Primary prevention with the implantable cardioverter-defibrillator in high-risk long-QT syndrome patients.

AIMS: Prospective data regarding the role of implantable cardioverter-defibrillator (ICD) for the primary prevention of sudden cardiac death in patients with long QT syndrome (LQTS) is scarce. Herein, we explore the prospective Rochester LQTS ICD registry to assess the risk for appropriate shock in primary prevention in a real-world setting. METHODS AND RESULTS: We studied 212 LQTS patients that had ICD implantation for primary prevention. Best-subsets proportional-hazards regression analysis was used to identify clinical variables that were associated with the first appropriate shock. Conditional models of Prentice, Williams, and Peterson were utilized for the analysis of recurrent appropriate shocks. During a median follow-up of 9.2 ± 4.9 years, there were 42 patients who experienced at least one appropriate shock and the cumulative probability of appropriate shock at 8 years was 22%. QTc ≥ 550 ms [hazard ratio (HR) 3.94, confidence interval (CI) 2.08-7.46; P < 0.001) and prior syncope on ß-blockers (HR 1.92, CI 1.01-3.65; P = 0.047) were associated with increased risk of appropriate shock. History of syncope while on ß-blocker treatment (HR 1.87, CI 1.28-2.72; P = 0.001), QTc 500-549 ms (HR 1.68, CI 1.10-2.81; P = 0.048), and QTc ≥ 550 ms (HR 3.66, CI 2.34-5.72; P < 0.001) were associated with increased risk for recurrent appropriate shocks, while ß-blockers were not protective (HR 1.03, CI 0.63-1.68, P = 0.917). LQT2 (HR 2.10, CI 1.22-3.61; P = 0.008) and multiple mutations (HR 2.87, CI 1.49-5.53; P = 0.002) were associated with higher risk for recurrent shocks as compared with LQT1. CONCLUSION: In this prospective ICD registry, we identified clinical and genetic variables that were associated appropriate shock risk. These data can be used for risk stratification in high-risk patients evaluated for primary prevention with ICD.

For Whom the Bell Tolls : Refining Risk Assessment for Sudden Cardiac Death.

Sudden cardiac death is one of the most important causes of death worldwide. Advancements in medical treatment, percutaneous interventions, and device therapy (ICD and CRTD) showed consistent reduction in mortality, mainly in survivors of SCD and in patients with ischemic cardiomyopathy and depressed left ventricular function. Patients with non-ischemic cardiomyopathies, mildly reduced LV function, and channelopathies have increased risk for SCD. Identifying the subgroup of these patients before they experience life-threatening or fatal events is essential to further improve outcomes. In this review, we aimed to summarize the current knowledge for risk stratification and primary prevention, to describe the gaps in evidence, and to discuss future directions for screening and treating patients at risk for SCD. PURPOSE OF REVIEW: The purpose of this review is to provide a comprehensive description of the etiologies of sudden cardiac death, risk stratification strategies, and to describe the current medical and interventional therapies. We aimed to discuss the current gaps in our knowledge of primary prevention of SCD and to review novel approaches and interventions. RECENT FINDINGS: The incidence of SCD has decreased in the last two decades due to improved pharmacological treatment and ICD implantation in SCD survivors and in patients with reduced left ventricular function and ischemic cardiomyopathy. The efficacy of ICD in patients with non-ischemic cardiomyopathy is challenged by new findings from the DANISH trial. Catheter ablation is new emerging strategy to prevent SCD in patients with scar relater or PVC-triggered ventricular arrhythmias. Despite the new treatments, SCD is still a major burden. ICD remains the cornerstone for patients with ischemic cardiomyopathy, whereas appropriate risk stratification of the patients with non-ischemic cardiomyopathy and channelopathies is needed to further improve outcomes. The future of ablation as the treatment and prevention of SCD remains to be studied.

Baseline adverse electrical remodeling and the risk for ventricular arrhythmia in Cardiac Resynchronization Therapy Recipients (MADIT CRT).

