Updated Recommendations for Athletes with Heart Disease.

Professional society recommendations to decrease sudden cardiac death in athletes, including eligibility requirements with disqualification for athletes with diagnosed disease as well as preparticipation screening and emergency preparedness, were updated in 2015. The update includes new sections on aortic disease, channelopathies, and sickle cell trait, as well as a change in format from the previous binary yes/no format to the more nuanced and contemporary "class and level of evidence" format. Eighty-four of the 246 recommendations now carry Class II designation-"reasonable," or "may be considered." New language in the document emphasizes counseling as part of the decision process. New data on athletes with implantable cardioverter-defibrillators, and on those with long QT syndrome, have led to a change from blanket restriction of competitive sports participation to a Class IIB "may be considered" recommendation.

Association of the US Department of Justice Investigation of Implantable Cardioverter-Defibrillators and Devices Not Meeting the Medicare National Coverage Determination, 2007-2015.

Importance: The US Department of Justice (DOJ) conducted an investigation into implantable cardioverter-defibrillators (ICDs) not meeting the Centers for Medicare & Medicaid Services National Coverage Determination (NCD) criteria. Objective: To examine changes in the proportion of initial primary prevention ICDs that did not meet NCD criteria following the announcement of the DOJ investigation at hospitals that reached settlements (settlement hospitals) and those that did not (nonsettlement hospitals). Design, Setting, and Participants: Multicenter, longitudinal, serial cross-sectional analysis of 300 151 initial primary prevention ICDs among Medicare beneficiaries from January 1, 2007, through December 31, 2015, at 1809 US hospitals in the National Cardiovascular Data Registry (NCDR) ICD Registry, of which 452 hospitals (with 99 591 primary prevention ICDs) reached settlements with the DOJ. Exposures: The DOJ investigation announcement in 2010. Main Outcomes and Measures: Proportion of initial primary prevention ICDs not meeting NCD criteria. Results: In January 2007, the proportion of initial ICDs not meeting NCD criteria was 25.8% (95% CI, 24.7% to 26.8%) at settlement hospitals and 22.8% (95% CI, 22.1% to 23.5%) at nonsettlement hospitals (P < .001). Over the study period, there was a 62.7% (95% CI, 59.2% to 66.1%) relative decrease and 16.1% (95% CI, 14.8% to 17.5%) absolute decrease in the proportion of ICDs not meeting NCD criteria at settlement hospitals compared with a 53.2% (95% CI, 50.4% to 56.0%) relative decrease and 12.1% (95% CI, 11.2% to 13.0%) absolute decrease in proportion at nonsettlement hospitals (P < .001 for both; P for interaction < .001). Trends significantly differed between hospital groups only in the period following the announcement of the DOJ investigation (January 2010-June 2011) [corrected], with larger and more rapid decreases at settlement hospitals (P for interaction = .01). Over the study period, there was a 32.8% (95% CI, 29.9% to 35.7%) relative decrease and a 1703 ICDs (95% CI, 1520 to 1886) absolute decrease in the volume of primary prevention ICDs implanted at settlement hospitals compared with a 17.4% (95% CI, 14.8% to 20.0%) relative decrease and a 1495 ICDs (95% CI, 1249 to 1741) absolute decrease in volume at nonsettlement hospitals (P < .001 for both; P for interaction < .001), with more modest decreases or slight increases in secondary prevention ICD volume. These patterns were similar when examining ICD utilization among non-Medicare beneficiaries. Conclusions and Relevance: From 2007 through 2015, the volume of primary prevention implantable cardioverter-defibrillators and the proportion of devices not meeting the Centers for Medicare & Medicaid Services National Coverage Determination criteria decreased at all hospitals with substantially larger decreases at hospitals that reached settlements in the US Department of Justice investigation. These patterns extended to implantable cardioverter-defibrillators placed in non-Medicare beneficiaries, which were not the focus of the US Department of Justice investigation.

Clinical neurocardiology defining the value of neuroscience-based cardiovascular therapeutics.

The autonomic nervous system regulates all aspects of normal cardiac function, and is recognized to play a critical role in the pathophysiology of many cardiovascular diseases. As such, the value of neuroscience-based cardiovascular therapeutics is increasingly evident. This White Paper reviews the current state of understanding of human cardiac neuroanatomy, neurophysiology, pathophysiology in specific disease conditions, autonomic testing, risk stratification, and neuromodulatory strategies to mitigate the progression of cardiovascular diseases.

Role of the autonomic nervous system in modulating cardiac arrhythmias.

