Interventional versus Surgical Treatment of Degenerated Freestyle Prosthesis.

BACKGROUND: Bioprosthetic stentless aortic valves may degenerate over time and will require replacement. This study aimed to evaluate early- and mid-term outcomes after isolated surgical redo aortic valve replacement (redo-SAVR) and transcatheter valve-in-valve implantation (TAVI-VIV) for degenerated stentless Freestyle bioprostheses. METHODS: We reviewed records of 56 patients at a single center. Overall, 37 patients (66.1%) received TAVI-VIV and 19 (33.9%) received redo-SAVR. RESULTS: Thirty-day survival was similar in both groups (100%). One-year survival was comparable between groups (97.3% in TAVI-VIV and 100% in redo-SAVR, p = 1.0). The difference in mid-term survival after adjusting for age and EuroScore II was not significant (p = 0.41). The incidence of pacemaker implantation after TAVI-VIV was higher than after redo-SAVR (19.4% vs. 0%, p = 0.08). CONCLUSION: The 30-day and 1-year survival rates after both procedures were outstanding, irrespective of baseline characteristics. Isolated redo-SAVR should be favored in young patients, as the pacemaker implantation rate is lower. TAVI-VIV for degenerated Freestyle prosthesis can be a method of choice in elderly patients and those with high operative risk.

ISAR-SAFE: a randomized, double-blind, placebo-controlled trial of 6 vs. 12 months of clopidogrel therapy after drug-eluting stenting.

BACKGROUND: In patients receiving aspirin, the optimal duration of clopidogrel therapy after drug-eluting stent (DES) implantation remains unclear. METHODS: This multicentre, randomized, double-blind, placebo-controlled trial tested the hypothesis that in patients undergoing DES implantation, 6 months of clopidogrel is non-inferior to 12 months in terms of clinical outcomes. At 6 months after DES implantation, patients on clopidogrel were randomly assigned to either a 6-month period of placebo or an additional 6-month period of clopidogrel. The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, and thrombolysis in myocardial infarction major bleeding at 9 months after randomization. RESULTS: Owing to slow recruitment and low event rates, the trial was stopped prematurely after enrolment of 4005 of 6000 planned patients. Of 4000 patients included in the final analysis, 1997 received 6 months of clopidogrel and 2003 received 12 months. The primary endpoint occurred in 29 patients (1.5%) assigned to 6 months of clopidogrel and 32 patients (1.6%) assigned to 12 months, observed difference -0.1%, upper limit of one-sided 95% confidence interval (CI) 0.5%, limit of non-inferiority 2%, Pfor noninferiority <0.001. Stent thrombosis was observed in five patients (0.3%) assigned to 6 months of clopidogrel and three patients (0.2%) assigned to 12 months; hazard ratio (HR) 1.66, 95% CI: 0.40-6.96, P = 0.49. Thrombolysis in myocardial infarction major bleeding was observed in 4 patients (0.2%) assigned to 6 months clopidogrel and 5 patients (0.3%) assigned to 12 months; HR 0.80, 95% CI: 0.21-2.98, P = 0.74. CONCLUSIONS: In the present trial, characterized by low event rates, we did not observe a significant difference in net clinical outcome between 6 and 12 months of clopidogrel therapy after DES implantation. However, the results of the trial must be considered in view of its premature termination and lower than expected event rates. The trial is registered with ClinicalTrials.gov, Identifier: NCT00661206.

Management of protamine allergy with bivalirudin during coronary artery revascularization.

A patient with impaired left ventricular function was scheduled for coronary artery bypass grafting. The patient's history revealed a life-threatening allergy to fish proteins. Therefore, because of the threat of cross-reactivity to protamine, a standard anticoagulation protocol with heparin/protamine was disapproved. Instead, complete coronary artery revascularization was successfully performed off-pump using bivalirudin as the anticoagulant.

Variation in the human soluble epoxide hydrolase gene and risk of restenosis after percutaneous coronary intervention.

