Antithrombotic Therapy in Nonvalvular Atrial Fibrillation: Consensus and Challenges.

Atrial fibrillation (AF) is associated with high risk of systemic thromboembolism leading to significant morbidity and mortality. Warfarin, previously the mainstay for stroke prevention in AF, requires close monitoring because of multiple food and drug interactions. In recent years, food and drug administration has approved several direct oral anticoagulants (DOACs) for use in patients with nonvalvular AF. These agents have not been studied in patients with valvular AF who are at an even higher risk of systemic thromboembolism. DOACs do not require frequent blood testing or changes in dosage except when renal function deteriorates, however, the lack of established antidotes for many of these agents remains a challenge. Also, currently there is no head-to-head comparison between these agents to guide clinical choice. This article discusses the advantages and disadvantages of currently approved oral antithrombotics in nonvalvular AF, with a special emphasis on the DOACs and their individual characteristics.

Implantable Defibrillator Therapy in Cardiac Arrest Survivors With a Reversible Cause.

BACKGROUND: Current guidelines recommend implantable cardioverter-defibrillator (ICD) therapy in survivors of sudden cardiac arrest (SCA), except in those with completely reversible causes. We sought to examine the impact of ICD therapy on mortality in survivors of SCA associated with reversible causes. METHODS AND RESULTS: We evaluated the records of 1433 patients managed at our institution between 2000 and 2012 who were discharged alive after SCA. A reversible and correctable cause was identified in 792 (55%) patients. Reversible SCA cause was defined as significant electrolyte or metabolic abnormality, evidence of acute myocardial infarction or ischemia, recent initiation of antiarrhythmic drug or illicit drug use, or other reversible circumstances. Of the 792 SCA survivors because of a reversible and correctable cause (age 61±15 years, 40% women), 207 (26%) patients received an ICD after their index SCA. During a mean follow-up of 3.8±3.1 years, 319 (40%) patients died. ICD implantation was highly associated with lower all-cause mortality (P<0.001) even after correcting for unbalanced baseline characteristics (P<0.001). In subgroup analyses, only patients whose SCA was not associated with myocardial infarction extracted benefit from ICD (P<0.001). CONCLUSIONS: In survivors of SCA because of a reversible and correctable cause, ICD therapy is associated with lower all-cause mortality except if the SCA was because of myocardial infarction. These data deserve further investigation in a prospective multicenter randomized controlled trial, as they may have important and immediate clinical implications.

Cardiac amyloidosis is prevalent in older patients with aortic stenosis and carries worse prognosis.

BACKGROUND: Non-invasive cardiac imaging allows detection of cardiac amyloidosis (CA) in patients with aortic stenosis (AS). Our objective was to estimate the prevalence of clinically suspected CA in patients with moderate and severe AS referred for cardiovascular magnetic resonance (CMR) in age and gender categories, and assess associations between AS-CA and all-cause mortality. METHODS: We retrospectively identified consecutive AS patients defined by echocardiography referred for further CMR assessment of valvular, myocardial, and aortic disease. CMR identified CA based on typical late-gadolinium enhancement (LGE) patterns, and ancillary clinical evaluation identified suspected CA. Survival analysis with the Log rank test and Cox regression compared associations between CA and mortality. RESULTS: There were 113 patients (median age 74 years, Q1-Q3: 62-82 years), 96 (85%) with severe AS. Suspected CA was present in 9 patients (8%) all > 80 years. Among those over the median age of 74 years, the prevalence of CA was 9/57 (16%), and excluding women, the prevalence was 8/25 (32%). Low-flow, low-gradient physiology was very common in CA (7/9 patients or 78%). Over a median follow-up of 18 months, 40 deaths (35%) occurred. Mortality in AS + CA patients was higher than AS alone (56% vs. 20% at 1-year, log rank 15.0, P < 0.0001). Adjusting for aortic valve replacement modeled as a time-dependent covariate, Society of Thoracic Surgery predicted risk of mortality, left ventricular ejection fraction, CA remained associated with all-cause mortality (HR = 2.92, 95% CI = 1.09-7.86, P = 0.03). CONCLUSIONS: Suspected CA appears prevalent among older male patients with AS, especially with low flow, low gradient AS, and associates with all-cause mortality. The importance of screening for CA in older AS patients and optimal treatment strategies in those with CA warrant further investigation, especially in the era of transcatheter aortic valve implantation.

Lead related complications in quadripolar versus bipolar left ventricular leads.

BACKGROUND: Quadripolar left ventricular (LV) leads are capable of pacing from four different electrodes which allows for easier and more stable intra-operative lead positioning with optimal pacing parameters. We therefore investigated the rate of combined intra-operative and post-operative LV lead related events in quadripolar vs. bipolar LV lead cardiac resynchronization therapy (CRT) recipients in the real world setting. METHODS: We retrospectively collected data for N = 1441 patients at our institution implanted with quadripolar (n = 292) or bipolar (n = 1149) LV leads from 2012 to 2014 and followed them to the primary end-point of composite lead outcome defined as intra-operative lead implant failure or post-operative lead dislodgement or deactivations. RESULTS: Patients implanted with a quadripolar lead were younger (70.6 ± 11.4 vs 72.5 ± 11.6, p = 0.014) and had higher incidence of diabetes (41.8% vs 32.8%, p = 0.004) compared to those with bipolar leads. All other baseline characteristics were comparable. Patients implanted with a quadripolar were significantly less likely to reach the primary endpoint in the first 12 months after LV lead implantation (Hazard Ratio 0.22, 95% Confidence Interval 0.08-0.60, p = 0.001). There were no differences between the two groups in rates of hospitalization for any cause or in mortality. CONCLUSION: In this real world study, quadripolar LV leads have significantly lower rates of implantation failure and post-operative lead dislodgement or deactivation. These results have important clinical implications to CRT recipients.

