Jose A. Silva

Unstable Angina A Comparison of Angioscopic Findings Between Diabetic and Nondiabetic Patients

BACKGROUND Patients with diabetes mellitus have a higher prevalence of atherosclerotic heart disease and a higher incidence of myocardial infarction than the general population. Diabetic patients also have several hematologic, rheologic, and metabolic abnormalities not present in their nondiabetic counterparts that may predispose them to atherosclerotic plaque rupture and intraluminal thrombosis and consequently may lead to the formation of morphologically complex plaques and the development of acute coronary syndromes. METHODS AND RESULTS Percutaneous coronary angioscopy was performed in 55 consecutive patients with unstable angina. We observed plaque color, texture, and the incidence of intracoronary thrombus associated with the culprit lesions of these patients. The population consisted of 17 (31%) diabetic and 38 (69%) nondiabetic patients. The presence of coronary risk factors was not significantly different between the two populations. Ulcerated plaque was found in 16 of 17 (94%) diabetic patients versus 23 of 38 (60%) nondiabetic patients (P = .01). Intracoronary thrombi were seen in 16 of 17 (94%) diabetic patients versus 21 of 38 (55%) nondiabetic patients (P = .004). CONCLUSIONS The results of the angioscopic examination show that diabetic patients with unstable angina have a higher incidence of plaque ulceration and intracoronary thrombus formation than nondiabetic patients. This increased frequency of complex lesion morphology is consistent with the disproportionately higher risk for development of acute coronary syndromes in these patients.

Elevated brain natriuretic peptide predicts blood pressure response after stent revascularization in patients with renal artery stenosis.

Background—A significant number (20% to 40%) of hypertensive patients with renal artery stenosis will not have blood pressure improvement after successful percutaneous revascularization. Identifying a group of patients with refractory hypertension and renal artery stenosis who are likely to respond to renal stent placement would be beneficial. Methods and Results—Brain natriuretic peptide (BNP) was measured in 27 patients with refractory hypertension and significant renal artery stenosis before and after successful renal artery stent placement. This neuropeptide was elevated (median, 187 pg/mL; 25th to 75th percentiles, 89 to 306 pg/mL) before stent placement and fell within 24 hours of the successful stent procedure (96 pg/mL; 25th to 75th percentiles, 61 to 182 pg/mL; P=0.002), remaining low (85 pg/mL; 25th to 75th percentiles, 43 to 171 pg/mL) at follow-up. Clinical improvement in hypertension was observed in the patients with a baseline BNP >80 pg/mL (n=22) in 17 patients (77%) compared with 0% of the patients with a baseline BNP ≤80 pg/mL (n=5) (P=0.001). After correction for glomerular filtration rate, BNP was strongly correlated with improvement in hypertension. Conclusions—BNP is increased in patients with severe renal artery stenosis and decreases after successful stent revascularization. In addition, an elevated baseline BNP level of >80 pg/mL appears to be a good predictor of a blood pressure response after successful stent revascularization.

Rheolytic thrombectomy in the treatment of acute limb-threatening ischemia: Immediate results and six-month follow-up of the multicenter AngioJet® registry

We tested the efficacy of rheolytic thrombectomy in treating 21 patients (mean age 68+/-12 years; 66% male) and 22 vessels (limbs) who presented to the hospital within 2 weeks of the development of limb-threatening ischemia. Fifty-two percent had contraindications to use thrombolytics, and 57% had severe comorbidities. All of the vessels were occluded with thrombus on the initial angiogram. Procedural success was achieved in 20 limbs (91%). Three patients expired in the hospital, and one expired at follow-up due to nonvascular causes. Acute limb salvage was achieved in 18 of 19 limbs (95%) in the 18 survivors, and 6-month limb salvage was achieved in 16 of 18 limbs (89%) in the 17 survivors. Rheolytic thrombectomy is effective in restoring immediate blood flow in acute limb-threatening ischemia, especially in high-risk surgical patients or patients with contraindications to thrombolytic therapy.

