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3.  Preoperative Cardiac Variables of Diastolic Dysfunction and Clinical Outcomes in Lung Transplant Recipients 
Journal of Transplantation  2013;2013:391620.
Background. Orthotopic lung transplantation is now widely performed in patients with advanced lung disease. Patients with moderate or severe ventricular systolic dysfunction are typically excluded from lung transplantation; however, there is a paucity of data regarding the prognostic significance of abnormal left ventricular diastolic function and elevated pretransplant pulmonary pressures. Methods. We reviewed the characteristics of 111 patients who underwent bilateral and unilateral lung transplants from 200 to 2009 in order to evaluate the prognostic significance of preoperative markers of diastolic function, including invasively measured pulmonary capillary wedge pressure (PCWP) and echocardiographic variables of diastolic dysfunction including mitral A > E and A′ > E′. Results. Out of 111 patients, 62 were male (56%) and average age was 54.0 ± 10.5 years. Traditional echocardiographic Doppler variables of abnormal diastolic function, including A′ > E′ and A > E, did not predict adverse events (P = 0.49). Mildly elevated pretransplant PCWP (16–20 mmHg) and moderately/severely elevated PCWP (>20 mmHg) were not associated with adverse clinical events after transplant (P = 0.30). Additionally, all clinical endpoints did not show any statistical significance between the two groups. Conclusions. Pre-lung transplant invasive and echocardiographic findings of elevated pulmonary pressures and abnormal left ventricular diastolic function are not predictive of adverse posttransplant clinical events.
PMCID: PMC3791796  PMID: 24163757
4.  Coronary and Intracerebral Arterial Aneurysms in a Young Adult with Acute Coronary Syndrome 
Texas Heart Institute Journal  2012;39(3):380-383.
A 21-year-old man with no known medical history presented with substernal chest pain. Serial 12-lead electrocardiography showed dynamic ST-segment elevations in the anterolateral leads. Emergent coronary angiography revealed diffuse coronary aneurysmal disease and thrombotic occlusion of the left anterior descending coronary artery. The patient underwent urgent coronary artery bypass grafting. Subsequent imaging showed intracerebral aneurysms that involved his right and left middle cerebral arteries. The incidence, multiple causes, and proposed mechanisms of coronary artery aneurysmal formation are discussed, as is the rare association of these lesions with extracardiac arterial aneurysms.
This association between coronary and extracardiac aneurysms is a phenomenon that warrants further study to determine its prevalence and possible causes. Findings could influence recommendations for further screening of patients diagnosed with coronary aneurysmal disease.
PMCID: PMC3368465  PMID: 22719148
Acute coronary syndrome; cerebrovas-cular aneurysms; congenital heart disease; coronary aneurysm/etiology; coronary vessel anomalies; dilatation, pathologic/etiology; intra-cranial aneurysm; Kawasaki disease
5.  Coronary microcirculatory vasodilator function in relation to risk factors among patients without obstructive coronary disease and low to intermediate Framingham score 
European Heart Journal  2009;31(8):936-942.
The study aim was to evaluate the relation between the Framingham risk score (FRS) and the presence of coronary risk factors to coronary microcirculatory vasodilator function in patients with early coronary atherosclerosis.
Methods and results
We evaluated 1063 patients (age: 50 ± 12 years, 676 (64%) females) without significant narrowing (<30%) on coronary angiography who underwent invasive assessment of coronary endothelial function. Coronary blood flow (CBF) in response to the endothelium-dependent vasodilator acetylcholine was evaluated as well as the microvascular (endothelium-independent) coronary flow reserve (CFR) in response to intracoronary adenosine. Coronary blood flow and CFR were analysed in relation to the FRS and the presence of traditional and novel risk factors. The estimated 10 years risk in this group was 5.4 ± 5.2%. Higher FRS was associated with lower CBF in men (P = 0.008), and was a univariate predictor of lower CFR (P = 0.012) in all patients. Multivariable analysis identified a higher FRS (P < 0.001), female sex (P < 0.001) and a positive family history of coronary disease (P = 0.043) as independent predictors of reduced CFR.
