Research Spotlight

Lo, K.B., Toroghi, H.M., Salacup, G., Jiang, J., Bhargav, R., Quintero, E., Balestrini, K., Shahzad, A., Mathew, R.O., McCullough, P.A. and Rangaswami, J. (2021). “Angiotensin converting enzyme inhibitors and angiotensin receptor blockers in acute heart failure: invasive hemodynamic parameters and clinical outcomes.” Rev Cardiovasc Med 22(1): 199-206.

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There are limited data regarding the use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) in acute heart failure (AHF). The purpose is to determine the patterns of ACEi/ARB use at the time of admission and discharge in relation to invasive hemodynamic data, mortality, and heart failure (HF) readmissions. This is a retrospective single-center study in patients with AHF who underwent right heart catheterization between January 2010 and December 2016. Patients on dialysis, evidence of shock, or incomplete follow up were excluded. Multivariate logistic regression analysis was used to analyze the factors associated with continuation of ACEi/ARB use on discharge and its relation to mortality and HF readmissions. The final sample was 626 patients. Patients on ACEi/ARB on admission were most likely continued on discharge. The most common reasons for stopping ACEi/ARB were worsening renal function (WRF), hypotension, and hyperkalemia. Patients with ACEi/ARB use on admission had a significantly higher systemic vascular resistance (SVR) and mean arterial pressure (MAP), but lower cardiac index (CI). Patients with RA pressures above the median received less ACEi/ARB (P = 0.025) and had significantly higher inpatient mortality (P = 0.048). After multivariate logistic regression, ACEi/ARB use at admission was associated with less inpatient mortality; OR 0.32 95% CI (0.11 to 0.93), and this effect extended to the subgroup of patients with HFpEF. Patients discharged on ACEi/ARB had significantly less 6-month HF readmissions OR 0.69 95% CI (0.48 to 0.98). ACEi/ARB use on admission for AHF was associated with less inpatient mortality including in those with HFpEF.

Lo, E.Y., Rizkalla, J., Montemaggi, P., Majekodunmi, T. and Krishnan, S.G. (2021). “Clinical and radiographic outcomes of cementless reverse total shoulder arthroplasty for proximal humeral fractures.” J Shoulder Elbow Surg Mar 13;S1058-2746(20)30930-7. [Epub ahead of print].

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BACKGROUND: Reverse total shoulder arthroplasty (RTSA) has demonstrated successful outcomes in the treatment of both acute and chronic proximal humeral fractures (PHFs). The traditional RTSA surgical technique uses a methyl methacrylate cemented humeral component to restore and maintain both humeral height and retroversion. However, use of humeral bone cement has been associated intraoperatively with cardiopulmonary risk, increased operative cost, and postoperatively with difficulty if revision arthroplasty is required. We report the clinical and radiographic outcomes of a completely cementless RTSA technique for PHF surgery. METHODS: Between 2013 and 2018, 60 consecutive patients underwent surgical management of a PHF with cementless RTSA. All surgical procedures were performed by a single senior shoulder surgeon using a modified deltopectoral approach and a completely uncemented RTSA technique. Fractures were defined as either acute or chronic based on a 4-week injury-to-surgery benchmark. The mean age was 67 years (range, 47-85 years). There were 18 acute and 42 chronic fractures. The mean time from injury to surgery was 2 weeks (range, 0.4-4 weeks) for acute fractures and 60 months (range, 1-482 months) for chronic fractures. We excluded 17 cases from postoperative evaluation because of revision and/or loss to follow-up. The remaining 43 cases underwent clinical and radiographic evaluation by 2 independent fellowship-trained shoulder surgeons at a mean of 21 months (range, 10-46 months) postoperatively. Independent statistical analysis was performed using the paired t test and Wilcoxon signed rank test. RESULTS: At final review, mean active anterior elevation was 157° (range, 100°-170°); active external rotation, 52° (range, 6°-80°); and active internal rotation, 66° (range, 0°-80°). Improvements were seen in the visual analog scale pain score (from 6 to 0.2, P < .001), Simple Shoulder Test score (from 9 to 93, P < .001), American Shoulder and Elbow Surgeons score (from 19 to 91, P < .001), and Single Assessment Numeric Evaluation score (from 21% to 89%, P < .001). Overall, 39 of 43 greater tuberosities (91%) demonstrated osseous healing to the humeral shaft. No significant differences in clinical and radiographic outcomes were found in acute vs. chronic cases, as well as cases with minimum follow-up of 1 year vs. 2 years. Overall, there were 4 major complications necessitating surgical revision (6.7%) and no cases of aseptic humeral stem loosening. CONCLUSION: Cementless RTSA for acute and chronic PHFs demonstrates clinical and radiographic outcomes similar to those after traditional cemented RTSA. The successful greater tuberosity healing and absence of humeral stem loosening in this short-term cohort are encouraging for the continued long-term success of this technique. By avoiding cemented humeral implants, surgeons may minimize intraoperative complications, operative cost, and postoperative revision difficulty.

Leon, M.B., Mack, M.J., Hahn, R.T., Thourani, V.H., Makkar, R., Kodali, S.K., Alu, M.C., Madhavan, M.V., Chau, K.H., Russo, M., Kapadia, S.R., Malaisrie, S.C., Cohen, D.J., Blanke, P., Leipsic, J.A., Williams, M.R., McCabe, J.M., Brown, D.L., Babaliaros, V., Goldman, S., Herrmann, H.C., Szeto, W.Y., Genereux, P., Pershad, A., Lu, M., Webb, J.G., Smith, C.R. and Pibarot, P. (2021). “Outcomes 2 Years After Transcatheter Aortic Valve Replacement in Patients at Low Surgical Risk.” J Am Coll Cardiol 77(9): 1149-1161.

