The effects of gender on electrical therapies for the heart: physiology, epidemiology, and access to therapies: A report from the XII Congress of the Italian Association on Arrhythmology and Cardiostimulation (AIAC)

The difference between men and women is clear even just by looking at an electrocardiogram: females present higher resting heart rate, a shorter QRS complex length and greater corrected QT interval. The development of these differences from pubertal age onward suggests that sexual hormones play a key role, although their effect is far from being completely understood. Different incidences between sexes have been reported for many arrhythmias, both ventricular and supraventricular, and also for sudden cardiac death. Moreover, arrhythmias are an important issue during pregnancy, both for diagnosis and treatment. Interestingly, cardiovascular structural and electrophysiological remodelling promoted by exercise training enhances this 'gender effect'. Despite all these relevant issues, we lack gender specific recommendations in the current guidelines for electrical therapies for heart rhythm disorders and heart failure. Even more, we continue to see that fewer women are included in clinical trials and are less referred than men for these treatments

Mathematical modelling of the action potential of human embryonic stem cell derived cardiomyocytes

BACKGROUND: Human embryonic stem cell derived cardiomyocytes (hESC-CMs) hold high potential for basic and applied cardiovascular research. The development of a reliable simulation platform able to mimic the functional properties of hESC-CMs would be of considerable value to perform preliminary test complementing in vitro experimentations. METHODS: We developed the first computational model of hESC-CM action potential by integrating our original electrophysiological recordings of transient-outward, funny, and sodium-calcium exchanger currents and data derived from literature on sodium, calcium and potassium currents in hESC-CMs. RESULTS: The model is able to reproduce basal electrophysiological properties of hESC-CMs at 15 40 days of differentiation (Early stage). Moreover, the model reproduces the modifications occurring through the transition from Early to Late developmental stage (50-110, days of differentiation). After simulated blockade of ionic channels and pumps of the sarcoplasmic reticulum, Ca2+ transient amplitude was decreased by 12% and 33% in Early and Late stage, respectively, suggesting a growing contribution of a functional reticulum during maturation. Finally, as a proof of concept, we tested the effects induced by prototypical channel blockers, namely E4031 and nickel, and their qualitative reproduction by the model. CONCLUSIONS: This study provides a novel modelling tool that may serve useful to investigate physiological properties of hESC-CMs

Tannin based foams modified to be semi-conductive: Synthesis and characterization

Introduction Hypertrophic cardiomyopathy (HCM) is a cause of sudden arrhythmic death, but the understanding of its pro-arrhythmic mechanisms and an effective pharmacological treatment are lacking. HCM electrophysiological remodelling includes both increased inward and reduced outward currents, but their role in promoting repolarisation abnormalities remains unknown. The goal of this study is to identify key ionic mechanisms driving repolarisation abnormalities in human HCM, and to evaluate anti-arrhythmic effects of single and multichannel inward current blocks. Methods Experimental ionic current, action potential (AP) and Ca2 +-transient (CaT) recordings were used to construct populations of human non-diseased and HCM AP models (n = 9118), accounting for inter-subject variability. Simulations were conducted for several degrees of selective and combined inward current block. Results Simulated HCM cardiomyocytes exhibited prolonged AP and CaT, diastolic Ca2 + overload and decreased CaT amplitude, in agreement with experiments. Repolarisation abnormalities in HCM models were consistently driven by L-type Ca2 + current (ICaL) re-activation, and ICaL block was the most effective intervention to normalise repolarisation and diastolic Ca2 +, but compromised CaT amplitude. Late Na+ current (INaL) block partially abolished repolarisation abnormalities, with small impact on CaT. Na+/Ca2 + exchanger (INCX) block effectively restored repolarisation and CaT amplitude, but increased Ca2 + overload. Multichannel block increased efficacy in normalising repolarisation, AP biomarkers and CaT amplitude compared to selective block. Conclusions Experimentally-calibrated populations of human AP models identify ICaL re-activation as the key mechanism for repolarisation abnormalities in HCM, and combined INCX, INaL and ICaL block as effective anti-arrhythmic therapies also able to partially reverse the HCM electrophysiological phenotype

The importance of integrated left atrial evaluation: From hypertension to heart failure with preserved ejection fraction

