Automated analysis of limited echocardiograms: Feasibility and relationship to outcomes in COVID-19.

Background: As automated echocardiographic analysis is increasingly utilized, continued evaluation within hospital settings is important to further understand its potential value. The importance of cardiac involvement in patients hospitalized with COVID-19 provides an opportunity to evaluate the feasibility and clinical relevance of automated analysis applied to limited echocardiograms. Methods: In this multisite US cohort, the feasibility of automated AI analysis was evaluated on 558 limited echocardiograms in patients hospitalized with COVID-19. Reliability of automated assessment of left ventricular (LV) volumes, ejection fraction (EF), and LV longitudinal strain (LS) was assessed against clinically obtained measures and echocardiographic findings. Automated measures were evaluated against patient outcomes using ROC analysis, survival modeling, and logistic regression for the outcomes of 30-day mortality and in-hospital sequelae. Results: Feasibility of automated analysis for both LVEF and LS was 87.5% (488/558 patients). AI analysis was performed with biplane method in 300 (61.5%) and single plane apical 4- or 2-chamber analysis in 136 (27.9%) and 52 (10.7%) studies, respectively. Clinical LVEF was assessed using visual estimation in 192 (39.3%), biplane in 163 (33.4%), and single plane or linear methods in 104 (21.2%) of the 488 studies; 29 (5.9%) studies did not have clinically reported LVEF. LV LS was clinically reported in 80 (16.4%). Consistency between automated and clinical values demonstrated Pearson's R, root mean square error (RMSE) and intraclass correlation coefficient (ICC) of 0.61, 11.3% and 0.72, respectively, for LVEF; 0.73, 3.9% and 0.74, respectively for LS; 0.76, 24.4ml and 0.87, respectively, for end-diastolic volume; and 0.82, 12.8 ml, and 0.91, respectively, for end-systolic volume. Abnormal automated measures of LVEF and LS were associated with LV wall motion abnormalities, left atrial enlargement, and right ventricular dysfunction. Automated analysis was associated with outcomes, including survival. Conclusion: Automated analysis was highly feasible on limited echocardiograms using abbreviated protocols, consistent with equivalent clinically obtained metrics, and associated with echocardiographic abnormalities and patient outcomes.

Impact of Racial Disparities in Preoperative Cardiovascular Evaluation and Surgical Outcomes in Patients Undergoing Metabolic and Bariatric Surgery: A Retrospective Cohort Analysis.

Background We investigated preoperative referral patterns, rates of cardiovascular testing, surgical wait times, and postoperative outcomes in White versus Black, Hispanic, or other racial or ethnic groups of patients undergoing metabolic and bariatric surgery. Methods and Results This was a single center retrospective cohort analysis of 797 consecutive patients undergoing metabolic and bariatric surgery from January 2014 to December 2018; 86% (n=682) were Black, Hispanic, or other racial or ethnic groups. White versus Black, Hispanic, or other racial or ethnic groups had similar baseline comorbidities and were referred for preoperative cardiovascular evaluation in similar proportion (65% versus 68%, P=0.529). Black, Hispanic, or other racial or ethnic groups of patients were less likely to undergo preoperative cardiovascular testing (unadjusted odds ratio [OR], 0.56; 95% CI, 0.33-0.95; P=0.031; adjusted for Revised Cardiac Risk Index OR, 0.59; 95% CI, 0.35-0.996; P=0.049). White patients had a shorter wait time for surgery (unadjusted hazard ratio [HR], 0.7; 95% CI, 0.58-0.87; P=0.001; adjusted HR, 0.7; 95% CI, 0.56-0.95; P=0.018). Reduction in body mass index at 6 months was greater in White patients (12.9 kg/m2 versus 12.0 kg/m2, P=0.0289), but equivalent at 1 year (14.9 kg/m2 versus 14.3 kg/m2, P=0.330). Conclusions White versus Black, Hispanic, or other racial or ethnic groups of patients were referred for preoperative cardiovascular evaluation in similar proportion. White patients underwent more preoperative cardiac testing yet had a shorter wait time for surgery. Early weight loss was greater in White patients, but equivalent between groups at 12 months.

Racial and ethnic differences in left atrial appendage occlusion wait time, complications, and periprocedural management.

