Browsing by Subject "Cardiology"

Now showing 1 - 10 of 28
  • Thumbnail Image
    Item
    Alkaline Phosphatase Treatment of Acute Kidney Injury in an Infant Piglet Model of Cardiopulmonary Bypass with Deep Hypothermic Circulatory Arrest
    (Springer Nature, 2019-10-02) Davidson, Jesse A.; Khailova, Ludmila; Treece, Amy; Robison, Justin; Soranno, Danielle E.; Jaggers, James; Ing, Richard J.; Lawson, Scott; Osorio Lujan, Suzanne; Pediatrics, School of Medicine
    Acute kidney injury (AKI) is associated with prolonged hospitalization and mortality following infant cardiac surgery, but therapeutic options are limited. Alkaline phosphatase (AP) infusion reduced AKI in phase 2 sepsis trials but has not been evaluated for cardiac surgery-induced AKI. We developed a porcine model of infant cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest (DHCA) to investigate post-CPB/DHCA AKI, measure serum/renal tissue AP activity with escalating doses of AP infusion, and provide preliminary assessment of AP infusion for prevention of AKI. Infant pigs underwent CPB with DHCA followed by survival for 4 h. Groups were treated with escalating doses of bovine intestinal AP (1, 5, or 25U/kg/hr). Anesthesia controls were mechanically ventilated for 7 h without CPB. CPB/DHCA animals demonstrated histologic and biomarker evidence of AKI as well as decreased serum and renal tissue AP compared to anesthesia controls. Only high dose AP infusion significantly increased serum or renal tissue AP activity. Preliminary efficacy evaluation demonstrated a trend towards decreased AKI in the high dose AP group. The results of this dose-finding study indicate that AP infusion at the dose of 25U/kg/hr corrects serum and tissue AP deficiency and may prevent AKI in this piglet model of infant CPB/DHCA.
  • Thumbnail Image
    Item
    Cardiomyocyte microRNA-150 confers cardiac protection and directly represses proapoptotic small proline–rich protein 1A
    (American Society for Clinical Investigation, 2021-09-22) Aonuma, Tatsuya; Moukette, Bruno; Kawaguchi, Satoshi; Barupala, Nipuni P.; Sepúlveda, Marisa N.; Corr, Christopher; Tang, Yaoliang; Liangpunsakul, Suthat; Payne, R. Mark; Willis, Monte S.; Kim, Il-man; Anatomy, Cell Biology and Physiology, School of Medicine
    MicroRNA-150 (miR-150) is downregulated in patients with multiple cardiovascular diseases and in diverse mouse models of heart failure (HF). miR-150 is significantly associated with HF severity and outcome in humans. We previously reported that miR-150 is activated by β-blocker carvedilol (Carv) and plays a protective role in the heart using a systemic miR-150 KO mouse model. However, mechanisms that regulate cell-specific miR-150 expression and function in HF are unknown. Here, we demonstrate that potentially novel conditional cardiomyocyte–specific (CM-specific) miR-150 KO (miR-150 cKO) in mice worsens maladaptive cardiac remodeling after myocardial infarction (MI). Genome-wide transcriptomic analysis in miR-150 cKO mouse hearts identifies small proline–rich protein 1a (Sprr1a) as a potentially novel target of miR-150. Our studies further reveal that Sprr1a expression is upregulated in CMs isolated from ischemic myocardium and subjected to simulated ischemia/reperfusion, while its expression is downregulated in hearts and CMs by Carv. We also show that left ventricular SPRR1A is upregulated in patients with HF and that Sprr1a knockdown in mice prevents maladaptive post-MI remodeling. Lastly, protective roles of CM miR-150 are, in part, attributed to the direct and functional repression of proapoptotic Sprr1a. Our findings suggest a crucial role for the miR-150/SPRR1A axis in regulating CM function post-MI.