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BACKGROUND: In low surgical risk patients with symptomatic severe aortic stenosis, the PARTNER 3 (Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis) trial demonstrated superiority of transcatheter aortic valve replacement (TAVR) versus surgery for the primary endpoint of death, stroke, or re-hospitalization at 1 year. OBJECTIVES: This study determined both clinical and echocardiographic outcomes between 1 and 2 years in the PARTNER 3 trial. METHODS: This study randomly assigned 1,000 patients (1:1) to transfemoral TAVR with the SAPIEN 3 valve versus surgery (mean Society of Thoracic Surgeons score: 1.9%; mean age: 73 years) with clinical and echocardiography follow-up at 30 days and at 1 and 2 years. This study assessed 2-year rates of the primary endpoint and several secondary endpoints (clinical, echocardiography, and quality-of-life measures) in this as-treated analysis. RESULTS: Primary endpoint follow-up at 2 years was available in 96.5% of patients. The 2-year primary endpoint was significantly reduced after TAVR versus surgery (11.5% vs. 17.4%; hazard ratio: 0.63; 95% confidence interval: 0.45 to 0.88; p = 0.007). Differences in death and stroke favoring TAVR at 1 year were not statistically significant at 2 years (death: TAVR 2.4% vs. surgery 3.2%; p = 0.47; stroke: TAVR 2.4% vs. surgery 3.6%; p = 0.28). Valve thrombosis at 2 years was increased after TAVR (2.6%; 13 events) compared with surgery (0.7%; 3 events; p = 0.02). Disease-specific health status continued to be better after TAVR versus surgery through 2 years. Echocardiographic findings, including hemodynamic valve deterioration and bioprosthetic valve failure, were similar for TAVR and surgery at 2 years. CONCLUSIONS: At 2 years, the primary endpoint remained significantly lower with TAVR versus surgery, but initial differences in death and stroke favoring TAVR were diminished and patients who underwent TAVR had increased valve thrombosis. (Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis [PARTNER 3]; NCT02675114).

Mahmud, N., Asrani, S.K., Reese, P.P., Kaplan, D.E., Taddei, T.H., Nadim, M.K. and Serper, M. (2021). “Race Adjustment in eGFR Equations Does Not Improve Estimation of Acute Kidney Injury Events in Patients with Cirrhosis.” Dig Dis Sci Mar 24. [Epub ahead of print].

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BACKGROUND: Accuracy of glomerular filtration rate estimating (eGFR) equations has significant implications in cirrhosis, potentially guiding simultaneous liver kidney allocation and drug dosing. Most equations adjust for Black race, partially accounted for by reported differences in muscle mass by race. Patients with cirrhosis, however, are prone to sarcopenia which may mitigate such differences. We evaluated the association between baseline eGFR and incident acute kidney injury (AKI) in patients with cirrhosis with and without race adjustment. METHODS: We conducted a retrospective national cohort study of veterans with cirrhosis. Baseline eGFR was calculated using multiple eGFR equations including Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), both with and without race adjustment. Poisson regression was used to investigate the association between baseline eGFR and incident AKI events per International Club of Ascites criteria. RESULTS: We identified 72,267 patients with cirrhosis, who were 97.3% male, 57.8% white, and 19.7% Black. Over median follow-up 2.78 years (interquartile range 1.22-5.16), lower baseline eGFR by CKD-EPI was significantly associated with higher rates of AKI in adjusted models. For all equations this association was minimally impacted when race adjustment was removed. For example, removal of race adjustment from CKD-EPI resulted in a 0.1% increase in the association between lower eGFR and higher rate of AKI events per 15 mL/min/1.73 m(2) change (p < 0.001). CONCLUSIONS: Race adjustment in eGFR equations did not enhance AKI risk estimation in patients with cirrhosis. Further study is warranted to assess the impacts of removing race from eGFR equations on clinical outcomes and policy.

Kosky, K.M., Phenis, R. and Kiselica, A.M. (2021). “Neuropsychological functioning in dysgenesis of the corpus callosum with colpocephaly.” Appl Neuropsychol Adult Mar 15;1-7. [Epub ahead of print]. 1-7.

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Dysgenesis of the corpus callosum is a rare developmental abnormality in brain structure that is associated with changes in physical appearance, as well as behavioral and cognitive consequences. A relatively commonly co-occurring structural abnormality with callosal dysgenesis is colpocephaly, characterized by enlargement of the posterior lateral ventricles and reductions in posterior brain volume. Although some case studies of individuals with this combination of structural malformations exist, they do not often report results of neuropsychological evaluation. Furthermore, those that do contain neuropsychological data may be of limited generalizability due to unique patient characteristics. The current manuscript overcomes these limitations by presenting the case of a 55-year-old male with callosal dysgenesis and colpocephaly identified in adulthood. The paper includes a full profile of his performance on a comprehensive neuropsychological test battery with discussion of differential diagnosis and treatment planning. Findings indicated low average intellectual abilities with deficits in processing speed, executive functions, and social cognition, consistent with expectations based on callosal dysgenesis. One surprising finding was that despite the significant posterior involvement of colpocephaly, visuospatial skills were a relative strength. The manuscript provides a clear characterization of callosal dysgenesis with colpocephaly to facilitate future clinical comparisons and set the stage for future research on this rare neuromorphological presentation.