Aadhavi Sridharan

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Journals/Publications

• Agarwal, M. A., Sridharan, A., Pimentel, R. C., Markowitz, S. M., Rosenfeld, L. E., Fradley, M. G., & Yang, E. H. (2023). Ventricular Arrhythmia in Cancer Patients: Mechanisms, Treatment Strategies and Future Avenues. Arrhythmia & electrophysiology review, 12, e16.
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  Cardiovascular disease and cancer are the leading causes of morbidity and mortality in the US. Despite the significant progress made in cancer treatment leading to improved prognosis and survival, ventricular arrhythmias (VA) remain a known cardiovascular complication either exacerbated or induced by the direct and indirect effects of both traditional and novel cancer treatments. Although interruption of cancer treatment because of VA is rarely required, knowledge surrounding this issue is essential for optimising the overall care of patients with cancer. The mechanisms of cancer-therapeutic-induced VA are poorly understood. This review will discuss the ventricular conduction (QRS) and repolarisation abnormalities (QTc prolongation), and VAs associated with cancer therapies, as well as existing strategies for the identification, prevention and management of cancer-treatment-induced VAs.
• Mori, S., Hayase, J., Sridharan, A., Fukuzawa, K., Shivkumar, K., & Bradfield, J. S. (2023). Revisiting the Anatomy of the Left Ventricular Summit. Cardiac electrophysiology clinics, 15(1), 1-8.
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  The left ventricular summit corresponds to the epicardial side of the basal superior free wall, extending from the base of the left coronary aortic sinus. The summit composes the floor of the compartment surrounded by the aortic root, infundibulum, pulmonary root, and left atrial appendage. The compartment is filled with thick adipose tissue, carrying the coronary vessels. Thus, the treatment of ventricular tachycardia originating from the summit is challenging, and three-dimensional understanding of this complicated region is fundamental. We revisit the clinical anatomy of the left ventricular summit with original images from the Wallace A. McAlpine collection.
• Sridharan, A., & Hutchinson, M. D. (2023). Coronary arterial injury during right ventricular outflow tract ablation: Know your neighbors. Journal of cardiovascular electrophysiology, 34(5), 1310-1311.
• Sridharan, A., Tang, A., Sorg, J. M., Hoftman, N. N., Lee, J. M., Yanagawa, J., & Vaseghi, M. (2023). Effect of Bilateral Cardiac Sympathetic Denervation on Burden of Premature Ventricular Contractions. Circulation. Arrhythmia and electrophysiology, 16(4), e011546.
• Sridharan, A., & Patel, A. R. (2022). Response to letter to the editor. Clinical cardiology, 45(8), 819.
• Sridharan, A., & Vaseghi, M. (2022). Uni vs bi: What to do when they don't see eye to eye?. Heart rhythm, 19(7), 1074-1075.
• Sridharan, A., Bradfield, J. S., Shivkumar, K., & Ajijola, O. A. (2022). Autonomic nervous system and arrhythmias in structural heart disease. Autonomic neuroscience : basic & clinical, 243, 103037.
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  The autonomic nervous system functions in a fine-tuned manner to dynamically modulate cardiac function during normal physiological state. Autonomic dysregulation in cardiac disease states such as myocardial infarction and heart failure alters this fine balance, which in turn promotes disease progression and arrhythmogenesis. Neuromodulatory interventions that aim to restore this balance at distinct levels of the cardiac neuraxis thus have been shown to be effective in the treatment of arrhythmias. This review first describes the anatomy of the cardiac autonomic nervous system and the pathological changes that occur with neural remodeling in the setting of scar and cardiomyopathy, followed by therapeutic interventions for neuraxial modulation of arrhythmias such as atrial fibrillation and ventricular tachyarrhythmias.
• Sridharan, A., Dehn, M. M., Cooper, C., Madineedi, V. S., Ordway, L. J., DeNofrio, D., & Patel, A. R. (2022). Accuracy of echocardiographic estimations of right heart pressures in adult heart transplant recipients. Clinical cardiology, 45(7), 752-758.
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  Accurate assessment of right atrial pressure (RAP) and pulmonary artery systolic pressure (PASP) is critical in the management of heart transplant recipients. The accuracy of echocardiography in estimating these pressures has been debated.
• Sridharan, A., Maron, M. S., Carrick, R. T., Madias, C. A., Huang, D., Cooper, C., Drummond, J., Maron, B. J., & Rowin, E. J. (2022). Impact of comorbidities on atrial fibrillation and sudden cardiac death in hypertrophic cardiomyopathy. Journal of cardiovascular electrophysiology, 33(1), 20-29.
