Low-Level Tragus Stimulation Modulates Atrial Alternans and Fibrillation Burden in Patients With Paroxysmal Atrial Fibrillation.

Background Low-level tragus stimulation (LLTS) has been shown to significantly reduce atrial fibrillation (AF) burden in patients with paroxysmal AF. P-wave alternans (PWA) is believed to be generated by the same substrate responsible for AF. Hence, PWA may serve as a marker in guiding LLTS therapy. We investigated the utility of PWA in guiding LLTS therapy in patients with AF. Methods and Results Twenty-eight patients with AF were randomized to either active LLTS or sham (earlobe stimulation). LLTS was delivered through a transcutaneous electrical nerve stimulation device (pulse width 200 µs, frequency 20 Hz, amplitude 10-50 mA), for 1 hour daily over a 6-month period. AF burden over 2-week periods was assessed by noninvasive continuous ECG monitoring at baseline, 3 months, and 6 months. A 5-minute control ECG for PWA analysis was recorded during all 3 follow-up visits. Following the control ECG, an additional 5-minute ECG was recorded during active LLTS in all patients. At baseline, acute LLTS led to a significant rise in PWA burden. However, active patients receiving chronic LLTS demonstrated a significant reduction in both PWA and AF burden after 6 months (P<0.05). Active patients who demonstrated an increase in PWA burden with acute LLTS showed a significant drop in AF burden after 6 months of chronic LLTS. Conclusions Chronic, intermittent LLTS resulted in lower PWA and AF burden than did sham control stimulation. Our results support the use of PWA as a potential marker for guiding LLTS treatment of paroxysmal AF.

Evolving Cardiac Electrical Therapies for Advanced Heart Failure Patients.

Symptomatic heart failure (HF) patients despite optimal medical therapy and advances such as invasive hemodynamic monitoring remain challenging to manage. While cardiac resynchronization therapy remains a highly effective therapy for a subset of HF patients with wide QRS, a majority of symptomatic HF patients are poor candidates for such. Recently, cardiac contractility modulation, neuromodulation based on carotid baroreceptor stimulation, and phrenic nerve stimulation have been approved by the US Food and Drug Administration and are emerging as therapeutic options for symptomatic HF patients. This state-of-the-art review examines the role of these evolving electrical therapies in advanced HF.

Marijuana: A systems-based primer of adverse effects associated with use and an overview of its therapeutic utility.

Marijuana use is on the rise in the United States. By the end of 2019, 33 states have legalized marijuana use and marijuana byproduct use for medical purposes. However, marijuana use does not come without side effects. This manuscript reviews the increasing usage of marijuana and the different forms (natural and synthetic) that patients may use when presenting to clinicians. It also addresses the biochemical and behavioral changes observed with marijuana use, including the location and changes associated with cannabinoid receptors (abbreviated CB1 and CB2). These two topics lead into an extensive review of the side effects of marijuana use. This manuscript discusses gastrointestinal side-effects, such as Cannabinoid Hyperemesis Syndrome, pancreatitis, and hepatotoxicity. It also briefly reviews cardiovascular, neurologic, and pulmonary side effects. This article provides an overview of therapeutic effects of marijuana including the antiemetic effect, its medical utility as an appetite stimulant, and usefulness in cancer patients post-chemotherapy. A thorough social history pertaining to marijuana use is an important consideration for clinicians in patients presenting with a variety of symptoms, including those effecting the gastrointestinal, cardiovascular, pulmonary, or neurologic systems.

Association of an Acute Myocardial Infarction Readmission-Reduction Program With Mortality and Readmission.

BACKGROUND: Reducing hospital readmission after acute myocardial infarction (AMI) has the potential to both improve quality and reduce costs. As such, readmission after AMI has been a target of financial penalties through Medicare. However, substantial concern exists about potential adverse effects and efficacious readmission-reduction strategies are not well validated. METHODS AND RESULTS: We started an AMI readmissions reduction program in November 2017. Between July 2016 and February 2019, hospital billing data were queried to detect all inpatient hospitalizations at the Massachusetts General Hospital for AMI. Thirty-day readmission was identified through hospital billing data, and mortality was extracted from our electronic health record. The data set was merged with claims data for patients in accountable care organizations to detect readmission at other hospitals. We performed segmented linear regression, adjusting for secular trend and case mix, to assess the independent association of our program on both outcome variables. After inclusion and exclusion criteria were applied, the study population included 2020 patients. The overall 30-day readmission rate was higher before the intervention than after the intervention (15.5% versus 10.7%, P=0.002). The overall 30-day mortality rate was similar in both time periods (1.8% versus 1.4%, P=0.457). The program was associated with initial reduction in 30-day readmission (-9.8%, P=0.0002) and 30-day mortality (-2.6%, P=0.041). The program did not change trend in 30-day readmission (+0.19% readmissions/mo, P=0.554) and trend in 30-day mortality (-0.21% deaths/mo, P=0.119). CONCLUSIONS: An AMI readmissions reduction program that increases outpatient and emergency department (ED) access to cardiology care is associated with reduced 30-day readmission and 30-day mortality. Similar statistical techniques can be used to conduct a rigorous, mechanistic program evaluation of other quality improvement initiatives.

