Arabindra B Katwal

University of Virginia, Charlottesville, Virginia, United States

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Publications (8)17.44 Total impact

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    ABSTRACT: -LGE by CMR is a predictor of adverse cardiovascular outcomes in non-ischemic cardiomyopathy (NICM) patients. However, these findings are limited by single center studies, small sample sizes, and low event rates. We performed a meta-analysis to evaluate the prognostic role of late-gadolinium enhancement by cardiac magnetic resonance (LGE-CMR) imaging in NICM patients. -PubMed, Cochrane CENTRAL and EMBASE were searched for studies looking at the prognostic value of LGE-CMR in NICM patients. The primary end-points included all-cause mortality, heart failure hospitalization (HFH), and a composite end point of sudden cardiac death (SCD) or aborted SCD. Pooling of odds ratios (OR) was performed using a random-effect model and annualized event rates (AER) were assessed. Data was included from 9 studies with a total of 1,488 patients and a mean follow-up of 30 months. Patients had a mean age of 52 years, 67% were male and the average LVEF was 37% on CMR. LGE was present in 38% of patients. Patients with LGE had increased overall mortality (OR 3.27, p<0.00001), HFH (OR 2.91, p=0.02), and SCD/aborted SCD (OR 5.32, p<0.00001) when compared with those without LGE. The AERs for mortality were 4.7% for LGE+ subjects vs. 1.7% for LGE- subjects (p=0.01), 5.03% vs. 1.8% for HFH (p=0.002), and 6.0% vs. 1.2% for SCD/aborted SCD (p<0.001). -LGE in NICM patients is associated with increased risk of all-cause mortality, HFH, and SCD. Detection of LGE by CMR has excellent prognostic characteristics and may help guide risk stratification and management in NICM patients.
    Circulation Cardiovascular Imaging 12/2013; 7(2). DOI:10.1161/CIRCIMAGING.113.001144 · 5.32 Impact Factor
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    ABSTRACT: Targeting therapeutic gene expression to the skeletal muscle following intravenous (IV) administration is an attractive strategy for treating peripheral arterial disease (PAD), except that vector access to the ischemic limb could be a limiting factor. As adeno-associated virus serotype 9 (AAV-9) transduces skeletal muscle at high efficiency following systemic delivery, we employed AAV-9 vectors bearing luciferase or enhanced green fluorescent protein (eGFP) reporter genes to test the hypothesis that increased desialylation of cell-surface glycans secondary to hindlimb ischemia (HLI) might help offset the reduction in tissue perfusion that occurs in mouse models of PAD. The utility of the creatine kinase-based (CK6) promoter for restricting gene expression to the skeletal muscle was also examined by comparing it with the cytomegalovirus (CMV) promoter after systemic administration following surgically induced HLI. Despite reduced blood flow to the ischemic limbs, CK6 promoter-driven luciferase activities in the ischemic gastrocnemius (GA) muscles were ∼34-, ∼28- and ∼150-fold higher than in the fully perfused contralateral GA, heart and liver, respectively, 10 days after IV administration. Furthermore, luciferase activity from the CK6 promoter in the ischemic GA muscles was ∼twofold higher than with CMV, while in the liver CK6-driven activity was ∼42-fold lower than with CMV, demonstrating that the specificity of ischemic skeletal muscle transduction can be further improved with the muscle-specific promoters. Studies with Evans blue dye and fluorescently labeled lectins revealed that vascular permeability and desialylation of the cell-surface glycans were increased in the ischemic hindlimbs. Furthermore, AAV9/CK6/Luc vector genome copy numbers were ∼sixfold higher in the ischemic muscle compared with the non-ischemic muscle in the HLI model, whereas this trend was reversed when the same genome was packaged in the AAV-1 capsid (which binds sialylated, as opposed to desialylated glycans), further underscoring the importance of desialylation in the ischemic enhancement of transduction displayed by AAV-9. Taken together, these findings suggest two complementary mechanisms contributing to the preferential transduction of ischemic muscle by AAV-9: increased vascular permeability and desialylation. In conclusion, ischemic muscle is preferentially targeted following systemic administration of AAV-9 in a mouse model of HLI. Unmasking of the primary AAV-9 receptor as a result of ischemia may contribute importantly to this effect.Gene Therapy advance online publication, 28 March 2013; doi:10.1038/gt.2013.16.
    Gene therapy 03/2013; 20(9). DOI:10.1038/gt.2013.16 · 3.10 Impact Factor
  • Katwal AB · Konkalmatt PR · Sanders JM · Ferrante EA · Lye RJ · Annex BH · French BA ·