  • Thumbnail Image
    Item
    A Case for Inclusion of Genetic Counselors in Cardiac Care
    (Wolters Kluwer, 2016-03) Arscott, Patricia; Caleshu, Colleen; Kotzer, Katrina; Kreykes, Sarah; Kruisselbrink, Teresa; Orland, Kate; Rigelsky, Christina; Smith, Emily; Spoonamore, Katherine; Larsen Haidle, Joy; Marvin, Monica; Ackerman, Michael J.; Hadi, Azam; Mani, Arya; Ommen, Steven; Cherny, Sara; Department of Medicine, IU School of Medicine
    Recent advances in genetic testing for heritable cardiac diseases have led to an increasing involvement of the genetic counselor in cardiology practice. We present a series of cases collected from a nationwide query of genetics professionals regarding issues related to cost and utilization of genetic testing. Three themes emerged across cases: (1) choosing the most appropriate genetic test, (2) choosing the best person to test, and (3) interpreting results accurately. These cases demonstrate that involvement of a genetic counselor throughout the evaluation, diagnosis, and continuing management of individuals and families with inherited cardiovascular conditions helps to promote the efficient use of healthcare dollars.
  • Thumbnail Image
    Item
    Concomitant SK current activation and sodium current inhibition cause J wave syndrome
    (American Society for Clinical Investigation, 2018-11-15) Chen, Mu; Xu, Dong-Zhu; Wu, Adonis Z.; Guo, Shuai; Wan, Juyi; Yin, Dechun; Lin, Shien-Fong; Chen, Zhenhui; Rubart-von der Lohe, Michael; Everett, Thomas H., IV; Qu, Zhilin; Weiss, James N.; Chen, Peng-Sheng; Medicine, School of Medicine
    The mechanisms of J wave syndrome (JWS) are incompletely understood. Here, we showed that the concomitant activation of small-conductance calcium-activated potassium (SK) current (IKAS) and inhibition of sodium current by cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) recapitulate the phenotypes of JWS in Langendorff-perfused rabbit hearts. CyPPA induced significant J wave elevation and frequent spontaneous ventricular fibrillation (SVF), as well as sinus bradycardia, atrioventricular block, and intraventricular conduction delay. IKAS activation by CyPPA resulted in heterogeneous shortening of action potential (AP) duration (APD) and repolarization alternans. CyPPA inhibited cardiac sodium current (INa) and decelerated AP upstroke and intracellular calcium transient. SVFs were typically triggered by short-coupled premature ventricular contractions, initiated with phase 2 reentry and originated more frequently from the right than the left ventricles. Subsequent IKAS blockade by apamin reduced J wave elevation and eliminated SVF. β-Adrenergic stimulation was antiarrhythmic in CyPPA-induced electrical storm. Like CyPPA, hypothermia (32.0°C) also induced J wave elevation and SVF. It facilitated negative calcium-voltage coupling and phase 2 repolarization alternans with spatial and electromechanical discordance, which were ameliorated by apamin. These findings suggest that IKAS activation contributes to the development of JWS in rabbit ventricles.
  • Thumbnail Image
    Item
    Correlates of palpitations during menopause: A scoping review
    (Sage, 2022) Carpenter, Janet S.; Sheng, Ying; Pike, Caitlin; Elomba, Charles D.; Alwine, Jennifer S.; Chen, Chen X.; Tisdale, James E.; School of Nursing
    Objective: Palpitations during peri- and post-menopause are common. It is unclear what variables are related to palpitations in peri- and post-menopausal women. The purpose of this scoping review was to summarize potential correlates of palpitations in women transitioning through menopause. Methods: The review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Authors included English-language, full-length, peer-reviewed, cross-sectional research articles on palpitations in menopausal women published through December 18, 2021, from PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycINFO searches. Following de-duplication, screening of titles and abstracts, and review of full-texts, independent reviewers extracted data on variables studied in relationship to palpitations from 84 articles and resolved discrepancies. Authors extracted data on (1) demographic, clinical, biomarker, and symptom/quality of life variables and (2) data analysis method (bivariate, multivariate). Authors classified each variable as a likely, unlikely, or unclear correlate of palpitations. Results: Articles were diverse in region of origin, sample sizes, and variables assessed in relationship to palpitations. Evidence for any one variable was sparse. Likely correlates of palpitations included race/ethnicity, lower physical activity, worse vasomotor symptoms (VMSs), worse sleep, and worse quality of life. Unlikely correlates included age, employment, education, marital status, socioeconomic status, comorbidities, body mass index, and sexual difficulties. Unclear correlates due to equivocal evidence were menopausal status, smoking, and depression. Unclear correlates due to insufficient evidence (less than three articles) included all of the assessed biomarkers, anxiety, and stress. Conclusion: Likely correlates were identified including race/ethnicity, physical activity, VMS, sleep, and quality of life. However, additional research is needed to better understand potential correlates of palpitations.