Clinical Characteristics and Outcomes of Older Cardiac Resynchronization Therapy Recipients Using a Pacemaker versus a Defibrillator.

BACKGROUND: Cardiac resynchronization therapy (CRT) is commonly used to manage heart failure, yet published guidelines do not distinguish between recommendations for pacemakers (CRT-P) and defibrillators (CRT-D) despite significant differences in size, longevity, and cost between these devices. The purpose of this study is to compare the clinical characteristics and outcomes between elderly recipients of CRT-P and CRT-D. METHODS AND RESULTS: Data from 512 patients (405 CRT-D, 107 CRT-P) aged ≥75 years with LV ejection fraction ≤35% and QRS duration >120 milliseconds were retrospectively analyzed for baseline characteristics and followed to the primary outcome of all-cause mortality. Cox proportional hazards models were used to adjust for possible confounders. Results were further validated through propensity matching cohorts. Compared to CRT-D recipients, CRT-P patients were older (83 years vs. 81 years, P < 0.001) and had more comorbid conditions (Charlson index = 5 [3-6] vs. 4 [3-5], P = 0.007). During 40.8 months of follow-up, there were 280 deaths. Compared to CRT-D patients, CRT-P recipients had higher unadjusted mortality (HR 1.54, 95% CI 1.15-2.08, P = 0.004). However, this difference lost significance after adjusting for baseline differences between the groups (HR 1.18, 95% CI 0.78-1.77, P = 0.435). CONCLUSION: Higher all-cause mortality in older CRT-P versus CRT-D patients is largely explained by baseline clinical and demographic differences between the two groups, which are likely the drivers of device selection in real-world clinical practice, where the published guidelines remain ambiguous. There is a need for randomized studies to determine optimal CRT device selection.

Right Ventricular Function and Prognosis in Patients with Low-Flow, Low-Gradient Severe Aortic Stenosis.

BACKGROUND: Patients with low left ventricular ejection fractions and low-flow, low-gradient aortic stenosis (AS) represent a challenging cohort with high morbidity and mortality. The prevalence and clinical impact of right ventricular dysfunction (RVD) on risk stratification and prognosis in these patients is unknown. METHODS: A retrospective analysis was performed of 65 patients with low-flow, low-gradient AS who underwent low-dose dobutamine stress echocardiography to determine AS severity and to ascertain flow reserve status (≥20% stroke volume increase). Clinical, demographic, and imaging data were prospectively collected. Per guidelines, RVD was defined as tricuspid annular plane systolic excursion < 16 mm in the apical four-chamber view and measured at baseline. Cox proportional hazards modeling was used to risk-adjust comparisons for the end point of all-cause mortality. RESULTS: The mean age was 74 ± 9 years, the mean left ventricular ejection fraction was 29 ± 10%, the mean indexed aortic valve (AV) area was 0.49 ± 0.1 cm(2)/m(2), and the mean AV gradient 22 ± 7 mm Hg. RVD was present in 37 patients (57% of the study cohort). After a median follow-up period of 13 months (interquartile range, 5-30 months), there were 29 AV replacements and 30 deaths. The presence of RVD (hazard ratio, 2.86; 95% CI, 1.21-6.75; P = .02) was an independent risk factor associated with all-cause mortality despite many adjustments for potential clinical and echocardiographic confounders such as AV replacement, Society of Thoracic Surgeons Predicted Risk of Mortality score, severity of tricuspid regurgitation, and left ventricular global longitudinal strain. CONCLUSIONS: Baseline RVD is prevalent in patients with low-flow, low-gradient AS undergoing dobutamine stress echocardiography. Quantification of right ventricular systolic function in these complex patients provides important prognostic value and risk stratification adjunctive to Society of Thoracic Surgeons Predicted Risk of Mortality score and should be incorporated into the decision-making process.

Extracting versus abandoning sterile pacemaker and defibrillator leads.

Nonfunctional or recalled cardiac implantable electronic device leads can be revised with either lead extraction (LE) or lead capping (LC). Factors that influence this decision and comparative outcomes of these strategies are unclear. We reviewed data from our institution to identify patients who received LE (n = 296) or LC (n = 192) from 2006 to 2012. Patients with infectious indications for lead removal were excluded. We compared unanticipated device-related procedures, defined as cardiac implantable electronic device procedures not for device upgrade or battery depletion, using a proportional hazards model adjusted for differences in baseline characteristics. Secondary outcomes were procedural complications, hospitalizations, and all-cause mortality. Patients who received LE were younger and more likely to have an operator with extraction experience (76% vs 26%, p <0.001). Leads removed by experienced extractors versus nonextractors had longer dwell times (4.2 ± 3.6 vs 0.9 ± 1.1 years, p <0.001). Over a median follow-up of 3.0 (interquartile range = 3.2) years, the adjusted risk of unanticipated device-related procedures was similar for LE versus LC (hazard ratio 1.04, 95% confidence interval 0.62 to 1.75). Complications, hospitalization rates, and mortality rates were also similar between the 2 groups. In conclusion, lead revision strategy is influenced by operator extraction experience and dwell time of leads. In our analysis, we found no difference in outcomes between the 2 strategies.