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Ambardekar A.V.,Aurora University | Lindenfeld J.,Aurora University | Lindenfeld J.,Vanderbilt Heart and Vascular Institute
Circulation: Heart Failure | Year: 2015

The effects of nonpulsatile flow on the aorta are unknown. Our aim was to examine the structure of the aorta from patients with continuous-flow left ventricular assist devices (LVADs) and directly measure aortic wall composition and stiffness. Methods and Results-Age-matched aortic wall samples were collected from consecutive patients with heart failure (HF) at the time of transplantation and compared with nonfailing donor hearts. An unbiased stereological approach was used to quantify aortic morphometry and composition, and biomechanical testing was performed to determine the stress-strain relationship of the vessel. Data were obtained from 4 patients without a left ventricular assist device (HF group: mean age, 58.3±8.0 years), 7 patients with a continuous-flow LVAD (HF+LVAD group: mean, 57.7±5.6 years), and 3 nonfailing donors (mean, 53.3±12.9 years). Compared with HF, the aortic walls from HF+LVAD had an increase in wall thickness, collagen, and smooth muscle content accompanied by a reduction in elastin and mucinous ground-substance content. Stress-strain curves from the aortas revealed increased vessel stiffness in HF+LVAD compared with HF and nonfailing. The physiological modulus of the aorta progressively stiffened from 74.3±5.5 kPa in the nonfailing to 134.4±35.0 kPa in the HF to 201.7±36.4kPa in the HF+LVAD groups (P<0.001). Conclusions-Among continuous-flow LVAD patients without aortic valve opening, there are changes in the structure and composition of the aorta as well as an increase in aortic wall stiffness compared with age-matched HF patients and nonfailing donors. Further studies examining the role of nonpulsatile blood flow on aortic function and the potential resultant systemic sequelae are needed. © 2015 American Heart Association, Inc.


Lenihan D.J.,Vanderbilt Heart and Vascular Institute | Cardinale D.M.,Italian National Cancer Institute
Journal of Clinical Oncology | Year: 2012

Cardiac toxicities from cancer therapy can become evident many years after treatment, and these late cardiac effects can have a profound impact on cancer survivors. There are a myriad of potential cardiovascular complications from cancer therapy, but these can be grouped into three main categories. First, vascular conditions including atherosclerosis, thrombosis, and hypertension predominate. Second, cardiac structural problems, especially valvular degeneration, can have a dramatic impact long term. Lastly, and most importantly, cardiac dysfunction and heart failure are potentially common late cardiac effects and can certainly be prevented or detected early during active cancer therapy to result in optimal outcomes. Future research on late cardiac effects in cancer survivors needs to include advanced cardiac imaging techniques, novel cardiac biomarkers, and genetic determinants of response to cancer treatment. © 2012 by American Society of Clinical Oncology.


Griffith M.L.,Vanderbilt University | Griffith M.L.,Veterans Administration Tennessee Valley Health System | Savani B.N.,Veterans Administration Tennessee Valley Health System | Savani B.N.,Vanderbilt University | And 2 more authors.
Blood | Year: 2010

Currently, approximately 15 000 to 20 000 patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) annually throughout the world, with the number of long-term survivors increasing rapidly. In long-term follow-up after transplantation, the focus of care moves beyond cure of the original disease to the identification and treatment of late effects after HSCT. One of the more serious complications is therapy-related cardiovascular disease. Long-term survivors after HSCT probably have an increased risk of premature cardiovascular events. Cardiovascular complications related to dyslipidemia and other risk factors account for a significant proportion of late nonrelapse morbidity and mortality. This review addresses the risk and causes of dyslipidemia and impact on cardiovascular complications after HSCT. Immunosuppressive therapy, chronic graft-versus-host disease, and other long-term complications influence the management of dyslipidemia. There are currently no established guidelines for evaluation and management of dyslipidemia in HSCT patients; in this review, we have summarized our suggested approach in the HSCT population. © 2010 by The American Society of Hematology.


Ellis C.R.,Vanderbilt Heart and Vascular Institute | Kaiser D.W.,Vanderbilt Heart and Vascular Institute
Vascular Health and Risk Management | Year: 2013

The use of novel oral anticoagulants (NOACs) for stroke and systemic embolism prevention in the setting of specifically non valvular atrial fibrillation has provided clinicians with a realistic treatment alternative to the traditional dose-adjusted, warfarin-based anticoagulation that is targeted to a therapeutic international normalized ratio range of 2.0-3.0. We discuss the use of dabigatran in the setting of mechanical heart valves, atrial fibrillation or left atrial catheter ablation procedures, reversal of the drug in the setting of adverse bleeding events, and background on the molecular biology and development of this novel treatment for stroke reduction. © 2013 Ellis and Kaiser, publisher and licensee Dove Medical Press Ltd.


