The Effect of Implantable Loop Recorder based Continuous Rhythm Monitoring on Incident Atrial Fibrillation and Stroke: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: In patients with a history of stroke or those at high risk of developing stroke, a continuous rhythm monitoring strategy using implantable loop recorders (ILR) is often performed to screen for atrial fibrillation (AF). OBJECTIVES: We performed a systematic review (MEDLINE and EMBASE) including randomized controlled trials comparing ILR-based continuous rhythm monitoring versus usual care in patients with a history of stroke or patients at high risk of developing stroke. METHODS: A meta-analysis was performed and aggregate risk ratios (RR) and risk difference (RD) with their 95% confidence intervals were calculated. RESULTS: Four randomized controlled trials with 7,237 patients (ILR=2,114 and non-ILR=5,123) were included. ILR vs. non-ILR was associated with increased detection of incident AF (RR 3.88; 95% CI [2.23 - 6.75]; p<0.00001; NNT=7.7, I2=61%), increased appropriate initiation of anticoagulation (RR 2.29; 95% CI [2.07 - 2.55]; p<0.00001; NNT=6.7, I2=0), and a 25% lower risk of developing stroke (RR 0.75; 95% CI [0.59 - 0.95]; p=0.02; NNT=100, I2=0%). In patients with history of stroke there was no difference in the risk of developing incident stroke (RR 0.83; 95% CI [0.61 - 1.14]; p=0.25; I2=0%). CONCLUSION: Our meta-analysis shows that screening for AF with ILR is associated with increased detection of AF, and increased initiation of appropriate anticoagulation in patients with a history of stroke or those with risk factors for stroke. The benefit of stroke risk reduction with ILR remains unclear, and future studies focused on the inclusion of patients without a history of stroke are needed to elucidate this uncertainty.

Outcomes of patients with cardiac amyloidosis undergoing percutaneous left atrial appendage occlusion.

BACKGROUND: There is limited data on the safety and efficacy of left atrial appendage occlusion (LAAO) devices in patients with cardiac amyloidosis. We examined the outcomes of patients with cardiac amyloidosis undergoing LAAO device implantation in a nationally representative cohort of patients. METHODS: The National Readmissions Database (NRD) was analyzed from 2016 to 2019 to identify patients ≥ 18 years old with atrial fibrillation (AF) undergoing LAAO. Patients were divided into those with cardiac amyloidosis and those without cardiac amyloidosis. A multivariable logistic regression model was utilized to assess the independent association of cardiac amyloidosis with in-hospital, 30-day/90-day/180-day outcomes after adjusting for confounders. RESULTS: Our cohort included 54,900 LAAO implantation procedures, of which 220 (0.4%) had cardiac amyloidosis. Patients with cardiac amyloidosis had a lower proportion of women and a lower prevalence of comorbidities including anemia, obesity, diabetes, and peripheral vascular disorders but a higher prevalence of stroke, as compared to those without cardiac amyloidosis. On multivariable analysis, cardiac amyloidosis was associated with significantly higher odds of peri-procedural major adverse events (adjusted odds ratio [aOR]: 2.69; 95% confidence interval [CI]: 1.41-5.14; p<0.01) and neurological complications (aOR: 5.48; 95% CI: 2.47-12.8; p<0.01). There was no difference in the odds of other peri-procedural complications, in-hospital mortality, hospital resource utilization, and 30/90/180-day all-cause/bleeding/stroke-related readmissions between both groups. CONCLUSION: Patients with cardiac amyloidosis undergoing LAAO device implantation have an increased risk of peri-procedural complications without any difference in bleeding/stroke-related readmissions. These hypothesis-generating findings need validation in future prospective studies.

Sex differences in atrial fibrillation ablation outcomes in patients with heart failure.