Electrocardiographic optimization techniques in resynchronization therapy.

Cardiac resynchronization therapy (CRT) is a cornerstone of therapy for patients with heart failure, reduced left ventricular (LV) ejection fraction, and a wide QRS complex. However, not all patients respond to CRT: 30% of CRT implanted patients are currently considered clinical non-responders and up to 40% do not achieve LV reverse remodelling. In order to achieve the best CRT response, appropriate patient selection, device implantation, and programming are important factors. Optimization of CRT pacing intervals may improve results, increasing the number of responders, and the magnitude of the response. Echocardiography is considered the reference method for atrioventricular and interventricular (VV) intervals optimization but it is time-consuming, complex and it has a large interobserver and intraobserver variability. Previous studies have linked QRS shortening to clinical response, echocardiographic improvement and favourable prognosis. In this review, we describe the electrocardiographic optimization methods available: 12-lead electrocardiogram; fusion-optimized intervals (FOI); intracardiac electrogram-based algorithms; and electrocardiographic imaging. Fusion-optimized intervals is an electrocardiographic method of optimizing CRT based on QRS duration that combines fusion with intrinsic conduction. The FOI method is feasible and fast, further reduces QRS duration, can be performed during implant, improves acute haemodynamic response, and achieves greater LV remodelling compared with nominal programming of CRT.

Effect of Interventricular Electrical Delay on Atrioventricular Optimization for Cardiac Resynchronization Therapy.

BACKGROUND: Routine atrioventricular optimization (AVO) has not been shown to improve outcomes with cardiac resynchronization therapy (CRT). However, more recently subgroup analyses of multicenter CRT trials have identified electrocardiographic or lead positions associated with benefit from AVO. Therefore, the purpose of this analysis was to evaluate whether interventricular electrical delay modifies the impact of AVO on reverse remodeling with CRT. METHODS: This substudy of the SMART-AV trial (SMARTDELAY Determined AV Optimization) included 275 subjects who were randomized to either an electrogram-based AVO (SmartDelay) or nominal atrioventricular delay (120 ms). Interventricular delay was defined as the time between the peaks of the right ventricular (RV) and left ventricular (LV) electrograms (RV-LV duration). CRT response was defined prospectively as a >15% reduction in LV end-systolic volume from implant to 6 months. RESULTS: The cohort was 68% men, with a mean age of 65±11 years and LV ejection fraction of 28±8%. Longer RV-LV durations were significantly associated with CRT response ( P<0.01) for the entire cohort. Moreover, the benefit of AVO increased as RV-LV duration prolonged. At the longest quartile, there was a 4.26× greater odds of a remodeling response compared with nominal atrioventricular delays ( P=0.010). CONCLUSIONS: Baseline interventricular delay predicted CRT response. At long RV-LV durations, AVO can increase the likelihood of reverse remodeling with CRT. AVO and LV lead location optimized to maximize interventricular delay may work synergistically to increase CRT response. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00874445.

Incidence and Clinical Significance of New-Onset Device-Detected Atrial Tachyarrhythmia: A Meta-Analysis.

