Double layered stents for carotid angioplasty: A meta-analysis of available clinical data.

OBJECTIVES: The objective of this meta-analysis is to evaluate clinical efficacy of double layered mesh covered carotid stent systems in the clinical practice. BACKGROUND: The need for an increase plaque coverage to decrease the risk of debris dislodgement through the stent struts, following carotid artery stenting (CAS), has brought to the design of a new generation of double layered carotid stents. Several small sized clinical studies evaluating two different devices have been recently published, unfortunately these are not sufficiently powered to test for device related and clinical endpoints and no comparison, between the two available devices, has been reported yet. METHODS: Ten studies, enrolling 635 patients, were included in the present meta-analysis. Our study analyzed a composite endpoint of 30-day stroke and death and the occurrence of procedural unsuccess after CAS with the use of two different double layered carotid stent systems. RESULTS: Thirty-day stroke and death rate was quite low (patients 635, event rate 0.02, 95% CI: 0.01-0.04, P < 0.0001). The incidence of procedural unsuccess with these devices was relatively low (patients 635, event rate 0.03, 95% CI: 0.01-0.08, P < 0.0001). When a subgroup analysis was performed, according to the specific subtype of carotid stent, no differences in the occurrence of 30-day death and stroke rate and procedural unsuccess were observed (P = 0.979). CONCLUSIONS: This meta-analysis suggests that dual layered carotid stents could be safely used for the treatment of extracranial carotid artery stenosis, with a relatively low rate of procedural unsuccess, and allow achieving a quite low rate of postprocedural adverse events.

Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: a systematic review and dose-response meta-analysis.

AIMS: Gut microbiota-derived metabolite trimethylamine-N-oxide (TMAO) is emerging as a new potentially important cause of increased cardiovascular risk. The purpose of this meta-analysis was to systematically estimate and quantify the association between TMAO plasma levels, mortality, and major adverse cardio and cerebrovascular events (MACCE). METHODS AND RESULTS: MEDLINE, ISI Web of Science, and SCOPUS databases were searched for ad hoc studies published up to April 2017. Associations between TMAO plasma levels, all-cause mortality (primary outcome) and MACCE (secondary outcome) were systematically addressed. A total of 17 clinical studies were included in the analytic synthesis, enrolling 26 167 subjects. The mean follow-up in our study population was 4.3 ± 1.5 years. High TMAO plasma levels were associated with increased incidence of all-cause mortality [14 studies for 16 cohorts enrolling 15 662 subjects, hazard ratio (HR): 1.91; 95% confidence interval (CI): 1.40-2.61, P < 0.0001, I2 = 94%] and MACCE (5 studies for 6 cohorts enrolling 13 944 subjects, HR: 1.67, 95% CI: 1.33-2.11, P < 0.00001, I2 = 46%,). Dose-response meta-analysis revealed that the relative risk (RR) for all-cause mortality increased by 7.6% per each 10 µmol/L increment of TMAO [summary RR: 1.07, 95% CI (1.04-1.11), P < 0.0001; based on seven studies]. Association of TMAO and mortality persisted in all examined subgroups and across all subject populations. CONCLUSIONS: This is the first systematic review and meta-analysis demonstrating the positive dose-dependent association between TMAO plasma levels and increased cardiovascular risk and mortality.

Aortic and Mitral Calcification Is Marker of Significant Carotid and Limb Atherosclerosis in Patients with First Acute Coronary Syndrome.

