Prediction of Extensive Myocardial Fibrosis in Nonhigh Risk Patients With Hypertrophic Cardiomyopathy
2018; Elsevier BV; Volume: 122; Issue: 3 Linguagem: Inglês
10.1016/j.amjcard.2018.04.020
ISSN1879-1913
AutoresD.H. Frank Gommans, G. Etienne Cramer, Michael A. Fouraux, Jeannette Bakker, Michelle Michels, Hendrik-Jan Dieker, Janneke Timmermans, Carlo Marcelis, Freek W.A. Verheugt, Menko‐Jan de Boer, Marcel J.M. Kofflard, Rudolf A. de Boer, Marc A. Brouwer,
Tópico(s)Viral Infections and Immunology Research
ResumoIn nonhigh risk patients with hypertrophic cardiomyopathy (HC), the presence of extensive late gadolinium enhancement (LGEext) 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 LGEext could markedly affect efficacious CMR imaging. Our aim was to study the potential of clinical variables and biomarkers to predict LGEext. 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 LGEext, that is, LGE ≥15% of the left ventricular mass. LGEext 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 LGEext, in addition to the improved clinical model of diagnostic accuracy (p = 0.04). A biomarker-only strategy allowed the exclusion of LGEext 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 LGEext 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. In nonhigh risk patients with hypertrophic cardiomyopathy (HC), the presence of extensive late gadolinium enhancement (LGEext) 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 LGEext could markedly affect efficacious CMR imaging. Our aim was to study the potential of clinical variables and biomarkers to predict LGEext. 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 LGEext, that is, LGE ≥15% of the left ventricular mass. LGEext 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 LGEext, in addition to the improved clinical model of diagnostic accuracy (p = 0.04). A biomarker-only strategy allowed the exclusion of LGEext 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 LGEext 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. Hypertrophic cardiomyopathy (HC) is a major cause of sudden cardiac death (SCD) with an incidence of <1% per year, which poses a major clinical challenge for its prediction.1Elliott PM Anastasakis A Borger MA Borggrefe M Cecchi F Charron P Hagege AA Lafont A Limongelli G Mahrholdt H McKenna WJ Mogensen J Nihoyannopoulos P Nistri S Pieper PG Pieske B Rapezzi C Rutten FH Tillmanns C Watkins H Authors/Task Force MembersESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: the task force for the diagnosis and management of hypertrophic cardiomyopathy of the European Society of Cardiology (ESC).Eur Heart J. 2014; 35: 2733-2779Crossref PubMed Scopus (37) Google Scholar, 2Gersh BJ Maron BJ Bonow RO Dearani JA Fifer MA Link MS Naidu SS Nishimura RA Ommen SR Rakowski H Seidman CE Towbin JA Udelson JE Yancy CW ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.Circulation. 2011; 124: 783-831Crossref PubMed Scopus (666) Google Scholar Importantly, the highest absolute number of SCDs still occur in the large group of nonhigh risk HC patients without a clear indication for an implantable cardioverter defibrillator.1Elliott PM Anastasakis A Borger MA Borggrefe M Cecchi F Charron P Hagege AA Lafont A Limongelli G Mahrholdt H McKenna WJ Mogensen J Nihoyannopoulos P Nistri S Pieper PG Pieske B Rapezzi C Rutten FH Tillmanns C Watkins H Authors/Task Force MembersESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: the task force for the diagnosis and management of hypertrophic cardiomyopathy of the European Society of Cardiology (ESC).Eur Heart J. 2014; 35: 2733-2779Crossref PubMed Scopus (37) Google Scholar, 2Gersh BJ Maron BJ Bonow RO Dearani JA Fifer MA Link MS Naidu SS Nishimura RA Ommen SR Rakowski H Seidman CE Towbin JA Udelson JE Yancy CW ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.Circulation. 2011; 124: 783-831Crossref PubMed Scopus (666) Google Scholar, 3Spirito P Autore C Formisano F Assenza GE Biagini E Haas TS Bongioanni S Semsarian C Devoto E Musumeci B Lai F Yeates L Conte MR Rapezzi C Boni L Maron BJ Risk of sudden death and outcome in patients with hypertrophic cardiomyopathy with benign presentation and without risk factors.Am J Cardiol. 2014; 113: 1550-1555Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar, 4Maron BJ Casey SA Chan RH Garberich RF Rowin EJ Maron MS Independent assessment of the European Society of Cardiology sudden death risk model for hypertrophic cardiomyopathy.Am J Cardiol. 