The autonomic nervous system plays an important role in the modulation of cardiac electrophysiology and arrhythmogenesis. Decades of research has contributed to a better understanding of the anatomy and physiology of cardiac autonomic nervous system and provided evidence supporting the relationship of autonomic tone to clinically significant arrhythmias. The mechanisms by which autonomic activation is arrhythmogenic or antiarrhythmic are complex and different for specific arrhythmias. In atrial fibrillation, simultaneous sympathetic and parasympathetic activations are the most common trigger. In contrast, in ventricular fibrillation in the setting of cardiac ischemia, sympathetic activation is proarrhythmic, whereas parasympathetic activation is antiarrhythmic. In inherited arrhythmia syndromes, sympathetic stimulation precipitates ventricular tachyarrhythmias and sudden cardiac death except in Brugada and J-wave syndromes where it can prevent them. The identification of specific autonomic triggers in different arrhythmias has brought the idea of modulating autonomic activities for both preventing and treating these arrhythmias. This has been achieved by either neural ablation or stimulation. Neural modulation as a treatment for arrhythmias has been well established in certain diseases, such as long QT syndrome. However, in most other arrhythmia diseases, it is still an emerging modality and under investigation. Recent preliminary trials have yielded encouraging results. Further larger-scale clinical studies are necessary before widespread application can be recommended.

Interventional and device-based autonomic modulation in heart failure.

"Heart failure is an increasingly prevalent disease with high mortality and public health burden. It is associated with autonomic imbalance characterized by sympathetic hyperactivity and parasympathetic hypoactivity. Evolving novel interventional and device-based therapies have sought to restore autonomic balance by neuromodulation. Results of preclinical animal studies and early clinical trials have demonstrated the safety and efficacy of these therapies in heart failure. This article discusses specific neuromodulatory treatment modalities individually-spinal cord stimulation, vagus nerve stimulation, baroreceptor activation therapy, and renal sympathetic nerve denervation."

Safety of sports for athletes with implantable cardioverter-defibrillators: results of a prospective, multinational registry.

BACKGROUND: The risks of sports participation for implantable cardioverter-defibrillator (ICD) patients are unknown. METHODS AND RESULTS: Athletes with ICDs (age, 10-60 years) participating in organized (n=328) or high-risk (n=44) sports were recruited. Sports-related and clinical data were obtained by phone interview and medical records. Follow-up occurred every 6 months. ICD shock data and clinical outcomes were adjudicated by 2 electrophysiologists. Median age was 33 years (89 subjects <20 years of age); 33% were female. Sixty were competitive athletes (varsity/junior varsity/traveling team). A pre-ICD history of ventricular arrhythmia was present in 42%. Running, basketball, and soccer were the most common sports. Over a median 31-month (interquartile range, 21-46 months) follow-up, there were no occurrences of either primary end point-death or resuscitated arrest or arrhythmia- or shock-related injury-during sports. There were 49 shocks in 37 participants (10% of study population) during competition/practice, 39 shocks in 29 participants (8%) during other physical activity, and 33 shocks in 24 participants (6%) at rest. In 8 ventricular arrhythmia episodes (device defined), multiple shocks were received: 1 at rest, 4 during competition/practice, and 3 during other physical activity. Ultimately, the ICD terminated all episodes. Freedom from lead malfunction was 97% at 5 years (from implantation) and 90% at 10 years. CONCLUSIONS: Many athletes with ICDs can engage in vigorous and competitive sports without physical injury or failure to terminate the arrhythmia despite the occurrence of both inappropriate and appropriate shocks. These data provide a basis for more informed physician and patient decision making in terms of sports participation for athletes with ICDs.

Sudden cardiac arrest and death following application of shocks from a TASER electronic control device.

BACKGROUND: The safety of electronic control devices (ECDs) has been questioned. The goal of this study was to analyze in detail cases of loss of consciousness associated with ECD deployment. METHODS AND RESULTS: Eight cases of TASER X26 ECD-induced loss of consciousness were studied. In each instance, when available, police, medical, and emergency response records, ECD dataport interrogation, automated external defibrillator information, ECG strips, depositions, and autopsy results were analyzed. First recorded rhythms were ventricular tachycardia/fibrillation in 6 cases and asystole (after ≈ 30 minutes of nonresponsiveness) in 1 case. An external defibrillator reported a shockable rhythm in 1 case, but no recording was made. This report offers evidence detailing the mechanism by which an ECD can produce transthoracic stimulation resulting in cardiac electrical capture and ventricular arrhythmias leading to cardiac arrest. CONCLUSIONS: ECD stimulation can cause cardiac electrical capture and provoke cardiac arrest resulting from ventricular tachycardia/ventricular fibrillation. After prolonged ventricular tachycardia/ventricular fibrillation without resuscitation, asystole develops.

Vigorous Exercise in Patients With Hypertrophic Cardiomyopathy.

