to December 2020, there were 566 AF patients who concurrently had active cancer. Mean age ± standard deviation was 76.2 ± 10.7 and 57.6% were males. Comparing to warfarin, patients who received direct oral anticoagulant (DOACs) were associated with similar risk of stroke (adjusted hazard ratio, aHR 0.8, 95% confidence interval [CI] 0.2-2.7, P = 0.67). On contrary, those who received low-molecular-weight heparin (LMWH) were associated with significantly higher risk of stroke comparing to warfarin (aHR 2.4, 95% CI 1.0-5.6, P = 0.04). Comparing to warfarin, DOACs and LMWH was associated with similar risk of overall bleeding with aHR 1.1 (95% CI 0.7-1.6, P = 0.73) and aHR 1.1 (95% CI 0.6-1.7, P = 0.83), respectively. Patients who received LMWH but not DOACs were associated with increased risk of death as compared to warfarin, aHR 4.5 (95% CI 2.8-7.2, P < 0.001) and 1.2 (95% CI 0.7-2.2, P = 0.47). In patients with active cancer and AF, LMWH, compared to warfarin, was associated with an increased risk of stroke and all-cause mortality. Furthermore, DOACs was associated with similar risk of stroke, bleeding and death as compared to warfarin.

High-risk phenotypes of arrhythmic mitral valve prolapse: a systematic review and meta-analysis.

BACKGROUND: Mitral valve prolapse (MVP) is associated with aggravated risk of ventricular tachycardia (VT), ventricular fibrillation (VF) and sudden cardiac death (SCD). There is a lack of specific guideline recommendation regarding risk stratification and management, despite multiple proposed high-risk phenotypes. We performed systematic review and meta-analysis to evaluate high-risk phenotypes for malignant arrhythmias in patients with MVP. METHODS: We comprehensively searched the databases of MEDLINE, SCOPUS, and EMBASE from inception to April 2023. Included studies were cohort and case-control comparing between MVP patients with and without VT, VF, cardiac arrest, ICD placement, or SCD. Data from each study were combined using the random-effects. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: Nine studies from 1985 to 2023 were included involving 2,279 patients with MVP. We found that T-wave inversion (OR 2.52; 95% CI: 1.90-3.33; p < 0.001), bileaflet involvement (OR 2.28; 95% CI: 1.69-3.09; p < 0.001), late gadolinium enhancement (OR 17.05; 95% CI: 3.41-85.22; p < 0.001), mitral annular disjunction (OR 3.71; 95% CI: 1.63-8.41; p < 0.002), and history of syncope (OR 6.96; 95% CI: 1.05-46.01; p = 0.044), but not female (OR 0.96; 95% CI: 0.46-2.01; p = 0.911), redundant leaflets (OR 4.30; 95% CI: 0.81-22.84; p = 0.087), or moderate-to-severe mitral regurgitation (OR 1.24; 95% CI: 0.65-2.37; p = 0.505), were associated with those events. CONCLUSION: Bileaflet prolapse, T-wave inversion, mitral annular disjunction, late gadolinium enhancement, and history of syncope are high-risk phenotypes among population with MVP. Further research is needed to validate the risk stratification model and justify the role of primary prophylaxis against malignant arrhythmias.

Major drivers of healthcare system costs and cost variability for routine atrial fibrillation ablation.

