The mechanisms of J wave syndrome (JWS) are incompletely understood. Here, we showed that the concomitant activation of small-conductance calcium-activated potassium (SK) current ( I _KAS ) and inhibition of sodium current by cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) recapitulate the phenotypes of JWS in Langendorff-perfused rabbit hearts. CyPPA induced significant J wave elevation and frequent spontaneous ventricular fibrillation (SVF), as well as sinus bradycardia, atrioventricular block, and intraventricular conduction delay. I _KAS activation by CyPPA resulted in heterogeneous shortening of action potential (AP) duration (APD) and repolarization alternans. CyPPA inhibited cardiac sodium current ( I _Na ) and decelerated AP upstroke and intracellular calcium transient. SVFs were typically triggered by short-coupled premature ventricular contractions, initiated with phase 2 reentry and originated more frequently from the right than the left ventricles. Subsequent I _KAS blockade by apamin reduced J wave elevation and eliminated SVF. β-Adrenergic stimulation was antiarrhythmic in CyPPA-induced electrical storm. Like CyPPA, hypothermia (32.0°C) also induced J wave elevation and SVF. It facilitated negative calcium-voltage coupling and phase 2 repolarization alternans with spatial and electromechanical discordance, which were ameliorated by apamin. These findings suggest that I _KAS activation contributes to the development of JWS in rabbit ventricles.

The dynamic trends of pulmonary function in coronavirus disease 2019 (COVID-19) survivors since discharge have been rarely described. We aimed to describe the changes of lung function and identify risk factors for impaired diffusion capacity. Non-critical COVID-19 patients admitted to the Guangzhou Eighth People's Hospital, China, were enrolled from March to June 2020. Subjects were prospectively followed up with pulmonary function tests at discharge, three and six months after discharge. Eighty-six patients completed diffusion capacity tests at three timepoints. The mean diffusion capacity for carbon monoxide (D_LCO)% pred was 79.8% at discharge and significantly improved to 84.9% at Month-3. The transfer coefficient of the lung for carbon monoxide (K_CO)% pred significantly increased from 91.7% at discharge to 95.7% at Month-3. Both of them showed no further improvement at Month-6. The change rates of D_LCO% pred and K_CO% pred were significantly higher in 0–3 months than in 3–6 months. The alveolar ventilation (V_A) improved continuously during the follow-ups. At Month-6, impaired D_LCO% pred was associated with being female (OR 5.2 [1.7–15.8]; p = 0.004) and peak total lesion score (TLS) of chest CT > 8.5 (OR 6.6 [1.7–26.5]; p = 0.007). D_LCO% pred and K_CO% pred were worse in females at discharge. And in patients with impaired diffusion capacity, females’ D_LCO% pred recovered slower than males. The first three months is the critical recovery period for diffusion capacity. The impaired diffusion capacity was more severe and recovered slower in females than in males. Early pulmonary rehabilitation and individualized interventions for recovery are worthy of further investigations.

