Mortality Risk Assessment Using CHA(2)DS(2)-VASc Scores in Patients Hospitalized With Coronavirus Disease 2019 Infection.

Early risk stratification for complications and death related to Coronavirus disease 2019 (COVID-19) infection is needed. Because many patients with COVID-19 who developed acute respiratory distress syndrome have diffuse alveolar inflammatory damage associated with microvessel thrombosis, we aimed to investigate a common clinical tool, the CHA(2)DS(2)-VASc, to aid in the prognostication of outcomes for COVID-19 patients. We analyzed consecutive patients from the multicenter observational CORACLE registry, which contains data of patients hospitalized for COVID-19 infection in 4 regions of Italy, according to data-driven tertiles of CHA(2)DS(2)-VASc score. The primary outcomes were inpatient death and a composite of inpatient death or invasive ventilation. Of 1045 patients in the registry, 864 (82.7%) had data available to calculate CHA(2)DS(2)-VASc score and were included in the analysis. Of these, 167 (19.3%) died, 123 (14.2%) received invasive ventilation, and 249 (28.8%) had the composite outcome. Stratification by CHA(2)DS(2)-VASc tertiles (T1: ≤1; T2: 2 to 3; T3: ≥4) revealed increases in both death (8.1%, 24.3%, 33.3%, respectively; p <0.001) and the composite end point (18.6%, 31.9%, 43.5%, respectively; p <0.001). The odds ratios for mortality and the composite end point for T2 patients versus T1 CHA(2)DS(2)-VASc score were 3.62 (95% CI:2.29 to 5.73,p <0.001) and 2.04 (95% CI:1.42 to 2.93, p <0.001), respectively. Similarly, the odds ratios for mortality and the composite end point for T3 patients versus T1 were 5.65 (95% CI:3.54 to 9.01, p <0.001) and 3.36 (95% CI:2.30 to 4.90,p <0.001), respectively. In conclusion, among Italian patients hospitalized for COVID-19 infection, the CHA(2)DS(2)-VASc risk score for thromboembolic events enhanced the ability to achieve risk stratification for complications and death.

The economic impact of clinically significant tricuspid regurgitation in a large, administrative claims database.

Aim: This study aimed to quantify the healthcare burden of clinically significant tricuspid regurgitation (TR) in patients with and without heart failure (HF).Materials and Methods: Data were from the IBM MarketScan Research Databases from October 2011 to September 2016. Eligible patients met the following inclusion criteria: age ≥18 with a TR diagnosis, 12 months pre (baseline), and 6 months post (landmark) medical enrollment. The landmark period was used to categorize TR severity, defined as a record of pulmonary hypertension with ascites, lower extremity edema or hepatic insufficiency, or tricuspid valve surgery. Cohorts were defined based on TR etiology and severity: (1) no HF and no clinically significant TR; (2) HF with no clinically significant TR; (3) no HF with clinically significant TR; and (4) HF with clinically significant TR. Outcomes of interest were all-cause hospitalizations, hospital days, and expenditures. Multivariable models were fit for each of the annualized outcomes and adjusted for patient demographics, comorbidities, and other concomitant valve diseases.Results: There were 92,994 patients eligible for analysis. Patients with no HF and no clinically significant TR had the annualized healthcare burden of 0.20 all-cause hospitalizations (approximately one inpatient hospitalization every 5 years), 1.07 hospital days, and $17,478 in expenditures. The presence of clinically significant TR, alone or with HF, significantly increased healthcare utilization and expenditures. For patients with no HF with clinically significant TR, the annualized economic burden increased to 0.41 all-cause hospitalizations, 3.13 hospital days, and $29,985 in expenditures. For patients with HF and clinically significant TR, the annualized economic burden was even greater with 0.59 all-cause hospitalizations, 4.31 hospital days, and $42,255 in expenditures.Conclusion: The presence of clinically significant TR is associated with an increase in healthcare utilization and expenditures, irrespective of the presence of HF.

The Economic Impact of Mitral Regurgitation on Patients With Medically Managed Heart Failure.

