Oliver G. Abela

Plaque Rupture and Thrombosis Are Reduced by Lowering Cholesterol Levels and Crystallization With Ezetimibe and Are Correlated With Fluorodeoxyglucose Positron Emission Tomography

Objective— This study evaluated effects of lipid lowering with ezetimibe on plaque burden and associated cholesterol crystallization and inflammation in a rabbit model of plaque disruption and thrombosis. Methods and Results— Atherosclerotic rabbits (Group I, n=10 without; Group II, n=12 with ezetimibe, 1 mg/kg per day) were pharmacologically triggered for plaque disruption. Fluorodeoxyglucose positron emission tomography, RAM 11 macrophage staining, and serum inflammatory markers detected arterial inflammation. Serum and aortic wall cholesterol levels were measured, and thrombus area was planimetered. Cholesterol crystal density on aortic surface was scored (0 to +3) by scanning electron microscopy. Serum and aortic wall cholesterol, plaque area, and thrombosis area were significantly lower in Group II versus Group I (83.4±106.4 versus 608±386 mg/dL, P=0.002; 3.12±1.40 versus 9.39±5.60 mg/g, P=0.003; 10.84±1.6 versus 17.48±1.8 mm2, P<0.001; and 0.05±0.15 versus 0.72±0.58 mm2, P=0.01, respectively). There were significant correlations between crystal density and plaque area (r=0.75, P<0.003) and between crystal density and RAM 11 (r=0.82, P<0.001). Scanning electron microscopy demonstrated that there were fewer crystals in Group II versus Group I (+1.2±0.61 versus +2.4±0.63, P<0.001) and less inflammation detected by fluorodeoxyglucose positron emission tomography and RAM 11 (P<0.004 and P<0.04, respectively). Conclusion— Lowering cholesterol levels with ezetimibe reduced plaque burden, crystallization, and inflammation, preventing plaque disruption and thrombosis.

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.

Potassium toxicity at low serum potassium levels with refeeding syndrome.

Refeeding syndrome is a life-threatening condition occurring in severely malnourished patients after initiating feeding. Severe hypophosphatemia with reduced adenosine triphosphate production has been implicated, but little data are available regarding electrolyte abnormalities. In this case, we report electrocardiographic changes consistent with hyperkalemia during potassium replacement after a serum level increase from 1.9 to 2.9 mEq/L. This was reversed by lowering serum potassium back to 2.0 mEq/L. In conclusion, the patient with prolonged malnutrition became adapted to low potassium levels and developed potassium toxicity with replacement.

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.

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