Importance: Whether vigorous intensity exercise is associated with an increase in risk of ventricular arrhythmias in individuals with hypertrophic cardiomyopathy (HCM) is unknown. Objective: To determine whether engagement in vigorous exercise is associated with increased risk for ventricular arrhythmias and/or mortality in individuals with HCM. The a priori hypothesis was that participants engaging in vigorous activity were not more likely to have an arrhythmic event or die than those who reported nonvigorous activity. Design, Setting, and Participants: This was an investigator-initiated, prospective cohort study. Participants were enrolled from May 18, 2015, to April 25, 2019, with completion in February 28, 2022. Participants were categorized according to self-reported levels of physical activity: sedentary, moderate, or vigorous-intensity exercise. This was a multicenter, observational registry with recruitment at 42 high-volume HCM centers in the US and internationally; patients could also self-enroll through the central site. Individuals aged 8 to 60 years diagnosed with HCM or genotype positive without left ventricular hypertrophy (phenotype negative) without conditions precluding exercise were enrolled. Exposures: Amount and intensity of physical activity. Main Outcomes and Measures: The primary prespecified composite end point included death, resuscitated sudden cardiac arrest, arrhythmic syncope, and appropriate shock from an implantable cardioverter defibrillator. All outcome events were adjudicated by an events committee blinded to the patient's exercise category. Results: Among the 1660 total participants (mean [SD] age, 39 [15] years; 996 male [60%]), 252 (15%) were classified as sedentary, and 709 (43%) participated in moderate exercise. Among the 699 individuals (42%) who participated in vigorous-intensity exercise, 259 (37%) participated competitively. A total of 77 individuals (4.6%) reached the composite end point. These individuals included 44 (4.6%) of those classified as nonvigorous and 33 (4.7%) of those classified as vigorous, with corresponding rates of 15.3 and 15.9 per 1000 person-years, respectively. In multivariate Cox regression analysis of the primary composite end point, individuals engaging in vigorous exercise did not experience a higher rate of events compared with the nonvigorous group with an adjusted hazard ratio of 1.01. The upper 95% 1-sided confidence level was 1.48, which was below the prespecified boundary of 1.5 for noninferiority. Conclusions and Relevance: Results of this cohort study suggest that among individuals with HCM or those who are genotype positive/phenotype negative and are treated in experienced centers, those exercising vigorously did not experience a higher rate of death or life-threatening arrhythmias than those exercising moderately or those who were sedentary. These data may inform discussion between the patient and their expert clinician around exercise participation.

Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines.

BACKGROUND: We hypothesize that left-sided low-level vagus nerve stimulation (LL-VNS) can suppress sympathetic outflow and reduce atrial tachyarrhythmias in ambulatory dogs. METHODS AND RESULTS: We implanted a neurostimulator in 12 dogs to stimulate the left cervical vagus nerve and a radiotransmitter for continuous recording of left stellate ganglion nerve activity, vagal nerve activities, and ECGs. Group 1 dogs (N=6) underwent 1 week of continuous LL-VNS. Group 2 dogs (N=6) underwent intermittent rapid atrial pacing followed by active or sham LL-VNS on alternate weeks. Integrated stellate ganglion nerve activity was significantly reduced during LL-VNS (7.8 mV/s; 95% confidence interval [CI] 6.94 to 8.66 versus 9.4 mV/s [95% CI, 8.5 to 10.3] at baseline; P=0.033) in group 1. The reduction was most apparent at 8 am, along with a significantly reduced heart rate (P=0.008). Left-sided low-level vagus nerve stimulation did not change vagal nerve activity. The density of tyrosine hydroxylase-positive nerves in the left stellate ganglion 1 week after cessation of LL-VNS were 99 684 µm(2)/mm(2) (95% CI, 28 850 to 170 517) in LL-VNS dogs and 186 561 µm(2)/mm(2) (95% CI, 154 956 to 218 166; P=0.008) in normal dogs. In group 2, the frequencies of paroxysmal atrial fibrillation and tachycardia during active LL-VNS were 1.4/d (95% CI, 0.5 to 5.1) and 8.0/d (95% CI, 5.3 to 12.0), respectively, significantly lower than during sham stimulation (9.2/d [95% CI, 5.3 to 13.1]; P=0.001 and 22.0/d [95% CI, 19.1 to 25.5], P<0.001, respectively). CONCLUSIONS: Left-sided low-level vagus nerve stimulation suppresses stellate ganglion nerve activities and reduces the incidences of paroxysmal atrial tachyarrhythmias in ambulatory dogs. Significant neural remodeling of the left stellate ganglion is evident 1 week after cessation of continuous LL-VNS.

Device therapy to modulate the autonomic nervous system to treat heart failure.

