Heart rhythm最新文献

Background: Friedreich's ataxia (FA) is a rare inherited neuromuscular disorder, where most patients die from lethal cardiomyopathy and arrhythmias. Mechanisms leading to arrhythmic events in FA patients are poorly understood.

Objective: This study aims to examine cardiac electrical signal propagation in mouse model of FA with severe cardiomyopathy and evaluate effects of omaveloxolone (OMAV), the first FDA-approved therapy.

Methods: Cardiac-specific MCK-Cre frataxin knockout (FXN-cKO) mice were used to mimic FA cardiomyopathy. In vivo surface ECG recordings, western blotting, qPCR, and histochemistry were performed.

Results: Characteristics like long QT syndrome, interatrial block, and ST-segment abnormalities in FA patients were identified in FXN-cKO mice. FXN-cKO mice exhibited sexual dimorphism in electrical signal propagation and cardiac structural integrity. Untreated FA males showed increased ventricular propagation intervals, while females exhibited delayed atrial propagation. OMAV showed no significant therapeutic effect on average ECG time intervals but improved chamber-specific waveforms when aggregated frequency distributions were analyzed. The J-wave was absent in FXN-cKO male mice but reappeared with OMAV treatment. Poincaré plots revealed disparate idiopathic arrhythmias with multi-clustering events in individual mice with high incidence in FXN-cKO males. OMAV treatment reduced multi-clustering events to a single cluster; however, ANS dysfunction still remained.

Conclusion: Our study revealed significant electrical propagation disturbances and sexual dimorphism in FXN-cKO mice with severe cardiomyopathy. Poincaré plots identified irregularities in heart rhythm and ANS dysfunction. OMAV improved heart function by stabilizing early repolarization and reducing disparate arrhythmias. This work stresses sex-specific ECG interpretations and alternative mathematical approaches for drug testing in FA models.

Background: Sudden cardiac arrest (SCA) risk stratification in patients with mitral valve prolapse (MVP) may be complicated by other potential causes of arrhythmia.

Objectives: We aimed to characterize SCA survivors with isolated (iMVP) and non-isolated MVP (non-iMVP) and to assess their long-term follow-up.

Methods: This ambispective study included 75 patients with MVP who experienced SCA and were treated in our center between 2009-2024. They were divided into three groups depending on probability of relation between SCA and comorbidities. The control group comprised 112 subjects with MVP but without a history of SCA. We analyzed all available electrocardiograms, Holter ECG monitoring and echocardiograms, including longitudinal strain. A novel parameter, the systolic atrial-directed notch (SADN) was tested.

Results: SCA survivors with iMVP (n=28) had higher prevalence of mitral annular disjunction (MAD) (80% vs. 35.7%, P=0.006), Pickelhaube sign (60% vs. 8.3%, P=0.008), SADN > 2 mm (69.6% vs. 14.3%, P=0.001) as well as higher absolute longitudinal strain values in basal and mid segments of inferior and inferolateral wall than patients with SCA and non-iMVP without other defined structural heart diseases (SHD(-)) (n=14). The differences were also observed in comparison to control group. The cumulative incidence of appropriate implantable cardioverter-defibrillator shocks within 6 years was 62% in patients with iMVP and 23% in the group with non-iMVP SHD(-).

Conclusions: Echocardiographic findings such as MAD, SADN, Pickelhaube sign and increased segmental strain may be useful in the assessment of relation between SCA and MVP. Malignant arrhythmias often recur in SCA survivors with iMVP.

Background: Promising as a treatment option for life-threatening ventricular arrhythmias, cardiac stereotactic body radiotherapy (cSBRT) has demonstrated early antiarrhythmic effects within days of treatment. The mechanisms underlying the immediate and short-term antiarrhythmic effects are poorly understood.

Objective: We hypothesize that cSBRT has a direct antiarrhythmic effect on cellular electrophysiology through reprogramming of ion channel and gap junction protein expression.

Methods: After exposure to 20 Gy of x-rays in a single fraction, neonatal rat ventricular cardiomyocytes were analyzed 24 and 96 hours postradiation to determine changes in conduction velocity, beating frequency, calcium transients, and action potential duration in both monolayers and single cells. In addition, the expression of gap junction proteins, ion channels, and calcium handling proteins was evaluated at protein and messenger RNA levels.

Results: After irradiation with 20 Gy, neonatal rat ventricular cardiomyocytes exhibited increased beat rate and conduction velocity 24 and 96 hours after treatment. Messenger RNA and protein levels of ion channels were altered, with the most significant changes observed at the 96-hour mark. Upregulation of Cacna1c (Ca_v1.2), Kcnd3 (K_v4.3), Kcnh2 (K_v11.1), Kcnq1 (K_v7.1), Kcnk2 (K_2P2.1), Kcnj2 (K_ir2.1), and Gja1 (Cx43) was noted, along with improved gap junctional coupling. Calcium handling was affected, with increased Ryr2 ryanodin-rezeptor 2 and Slc8a1 Na⁺/Ca²⁺ exchanger expression and altered properties 96 hours posttreatment. Fibroblast and myofibroblast levels remained unchanged.

Conclusion: cSBRT modulates the expression of various ion channels, calcium handling proteins, and gap junction proteins. The described alterations in cellular electrophysiology may be the underlying cause of the immediate antiarrhythmic effects observed after cSBRT.

In the 2000s, cardiac resynchronization therapy (CRT) became a revolutionary treatment for heart failure with reduced left ventricular ejection fraction (HFrEF) and wide QRS. However, about one-third of CRT recipients do not show a favorable response. This review of the current literature aims to better define the concept of CRT response/nonresponse. The diagnosis of CRT nonresponder should be viewed as a continuum, and it cannot rely solely on a single parameter. Moreover, baseline features of some patients might predict an unfavorable response. A strong collaboration between heart failure specialists and electrophysiologists is key to overcoming this challenge with multiple strategies. In the contemporary era, new pacing modalities, such as His-bundle pacing and left bundle branch area pacing, represent a promising alternative to CRT. Observational studies have demonstrated their potential; however, several limitations should be addressed. Large randomized controlled trials are needed to prove their efficacy in HFrEF with electromechanical dyssynchrony.

The electromechanical window (EMW) is calculated by subtracting the repolarization duration from a mechanical reference representing contraction duration in the same heartbeat (eg, aortic valve closure during echocardiography with simultaneous electrocardiography). Here, we review the current knowledge on the role of the EMW as an independent parameter for ventricular arrhythmia-risk stratification. We (1) provide a standardized approach to echocardiographic EMW assessment, (2) define relevant cutoff values for both abnormal EMW negativity and positivity, (3) discuss pathophysiological underpinnings of EMW negativity, and (4) outline the potential future role of cardiac electromechanical relations in patients with proarrhythmic conditions.