PURPOSE: Non-white patients are underrepresented in left atrial appendage occlusion (LAAO) trials, and racial disparities in LAAO periprocedural management are unknown. METHODS: We assessed sociodemographics and comorbidities of consecutive patients at our institution undergoing LAAO between 2015 and 2020, then in adjusted analyses, compared procedural wait time, procedural complications, and post-procedure oral anticoagulation (OAC) use in whites versus non-whites. RESULTS: Among 109 patients undergoing LAAO (45% white), whites had lower CHA2 DS2 VASc scores, on average, than non-whites (4.0 vs. 4.8, p = .006). There was no difference in median time from index event (IE) or initial outpatient cardiology encounter to LAAO procedure (whites 10.5 vs. non-whites 13.7 months, p = .9; 1.9 vs. 1.8 months, p = .6, respectively), and there was no difference in procedural complications (whites 4% vs. non-whites 5%, p = .33). After adjusting for CHA2 DS2 VASc score, OAC use at discharge tended to be higher in whites (OR 2.4, 95% CI [0.9-6.0], p = .07). When restricting the analysis to those with prior gastrointestinal (GI) bleed, adjusting for CHA2 DS2 VASc score and GI bleed severity, whites had a nearly five-fold odds of being discharged on OAC (OR 4.6, 95% CI [1-21.8], p = 0.05). The association between race and discharge OAC was not mediated through income category (total mediation effect 19% 95% CI [-.04-0.11], p = .38). CONCLUSION: Despite an increased prevalence of comorbidities amongst non-whites, wait time for LAAO and procedural complications were similar in whites versus non-whites. Among those with prior GI bleed, whites were nearly five-fold more likely to be discharged on OAC than non-whites, independent of income.

Cardiovascular safety of fenfluramine in the treatment of Dravet syndrome: Analysis of an ongoing long-term open-label safety extension study.

OBJECTIVE: Fenfluramine, which was previously approved as a weight loss drug, was withdrawn in 1997 when reports of cardiac valvulopathy emerged. The present study was conducted in part to characterize the cardiovascular safety profile of low-dose fenfluramine when used in a pediatric population to reduce seizure frequency in patients with Dravet syndrome. METHODS: Patients 2- to 18-years-old with Dravet syndrome who had completed any of three randomized, placebo-controlled clinical trials of fenfluramine were offered enrollment in this open-label extension (OLE) study. All patients were treated with fenfluramine starting at a dose of 0.2 mg/kg/day (oral solution dosed twice per day), which was titrated to maximal effect with a dose limit of 0.7 mg/kg/day (maximum 26 mg/day) or 0.4 mg/kg/day (maximum 17 mg/day) in patients receiving concomitant stiripentol. Standardized echocardiographic examinations were conducted at Week 4 or 6 and then every 3 months during the OLE study to monitor cardiac valve function and structure and pulmonary artery pressure. The primary end point for the echocardiography analysis was the number of patients who developed valvular heart disease or pulmonary artery hypertension (PAH) during treatment. RESULTS: A total of 232 patients were enrolled in the study. The average age of patients was 9.1 ± 4.7 years, and 55.2% were male. The median duration of treatment with fenfluramine was 256 days (range = 58-634 days), and the mean dose of fenfluramine was 0.41 mg/kg/day. No cases of valvular heart disease or PAH were observed. SIGNIFICANCE: Longitudinal echocardiography over a median 8.4 months of treatment with fenfluramine suggests a low risk of developing cardiac valvulopathy and PAH when used to treat pediatric patients with Dravet syndrome.

Evolution of Echocardiographic Measures of Cardiac Disease From CKD to ESRD and Risk of All-Cause Mortality: Findings From the CRIC Study.