Heart failure is the final common pathway in many forms of heart disease, and is associated with excessive morbidity and mortality. Pathophysiologic alterations in the interaction between the heart and the autonomic nervous system in advanced heart failure have been noted for decades. Over the last decade, great advances have been made in the medical and surgical treatment of heart failure - and some of these modalities target the neuro-cardiac axis. Despite these advances, many patients progress to end-stage heart failure and death. Recently, device-based therapy targeting the neuro-cardiac axis with various forms of neuromodulatory stimuli has been shown to improve heart function in experimental heart failure models. These include spinal cord stimulation, vagal nerve stimulation, and baroreflex modulation. Human trials are now underway to evaluate the safety and efficacy of these device-based neuromodulatory modalities in the heart failure population.

Spinal cord stimulation therapy for patients with refractory angina who are not candidates for revascularization.

OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of spinal cord stimulation (SCS) for refractory angina. MATERIALS AND METHODS: This multicenter, randomized, single-blind, controlled trial evaluated SCS in two patient groups: high stimulation (HS) (treatment) and low stimulation (LS) (control). The HS group controlled SCS with a programmer for a minimum of two hours four times daily. The LS group received SCS therapy above the paresthesia threshold for one min once daily. The primary efficacy endpoint was number of angina attacks recorded by patients at six months. The primary safety endpoint was the major adverse cardiac event (MACE) rate at six months. RESULTS: Due to slow enrollment, a futility analysis was performed, resulting in early termination of the study. Sixty-eight patients were randomized after implantation. Mean change in angina attacks per day from baseline to six months was -1.19 ± 2.13 (HS) and -1.29 ± 1.66 (LS). The difference from baseline was significant within each group (both p < 0.001) but not between groups (p = 0.45). Total exercise time and time to angina onset increased significantly from baseline to six months within each group (both p = 0.02 and 0.002) but not between groups (p = 0.52 and 0.51). MACE was similar between groups. CONCLUSION: Although this study was terminated early, the results obtained at six months suggest that SCS (HS) is not more effective than the control (LS) in patients with refractory angina.

Electrocardiographic abnormalities and sudden death in myotonic dystrophy type 1.

BACKGROUND: Sudden death can occur as a consequence of cardiac-conduction abnormalities in the neuromuscular disease myotonic dystrophy type 1. The determinants of the risk of sudden death remain imprecise. METHODS: We assessed whether the electrocardiogram (ECG) was useful in predicting sudden death in 406 adult patients with genetically confirmed myotonic dystrophy type 1. A patient was characterized as having a severe abnormality if the ECG had at least one of the following features: rhythm other than sinus, PR interval of 240 msec or more, QRS duration of 120 msec or more, or second-degree or third-degree atrioventricular block. RESULTS: Patients with severe abnormalities according to the entry ECG were older than patients without severe abnormalities, had more severe skeletal-muscle impairment, and were more likely to have heart failure, left ventricular systolic dysfunction, or atrial tachyarrhythmia. Such patients were more likely to receive a pacemaker or an implantable cardioverter-defibrillator during the follow-up period. During a mean follow-up period of 5.7 years, 81 patients died; there were 27 sudden deaths, 32 deaths from progressive neuromuscular respiratory failure, 5 nonsudden deaths from cardiac causes, and 17 deaths from other causes. Among the 17 patients who died suddenly in whom postcollapse rhythm was evaluated, a ventricular tachyarrhythmia was observed in 9. A severe ECG abnormality (relative risk, 3.30; 95% confidence interval [CI], 1.24 to 8.78) and a clinical diagnosis of atrial tachyarrhythmia (relative risk, 5.18; 95% CI, 2.28 to 11.77) were independent risk factors for sudden death. CONCLUSIONS: Patients with adult myotonic dystrophy type 1 are at high risk for arrhythmias and sudden death. A severe abnormality on the ECG and a diagnosis of an atrial tachyarrhythmia predict sudden death. (ClinicalTrials.gov number, NCT00622453.)

Atrial fibrillation ablation strategies and technologies: past, present, and future.

Catheter ablation is an established treatment option for atrial fibrillation (AF), and pulmonary vein isolation (PVI) has become the gold standard in AF ablation. AF recurrence after PVI remains an important clinical problem. Recovery of conduction from the pulmonary veins (PVs) is considered the dominant mechanism for AF recurrence in paroxysmal AF. However, the underlying mechanism of AF recurrence after PVI is more complex in patients with persistent and longstanding persistent AF. Different ablation technologies and energy sources have been developed aimed at improving lesion quality and durability with an acceptable safety profile. Novel technologies are under evaluation which have a great potential to produce permanent PVI after a single ablation procedure. However, clinical value of these novel devices needs to be tested in adequately powered randomized controlled trials. In this article, we review the history of catheter ablation for AF and discuss the present and future ablation technologies.