Primary stenting in acute myocardial infarction: influence of diabetes mellitus in angiographic results and clinical outcome.

BACKGROUND The outcome of patients with diabetes after myocardial infarction (MI) has traditionally been worse than in their nondiabetic counterparts before and during the thrombolytic therapy era. Whether the fate of patients with diabetes might improve with mechanical intervention, particularly with primary stenting, has not previously been studied. METHODS We compared the angiographic and clinical outcome of 76 nondiabetic patients (aged 61 +/- 14 years; 66% male) and 28 patients with diabetes (aged 65 +/- 12 years; 64% male) consecutively treated with primary stenting for acute MI. Coronary Thrombolysis In Myocardial Infarction grade 3 flow was restored in 96% of diabetic and 97% of nondiabetic patients. RESULTS Angiographic results after stent deployment were similar in the 2 groups. At 1-month follow-up, all patients in both groups were alive. Patients with diabetes had a much higher incidence of stent thrombosis (18% vs 1%; P =.003), which accounted for the majority of the major cardiac events at 1 month (21% vs 4%; P =.009). At a mean follow-up of 315 +/- 13 days, 99% of nondiabetic and 89% of patients with diabetes were alive (P =.04). Overall freedom from a major cardiac event (death, MI, target vessel revascularization) at 315 +/- 13 day follow-up was 88% for nondiabetics and 54% for patients with diabetes (P =.0003). By multivariate analysis, diabetes mellitus was the most important predictor for development of 1-month (RR 9.89; 95% confidence interval, 1.6-30) and late major cardiovascular events (RR 8.39; 95% confidence interval, 2.93-24). CONCLUSIONS Primary stenting in acute MI is highly effective in restoring immediate TIMI 3 coronary flow in nondiabetic patients and patients with diabetes. This procedure may improve benefit in terms of mortality rate to both groups, particularly in patients with diabetes, compared with previous reports with thrombolytic therapy. Nevertheless, stent thrombosis and major cardiovascular events at 1 month and late follow-up are more frequent in patients with diabetes.

Percutaneous revascularization of the common femoral artery for limb ischemia.

We performed percutaneous transluminal intervention in 20 consecutive patients (21 limbs) with common femoral artery (CFA) lesions causing symptomatic limb ischemia. In 12 limbs, concurrent additional percutaneous intervention proximal or distal to the target CFA lesion was performed. Angiographic success was obtained in 100%, with procedural success (angiographic success without a major in‐hospital complications) in 90% and clinical success (procedural success and in‐hospital improvement by at least one Fontaine functional class) in 81% of the limbs. The in‐hospital Fontaine class improved by at least one functional class in 17 of 19 patients (89%), and the overall in‐hospital event‐free survival was 90% (18 of 20 patients). At follow‐up (11.4 ± 6 months), the overall event‐free survival was 90% (18 of 20 patients) and 17 of 19 patients (89%) continue to show improvement by at least one functional (Fontaine) class. Percutaneous intervention of the CFA can be performed with a rate of high technical success and a low complication rate. It provides excellent clinical results at mid‐term follow‐up and appears to be a reasonable alternative to surgical therapy in patients at high risk for surgery. Catheter Cardiovasc Interv 2004;62:230–233.

Morphologic comparison of atherosclerotic lesions in native coronary arteries and saphenous vein graphs with intracoronary angioscopy in patients with unstable angina

