Heart failure is associated with increased risk of all-cause mortality after transvenous lead extraction: A systematic review and meta-analysis.

Background: Transvenous lead extraction (TLE) is increasingly considered in cardiac implantable electronic device management. Heart failure (HF) might be associated with mortality risks after the TLE procedure. This study aims to assess mortality risk in HF patients undergoing TLE. Method: We searched MEDLINE and Embase databases from inception to June 2022 to identify articles that included patients with and without HF who underwent TLE, which reported mortality in both groups. The pooled effect size was calculated with a random-effects model and 95% CI to compare post-TLE mortality between the two groups. Results: Eleven studies were included in the analysis. Each left ventricular ejection fraction (LVEF) increased by 1% was associated with reduced mortality by 2% (HR = 0.98, 95% CI: 0.97-0.99, I 2 = 74.9%, p < .01). The presence of HF compared to those without HF was associated with higher mortality rates (OR: 3.04, 95% CI: 2.56-3.61, I 2 = 0.0%, p < .531). There was a significant increase in the mortality rates in patients with New York Heart Association (NYHA) function class III (OR: 2.29, 95% CI: 1.29-4.06, I 2 = 0.0%, p = .498) and NYHA IV (OR: 8.5, 95% CI: 2.98-24.3, I 2 = 0.0%, p = .997). Conclusions: Our study found that post-TLE mortality decreases by 2% as LVEF increases by 1%, also mortality is higher in patients with NYHA III and IV.

Impact of obesity on catheter ablation of ventricular tachycardia: In-hospital and 30-day outcomes.

Background: Evidence on the impact of obesity on catheter ablation for ventricular tachycardia (VT) is scarce. Method and Results: We queried the Nationwide Readmissions Database to determine the hospital outcomes and procedural complications of VT ablation among the obese and nonobese populations. Obesity was associated with a more prolonged length of stay (p < .01), higher cost of hospitalization (p < .01), and higher rates of pericardial effusion or hemopericardium (p = .05) and vascular complications (p = .05). There was no significant difference in early mortality, 30-day readmissions, and other procedural complications. Conclusion: VT ablation could be performed relatively safely among patients with obesity.

Prognostic Value of Coronary Computed Tomography Angiography in Coronary Artery Bypass Graft Patients Systematic Review and Meta-Analysis.

We sought to assess the prognostic value of coronary computed tomographic angiography (CCTA) in patients with coronary artery bypass graft (CABG) by meta-analysis. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus were searched for relevant original articles published up to July 2021. CCTA prognostic studies enrolling patients with CABG were screened and included if outcomes included all-cause mortality or major adverse cardiac events. Maximally adjusted hazard ratios (HRs) were extracted for CCTA-derived prognostic factors. HRs were log-transformed and pooled across studies using the DerSimonian-Laird random-effects model and statistical heterogeneity was assessed using the I2 statistic. Of 1,576 screened articles, 4 retrospective studies fulfilled all inclusion criteria. Collectively, a total of 1,809 patients with CABG underwent CCTA (mean [SD] age 67.0 [8.5] years across 3 studies, 81.5% male across 4 studies). Coronary artery disease severity and revascularization were categorized using 2 models: unprotected coronary territories and coronary artery protection score. The pooled HRs from the random-effects models using the most highly adjusted study estimate were 3.64 (95% confidence interval 2.48 to 5.34, I2 = 57.8%, p <0.001; 4 studies) and 4.85 (95% confidence interval 3.17 to 7.43, I2 = 39.9%, p <0.001; 2 studies) for unprotected coronary territories and coronary artery protection score, respectively. In conclusion, in a limited number of studies, CCTA is an independent predictor of adverse events in patients with CABG. Larger studies using uniform models and endpoints are needed.

Predicting arrhythmic event score in Brugada syndrome: Worldwide pooled analysis with internal and external validation.

