Research Spotlight

Lam, P. H., M. Packer, G. C. Fonarow, C. Faselis, R. M. Allman, C. J. Morgan, S. N. Singh, B. Pitt and A. Ahmed (2020). “Early Effects of Starting Doses of Enalapril in Patients with Chronic Heart Failure in the SOLVD Treatment Trial.” Am J Med 133(2): e25-e31.

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BACKGROUND: In the Studies of Left Ventricular Dysfunction (SOLVD) treatment trial, similar clinical benefits were observed between starting doses of enalapril and the target dose achieved by postrandomization up-titration. In our current analysis, protecting the randomization, we examined the early effects of starting doses of enalapril. METHODS: There were 2569 patients with mild-to-moderate chronic heart failure with reduced ejection fraction (ejection fraction less-than-or-equal-to 35%) randomized to receive starting doses (5-10 mg/day) of placebo (n = 1284) or enalapril (n = 1285). At day 14, both study drugs were blindly up-titrated to the target dose (20 mg/day). Overall, 96% (2458/2569) of the patients returned for dose up-titration, which was achieved in 59% (1444/2458), 48% (696/1444) of whom were in the enalapril group. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes in the enalapril group were estimated. RESULTS: HRs (95% CIs) for all-cause mortality, heart failure hospitalization, and the combined endpoint of heart failure hospitalization or all-cause mortality at 14 days after randomization were 0.80 (0.32-2.03), 0.63 (0.35-1.12), and 0.65 (0.39-1.06), respectively. Corresponding HRs (95% CIs) at 30 days were 0.82 (0.41-1.67), 0.43 (0.27-0.68), and 0.43 (0.27-0.68), respectively. The magnitude of these early effects of starting doses of enalapril is similar to its previously reported long-term effects at the target dose. CONCLUSION: These data suggest that in stable ambulatory patients with heart failure with reduced ejection fraction, the magnitude of the early effect of starting doses of enalapril is similar to that observed during longer-term therapy with the target doses of the drug.

Kumano, K., M. Takita, S. Vasu, C. Darden, M. Lawrence, E. Beecherl, A. Gupta, N. Onaca and B. Naziruddin (2020). “Impact of microbial contamination of the islet product during total pancreatectomy with islet autotransplantation.” J Hepatobiliary Pancreat Sci Jan 16. [Epub ahead of print].

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BACKGROUND: The combined use of interleukin-1beta and tumor necrosis factor-alpha blockers in the peritransplant period has improved outcomes of total pancreatectomy with islet autotransplantation (TPIAT). However, these drugs may suppress the immune system, resulting in severe infection. METHODS: We retrospectively investigated the impact of microbial-contaminated islet product on posttransplant complications and metabolic outcomes of TPIAT patients receiving the IL-1 and TNF-blockade treatment at our center. RESULTS: Among 108 TPIAT patients, 37 patients (34%) received contaminated products. Preoperative stent treatment and fibrosis score were independent risk factors for the contamination. There were no significant differences between the contaminated and noncontaminated product groups in posttransplant infectious complication rate, length of hospitalization, or readmission rate. However, islet equivalents (P < 0.0001) and insulin independence rate (P = 0.036) at 6 months were significantly lower for patients receiving contaminated product. CONCLUSIONS: These results suggest that combined anti-inflammatory drug use is safe and well tolerated in TPIAT patients who receive contaminated islet product and does not increase the rate of infectious complications; however, contaminated islet product is associated with poor metabolic outcomes.

Kline, J. A., J. S. Garrett, E. J. Sarmiento, C. C. Strachan and D. M. Courtney (2020). “Over-Testing for Suspected Pulmonary Embolism in American Emergency Departments: The Continuing Epidemic.” Circ Cardiovasc Qual Outcomes Jan 20. [Epub ahead of print]

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BACKGROUND: No recent data have investigated rates of diagnostic testing for pulmonary embolism (PE) in US emergency departments (EDs), and no data have examined computed tomographic pulmonary angiography (CTPA) rates in subgroups at high risk for adverse imaging outcomes, including young women and children. We hypothesized that over-testing for PE remains a problem. METHODS AND RESULTS: We used electronic health record and billing data for 16 EDs in Indiana and 11 hospitals in the Dallas-Fort Worth area from 2016 to 2019 to locate ED patients who had any of the following: D-dimer, CTPA, scintillation ventilation perfusion lung scanning or formal pulmonary angiography. The primary outcomes were ED encounter volume-adjusted CTPA rate, PE yield rate with subgroup reporting for children (<18 years) and women under 45 years. We also examined the most frequent diagnoses. From a total visit volume of 1 828 010 patient encounters, 97 125 (5.3% of the total volume) had a diagnostic test for PE, including 25 870 patients who had CTPA order without D-dimer (59% of all tests for PE). The yield rate for PE from CTPA scans was 1.3% (1.1%-1.5%) in Indiana and 4.8% (4.2%-5.1%) in Dallas-Fort Worth (pooled rate 3.1%). Linear regression showed that increased D-dimer ordering correlated with increased PE yield rate (Pearson's R(2)=0.43; P<0.001). From the pooled sample, 59% of CTPAs done were in women, with 21% of all CTPAs performed on women under 45 years of age, and 1.4% (1.3%-1.5%) on children. The most frequent diagnoses were symptom-based descriptions of chest pain (34%) and shortness of breath (6.5%) and the condition-based diagnosis of pneumonia (4.1%). CONCLUSIONS: Over-testing for PE in American EDs remains a major public health problem. Centers with higher D-dimer ordering had higher yield of PE on CTPA. These data suggest the potential for implementation of D-dimer based protocols to reduce low-yield CTPA ordering.

