Ibraim Pinto

A next-generation bioresorbable coronary scaffold system: from bench to first clinical evaluation: 6- and 12-month clinical and multimodality imaging results.

OBJECTIVES This study sought to perform clinical and imaging assessments of the DESolve Bioresorbable Coronary Scaffold (BCS). BACKGROUND BCS, which is drug eluting, may have potential advantages compared with conventional metallic drug-eluting stents. The DESolve system, designed to provide vessel support and neointimal suppression, combines a poly-l-lactic acid-based scaffold with the antiproliferative myolimus. METHODS The DESolve First-in-Man (a non-randomized, consecutive enrollment evaluation of the DESolve myolimus eluting bioresorbable coronary stent in the treatment of patients with de novo native coronary artery lesions) trial was a prospective multicenter study enrolling 16 patients eligible for treatment. The principal safety endpoint was a composite of cardiac death, myocardial infarction, and clinically indicated target lesion revascularization. The principal imaging endpoint was in-scaffold late lumen loss (LLL) assessed by quantitative coronary angiography (QCA) at 6 months. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) imaging was performed at baseline and 6 months; multislice computed tomography (MSCT) was performed at 12 months. RESULTS Acute procedural success was achieved in 15 of 15 patients receiving a study scaffold. At 12 months, there was no scaffold thrombosis and no major adverse cardiac events directly attributable to the scaffold. At 6 months, in-scaffold LLL (by QCA) was 0.19 ± 0.19 mm; neointimal volume (by IVUS) was 7.19 ± 3.56%, with no evidence of scaffold recoil or late malapposition. Findings were confirmed with OCT and showed uniform, thin neointimal coverage (0.12 ± 0.04 mm). At 12 months, MSCT demonstrated excellent vessel patency. CONCLUSIONS This study demonstrated the feasibility and efficacy of the DESolve BCS. Results showing low in-scaffold LLL, low % neointimal volume at 6 months, no chronic recoil, and maintenance of lumen patency at 12 months prompt further study. (DESolve First-in-Man; EudraCT number 2011-000027-32).

Comparison of automated quantitative coronary angiography with caliper measurements of percent diameter stenosis

Measurement of coronary artery stenosis is an invaluable tool in the study of coronary artery disease. Clinical trials and even day-to-day decision making should ideally be based on accurate and reproducible quantitative methods. Quantitative coronary angiography (QCA) using digital angiographic techniques has been shown to fulfill these requirements. Yet many laboratories have abandoned visual analysis in favor of the intermediate quantitative approach involving hand-held calipers. Thus, the purpose of this study was to determine the relation between QCA and the commonly used caliper measurements. Percent stenosis was assessed in 155 lesions using 3 techniques: QCA, caliper measures from a 35-mm cine viewer (cine) and caliper measures from a video display (CRT). Good overall correlation was noted among the 3 different techniques (r greater than or equal to 0.72). Both of the caliper methods underestimated QCA for stenosis greater than or equal to 75% (p less than or equal to 0.001) and overestimated stenosis less than 75% (p less than 0.05). Reproducibility assessed in 52 lesions by independent observers showed QCA to be superior (r = 0.95) to either of the caliper measurements (cine: r = 0.63; CRT: r = 0.73). Therefore, the commonly used caliper method is not an adequate substitute for QCA because overestimation of noncritical stenoses and underestimation of severe stenoses may occur and the measurements have poor reproducibility. These factors definitely preclude its use in rigorous clinical trials. Moreover, since they do not appear to overcome known deficiencies of visual analysis, caliper measurements for day-to-day clinical use must also be seriously questioned.

Automated quantitation of indexes of coronary lesion complexity. Comparison between patients with stable and unstable angina.

Analysis of lesion morphology is becoming increasingly important in the study of coronary artery disease. Lesion irregularity has been shown to be one of the most important predictive features for development of myocardial infarction. Most studies to date have used only qualitative assessments of morphology and are thus subject to variability and lack of standardization inherent in subjective visual inspection. We describe a new approach that allows quantitation of lesion morphology. Fifty-nine patients with unstable angina and 17 patients with stable angina were compared. Five morphometric parameters were tested (peaks per centimeter, summed maximum error per centimeter, integrated error per centimeter, number of major features per centimeter, and scaled edge length ratio), four of which were significantly different between the two groups and indicated greater lesion complexity in unstable compared with stable angina patients. No correlation was found between the parameters tested and the degree of luminal narrowing, showing the methods independence from traditional assessments of lesion severity. Excellent intraobserver and interobserver reproducibility was found for all of the parameters. This technique provides a more rigorous approach for analysis of lesion morphology than has previously been available, may provide a method for premorbid detection of high-risk lesions amenable to interventional therapy, and is especially well suited to detect subtle changes in lesion morphology after therapeutic interventions because the parameters are derived on a continuous scale and are not categorical.