INTRODUCTION: Adverse electrical remodeling (AER), represented here as the sum absolute QRST integral (SAI QRST), has previously been shown to be directly associated with the risk for ventricular arrhythmia (VA). Cardiac resynchronization therapy (CRT) is known to reduce the risk for VA through various mechanisms, including reverse remodeling, and we aimed to evaluate the association between baseline AER and the risk for VA in CRT recipients. METHODS AND RESULTS: The study population comprised 961 CRT-D implanted patients from the MADIT CRT study. The relationship between SAI QRST, VA risk, and VA risk/death was evaluated as a continuous and as a categorical variable-tertiles (T1 ≤ 0.527, T2 0.528-0.766, T3 > 0.766). In a multivariable model, AER was inversely associated with the risk of VA. Each unit increase in SAI QRST was associated with 64% (P  =  0.007) and 54% (P  =  0.003) decrease in the risk of VA and VA/death, respectively. Patients with high SAI QRST (T3) and medium SAI QRST (T2) had 52% (P < 0.001) and 32% (P  =  0.027) reduced risk for VA and 44% (P  =  0.002) and 26% (P  =  0.055) reduced risk for VA/death as compared with patients with low SAI QRST (T1), respectively. CONCLUSION: In CRT implanted patients with mild heart failure, baseline AER was inversely associated with the risk for VA and VA/death; this is a finding that contradicts the relationship previously reported in non-CRT implanted patients. We theorize that CRT may abate the process of AER; however, characterization of this mechanism requires further study.

Percutaneous left atrial appendage occlusion in the prevention of stroke in atrial fibrillation: a systematic review.

Atrial fibrillation is commonly coexistent with heart failure, and the management of the heart failure patient would be incomplete without an appreciation for atrial fibrillation management. There are many complications associated with oral anticoagulation in the prevention of stroke related to atrial fibrillation. In recent years, the advent of several percutaneous left atrial appendage (LAA) occlusion/closure strategies has sought to provide an alternative treatment modality. Here, we systematically review the published literature to investigate the efficacy and safety of percutaneous LAA occlusion/closure devices. We searched PubMed, EMBASE, Cochrane database of systematic reviews, and the FDA Medical Devices database. Using prespecified criteria, we identified studies of the Amplatzer Cardiac Plug (St. Jude Medical), Amplatzer Amulet (St. Jude Medical), Lariat suture delivery device (SentreHeart), and Watchman device (Boston Scientific). We analyzed 2 randomized controlled trials (RCT) and 15 non-randomized registries that satisfied the study criteria. The two RCT both studied the Watchman device versus standard warfarin therapy; the studies indicate that the Watchman may be non-inferior to warfarin. Long-term efficacy outcomes for the Watchman device are promising. Data regarding the Amplatzer Cardiac Plug, Amplatzer Amulet, and Lariat suture delivery device are limited by the paucity of RCT data. High-quality prospective research is needed to directly compare LAA occlusion/closure strategies against one another as well as versus the direct oral anticoagulation medications. Data regarding the role of LAA occlusion in the heart failure population are lacking.

Study of the wearable cardioverter defibrillator in advanced heart-failure patients (SWIFT).

INTRODUCTION: The wearable cardioverter defibrillator (WCD) may allow stabilization until reassessment for an implantable cardioverter defibrillator (ICD) among high-risk heart failure (HF) patients. However, there are limited data on the WCD benefit in the acute decompensated HF setting. METHODS AND RESULTS: The Study of the Wearable Cardioverter Defibrillator in Advanced Heart Failure Patients (SWIFT) was a prospective clinical trial carried out at two medical centers. Patients hospitalized with advanced HF symptoms and reduced left ventricular ejection function (LVEF) were enrolled and prescribed a WCD prior to discharge for a total of 3 months. Outcome measures included arrhythmic events, WCD discharge, and death. Study patients (n = 75, mean age 51 ± 14 years, 31% women) had a mean LVEF of 21.5 ± 10.4%. Non-ischemic cardiomyopathy was present in 66% of patients. The median WCD wearing time was 59 (interquartile range 17-97) days, and 80% of patients wore the device >50% of daily hours. WCD interrogations showed a total of 8 arrhythmic events in 5 patients, including 3 nonsustained or self-terminating ventricular tachycardia (VT) events, and one polymorphic VT successfully terminated by the WCD. None of the patients died while wearing the device and no inappropriate device therapies occurred. Upon termination of treatment with the WCD, 21 patients (28%) received an ICD. At 3 years, the cumulative death rate was 20% in the ischemic and 21% in non-ischemic cardiomyopathy patients. CONCLUSION: A management strategy incorporating the WCD can be safely used to bridge the decision regarding the need for ICD implantation in high-risk patients with advanced HF.