RATIONALE & OBJECTIVE: Abnormal cardiac structure and function are common in chronic kidney disease (CKD) and end-stage renal disease (ESRD) and linked with mortality and heart failure. We examined changes in echocardiographic measures during the transition from CKD to ESRD and their associations with post-ESRD mortality. STUDY DESIGN: Prospective study. SETTING & PARTICIPANTS: We studied 417 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) who had research echocardiograms during CKD and ESRD. PREDICTOR: We measured change in left ventricular mass index, left ventricular ejection fraction (LVEF), diastolic relaxation (normal, mildly abnormal, and moderately/severely abnormal), left ventricular end-systolic (LVESV), end-diastolic (LVEDV) volume, and left atrial volume from CKD to ESRD. OUTCOMES: All-cause mortality after dialysis therapy initiation. ANALYTICAL APPROACH: Cox proportional hazard models were used to test the association of change in each echocardiographic measure with postdialysis mortality. RESULTS: Over a mean of 2.9 years between pre- and postdialysis echocardiograms, there was worsening of mean LVEF (52.5% to 48.6%; P<0.001) and LVESV (18.6 to 20.2mL/m2.7; P<0.001). During this time, there was improvement in left ventricular mass index (60.4 to 58.4g/m2.7; P=0.005) and diastolic relaxation (11.11% to 4.94% with moderately/severely abnormal; P=0.02). Changes in left atrial volume (4.09 to 4.15mL/m2; P=0.08) or LVEDV (38.6 to 38.4mL/m2.7; P=0.8) were not significant. Worsening from CKD to ESRD of LVEF (adjusted HR for every 1% decline in LVEF, 1.03; 95% CI, 1.00-1.06) and LVESV (adjusted HR for every 1mL/m2.7 increase, 1.04; 95% CI, 1.02-1.07) were independently associated with greater risk for postdialysis mortality. LIMITATIONS: Some missing or technically inadequate echocardiograms. CONCLUSIONS: In a longitudinal study of patients with CKD who subsequently initiated dialysis therapy, LVEF and LVESV worsened and were significantly associated with greater risk for postdialysis mortality. There may be opportunities for intervention during this transition period to improve outcomes.

Initial clinical and hemodynamic results of a regional pulmonary thromboendarterectomy program.

BACKGROUND: Pulmonary thromboendarterectomy (PTE) is the treatment of choice for eligible patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, access to CTEPH and PTE care is limited. There is a paucity of published data on PTE efficacy and outcomes from alternative, regional centers of excellence in CTEPH and PTE care in the USA, outside a single national and international referral center. METHODS: We performed a retrospective review of patients undergoing PTE at our institution from June 2013 to December 2016 (42 months), and collected clinical, echocardiographic and hemodynamic data on our patients pre- and post-PTE (N.=71). RESULTS: Patients age ranged between 20-83 years (mean±SD: 56±16), with 54% of patients female and 61% Caucasians. The predominant symptom was shortness of breath with a median duration of symptoms of 17 months. Following PTE, clinical improvements included a reduction in NYHA class from 3.1±1.1 to 2.2±1.2. There were major improvements in hemodynamics and echocardiographic parameters pre- versus post-PTE: mean pulmonary artery pressure (mmHg) 45±11 to 24±8, cardiac index (L/min/m2) 2.1±0.5 to 2.8±0.5, pulmonary vascular resistance (mmHg/L/min) 8.9±4.5 to 2.8±1.8, ratio of right ventricle (RV): left ventricle (LV) 1.2±0.3 to 0.9±0.2, RV fractional area change (%) 23±14 to 44±13, reduction in the incidence of RV outflow tract Doppler notching and improved pulmonary artery acceleration time (96% to 30%, and 74±19 to 111±21). In-hospital mortality was 4.2% (3 patients). CONCLUSIONS: Herein, we report for the first time, the improvements in patient functionality, hemodynamics, right heart function and outcomes at a major regional PTE program.

Differences in right ventricular morphology, not function, indicate the nature of increased afterload in pulmonary hypertensive subjects with normal left ventricular function.

BACKGROUND: The aim of study was to assess whether a specific morphology of the right ventricle (RV) by 2D echo predicts the hemodynamic nature of pulmonary hypertension (PH). METHODS: We reviewed clinical, 2D echo, and hemodynamic data of 100 patients with PH: divided into three groups: PH from pulmonary vascular disease (PHPVD ; n = 34) with pulmonary vascular resistance (PVR) > 3 mm Hg/L/min (Wood unit [WU]) and pulmonary artery wedge pressure (PAWP) ≤ 15 mm Hg, pulmonary venous hypertension (PVH; n = 33) with PVR < 3 WU and PAWP > 15 mm Hg and PHMIXED (n = 33) with PVR > 3 WU and PAWP > 15 mm Hg. We analyzed several two-dimensional parameters of right heart morphology and function, including the degree of tapering of the RV diameter from base (just above tricuspid annulus) to apex (level of moderator band) in the apical four-chamber view. P = <.05. RESULTS: Baseline characteristics were similar in all three groups: age 62 ± 14.4 years, 69% females, 57% Caucasians. Hemodynamics and 2D echo data of PHPVD vs PVH vs PHMIXED were as follows: PVR 13 ± 6 vs 2 ± 1 vs 7 ± 2 WU, mean pulmonary artery pressure 53 ± 14 vs 34 ± 8 vs 49 ± 8 mm Hg and cardiac index 2.0 ± 0.5 vs 2.8 ± 0.7 vs 2.2 ± 0.7 L/m2 , RV base/apex ratio during systole (sRVb/a ) 1.3 ± 0.2 vs 2.6 ± 0.5 vs 1.5 ± 0.3. Thus, sRVb/a was twofold higher in the PVH vs PHPVD cohort. On ROC analysis, the AUC for sRVb/a for predicting PVR > 3 WU was 0.873, with optimal cutoff of 1.5. CONCLUSION: Systolic RV base/apex ratio is a simple 2D index of RV shape that powerfully predicts a PVR > 3 WU and provides powerful discriminating ability between PVH and PHPVD .

