Noninvasive electrocardiographic risk factors for sudden cardiac death in dilated ca rdiomyopathy: is ambulatory electrocardiography still relevant?

Risk stratification for sudden cardiac death in dilated cardiomyopathy is a field of constant debate, and the currently proposed criteria have been widely questioned due to their low positive and negative predictive value. In this study, we conducted a systematic review of the literature utilizing the PubMed and Cochrane library platforms, in order to gain insight about dilated cardiomyopathy and its arrhythmic risk stratification utilizing noninvasive risk markers derived mainly from 24 h electrocardiographic monitoring. The obtained articles were reviewed in order to register the various electrocardiographic noninvasive risk factors used, their prevalence, and their prognostic significance in dilated cardiomyopathy. Premature ventricular complexes, nonsustained ventricular tachycardia, late potentials on Signal averaged electrocardiography, T wave alternans, heart rate variability and deceleration capacity of the heart rate, all have both some positive and negative predictive value to identify patients in higher likelihood for ventricular arrhythmias and sudden cardiac death. Corrected QT, QT dispersion, and turbulence slope-turbulence onset of heart rate have yet to establish a predictive correlation in the literature. Although ambulatory electrocardiographic monitoring is frequently used in clinical practice in DCM patients, no single risk marker can be used for the selection of patients at high-risk for malignant ventricular arrhythmic events and sudden cardiac death who could benefit from the implantation of a defibrillator. More studies are needed in order to establish a risk score or a combination of risk factors with the purpose of selecting high-risk patients for ICD implantation in the context of primary prevention.

The Role of Genetics in Risk Stratification Strategy of Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is a heart disorder of diverse etiologies that affects millions of people worldwide, associated with increased mortality rate and high risk of sudden cardiac death. Patients with DCM are characterized by a wide range of clinical and pre-clinical phenotypes which are related with different outcomes. Dominant studies have failed to demonstrate the value of the left ventricular ejection fraction as the only indicator for patients' assessment and arrhythmic events prediction, thus making sudden cardiac death (SCD) risk stratification strategy improvement, more crucial than ever. The multifactorial two-step approach, examining non-invasive and invasive risk factors, represents an alternative process that enhances the accurate diagnosis and the individualization of patients' management. The role of genetic testing, regarding diagnosis and decision making, is of great importance, as pathogenic variants have been detected in several patients either they had a disease relative family history or not. At the same time there are specific genes mutations that have been associated with the prognosis of the disease. The aim of this review is to summarize the latest data regarding the genetic substrate of DCM and the value of genetic testing in patients' assessment and arrhythmic risk evaluation. Undoubtedly, the appropriate application of genetic testing and the thoughtful analysis of the results will contribute to the identification of patients who will receive major benefit from an implantable defibrillator as preventive treatment of SCD.

Reactive Vasodilation Predicts Mortality in Primary Systemic Light-Chain Amyloidosis.

Rationale: Cardiac involvement and hypotension dominate the prognosis of light-chain amyloidosis (AL). Evidence suggests that there is also peripheral vascular involvement in AL but its prognostic significance is unknown. Objective: To evaluate vascular dysfunction in patients with AL as a potential future area of intervention, we assessed the prognostic utility of flow-mediated dilatation (FMD), a marker of vascular reactivity, which is augmented under conditions of hypotension and autonomic dysfunction. Methods and Results: We prospectively evaluated 115 newly diagnosed untreated AL patients in whom FMD was measured. FMD in AL patients was significantly higher than age-, sex- and risk factors-matched controls (4.0% versus 2.32%; P=0.006) and comparable with control groups at lower cardiovascular risk (P>0.1). Amyloidosis patients presented increased plasma and exhaled markers of the NO pathway while their FMD significantly correlated with augmented sustained vasodilatation after sympathetic stimulation. Increased FMD (≥4.5%) was associated with early mortality (hazard ratio, 4.36; 95% CI, 1.41-13.5; P=0.010) and worse survival (hazard ratio, 2.11; 95% CI, 1.17-3.82; P=0.013), even after adjustment for Mayo stage, nerve involvement and low systolic blood pressure. This finding was confirmed in a temporal validation AL cohort (n=55; hazard ratio, 4.2; 95% CI, 1.45-12.3; P=0.008). FMD provided significant reclassification value over the best prognostic model (continuous Net Reclassification Index, 0.61; P=0.001). Finally, better hematologic response was associated with lower posttreatment FMD. Conclusions: FMD is relatively increased in AL and independently associated with inferior survival with substantial reclassification value. Reactive vasodilation merits further investigation as a novel risk biomarker in AL.Visual Overview: An online visual overview is available for this article.

