Peter A. McCullough M.D.

McCullough, P. A., G. David, T. M. Todoran, E. S. Brilakis, M. P. Ryan and C. Gunnarsson (2018). “Iso-osmolar contrast media and adverse renal and cardiac events after percutaneous cardiovascular intervention.” J Comp Eff Res 7(4): 331-341.

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AIM: To assess the relationship between type of contrast media (CM), iso-osmolar contrast media (IOCM) or low-osmolar contrast media (LOCM), and major adverse renal and cardiovascular events (MARCE). MATERIALS & METHODS: Coronary or peripheral angioplasty visits were stratified into CM cohorts: IOCM or LOCM. Multivariable regression analysis used hospital fixed effects to assess the relationship between MARCE events and type of CM. RESULTS: Among 333,533 visits (357 hospitals), the incidence of MARCE was 7.41%. After controlling for observable and unobservable time invariant within-hospital characteristics, administration of IOCM versus LOCM was associated with a 0.69% absolute and 9.32% relative risk reduction in MARCE rate. CONCLUSION: Our study indicates that as compared with LOCM, IOCM may be associated with reduction of MARCE events in coronary or peripheral angioplasty patients.

Keuffel, E., P. A. McCullough, T. M. Todoran, E. S. Brilakis, S. R. Palli, M. P. Ryan and C. Gunnarsson (2018). “The effect of major adverse renal cardiovascular event (MARCE) incidence, procedure volume, and unit cost on the hospital savings resulting from contrast media use in inpatient angioplasty.” J Med Econ 21(4): 356-364.

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OBJECTIVE: To determine the net economic impact of switching from low-osmolar contrast media (LOCM) to iso-osmolar contrast media (IOCM; iodixanol) in patients undergoing inpatient coronary or peripheral angioplasty in the United States (US). METHODS: A budget impact model (BIM) was developed from a hospital perspective. Nationally representative procedural and contrast media prevalence rates, along with MARCE (major adverse renal cardiovascular event) incidence and episode-related cost data were derived from Premier Hospital Data (October 2014 to September 2015). A previously estimated relative risk reduction in MARCE associated with IOCM usage (9.3%) was applied. The higher cost of IOCM was included when calculating the net impact estimates at the aggregate, hospital type, and per hospital levels. One-way (+/-25%) and probabilistic sensitivity analyses identified the model’s most important inputs. RESULTS: Based on weighted analysis, 513,882 US inpatient angioplasties and 35,610 MARCE cases were estimated annually. Switching to an “IOCM only” strategy from a “LOCM only” strategy increases contrast media cost, but prevents 2,900 MARCE events. The annual budget impact was an estimated saving of $30.71 million, aggregated across all US hospitals, $6,316 per hospital, or $60 per procedure. Net savings were maintained across all univariate sensitivity analyses. While MARCE/event-free cost differential was the most important factor driving total net savings for hospitals in the Northeast and West, procedural volume was important in the Midwest and rural locations. CONCLUSIONS: Switching to an “IOCM only” strategy from a “LOCM only” approach yields substantial net global savings to hospitals, both at the national level and within hospital sub-groups. Hospital administrators should maintain awareness of the factors that are likely to be more influential for their hospital and recognize that purchasing on the basis of lower contrast media cost may result in higher overall costs for patients undergoing inpatient angioplasty.

Rangaswami, J., M. Naranjo and P. A. McCullough (2018). “Preeclampsia as a Form of Type 5 Cardiorenal Syndrome: An Underrecognized Entity in Women’s Cardiovascular Health.” Cardiorenal Med 8(2): 160-172.

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BACKGROUND: Preeclampsia is a multisystem vascular disorder of pregnancy that remains a leading cause of maternal and fetal morbidity and mortality. Preeclampsia remains an underrecognized risk factor for future cardiovascular and kidney disease in women and represents the confluence of preexisting vascular risk factors with superimposed endothelial injury from placental mediated anti-angiogenic factors. SUMMARY: This review highlights the close relationship between preeclampsia and future cardiovascular and kidney disease. It describes the pathophysiology and current understanding of biomarkers that form the molecular signature for long-term endothelial dysfunction in preeclamptic women. Finally, it describes strategies for early identification and management of women with preeclampsia with elevated risk for cardiovascular and kidney disease. Key Messages: Future rigorous studies on cardiovascular risk modification in this phenotype of disease are essential to reduce the burden of cardiovascular and kidney disease, in women with preeclampsia.

