Sex-Specific Ventricular Arrhythmias and Mortality in Cardiac Resynchronization Therapy Recipients

Quesada, Aurelio; Arteaga, Francisco; Romero-Villafranca, Rafael; Pérez-Álvarez, Luisa; Martínez-Ferrer, José; Alzueta-Rodríguez, Javier; Concha, Joaquín Fernández de la; Martı́nez, Juan Gabriel; Viñolas, Xavier; Porres, José Manuel; Anguera, Ignasi; Porro-Fernández, Rosa; Quesada-Ocete, B; Guía-Galipienso, Fernando de la; Palanca, Víctor; Jiménez, Javier; Quesada-Ocete, Javier; Sanchís-Gomar, Fabián

doi:10.1016/j.jacep.2020.10.009

Cited by 7 publications

(3 citation statements)

References 43 publications

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“…In this group, women had a 76% reduction in heart failure or death (absolute CRT-D to ICD difference, 23%; HR 0.24, 95% CI 0.11-0.53; p < 0.001) (236, 237). Women who receive CRT therapy show a therapy response of 90% over a wide range of QRS duration (130-175 ms) (238). Women with left bundle branch block and CRT do have significantly higher ventricular tachycardia-free survival than men, as shown in a multicenter retrospective study in 460 patients (105 women) of the Incidence of Arrhythmia in Spanish Population With a Medtronic Implantable Cardiac Defibrillator Implant national registry (UMBRELLA) (239).…”

Section: Cardiac Resynchronization Therapymentioning

confidence: 99%

Sex and gender differences in myocarditis and dilated cardiomyopathy: An update

Fairweather

Beetler

Musigk

et al. 2023

Front. Cardiovasc. Med.

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In the past decade there has been a growing interest in understanding sex and gender differences in myocarditis and dilated cardiomyopathy (DCM), and the purpose of this review is to provide an update on this topic including epidemiology, pathogenesis and clinical presentation, diagnosis and management. Recently, many clinical studies have been conducted examining sex differences in myocarditis. Studies consistently report that myocarditis occurs more often in men than women with a sex ratio ranging from 1:2–4 female to male. Studies reveal that DCM also has a sex ratio of around 1:3 women to men and this is also true for familial/genetic forms of DCM. Animal models have demonstrated that DCM develops after myocarditis in susceptible mouse strains and evidence exists for this progress clinically as well. A consistent finding is that myocarditis occurs primarily in men under 50 years of age, but in women after age 50 or post-menopause. In contrast, DCM typically occurs after age 50, although the age that post-myocarditis DCM occurs has not been investigated. In a small study, more men with myocarditis presented with symptoms of chest pain while women presented with dyspnea. Men with myocarditis have been found to have higher levels of heart failure biomarkers soluble ST2, creatine kinase, myoglobin and T helper 17-associated cytokines while women develop a better regulatory immune response. Studies of the pathogenesis of disease have found that Toll-like receptor (TLR)2 and TLR4 signaling pathways play a central role in increasing inflammation during myocarditis and in promoting remodeling and fibrosis that leads to DCM, and all of these pathways are elevated in males. Management of myocarditis follows heart failure guidelines and there are currently no disease-specific therapies. Research on standard heart failure medications reveal important sex differences. Overall, many advances in our understanding of the effect of biologic sex on myocarditis and DCM have occurred over the past decade, but many gaps in our understanding remain. A better understanding of sex and gender effects are needed to develop disease-targeted and individualized medicine approaches in the future.

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Section: Cardiac Resynchronization Therapymentioning

confidence: 99%

Sex and gender differences in myocarditis and dilated cardiomyopathy: An update

Fairweather

Beetler

Musigk

et al. 2023

Front. Cardiovasc. Med.

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“…Patient‐specific factors to consider involve comorbidities, frailty, quality of life, projected lifespan, and patient preference. There is evidence suggesting that the risk of ventricular arrhythmias is lower in women with CRT, 19 and leaning on this evidence the choice of CRT‐P in the majority of older patients with pacemaker associated heart failure may be reasonable, also reducing perioperative risks and total cost. In general, adding a defibrillator in older patients with limited life expectancy does not necessarily lead to a survival benefit, whereas successful CRT treatment improves quality of life and reduces heart failure hospitalizations.…”

Section: Discussionmentioning

confidence: 99%

Sex‐based differences in cardiac resynchronization therapy upgrade and outcome for patients with pacemaker and new‐onset heart failure

