Zankhana Raval

Northwestern University, Evanston, Illinois, United States

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Publications (9)82.65 Total impact

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    ABSTRACT: This chapter reviews emerging evidence from the fields of gene and cell-based therapies for the management of patients with critical limb ischemia (CLI). Arteriogenesis, also called collateral growth, is the increase in the caliber of pre-existing collateral arterioles capable of compensating for the loss of function of occluded arteries. Vascular endothelial growth factor was one of the early growth factors to be investigated to induce angiogenesis in ischemic tissues. Hypoxia inducible factor-1 (HIF-1) is a recently investigated target for gene therapy in CLI. More than just an endothelial growth factor, it is a transcriptional activator and serves as a master regulator of oxygen homeostasis. A logical direction for future research may be to combine growth factor and cell-based therapy; intramuscular gene therapy could be administered in the ischemic tissue as pretreatment of the target tissue to augment homing of implanted stem cells.
    Urgent Interventional Therapies, 11/2014: pages 514-533; , ISBN: 9780470672020
  • Zankhana Raval · Matthew E Harinstein · James D Flaherty
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    ABSTRACT: End stage liver disease (ESLD) is associated with many specific derangements in cardiovascular physiology, which influence perioperative outcomes and may profoundly influence diagnostic and management strategies in the preoperative period. This review focuses on evidence-based diagnosis and management of coronary, hemodynamic and pulmonary vascular disease in this population with an emphasis on specific strategies that may provide a bridge to transplantation. Specifically, we address the underlying prevalence of cardiovascular disease states in the ESLD population, and relevant diagnostic criteria thereof. We highlight traditional and non-traditional predictors of cardiovascular outcomes following liver transplant, as well as data to guide risk-factor based diagnostic strategies. We go on to discuss the alterations in cardiovascular physiology which influence positive- and negative-predictive values of standard noninvasive testing modalities in the ESLD population, and review the data regarding the safety and efficacy of invasive testing in the face of ESLD and its co-morbidities. Finally, based upon the totality of available data, we outline an evidence-based approach for the management of ischemia, heart failure and pulmonary vascular disease in this population. It is our hope that such evidence-driven strategies can be employed to more safely bridge appropriate candidates to liver transplant, and to improve their cardiovascular health and outcomes in the peri-operative period.
    World Journal of Gastroenterology 08/2014; 20(31):10651-10657. DOI:10.3748/wjg.v20.i31.10651 · 2.37 Impact Factor
  • Journal of Hospital Medicine 03/2014; 9(3). DOI:10.1002/jhm.2144 · 2.30 Impact Factor
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    Zankhana Raval · Douglas W Losordo
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    ABSTRACT: The age-adjusted prevalence of peripheral arterial disease in the US population was estimated to approach 12% in 1985, and as the population ages, the overall population having peripheral arterial disease is predicted to rise. The clinical consequences of occlusive peripheral arterial disease include intermittent claudication, that is, pain with walking, and critical limb ischemia (CLI), which includes pain at rest and loss of tissue integrity in the distal limbs, which may ultimately lead to amputation of a portion of the lower extremity. The risk factors for CLI are similar to those linked to coronary artery disease and include advanced age, smoking, diabetes mellitus, hyperlipidemia, and hypertension. The worldwide incidence of CLI was estimated to be 500 to 1000 cases per million people per year in 1991. The prognosis is poor for CLI subjects with advanced limb disease. One study of >400 such subjects in the United Kingdom found that 25% required amputation and 20% (including some subjects who had required amputation) died within 1 year. In the United States, ≈280 lower-limb amputations for ischemic disease are performed per million people each year. The first objective in treating CLI is to increase blood circulation to the affected limb. Theoretically, increased blood flow could be achieved by increasing the number of vessels that supply the ischemic tissue with blood. The use of pharmacological agents to induce new blood vessel growth for the treatment or prevention of pathological clinical conditions has been called therapeutic angiogenesis. Since the identification of the endothelial progenitor cell in 1997 by Asahara and Isner, the field of cell-based therapies for peripheral arterial disease has been in a state of continuous evolution. Here, we review the current state of that field.
    Circulation Research 04/2013; 112(9):1288-302. DOI:10.1161/CIRCRESAHA.113.300565 · 11.02 Impact Factor
  • Zankhana Raval · Douglas W Losordo
