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Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis.

ABSTRACT: BACKGROUND:Left ventricular (LV) hypertrophy, a key process in human cardiac disease, results from cellular (hypertrophy) and extracellular matrix expansion (interstitial fibrosis). OBJECTIVES:This study sought to investigate whether human myocardial interstitial fibrosis in aortic stenosis (AS) is plastic and can regress. METHODS:Patients with symptomatic, severe AS (n = 181; aortic valve area index 0.4 ± 0.1 cm2/m2) were assessed pre-aortic valve replacement (AVR) by echocardiography (AS severity, diastology), cardiovascular magnetic resonance (CMR) (for volumes, function, and focal or diffuse fibrosis), biomarkers (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T), and the 6-min walk test. CMR was used to measure the extracellular volume fraction (ECV), thereby deriving matrix volume (LV mass × ECV) and cell volume (LV mass × [1 - ECV]). Biopsy excluded occult bystander disease. Assessment was repeated at 1 year post-AVR. RESULTS:At 1 year post-AVR in 116 pacemaker-free survivors (age 70 ± 10 years; 54% male), mean valve gradient had improved (48 ± 16 mm Hg to 12 ± 6 mm Hg; p < 0.001), and indexed LV mass had regressed by 19% (88 ± 26 g/m2 to 71 ± 19 g/m2; p < 0.001). Focal fibrosis by CMR late gadolinium enhancement did not change, but ECV increased (28.2 ± 2.9% to 29.9 ± 4.0%; p < 0.001): this was the result of a 16% reduction in matrix volume (25 ± 9 ml/m2 to 21 ± 7 ml/m2; p < 0.001) but a proportionally greater 22% reduction in cell volume (64 ± 18 ml/m2 to 50 ± 13 ml/m2; p < 0.001). These changes were accompanied by improvement in diastolic function, N-terminal pro-B-type natriuretic peptide, 6-min walk test results, and New York Heart Association functional class. CONCLUSIONS:Post-AVR, focal fibrosis does not resolve, but diffuse fibrosis and myocardial cellular hypertrophy regress. Regression is accompanied by structural and functional improvements suggesting that human diffuse fibrosis is plastic, measurable by CMR and a potential therapeutic target. (Regression of Myocardial Fibrosis After Aortic Valve Replacement; NCT02174471).

SUBMITTER: Treibel TA

PROVIDER: S-EPMC5821681 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis.

Treibel Thomas A TA Kozor Rebecca R Schofield Rebecca R Benedetti Giulia G Fontana Marianna M Bhuva Anish N AN Sheikh Amir A López Begoña B González Arantxa A Manisty Charlotte C Lloyd Guy G Kellman Peter P Díez Javier J Moon James C JC

Journal of the American College of Cardiology 20180201 8

<h4>Background</h4>Left ventricular (LV) hypertrophy, a key process in human cardiac disease, results from cellular (hypertrophy) and extracellular matrix expansion (interstitial fibrosis).<h4>Objectives</h4>This study sought to investigate whether human myocardial interstitial fibrosis in aortic stenosis (AS) is plastic and can regress.<h4>Methods</h4>Patients with symptomatic, severe AS (n = 181; aortic valve area index 0.4 ± 0.1 cm<sup>2</sup>/m<sup>2</sup>) were assessed pre-aortic valve rep ...[more]

PMID: 29471937

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Project description:ImportanceThe outcomes of transcatheter aortic valve replacement (TAVR) in low-risk patients with bicuspid aortic valve stenosis have not been studied in a large scale, multicentered, prospective fashion.ObjectiveTo evaluate the procedural safety, efficacy, and 30-day outcomes of TAVR in patients with bicuspid aortic stenosis at low surgical risk.Design, setting, and participantsThe Low Risk Bicuspid Study is a prospective, single-arm trial study with inclusion/exclusion criteria developed from the Evolut Low Risk Randomized Trial. Follow-up is planned for 10 years. Patients underwent TAVR at 25 centers in the United States who were also participating in the Evolut Low Risk Randomized Trial from December 2018 to October 2019. Eligible patients had severe bicuspid aortic valve stenosis and met American Heart Association/American College of Cardiology guideline indications for aortic valve replacement.InterventionsPatients underwent attempted implant of an Evolut or Evolut PRO transcatheter aortic valve, with valve size based on annular measurements.Main outcomes and measuresThe prespecified primary end point was the incidence of all-cause mortality or disabling stroke at 30 days. The prespecified primary efficacy end point was device success defined as the absence of procedural mortality, the correct position of 1 bioprosthetic heart valve in the proper anatomical location, and the absence of more than mild aortic regurgitation postprocedure.ResultsA total of 150 patients underwent an attempted implant. Baseline characteristics include mean age of 70.3 (5.5) years, 48.0% female (n = 72), and a mean Society of Thoracic Surgeons score of 1.4 (0.6%). Most patients (136; 90.7%) had Sievers type I valve morphology. The incidence of all-cause mortality or disabling stroke was 1.3% (95% CI, 0.3%-5.3%) at 30 days. The device success rate was 95.3% (95% CI, 90.5%-98.1%). At 30 days, the mean (SD) AV gradient was 7.6 (3.7) mm Hg and effective orifice area was 2.3 (0.7) cm2. A new permanent pacemaker was implanted in 22 patients (15.1%). No patients had greater than mild paravalvular leak.Conclusions and relevanceTranscatheter aortic valve replacement in low-surgical risk patients with bicuspid aortic valve stenosis achieved favorable 30-day results, with low rates of death and stroke and high device success rate.Trial registrationClinicalTrials.gov Identifier: NCT03635424.