Cardiovascular safety of low-dose fenfluramine in Dravet syndrome: a review of its benefit-risk profile in a new patient population.

OBJECTIVE: Dravet syndrome (DS) is a rare, treatment-resistant epilepsy syndrome for which current treatment regimens are often ineffective. Fenfluramine is currently in development for treatment of DS, based on reports in the 1980s and 1990s of its anti-epileptic activity in pediatric patients with intractable epilepsy. However, fenfluramine was withdrawn from global markets in 1997 following reports of its association with pulmonary hypertension and heart valve disease in adult patients treated for obesity. This review was conducted to assess cardiac safety of fenfluramine when used at lower doses for treatment of DS. METHODS: Pubmed was searched for clinical studies of fenfluramine in obese adults who reported incidence of heart valve disease. These data were reviewed against published results from Belgian patients with DS who have been treated with low-dose fenfluramine for up to 28 years. RESULTS: Nine controlled studies of fenfluramine and related compounds (dexfenfluramine and/or phentermine) which assessed incidence and severity of cardiac valve disease in 3,268 treated patients and 2,017 control subjects have been reported. Mild or greater aortic valve regurgitation was found in 9.6% of treated patients compared with 3.9% of control subjects, and moderate or greater mitral valve regurgitation was found in 3.1% of treated patients and 2.5% of control subjects. Nineteen DS patients have been treated for up to 28 years with 10-20 mg/day fenfluramine, with no clinical signs or symptoms of cardiac valve disease or pulmonary hypertension. Slight and clinically unimportant changes in valve structure have been seen on echocardiography in five patients at some time during the observation period. CONCLUSIONS: A different benefit-risk relationship appears to be emerging when fenfluramine is used at low doses for extended periods in young patients with DS. Continued cardiac assessments during ongoing Phase 3 clinical trials will provide additional safety information for this potential new and effective treatment.

Racial/Ethnic Differences in Left Ventricular Structure and Function in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease (CVD) and it is especially common among Blacks. Left ventricular hypertrophy (LVH) is an important subclinical marker of CVD, but there are limited data on racial variation in left ventricular structure and function among persons with CKD. METHODS: In a cross-sectional analysis of the Chronic Renal Insufficiency Cohort Study, we compared the prevalence of different types of left ventricular remodeling (concentric hypertrophy, eccentric hypertrophy, and concentric remodeling) by race/ethnicity. We used multinomial logistic regression to test whether race/ethnicity associated with different types of left ventricular remodeling independently of potential confounding factors. RESULTS: We identified 1,164 non-Hispanic Black and 1,155 non-Hispanic White participants who completed Year 1 visits with echocardiograms that had sufficient data to categorize left ventricular geometry type. Compared to non-Hispanic Whites, non-Hispanic Blacks had higher mean left ventricular mass index (54.7 ± 14.6 vs. 47.4 ± 12.2 g/m2.7; P < 0.0001) and prevalence of concentric LVH (45.8% vs. 24.9%). In addition to higher systolic blood pressure and treatment with >3 antihypertensive medications, Black race/ethnicity was independently associated with higher odds of concentric LVH compared to White race/ethnicity (odds ratio: 2.73; 95% confidence interval: 2.02, 3.69). CONCLUSION: In a large, diverse cohort with CKD, we found significant differences in left ventricular mass and hypertrophic morphology between non-Hispanic Blacks and Whites. Future studies will evaluate whether higher prevalence of LVH contribute to racial/ethnic disparities in cardiovascular outcomes among CKD patients.

Sodium Excretion and the Risk of Cardiovascular Disease in Patients With Chronic Kidney Disease.

