Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial.

BACKGROUND: c-kit-positive, lineage-negative cardiac stem cells (CSCs) improve post-infarction left ventricular (LV) dysfunction when administered to animals. We undertook a phase 1 trial (Stem Cell Infusion in Patients with Ischemic cardiOmyopathy [SCIPIO]) of autologous CSCs for the treatment of heart failure resulting from ischaemic heart disease. METHODS: In stage A of the SCIPIO trial, patients with post-infarction LV dysfunction (ejection fraction [EF] ≤40%) before coronary artery bypass grafting were consecutively enrolled in the treatment and control groups. In stage B, patients were randomly assigned to the treatment or control group in a 2:3 ratio by use of a computer-generated block randomisation scheme. 1 million autologous CSCs were administered by intracoronary infusion at a mean of 113 days (SE 4) after surgery; controls were not given any treatment. Although the study was open label, the echocardiographic analyses were masked to group assignment. The primary endpoint was short-term safety of CSCs and the secondary endpoint was efficacy. A per-protocol analysis was used. This study is registered with ClinicalTrials.gov, number NCT00474461. FINDINGS: This study is still in progress. 16 patients were assigned to the treatment group and seven to the control group; no CSC-related adverse effects were reported. In 14 CSC-treated patients who were analysed, LVEF increased from 30·3% (SE 1·9) before CSC infusion to 38·5% (2·8) at 4 months after infusion (p=0·001). By contrast, in seven control patients, during the corresponding time interval, LVEF did not change (30·1% [2·4] at 4 months after CABG vs 30·2% [2·5] at 8 months after CABG). Importantly, the salubrious effects of CSCs were even more pronounced at 1 year in eight patients (eg, LVEF increased by 12·3 ejection fraction units [2·1] vs baseline, p=0·0007). In the seven treated patients in whom cardiac MRI could be done, infarct size decreased from 32·6 g (6·3) by 7·8 g (1·7; 24%) at 4 months (p=0·004) and 9·8 g (3·5; 30%) at 1 year (p=0·04). INTERPRETATION: These initial results in patients are very encouraging. They suggest that intracoronary infusion of autologous CSCs is effective in improving LV systolic function and reducing infarct size in patients with heart failure after myocardial infarction, and warrant further, larger, phase 2 studies. FUNDING: University of Louisville Research Foundation and National Institutes of Health.

Case of homozygous familial hypercholesterolaemia with premature coronary artery disease.

Familial hypercholesterolaemia is a genetic disorder secondary to mutation of one or more of the genes critical for low-density lipoprotein cholesterol (LDL-C) metabolism; these mutation(s) cause highly elevated serum LDL-C, significantly increasing the risk of early cardiovascular events and mortality. Homozygous familial hypercholesterolaemia (HoFH) is rare and often leads to accelerated coronary atherosclerosis presenting within the first two decades of life. We report a case of a 14-year-old boy who presented after surviving a ventricular fibrillation cardiac arrest. His highly elevated LDL-C level prompted further workup and led to a diagnosis of HoFH. The treatment included medical therapy and coronary artery bypass grafting. The patient also required referral for lipid apheresis to meet goal LDL-C level, and an automated implantable cardioverter defibrillator for secondary prevention of sudden cardiac death. HoFH, if left untreated, can have devastating consequences Therefore, timely diagnosis initiating appropriate therapy is important.

Coronary allograft vasculopathy managed by Flash ostial balloon in a pediatric patient.

Coronary allograft vasculopathy (CAV) is the most significant cause of morbidity and mortality in heart transplant recipients. Inflammation and endothelial dysfunction caused by graft rejection and viral infections leads to a combination of circumferential intimal fibromuscular hyperplasia, atherosclerosis, and inflammation affecting all layers of the vessel wall. Though obstructive CAV is often asymptomatic, posing a diagnostic challenge in post-transplant patients, early diagnosis and treatment aid faster recovery and improved outcomes. The role of percutaneous coronary intervention in the treatment of CAV is unknown and not well studied in the pediatric population. We present a first-in-human case of ostial left main coronary artery disease managed with flaring of the ostial coronary stent using a Flash ostial balloon in a pediatric patient with history of an orthotopic heart transplant.

Anomalous origin of the left main from the right coronary sinus presenting with sudden cardiac death: utility of mechanical circulatory support.

Anomalies involving the origin of the coronary arteries are extremely rare, with the left main artery coronary artery (LMCA) originating from the right coronary sinus (RCS) one of its rarest forms. Anomalous origin of left main from right coronary sinus poses a high risk of sudden cardiac arrest. In our report, we shed light on the case of a 43-year-old female who suffered a witnessed cardiac arrest due to underlying anomalous origin of the left main artery from right coronary sinus. The patient was initially pronounced dead until return of spontaneous rhythm with concomitant myocardial infarction led to the diagnosis of anomalous coronary artery. This case stresses important points to consider when dealing with the acute management and chronic treatment plan for this subset of high-risk patients. We also consider the utility of mechanical circulatory support in the management of this condition.

Physiological assessment of renal artery stenosis: comparisons of resting with hyperemic renal pressure measurements.

