Eplerenone Survival Benefits in Heart Failure Patients Post-Myocardial Infarction

Reduced left ventricular ejection fraction (≤40%) and/or signs of clinical heart failure after acute myocardial infarction (AMI) are associated with a relatively high incidence of mortality and hospitalization for heart failure. The potential of eplerenone to impact on mortality and morbidity of post-infarction heart failure patients was the subject of the EPHESUS trial (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study). That trial concluded that eplerenone reduced total mortality by 31%, cardiovascular mortality by 32% and sudden cardiac death by 37% within 30 days of randomization after AMI. Risk reduction in mortality with eplerenone seemed to occur as early as 10 days after randomization and continued through the end of the study. In conclusion, eplerenone improves survival in heart failure patients post-AMI

Mid-ventricular obstructive hypertrophic cardiomyopathy

Mid-ventricular obstructive hypertrophic cardiomyopathy was diagnosed in a 72-year-old woman, referred to our hospital because of an episode of syncope. It was characterized by an abnormal ECG (ST segment elevation in leads V3 through V6 ) and the presence of pressure gradient between apical and basal sites in the left ventricle, asymmetric left ventricular hypertrophy and an apical aneurysm on echocardiography

Uncommon Cardiomyopathies

Anderson-Fabry Disease (AFD) is an X-linked recessive lysosomal disorder, leading to multisystemic disease because of abnormal glycosphyngolipids widespread accumulation, the result of α-galactosidaseA deficient activity. Cardiac involvement is common; includes left ventricular hypertrophy and gradually impairing cardiac function. Although the disease is unveiled in childhood and culminates in cardiac, cerebrovascular and end-stage renal disease, diagnosis is often delayed or missed. Recently established enzyme replacement therapy (ERT) may improve most of the disease’s manifestations. Early diagnosis is thus crucial for AFD patient management. Isolated non-compaction of the ventricular myocardium (IVNC) is a rare congenital form of cardiomyopathy. It is characterized by the postnatal persistence of the embryonic pattern of myoarchitecture, consistent of prominent trabeculations and deep intertrabecular recesses, and assumed to occur as a consequence of intrauterine arrest of myocardial compaction. Contemporary diagnosis has been facilitated by the introduction of specific morphologic criteria by echocardiography and magnetic resonance imaging. Management issues revolve around the management of heart failure, arrhythmias and thromboembolic events in order to prevent the significant morbidity and even mortality that has been associated with this entity. Significant overlapping with many other forms of cardiomyopathies suggest that non-compaction may be a morphologic trait rather than a distinct cardiomyopathy

Right ventricular outflow tract endocardial unipolar substrate mapping: implications in risk stratification of Brugada syndrome

Brugada syndrome (BrS) is a complex arrhythmogenic disease displaying electrical and micro-structural abnormalities mainly located at the epicardium of the right ventricular outflow tract (RVOT). It is well-known that fibrosis, fatty infiltration, inflammation and reduced gap junction expression have been demonstrated at the epicardial anterior aspect of the RVOT providing the arrhythmogenic substrate for ventricular arrhythmic events in BrS. A number of models have been proposed for the risk stratification of patients with BrS. Endocardial unipolar electroanatomical mapping is an emerging tool that has been reintroduced to identify and quantify epicardial electrical abnormalities. Interestingly, current findings correlate the presence of large-sized endocardial unipolar electroanatomical abnormalities with either ventricular fibrillation inducibility during programmed ventricular stimulation or symptom status. This review aims to present existing data about the role of endocardial unipolar electroanatomical mapping for the identification of RVOT epicardial abnormalities as well as its potential clinical implications in risk stratification of BrS

Application of next generation sequencing in cardiology: current and future precision medicine implications

Inherited cardiovascular diseases are highly heterogeneous conditions with multiple genetic loci involved. The application of advanced molecular tools, such as Next Generation Sequencing, has facilitated the genetic analysis of these disorders. Accurate analysis and variant identification are required to maximize the quality of the sequencing data. Therefore, the application of NGS for clinical purposes should be limited to laboratories with a high level of technological expertise and resources. In addition, appropriate gene selection and variant interpretation can result in the highest possible diagnostic yield. Implementation of genetics in cardiology is imperative for the accurate diagnosis, prognosis and management of several inherited disorders and could eventually lead to the realization of precision medicine in this field. However, genetic testing should also be accompanied by an appropriate genetic counseling procedure that clarifies the significance of the genetic analysis results for the proband and his family. In this regard, a multidisciplinary collaboration among physicians, geneticists, and bioinformaticians is imperative. In the present review, we address the current state of knowledge regarding genetic analysis strategies employed in the field of cardiogenetics. Variant interpretation and reporting guidelines are explored. Additionally, gene selection procedures are accessed, with a particular emphasis on information concerning gene-disease associations collected from international alliances such as the Gene Curation Coalition (GenCC). In this context, a novel approach to gene categorization is proposed. Moreover, a sub-analysis is conducted on the 1,502,769 variation records with submitted interpretations in the Clinical Variation (ClinVar) database, focusing on cardiology-related genes. Finally, the most recent information on genetic analysis's clinical utility is reviewed