BACKGROUND: There is a lack of data on the impact of sex on the outcomes of patients with heart failure (HF) undergoing atrial fibrillation (AF) ablation. We aimed to analyze the association of sex with outcomes of atrial fibrillation ablation in patients with heart failure. METHODS: The National Readmissions Database (NRD) was analyzed from 2016 to 2019 to identify patients ≥ 18 years old with heart failure (HF) undergoing AF ablation. The outcomes of interest included peri-procedural complications, in-hospital mortality, resource utilization, and unplanned 1-year readmissions. The final cohort was divided into patients with HFrEF and HFpEF and outcomes were compared between males and females in both cohorts. RESULTS: A total of 23,277 patients with HF underwent AF ablation between 2016 and 2019, of which 14,480 had HFrEF and 8,797 had HFpEF. Among patients with HFrEF, 61.6% were males and 38.4% were females whereas, among patients with HFpEF, 35.4% were males and 64.6% were females. On a multivariable-adjusted analysis, in patients with HFrEF, there was no difference in the odds of in-hospital mortality, peri-procedural complications, or 1-year HF-related/AF-related/all-cause readmissions between males and females. In patients with HFpEF, females had a higher risk 1-year HF-related readmissions (adjusted hazards ratio: 1.46; 95% CI: 1.13-1.87; p = 0.01), without any difference in the 1-year AF-related/all-cause readmissions, in-hospital mortality, or peri-procedural complications. CONCLUSION: Our results show that females with HFrEF undergoing AF ablation have similar outcomes whereas females with HFpEF have higher 1-year HF readmissions with no difference in the other outcomes, compared to males.

Contemporary trends of leadless pacemaker implantation in the United States.

INTRODUCTION: Leadless pacemakers (LPM) have established themselves as the important therapeutic modality in management of selected patients with symptomatic bradycardia. To determine real-world utilization and in-hospital outcomes of LPM implantation since its approval by the Food and Drug Administration in 2016. METHODS: For this retrospective cohort study, data were extracted from the National Inpatient Sample database from the years 2016-2020. The outcomes analyzed in our study included implantation trends of LPM over study years, mortality, major complications (defined as pericardial effusion requiring intervention, any vascular complication, or acute kidney injury), length of stay, and cost of hospitalization. Implantation trends of LPM were assessed using linear regression. Using years 2016-2017 as a reference, adjusted outcomes of mortality, major complications, prolonged length of stay (defined as >6 days), and increased hospitalization cost (defined as median cost >34 098$) were analyzed for subsequent years using a multivariable logistic regression model. RESULTS: There was a gradual increased trend of LPM implantation over our study years (3230 devices in years 2016-2017 to 11 815 devices in year 2020, p for trend <.01). The adjusted mortality improved significantly after LPM implantation in subsequent years compared to the reference years 2016-2017 (aOR for the year 2018: 0.61, 95% CI: 0.51-0.73; aOR for the year 2019: 0.49, 95% CI: 0.41-0.59; and aOR for the year 2020: 0.52, 95% CI: 0.44-0.62). No differences in adjusted rates of major complications were demonstrated over the subsequent years. The adjusted cost of hospitalization was higher for the years 2019 (aOR: 1.33, 95% CI: 1.22-1.46) and 2020 (aOR: 1.69, 95% CI: 1.55-1.84). CONCLUSION: The contemporary US practice has shown significantly increased implantation rates of LPM since its approval with reduced rates of inpatient mortality.

Trends and disparities in cardiac implantable electronic device infection-related mortality in the United States.

INTRODUCTION: We performed a cross-sectional study using the Centers for Disease Control and Prevention's (CDC's) Wide-Ranging Online Data for Epidemiologic Research (WONDER) database to analyze the trends in cardiac implantable electronic device (CIED) infection-related mortality from 1999 to 2020. METHODS: We analyzed the death certificate data from the CDC WONDER database from 1999 to 2020 for CIED infections in the US population aged ≥25 years using International Classification of Diseases, Tenth Revision (ICD-10) codes, listed as the underlying or contributing cause of death. Age-adjusted mortality rates (AAMR) and 95% confidence intervals (CIs) were computed per 1 million population by standardizing crude mortality rates to the 2000 US census population. To assess annual mortality trends, we employed the Joinpoint regression model, calculating the annual percent change (APC) in AAMR and corresponding 95% CIs. RESULTS: Overall, there was an observed declining trend in AAMRs related to CIED infection-related mortality. Males accounted for 55% of the total deaths, with persistently higher AAMRs compared to females over the study duration. Both males and females had an overall decreasing trend in AAMRs throughout the study duration. On race/ethnicity stratified analysis, non-Hispanic (NH) Blacks exhibited the highest overall AAMR, followed by NH American Indians or Alaska Natives, NH Whites, Hispanic or Latinos, and NH Asian or Pacific Islanders. On a stratified analysis based on region, the South region had the highest overall AAMR, followed by the Midwest, West, and Northeast regions. CONCLUSION: Our study demonstrates a significant decline in CIED infection-related mortality in patients over the last two decades. Notable gender, racial/ethnic, and regional differences exist in the rates of mortality related to CIED infections.

