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

Since the first report of an association between cardiac troponin (cTn) and adverse outcome in hypertrophic cardiomyopathy (HD), there is a paucity confirmative data. We performed prospective, prespecified 5-year follow-up cohort study 135 HC patients who participated national multicenter project underwent clinical evaluation, MRI (cine, LGE T2-weighted imaging) biomarker assessment (high-sensitivity cTnT (hs-cTnT), N-terminal pro-B-type natriuretic peptide, soluble tumorgenicity suppressor-2, Galectin-3, Growth differentiation factor-15, C-terminal Propeptide Type I Collagen (CICP)). An elevated hs-cTnT concentration was defined as ≥14ng/L. Follow-up systematically for primary endpoint: composite sudden death, heart failure related stroke-related hospitalization, hospitalization stroke, spontaneous sustained ventricular tachycardia (VT) or appropriate ICD discharge, progression to NYHA class III-IV. Elevated present 33 (24%) patients. During median 5.0 years (IQR: 4.9-5.1) 18 reached endpoint. Using Cox regression analysis, univariately associated with endpoint (HR: 3.4 (95%CI: 1.4-8.7, p=0.009). Also female sex, previous syncope, non-sustained VT, reduced LV ejection fraction (<50%) CICP were In multivariable remained independently (aHR: 4.7 1.8-12.6, p = 0.002). conclusion, this prospectively confirm outcomes. addition established variables, cTn seems interest further improve risk prediction HC, which should be evaluated larger prospective registries. Hypertrophic (HC) clinically characterized by very heterogeneous disease presentation ranging from asymptomatic death (SCD) progressive (HF).1Elliott PM Anastasakis A Borger MA Borggrefe M Cecchi F Charron P Hagege AA Lafont Limongelli G Mahrholdt H McKenna WJ Mogensen J Nihoyannopoulos Nistri S Pieper PG Pieske B Rapezzi C Rutten FH Tillmanns Watkins 2014 ESC Guidelines on diagnosis management cardiomyopathy: The Task Force Diagnosis Management Cardiomyopathy European Society Cardiology (ESC).Eur Heart J. 2014; 35: 2733-2779Crossref PubMed Scopus (27) Google Scholar,2Gersh BJ Maron Bonow RO Dearani JA Fifer Link MS Naidu SS Nishimura RA Ommen SR Rakowski Seidman CE Towbin Udelson JE Yancy CW. 2011 ACCF/AHA guideline treatment American College Foundation/American Association Practice Guidelines.Circulation. 2011; 124: e783-e831Crossref (630) Scholar Despite ongoing initiatives stratification SCD, limited information how discriminate low high regard broader spectrum endpoints.3Kramer CM Appelbaum E Desai MY Desvigne-Nickens DiMarco JP Friedrich MG Geller N Heckler Ho CY Jerosch-Herold Ivey EA Keleti Kim DY Kolm Kwong RY Schulz-Menger Piechnik Weintraub WS Wu Neubauer S. Registry: rationale design international, observational cardiomyopathy.Am 2015; 170: 223-230Crossref (88) Ischemia result imbalance increased myocardial oxygen demand presence hypertrophy, supply due microvascular importantly contributes HC.1Elliott that regard, it surprising role has not been extensively studied.4Gommans DF Cramer GE Bakker Michels Dieker HJ Timmermans Fouraux Marcelis CL Verheugt FW Brouwer Kofflard MJ. High signal intensity T cardiomyopathy.Heart. 2017; 103: 293-299Crossref (13) Scholar, 5Gommans FWA De Boer M-J MJM MA. Prediction extensive fibrosis Cardiomyopathy.Am Cardiol. 2018; 122: 483-489Abstract Full Text PDF (3) 6Kubo Kitaoka Yamanaka Hirota Baba Y Hayashi K Iiyama Kumagai Tanioka Yamasaki Matsumura Furuno Sugiura Doi YL. Significance High-Sensitivity Cardiac Troponin Cardiomyopathy.J Am Coll 2013; 62: 1252-1259Crossref (85) 7Cramer Gommans Kurvers M. Relation highly sensitive left mass cardiovascular risk.Am 113: 1240-1245Abstract (25) common finding characteristics, such wall thickness late gadolinium enhancement (LGE).4Gommans 8Sato Taniguchi R Nagai Makiyama Okada Yamada Matsumori Takatsu Y. Measurements 2003; 89: 659-660Crossref (44) 2013, published demonstrated cTnT, assessed high-sensitivity assay (hs-cTnT) long-term HC.6Kubo Ever since, however, confirmatory data.3Kramer Scholar,8Sato 9Hasler Manka Greutmann Gamperli O Schmied Tanner FC Biaggi Luscher TF Keller DI Gruner C. levels