The objective of this study was to quantify the financial healthcare burden of mitral regurgitation (MR) on medically managed heart failure (HF) patients. Data from the Truven Health MarketScan Commercial Claims and Medicare Supplemental Databases were analyzed. Included patients had a minimum of 1 inpatient or 2 outpatient claims for HF with a 6-month preperiod (baseline). A 6-month postperiod (landmark) after HF index was used to capture MR diagnosis and severity. Following the landmark period, patients had to have 12 months of continuous medical and prescription drug plan enrollment with at least 2 records of HF medication refills. A therapeutic intensity score was calculated based on HF medication usage. Medically managed HF patients were separated into 3 cohorts: without MR (no MR), insignificant MR (iMR), and significant MR (sMR). Healthcare utilization and all-cause expenditures were modeled to quantify the burden of MR. All models controlled for baseline demographics, co-morbid conditions, and HF therapeutic intensity. Medically managed incident HF patients with sMR had significantly more hospital days (1.91 vs 1.72 days; p = 0.0096) and annual expenditures ($23,988 vs $21,530; p < 0.0001) compared with no MR patients. No differences were identified when comparing iMR and no MR. When evaluating HF admissions, sMR patients had an estimated 50% greater HF admissions rate (0.036 vs 0.024; p < 0.0001) compared with no MR patients. Additionally, HF admits for iMR were 23% more than those with no MR (0.029 vs 0.024; p = 0.0064). In conclusion, evidence of MR in retrospective claims significantly increases the healthcare impact of medically managed HF patients. Both utilization and financial burden is more pronounced when MR is clinically significant.

The healthcare burden of disease progression in medicare patients with functional mitral regurgitation.

Objective: This retrospective database analysis estimated the incremental effect that disease progression from non-clinically significant functional mitral regurgitation (nsFMR) to clinically significant FMR (sFMR) has on clinical outcomes and costs. Methods: Medicare Fee for Service beneficiaries with nsFMR were examined, defined as those with a heart failure diagnosis prior to MR. Patients were classified as ischemic if there was a history of: CAD, AMI, PCI, or CABG. The primary outcome was time to sFMR, defined as pulmonary hypertension, atrial fibrillation, mitral valve surgery, serial echocardiography, or death, using a Cox hazard regression model. Annualized hospitalizations, inpatient hospital days, and healthcare expenditures were also modeled. Results: Patients with IHD had higher risk (Hazard Ratio = 1.22 [1.14-1.30]) for disease progression compared to patients without. The progression cohort had significantly more annual inpatient hospitalizations (non-IHD = 1.32; IHD = 1.40) than the non-progression cohort (non-IHD = 0.36; IHD = 0.34), and significantly more annual inpatient hospital days (non-IHD = 13.07; IHD = 13.52) than the non-progression cohort (non-IHD = 2.29; with IHD = 2.08). The progression cohort had over 3.5-times higher costs vs the non-progression cohort, independent of IHD (non-IHD = $12,798 vs $46,784; IHD = $12,582 vs $49,348). Conclusion: Treating FMR patients earlier in their clinical trajectory may prevent disease progression and reduce high rates of healthcare utilization and expenditures.

Cardiovascular disease in the kidney transplant recipient: epidemiology, diagnosis and management strategies.

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.

Cardionephrology: Proposal for a Futuristic Educational Approach to a Contemporary Need.

The field of cardiorenal medicine is vast, rapidly expanding, and complex. Conventional nephrology training programs provide the fellows with the necessary core knowledge to provide general care for patients with renal and cardiovascular diseases. However, there is a need for focused training of interested physicians to master the specialized aspects of these exceedingly common clinical scenarios and optimize the care of such patients. A cardionephrology-focused training can add value to the nephrology subspecialty and potentially increase its attractiveness for a significant subset of trainees. Herein, we provide a proposal for the framework and content of such an educational activity. Creation of an international multidisciplinary workgroup to formulate a comprehensive curriculum for a dedicated cardionephrology track would be the first step. A variety of practical aspects such as implementation methods, the identification of the required skills, and the development of educational assessment tools are discussed. While this proposal primarily focuses on the integration of the curriculum into the training of nephrology fellows, it would also be appropriate (albeit in a modified and customized format) for a wider range of trainees, including cardiology fellows.

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.

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.