Subclinical atherosclerosis and vascular stiffness in premenopausal women: association with NOS3 and CYBA polymorphisms.

Genetic variations of genes encoding the endothelial nitric oxide synthase (eNOS) and the NADH/NADPH oxidase system are related with atherosclerosis in the general population, but their significance in women is not sufficiently assessed. We investigated the potential association between the G894T polymorphism of the NOS3 gene and the C242T polymorphism of the CYBA gene with subclinical vascular disease. Seventy (70) healthy, normally ovulating, premenopausal women were recruited for this study. Venous blood samples were obtained for biochemical/hormonal assessment as well as for genotyping, using real-time PCR. Sonographically assessed indices of vascular structure and function included carotid and femoral intima-media thickness (IMT), flow-mediated dilation (FMD), carotid-femoral pulse-wave velocity (PWV), and augmentation index. The prevalence of wild type, heterozygote, and homozygote genotype was 44.3% (31/70), 54.3% (38/70), and 1.4% (1/70) for the G894T polymorphism and 38.6% (27/70), 31.4% (22/70), and 30.0% (21/70) for the C242T polymorphism, respectively. After multivariable adjustment, the hC242T polymorphism was a predictor of both internal carotid IMT (b-coefficient - 0.119, p = 0.011) and combined-IMT (b-coefficient - 0.061, p = 0.015). Systolic blood pressure, lipids, and hC242T determined values of FMD (b-coefficient - 1.604, p = 0.034). Concerning the NOS3 G894T polymorphism, carriers of the polymorphic variant had higher values of IMT and PWV compared to the wild-type subgroup (carotid bulb-IMT and PWV, heterozygotes/homozygotes vs wild type 0.7 ± 0.2 vs 0.6 ± 0.1 mm; 7.1 ± 0.8 vs 6.6 ± 0.7 m/s; p = 0.048 and p = 0.029, respectively). These differences, however, were rendered non-significant in the multivariable analysis. In healthy premenopausal women, the CYBA C242T polymorphism is an independent determinant of endothelial function and subclinical atherosclerosis of the carotid arteries. The NOS3 G894T polymorphic variant also correlated with atherosclerosis, an association probably mediated by the traditional risk factors for CVD. The relevance of these findings in the clinical setting remains to be elucidated.

Aggressive Rhythm Control Strategy in Atrial Fibrillation Patients Presenting at the Emergency Department: The HEROMEDICUS Study Design and Initial Results.

Atrial fibrillation has progressively become a more common reason for emergency department visits, representing 0.5% of presenting reasons. Registry data have indicated that about 60% of atrial fibrillation patients who present to the emergency department are admitted, emphasizing the need for more efficient management of atrial fibrillation in the acute phase. Management of atrial fibrillation in the setting of the emergency department varies between countries and healthcare systems. The most plausible reason to justify a conservative rather than an aggressive strategy in the management of atrial fibrillation is the absence of specific guidelines from diverse societies. Several trials of atrial fibrillation treatment strategies, including cardioversion, have demonstrated that atrial fibrillation in the emergency department can be treated safely and effectively, avoiding admission. In the present study, we present the epidemiology and characteristics of atrial fibrillation patients presenting to the emergency department, as well as the impact of diverse management strategies on atrial-fibrillation-related hospital admissions. Lastly, the design and initial data of the HEROMEDICUS protocol will be presented, which constitutes an electrophysiology-based aggressive rhythm control strategy in patients with atrial fibrillation in the emergency department setting.

Cardiac mechanics in response to proteasome inhibition: a prospective study.

AIM: Ubiquitin-Proteasome System (UPS) is of paramount importance regarding the function of the myocardial cell. Consistently, inhibition of this system has been found to affect myocardium in experimental models; yet, the clinical impact of UPS inhibition on cardiac function has not been comprehensively examined. Our aim was to gain insight into the effect of proteasome inhibition on myocardial mechanics in humans. METHODS AND RESULTS: We prospectively evaluated 48 patients with multiple myeloma and an indication to receive carfilzomib, an irreversible proteasome inhibitor. All patients were initially evaluated and underwent echocardiography with speckle tracking analysis. Carfilzomib was administered according to Kd treatment protocol. Follow-up echocardiography was performed at the 3rd and 6th month. Proteasome activity (PrA) was measured in peripheral blood mononuclear cells.At 3 months after treatment, we observed early left ventricular (LV) segmental dysfunction and deterioration of left atrial (LA) remodelling, which was sustained and more pronounced than that observed in a cardiotoxicity control group. At 6 months, LV and right ventricular functions were additionally attenuated (P < 0.05 for all). These changes were independent of blood pressure, endothelial function, inflammation, and cardiac injury levels. Changes in PrA were associated with changes in global longitudinal strain (GLS), segmental LV strain, and LA markers (P < 0.05 for all). Finally, baseline GLS < -18% or LA strain rate > 1.71 were associated with null hypertension events. CONCLUSION: Inhibition of the UPS induced global deterioration of cardiac function.

