Prediction of Extensive Myocardial Fibrosis in Nonhigh Risk Patients With Hypertrophic Cardiomyopathy

Abstract

In nonhigh risk patients with hypertrophic cardiomyopathy (HC), the presence of extensive late gadolinium enhancement (LGE) at cardiovascular magnetic resonance (CMR) imaging has been proposed as a risk modifier in the decision process for implantable cardioverter defibrillator implantation. With a pretest risk of about 10%, a strategy that alters the likelihood of LGE could markedly affect efficacious CMR imaging. Our aim was to study the potential of clinical variables and biomarkers to predict LGE. In 98 HC patients without any clear indication for implantable cardioverter defibrillator implantation, we determined the discriminative values of a set of clinical variables and a panel of biomarkers (hs-cTnT, NTproBNP, GDF-15, and Gal-3, CICP) for LGE, that is, LGE ≥15% of the left ventricular mass. LGE was present in 10% (10/98) of patients. The clinical prediction model contained a history of nonsustained ventricular tachycardia, maximal wall thickness and reduced systolic function (c-statistic: 0.868, p <0.001). Of all biomarkers, only hs-cTnT was associated with LGE, in addition to the improved clinical model of diagnostic accuracy (p = 0.04). A biomarker-only strategy allowed the exclusion of LGE in half of the cohort, in case of a hs-cTnT concentration less than the optimal cutoff (Youden index; 8 ng/L-sensitivity 100%, specificity 54%). In conclusion, in this nonhigh risk HC cohort, the pretest likelihood of LGE can be altered using clinical variables and the addition of hs-cTnT. The promising findings with the use of hs-cTnT only call for new initiatives to study its impact on efficacious CMR imaging in a larger HC population, either with or without additional use of clinical variables.

Usefulness of High-Sensitivity Cardiac Troponin T to Predict Long-Term Outcome in Patients with Hypertrophic Cardiomyopathy

“…Our biomarker panel also included: N-terminal-pro-B-type-Natriuretic Peptide, Galectin-3, soluble Tumorigenicity Suppressor2, Growth Differentation Factor-15 and C-terminal Propeptide of Type I Collagen (CICP (Appendix for detailed description of the assays). 5 Variability and performance in healthy controls and patients with heart failure have been published. 12 CMR imaging with cine, LGE and T2-weighted sequences was performed on 1.5T CMR systems (Philips Achieva (Philips Healthcare, Best, The Netherlands) or (Siemens Avanto (Siemens Health Care, Erlangen, Germany)) according to local imaging protocols, as previously described.…”

“…1,2 In that regard, it is surprising that the role of cardiac troponin (cTn) in HC patients has not been extensively studied. [4][5][6][7] Elevated cTn is a common finding and associated with adverse disease characteristics, such as wall thickness and late gadolinium enhancement (LGE). [4][5][6][7][8] In 2013, the first report was published that demonstrated an association between elevated cTnT, assessed with a high-sensitivity assay (hs-cTnT) and adverse long-term outcome in HC.…”

“…[4][5][6][7] Elevated cTn is a common finding and associated with adverse disease characteristics, such as wall thickness and late gadolinium enhancement (LGE). [4][5][6][7][8] In 2013, the first report was published that demonstrated an association between elevated cTnT, assessed with a high-sensitivity assay (hs-cTnT) and adverse long-term outcome in HC. 6 Ever since, however, there is a paucity of confirmatory prospective data.…”

The Time Has Come to Explore Plasma Biomarkers in Genetic Cardiomyopathies

“…This strongly suggests that in HCM, Gal-3 is predominantly related to HF severity, which is corroborated by the observation that no association between Gal-3 levels and LV hypertrophy exists in HCM patients with predominantly mild HF symptoms [73]. In addition, Gal-3 plasma levels did not correlate with LGE-detected fibrosis in HCM patients [73,77,111]. For GDF15, plasma levels were also associated with disease severity in HCM patients [112].…”

“…Interestingly, it was shown that exercise increased BNP plasma levels particularly in HCM patients with silent ischemia [75]. Importantly, BNP and cTn levels were also associated with fibrosis in HCM patients and cTn levels were predictive for the detection of extensive myocardial fibrosis in non-high risk patients with HCM [76,77]. Troponin measurements could therefore be used as a pretest to select patients for CMR imaging with LGE or T1 mapping to establish cardiac fibrosis.…”