Changes in the Organization of Excitation-Contraction Coupling Structures in Failing Human Heart

The cardiac myocyte t-tubular system ensures rapid, uniform cell activation and several experimental lines of evidence suggest changes in the t-tubular system and associated excitation-contraction coupling proteins may occur in heart failure

973-108 Unstable Angina Patients Fare No Worse than Stable Patients Ten Years After Balloon Angioplasty

AimThis study was designed to assess the 10 year clinical status of all 856 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) in the first 5 years of our experience (1980-1985) and compare those with stable (SAP) and unstable angina (UAP).MethodsAll patients were contacted via letter, telephone or family doctor and details of cardiac events (death, infarction, rePTCA, coronary artery surgery) checked against hospital records. Actuarial survival and event-free survival curves were constructed and SAP and UAP patients compared.ResultsThe overall 5 and 10 year actuarial survival was 91% and 79% respectively. The 10 year event-free survival for all patients was 35%. The outcome of SAP and UAP patients are compared and displayed in the table. There is no significant difference in survival or clinical events.ConclusionsTen year survival after PTCA is good although the majority of patients suffer a further cardiac event. There is no significant long-term difference in cardiac events between SAP and UAP patients

Women fare no worse than men 10 years after attempted coronary angioplasty.

A retrospective review of cardiac events occurring in all patients who underwent attempted coronary angioplasty in the first 5 years of our experience (1980-1985) was undertaken. Follow-up data were obtained from the civil registry, hospital records, patient, family, and referring physician. Patient survival curves were constructed and the outcome of women and men was compared. Eight hundred fifty-six patients, 172 women and 684 men with a mean age of 60.0 and 55.3 years, respectively, underwent attempted coronary angioplasty with an overall procedural success rate of 82%, 77.7% in women and 83.1% in men. Follow-up data were obtained in 837 patients (97.8%) with a mean period of 9.6 years (range 0-13.3 years). The estimated 10 year survival in women was identical to men [79%, 95% confidence interval (CI) 72.6–85.4% vs. 78%, 95% C

Acute clinical and angiographic results with the new AVE Micro coronary stent in bailout management.

To determine the feasibility and safety of development of this new stent, we deployed 28 AVE Micro stents in 23 native coronary artery lesions in 20 patients who developed acute or threatened closure after balloon angioplasty (BA). Ten stents were deployed in the left anterior descending artery, 10 in the circumflex, and 8 in the right coronary artery. Luminal dimensions were measured using a computer-based quantitative coronary angiographic analysis system (CAAS II). Stent deployment was successful in 27 of 28 attempts (96%). In 1 patient with a threatened closure of the left anterior descending artery associated with proximal vessel tortuosity, attempted stent deployment was unsuccessful. The clinical course of the other 19 patients in whom stent deployment was successfu

T-tubule disease:Relationship between t-tubule organization and regional contractile performance in human dilated cardiomyopathy

Evidence from animal models suggest that t-tubule changes may play an important role in the contractile deficit associated with heart failure. However samples are usually taken at random with no regard as to regional variability present in failing hearts which leads to uncertainty in the relationship between contractile performance and possible t-tubule derangement. Regional contraction in human hearts was measured by tagged cine MRI and model fitting. At transplant, failing hearts were biopsy sampled in identified regions and immunocytochemistry was used to label t-tubules and sarcomeric z-lines. Computer image analysis was used to assess 5 different unbiased measures of t-tubule structure/organization. In regions of failing hearts that showed good contractile performance, t-tubule organization was similar to that seen in normal hearts, with worsening structure correlating with the loss of regional contractile performance. Statistical analysis showed that t-tubule direction was most highly correlated with local contractile performance, followed by the amplitude of the sarcomeric peak in the Fourier transform of the t-tubule image. Other area based measures were less well correlated. We conclude that regional contractile performance in failing human hearts is strongly correlated with the local t-tubule organization. Cluster tree analysis with a functional definition of failing contraction strength allowed a pathological definition of ‘t-tubule disease’. The regional variability in contractile performance and cellular structure is a confounding issue for analysis of samples taken from failing human hearts, although this may be overcome with regional analysis by using tagged cMRI and biopsy mapping

Initial results of combined anterior mitral leaflet extension and myectomy in patients with obstructive hypertrophic cardiomyopathy

Objectives. The purpose of this study was to describe the clinical and functional results of combined anterior mitral leaflet extension and myectomy in patients with hypertrophic obstructive cardiomyopathy. Background. Septal myectomy is the most commonly performed surgical procedure in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction. Because of the role of the mitral valve in creating the outflow tract gradient, mitral valve replacement or plication is performed in selected cases in combination with myectomy, often with better hemodynamic results than those of myectomy alone. Mitral valve leaflet extension, in which a glutaraldehyde-preserved autologous pericardial patch is used to enlarge the mitral valve along its horizontal axis, is a novel surgical approach in patients with hypertrophic obstructive cardiomyopathy. Methods. Eight patients with hypertrophic obstructive cardiomyopathy were treated with mitral leaflet extension and myectomy. Preoperative and postoperative data (New York Heart Association functional class, number of drugs prescribed, width of the interventricular septum, severity of mitral valve regurgitation, severity of systolic anterior motion of the mitral valve and outflow tract gradient) were compared with those of 12 patients undergoing myectomy alone. Results. Preoperative evaluation demonstrated that mitral regurgitation and systolic anterior motion of the mitral valve were more severe in the group undergoing mitral valve extension (p < 0.001 and p < 0.05, respectively). There were no deaths associated with either surgical procedure. Two patients, both treated by myectomy alone, died during the follow-up period. Postoperatively, patients treated with mitral valve extension had less mitral regurgitation (p < 0.005), less residual systolic anterior motion (p < 0.01), greater improvement in functional class (p = 0.05) and greater reduction in the number of drugs (p < 0.005) and in septal thickness (p < 0.05). Conclusions. Mitral leaflet extension in combination with myectomy is a promising new surgical approach that may provide superior results to those of myectomy alone. Further studies are needed to determine the clinical value of this procedure