Resuscitation for the specialty of nephrology: is cardionephrology the answer?

The specialty of nephrology faces major fellowship recruitment challenges, with ongoing declining interest among internal medicine residents. The field of Cardionephrology can help instill new interest and enthusiasm in choosing nephrology as a career amongst trainee physicians.

Assessment of cardiovascular risk of new drugs for the treatment of diabetes mellitus: risk assessment vs. risk aversion.

The Food and Drug Administration issued guidance for evaluating the cardiovascular risk of new diabetes mellitus drugs in 2008. Accumulating evidence from several completed trials conducted within this framework raises questions as to whether requiring safety outcome studies for all new diabetes mellitus therapies remains justified. Given the burden of cardiovascular disease in patients with diabetes, the focus should shift towards cardiovascular outcome studies designed to evaluate efficacy (i.e. to determine the efficacy of a drug over placebo or standard care) rather than demonstrating that risk is not increased by a pre-specified safety margin. All stakeholders are responsible for ensuring that new drug approvals occur under conditions of appropriate safety and effectiveness. It is also a shared responsibility to avoid unnecessary hurdles that may compromise access to useful drugs and threaten the sustainability of health systems. It is critical to renew this debate so that stakeholders can collectively determine the optimal approach for developing new drugs to treat type 2 diabetes mellitus.

Reducing contrast-induced acute kidney injury using a regional multicenter quality improvement intervention.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is associated with increased morbidity and mortality after percutaneous coronary interventions and is a patient safety objective of the National Quality Forum. However, no formal quality improvement program to prevent CI-AKI has been conducted. Therefore, we sought to determine whether a 6-year regional multicenter quality improvement intervention could reduce CI-AKI after percutaneous coronary interventions. METHODS AND RESULTS: We conducted a prospective multicenter quality improvement study to prevent CI-AKI (serum creatinine increase ≥0.3 mg/dL within 48 hours or ≥50% during hospitalization) among 21 067 nonemergent patients undergoing percutaneous coronary interventions at 10 hospitals between 2007 and 2012. Six intervention hospitals participated in the quality improvement intervention. Two hospitals with significantly lower baseline rates of CI-AKI, which served as benchmark sites and were used to develop the intervention, and 2 hospitals not receiving the intervention were used as controls. Using time series analysis and multilevel poisson regression clustering to the hospital level, we calculated adjusted risk ratios for CI-AKI comparing the intervention period to baseline. Adjusted rates of CI-AKI were significantly reduced in hospitals receiving the intervention by 21% (risk ratio, 0.79; 95% confidence interval: 0.67-0.93; P=0.005) for all patients and by 28% in patients with baseline estimated glomerular filtration rate <60 mL/min per 1.73 m(2) (risk ratio, 0.72; 95% confidence interval: 0.56-0.91; P=0.007). Benchmark hospitals had no significant changes in CI-AKI. Key qualitative system factors associated with improvement included multidisciplinary teams, limiting contrast volume, standardized fluid orders, intravenous fluid bolus, and patient education about oral hydration. CONCLUSIONS: Simple cost-effective quality improvement interventions can prevent ≤1 in 5 CI-AKI events in patients with undergoing nonemergent percutaneous coronary interventions.

Association between lack of health insurance and risk of death and ESRD: results from the Kidney Early Evaluation Program (KEEP).

