Design and rationale of a prospective, randomized, non-inferiority trial to determine the safety and efficacy of the Biolimus A9™ drug coated balloon for the treatment of in-stent restenosis: First-in-man trial (REFORM).

BACKGROUND: Drug-coated balloon (DCB) angioplasty with paclitaxel-eluting devices is an established treatment for coronary in-stent restenosis (ISR). Biolimus A9™ (BA9), a sirolimus analogue with enhanced lipophilicity, may facilitate enhanced local drug delivery into vascular tissue. A novel DCB coated with Biolimus A9™ represents an alternative to traditional paclitaxel- and sirolimus-coated devices. Hence, we sought to investigate the safety and efficacy of this novel DCB in the treatment of coronary ISR. METHODS AND DESIGN: REFORM (NCT04079192) is a prospective, multicenter, single blind, randomized controlled trial comparing the BA9-DCB (Biosensors Europe SA, Morges, Switzerland) to the paclitaxel-coated SeQuent® Please DCB (Braun Melsungen AG, Germany) in the treatment of coronary ISR. A total of 201 patients with coronary artery disease and an indication for interventional treatment of ISR in a bare-metal stent (BMS) or drug-eluting stent (DES) have been randomized 2:1 to receive treatment with the BA9- or the paclitaxel-DCB comparator. Patients were enrolled across 24 investigational centers in Europe and Asia. The primary endpoint is percent diameter stenosis (%DS) of the target segment as assessed by quantitative coronary angiography (QCA) at 6 months. Key secondary endpoints are in-stent late lumen loss, binary restenosis, target lesion failure, target vessel failure, myocardial infarction and death at 6 months. Subjects will be followed for 24 months from enrolment. IMPLICATIONS: The REFORM trial will seek to prove that the BA9-DCB is non-inferior to the standard paclitaxel-DCB comparator in the treatment of coronary ISR with respect to %DS at 6 months and has similar safety characteristics.

Improving ECG Competence in Medical Trainees in a UK District General Hospital.

BACKGROUND: Competency in electrocardiogram (ECG) interpretation is central to undergraduate and postgraduate clinical training. Studies have demonstrated ECGs are interpreted sub-optimally. Our study compares the effectiveness of two learning strategies to improve competence and confidence. METHOD: A 1-month prospective randomized study compared the strategies in two cohorts: undergraduate third year medical students and postgraduate foundation year one (FY1) doctors. Both had blinded randomization to one of these learning strategies: focused teaching program (FTP) and self-directed learning (SDL). All volunteers completed a confidence questionnaire before and after allocation learning strategy and an ECG recognition multiple choice question (MCQ) paper at the end of the learning period. RESULTS: The FTP group of undergraduates demonstrated a significant difference in successfully interpreting "ventricular tachycardia" (P = 0.046) and "narrow complex tachycardia" (P = 0.009) than the SDL group. Participant confidence increased in both learning strategies. FTP confidence demonstrated a greater improvement than SDL for both cohorts. CONCLUSION: A dedicated teaching program can improve trainee confidence and competence in ECG interpretation. A larger benefit is observed in undergraduates and those undertaking a FTP.

Intramural hemotoma presenting as acute coronary syndrome: the importance of intravascular ultrasound.

Intramural hematoma in major coronary epicardial vessels is a rare cause of chest pain. Afflicted individuals may present with acute coronary syndrome (ACS) or even sudden cardiac death. Spontaneous, isolated intramural hematoma may occur in the absence of associated intimal dissection. In this situation, lesions may be angiographically indistinguishable from ruptured atherosclerotic plaque. Intravascular ultrasound is important in the accurate diagnosis of isolated intramural hematoma. Although coronary stenting may be required in the presence of ongoing ischemia, intramural hematoma may be successfully managed medically. We describe the case of a middle-aged woman who presented with ACS due to an intramural hematoma and discuss the diagnosis and management of this rare illness.

Effect of enalapril and losartan on cytokines in patients with stable angina pectoris awaiting coronary artery bypass grafting and their interaction with polymorphisms in the interleukin-6 gene.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may have anti-inflammatory actions, an effect that could explain some of their beneficial effects on cardiovascular events in clinical trials. Coronary artery bypass grafting (CABG) is associated with a systemic inflammatory response and provides a convenient model to examine the effects of such agents. Genetic polymorphisms may be important in influencing the expression of cytokines, such as interleukin-6 (IL-6). We randomized men awaiting CABG to treatment with enalapril, losartan, or control for 2 months before surgery. Systemic IL-6, IL-8, IL-10, and IL-1 receptor agonists were measured before and after surgery, and genotypes for the -174 G/C and -572 G/C IL-6 gene polymorphisms were determined. Total release of the IL-1 receptor agonist was decreased 29% by enalapril and 31% by losartan (adjusted p = 0.041). IL-6 was decreased 17% by enalapril and 20% by losartan. Subjects possessing the -174 GG genotype produced 20% more IL-6 (adjusted p = 0.029). In these high producers of IL-6, release of IL-6 was decreased 51% by enalapril (adjusted p = 0.001) and 32% by losartan (adjusted p = 0.068). Release of IL-10 was nonsignificantly decreased 26% by enalapril and 21% by losartan, whereas IL-8 was not detected. In conclusion, enalapril and losartan significantly decreased release of the IL-1 receptor agonist after CABG. Enalapril produced a highly significant decrease of 51% in the release of IL-6 in patients identified as high producers of IL-6 by the -174 G/C polymorphism, whereas losartan has a similar but less marked effect. The production of IL-6 in this setting is influenced by the -174 G/C polymorphism.

Impact of the recommendations for the redefinition of myocardial infarction on diagnosis and prognosis in an unselected United Kingdom cohort with suspected cardiac chest pain.

We prospectively and blindly assessed the diagnostic and prognostic impact of implementation of the European Society of Cardiology/American College of Cardiology recommendations for redefinition of myocardial infarction (MI) in an unselected cohort of patients with suspected cardiac chest pain, with particular attention to prespecified clinical groups. All patients admitted to our institute with suspected cardiac chest pain were enrolled. Physicians provided usual care using serial electrocardiograms/creatine kinase (CK)/aspartate transaminase according to World Health Organization (WHO) criteria for MI, while blinded to additional measurements of cardiac troponin T (cTnT) and CK-MB mass. After discharge, diagnoses based on WHO and new criteria were compared, and major adverse cardiac events monitored for 6 months. Implementation of the new recommendations classified an additional 26.1% of patients as having MI compared with WHO criteria, and produced an overall diagnostic alteration in 11.5%. Two thirds of the additional patients with MI were previously diagnosed with unstable angina, whereas one third had "other cardiac" or "noncardiac" diagnoses. A similar MI cohort to the cTnT diagnosis was identified using a CK-MB mass discriminator value of 5 microg/L, but not 10 microg/L. The 6-month prognosis was similar in patients diagnosed with MI by new (cTnT) and WHO criteria, with the new criteria thus identifying a further high-risk cohort in the WHO negative group. In our cohort, the new Joint European Society of Cardiology/American College of Cardiology recommendations identify one fourth more patients as having MI. The 6-month prognosis of those patients reclassified as having MI was similar to those diagnosed with MI by both criteria.