Aim: Functional analysis and measurement of left atrium are an integral part of cardiac evaluation, and they represent a key element during non-invasive analysis of diastolic function in patients with hypertension (HT) and/or heart failure with preserved ejection fraction (HFpEF). However, diastolic dysfunction remains quite elusive regarding classification, and atrial size and function are two key factors for left ventricular (LV) filling evaluation. Chronic left atrial (LA) remodelling is the final step of chronic intra-cavitary pressure overload, and it accompanies increased neurohormonal, proarrhythmic and prothrombotic activities. In this systematic review, we aim to purpose a multi-modality approach for LA geometry and function analysis, which integrates diastolic flow with LA characteristics and remodelling through application of both traditional and new diagnostic tools. Methods: The most important studies published in the literature on LA size, function and diastolic dysfunction in patients with HFpEF, HT and/or atrial fibrillation (AF) are considered and discussed. Results: In HFpEF and HT, pulsed and tissue Doppler assessments are useful tools to estimate LV filling pressure, atrio-ventricular coupling and LV relaxation but they need to be enriched with LA evaluation in terms of morphology and function. An integrated evaluation should be also applied to patients with a high arrhythmic risk, in whom eccentric LA remodelling and higher LA stiffness are associated with a greater AF risk. Conclusion: Evaluation of LA size, volume, function and structure are mandatory in the management of patients with HT, HFpEF and AF. A multi-modality approach could provide additional information, identifying subjects with more severe LA remodelling. Left atrium assessment deserves an accurate study inside the cardiac imaging approach and optimised measurement with established cut-offs need to be better recognised through multicenter studies

Resistant hypertension: an overview

Despite the availability of anti-hypertensive medications with proven efficacy and good tolerability, many hypertensive patients have blood pressure levels(BP) not at the goals set by international societies. Some of these patients are either non-adherent to the prescribed drugs or not optimally treated. However, a proportion, despite adequate treatment, has resistant hypertension(RH) defined as office BP above goal despite the use of ≥3 antihypertensive medications at maximally tolerated doses (one ideally being a diuretic). Diagnosis of RH based upon office measurements, however, needs confirmation through 24-h BP monitoring to exclude "white coat" RH since cardiovascular events and mortality rates follow mean ambulatory BPs. Although several studies have approached the issue of the prevalence of RH in the hypertensive population, its prevalence is by and large based upon reasonable but approximate estimates for reasons detailed in the text. Standardized combination therapy based upon angiotensin converting enzyme inhibitors or angiotensin receptor blockers, amlodipine or other dihydropiridine calcium channel blockers and a diuretic (thiazide and thiazide-like compounds as cholrthalidone or indapamide) has been advocated to treat RH with spironolactone as fourth add-on drug. Interventional procedures such as renal denervation have been devised to treat RH and implemented in some patients with RH not responding to medical treatment. However, the results of this interventional procedure have insofar not been positive. It is unclear whether RH constitutes a specific phenotype of EH or should rather be considered a more serious form of uncontrolled hypertension. Whatever the case, its presence associates with and increased cardio- and cerebrovascular risk and deserves, therefore, particular care

Arterial hypertension and atrial fibrillation: standard and advanced echocardiography from diagnosis to prognostication

Structural changes in left and right cardiac chambers that occur in arterial hypertension (AH) may lead to an increased risk of atrial fibrillation. Considering that AH is currently the most common cardiovascular disease in the general population, it represents a major risk factor for atrial fibrillation development. This review explores the complex relationship between atrial fibrillation and AH, starting from its pathophysiological basis. It focuses on the role of echocardiography in the management of hypertensive and atrial fibrillation patients, with emphasis on what should be evaluated about left ventricular remodeling, diastolic and systolic function, left atrial (LA) size and function and right ventricular deformation in patients with AH

Myocardial 123I-metaiodobenzylguanidine imaging in hypertension and left ventricular hypertrophy

Sympathetic nervous system plays a pivotal role in essential hypertension and in the development of left ventricular hypertrophy. Moreover, cardiac sympathetic dys-regulation has been demonstrated as a key con-causal factor in the genesis and progression of pathologic conditions such as congestive heart failure and ischemic heart disease to which hypertension predisposes as a risk factor. However, despite its fundamental role in cardiac pathophysiology, the evaluation of cardiac sympathetic nervous system has never gained a wide clinical application, remaining mostly a research tool. In this context, nuclear imaging techniques are the only modalities to allow the direct evaluation of cardiac sympathetic nervous integrity, giving the chance to obtain objective measures of the sympathetic tone. This review, while summarizing the general profile of currently available tests for autonomic evaluation, focuses on 123I-metaiodobenzylguanidine nuclear imaging as a preferential tool to assess cardiac sympathetic status. Specifically, the review discusses the available evidence on cardiac 123I-metaiodobenzylguanidine scintigraphy in arterial hypertension and left ventricular hypertrophy and its diagnostic and prognostic potential in congestive heart failure and ischemic heart disease