Prognostic Impact of Atrial Rhythm and Dimensions in Patients with Structural Heart Disease Undergoing Cardiac Sympathetic Denervation for Ventricular Arrhythmias

Background: Cardiac sympathetic denervation (CSD) is a promising treatment for patients with structural heart disease (SHD) and refractory ventricular tachyarrhythmias (VT). The prognostic impact of atrial arrhythmias (AAs) and left atrial volume index (LAVI) on CSD outcome is unknown, as is the effect of CSD on atrial rhythm. Objective: Assess the impact of AAs and LAVI on CSD outcome, as well as changes in atrial rhythm after CSD. Methods: Patients with SHD undergoing CSD for VTs were analyzed. Hazard models were built to assess predictors of sustained VT/ICD shocks and death/orthotopic heart transplant (OHT). Changes before versus after CSD were assessed on ICD, clinical and echocardiographic data. A drug index was devised to correct for medication use. Results: Between 2009 and 2018, 91 patients (56 ± 13 years, LVEF 34 ±14%, 47% with a history of AAs) underwent left (16%) or bilateral CSD: the median FU was 14 months (IQR 4-37). Using multivariable analysis, neither LAVI nor AAs were associated with ICD shock recurrences. LAVI was an independent predictor of death/OHT. AAs burden did not change after CSD, while the percentage of atrial pacing increased from a median of 28% to 72% (p <0.01). LV end-diastolic diameter mildly increased; however, sustained VT/ICD shocks were reduced. Conclusions: In patients with SHD undergoing CSD a history of AAs did not impact outcome, LAVI is associated with death/OHT occurrence. In the absence of changes in the drug index, AAs burden, already low at baseline, was unchanged after CSD, despite a mild progression of cardiomyopathy, while atrial pacing increased

Vagal stimulation in heart failure

Vagal nerve stimulation (VNS) has a strong pathophysiological rationale as a potentially beneficial treatment for heart failure with reduced ejection fraction. Despite several promising preclinical studies and pilot clinical studies, the two large, controlled trials—NECTAR-HF and INOVATE-HF—failed to demonstrate the expected benefit. It is likely that clinical application of VNS in phase III studies was performed before a sufficient degree of understanding of the complex pathophysiology of autonomic electrical modulation had been achieved, therefore leading to an underestimation of its potential benefit. More knowledge on the complex dose–response issue of VNS (i.e., pulse amplitude, frequency, duration and duty cycle) has been gathered since these trials and a new randomized study is currently underway with an adaptive design and a refined approach in an attempt to deliver the proper dose to a more selected group of patients

Cardiac Sympathetic Denervation in Channelopathies

Left cardiac sympathetic denervation (LCSD) is a surgical antiadrenergic intervention with a strong antiarrhythmic effect, supported by preclinical as well as clinical data. The mechanism of action of LCSD in structurally normal hearts with increased arrhythmic susceptibility (such as those of patients with channelopathies) is not limited to the antagonism of acute catecholamines release in the heart. LCSD also conveys a strong anti-fibrillatory action that was first demonstrated over 40 years ago and provides the rationale for its use in almost any cardiac condition at increased risk of ventricular fibrillation. The molecular mechanisms involved in the final antiarrhythmic effect of LCSD turned out to be much broader than anticipated. Beside the vagotonic effect at different levels of the neuraxis, other new mechanisms have been recently proposed, such as the antagonism of neuronal remodeling, the antagonism of neuropeptide Y effects, and the correction of neuronal nitric oxide synthase (nNOS) imbalance. The beneficial effects of LCSD have never been associated with a detectable deterioration of cardiac performance. Finally, patients express a high degree of satisfaction with the procedure. In this review, we focus on the rationale, results and our personal approach to LCSD in patients with channelopathies such as long QT syndrome and catecholaminergic polymorphic ventricular tachycardia

Capecitabine-induced cardiotoxicity: More evidence or clinical approaches to protect the patients' heart?

Fluoropyrimidines, such as capecitabine and 5-fluorouracil, may cause cardiac toxicity. In recent years, the incidence of this side effect has increased and it is expected to further rise due to the population aging and the disproportionate incidence of breast and gastrointestinal cancers in older individuals. The spectrum of cardiac manifestations includes different signs and symptoms and the diagnosis may be difficult. Here, we report the case of a 43-year-old woman with advanced breast cancer who was rechallenged with a capecitabine-based regimen after experiencing a cardiac adverse event during the first fluoropyrimidine exposure. This real-practice case serves as a springboard for discussion about the current evidence on differential diagnosis of capecitabine-related cardiac toxicity, its risk factors, and the underpinning mechanisms of early onset. Moreover, we discussed whether a rechallenge with fluoropyrimidines could be safe in patients who had experienced a previous cardiac adverse even