Marco Moccetti

Predictors for efficacy of percutaneous mitral valve repair using the MitraClip system: the results of the MitraSwiss registry

Background Percutaneous mitral valve repair (MVR) using the MitraClip system has become a valid alternative for patients with severe mitral regurgitation (MR) and high operative risk. Objective To identify clinical and periprocedural factors that may have an impact on clinical outcome. Design Multi-centre longitudinal cohort study. Setting Tertiary referral centres. Patients Here we report on the first 100 consecutive patients treated with percutaneous MVR in Switzerland between March 2009 and April 2011. All of them had moderate–severe (3+) or severe (4+) MR, and 62% had functional MR. 82% of the patients were in New York Heart Association (NYHA) class III/IV, mean left ventricular ejection fraction was 48% and the median European System for Cardiac Operative Risk Evaluation was 16.9%. Interventions MitraClip implantation performed under echocardiographic and fluoroscopic guidance in general anaesthesia. Main outcome measures Clinical, echocardiographic and procedural data were prospectively collected. Results Acute procedural success (APS, defined as successful clip implantation with residual MR grade ≤2+) was achieved in 85% of patients. Overall survival at 6 and 12 months was 89.9% (95% CI 81.8 to 94.6) and 84.6% (95% CI 74.7 to 91.0), respectively. Univariate Cox regression analysis identified APS (p=0.0069) and discharge MR grade (p=0.03) as significant predictors of survival. Conclusions In our consecutive cohort of patients, APS was achieved in 85%. APS and residual discharge MR grade are important predictors of mid-term survival after percutaneous MVR.

Acute haemodynamic changes after percutaneous mitral valve repair: relation to mid-term outcomes

Background Percutaneous mitral valve repair (MVR) using the Evalve MitraClip has been recently introduced as a potential alternative to surgical MVR. Objective To assess immediate haemodynamic changes after percutaneous MVR using right heart catheterisation. Design Single-centre longitudinal cohort study. Setting Tertiary referral centre. Patients Fifty consecutive non-surgical patients (age 74±14 years, EuroSCORE 26±14) with moderate to severe (3+) and severe (4+) mitral regurgitation (MR) due to functional (56%), degenerative (30%) or mixed (14%) disease were selected. Interventions MitraClip implantation was performed under general anaesthesia with fluoroscopy and echocardiographic guidance. Haemodynamic variables were obtained before and after MVR using standard right heart catheterisation and oximetry. Main outcome measures Haemodynamic changes immediately before and after MVR. Results Acute procedural success (reduction in MR to grade 2+ or less) was achieved in 46 (92%) patients. Mitral valve clipping reduced mean pulmonary capillary wedge pressure (mPCWP) (from 17±7 to 12±5 mm Hg), PCWP v-wave (from 24±11 to 16±7 mm Hg) and mean pulmonary artery pressure (mPAP) (from 29±12 to 24±6 mm Hg), and increased the cardiac index (CI) (from 3.1±1.0 to 3.9±1.1 l/min/m2) (all p<0.05). On Cox univariate regression analysis, mPCWP, PCWP v-wave- and mPAP-changes were associated with death, open-heart surgery for MR and/or hospitalisation for heart failure on follow-up. Conclusion In a heterogeneous population with predominantly functional MR, percutaneous MVR with the Evalve MitraClip system lowers mPCWP, PCWP v-wave and mPAP by 20%, 20% and 8%, respectively, and increases the CI by 32%.

Whole-heart dynamic three-dimensional magnetic resonance perfusion imaging for the detection of coronary artery disease defined by fractional flow reserve: determination of volumetric myocardial ischaemic burden and coronary lesion location

AIMS Dynamic three-dimensional-cardiac magnetic resonance (3D-CMR) perfusion proved highly diagnostic for the detection of angiographically defined coronary artery disease (CAD) and has been used to assess the efficacy of coronary stenting procedures. The present study aimed to relate significant coronary lesions as assessed by fractional flow reserve (FFR) to the volume of myocardial hypoenhancement on 3D-CMR adenosine stress perfusion imaging and to define the inter-study reproducibility of stress inducible 3D-CMR hypoperfusion. METHODS AND RESULTS A total of 120 patients with known or suspected CAD were examined in two CMR centres using 1.5 T systems. The protocol included cine imaging, 3D-CMR perfusion during adenosine infusion, and at rest followed by delayed enhancement (DE) imaging. Fractional flow reserve was recorded in epicardial coronary arteries and side branches with ≥2 mm luminal diameter and >40% severity stenosis (pathologic FFR < 0.75). Twenty-five patients underwent an identical repeat CMR examination for the determination of inter-study reproducibility of 3D-CMR perfusion deficits induced by adenosine. Three-dimensional CMR perfusion scans were visually classified as pathologic if one or more segments showed an inducible perfusion deficit in the absence of DE. Myocardial ischaemic burden (MIB) was measured by segmentation of the area of inducible hypoenhancement and normalized to left ventricular myocardial volume (MIB, %). Three-dimensional CMR perfusion resulted in a sensitivity, specificity, and diagnostic accuracy of 90, 82, and 87%, respectively. Substantial concordance was found for inter-study reproducibility [Lins correlation coefficient: 0.98 (95% confidence interval: 0.96-0.99)]. CONCLUSION Three-dimensional CMR stress perfusion provided high diagnostic accuracy for the detection of functionally significant CAD. Myocardial ischaemic burden measurements were highly reproducible and allowed the assessment of CAD severity.

