Cardiology

Ring, W. S., J. R. Edgerton, M. Herbert, S. Prince, C. Knoff, K. M. Jenkins, M. E. Jessen and B. L. Hamman (2017). “Impact of accurate 30-day status on operative mortality: Wanted dead or alive, not unknown.” Ann Thorac Surg: 2017 Aug [Epub ahead of print].

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BACKGROUND: Risk-adjusted operative mortality is the most important quality metric in cardiac surgery for determining The Society of Thoracic Surgeons (STS) Composite Score for star ratings. Accurate 30-day status is required to determine STS operative mortality. The goal of this study was to determine the effect of unknown or missing 30-day status on risk-adjusted operative mortality in a regional STS Adult Cardiac Surgery Database cooperative and demonstrate the ability to correct these deficiencies by matching with an administrative database. METHODS: STS Adult Cardiac Surgery Database data were submitted by 27 hospitals from five hospital systems to the Texas Quality Initiative (TQI), a regional quality collaborative. TQI data were matched with a regional hospital claims database to resolve unknown 30-day status. The risk-adjusted operative mortality observed-to-expected (O/E) ratio was determined before and after matching to determine the effect of unknown status on the operative mortality O/E. RESULTS: TQI found an excessive (22%) unknown 30-day status for STS isolated coronary artery bypass grafting cases. Matching the TQI data to the administrative claims database reduced the unknowns to 7%. The STS process of imputing unknown 30-day status as alive underestimates the true operative mortality O/E (1.27 before vs 1.30 after match), while excluding unknowns overestimates the operative mortality O/E (1.57 before vs 1.37 after match) for isolated coronary artery bypass grafting. CONCLUSIONS: The current STS algorithm of imputing unknown 30-day status as alive and a strategy of excluding cases with unknown 30-day status both result in erroneous calculation of operative mortality and operative mortality O/E. However, external validation by matching with an administrative database can improve the accuracy of clinical databases such as the STS Adult Cardiac Surgery Database.

Roberts, W. C. (2017). “Proceedings of the editorial board meeting of the american journal of cardiology on march 17, 2017.” Am J Cardiol 120(4): 718-719.

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The annual editorial board meeting of The American Journal of Cardiology ( AJC ) was held on March 17, 2017, at the time of the Annual Scientific Sessions of the American College of Cardiology. The major purpose of the meeting was to thank the editorial board members for their considerable help during the previous year in reviewing manuscripts and to seek their suggestions for improving the journal. Several changes occurred during 2016: there was a publisher change from Ms. Joan Anuels to Ms. Heather Luciano, and the Managing Editor in the Dallas office changed from Ms. Lynn Guillen to Ms. Jill Rutherford. In early 2017, the Journal Manager in St. Louis changed from Ms. Ashley Rodenberry to Mr. John Beckemeier. I think these changes will be advantageous for the journal.

Butler, J., C. E. Hamo, G. Filippatos, S. J. Pocock, R. A. Bernstein, M. Brueckmann, A. K. Cheung, J. T. George, J. B. Green, J. L. Januzzi, S. Kaul, C. S. P. Lam, G. Y. H. Lip, N. Marx, P. A. McCullough, C. R. Mehta, P. Ponikowski, J. Rosenstock, N. Sattar, A. Salsali, B. M. Scirica, S. J. Shah, H. Tsutsui, S. Verma, C. Wanner, H. J. Woerle, F. Zannad and S. D. Anker (2017). “The potential role and rationale for treatment of heart failure with sodium-glucose co-transporter 2 inhibitors.” Eur J Heart Fail: 2017 Aug [Epub ahead of print].

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Heart failure (HF) and type 2 diabetes mellitus (T2DM) are both growing public health concerns contributing to major medical and economic burdens to society. T2DM increases the risk of HF, frequently occurs concomitantly with HF, and worsens the prognosis of HF. Several anti-hyperglycaemic medications have been associated with a concern for worse HF outcomes. More recently, the results of the EMPA-REG OUTCOME trial showed that the sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin was associated with a pronounced and precocious 32% reduction in cardiovascular mortality in subjects with T2DM and established cardiovascular disease. These benefits were more related to a reduction in incident HF events rather than to ischaemic vascular endpoints. Several mechanisms have been put forward to explain these benefits, which also raise the possibility of using these drugs as therapies not only in the prevention of HF, but also for the treatment of patients with established HF regardless of the presence or absence of diabetes. Several large trials are currently exploring this postulate.

