Clonal Hematopoiesis of Indeterminate Potential and Long-term Outcomes in Heart Transplantation

Clonal hematopoiesis of indeterminate potential (CHIP) mutations, a trait of aging, has been associated with the progression of cardiovascular disease and the development of malignancy. Uncertainty prevails regarding a robust association between CHIP and heart-transplantation (HT) outcomes. To deter...

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Veröffentlicht in:Journal of cardiac failure 2024-06
Hauptverfasser: SIMITSIS, PANAGIOTIS, NOHRIA, ANJU, KELLEHER, JANE, BOULET, JACINTHE, WANDERLEY, MAURO R.B., NATARAJAN, PRADEEP, LIBBY, PETER, MEHRA, MANDEEP R.
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container_title Journal of cardiac failure
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creator SIMITSIS, PANAGIOTIS
NOHRIA, ANJU
KELLEHER, JANE
BOULET, JACINTHE
WANDERLEY, MAURO R.B.
NATARAJAN, PRADEEP
LIBBY, PETER
MEHRA, MANDEEP R.
description Clonal hematopoiesis of indeterminate potential (CHIP) mutations, a trait of aging, has been associated with the progression of cardiovascular disease and the development of malignancy. Uncertainty prevails regarding a robust association between CHIP and heart-transplantation (HT) outcomes. To determine the prevalence of CHIP mutations in HT and their association with long-term outcomes, including cardiac allograft vasculopathy (CAV), graft failure, malignancy, and all-cause mortality. We conducted a mixed retrospective-prospective observational study of HT recipients with targeted sequencing for CHIP mutations (variant allele frequency [VAF] of ≥ 2%). The primary composite outcome was the first occurrence of CAV grade ≥ 2, graft failure, malignancy, cardiac retransplantation, or all-cause death. Secondary outcomes were the individual components of the composite primary outcome. Sensitivity analyses with base-case and extreme scenarios were performed. Among 95 HT recipients, 30 had CHIP mutations (31.6%). DNMT3A mutations were most common (44.7%), followed by PPM1D (13.2%), SF3B1 (10.5%), TET2 (7.9%), and TP53 (7.9%). The only significant independent predictor of CHIP was age at enrollment or age at transplantation. After multivariable adjustment, CHIP mutations were not associated with the primary outcome, which occurred in 44 (46.3%) patients (HR = 0.487; 95% CI:0.197–1.204; P = 0.119), nor were they associated with mlalignancy alone, or death. We demonstrated no association between CHIP mutations and post-transplant outcomes, including CAV, graft failure, malignancy, and all-cause mortality. In line with previously published data, our analysis provides additional evidence about the lack of clinical value of using CHIP mutations as a biomarker for surveillance in outcomes after HT. Visual take-home graphic: Prevalence of CHIP mutations in patients after heart transplantation and association with long-term outcomes post-transplant. [Display omitted]
doi_str_mv 10.1016/j.cardfail.2024.05.011
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Uncertainty prevails regarding a robust association between CHIP and heart-transplantation (HT) outcomes. To determine the prevalence of CHIP mutations in HT and their association with long-term outcomes, including cardiac allograft vasculopathy (CAV), graft failure, malignancy, and all-cause mortality. We conducted a mixed retrospective-prospective observational study of HT recipients with targeted sequencing for CHIP mutations (variant allele frequency [VAF] of ≥ 2%). The primary composite outcome was the first occurrence of CAV grade ≥ 2, graft failure, malignancy, cardiac retransplantation, or all-cause death. Secondary outcomes were the individual components of the composite primary outcome. Sensitivity analyses with base-case and extreme scenarios were performed. Among 95 HT recipients, 30 had CHIP mutations (31.6%). DNMT3A mutations were most common (44.7%), followed by PPM1D (13.2%), SF3B1 (10.5%), TET2 (7.9%), and TP53 (7.9%). The only significant independent predictor of CHIP was age at enrollment or age at transplantation. After multivariable adjustment, CHIP mutations were not associated with the primary outcome, which occurred in 44 (46.3%) patients (HR = 0.487; 95% CI:0.197–1.204; P = 0.119), nor were they associated with mlalignancy alone, or death. We demonstrated no association between CHIP mutations and post-transplant outcomes, including CAV, graft failure, malignancy, and all-cause mortality. In line with previously published data, our analysis provides additional evidence about the lack of clinical value of using CHIP mutations as a biomarker for surveillance in outcomes after HT. Visual take-home graphic: Prevalence of CHIP mutations in patients after heart transplantation and association with long-term outcomes post-transplant. 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Uncertainty prevails regarding a robust association between CHIP and heart-transplantation (HT) outcomes. To determine the prevalence of CHIP mutations in HT and their association with long-term outcomes, including cardiac allograft vasculopathy (CAV), graft failure, malignancy, and all-cause mortality. We conducted a mixed retrospective-prospective observational study of HT recipients with targeted sequencing for CHIP mutations (variant allele frequency [VAF] of ≥ 2%). The primary composite outcome was the first occurrence of CAV grade ≥ 2, graft failure, malignancy, cardiac retransplantation, or all-cause death. Secondary outcomes were the individual components of the composite primary outcome. Sensitivity analyses with base-case and extreme scenarios were performed. Among 95 HT recipients, 30 had CHIP mutations (31.6%). DNMT3A mutations were most common (44.7%), followed by PPM1D (13.2%), SF3B1 (10.5%), TET2 (7.9%), and TP53 (7.9%). The only significant independent predictor of CHIP was age at enrollment or age at transplantation. After multivariable adjustment, CHIP mutations were not associated with the primary outcome, which occurred in 44 (46.3%) patients (HR = 0.487; 95% CI:0.197–1.204; P = 0.119), nor were they associated with mlalignancy alone, or death. We demonstrated no association between CHIP mutations and post-transplant outcomes, including CAV, graft failure, malignancy, and all-cause mortality. In line with previously published data, our analysis provides additional evidence about the lack of clinical value of using CHIP mutations as a biomarker for surveillance in outcomes after HT. Visual take-home graphic: Prevalence of CHIP mutations in patients after heart transplantation and association with long-term outcomes post-transplant. 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The only significant independent predictor of CHIP was age at enrollment or age at transplantation. After multivariable adjustment, CHIP mutations were not associated with the primary outcome, which occurred in 44 (46.3%) patients (HR = 0.487; 95% CI:0.197–1.204; P = 0.119), nor were they associated with mlalignancy alone, or death. We demonstrated no association between CHIP mutations and post-transplant outcomes, including CAV, graft failure, malignancy, and all-cause mortality. In line with previously published data, our analysis provides additional evidence about the lack of clinical value of using CHIP mutations as a biomarker for surveillance in outcomes after HT. Visual take-home graphic: Prevalence of CHIP mutations in patients after heart transplantation and association with long-term outcomes post-transplant. 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subjects advanced heart failure
cardiac allograft vasculopathy
Clonal hematopoiesis of indeterminate potential
de novo malignancy
graft failure
heart transplantation
mortality
title Clonal Hematopoiesis of Indeterminate Potential and Long-term Outcomes in Heart Transplantation
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