Kennedy, Austin M

Background: Total kidney volume (TKV), a prognostic biomarker in ADPKD, is used to stratify high risk individuals. eGFR measures may carry significant error in ADPKD compared to measured GFR(mGFR). This retrospective study investigates the association between height adjusted TKV (htTKV) and eGFR derived from race-free CKD-EPI equations utilizing creatinine and cystatin C. Methods: eGFR was calculated using 3 race-free CKD-EPI formulas: creatinine-based (CKD-EPI creatinine), cystatin C (CKD-EPI cys), and creatinine-cystatin C (CKD-EPI creatinine-cystatin C) equations on 697 Mayo Clinic ADPKD patients. Correlations between eGFR and TKV measures were estimated and stratified by MIC class risk groups and CKD. Linear regression models were computed to predict ln(htTKV) from the 3 eGFR data sets. The eGFR measures were compared to iothalamate-based mGFR in a subset of patients (n=50). Results: A correlation between eGFR measures and htTKV (Pearson correlation r of -0.53 to -0.54), varied by MIC stratification. Pearson correlation was -0.47 to -0.48 for MIC 1A and 1B, -0.67 to -0.71 for MIC 1C, and -0.67 to -0.68 for MIC 1D and 1E. All equations were significantly associated with htTKV levels, with similar adjusted beta values (95% CI) of -0.15 (-0.17 to -0.13), -0.14 (-0.16 to -0.12), -0.15 (-0.16 to -0.13), for CKD-EPI creatinine, CKD-EPI cystatin C, and CKD-EPI creatinine-cystatin C, respectively. Compared to mGFR, the CKD-EPI creatinine-cystatin C equation was the least biased (mean -0.86 (95% CI: -3.09 to 1.37)) versus CKD-EPI creatinine (2.31 (-0.73 to 5.34)) or CKD-EPI cystatin C (-3.54 (-5.86 to -1.21)), and most precise, with 1-P30 of 16% (95% CI 7.2% to 29.1%), compared to 18% (8.6% to 31.4%) for CKD-EPI creatinine, or 20% (10.0% to 33.7%) for CKD-EPI cystatin C. Conclusion: A moderate correlation between eGFR and htTKV associated with MIC stratification. Associations between htTKV and all 3 CKD-EPI equations were similar. CKDEPIcrcys tended to be the least biased and most precise equation when compared to mGFR and may be a reasonable alternative.

Abstract Aims We aimed to assess regression and development rates of ≥moderate secondary mitral regurgitation (MR) and tricuspid regurgitation (TR) in patients with heart failure and reduced ejection fraction (HFrEF) receiving contemporary guideline-directed medical therapy (GDMT). Methods Patients with a <1 year diagnosis of HFrEF with mildly (40% ≤ EF < 50%) or moderately (<40%) reduced EF enrolled in GDMT titration programme 2019–2024 were identified. Regression rates of ≥moderate MR/TR to ≤mild and development rates of incident ≥moderate MR/TR were calculated. Results Among 844 patients [median age 64; 68% men; 26% mildly reduced EF; 24% New York Heart Association (NYHA) Class III/IV], 28% had ≥moderate MR and 14% had ≥moderate TR. Over median 7.1 months, 171 (75%) patients with ≥moderate MR and 87 (75%) of patients with ≥moderate TR experienced regression to no/mild MR and TR, respectively. Conversely, over median 13 months, incident ≥moderate MR and TR developed in 5% and 6%, respectively, of patients with no/mild baseline MR and TR. Number of GDMT medications at follow-up was less in patients who did not have MR/TR regression (vs who did) and in patients who developed MR/TR (vs who did not). Patients with NYHA Class I/II received a similar number of GDMT and had a similar rate of MR and TR regression and development vs patients with NYHA Class III/IV. However, patients with mildly reduced EF received less GDMT medications vs patients with moderately reduced EF and experienced less MR regression. Conclusion In patients with a recent diagnosis of HFrEF receiving contemporary GDMT, the majority with ≥moderate secondary MR and TR achieved regression of MR/TR, and the minority without significant baseline MR/TR developed ≥moderate regurgitation at follow-up.

