[show abstract][hide abstract] ABSTRACT: Whether renal revascularization reduces left ventricular hypertrophy in patients with coronary artery disease is uncertain.
Randomized clinical trial testing the effect of renal artery stenting versus medical therapy on left ventricular hypertrophy progression in patients affected by ischemic heart disease and renal artery stenosis.
Incident patients with ischemic heart disease undergoing cardiac catheterization with renal artery stenosis >50%-≤80%.
Revascularization plus standard medical therapy versus medical therapy alone.
Primary end point was change in echocardiographic left ventricular mass index (LVMI).
Clinical and echocardiographic studies were performed at baseline and after 1 year.
84 patients were randomly assigned: 43 to revascularization plus standard medical therapy and 41 to medical therapy alone. At baseline, clinical characteristics were similar in the 2 study groups. After 1 year, there was no statistically significant difference between longitudinal change in the medical therapy group versus that in the medical therapy plus revascularization group for LVMI (2.1; 95% CI, -6.1 to 10.3 g/m(2)), blood pressure (systolic, -0.2 [95% CI, -9.1 to 8.8 mm Hg]; diastolic, -3.3 [95% CI, -8.4 to 1.8 mm Hg]), or estimated glomerular filtration rate (1.5; 95% CI, -5.8 to 8.9 mL/min/1.73 m(2)). The number of major cardiovascular events was similar in the 2 groups (revascularization plus standard medical therapy [fatal, n = 2; nonfatal, n = 11] and medical therapy alone [fatal, n = 2; nonfatal, n = 11]).
Patients with very severe renal artery stenosis were excluded from the study.
Our study was unable to detect a clinically significant benefit of renal revascularization on LVMI in patients with coronary artery disease and renal artery stenosis of 50%-80%.
American Journal of Kidney Diseases 04/2012; 60(1):39-46. · 5.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: Long-term anticoagulation with warfarin is the mainstay of treatment in patients with diseases with high thromboembolic potential, such as atrial fibrillation. However, warfarin therapy carries a number of inherent limitations, including slow onset and offset of action, interindividual variability, food and drug interactions, lack of selectivity and a narrow therapeutic window. Recently developed oral anticoagulants that selectively block key factors in the coagulation cascade, with no need for monitoring or dose adjustment, have the potential to replace warfarin in clinical practice. The safety and efficacy of these agents in patients with atrial fibrillation, venous thromboembolisms and acute coronary syndromes have been the object of numerous recent large-scale clinical investigations. This article provides an overview of the evidence currently available on the use of novel, orally available, selective anticoagulants in patients at risk for thromboembolic events.
Expert Review of Cardiovascular Therapy 04/2012; 10(4):473-88.
[show abstract][hide abstract] ABSTRACT: Left main coronary artery disease revascularization is one of the most debated topics in the setting of interventional cardiology. Although the gold standard therapy for left main disease is coronary artery bypass grafting, growing evidences suggest similar outcomes for percutaneous coronary intervention compared to cardiac surgery. The decision-making process aimed at selecting the best treatment option is a complex task requiring advanced expertise, Heart Team discussion, and risk stratification. The aim of this review is to provide an updated overview of treatment options for left main revascularization, highlighting current indications based on the latest international guidelines, reviewing the most important risk stratification systems with a glimpse to further clinical development in the field.
Recenti progressi in medicina 03/2012; 103(3):119-27.
[show abstract][hide abstract] ABSTRACT: This study sought to assess the presence of a dose-response effect of cigarette smoking and its impact on high on-treatment platelet reactivity (HPR) in patients with diabetes mellitus treated with clopidogrel.
Cigarette smoking is an inducer of cytochrome P450 1A2, a hepatic enzyme involved in clopidogrel metabolism. If cigarette smoking is associated with a dose-response effect on pharmacodynamic measures in clopidogrel-treated patients is unknown.
