Research Spotlight

Zile, M. R., B. L. Claggett, M. F. Prescott, J. J. McMurray, M. Packer, J. L. Rouleau, K. Swedberg, A. S. Desai, J. Gong, V. C. Shi and S. D. Solomon (2016). “Prognostic implications of changes in n-terminal pro-b-type natriuretic peptide in patients with heart failure.” J Am Coll Cardiol 68(22): 2425-2436.

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BACKGROUND: Natriuretic peptides (NP) have prognostic value in heart failure (HF), although the clinical importance of changes in NP from baseline is unclear. OBJECTIVES: The authors assessed whether a reduction in N-terminal pro-B-type NP (NT-proBNP) was associated with a decrease in HF hospitalization and cardiovascular mortality (primary endpoint) in patients with HF and reduced ejection fraction, whether treatment with sacubitril/valsartan reduced NT-proBNP below specific partition values more than enalapril, and whether the relationship between changes in NT-proBNP and changes in the primary endpoint were dependent on assigned treatment. METHODS: In PARADIGM-HF (Prospective Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] with ACEI [Angiotensin-Converting-Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial), baseline NT-proBNP was measured in 2,080 patients; 1,292 had baseline values >1,000 pg/ml and were reassessed at 1 and 8 months. We related change in NT-proBNP to outcomes. RESULTS: One month after randomization, 24% of the baseline NT-proBNP levels 1,000 pg/ml had fallen to /=1,000 pg/ml. Risk of the primary endpoint was 59% lower in patients with a fall in NT-proBNP to /=1,000 pg/ml than in those without such a fall. In sacubitril/valsartan-treated patients, median NT-proBNP was significantly lower 1 month after randomization than in enalapril-treated patients, and it fell to =1,000 pg/ml in 31% versus 17% of patients treated with sacubitril/valsartan and enalapril, respectively. There was no significant interaction between treatment and the relationship between change in NT-proBNP and the subsequent risk of the primary endpoint. CONCLUSIONS: Patients who attained a significant reduction in NT-proBNP had a lower subsequent rate of cardiovascular death or HF hospitalization independent of the treatment group. Treatment with sacubitril/valsartan was nearly twice as likely as enalapril to reduce NT-proBNP to values /=1,000 pg/ml. (Prospective Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] with ACEI [Angiotensin-Converting-Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial)

Zimmerman, R. K., M. P. Nowalk, J. Chung, M. L. Jackson, L. A. Jackson, J. G. Petrie, A. S. Monto, H. Q. McLean, E. A. Belongia, M. Gaglani, K. Murthy, A. M. Fry and B. Flannery (2016). “2014-2015 influenza vaccine effectiveness in the united states by vaccine type.” Clin Infect Dis 63(12): 1564-1573.

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BACKGROUND: Circulating A/H3N2 influenza viruses drifted significantly after strain selection for the 2014-2015 vaccines. Also in 2014-2015, the Advisory Committee on Immunization Practices recommended preferential use of live attenuated influenza vaccine (LAIV) over inactivated influenza vaccine (IIV) among children aged 2-8 years. METHODS: Vaccine effectiveness (VE) across age groups and vaccine types was examined among outpatients with acute respiratory illness at 5 US sites using a test-negative design, that compared the odds of vaccination among reverse transcription polymerase chain reaction-confirmed influenza positives and negatives. RESULTS: Of 9311 enrollees with complete data, 7078 (76%) were influenza negative, 1840 (19.8%) were positive for influenza A (A/H3N2, n = 1817), and 395 (4.2%) were positive for influenza B (B/Yamagata, n = 340). The overall adjusted VE was 19% (95% confidence interval [CI], 10% to 27%) and was statistically significant in all age strata except those aged 18-64 years. The adjusted VE of 6% (95%CI, -5% to 17%) against A/H3N2-associated illness was not statistically significant, unlike VE for influenza B/Yamagata, which was 55% (95%CI, 43% to 65%). Among those aged 2-8 years, VE against A/H3N2 was 15% (95%CI, -16% to 38%) for IIV and -3% (CI, -50% to 29%) for LAIV; VE against B/Yamagata was 40% (95%CI, -20% to 70%) for IIV and 74% (95%CI, 25% to 91%) for LAIV. CONCLUSIONS: The 2014-2015 influenza vaccines offered little protection against the predominant influenza A/H3N2 virus but were effective against influenza B. Preferential use of LAIV among young children was not supported.

Alias, T., P. Hoof, M. Lee and D. Davis (2016). “Wernicke’s encephalopathy after conversion from sleeve gastrectomy to gastric bypass.” Surg Obes Relat Dis 12(10): e89-e91.

