Cardiology

Sudhakaran, S., Tandon, A., Rafael, A.E. and Choi, J.W. (2021). “Severe Mitral Paravalvular Leak Treated with Percutaneous Paravalvular Leak Closure with Underlying Severe Mitral Annular Calcium.” Am J Cardiol Jun 20;S0002-9149(21)00425-2. [Epub ahead of print].

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Standard operative mitral valve replacement for mitral stenosis in the setting of severe mitral annular calcium has been associated with increased morbidity and mortality. Inability to ensure a well seated prosthesis may lead to periprosthetic leak. We present a case of severe paravalvular leak, causing significant hemolysis, after mitral valve replacement with underling severe mitral annular calcium. The leak was successfully repaired using a transseptal percutaneous approach, with subsequent resolution of hemolysis.

Squiers, J.J., DiMaio, J.M., Van Zyl, J., Lima, B., Gonzalez-Stawisnksi, G., Rafael, A.E., Meyer, D.M. and Hall, S.A. (2021). “Long-term outcomes of patients with primary graft dysfunction after cardiac transplantation.” Eur J Cardiothorac Surg Jun 7;ezab177. [Epub ahead of print].

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OBJECTIVES: The International Society of Heart and Lung Transplantation (ISHLT) criteria for primary graft dysfunction (PGD) after cardiac transplantation have been shown to stratify patient outcomes up to 1 year after transplantation, but scarce data are available regarding outcomes beyond the 1st year. We sought to characterize survival of patients with PGD following cardiac transplantation beyond the 1st year. METHODS: A retrospective review of consecutive patients undergoing isolated cardiac transplantation at a single centre between 2012 and 2015 was performed. Patients were diagnosed with none, mild, moderate or severe PGD by the ISHLT criteria. Survival was ascertained from the United Network for Organ Sharing database and chart review. Kaplan-Meier curves were plotted to compare survival. The hazard ratio for mortality associated with PGD severity was estimated using Cox-proportional hazards modelling, with a pre-specified conditional survival analysis at 90 days. RESULTS: A total of 257 consecutive patients underwent cardiac transplantation during the study period, of whom 73 (28%) met ISHLT criteria for PGD: 43 (17%) mild, 12 (5%) moderate and 18 (7%) severe. Patients with moderate or severe PGD had decreased survival up to 5 years after transplantation (log-rank P < 0.001). Landmark analyses demonstrated that patients with moderate or severe PGD were at increased risk of mortality during the first 90-days after transplantation as compared to those with none or mild PGD [hazard ratio (95% confidence interval) 18.9 (7.1-50.5); P < 0.001], but this hazard did not persist beyond 90-days in survivors (P = 0.64). CONCLUSIONS: A diagnosis of moderate or severe PGD is associated with increased mortality up to 5 years after cardiac transplantation. However, patients with moderate or severe PGD who survive to post-transplantation day 90 are no longer at increased risk for mortality as compared to those with none or mild PGD.

Schaffer, J.M., Squiers, J.J., Banwait, J.K., Hale, S., Ryan, W.H., Mack, M.J. and DiMaio, J.M. (2021). “Differences in Administrative Claims Data for Coronary Artery Bypass Grafting Between International Classification of Diseases, Ninth Revision and Tenth Revision Coding.” JAMA Cardiol Jun 9;e211595. [Epub ahead of print].

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This cross-sectional study examines the changes in coding of coronary artery bypass graft procedures after the transition from the International Classification of Diseases, Ninth Revision to the Tenth Revision.

McCullough, P.A. (2021). “Phosphate Control: The Next Frontier in Dialysis Cardiovascular Mortality.” Cardiorenal Med 11(3): 123-132.