BACKGROUND: Restenosis represents the major limiting factor for the long-term efficacy of percutaneous coronary intervention (PCI). Several genetic factors involved in the regulation of the vascular system have been described to play a role in the pathogenesis of restenosis. We investigated whether the EPHX2 K55R polymorphism, previously linked to significantly higher risk for coronary heart disease (CHD), was associated with the occurrence of restenosis after PCI. The association with incident CHD should have been confirmed and a potential correlation of the EPHX2 K55R variant to an increased risk of hypertension was analysed. METHODS: An overall cohort of 706 patients was studied: This cohort comprised of 435 CHD patients who had undergone successful PCI. Follow-up coronary angiography in all patients was performed 6 months after intervention. Another 271 patients in whom CHD had been excluded by coronary angiography served as controls. From each patient EDTA-blood was drawn at the baseline ward round. Genomic DNA was extracted from these samples and genotyping was performed by real-time PCR and subsequent melting curve analysis. RESULTS: In CHD patients 6 month follow-up coronary angiography revealed a restenosis rate of 29.4%, classified as late lumen loss as well as lumen re-narrowing >or= 50%.Statistical analysis showed an equal genotype distribution in restenosis patients and non-restenosis patients (A/A 82.0% and A/G + G/G 18.0% versus A/A 82.1% and A/G + G/G 17.9%). Moreover, neither a significant difference in the genotype distribution of CHD patients and controls nor an association with increased risk of hypertension was found. CONCLUSION: The results of the present study indicate that the EPHX2 K55R polymorphism is not associated with restenosis after PCI, with incidence of CHD, or with an increased risk of hypertension and therefore, can not serve as a predictor for risk of CHD or restenosis after PCI.

Evaluation of the effect of oral verapamil on clinical outcome and angiographic restenosis after percutaneous coronary intervention: the randomized, double-blind, placebo-controlled, multicenter Verapamil Slow-Release for Prevention of Cardiovascular Events After Angioplasty (VESPA) Trial.

OBJECTIVES: We investigated the effect of oral verapamil on clinical outcome and angiographic restenosis after percutaneous coronary intervention (PCI). BACKGROUND: Thus far, there is no established systemic pharmacologic approach for the prevention of restenosis after PCIs. Five small studies reported encouraging results for calcium channel blockers. METHODS: Our randomized double-blind trial included 700 consecutive patients with successful PCI of a native coronary artery. Patients received the calcium channel blocker verapamil, 240 mg twice daily for six months, or placebo. Primary clinical end point was the composite rate of death, myocardial infarction, and target vessel revascularization (TVR) during one-year follow-up; the angiographic end point was late lumen loss at the six-month follow-up angiography. RESULTS: We obtained complete clinical follow-up in 95% of the patients, and scheduled angiography was performed in 94%. The proportion of patients treated with stents was 83%. The primary clinical end point was reached in 67 (19.3%) patients on verapamil and in 103 (29.3%) patients on placebo (relative risk [RR] 0.66 [95% confidence interval (CI) 0.48 to 0.89]; p = 0.002). This difference between the groups was driven by TVR (17.5% with verapamil vs. 26.2% with placebo; RR 0.67 [95% CI 0.49 to 0.93]; p = 0.006). Late lumen loss was 0.74 +/- 0.70 mm with verapamil and 0.81 +/- 0.75 mm with placebo (p = 0.11). Compared with placebo, verapamil reduced the rate of restenosis > or =75% (7.8% vs. 13.7%; RR 0.57 [95% CI 0.35 to 0.92]; p = 0.014). CONCLUSIONS: Verapamil compared with placebo improves long-term clinical outcome after PCI of native coronary arteries by reducing the need for TVR. This was caused by a reduction in the rate of high-grade restenosis.

Mutations in the human muscle LIM protein gene in families with hypertrophic cardiomyopathy.

BACKGROUND: Muscle LIM protein (MLP) is an essential nuclear regulator of myogenic differentiation. Additionally, it may act as an integrator of protein assembly of the actin-based cytoskeleton. MLP-knockout mice develop a marked cardiac hypertrophy reaction and dilated cardiomyopathy (DCM). MLP is therefore a candidate gene for heritable forms of hypertrophic cardiomyopathy (HCM) and DCM in humans. METHODS AND RESULTS: We analyzed 1100 unrelated individuals (400 patients with DCM, 200 patients with HCM, and 500 controls) for mutations in the human CRP3 gene that encodes MLP. We found 3 different missense mutations in 3 unrelated patients with familial HCM but detected no mutation in the DCM group or the controls. All mutations predicted an amino acid exchange at highly conserved residues in the functionally important LIM1 domain, which is responsible for interaction with alpha-actinin and with certain muscle-specific transcription factors. Protein-binding studies indicate that mutations in the CRP3 gene lead to a decreased binding activity of MLP to alpha-actinin. All 3 index patients were characterized by typical asymmetrical septal hypertrophy. Family studies revealed cosegregation of clinically affected individuals with the respective mutations in MLP. CONCLUSION: Here, we present evidence that mutations in the CRP3/MLP gene can cause HCM.