Background: Catheter ablation is an effective treatment for atrial fibrillation (AF) but incurs significant financial costs to payers. Reducing variability may improve cost effectiveness. Objectives: We aimed to measure (1) the components of direct and indirect costs for routine AF ablation procedures, (2) the variability of those costs, and (3) the main factors driving ablation cost variability. Methods: Using data from the University of Utah Health Value Driven Outcomes system, we were able to measure direct, inflation-adjusted costs of uncomplicated, routine AF ablation to the healthcare system. Direct costs were considered costs incurred by pharmacy, disposable supplies, patient labs, implants, and other services categories (primarily anesthesia support) and indirect costs were considered within imaging, facility, and electrophysiology lab management categories. Results: A total of 910 patients with 1060 outpatient ablation encounters were included from January 1, 2013, to December 31, 2020. Disposable supplies accounted for the largest component of cost with 44.8 ± 9.7%, followed by other services (primarily anesthesia support) with 30.4 ± 7.7% and facility costs with 16.1 ± 5.6%; pharmacy, imaging, and implant costs each contributed <5%. Direct costs were larger than indirect costs (82.4 ± 5.6% vs 17.6 ± 5.6%). Multivariable regression showed that procedure operator was the primary factor associated with AF ablation overall cost (up to 12% differences depending on operator). Conclusions: Direct costs and other services (primarily anesthesia) drive the majority costs associated with AF ablations. There is significant variability in costs for these routine, uncomplicated AF ablation procedures. The procedure operator, and not patient characteristic, is the main driver for cost variability.

Gender Disparities after Transcatheter Aortic Valve Replacement with Newer Generation Transcatheter Heart Valves: A Systematic Review and Meta-Analysis.

Previous studies have demonstrated gender disparities in mortality and vascular complications after transcatheter aortic valve replacement (TAVR) with early generation transcatheter heart valves (THVs). It is unclear, however, whether gender-related differences persist with the newer generation THVs. We aim to assess gender disparities after TAVR with newer generation THVs. The MEDLINE and Embase databases were thoroughly searched from inception to April 2023 to identify studies that reported gender-specific outcomes after TAVR with newer generation THVs (Sapien 3, Corevalve Evolut R, and Evolut Pro). The outcomes of interest included 30-day mortality, 1-year mortality, and vascular complications. In total, 5 studies (4 databases) with a total of 47,933 patients (21,073 females and 26,860 males) were included. Ninety-six percent received TAVR via the transfemoral approach. The females had higher 30-day mortality rates (odds ratio (OR) = 1.53, 95% confidence interval (CI) 1.31-1.79, p-value (p) < 0.001) and vascular complications (OR = 1.43, 95% CI 1.23-1.65, p < 0.001). However, one-year mortality was similar between the two groups (OR = 0.78, 95% CI 0.61-1.00, p = 0.28). The female gender continues to be associated with higher 30-day mortality rates and vascular complications after TAVR with newer generation transcatheter heart valves, while there was no difference in 1-year mortality between the genders. More data is needed to explore the causes and whether we can improve TAVR outcomes in females.

Electrical Cardioversion-Associated Takotsubo Cardiomyopathy: A National Readmission Database 2018 Analysis and Systematic Review.

The incidence of cardioversion-associated takotsubo cardiomyopathy in patients with atrial fibrillation undergoing electrical cardioversion is unknown. We aimed to determine the incidence of cardioversion-associated takotsubo cardiomyopathy using a National Readmission Database 2018 and a systematic review. We identified all patients with the index diagnosis of atrial fibrillation who underwent electrical cardioversion and were readmitted within 30 days with a primary diagnosis of takotsubo cardiomyopathy by International Classification of Diseases, Tenth Revision, Clinical Modification codes to find the incidence and risk factors of the disease. A systematic review was performed by searching PubMed and Embase for patients with atrial fibrillation who underwent electrical cardioversion and developed takotsubo cardiomyopathy from inception to February 2022. Baseline characteristics and clinical presentation were displayed. Among 154 919 patients admitted with atrial fibrillation who underwent electrical cardioversion in National Readmission Database 2018, 0.027% were readmitted with takotsubo cardiomyopathy (mean age of 71.0 ± 3.5 years and 96.7% were female). Female sex is an independent predictor of electrical cardioversion-associated takotsubo cardiomyopathy [adjusted odds ratio = 49.77 (95% CI: 5.90-419.87)], while diabetes mellitus is associated with less risk of electrical cardioversion-associated takotsubo cardiomyopathy [adjusted odds ratio = 0.31 (95% CI: 0.10-0.99)]. The systematic review included 13 patients (mean age of 74.8 ± 9.6 years and 77% were female). Acute heart failure due to apical type takotsubo cardiomyopathy is the most common presentation within 48 hours. The recovery time is less than 1 week in milder cases but can take up to 2 weeks in severe cases. Cardioversion-associated takotsubo cardiomyopathy is a rare complication in patients with atrial fibrillation who underwent electrical cardioversion. Female patients have a 50-fold increased risk, but DM is associated with a 3-fold risk reduction. The majority of patients recover within 2 weeks with supportive care.

