Rationale and design of the NODE-303 study: evaluating the safety of symptom-prompted, self-administered etripamil for paroxysmal supraventricular tachycardia episodes in real-world settings.

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) is a common episodic arrhythmia characterized by unpredictable onset and burdensome symptoms including palpitations, dizziness, chest pain, distress, and shortness of breath. Treatment of acute episodes of PSVT in the clinical setting consists of intravenous adenosine, beta-blockers, and calcium channel blockers (CCBs). Etripamil is an intranasally self-administered L-type CCB in development for acute treatment of AV-nodal dependent PSVT in a nonmedical supervised setting. METHODS: This paper summarizes the rationale and study design of NODE-303 that will assess the efficacy and safety of etripamil. In the randomized, double-blinded, placebo-controlled, Phase 3 RAPID trial, etripamil was superior to placebo in the conversion of single PSVT episodes by 30 minutes post initial dose when administered in the nonhealthcare setting; this study required a mandatory and observed test dosing prior to randomization. The primary objective of NODE-303 is to evaluate the safety of symptom-prompted, self-administered etripamil for multiple PSVT episodes in real-world settings, without the need for test dosing prior to first use during PSVT. Secondary endpoints include efficacy and disease burden. Upon perceiving a PSVT episode, the patient applies an electrocardiographic monitor, performs a vagal maneuver, and, if the vagal maneuver is unsuccessful, self-administers etripamil 70 mg, with an optional repeat dose if symptoms do not resolve within 10 minutes after the first dose. A patient may treat up to four PSVT episodes during the study. Adverse events are recorded as treatment-emergent if they occur within 24 hours after the administration of etripamil. RESULTS: Efficacy endpoints include time to conversion to sinus rhythm within 30 and 60 minutes after etripamil administration, and the proportion of patients who convert at 3, 5, 10, 20, 30, and 60 minutes. Patient-reported outcomes are captured by the Brief Illness Perception Questionnaire, the Cardiac Anxiety Questionnaire, the Short Form Health Survey 36, the Treatment Satisfaction Questionnaire for Medication and a PSVT survey. CONCLUSIONS: Overall, these data will support the development of a potentially paradigm-changing long-term management strategy for recurrent PSVT.

The Experiences of Endurance Athletes With Atrial Fibrillation: Tensions and Takeaways.

BACKGROUND: Growing evidence indicates that chronic high-intensity endurance exercise predisposes male, middle-aged athletes to increased risk of atrial fibrillation (AF). The aetiology of AF in endurance athletes is multifactorial and remains incompletely understood. Despite their unique training demands, AF care in athletes remains largely based on evidence derived from the general population. Understanding the experiences of athletes with AF provides a necessary foundation for addressing challenges in managing their condition and identifying gaps in care. AIM: The purpose of this interpretive descriptive qualitative study was to describe the experiences and perspectives of endurance athletes living with AF. METHOD: Masters athletes diagnosed with AF and aged between 35 and 60 years were recruited internationally through cardiology practices and social media. Ten middle-aged, male endurance athletes with AF and >1,500 lifetime training hours participated in individual, semi-structured interviews. Data were analysed using inductive thematic analysis. RESULTS: Three key themes were constructed: (1) tensions with training, (2) tensions with treatment plans, and (3) tensions with clinicians. Participants experienced a wide range of symptoms from AF that significantly affected their ability to train, and reacted negatively to medical treatment strategies that affected their exercise capacity and training performance. Athletes experienced tensions with providers who failed to acknowledge their athletic needs. CONCLUSIONS: Our results highlight the unique difficulties that male athletes with AF face in navigating between training and their disease, treatment, and clinicians. Shared decision-making between the athlete and provider is likely necessary for effective management of athletic AF.

Electrocardiographic Findings in Professional Male Athletes.

OBJECTIVE: To generate granular normative electrocardiogram (ECG) data and characterize the variation by ethnicity and sport played. DESIGN: Cross-sectional study; ECGs were collected from preseason screening programs from 2012 to 2019 and interpreted in accordance with athlete-specific guidelines. SETTING: Of the professional athletes based in Vancouver, the North Shore Heart Centre performs the annual preparticipation ECG screening. PARTICIPANTS: Seven hundred fifty-three professional male athletes competing in hockey, football, lacrosse, skiing, and snowboarding. INTERVENTIONS: Independent variables include commonly transcribed electrocardiographic findings, for example, those indicating benign and pathologic findings. MAIN OUTCOME MEASURES: Prevalence of and variance in electrocardiographic findings by sport played and ethnicity. RESULTS: Of the 753 athletes, 171 (22.3%) were National Hockey League, 358 (47.5%) were Canadian Football League, 163 (21.6%) were Major League Soccer and/or the Canadian National Soccer team, and 61 (8%) others. The most common finding, sinus bradycardia, was more likely in both soccer (P < 0.001) and hockey (P < 0.001) versus football players. Early repolarization (ER) was more likely in soccer players versus both hockey (P < 0.001) and football players (P = 0.001). Within football, Black athletes (BA) were more likely than White athletes to display ER (P = 0.009), left ventricular hypertrophy (P = 0.004), and nonspecific ST changes (P = 0.027). CONCLUSION: Our study contributes to the generation of normative data for ECG findings while accounting for ethnic and sport-specific variation. The expected clinical presentation of endurance athletes, including soccer players, and the possible predisposition of BA to develop distinct adaptations can augment clinical care by delineating physiology from pathologic changes.