A total of 134 type 2 diabetes mellitus patients on maintenance aspirin and clopidogrel therapy were studied. Patients were divided into 3 groups according to cotinine levels: <3 ng/ml (nonsmokers), 3 to 199 ng/ml (light smokers), and ≥ 200 ng/ml (heavy smokers). Platelet function was assessed by light transmittance aggregometry, VerifyNow P2Y12 assay (Accumetrics, San Diego, California), and vasodilator-stimulated phosphoprotein. Rates of HPR were defined using established cutoff values.
A dose-response effect was observed for all pharmacodynamic parameters tested. Serum cotinine levels were inversely associated with platelet reactivity as assessed by light transmittance aggregometry using 5 and 20 μmol/l adenosine diphosphate (p < 0.0001 for all). Accordingly, platelet disaggregation increased with levels of serum cotinine (p < 0.0001). Similar results were found with P2Y(12) reaction units (p < 0.0001) and inhibition of platelet aggregation (p = 0.005) as defined by VerifyNow P2Y12 testing, and platelet reactivity index (p = 0.002) as assessed by vasodilator-stimulated phosphoprotein. Higher serum cotinine levels were significantly associated with lower rates of HPR, as defined according to various pharmacodynamic cutoff measures.
Cigarette smoking is associated with a dose-response effect on clopidogrel-induced antiplatelet effects and lower rates of HPR in diabetes mellitus patients.
[show abstract][hide abstract] ABSTRACT: Comparisons of transcatheter aortic valve implantation (TAVI) to surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis remain sparse or limited by a short follow-up. We sought to evaluate early and midterm outcomes of consecutive patients (n = 618) undergoing successful TAVI (n = 218) or isolated SAVR (n = 400) at 2 centers. The primary end point was incidence of Valvular Academic Research Consortium-defined major adverse cerebrovascular and cardiac events (MACCEs) up to 1 year. Control of potential confounders was attempted with extensive statistical adjustment by covariates and/or propensity score. In-hospital MACCEs occurred in 73 patients (11.8%) and was more frequent in patients treated with SAVR compared to those treated with TAVI (7.8% vs 14.0%, p = 0.022). After addressing potential confounders using 3 methods of statistical adjustment, SAVR was consistently associated with a higher risk of MACCEs than TAVI, with estimates of relative risk ranging from 2.2 to 2.6 at 30 days, 2.3 to 2.5 at 6 months, and 2.0 to 2.2 at 12 months. This difference was driven by an adjusted increased risk of life-threatening bleeding at 6 and 12 months and stroke at 12 months with SAVR. Conversely, no differences in adjusted risk of death, stroke and myocardial infarction were noted between TAVI and SAVR at each time point. In conclusion, in a large observational registry with admitted potential for selection bias and residual confounding, TAVI was not associated with a higher risk of 1-year MACCEs compared to SAVR.
The American journal of cardiology 02/2012; 109(10):1487-93. · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) score is a useful tool to guide decision-making in patients undergoing three-vessel disease and left main percutaneous coronary intervention. However, someone perceives the SYNTAX score as a labor-intensive surrogate with no added utility over clinical judgment and technical experience. We aimed at reviewing the current limitations of the SYNTAX score and provided practical considerations on how and when this angiographic tool should be used with the goal in mind to maximize its usefulness in the catheterization laboratory.
International journal of cardiology 02/2012; 159(3):165-8. · 7.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: OPINION STATEMENT: Antithrombotic pharmacotherapy is an essential component in the pharmacologic arsenal of physicians dealing with diseases at high thromboembolic potential, such as coronary artery disease and atrial fibrillation. Age has a non-negligible impact on the pharmacokinetic and pharmacodynamic effects of antithrombotic medications. Although the benefits of antithrombotic pharmacotherapy in the elderly are well established, the elderly are generally more vulnerable to the adverse effects of antithrombotic drugs, particularly bleeding. Factors that may affect therapeutic agents in general (e.g., renal function, hepatic metabolism, body mass distribution) as well as factors more specific to thrombosis and hemostasis (e.g., platelet dysfunction, coagulation disorders) may partially account for such higher vulnerability, demanding careful consideration. The lack of studies performed specifically in the elderly and their under-representation in many large-scale clinical trials often lead guidelines to give neutral recommendations or even arbitrary assumptions. The development of novel antithrombotic agents with a more favorable safety profile may have a promising role in the ever-growing population of elderly individuals.