Right ventricular outflow tract endocardial unipolar substrate mapping: implications in risk stratification of Brugada syndrome

Brugada syndrome (BrS) is a complex arrhythmogenic disease displaying electrical and micro-structural abnormalities mainly located at the epicardium of the right ventricular outflow tract (RVOT). It is well-known that fibrosis, fatty infiltration, inflammation and reduced gap junction expression have been demonstrated at the epicardial anterior aspect of the RVOT providing the arrhythmogenic substrate for ventricular arrhythmic events in BrS. A number of models have been proposed for the risk stratification of patients with BrS. Endocardial unipolar electroanatomical mapping is an emerging tool that has been reintroduced to identify and quantify epicardial electrical abnormalities. Interestingly, current findings correlate the presence of large-sized endocardial unipolar electroanatomical abnormalities with either ventricular fibrillation inducibility during programmed ventricular stimulation or symptom status. This review aims to present existing data about the role of endocardial unipolar electroanatomical mapping for the identification of RVOT epicardial abnormalities as well as its potential clinical implications in risk stratification of BrS. [Abstract copyright: © 2022 The Author(s). Published by IMR Press.

Clinical Significance of Epsilon Waves in Arrhythmogenic Cardiomyopathy

Epsilon Waves in ACM IntroductionEpsilon waves are hallmark features of arrhythmogenic cardiomyopathy (ACM) but information about their clinical significance is variable. We evaluated epsilon wave prevalence, characteristics, and their clinical significance in an ACM population. Methods and ResultsEighty-six unselected patients fulfilling the 2010 Task Force criteria were enrolled. Seventy-six of them were carriers of desmosomal mutations. All subjects were serially evaluated with standard 12-lead ECG and 2-dimensional echocardiography. Epsilon waves were evaluated in all precordial and inferior leads. Novel parameters assessed included their duration and precordial/inferior lead extension. Twenty-five subjects (29%) had epsilon waves that were present in lead V3 and beyond in 9, and in the inferior leads in 7. Epsilon waves were associated with right ventricular outflow tract (RVOT) (P = 0.001) but not RV posterior wall (P = 0.21), RV apex (P = 0.30), or left ventricular (P = 0.94) wall motion abnormalities. Patients with epsilon waves had increased RVOT diameter (P < 0.0001). Extension of epsilon waves in lead V3 and beyond was associated with increased epsilon wave duration (P = 0.002) and RVOT diameter (P = 0.04). The duration of epsilon waves was positively correlated with RVOT diameter (r = 0.70, P = 0.0001). Epsilon waves were also associated with episodes of sustained ventricular tachycardia (P = 0.004) but not with heart failure (P = 0.41) or sudden cardiac death (P = 0.31). ConclusionDetection of epsilon waves on 12-lead ECG reflects significant RVOT involvement, which was associated with episodes of sustained ventricular tachycardia but not sudden cardiac death

Right ventricular outflow tract electroanatomical abnormalities in asymptomatic and high-risk symptomatic patients with Brugada syndrome: Evidence for a new risk stratification tool?

Introduction: Microstructural abnormalities at the epicardium of the right ventricular outflow tract (RVOT) may provide the arrhythmia substrate in Brugada syndrome (BrS). Endocardial unipolar electroanatomical mapping allows the identification of epicardial abnormalities. We evaluated the clinical implications of an abnormal endocardial substrate as perceived by high-density electroanatomical mapping (HDEAM) in patients with BrS. Methods: Fourteen high-risk BrS patients with aborted sudden cardiac death (SCD) (12 males, mean age: 41.9 ± 11.8 years) underwent combined endocardial-epicardial HDEAM of the right ventricle/RVOT, while 40 asymptomatic patients (33 males, mean age: 42 ± 10.7 years) underwent endocardial HDEAM. Based on combined endocardial-epicardial procedures, endocardial HDEAM was considered abnormal in the presence of low voltage areas (LVAs) more than 1 cm2 with bipolar signals less than 1 mV and unipolar signals less than 5.3 mV. Programmed ventricular stimulation (PVS) was performed in all patients. Results: The endocardial unipolar LVAs were colocalized with epicardial bipolar LVAs (p = .0027). Patients with aborted SCD exhibited significantly wider endocardial unipolar (p < .01) and bipolar LVAs (p < .01) compared with asymptomatic individuals. A substrate size of unipolar LVAs more than 14.5 cm2 (area under the curve [AUC]: 0.92, p < .001] and bipolar LVAs more than 3.68 cm2 (AUC: 0.82, p = .001) distinguished symptomatic from asymptomatic patients. Patients with ventricular fibrillation inducibility (23/54) demonstrated broader endocardial unipolar (p < .001) and bipolar LVAs (p < .001) than noninducible patients. The presence of unipolar LVAs more than 13.5 cm2 (AUC: 0.95, p < .001) and bipolar LVAs more than 2.97 cm2 (AUC: 0.78, p < .001) predicted a positive PVS. Conclusion: Extensive endocardial electroanatomical abnormalities identify high-risk patients with BrS. Endocardial HDEAM may allow risk stratification of asymptomatic patients referred for PVS