MicroRNA Let-7a, -7e and -133a Attenuate Hypoxia-Induced Atrial Fibrosis via Targeting Collagen Expression and the JNK Pathway in HL1 Cardiomyocytes.

Fibrosis is a hallmark of atrial structural remodeling. The main aim of this study was to investigate the role of micro-ribonucleic acids (miRNAs) in the modulation of fibrotic molecular mechanisms in response to hypoxic conditions, which may mediate atrial fibrosis. Under a condition of hypoxia induced by a hypoxia chamber, miRNA arrays were used to identify the specific miRNAs associated with the modulation of fibrotic genes. Luciferase assay, real-time polymerase chain reaction, immunofluorescence and Western blotting were used to investigate the effects of miRNAs on the expressions of the fibrotic markers collagen I and III (COL1A, COL3A) and phosphorylation levels of the stress kinase c-Jun N-terminal kinase (JNK) pathway in a cultured HL-1 atrial cardiomyocytes cell line. COL1A and COL3A were found to be the direct regulatory targets of miR-let-7a, miR-let-7e and miR-133a in hypoxic atrial cardiac cells in vitro. The expressions of COL1A and COL3A were influenced by treatment with miRNA mimic and antagomir while hypoxia-induced collagen expression was inhibited by the delivery of miR-133a, miR-let-7a or miR-let-7e. The JNK pathway was critical in the pathogenesis of atrial fibrosis. The JNK inhibitor SP600125 increased miRNA expressions and repressed the fibrotic markers COL1A and COL3A. In conclusion, MiRNA let-7a, miR-let-7e and miR-133a play important roles in hypoxia-related atrial fibrosis by inhibiting collagen expression and post-transcriptional repression by the JNK pathway. These novel findings may lead to the development of new therapeutic strategies.

The Impact of Oxygen Pulse and Its Curve Patterns on Male Patients with Heart Failure, Chronic Obstructive Pulmonary Disease, and Healthy Controls-Ejection Fractions, Related Factors and Outcomes.

Oxygen pulse (O2P) is a function of stroke volume and cellular oxygen extraction and O2P curve pattern (O2PCP) can provide continuous measurements of O2P. However, measurements of these two components are difficult during incremental maximum exercise. As cardiac function is evaluated using ejection fraction (EF) according to the guidelines and EF can be obtained using first-pass radionuclide ventriculography, the aim of this study was to investigate associations of O2P%predicted and O2PCP with EF in patients with heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) and chronic obstructive pulmonary disease (COPD), and also in normal controls. This was a prospective observational cross-sectional study. Correlations of resting left ventricular EF, dynamic right and left ventricular EFs and outcomes with O2P% and O2PCP across the three participant groups were analyzed. A total of 237 male subjects were screened and 90 were enrolled (27 with HFrEF/HFmrEF, 30 with COPD and 33 normal controls). O2P% and the proportions of the three types of O2PCP were similar across the three groups. O2P% reflected dynamic right and left ventricular EFs in the control and HFrEF/HFmrEF groups, but did not reflect resting left ventricular EF in all participants. O2PCP did not reflect resting or dynamic ventricular EFs in any of the subjects. A decrease in O2PCP was significantly related to nonfatal cardiac events in the HFrEF/HFmrEF group (log rank test, p = 0.01), whereas O2P% and O2PCP did not predict severe acute exacerbations of COPD. The findings of this study may clarify the utility of O2P and O2PCP, and may contribute to the currently used interpretation algorithm and the strategy for managing patients, especially those with HFrEF/HFmrEF. (Trial registration number NCT05189301.).

Long-Term Prognosis of Febrile Individuals with Right Precordial Coved-Type ST-Segment Elevation Brugada Pattern: A 10-Year Prospective Follow-Up Study.

A febrile state may provoke a Brugada electrocardiogram (ECG) pattern and trigger ventricular tachyarrhythmias in susceptible individuals. However, the prognostic value of fever-induced Brugada ECG pattern remains unclear. We analyzed the clinical and extended long-term follow-up data of consecutive febrile patients with a type 1 Brugada ECG presented to the emergency department. A total of 21 individuals (18 males; mean age, 43.7 ± 18.6 years at diagnosis) were divided into symptomatic (resuscitated cardiac arrest in one, syncope in two) and asymptomatic (18, 86%) groups. Sustained polymorphic ventricular tachycardias were inducible in two patients with previous syncope. All 18 asymptomatic patients had no spontaneous type 1 Brugada ECG recorded at second intercostal space and no family history of sudden death. Among asymptomatic individuals, 4 had a total 12 of repeated non-arrhythmogenic febrile episodes all with recurrent type 1 Brugada ECGs, and none had a ventricular arrhythmic event during 116 ± 19 months of follow-up. In the symptomatic group, two had defibrillator shocks for a new arrhythmic event at 31- and 49 months follow-up, respectively, and one without defibrillator therapy died suddenly at 8 months follow-up. A previous history of aborted sudden death or syncope was significantly associated with adverse outcomes in symptomatic compared with asymptomatic individuals (log-rank p < 0.0001). In conclusion, clinical presentation or history of syncope is the most important parameter in the risk stratification of febrile patients with type 1 Brugada ECG. Asymptomatic individuals with a negative family history of sudden death and without spontaneous type 1 Brugada ECG, have an exceptionally low future risk of arrhythmic events. Careful follow-up with timely and aggressive control of fever is an appropriate management option.

Conservative management of bronchopulmonary artery perforation without associated haemothorax occurring at thoracentesis: a case report.

Puncture or laceration of the pulmonary, intercostal, or peripheral vessels is an uncommon, but potentially life-threatening, complication of thoracentesis, which has been reported to result in severe haemothorax in 75% of patients. Damage to these vessels typically requires surgical intervention or intra-arterial embolisation. We report the successful non-surgical management of an unusual case of pulmonary artery perforation without concomitant haemothorax in an 82-year-old man who underwent thoracentesis.

Fourteen-year follow-up in a teenager with congenital long QT syndrome masquerading as idiopathic generalized epilepsy.

Long QT syndrome is a potentially lethal cardiac channelopathy that can be mistaken for epilepsy in young people. We report a 17-year-old man who was initially treated as having both daytime and nocturnal idiopathic epilepsy for 5 years. A series of electrocardiograms showed the time of the convulsive episodes, and genetic testing lead to the final diagnosis. The combined use of a beta-blocker and a pacemaker implant incompletely abolished the torsade de pointes. After an additional near-fatal event, a cardioverter defibrillator was implanted as final bridge therapy. An electrocardiogram with the correct calculation of the QT interval should be performed on all young people with a suggestive history; that is, treat refractory convulsive episodes specifically with nondiagnostic electroencephalograms.

Spontaneous and simultaneous multivessel coronary spasm causing multisite myocardial infarction, cardiogenic shock, atrioventricular block, and ventricular fibrillation.

A 57-year-old Taiwanese man with a past history of variant angina developed simultaneous anterior and inferior myocardial infarction, atrioventricular block, cardiogenic shock, and eventually ventricular fibrillation. Left coronary angiography revealed simultaneous occlusion of the left anterior descending and the left circumflex coronary arteries, which was relieved by intracoronary administration of isosorbide dinitrate. This is the first report of such a case in the English-language medical literature.