Davide Capodanno

Incidence and Predictors of Early and Late Mortality After Transcatheter Aortic Valve Implantation in 663 Patients With Severe Aortic Stenosis

Background— There is a lack of information on the incidence and predictors of early mortality at 30 days and late mortality between 30 days and 1 year after transcatheter aortic valve implantation (TAVI) with the self-expanding CoreValve Revalving prosthesis. Methods and Results— A total of 663 consecutive patients (mean age 81.0±7.3 years) underwent TAVI with the third generation 18-Fr CoreValve device in 14 centers. Procedural success and intraprocedural mortality were 98% and 0.9%, respectively. The cumulative incidences of mortality were 5.4% at 30 days, 12.2% at 6 months, and 15.0% at 1 year. The incidence density of mortality was 12.3 per 100 person-year of observation. Clinical and hemodynamic benefits observed acutely after TAVI were sustained at 1 year. Paravalvular leakages were trace to mild in the majority of cases. Conversion to open heart surgery (odds ratio [OR] 38.68), cardiac tamponade (OR 10.97), major access site complications (OR 8.47), left ventricular ejection fraction <40% (OR 3.51), prior balloon valvuloplasty (OR 2.87), and diabetes mellitus (OR 2.66) were independent predictors of mortality at 30 days, whereas prior stroke (hazard ratio [HR] 5.47), postprocedural paravalvular leak ≥2+ (HR 3.79), prior acute pulmonary edema (HR 2.70), and chronic kidney disease (HR 2.53) were independent predictors of mortality between 30 days and 1 year. Conclusions— Benefit of TAVI with the CoreValve Revalving System is maintained over time up to 1 year, with acceptable mortality rates at various time points. Although procedural complications are strongly associated with early mortality at 30 days, comorbidities and postprocedural paravalvular aortic regurgitation ≥2+ mainly impact late outcomes between 30 days and 1 year.

Incidence, Predictors, and Outcomes of Aortic Regurgitation After Transcatheter Aortic Valve Replacement Meta-Analysis and Systematic Review of Literature

OBJECTIVES This study was designed to establish the incidence, impact, and predictors of post-transcatheter aortic valve replacement (TAVR) aortic regurgitation (AR). BACKGROUND AR is an important limitation of TAVR with ill-defined predictors and unclear long-term impact on outcomes. METHODS Studies published between 2002 and 2012 with regard to TAVR were identified using an electronic search and reviewed using the random-effects model of DerSimonian and Laird. From 3,871 initial citations, 45 studies reporting on 12,926 patients (CoreValve [Medtronic CV Luxembourg S.a.r.l., Tolochenaz, Switzerland] n = 5,261 and Edwards valve [Edwards Lifesciences, Santa Ana, California] n = 7,279) were included in the analysis of incidence and outcomes of post-TAVR AR. RESULTS The pooled estimate for moderate or severe AR post-TAVR was 11.7% (95% confidence interval [CI]: 9.6 to 14.1). Moderate or severe AR was more common with use of the CoreValve (16.0% vs. 9.1%, p = 0.005). The presence of moderate or severe AR post-TAVR increased mortality at 30 days (odds ratio: 2.95; 95% CI: 1.73 to 5.02) and 1 year (hazard ratio: 2.27; 95% CI: -1.84 to 2.81). Mild AR was also associated with an increased hazard ratio for mortality, 1.829 (95% CI: 1.005 to 3.329) that was overturned by sensitivity analysis. Twenty-five studies reported on predictors of post-TAVR AR. Implantation depth, valve undersizing, and Agatston calcium score (r = 0.47, p = 0.001) were identified as important predictors. CONCLUSIONS Moderate or severe aortic regurgitation is common after TAVR and an adverse prognostic indicator of short- and long-term survival. Incidence of moderate or severe AR is higher with use of the CoreValve. Mild AR may be associated with increased long-term mortality. Therefore, every effort should be made to minimize AR by a comprehensive pre-procedural planning and meticulous procedural execution.

Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS)

Atrial fibrillation (AF) confers a substantial risk of mortality and morbidity from stroke and thrombo-embolism, and this common cardiac arrhythmia represents a major healthcare burden in Europe.1 Stroke prevention is central to the management of AF patients, with the 2012 focused update of the European Society of Cardiology (ESC) guidelines2 recommending oral anticoagulation (OAC) using well-controlled adjusted dose vitamin K antagonists (VKAs, e.g. warfarin) or non-VKA oral anticoagulants (NOACs, previously referred to as new or novel OACs3) for patients with AF and ≥1 stroke risk factor(s). Also, these guidelines strongly advocate a clinical practice shift so that the initial decision step now is the identification of ‘truly low risk’ patients, essentially those aged <65 years without any stroke risk factor (both male and female), who do not need any antithrombotic therapy.2 The ESC guidelines also recommend the use of the CHA2DS2-VASc score4 for stroke risk assessment, and define ‘low-risk’ patients as those with a CHA2DS2-VASc score = 0 (males) or score = 1 (females). Subsequent to this initial step of identifying the low-risk patients, effective stroke prevention (which is essentially OAC) can then be offered to AF patients with ≥1 stroke risk factor(s), with treatment decisions made in consultation with patients and incorporating their preferences. In everyday clinical practice, over 80% of all patients with AF have an indication for OAC, and vascular disease co-exists in ∼30% of them.5–7 With an estimated prevalence of AF of 1–2% and ∼20% of these requiring percutaneous cardiovascular interventions over time,8 ∼1–2 million AF patients in Europe who are …

Transcatheter aortic valve implantation: 3-year outcomes of self-expanding CoreValve prosthesis

AIMS The paucity of evidences about the long-term durability of currently available transcatheter prostheses is one of the main issues of transcatheter aortic valve implantation (TAVI). We sought to assess 3-year clinical and echocardiographic outcomes of patients undergoing TAVI with the third generation CoreValve prosthesis (Medtronic Incorporation, MN, USA). METHODS AND RESULTS From the Italian CoreValve registry, 181 who underwent TAVI from June 2007 to August 2008 and eligible for 3-year follow-up were analysed. All outcomes were defined according to the Valve Academic Research Consortium. All-cause mortality at 1, 2, and 3 years was 23.6, 30.3, and 34.8%, respectively. Cardiovascular death at 1, 2, and 3 years was 11.2, 12.1, and 13.5%, respectively. The actuarial survival free from a composite of death, major stroke, myocardial infarction, and life-threatening bleeding was 69.6% at 1 year, 63.5% at 2 years, and 59.7% at 3 years. Patients with renal insufficiency had a higher mortality at 3-year follow-up (49.0 vs. 29.2%, P = 0.007); moreover, patients experiencing post-procedural major or life-threatening bleeding had a higher rate of mortality already seen at 30 days (21.6 vs. 2.8%; P < 0.001) and this result was sustained at 3-year follow-up (62.2 vs. 27.7%; P < 0.001). Mean pressure gradients decreased from 52.2 ± 18.1 mmHg (pre-TAVI) to 10.3 ± 3.1 mmHg (1-year post-TAVI) (P < 0.001); aortic valve area increased from 0.6 ± 0.2 cm(2) (pre-TAVI) to 1.8 ± 0.4 cm(2) (1-year post-TAVI); these results remained stable over the 3 years of follow-up. Paravalvular leak was observed in the majority of patients. There were no cases of progression to moderate or severe regurgitation. No cases of structural valve deterioration were observed. CONCLUSION This multicentre study demonstrates that TAVI with the 18-Fr CoreValve ReValving System is associated with sustained clinical and functional cardiovascular benefits in high-risk patients with symptomatic aortic stenosis up to 3-year follow-up. Non-cardiac causes accounted for the majority of deaths at follow-up.

Percutaneous mitral valve repair with the MitraClip system: acute results from a real world setting.

Aims This study sought to evaluate the feasibility and early outcomes of a percutaneous edge-to-edge repair approach for mitral valve regurgitation with the MitraClip® system (Evalve, Inc., Menlo Park, CA, USA). Methods and results Patients were selected for the procedure based on the consensus of a multidisciplinary team. The primary efficacy endpoint was acute device success defined as clip placement with reduction of mitral regurgitation to ≤2+. The primary acute safety endpoint was 30-day freedom from major adverse events, defined as the composite of death, myocardial infarction, non-elective cardiac surgery for adverse events, renal failure, transfusion of >2 units of blood, ventilation for >48 h, deep wound infection, septicaemia, and new onset of atrial fibrillation. Thirty-one patients (median age 71, male 81%) were treated between August 2008 and July 2009. Eighteen patients (58%) presented with functional disease and 13 patients (42%) presented with organic degenerative disease. A clip was successfully implanted in 19 patients (61%) and two clips in 12 patients (39%). The median device implantation time was 80 min. At 30 days, there was an intra-procedural cardiac tamponade and a non-cardiac death, resulting in a primary safety endpoint of 93.6% [95% confidence interval (CI) 77.2–98.9]. Acute device success was observed in 96.8% of patients (95% CI 81.5–99.8). Compared with baseline, left ventricular diameters, diastolic left ventricular volume, diastolic annular septal–lateral dimension, and mitral valve area significantly diminished at 30 days. Conclusion Our initial results with the MitraClip device in a very small number of patients indicate that percutaneous edge-to-edge mitral valve repair is feasible and may be accomplished with favourable short-term safety and efficacy results.

