Balram Bhargava

Intracoronary gamma-radiation therapy after angioplasty inhibits recurrence in patients with in-stent restenosis

BACKGROUND Treatment of in-stent restenosis presents a critical limitation of intracoronary stent implantation. Ionizing radiation has been shown to decrease neointimal formation within stents in animal models and in initial clinical trials. We studied the effects of intracoronary gamma-radiation therapy versus placebo on the clinical and angiographic outcomes of patients with in-stent restenosis. METHODS AND RESULTS One hundred thirty patients with in-stent restenosis underwent successful coronary intervention and were then blindly randomized to receive either intracoronary gamma-radiation with (192)Ir (15 Gy) or placebo. Four independent core laboratories blinded to the treatment protocol analyzed the angiographic and intravascular ultrasound end points of restenosis. Procedural success and in-hospital and 30-day complications were similar among the groups. At 6 months, patients assigned to radiation therapy required less target lesion revascularization and target vessel revascularization (9 [13.8%] and 17 [26.2%], respectively) compared with patients assigned to placebo (41 [63.1%, P=0.0001] and 44 [67.7%, P=0.0001], respectively). Binary angiographic restenosis was lower in the irradiated group (19% versus 58% for placebo, P=0.001). Freedom from major cardiac events was lower in the radiation group (29.2% versus 67.7% for placebo, P<0.001). CONCLUSIONS Intracoronary gamma-radiation used as adjunct therapy for patients with in-stent restenosis significantly reduces both angiographic and clinical restenosis.

Prevalence and outcome of subclinical rheumatic heart disease in India: The RHEUMATIC (Rheumatic Heart Echo Utilisation and Monitoring Actuarial Trends in Indian Children) study

Objective To study the prevalence and medium term outcome of subclinical rheumatic heart disease (RHD) in India. Design Cross sectional echocardiographic screening study. Setting School children aged 5–15 years living in rural areas of north India. Patients A cross sectional echocardiographic screening study was carried out among 6270 randomly selected school children aged 5–15 years (10.8±2.6 years; 52.7% male). Of all the abnormal cases, 100 children (78%) were restudied at a mean follow-up of 15.4±6.6 months. Intervention Echocardiographic screening. Main outcome measure Echocardiography–Doppler criteria based prevalence of RHD. Results Clinical examination detected mitral regurgitation in five patients and the estimated prevalence of clinical RHD was 0.8/1000 school children. Echocardiography–Doppler diagnosed RHD in 128 cases, giving a prevalence of 20.4/1000 school children (95% CI 16.9 to 23.9/1000 children). On multivariate analysis, older age (OR 1.93, 95% CI 1.29 to 2.88; p=0.001), female sex (OR 1.84, 95% CI 1.25 to 2.72; p=0.002) and government funded school student, which is a surrogate measure of lower socioeconomic status (OR 1.55, 95% CI 1.02 to 2.34; p=0.039) were found to be independent predictors of RHD. On follow up, the severity of subclinical RHD was non-progressive in 68 children (68%) while it worsened in four (4%) and regressed in 28 children (28%). Conclusions The prevalence of RHD is several fold higher using echocardiographic screening compared with clinical examination. The prevalence is higher among girls and children of lower socioeconomic status. In the majority of cases, subclinical RHD appears to be non-progressive on medium term follow up. Routine echocardiographic screening may be indicated in populations at high risk of RHD.

Edge stenosis and geographical miss following intracoronary gamma radiation therapy for in-stent restenosis.

OBJECTIVES We sought to determine the relationship between geographical miss (GM) and edge restenosis (ERS) following intracoronary radiation therapy. BACKGROUND Edge restenosis may be a limitation of intracoronary irradiation to prevent in-stent restenosis (ISR). Inadequate radiation source coverage of the injured segment (GM) has been proposed as a cause of ERS. We studied the relationship between GM and ERS following 192Ir treatment of ISR. METHODS There were 100 patients with native vessel ISR in WRIST (Washington Radiation for In-Stent Restenosis Trial), in which patients with ISR were first treated with conventional techniques and then randomized to gamma irradiation (192Ir) or placebo. Geographical miss was defined as segments proximal or distal to the treated lesion that were subjected to injury during primary intervention but were not covered by the radiation source. RESULTS Geographical miss was documented in 56 of 164 edges (34%). Edge restenosis was noted at eight of 80 radiated edges and in four of 84 placebo edges. In the irradiated group, ERS was observed in 21% of edges with GM and in 40% of edges without GM (p = 0.035). In contrast, in the placebo group, ERS was observed in only 7% of edges with GM and in 4% of edges without GM (p = NS). The late edge lumen loss was higher in the irradiated group with GM as compared to placebo with GM (0.74 +/- 0.57 vs. 0.41 +/- 0.50 mm, p = 0.016). CONCLUSIONS Edge restenosis following gamma irradiation treatment of ISR is related to GM: a mismatch between the segment of artery injured during the primary catheter-based intervention and the length of the radiation source.