BACKGROUND: Uninsured adults in the United States have poor access to health care services and worse health outcomes than insured adults. Little is known about the association between lack of insurance and chronic kidney disease (CKD) progression to end-stage renal disease (ESRD) or death in patients at high risk of kidney disease. We used 2000-2011 data from the National Kidney Foundation's Kidney Early Evaluation Program (KEEP) to examine this association. METHODS: The study population included KEEP participants younger than 65 years. Outcomes were time to ESRD (chronic kidney failure treated by renal replacement therapy) and time to death. Incident ESRD was ascertained by linkage to the US Renal Data System, and vital status, by linkage to the Social Security Administration Death Master File. We used Cox proportional hazard regression to examine the association between insurance and risk of death or ESRD after adjusting for demographic variables. RESULTS: Of 86,588 participants, 27.8% had no form of insurance, 10.3% had public insurance, and 61.9% had private insurance; 15.0% had CKD (defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2) or urine albumin-creatinine ratio ≥ 30 mg/g), 63.3% had hypertension, and 27.7% had diabetes. Of participants with CKD, 29.3% had no health insurance. Participants without insurance were younger, more likely to be Hispanic and to have 12 or fewer years of education, and less likely to have seen a physician in the past year. After adjustment for demographic characteristics, uninsured KEEP participants were 82% more likely than privately insured participants to die (HR, 1.82; 95% CI, 1.56-2.12; P < 0.001) and 72% more likely to develop ESRD (HR, 1.72; 95% CI, 1.33-2.22; P < 0.001). The association between insurance and outcomes varied by CKD stage. CONCLUSIONS: Lack of insurance is an independent risk factor for early death and ESRD in this population at high risk of kidney disease. Considering the high morbidity and mortality and increasing cost associated with ESRD, access to appropriate health insurance coverage is warranted.

The association of parathyroid hormone with ESRD and pre-ESRD mortality in the Kidney Early Evaluation Program.

CONTEXT: Studies have suggested that PTH may influence mortality and progression of chronic kidney disease. However, the development of either event may influence the development of the other as a competing risk. OBJECTIVE: The objective of the study was to examine the association of PTH with end-stage renal disease (ESRD) and pre-ESRD death using a competing risk survival model. DESIGN, SETTING, AND PATIENTS: A total of 10,823 participants in the Kidney Early Evaluation Program with chronic kidney disease (estimated glomerular filtration rate < 60 ml/min per 1.73 m(2)) were examined from 2005 to 2010. MAIN OUTCOME MEASURES: The association of PTH levels with ESRD and pre-ESRD mortality was ascertained by linking Kidney Early Evaluation Program data to the Social Security Administration Death Master File and the U.S. Renal Data System. RESULTS: Among the cohort, the incidence of ESRD and pre-ESRD mortality was 6.4 and 20.1 events per 1000 person-years. Higher PTH levels were associated with increasing age, black race, lack of a high school education, cardiovascular disease, hypertension, and lower glomerular filtration rate. The incidence of ESRD and pre-ESRD mortality was lowest among participants in the second PTH quintile. After multivariate adjustment, as compared with the second quintile, the risk of pre-ESRD mortality was higher in the third [subhazard ratio (SHR) 1.52 (95% confidence interval 1.04-2.22)], fourth [SHR 1.73 (95% confidence interval 1.19-2.52)], and fifth [SHR 1.86 (1.28-2.52)] quintiles, respectively. Conversely, PTH was not associated with ESRD after multivariate adjustment. The association was not modified by diabetic status, gender, race, or glomerular filtration rate status. CONCLUSIONS: Elevated PTH levels are associated with increased pre-ESRD mortality but not with ESRD.

Awareness of kidney disease and relationship to end-stage renal disease and mortality.

BACKGROUND: Often, patients with chronic kidney disease are reported to be unaware of it. We prospectively evaluated the association between awareness of kidney disease to end-stage renal disease and mortality. METHODS: We utilized 2000-2009 data from the National Kidney Foundation's Kidney Early Evaluation Program. Mortality was determined by cross reference to the Social Security Administration Death Master File and development of end stage by cross reference with the United States Renal Data System. RESULTS: Of 109,285 participants, 28,244 (26%) had chronic kidney disease defined by albuminuria or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2). Only 9% (n=2660) reported being aware of kidney disease. Compared with those who were not aware, participants aware of chronic kidney disease had lower eGFR (49 vs 62 mL/min/1.73 m(2)) and a higher prevalence of albuminuria (52% vs. 46%), diabetes (47% vs 42%), cardiovascular disease (43% vs 28%), and cancer (23% vs 14%). Over 8.5 years of follow-up, aware participants compared with those unaware had a lower rate of survival for end stage (83% and 96%) and mortality (78% vs 81%), P <.001. After adjustment for demographics, socioeconomic factors, comorbidity, and severity of kidney disease, aware participants continued to demonstrate an increased risk for end-stage renal disease (hazard ratio 1.37; 95% confidence interval, 1.07-1.75; P <.0123) and mortality (hazard ratio 1.27; 95% confidence interval, 1.07-1.52; P <.0077) relative to unaware participants with chronic kidney disease. CONCLUSIONS: Among patients identified as having chronic kidney disease at a health screening, only a small proportion had been made aware of their diagnosis previously by clinicians. This subgroup was at a disproportionately high risk for mortality and end-stage renal disease.