Platelet thrombin receptor antagonism and atherothrombosis

Clinical manifestations of atherothrombotic disease, such as acute coronary syndromes, cerebrovascular events, and peripheral arterial disease, are major causes of mortality and morbidity worldwide. Platelet activation and aggregation are ultimately responsible for the progression and clinical presentations of atherothrombotic disease. The current standard of care, dual oral antiplatelet therapy with aspirin and the P2Y12 adenosine diphosphate (ADP) receptor inhibitor clopidogrel, has been shown to improve outcomes in patients with atherothrombotic disease. However, aspirin and P2Y12 inhibitors target the thromboxane A2 and the ADP P2Y12 platelet activation pathways and minimally affect other pathways, while agonists such as thrombin, considered to be the most potent platelet activator, continue to stimulate platelet activation and thrombosis. This may help explain why patients continue to experience recurrent ischaemic events despite receiving such therapy. Furthermore, aspirin and P2Y12 receptor antagonists are associated with bleeding risk, as the pathways they inhibit are critical for haemostasis. The challenge remains to develop therapies that more effectively inhibit platelet activation without increasing bleeding complications. The inhibition of the protease-activated receptor-1 (PAR-1) for thrombin has been shown to inhibit thrombin-mediated platelet activation without increasing bleeding in pre-clinical models and small-scale clinical trials. PAR-1 inhibition in fact does not interfere with thrombin-dependent fibrin generation and coagulation, which are essential for haemostasis. Thus PAR-1 antagonism coupled with existing dual oral antiplatelet therapy may potentially offer more comprehensive platelet inhibition without the liability of increased bleeding.

Usefulness of the SYNTAX Score for Predicting Clinical Outcome After Percutaneous Coronary Intervention of Unprotected Left Main Coronary Artery Disease

Background—The SYNTAX score (SXscore) has been proposed recently as a valuable tool to characterize the coronary vasculature prospectively with respect to the number of lesions and their functional impact, location, and complexity. However, the prognostic value of SXscores in patients undergoing percutaneous coronary intervention of the left main artery has not been validated. Methods and Results—We applied the SXscore in 255 consecutive patients who underwent percutaneous coronary intervention for left main disease and explored its performance with respect to their clinical outcome. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate the relation between the SXscore and the incidence of cardiac mortality, the primary end point of the study, and major adverse cardiac events (MACE). At 1 year, the SXscore significantly predicted the risk of cardiac death (hazard ratio, 1.12/unit increase; 95% CI, 1.06 to 1.18; P<0.001) and MACE (hazard ratio, 1.59/unit increase; 95% CI, 1.02 to 2.48; P=0.043). After adjustment for potential confounders, a higher SXscore remained significantly associated with cardiac mortality (adjusted hazard ratio, 1.15; 95% CI, 1.05 to 1.26; P=0.003) and MACE (adjusted hazard ratio, 1.06; 95% CI, 1.02 to 1.10; P=0.005). C-indexes for SXscores in terms of cardiac death and MACE were 0.83 and 0.64, respectively. Using classification tree analysis, discrimination levels of 34 and 37 were identified as the optimal cutoff to distinguish between patients at low and high risk of cardiac death and MACE, respectively. Conclusions—The SXscore is a useful tool to predict cardiac mortality and MACE in patients undergoing percutaneous revascularization of the left main coronary artery.

Impact of Chronic Kidney Disease on Platelet Function Profiles in Diabetes Mellitus Patients With Coronary Artery Disease Taking Dual Antiplatelet Therapy