BACKGROUND: Brugada syndrome is an inherited arrhythmic disease associated with major arrhythmic events (MAE). Risk predictive scores were previously developed with various performances. OBJECTIVE: The purpose of this study was to create a novel score-Predicting Arrhythmic evenT (PAT)-with internal and external validation. METHODS: A systematic review was performed to identify risk factors for MAE. The odds ratios (ORs) of each factor were pooled across studies. The PAT scoring scheme was developed based on pooled ORs. The PAT score was internally validated with published 105 Asian patients (follow-up 8.0 ± 4.1 [SD] years) and externally validated with unpublished 164 multiracial patients (82.3% White, 14.6% Asian, 3.2% Black; mean follow-up 8.0 ± 6.9 years) with Brugada syndrome. Performances were assessed and compared with previous scores using receiver operating characteristic curve (ROC) analysis. RESULTS: Sixty-seven studies published between 2002 and 2022 from 26 countries (7358 patients) were included. Pooled ORs were estimated, indicating that 15 of 23 risk factors were significant. The PAT score was then developed accordingly. The PAT score had significantly better discrimination (ROC 0.9671) than the BRUGADA-RISK score (ROC 0.7210; P = .006), Shanghai Score System (ROC 0.7079; P = .003), and Sieira et al score (ROC 0.8174; P = .026) in an external validation cohort. PAT score ≥ 10 predicted the first MAE with 95.5% sensitivity and 89.1% specificity (ROC 0.9460) and the recurrent MAE (ROC 0.7061) with 15.4% sensitivity and 93.3% specificity. CONCLUSION: The PAT score was shown to be useful in predicting MAE for primary prevention in patients with Brugada syndrome.

Causes of Early Mortality After Catheter Ablation of Atrial Fibrillation.

BACKGROUND: Recognition of the causes of early mortality after atrial fibrillation (AF) catheter ablation is essential for the improvement of patient safety. This study sought to determine the causes of early mortality (≤90 days) after AF ablation. METHODS: We performed a retrospective analysis of AF ablation from January 1, 2013, to December 1, 2021 at the Mayo Clinic (Rochester, Phoenix, and Jacksonville). Causes of death were identified through a comprehensive chart review of the electronic health record from within the Mayo Clinic system and outside records when available. RESULTS: A total of 6723 patients were included in the study. The 90-day all-cause mortality rate was 0.22% (n=15). Among all 90-day deaths, majority of the deaths (73.3%) did not have a direct relationship with the procedure. Sudden death was the most common cause of early death (20%), followed by peri-procedural stroke (13%), respiratory failure (13%), atrioesophageal fistula (13%), infection (7%), heart failure (7%), and traumatic brain injury (7%). The 90-day mortality rate directly due to AF ablation procedural complications was 0.06% (n=4). CONCLUSIONS: AF ablation procedure has a 90-day mortality of 0.22%, and the most common cause of early mortality was sudden death. The majority (73.3%) of early mortality was not directly associated with a procedural complication, and the mortality rate due to complications associated with the AF ablation procedure was low at 0.06%. Further studies are required to investigate causes and risk factors associated with sudden death in this patient population.

Type of syncope and outcome in Brugada syndrome: A systematic review and meta-analysis.

Introduction: Brugada syndrome is an inherited arrhythmic disease associated with major arrhythmic events (MAE). The importance of primary prevention of sudden cardiac death (SCD) in Brugada syndrome is well recognized; however, ventricular arrhythmia risk stratification remains challenging and controversial. We aimed to assess the association of type of syncope with MAE via systematic review and meta-analysis. Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to December 2021. Included studies were cohort (prospective or retrospective) studies that reported the types of syncope (cardiac, unexplained, vasovagal, and undifferentiated) and MAE. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate the odds ratio (OR) and 95% confidence intervals (CIs). Results: Seventeen studies from 2005 to 2019 were included in this meta-analysis involving 4355 Brugada syndrome patients. Overall, syncope was significantly associated with an increased risk of MAE in Brugada syndrome (OR = 3.90, 95% CI: 2.22-6.85, p < .001, I 2 = 76.0%). By syncope type, cardiac (OR = 4.48, 95% CI: 2.87-7.01, p < .001, I 2 = 0.0%) and unexplained (OR = 4.71, 95% CI: 1.34-16.57, p = .016, I 2 = 37.3%) syncope was significantly associated with increased risk of MAE in Brugada syndrome. Vasovagal (OR = 2.90, 95% CI: 0.09-98.45, p = .554, I 2 = 70.9%) and undifferentiated syncope (OR = 2.01, 95% CI: 1.00-4.03, p = .050, I 2 = 64.6%, respectively) were not. Conclusion: Our study demonstrated that cardiac and unexplained syncope was associated with MAE risk in Brugada syndrome populations but not in vasovagal syncope and undifferentiated syncope. Unexplained syncope is associated with a similar increased risk of MAE compared to cardiac syncope.