Admission blood glucose and 10-year mortality among patients with or without pre-existing diabetes mellitus hospitalized with heart failure.

BACKGROUND: High admission blood glucose (ABG) level has been associated with a poor short-term outcome among non-diabetic patients with heart failure (HF). We aimed to investigate the association between ABG levels and long-term (10 years) mortality in patients with or without pre-existing diabetes mellitus (DM) admitted with HF. METHODS: We analyzed data on 1811 patients with DM and 2182 patients without pre-existing DM who were hospitalized with HF during a prospective national survey. The relationship between ABG and 10-year mortality was assessed using the Cox proportional hazard model adjusting for multiple variables. ABG was analyzed both as a categorical (<110, 110-140, 140-200, and >200 mg/dL) and as a continuous variable. RESULTS: At 10 years of follow-up the cumulative probability of mortality was 85 and 78% among patients with DM and patients with no pre-existing DM (p < 0.001), respectively. Among patients with no pre-existing DM, glucose levels of 110-140, 140-200 and ≥200 mg/dL were associated with 9% (p = 0.140), 16% (p = 0.031) and 53% (p < 0.001) increased mortality risk compared to ABG < 110 mg/dL. Each 18-mg/dL (1-mmol/L) increase in glucose level was associated with a 5% increased risk of mortality (p < 0.001) among patients with no-pre-existing DM. In contrast, among patients with DM, only those with glucose levels >200 mg/dL had an increased mortality risk (>200 mg/dL versus <110 mg/dL; HR = 1.20, p = 0.032). CONCLUSION: Among hospitalized HF patients with no pre-existing DM there is a linear relationship between ABG level and long-term mortality, whereas among patients with DM only ABG level >200 mg/dL is associated with increased mortality risk.

Effect of Significant Weight Change on Inappropriate Implantable Cardioverter-Defibrillator Therapy.

BACKGROUND: Weight loss has been associated with adverse outcomes among heart failure (HF) patients, including those receiving cardiac resynchronization therapy with defibrillator (CRT-D). The effect of significant weight change on inappropriate implantable cardioverter-defibrillator (ICD) therapy among CRT-D patients is not well understood. METHODS: We evaluated the impact of significant weight change at 1 year on subsequent inappropriate ICD therapy during follow-up among 993 CRT-D patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy. Patients were divided into three subgroups based on weight change at 1 year after enrollment: weight loss (weight loss ≥ 5%), weight gain (weight gain ≥ 5%), and stable weight (weight loss and weight gain < 5%). The primary end point was inappropriate ICD therapy. Secondary end point included inappropriate ICD therapy related to supraventricular arrhythmias (SVAs). RESULTS: There were 102 (10.3%) patients who experienced weight loss, 689 (69.4%) whose weight was stable, and 202 (20.3%) who gained weight at 1 year. Patients with weight loss had increased risk of subsequent inappropriate ICD therapy relative to patients with stable weight (hazard ratio [HR] = 2.35, 95% confidence interval [CI]: 1.39-3.98, P = 0.001) or weight gain (HR = 2.27, 95% CI: 1.18-4.38, P = 0.014). Furthermore, patients losing weight were at greater risk of subsequent inappropriate ICD therapy related to SVAs when compared to patients with stable weight (HR = 2.16, 95% CI: 1.18-3.95, P = 0.013) or weight gain (HR = 2.02, 95% CI: 0.95-4.29, P = 0.068). CONCLUSION: In mild HF patients receiving CRT-D, significant weight loss at 1 year is associated with increased risk of subsequent inappropriate ICD therapy, including risk related to SVAs.

Effect of cardiac resynchronization therapy on the risk of ventricular tachyarrhythmias in patients with chronic kidney disease.