PURPOSE: Atherosclerosis is a systemic disease and coronary artery disease is frequently associated with peripheral artery disease. As aortic and mitral valvular calcification (VC) share some etiopathogenetic mechanisms with atherosclerosis, we analyzed the risk profile and the echocardiographic characteristics of patients admitted for first acute coronary syndrome (ACS) to investigate whether the presence of VC could be a marker of asymptomatic hemodynamically significant peripheral atherosclerosis. METHODS: A total of 151 patients admitted for ACS without previous history of cardiovascular disease were consecutively enrolled. The presence of VC was identified by echocardiography; a carotid stenosis ≥50% by ultrasound identified carotid artery disease (CarAD); an ankle-brachial index ≤0.9 or ≥1.4 identified lower extremity artery disease (LEAD). Significant peripheral atherosclerosis was defined by the presence of CarAD and/or LEAD. RESULTS: Peripheral atherosclerosis was diagnosed in 82 (54.3%) patients; isolated CarAD in 24, isolated LEAD in 20, both diseases in 38 patients. VC was present in 103 (68.2%) patients. By multivariate analysis, age (OR = 1.059, 95% CI 1.007-1.113, P = 0.025), diabetes mellitus (OR = 5.068, 95% CI 1.480-17.351, P = 0.010), VC (OR = 7.422, 95% CI 2.421-22.880, P < 0.001), and multivessel CAD (OR = 3.317, 95% CI 1.281-8.586, P = 0.013) were the only independent predictors of having peripheral atherosclerosis. C-statistic for VC was not inferior to that obtained by age (0.728, 95% CI 0.649-0.797 vs. 0.800, 95% CI 0.727-0.861, P = 0.101) and to that obtained by the combination of multivessel CAD with diabetes (0.750; 95% CI 0.673-0.817, P = 0.635), and, furthermore, it was higher than that obtained by diabetes alone (0.620, 95% CI 0.538-0.698, P = 0.036). CONCLUSION: Ruling out the presence of significant peripheral atherosclerosis should be routinely considered in patients with ACS showing VC at echocardiography.

Renal Denervation in End-Stage Renal Disease: Current Evidence and Perspectives.

In patients with end-stage renal disease (ESRD) undergoing haemodialysis, hypertension is of common detection and frequently inadequately controlled. Multiple pathophysiological mechanisms are involved in the development and progression of the ESRD-related high blood pressure state, which has been implicated in the increased cardiovascular risk reported in this hypertensive clinical phenotype. Renal sympathetic efferent and afferent nerves play a relevant role in the development and progression of elevated blood pressure values in patients with ESRD, often leading to resistant hypertension. Catheter-based bilateral renal nerves ablation has been shown to exert blood pressure lowering effects in resistant hypertensive patients with normal kidney function. Promising data on the procedure in ESRD patients with resistant hypertension have been reported in small scale pilot studies. Denervation of the native non-functioning kidney's neural excitatory influences on central sympathetic drive could reduce the elevated cardiovascular morbidity and mortality seen in ESRD patients. The present review article will focus on the promising results obtained with renal denervation in patients with ESRD, its mechanisms of action and future perspectives in these high risk patients.

Percutaneous Treatment of Severe Aortic Regurgitation After Surgical Mitral Valve Repair.

A 54-year-old woman who had recently undergone surgical mitral and tricuspid valve repair was diagnosed with severe aortic regurgitation. She was scheduled for percutaneous treatment and underwent successful transcatheter aortic valve implantation with a 27-mm Trilogy valve (JenaValve Technology). The case documents feasibility of percutaneous treatment in the presence of a mitral ring.

[Percutaneous transcatheter treatment of hypertension and heart failure: results of the SICI-GISE national survey promoted by the GISE Young Committee]. / Trattamento transcatetere dell'ipertensione arteriosa e dello scompenso cardiaco: risultati della survey nazionale SICI-GISE promossa dal Comitato GISE Young.

BACKGROUND: During the last decade, thanks to contemporary evidence and technological improvements, the role of interventional cardiology in the field of cardiac conditions that are mainly treated conservatively has grown a lot. In such scenario, drug-resistant arterial hypertension and heart failure (HF) have a significant role, considering the huge number of involved patients and their impact on mortality and quality of life. METHODS: This survey was jointly performed by the GISE Young Committee with the support of the SICI-GISE Society and the ICOT group with the aim of evaluating the view of the cardiology community on interventional therapies for arterial hypertension and HF. A web-based questionnaire based on 22 questions was distributed online to SICI-GISE members. RESULTS: The survey was distributed to 1550 physicians with 156 (10%) responses, 58% of whom was under 35 years of age. Renal denervation was available in 49% of Centers, its principal indication was the evidence of severe adverse reactions to anti-hypertensive drugs (80%). Most participants agreed that, compared to past years, there is more understanding of anatomical characteristics and improvement of devices, thus increasing procedural safety; however, main limitations were: appropriate patients' selection criteria (45%), lack of robust evidence (41%) and regulatory (36%) and economical (33%) factors. In the field of HF, this survey enlightened a wide availability of conventional therapies (i.e. mechanical circulatory support, defibrillators, resynchronization) in Italy; on the other side, there is limited availability of innovative devices (i.e. atrial decompression systems, transcatheter left ventricular reshaping). Many participants expressed enthusiastic attitude in this new field, with a look for the need of further evidence in terms of safety and efficacy. Finally, in the treatment of both acute and chronic HF, many participants expressed a problem of limited patient access to advanced therapies, mainly associated with suboptimal networking among institutions. CONCLUSIONS: Device-based therapies for arterial hypertension and HF represent a promising option for selected patients; this survey highlights the importance of achieving good quality evidence in both fields, with the goal of proper identification of defined criteria for patients' selection and improvement of procedural and long-term safety and efficacy.