IMPORTANCE: Patients with chronic kidney disease (CKD) are at an increased risk of cardiovascular disease (CVD) compared with the general population. Prior studies have produced contradictory results on the association of dietary sodium intake with risk of CVD, and this relationship has not been investigated in patients with CKD. OBJECTIVE: To evaluate the association between urinary sodium excretion and clinical CVD events among patients with CKD. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of patients with CKD from 7 locations in the United States enrolled in the Chronic Renal Insufficiency Cohort Study and followed up from May 2003 to March 2013. EXPOSURES: The cumulative mean of urinary sodium excretion from three 24-hour urinary measurements and calibrated to sex-specific mean 24-hour urinary creatinine excretion. MAIN OUTCOMES AND MEASURES: A composite of CVD events defined as congestive heart failure, stroke, or myocardial infarction. Events were reported every 6 months and confirmed by medical record adjudication. RESULTS: Among 3757 participants (mean age, 58 years; 45% women), 804 composite CVD events (575 heart failure, 305 myocardial infarction, and 148 stroke) occurred during a median 6.8 years of follow-up. From lowest (<2894 mg/24 hours) to highest (≥4548 mg/24 hours) quartile of calibrated sodium excretion, 174, 159, 198, and 273 composite CVD events occurred, and the cumulative incidence was 18.4%, 16.5%, 20.6%, and 29.8% at median follow-up. In addition, the cumulative incidence of CVD events in the highest quartile of calibrated sodium excretion compared with the lowest was 23.2% vs 13.3% for heart failure, 10.9% vs 7.8% for myocardial infarction, and 6.4% vs 2.7% for stroke at median follow-up. Hazard ratios of the highest quartile compared with the lowest quartile were 1.36 (95% CI, 1.09-1.70; P = .007) for composite CVD events, 1.34 (95% CI, 1.03-1.74; P = .03) for heart failure, and 1.81 (95% CI, 1.08-3.02; P = .02) for stroke after multivariable adjustment. Restricted cubic spline analyses of the association between sodium excretion and composite CVD provided no evidence of a nonlinear association (P = .11) and indicated a significant linear association (P < .001). CONCLUSIONS AND RELEVANCE: Among patients with CKD, higher urinary sodium excretion was associated with increased risk of CVD.

Atrial Fibrillation and Risk of ESRD in Adults with CKD.

BACKGROUND AND OBJECTIVES: Atrial fibrillation frequently complicates CKD and is associated with adverse outcomes. Progression to ESRD is a major complication of CKD, but the link with atrial fibrillation has not been fully delineated. In this study, we examined the association of incident atrial fibrillation with the risk of ESRD in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied participants in the prospective Chronic Renal Insufficiency Cohort Study without atrial fibrillation at entry. Incident atrial fibrillation was identified by study visit ECGs, self-report, and hospital discharge diagnostic codes, with confirmation by physician adjudication. ESRD through 2012 was ascertained by participant self-report, medical records, and linkage to the US Renal Data System. Data on potential confounders were obtained from self-report, study visits, and laboratory tests. Marginal structural models were used to study the potential association of incident atrial fibrillation with risk of ESRD after adjustment for time-dependent confounding. RESULTS: Among 3091 participants, 172 (5.6%) developed incident atrial fibrillation during follow-up. During mean follow-up of 5.9 years, 43 patients had ESRD that occurred after development of incident atrial fibrillation (11.8/100 person-years) compared with 581 patients without incident atrial fibrillation (3.4/100 person-years). In marginal structural models with inverse probability weighting, incident atrial fibrillation was associated with a substantially higher rate of ESRD (hazard ratio, 3.2; 95% confidence interval, 1.9 to 5.2). This association was consistent across important subgroups by age, sex, race, diabetes status, and baseline eGFR. CONCLUSIONS: Incident atrial fibrillation was associated with higher risk of developing ESRD in CKD. Additional study is needed to identify potentially modifiable pathways through which atrial fibrillation was associated with a higher risk of progression to ESRD. More aggressive monitoring and treatment of patients with CKD and atrial fibrillation may improve outcomes in this high-risk population.

Masked Hypertension and Elevated Nighttime Blood Pressure in CKD: Prevalence and Association with Target Organ Damage.