Abstract Aims Pulmonary regurgitation (PR) after reparative intervention for congenital heart disease has been studied extensively. However, the burden, distribution of causes, and outcome of PR in adults is unknown. The study aimed to evaluate the prevalence, types, and outcomes of moderate/severe PR in adults in the community setting. Methods and results A total of 398 adult residents of Olmsted County who had clinically indicated echocardiography 2004–2023 at Mayo Clinic, Rochester, and had moderate or severe PR were identified retrospectively. The median age was 77 years, 48% were females, and 61 (51%) had severe PR. The age- and sex-adjusted US prevalence was 0.11% (vs. 0.67% for ≥moderate tricuspid regurgitation). Moderate/severe PR was due to pulmonary hypertension in 77%, congenital/iatrogenic in 11%, primary pulmonary valve disease in 2% (88% due to carcinoid), and idiopathic isolated in 10%. In contrast, severe PR was due to congenital/iatrogenic disease in 52%, pulmonary hypertension in 39%, primary PR in 5%, and isolated idiopathic in 3%. The all-cause mortality rate per 100 person-year was 73 in primary (mostly carcinoid) PR, 16 in pulmonary hypertension–related PR (not different vs. propensity-matched patients without PR), and 6 in isolated idiopathic PR (not different vs. matched patients without PR). Conclusion Moderate or severe PR had a lower prevalence vs. TR. The most frequent cause was pulmonary hypertension for ≥moderate PR and congenital/iatrogenic for severe PR. Mortality in patients with acquired ≥moderate PR appeared to be related to the underlying cause, with no excess mortality compared with matched patients without PR. Whether specifically severe PR confers excess mortality requires future investigation.

Abstract Background and Aims Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are intimately associated disorders; HFpEF may be overlooked in AF when symptoms are simply attributed to dysrhythmia, and incident AF may identify patients at risk for developing diastolic dysfunction (DD). This study aimed to investigate the prevalence and incidence of DD in patients with new-onset AF compared with sinus rhythm (SR). Methods Adults with new-onset AF (n = 1747) or SR (n = 29 623) and no structural heart disease were identified. Propensity score matching was performed (1:3 ratio) between AF and SR based on age, sex, body mass index, and comorbidities. Severe DD (SDD) was defined by ≥3/four abnormal parameters (medial e’, medial E/e’, tricuspid regurgitation velocity, and left atrial volume index) and ≥moderate DD (>MDD) by ≥2/4. Annualized changes in DD indices were determined. Results New-onset AF was independently associated with SDD (8% vs. 3%) and ≥MDD (25% vs. 16%); 62% of patients with AF had high-risk H2FPEF scores, and 5% had clinically recognized HFpEF. Over a median follow-up of 3.2 (interquartile range 1.6–5.8) years, DD progressed two–four-fold more rapidly in those with new-onset AF (P < .001 for all). The risk for incident DD was increased in new-onset AF [hazard ratio (95% confidence interval) 2.69 (2.19–3.32) for SDD and 1.73 (1.49–2.02) for ≥MDD]. Conclusions Patients with new-onset AF display high-risk features for HFpEF at diagnosis, emphasizing the importance of evaluating for HFpEF among symptomatic patients with AF. Patients with new-onset AF have accelerated progression in DD over time, which may identify patients with preclinical HFpEF, where preventive therapies may be tested.

Abstract Aims Atrial functional mitral regurgitation (AFMR) has been associated with atrial fibrillation (AF) and heart failure with preserved ejection fraction. However, data on incident AFMR are scarce. We aimed to study the incidence, risk factors, and clinical significance of AFMR in AF or sinus rhythm (SR). Methods and results Adults with new diagnosis of AF and adults in SR were identified. Patients with >mild MR at baseline, primary mitral disease, cardiomyopathy, left-sided valve disease, previous cardiac surgery, or with no follow-up echocardiogram were excluded. Diastolic dysfunction (DD) was indicated by ≥2/4 abnormal diastolic function parameters [mitral medial e′, mitral medial E/e′, tricuspid regurgitation velocity, left atrial volume index (LAVI)]. Overall, 1747 patients with AF and 29 623 in SR were included. Incidence rate of >mild AFMR was 2.6 per 100 person-year in new-onset AF and 0.7 per 100 person-year in SR, P < 0.001. AF remained associated with AFMR in a propensity score-matched analysis based on age, sex, and comorbidities between AF and SR [hazard ratio: 3.80 (95% confidence interval 3.04–4.76)]. Independent risk factors associated with incident AFMR were age ≥65 years, female sex, LAVI, and DD in both AF and SR, in addition to rate (vs. rhythm) control in AF. Incident AFMR was independently associated with all-cause death in both groups (both P < 0.001). Conclusions AF conferred a three-fold increase in the risk of incident AFMR. DD, older age, left atrial size, and female sex were independent risk factors in both SR and AF, while rhythm control was protective. AFMR was universally associated with worse mortality.