Radial artery in CABG: could the early results be comparable to internal mammary artery graft?

BACKGROUND The accidental detection of patency of radial artery grafts, by Acar, which had been labeled as blocked 18 years earlier, has led to its revival as a conduit in coronary artery bypass surgery. We used radial artery as one of the grafts in 287 patients from February 1996 to June 1998. Here we present our early clinical experience and the midterm angiographic follow up of the initial 62 patients. METHODS A no touch, atraumatic harvesting technique coupled with gentle hydrostatic and pharmacological dilatation of the radial artery graft was employed. Radial artery was used to revascularize coronary vessels with >80% proximal stenosis. Postoperatively, the patients were administered a low dose nifedipine that was continued for 6 months thereafter. The patients were followed up clinically after discharge from the hospital and angiographic evaluation of the grafted radial artery by selective injection was done at a mean interval of 16.2 +/- 5.1 months (3-24 months) postoperatively. RESULTS There was no perioperative or late myocardial infarction or mortality. No significant complications related to the harvesting of radial artery were encountered. Angiographically, the radial artery grafts were found to be patent in 96.8% of patients (60/62). Mild distal anastomotic narrowing was seen in angiogram of one patient with good filling of the target vessel. Another patient showed diffuse spasm of radial artery graft. The patency of the pedicled left internal mammary grafts was also 98.2% (56/57). All the patients were asymptomatic. CONCLUSIONS Radial artery seems to be an excellent alternate arterial conduit for myocardial revascularization with early and midterm patency rates equivalent to that of pedicled internal mammary artery, and it should be used more often for myocardial revascularization as an adjunct to pedicled internal mammary artery graft.

The ABCD (Autologous Bone Marrow Cells in Dilated Cardiomyopathy) trial a long-term follow-up study.

To the Editor: We reported the short-term results (6-month follow-up) of a pilot study of the role of stem cell therapy in ischemic cardiomyopathy ([1][1]). We now present the final long-term (3-year follow-up) results of the trial. The study included patients between 15 and 70 years of age with

Intramural coronary delivery of advanced antisense oligonucleotides reduces neointimal formation in the porcine stent restenosis model

OBJECTIVES We evaluated the long-term influence of intramural delivery of advanced c-myc neutrally charged antisense oligonucleotides (Resten-NG) on neointimal hyperplasia after stenting in a pig model. BACKGROUND Neointimal hyperplasia after percutaneous coronary interventions is one of the key components of the restenotic process. The c-myc is a critical cell division cycle protein involved in the formation of neointima. METHODS In short-term experiments, different doses (from 500 microg to 5 mg) of Resten-NG or saline were delivered to the stent implantation site with an infiltrator delivery system (Interventional Technologies, San Diego, California). Animals were euthanized at 2, 6 and 18 h after interventions, and excised vessels were analyzed for c-myc expression by Western blot. In long-term experiments, either saline or a dose of 1, 5 or 10 mg of Resten-NG was delivered in the same fashion, and animals were euthanized at 28 days after the intervention. RESULTS Western blot analysis demonstrated inhibition of c-myc expression and was dose dependent. Morphometry showed that the intimal area was 3.88 +/- 1.04 mm(2) in the control. There was statistically significant reduction of intimal areas in the 5 and 10 mg groups (2.01 +/- 0.66 and 1.95 +/- 0.91, respectively, p < 0.001) but no significant reduction in the 1 mg group (2.81 +/- 0.56, p > 0.5) in comparison with control. CONCLUSIONS This study demonstrated that intramural delivery of advanced c-myc neutrally charged antisense morpholino compound completely inhibits c-myc expression and dramatically reduces neointimal formation in a dose dependent fashion in a porcine coronary stent restenosis model, while allowing for complete vascular healing.