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  The impact of comorbid disease states on the development of atrial and ventricular arrhythmias in patients with hypertrophic cardiomyopathy (HCM) remains unresolved.
• Carrick, R. T., Maron, M. S., Adler, A., Wessler, B., Hoss, S., Chan, R. H., Sridharan, A., Huang, D., Cooper, C., Drummond, J., Rakowski, H., Maron, B. J., & Rowin, E. J. (2021). Development and Validation of a Clinical Predictive Model for Identifying Hypertrophic Cardiomyopathy Patients at Risk for Atrial Fibrillation: The HCM-AF Score. Circulation. Arrhythmia and electrophysiology, 14(6), e009796.
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  [Figure: see text].
• Sridharan, A., Han, J. K., & Feliciano, Z. (2021). An Ominous ECG. Circulation, 144(3), 246-248.
• Rowin, E. J., & Sridharan, A. (2020). Thinking Outside the Heart to Treat Atrial Fibrillation in Hypertrophic Cardiomyopathy. Journal of the American Heart Association, 9(8), e016260.
• Rowin, E. J., Sridharan, A., Madias, C., Firely, C., Koethe, B., Link, M. S., Maron, M. S., & Maron, B. J. (2020). Prediction and Prevention of Sudden Death in Young Patients (<20 years) With Hypertrophic Cardiomyopathy. The American journal of cardiology, 128, 75-83.
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  Highly reliable identification of adults with hypertrophic cardiomyopathy (HC) at risk for sudden death (SD) has been reported. A significant controversy remains, however, regarding the most reliable risk stratification methodology for children and adolescents with HC. The present study assesses the accuracy of SD prediction and prevention with prophylactic implantable cardioverter-defibrillators (ICDs) in young HC patients. The study group is comprised of 146 HC patients
• Sridharan, A., & Kimmelstiel, C. (2020). Morphine in primary percutaneous coronary intervention-No pain, questionable gain. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions, 96(1), 89-90.
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  The clinical impact of concurrently administered morphine and P2Y12 inhibitors in primary percutaneous coronary intervention (PCI) is not well understood. Large, randomized clinical trials are required to assess clinical outcomes with concurrent morphine and P2Y12 inhibitor use in ST-segment elevation myocardial infarction patients undergoing PCI. Based on the currently available pharmacologic data, cautious use of morphine in primary PCI would seem prudent.
• Sridharan, A., Bendlin, B. B., Gallagher, C. L., Oh, J. M., Willette, A. A., Alexander, A. L., Kemnitz, J. W., Colman, R. J., Weindruch, R. H., & Johnson, S. C. (2014). Effect of age and calorie restriction on corpus callosal integrity in rhesus macaques: a fiber tractography study. Neuroscience letters, 569, 38-42.
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  The rhesus macaque exhibits age-related brain changes similar to humans, making an excellent model of normal aging. Calorie restriction is a dietary intervention that reduces age-related comorbidities in short-lived animals, and its effects are still under study in rhesus macaques. Here, using deterministic fiber tracking method, we examined the effects of age and calorie restriction on a diffusion tensor imaging measure of white matter integrity, fractional anisotropy (FA), within white matter tracks traversing the anterior (genu) and posterior (splenium) corpus callosum in rhesus monkeys. Our results show: (1) a significant inverse relationship between age and mean FA of tracks traversing the genu and splenium; (2) higher mean FA of the splenium tracks as compared to that of genu tracks across groups; and (3) no significant diet effect on mean track FA through either location. These results are congruent with the age-related decline in white matter integrity reported in humans and monkeys, and the anterior-to-posterior gradient in white matter vulnerability to normal aging in humans. Further studies are warranted to critically evaluate the effect of calorie restriction on brain aging in this unique cohort of elderly primates.
• Sridharan, A., Pehar, M., Salamat, M. S., Pugh, T. D., Bendlin, B. B., Willette, A. A., Anderson, R. M., Kemnitz, J. W., Colman, R. J., Weindruch, R. H., Puglielli, L., & Johnson, S. C. (2013). Calorie restriction attenuates astrogliosis but not amyloid plaque load in aged rhesus macaques: a preliminary quantitative imaging study. Brain research, 1508, 1-8.