Long-term clinical outcome after stent implantation in saphenous vein grafts

Objectives. We sought to determine the role of stent implantation in vein grafts by evaluating the long-term clinical outcome and estimated event-free survival at 5 years in 62 patients and by comparing our data with those of other treatment modalities previously reported. Background. Patients with recurrent angina after coronary artery bypass graft surgery pose a problem. Stent implantation has been advocated in an effort to avoid repeat operation and to address the limitations of balloon angioplasty. Methods. Patients undergoing stenting of a vein graft were entered into a dedicated data base. They were screened for death, infarction, bypass surgery and repeat angioplasty. Procedure-related events were included in the follow-up analysis. Survival and event-free survival curves were constructed by the Kaplan-Meier method. Results. A total of 93 stents (84 Wallstent and 9 Palmaz-Schatz) were implanted in 62 patients. During the in- hospital period, seven patients (11%) sustained a major cardiac eve

Pharmacogenetic Testing for Clopidogrel Using the Rapid INFINITI Analyzer A Dose-Escalation Study

ObjectivesOur aim was to assess whether a higher clopidogrel maintenance dose has a greater antiplatelet effect in CYP2C19*2 allele carriers compared with noncarriers.BackgroundClopidogrel is a prodrug that is biotransformed by the cytochrome P450 enzymes CYP2C19, 2C9, and 3A4, 2B6, 1A2. The CYPC219*2 loss of function variant has been associated with a reduced antiplatelet response to clopidogrel and a 3-fold risk of stent thrombosis.MethodsForty patients on standard maintenance dosage clopidogrel (75 mg), for 9.4 ± 9.2 weeks, were enrolled into a dose escalation study. Platelet function was assessed at baseline and after 1 week of 150 mg once daily using the VerifyNow platelet function analyzer (Accumetrics Ltd., San Diego, California). Genomic DNA was hybridized to a BioFilmChip microarray on the INFINITI analyzer (AutoGenomics Inc., Carlsbad, California) and analyzed for the CYP19*2, *4, *17, and CYP2C9*2, *3 polymorphisms.ResultsPlatelet inhibition increased over 1 week, mean +8.6 ± 13.5% (p = 0.0003). Carriers of the CYP2C19*2 allele had significantly reduced platelet inhibition at baseline (median 18%, range 0% to 72%) compared with wildtype (wt) (median 59%, range 11% to 95%, p = 0.01) and at 1 week (p = 0.03). CYP2C19*2 allele carriers had an increase in platelet inhibition of (mean +9 ± 11%, p = 0.03) and reduction in platelet reactivity (mean −26 ± 38 platelet response unit, p = 0.04) with a higher dose. Together CYP2C19*2 and CYP2C9*3 loss of function carriers had a greater change in platelet inhibition with 150 mg daily than wt/wt (+10.9% vs. +0.7%, p = 0.04).ConclusionsIncreasing the dose of clopidogrel in patients with nonresponder polymorphisms can increase antiplatelet response. Personalizing clopidogrel dosing using pharmacogenomics may be an effective method of optimizing treatment

Clinical and Angiographic Factors Associated With Asymptomatic Restenosis After Percutaneous Coronary Intervention

BACKGROUND: Angiographic restenosis after percutaneous coronary interventional procedures is more common than recurrent angina. Clinical and angiographic factors associated with asymptomatic versus symptomatic restenosis after percutaneous coronary intervention were compared. METHODS AND RESULTS: All patients with angiographic restenosis from the BENESTENT I, BENESTENT II pilot, BENESTENT II, MUSIC, WEST 1, DUET, FINESS 2, FLARE, SOPHOS, and ROSE studies were analyzed. Multivariate analysis evaluated 46 clinical and angiographic variables, comparing those with and without angina. The 10 studies recruited 2690 patients who underwent percutaneous revascularization and 6-month follow-up angiography (86% of those eligible). Restenosis (>/=50% diameter stenosis) occurred in 607 patients and was clinically silent in 335 (55%). Male sex (P=0.008), absence of antianginal therapy with nitrates (P=0.0002) and calcium channel blockers (P=0.02) at 6 months, greater reference diameter after the procedure (P=0.04), greater reference diameter at follow-up (P=0.004), and lesser lesion severity (percent stenosis) at 6 months (P=0.0004) were univariate predictors of asymptomatic restenosis. By multivariate analysis, only male sex (P=0.04), greater reference diameter at follow-up (P=0.002), and lesser lesion severity at 6 months (P=0.0001) were associated with restenosis without angina. CONCLUSIONS: Approximately half of patients with angiographic restenosis have no symptoms. The only multivariate predictors of silent restenosis at 6 months were male sex, greater reference diameter at follow-up, and lesser lesion severity on follow-up angiography