Subbiah I.M.,University of Houston | Lenihan D.J.,Vanderbilt Heart and Vascular Institute | Tsimberidou A.M.,University of Houston
Oncologist | Year: 2011

Background. Vascular-disrupting agents (VDAs) represent a new class of chemotherapeutic agent that targets the existing vasculature in solid tumors. Preclinical and earlyphase trials have demonstrated the promising therapeutic benefits ofVDAsbut have also uncovered a distinctive toxicity profile highlighted by cardiovascular events. Methods. We reviewed all preclinical and prospective phase I-III clinical trials published up to August 2010 in MEDLINE and the American Association of Cancer Research and American Society of Clinical Oncology meeting abstracts of small-molecule VDAs, including combretastatin A4 phosphate (CA4P), combretastatin A1 phosphate (CA1P), MPC-6827, ZD6126, AVE8062, and ASA404. Results. Phase I and II studies of CA1P, ASA404, MPC-6827, and CA4P all reported cardiovascular toxicities, with the most common cardiac events being National Cancer Institute Common Toxicity Criteria (version 3) grade 1-3 hypertension, tachyarrhythmias and bradyarrhythmias, atrial fibrillation, and myocardial infarction. Cardiac events were dose-limiting toxicities in phase I trials with VDA monotherapy and combination therapy. Conclusions. Early-phase trials of VDAs have revealed a cardiovascular toxicity profile similar to that of their vascular-targeting counterparts, the angiogenesis inhibitors. As these agents are added to the mainstream chemotherapeutic arsenal, careful identification of baseline cardiovascular risk factors would seem to be a prudent strategy. Close collaboration with cardiology colleagues for early indicators of serious cardiac adverse events will likely minimize toxicity while optimizing the therapeutic potential of VDAs and ultimately enhancing patient outcomes.


Kolek M.J.,Vanderbilt Heart and Vascular Institute | Dresen W.F.,Vanderbilt Heart and Vascular Institute | Wells Q.S.,Vanderbilt Heart and Vascular Institute | Ellis C.R.,Vanderbilt Heart and Vascular Institute
PACE - Pacing and Clinical Electrophysiology | Year: 2013

Introduction The incidence of cardiac implantable electronic device (CIED) infections has risen rapidly since 2004. A commercially available minocycline and rifampin impregnated antibacterial envelope has been associated with a low CIED infection rate. We performed a retrospective cohort study analyzing CIED infection rates in patients receiving an antibacterial envelope. Methods Prospectively applied criteria for use of the antibacterial envelope included ≥2 of the following: diabetes, renal insufficiency, anticoagulation, chronic corticosteroid use, fever or leukocytosis at the time of implantation, prior CIED infection, ≥3 leads (cardiac resynchronization therapy or abandoned leads), pacemaker dependence, or early pocket reentry. CIED infection rate was compared to a cohort of patients with matched risk factors and a CIED implanted prior to use of the antibacterial envelope. Results A total of 260 antibacterial envelopes were implanted from November 1, 2009 to April 30, 2012. The mean number of CIED infection risk factors was 2.8 ± 1.2. The control cohort (N = 639) was matched for mean number of CIED infection risk factors (2.8 ± 1.2), though individual risk factors differed. After a minimum of 90 days of follow-up, there was one CIED infection among patients who received an antibacterial envelope (0.4%), compared to 19 (3%) in controls (odds ratio [95% confidence interval] 0.13 [0.02-0.95], P = 0.04). This difference persisted after adjustment for covariates (0.09 [0.01-0.73], P = 0.02) and propensity score matching (0.11 [0.01-0.85], P = 0.04). Conclusions In patients prospectively identified at high risk for CIED infection, use of a commercially available antibacterial envelope was associated with a marked reduction in CIED infections when compared to a matched control cohort. © 2012 Wiley Periodicals, Inc.


Green K.D.,Vanderbilt Heart and Vascular Institute
Current cardiology reports | Year: 2013

Hybrid coronary revascularization combines the benefits of both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in the treatment of multivessel coronary artery disease (CAD) by combining the benefits of the LIMA-to-LAD graft and drug eluting stent (DES) to non-LAD regions. Through this approach, a patient receives the long-term benefit of the LIMA graft and avoids the morbidity of a full sternotomy and saphenous vein grafts. Available data related to outcomes following hybrid revascularization is limited to small studies. In this review we seek to provide an overview of hybrid revascularization in the era of modern drug eluting stent technology, discuss appropriate patient selection, and comment on future trial design. Additionally, we review the recent literature pertaining to the hybrid approach.