Volumetric Analysis of In-Stent Intimal Hyperplasia in Diabetic Patients Treated With or Without Abciximab Results of the Diabetes Abciximab steNT Evaluation (DANTE) Randomized Trial

Background—In diabetic patients in the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trial, abciximab reduced target vessel revascularization by ≈50% compared with placebo. Whether this is a result of a lower restenosis rate caused by inhibition of intimal hyperplasia remains to be defined. Methods and Results—The purpose of this study was to determine whether abciximab at the time of stent implantation would reduce in-stent intimal hyperplasia measured by intravascular ultrasound at 6-month follow-up in type 2 diabetics. Ninety-six diabetic patients (96 lesions) who underwent elective stent implantation for a de novo lesion in a native coronary artery were randomly assigned to receive abciximab or no abciximab. In-stent intimal hyperplasia volume, expressed as percentage of stent volume, did not differ between groups: 41.3±21.0% for those treated with abciximab versus 40.5±18.3% for those treated without abciximab (P =0.9). There were also no significant differences in angiographic minimal luminal diameter at follow-up (1.74±0.69 versus 1.66±0.63 mm; P =0.5), late loss (1.03±0.63 versus 1.07±0.58 mm; P =0.7), restenosis rate (17.8% versus 22.9%; P =0.5), or cumulative incidence of major adverse cardiac events at 12 months (19.1% versus 20.4%; P =0.9). Conclusions—Six-month intravascular ultrasound volumetric analysis showed that abciximab, at the time of coronary stent implantation, was not associated with a reduction of in-stent intimal hyperplasia in diabetic patients.

Hipertrofia ventricular esquerda do atleta: resposta adaptativa fisiológica do coração

OBJECTIVE To verify whether left ventricular hypertrophy (LVH) of elite competition athletes (marathoners) represents a purely physiological, adaptative process, or it may involve pathological aspects in its anatomical and functional characteristics. METHODS From November 1999 to December 2000, consecutive samples from 30 under 50-year-old marathoners in full sportive activity, with previously documented LVH and absence of cardiopathy were selected. They were submitted to clinical exams, electrocardiogram, color Doppler echocardiogram and exercise treadmill test (ETT). Fifteen were assorted to be also submitted to ergoespirometric test and heart magnetic resonance imaging (MRI). RESULTS In ETT, all of them showed good physical pulmonary capacity, with no evidences of ischemic response to exercise, symptoms or arrhythmias. In Doppler echocardiogram, values of diameter and diastolic thickness of LV posterior wall, interventricular septum, LV mass and left atrium diameter, were significantly higher when compared to non-athlete control group, with similar ages and anthropometric measurements. The mean of LV mass of athletes indexed to body surface (126 g/m2) was significantly greater than the one in control group (70 g/m2) (p < 0.001). Magnetic resonance imaging (MRI) showed there was not impairment of contractile strength or LV performance, and values of end diastolic volume, end systolic volume and EF within limits of normality. On the other hand, average ventricular parietal mass, 162.93 +/- 17.90 g, and LV parietal thickness, 13.67 +/- 2.13 mm, at the end of diastole in athlete group, differed significantly from control group: 110 +/- 14.2 g (p = 0.0001) and 8 +/- 0.9 mm, respectively (p = 0.0001). The same happened to the thickness at the end of systole, which was 18.87 +/- 3.40 mm (control group: 10 +/- 1.80 mm, p = 0.0001). CONCLUSION Results allowed for concluding that LVH in marathoners in full sportive activity period, assessed by non-invasive methods, represents an adaptative response to intensive and prolonged physical training, with purely physiological characteristics.OBJETIVO: Verificar se a hipertrofia ventricular esquerda (HVE) de atletas competitivos de resistencia (maratonistas) representa processo adaptativo, puramente fisiologico, ou se pode envolver aspectos patologicos em suas caracteristicas anatomicas e funcionais. METODOS: De novembro de 1999 a dezembro de 2000, foram separados consecutivamente de 30 maratonistas em atividade esportiva plena, idade inferior a 50 anos, com HVE, previamente documentada, e sem cardiopatia subjacente. Foram submetidos aos exames: clinico, eletrocardiograma, ecodopplercardiograma, e teste ergometrico (TE). Quinze foram sorteados para realizar, tambem, teste ergoespirometrico e ressonância magnetica (RM) do coracao. RESULTADOS: Nos TE, todos apresentavam boa capacidade fisica cardiopulmonar, sem evidencias de resposta isquemica ao exercicio, sintomas ou arritmias. No ecodopplercardiograma, os valores do diâmetro e espessura diastolica da parede posterior do ventriculo esquerdo (VE), do septo interventricular, massa do VE e diâmetro do atrio esquerdo, foram significativamente maiores que os do grupo de nao atletas, com idades e medidas antropometricas semelhantes. A media da massa do VE dos atletas indexada a superficie corporea (126 g/m2) foi significativamente maior que a do grupo controle (70 g/m2) (p<0,001). A RM mostrou que nao havia prejuizo da forca contratil ou da performance ventricular esquerda e valores de volume diastolico final, volume sistolico final e fracao de ejecao dentro dos limites da normalidade. Por outro lado, a massa do VE media, 162,93±17,90 g, e a espessura parietal ventricular, 13,67±2,13 mm, ao final da diastole no grupo atleta, diferiu significativamente do controle: 110±14,2 g (p=0,0001) e 8±0,9 mm, respectivamente (p=0,0001). O mesmo ocorreu na media da espessura ao final da sistole, que foi 18,87±3,40 mm (controle: 10± 1,80 mm, p=0,0001). CONCLUSAO: Os resultados permitiram concluir que a HVE de maratonistas em periodo de atividade esportiva plena, avaliada por metodos nao invasivos, representa resposta adaptativa ao treinamento fisico intensivo e prolongado, com caracteristicas fisiologicas.