Background: With population aging, the prevalence of both cancer and atrial fibrillation (AF) have increased. However, there is scarce epidemiological data concerning the comorbid state of cancer and AF in low- and middle-income countries, including China. Objective: We aimed to evaluate the site-, sex-, and age-specific profiles of cancer and AF comorbidities in Chinese populations. Methods: Data from the Shanghai Municipal Health Commission database between 2015 and 2020 were screened, covering all medical records of Shanghai residents with medical insurance. Site-specific cancer profiles were evaluated for the population with AF relative to the age- and sex-adjusted population of residents without AF. The sex distribution and peak age of cancer diagnosis were also assessed. Results: A total of 25,964,447 adult patients were screened. Among them, 22,185 patients presented cancers comorbid with AF (median 77, IQR 67-82 years of age; men: n=13,631, 61.44%), while 839,864 presented cancers without AF (median 67, IQR 57-72 years of age; men: n=419,020, 49.89%), thus yielding a higher cancer prevalence among residents with AF (8.27%) than among those without AF (6.05%; P<.001). In the population with AF, the most prevalent cancer type was lung cancer, followed by colorectal, male genital organ, stomach, breast, liver, bladder, thyroid, leukemia, and esophageal cancers. AF was associated with an average of nearly 1.4-fold (prevalence ratio [PR] 1.37, 95% CI 1.35-1.38) increased prevalence of cancer after adjusting for age and sex. For site-specific analyses, an increased prevalence of cancer in the population with AF was observed in 20 of 21 cancer sites. This increased prevalence was most prominent for nonsolid tumors, including multiple myeloma (PR 2.56, 95% CI 2.28-2.87), leukemia (PR 1.73, 95% CI 1.57-1.90), and non-Hodgkin lymphoma (PR 1.59, 95% CI 1.43-1.77); intrathoracic malignancies, including mediastinum (PR 2.34, 95% CI 1.89-2.90), lung (PR 1.64, 95% CI 1.59-1.69), and esophageal cancers (PR 1.41, 95% CI 1.28-1.56); bone and soft tissue neoplasms (PR 1.56, 95% CI 1.37-1.77); and kidney cancer (PR 1.53, 95% CI 1.36-1.72). Cancer prevalence in the population with AF relative to that in the population without AF was higher in men than in women in 14 of 18 cancer sites, and female predominance was only observed for thyroid cancer. The peak age of index cancer diagnosis was lower in the population with AF (age group: 70-74 years) than in that without AF (age group: 75-79 years), especially for specific cancer types, including thyroid, central nervous system, mediastinum, esophageal, bladder, and biliary cancers. Conclusions: Patients with AF are associated with increased prevalence, heightened male predominance, and younger peak age of cancer. Further studies are needed to determine whether early screening of specific cancers is cost-effective and beneficial for patients with AF.

BACKGROUND: The prognostic impact of left atrial appendage (LAA) patency, including those with and without visible peri-device leak (PDL), post–LAA closure in patients with atrial fibrillation, remains elusive. METHODS: Patients with atrial fibrillation implanted with the WATCHMAN 2.5 device were prospectively enrolled. The device surveillance by cardiac computed tomography angiography was performed at 3 months post-procedure. Adverse events, including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular death, all-cause death, and the combined major adverse events (MAEs), were compared between patients with complete closure and LAA patency. RESULTS: Among 519 patients with cardiac computed tomography angiography surveillance at 3 months post–LAA closure, 271 (52.2%) showed complete closure, and LAA patency was detected in 248 (47.8%) patients, including 196 (37.8%) with visible PDL and 52 (10.0%) without visible PDL. During a median of 1193 (787–1543) days follow-up, the presence of LAA patency was associated with increased risks of stroke/TIA (adjusted hazard ratio for baseline differences, 3.22 [95% CI, 1.17–8.83]; P =0.023) and MAEs (adjusted hazard ratio, 1.12 [95% CI, 1.06–1.17]; P =0.003). Specifically, LAA patency with visible PDL was associated with increased risks of stroke/TIA (hazard ratio, 3.66 [95% CI, 1.29–10.42]; P =0.015) and MAEs (hazard ratio, 3.71 [95% CI, 1.71–8.07]; P =0.001), although LAA patency without visible PDL showed higher risks of MAEs (hazard ratio, 3.59 [95% CI, 1.28–10.09]; P =0.015). Incidences of stroke/TIA (2.8% versus 3.0% versus 6.7% versus 22.2%; P =0.010), cardiovascular death (0.9% versus 0% versus 1.7% versus 11.1%; P =0.005), and MAEs (4.6% versus 9.0% versus 11.7% versus 22.2%; P =0.017) increased with larger PDL (0, >0 to ≤3, >3 to ≤5, or >5 mm). Older age and discontinuing antiplatelet therapy at 6 months were independent predictors of stroke/TIA and MAEs in patients with LAA patency. CONCLUSIONS: LAA patency detected by cardiac computed tomography angiography at 3 months post–LAA closure is associated with unfavorable prognosis in patients with atrial fibrillation implanted with WATCHMAN 2.5 device. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03788941.