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  While moderate calorie restriction (CR) in the absence of malnutrition has been consistently shown to have a systemic, beneficial effect against aging in several animals models, its effect on the brain microstructure in a non-human primate model remains to be studied using post-mortem histopathologic techniques. In the present study, we investigated differences in expression levels of glial fibrillary acid protein (GFAP) and β-amyloid plaque load in the hippocampus and the adjacent cortical areas of 7 Control (ad libitum)-fed and 6 CR male rhesus macaques using immunostaining methods. CR monkeys expressed significantly lower levels (∼30% on average) of GFAP than Controls in the CA region of the hippocampus and entorhinal cortex, suggesting a protective effect of CR in limiting astrogliosis. These results recapitulate the neuroprotective effects of CR seen in shorter-lived animal models. There was a significant positive association between age and average amyloid plaque pathology in these animals, but there was no significant difference in amyloid plaque distribution between the two groups. Two of the seven Control animals (28.6%) and one of the six CR animal (16.7%) did not express any amyloid plaques, five of seven Controls (71.4%) and four of six CR animals (66.7%) expressed minimal to moderate amyloid pathology, and one of six CR animals (16.7%) expressed severe amyloid pathology. That CR affects levels of GFAP expression but not amyloid plaque load provides some insight into the means by which CR is beneficial at the microstructural level, potentially by offsetting the increased load of oxidatively damaged proteins, in this non-human primate model of aging. The present study is a preliminary post-mortem histological analysis of the effects of CR on brain health, and further studies using molecular and biochemical techniques are warranted to elucidate underlying mechanisms.
• Sridharan, A., Willette, A. A., Bendlin, B. B., Alexander, A. L., Coe, C. L., Voytko, M. L., Colman, R. J., Kemnitz, J. W., Weindruch, R. H., & Johnson, S. C. (2012). Brain volumetric and microstructural correlates of executive and motor performance in aged rhesus monkeys. Frontiers in aging neuroscience, 4, 31.
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  The aged rhesus macaque exhibits brain atrophy and behavioral deficits similar to normal aging in humans. Here we studied the association between cognitive and motor performance and anatomic and microstructural brain integrity measured with 3T magnetic resonance imaging in aged monkeys. About half of these animals were maintained on moderate calorie restriction (CR), the only intervention shown to delay the aging process in lower animals. T1-weighted anatomic and diffusion tensor images were used to obtain gray matter (GM) volume and fractional anisotropy (FA) and mean diffusivity (MD), respectively. We tested the extent to which brain health indexed by GM volume, FA, and MD were related to executive and motor function, and determined the effect of the dietary intervention on this relationship. We hypothesized that fewer errors on the executive function test and faster motor response times would be correlated with higher volume, higher FA, and lower MD in frontal areas that mediate executive function, and in motor, premotor, subcortical, and cerebellar areas underlying goal-directed motor behaviors. Higher error percentage on a cognitive conceptual shift task was significantly associated with lower GM volume in frontal and parietal cortices, and lower FA in major association fiber bundles. Similarly, slower performance time on the motor task was significantly correlated with lower volumetric measures in cortical, subcortical, and cerebellar areas and decreased FA in several major association fiber bundles. Notably, performance during the acquisition phase of the hardest level of the motor task was significantly associated with anterior mesial temporal lobe volume. Finally, these brain-behavior correlations for the motor task were attenuated in CR animals compared to controls, indicating a potential protective effect of the dietary intervention.
• Willette, A. A., Bendlin, B. B., Colman, R. J., Kastman, E. K., Field, A. S., Alexander, A. L., Sridharan, A., Allison, D. B., Anderson, R., Voytko, M. L., Kemnitz, J. W., Weindruch, R. H., & Johnson, S. C. (2012). Calorie restriction reduces the influence of glucoregulatory dysfunction on regional brain volume in aged rhesus monkeys. Diabetes, 61(5), 1036-42.
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  Insulin signaling dysregulation is related to neural atrophy in hippocampus and other areas affected by neurovascular and neurodegenerative disorders. It is not known if long-term calorie restriction (CR) can ameliorate this relationship through improved insulin signaling or if such an effect might influence task learning and performance. To model this hypothesis, magnetic resonance imaging was conducted on 27 CR and 17 control rhesus monkeys aged 19-31 years from a longitudinal study. Voxel-based regression analyses were used to associate insulin sensitivity with brain volume and microstructure cross-sectionally. Monkey motor assessment panel (mMAP) performance was used as a measure of task performance. CR improved glucoregulation parameters and related indices. Higher insulin sensitivity predicted more gray matter in parietal and frontal cortices across groups. An insulin sensitivity × dietary condition interaction indicated that CR animals had more gray matter in hippocampus and other areas per unit increase relative to controls, suggesting a beneficial effect. Finally, bilateral hippocampal volume adjusted by insulin sensitivity, but not volume itself, was significantly associated with mMAP learning and performance. These results suggest that CR improves glucose regulation and may positively influence specific brain regions and at least motor task performance. Additional studies are warranted to validate these relationships.