Research Spotlight

Mutnal, M.B., Lanham, J.A., Walker, K. and Rao, A. (2021). “False positive Influenza rapid tests using newly EUA cleared multiplex assay in a low prevalence setting.” J Med Virol Jan 26. [Epub ahead of print].

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Influenza activity in the United States between September 2020 and mid‐December 2020 was relatively low with laboratory‐confirmed influenza test positivity rate at 0.2%.1 It is very well‐known in the clinical laboratory community that rapid antigen tests lack sensitivity. Studies have shown that the sensitivity of these tests can be less than 60% in a normal Influenza season. It can be speculated that due to very low prevalence of Influenza viruses, rapid antigen tests might be experiencing some assay interference, producing false positive results. When the prevalence of the disease is low, the positive predictive value of the test is low, and false‐positive test results are more likely.2-4 The false‐positive influenza results reported here may have resulted in increased health care costs and potential inappropriate use of antiviral medications. [No abstract; excerpt from Letter].

Raj, S.D., Clayton, J.T., Raj, K.M., Fishman, S.F. and Fishman, M.D.C. (2021). “Motivation: how to create a cohort of engaged, energized, and happy radiology trainees.” Clin Imaging Jan 8;76:83-87. [Epub ahead of print]. 83-87.

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Burnout among physicians continues to be a “hot topic” as medical culture struggles to adapt to the changing marketplace, where clinical demands are ever increasing but healthcare systems are pivoting to prefer value and cost-savings. To date, many attempts to understand and battle burnout center around the individual physician, rather than the system, limiting the medical community’s ability to counter it successfully. The training environment is a common nidus for burnout. By promoting an understanding of motivation, happiness, and engagement in the workplace, we suggest several changes that training programs can make to minimize burnout and promote resident wellness. Creating a culture of support, promoting a positive work environment, building a cohesive team, and encouraging wellness both inside and outside the workplace stands to create engaged, happy, and motivated trainees who will hopefully continue to promote those strategies as they advance their careers.

Patel, R.B., Ter Maaten, J.M., Ferreira, J.P., Mc Causland, F.R., Shah, S.J., Rossignol, P., Solomon, S.D., Vaduganathan, M., Packer, M., Thompson, A., Stockbridge, N. and Zannad, F. (2021). “Challenges of Cardio-Kidney Composite Outcomes in Large-Scale Clinical Trials.” Circulation Jan 7.[ Epub aheaad of print].

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Patients with chronic cardiovascular or metabolic diseases, including diabetes, hypertension, obesity, and heart failure, often have comorbid kidney disease. Indeed, long-term outcomes are worse in the setting of both cardiac and kidney disease compared with either disease in isolation. In addition, the clinical presentations of certain acute cardiovascular events (such as heart failure) and worsening kidney function are overlapping and may be challenging to distinguish. Recently, certain novel treatments have demonstrated beneficial effects on both cardiac and kidney outcomes. Sodium-glucose cotransporter-2 inhibitors have exhibited concordant risk reduction and clinically important benefits in chronic kidney disease with and without diabetes, diabetes and established cardiovascular disease or multiple atherosclerotic vascular disease risk
factors, and heart failure with reduced ejection fraction with and without diabetes mellitus. In addition, primary trial results have revealed that sacubitril-valsartan therapy improves cardiovascular outcomes in patients with chronic heart failure with reduced ejection fraction and post-hoc analyses suggest favorable kidney effects. A concordant pattern of kidney benefit with sacubitril-valsartan has also been observed in chronic heart failure with preserved ejection fraction. Given the complex interplay between cardiac and kidney disease and the possibility that treatments may show concordant cardio-kidney benefits, there has been recent interest to acknowledge formally, define, and utilize composite cardio-kidney outcomes in future cardiovascular trials. This review describes potential challenges in utilization of such outcomes that should be considered and addressed prior to their incorporation into such trials.

Ehteshami-Afshar, S., Mooney, L., Dewan, P., Desai, A.S., Lang, N.N., Lefkowitz, M.P., Petrie, M.C., Rizkala, A.R., Rouleau, J.L., Solomon, S.D., Swedberg, K., Shi, V.C., Zile, M.R., Packer, M., McMurray, J.J.V., Jhund, P.S. and Hawkins, N.M. (2021). “Clinical Characteristics and Outcomes of Patients With Heart Failure With Reduced Ejection Fraction and Chronic Obstructive Pulmonary Disease: Insights From PARADIGM-HF.” J Am Heart Assoc 10(4): e019238.