Safety and efficacy of balloon angioplasty compared to stent-based-strategies with pulmonary vein stenosis: A systematic review and meta-analysis.

BACKGROUND: Pulmonary vein stenosis (PVS) is an uncommon but known cause of morbidity and mortality in adults and children and can be managed with percutaneous re-vascularization strategies of pulmonary vein balloon angioplasty (PBA) or pulmonary vein stent implantation (PSI). AIM: To study the safety and efficacy outcomes of PBA vs PSI in all patient categories with PVS. METHODS: We performed a literature search of all studies comparing outcomes of patients evaluated by PBA vs PSI for PVS. We selected all published studies comparing PBA vs PSI for PVS with reported outcomes of restenosis and procedure-related complications in all patient categories. In adults, PVS following atrial fibrillation ablation and in children PVS related to congenital etiology or post-procedural PVS following total or partial anomalous pulmonary venous return repair were included. The patient-centered outcomes were risk of restenosis requiring re-intervention and procedural-related complications. The meta-analysis was performed by computing odds ratios (ORs) using the random effects model based on underlying statistical heterogeneity. RESULTS: Eight observational studies treating 768 severe PVS in 487 patients met our inclusion criteria. The age range of patients was 6 months to 70 years and 67% were males. The primary outcome of the re-stenosis requiring re-intervention occurred in 196 of 325 veins in the PBA group and 111 of 443 veins in the PSI group. Compared to PSI, PBA was associated with a significantly increased risk of re-stenosis (OR 2.91, 95%CI: 1.15-7.37, P = 0.025, I 2 = 79.2%). Secondary outcomes of the procedure-related complications occurred in 7 of 122 patients in the PBA group and 6 of 69 in the PSI group. There were no statistically significant differences in the safety outcomes between the two groups (OR: 0.94, 95%CI: 0.23-3.76, P = 0.929), I 2 = 0.0%). CONCLUSION: Across all patient categories with PVS, PSI is associated with reduced risk of re-intervention and is as safe as PBA and should be considered first-line therapy for PVS.

Chronic kidney disease is associated with increased all-cause mortality in transvenous lead extraction: A systematic review and meta-analysis.

BACKGROUND: The impact of chronic kidney disease (CKD) or end-stage renal disease (ESRD) on patients receiving transvenous lead extraction (TLE) is not well-established. We performed a systematic review and meta-analysis to explore the association between CKD and all-cause mortality in TLE. METHODS: We searched the databases of PubMed and EMBASE from inception to April 2022. Included studies were published TLE studies that compared the risk of mortality in CKD patients compared to control patients. Data from each study were combined using the random-effects model. RESULTS: Eight studies (5,013 patients) were included. Compared with controls, CKD patients had a significantly higher risk of overall all-cause mortality (hazard ratio [HR] = 2.14, 95% confidence interval [CI]: 1.65-2.77, I2  = 51.1%, p < .001). The risk of overall all-cause mortality increased with the severity of CKD for nonspecific CKD (HR = 2.01, 95% CI: 1.49-2.69, I2  = 53.4, p < .001) and ESRD (HR = 2.79, 95% CI: 1.85-4.23, I2  = 0%, p < .001). The risk of all-cause mortality in CKD is double at follow-up ≤1 year (HR = 1.99, 95% CI: 1.29-3.09, I2  = 50.9%, p = .002) and higher at follow-up >1 year (HR = 2.36, 95% CI: 1.63-3.42, I2   = 59.7%, p < .001). CONCLUSIONS: Our meta-analysis demonstrates a significantly increased risk of overall all-cause mortality in patients with CKD who underwent TLE compared to controls.