Progression of human carotid and femoral atherosclerosis: a prospective follow-up study by magnetic resonance vessel wall imaging

AIMS The time course of atherosclerosis burden in distinct vascular territories remains poorly understood. We longitudinally evaluated the natural history of atherosclerotic progression in two different arterial territories using high spatial resolution magnetic resonance imaging (HR-MRI), a powerful, safe, and non-invasive tool. METHODS AND RESULTS We prospectively studied a cohort of 30 patients (mean age 68.3, n = 9 females) with high Framingham general cardiovascular disease 10-year risk score (29.5%) and standard medical therapy with mild-to-moderate atherosclerosis intra-individually at the level of both carotid and femoral arteries. A total of 178 HR-MRI studies of carotid and femoral arteries performed at baseline and at 1- and 2-year follow-up were evaluated in consensus reading by two experienced readers for lumen area (LA), total vessel area (TVA), vessel wall area (VWA = TVA - LA), and normalized wall area index (NWI = VWA/TVA). At the carotid level, LA decreased (-3.19%/year, P = 0.018), VWA increased (+3.83%/year, P = 0.019), and TVA remained unchanged. At the femoral level, LA remained unchanged, VWA and TVA increased (+5.23%/year and +3.11%/year, both P < 0.01), and NWI increased for both carotid and femoral arteries (+2.28%/year, P = 0.01, and +1.8%/year, P = 0.033). CONCLUSION The atherosclerotic burden increased significantly in both carotid and femoral arteries. However, carotid plaque progression was associated with negative remodelling, whereas the increase in femoral plaque burden was compensated by positive remodelling. This finding could be related to anatomic and flow differences and/or to the distinct degree of obstruction in the two arterial territories.

Echocardiographic-Fluoroscopic Fusion Imaging in Transseptal Puncture: A New Technology for an Old Procedure

In an era of catheter-based structural heart disease and left-side electrophysiologic interventions, transseptal puncture (TSP) is probably the most common transcatheter procedure. Experienced interventional cardiologists and electrophysiologists may safely perform TSP using fluoroscopic guidance alone. However, at present TSP is usually the first step in complex percutaneous catheter-based structural heart disease procedures and necessitate a precise site-specific TSP. Thus, in these procedures most interventional cardiologists perform TSP under fluoroscopic and two- or three-dimensional transesophageal echocardiographic guidance. The EchoNavigator system may provide a solution by fusing fluoroscopic and transesophageal echocardiographic images. In this review, the authors describe advantages and limitations of this new imaging system in guiding TSP and suggest specific echocardiographic-fluoroscopic fusion imaging perspectives that may facilitate TSP, making it potentially easier and safer.

Cardiac toxicity of trastuzumab in elderly patients with breast cancer

Breast cancer (BC) is diagnosed in ≥ 65 year old women in about half of cases. Experts currently recommend that systemic therapy is offered to elderly patients with BC, if, based on their overall conditions and life expectancy, it can be reasonably anticipated that the benefits will outweigh the risks of treatment. Like for young subjects, the monoclonal antibody against human epidermal growth factor receptor-2 (HER-2), trastuzumab, represents a valid therapeutic option when BC over-expresses this receptor. Unfortunately, administration of trastuzumab is associated with the occurrence of left ventricular dysfunction and chronic heart failure (CHF), possibly because of interference with the homeostatic functions of HER-2 in the heart. Registry-based, retrospective analyses have reported an incidence of CHF around 25% in elderly women receiving trastuzumab compared with 10%–15% in those not given any therapy for BC, and the risk of CHF has been estimated to be two-fold higher in > 60–65 year old trastuzumab users vs. non-users. Extremely advanced age and preexisting cardiac disease have been shown to predispose to trastuzumab cardiotoxicity. Therefore, selection of older patients for treatment with trastuzumab should be primarily based on their general status and the presence of comorbidities; previous chemotherapy, especially with anthracyclines, should be also taken into account. Once therapy has started, efforts should be made to ensure regular cardiac surveillance. The role of selected biomarkers, such as cardiac troponin, or new imaging techniques (three-dimension, tissue Doppler echocardiography, magnetic resonance imaging) is promising, but must be further investigated especially in the elderly. Moreover, additional studies are needed in order to better understand the mechanisms by which trastuzumab affects the old heart.

