Ability of ambulatory ECG-based T-wave alternans to modify risk assessment of cardiac events: a systematic review.

BACKGROUND: Exercise-based spectral T-wave alternans (TWA) has been proposed as a noninvasive tool-identifying patients at risk of sudden cardiac death (SCD) and cardiac mortality. Prior studies have indicated that ambulatory electrocardiogram (AECG)-based TWA is an important alternative platform to exercise for risk stratification of cardiac events. This study sought to review data regarding 24-hour AECG-based TWA and to discuss its potential role in risk stratification of fatal cardiac events across a series of patient risk profiles. METHODS: Prospective clinical studies of the predictive value of AECG-based TWA obtained with daily activity published between January 1990 and November 2014 were retrieved. Major endpoints included composite endpoint of SCD, cardiac mortality, and severe arrhythmic events. RESULTS: Data were accumulated from 5 studies involving a total of 1,588 patients, including 317 positive and 1,271 negative TWA results. Compared with the negative group, positive group showed increased rates of SCD (hazard ratio [HR]: 7.49, 95% confidence interval [CI]: 2.65 to 21.15), cardiac mortality (HR: 4.75, 95% CI: 0.42 to 53.55), and composite endpoint (SCD, cardiac mortality, and severe arrhythmic events, HR: 5.94, 95% CI: 1.80 to 19.63). For the 4 studies evaluating TWA measured using the modified moving average method, the HR associated with a positive versus negative TWA result was 9.51 (95% CI: 4.99 to 18.11) for the composite endpoint. CONCLUSIONS: The positive group of AECG-based TWA has a nearly six-fold risk of severe outcomes compared with the negative group. Therefore, AECG-based TWA provides an accurate means of predicting fatal cardiac events.

Inhibitory effects of roscovitine on proliferation and migration of vascular smooth muscle cells in vitro.

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are the major cause of in-stent restenosis (ISR). Intervention proliferation and migration of VSMCs is an important strategy for antirestenotic therapy. Roscovitine, a second-generation cyclin-dependent kinase inhibitor, can inhibit cell cycle of multiple cell types. We studied the effects of roscovitine on cell cycle distribution, proliferation and migration of VSMCs in vitro by flow cytometry, BrdU incorporation and wound healing assay, respectively. Our results showed that roscovitine increased the proportion of G0/G1 phase cells after 12 h (69.57±3.65 vs. 92.50±1.68, P=0.000), 24 h (80.87±2.24 vs. 90.25±0.79, P=0.000) and 48 h (88.08±3.86 vs. 88.87±2.43, P=0.427) as compared with control group. Roscovitine inhibited proliferation and migration of VSMCs in a concentration-dependent way. With the increase of concentration, roscovitine showed increased capacity for growth and migration inhibition. Roscovitine (30 µmol/L) led to an almost complete VSMCs growth and migration arrest. Combined with its low toxicity and selective inhibition to ISR-VSMCs, roscovitine may be a potential drug in the treatment of vascular stenosis diseases and particularly useful in the prevention and treatment of ISR.

KN-93, A CaMKII inhibitor, suppresses ventricular arrhythmia induced by LQT2 without decreasing TDR.

Abnormal enhanced transmural dispersion of repolarization (TDR) plays an important role in the maintaining of the severe ventricular arrhythmias such as torsades de pointes (TDP) which can be induced in long-QT (LQT) syndrome. Taking advantage of an in vitro rabbit model of LQT2, we detected the effects of KN-93, a CaM-dependent kinase (CaMK) II inhibitor on repolarization heterogeneity of ventricular myocardium. Using the monophasic action potential recording technique, the action potentials of epicardium and endocardium were recorded in rabbit cardiac wedge infused with hypokalemic, hypomagnesaemic Tyrode's solution. At a basic length (BCL) of 2000 ms, LQT2 model was successfully mimicked with the perfusion of 0.5 µmol/L E-4031, QT intervals and the interval from the peak of T wave to the end of T wave (Tp-e) were prolonged, and Tp-e/QT increased. Besides, TDR was increased and the occurrence rate of arrhythmias like EAD, R-on-T extrasystole, and TDP increased under the above condition. Pretreatment with KN-93 (0.5 µmol/L) could inhibit EAD, R-on-T extrasystole, and TDP induced by E-4031 without affecting QT interval, Tp-e, and Tp-e/QT. This study demonstrated KN-93, a CaMKII inhibitor, can inhibit EADs which are the triggers of TDP, resulting in the suppression of TDP induced by LQT2 without affecting TDR.

Trends in Coronavirus Disease 2019 Hospitalization and Prognosis: Gender Effect.

We here aimed to investigate the impact of gender on the clinical characteristics and laboratory results of patients with coronavirus disease 2019 (COVID-19) and provide clues to the pathological mechanisms underlying COVID-19. A retrospective study was performed. Clinical characteristics, severity of lung infection, laboratory results, and prognoses of patients of different gender were analyzed. A total of 242 patients were finally included. The median age was 58 years (IQR: 40-68), including 54 (22.3%) hospital staffs. Ninety-four (38.8%) were male and 148 (61.1%) were female. The proportion of patients with diabetes was significantly higher in the male group than in the female group (P=0.034). Male patients had a significantly larger proportion of severe lung infection, higher leukocyte count, neutrophil count, neutrophil-to-lymphocyte ratio, C-reactive protein, and procalcitonin than female. Furthermore, male patients had worse liver, cardiac, and coagulation function than their female counterparts. Male patients with COVID-19 showed more severe inflammation reaction and coagulation dysfunction than female patients. In conclusion, gender is associated with host response to SARS-CoV-2 infection.

Verapamil suppresses cardiac alternans and ventricular arrhythmias in acute myocardial ischemia via ryanodine receptor inhibition.

T-wave alternans (TWA) is a potent arrhythmia substrate under the conditions of acute myocardial ischemia. Abnormal intracellular calcium cycling contributes to the genesis of cardiac alternans. Ryanodine receptor (RyR) is a pivotal Ca2+ cycling protein central to Ca2+ signaling in the heart. Here, we investigated the potential role of RyR in cardiac alternans and ventricular arrhythmias in acute myocardial ischemia. Transmembrane action potentials were simultaneously recorded from epicardium and endocardium together with a transmural ECG and isometric contraction force in the arterially perfused left ventricular wedge preparations. Calcium alternans were induced by incremental frequency of field stimulation in rat ventricular myocytes. TWA, mechanical alternans and ventricular arrhythmias were reproducibly induced by rapid pacing in the acute ischemic wedge preparations. Compared with control group, calcium alternans ratio and spontaneous calcium release were increased in acute ischemic myocytes. Verapamil, a phenylalkylamine calcium channel blocker, can successfully abolish spontaneous calcium release, TWA, and ventricular arrhythmias. The inhibition effect of verapamil could be diminished by low concentration of ryanodine (10 nmol/L). However, nifedipine, a dihydropyridine calcium channel blocker, could not block TWA or arrhythmias. Moreover, verapamil, but not nifedipine, significantly decreased ROS production in ischemic myocytes. Collectively, our results indicate that verapamil can significantly inhibit the development of cardiac alternans and ventricular arrhythmias in acute myocardial ischemia, and the mechanism was related to the inhibition of RyR and the protective function to oxidative stress.