Project description:Importance:Clinical practice guidelines currently endorse a reliance on clinical symptoms of overt left ventricular (LV) failure to time aortic valve replacement for severe aortic stenosis; however, delayed aortic valve replacement can result in irreversible LV injury and adverse outcomes. Blood metabolomic signatures possess prognostic value in heart failure; this study assesses whether they are informative in aortic stenosis. Objective:To evaluate the value of metabolomic signatures in reflecting the extent of maladaptive LV remodeling in patients with end-stage aortic stenosis undergoing transcatheter aortic valve replacement, and to assess whether this procedure reverses metabolomic aberrations. Design, Setting, and Participants:This study of 44 patients with symptomatic severe aortic stenosis who underwent transfemoral transcatheter aortic valve replacement at a single-center tertiary care hospital. Liquid chromatography-mass spectrometry-based metabolomic profiling was performed on blood samples collected before and 24 hours after the procedure, and analyses were conducted to identify metabolites related to the measures of LV remodeling. Main Outcomes and Measures:We evaluated LV ejection fraction, LV mass index, and relative wall thickness, as well as levels of the acylcarnitines C16, C18:1, C18:2, C18, C26, choline, and kynurenine. Results:We enrolled 44 patients with severe aortic stenosis with a mean (SD) age of 81.9 (8.5) years, of whom 23 (52%) were women. The mean (SD) LV ejection fraction was 56.7% (18.2%), mean (SD) LV mass index was 117.3 (41.4) g/m2, and relative wall thickness was 0.53 (0.14). The mean ? values of acylcarnitines C16, C18:1, C18:2, C18, and C26 were independently associated with LV mass index (C16: mean, 19.24; 95% CI, 5.48-33.01; P?=?.008; C18:1: mean, 26.18; 95% CI, 14.04-38.32; P?<?1.0?×?10-4; C18:2: mean, 17.42; 95% CI, 3.40-31.43; P?=?.02; C18: mean, 25.25; 95% CI, 10.91-39.58; P?=?.001; C26: mean, 19.93; 95% CI, 4.41-35.45; P?=?.01), even after adjustments for age, sex, diabetes status, renal function, and B-type natriuretic peptide (BNP). Circulating levels of C18:2 acylcarnitine were associated with LV ejection fraction before and after multivariable adjustment (mean, -6.11; 95% CI, -10.88 to 1.34; P?=?.01). Blood metabolite levels did not independently relate to relative wall thickness. Within 24 hours of transcatheter aortic valve replacement, circulating levels of C16 decreased by 30.2% (P?=?7.3?×?10-6), C18:1 by 42.7% (P?=?3.7?×?10-8), C18:2 by 37.3% (P?=?5.1?×?10-6), and C18 by 38.3% (P?=?3.4?×?10-5). Conclusions and Relevance:In symptomatic patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, circulating levels of long-chain acylcarnitines were independently associated with measures of maladaptive LV remodeling, and metabolic perturbations lessened after procedure completion. Further efforts are needed to determine the clinical applicability of these novel biomarkers.

Project description:BackgroundCirculatory efficiency reflects the ratio between total left ventricular work and the work required for maintaining cardiovascular circulation. The effect of severe aortic valve stenosis (AS) and aortic valve replacement (AVR) on left ventricular/circulatory mechanical power and efficiency is not yet fully understood. We aimed to quantify left ventricular (LV) efficiency in patients with severe AS before and after surgical AVR.MethodsCirculatory efficiency was computed from cardiovascular magnetic resonance (CMR) imaging derived volumetric data, echocardiographic and clinical data in patients with severe AS (n?=?41) before and 4 months after AVR and in age and sex-matched healthy subjects (n?=?10).ResultsIn patients with AS circulatory efficiency was significantly decreased compared to healthy subjects (9?±?3% vs 12?±?2%; p?=?0.004). There were significant negative correlations between circulatory efficiency and LV myocardial mass (r?=?-?0.591, p?<?0.001), myocardial fibrosis volume (r?=?-?0.427, p?=?0.015), end systolic volume (r?=?-?0.609, p?<?0.001) and NT-proBNP (r?=?-?0.444, p?=?0.009) and significant positive correlation between circulatory efficiency and LV ejection fraction (r?=?0.704, p?<?0.001). After AVR, circulatory efficiency increased significantly in the total cohort (9?±?3 vs 13?±?5%; p?<?0.001). However, in 10/41 (24%) patients, circulatory efficiency remained below 10% after AVR and, thus, did not restore to normal values. These patients also showed less reduction in myocardial fibrosis volume compared to patients with restored circulatory efficiency after AVR.ConclusionIn our cohort, circulatory efficiency is reduced in patients with severe AS. In 76% of cases, AVR leads to normalization of circulatory efficiency. However, in 24% of patients, circulatory efficiency remained below normal values even after successful AVR. In these patients also less regression of myocardial fibrosis volume was seen. Trial Registration clinicaltrials.gov NCT03172338, June 1, 2017, retrospectively registered.

Dataset Information

Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis.

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Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis.

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