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Spokane, WA, United States

Nair N.,Providence Spokane Heart Institute | Gongora E.,Memorial Cardiac and Vascular Institute
Biomolecular Concepts | Year: 2014

The identification of biomarkers for cardiomyopathy presents a distinct challenge as the etiologies are widely varied. The discovery of small non-coding miRNAs with gene regulatory function has opened new avenues of investigation in basic and clinical sciences. The search for regulatory nucleotide sequences that have specific gene targets have put miRNAs at the forefront of development of therapeutics, and may serve as valuable diagnostic and/or therapeutic targets. MiRNAs appear to influence both positive and negative remodeling. As cardiac remodeling is a complex process, global molecular networks and miRNA profiles may be required to fulfill the roles of macroregulators. The type of cardiomyopathy leading to heart failure in the long run appears to have a distinct molecular pattern underlying the pathophysiology. This review discusses in brief the existing literature on the molecular signatures in dilated, ischemic, hypertrophic, stress, and peripartum cardiomyopathies that may be used to target therapies for specific etiologies once diagnosed, therefore exploring the utility of specific miRNAs in tailoring therapy for heart failure based on etiology. © 2014 by De Gruyter.

Voeks J.H.,Medical University of South Carolina | Leimgruber P.P.,Providence Spokane Heart Institute | Mantese V.A.,Vascular Surgery | Timaran C.H.,University of Texas Southwestern Medical Center | And 5 more authors.
Journal of the American Heart Association | Year: 2014

Background-The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) is a multicenter randomized trial of stenting versus endarterectomy in patients with symptomatic and asymptomatic carotid disease. This study assesses management of vascular risk factors. Methods and Results-Management was provided by the patient's physician, with biannual monitoring results collected by the local site. Therapeutic targets were low-density lipoprotein, cholesterol <100 mg/dL, systolic blood pressure <140 mm Hg, fasting blood glucose <126 mg/dL, and nonsmoking status. Optimal control was defined as achieving all 4 goals concurrently. Generalized estimating equations were used to compare risk factors at baseline with those observed in scheduled follow-up visits for up to 48 months. In the analysis cohort of 2210, significant improvements in risk-factor control were observed across risk factors for all follow-up visits compared with baseline. At 48 months, achievement of the low-density lipoprotein cholesterol goal improved from 59.1% to 73.6% (P<0.001), achievement of the systolic blood pressure goal improved from 51.6% to 65.1% (P<0.001), achievement of the glucose goal improved from 74.9% to 80.7% (P=0.0101), and nonsmoking improved from 74.4% to 80.9% (P<0.0001). The percentage with optimal risk-factor control also improved significantly, from 16.7% to 36.2% (P<0.001), but nearly 2 of 3 study participants did not achieve optimal control during the study. Conclusions-Site-based risk-factor control improved significantly in the first 6 months and over the long term in CREST but was often suboptimal. Intensive medical management should be considered for future trials of carotid revascularization. © 2014 The Authors.

De Marchena E.,University of Miami | Mesa J.,University of Miami | Pomenti S.,University of Miami | Marin Y Kall C.,University of Miami | And 9 more authors.
JACC: Cardiovascular Interventions | Year: 2015

Objectives This paper reviews the published data and reports 3 cases of thrombosis involving CoreValve (Medtronic, Minneapolis, Minnesota) and 1 involving Edward Sapien (Edwards Lifesciences, Irvine, California) devices. Three of these cases had pathological findings at autopsy. Background Only a limited number of cases of valve dysfunction with rapid increase of transvalvular aortic gradients or aortic insufficiency post-transcatheter aortic valve replacement (TAVR) have been described. This nonstructural valvular dysfunction has been presumed to be because of early pannus formation or thrombosis. Methods Through reviews of the published reports and 4 clinical cases, pathological and clinical findings of early valve thrombosis are examined to elucidate methods for recognition and identifying potential causes and treatments. Results This paper presents 4 cases, 2 of which had increasing gradients post-TAVR. All 3 pathology cases showed presence of a valve thrombosis in at least 2 TAV leaflets on autopsy, but were not visualized by transthoracic echocardiogram or transesophageal echocardiogram. One case was medically treated with oral anti coagulation with normalization of gradients. The consequence of valve thrombosis in all 3 pathology patients either directly or indirectly played a role in their early demise. At least 18 case reports of early valve thrombosis have been published. In 12 of these cases, the early treatment with anticoagulation therapy resolved the thrombus formation and normalized aortic pressures gradients successfully. Conclusions These 4 cases elucidate the occurrence of valve thrombosis post-TAVR. Consideration should be given to treatment with dual antiplatelet therapy and oral anticoagulation in patients post-TAVR with increasing mean pressure gradients and maximum aortic valve velocity. Further research should be conducted to create guidelines for antithrombotic therapy following TAVR procedure. © 2015 American College of Cardiology Foundation.