Association of physician care with mortality in Kidney Early Evaluation Program (KEEP) participants.

BACKGROUND: People with or at high risk of chronic kidney disease (CKD) are at increased risk of premature morbidity and mortality. We sought to examine the effect of care provided by a primary care physician (PCP) on survival for all participants in the National Kidney Foundation's Kidney Early Evaluation Program (KEEP) and the effect of care provided by a nephrologist on survival for KEEP participants with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2). METHODS: Provision of care by a PCP (n = 138,331) or nephrologist (n = 10,797) was defined using self-report of seeing that provider within the past year. Survival was ascertained by linking KEEP data to the Social Security Administration Death Master File. Multivariable Cox proportional hazards models examining the relationship between primary care and nephrologist provider status adjusted for age, sex, race, smoking status, education, health insurance, diabetes, cardiovascular disease, hypertension, cancer, albuminuria, body mass index, baseline eGFR, and hemoglobin level, with nephrology models further adjusting for calcium, phosphorus, and parathyroid hormone levels. RESULTS: Of all participants, 70.9% (98,050 of 138,331) reported receiving PCP care; older age and female sex were associated with this care. During a median follow-up of 4.2 years, 4,836 deaths occurred. After multivariable adjustment, receiving PCP care and mortality were not associated (HR, 0.94; 95% CI, 0.86-1.03; P = 0.2). Of participants with eGFR <60 mL/min/1.73 m(2), 10.1% (1,095 of 10,797) reported receiving nephrology care; younger age and male sex were associated with receipt of nephrology care. During a mean follow-up of 2.2 years, 558 deaths occurred. After multivariable adjustment, nephrologist care was not associated with mortality (HR, 1.01; 95% CI, 0.75-1.36; P = 0.9). These associations were not modified by other specialist care (endocrinologist or cardiologist). CONCLUSIONS: For all KEEP participants, neither PCP nor nephrology care was associated with improved survival. These results highlight the need to explore the connection between access to health care and outcomes in persons at high risk of or with CKD.

Validity of estimated glomerular filtration rates for assessment of baseline and serial renal function in patients with atherosclerotic renal artery stenosis: implications for clinical trials of renal revascularization.

BACKGROUND: Despite routine use of estimated glomerular filtration rates (GFRs) as major renal end points in clinical trials of renal revascularization, serial GFR estimates have never been validated in patients with renal artery stenosis (RAS). The purpose of this study was to evaluate the validity of GFR estimates in patients with atherosclerotic RAS. METHODS AND RESULTS: Serum creatinine (SCr) and (125)I-iothalamate GFR (I-GFR) were measured in patients with RAS. GFR estimates were calculated from Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockroft-Gault (CG) formulas. Using I-GFR as the reference standard, the sensitivity, specificity, and receiver operating characteristic area under the curve (AUC) were determined for MDRD, CKD-EPI, CG, and reciprocal SCr for identifying I-GFR <60 mL/min per 1.73 m(2) and a 20% change in I-GFR over time. Between 1998 and 2007, 541 I-GFR measurements were performed in 254 consecutive patients with RAS. MDRD, CKD-EPI, and CG GFR estimates demonstrated good sensitivity (86% to 95%), modest specificity (67% to 71%), and good reliability (AUC, 0.86 to 0.94) for identifying I-GFR <60 mL/min per 1.73 m(2). GFR estimates had good specificity (87% to 95%), poor sensitivity (0% to 45%), and poor reliability (AUC, 0.61 to 0.65) for detecting 20% changes in I-GFR over follow-up. CONCLUSIONS: In patients with RAS, GFR estimates demonstrate good sensitivity and modest specificity for identifying I-GFR <60 mL/min per 1.73 m(2) but poor sensitivity and reliability for detecting 20% changes in I-GFR. GFR estimates should not be used in clinical trials as major end points to assess serial GFR after renal revascularization.