Current Treatment Options in Cardiovascular Medicine 02/2012; 14(1):57-68.
[show abstract][hide abstract] ABSTRACT: The paucity of longitudinal, serial high-resolution imaging studies has limited our understanding of in vivo arterial response to drug-eluting stents. We sought to investigate the human coronary response to paclitaxel-eluting stent implantation, using serial optical coherence tomography assessments.
Thirty patients with at least 2 significant coronary lesions in different vessels were treated with a paclitaxel-eluting stent. The most severe stenosis (lesion A) was treated at the initial procedure, and the second target vessel (lesion B) was stented 3 months later. Optical coherence tomography was performed at baseline, 3-, and 9-month follow-up for lesions A and baseline and 6 months for lesions B. Prespecified end points were percent of uncovered and malapposed struts over time. In lesions A, uncovered struts were 3.77±4.94% and 3.02±4.35% at 3 versus 9 months (P=NS). Malapposed struts were 3.55±5.16% at post-procedure, 1.51±3.52% at 3 months, and 0.60±1.82% at 9 months (P<0.05, at 3 versus 9 months). Strut-level neointimal thickness was 0.19±0.09 mm and 0.20±0.11 mm (P=NS) over time. Newly acquired malapposition was detected in 10.4% and 3.3% of 2.5-mm segments at 3- and 9-month follow-up. In lesions B, uncovered struts were 2.91±5.47% at 6-months. Malapposed struts were 4.94±6.70% post-procedure and 1.01±3.11% at 6 months (P<0.01), with 0.19±0.09-mm neointimal thickness at follow-up.
Optical coherence tomography imaging suggested the first 3 months to be the period with most biological activity after paclitaxel-eluting stent implantation, when the proliferative reaction mainly occurs and malapposition resolves. A less active, yet continuous, dynamic arterial response, with resolution and development of malapposition, occurs through 9 months post-treatment.
[show abstract][hide abstract] ABSTRACT: 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).
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.
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.
European Heart Journal 01/2012; 33(8):969-76. · 14.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: The major cause of acute coronary syndrome (ACS) is vessel thrombosis related to plaque rupture. Optical coherence tomography (OCT) is a feasible and effective technique to visualise a thrombus in vivo.
To present the relationship between cardiac enzymes leakage before coronary angioplasty and thrombus visualised by OCT.
A population of 48 consecutive patients (mean age 64.8 ± 9 years) with non ST elevation syndromes treated with primary coronary angioplasty was selected for the study. Angiographic and OCT quantitative assessment was performed for all patients, as well as qualitative thrombus assessment with a new index--the thrombus score (TS). Troponin I and creatine kinase and its MB fraction were measured for all patients at baseline and at least 6-8 hours after coronary angioplasty.
The troponin level assessed before coronary angioplasty was 3.42 ± 7.31 ng/dL. The mean TS assessed before coronary angioplasty was 96 ± 56, and in 17 (35.4%) patients the score was greater than 100 points. Mean artery length occupied by thrombus was 7.8 ± 3.8 mm. There was a significant correlation between troponin level and thrombus score (r = 0.44, p 〈 0.05) in the whole studied population.
Initial troponin level may be associated with larger thrombus burden within a coronary artery. This finding may influence coronary flow and needs to taken into consideration during primary coronary intervention.
Kardiologia polska 01/2012; 70(5):457-62. · 0.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: The pivotal ATLANTA first-in-man study showed the promising safety and efficacy profile of the novel Catania™ stent in a population with ~20% American College of Cardiology/American Heart Association (ACC/AHA) type C coronary lesions. The ATLANTA 2 registry was designed to evaluate the 12-month safety and efficacy of the Catania stent in a broader real world scenario.
