Research Spotlight

Vidic, A., J. E. Shuster, Z. D. Goff, A. Godishala, S. M. Joseph, J. T. Chibnall and P. J. Hauptman (2019). “Vasopressin antagonism for decompensated right-sided heart failure.” Int J Cardiol 274: 245-247.

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BACKGROUND: Targeted treatment for decompensated right heart failure (RHF) with or without left heart failure is lacking. Vasopressin antagonists (vaptans) may offer an option by increasing urine output and fluid mobilization when used in acute decompensated RHF without impacting blood pressure or renal function, both common complications of loop diuretics. METHODS AND RESULTS: We searched electronic medical records from 2 institutions over 4years for patients with RHF treated with vaptans. Urine output, creatinine, BUN and sodium, 1day pre- versus 1day post-vaptan initiation were compared. Baseline (admission) pre-vaptan values for patients with RHF who met inclusion criteria (n=112) were RAP, median (interquartile range)=19 (13-24) mmHg; cardiac index, mean+/-standard deviation=1.8+/-0.4L/min/m2; BNP, 1078 (523-1690) pg/ml; creatinine clearance of 51 (39-69) ml/min, BUN, 37 (26-54) mg/dl, and serum [Na+] 132 (126-135) mEq/L. Most patients (n=103/112) received intravenous inotrope (prior to vaptan, n=91). Overall length of stay was 27 (16-43) days. Vaptan treatment (90% tolvaptan, 10% conivaptan) was associated with increased 24h urine output, 1517 (906-2394) vs 2337 (1425-3744) mL, p=0.005, and [Na+], 127 (124-130) vs 130 (126-135) mEq/L, p=0.001, without significant change in Cr or BUN. Furosemide IV dose equivalent decreased or remained unchanged in 75% of patients at 24h and 64% at 72h compared to the 24h prior to vaptan use. CONCLUSION: Vaptans were associated with a significant increase in urine output and serum sodium with an apparent reduction or stabilization of furosemide equivalent dosing in the early treatment period in patients with decompensated RHF. Vaptans may offer a management option for patients failing conventional diuretic-based treatment.

Tran, H. V., N. A. Erskine, H. L. Nguyen, D. D. McManus, H. H. Awad, C. I. Kiefe and R. J. Goldberg (2019). “Increase in white blood cell count is associated with the development of atrial fibrillation after an acute coronary syndrome.” Int J Cardiol 274: 138-143.

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BACKGROUND: Evidence linking an elevated white blood cell count (WBCC), a marker of inflammation, to the development of atrial fibrillation (AF) after an acute coronary syndrome (ACS) is limited. We examined the association between WBCC at hospital admission, and changes in WBCC during hospitalization, with the development of new-onset AF during hospitalization for an ACS. METHODS: Development of AF was based on typical ECG changes in a systematic review of hospital medical records. Increase in WBCC was calculated as the difference between maximal WBCC during hospitalization and WBCC at hospital admission. Multiple logistic regression analysis was used to adjust for several potentially confounding demographic and clinical variables in examining the association between WBCC, and changes over time therein, with the occurrence of AF. RESULTS: The median age of study patients (n=1325) was 60years, 31.8% were women, and 80.1% were non-Hispanic whites. AF developed in 7.3% of patients with an ACS. Patients who developed AF, as compared with those who did not, had a similar WBCC at admission, but a greater increase in WBCC during hospitalization (6.0×10(9)cell/L vs. 2.7×10(9) cell/L, p<0.001). After adjusting for several potentially confounding factors, an increase in WBCC was associated with the development of AF. This association was observed in patients with different ACS subtypes, types of treatment received, and according to time of acute symptom onset. CONCLUSION: Increase in the WBCC during hospitalization for an ACS should be further studied as a potentially simple predictor for new-onset AF in these patients.

Tolia, V. N., T. M. Bahr, M. M. Bennett, G. Martin, R. G. Greenberg, M. M. Laughon and R. H. Clark (2018). “The Association of Hydrocortisone Dosage on Mortality in Infants Born Extremely Premature.” J Pediatr Dec 21. [Epub ahead of print].

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OBJECTIVE: To characterize common dosing strategies and to investigate the association between hydrocortisone dosage and in-hospital mortality in infants born extremely premature. STUDY DESIGN: We performed a retrospective review of a cohort of infants born less-than-or-equal-to 30 weeks’ gestational age from 2010 to 2016 from the Pediatrix Clinical Data Warehouse who received hydrocortisone in the first 14 postnatal days. Infants were divided by initial hydrocortisone dosage (high: >2 mg/kg/d vs low: less-than-or-equal-to 2 mg/kg/d). Baseline characteristics and medication coexposures were compared and mortality was evaluated in a multivariable analysis. RESULTS: A total of 1427 infants were included, 733 with high dosage (51%) and 694 with low dosage (49%). The groups were similar with regard to baseline characteristics. Infants in the high-dosage group had significantly more exposure to any vasopressors (89% vs 84%, P < .001) and greater mortality (50% vs 23%, P < .001) vs the low-dosage group. High dosage of hydrocortisone was associated independently with death (aOR 3.27, 95% CI 2.47-4.34, P < .001) in a multivariable regression analysis including propensity scoring for dosage and other covariates. When the cohort was split into quartiles by dosage, mortality was lower in the lower-dosage quartiles compared with the higher quartiles (mortality range 13%-50%). CONCLUSIONS: In this retrospective analysis of a large sample of infants born premature, increased initial hydrocortisone dosage was associated independently with increased mortality. Trials to assess the impact of hydrocortisone dosage in this population are needed.