In patients without obstructive coronary disease, a higher FRS was an independent predictor of reduced CFR. The current study provides insight into the relation between cardiac risk profile and coronary microcirculatory function, and suggests that impaired microcirculatory vasodilator function may be present even in patients with a low to intermediate Framingham score.
PMCID: PMC2854505  PMID: 19897496
Coronary atherosclerosis; Female; Framingham risk score; Endothelial function; Microcirculation
6.  Left Main Stent Thrombosis Complicated by Eptifibatide-Induced Acute Thrombocytopenia 
Texas Heart Institute Journal  2011;38(2):174-178.
A 57-year-old man with a history of coronary artery disease and placement of an implantable cardioverter-defibrillator presented at our emergency room with an anterior ST-elevation myocardial infarction. Cardiac catheterization revealed an acutely occluded left main coronary artery, which was revascularized successfully with a bare-metal stent. Periprocedurally, the patient received aspirin, clopidogrel, unfractionated heparin, and eptifibatide.
The patient was discharged a week later, but he returned to the emergency room the same day with recurrence of severe chest pain. Repeat cardiac catheterization revealed an acutely occluded stent, and the patient underwent repeat bare-metal stent placement and readministration of eptifibatide. On the next day, the patient's platelet count dropped acutely to less than 12,000/mm3. A test for heparin-induced thrombocytopenia antibody was negative. After discontinuation of eptifibatide, the patient's platelet count gradually returned to normal, and he was later discharged from the hospital with no complications.
Eptifibatide-induced acute thrombocytopenia is a known but rare adverse effect. We review the handful of case reports in the medical literature, with emphasis on the prevalence, observed clinical course, and recently proposed physiologic mechanisms that probably are responsible for this phenomenon.
PMCID: PMC3066830  PMID: 21494531
Acute coronary syndrome; antibodies, monoclonal/adverse effects; coronary stenosis/blood; eptifibatide; GPIIb/IIIa inhibitor; megakaryocytes; peptides/adverse effects; platelet aggregation inhibitors/therapeutic use; platelet glycoprotein GPIIb-IIIa complex/antagonists & inhibitors; ST-elevation myocardial infarction; stents; thrombocytopenia/chemically induced/etiology
7.  Identification of Global Transcriptional Dynamics 
PLoS ONE  2009;4(7):e5992.
One of the challenges in exploiting high throughput measurement techniques such as microarrays is the conversion of the vast amounts of data obtained into relevant knowledge. Of particular importance is the identification of the intrinsic response of a transcriptional experiment and the characterization of the underlying dynamics.
Methodology and Findings
The proposed algorithm seeks to provide the researcher a summary as to various aspects relating to the dynamic progression of a biological system, rather than that of individual genes. The approach is based on the identification of smaller number of expression motifs that define the transcriptional state of the system which quantifies the deviation of the cellular response from a control state in the presence of an external perturbation. The approach is demonstrated with a number of data sets including a synthetic base case and four animal studies. The synthetic dataset will be used to establish the response of the algorithm on a “null” dataset, whereas the four different experimental datasets represent a spectrum of possible time course experiments in terms of the degree of perturbation associated with the experiment as well as representing a wide range of temporal sampling strategies. This wide range of experimental datasets will thus allow us to explore the performance of the proposed algorithm and determine its ability identify relevant information.
Conclusions and Significance
In this work, we present a computational approach which operates on high throughput temporal gene expression data to assess the information content of the experiment, identify dynamic markers of important processes associated with the experimental perturbation, and summarize in a concise manner the evolution of the system over time with respect to the experimental perturbation.
PMCID: PMC2705787  PMID: 19593450

Results 1-7 (7)