Ostermann, M., P. A. McCullough, L. G. Forni, S. M. Bagshaw, M. Joannidis, J. Shi, K. Kashani, P. M. Honore, L. S. Chawla and J. A. Kellum (2018). “Kinetics of Urinary Cell Cycle Arrest Markers for Acute Kidney Injury Following Exposure to Potential Renal Insults.” Crit Care Med 46(3): 375-383.

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OBJECTIVES: Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 predict the development of acute kidney injury following renal insults of varied aetiology. To aid clinical interpretation, we describe the kinetics of biomarker elevations around an exposure. DESIGN: In an ancillary analysis of the multicenter SAPPHIRE study, we examined the kinetics of the urinary [tissue inhibitor of metalloproteinase-2]*[insulin-like growth factor binding protein 7] in association with exposure to common renal insults (major surgery, IV radiocontrast, vancomycin, nonsteroidal anti-inflammatory drugs, and piperacillin/tazobactam). SETTING: Thirty-five sites in North America and Europe between September 2010 and June 2012. PATIENTS: Seven hundred twenty-three critically ill adult patients admitted to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared the urinary [tissue metalloproteinase-2]*[insulin growth factor binding protein 7] kinetics from the day prior to exposure up to 5 days after exposure in patients developing acute kidney injury stage 2-3, stage 1, or no acute kidney injury by Kidney Disease Improving Global Outcome criteria. Among the 723 patients, 679 (94%) had at least one, 70% had more than one, and 35% had three or more exposures to a known renal insult. There was a significant association between cumulative number of exposures up to study day 3 and risk of acute kidney injury (p = 0.02) but no association between the specific type of exposure and acute kidney injury (p = 0.22). With the exception of radiocontrast, patients who developed acute kidney injury stage 2-3 after one of the five exposures, had a clear rise and fall of urinary [tissue inhibitor of metalloproteinase-2]*[insulin-like growth factor binding protein 7] from the day of exposure to 24-48 hours later. In patients without acute kidney injury, there was no significant elevation in urinary [tissue inhibitor of metalloproteinase-2]*[insulin-like growth factor binding protein 7]. CONCLUSIONS: Exposure to potential renal insults is common. In patients developing acute kidney injury stage 2-3, the kinetics of urinary [tissue inhibitor of metalloproteinase-2]*[insulin-like growth factor binding protein 7] matched the exposure except in the case of radiocontrast.

Tecson, K. M., D. Brown, J. W. Choi, G. Feghali, G. V. Gonzalez-Stawinski, B. L. Hamman, R. Hebeler, S. R. Lander, B. Lima, S. Potluri, J. M. Schussler, R. C. Stoler, C. Velasco and P. A. McCullough (2018). “Major Adverse Renal and Cardiac Events Following Coronary Angiography and Cardiac Surgery.” Ann Thorac Surg. Feb 2. [Epub ahead of print].

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BACKGROUND: Patients at high risk for developing post-procedural complications may receive iodixanol, an iso-osmolar contrast, during coronary angiography to minimize the risk of renal toxicity. For those who additionally require cardiac surgery, the wait-time between angiography and surgery may be a modifiable factor capable of mitigating poor surgical outcomes; however, there have been inconsistsent reports regarding the optimal wait-time. We sought to determine the effects of wait time between angiogram and cardiac surgery, as well as contrast induced acute injury (CI-AKI) on the development of major adverse renal and cardiac events (MARCE). METHODS: We merged datasets to identify adults who underwent coronary angiography with iodixanol and subsequent cardiac surgery. RESULTS: Of 965 patients, 126 (13.1%) developed CI-AKI; 133 (13.8%) experienced MARCE within 30 days and 253 (26.2%) within 1 year of surgery. After adjusting for CI-AKI, age, and Thakar acute renal failure score, the effect of wait-time lost significance for the full cohort, but remained for the 654 who had coronary artery bypass grafting. Those with coronary artery bypass grafting within 1 day of coronary angiography had an approximate 2-fold increase in risk of MARCE (30-day hazard ratio =2.13, 95% confidence interval 1.16-3.88, p=0.014; 1-year hazard ratio =2.07, 95% confidence interval 1.32, 3.23, p = 0.002) compared to those who waited 5 or more days. CONCLUSIONS: Patients who suffered CI-AKI and had cardiac surgery within 1 day of angiography had increased risk of MARCE.