Thourani, V. H., S. M. O’Brien, J. J. Kelly, D. J. Cohen, E. D. Peterson, M. J. Mack, D. M. Shahian, F. L. Grover, E. J. Carroll, J. M. Brennan, J. Forcillo, S. V. Arnold, S. Vemulapalli, S. Fitzgerald, D. R. Holmes, J. E. Bavaria and F. H. Edwards (2018). “Development and Application of a Risk Prediction Model for In-Hospital Stroke After Transcatheter Aortic Valve Replacement – A Report from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry.” Ann Thorac Surg Dec 7. [Epub ahead of print].

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BACKGROUND: Stroke is a serious complication following transcatheter aortic valve replacement (TAVR), yet predictive models are not available. A new risk model for in-hospital stroke following TAVR was developed and used to estimate site-specific performance. METHODS: We included 97,600 TAVR procedures from 521 sites in the STS/ACC Transcatheter Valve Therapy (TVT) Registry from July 2014 through June 2017. Association between baseline covariates and in-hospital stroke was estimated by logistic regression. Discrimination was evaluated by C statistic. Calibration was tested internally via cross validation. Hierarchical modeling was used to estimate risk-adjusted site-specific performance. RESULTS: Median age was 82 years, 44,926 (46.0%) were female, and 1,839 (1.9%) had in-hospital stroke. Covariates associated with stroke (odds ratio) included transapical access (1.44), access excluding transapical and transfemoral (1.77), prior stroke (1.57), prior TIA (1.50), pre-procedural shock, inotropes or mechanical assist device (1.48), smoking (1.28), porcelain aorta (1.23), peripheral arterial disease (1.21), age per 5 years (1.11), glomerular filtration rate per 5 ml/min (0.97), body surface area per m(2) (0.55 male; 0.43 female), and prior aortic valve (0.78) and non-aortic valvular (0.42) procedures. The C statistic was 0.622. Calibration curves demonstrated agreement between observed and expected stroke rates. Hierarchical modeling showed 10 centers (1.9%) with significantly higher odds ratios for in-hospital stroke than their peers. CONCLUSIONS: A risk model for in-hospital stroke following TAVR was developed from the STS/ACC TVT Registry and used to estimate site-specific stroke performance. This model can serve as a valuable resource for quality improvement, clinical decision-making, and patient counseling.

Spratlen, M. J., M. Grau-Perez, J. G. Umans, J. Yracheta, L. G. Best, K. Francesconi, W. Goessler, T. Bottiglieri, M. V. Gamble, S. A. Cole, J. Zhao and A. Navas-Acien (2019). “Targeted metabolomics to understand the association between arsenic metabolism and diabetes-related outcomes: Preliminary evidence from the Strong Heart Family Study.” Environ Res 168: 146-157.

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BACKGROUND: Inorganic arsenic exposure is ubiquitous and both exposure and inter-individual differences in its metabolism have been associated with cardiometabolic risk. A more efficient arsenic metabolism profile (lower MMA%, higher DMA%) has been associated with reduced risk for arsenic-related health outcomes. This profile, however, has also been associated with increased risk for diabetes-related outcomes. OBJECTIVES: The mechanism behind these conflicting associations is unclear; we hypothesized the one-carbon metabolism (OCM) pathway may play a role. METHODS: We evaluated the influence of OCM on the relationship between arsenic metabolism and diabetes-related outcomes (HOMA2-IR, waist circumference, fasting plasma glucose) using metabolomic data from an OCM-specific and P180 metabolite panel measured in plasma, arsenic metabolism measured in urine, and HOMA2-IR and FPG measured in fasting plasma. Samples were drawn from baseline visits (2001-2003) in 59 participants from the Strong Heart Family Study, a family-based cohort study of American Indians aged >/=14 years from Arizona, Oklahoma, and North/South Dakota. RESULTS: In unadjusted analyses, a 5% increase in DMA% was associated with higher HOMA2-IR (geometric mean ratio (GMR)= 1.13 (95% CI: 1.03, 1.25)) and waist circumference (mean difference=3.66 (0.95, 6.38). MMA% was significantly associated with lower HOMA2-IR and waist circumference. After adjustment for OCM-related metabolites (SAM, SAH, cysteine, glutamate, lysophosphatidylcholine 18.2, and three phosphatidlycholines), associations were attenuated and no longer significant. CONCLUSIONS: These preliminary results indicate that the association of lower MMA% and higher DMA% with diabetes-related outcomes may be influenced by OCM status, either through confounding, reverse causality, or mediation.