BACKGROUND Coronary vein grafts develop accelerated atherosclerosis after aortocoronary bypass surgery. Previous pathologic studies have suggested that the morphologic appearance of atherosclerotic lesions in saphenous vein grafts may have subtle differences compared with those of native coronary arteries and may be more prone to disruption and thrombus formation. However, a comparative in vivo assessment of the angioscopic morphology differences between these two types of vessels has not been reported previously. We compared the angioscopic lesion morphology of native coronary arteries and saphenous vein grafts in patients with unstable angina. METHODS AND RESULTS Percutaneous coronary angioscopy was performed in 60 consecutive patients with unstable angina. Plaque color, texture, friability, and the presence of atherosclerotic plaque ulceration or intracoronary thrombus were noted in the culprit lesion. The culprit lesion was located in native coronary arteries in 42 (70%) patients and in a saphenous vein graft in 18 (30%) patients. There were no significant differences in age, sex, and coronary risk factors including tobacco use, hypertension, hypercholesterolemia, or diabetes mellitus between the two populations. There were also no significant differences between the two groups in terms of plaque color, surface texture, or the incidence of complex plaque morphology (plaque ulceration and intracoronary thrombosis). Loosely adherent, friable plaque, detected by angioscopy, was absent in native coronary arteries and was present in 44% of the saphenous vein grafts (p < 0.0001). CONCLUSIONS The results of our angioscopic study indicate that other than a high incidence of plaque friability in vein grafts, the surface morphology of culprit lesions in unstable angina patients is quite similar for saphenous vein grafts and native coronary arteries.

Combination stem cell therapy for the treatment of medically refractory coronary ischemia: a Phase I study

PURPOSE Infusion of a source of endothelial progenitor cells (EPC) into the ischemic myocardium is emerging as a promising therapy for coronary ischemia, probably mediated by the formation of new blood vessels. Studies have shown that while the procedure is safe and feasible, efficacy results are contentious. The investigators hypothesized that the infusion of a combination cell product consisting of a source of EPC and mesenchymal stem cells (MSC) is safe and promotes the formation of more stable and mature blood vessels resulting in improved clinical outcomes. METHODS Ten patients with stable angina pectoris (class III to IV) on maximal medical therapy were included. All patients had ≥ 70% stenosis in at least one coronary artery, and none was considered a candidate for percutaneous coronary intervention or coronary artery bypass graft. End points were feasibility and safety of intracoronary infusion of the combination cell product and assessment of myocardial ischemia, left ventricular ejection fraction (LVEF), and quality of life at 6 months postinfusion. RESULTS Six months after cell infusion there were no adverse clinical events. Functional cardiac evaluation during the same period showed significant improvements in LVEF (average increase: 11%, P = .02) and myocardial ischemia (average decrease: 1.8 fold, P = .02). Additionally, all patients described significant improvements in quality of life. CONCLUSIONS Despite the inherent limitations associated with a Phase I clinical trial, this study demonstrates that the intracoronary infusion of the combination cell product is feasible and safe and also insinuates that this form of therapy may be beneficial.

Therapeutic angiogenesis in patients with severe limb ischemia by transplantation of a combination stem cell product

OBJECTIVE Angiogenesis involves the interplay of endothelial progenitor cells, pericytes, growth factors, and cellular matrix components. The use of mesenchymal stem cells, which are closely related to pericytes and produce diverse angiogenic growth factors and matrix molecules, seems to be a promising therapeutic modality. We postulate that the use of a combination cell product (mesenchymal stem cells in conjunction with a source of endothelial progenitor cells) is safe and efficient and may optimize the clinical results obtained with the use of endothelial progenitor cells alone. This study assessed whether the intramuscular infusion of a combination cell product represents a viable, effective, and lasting therapeutic modality to improve perfusion in severely ischemic limbs. METHODS Patients with limb ischemia (n=26) received an intramuscular (gastrocnemius) infusion of the combination cell product in the most ischemic leg and a placebo product in the (less ischemic) contralateral leg. Clinical follow-up (months 0.5, 1, 2, and 4 postinfusion) included evaluation of pain-free walking time, ankle-brachial index, perfusion scintigraphy, and quality of life survey. RESULTS No adverse events occurred after infusion. Efficacy assessment indicated that after cell infusion there was a significant improvement in walking time and ankle-brachial index. In addition, technetium-99m-tetrofosmin scintigraphy demonstrated a significant increase of perfusion in the treated limbs compared with the respective control legs. CONCLUSIONS This phase II clinical trial shows that the use of a combination cell therapy is safe and effective in increasing blood flow in the ischemic legs of patients with limb ischemia.