Remodeling the Human Adult Stem Cell Niche for Regenerative Medicine Applications

The interactions between stem cells and their surrounding microenvironment are pivotal to determine tissue homeostasis and stem cell renewal or differentiation and regeneration in vivo. Ever since they were postulated in 1978, stem cell niches have been identified and characterized in many germline and adult tissues. Comprehensive studies over the last decades helped to clarify the critical components of stem cell niches that include cellular, extracellular, biochemical, molecular, and physical regulators. This knowledge has direct impact on their inherent regenerative potential. Clinical applications demand readily available cell sources that, under controlled conditions, provide a specific therapeutic function. Thus, translational medicine aims at optimizing in vitro or in vivo the various components and complex architecture of the niche to exploit its therapeutic potential. Accordingly, the objective is to recreate the natural niche microenvironment during cell therapy process development and closely comply with the requests of regulatory authorities. In this paper, we review the most recent advances of translational medicine approaches that target the adult stem cell natural niche microenvironment for regenerative medicine applications.

J-wave duration and slope as potential tools to discriminate between benign and malignant early repolarization

Yvonne Cristoforetti, MD, Luigi Biasco, MD, Carla Giustetto, MD, Ole De Backer, MD, PhD, Davide Castagno, MD, Piero Astegiano, MD, Gianpasquale Ganzit, MD, Carlo Gabriele Gribaudo, MD, Marco Moccetti, MD, Fiorenzo Gaita, MD From the Division of Cardiology, Department of Medical Science, University of Turin, Citta della Salute e della Scienza Hospital, Turin, Italy, Fondazione Cardiocentro Ticino, University of Zurich, Lugano, Switzerland, The Heart Centre, Rigshospitalet, Copenhagen, Denmark, and Institute of Sports Medicine, Turin, Italy.

Three Recurrent Episodes of Apical-Ballooning Takotsubo Cardiomyopathy in a Man

A 66-year-old man was admitted to the emergency room because of 3-hour-long acute chest pain with dyspnea and nausea while fishing on a high-altitude (2400 m) lake in the very early morning. The patient was transferred by helicopter. Persistent chest pain without pathological clinical findings (Spo2, 99%; shock index, 0.9; axillary temperature, 36.7°C) was present. Medical history revealed no previous cardiovascular events and no further cardiovascular risk factors except smoking (40 packs a year). ECG demonstrated ST-segment elevation (Figure 1A). ST-segment–elevation acute coronary syndrome was initially suspected. Immediate selective coronary angiography demonstrated neither stenosis nor dissections. Ventriculography showed extensive left ventricular (LV) apical and midventricular akinesia with hyperkinesia in the basal segments and a moderate reduction in the estimated LV ejection fraction (Figure 1B and Movie I in the online-only Data Supplement). These large LV wall motion abnormalities were inconsistent with slightly elevated cardiac enzymes (troponin I, 0.48 μg/L [normal, <0.09 μg/L]; creatine kinase-MB, 18.7 UI/L [normal, <24 UI/L]). Clinical presentation and the absence of elevation of inflammation markers elevation and …

PCSK9 inhibitors: an overview on a new promising lipid-lowering therapy

Atherosclerosis is characterized by cholesterol deposition in the arterial intima, with subsequent plaque formation and arterial disease. Low-density lipoprotein cholesterol (LDL-C) plays the most important role in the atherogenesis process, which is the substrate of cardiovascular disease and is the leading cause of death worldwide. Several studies show that a strict control of risk factors, particularly the reduction of LDL-C levels, is a cornerstone in primary and secondary prevention of coronary heart disease. Statins are currently the most effective drugs for lowering LDL-C, but the discovery of proprotein convertase subtilisin kexin 9 (PCSK9) has opened up new therapeutic options in lipid management. PCSK9 reduces LDL-receptors’ recycling resulting in a decrease of LDL-C receptors on the surface of hepatocytes and an increase of LDL-C levels in plasma. Obviously, inhibition of PCSK9 has been associated with an increase of LDL-C receptors with subsequent lowering of plasma levels of LDL-C. The clinical development of monoclonal antibodies against PCSK9 has been achieved through phase I and II studies, and nowadays there are many ongoing phase III trials with promising preliminary results. The aim of this review is to update the evidence for PCSK9 monoclonal antibodies, such as evolocumab, alirocumab and bococizumab, in LDL-C management and to discuss their therapeutic perspectives based on the most recent clinical studies, with attention to side-effects.