The efficacy of posterior wall isolation in atrial fibrillation ablation: A systematic review and meta-analysis of randomized controlled trials.

Background: Posterior wall isolation (PWI) is an emerging approach in atrial fibrillation (AF) ablation, yet its efficacy remains controversial. This is the first meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy of PWI in AF ablation. Objective: To assess the efficacy of PWI in reducing atrial arrhythmia recurrence following initial AF ablation at long-term follow-ups when compared to conventional methods. Methods: We conducted a literature search from inception through September 2021 in EMBASE and MEDLINE databases. We included RCTs that compared outcomes in PWI and conventional approaches of AF ablation. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate odds ratio (OR), and 95% confidence interval (CI). Results: Eight RCT from 2009 to 2020, including 1024 AF patients, were included. PWI did not decrease overall atrial arrhythmias recurrence (RR 0.96, 95% CI:0.88-1.05, I 2 = 31.6%, p-value 0.393). However, the pooled analysis showed a significant decrease in AF recurrence in PWI compared to controlled approaches (RR 0.88, 95% CI:0.81-0.96, I 2 = 48.2%, p-value .004). In the subgroup analysis, PWI significantly decreased AF recurrence in the studies that included only persistent AF (RR = 0.89, 95% CI:0.80-0.98, I 2 = 65.2%, p-value .014). PWI significantly decreased AF recurrence when compared to PVI with roof line (RR 0.84, 95% CI 0.74-0.95, I 2 0.00%, p-value .008). Conclusion: Our study suggests that adding PWI significantly decreased AF recurrence in patients with persistent AF compared to controlled approaches. It highlights the importance of considering PWI during the initial procedure in this patient population.

Impact of early ventricular tachycardia ablation in patients with an implantable cardioverter-defibrillator: An updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: There is limited information on whether early catheter ablation (CA) for ventricular tachycardia (VT) is associated with better outcomes compared with alternative strategies in patients with implantable cardioverter-defibrillator (ICD). OBJECTIVE: The purpose of this article was to assess the efficacy of early VT CA in patients with ICD. METHODS: EMBASE, PubMed, and Cochrane were searched from inception to April 2022. Randomized controlled trials comparing the efficacy of early VT CA with control groups, both in patients with ICD, were included in the analysis. Data on effect estimates in individual studies were extracted and combined via random effects meta-analysis using the DerSimonian and Laird method, a generic inverse variance strategy. RESULTS: Nine randomized controlled trials with 1106 patients (n = 1018, 92.1% with ischemic cardiomyopathy and n = 88, 7.9% with nonischemic cardiomyopathy) were evaluated. VT CA was associated with reduced VT recurrences (odds ratio [OR] 0.64; P = .007), appropriate ICD shocks (OR 0.53; P = .002), ICD therapies (OR 0.54; P = .002), and cardiovascular hospitalization (OR 0.67; P = .004). However, no significant differences were observed in terms of mortality rate, heart failure hospitalization, and quality of life between the early VT CA and control groups. CONCLUSION: Early CA was beneficial in reducing VT burden and ICD therapies. However, it did not affect mortality rate and quality of life. Since most patients in the included studies presented with ischemic cardiomyopathy, further studies on nonischemic cardiomyopathy should be conducted to validate if early CA has similar outcomes.

Vaping tetrahydrocannabinol unmasks Brugada pattern and induces ventricular fibrillation in Brugada syndrome: a case report.