BACKGROUND AND OBJECTIVES: Masked hypertension and elevated nighttime BP are associated with increased risk of hypertensive target organ damage and adverse cardiovascular and renal outcomes in patients with normal kidney function. The significance of masked hypertension for these risks in patients with CKD is less well defined. The objective of this study was to evaluate the association between masked hypertension and kidney function and markers of cardiovascular target organ damage, and to determine whether this relationship was consistent among those with and without elevated nighttime BP. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a cross-sectional study. We performed 24-hour ambulatory BP in 1492 men and women with CKD enrolled in the Chronic Renal Insufficiency Cohort Study. We categorized participants into controlled BP, white-coat, masked, and sustained hypertension on the basis of clinic and 24-hour ambulatory BP. We obtained echocardiograms and measured pulse wave velocity in 1278 and 1394 participants, respectively. RESULTS: The percentages of participants with controlled BP, white-coat, masked, and sustained hypertension were 49.3%, 4.1%, 27.8%, and 18.8%, respectively. Compared with controlled BP, masked hypertension independently associated with low eGFR (-3.2 ml/min per 1.73 m(2); 95% confidence interval, -5.5 to -0.9), higher proteinuria (+0.9 unit higher in log2 urine protein; 95% confidence interval, 0.7 to 1.1), and higher left ventricular mass index (+2.52 g/m(2.7); 95% confidence interval, 0.9 to 4.1), and pulse wave velocity (+0.92 m/s; 95% confidence interval, 0.5 to 1.3). Participants with masked hypertension had lower eGFR only in the presence of elevated nighttime BP (-3.6 ml/min per 1.73 m(2); 95% confidence interval, -6.1 to -1.1; versus -1.4 ml/min per 1.73 m(2); 95% confidence interval, -6.9 to 4.0, among those with nighttime BP <120/70 mmHg; P value for interaction with nighttime systolic BP 0.002). CONCLUSIONS: Masked hypertension is common in patients with CKD and associated with lower eGFR, proteinuria, and cardiovascular target organ damage. In patients with CKD, ambulatory BP characterizes the relationship between BP and target organ damage better than BP measured in the clinic alone.

Association between Inflammation and Cardiac Geometry in Chronic Kidney Disease: Findings from the CRIC Study.

BACKGROUND: Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function. METHODS: Plasma levels of interleukin (IL)-1ß, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted at a centralized core laboratory. RESULTS: LVH, systolic dysfunction and diastolic dysfunction were present in 52.3%, 11.8% and 76.3% of the study subjects, respectively. In logistic regression analysis adjusted for age, sex, race/ethnicity, diabetic status, current smoking status, systolic blood pressure, urinary albumin- creatinine ratio and estimated glomerular filtration rate, hs-CRP (OR 1.26 [95% CI 1.16, 1.37], p<0.001), IL-1RA (1.23 [1.13, 1.34], p<0.0001), IL-6 (1.25 [1.14, 1.36], p<0.001) and TNF-α (1.14 [1.04, 1.25], p = 0.004) were associated with LVH. The odds for systolic dysfunction were greater for subjects with elevated levels of hs-CRP (1.32 [1.18, 1.48], p<0.001) and IL-6 (1.34 [1.21, 1.49], p<0.001). Only hs-CRP was associated with diastolic dysfunction (1.14 [1.04, 1.26], p = 0.005). CONCLUSION: In patients with CKD, elevated plasma levels of hs-CRP and IL-6 are associated with LVH and systolic dysfunction.

Relation of aortic valve calcium to chronic kidney disease (from the Chronic Renal Insufficiency Cohort Study).

Although subjects with chronic kidney disease (CKD) are at markedly increased risk for cardiovascular mortality, the relation between CKD and aortic valve calcification has not been fully elucidated. Also, few data are available on the relation of aortic valve calcification and earlier stages of CKD. We sought to assess the relation of aortic valve calcium (AVC) with estimated glomerular filtration rate (eGFR), traditional and novel cardiovascular risk factors, and markers of bone metabolism in the Chronic Renal Insufficiency Cohort (CRIC) Study. All patients who underwent aortic valve scanning in the CRIC study were included. The relation between AVC and eGFR, traditional and novel cardiovascular risk factors, and markers of calcium metabolism were analyzed using both unadjusted and adjusted regression models. A total of 1,964 CRIC participants underwent computed tomography for AVC quantification. Decreased renal function was independently associated with increased levels of AVC (eGFR 47.11, 44.17, and 39 ml/min/1.73 m2, respectively, p<0.001). This association persisted after adjusting for traditional, but not novel, AVC risk factors. Adjusted regression models identified several traditional and novel risk factors for AVC in patients with CKD. There was a difference in AVC risk factors between black and nonblack patients. In conclusion, our study shows that eGFR is associated in a dose-dependent manner with AVC in patients with CKD, and this association is independent of traditional cardiovascular risk factors.