Protocol Development and Initial Experience With Intravenous Sotalol Loading for Atrial Arrhythmias.

BACKGROUND: Oral sotalol is a class III antiarrhythmic commonly used for the maintenance of sinus rhythm in patients with atrial fibrillation (AF). Recently, the Food and Drug Administration (FDA) approved the use of IV sotalol loading, based primarily on modeling data for the infusion. We aimed to describe a protocol and experience with IV sotalol loading for elective treatment of adult patients with AF and atrial flutter (AFL). METHODS: We present our institutional protocol and retrospective review of initial patients treated with IV sotalol for AF/AFL at the University of Utah Hospital between September 2020 and April 2021. RESULTS: Eleven patients received IV sotalol for initial loading or dose escalation. All patients were male, aged 56-88 years (median 69). Mean QT interval (QTc) intervals increased from baseline (mean 384 ms) immediately after infusion of IV sotalol (mean change 42ms), but no patient required discontinuation of the medication. Six patients were discharged after 1 night; 4 patients were discharged after 2 nights; and 1 patient was discharged after 4 nights. Nine patients underwent electrical cardioversion prior to discharge (2 prior to load; 7 post-load on the day of discharge). There were no adverse events during the infusion or within 6 months of discharge. Persistence of therapy was 73% (8 of 11) at mean 9.9 weeks to follow up, with no discontinuations for adverse effects. CONCLUSIONS: We employed a streamlined protocol that was successfully implemented to facilitate the use of IV sotalol loading for atrial arrhythmias. Our initial experience suggests feasibility, safety, and tolerability while reducing hospitalization duration. Additional data are needed to augment this experience as IV sotalol use is broadened across different patient populations.

Reverse of left ventricular remodeling in heart failure patients with left bundle branch area pacing: Systematic review and meta-analysis.

BACKGROUND: Left bundle branch area pacing (LBBAP) has recently become a promising option for the near-natural restoration of electrical activation. However, the clinical relevance of therapeutic effects in individuals with heart failure with reduced ejection fraction (HFrEF) and dyssynchrony remains unknown. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched from inception until June 2022. Data from each study was combined using a random-effects model, the generic inverse variance method of DerSimonian and Laird, to calculate standard mean differences and pooled incidence ratio, with 95% confidence intervals (CIs). RESULTS: A total of 772 HFrEF patients were analyzed from 15 observational studies per protocol. The success rate of LBBAP implantation was 94.8% (95% CI 89.9-99.6, I2 = 79.4%), which was strongly correlated with shortening QRS duration after LBBAP implantation, with a mean difference of -48.10 ms (95% CI -60.16 to -36.05, I2 = 96.7%). Over a period of 6-12 months of follow-up, pacing parameters were stable over time. There were significant improvements in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-diastolic volume (LVEDV) with mean difference of 16.38% (95% CI 13.13-19.63, I2 = 90.2%), -46.23 ml (95% CI -63.17 to -29.29, I2 = 86.82%), -7.21 mm (95% CI -9.71 to -4.71, I2 = 84.6%), and -44.52 ml (95% CI -64.40 to -24.64, I2 = 85.9%), respectively. CONCLUSIONS: LBBAP was associated with improvements in both cardiac function and electrical synchrony. The benefits of LBBAP in individuals with HFrEF and dyssynchrony should be further validated by randomized studies.