A novel paclitaxel-eluting porous carbon-carbon nanoparticle coated, nonpolymeric cobalt-chromium stent : Evaluation in a porcine model

Objectives: We aimed to evaluate the response of porcine coronary arteries to a novel paclitaxel‐eluting porous carbon–carbon nanoparticle coated, nonpolymeric cobalt chromium stent. Background: Polymer based drug‐eluting stents significantly reduce restenosis. However, the indefinite presence of polymer is thought to initiate and sustain inflammation and contribute to the occurrence of late complications. Methods: Sixteen carbon–carbon coated, nonpolymeric cobalt chromium stents with two different doses of paclitaxel (eight of each) were implanted in porcine coronary arteries. In addition, eight cobalt chromium stents coated with a biodegradable polymer were also studied. Animals were sacrificed 6 weeks after stent implantation and histomorphometric analysis was performed. Results were compared among the three groups of stents. Results: The cobalt chromium stents coated with carbon–carbon with low and medium doses of paclitaxel both showed acceptable performance characteristics, with respect to endothelialization, neointimal hyperplasia, percentage diameter stenosis, inflammatory response, and tendency to fibrin deposition, when compared to historical data with the Cypher stent. On the other hand, the stents coated with poly(lactide) and poly(lactide‐co‐glycolide) biodegradable polymers and 0.7 μg/mm2 paclitaxel showed poor performance. There was a significant tendency to poor endothelialization, greater neointimal hyperplasia, percentage diameter stenosis, greater inflammatory response, and tendency to fibrin deposition (P < 0.01 for all parameters). Conclusions: This preclinical evaluation demonstrates the safety and efficacy of a novel cobalt chromium stent with a carbon–carbon coating and low and medium doses of paclitaxel.

Late thrombosis following intracoronary brachytherapy

Vascular brachytherapy has been the subject of an extensive ongoing investigation into the safety and efficacy of this technique for preventing restenosis. Preclinical studies have demonstrated reduction of the neointimal proliferation and the late vascular constriction with radiation therapy. However, radiation is also known to delay the healing process and may contribute to a new phenomenon of late thrombosis. We report on two cases of patients with in‐stent restenosis who underwent intervention followed by intracoronary vascular radiation therapy (utilizing beta and gamma radiation) and presented with acute onset of unstable angina. Angiographic study demonstrated late thrombosis, which were treated successfully with the Angiojet thrombectomy device. Cathet. Cardiovasc. Intervent. 49:344–347, 2000.

TGFβ1 contributes to cardiomyogenic-like differentiation of human bone marrow mesenchymal stem cells

BACKGROUND The majority of the protocols for cardiomyocyte differentiation of MSC use 5-azacytidine as an inducer. As transforming growth factor β1 and 5-azacytidine share similar target signaling pathways, we examined whether transforming growth factor β1 can play a role in cardiac differentiation process in human mesenchymal stem cell of bone marrow origin. METHODS The differentiation protocol involving transforming growth factor β1 was compared with that of 5-azacytidine in these cells. The two differentiation regimes were compared using reverse transcriptase PCR, flow cytometry, and quantitative PCR. RESULTS We observed that in both cases, acquired morphological features were similar. Protein and gene expression assays also indicated similar cardiac marker expression profile in both the differentiation conditions. Furthermore, transforming growth factor β1 and 5-azacytidine allowed the acquisition of comparable levels of cardiac cell like molecular characteristic as attested by evaluation of myosin light chain-2v expression. CONCLUSION In conclusion, we demonstrate that transforming growth factor β1 can play a similar role in cardiac differentiation process of human bone marrow mesenchymal stem cells.

Percutaneous balloon aortic valvuloplasty during pregnancy: Use of the Inoue balloon and the physiologic antegrade approach

We describe the use of the Inoue balloon to dilate the aortic valve by the physiologic antegrade route during pregnancy. A 27-year-old pregnant woman with severe aortic stenosis presented with progressive dyspnea and presyncope at 26 weeks of pregnancy. She subsequently underwent percutaneous valvuloplasty by the antegrade route utilizing the transseptal puncture. We conclude that percutaneous antegrade balloon valvuloplasty by the Inoue balloon (venous approach) is a safe and effective procedure. It markedly reduces fluoroscopy and is a palliative procedure that allows pregnancy to continue.