Age is the main determinant of COVID-19 related in-hospital mortality with minimal impact of pre-existing comorbidities, a retrospective cohort study.

BACKGROUND: Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown. METHODS: In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58-77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis. RESULTS: In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02-5.45], OR0.68[0.59-0.79], respectively;both p<  0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55-0.75], DM OR1.47[1.26-1.72], CKD OR1.61[1.32-1.97], COPD OR1.30[1.07-1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome. CONCLUSIONS: Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities. TRIAL REGISTRATION: CAPACITY-COVID ( NCT04325412 ).

Clinical determinants of early spontaneous conversion to sinus rhythm in patients with atrial fibrillation.

BACKGROUND: The current standard of care for acute atrial fibrillation (AF) focuses primarily on immediate restoration of sinus rhythm by cardioversion, although AF often terminates spontaneously. OBJECTIVE: To identify determinants of early spontaneous conversion (SCV) in patients presenting at the emergency department (ED) because of AF. METHODS: An observational study was performed of patients who visited the ED with documented AF between July 2014 and December 2016. The clinical characteristics and demographics of patients with and without SCV were compared. RESULTS: We enrolled 943 patients (age 69 ± 12 years, 47% female). SCV occurred within 3 h of presentation in 158 patients (16.8%). Logistic regression analysis showed that duration of AF <24 h [odds ratio (OR) 7.7, 95% confidence interval (CI) 3.5-17.2, p < 0.001], left atrial volume index <42 ml/m2 (OR 1.8, 95% CI 1.2-2.8, p = 0.010), symptoms of near-collapse at presentation (OR 2.4, 95% CI 1.2-5.1, p = 0.018), a lower body mass index (BMI) (OR 0.9, 95% CI 0.91-0.99, p = 0.028), a longer QTc time during AF (OR 1.01, 95% CI 1.0-1.02, p = 0.002) and first-detected AF (OR 2.5, 95% CI 1.6-3.9, p < 0.001) were independent determinants of early SCV. CONCLUSION: Early spontaneous conversion of acute AF occurs in almost one-sixth of admitted patients during a short initial observation in the ED. Spontaneous conversion is most likely to occur in patients with first-onset, short-duration AF episodes, lower BMI, and normal left atrial size.

Catheter ablation in highly symptomatic Brugada patients: a Dutch case series.

AIMS: In the past few years, promising results were described in targeting the arrhythmogenic substrate of the epicardial right ventricular outflow tract (RVOT) region in patients with Brugada syndrome (BrS). In this report, we describe our experience with endo- and epicardial substrate mapping and ablation in a series of highly symptomatic BrS patients. METHODS: This case series consists of seven patients with clinical BrS diagnosis who underwent catheter ablation in two Dutch hospitals (Isala hospital Zwolle; and Amsterdam University Medical Centre, location AMC, Amsterdam) and Hamad Heart Hospital in Qatar between 2013 and 2017. All patients had an ICD and recurrent ventricular arrhythmia (VA) episodes. All patients underwent endo-and epicardial mapping of the RVOT region. Elimination of all abnormal potentials and disappearance of BrS ECG pattern during the ablation procedure was the aimed endpoint. RESULTS: The study group consisted of seven patients with mean age 45.6 ± 16.9 years. Five patients had SCN5A mutations. One patient was excluded from analysis, since ablation could not be performed due to a very large low-voltage area and was later diagnosed with arrhythmogenic right ventricular cardiomyopathy, associated with an SCN5A mutation. One patient underwent both endo- and epicardial ablation to eliminate VA. During a mean follow-up of 3.6 ± 1.5 years, 5/6 patients remained VA free with two patients continuing quinidine. CONCLUSION: In patients with BrS and drug-refractory VA, ablation of the arrhythmogenic substrate in the RVOT region was associated with excellent long-term VA-free survival. The majority of these highly symptomatic BrS patients had an SCN5A mutation and also low-voltage areas epicardially.

The role of the SCN5A-encoded channelopathy in irritable bowel syndrome and other gastrointestinal disorders.

BACKGROUND: Gastrointestinal functional and motility disorders, like irritable bowel syndrome (IBS), have a high prevalence in the Western population and cause significant morbidity and loss of quality of life leading to considerable costs for health care. A decade ago, it has been demonstrated that interstitial cells of Cajal and intestinal smooth muscle cells, cells important for gastrointestinal motility, express the sodium channel alpha subunit Nav 1.5. In the heart, aberrant variants in this sodium channel, encoded by SCN5A, are linked to inherited arrhythmia syndromes, like the long-QT syndrome type 3 and Brugada syndrome. Mounting data show a possible contribution of SCN5A mutants to gastrointestinal functional and motility disorders. Two percent of IBS patients harbor SCN5A mutations with electrophysiological evidence of loss- and gain-of-function. In addition, gastrointestinal symptoms are more prevalent in cardiac SCN5A-mutation positive patients. PURPOSE: This review firstly describes the Nav 1.5 channel and its physiological role in ventricular cardiomyocytes and gastrointestinal cells, then we focus on the involvement of mutant Nav 1.5 in gastrointestinal functional and motility disorders. Future research might uncover novel mutation-specific treatment strategies for SCN5A-encoded gastrointestinal channelopathies.