The ATLANTA 2 registry was a prospective, non-randomised, single-arm study of patients with symptomatic ischaemic heart disease and de novo lesions of native coronary arteries. A total of 300 patients (396 lesions) were recruited and 482 Catania stents were implanted. At 12 months, major adverse cardiac events were 8.8%, mainly driven by target lesion revascularisation (6.5%). Cardiac death and non-fatal myocardial infarction occurred in 2.5% and 0.7% of patients, respectively. Subacute definite or probable stent thrombosis was 0.7%. No late stent thrombosis was recorded. Compared with patients treated with drug-eluting stents or bare metal stents in the study period, those treated with Catania stents experienced similar outcomes at one year.
The 12-month results of the ATLANTA 2 registry confirmed the positive results of the ATLANTA first-in-man trial in a more complex population. A randomised trial is needed to assess the comparative value of the Catania stent over currently-used drug-eluting stents or bare metal stents.
EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 12/2011; 7(9):1062-8. · 3.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: Before trans-catheter aortic valve implantation (TAVI), assessment of cardiac function and accurate measurement of the aortic root are key to determine the correct size and type of the prosthesis. The aim of this study was to compare cardiovascular magnetic resonance (CMR) and trans-thoracic echocardiography (TTE) for the assessment of aortic valve measurements and left ventricular function in high-risk elderly patients submitted to TAVI.
Consecutive patients with severe aortic stenosis and contraindications for surgical aortic valve replacement were screened from April 2009 to January 2011 and imaged with TTE and CMR.
Patients who underwent both TTE and CMR (n = 49) had a mean age of 80.8 ± 4.8 years and a mean logistic EuroSCORE of 14.9 ± 9.3%. There was a good correlation between TTE and CMR in terms of annulus size (R2 = 0.48, p < 0.001), left ventricular outflow tract (LVOT) diameter (R2 = 0.62, p < 0.001) and left ventricular ejection fraction (LVEF) (R2 = 0.47, p < 0.001) and a moderate correlation in terms of aortic valve area (AVA) (R2 = 0.24, p < 0.001). CMR generally tended to report larger values than TTE for all measurements. The Bland-Altman test indicated that the 95% limits of agreement between TTE and CMR ranged from -5.6 mm to + 1.0 mm for annulus size, from -0.45 mm to + 0.25 mm for LVOT, from -0.45 mm2 to + 0.25 mm2 for AVA and from -29.2% to 13.2% for LVEF.
In elderly patients candidates to TAVI, CMR represents a viable complement to transthoracic echocardiography.
Journal of Cardiovascular Magnetic Resonance 12/2011; 13:82. · 4.44 Impact Factor
[show abstract][hide abstract] ABSTRACT: Studies specifically designed to assess clopidogrel response in the elderly as well as treatment alternatives to improve platelet inhibition in this high-risk population are lacking. This study aimed to define pharmacodynamic (PD) profiles, including high platelet reactivity (HPR) rates, among elderly patients on maintenance clopidogrel therapy and to assess the PD effects of prasugrel 5 mg/day in elderly with HPR. This was a prospective observational PD study enrolling consecutive ≥ 75-year-old patients on maintenance clopidogrel therapy (75 mg/day) who were tested for clopidogrel response by the VerifyNow P2Y12 assay and light transmittance aggregometry (LTA). HPR rates were estimated using multiple definitions. HPR patients identified by the VerifyNow P2Y12 assay [P2Y12 reaction unit (PRU) ≥ 230] were switched to prasugrel 5 mg/day, and platelet function testing was performed after 15 days of treatment. PD testing was completed in 100 patients. The HPR prevalence varied between 25% and 32%, depending on the definition used. A PRU ≥ 230 was observed in 25 patients; of these, 20 switched to prasugrel 5 mg/day. This resulted in significant reduction in PRU mean values (279.8 ± 45.1 vs. 171.7 ± 65.2, p=0.0002) with an absolute between-treatment difference of 108.1 (95% confidence intervals 75.2-140.9). Accordingly, switching to prasugrel 5 mg/day overcame HPR in most (80%) patients. Consistently, all LTA measures were significantly lower after prasugrel compared with clopidogrel. In conclusion, a considerable proportion of elderly patients exhibit HPR while on standard clopidogrel therapy. Switching to 5 mg/day prasugrel in elderly patients with HPR is associated with enhanced platelet inhibition and overcomes HPR in the majority of these patients.