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Background Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure with reduced ejection fraction, associated with undertreatment and worse outcomes. New treatments for heart failure with reduced ejection fraction may be particularly important in patients with concomitant COPD. Methods and Results We examined outcomes in 8399 patients with heart failure with reduced ejection fraction, according to COPD status, in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Blocker-Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Cox regression models were used to compare COPD versus non-COPD subgroups and the effects of sacubitril/valsartan versus enalapril. Patients with COPD (n=1080, 12.9%) were older than patients without COPD (mean 67 versus 63 years; P<0.001), with similar left ventricular ejection fraction (29.9% versus 29.4%), but higher NT-proBNP (N-terminal pro-B-type natriuretic peptide; median, 1741 pg/mL versus 1591 pg/mL; P=0.01), worse functional class (New York Heart Association III/IV 37% versus 23%; P<0.001) and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (73 versus 81; P<0.001), and more congestion and comorbidity. Medical therapy was similar in patients with and without COPD except for beta-blockade (87% versus 94%; P<0.001) and diuretics (85% versus 80%; P<0.001). After multivariable adjustment, COPD was associated with higher risks of heart failure hospitalization (hazard ratio [HR], 1.32; 95% CI, 1.13-1.54), and the composite of cardiovascular death or heart failure hospitalization (HR, 1.18; 95% CI, 1.05-1.34), but not cardiovascular death (HR, 1.10; 95% CI, 0.94-1.30), or all-cause mortality (HR, 1.14; 95% CI, 0.99-1.31). COPD was also associated with higher risk of all cardiovascular hospitalization (HR, 1.17; 95% CI, 1.05-1.31) and noncardiovascular hospitalization (HR, 1.45; 95% CI, 1.29-1.64). The benefit of sacubitril/valsartan over enalapril was consistent in patients with and without COPD for all end points. Conclusions In PARADIGM-HF, COPD was associated with lower use of beta-blockers and worse health status and was an independent predictor of cardiovascular and noncardiovascular hospitalization. Sacubitril/valsartan was beneficial in this high-risk subgroup.

Butler, J., Anker, S.D., Filippatos, G., Khan, M.S., Ferreira, J.P., Pocock, S.J., Giannetti, N., Januzzi, J.L., Piña, I.L., Lam, C.S.P., Ponikowski, P., Sattar, N., Verma, S., Brueckmann, M., Jamal, W., Vedin, O., Peil, B., Zeller, C., Zannad, F. and Packer, M. (2021). “Empagliflozin and health-related quality of life outcomes in patients with heart failure with reduced ejection fraction: the EMPEROR-Reduced trial.” Eur Heart J Jan 9;ehaa1007. ]Epub ahead of print].

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AIMS: In this secondary analysis of the EMPEROR-Reduced trial, we sought to evaluate whether the benefits of empagliflozin varied by baseline health status and how empagliflozin impacted patient-reported outcomes in patients with heart failure with reduced ejection fraction. METHODS AND RESULTS: Health status was assessed by the Kansas City Cardiomyopathy Questionnaires-clinical summary score (KCCQ-CSS). The influence of baseline KCCQ-CSS (analyzed by tertiles) on the effect of empagliflozin on major outcomes was examined using Cox proportional hazards models. Responder analyses were performed to assess the odds of improvement and deterioration in KCCQ scores related to treatment with empagliflozin. Empagliflozin reduced the primary outcome of cardiovascular death or heart failure hospitalization regardless of baseline KCCQ-CSS tertiles [hazard ratio (HR) 0.83 (0.68-1.02), HR 0.74 (0.58-0.94), and HR 0.61 (0.46-0.82) for <62.5, 62.6-85.4, and ≥85.4 score tertiles, respectively; P-trend = 0.10]. Empagliflozin improved KCCQ-CSS, total symptom score, and overall summary score at 3, 8, and 12 months. More patients on empagliflozin had ≥5-point [odds ratio (OR) 1.20 (1.05-1.37)], 10-point [OR 1.26 (1.10-1.44)], and 15-point [OR 1.29 (1.12-1.48)] improvement and fewer had ≥5-point [OR 0.75 (0.64-0.87)] deterioration in KCCQ-CSS at 3 months. These benefits were sustained at 8 and 12 months and were similar for other KCCQ domains. CONCLUSION: Empagliflozin improved cardiovascular death or heart failure hospitalization risk across the range of baseline health status. Empagliflozin improved health status across various domains, and this benefit was sustained during long-term follow-up.