John M. Buergler

Alcohol Septal Ablation for the Treatment of Hypertrophic Obstructive Cardiomyopathy: A Multicenter North American Registry

OBJECTIVES The purpose of the study is to identify the predictors of clinical outcome (mortality and survival without repeat septal reduction procedures) of alcohol septal ablation for the treatment of patients with hypertrophic obstructive cardiomyopathy. BACKGROUND Alcohol septal ablation is used for treatment of medically refractory hypertrophic obstructive cardiomyopathy patients with severe outflow tract obstruction. The existing literature is limited to single-center results, and predictors of clinical outcome after ablation have not been determined. Registry results can add important data. METHODS Hypertrophic obstructive cardiomyopathy patients (N = 874) who underwent alcohol septal ablation were enrolled. The majority (64%) had severe obstruction at rest, and the remaining had provocable obstruction. Before ablation, patients had severe dyspnea (New York Heart Association [NYHA] functional class III or IV: 78%) and/or severe angina (Canadian Cardiovascular Society angina class III or IV: 43%). RESULTS Significant improvement (p < 0.01) occurred after ablation (~5% in NYHA functional classes III and IV, and 8 patients in Canadian Cardiovascular Society angina class III). There were 81 deaths, and survival estimates at 1, 5, and 9 years were 97%, 86%, and 74%, respectively. Left anterior descending artery dissections occurred in 8 patients and arrhythmias in 133 patients. A lower ejection fraction at baseline, a smaller number of septal arteries injected with ethanol, a larger number of ablation procedures per patient, a higher septal thickness post-ablation, and the use beta-blockers post-ablation predicted mortality. CONCLUSIONS Variables that predict mortality after ablation, include baseline ejection fraction and NYHA functional class, the number of septal arteries injected with ethanol, post-ablation septal thickness, beta-blocker use, and the number of ablation procedures.

Long-term effects of intracoronary β-radiation in balloon- and stent-injured porcine coronary arteries

Background—The data on the long-term safety and efficacy of intracoronary β-radiation in animal models are limited. Methods and Results—A total of 30 coronary arteries in 15 swine were subjected to balloon or stent injury followed by β-radiation from a centered 32P source (2000 cGy to 1 mm beyond lumen surface) or a sham radiation procedure. The animals received aspirin for 6 months and ticlopidine for 30 days. Five of the 10 animals subjected to radiation died (at 5 days, 7 days, 3 months [n=2], and 4 months) as a result of layered, occlusive thrombus at the intervention site (3 stent and 2 balloon injury sites). No deaths occurred in the control group. In the surviving animals, balloon-injured and irradiated vessels showed a trend toward larger lumens than controls (2.15±0.17 versus 1.80±0.08 mm2, P=0.06) and larger external elastic lamina areas (3.32±0.21 versus 2.62±0.10 mm2, P=0.003). In the stent-injured vessels from surviving animals, lumen, neointimal, and external elastic lamina areas were 3.58±0...

Effects of SolCD39, a novel inhibitor of platelet aggregation, on platelet deposition and aggregation after PTCA in a porcine model

Introduction: This study evaluated CD39 in a porcine model of balloon angioplasty and in plasma of patients undergoing percutaneous intervention. CD39 (E-NTPDase1), is the endothelial ecto-ADPase inhibiting platelet function via hydrolysis of released platelet ADP.Methods and Results: A recombinant soluble form of CD39 (solCD39) given intravenously to pigs had an elimination half life of 5–7 days, increased the bleeding time to an extent similar to aspirin, and inhibits platelet aggregation by > 90%. Platelet counts and clot retraction remained normal following solCD39 administration. In a pig model of acute coronary balloon injury, solCD39 resulted in non-statistically significant decreases in platelet (7.7 ± 1.4 versus 11.7 ± 3.4) and fibrin (3.5 ± 0.4 versus 4.2 ± 0.7) deposition ratios. Adding ex vivo to human platelet rich plasma (PRP) solCD39 produced nearly 100% inhibition of ADP-induced platelet aggregation. A dose-response effect of solCD39 on platelet aggregation induced by collagen or a thrombin receptor activating peptide (TRAPSFLLRN) was noted in PRP obtained from volunteers and patients receiving aspirin, clopidogrel or ticlopidine. SolCD39 also provided additional and complete inhibition of TRAP-induced platelet aggregation in PRP from patients who had received abciximab, aspirin and clopidogrel.Conclusions: SolCD39, a novel inhibitor of platelet activation and recruitment with a relatively long half-life appears to be well tolerated and is a potent inhibitor of ADP-, collagen-, or TRAP-induced platelet activation. Its potential use in percutaneous coronary intervention requires further study.Abbreviated Abstract. E-NTPDase1/CD39 is the endothelial ecto-ADPase responsible for inhibition of platelet function. A recombinant soluble form (solCD39) had an elimination half life of 5–7 days in pigs, elevated bleeding times similar to aspirin, did not affect clot retraction, and inhibited platelet aggregation by > 90%. When combined with standard heparin therapy in a pig model of acute coronary balloon injury, solCD39 resulted in a trend toward a decrease in platelet and fibrin deposition. SolCD39 added ex vivo to human platelet rich plasma yielded nearly 100% inhibition of ADP-induced platelet aggregation and provided further inhibition when combined with standard therapy.

Use of nitric-oxide-eluting polymer-coated coronary stents for prevention of restenosis in pigs.

BackgroundRestenosis after angioplasty remains an unresolved problem despite an increase in use of coronary stents. It has been theorized that nitric oxide (NO) exerts several actions that can prevent restenosis. These include inhibition of proliferation of smooth muscle cells, prevention of arterial spasms, and decreasing aggregation of platelets in response to exposure to collagen. ObjectiveTo determine whether NO coated stents decrease restenosis in a pig balloon injury model. MethodsWe used coronary stents impregnated with a slow‐release precursor of NO in the porcine model of restenosis. Tantalum coil coronary stents (Cordis) were coated with a polymer impregnated with a slow‐release precursor of NO. Polymer‐coated stents without active precursors were used as controls. Oversized stents were mounted on a delivery balloon and subsequently deployed in the right coronary and left anterior descending arteries of each animal. ResultsRepeated recording of angiograms demonstrated that changes in minimum lumen diameter on going from immediately after stenting to 28‐day follow‐up for the control and NO‐eluting‐stent groups were similar, namely decreases of 1.89 ± 0.33 and 2.08 ± 0.28 mm, respectively. The morphometric results, showing that severe luminal narrowing occurred for both groups, were similar. The percentage area stenoses were 85 ± 5% for the control group and 84 ± 6% for the NO‐eluting group. Histology demonstrated that profuse formation of neointima and an inflammatory cell infiltrate occurred. ConclusionsSevere diameter stenosis occurred both for control and for treatment groups. The degree of angiographic stenosis was markedly worse than that previously reported for this model. Sustained release of a precursor of NO did not prevent restenosis in this model. This might have been due to a lack of efficacy of nitric oxide or to a profuse and overwhelming stimulatory effect of the polymer in the coated stents.

Vortex Formation Time Index in Patients With Hypertrophic Cardiomyopathy

Vortex ring formation in early diastole helps with left ventricular (LV) filling without an increase in left atrial (LA) pressure. Vortex formation time (VFT) is a dimensionless parameter derived from LV geometry and indexes of LV systolic and diastolic performance [(1)][1]. The optimal range was