Background: Fever, alcohol, and sodium channel blockers can unmask Brugada pattern and may also induce arrhythmias in Brugada syndrome. We report a case of unmasked Type-1 Brugada pattern presenting with ventricular fibrillation that was induced by a tetrahydrocannabinol vaping. Case summary: A 48-year-old male with a past medical history of hypertension treated with hydrochlorothiazide and back pain controlled with tetrahydrocannabinol vaping presented with sudden cardiac arrest from ventricular fibrillation, which was terminated with defibrillation. Electrocardiogram after resuscitation showed a new Type-1 Brugada pattern compared to a previous normal baseline electrocardiogram. Echocardiography and coronary angiogram were unremarkable. Complete blood count and chemistries were unremarkable except for mild hypokalaemia (K = 3.3 mmol/L). After correction of the hypokalaemia, the Type-1 Brugada pattern persisted. Urine drug screen was positive for tetrahydrocannabinol (60 ng/mL). Genetic testing was negative for inherited arrhythmic disease and cardiomyopathy gene panels. Discussion: The patient's type-1 Brugada pattern and ventricular fibrillation were likely induced by vaping tetrahydrocannabinol. He underwent secondary prevention with an implantable cardioverter-defibrillator. He abstains from cannabis and Type-1 Brugada pattern is normalized. There was no arrhythmic event at his 18-month follow-up appointment with abstinence from tetrahydrocannabinol.

Surgical versus catheter ablation in atrial fibrillation: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia with a high stroke and mortality rate. The video-assisted thoracoscopic radiofrequency pulmonary vein ablation is a treatment option for patients who fail catheter ablation. Randomized data comparing surgical versus catheter ablation are limited. We performed a meta-analysis of randomized control trials to explore the outcome efficacy between surgical and catheter radiofrequency pulmonary vein ablation in patients with AF. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to December 2020. Included studies were published randomized control trials that compared video-assisted thoracoscopic and catheter radiofrequency pulmonary vein ablation. Data from each study were combined using the fixed-effects, generic inverse variance method of DerSimonian, and Laird to calculate odds ratios and 95% confidence intervals. RESULTS: Six studies from November 2013 to 2020 were included in this meta-analysis involving 511 AF patients (79% paroxysmal) with 263 catheter ablation (mean age 56 ± 3 years) and 248 surgical ablations (mean age 52 ± 4 years). Catheter ablation was associated with increased atrial arrhythmias recurrence when compared to surgical ablation (pooled relative risk = 1.85, 95% confidence interval: 1.44-2.39, p < .001, I2 = 0.0%) but associated with less total major adverse events (pooled relative risk = 0.29, 95% confidence interval: 0.16-0.53, p < .001, I2 = 0.0%). In subgroup analysis, catheter ablation was associated with increased AF recurrence in refractory paroxysmal AF when compared to surgical ablation (pooled relative risk = 2.47, 95% confidence interval: 1.31-4.65, p = .005, I2 = 0.0%) but not in persistent AF (relative risk = 1.09, 95% confidence interval: 0.60-2.0, p = .773). CONCLUSION: Catheter ablation was associated with higher atrial arrhythmia recurrence when compared with surgical ablation. However, our study suggests that the benefit of surgical ablation in patients with persistent AF is unclear. More studies and alternative ablation strategies investigation in persistent AF are warranted.

Gender difference in outcomes of patients undergoing MitraClip therapy: A systematic review and meta-analysis.

INTRODUCTION: Transcatheter edge-to-edge repair (TEER) of the mitral valve with MitraClip therapy is an emerging treatment in selected patients with severe mitral regurgitation. Identifying the patient with increased risk of poorer outcomes, including mortality, is crucial in these patients. Recent studies suggested conflicting data regarding the effects of gender on outcome in this patient population. We evaluate the impact of gender on the outcome of patients undergoing MitraClip therapy by systematic review and meta-analysis. METHODS: The authors comprehensively searched the databases of EMBASE and MEDLINE from inception to April 2021. Included studies were published cohorts reporting univariate or multivariate analysis of the effects of gender on in-hospital and overall mortality among patients undergoing MitraClip therapy. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonioan and Laird. RESULTS: A total of nine studies were included in this meta-analysis, including 9062 patients. Male gender is associated with higher in-hospital mortality with pooled OR 1.81 (95% confidence interval 1.01-3.22, p-value 0.045) and overall mortality with pooled OR 1.19 (95% CI 1.06-1.33, p-value 0.003). CONCLUSIONS: According to our meta-analysis, the male gender increases the risk of in-hospital mortality up to 1.81 folds and overall mortality up to 1.19 folds.

