Peter A. McCullough M.D.

Sudhakaran, S. and P. A. McCullough (2019). “Common laboratory parameters as indicators of multi-organ dysfunction in acute heart failure.” Eur J Heart Fail Apr 11. [Epub ahead of print].

Full text of this article.

Understanding of diagnosis, classification, pathophysiology, prognosis, and treatment of heart failure remains of major interest in clinical cardiology. There are approximately 23 million people with heart failure worldwide, and that estimate is expected to increase by roughly 772 000 by the year 2040. Patients on average have a 5‐year mortality of 50% after the diagnosis is established, most commonly in the setting of hospitalization for acute heart failure (AHF), and clinically, prognostication when admitted to the inpatient setting is challenging. In this issue of the Journal, the retrospective analysis by Zymliński et al.demonstrates how multi‐organ dysfunction as reflected by commonly measured laboratory parameters impacts AHF outcomes. The authors evaluated worsening heart failure and 1‐year mortality in AHF stratified by laboratory evidence of concomitant multi‐organ failure (namely cardiac, kidney, and liver injury/dysfunction) . . . The data presented by Zymliński et al. incites numerous areas of future direction that warrant further investigation. The sample size was small at 284 for multiple comparisons, and thus, it would be beneficial to validate these findings in a larger, prospective cohort. Finally, utilizing these data to delineate a scoring system for prognostication and to assess disease acuity, similar to Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) or Sequential Organ Failure Assessment (SOFA), but tailored specifically for AHF, would be a practical tool for those involved in the care of patients with AHF. (Excerpts from text, p. 1, 2; no abstract available; commenting on a study in the same issue, Zymliński R, et al., Multi‐organ dysfunction/injury on admission identifies acute heart failure patients at high risk of poor outcome; no abstract available.)

Rangaswami, J., S. Soman and P. A. McCullough (2019). “Key Updates in Cardio-Nephrology from 2018: Springboard to a Bright Future.” Cardiorenal Med 9(4): 222-228.

Full text of this article.

Overall, the field of cardio-nephrology made significant strides in 2018 with novel approaches to the dilemma of pathological heart-kidney interactions, a problem well described and rooted in history. The increasing relevance of this interface was recognized appropriately in publications as well as national conferences in cardiology and nephrology. Notably, collaborative efforts between key organizations such as the American Heart Association (Kidney Council), the American Society of Nephrology, and the Cardiorenal Society of America have been successful in highlighting the importance of this niche field. In a welcome trend deviating from the well-documented exclusion of patients with kidney disease from cardiovascular trials, key trials in cardio-renal medicine such as the International Study of Comparative Health Effectiveness of Medical and Invasive Approaches-CKD (NCT01985360), the Coronary Artery Disease Screening in Kidney Transplant Candidates trial (CARSK) (NCT02082483), the RENAL-AF trial (NCT02942407), and the STOP ACEi trial (SRCTN62869767) will report in the near future, allowing important questions to be answered with randomized controlled data in cardiorenal medicine. Obtaining high-quality data unique to this subset of patients is the biggest service that can ultimately be provided by cardiologists and nephrologists caring for patients with cardiorenal disease. Given the widening scope of the field of cardio-nephrology, efforts to create center-specific cardio-renal teams to accelerate and spearhead clinical care and research in this field are necessary to be able to train physician- scientists of the future to integrate the care of these patients in the best possible way. To that end, the growth of the field witnessed in 2018 is very encouraging. We look forward to participating in the continuation of the growth of cardio-nephrology in 2019 and beyond, to provide the best evidence-based multidisciplinary care for this vulnerable group of patients. (Excerpt from text, p. 226; no abstract available.)

Rangaswami, J., R. O. Mathew, R. Parasuraman, E. Tantisattamo, M. Lubetzky, S. Rao, M. S. Yaqub, K. A. Birdwell, W. Bennett, P. Dalal, R. Kapoor, E. V. Lerma, M. Lerman, N. McCormick, S. Bangalore, P. A. McCullough and D. M. Dadhania (2019). “Cardiovascular disease in the kidney transplant recipient: epidemiology, diagnosis and management strategies.” Nephrol Dial Transplant 34(5): 760-773.

Full text of this article.