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    ABSTRACT: With the publication of De humani corporis fabrica in 1543, Andreas Vesalius bestowed some of the greatest advancements of anatomic understanding since the time of Galen, correcting major misconceptions, for example the notion that the great vessels originated in the liver. It took nearly 1500 years for this evolution in anatomic thinking to transpire. It is simultaneously humbling and invigorating to note that nearly 500 years later the study of anatomy is just as lively and full of evolutionary change. In this issue of Circulation Anversa and colleagues definitively dispatch the dogma of the heart as a terminally differentiated organ, a concept formulated a mere 40 years earlier, and in so doing completely recalibrate our understanding of cellular homeostasis in the healthy and diseased heart.(1).
    Circulation 09/2012; 126(15):1812-4. DOI:10.1161/CIRCULATIONAHA.112.136127 · 14.43 Impact Factor
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    ABSTRACT: This study investigated whether higher body mass index (BMI) is associated with more adverse lower extremity muscle characteristics at baseline and more adverse changes in muscle over time among participants with lower extremity peripheral arterial disease (PAD). This was a longitudinal, observational study of 425 men and women with PAD and 261 without PAD. Computed tomography was used to measure calf muscle characteristics at baseline and every 2 years. Knee extension isometric strength, power, and 6-minute walk distance were measured at baseline and annually. Baseline BMI (kg/m(2)) categories were ideal (20-25), overweight (>25-30), and obese (>30). Analyses adjust for age, race, sex, ankle brachial index, comorbidities, and other covariates. At baseline, higher BMI among participants with PAD was associated with greater calf muscle area (ideal BMI: 5181 mm(2); overweight: 5513 mm(2); obese: 5695 mm(2); P = .0009 for trend), higher calf muscle percentage of fat (6.38%, 10.28%, 17.44%, respectively, P < .0001 for trend), lower calf muscle density (P < .0001 for trend), and higher isometric knee extension strength (P = .015 for trend). Among participants with PAD, higher BMI was associated with greater declines in calf muscle area (P = .030 for trend) and greater increases in calf muscle percentage of fat (P = .023 for trend). Among participants without PAD, there were no significant associations of baseline BMI with changes in lower extremity muscle outcomes over time. Among PAD participants, higher BMI is associated with greater calf muscle area at baseline. However, higher BMI is associated with more adverse calf muscle density and calf muscle percentage of fat at baseline and greater declines in calf muscle area over time.
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 02/2012; 55(4):1015-24. DOI:10.1016/j.jvs.2011.10.105 · 3.02 Impact Factor
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    Article: Reply.
    Journal of the American College of Cardiology 12/2011; 58(25):2701. DOI:10.1016/j.jacc.2011.09.029 · 16.50 Impact Factor
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    ABSTRACT: Liver transplantation (LT) candidates today are increasingly older, have greater medical acuity, and have more cardiovascular comorbidities than ever before. Steadily rising model for end-stage liver disease (MELD) scores at the time of transplant, resulting from high organ demand, reflect the escalating risk profiles of LT candidates. In addition to advanced age and the presence of comorbidities, there are specific cardiovascular responses in cirrhosis that can be detrimental to the LT candidate. Patients with cirrhosis requiring LT usually demonstrate increased cardiac output and a compromised ventricular response to stress, a condition termed cirrhotic cardiomyopathy. These cardiac disturbances are likely mediated by decreased beta-agonist transduction, increased circulating inflammatory mediators with cardiodepressant properties, and repolarization changes. Low systemic vascular resistance and bradycardia are also commonly seen in cirrhosis and can be aggravated by beta-blocker use. These physiologic changes all contribute to the potential for cardiovascular complications, particularly with the altered hemodynamic stresses that LT patients face in the immediate post-operative period. Post-transplant reperfusion may result in cardiac death due to a multitude of causes, including arrhythmia, acute heart failure, and myocardial infarction. Recognizing the hemodynamic challenges encountered by LT patients in the perioperative period and how these responses can be exacerbated by underlying cardiac pathology is critical in developing recommendations for the pre-operative risk assessment and management of these patients. The following provides a review of the cardiovascular challenges in LT candidates, as well as evidence-based recommendations for their evaluation and management.
    Journal of the American College of Cardiology 07/2011; 58(3):223-31. DOI:10.1016/j.jacc.2011.03.026 · 16.50 Impact Factor
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    Zankhana Raval · Mary M. McDermott
    Journal of the American College of Cardiology 03/2010; 55(10). DOI:10.1016/S0735-1097(10)61473-8 · 16.50 Impact Factor