Hemodynamic outcomes of transcatheter aortic valve replacement and medical management in severe, inoperable aortic stenosis: a longitudinal echocardiographic study of cohort B of the PARTNER trial.

BACKGROUND: Inoperable aortic stenosis may be treated with either transcatheter aortic valve replacement (TAVR) or medical management (MM) with or without balloon aortic valvuloplasty (BAV). The aim of this study was to compare the long-term echocardiographic findings among TAVR, MM, and BAV in patients with severe, inoperable aortic stenosis. METHODS: A total of 358 inoperable patients in the Placement of Aortic Transcatheter Valves trial were randomized to MM or TAVR. Echocardiograms obtained at baseline, 30 days, and 1, 2, and 3 years were analyzed by a central core laboratory. RESULTS: At baseline, TAVR and MM were similar, with more frequent Society of Thoracic Surgeons score > 10 (51.7% vs 65.0%, P = .03) and larger end-systolic volumes (54.5 ± 29.3 vs 69.1 ± 48.0 mL, P = .03) in MM. By 30 days after TAVR, mean aortic valve gradient had decreased (from 43.8 ± 14.7 to 10.0 ± 4.3 mm Hg, P < .001), ejection fraction had increased (from 53.2 ± 12.4% to 56.7 ± 10.0%, P < .001), and left ventricular (LV) mass index had decreased (from 144.7 ± 36.1 to 140.0 ± 37.9 gm/m(2), P < .05). After 1 year, aortic valve gradients and area were unchanged, while LV mass index had decreased by another 16 gm/m(2) (to 124 gm/m(2)). By 30 days after BAV, mean aortic valve gradient had decreased from 43.4 ± 15.0 to 31.9 ± 11.1 mm Hg, while ejection fraction and LV mass index were unchanged; gradient reverted to baseline at 1 year. No changes in gradients or mass were seen in MM patients. CONCLUSIONS: TAVR results in immediate and sustained relief in pressure overload and improved LV systolic function, with continued regression of hypertrophy over 3 years. Poor clinical results with BAV are explained by the modest and transient reductions in pressure overload with BAV, which were not accompanied by improved LV function or remodeling. TAVR is the preferred treatment in eligible inoperable patients (ClinicalTrials.gov identifier NCT00530894).

Serum aldosterone and death, end-stage renal disease, and cardiovascular events in blacks and whites: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

Prior studies have demonstrated that elevated aldosterone concentrations are an independent risk factor for death in patients with cardiovascular disease. Limited studies, however, have evaluated systematically the association between serum aldosterone and adverse events in the setting of chronic kidney disease. We investigated the association between serum aldosterone and death and end-stage renal disease in 3866 participants from the Chronic Renal Insufficiency Cohort. We also evaluated the association between aldosterone and incident congestive heart failure and atherosclerotic events in participants without baseline cardiovascular disease. Cox proportional hazards models were used to evaluate independent associations between elevated aldosterone concentrations and each outcome. Interactions were hypothesized and explored between aldosterone and sex, race, and the use of loop diuretics and renin-angiotensin-aldosterone system inhibitors. During a median follow-up period of 5.4 years, 587 participants died, 743 developed end-stage renal disease, 187 developed congestive heart failure, and 177 experienced an atherosclerotic event. Aldosterone concentrations (per SD of the log-transformed aldosterone) were not an independent risk factor for death (adjusted hazard ratio, 1.00; 95% confidence interval, 0.93-1.12), end-stage renal disease (adjusted hazard ratio, 1.07; 95% confidence interval, 0.99-1.17), or atherosclerotic events (adjusted hazard ratio, 1.04; 95% confidence interval, 0.85-1.18). Aldosterone was associated with congestive heart failure (adjusted hazard ratio, 1.21; 95% confidence interval, 1.02-1.35). Among participants with chronic kidney disease, higher aldosterone concentrations were independently associated with the development of congestive heart failure but not for death, end-stage renal disease, or atherosclerotic events. Further studies should evaluate whether mineralocorticoid receptor antagonists may reduce adverse events in individuals with chronic kidney disease because elevated cortisol levels may activate the mineralocorticoid receptor.