Hyponatremia induced Brugada syndrome mimicking ST segment elevation myocardial infarction.

Seventy-three year-old male with history of diabetes, hypertension, and chronic kidney disease stage 3 presented with epigastric pain and hyponatremia. ECG showed new ST segment elevation at precordial leads consistent with Cove-type Brugada ECG pattern. Cardiac catheterization revealed non-significant coronary artery stenosis. He experienced pre-syncope and palpitations a year prior to admission with family history sudden cardiac death. Brugada syndrome was diagnosed. Cove-type Brugada ECG pattern and palpitations resolved with corrected sodium to 135.

Zero fluoroscopy approach versus fluoroscopy approach for cardiac arrhythmia ablations: A systematic review and meta-analysis.

BACKGROUND: Radiofrequency catheter ablation for cardiac arrhythmias has traditionally been guided by fluoroscopy. Fluoroscopy exposes the patient, operator, and staff to ionizing radiation which has no safe dose void of stochastic and deterministic biologic risks. Zero fluoroscopy (ZF) approaches for catheter ablation have been advocated to eliminate these risks. We conducted a meta-analysis comparing acute procedure success, recurrence-free survival, complications, and procedure times between the approaches. METHODS: We conducted a literature search from inception through December 2020 in the databases of EMBASE and MEDLINE. We included randomized controlled trials and cohorts that compared the outcomes of interest in ZF and conventional/low fluoroscopy (CF/LF) approaches. The outcomes sought were acute procedure success, recurrence-free survival, complications, and procedure times. Effect estimates were combined, using the random-effects, generic inverse variance method of DerSimonian and Laird. RESULTS: Sixteen studies from 2013 to 2020, including 6052 patients (2219 ZF, 3833 CF/LF) were included. There were no significant differences in acute procedure success rate (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 0.75-1.59), recurrence-free survival (OR: 1.08, 95% CI: 0.78-1.49), periprocedural complication rate (OR: 0.72, 95% CI: 0.45-1.16), or total procedure time (weighted mean difference 2.32 min, 95% CI: -2.85-7.50) between ZF and CF/LF approaches, respectively. Overall, only 1.26% of patients crossed over from ZF to CF/LF arm. CONCLUSIONS: Periprocedural and postprocedural outcomes with a ZF approach compared favorably with traditional fluoroscopic guidance without increasing procedural times. As comfort with ZF grows, coupled with evolving mapping technologies, this method has potential to become the standard approach for catheter ablation.

Empirical Ablation to Prevent Sequential Purkinje System Recruitment: A Novel Therapy for Idiopathic Ventricular Fibrillation.

We report 3 cases (mean age 48.3 ± 11.6 years) of idiopathic ventricular fibrillation (IVF), in which a triggering premature ventricular complex leading to IVF could not be identified. All patients underwent posterior fascicle transection with empirical linear ablation of the mid-Purkinje potentials identified along the left ventricular interventricular inferior septum, and no ventricular fibrillation recurrence was documented in any of the patients. (Level of Difficulty: Advanced.).

Does the Age of Sudden Cardiac Death in Family Members Matter in Brugada Syndrome?