Association between atrial fibrillation and heart failure patient reported outcomes across the ejection fraction spectrum.

BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure (HF) and is associated with worse clinical outcomes. We evaluated the relationship between AF and longitudinal changes in health-related quality of life (HRQoL) measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) in both HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). METHODS: This is a post-hoc analysis of the TOPCAT and HF-ACTION trials. The effect of AF on KCCQ overall summary scores (OSS), in both trials, was examined using a mixed effects regression model. Patients were divided into 3 groups according to AF status at baseline: patients with a history of AF but no AF detected on ECG at enrollment (Hx AF group), patients with history of AF and AF detected on ECG at enrollment (ECG AF group) and patients with post-randomization new-onset AF (New AF group). RESULTS: In TOPCAT, among 1,710 patients with KCCQ data available, AF was associated with a significantly lower KCCQ-OSS (-3.98; 95% CI -7.21: -0.74) at 48 months, with a significant AF status by time interaction (P = .03). In HF-ACTION, among 1,814 patients with available KCCQ data, AF was associated with a significantly lower KCCQ-OSS (-3.67; 95% CI -6.21: -1.41) at 24 months but there was no significant AF status by time interaction. In both trials, the type of AF was not associated with significant changes in KCCQ-OSS score. CONCLUSION: Ιn patients with both HFpEF and HFrEF, AF was independently associated with worse HRQoL measured by KCCQ.

Prevalence and Predictors of Readmissions in Patients With Hypertrophic Cardiomyopathy and Atrial Fibrillation/Flutter.

Atrial fibrillation/flutter (AF) is the most common dysrhythmia in patients with hypertrophic cardiomyopathy (HCM). Unexplained left ventricular hypertrophy and left ventricular outflow tract obstruction are integral components of HCM pathology which can cause increased left atrial pressure and atrial myopathy contributing to the substrate for AF. We aimed to determine the impact of AF on hospital readmissions in patients with HCM. We conducted a retrospective analysis using the 2015 to 2019 Nationwide Readmission Database to analyze the effect of AF on 30-day readmission and causes of 30-day readmission in patients with HCM. We also determined the hospital, patient, and procedure-specific independent predictors of readmission in patients with HCM and AF. Of 191,235 index HCM hospitalizations, 81,390 (42.6%) had a secondary diagnosis of AF. A total of 16.9% of patients with HCM and AF were readmitted within 30 days as compared with 14% of HCM patients without AF. The presence of AF was independently associated with a higher risk of all-cause 30-day readmission (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.17 to 1.25, p <0.001). The foremost etiology of 30-day readmission in HCM patients with AF was hypertensive heart and chronic kidney disease with heart failure, whereas the foremost etiology of 30-day readmission in HCM patients without AF was sepsis. Interventions aimed toward AF management (electrical cardioversion: adjusted HR 0.91, 95% CI 0.82 to 1.01. p = 0.074, AF ablation: HR 0.92, 95% CI 0.74 to 1.13, p = 0.409, Watchman procedure: HR 1.50, 95% CI 0.16 to 14.6, p = 0.725) during index admission did not significantly impact the 30-day readmission in HCM patients with AF. Myectomy during index hospitalization (adjusted HR 0.54, 95% CI 0.34 to 0.86, p = 0.010) was most strongly associated with a lower risk of 30-day readmission in HCM patients with AF. In conclusion, in patients hospitalized for HCM, presence of AF was associated with excess risk of 30-day all-cause readmission. Interventions aimed toward HCM management, that is, myectomy rather than interventions aimed toward AF management predicted lower readmission rate in this patient population.

Risk factors, clinical implications, and management of peridevice leak following left atrial appendage closure: A systematic review.