are remodelling cardiomyopathy.Swiss Med Wkly. 2016; 146: w14285PubMed 10Nakamura Takano Matsuda Chinen D Kitamura Murai Asai Yasutake Takayama Shimizu W. Prognostic values B-type peptide features obstructive cross-sectional study.BMJ Open. 4e005968Crossref (14) Therefore, we aimed validate outcomes 5 follow-up. From Dutch biomarkers, exercise, selected whom baseline available.11Cramer DHF de MJ Exercise injury 2020; 106: 1169-1175Crossref (7) short, adult different hospitals enrolled at 2 outpatient clinics (Radboud University Medical Center, Nijmegen Albert Schweitzer Hospital, Dordrecht, Netherlands) 2008 2014. Patients had fulfill diagnostic criteria according prevailing guidelines no history coronary artery septal reduction therapy. complies Declaration Helsinki. protocol approved local ethical committees conducted accordingly. All participants provided written informed consent. Blood samples processed within 60 minutes after phlebotomy, stored –80°C until analysis. Serum used hs-cTnT. Our panel also included: N-terminal-pro-B-type-Natriuretic Peptide, Tumorigenicity Suppressor2, Differentation Factor-15 (CICP (Appendix detailed description assays).5Gommans Variability performance healthy controls have published.12Meijers WC van der Velde AR Muller Kobold AC Dijck-Brouwer AH Jaffe biomarkers chronic controls.Eur Fail. 19: 357-365Crossref (78) CMR imaging cine, sequences 1.5T systems (Philips Achieva Healthcare, Best, (Siemens Avanto Health Care, Erlangen, Germany)) protocols, previously described.4Gommans Images analyzed commercially available software (QMass 7.5, Medis, Leiden, three observers unaware subjects’ information. extent scored visually semi-quantitative score.4Gommans HF–related HF implantable cardioverter-defibrillator (ICD) New York (NYHA) functional III IV status.6Kubo As secondary aim mentioned project, telephone two five years. case patient reported potential endpoint, patients’ medical file reviewed event adjudication, investigators based consensus (FG EC); non-consensus third investigator final adjudication (MK). Continuous variables presented means (± standard deviations) medians (interquartile ranges (IQR)) compared without using Student's t Mann-Whitney U test, whichever appropriate. Dichotomous Chi-square Fisher exact our univariate multivariate survival analyses occurrence addition, continuous variable. Variables significantly analysis stepwise forward (p-in: <0.05; p-out: >0.10). p-value <0.05 considered significant (two-sided). Statistical SPSS Statistics 25 (IBM Corp, Armonk, NY, USA). For current population comprised patients, 6 available. Baseline characteristics stratified (n 33) 102) Table 1. Median duration none lost-to-follow-up. met SCD (n=1), HF-related 1), 2), 5), stroke 0); VT discharge 3), status 9).Table 1Baseline characteristicsVariableTotal(n 135)Elevated hs-cTnTpYes(n 33)No(n 102)Age participation (years)54 ± 1454 1654 140.96Men79 (59%)20 (61%)59 (58%)0.78Age (years)47 1645 1647 160.47Pathogenic mutation present72 (59%)16 (53%)56 (61%)0.52Atrial fibrillation21 (16%)8 (24%)13 (13%)0.11Hypertension48 (36%)14 (42%)34 (33%)0.34Current smoker23 (17%)5 (15%)18 (18%)0.74Dyslipidaemia30 (22%)6 (18%)24 (24%)0.52Diabetes7 (5%)3 (9%)4 (4%)0.36Recent creatinine (μmol/l)83 1690 2081 140.008Systolic blood pressure (mmHg)129 22127 18129 230.61Heart rate (beats/minute)74 1378 1472 120.01Framingham 10-year (%)12 (5-25)14 (5-28)12 (5-23)0.65History aborted arrest3 (2%)1 (3%)2 (2%)0.57Family SCD18 (13%)4 (12%)14 (14%)1.0Previous syncope5 (4%)3 (9%)2 (2%)0.09History VT25 (21%)5 (18%)20 (21%)0.69Abnormal BP response18 (14%)6 (19%)12 (12%)0.38Maximal ≥30mm3 (2%)0.57SymptomsChest pain22 (24%)14 (14%)0.16Dyspnea (NYHA ≥ II)60 (44%)23 (70%)37 (36%)0.001EchocardiographyLV outflow tract gradient rest ≥30mmHg20 (15%)4 (12%)16 (16%)0.78Left atrial diameter (mm)43 (39-49)45 (42-53)42 (39-48)0.02Magnetic resonance imagingMaximal (mm)17 (14-21)20 (18-23)16 (13-20)0.001LV indexed BSA (g/m2)63 (52-84)80 (63-115)60 (51-74)<0.001LV fraction60 757 760 70.04LGE presence71 (62%)23 (85%)48 (55%)0.005LGE (% mass)3 (0-10)10 (1-18)1 (0-7)<0.001High intensity29 (27%)16 (59%)13 (17%)<0.001Biomarker panelNT-proBNP (ng/l)138 (76-368)302 (130-573)116 (61-250)0.001sST2 (ng/ml)23 (19-32)26 (21-31)22 (18-33)0.17GDF-15 (ng/l)800 (481-1007)967 (573-1322)706 (475-961)0.03Gal-3 (ng/ml)17 (14-20)18 (14-21)16 (13-19)0.15CICP (ng/ml)126 (105-157)130 (108-167)125 (100-156)0.23TherapyBeta-blocker64 (47%)18 (55%)46 (45%)0.35Calciumantagonist20 (15%)5 (15%)15 (15%)1.0Data deviations, ranges) numbers (percentages). Hs-cTnT assay; pressure; Late enhancement; Left ventricle; LVMI body surface area; Association; Sudden death; Ventricular tachycardia. Open table new tab Data more than threefold higher (hazard ratio (HR): 0.009) (Table 2). Other predictors Holter monitoring, <50% echocardiography serum concentration. endpoint; together monitoring (Figure 1 variable 1.031(95%CI: 1.004-1.059, 0.03), whereas longer (p 0.096); sex (adjusted HRs: 3.1 1.1-9.0, 0.04) 4.6 1.7-12.2, 0.003), respectively). ancillary restricted conventional factors HR: 1.03 1.002-1.07, 0.04).Table 2Cox endpointHazard ratio95% Confidence intervalpElevated (univariate)3.41.4-8.70.009Independent predictorsAdjusted hazard hs-cTnT4.71.8-12.60.002Previous NSVT5.92.2-16.20.001Data deviations ranges). Female only NSVT Non-sustained well-defined national, study, reproduce independent HC. Kubo et al. time 2013,6Kubo results underscore need data registries investigate improvement models, but morbidity mortality.3Kramer Historically, mostly focused probably most devastating their families. Although models advent improved outcome, debate remains optimize schemes. Perhaps even important, become increasingly evident suffer substantial mortality specific tool available.13Maron Rowin EJ Casey SA MS. How became contemporary treatable genetic mortality: shaped 50 research practice.JAMA cardiol. 1: 98-105Crossref (112) Scholar,14Maron After Years Finally Recognized Contemporary Treatable Disease With Low Mortality Morbidity, But Paradigm Under-Recognized Literature?.Am 142: 136-137Abstract (1) mainstay taking, echocardiography. Possible modalities techniques LGE, T1- mapping techniques, easily patient-friendly may attractive.3Kramer Scholar,4Gommans Scholar,11Cramer report, HC,6Kubo majority events rather arrhythmias. variable, while statistical significance 0.096), might size rate. Yet, added daily practice, shows its promising potential. Acknowledging anticipated rate, both arrhythmic endpoints, similar al.6Kubo composition observed line reports, true arrhythmias particular.6Kubo Scholar,9Hasler Scholar,10Nakamura relatively (e.g. HC-SCD score 2.5%), arrythmias 3% 8 out 181 (4%) patients.6Kubo Similar did observe arrythmias, single parameter. Apart considerations, better predicts events, general well.15deFilippi CR Lemos Christenson RH Gottdiener JS Kop Zhan Seliger SL. serial measures incident older adults.JAMA. 2010; 304: 2494-2502Crossref (546) Importantly, stress during light above, Registry Kramer awaited.3Kramer This large will best set evaluate well endpoints. Regarding associations systolic function On other hand, cohort. focus collection these driven, not.11Cramer acknowledge echocardiographic parameters diastolic could prediction. future studies include protocol-driven work-up assess variables. exploratory analyses, consider predictive outcome. would like absence (and particular) merely issue lack power. important restriction substantiated analyses. Moreover, yet alternative explanation markers properties. Hypothetically, especially indicative events. datasets required whether cut-offs 99th percentile aid particular. initial publication prognostic impact herein provide corroborative evidence myocyte injury, therefore perhaps serve identify HC-related HF. Frank Gommans: curation, formal investigation, writing original draft Etienne Cramer: conceptualization, review & editing Michael Fouraux: resources, Sanne Heijmans: investigation Michelle Michels: Janneke Timmermans: supervision, Freek Verheugt: funding acquisition, Rudolf Boer: methodology, Marcel Kofflard: Marc Brouwer: authors declare they known competing financial interests personal relationships appeared influence work paper Download .docx (.01 MB) Help docx files