Background Brugada syndrome is an inherited cardiac channelopathy associated with major arrhythmic events (MAEs). The presence of a positive family history of sudden cardiac death (SCD) as a risk predictor of MAE remains controversial. We aimed to examine the association between family history of SCD and MAEs stratified by age of SCD with a systematic review and meta-analysis. Methods and Results We searched the databases of MEDLINE and EMBASE from January 1992 to January 2020. Data from each study were combined using the random-effects model. Fitted metaregression was performed to evaluate the association between the age of SCD in families and the risk of MAE. Twenty-two studies from 2004 to 2019 were included in this meta-analysis involving 3386 patients with Brugada syndrome. The overall family history of SCD was not associated with increased risk of MAE in Brugada syndrome (pooled odds ratio [OR], 1.11; 95% CI, 0.82-1.51; P=0.489, I2=45.0%). However, a history of SCD in family members of age younger than 40 years of age did increase the risk of MAE by ≈2-fold (pooled OR, 2.03; 95% CI, 1.11-3.73; P=0.022, I2=0.0%). When stratified by the age of cut point at 50, 45, 40, and 35 years old, a history of SCD in younger family member was significantly associated with a higher risk of MAE (pooled OR, 0.49, 1.30, 1.51, and 2.97, respectively; P=0.046). Conclusions A history of SCD among family members of age younger than 40 years was associated with a higher risk of MAE.

Long-Term Clinical Outcomes of Underdosed Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Atrial Flutter.

BACKGROUND: Although direct oral anticoagulants (DOACs) have been shown to be effective at reducing the risk of stroke in patients with atrial fibrillation/flutter (AF), they are sometimes underdosed off-label to mitigate their associated higher bleeding risk. We sought to evaluate frequency and clinical outcomes of inappropriate underdosing of DOACS in patients with AF. METHODS: We conducted a study of subjects with AF who had a clinical indication for stroke prophylaxis (with a congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 47 years, sex category [CHA2DS2-VASc] of 2 or greater) and were prescribed 1 of the 4 clinically approved DOACs (apixaban, rivaroxaban, dabigatran, or edoxaban). We compared all-cause mortality, composite of stroke and systemic embolism, composite of myocardial infarction (MI), acute coronary syndromes (ACS), and coronary revascularization, and major bleeding between patients appropriately dosed and inappropriately underdosed. RESULTS: A total of 8125 patients met inclusion criteria, with a mean follow up of 2.2 ± 2 years. Of those, 1724 patients (21.2%) were inappropriately dosed. After adjusting for baseline variables, there was no difference in all-cause mortality, risk of stroke or systemic embolism, International Society on Thrombosis and Haemostasis (ISTH) major bleeding, or composite of myocardial infarction, acute coronary syndromes, or coronary revascularization between patients appropriately dosed and inappropriately underdosed. In subgroup analysis, only apixaban demonstrated an increased incidence all-cause mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.03-1.49) with inappropriate underdosing. There was no difference in the remaining clinical outcomes noted on subgroup analysis. CONCLUSION: Underdosing of DOACs did not minimize risk of bleeding, systemic embolization or all-cause mortality in patients with AF. Inappropriate underdosing with apixaban in particular was associated with increased all-cause mortality.

Angiotensin II antagonists and gastrointestinal bleeding in left ventricular assist devices: A systematic review and meta-analysis.

Gastrointestinal bleeding (GIB) especially from arteriovenous malformations (AVM) remains one of the devastating complications following continuous-flow left ventricular device (CF-LVAD) implantation. Blockade of angiotensin II pathway using angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) was reported to mitigate the risk of GIB and AVM-related GIB by suppressing angiogenesis. We performed a systematic review and meta-analysis to evaluate the association between ACEI/ARB treatment and GIB in CF-LVAD population. Comprehensive literature search was performed through December 2019. We included studies reporting risk of GIB and/or AVM-related GIB events in LVAD patients who received ACEI/ARB with those who did not. Data from each study were combined using the random-effects to calculate odd ratios and 95% confidence intervals. Three retrospective cohort studies were included in this meta-analysis involving 619 LVADs patients (467 patients receiving ACEI/ARB). The use of ACEI/ARB was statistically associated with decreased incidence of overall GIB (pooled OR 0.35, 95% CI 0.22-0.56, I2 = 0.0%, p < 0.001). There was a non-significant trend toward lower risk for AVM-related GIB in patients who received ACEI/ARB (pooled OR 0.46, 95% CI 0.19-1.07, I2 = 51%, p = 0.07). Larger studies with specific definitions of ACEI/ARB use and GIB are warranted to accurately determine the potential non-hemodynamic benefits of ACEI/ARB in CF-LVAD patients.