Global longitudinal strain predicts outcome after MitraClip implantation for secondary mitral regurgitation

AIM: The aim of this study was to assess preoperative determinants, prevalence, and prognostic impact of left ventricular (LV) reverse remodeling (LVRR) in patients with secondary mitral regurgitation (SMR), undergoing MitraClip implantation (MCi). METHODS: From March 2012 to January 2015, a total of 41 consecutive patients with moderate-to-severe SMR treated successfully with MCi were enrolled. All patients underwent clinical and echocardiographic follow-up after MCi. Global longitudinal strain (GLS) was obtained using two dimensional speckle tracking analysis. A reduction in LV end-systolic volume more than 10% compared with baseline was considered as a marker of LVRR. Patients were divided into two groups according to the presence or absence of LVRR. Cardiac events were defined as the occurrence of cardiac death, rehospitalization for worsening heart failure, and mitral valve surgery. RESULTS: On univariable analysis, EuroSCORE II and GLS were associated with LVRR. On multivariable logistic regression analysis, GLS was the only independent correlate of LVRR (P = 0.004). A receiver operating characteristic curve identified a cutoff value for GLS of -9.25% (P < 0.001) associated with LVRR, with a sensitivity and specificity of 81 and 74%, respectively. New York Heart Failure Association class more than 2 after MCi, absence of LVRR after MCi, and preoperative GLS more than -9.25% were significantly correlated with adverse cardiac events at long-term follow-up. On multivariable logistic regression analysis, GLS was the only independent predictor of composite adverse cardiac events at 2-year follow-up. CONCLUSION: A worse preoperative GLS predicts no LVRR and is associated with adverse long-term outcome after successful MCi for SMR

Predictors of outcome in heart failure patients with severe functional mitral regurgitation undergoing MitraClip treatment

Background: The prognostic predictors of outcome in patients with functional mitral regurgitation (FMR) undergoing MitraClip implantation (MCi) are still poorly known. The aim of our study is to identify the baseline predictors of outcome in FMR patients candidate to MCi. Methods: All patients with symptomatic moderate-to-severe or severe FMR undergoing MCi at our institution were consecutively and prospectively enrolled. Baseline clinical and instrumental data were collected. Primary endpoint was the occurrence of cardiac death; secondary endpoints were all-cause death and the composite of cardiac death or rehospitalization for heart failure. Results: 74 patients (mean 71.6 ± 8.3 years) were enrolled. During follow-up (median 416.0 days), the primary endpoint occurred in 15 (20.3%), all-cause death in 26 (35.1%) and the composite endpoint in 25 (33.8%). At multivariate analysis, the left atrial volume index (LAVi; HR:1.02; P = 0.048) and the low peak oxygen uptake (peak VO2; HR:0.73; P = 0.018) increased the risk of cardiac death at follow-up; atrial fibrillation (AF; HR:2.69; P = 0.027) was independently associated to all-cause death and the low level of peak VO2 was an independent predictor of overall mortality (HR:0.70; P &lt; 0.001) as well as of the composite endpoint (HR:0.73; P &lt; 0.001). The ROC analysis identified a peak VO2 cut-off of 10.0 mL/kg/min as the best predictor for the three study endpoints; the best LAVi cut-off for cardiac death was 67 mL/m2. Kaplan-Meier analysis for the individual and combined outcome predictors confirmed their significant stratification ability during follow-up. Conclusions: Peak VO2, along with LAVi and AF, identify FMR patients with the worst prognosis after MCi

Coronary vasomotion dysfunction after everolimus-eluting stent implantation

First generation drug-eluting stent can cause a paradoxical "in-segment" coronary vasoconstriction. This phenomenon was seen with sirolimus, paclitaxel, and, more recently, also with zotarolimus-eluting stent. For the first time, we describe a case of coronary-induced vasoconstriction by everolimus-eluting stents (EES)

Characterization of three novel pathogenic SLC40A1 mutations and genotype/phenotype correlations in 7 Italian families with type 4 hereditary hemochromatosis

Mutations of SLC40A1 encoding ferroportin (Fpn), the unique cellular iron exporter, severely affect iron homeostasis causing type 4 hereditary hemochromatosis, an autosomal dominant iron overload condition with variable phenotypic manifestations. This disease can be classified as type 4A, better known as “ferroportin disease”, which is due to “loss of function” mutations that lead to decreased iron export from cells, or as type 4B hemochromatosis, which is caused by “gain of function” mutations, conferring partial or complete resistance to hepcidin-mediated Fpn degradation. In this work, we discuss clinical and molecular findings on a group of patients in whom a SLC40A1 single copy missense variant was identified. Three novel variants, p.D181N, p.G204R and p.R296Q were functionally characterized. Fpn D181N and R296Q mutants can be classified as full or partial loss of function, respectively. Replacement of G204 with arginine appears to cause a more complex defect with impact both on iron export function and hepcidin sensitivity. This finding confirms the difficulty of predicting the effect of a mutation on the molecular properties of Fpn in order to provide an exhaustive explanation to the wide variability of the phenotype in type 4 hereditary hemochromatosi

Soluble PCSK9 Inhibition: Indications, Clinical Impact, New Molecular Insights and Practical Approach-Where Do We Stand?