Rorsman,

Farouq,

Marinko

et al. 2023

Pacing Clinical Electrophis

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BackgroundPatients with chronic right ventricular (RV) pacing are at an increased risk of heart failure. Previous studies have indicated that cardiac resynchronization therapy (CRT) is underused in this setting, and that there may be sex‐based differences in both CRT use and clinical outcome.ObjectiveTo evaluate sex‐based differences in CRT use and clinical outcome for patients with new‐onset heart failure post RV pacing.MethodsData from the Swedish pacemaker registry was matched with data from the national death and disease registries. Patients with de novo pacemaker implant due to AV block during the period 2005–2020 were included. New‐onset heart‐failure within two years post‐implant was evaluated, primary outcome was all‐cause mortality.ResultsIn all, 30183 patients (37% female) were included. Women were on average 3 years older, but had less comorbidities than men. Median follow‐up time was 4.5 [2.0–8.0] years. Women had better age‐ and comorbidity‐adjusted survival (HR 0.78 [0.73–0.84], p < .001). For the 3560 patients (12.4% men and 10.7% women, p < .001) who were diagnosed with new‐onset heart failure, 5‐year mortality was similar for men and women (50% vs. 48%, p = .29). However, women were less likely to receive CRT‐upgrade (3.8% vs. 9.1%, p < .001), and those who did were almost ten years younger than the men.ConclusionWomen with pacemaker due to AV block are older but have less comorbidities than men. They are less likely to develop new‐onset heart failure, but also less likely to receive a CRT upgrade if they do develop heart failure. Increased awareness of the positive effects of CRT upgrade and potential sex‐ and age‐based discrimination is warranted.

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“…It has been reported that the risk of the first and subsequent episodes of VT/VF and ICD shocks are lower in women than in men with cardiomyopathy and ventricular dysfunction (7). Women are also less likely to have inducible ventricular arrhythmias in the setting of ischemic cardiomyopathy and prior MI, and less likely to have ICD shocks and appropriate ICD therapies for spontaneous VT/VF, even in the setting of significant structural heart disease (4,7,41). Finally, decreased rates of age adjusted sudden cardiac death are noted in women (42), but this difference diminishes post-menopause, so that at the age of 65 or greater, the incidence of sudden cardiac death is similar in men and women (43).…”

Section: Vagal Afferent and Efferent Function After Myocardial Infarc...mentioning

confidence: 99%

Myocardial infarction causes sex-dependent dysfunction in vagal sensory glutamatergic neurotransmission that is mitigated by 17β-estradiol

Devarajan,

Wang,

Lokhandwala

et al. 2024

JCI Insight

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Parasympathetic dysfunction after chronic myocardial infarction (MI) is known to predispose ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]). VT/VF after MI is more common in males than females. The mechanisms underlying the decreased vagal tone and the associated sex difference in the occurrence of VT/VF after MI remain elusive. In this study, using optogenetic approaches, we found that responses of glutamatergic vagal afferent neurons were impaired following chronic MI in male mice, leading to reduced reflex efferent parasympathetic function. Molecular analyses of vagal ganglia demonstrated reduced glutamate levels, accompanied by decreased mitochondrial function and impaired redox status in infarcted males versus sham animals. Interestingly, infarcted females demonstrated reduced vagal sensory impairment, associated with greater vagal ganglia glutamate levels and decreased vagal mitochondrial dysfunction and oxidative stress compared with infarcted males. Treatment with 17β-estradiol mitigated this pathological remodeling and improved vagal neurotransmission in infarcted male mice. These data suggest that a decrease in efferent vagal tone following MI results from reduced glutamatergic afferent vagal signaling that may be due to impaired redox homeostasis in the vagal ganglia, which subsequently leads to pathological remodeling in a sex-dependent manner. Importantly, estrogen prevents pathological remodeling and improves parasympathetic function following MI.

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Sex-Specific Ventricular Arrhythmias and Mortality in Cardiac Resynchronization Therapy Recipients

Cited by 7 publications

References 43 publications

Sex and gender differences in myocarditis and dilated cardiomyopathy: An update

Sex and gender differences in myocarditis and dilated cardiomyopathy: An update

Sex‐based differences in cardiac resynchronization therapy upgrade and outcome for patients with pacemaker and new‐onset heart failure

Myocardial infarction causes sex-dependent dysfunction in vagal sensory glutamatergic neurotransmission that is mitigated by 17β-estradiol

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