Fernando Scudiero

Increased mortality after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis and low ejection fraction: A meta-analysis of 6898 patients

BACKGROUND There is conflicting evidence regarding the safety and efficacy of transcatheter aortic valve implantation (TAVI) procedures in patients with severe aortic stenosis and low left ventricular ejection fraction (EF). The primary aim of this study was to determine the impact of TAVI on short- and long-term mortality in patients with low EF (EF <50%); the secondary aim was to analyze the impact of TAVI procedure on EF recovery in the same setting of patients. METHODS AND RESULTS Twenty-six studies enrolling 6898 patients with severe aortic stenosis undergoing TAVI procedure were included in the meta-analysis and analyzed for 30-day, 6-month and 1-year all-cause and cardiovascular mortality; a further meta-analysis was also performed in patients with low EF to assess EF changes post TAVI. In low EF patients, both all-cause and cardiovascular short- and long-term mortality were significantly higher when compared to patients with normal EF (30-day-all-cause mortality: 0.13; 95% confidence interval [CI]: 0.01 to 0.25, I(2)=49.65, Q=21.85; 1-year-all-cause mortality: 0.25; 95% [CI]: 0.16 to 0.34, I(2)=25.57, Q=16.12; 30-day-cardiovascular mortality: 0.03; 95% [CI]: -0.31 to 0.36, I(2)=66.84, Q=6.03; 1-year-cardiovascular mortality: 0.29; 95% [CI]: 0.12 to 0.45, I(2)=0.00, Q=1.88). Nevertheless, in low EF patients TAVI was associated with a significant recovery of EF, which started at discharge and proceeded up to 1-year-follow-up. CONCLUSIONS Patients with low EF severe aortic stenosis have higher mortality following TAVI compared to normal EF patients, despite a significant and sustained improvement in EF.

Abdominal aortic aneurysm in patients affected by intermittent claudication: prevalence and clinical predictors

BackgroundAbdominal aortic aneurysm (AAA) is a frequent cause of death among elderly. Patients affected by lower extremity peripheral arterial disease (LE-PAD) seem to be particularly at high risk for AAA. We aimed this study at assessing the prevalence and the clinical predictors of the presence of AAA in a homogeneous cohort of LE-PAD patients affected by intermittent claudication.MethodsWe performed an abdominal ultrasound in 213 consecutive patients with documented LE-PAD (ankle/brachial index ≤0.90) attending our outpatient clinic for intermittent claudication. For each patient we registered cardiovascular risk factors and comorbidities, and measured neutrophil count.ResultsThe ultrasound was inconclusive in 3 patients (1.4%), thus 210 patients (169 males, 41 females, mean age 65.9 ± 9.8 yr) entered the study. Overall, AAA was present in 19 patients (9.0%), with a not significant higher prevalence in men than in women (10.1% vs 4.9%, p = 0.300). Patients with AAA were older (71.2 ± 7.0 vs 65.4 ± 9.9 years, p = 0.015), were more likely to have hypertension (94.7% vs 71.2%, p = 0.027), and greater neutrophil count (5.5 [4.5 – 6.2] vs 4.1 [3.2 – 5.5] x103/μL, p = 0.010). Importantly, the c-statistic for neutrophil count (0.73, 95% CI 0.60 – 0.86, p =0.010) was higher than that for age (0.67, CI 0.56–0.78, p = 0.017). The prevalence of AAA in claudicant patients with a neutrophil count ≥ 5.1 x103/μL (cut-off identified at ROC analysis) was as high as 29.0%.ConclusionsPrevalence of AAA in claudicant patients is much higher than that reported in the general population. Ultrasound screening should be considered in these patients, especially in those with an elevated neutrophil count.