BACKGROUND: The effect of chronic kidney disease (CKD) on benefit from cardiac resynchronization therapy with defibrillator (CRT-D) in reducing ventricular tachyarrhythmia (VTA) risk among mild heart failure (HF) patients is not well understood. METHODS: We evaluated the impact of baseline renal function on VTAs in 1274 left bundle branch block (LBBB) patients enrolled in MADIT-CRT. Two prespecified subgroups were created based on estimated glomerular filtration rate (GFR): GFR <60 (n = 413) and GFR ≥60 ml/min/1.73 m2 (n = 861). Primary end point was ventricular tachycardia/ventricular fibrillation/death (VT/VF/death). Secondary end points were any VT/VF and ventricular tachycardia ≥ 200 bpm or VF (fast VT/VF). RESULTS: There were 413 (32%) LBBB patients presenting with CKD, primarily of moderate severity (GFR mean 48.1 ± 8.3). For patients with and without CKD, CRT-D was associated with lower risk of the primary end point (GFR<60: HR = 0.61, 95% CI: 0.41-0.89, p = .010; GFR≥60: HR = 0.58, 95% CI: 0.52-0.89, p = .005), relative to ICD-only treatment. For patients in both renal function categories, CRT-D in comparison to ICD alone was associated with lower risk of VT/VF (GFR<60: HR = 0.68, 95% CI: 0.42-1.10, p = .113; GFR≥60: HR = 0.65, 95% CI: 0.48-0.88, p = .005) and fast VT/VF (GFR<60: HR = 0.49, 95% CI: 0.25-0.96, p = .038; GFR≥60: HR = 0.55, 95% CI: 0.39-0.80, p = .001), when accounting for competing mortality risk. This effect was independent of CRT-induced reverse remodeling. CONCLUSION: Among mild HF patients with LBBB, those with and without CKD both derived benefit from CRT-D in risk reduction in VTAs, independent of cardiac reverse remodeling.

Use of the wearable cardioverter defibrillator in high-risk cardiac patients: data from the Prospective Registry of Patients Using the Wearable Cardioverter Defibrillator (WEARIT-II Registry).

BACKGROUND: Prospective data on the safety and efficacy of the wearable cardioverter defibrillator (WCD) in a real-world setting are lacking. The Prospective Registry of Patients Using the Wearable Defibrillator (WEARIT-II) Registry was designed to provide real-world data on the WCD as a strategy during a period of risk stratification. METHODS AND RESULTS: The WEARIT-II Registry enrolled 2000 patients with ischemic (n=805, 40%), or nonischemic cardiomyopathy (n=927, 46%), or congenital/inherited heart disease (n=268) prescribed WCD between August 2011 and February 2014. Clinical data, arrhythmia events, implantable cardioverter defibrillator implantation, and improvement in ejection fraction were captured. The median age was 62 years; the median ejection fraction was 25%. The median WCD wear time was 90 days, with median daily use of 22.5 hours. There was a total of 120 sustained ventricular tachyarrhythmias in 41 patients, of whom 54% received appropriate WCD shock. Only 10 patients (0.5%) received inappropriate WCD therapy. The rate of sustained ventricular tachyarrhythmias by 3 months was 3% among patients with ischemic cardiomyopathy and congenital/inherited heart disease, and 1% among nonischemic patients (P=0.02). At the end of WCD use, 840 patients (42%) were implanted with an implantable cardioverter defibrillator. The most frequent reason not to implant an implantable cardioverter defibrillator following WCD use was improvement in ejection fraction. CONCLUSIONS: The WEARIT-II Registry demonstrates a high rate of sustained ventricular tachyarrhythmias at 3 months in at-risk patients who are not eligible for an implantable cardioverter defibrillator, and suggests that the WCD can be safely used to protect patients during this period of risk assessment.

Cardiac Resynchronization in Different Age Groups: A MADIT-CRT Long-Term Follow-Up Substudy.

BACKGROUND: Cardiac resynchronization with defibrillators (CRT-D) reduces heart failure and mortality compared with defibrillators alone. Whether this applies to all ages is unclear. METHODS AND RESULTS: We assessed the association of age on heart failure and death as a post hoc analysis of the MADIT-CRT follow-up study, in which 1,281 patients with class I/II heart failure (HF) were randomized to CRT-D or implantable cardioverter-defibrillators alone. Different age groups (<60, 60-74, and ≥75 years) were evaluated over 7 years for mortality and HF events. Among the 3 age groups, there were 399, 651, and 231 patients, respectively. We compared events with the use of a multivariate regression model. CRT-D compared with defibrillators alone significantly reduced the composite of HF or death across all age groups: <60 years: relative risk reduction (RRR) = 36%; 60-74 years: RRR = 61%; ≥75 years: RRR = 56%. CRT-D significantly reduced HF in all age groups: <60 years: RRR = 49%; 60-74 years: RRR = 62%; ≥75 years: RRR = 74%. CRT-D was associated with significant mortality reduction only in the 60-74 year age group: RRR = 59%. CONCLUSIONS: CRT-D reduced HF events and the composite of mortality or HF events during long-term follow-up in all age groups. CRT-D reduced mortality only in the 60-74 year age group.