Patients younger than 70 undergoing transcatheter aortic valve implantation: Procedural outcomes and mid-term survival.

INTRODUCTION: Based on recent data, the indication for transcatheter aortic valve implantation (TAVI) is expanding to individuals at lower surgical risk, who are generally younger than subjects historically treated for severe aortic stenosis. Indeed, younger patients have traditionally been under-represented in current TAVI literature. The aim of the present study is to report about clinical features, procedural outcomes and mid-term outcomes of patients younger than 70 who underwent TAVI in a single high-volume center. MATERIALS AND METHODS: Consecutive patients younger than 70 years of age who underwent TAVI for severe, symptomatic aortic stenosis between 2007 and 2019 at a single, tertiary referral center have been included in this retrospective study. Procedural and mid-term outcomes were analyzed, comparing 1st generation with 2nd generation devices. RESULTS: Between 2007 and 2019, 1740 TAVI procedures were performed in our center. Among these, one hundred twenty-nine (7.4%) patients were younger than 70 years at the time of the intervention and were included in the present analysis. Fifty-eight patients (45%) were implanted with a 1st generation prosthesis while seventy-one patients (55%) were implanted with a 2nd generation device. Reasons which lead to a transcatheter approach in this population were: previous CABG (27.9%); porcelain aorta (24%); severe left ventricular systolic dysfunction (21.7%); prior chest radiation (19.4%); severe lung disease (8.5%); hemodynamic instability (7.0%); advanced liver disease (4.6%) and active cancer (3.9%). Overall device success rate was 89%, with no differences among 1st and 2nd generation devices. Threeyears all-cause mortality was 34%, with no difference among the two groups. Low incidence of aortic-valve re-intervention was observed at mid-term follow-up (late valve re-intervention = 2.3%). CONCLUSIONS: TAVI in young patient with appropriate indication for intervention is a safe procedure, associated with low rate of in hospital mortality and low rate of severe complications both with 1st and with 2nd generation devices. When considering long term durability, more data are needed; in our case series long-term follow up shows a good survival and also an extremely low rate of valve re-intervention.

Long-Term Outcomes of Chronic Total Occlusion Recanalization Versus Percutaneous Coronary Intervention for Complex Non-Occlusive Coronary Artery Disease.

The durability of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is uncertain. We aimed to compare the long-term outcomes of CTO PCI with those of complex non-CTO PCI. We built a single-center registry including all patients who underwent CTO and complex non-CTO PCI between 2012 and 2017. Complex non-CTO PCI was defined as: 3 vessels treated, ≥3 stents implanted, total stent length >60 mm, saphenous vein graft intervention, 2-stent bifurcation intervention, left main PCI, protected PCI, or rotational/laser atherectomy. The primary endpoint was target-lesion failure, a composite of cardiac death, myocardial infarction, and target-lesion revascularization. A total of 2,396 patients were included (n=609 CTO PCI, n=1,787 complex non-CTO PCI). Patients who underwent CTO PCI were younger and had higher prevalence of cardiovascular comorbidities. CTO PCI patients exhibited worse procedural metrics and success rate (74% vs 98%, p <0.001). They also suffered a higher incidence of coronary perforation (3.5% vs 2.0%, p = 0.04) and cardiac tamponade (0.8% vs 0.1%, p = 0.001). However, there was no difference in the overall incidence of in-hospital major adverse cardiac and cerebrovascular events (4.1% vs 5.0%, p = 0.40). At 36 months, there were no differences in the incidence of target-lesion failure (10.1% vs 9.9%, p = 0.91) or its individual components, between the CTO and complex non-CTO group. This finding was confirmed on multivariable analysis. In conclusion, CTO PCI is associated with lower success rates and higher risk for coronary perforation and tamponade compared with complex non-CTO PCI. The incidence of other in-hospital and long-term adverse events is similar and reasonably low.