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A 22-year-old white female presented to the emergency room for numbness from her breasts to her knees bilaterally, confusion, and memory loss over the preceding 2 days. Two weeks before presentation, she developed vertigo and gait instability that were evaluated at her local urgent care clinic. She was diagnosed with benign positional vertigo after a computed tomography (CT) scan of the brain revealed no abnormalities and was prescribed a 5-day course of meclizine. Further investigation revealed that she had undergone a sleeve gastrectomy (SG) that was converted to a Roux-en-Y gastric bypass (RYGB) 1 month previously because she had developed recurrent vomiting after the SG due to a stricture in the superior portion of the sleeve that was not relieved by balloon dilation. However, she continued having intractable vomiting after the RYGB, which limited her dietary intake . . . Given her history of recent RYGB and vomiting, further laboratory studies were obtained to evaluate for vitamin deficiency. An empiric regimen that included intravenous thiamine bolus at a dose of 100 mg; oral vitamins A, B12, C, D, and E; and folic acid was started in the meanwhile. Magnetic resonance imaging (MRI) of the brain revealed increased T2 signal symmetrically in the medial thalami and enhancement of bilateral mammillary bodies compatible with Wernicke encephalopathy . . . Wernicke encephalopathy after bariatric surgery is an underreported condition that mandates prompt treatment to avoid irreversible neurologic damage and death. In our case, the patient underwent SG and subsequent RYGB due to failure of the sleeve. She developed Wernicke encephalopathy due to vomiting after the bypass surgery, which was evident through low thiamine levels in her blood and brain MRI findings. By discharge, her symptoms had partially resolved with the administration of parenteral thiamine. With the rising number of bariatric surgeries, it is imperative for clinicians to promptly recognize Wernicke encephalopathy so that treatment can be initiated without delay. (Excerpt from text, p. e89-e90.)

Askar, M., R. Sobecks, T. Wang, M. Haagenson, N. Majhail, A. Madbouly, D. Thomas, A. Zhang, K. Fleischhauer, K. Hsu, M. Verneris, S. J. Lee, S. R. Spellman and M. Fernandez-Vina (2016). “Mhc class i chain-related gene a (mica) donor-recipient mismatches and mica-129 polymorphism in unrelated donor hematopoietic cell transplantations has no impact on outcomes in acute lymphoblastic leukemia, acute myeloid leukemia, or myelodysplastic syndrome: A center for international blood and marrow transplant research study.” Biol Blood Marrow Transplant: 2016 Dec. [Epub ahead of print].

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Single-center studies have previously reported associations of MHC Class I Chain-Related Gene A (MICA) polymorphisms and donor-recipient MICA mismatching with graft-versus-host disease (GVHD) after unrelated donor hematopoietic cell transplantation (HCT). In this study, we investigated the association of MICA polymorphism (MICA-129, MM versus MV versus VV) and MICA mismatches after HCT with 10/10 HLA-matched (n = 552) or 9/10 (n = 161) unrelated donors. Included were adult patients with a first unrelated bone marrow or peripheral blood HCT for acute lymphoblastic leukemia, acute myeloid leukemia, or myelodysplastic syndrome that were reported to the Center for International Blood and Marrow Transplant Research between 1999 and 2011. Our results showed that neither MICA mismatch nor MICA-129 polymorphism were associated with any transplantation outcome (P < .01), with the exception of a higher relapse in recipients of MICA-mismatched HLA 10/10 donors (hazard ratio [HR], 1.7; P = .003). There was a suggestion of association between MICA mismatches and a higher risk of acute GVHD grades II to IV (HR, 1.4; P = .013) There were no significant interactions between MICA mismatches and HLA matching (9/10 versus 10/10). In conclusion, the findings in this cohort did not confirm prior studies reporting that MICA polymorphism and MICA mismatches were associated with HCT outcomes.

Abramowitz, Y., Y. Kazuno, T. Chakravarty, H. Kawamori, Y. Maeno, D. Anderson, Z. Allison, G. Mangat, W. Cheng, A. Gopal, H. Jilaihawi, M. J. Mack and R. R. Makkar (2016). “Concomitant mitral annular calcification and severe aortic stenosis: Prevalence, characteristics and outcome following transcatheter aortic valve replacement.” Eur Heart J: 2016 Dec [Epub ahead of print].

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AIMS: Calcified aortic stenosis (AS) and mitral annular calcification (MAC) have certain similar etiology and pathophysiological mechanisms. MAC is frequently encountered in pre-procedural computed tomography (CT) imaging of patients that undergo transcatheter aortic valve replacement (TAVR), but its prognostic implications for these patients have not been thoroughly investigated. This study sought to evaluate the prevalence of MAC among patients with severe AS and to assess the clinical implications of MAC on these patients during and following TAVR. METHODS AND RESULTS: Consecutive patients that underwent TAVR were compared according to the existence of MAC and its severity in pre-TAVR CT scans. From the entire cohort of 761 patients, 49.3% had MAC, and 50.7% did not have MAC. Mild MAC was present in 231 patients (30.4%), moderate MAC in 72 patients (9.5%), and severe MAC in 72 patients (9.5%). Thirty-day mortality and major complications were similar between patients with and without MAC. In a multivariable survival analysis, severe MAC was found to be an independent strong predictor of overall mortality following TAVR (all-cause mortality: hazards ratio [HR] 1.95, 95% confidence interval [CI] 1.24-3.07, P = 0.004; cardiovascular mortality: HR 2.35, 95% CI 1.19-4.66; P = 0.01). Severe MAC was also found to be an independent strong predictor of new permanent pacemaker implantation (PPI) after TAVR (OR 2.83, 95% CI 1.08-7.47; P = 0.03). CONCLUSION: Half of the patients with severe AS evaluated for TAVR were found to have MAC. Severe MAC is associated with increased all-cause and cardiovascular mortality and with conduction abnormalities following TAVR and should be included in future risk stratification models for TAVR.