BACKGROUND: Despite the clear association between atrial fibrillation and risk for thromboembolic events (TEs), the clinical significance of new-onset device-detected atrial tachyarrhythmia (DDAT) and TE remains disputed. We aimed to determine the risk of TE in patients with new-onset DDAT. METHODS AND RESULTS: The OVID Medline, Cochrane, and Scopus databases (inception to November 2016) were searched. Randomized controlled trials, prospective, or retrospective studies of pacemaker or defibrillator patients reporting incidence of DDAT were selected. Summary statistics were used for analysis. Of 4893 reports identified, 28 studies following 24 984 patients were included: average age 69.9 years, 34.7% women, mean study duration 21.8±18.6 months. New-onset DDAT was observed in 23% of patients. Among 9 studies (n=8181) reporting TE, the absolute incidence was 2.1%. TE risk was significantly greater among patients with new-onset DDAT (relative risk [RR], 2.88; 95% CI, 1.79-4.64; P<0.001). TE risk was correlated with DDAT duration, with an increased risk associated with DDAT ≥5 minutes (RR, 3.86; 95% CI, 2.04-7.30; P<0.001) compared with <1 minute (RR, 1.77; 95% CI, 1.15-2.74; P=0.01). Notably, the risk of TE was also increased in patients with adjudicated atrial electrograms (RR, 3.60; 95% CI, 2.06-6.30; P<0.001) compared with nonadjudicated electrograms (RR, 2.05; 95% CI, 1.06-3.97; P=0.03), even when lower mean thresholds for detection were used. CONCLUSIONS: New-onset DDAT is common, affecting close to one quarter of all patients with implanted pacemakers or defibrillators. Adjudication of atrial electrograms further identifies at-risk patients, even when relatively short detection thresholds are used.

Advances in Heart Failure Management: Improving Outcomes With Innovation.

Heart failure (HF) is a chronic and complex disease entity with an enormous morbidity and mortality. Many of the therapies used in the management of HF were developed decades ago, but recently more novel monitoring and therapeutic strategies have emerged. The employment of these strategies may reduce morbidity and mortality in patients with HF. This article reviews the epidemiology of HF and some of the novel strategies developed to assess risk and monitor these challenging patients. It also discusses the evidence behind some of the newer treatments available that are recently included in the HF management guidelines. Various devices used in the treatment of HF, some of which remain investigational, are also discussed. Novel strategies for remote monitoring and new pharmacologic therapies may be useful in improving morbidity and mortality in patients with HF.

Novel Interventional Therapies to Modulate the Autonomic Tone in Heart Failure.

Heart failure (HF) represents a significant and expanding public health burden associated with increasing prevalence and exponential growth in related health care costs. Contemporary advances in both pharmacological and nonpharmacological therapies have often been restricted in application and benefit. Given the critical role of the autonomic nervous system (ANS) in maintaining cardiovascular homeostasis in the failing heart, there has been increasing interest in the role of ANS modulation as a therapeutic modality in HF. In this review, we highlight the anatomy of the ANS and its role in the pathophysiology of HF, as well as metrics of its assessment. Given the limitations associated with pharmacological ANS modulation, including lack of specificity and medication intolerance, we focus in this review on contemporary nonpharmacological ANS modulation therapies. For each therapy-vagal nerve stimulation, carotid baroreceptor stimulation, spinal cord stimulation, and renal denervation-we review the rationale for modulation, pre-clinical and clinical assessments, as well as procedural considerations and limitations. We conclude by commenting on novel technologies and strategies for ANS modulation on the horizon.

Non-pharmacological modulation of the autonomic tone to treat heart failure.

The autonomic nervous system has a significant role in the pathophysiology and progression of heart failure. The absence of any recent breakthrough advances in the medical therapy of heart failure has led to the evolution of innovative non-pharmacological interventions that can favourably modulate the cardiac autonomic tone. Several new therapeutic modalities that may act at different levels of the autonomic nervous system are being investigated for their role in the treatment of heart failure. The current review examines the role of renal denervation, vagal nerve stimulators, carotid baroreceptors, and spinal cord stimulators in the treatment of heart failure.

A novel method for determining the phase of T-wave alternans: diagnostic and therapeutic implications.

BACKGROUND: T-wave alternans (TWA) has been implicated in the pathogenesis of ventricular arrhythmias and sudden cardiac death. However, to estimate and suppress TWA effectively, the phase of TWA must be accurately determined. METHODS AND RESULTS: We developed a method that computes the beat-by-beat integral of the T-wave morphology, over time points within the T-wave with positive alternans. Then, we estimated the signed derivative of the T-wave integral sequence, which allows the classification of each beat to a binary phase index. In animal studies, we found that this method was able to accurately identify the T-wave phase in artificially induced alternans (P<0.0001). The coherence of the phase increased consistently after acute ischemia induction in all body-surface and intracardiac leads (P<0.0001). Also, we developed a phase-resetting detection algorithm that enhances the diagnostic utility of TWA. We further established an algorithm that uses the phase of TWA to deliver appropriate polarity-pacing pulses (all interventions compared with baseline, P<0.0001 for alternans voltage; P<0.0001 for K(score)), to suppress TWA. Finally, we demonstrated that using the phase of TWA we can suppress spontaneous TWA during acute ischemia; 77.6% for alternans voltage (P<0.0001) and 92.5% for K(score) (P<0.0001). CONCLUSIONS: We developed a method to quantify the temporal variability of the TWA phase. This method is expected to enhance the utility of TWA in predicting ventricular arrhythmias and sudden cardiac death and raises the possibility of using upstream therapies to abort a ventricular tachyarrhythmia before its onset.