Bastarrachea, R. A., J. Chen, J. W. Kent, Jr., E. J. Nava-Gonzalez, E. Rodriguez-Ayala, M. M. Daadi, B. Jorge, H. Laviada-Molina, A. G. Comuzzie, S. Chen and P. A. Grayburn (2017). “Engineering brown fat into skeletal muscle using ultrasound-targeted microbubble destruction gene delivery in obese zucker rats: Proof of concept design.” IUBMB Life 69(9): 745-755.

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Ultrasound-targeted microbubble destruction (UTMD) is a novel means of tissue-specific gene delivery. This approach systemically infuses transgenes precoupled to gas-filled lipid microbubbles that are burst within the microvasculature of target tissues via an ultrasound signal resulting in release of DNA and transfection of neighboring cells within the tissue. Previous work has shown that adenovirus containing cDNA of UCP-1, injected into the epididymal fat pads in mice, induced localized fat depletion, improving glucose tolerance, and decreasing food intake in obese diabetic mice. Our group recently demonstrated that gene therapy by UTMD achieved beta cell regeneration in streptozotocin (STZ)-treated mice and baboons. We hypothesized that gene therapy with BMP7/PRDM16/PPARGC1A in skeletal muscle (SKM) of obese Zucker diabetic fatty (fa/fa) rats using UTMD technology would produce a brown adipose tissue (BAT) phenotype with UCP-1 overexpression. This study was designed as a proof of concept (POC) project. Obese Zucker rats were administered plasmid cDNA contructs encoding a gene cocktail with BMP7/PRDM16/PPARGC1A incorporated within microbubbles and intravenously delivered into their left thigh. Controls received UTMD with plasmids driving a DsRed reporter gene. An ultrasound transducer was directed to the thigh to disrupt the microbubbles within the microcirculation. Blood samples were drawn at baseline, and after treatment to measure glucose, insulin, and free fatty acids levels. SKM was harvested for immunohistochemistry (IHC). Our IHC results showed a reliable pattern of effective UTMD-based gene delivery in enhancing SKM overexpression of the UCP-1 gene. This clearly indicates that our plasmid DNA construct encoding the gene combination of PRDM16, PPARGC1A, and BMP7 reprogrammed adult SKM tissue into brown adipose cells in vivo. Our pilot established POC showing that the administration of the gene cocktail to SKM in this rat model of genetic obesity using UTMD gene therapy, engineered a BAT phenotype with UCP-1 over-expression.

Gottlieb, R. L., T. Sam, S. Y. Wada, J. F. Trotter, S. K. Asrani, B. Lima, S. M. Joseph, G. Gonzalez-Stawinski and S. A. Hall (2017). “Rational heart transplant from hepatitis c donor: New antiviral weapons conquer the trojan.” J Card Fail: 2017 Aug [Epub ahead of print].

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BACKGROUND: Donors with hepatitis C (HCV) viremia are rarely utilized for orthotopic heart transplantation (OHTx) due to post-transplant risks. New, highly effective HCV antivirals may alter the landscape. METHODS: An adult patient unsuitable for bridging mechanical support therapy accepted a heart transplant offer from a donor with HCV viremia. Upon daily logarithmic rise in HCV viral load and adequate titers to ensure successful genotyping, once daily sofosbuvir 400 mg / velpatasvir 100 mg (Epclusa) was initiated empirically pending HCV genotype (genotype 3a confirmed after initiation of therapy). RESULTS: We report the kinetics of acute Hepatitis C viremia and therapeutic response to treatment with a new pangenotypic antiviral agent after donor-derived acute HCV infection transmitted incidental to successful cardiac transplant into a HCV negative OHTx recipient. Prompt resolution of viremia was noted by the first week of a 12 week course of antiviral therapy. Sustained virologic remission continues beyond 12 weeks after completion of HCV therapy (SVR-12). CONCLUSIONS: The availability of effective pangenotypic therapy for HCV may expand donor availability. The feasibility of early versus late treatment of HCV remains to be determined through formalized protocols. We hypothesize pharmacoeconomics to be the greatest limitation to widespread availability of this promising tool.