Kiani, S., A. Stebbins, V. H. Thourani, J. Forcillo, S. Vemulapalli, A. S. Kosinski, V. Babaliaros, D. Cohen, S. K. Kodali, A. J. Kirtane, J. B. Hermiller, Jr., J. Stewart, A. Lowenstern, M. J. Mack, R. A. Guyton and C. Devireddy (2020). “The Effect and Relationship of Frailty Indices on Survival After Transcatheter Aortic Valve Replacement.” JACC Cardiovasc Interv 13(2): 219-231.

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OBJECTIVES: This study sought to evaluate the ability of individual markers of frailty to predict outcomes after transcatheter aortic valve replacement (TAVR) and of their discriminatory value in different age groups. BACKGROUND: Appropriate patient selection for TAVR remains a dilemma, especially among the most elderly and potentially frail. METHODS: The study evaluated patients >/=65 years of age in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy registry, linked to Centers for Medicare and Medicaid administrative claims data, receiving elective TAVR from November 2011 to June 2016 (n = 36,242). Indices of frailty included anemia, albumin level, and 5-m walk speed. We performed Cox proportional hazards regression for 30-day and 1-year mortality, adjusting for risk factors known to be predictive of 30-day mortality in the Transcatheter Valve Therapy registry, as well as survival analysis. RESULTS: These indices are independently associated with mortality at 30 days and 1 year and provide incremental value in risk stratification for mortality, with low albumin providing the largest value (hazard ratio: 1.52). Those with low albumin and slower walking speed had longer lengths of stay and higher rates of bleeding and readmission (p < 0.001). Those with anemia also had higher rates of bleeding, readmission, and subsequent myocardial infarction (p < 0.001). CONCLUSIONS: This represents the largest study to date of the role of frailty indices after TAVR, further facilitating robust modeling and adjusting for a large number of confounders. These simple indices are easily attainable, and clinically relevant markers of frailty that may meaningfully stratify patients at risk for mortality after TAVR.

Kataria, V., L. Moore, S. Harrison, O. Hernandez, N. Vaughan and G. Schwartz (2020). “Evaluation of Serotonin Release Assay and Enzyme-Linked Immunosorbent Assay Optical Density Thresholds for Heparin-Induced Thrombocytopenia in Patients on Extracorporeal Membrane Oxygenation.” Crit Care Med 48(2): e82-e86.

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OBJECTIVES: Heparin-induced thrombocytopenia is a recognized concern in patients on extracorporeal life support. The purpose of this study was to evaluate the applicability of an enzyme-linked immunosorbent assay optical density threshold less than 1 to rule out heparin-induced thrombocytopenia in patients on extracorporeal membrane oxygenation. DESIGN: Retrospective, single-center study. SETTING: Patients were recruited from a prospectively maintained database of all patients on extracorporeal membrane oxygenation from 2012 to 2018 at a tertiary referral center. PATIENTS: Forty-seven patients on extracorporeal membrane oxygenation support. INTERVENTIONS: The primary objective was to evaluate the application of enzyme-linked immunosorbent assay optical density thresholds and the serotonin release assay in patients on extracorporeal membrane oxygenation. Patients were divided into two cohorts, serotonin release assay negative and serotonin release assay positive. In order to perform a sensitivity and specificity analysis of enzyme-linked immunosorbent assay optical density thresholds, heparin-induced thrombocytopenia negative was defined as an optical density less than 1.0 and heparin-induced thrombocytopenia positive as an optical density greater than or equal to 1.0. MEASUREMENTS AND MAIN RESULTS: Utilizing the prespecified optical density thresholds, a specificity and negative predictive value of 89% and 95% were achieved, respectively. CONCLUSIONS: This assessment has helped to identify optical density thresholds for patients undergoing extracorporeal membrane oxygenation. Our data suggest that an optical density threshold of 1.0 may aid clinicians in objectively ruling out heparin-induced thrombocytopenia without sending a confirmatory serotonin release assay. Increasing the optical density threshold to 1.0 resulted in a high specificity and negative predictive value.