Roles and indications for use of implantable defibrillator and resynchronization therapy in the prevention of sudden cardiac death in heart failure.

Implantable devices are indicated in the primary and secondary prevention of potentially life-threatening ventricular tachyarrhythmias in patients with heart failure. Early studies, including the landmark MADIT trials, showed that implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) devices can play a significant role in aborting and preventing ventricular arrhythmias, respectively, that can cause sudden cardiac death. To this day, there have been a number of randomized controlled trials, with respective substudy analyses, that have attempted to better understand the indications for these interventions in patient care. Here, we summarize the major results of these studies, and we discuss the role of ICD therapy for both ischemic and non-ischemic cardiomyopathy, emerging evidence in support of wearable defibrillators, and the impact of modified ICD programming strategies on patient outcomes. Regarding CRT therapy, the phenomenon of ventricular reverse remodeling is an important prognostic indicator in preventing future ventricular tachyarrhythmia episodes. In summation, we provide an overview of the possible selection criteria that can be used in identifying appropriate patients for ICD and/or CRT therapy, as supported by the data.

Effect of obesity on the effectiveness of cardiac resynchronization to reduce the risk of first and recurrent ventricular tachyarrhythmia events.

BACKGROUND: Obesity is associated with multiple adverse cardiovascular conditions and may increase the risk of ventricular tachyarrhythmias (VT/VF). There is limited data on the association between obesity and risk of VT/VF requiring appropriate implantable cardioverter-defibrillator (ICD) therapies and the effectiveness of cardiac resynchronization therapy (CRT) to reduce risk for VT/VF. The multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy (MADIT-CRT) was design to investigate effectiveness of CRT therapy to reduce cardiovascular outcome for patients with heart failure (HF) and reduced ejection fraction. METHODS AND RESULTS: We identified patients enrolled in the MADIT CRT trial as obese (n = 433) and non-obese (n = 845) and analyzed their risk for appropriate device therapy for VT/VF, repeated VT/VF events, fast VT/VF, as well as events after first VT/VF episodes. Obesity was defined as body mass index (BMI) ≥30 kg/m(2). Among ICD patients, the risk of first appropriate ICD therapy for VT/VF at 3 years was similar between obese and non-obese patients (23 vs. 21 %, p = 0.76). CRT-D treatment reduced the risk of first appropriate ICD therapy both in non-obese ([HR]; 0.58 [CI]: 0.42-0.79; p < 0.001) and obese patients (HR 0.75, 95 % CI 0.5-1.38; p = 0.179) (interaction p value 0.323). Similarly, a significant reduction in the risk of fast VT/VF was observed in non-obese patients ([HR]; 0.49 [CI]: 0.33-0.73; p < 0.001) and obese ([HR]; 0.49 [CI]: 0.29-0.81; p < 0.01), (interaction p value 0.984). CONCLUSION: Obese and non-obese patients with mild heart failure have a similar risk of ventricular tachyarrhythmias. Obesity in mild heart failure did not diminish the clinical benefit of cardiac resynchronization therapy to reduce risk for appropriate ICD therapy. Clinical trial registration http://clinicaltrials.gov/ct2/show/NCT00180271.

Long-term outcome with cardiac resynchronization therapy in mild heart failure patients with left bundle branch block from US and Europe MADIT-CRT.

