Echocardiographic Normal Reference Ranges for Non-invasive Myocardial Work Parameters in Pediatric Age: Results From an International Multi-Center Study

This international multi-center study aimed to demonstrate the feasibility and reliability of non-invasive myocardial work (MW) parameters in the pediatric population, and to provide normal reference ranges for this useful echocardiographic tool in this specific subset of patients

Takotsubo Syndrome after Pacemaker Implantation: A Systematic Review

Background: Takotsubo syndrome (TTS) is an acute cardiac condition characterized by a temporary wall motion abnormality of the left ventricle that mimics an acute coronary syndrome (ACS). TTS usually occurs following emotional or physical triggering event. More recently, sporadic cases of TTS arising after pacemaker implantation were reported. Methods: We performed a systematic review of the available literature to provide a comprehensive overview of the current knowledge about pacemaker implantation-induced TTS. Results: The articles selected included case reports and one registry on 28 patients. Most cases occurred in women (75%), encompassing a broad age range. The mean age of the cases described was 74 years. Full recovery of cardiac function was reported in most cases (92.3%), with largely varying recovery times, on average 7 weeks. The most common comorbidity was arterial hypertension and the average ejection fraction at admission was approximately 62%. Clinical severity ranges from asymptomatic cases to severe clinical heart failure syndrome. Altogether the case fatality rate was 3.6%. Conclusions: For rare it might be, awareness about the potential to develop TTS after pacemaker implantation should prompt careful clinical monitoring, with daily electrocardiogram (ECG) monitoring and at least one echocardiographic examination prior to patients’ discharge to allow early diagnosis and minimize the clinical risk

Prediction of Significant Coronary Artery Disease Through Advanced Echocardiography: Role of Non-invasive Myocardial Work

Background: Non-invasive prediction of critical coronary artery stenosis (CAST) in patients with coronary artery disease (CAD) is challenging. Strain parameters can often capture an impairment of regional longitudinal function; however, they are load dependent. A novel non-invasive method to estimate Myocardial Work (MW) has been recently proposed, showing a strong correlation with invasive work measurements. Our aim was to investigate the ability of non-invasive MW to predict the ischaemic risk area underlying a CAST. Methods and Results: The study population comprises 80 individuals: 50 patients with CAST and 30 controls (CTRL). Echocardiography recordings were obtained before coronary angiography to measure global longitudinal strain (GLS), Myocardial Work Index (MWI), Myocardial Constructive Work (MCW), Myocardial Wasted work (MWW), Myocardial Work Efficiency (MWE). Global MWI (p = 0.048), MWE (p < 0.001), and MCW (p = 0.048) at baseline were significantly reduced in patients with CAST compared to controls (p < 0.05). Regional MWE within the myocardial segments underlying the CAST, but not LS, was significantly reduced compared to non-target segments (p < 0.001). At ROC analysis, the diagnostic performance to predict CAST for regional MWE (AUC = 0.920, p < 0.001) was higher compared to both regional post-systolic shortening index (PSI) (AUC = 0.600, p = 0.129) and regional LS (AUC = 0.546, p = 0.469). Conclusions: Non-invasive estimation of MW work indices is able to predict a CAST before invasive angiography

Mechanisms of Cardiovascular Calcification and Experimental Models: Impact of Vitamin K Antagonists

Cardiovascular calcification is a multifactorial and complex process involving an array of molecular mechanisms eventually leading to calcium deposition within the arterial walls. This process increases arterial stiffness, decreases elasticity, influences shear stress events and is related to an increased risk of morbidity and mortality associated with cardiovascular disease. In numerous in vivo and in vitro models, warfarin therapy has been shown to cause vascular calcification in the arterial wall. However, the exact mechanisms of calcification formation with warfarin remain largely unknown, although several molecular pathways have been identified. Circulating miRNA have been evaluated as biomarkers for a wide range of cardiovascular diseases, but their exact role in cardiovascular calcification is limited. This review aims to describe the current state-of-the-art research on the impact of warfarin treatment on the development of vascular calcification and to highlight potential molecular targets, including microRNA, within the implicated pathways