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BACKGROUND: Cardiovascular disease (CVD) is a major cause of death in patients with chronic kidney disease (CKD) on dialysis. Mortality rates are still unacceptably high even though they have fallen in the past 2 decades. Hyperphosphatemia (elevated serum phosphate levels) is seen in almost all patients with advanced CKD and is by far the largest remaining modifiable contributor to CKD mortality. SUMMARY: Phosphate retention drives multiple physiological mechanisms linked to increased risk of CVD. Fibroblast growth factor 23 and parathyroid hormone (PTH) levels, both of which have been suggested to have direct pathogenic CV effects, increase in response to phosphate retention. Phosphate, calcium, and PTH levels are linked in a progressively worsening cycle. Maladaptive upregulation of phosphate absorption is also likely to occur further exacerbating hyperphosphatemia. Even higher phosphate levels within the normal range may be a risk factor for vascular calcification and, thus, CV morbidity and mortality. A greater degree of phosphate control is important to reduce the risk of CV morbidity and mortality. Improved phosphate control and regular monitoring of phosphate levels are guideline-recommended, established clinical practices. There are several challenges with the current phosphate management approaches in patients with CKD on dialysis. Dietary restriction of phosphate and thrice-weekly dialysis alone are insufficient/unreliable to reduce phosphate to <5.5 mg/dL. Even with the addition of phosphate binders, the only pharmacological treatment currently indicated for hyperphosphatemia, the majority of patients are unable to achieve and maintain phosphate levels <5.5 mg/dL (or more normal levels) [PhosLo® gelcaps (calcium acetate): 667 mg (prescribing information), 2011, VELPHORO®: (Sucroferric oxyhydroxide) (prescribing information), 2013, FOSRENAL®: (Lanthanum carbonate) (prescribing information), 2016, AURYXIA®: (Ferric citrate) tablets (prescribing information), 2017, RENVELA®: (Sevelamer carbonate) (prescribing information), 2020, RealWorld dynamix. Dialysis US: Spherix Global Insights, 2019]. Phosphate binders do not target the primary pathway of phosphate absorption (paracellular), have limited binding capacity, and bind nonspecifically [PhosLo® gelcaps (calcium acetate): 667 mg (prescribing information). 2013, VELPHORO®: (Sucroferric oxyhydroxide) (prescribing information), 2013, FOSRENAL®: (Lanthanum carbonate) (prescribing information), 2016, AURYXIA®: (Ferric citrate) tablets (prescribing information), 2017, RENVELA®: (Sevelamer carbonate) (prescribing information) 2020]. Key Messages: Despite current phosphate management strategies, most patients on dialysis are unable to consistently achieve target phosphate levels, indicating a need for therapeutic innovations [RealWorld dynamix. Dialysis US: Spherix Global Insights, 2019]. Given a growing evidence base that the dominant mechanism of phosphate absorption is the intestinal paracellular pathway, new therapies are investigating ways to reduce phosphate levels by blocking absorption through the paracellular pathway.

Lam, C.S.P., Ferreira, J.P., Pfarr, E., Sim, D., Tsutsui, H., Anker, S.D., Butler, J., Filippatos, G., Pocock, S.J., Sattar, N., Verma, S., Brueckmann, M., Schnee, J., Cotton, D., Zannad, F. and Packer, M. (2021). “Regional and ethnic influences on the response to empagliflozin in patients with heart failure and a reduced ejection fraction: the EMPEROR-Reduced trial.” Eur Heart J Jun 29;ehab360. [Epub ahead of print].

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AIMS: The aim of this article is to explore the influence of region and race/ethnicity on the effects of empagliflozin in the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction (EMPEROR-Reduced) trial. METHODS AND RESULTS: Of 3730 patients, 1353 (36.3%) were enrolled in Europe, 1286 (34.5%) in Latin America, 425 (11.4%) in North America, and 493 (13.2%) in Asia; 2629 (70.5%) were White, 257 (6.9%) Black, and 672 (18.0%) Asian. Placebo event rates (per 100 patient-years) for cardiovascular death or heart failure (HF) hospitalization varied by region (Asia 27.7, North America 26.4, Latin America 21.4, and Europe 17.5) and race/ethnicity (Black 34.4, Asian 24.3, and White 18.7); driven by differences in HF hospitalization. The ratio of total HF hospitalization to cardiovascular death varied from 5.4 in Asia and 4.8 in North America to 2.1 in Europe; and from 4.8 in Black and 4.2 in Asian to 2.2 in White patients. Groups with the highest ratio had the greatest reduction in the primary outcome with empagliflozin. Inclusion of outpatient worsening HF episodes added more events in Europe vs. other regions; enhanced the placebo event rates in Europe vs. other regions; and increased the relative risk reduction with empagliflozin in Europe from 6% to 26%. CONCLUSIONS: There were notable differences in the placebo event rates for major HF events across diverse regions and race/ethnic groups. The benefit of empagliflozin was most pronounced in groups with the highest ratio of HF hospitalization to cardiovascular death. Regional differences were attenuated when the definition of HF events was expanded to include outpatient worsening HF events.