UNLABELLED: Early intervention with cardiac resynchronization therapy with defibrillator (CRT-D) in mild heart failure (HF) patients with a left bundle branch block (LBBB) ECG pattern was associated with a significant reduction in mortality in the long-term MADIT-CRT trial. Whether patients in MADIT-CRT enrolled from centers in the USA and in Europe have different long-term clinical response to CRT-D remains unknown. We compared the baseline clinical characteristics and clinical and echocardiographic long-term clinical response to CRT-D between MADIT-CRT patients with LBBB who were enrolled in USA (n = 871) and European centers (n = 392). Although European patients had more advanced heart disease than US patients, CRT-D was associated with similar 60 % (p < 0.001) reductions in the risk of HF in US and European patients when compared to ICD-only therapy after adjustment for relevant baseline clinical covariates. US patients had significant long-term mortality reduction (38 %, p = 0.02) while among European patients the survival benefit associated with CRT-D was not statistically significant (HR 0.73, p = 0.18); subgroup analyses revealed a significantly greater CRT-D benefit among women who were enrolled in the USA, whereas no significant gender difference in the clinical benefit of CRT-D was observed in the European cohort. Reverse remodeling at 1 year was associated with significantly better clinical outcomes in both groups. Despite differences in baseline disease severity, European and US patients with LBBB experienced a similar clinical and echocardiographic response to cardiac resynchronization therapy during long-term follow-up. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov/ct2/show/NCT00180271 .

AI-based cluster analysis enables outcomes prediction among patients with increased LVM.

Background: The traditional classification of left ventricular hypertrophy (LVH), which relies on left ventricular geometry, fails to correlate with outcomes among patients with increased LV mass (LVM). Objectives: To identify unique clinical phenotypes of increased LVM patients using unsupervised cluster analysis, and to explore their association with clinical outcomes. Methods: Among the UK Biobank participants, increased LVM was defined as LVM index ≥72 g/m2 for men, and LVM index ≥55 g/m2 for women. Baseline demographic, clinical, and laboratory data were collected from the database. Using Ward's minimum variance method, patients were clustered based on 27 variables. The primary outcome was a composite of all-cause mortality with heart failure (HF) admissions, ventricular arrhythmia, and atrial fibrillation (AF). Cox proportional hazard model and Kaplan-Meier survival analysis were applied. Results: Increased LVM was found in 4,255 individuals, with an average age of 64 ± 7 years. Of these patients, 2,447 (58%) were women. Through cluster analysis, four distinct subgroups were identified. Over a median follow-up period of 5 years (IQR: 4-6), 100 patients (2%) died, 118 (2.8%) were admissioned due to HF, 29 (0.7%) were admissioned due to VA, and 208 (5%) were admissioned due to AF. Univariate Cox analysis demonstrated significantly elevated risks of major events for patients in the 2nd (HR = 1.6; 95% CI 1.2-2.16; p < .001), 3rd (HR = 2.04; 95% CI 1.49-2.78; p < .001), and 4th (HR = 2.64; 95% CI 1.92-3.62; p < .001) clusters compared to the 1st cluster. Further exploration of each cluster revealed unique clinical phenotypes: Cluster 2 comprised mostly overweight women with a high prevalence of chronic lung disease; Cluster 3 consisted mostly of men with a heightened burden of comorbidities; and Cluster 4, mostly men, exhibited the most abnormal cardiac measures. Conclusions: Unsupervised cluster analysis identified four outcomes-correlated clusters among patients with increased LVM. This phenotypic classification holds promise in offering valuable insights regarding clinical course and outcomes of patients with increased LVM.

Trends in Atrial Fibrillation Management-Results from a National Multi-Center Urgent Care Network Registry.

BACKGROUND: Atrial fibrillation (AF) is a common diagnosis in patients presenting to urgent care centers (UCCs), yet there is scant research regarding treatment in these centers. While some of these patients are managed within UCCs, some are referred for further care in an emergency department (ED). OBJECTIVES: We aimed to identify the rate of patients referred to an ED and define predictors for this outcome. We analyzed the rates of AF diagnosis and hospital referral over the years. Finally, we described trends in patient anticoagulation (AC) medication use. METHODS: This retrospective study included 5873 visits of patients over age 18 visiting the TEREM UCC network with a diagnosis of AF over 11 years. Multivariate analysis was used to identify predictors for ED referral. RESULTS: In a multivariate model, predictors of referral to an ED included vascular disease (OR 1.88 (95% CI 1.43-2.45), p < 0.001), evening or night shifts (OR 1.31 (95% CI 1.11-1.55), p < 0.001; OR 1.68 (95% CI 1.32-2.15), p < 0.001; respectively), previously diagnosed AF (OR 0.31 (95% CI 0.26-0.37), p < 0.001), prior treatment with AC (OR 0.56 (95% CI 0.46-0.67), p < 0.001), beta blockers (OR 0.63 (95% CI 0.52-0.76), p < 0.001), and antiarrhythmic medication (OR 0.58 (95% CI 0.48-0.69), p < 0.001). Visits diagnosed with AF increased over the years (p = 0.030), while referrals to an ED decreased over the years (p = 0.050). The rate of novel oral anticoagulant prescriptions increased over the years. CONCLUSIONS: The rate of referral to an ED from a UCC over the years is declining but remains high. Referrals may be predicted using simple clinical variables. This knowledge may help to reduce the burden of hospitalizations.