Non-Invasive Myocardial Work in Patients with Severe Aortic Stenosis

Changes in cardiac mechanics after correction of severe Aortic Stenosis (AS) are under-investigated. Myocardial Work (MW) is emerging as a useful non-invasive correlate of invasively measured myocardial performance and oxygen consumption. The aim of this study was to assess the usefulness of MW in the clinical management of patients with AS undergoing transcatheter aortic valve implantation (TAVI). Consecutive patients referred for TAVI were included in this observational study. Echocardiograms were performed before and after TAVI to measure Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW), and Global Work Efficiency (GWE). Mean transvalvular gradient was significantly improved (p p p p = 0.241) nor GWE (p = 0.854) were significantly reduced after TAVI. Patients with a low flow low gradient (LF-LG) AS had lower left ventricular ejection fraction (LVEF) (p p p p p = 0.003). The improvement in GWI and GCW observed after TAVI in the general study population were abolished among LF-LG patients. In conclusion, non-invasive MW might be useful to further classify patients with AS and to predict non responders

Transcoronary concentration gradients of circulating microRNAs in heart failure

Aims: Circulating levels of microRNAs (miRNAs) are emergent promising biomarkers for cardiovascular disease. Altered expression of miRNAs has been related to heart failure (HF) and cardiac remodelling. We measured the concentration gradients across the coronary circulation to assess their usefulness to diagnose HF of different aetiologies. Methods and results: Circulating miRNAs were measured in plasma samples simultaneously obtained from the aorta and the coronary venous sinus in patients with non-ischaemic HF (NICM-HF, n\ua0= 23) ischaemic HF (ICM-HF, n\ua0= 41), and in control patients (n\ua0= 11). A differential modulation of circulating levels of miR-423, -34a, -21-3p, -126, -199 and -30a was found across the aetiology groups. Interestingly, a positive transcoronary gradient was found for miR-423 (P\ua0< 0.001) and miR-34a (P\ua0< 0.001) only in the ICM-HF group. On the contrary, a positive gradient was found for miR-21-3p (P\ua0< 0.001) and miR-30a (P\ua0= 0.030) only in the NICM-HF group. Finally, no significant variations were observed in the transcoronary gradient of miR-126 or miR-199. Conclusions: The present findings suggest that circulating levels of miRNAs are differentially expressed in patients with HF of different aetiologies. The presence of a transcoronary concentration gradient suggests a selective release of miRNAs by the failing heart into the coronary circulation. The presence of aetiology-specific transcoronary concentration gradients in HF patients might provide important information to better understand their role in HF, and suggests they could be useful biomarkers to distinguish HF of different aetiologies

Effects of the Covid-19 pandemic on the formation of fellows in training in cardiology

none16noCOronaVIrus Disease-19 (COVID-19) had a huge impact on human health and economy. However, to this date, the effects of the pandemic on the training of young cardiologists are only partially known. To assess the consequences of the pandemic on the education of the cardiologists in training, we performed a 23-item national survey that has been delivered to 1443 Italian cardiologists in training, registered in the database of the Italian Society of Cardiology (SIC). Six hundred and thirty-three cardiologists in training participated in the survey. Ninety-five percent of the respondents affirmed that the training programme has been somewhat stopped or greatly jeopardized by the pandemic. For 61% of the fellows in training (FITs), the pandemic had a negative effect on their education. Moreover, 59% of the respondents believe that they would not be able to fill the gap gained during that period over the rest of their training. A negative impact on the psycho-physical well being has been reported by 86% of the FITs. The COVID-19 pandemic had an unparalleled impact on the education, formation and mental state of the cardiologists in training. Regulatory agencies, universities and politicians should make a great effort in the organization and reorganization of the teaching programs of the cardiologists of tomorrow.noneStrangio, Antonio; Leo, Isabella; Spaccarotella, Carmen Anna Maria; Barillà, Francesco; Basso, Cristina; Calabrò, Maria Pia; Curcio, Antonio; Filardi, Pasquale Perrone; Mancone, Massimo; Mercuro, Giuseppe; Muscoli, Saverio; Nodari, Savina; Pedrinelli, Roberto; Romeo, Francesco; Sinagra, Gianfranco; Indolfi, CiroStrangio, Antonio; Leo, Isabella; Spaccarotella, Carmen Anna Maria; Barillà, Francesco; Basso, Cristina; Calabrò, Maria Pia; Curcio, Antonio; Filardi, Pasquale Perrone; Mancone, Massimo; Mercuro, Giuseppe; Muscoli, Saverio; Nodari, Savina; Pedrinelli, Roberto; Romeo, Francesco; Sinagra, Gianfranco; Indolfi, Cir

