Assessment of cardio-renal-hepatic function in patients with valvular heart disease: a multi-biomarker approach—the cardio-renal-hepatic score

Abstract

Background Valvular heart disease (VHD) can cause damage to extra-cardiac organs, and lead to multi-organ dysfunction. However, little is known about the cardio-renal-hepatic co-dysfunction, as well as its prognostic implications in patients with VHD. The study sought to develop a multi-biomarker index to assess heart, kidney, and liver function in an integrative fashion, and investigate the prognostic role of cardio-renal-hepatic function in VHD. Methods Using a large, contemporary, prospective cohort of 6004 patients with VHD, the study developed a multi-biomarker score for predicting all-cause mortality based on biomarkers reflecting heart, kidney, and liver function (N-terminal pro-B-type natriuretic peptide [NT-proBNP], creatinine, and albumin). The score was externally validated in another contemporary, prospective cohort of 3156 patients with VHD. Results During a median follow up of 731 (704–748) days, 594 (9.9%) deaths occurred. Increasing levels of NT-proBNP, creatinine, and albumin were independently and monotonically associated with mortality, and a weighted multi-biomarker index, named the cardio-renal-hepatic (CRH) score, was developed based on Cox regression coefficients of these biomarkers. The CRH score was a strong and independent predictor of mortality, with 1-point increase carrying over two times of mortality risk (overall adjusted hazard ratio [95% confidence interval]: 2.095 [1.891–2.320], P < 0.001). The score provided complementary prognostic information beyond conventional risk factors (C index: 0.78 vs 0.81; overall net reclassification improvement index [95% confidence interval]: 0.255 [0.204–0.299]; likelihood ratio test P < 0.001), and was identified as the most important predictor of mortality by the proportion of explainable log-likelihood ratio χ2 statistics, the best subset analysis, as well as the random survival forest analysis in most types of VHD. The predictive performance of the score was also demonstrated in patients under conservative treatment, with normal left ventricular systolic function, or with primary VHD. It achieved satisfactory discrimination (C index: 0.78 and 0.72) and calibration in both derivation and validation cohorts. Conclusions A multi-biomarker index was developed to assess cardio-renal-hepatic function in patients with VHD. The cardio-renal-hepatic co-dysfunction is a powerful predictor of mortality and should be considered in clinical management decisions.

Prevalence and impact of diabetes in patients with valvular heart disease

“…Besides, albumin is also a marker of liver synthetic function, which is often vulnerable and prognostically relevant in patients with significant VHD. 32 Noteworthy, all aforementioned mentioned variables are readily accessible, and thus our prognostic instrument, visualized as a nomogram, can be friendly-to-use in routine clinical practice. After further validation in future studies, this model may improve risk stratification of patients with both diabetes and VHD patients, and thereby guide therapeutic decision making.…”

“…Detailed echocardiographic criteria for significant VHD in the China-VHD study were the following: AS with a valve area ≤1.5cm 2 , or a maximal jet velocity ≥3 m/s, or a mean pressure gradient ≥20mmHg, AR with an effective regurgitation orifice ≥0.10cm 2 , or regurgitant fraction ≥30%, or regurgitant volume ≥30mL/beat, or jet width ≥25% of LV outflow tract, or vena contracta ≥0.3cm, MS with a valve area ≤1.5cm 2 , MR with an effective regurgitation orifice ≥0.20cm 2 , or vena contracta ≥0.3cm, or regurgitant volume ≥30mL/beat, or central jet MR>20% left atrium, and TR with at least moderate grade regurgitation, or a central jet area >5 cm 2 . 30 , 32 The echocardiographic criteria of severe VHD were the following: AS with a valve area ≤1.0cm 2 , or a maximal jet velocity ≥4 m/s, or a mean pressure gradient ≥40mmHg, AR with an effective regurgitation orifice ≥0.30cm 2 , or regurgitant fraction ≥50%, or regurgitant volume ≥60mL/beat, or jet width ≥65% of LV outflow tract, or vena contracta ≥0.6cm, or regurgitant jet reaching the level of left ventricular chordae tendineae or apex, or holodiastolic flow reversal in descending aorta, MS with a valve area ≤1.0cm 2 , MR with an effective regurgitation orifice ≥0.40cm 2 (primary MR) or ≥0.20cm 2 (secondary MR), or vena contracta ≥0.7cm, or regurgitant volume ≥60mL/beat (primary MR) or ≥30mL/beat (secondary MR), or central jet MR>40% left atrium, or regurgitant jet reaching the posterior wall or the top of the left atrium, and TR with an effective regurgitant orifice area ≥40 mm 2 , or regurgitant volume ≥45 ml/beat, or vena contracta width >0.7 cm, or central jet area >10 cm 2 , or central jet TR > 2/3 right atrium, or flow reversal to the top of right atrium or in the inferior vena cava. Mixed VHD was defined as both at least moderate regurgitant and stenotic lesions on a single valve, and severe mixed VHD was the mixed VHD with at least one severe valvular lesion.…”

“…MVHD was defined as the combination of at least moderate regurgitant or stenotic lesions on at least two valves, and severe MVHD was the MVHD with at least one severe valvular lesion. 30 , 32 …”