Two-year cardiac mortality after MitraClip treatment of functional mitral regurgitation in ischemic and non-ischemic dilated cardiomyopathy.

BACKGROUND: MitraClip implantation has evolved as a new tool for treatment of inoperable or high-risk patients with severe functional mitral regurgitation (FMR) due to dilated cardiomyopathy (DCM). Limited data are available regarding MitraClip outcomes comparing patients with ischemic and non-ischemic DCM. METHODS: From 2008 to 2016, 314 patients received MitraClip for FMR at four institutions: Brescia, Zurich and Milan. Patients were stratified according to MR aetiology in non-ischemic FMR (n = 99) and ischemic FMR (n = 215). Preoperative risk factors, operative variables and outcomes up to 2-year were evaluated. A multivariable Cox Proportional Hazards survival model with covariate adjustments was used to assess the relationship between FMR aetiology and 2-year cardiac mortality. RESULTS: As expected, patients with ischemic FMR had significantly more risk factors and comorbidities. Overall procedural success rate was 80% and in-hospital cardiac mortality was 3% without significant differences between aetiology. Two-year overall (25% vs. 19%, p = 0.574) and cardiac (18% vs. 16%, p = 0.990) mortality rates were comparable. No differences were detected in terms of re-hospitalization rates (32%), LVAD implantation (4.5%) and mitral valve surgery (1%). LVEF ≤ 25%, LVEDV > 216 ml, NT-proBNP ≥ 10.000 pg/ml and AF were the strongest baseline predictors of 2-year cardiac mortality. Greater improvements of 6MWT and NYHA functional class were observed in patients with non-ischemic FMR. CONCLUSIONS: The ischemic or non-ischemic aetiology of DCM did not affect in-hospital and 2-year cardiac mortality after MitraClip in patients with FMR. In case of unfavorable baseline clinical condition, the indication for MitraClip should be carefully weighed in favour of conservative medical therapy alone or left ventricular assist device.

Meta-Analysis of Effect of Body Mass Index on Outcomes After Transcatheter Aortic Valve Implantation.

Controversial data exist regarding the impact of body mass index (BMI) on TAVI outcomes. Thirteen TAVI studies were included and analyzed for the incidence of procedural complications, 30-day, and long-term all-cause mortality. Three comparisons were executed: (1) underweight versus normal weight, (2) overweight versus normal weight, and (3) obese versus normal weight patients. Underweight patients (BMI <20 kg/m2) had similar 30-day all-cause mortality compared with the normal, although they displayed a significant worse survival at long-term follow-up (hazard ratio 1.68, 95% confidence interval (CI) 1.09 to 2.59, p = 0.02). Underweight patients showed a higher incidence of major and life-threatening bleedings (2,566 patients, odds ratio 1.64, 95% CI 1.10 to 2.45, p = 0.02) and of major vascular complications (2,566 patients, odds ratio 1.86, 95% CI 1.16 to 2.98, p = 0.01), compared with normal weight patients. Overweight patients (BMI ≥25 and <30 kg/m2) display similar 30-day and long-term all-cause mortality, as well as similar procedural complication rate compared with normal weight patients. Obese patients (BMI >30 kg/m2) had similar 30-day all-cause mortality rates compared with the normal weight category, whereas they displayed a significant better survival at long-term (hazard ratio 0.79, 95% CI 0.67 to 0.93, p = 0.004). Procedural complications did not differ between obese and normal body weight patients. In conclusion, a low BMI is linked to a significantly worse prognosis after TAVI. Therefore, BMI represents an important and handily tool that might be used in the risk prediction of patients to be addressed for TAVI.

Cerebral embolic lesions detected with diffusion-weighted magnetic resonance imaging following carotid artery stenting: a meta-analysis of 8 studies comparing filter cerebral protection and proximal balloon occlusion.

