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Novel Heart Failure Biomarkers Predict Improvement of Mitral Regurgitation in Patients Receiving Cardiac Resynchronization Therapy-The BIOCRT Study.

ABSTRACT: Cardiac resynchronization therapy (CRT) improves mitral regurgitation (MR) in a subset of patients. We hypothesized that biomarkers (amino-terminal pro-B type natriuretic peptide, high-sensitivity troponin I, galectin-3 [gal-3], and soluble ST2) might predict MR response after CRT.We measured levels of biomarkers during CRT implantation in 132 patients with a subsequent 2-year follow-up. MR was graded as no-trace, mild, moderate, or severe at baseline and at 6 months.In patients with baseline at least mild MR, 56% had improvement at 6 months, with lower 2-year mortality vs patients without improvement (0% vs 18%; P = 0.002). At baseline, patients with MR improvement had lower high-sensitivity troponin I and gal-3 levels compared with those without improvement (19 vs 40 pg/L; P = 0.01; 14 vs 18 ng/mL; P = 0.007). In multivariable analyses, higher log-transformed gal-3 (odds ratio, 0.15; 95% confidence interval, 0.04-0.65; P = 0.01) remained an independent predictor for MR nonimprovement. Levels of pro-B type natriuretic peptide and soluble ST2 were lower at follow-up in patients with MR improvement (potentially reflecting reduced myocardial stretch and stress) without reaching statistical significance.Higher galectin levels at the time of CRT implantation are associated with MR nonresponse.

SUBMITTER: Beaudoin J

PROVIDER: S-EPMC5123954 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Novel Heart Failure Biomarkers Predict Improvement of Mitral Regurgitation in Patients Receiving Cardiac Resynchronization Therapy-The BIOCRT Study.

Beaudoin Jonathan J Singh Jagmeet P JP Szymonifka Jackie J Zhou Qing Q Levine Robert A RA Januzzi James L JL Truong Quynh A QA

The Canadian journal of cardiology 20160602 12

<h4>Background</h4>Cardiac resynchronization therapy (CRT) improves mitral regurgitation (MR) in a subset of patients. We hypothesized that biomarkers (amino-terminal pro-B type natriuretic peptide, high-sensitivity troponin I, galectin-3 [gal-3], and soluble ST2) might predict MR response after CRT.<h4>Methods</h4>We measured levels of biomarkers during CRT implantation in 132 patients with a subsequent 2-year follow-up. MR was graded as no-trace, mild, moderate, or severe at baseline and at 6 ...[more]

PMID: 27527259

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Project description:Objectives: To assess the prevalence and impact of mitral regurgitation (MR) on survival in patients presenting to hospital in acute heart failure (AHF) using traditional echocardiographic assessment alongside more novel indices of proportionality. Background: It remains unclear if the severity of MR plays a significant role in determining outcomes in AHF. There is also uncertainty as to the clinical relevance of indexing MR to left ventricular volumes. This concept of disproportionality has not been assessed in AHF. Methods: A total of 418 consecutive patients presenting in AHF over 12 months were recruited and followed up for 2 years. MR was quantitatively assessed within 24 h of recruitment. Standard proximal isovelocity surface area (PISA) and a novel proportionality index of effective regurgitant orifice/left ventricular end-diastolic volume (ERO/LVEDV) >0.14 mm2/ml were used to identify severe and disproportionate MR. Results: Every patient had MR. About 331/418 (78.9%) patients were quantifiable by PISA. About 165/418 (39.5%) patients displayed significant MR. A larger cohort displayed disproportionate MR defined by either a proportionality index using ERO/LVEDV > 0.14 mm2/ml or regurgitant volumes/LVEDV > 0.2 [217/331 (65.6%) and 222/345 (64.3%), respectively]. The LVEDV was enlarged in significant MR-129.5 ± 58.95 vs. 100.0 ± 49.91 ml in mild, [p < 0.0001], but remained within the normal range. Significant MR was associated with a greater mortality at 2 years {44.2 vs. 34.8% in mild MR [hazard ratio (HR) 1.39; 95% CI: 1.01-1.92, p = 0.04]}, which persisted with adjustment for comorbid conditions (HR; 1.43; 95% CI: 1.04-1.97, p = 0.03). Disproportionate MR defined by ERO/LVEDV >0.14 mm2/ml was also associated with worse outcome [42.4 vs. 28.3% (HR 1.62; 95% CI 1.12-2.34, p = 0.01)]. Conclusions: MR was a universal feature in AHF and determines outcome in significant cases. Furthermore, disproportionate MR, defined either by effective regurgitant orifice (ERO) or volumetrically, is associated with a worse prognosis despite the absence of adverse left ventricular (LV) remodeling. These findings outline the importance of adjusting acute volume overload to LV volumes and call for a review of the current standards of MR assessment. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02728739, identifier NCT02728739.