Magnusson M.,Skåne University Hospital | Wang T.J.,Vanderbilt Heart and Vascular Institute | Clish C.,The Broad Institute of MIT and Harvard | Engstrom G.,Lund University | And 3 more authors.
Diabetes | Year: 2015

Experimental studies have suggested possible protective effects of dimethylglycine (DMG) on glucose metabolism. DMG is degraded to glycine through a DMG-dehydrogenase (DMGDH)-catalyzed reaction, and this is the only known pathway for the breakdown of DMG in mammals. In this study, we aimed to identify the strongest genetic determinant of circulating DMG concentration and to investigate its associations with metabolic traits and incident diabetes. In the cohort with full metabolomics data (n = 709), low plasma levels of DMG were significantly associated with higher blood glucose levels (P = 3.9E(-4)). In the genome-wide association study (GWAS) of the discovery cohort (n = 5,205), the strongest genetic signal of plasma DMG was conferred by rs2431332 at the DMGDH locus, where the major allele was associated with lower DMG levels (P = 2.5E(-15)). The same genetic variant (major allele of rs2431332) was also significantly associated with higher plasma insulin (P = 0.019), increased HOMA insulin resistance (P = 0.019), and an increased risk of incident diabetes (P = 0.001) in the pooled analysis of the discovery cohort together with the two replication cohorts (n = 20,698 and n = 7,995). These data are consistent with a possible causal role of DMG deficiency in diabetes development and encourage future studies examining if inhibition of DMGDH, or alternatively, supplementation of DMG, might prove useful for the treatment/prevention of diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.


Monahan K.,Vanderbilt Heart and Vascular Institute | Redline S.,Harvard University
Current Opinion in Cardiology | Year: 2011

Purpose of review: To provide an update on the connection between obstructive sleep apnea (OSA) and cardiovascular disease. Recent findings: Large prospective studies have established that OSA is associated with an increased incidence of hypertension and, in men, of coronary disease, stroke, and heart failure. Advances in understanding the pathophysiologic basis for these associations include identification of a role for OSA in inducing abnormalities in hepatic lipid-metabolizing enzymes, endothelial dysfunction, and upregulation of pro-inflammatory and pro-thrombotic mediators. A large body of data implicates OSA as playing a significant role in the occurrence and resistance to treatment of atrial fibrillation. Clinical trials have shown small-to-modest improvements in blood pressure associated with continuous positive airway pressure (CPAP) use, with smaller or uncontrolled studies suggesting that CPAP may improve cardiovascular outcomes or intermediate markers. Summary: OSA and cardiovascular disease commonly co-aggregate. Multiple studies indicate that OSA contributes to or exacerbates cardiovascular disease, and thus may be a novel target for cardiovascular risk reduction. Although the evidence supports screening and treatment of OSA in patients at risk for cardiovascular disease, it also underscores a need for well powered clinical trials to examine the role of CPAP and other therapies in these populations. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Lenihan D.J.,Vanderbilt Heart and Vascular Institute
Oncologist | Year: 2013

Background. Small-molecule tyrosine kinase inhibitors (TKIs) may provide an effective therapeutic option in patients with hematologic malignancies and solid tumors. However, cardiovascular (CV) events, including hypertension, heart failure, left ventricular systolic dysfunction, and QT prolongation, have emerged as potential adverse events (AEs) with TKI therapy. Purpose. We review what is known about the mechanism of action of CV AEs associated with TKI use and discuss therapeutic interventions that may prevent and manage these events in clinical practice. Methods. References for this review were identified through searches of PubMed and Medline databases, and only papers published in English were considered. Search terms included "cardiac," "cardiovascular," "cancer," and "kinase inhibitor." Related links in the databases were reviewed, along with relevant published guidelines. Results. Although the link between rising blood pressure (BP) and CV AEs is observed but not proven, good clinical practice supports an aggressive policy on proper long-term BP management. There are insufficient data from randomized controlled clinical trials to show indisputably that aggressive or effective heart failure therapy in patients receiving TKIs will fundamentally change outcomes; however, clinical practice suggests that this is an effective long-term approach. Recognizing that QT prolongation is associated with TKI use facilitates identification of patients at high risk for this CV AE and increases awareness of the need for routine electrocardiograms and electrolyte monitoring for those receiving TKI treatment. Conclusion. Regular monitoring, early recognition, and appropriate interventions for CV AEs can help more patients derive the benefit of long-term TKI therapy. © AlphaMed Press 2013.

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