OBJECTIVES: The aim of this meta-analysis was to evaluate and compare the efficacy of the 2 different neuroprotection systems in preventing embolization during carotid artery stenting (CAS), as detected by diffusion-weighted magnetic resonance imaging (DW-MRI). BACKGROUND: Data from randomized and nonrandomized studies comparing both types of embolic protection devices revealed contrasting evidence about their efficacy in neuroprotection, as assessed by the incidence of new ischemic lesions detected by DW-MRI. METHODS: Eight studies, enrolling 357 patients, were included in the meta-analysis. Our study analyzed the incidence of new ischemic lesions/patient, comparing filter cerebral protection and proximal balloon occlusion. RESULTS: Following CAS, the incidence of new ischemic lesions/patient detected by DW-MRI was significantly lower in the proximal balloon occlusion group (effect size [ES]: -0.43; 95% confidence interval [CI]: -0.84 to -0.02, I(2) = 70.08, Q = 23.40). Furthermore, following CAS, the incidence of lesions at the contralateral site was significantly lower in the proximal protection group (ES: -0.50; 95% CI: -0.72 to -0.27, I(2) = 0.00, Q = 3.80). CONCLUSIONS: Our meta-analysis supports the concept that the use of proximal balloon occlusion compared with filter cerebral protection is associated with a reduction of the amount of CAS-related brain embolization. The data should be confirmed by a randomized clinical trial.

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.

Meta-analysis of mortality outcomes and mitral regurgitation evolution in 4,839 patients having transcatheter aortic valve implantation for severe aortic stenosis.

Transcatheter aortic valve implantation (TAVI) is an effective alternative therapy in selected patients with severe aortic stenosis. The role and effects of coexistent moderate to severe mitral regurgitation (msMR) in patients who undergo TAVI remain unclear. Thirteen studies enrolling 4,839 patients who underwent TAVI, including patients with msMR, were considered in a meta-analysis and analyzed for all-cause-mortality; a further meta-analysis was performed to assess mitral regurgitation (MR) evolution after TAVI. In patients with msMR, all-cause-mortality after TAVI was significantly increased at 30-day (effect size [ES] -0.18, 95% confidence interval [CI] -0.31 to -0.04, I(2) = 46.51, Q = 7.48), 1-year (ES -0.22, 95% CI -0.36 to -0.08, I(2) = 56.20, Q = 11.41), and 2-year (ES -0.15, 95% CI -0.27 to -0.02, I(2) = 0.00, Q = 2.64) follow-up compared with patients with absent or mild MR, independent of baseline left ventricular ejection fraction. Interestingly, the impact of msMR on outcomes was statistically stronger when the CoreValve system was used. TAVI was also associated with an improvement in MR entity at 3- and 6-month follow-up (overall ES -0.19, 95% CI -0.37 to -0.01, I(2) = 61.52, Q = 10.39). In conclusion, the presence of preoperative msMR in patients with severe, symptomatic aortic stenosis who undergo TAVI negatively affects outcomes after TAVI. In addition, in the same group of patients, a trend toward a reduction in MR severity was observed. Whether the decrease in MR severity affects mortality after TAVI remains to be defined.

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.

Physical activity in the prevention of peripheral artery disease in the elderly.

Aging is a well-known cardiovascular risk factor and cardiovascular diseases (CVD) are estimated to be the most common cause of death in the elderly. Peripheral arterial disease (PAD) represents an important clinical manifestation of CVD leading to increase morbidity and mortality, especially in elderly population. The correct management of PAD population includes the prevention of cardiovascular events and relief of symptoms, most commonly intermittent claudication. Progressive physical activity is an effective treatment to improve walking distance and to reduce mortality and cardiovascular events in patients with PAD, however the ability to effectively engage in physical activity often declines with increasing age. The maintenance and increase of reserve functional capacity are important concepts in the elderly population. Ultimately, the goal in participation of physical activity in the healthy elderly population is maintenance and development of physical functional reserve capacity. Therefore, for individuals suffering of PAD, appropriate physical activity in the form of supervised exercise may serve as a primary therapy. Although there are few direct comparisons of therapeutic exercise programs vs. pharmacological or surgical interventions, these increases in walking distance are greater than those reported for the most widely used agents for claudication, pentoxyphylline, and cilostazol. Despite a reduction in mortality and improvement of quality of life caused by physical activity in the PAD population, the molecular, cellular, and functional changes that occur during physical activity are not completely understood. Therefore, this review article aims at presenting an overview of recent established clinical and molecular findings addressing the role of physical activity on PAD in the older population.