Vascular Healing 4 Years After the Implantation of Sirolimus-Eluting Stent in Humans A Histopathological Examination

A 60-year-old male patient with coronary disease was included in the “First-in Man” study1 and received a single sirolimus-eluting stent (SES, fast release) in December 1999 to treat a 90% diameter stenosis lesion located in the proximal right coronary artery (RCA). The patient had mild to moderate (<50% diameter stenosis) obstructions in the left anterior descending and left circumflex arteries. Coronary angiography and intravascular ultrasound (IVUS) revealed minimal neointimal growth in the midstent region at 4 months, 1 year, and 2 years after implantation. The patient underwent aortic and mitral valve replacement without complication 3 years after SES implantation. Left ventricle ejection fraction was 22%. He had a cardiac arrest out of the hospital in January 2004 (4-year follow-up). The patient was resuscitated but suffered severe cerebral damage. Postarrest angiography showed a widely patent …A 60-year-old male patient with coronary disease was included in the “First-in Man” study1 and received a single sirolimus-eluting stent (SES, fast release) in December 1999 to treat a 90% diameter stenosis lesion located in the proximal right coronary artery (RCA). The patient had mild to moderate (<50% diameter stenosis) obstructions in the left anterior descending and left circumflex arteries. Coronary angiography and intravascular ultrasound (IVUS) revealed minimal neointimal growth in the midstent region at 4 months, 1 year, and 2 years after implantation. The patient underwent aortic and mitral valve replacement without complication 3 years after SES implantation. Left ventricle ejection fraction was 22%. He had a cardiac arrest out of the hospital in January 2004 (4-year follow-up). The patient was resuscitated but suffered severe cerebral damage. Postarrest angiography showed a widely patent …

Visceral fat and coronary artery calcification in patients with chronic kidney disease

BACKGROUND Abdominal fat is a metabolically active tissue which has been associated with cardiovascular events and death in chronic kidney disease (CKD) patients. We explore here the association between surrogates of abdominal fat and coronary artery calcium score (CACs). METHODS Cross-sectional analysis of 232 non-dialysis-dependent CKD patients Stages 3-5 (median age 60 [25th-75th percentile 52-67] years; 60% men). Visceral adipose tissue (VAT) and CACs were assessed by computed tomography. Surrogates of abdominal fat included VAT and waist circumference (WC). RESULTS VAT was positively associated with CACs in univariate analysis (ρ = 0.23). Across increasing VAT quartiles, patients were older, more often men and smokers. Although increasing VAT quartiles associated with higher glomerular filtration rate and leptin, better nutritional status (subjective global assessment) as well as larger muscle stores and strength, they were also more insulin resistant (HOMA-IR), dyslipidemic and inflamed (C-reactive protein and white blood cells). In addition, CACs were incrementally higher. Clinically evident coronary artery calcification (CACs ≥ 10 Agatston) was present in 63% of the patients. Both increased visceral fat (odd ratio 1.60 [95% CI 1.23-2.09] per standard deviation increase) and increased WC (1.05 [1.01-1.12] per cm increase), augmented the odds to present calcification. Such associations remained statistically significant after extensive multivariate adjustment for confounders. CONCLUSIONS Abdominal fat is associated with coronary artery calcification in non-dialysis dependent CKD patients, supporting its potential role as a cardiovascular risk factor in uremia.