BACKGROUND: Left atrial appendage closure (LAAC) is a treatment modality for stroke prevention in patients with atrial fibrillation (AF). One of the potential complications of LAAC is a peri-device leak (PDL), which could potentially increase the risk of thromboembolism formation. METHODS: This systematic review was done according to PRISMA guidelines. Using four databases, all primary studies through April 2022 that met selection criteria were included. Outcomes of interest were studies reporting on PDL characteristics, risk factors and management. RESULTS: A total of 116 studies met selection criteria (97 original studies and 19 case reports/series). In the original studies (n = 30,133 patients), the weighted mean age was 72.0 ± 7.4 years (57% females) with a HAS-BLED and CHA2DS2-VASc weighted means of 2.8 ± 1.1 and 3.8 ± 1.3, respectively. The most common definition of PDL was based on size; 5 mm: major, 3-5 mm: moderate, < 1 mm minor, or trivial. Follow up time for PDL detection was 7.15 ± 9.0 months. 33% had PDL, irrespective of PDL severity/size, and only 0.9% had PDL of greater than 5 mm. The main risk factors for PDL development included lower degree of over-sizing, lower left ventricular ejection fraction, device/LAA shape mismatch, previous radiofrequency ablation, and male sex. The most common methods to screen for PDL included transesophageal echocardiogram and cardiac CT. PDL Management approaches include Amplatzer Patent Foramen Ovale occluder, Hookless ACP, Amplatzer vascular plug II, embolic coils, and detachable vascular coils; removal or replacement of the device; and left atriotomy. CONCLUSION: Following LAAC, the emergence of a PDL is a significant complication to be aware of. Current evidence suggests possible risk factors that are worth assessing in-depth. Additional research is required to assess suitable candidates, timing, and strategies to managing patients with PDL.

Treatment-related adverse events, including fatal toxicities, in patients with solid tumours receiving neoadjuvant and adjuvant immune checkpoint blockade: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Incorporating immune checkpoint blockade into perioperative cancer therapy has improved clinical outcomes. However, the safety of immune checkpoint blockade needs better evaluation, given the chances of more prolonged disease-free survival. We aimed to assess how adding immune checkpoint blockade to perioperative therapy affects treatment-related adverse events. METHODS: For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library from database inception until Aug 8, 2023, for randomised controlled trials that assessed the addition of immune checkpoint blockade to neoadjuvant or adjuvant therapy for cancer, reported treatment-related deaths, and had a design in which the experimental group assessed immune checkpoint blockade in combination with the therapy used in the control group. Meta-analysis was done to pool odds ratios (ORs) of treatment-related deaths, any grade and grade 3-4 treatment-related adverse events, serious adverse events, and adverse events leading to treatment discontinuation. The protocol is registered with PROSPERO, CRD42022343741. FINDINGS: 28 randomised controlled trials with 16 976 patients were included. The addition of immune checkpoint blockade was not significantly associated with increased treatment-related deaths (OR 1·76, 95% CI 0·95-3·25; p=0·073), consistent across immune checkpoint blockade subtype (I2=0%). 40 fatal toxicities were identified across 9864 patients treated with immune checkpoint blockade, with pneumonitis being the most common (six [15·0%]); 13 fatal toxicities occurred among 7112 patients who were not treated with immune checkpoint blockade. The addition of immune checkpoint blockade increased the incidence of grade 3-4 treatment-related adverse events (OR 2·73, 95% CI 1·98-3·76; p<0·0001), adverse events leading to treatment discontinuation (3·67, 2·45-5·51; p<0·0001), and treatment-related adverse events of any grade (2·60 [1·88-3·61], p<0·0001). The immune checkpoint blockade versus placebo design primarily used as adjuvant therapy was associated with increased incidence of treatment-related deaths (4·02, 1·04-15·63; p=0·044) and grade 3-4 adverse events (5·31, 3·08-9·15; p<0·0001), whereas the addition of immune checkpoint blockade in the neoadjuvant setting was not associated with increased incidence of treatment-related death (1·11, 95% CI 0·38-3·29; p=0·84) or grade 3-4 adverse events (1·17, 0·90-1·51; p=0·23). INTERPRETATION: The addition of immune checkpoint blockade to perioperative therapy was associated with an increase in grade 3-4 treatment-related adverse events and adverse events leading to treatment discontinuation. These findings provide safety insights for further clinical trials assessing neoadjuvant or adjuvant immune checkpoint blockade therapy. Clinicians should closely monitor patients for treatment-related adverse events to prevent treatment discontinuations and morbidity from these therapies in earlier-stage settings. FUNDING: None.

Left bundle branch area pacing vs biventricular pacing for cardiac resynchronization: A systematic review and meta-analysis.