Effects of the Covid-19 pandemic on the formation of fellows in training in cardiology

COronaVIrus Disease-19 (COVID-19) had a huge impact on human health and economy. However, to this date, the effects of the pandemic on the training of young cardiologists are only partially known. To assess the consequences of the pandemic on the education of the cardiologists in training, we performed a 23-item national survey that has been delivered to 1443 Italian cardiologists in training, registered in the database of the Italian Society of Cardiology (SIC). Six hundred and thirty-three cardiologists in training participated in the survey. Ninety-five percent of the respondents affirmed that the training programme has been somewhat stopped or greatly jeopardized by the pandemic. For 61% of the fellows in training (FITs), the pandemic had a negative effect on their education. Moreover, 59% of the respondents believe that they would not be able to fill the gap gained during that period over the rest of their training. A negative impact on the psycho-physical well being has been reported by 86% of the FITs. The COVID-19 pandemic had an unparalleled impact on the education, formation and mental state of the cardiologists in training. Regulatory agencies, universities and politicians should make a great effort in the organization and reorganization of the teaching programs of the cardiologists of tomorrow

Distinctive germline expression of class I human leukocyte antigen (HLA) alleles and DRB1 heterozygosis predict the outcome of patients with non-small cell lung cancer receiving PD-1/PD-L1 immune checkpoint blockade

Background Nivolumab is a human monoclonal antibody against programmed cell death receptor-1 (PD-1) able to rescue quiescent tumor infiltrating cytotoxic T lymphocytes (CTLs) restoring their ability to kill target cells expressing specific tumor antigen-derived epitope peptides bound to homologue human leukocyte antigen (HLA) molecules. Nivolumab is currently an active but expensive therapeutic agent for metastatic non-small cell lung cancer (mNSCLC), producing, in some cases, immune-related adverse events (irAEs). At the present, no reliable biomarkers have been validated to predict either treatment response or adverse events in treated patients.Methods We performed a retrospective multi-institutional analysis including 119 patients with mNSCLC who received PD-1 blockade since November 2015 to investigate the predictive role of germinal class I HLA and DRB1 genotype. We investigated the correlation among patients’ outcome and irAEs frequency with specific HLA A, B, C and DRB1 alleles by reverse sequence-specific oligonucleotide (SSO) DNA typing.Results A poor outcome in patients negative for the expression of two most frequent HLA-A alleles was detected (HLA: HLA-A*01 and or A*02; progression-free survival (PFS): 7.5 (2.8 to 12.2) vs 15.9 (0 to 39.2) months, p=0.01). In particular, HLA-A*01-positive patients showed a prolonged PFS of 22.6 (10.2 to 35.0) and overall survival (OS) of 30.8 (7.7 to 53.9) months, respectively. We also reported that HLA-A and DRB1 locus heterozygosis (het) were correlated to a worse OS if we considered het in the locus A; in reverse, long survival was correlated to het in DRB1.Conclusions This study demonstrate that class I and II HLA allele characterization to define tumor immunogenicity has relevant implications in predicting nivolumab efficacy in mNSCLC and provide the rationale for further prospective trials of cancer immunotherapy