Chowdhury Ahsan

Plaque Rupture and Thrombosis: the Value of the Atherosclerotic Rabbit Model in Defining the Mechanism

Persistent inflammation and mechanical injury associated with cholesterol crystal accretion within atherosclerotic plaques typically precedes plaque disruption (rupture and/or erosion) and thrombosis—often the terminal events of atherosclerotic cardiovascular disease. To elucidate the mechanisms of these events, the atherosclerotic rabbit model provides a unique and powerful tool that facilitates studies of atherogenesis starting with plaque buildup to eventual disruption. Examination of human coronary arteries obtained from patients who died with myocardial infarction demonstrates evidence of cholesterol crystals perforating the plaque cap and intimal surface of the arterial wall that can lead to rupture. These observations were made possible by omitting ethanol, an avid lipid solvent, from the tissue processing steps. Importantly, the atherosclerotic rabbit model exhibits a similar pathology of cholesterol crystals perforating the intimal surface as seen in ruptured human plaques. Local and systemic inflammatory responses in the model are also similar to those observed in humans. The strong parallel between the rabbit and human pathology validates the atherosclerotic rabbit model as a predictor of human pathophysiology of atherosclerosis. Thus, the atherosclerotic rabbit model can be used with confidence to evaluate diagnostic imaging and efficacy of novel anti-atherosclerotic therapy.

Prevalence of CYP2C19 alleles, pharmacokinetic and pharmacodynamic variation of clopidogrel and prasugrel in Bangladeshi population

The extent to which cytochrome P450 (CYP) 2C19 genotype influences the effectiveness of clopidogrel remains uncertain due to considerable heterogeneity between studies. We used the polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) method for genotyping loss of function (LOF) allele, CYP2C19*2 and gain of function (GOF) allele, CYP2C19*17 in 163 patients undergoing PCI and 165 healthy volunteers from an ethnically distinctive Bangladeshi population. Thirty‐eight patients took prasugrel and 125 patients took clopidogrel among whom 30 patients had their clopidogrel active metabolites (CAM) determined by LC‐MS/MS 1–1.5 h after clopidogrel intake. All patients who underwent PCI had their P2Y12 per cent inhibition (PRI) measured by VerifyNow System. The impact of different genotypes on CAM and PRI were also determined. We did not find significant variation of CYP2C19*2 (P > 0.05) and CYP2C9*17 (P > 0.05) alleles among healthy volunteers and patients. CAM concentration as well as PRI by clopidogrel varied significantly (P < 0.05) based on genotypic variation of CYP2C19*2 and CYP2C19*17 individually. Such influence was not observed in case of prasugrel. Genotypic variation did not impact PRI but as a whole PRI by prasugrel was better than that of clopidogrel (P < 0.05). Due to presence of both of alleles the effect on PRI by clopidogrel could not be predicted, effectively indicating possible involvement of other factors. Genotype guided clopidogrel dose adjustment would be beneficial and therefore we propose mandatory genotyping before clopidogrel dosing. Prasugrel proved to be less affected by genotypic variability, but due to lack of sufficient long‐term toxicity data, caution would be adopted before substituting clopidogrel.

Beta-blockers do not provide survival benefit in a population with angiographic coronary artery disease without myocardial infarction or reduced ejection fraction: A meta-analysis

BACKGROUND While beta-blockers have been widely used for patients with stable coronary artery disease (CAD), some concerns have been raised that beta blockers do not have survival benefit in this population. We conducted a meta-analysis to determine the effects of beta blockers on all-cause and cardiac mortality in adults with CAD without previous myocardial infarction (MI) or reduced ejection fraction. METHODS A systematic search of PubMed, Web of Science, Medline/Ovid and Google Scholar through March 2016 identified 4 studies that reported angiographic CAD without previous myocardial infarction or reduced ejection fraction. Fixed-effects pooled odds ratios and 95% confidence intervals of all-cause and cardiac mortality were estimated. We used the Grading of Recommendations Assessment, Development, and Evaluation system to assess overall quality of evidence. RESULTS A total of 17,397 patients were analyzed. In both all-cause and cardiac mortality analysis, no serious limitation was identified. Beta-blockers were not associated with reductions in all-cause mortality (odds ratios=0.910, 95% confidence intervals 0.797-1.039, p=.163) or cardiac mortality (odds ratio=0.926, 95% confidence interval 0.773-1.110, p=.407). CONCLUSION Beta-blockers do not provide any survival benefit in patients with angiographic CAD without history of MI or reduced ejection fraction.

Phasic disappearance of left circumflex coronary artery from an early complication of mitral valve surgery.

LV pseudoaneurysm can be a late complication of mitral valve replacement. In our case, it was an early postoperative complication. This pseudoaneurysm was causing compression of LCX artery during systole, leading to presentation of NSTEMI two weeks after the surgery.

Subvalvular aortic stenosis: a review of current literature

Subvalvular aortic stenosis (SAS) is one of the common adult congenital heart diseases, with a prevalence of 6.5%. It is usually diagnosed in the first decade of life. Echocardiography is the test of choice to diagnose SAS. Surgical correction is the best treatment modality, and the prognosis is usually excellent. In this review, we describe the pathophysiology, diagnosis, prognosis, and management of SAS with a focus on different pathophysiologic mechanisms, diagnostic approach, and prognosis of the disease by reviewing the current literature.

