Restoration of calcium release synchrony: A novel target for heart failure and ventricular arrhythmia.

Myocardial calcium (Ca2+) signaling plays a crucial role in contractile function and membrane electrophysiology. An abnormal myocardial Ca2+ transient is linked to heart failure and ventricular arrhythmias. At the subcellular level, the synchronous release of Ca2+ sparks from sarcoplasmic Ca2+ release units determines the configuration and amplitude of the global Ca2+ transient. This narrative review evaluates the role of aberrant Ca2+ release synchrony in the pathophysiology of cardiomyopathies and ventricular arrhythmias. The potential therapeutic benefits of restoration of Ca2+ release synchrony in heart failure and ventricular arrhythmias are also discussed.

Ventricular Fibrillation: A Rare Initial Presentation of Thyrotoxic Periodic Paralysis.

Thyrotoxic periodic paralysis is a life-threatening complication of hyperthyroidism characterized by transient episodes of muscle paralysis and hypokalemia, commonly seen in Asian men. We present a rare case of ventricular fibrillation as the initial presentation of thyrotoxic periodic paralysis. (Level of Difficulty: Intermediate.).

Cardioprotective effects of dantrolene in doxorubicin-induced cardiomyopathy in mice.

BACKGROUND: Doxorubicin (Dox) is a potent chemotherapeutic agent, but its usage is limited by dose-dependent cardiotoxicity. Intracellular calcium dysregulation has been reported to be involved in doxorubicin-induced cardiomyopathy (DICM). The cardioprotective role of RyR stabilizer dantrolene (Dan) on the calcium dynamics of DICM has not yet been explored. OBJECTIVE: To evaluate the effects of dantrolene on intracellular calcium dysregulation and cardiac contractile function in a DICM model. METHODS: Adult male C57BL/6 mice were randomized into 4 groups: (1) Control, (2) Dox Only, (3) Dan Only, and (4) Dan + Dox. Fractional shortening (FS) and left ventricular ejection fraction (LVEF) were assessed by echocardiography. In addition, mice were sacrificed 2 weeks after doxorubicin injection for optical mapping of the heart in a Langendorff setup. RESULTS: Treatment with Dox was associated with a reduction in both FS and LVEF at 2 weeks (P < .0001) and 4 weeks (P < .006). Dox treatment was also associated with prolongation of calcium transient durations CaTD50 (P = .0005) and CaTD80 (P < .0001) and reduction of calcium amplitude alternans ratio (P < .0001). Concomitant treatment with Dan prevented the Dox-induced decline in FS and LVEF (P < .002 at both 2 and 4 weeks). Dan also prevented Dox-induced prolongation of CaTD50 and CaTD80 and improved the CaT alternans ratio (P < .0001). Finally, calcium transient rise time was increased in the doxorubicin-treated group, indicating RyR2 dyssynchrony, and dantrolene prevented this prolongation (P = .02). CONCLUSION: Dantrolene prevents cardiac contractile dysfunction following doxorubicin treatment by mitigating dysregulation of calcium dynamics.

A comparison of manual electrocardiographic interval and waveform analysis in lead 1 of 12-lead ECG and Apple Watch ECG: A validation study.

Background: The Apple Watch Series 4 (AW) can detect atrial fibrillation and perform a single-lead electrocardiogram (ECG), but the clinical accuracy of AW ECG waveforms compared to lead 1 of a 12-lead ECG is unclear. Objective: The purpose of this study was to assess the accuracy of interval measurements on AW ECG tracings in comparison to lead 1 on a 12-lead ECG. Methods: We obtained ECGs at a university hospital of healthy volunteers age >18 years. ECG waveforms were measured with calipers to the nearest 0.25 mm. When possible, 3 consecutive waveforms in lead 1 were measured. Waveform properties, including intervals, were recorded. Concordance correlation coefficients and Bland-Altman plots were used to assess level of agreement between devices. Results: Twelve-lead (n = 113) and AW (n = 129) ECG waveforms from 43 volunteers (mean age 31 years; 65% female) were analyzed. Sinus rhythm interpretation between devices was 100% concordant. No arrhythmias were recorded. Mean difference (d) for heart rate was 1.16 ± 4.33 bpm (r = 0.94); 3.83 ± 113.54 ms for RR interval (r = 0.79); 5.43 ± 17 ms for PR interval (r = 0.83); -6.89 ± 14.81 ms for QRS interval (r = 0.65); -11.27 ± 22.9 ms for QT interval (r = 0.79); and -11.67 ± 27 ms for QTc interval (r = 0.57). There was moderate (d <40 ms) to strong (d <20 ms or < 5 bpm) agreement between devices represented by Bland-Altman plots. Conclusion: The AW produces accurate ECGs in healthy adults with moderate to strong agreement of basic ECG intervals.