Kidney transplantation (KT) is the optimal therapy for end-stage kidney disease (ESKD), resulting in significant improvement in survival as well as quality of life when compared with maintenance dialysis. The burden of cardiovascular disease (CVD) in ESKD is reduced after KT; however, it still remains the leading cause of premature patient and allograft loss, as well as a source of significant morbidity and healthcare costs. All major phenotypes of CVD including coronary artery disease, heart failure, valvular heart disease, arrhythmias and pulmonary hypertension are represented in the KT recipient population. Pre-existing risk factors for CVD in the KT recipient are amplified by superimposed cardio-metabolic derangements after transplantation such as the metabolic effects of immunosuppressive regimens, obesity, posttransplant diabetes, hypertension, dyslipidemia and allograft dysfunction. This review summarizes the major risk factors for CVD in KT recipients and describes the individual phenotypes of overt CVD in this population. It highlights gaps in the existing literature to emphasize the need for future studies in those areas and optimize cardiovascular outcomes after KT. Finally, it outlines the need for a joint ‘cardio-nephrology’ clinical care model to ensure continuity, multidisciplinary collaboration and implementation of best clinical practices toward reducing CVD after KT.

House, A. A., C. Wanner, M. J. Sarnak, I. L. Pina, C. W. McIntyre, P. Komenda, B. L. Kasiske, A. Deswal, C. R. deFilippi, J. G. F. Cleland, S. D. Anker, C. A. Herzog, M. Cheung, D. C. Wheeler, W. C. Winkelmayer and P. A. McCullough (2019). “Heart failure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.” Kidney Int. Apr 30. [Epub ahead of print].

Full text of this article.

The incidence and prevalence of heart failure (HF) and chronic kidney disease (CKD) are increasing, and as such a better understanding of the interface between both conditions is imperative for developing optimal strategies for their detection, prevention, diagnosis, and management. To this end, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international, multidisciplinary Controversies Conference titled Heart Failure in CKD. Breakout group discussions included (i) HF with preserved ejection fraction (HFpEF) and nondialysis CKD, (ii) HF with reduced ejection fraction (HFrEF) and nondialysis CKD, (iii) HFpEF and dialysis-dependent CKD, (iv) HFrEF and dialysis-dependent CKD, and (v) HF in kidney transplant patients. The questions that formed the basis of discussions are available on the KDIGO website http://kdigo.org/conferences/heart-failure-in-ckd/, and the deliberations from the conference are summarized here.

Vasudevan, A., J. W. Choi, G. A. Feghali, S. R. Lander, L. Jialiang, J. M. Schussler, R. C. Stoler, R. C. Vallabhan, C. E. Velasco and P. A. McCullough (2019). “Event dependence in the analysis of cardiovascular readmissions postpercutaneous coronary intervention.” J Investig Med Jan 18. [Epub ahead of print].

Full text of this article.

Recurrent hospitalizations are common in longitudinal studies; however, many forms of cumulative event analyses assume recurrent events are independent. We explore the presence of event dependence when readmissions are spaced apart by at least 30 and 60 days. We set up a comparative framework with the assumption that patients with emergency percutaneous coronary intervention (PCI) will be at higher risk for recurrent cardiovascular readmissions than those with elective procedures. A retrospective study of patients who underwent PCI (January 2008-December 2012) with their follow-up information obtained from a regional database for hospitalization was conducted. Conditional gap time (CG), frailty gamma (FG) and conditional frailty models (CFM) were constructed to evaluate the dependence of events. Relative bias (%RB) in point estimates using CFM as the reference was calculated for comparison of the models. Among 4380 patients, emergent cases were at higher risk as compared with elective cases for recurrent events in different statistical models and time-spaced data sets, but the magnitude of HRs varied across the models (adjusted HR [95% CI]: all readmissions [unstructured data]-CG 1.16 [1.09 to 1.22], FG 1.45 [1.33 to 1.57], CFM 1.24 [1.16 to 1.32]; 30-day spaced-CG1.14 [1.08 to 1.21], FG 1.28 [1.17 to 1.39], CFM 1.17 [1.10 to 1.26]; and 60-day spaced-CG 1.14 [1.07 to 1.22], FG 1.23 [1.13 to 1.34] CFM 1.18 [1.09 to 1.26]). For all of the time-spaced readmissions, we found that the values of %RB were closer to the conditional models, suggesting that event dependence dominated the data despite attempts to create independence by increasing the space in time between admissions. Our analysis showed that independent of the intercurrent event duration, prior events have an influence on future events. Hence, event dependence should be accounted for when analyzing recurrent events and challenges contemporary methods for such analysis.