Thrombosis and Haemostasis 12/2011; 106(6):1149-57. · 6.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: Conduction disorders and permanent pacemaker (PPM) implantation are common complications in patients undergoing transcatheter aortic valve implantation (TAVI). Previous studies, evaluating small populations, have identified several different predictors of PPM implantation after TAVI. The aim of this study was to assess the incidence rate of conduction disorders and the predictors of postoperative PPM requirement in a large series of patients undergoing TAVI.
Data were analyzed from 181 consecutive patients at high-risk surgery who underwent TAVI at our institute between July 2007 and April 2011. All patients underwent implantation of the third-generation percutaneous self-expanding CoreValve® prosthesis (CoreValve, Inc., Irvine, CA, USA). In all patients, a 12-lead electrocardiogram and a 24-h holter monitoring was recorded before and after the procedure in order to assess the presence of conduction disorders. Clinical data, preoperative conduction disorders, echocardiographic patterns, and procedural data were tested as predictors of PPM implantation after TAVI.
Left bundle branch block (LBBB) was the most common conduction disorder, with an incidence of 50.3% at discharge. Fifty-two (32.1%) patients developed a persistent complete AVB requiring PPM implantation. PPM implantation was strongly correlated with the presence of preoperative right bundle branch block (RBBB) which was found to be the only independent predictor of PPM implantation (HR 16.5, CI 3.3-82.3, p < 0.001).
LBBB and PPM implantation requirement after TAVI are common occurrences using the self-expanding CoreValve prosthesis. In this large series of consecutive patients, only RBBB was found to be a strong predictor of PPM requirement.
[show abstract][hide abstract] ABSTRACT: Bleeding has emerged as a predictor of early and late mortality after percutaneous coronary interventions. However, the prevalence and predictors of long-term bleeding events in patients on prolonged dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation has been poorly explored.
A total of 1,437 patients undergoing DES implantation discharged on DAPT with aspirin and clopidogrel for 1 year were studied. Patients were followed for up to 4 years (34.3 ± 14.4 months) and the prevalence and predictors of in-hospital and long-term thrombolysis in myocardial infarction (TIMI) major and minor bleeding events evaluated. The impact of bleeding events on major adverse cardiac events (MACE), overall death, and stent thrombosis (ST) was also assessed.
The incidences of 30 days major and minor bleeding were 1.3 and 3.3%, respectively. The incidences of 1-year major and minor bleeding were 3.0 and 5.6%, respectively. The incidences of major and minor bleeding up to 4-year follow-up were 3.6 and 6.9%, respectively. At multivariable analysis, 1-year major bleeding was positively predicted by use of oral anticoagulants at hospital discharge [odds ratio (OR) = 13.4, 95% confidence interval (CI) 3.0-59.2, P = 0.001], anemia at admission (OR = 6.7, 95% CI = 2.7-16.5, P < 0.001) and use of glycoprotein IIb/IIIa inhibitors (OR = 2.7, 95% CI = 1.1-6.5, P = 0.03) and negatively predicted by male gender (OR = 0.39, 95% CI = 0.16-0.97, P = 0.042). Overall, major bleeding at 1 year and at long-term follow-up was associated with an increased risk of MACE, cardiac death and ST. Patients who had any bleeding event were more likely to prematurely discontinue antiplatelet therapy (50% vs. 9.6%, P < 0.001).
In DES-treated patients on prolonged DAPT, major bleeding occurring at 1 year and up to 4 years following DES implantation in patients on prolonged DAPT is associated with poor long-term prognosis.
Catheterization and Cardiovascular Interventions 11/2011; 80(3):395-405. · 2.51 Impact Factor