OBJECTIVES We sought to assess the impact of renal function on platelet reactivity in patients with diabetes mellitus (DM) and coronary artery disease on aspirin and clopidogrel therapy. BACKGROUND Diabetes mellitus is a key risk factor for chronic kidney disease (CKD). In aspirin-treated DM patients the presence of moderate/severe CKD is associated with reduced clinical efficacy of adjunctive clopidogrel therapy. Whether these findings may be attributed to differences in clopidogrel-induced effects is unknown. METHODS This was a cross-sectional observational study in which DM patients taking maintenance aspirin and clopidogrel therapy were studied. Patients were categorized into 2 groups according to the presence or absence of moderate/severe CKD. Platelet aggregation after adenosine diphosphate (ADP) and collagen stimuli were assessed with light transmittance aggregometry and defined patients with high post-treatment platelet reactivity (HPPR). Markers of platelet activation, including glycoprotein IIb/IIIa activation and P-selectin expression, were also determined using flow cytometry. RESULTS A total of 306 DM patients were analyzed. Patients with moderate/severe CKD (n = 84) had significantly higher ADP-induced (60 +/- 13% vs. 52 +/- 15%, p = 0.001) and collagen-induced (49 +/- 20% vs. 41 +/- 20%, p = 0.004) platelet aggregation compared with those without (n = 222). After adjustment for potential confounders, patients with moderate/severe CKD were more likely to have HPPR after ADP (adjusted odds ratio: 3.8, 95% confidence interval: 1.7 to 8.5, p = 0.001) and collagen (adjusted odds ratio: 2.4; 95% confidence interval: 1.1 to 5.4; p = 0.029) stimuli. Markers of platelet activation were significantly increased in patients with HPPR. CONCLUSIONS In DM patients with coronary artery disease taking maintenance aspirin and clopidogrel therapy, impaired renal function is associated with reduced clopidogrel-induced antiplatelet effects and a greater prevalence of HPPR.

Percutaneous coronary intervention versus coronary artery bypass graft surgery in left main coronary artery disease: a meta-analysis of randomized clinical data

OBJECTIVES The purpose of this study was to determine the safety and efficacy of percutaneous coronary intervention (PCI) compared with coronary artery bypass graft (CABG) in patients with left main coronary artery (LMCA) disease. BACKGROUND Previous meta-analyses of PCI versus CABG in LMCA disease mainly included nonprospective, observational studies. Several new randomized trials have recently been reported. METHODS We identified 1,611 patients from 4 randomized clinical trials for the present meta-analysis. The primary endpoint was the 1-year incidence of major adverse cardiac and cerebrovascular events (MACCE), defined as death, myocardial infarction (MI), target vessel revascularization (TVR), or stroke. RESULTS PCI was associated with a nonsignificantly higher 1-year rate of MACCE compared with CABG (14.5% vs. 11.8%; odds ratio [OR]: 1.28; 95% confidence interval [CI]: 0.95 to 1.72; p = 0.11), driven by increased TVR (11.4% vs. 5.4%; OR: 2.25; 95% CI: 1.54 to 3.29; p < 0.001). Conversely, stroke occurred less frequently with PCI (0.1% vs. 1.7%; OR: 0.15; 95% CI: 0.03 to 0.67; p = 0.013). There were no significant differences in death (3.0% vs. 4.1%; OR: 0.74; 95% CI: 0.43 to 1.29; p = 0.29) or MI (2.8% vs. 2.9%; OR: 0.98; 95% CI: 0.54 to 1.78; p = 0.95). CONCLUSIONS In patients with LMCA disease, PCI was associated with nonsignificantly different 1-year rates of MACCE, death, and MI, a lower risk of stroke, and a higher risk of TVR compared with CABG.

Usefulness of SYNTAX score to select patients with left main coronary artery disease to be treated with coronary artery bypass graft.

OBJECTIVES The purpose of our study was to investigate the utility of the SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) score in aiding patient selection for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in a large contemporary registry of patients undergoing revascularization of left main coronary artery. BACKGROUND The SYNTAX score has been developed as a combination of several validated angiographic classifications aiming to grade the coronary lesions with respect to their functional impact, location, and complexity. METHODS Between March 2002 and December 2008, 819 patients with left main coronary artery disease underwent revascularization in 2 Italian centers. We compared clinical outcomes of PCI versus CABG in patients with SYNTAX score < or =34 and patients with SYNTAX score >34. RESULTS The rates of 2-year mortality were similar between CABG and PCI in the group of patients with SYNTAX score < or =34 (6.2% vs. 8.1%, p = 0.461). Among patients with SYNTAX score >34, those treated with CABG had lower rates of mortality (8.5% vs. 32.7%, p < 0.001) than those treated with PCI. After statistical adjustment, revascularization by PCI resulted in a similar risk of death compared with CABG in patients with SYNTAX score < or =34 (hazard ratio: 0.81, 95% confidence interval: 0.33 to 1.99, p = 0.64) and in a significantly higher risk in patients with SYNTAX score >34 (hazard ratio: 2.54, 95% confidence interval: 1.09 to 5.92, p = 0.031). CONCLUSIONS A SYNTAX score threshold of 34 may usefully identify a cohort of patients with left main disease who benefit most from surgical revascularization in terms of mortality.