Tratamento do tromboembolismo pulmonar maciço por fragmentação percutânea do trombo

OBJECTIVES: To evaluate the safety and efficacy of percutaneous thrombus fragmentation (PTF) for massive pulmonary embolism (PE) in patients with contraindications to the administration of thrombolytics. METHODS: Between July 1999 and August 2005, 10 patients (7 males, 3 females, age 57±18 years) with massive PE and contraindications to the administration of thrombolytics underwent PTF. A transthoracic doppler echocardiogram was used to evaluate arterial oxygen saturation (Sat O2), the Walsh index (WI), mean pulmonary artery pressure (PAP), mean systemic blood pressure (SBP) and right ventricular function (RVF) before and after the procedure. Statistical analysis was conducted using the paired Wilcoxon test, of which p was significant when < 0.05. RESULTS: After the PTF treatment there was an improvement in Sat. O2 [87.4 ± 1.3% vs 92.3 ± 3.1% (p < 0.001)], WI [6.4 ± 1.07 vs 4.4 ± 1.42 (p = 0.003)], PAP [31.8 ± 4.6 mmHg vs 25.5 ± 3.4 mmHg (p < 0.001)] and SBP [73.9 ± 8.7 vs 85 ± 8.3 (p = 0.001). The ten patients had severe RVF before the percutaneous treatment; however, within 10 days after PTF, 8 presented normal or discrete function and 1 presented mitigated function. There were no technical or vascular access site complications related to PTF. One patient died in the hospital (10%). The procedure was successful for the other nine patients. CONCLUSION: The lack of adverse complications related to the procedure, proves that PTF is safe. The improvement in Sat O2, WI, PAP, SBP and RVF in 90% of the cases demonstrates the efficacy of the procedure, indicating that it is an alternative treatment for massive PE in patients with contraindications for the administration of systemic thrombolytics.

Effects of video frame averaging, smoothing and edge enhancement on the accuracy and precision of quantitative coronary arteriography

Digital analysis of cine film provides numerous options for altering images by frame averaging or filtering algorithms that either smooth or enhance edges. While these may subjectively enhance image quality, there is no uniformity in their use among laboratories and effects on quantitative coronary analysis may not be ideal. To determine which processing algorithms might help or hinder quantitative coronary arteriography, cine film images of precision drilled stenotic cylinders (0.83 to 1.83 mm diameter) implanted in dog coronary arteries were analyzed with and without such algorithms. Video frame averaging of 1 to 49 frames had no effect on measures of accuracy (mean differences) but precision (standard deviation of mean differences) was improved from 0.23 to 0.17 mm (p<0.05) with video averaging of ≥25 frames. Edge enhancement filtering algorithms resulted in slight deterioration of accuracy and precision and smoothing filtering algorithms caused modest improvements in these parameters; however, these changes were not significantly different from unprocessed images. Using edge enhancement filtering algorithms, accuracy was significantly worse (−0.27 mm) compared to a smoothing filter enhancement algorithm (−0.08 mm, p<0.001). The combination of video averaging and smoothing algorithms had no additional beneficial effects. Thus, precision of quantitative coronary analysis of cine film can be optimized by appropriate video averaging. Edge enhancement filtering algorithms should be avoided whereas smoothing filter enhancement algorithms may improve accuracy.

Uma comparação entre a intervenção coronariana percutânea de resgate e primária realizadas no infarto agudo do miocárdio: relato multicêntrico de 9.371 pacientes

OBJECTIVE: To perform a comparative analysis of in-hospital results obtained from AMI patients who underwent rescue or primary PTCA. METHODS: From the Brazilian Interventional National Registry (CENIC), we selected all consecutive patients who underwent a percutaneous coronary intervention for myocardial infarction (< 24 hours), between 1997 and 2000, analyzing those undergoing a rescue (n=840) or a primary (n=8,531) procedure, and comparing their in-hospital results. RESULTS: Rescue patients were significantly younger males with anterior wall infarctions, associated with left ventricular dysfunction, but had less multivessel disease, compared with those treated with primary intervention. Coronary stents were implanted in at similar rates (56.9% vs. 54.9%; P=0.283). Procedural success were lower for rescue cases (88.1% vs. 91.2%; P<0.001), with higher mortality (7.4% vs. 5.6%; P=0.034), compared with the primary intervention group; target vessel revascularization (< 0.5%), emergency bypass surgery (< 0.3%) and reinfarction (< 2.6%) rates were similar for both strategies. Multivariate analysis identified the rescue procedure as a predictor of in-hospital death [OR(CI=95%) = 1.60 (1.17-2.19); P=0.003]. CONCLUSION: Patients who underwent a rescue coronary intervention had higher in-hospital death rates compared with those who underwent a primary coronary intervention.