  • Thumbnail Image
    Item
    Current approach to genetic testing and genetic evaluation referrals for adults with congenital heart disease
    (Frontiers Media, 2024-05-13) Oehlman, Laura B.; Opotowsky, Alexander R.; Weaver, Kathryn N.; Brown, Nicole M.; Barnett, Cara L.; Miller, Erin M.; He, Hua; Shikany, Amy R.; Medical and Molecular Genetics, School of Medicine
    Background: Congenital heart disease (CHD) is the most common congenital anomaly. Up to 33% have an identifiable genetic etiology. Improved medical and surgical management of CHD has translated into longer life expectancy and a rapidly growing population of adults living with CHD. The adult CHD (ACHD) population did not have access during childhood to the genetic technologies available today and therefore have not had a robust genetic evaluation that is currently recommended for infants with CHD. Given this potential benefit; the aims of this study were to determine how ACHD cardiologists offer genetics services to patients and identify the indications that influence decision-making for genetics care. Methods: We performed a descriptive cross-sectional study of ACHD cardiologists. A study-developed questionnaire was distributed via emailed REDCap link. The recruitment email was sent to 104 potential respondents. The survey was open from 06/2022 to 01/2023. Results: Thirty-five cardiologists participated in the study (response rate of 34%). Most cardiologists identified as white (77%) and male (66%). Cardiologists were more likely to refer patients to genetics (91%) than to order testing themselves (57%). Of the testing ordered, chromosomal testing (55%) was ordered more than gene sequencing (14%). Most cardiologists would refer a patient with a conotruncal lesion (interrupted aortic arch) over other indications for a genetics evaluation. There were more reported barriers to ordering genetic testing (66%) compared to referring to genetics for a genetics evaluation (23%). Cardiologists were more confident recognizing features suggestive of a genetic syndrome than ordering the correct test (p = 0.001). Regarding associations between clinical factors and current practices, more years in practice trended towards less referrals and testing. Evaluating a greater number of patients (p = 0.11) and greater confidence recognizing syndromic features (p = 0.12) and ordering the correct test (p = 0.09) were all associated with ordering more testing. Conclusion: Testing for microdeletion syndromes is being offered and completed in the ACHD population, however testing for single-gene disorders associated with CHD is being under-utilized. Developing guidelines for genetic testing in adults with CHD could increase access to genetic services, impact medical management, reduce uncertainty regarding prognosis, and inform recurrence risk estimates.