OBJECTIVES: We compared resting and hyperemic pressure gradients induced by intrarenal papaverine for the assessment of renal artery stenosis (RAS). We also investigated the incidence of the QT interval prolongation and ventricular arrhythmias. BACKGROUND: In the coronary circulation, maximal hyperemia is essential in determining the significance of a stenosis. In the renal circulation, the role of maximal hyperemia for the assessment of RAS has not been established. METHODS: In 55 patients with RAS (67 RAS), resting P(d)/P(a) ratio (the ratio between distal renal pressure to the aortic pressure), renal fractional flow reserve (FFR), and resting and hyperemic systolic gradients (RSG and HSG, respectively) were measured with a pressure guidewire. In a subset of 16 patients, renal vein renin activity (RVRA) was measured. RESULTS: HSG was significantly greater than RSG (20 ± 14 mm Hg vs. 9.0 ± 13 mm Hg, respectively; P < 0.001). Renal FFR was significantly lower than baseline P(d)/P(a) ratio (0.91 ± 0.06 vs. 0.94 ± 0.06 vs. respectively; P < 0.001). RVRA increased from 50 ± 66% at rest to 122 ± 112% at hyperemia, P < 0.01. At HSG of 21 mm Hg or renal FFR of 0.90, RVRA increased markedly (120%), but RVRA increased modestly (18%) when RSG was 16 mm Hg or resting P(d)/P(a) ratio was 0.93. The corrected QT intervals at baseline vs. hyperemia were not significantly different (433 ± 26 vs. 436 ± 25 msec, respectively; P = NS); no episodes of ventricular arrhythmias were noted. CONCLUSIONS: Renin production, an index of renal ischemia, was markedly greater at hyperemia than at rest, suggesting that RAS, with either an HSG of 21 mm Hg or a renal FFR of 0.90, can be considered a hemodynamically significant stenosis. Intrarenal papaverine neither prolonged the QT interval nor induced ventricular arrhythmias and the safety of which will need to be corroborated in a large study. © 2010 Wiley-Liss, Inc.

The Sinking Heart: A case of left anterior descending artery intervention complicated by perforation and cardiac tamponade.

Coronary interventions are one of the most commonly performed procedures in interventional medicine. They have provided a life-prolonging and -saving solution, but are not without their own complications. These, although rare, do occur and are important to recognize in order to promptly and efficiently provide a solution to prevent catastrophic consequences to the patient. We present a 70-year-old male with a past medical history significant for hypertension, hyperlipidemia, and myasthenia gravis; who presented to the hospital with substernal, pressure-like chest pain with associated nausea and diaphoresis. He was found to have ST segment elevations in anterolateral leads, prompting catherization lab activation revealing left anterior descending (LAD) artery stenosis. Percutaneous intervention via balloon dilation and stent placement was performed with periprocedural mid-intervention hemodynamic collapse occurring. Subsequent left ventricular (LV) angiography was performed revealing preserved LV function without perforation - however a rim of contrast was noted surrounding the LV. Thus, hemodynamic collapse was recognized as result of cardiac tamponade with pericardial drain emergently inserted resulting in hemodynamic recovery. Our case aims to present a case of vascular perforation with the uniqueness in our diagnostic approach via fluoroscopic imaging.

Prediction of hypertension improvement after stenting of renal artery stenosis: comparative accuracy of translesional pressure gradients, intravascular ultrasound, and angiography.

OBJECTIVES: We investigated the comparative accuracy of renal translesional pressure gradients (TPG), intravascular ultrasound (IVUS), and angiographic parameters in predicting hypertension improvement after stenting of renal artery stenosis (RAS). BACKGROUND: The degree of RAS that justifies stenting is unknown. METHODS: In 62 patients with RAS, TPG (resting and hyperemic systolic gradient [HSG], fractional flow reserve, and mean gradient) were measured by a pressure guidewire; IVUS and angiographic parameters (minimum lumen area and diameter, area stenosis, and diameter stenosis) were measured by quantitative analyses. RESULTS: The HSG had a larger area under the curve than most other parameters and an HSG >or=21 mm Hg had the highest sensitivity, specificity, and accuracy (82%, 84%, and 84%, respectively) in predicting hypertension improvement after stenting of RAS. The average IVUS area stenosis was markedly greater in RAS with an HSG >or=21 mm Hg versus <21 mm Hg (78% vs. 38%, respectively; p < 0.001). After stenting, hypertension improved in 84% of patients with an HSG >or=21 mm Hg (n = 36) versus 36% of patients with an HSG <21 mm Hg (n = 26) at 12 months, p < 0.01; the number of antihypertensive medications was significantly lower in patients with an HSG >or=21 mm Hg versus <21 mm Hg (2.30 +/- 0.90 vs. 3.40 +/- 0.50, respectively; p < 0.01). By multivariable analysis, HSG was the only independent predictor of hypertension improvement (odds ratio: 1.39; 95% confidence interval: 1.05 to 1.65; p = 0.013). CONCLUSIONS: An HSG >or=21 mm Hg provided the highest accuracy in predicting hypertension improvement after stenting of RAS, suggesting that an HSG >or=21 mm Hg is indicative of significant RAS.