Nair N.,Texas A&M University | Nair N.,Providence Spokane Heart Institute | Gongora E.,Hahnemann University | Mehra M.R.,Harvard University
Journal of Heart and Lung Transplantation | Year: 2014

Cancers in post-transplant patients exhibit the same molecular and cellular properties as those in their non-transplanted counterparts and arise secondary to uncontrolled/sustained growth, apoptosis resistance, inhibition of tumor suppressors, immortalization of cells with invasion, and and metastasis. Disruption of DNA repair mechanisms, upregulation of angiogenic growth factors, impaired viral immunity and activated oncogenic viruses contribute to the initiation of malignancies in this population. This article extends and addresses the concerns in this area. We propose potential cancer prevention strategies and a possible 4-pronged approach to prevent and treat malignancies in the post-transplant population. Future research should define strategies for immune modulation, immune suppression and malignancy prevention, including methods for naive B-cell repopulation, memory B-cell reduction and biomarker identification and utilization for predicting tolerance. Non-immune therapies, such as adjunct preventive methods and goals to modify risk factors, may reduce incidence of malignancies and pave the way to better outcomes. The role of statins is of particular interest in this context due to their pleiotropic effects on the cell cycle and their most direct role in inhibition of cholesterol biosynthesis. © 2014 International Society for Heart and Lung Transplantation. All rights reserved.

Blackshear J.L.,Mayo Medical School | Cutlip D.E.,Beth Israel Deaconess Medical Center | Roubin G.S.,New Hill | Hill M.D.,University of Calgary | And 9 more authors.
Circulation | Year: 2011

Background: The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) found a higher risk of stroke after carotid artery stenting and a higher risk of myocardial infarction (MI) after carotid endarterectomy. Methods and results: Cardiac biomarkers and ECGs were performed before and 6 to 8 hours after either procedure and if there was clinical evidence of ischemia. In CREST, MI was defined as biomarker elevation plus either chest pain or ECG evidence of ischemia. An additional category of biomarker elevation with neither chest pain nor ECG abnormality was prespecified (biomarker+ only). Crude mortality and risk-adjusted mortality for MI and biomarker+ only were assessed during follow-up. Among 2502 patients, 14 MIs occurred in carotid artery stenting and 28 MIs in carotid endarterectomy (hazard ratio, 0.50; 95% confidence interval, 0.26 to 0.94; P=0.032) with a median biomarker ratio of 40 times the upper limit of normal. An additional 8 carotid artery stenting and 12 carotid endarterectomy patients had biomarker+ only (hazard ratio, 0.66; 95% confidence interval, 0.27 to 1.61; P=0.36), and their median biomarker ratio was 14 times the upper limit of normal. Compared with patients without biomarker elevation, mortality was higher over 4 years for those with MI (hazard ratio, 3.40; 95% confidence interval, 1.67 to 6.92) or biomarker+ only (hazard ratio, 3.57; 95% confidence interval, 1.46 to 8.68). After adjustment for baseline risk factors, both MI and biomarker+ only remained independently associated with increased mortality. Conclusions: In patients randomized to carotid endarterectomy versus carotid artery stenting, both MI and biomarker+ only were more common with carotid endarterectomy. Although the levels of biomarker elevation were modest, both events were independently associated with increased future mortality and remain an important consideration in choosing the mode of carotid revascularization or medical therapy. © 2011 American Heart Association, Inc.

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