  • Thumbnail Image
    Item
    Early ascertainment of genetic diagnoses clarifies impact on medium-term survival following neonatal congenital heart surgery
    (American Society for Clinical Investigation, 2024-07-30) Landis, Benjamin J.; Helm, Benjamin M.; Durbin, Matthew D.; Helvaty, Lindsey R.; Herrmann, Jeremy L.; Johansen, Michael; Geddes, Gabrielle C.; Ware, Stephanie M.; Pediatrics, School of Medicine
  • Thumbnail Image
    Item
    Emergency physician risk tolerance in acute heart failure is higher than previously thought and compatible with modern disposition decision instruments
    (Wiley, 2023) Harrison, Nicholas E.; Koester, Jami; Farmer, Annabelle; Hannon, Aidan; Jakupco, Nicholas; Nanagas, Jill; Park, Seho; Li, Xiaochun; Collins, Sean; Monahan, Patrick; Pang, Peter S.; Emergency Medicine, School of Medicine
  • Thumbnail Image
    Item
    Imbalanced mitochondrial function provokes heterotaxy via aberrant ciliogenesis
    (American Society for Clinical Investigation, 2019-05-16) Burkhalter, Martin D.; Sridhar, Arthi; Sampaio, Pedro; Jacinto, Raquel; Burczyk, Martina S.; Donow, Cornelia; Angenendt, Max; Competence Network for Congenital Heart Defects Investigators; Hempel, Maja; Walther, Paul; Pennekamp, Petra; Omran, Heymut; Lopes, Susana S.; Ware, Stephanie M.; Philipp, Melanie; Pediatrics, School of Medicine
    About 1% of all newborns are affected by congenital heart disease (CHD). Recent findings identify aberrantly functioning cilia as a possible source for CHD. Faulty cilia also prevent the development of proper left-right asymmetry and cause heterotaxy, the incorrect placement of visceral organs. Intriguingly, signaling cascades such as mTor that influence mitochondrial biogenesis also affect ciliogenesis, and can cause heterotaxy-like phenotypes in zebrafish. Here, we identify levels of mitochondrial function as a determinant for ciliogenesis and a cause for heterotaxy. We detected reduced mitochondrial DNA content in biopsies of heterotaxy patients. Manipulation of mitochondrial function revealed a reciprocal influence on ciliogenesis and affected cilia-dependent processes in zebrafish, human fibroblasts and Tetrahymena thermophila. Exome analysis of heterotaxy patients revealed an increased burden of rare damaging variants in mitochondria-associated genes as compared to 1000 Genome controls. Knockdown of such candidate genes caused cilia elongation and ciliopathy-like phenotypes in zebrafish, which could not be rescued by RNA encoding damaging rare variants identified in heterotaxy patients. Our findings suggest that ciliogenesis is coupled to the abundance and function of mitochondria. Our data further reveal disturbed mitochondrial function as an underlying cause for heterotaxy-linked CHD and provide a mechanism for unexplained phenotypes of mitochondrial disease.
  • Thumbnail Image
    Item
    Impact of time between diagnosis to treatment in Acute Type A Aortic Dissection
    (Springer Nature, 2021-02-10) Matthews, Caleb R.; Madison, Mackenzie; Timsina, Lava R.; Namburi, Niharika; Faiza, Zainab; Lee, Lawrence S.; Medicine, School of Medicine
    There is a paucity of data describing the effect of time interval between diagnosis and surgery for Acute Type A Aortic Dissection. We describe our 8-year experience and investigate the impact of time interval between symptom onset, diagnosis and surgery on outcomes. Retrospective single-center study utilizing our Society of Thoracic Surgeons registry and patient records. Subjects were grouped by time interval between radiographic diagnosis and surgical treatment: Group A (0–4 h), Group B (4.1–8 h), Group C (8.1–12 h), and Group D (12.1 + h). Data were analyzed to identify factors associated with mortality and outcomes. 164 patients were included. Overall mortality was 21.3%. Group C had the greatest intervals between symptom onset to diagnosis to surgery, and also the highest mortality (66.7%). Preoperative tamponade, cardiac arrest, malperfusion, elevated creatinine, cardiopulmonary bypass time, and blood transfusions were associated with increased mortality, while distance of referring hospital was not. Time intervals between symptom onset, diagnosis and surgery have a significant effect on mortality. Surgery performed 8–12 h after diagnosis carries the highest mortality, which may be exacerbated by longer interval since symptom onset. Time-dependent effects should be considered when determining optimal strategy especially if inter-facility transfer is necessary.