Catheter ablation targeting complex fractionated atrial electrograms for the control of atrial fibrillation.

PURPOSE OF REVIEW: Catheter ablation of persistent atrial fibrillation has a lower success rate than for paroxysmal atrial fibrillation, due to structural, electrical and anatomical remodeling of the left atrium. Ablation strategies targeting complex fractionated atrial electrograms (CFAEs) are commonly employed to identify and eliminate the substrate responsible for atrial fibrillation maintenance in persistent cases. This review discusses the pathophysiology as well as the role of targeting CFAEs in catheter ablation of atrial fibrillation. RECENT FINDINGS: As our understanding regarding the origin and role of CFAEs in atrial fibrillation continues to evolve, there have been multiple recent studies looking at pathophysiology, distribution and significance of CFAEs in atrial fibrillation. In addition, different ablation strategies targeting CFAEs have been compared with the standard pulmonary vein isolation in persistent as well as paroxysmal atrial fibrillation. Recent meta-analysis studies have striven to identify atrial fibrillation patients who would benefit from CFAE ablation. SUMMARY: Whereas CFAE ablation in addition to standard pulmonary vein isolation improves outcomes in patients with persistent atrial fibrillation, there is no benefit of CFAE ablation in paroxysmal atrial fibrillation. Further studies are required to define and identify CFAEs more accurately, in a standardized manner, to enhance the success of catheter ablation and freedom from atrial fibrillation.

AV nodal ablation-induced Gerbode defect (LV-RA Shunt).

A Gerbode defect that comprises a left ventricular to right atrial shunt is usually a congenital cardiac condition. Rarely, acquired Gerbode defects secondary to aortic or tricuspid valve endocarditis have been reported. We present a case of a Gerbode defect caused by catheter ablation of the AV node in a patient with a severely dilated cardiomyopathy and refractory atrial fibrillation.

Pulmonary vein isolation with complex fractionated atrial electrogram ablation for paroxysmal and nonparoxysmal atrial fibrillation: A meta-analysis.

BACKGROUND: Pulmonary vein isolation (PVI) is recognized as a potentially curative treatment for atrial fibrillation (AF). Ablation of complex fractionated atrial electrograms (CFAEs) in addition to PVI has been advocated as a means to improve procedural outcomes, but the benefit remains unclear. OBJECTIVE: This study sought t synthesize the available data testing the incremental benefit of adding CFAE ablation to PVI. METHODS: We performed a meta-analysis of controlled studies comparing the effect of PVI with CFAE ablation vs. PVI alone in patients with paroxysmal and nonparoxysmal AF. RESULTS: Of the 481 reports identified, 8 studies met our inclusion criteria. There was a statistically significant increase in freedom from atrial tachyarrhythmia (AT) with the addition of CFAE ablation (relative risk [RR] 1.15, P = .03). In the 5 reports of nonparoxysmal AF (3 randomized controlled trials, 1 controlled clinical trial, and 1 trial using matched historical controls), addition of CFAE ablation resulted in a statistically significant increase in freedom from AT (n = 112 of 181 [62%] for PVI+CFAE vs. n = 84 of 179 [47%] for PVI alone; RR 1.32, P = .02). In trials of paroxysmal AF (3 randomized controlled trials and 1 trial using matched historical controls), addition of CFAE ablation did not result in a statistically significant increase in freedom from AT (n = 131 of 166 [79%] for PVI+CFAE vs. n = 122 of 164 [74%] for PVI alone; RR 1.04, P = .52). CONCLUSION: In these studies of patients with nonparoxysmal AF, addition of CFAE ablation to PVI results in greater improvement in freedom from AF. No additional benefit of this combined approach was observed in patients with paroxysmal AF.