Project description:AimsTherapeutic options for patients with heart failure with preserved ejection fraction (HFpEF) are sparse. Mitral regurgitation (MR) is a common feature of HFpEF and worsens heart failure symptoms and prognosis. Our study examines the outcome of patients with preserved left ventricular ejection fraction (LVEF) and elevated left atrial (LAP) or left ventricular filling pressures (LVEDP), indicative of HFpEF, after undergoing percutaneous edge-to-edge mitral valve repair (pMVR) for moderate-severe MR.Methods and resultsTwo hundred eleven patients with preserved LVEF (>50%), who underwent pMVR, were dichotomized by LAP (< / ≥15 mmHg) and LVEDP (< / ≥16 mmHg). Forty-nine per cent of patients showed elevated LAP, and LVEDP was elevated in 55%, both indicating HFpEF. Patients with elevated filling pressures featured typical clinical characteristics of HFpEF, higher N-terminal pro-brain natriuretic peptide levels (5544.9 pg/mL in high LAP group vs. 3071.7 pg/mL in normal LAP group, P = 0.06; 5061.0 pg/mL in high LVEDP group vs. 3230.3 pg/mL in normal LVEDP group, P = 0.08), and higher prevalence of pulmonary hypertension (mean pulmonary artery pressure 36.4 mmHg in high LAP group vs. 26.3 mmHg in normal LAP group, P < 0.001; 35.2 mmHg in high LVEDP group vs. 29.7 mmHg in normal LVEDP group, P = 0.004) and atrial fibrillation (78.8% in normal LAP group vs. 61.0% in high LAP group, P = 0.04; 75.3% in high LVEDP group vs. 67.5% in normal LVEDP group, P = 0.25). Pre-treatment MR grade and New York Heart Association (NYHA) class were similar in both normal filling pressure and HFpEF groups. pMVR in HFpEF patients achieved effective heart failure symptom relief comparable with patients with normal filling pressures: significant decrease of MR grade and NYHA class, as well as significant reduction of heart failure hospitalizations 12 months after compared with 12 months before MitraClip.ConclusionPercutaneous edge-to-edge mitral valve repair for moderate-severe MR is an effective treatment option for symptom relief in HFpEF patients.

Project description:BACKGROUND:In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) led to reduced heart failure (HF) hospitalizations and improved survival in patients with symptomatic HF and 3+ to 4+ secondary mitral regurgitation (MR) on maximally-tolerated medical therapy. Given the advanced age and comorbidities of these patients, improvement in health status is also an important treatment goal. OBJECTIVES:The purpose of this study was to understand the health status outcomes of patients with HF and 3+ to 4+ secondary MR treated with TMVr versus standard care. METHODS:The COAPT trial randomized patients with HF and 3+ to 4+ secondary MR to TMVr (n = 302) or standard care (n = 312). Health status was assessed at baseline and at 1, 6, 12, and 24 months with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the SF-36 health status survey. The primary health status endpoint was the KCCQ overall summary score (KCCQ-OS; range 0 to 100; higher = better; minimum clinically important difference = 5 points). RESULTS:At baseline, patients had substantially impaired health status (mean KCCQ-OS 52.4 ± 23.0). While health status was unchanged over time in the standard care arm, patients randomized to TMVr demonstrated substantial improvement in the KCCQ-OS at 1 month (mean between-group difference 15.9 points; 95% confidence interval [CI]: 12.3 to 19.5 points), with only slight attenuation of this benefit through 24 months (mean between-group difference 12.8 points; 95% CI: 7.5 to 18.2 points). At 24 months, 36.4% of TMVr patients were alive with a moderately large (≥10-point) improvement versus 16.6% of standard care patients (p < 0.001), for a number needed to treat of 5.1 patients (95% CI: 3.6 to 8.7 patients). TMVr patients also reported better generic health status at each timepoint (24-month mean difference in SF-36 summary scores: physical 3.6 points; 95% CI: 1.4 to 5.8 points; mental 3.6 points; 95% CI: 0.8 to 6.4 points). CONCLUSIONS:Among patients with symptomatic HF and 3+ to 4+ secondary MR receiving maximally-tolerated medical therapy, edge-to-edge TMVr resulted in substantial early and sustained health status improvement compared with medical therapy alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079).

Dataset Information

Novel Heart Failure Biomarkers Predict Improvement of Mitral Regurgitation in Patients Receiving Cardiac Resynchronization Therapy-The BIOCRT Study.

Publications

Novel Heart Failure Biomarkers Predict Improvement of Mitral Regurgitation in Patients Receiving Cardiac Resynchronization Therapy-The BIOCRT Study.

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