Dermcidin: a skeletal muscle myokine modulating cardiomyocyte survival and infarct size after coronary artery ligation

AIMS Coronary artery disease is the leading cause of death in western countries, and its association with lower extremity peripheral artery disease (LE-PAD) represents an independent predictor of worse outcome. However, the molecular mechanisms underlying these effects are currently unknown. METHODS AND RESULTS To investigate these processes, we used in vitro approaches and several mouse models: (i) unilateral limb ischaemia by left common femoral artery ligation [peripheral ischaemia (PI), n = 38]; (ii) myocardial infarction by permanent ligation of the left descending coronary artery (MI, n = 40); (iii) MI after 5 weeks of limb ischaemia (PI + MI, n = 44); (iv) sham operation (SHAM, n = 20). Compared with MI, PI + MI hearts were characterized by a significant increase in cardiomyocyte apoptosis, larger infarct areas, and decreased cardiac function. By using a proteomic approach, we identified a ≅ 8 kDa circulating peptide, Dermcidin (DCD), secreted by ischaemic skeletal muscles, enhancing cardiomyocytes apoptosis under hypoxic conditions and infarct size after permanent coronary artery ligation. siRNA interference experiments to reduce DCD circulating levels significantly reduced infarct size and ameliorated cardiac function after MI. CONCLUSION Our data demonstrate that chronic limb ischaemia activates detrimental pathways in the ischaemic heart through humoral mechanisms of remote organ crosstalk. Thus, DCD may represent a novel important myokine modulating cardiomyocyte survival and function.

Use of statins in lower extremity artery disease: a review

BackgroundLower extremity artery disease (LE-PAD) is one of the most common manifestations of atherosclerosis, particularly in elderly patients, and it is related to a high cardiovascular risk.DescriptionIt is well established that statin therapy is characterized by crucial benefits on cardiovascular system by limiting atherosclerotic progression and reducing cardiovascular events and mortality. A growing body of evidence support efficacy of statins in LE-PAD due to the ability of both reducing cardiovascular risk and improving walking distance and, hence, quality of life. Consequently, statin therapy should be considered in all LE-PAD patients and new LDL-cholesterol targets should be reached.ConclusionsOur opinion is that statin therapy remains still underutilized or with inadequate dosage, so therapy of LE-PAD patients should be improved to obtain all the demonstrated benefits of statins.

The role of atherectomy in the treatment of lower extremity peripheral artery disease

BackgroundThe incidence of lower extremity peripheral artery disease (LE-PAD) continues to increase and associated morbidity remains high. Despite the significant development of percutaneous revascularization strategies, over the past decade, LE-PAD still represents a unique challenge for interventional cardiologists and vascular surgeons.MethodTypical features of atherosclerosis that affects peripheral vascular bed (diffuse nature, poor distal runoff, critical limb ischemia, chronic total occlusion) contribute to the disappointing results of traditional percutaneous transluminal angioplasty (PTA). New technologies have been developed in attempt to improve the safety and effectiveness of percutaneous revascularization. Among these, atherectomy, debulking and removing atherosclerotic plaque, offers the potential advantage of eliminating stretch on arterial walls and reducing rates of restenosis.ConclusionsThis review summarizes the features and the current applications of new debulking devices.

Cardiac Side Effects of Chemotherapy: State of Art and Strategies for a Correct Management

In recent years, the development of more effective drugs has provided a better prognosis and an increase in life expectancy for patients at all-stages of cancer. On the other hand, the price for the improving effectiveness of therapies against malignant tumors is the development of severe and potentially life-threatening drug reactions. Among these, cardiac toxic effects have recently gained particular attention. The term cardiotoxicity includes many possible pathological manifestations, but the most frequent is the reduction in cardiac function, potentially leading to heart failure and death. Importantly, the development of cardiac dysfunction may occur immediately after drug administration, or after years. The purpose of this review is to discuss the clinical features of cardiotoxicity, its molecular basis and novel possible strategies to reduce the likelihood of serious cardiac complications.

Ankle/brachial index to everyone

BackgroundIn the last years significant attention has been paid in identifying markers of subclinical atherosclerosis or of increased cardiovascular risk.MethodAn abnormal ankle/brachial index (ABI) identifies patients affected by lower extremity peripheral arterial disease, and even more important, represents a powerful predictor of the development of future ischemic cardiovascular events.ConclusionsIn our opinion, ABI is a cardiovascular risk prediction tool with very desirable properties that might become a routine measurement in clinical practice.