Current research on cardiovascular prevention predominantly focuses on risk-stratification and management of patients with coronary artery disease (CAD) to optimize their prognosis. Several basic, translational and clinical research efforts aim to determine the etiological mechanisms underlying CAD pathogenesis and to identify lifestyle-dependent metabolic risk factors or genetic and epigenetic parameters responsible for CAD occurrence and/or progression. A log-linear association between the absolute exposure of LDL cholesterol (LDL-C) and the risk of atherosclerotic cardio-vascular disease (ASCVD) was well documented over the year. LDL-C was identified as the principal enemy to fight against, and soluble proprotein convertase subtilisin kexin type 9 (PCSK9) was attributed the role of a powerful regulator of blood LDL-C levels. The two currently available antibodies (alirocumab and evolocumab) against PCSK9 are fully human engineered IgG that bind to soluble PCSK9 and avoid its interaction with the LDLR. As documented by modern and dedicated "game-changer" trials, antibodies against soluble PCSK9 reduce LDL-C levels by at least 60 percent when used alone and up to 85 percent when used in combination with high-intensity statins and/or other hypolipidemic therapies, including ezetimibe. Their clinical indications are well established, but new areas of use are advocated. Several clues suggest that regulation of PCSK9 represents a cornerstone of cardiovascular prevention, partly because of some pleiotropic effects attributed to these newly developed drugs. New mechanisms of PCSK9 regulation are being explored, and further efforts need to be put in place to reach patients with these new therapies. The aim of this manuscript is to perform a narrative review of the literature on soluble PCSK9 inhibitor drugs, with a focus on their indications and clinical impact

Thrombosis and survival in essential thrombocythemia: A regional study of 1,144 patients

To identify prognostic factors affecting thrombosis-free survival (TFS) and overall survival (OS), we report the experience of a Regional cooperative group in a real-life cohort of 1,144 patients with essential thrombocythemia (ET) diagnosed from January 1979 to December 2010. There were 107 thrombotic events (9.4%) during follow-up [60 (5.3%) arterial and 47 (4.1%) venous thromboses]. At univariate analysis, risk factors for a shorter TFS were: age >60 years (P 60 years (P 15 × 10(9) /l (P = 0.0370) were independent risk factors. Previous thrombotic events in ET patients are crucial for TFS but their importance seems related not to the occurrence per se but mainly to the interval between the event and the diagnosisTo identify prognostic factors affecting thrombosis-free survival (TFS) and overall survival (OS), we report the experience of a Regional cooperative group in a real-life cohort of 1,144 patients with essential thrombocythemia (ET) diagnosed from January 1979 to December 2010. There were 107 thrombotic events (9.4%) during follow-up [60 (5.3%) arterial and 47 (4.1%) venous thromboses]. At univariate analysis, risk factors for a shorter TFS were: age >60 years (P < 0.0054, 95% CI 1.18-2.6), previous thrombosis (P < 0.0001, 95% CI 1.58-4.52) and the presence of at least one cardiovascular risk factor (P = 0.036, 95% CI 1.15-3.13). Patients with a previous thrombosis occurred ≥24 months before ET diagnosis had a shorter TFS compared to patients with a previous thrombosis occurred <24 months (P = 0.0029, 95% CI 1.5-6.1); furthermore, patients with previous thrombosis occurred <24 months did not show a shorter TFS compared with patients without previous thrombosis (P = 0.303, 95% CI 0.64-3

High platelet count at diagnosis is a protective factor for thrombosis in patients with essential thrombocythemia

To assess the role of platelet (PLT) count for thrombotic complications in Essential Thrombocythemia (ET), 1201 patients followed in 11 Hematological centers in the Latium region were retrospectively evaluated. At multivariate analysis, the following factors at diagnosis were predictive for a worse Thrombosis-free Survival (TFS): the occurrence of previous thrombotic events (p=0.0004), age>60years (p=0.0044), spleen enlargement (p=0.042) and a lower PLT count (p=0.03). Receiver Operating Characteristic (ROC) analyses based on thrombotic events during follow-up identified a baseline platelet count of 944×109/l as the best predictive threshold: thrombotic events were 40/384 (10.4%) in patients with PLT count >944×109/l and 109/817 (13.3%) in patients with PLT count <944×109/l, respectively (p=0.04). Patients with PLT count <944×109/l were older (median age 60.4years. vs 57.1years., p=0.016), had a lower median WBC count (8.8×109/l vs 10.6×109/l, p<0.0001), a higher median Hb level (14.1g/dl vs 13.6g/dl, p<0.0001) and a higher rate of JAK-2-V617F positivity (67.2% vs 41.6%, p<0.0001); no difference was observed as to thrombotic events before diagnosis, spleen enlargement and concomitant Cardiovascular Risk Factors. In conclusion, our results confirm the protective role for thrombosis of an high PLT count at diagnosis. The older age and the higher rate of JAK-2 V617F positivity in the group of patients with a baseline lower PLT count could in part be responsible of this counterintuitive finding