The rationale and design of the perindopril genetic association study (PERGENE): A pharmacogenetic analysis of angiotensin-converting enzyme inhibitor therapy in patients with stable coronary artery disease

Background: Angiotensin-converting enzyme (ACE) inhibitors reduce clinical symptoms and improve outcome in patients with hypertension, heart failure, and stable coronary artery disease (CAD) and are among the most frequently used drugs in these patient groups. For hypertension, treatment is guided by the level of blood pressure. In the secondary prevention setting, there are no means of guiding therapy. Prior attempts to target ACE-inhibitors to those patients that are most likely to benefit have not been successful, mainly due to the consistency in the treatment effect in clinical subgroups. Still, for prolonged prophylactic treatment with ACE-inhibitors it would be best to target treatment to only those patients most likely to benefit, which would considerably lower the number needed to treat and increase cost-effectiveness. A new approach for such "tailored-therapy" may be to integrate information on the genetic variation between patients. Until now, pharmacogenetic research of the efficacy of ACE-inhibitor therapy in CAD patients is still in a preliminary stage. Methods: The PERindopril GENEtic association study (PERGENE) is a substudy of the EUROPA trial, a randomized double-blind placebo-controlled multicentre clinical trial which demonstrated a beneficial effect of the ACE-inhibitor perindopril in reducing cardiovascular morbidity and mortality in 12.218 patients with stable coronary artery disease (mean follow-up 4.2 years). Blood tubes were received from patients at the beginning of the EUROPA trial and buffy coats were stored at -40°C at the central core laboratory. Candidate genes were selected in the renin-angiotensin-system and bradykinin pathways. Polymorphisms were selected based on haplotype tagging principles using the HapMap genome project, Seattle and other up-to-date genetic database platforms to comprehensively cover all common genetic variation within the genes. Selection also took into consideration the functionality of SNP's, location within the gene (promoter) and existing relevant literature. The main outcome measure of PERGENE is the effect of genetic factors on the treatment benefit with ACE-inhibitors. The size of this pharmacogenetic substudy allows detection with a statistical power of 98% to detect a difference in hazard ratios (treatment effect) of 20% between genotypes with minor allele frequency of 0.20 (two-sided alpha 0.05). Conclusion: The PERGENE study is a large cardiovascular pharmacogenetic study aimed to assess the feasibility of pharmacogenetic profiling of the treatment effect of ACE-inhibitor use with the perspective to individualize treatment in patients with stable coronary artery disease

Predominant tricuspid stenosis secondary to bacterial endocarditis in a patient with permanent pacemaker and, balloon dilatation of the stenosis: A case report

In a 49-year-old woman with sick sinus syndrome and a permanent VVI pacemaker, severe tricuspid stenosis and its clinical consequences developed 4 years after the attack of endocarditis. Besides the quite unusual occurrence of lead related tricuspid stenosis in the literature, successful treatment with balloon dilatation is the unique feature of this case

Predominant tricuspid stenosis secondary to bacterial endocarditis in a patient with permanent pacemaker and balloon dilatation of the stenosis

In a 49-year-old woman with sick sinus syndrome and a pemanent VVI pacemaker, severe tricuspid stenosis and ifs clinical consequences developed 4 years after the attack of endocarditis. Besides the quite unusual occurrence of lead related tricuspid stenosis, successful treatment with balloon dilatation is the unique feature of this case

Relationship between corrected Timi frame count and collateral flow in patients with recent myocardial infarction

TIMI frame count (TFC) is a quantitative index of coronary now. Catheter based revascularization normalizes resistance to flow and in this condition collateral flow can be considered as an important factor in determining antegrade coronary flow. The aim of this study was to investigate the relationship between corrected TFC (CTFC) which was determined after mechanical recanalization of the infarct related artery (IRA) and collateral flow determined by intracoronary pressure measurement in patients with recent acute myocardial infarction (AMI) who underwent late stent implantation to the IRA

Relationship between collateral blood flow and microvascular perfusion after reperfused acute myocardial infarction

During acute Occlusion of an epicardial vessel collaterals preserve the microvascular perfusion and limit the extent of myocardial damage. Pressure-derived collateral flow index (CFIp) assessed by intracoronary pressure measurement allow us to quantify collateral vessel development. The angiographic myocardial blush (MB) scores, based on the contrast dye density and washout in the infarcted myocardium, provide important information about microvascular perfusion after acute myocardial infarction (AMI). In this stud), we assessed the microvascular perfusion with MB and studied the relation between CFIp in patients with AMI who treated with thrombolytic therapy and TIMI grade III] now restored in the infarct related artery (IRA)

Renovascular hypertension secondary to spontaneous renal artery dissection and treatment with stenting

Renovascular disease is the cause of less than 1% of patients with hypertension; within this group aneurysm and dissection in renal artery are even rarer causes. It may be not only iatrogenic or traumatic, but may also develop spontaneously from fibromuscular disease or atherosclerotic lesions. We present a 26-year-old male patient with recently developed and progressive hypertension in whom renal angiography showed aneurysmal dilatation and dissection of the right renal artery. With the implantation of two stents in the true lumen, normal renal blood flow and thrombosis of the aneurysmal sac was established. As a result, stent implantation to renal artery dissection is effective, reliable and easy and can be an alternative to surgical treatment