Background: Left bundle branch area pacing (LBBAP) may offer greater physiological benefits than traditional biventricular pacing (BiVP). However, there are limited data comparing the efficacy of LBBAP vs BiVP in patients with systolic heart failure (HF). Objective: The purpose of this meta-analysis was to compare the feasibility and electromechanical and clinical outcomes of both LBBAP and BiVP. Methods: We conducted a systematic review of studies retrieved from various databases including PubMed, Embase, Google Scholar, Scopus, and Cochrane Central Register of Control Trials (CENTRAL) published up to May 22, 2023. The risk ratio (RR) and standardized mean difference (SMD) with corresponding 95% confidence intervals (CIs) were calculated for dichotomous and continuous outcomes, respectively. Results: We included 12 studies with a total of 3004 patients (LBBAP = 1242, BiVP = 1762). Pooled results showed that LBBAP resulted in a significant increase in left ventricular ejection fraction (SMD 0.40, 95% CI 0.25, 0.54, P < .00001), echocardiographic response (RR 1.19, 95% CI 1.10 to 1.29, P < .0001), improvement in New York Heart Association functional class (SMD -0.44, 95% CI -0.65 to -0.23, P < .0001), QRS duration reduction (SMD -0.90, 95% CI -1.14 to -0.66, P < .00001), left ventricular end-diastolic diameter reduction (SMD -0.31, 95% CI -0.57 to -0.05, P = .02), fewer HF hospitalizations (RR 0.72, 95% CI 0.62, 0.85, P < .0001), and improved survival (RR 0.73, 95% CI 0.58, 0.92, P = .007). In addition, LBBAP was associated with shorter fluoroscopy time (SMD -0.94, 95% CI -1.42 to -0.47, P < .0001) and lower pacing threshold at implantation (SMD -1.03, 95% CI -1.32 to -0.74, P < .00001) and at 6 months (SMD -1.44, 95% CI -2.11 to -0.77, P < .0001) as compared with BiVP. Conclusion: Compared with BiVP, LBBAP was associated with better electromechanical and clinical outcomes, including left ventricular ejection fraction, QRS duration, echocardiographic response, New York Heart Association functional class, HF hospitalization, and all-cause mortality in patients with systolic HF.

The effect of weight loss on recurrence of atrial fibrillation after catheter ablation: A systematic review and meta-analysis.

BACKGROUND: Obesity is associated with an increased risk of developing recurrent atrial fibrillation (AF) after catheter ablation (CA). However, the current data on weight loss interventions show inconsistent results in preventing the recurrence of AF after CA. METHODS: We conducted a systematic search in MEDLINE and EMBASE to identify studies that reported the outcome of recurrence of AF after CA in obese patients undergoing weight interventions. The subgroup analysis included: (1) Weight loss versus no weight loss, (2) >10% weight loss versus <10% weight loss, (3) <10% weight loss versus no weight loss, (4) Follow-up <12 months, and (5) Follow-up >12 months after CA. Mantel-Haenszel risk ratios with a 95% confidence interval (CI) were calculated using a random effects model and for heterogeneity, I2 statistics were reported. RESULTS: A total of 10 studies (one randomized controlled trial and nine observational studies) comprising 1851 patients were included. The recurrence of AF was numerically reduced in the weight loss group (34.5%) versus no weight loss group (58.2%), but no statistically significant difference was observed (risk ratio [RR] = 0.76; 95% CI: 0.49-1.18, p = .22). However, there was a statistically significant reduction in recurrence of AF with weight loss versus no weight loss at follow-up >12 months after CA (RR = 0.47; 95% CI: 0.32-0.68, p < .0001). At follow-up >12 months after CA, both >10% weight loss versus <10% weight loss (RR = 0.49; 95% CI: 0.31-0.80, p = .004) and <10% weight loss versus no weight loss (RR = 0.39; 95% CI: 0.31-0.49, p < .00001) were associated with a statistically significant reduction in recurrent AF. CONCLUSION: In patients with AF undergoing CA, weight loss is associated with reducing recurrent AF at > 12 months after ablation and these benefits are consistently seen with both >10% and <10% weight loss. The benefits of weight loss in preventing recurrent AF after CA should be examined in larger studies with extended follow-up duration.

Psychosocial risk factors and outcomes in patients undergoing catheter ablation for atrial fibrillation.

The association of psychosocial risk factors with cardiovascular disease is well-established, and there is a growing recognition of their influence on atrial fibrillation (AF) . A recent National Heart, Lung, and Blood Institute workshop called for transforming AF research to integrate social determinants of health. There is limited data examining the impact of psychosocial risk factors (PSRFs) on outcomes in patients with an established diagnosis of AF. Catheter ablation for AF has been shown to improve arrhythmia burden and quality of life compared with medical treatment alone. It is unknown how PSRFs affect clinical outcomes in patients undergoing AF ablation. It is important to understand this relationship, especially given the increasing adoption of catheter ablation in clinical practice.