    American Heart Association Scientific Session; 11/2011
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    ABSTRACT: Neovascularization is a physiologic repair process that partly depends on nitric oxide. Extracellular superoxide dismutase (EcSOD) is the major scavenger of superoxide. It is an important regulator of nitric oxide bioavailability and thus protects against vascular dysfunction. We hypothesized that overexpression of EcSOD in skeletal muscle would improve recovery from hind-limb ischemia. Adeno-associated virus serotype 9 (AAV9) vectors expressing EcSOD or luciferase (control) from the cytomegalovirus promoter were cross-packaged into AAV9 capsids and injected intramuscularly into the hind-limb muscles (1 × 10(11) viral genomes/limb) of 12-week-old mice. Ischemia was induced after intramuscular injections. Laser Doppler was used to measure limb perfusion on days 0, 7, and 14 after injection. Values were expressed as a ratio relative to the nonischemic limb. EcSOD expression was measured by Western blotting. Capillary density was documented by immunohistochemical staining for platelet endothelial cell adhesion molecule. Apoptosis was assessed by terminal deoxynucleotide transferase-mediated biotin-deoxy uridine triphosphate nick-end labeling and necrosis was visually evaluated daily. EcSOD expression was twofold upregulated in EcSOD treated vs control ischemic muscles at day 14. Capillary density (capillaries/fiber) was 1.9-fold higher in treated (1.65 ± 0.02) vs control muscle (0.78 ± 0.17, P < .05). Recovery of perfusion ratio at day 14 after ischemia was 1.5-fold greater in EcSOD vs control mice (P < .05). The percentage of apoptotic nuclei was 1.3% ± 0.4% in EcSOD-treated mice compared with 4.2% ± 0.2% in controls (P < .001). Limb necrosis was also significantly lower in EcSOD vs control mice. AAV9-mediated overexpression of EcSOD in skeletal muscle significantly improves recovery from hind-limb ischemia in mice, consistent with improved capillary density and perfusion ratios in treated mice.
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 07/2011; 54(3):810-8. DOI:10.1016/j.jvs.2011.03.278 · 3.02 Impact Factor
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    Arabindra B Katwal · Ayotunde O Dokun ·
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    ABSTRACT: Atherosclerotic occlusion of vessels outside of the heart is commonly referred to as peripheral arterial disease (PAD). The lower extremity is the most common site of PAD and its development is associated with the same risk factors involved in general atherosclerosis. However, there is emerging evidence that other risk factors may play a key role in the development of PAD. Over the past decade polymorphism in a number of genes has been shown to contribute to the risk of developing PAD. These genes can be classified into proartherosclerosis or proatherothrombosis based on the known gene function. Moreover, they can be categorized as "novel" polymorphism when the function of the genes is not known or when the specific gene within an associated genetic locus is not known. It is intriguing that not only are gene polymorphisms associated with PAD being identified, but more recently studies are now finding gene polymorphisms that may be important in development of this syndrome only in the contest of certain environmental factors such as diabetes. Currently how these gene-environment interactions contribute to the pathogenesis of PAD is poorly understood but will likely play a critical role in future understanding of this complex disease.
    Current Diabetes Reports 03/2011; 11(3):218-25. DOI:10.1007/s11892-011-0188-9 · 3.08 Impact Factor
  • Saqib A · Konkalmatt PR · Katwal AB · Lye RJ · French BA · Annex BH ·

    American Heart Association Scientific Session; 11/2010
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    Gregory W Natello · Christine M Carroll · Arabindra B Katwal ·
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    ABSTRACT: We describe a patient with rotational vertebrobasilar ischemia (RVBI) due to vertebral artery (VA) compressive stenoses during neck rotation, complicated by an ostial atherosclerotic stenosis (OAS). Referred for 'near-syncopal spells', inquiry revealed a symptom-complex consistent with vertebrobasilar transient ischemic attacks (TIAs) provoked by head rotation. VA dynamic angiography with imaging via prevertebral subclavian injections in neck-rotated positions while reproducing symptoms, demonstrated two compressive stenoses not present in the neck-neutral position, establishing the diagnosis of RVBI due to CT-demonstrated cervical spondylosis. There was an occluded contralateral VA, isolated posterior circulation, and absent vertebral collateral flow. Disabling symptoms persisted despite using a cervical collar. Surgical decompression of the dynamic stenoses would not address the OAS, was considered high risk, and absence of a suitable donor artery precluded distal VA reconstruction. RVBI resolved with ostial stent placement by improving perfusion pressure across the compressive stenoses. To our knowledge, this is the first report of RVBI in which the affected VA had an obstructive atherosclerotic stenosis in addition to the characteristic rotation-induced dynamic stenoses, and the first report of stent placement in the culprit artery to treat this disorder. Diagnosis depends on recognizing the association of symptoms with positional neck changes and VA dynamic angiography demonstrating the compressive stenosis while reproducing symptoms. This case illustrates the management complexities when there are coexisting abnormalities, emphasizing the need to individualize treatment. RVBI is a potentially correctable cause of TIAs and particularly relevant due to the aging population which has a significant incidence of both degenerative cervical and atherosclerotic cerebrovascular disease.
    Vascular Medicine 09/2009; 14(3):265-9. DOI:10.1177/1358863X08099707 · 1.79 Impact Factor
  • Arabindra B Katwal · Craig J McCotter ·
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    ABSTRACT: We report the case of a 54-year-old man with a previously implanted neurostimulator who presented with palpitations and was found to have sustained ventricular tachycardia on electrophysiologic study. A Medtronic wireless implantable cardioverter defibrillator (ICD; Medtronic Inc., Minneapolis, MN, USA) with home monitoring (HM) was successfully implanted. Interaction testing during implantation, follow-up, and HM showed that there was no device-device interaction.
    Pacing and Clinical Electrophysiology 07/2009; 32(6):822-4. DOI:10.1111/j.1540-8159.2009.02374.x · 1.13 Impact Factor