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- Kong, Jeremy, et al.
(författare)
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Incidence, Predictors, and Outcomes Associated With Worsening Renal Function in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial.
- 2023
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 12:14
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Tidskriftsartikel (refereegranskat)abstract
- Background The incidence and implications of worsening renal function (WRF) after mitral valve transcatheter edge-to-edge repair (TEER) in patients with heart failure (HF) are unknown. Therefore, the aim of this study was to determine the proportion of patients with HF and secondary mitral regurgitation who develop persistent WRF within 30 days following TEER, and whether this development portends a worse prognosis. Methods and Results In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, 614 patients with HF and severe secondary mitral regurgitation were randomized to TEER with the MitraClip plus guideline-directed medical therapy (GDMT) versus GDMT alone. WRF was defined as serum creatinine increase ≥1.5× or ≥0.3 mg/dL from baseline persisting to day 30 or requiring renal replacement therapy. All-cause death and HF hospitalization rates between 30 days and 2 years were compared in patients with and without WRF. WRF at 30 days was present in 11.3% of patients (9.7% in the TEER plus GDMT group and 13.1% in the GDMT alone group; P=0.23). WRF was associated with all-cause death (hazard ratio [HR], 1.98 [95% CI, 1.3-3.03]; P=0.001) but not HF hospitalization (HR, 1.47 [ 95% CI, 0.97-2.24]; P=0.07) between 30 days and 2 years. Compared with GDMT alone, TEER reduced both death and HF hospitalization consistently in patients with and without WRF (Pinteraction=0.53 and 0.57, respectively). Conclusions Among patients with HF and severe secondary mitral regurgitation, the incidence of WRF at 30 days was not increased after TEER compared with GDMT alone. WRF was associated with greater 2-year mortality but did not attenuate the treatment benefits of TEER in reducing death and HF hospitalization compared with GDMT alone. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.
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- Revechon, G, et al.
(författare)
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Splice-inhibition therapy targets progeria
- 2021
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 27:3, s. 377-379
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Tidskriftsartikel (refereegranskat)
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- Shah, Neeraj, et al.
(författare)
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Prediction of Death or HF Hospitalization in Patients With Severe FMR: The COAPT Risk Score.
- 2022
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Ingår i: JACC. Cardiovascular interventions. - 1876-7605. ; 15:19, s. 1893-1905
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Tidskriftsartikel (refereegranskat)abstract
- There are limited data on the predictors of death or heart failure hospitalization (HFH) in patients with heart failure (HF) with functional mitral regurgitation (FMR).The aim of this study was to develop a predictive risk score using the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial database.In COAPT, 614 symptomatic patients with HF and moderate to severe or severe FMR were randomized to MitraClip implantation plus guideline-directed medical therapy (GDMT) or GDMT alone. A risk score for the 2-year rate of death or HFH was generated from Cox proportional hazards models. The predictive value of the model was assessed using the area under the curve of receiver-operating characteristic plots. Kaplan-Meier curves were generated to estimate the proportion of patients experiencing death or HFH across quartiles of risk.During 2-year follow-up, 201 patients (64.4%) in the GDMT-alone group and 133 patients (44.0%) in the MitraClip group experienced death or HFH (P < 0.001). A risk score containing 4 clinical variables (New York Heart Association functional class, chronic obstructive pulmonary disease, atrial fibrillation or flutter, and chronic kidney disease) and 4 echocardiographic variables (left ventricular ejection fraction, left ventricular end-systolic dimension, right ventricular systolic pressure, and tricuspid regurgitation) in addition to MitraClip treatment was generated. The area under the curve of the risk score model was 0.74, and excellent calibration was present. The relative benefit of MitraClip therapy in reducing the 2-year hazard of death or HFH was consistent across the range of baseline risk.A simple risk score of clinical, echocardiographic, and treatment variables may provide useful prognostication in patients with HF and severe FMR.
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- Vincent, Flavien, et al.
(författare)
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Cerebrovascular Events After Transcatheter Edge-to-Edge Repair and Guideline-Directed Medical Therapy in the COAPT Trial.
- 2023
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Ingår i: JACC. Cardiovascular interventions. - 1936-8798 .- 1876-7605. ; 16:12, s. 1448-1459
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Tidskriftsartikel (refereegranskat)abstract
- Little is known regarding the risk of cerebrovascular events (CVE) in patients with heart failure and severe secondary mitral regurgitation treated with transcatheter edge-to-edge repair (TEER).The study sought to examine the incidence, predictors, timing, and prognostic impact of CVE (stroke or transient ischemic attack) in the COAPT (Cardiovascular Outcomes Assessment of the Mitraclip Percutaneous Therapy for HeartFailure Patients with Functional Mitral Regurgitation) trial.A total of 614 patients with heart failure and severe secondary mitral regurgitation were randomized to TEER plus guideline-directed medical therapy (GDMT) vs GDMT alone.At 4-year follow-up, 50 CVEs occurred in 48 (7.8%) of the 614 total patients enrolled in the COAPT trial; Kaplan-Meier event rates were 12.3% in the TEER group and 10.2 in the GDMT alone group (P=0.91). Within 30days of randomization, CVE occurred in 2 (0.7%) patients randomized to TEER and 0% randomized to GDMT (P=0.15). Baseline renal dysfunction and diabetes were independently associated with increased risk of CVE, while baseline anticoagulation was associated with a reduction of CVE. A significant interaction was present between treatment group and anticoagulation such that TEER compared with GDMT alone was associated with a reduced risk of CVE among patients with anticoagulation (adjusted HR: 0.24; 95%CI: 0.08-0.73) compared with an increased risk of CVE in patients without anticoagulation (adjusted HR: 2.27; 95%CI: 1.08-4.81; Pinteraction=0.001). CVE was an independent predictor of death within 30days after the event (HR: 14.37; 95%CI: 7.61, 27.14; P< 0.0001).In the COAPT trial, the 4-year rate of CVE was similar after TEER or GDMT alone. CVE was strongly associated with mortality. Whether anticoagulation is effective at reducing CVE risk after TEER warrants further study.(Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for HeartFailure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT); NCT01626079).
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- Whisenant, D, et al.
(författare)
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Transient expression of an adenine base editor corrects the Hutchinson-Gilford progeria syndrome mutation and improves the skin phenotype in mice
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 3068-
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Tidskriftsartikel (refereegranskat)abstract
- Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature ageing disorder caused by a point mutation in the LMNA gene (LMNA c.1824 C > T), resulting in the production of a detrimental protein called progerin. Adenine base editors recently emerged with a promising potential for HGPS gene therapy. However adeno-associated viral vector systems currently used in gene editing raise concerns, and the long-term effects of heterogeneous mutation correction in highly proliferative tissues like the skin are unknown. Here we use a non-integrative transient lentiviral vector system, expressing an adenine base editor to correct the HGPS mutation in the skin of HGPS mice. Transient adenine base editor expression corrected the mutation in 20.8-24.1% of the skin cells. Four weeks post delivery, the HGPS skin phenotype was improved and clusters of progerin-negative keratinocytes were detected, indicating that the mutation was corrected in both progenitor and differentiated skin cells. These results demonstrate that transient non-integrative viral vector mediated adenine base editor expression is a plausible approach for future gene-editing therapies.
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