Mitral annular disjunction in myxomatous mitral valve disease: a relevant abnormality recognizable by transthoracic echocardiography

BackgroundMitral annular disjunction (MAD) consists of an altered spatial relation between the left atrial wall, the attachment of the mitral leaflets, and the top of the left ventricular (LV) free wall, manifested as a wide separation between the atrial wall-mitral valve junction and the top of the LV free wall. Originally described in association with myxomatous mitral valve disease, this abnormality was recently revisited by a surgical group that pointed its relevance for mitral valve reparability. The aims of this study were to investigate the echocardiographic prevalence of mitral annular disjunction in patients with myxomatous mitral valve disease, and to characterize the clinical profile and echocardiographic features of these patients.MethodsWe evaluated 38 patients with myxomatous mitral valve disease (mean age 57 ± 15 years; 18 females) and used standard transthoracic echocardiography for measuring the MAD. Mitral annular function, assessed by end-diastolic and end-systolic annular diameters, was compared between patients with and without MAD. We compared the incidence of arrhythmias in a subset of 21 patients studied with 24-hour Holter monitoring.ResultsMAD was present in 21 (55%) patients (mean length: 7.4 ± 8.7 mm), and was more common in women (61% vs 38% in men; p = 0.047). MAD patients more frequently presented chest pain (43% vs 12% in the absence of MAD; p = 0.07). Mitral annular function was significantly impaired in patients with MAD in whom the mitral annular diameter was paradoxically larger in systole than in diastole: the diastolic-to-systolic mitral annular diameter difference was -4,6 ± 4,7 mm in these patients vs 3,4 ± 1,1 mm in those without MAD (p < 0.001). The severity of MAD significantly correlated with the occurrence of non-sustained ventricular tachycardia (NSVT) on Holter monitoring: MAD›8.5 mm was a strong predictor for (NSVT), (area under ROC curve = 0.74 (95% CI, 0.5-0.9); sensitivity 67%, specificity 83%). There were no differences between groups regarding functional class, severity of mitral regurgitation, LV volumes, and LV systolic function.ConclusionsMAD is a common finding in myxomatous mitral valve disease patients, easily recognizable by transthoracic echocardiography. It is more prevalent in women and often associated with chest pain. MAD significantly disturbs mitral annular function and when severe predicts the occurrence of NSVT.

Treatment of coronary stent thrombosis with rheolytic thrombectomy: Results from a multicenter experience

The objective of this study was to assess the feasibility, efficacy, and safety of rheolytic thrombectomy (RT) for treatment of coronary stent thrombosis. Stent thrombosis is an infrequent but potentially devastating complication. Conventional treatment with balloon angioplasty and/or thrombolysis has yielded suboptimal results. RT was used to treat 18 patients (mean age, 62 ± 8 years; 72% male) with in‐stent thrombosis (mean time to stent thrombosis, 2.4 ± 1.8 days). Device success, procedure success, in‐hospital and 30‐day major cardiovascular events (MACE) were assessed in the hospital and at 30 days. Device success was obtained in 94% and procedure success was achieved in 100% of patients. Following RT, 11 patients underwent balloon angioplasty and 7 patients received additional stents. TIMI 3 coronary flow was obtained in 94.4% and all (100%) patients achieved either TIMI 2 or 3 coronary flow. The angiographic thrombus area decreased from 113.7 ± 79 to 5.5 ± 5.7 mm2 after RT, and to 0.9 ± 2.1 mm2 (P < 0.001) after final treatment. Procedural complications were limited to transient no‐reflow in five patients. Only one patient evolved a Q‐wave MI. At 30 days of follow‐up, no patients suffered death, emergent bypass surgery, or stroke. Our data suggest that the adjunctive use of rheolytic thrombectomy offers improved outcomes compared to prior results of intervention after coronary stent thrombosis and should be strongly considered as a treatment option for this complication. Cathet Cardiovasc Intervent 2003;58:11–17.