Implantable cardioverter defibrillator for primary prevention in patients with non-ischemic cardiomyopathy in the era of novel therapeutic agents- meta-analysis.

Background: Evidence regarding the mortality benefit of implantable cardioverter defibrillator (ICD) non-ischemic dilated cardiomyopathy (NIDCM) is inconsistent. The most recent randomized study, the DANISH trial, did not find improved outcomes with ICD. However, based on previous studies and meta-analyses, current guidelines still highly recommend ICD implantation in NIDCM patients. The introduction of novel medications for heart failure improved the clinical outcome dramatically. We aimed in this study to evaluate the effect of Angiotensin Receptor-Neprilysin Inhibitors (ARNi) and sodium-glucose transport protein 2 inhibitors (SGLT2i) on the mortality benefit of ICD in NIDCM. Methods: We used a previous metanalysis algorithm and added an updated comprehensive literature search in PubMed for randomized control trials that examined the mortality benefit of ICD in NIDCM vs. optimal medical treatment. The primary outcome included death from any cause. We did a meta-regression analysis to search for a single independent factor affecting mortality. Using previous data, we evaluated the theoretical effect of ICD implementation on patients treated with SGLT2 inhibitors and ARNi. Results: No new articles were added to the results of the previous meta-analysis. 2,622 patients with NIDCM from 5 cohort studies published between 2002 and 2016 were included in the analysis. 50% of them underwent ICD implantation for primary prevention of sudden cardiac death, and 50% did not. ICD was associated with a significantly decreased risk for death from any cause compared to control (OR = 0.79, 95%CI: 0.66-0.95, p = 0.01, I2 = 0%). The theoretical addition of ARNi and the SGLT2 inhibitor dapagliflozin did not change the significant mortality effect of ICD (OR = 0.82, 95%CI: 0.7-0.9, p = 0.001, I2 = 0%) and (OR = 0.82, 95%CI: 0.7-0.9, p = 0.001, I2 = 0%). A meta-regression revealed no association between death from any cause and left bundle branch block (LBBB), use of amiodarone, use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers, year initiated enrollment, and the year ended enrollment (R2 = 0.0). Conclusion: In patients with NIDCM, the addition of ARNi and SGLT2i did not affect the mortality advantages of ICD for primary prevention. PROSPERO registry number: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023403210.

Direct Oral Anticoagulants in Special Patient Populations.

Anticoagulants are a cornerstone of treatment in atrial fibrillation. Nowadays, direct oral anticoagulants (DOACs) are extensively used for this condition in developed countries. However, DOAC treatment may be inappropriate in certain patient populations, such as: patients with chronic kidney disease in whom DOAC concentrations may be dangerously elevated; frail elderly patients with an increased risk of falls; patients with significant drug-drug interactions (DDI) affecting either DOAC concentration or effect; patients at the extremes of body mass in whom an "abnormal" volume of distribution may result in inappropriate drug concentrations; patients with recurrent stroke reflecting an unusually high thromboembolic tendency; and, lastly, patients who experience major hemorrhage on an anticoagulant and in whom continued anticoagulation is deemed necessary. Herein we provide a fictional case-based approach to review the recommendations for the use of DOACs in these special patient populations.

Determinants of Response to Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) is a well-established treatment modality for ambulatory patients with heart failure (HF) who have prolonged QRS, left bundle branch block, reduced left ventricular (LV) ejection fraction, and New York Heart Association class II-IV. CRT has been shown to induce reverse LV remodeling and improve HF symptoms and clinical outcomes. About one-third of CRT recipients are considered non-responders. Patient selection, LV lead location, LV lead selection, multipoint pacing, and optimization of the atrioventricular and ventriculo-ventricular intervals were all shown to be associated with a better CRT response rate. Herein, we review the determinants of CRT response.