Significance of inferior wall ischemia in non-dominant right coronary artery anatomy

AIM To investigate the relationship of inferior wall ischemia on myocardial perfusion imaging in patients with non-dominant right coronary artery anatomy. METHODS This was a retrospective observational analysis of consecutive patients who presented to the emergency department with primary complaint of chest pain. Only patients who underwent single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) were included. Patients who showed a reversible defect on SPECT MPI and had coronary angiography during the same hospitalization was analyzed. Patients with prior history of coronary artery disease (CAD) including history of percutaneous coronary intervention and coronary artery bypass graft surgerys were excluded. True positive and false positive results were identified on the basis of hemodynamically significant CAD on coronary angiography, in the same territory as identified on SPECT MPI. Coronary artery dominance was determined on coronary angiography. Patients were divided into group 1 and group 2. Group 1 included patients with non-dominant right coronary artery (RCA) (left dominant and codominant). Group 2 included patients with dominant RCA anatomy. Demographics, baseline characteristics and positive predictive value (PPV) were analyzed for the two groups. RESULTS The mean age of the study cohort was 57.6 years. Sixty-one point seven percent of the patients were males. The prevalence of self-reported diabetes mellitus, hypertension and dyslipidemia was 36%, 71.9% and 53.9% respectively. A comparison of baseline characteristics between the two groups showed that patients with a non-dominant RCA were more likely to be men. For inferior wall ischemia on SPECT MPI, patients in study group 2 had a significantly higher PPV, 32/42 (76.1%), compared to patients in group 1, in which only 3 out of the 29 patients (10.3%) had true positive results (P value < 0.001 Z test). The difference remained statistically significant even when only patients with left dominant coronary system (without co-dominant) were compared to patients with right dominant system (32/40, 76.1% in right dominant group, 3/19, 15.8% in left dominant group, P value < 0.001 Z test). There was no significant difference in mean hospital stay, re-hospitalization, and in-hospital mortality between the two groups. CONCLUSION The positive predictive value of SPECT MPI for inferior wall ischemia is affected by coronary artery dominance. More studies are needed to explain this phenomenon.

ST-segment elevation myocardial infarction, systems of care. An urgent need for policies to co-ordinate care in order to decrease in-hospital mortality

BACKGROUND Regional trends for ST-segment elevation myocardial infarction (STEMI) treatment is not known in the state of Nevada. HYPOTHESIS Great disparity exists for treatment for STEMI in different geographical areas of Nevada. There is a great potential to improve treatment and outcomes of STEMI patients in the State of Nevada. METHODS Admissions to non-federal hospitals in the state of Nevada, using 2011 to 2013 discharge data from the Nevada State Inpatient Data Base (acquired from Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality), were analyzed. Outpatient-onset STEMI patients were identified. The state of Nevada was divided into three divisions based on population densities, defined as population per square mile. Division A included counties with population density of <50 per square mile, Division B included counties with population density of 50 to 200 per square mile, and Division C included counties with population density of >200 per square mile. Trends in use of STEMI-related therapies and the impact on in-hospital mortality rates were compared. RESULTS Almost 20% of the patients with outpatient-onset STEMI do not get any STEMI-related therapy and have significantly higher mortality rate. Patients from Division A do not have direct access to percutaneous coronary intervention (PCI) centers. These patients receive less STEMI-related therapies. Low-volume PCI centers had equivalent mortality rates for STEMI patients who got PCI, compared to high-volume PCI centers. CONCLUSIONS Policies must be created and processes streamlined so all STEMI patients in Nevada receive appropriate treatment.

Hypertension in diabetes and the risk of cardiovascular disease

Hypertension (HTN) is an important risk factor for cardiovascular disease and its many manifestations. It shares pathogenic pathways with diabetes and is part of a common metabolic entity, the metabolic syndrome. When combined with diabetes, HTN has been shown to predict and promote increased risk for cardiovascular disease events over and above each risk factor alone. Of the components of this metabolic syndrome, HTN is relatively easy to diagnose and thereby more accessible for implementing preventive and treatment strategies. The recent release of Joint National Committee-8 guidelines for the treatment of HTN has fueled a debate on treatment target goals.

PREDICTORS OF TREATMENT AND OUTCOMES IN PATIENTS WITH ST SEGMENT ELEVATION MYOCARDIAL INFARCTION IN THE STATE OF NEVADA

Multiple factors can effect treatment and outcomes for ST segment elevation myocardial infarction (STEMI). We studied the characteristics and variables associated with treatment and outcomes of patients who received STEMI care in the state of Nevada. This is a retrospective study of STEMIs from

Recurrent intra-cardiac thrombosis—A unique presentation of prothrombin G20210 mutation

We report a 49-year-old female patient with recurrent large left ventricular thrombus on echocardiogram in an apparently normal heart and insignificant cardiac past medical history. She underwent an excision of the left ventricular mass, final biopsy on which proved it to be a thrombus. Postoperative anti-coagulation was initiated with enoxaparin and warfarin and the patient was followed up at a cardiology clinic 6 weeks later. A repeat trans-thoracic echocardiogram revealed a new mass arising from the left atrium. Considering the increased risk of repeat ventriculostomy, she was treated conservatively with her current management. During this time the patients pro-thrombotic work-up revealed positive prothrombin G20210 mutation. A follow up trans-thoracic echocardiogram done 2 months later surprisingly revealed complete resolution of the intracardiac mass. Our patient had prothrombin G20210 mutation, an entity primarily known for deep venous thrombosis, which rarely causes intra-arterial thrombus, intra-cardiac being unreported. There are no established protocols for management of these cases. The rate of embolic episodes in mobile pedunculated thrombi is reported as high as 60%. Patients with prior embolism must be offered immediate surgery, especially if the thrombus is large with an irregular surface, pedunculated, and multiple in number. Aggressive anti-coagulation with close monitoring is essential.