The Role of Antithrombotic Therapy in Heart Failure.

Heart failure is a major contributor to global morbidity and mortality burden affecting approximately 1-2% of adults in developed countries, mounting to over 10% in individuals aged >70 years old. Heart failure is characterized by a prothrombotic state and increased rates of stroke and thromboembolism have been reported in heart failure patients compared with the general population. However, the impact of antithrombotic therapy on heart failure remains controversial. Administration of antiplatelet or anticoagulant therapy is the obvious (and well-established) choice in heart failure patients with cardiovascular comorbidity that necessitates their use, such as coronary artery disease or atrial fibrillation. In contrast, antithrombotic therapy has not demonstrated any clear benefit when administered for heart failure per se, i.e. with heart failure being the sole indication. Randomized studies have reported decreased stroke rates with warfarin use in patients with heart failure with reduced left ventricular ejection fraction, but at the expense of excessive bleeding. Non-vitamin K oral anticoagulants have shown a better safety profile in heart failure patients with atrial fibrillation compared with warfarin, however, current evidence about their role in heart failure with sinus rhythm is inconclusive and further research is needed. In the present review, we discuss the role of antithrombotic therapy in heart failure (beyond coronary artery disease), aiming to summarize evidence regarding the thrombotic risk and the role of antiplatelet and anticoagulant agents in patients with heart failure.

The Mediterranean Diet Benefit on Cardiovascular Hemodynamics and Erectile Function in Chronic Heart Failure Male Patients by Decoding Central and Peripheral Vessel Rheology.

BACKGROUND: Mediterranean diet was evaluated on erectile performance and cardiovascular hemodynamics, in chronic heart failure patients. METHODS: 150 male stable heart failure patients were enrolled in the study (62 ± 10 years, New York Heart Association (NYHA) classes I-II, ejection fraction ≤40%). A detailed echocardiographic evaluation including estimation of the global longitudinal strain of the left ventricle and the systolic tissue doppler velocity of the tricuspid annulus was performed. Erectile dysfunction severity was assessed by the Sexual Health Inventory for Men-5 (SHIM-5) score. Adherence to the Mediterranean diet was evaluated by the MedDietScore. RESULTS: The SHIM-5 score was positively correlated with the MedDietScore (p = 0.006) and augmentation index (p = 0.031) and inversely correlated with age (p = 0.002). MedDietScore was negatively associated with intima-media-thickness (p < 0.001) and serum prolactin levels (p = 0.05). Multi-adjusted analysis revealed that the inverse relation of SHIM-5 and prolactin levels remained significant only among patients with low adherence to the Mediterranean diet (p = 0.012). CONCLUSION: Consumption of Mediterranean diet benefits cardiovascular hemodynamics, while suppressing serum prolactin levels. Such physiology may enhance erectile ability independently of the of the left ventricle ejection fraction.

Azilsartan as a Potent Antihypertensive Drug with Possible Pleiotropic Cardiometabolic Effects: A Review Study.

BACKGROUND: Hypertension related cardiovascular (CV) complications could be amplified by the presence of metabolic co-morbidities. Azilsartan medoxomil (AZL-M) is the eighth approved member of angiotensin II receptor blockers (ARBs), a drug class of high priority in the management of hypertensive subjects with diabetes mellitus type II (DMII). METHODS: Under this prism, we performed a systematic review of the literature for all relevant articles in order to evaluate the efficacy, safety, and possible clinical role of AZL-M in hypertensive diabetic patients. RESULTS: AZL-M was found to be more effective in terms of reducing indices of blood pressure over alternative ARBs or angiotensin-converting enzyme (ACE) inhibitors with minimal side effects. Preclinical studies have established pleiotropic effects for AZL-M beyond its primary antihypertensive role through differential gene expression, up-regulation of membrane receptors and favorable effect on selective intracellular biochemical and pro-atherosclerotic pathways. CONCLUSION: Indirect but accumulating evidence from recent literature supports the efficacy and safety of AZL-M among diabetic patients. However, no clinical data exist to date that evince a beneficial role of AZL-M in patients with metabolic disorders on top of its antihypertensive effect. Further clinical studies are warranted to assess the pleiotropic cardiometabolic benefits of AZL-M that are derived from preclinical research.