Endovascular treatment of lower extremity arteries is associated with an improved outcome in diabetic patients affected by intermittent claudication

BackgroundLower extremity peripheral arterial disease (LE-PAD) is a highly prevalent condition among diabetic patients, associated with reduced walking capacity and a high incidence of cardiovascular events. Endovascular revascularization of lower extremities arteries improves walking performance and quality of life of diabetic patients affected by intermittent claudication, but few studies evaluated the impact of revascularization on cardiovascular outcome in this high-risk population. Accordingly, in the present study we evaluated if leg-ischemia resolution by effective lower limbs percutaneous revascularization can also impact cardiovascular outcome in a homogeneous group of diabetic patients affected by intermittent claudication.Methods236 diabetic patients affected by LE-PAD at stage II of Fontaine’s classification, with ankle/brachial index ≤0.90 and one or more hemodynamically significant stenosis in at least one artery of the ileo-femoro-popliteal axis were enrolled in the study. According to the Trans-Atlantic Inter Society Consensus II recommendations, 123 (52.1%) underwent percutaneous transluminal angioplasty (PTA group), while 113 (47.9%) underwent conservative medical therapy only (MT group). The incidence of major cardiovascular events (cardiovascular death, myocardial infarction, ischemic stroke, coronary or carotid revascularization) was prospectively analyzed with Kaplan-Meier curves and the risk of developing a cardiovascular event calculated by Cox analyses.ResultsNo baseline difference in cardiovascular risk factors were observed between the PTA and MT groups, except for a lower prevalence of males in PTA group (74.8% vs. 85.8%, p=0.034). Furthermore, patients in the PTA group showed a worse walking capacity as expressed by maximum walking distance (108.7 ± 300.9 vs 378.4 ± 552.3 meters, p<0.001). During a median follow-up of 20 months (12.0-29.0), the incidence of cardiovascular events was markedly lower in patients in the PTA group with respect to patients in the MT group (7.3% vs. 22.1%, p=0.001), and patients of the MT group had at Cox analysis a 3.9 increased risk with respect to PTA group, after adjustment for potential confounding factors (95% CI 1.1-15.3, p=0.049).ConclusionsThe present study shows that lower limbs revascularization of diabetic patients affected by intermittent claudication, in addition to improve walking performance, is associated with a reduction in the incidence of future major cardiovascular events.

Risk stratification using the CHA2DS2-VASc score in Takotsubo syndrome: Data from the Takotsubo Italian network

Background The CHA2DS2‐VASc score predicts stroke in patients with atrial fibrillation and has been reported to have a prognostic role even in acute coronary syndrome patients. The Takotsubo syndrome is a condition that mimics acute coronary syndrome and may present several complications including stroke. We sought to assess the ability of CHA2DS2‐VASc score to predict adverse events in Takotsubo syndrome patients. Methods and Results Overall, 371 Takotsubo syndrome patients were enrolled in a prospective registry. Patients were divided into 3 groups according to the CHA2DS2‐VASc score: Group A (≤1), B (2–3), and C (≥4). The median CHA2DS2‐VASc score was 3 (interquartile range: 2–4). Overall, 9%, 42%, and 49% were included in Group A, B, and C, respectively. Follow‐up length was 26±20 months. The mortality rate was 6%, 7%, and 17% in Group A, B, and C, respectively (P=0.011). The stroke rate was 3% and not different among the 3 groups. Estimated major adverse cardiac and cerebrovascular events (the composite of death, myocardial infarction, and stroke) rates in the 3 groups were 6%, 9%, and 17% in Group A, B, and C, respectively (P=0.033). The CHA2DS2‐VASc score resulted as a predictor of major adverse cardiac and cerebrovascular events (odds ratio 2.1, 95% confidence interval, 1.2–3.6; P=0.01) and all‐cause mortality (odds ratio 1.5, 95% confidence interval, 1.2–1.9; P=0.001). Conclusions In Takotsubo syndrome, the CHA2DS2‐VASc score allows prediction of cardiovascular events and mortality at long‐term follow‐up.

Non-invasive vulnerable plaque imaging: how do we know that treatment works?

Atherosclerosis is an inflammatory disorder that can evolve into an acute clinical event by plaque development, rupture, and thrombosis. Plaque vulnerability represents the susceptibility of a plaque to rupture and to result in an acute cardiovascular event. Nevertheless, plaque vulnerability is not an established medical diagnosis, but rather an evolving concept that has gained attention to improve risk prediction. The availability of high-resolution imaging modalities has significantly facilitated the possibility of performing in vivo regression studies and documenting serial changes in plaque stability. This review summarizes the currently available non-invasive methods to identify vulnerable plaques and to evaluate the effects of the current cardiovascular treatments on plaque evolution.