Patient-Reported Experiences in Outpatient Telehealth Heart Failure Management.

BACKGROUND: With the onset of coronavirus disease 2019 (COVID-19), the delivery of routine outpatient heart failure (HF) care abruptly shifted to telehealth. Appropriate HF management extensively relies upon patient-reported symptoms. With the growing attention towards patient-centered care, our team recognized an invaluable opportunity to solicit patient-reported subjective experiences regarding telehealth. METHODS: In total, 127 patients with a known diagnosis of HF were contacted by phone for participation in an online questionnaire. The tool consisted of questions generated by the investigators and from prior validated patient-reported experience measures. The intention was to assess the quality of care in our HF clinic and to solicit feedback regarding telehealth. RESULTS: Thirty-five patients provided a response. Questions with the most favorable outcomes were in line with our predetermined themes of interpersonal matter, communication, and perceived quality of care. The worst performing questions exhibited a lack of satisfaction with and perceived quality of telehealth. Only 9% (n = 3) preferred follow-up via telehealth, 69% (n = 22) preferred in-person, and 22% (n = 7) were indifferent. CONCLUSIONS: Given the multitude of benefits of telehealth, especially appropriate social distancing, telehealth is quite likely here to stay. In sum, with the rapid change in care delivery, patients currently perceive the care delivered via telehealth to be of inferior quality. This lack of quality can be largely attributed to the lack of physical examination, depersonalization of healthcare, and likely, a lack of familiarity with the platform. We urge our colleagues to solicit similar feedback from their patients to improve their own telehealth efforts.

Comparison between a low glycemic load diet and a Canada Food Guide diet in cardiac rehabilitation patients in Ontario.

BACKGROUND: A high dietary glycemic load is associated with an increased risk of noninsulin-dependent diabetes mellitus and coronary artery disease. OBJECTIVE: To evaluate the effect of a low glycemic load diet on cardiac rehabilitation patients. METHODS: One hundred twenty patients who were advised to follow a low glycemic load diet were evaluated and compared with 1434 patients who were advised to follow the principles of Canada's Food Guide to Healthy Eating for People Four Years and Over as part of the Ontario Cardiac Rehabilitation Pilot Project. RESULTS: Patients on the low glycemic load diet lost more weight at six months (2.8 kg loss versus 0.2 kg gain, P < 0.0001), had a greater reduction in abdominal obesity (2.9 cm versus 0.4 cm, P < 0.0001), and had a greater improvement in high density lipoprotein cholesterol (0.14 mmol/L versus 0.02 mmol/L, P < 0.0001), triglycerides (-0.44 mmol/L versus -0.08 mmol/L, P < 0.0001) and glycemic control (fasting glucose -0.94 mmol/L versus 0.91 mmol/L, P = 0.0019). After one year of follow-up, the low glycemic load patients had maintained (weight gain 0.7 kg, triglycerides -0.07 mmol/L, fasting glucose -0.10 mmol/L and glycosylated hemoglobin A1c -0.18%; all not significant) or augmented (waist circumference -1.3 cm, P = 0.038; high density lipoprotein cholesterol 0.08 mmol/L, P < 0.0001) the initial results. CONCLUSIONS: Implementation of a low glycemic load diet was associated with substantial and sustained improvements in abdominal obesity, cholesterol and glycemic control.

Polymorphisms of microsomal triglyceride transfer protein gene and manganese superoxide dismutase gene in non-alcoholic steatohepatitis.

BACKGROUND/AIMS: The pathogenesis of non-alcoholic steatohepatitis (NASH) is poorly understood. The aim of this study was to examine genetic influences on NASH pathogenesis. METHODS: Blood samples from 63 patients with biopsy-proven NASH and 150 healthy controls were analyzed by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Two functional polymorphisms were studied: the -493 G/T polymorphism in the promoter of microsomal triglyceride transfer protein (MTP) and the 1183 T/C polymorphism in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD). RESULTS: NASH patients had a much higher incidence of the MTP gene G allele (P=0.001) and of the G/G genotype (P=0.002) compared to the controls. Fat occupied more area in liver lobules and the stage of NASH was advanced in patients with the G/G-genotype than in patients with G/T-genotype (P=0.04). NASH patients also had a higher incidence of the MnSOD T/T genotype (P=0.016). CONCLUSIONS: The G allele in the MTP promoter leads to decreased MTP transcription, less export of triglyceride from hepatocytes, and greater intracellular triglyceride accumulation. The T allele in MnSOD mitochondrial targeting sequence leads to less transport of MnSOD to the mitochondria. Therefore, functional polymorphisms in MTP and MnSOD may be involved in determining susceptibility of NASH.