2015; 116: 757-764Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar Recently, clinical experts have suggested to incorporate extensive late gadolinium enhancement (LGE) in clinical decision making for this category of HC patients.5Maron BJ Maron MS LGE means better selection of HCM patients for primary prevention implantable defibrillators.JACC Cardiovasc Imaging. 2016; 9: 1403-1407Crossref PubMed Scopus (18) Google Scholar As extensive LGE (≥15% of left ventricular [LV] mass) is only seen in about 10%,6Chan RH Maron BJ Olivotto I Pencina MJ Assenza GE Haas T Lesser JR Gruner C Crean AM Rakowski H Udelson JE Rowin E Lombardi M Cecchi F Tomberli B Spirito P Formisano F Biagini E Rapezzi C De Cecco CN Autore C Cook EF Hong SN Gibson CM Manning WJ Appelbaum E Maron MS Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy.Circulation. 2014; 130: 484-495Crossref PubMed Scopus (597) Google Scholar a strategy based on easily obtainable characteristics that would alter the pretest likelihood, would be a more cost-effective approach than routine LGE cardiovascular magnetic resonance (CMR) imaging.7McCarthy CP Yousuf O Alonso A Selvin E Calkins H McEvoy JW High-sensitivity troponin as a biomarker in heart rhythm disease.Am J Cardiol. 2017; 119: 1407-1413Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 8Kehl DW Buttan A Siegel RJ Rader F Clinical utility of natriuretic peptides and troponins in hypertrophic cardiomyopathy.Int J Cardiol. 2016; 218: 252-258Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar In addition to various clinical variables (e.g., LV mass, wall thickness, and nonsustained ventricular tachycardia [NSVT]9Olivotto I Maron MS Autore C Lesser JR Rega L Casolo G De Santis M Quarta G Nistri S Cecchi F Salton CJ Udelson JE Manning WJ Maron BJ Assessment and significance of left ventricular mass by cardiovascular magnetic resonance in hypertrophic cardiomyopathy.J Am Coll Cardiol. 2008; 52: 559-566Crossref PubMed Scopus (225) Google Scholar, 10Hen Y Iguchi N Utanohara Y Takada K Machida H Takara A Teraoka K Sumiyoshi T Takamisawa I Takayama M Yoshikawa T Extent of late gadolinium enhancement on cardiac magnetic resonance imaging in Japanese hypertrophic cardiomyopathy patients.Circ J. 2016; 80: 950-957Crossref PubMed Scopus (11) Google Scholar, 11Adabag AS Maron BJ Appelbaum E Harrigan CJ Buros JL Gibson CM Lesser JR Hanna CA Udelson JE Manning WJ Maron MS Occurrence and frequency of arrhythmias in hypertrophic cardiomyopathy in relation to delayed enhancement on cardiovascular magnetic resonance.J Am Coll Cardiol. 2008; 51: 1369-1374Crossref PubMed Scopus (545) Google Scholar) biomarkers like cardiac troponin, natriuretic peptides, and markers of collagen turnover have repeatedly been associated with LGE in HC.12Kawasaki T Sakai C Harimoto K Yamano M Miki S Kamitani T Usefulness of high-sensitivity cardiac troponin T and brain natriuretic peptide as biomarkers of myocardial fibrosis in patients with hypertrophic cardiomyopathy.Am J Card. 2013; 112: 867-872Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar, 13Zhang C Liu R Yuan J Cui J Hu F Yang W Zhang Y Chen Y Qiao S Predictive values of N-terminal Pro-B-type natriuretic peptide and cardiac troponin I for myocardial fibrosis in hypertrophic obstructive cardiomyopathy.PLoS ONE. 2016; 11e0146572PubMed Google Scholar, 14Elmas E Doesch C Fluechter S Freundt M Weiss C Lang S Kalsch T Haghi D Papassotiriou J Kunde J Schoenberg SO Borggrefe M Papavassiliu T Midregional pro-atrial natriuretic peptide: a novel marker of myocardial fibrosis in patients with hypertrophic cardiomyopathy.Int J Cardiovasc Imaging. 2011; 27: 547-556Crossref PubMed Scopus (9) Google Scholar, 15Moreno V Hernandez-Romero D Vilchez JA Garcia-Honrubia A Cambronero F Casas T Gonzalez J Martinez P Climent V de la Morena G Valdes M Marin F Serum levels of high-sensitivity troponin T: a novel marker for cardiac remodeling in hypertrophic cardiomyopathy.J Card Fail. 2010; 16: 950-956Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar, 16Park JR Choi JO Han HJ Chang SA Park SJ Lee SC Choe YH Park SW Oh JK Degree and distribution of left ventricular hypertrophy as a determining factor for elevated natriuretic peptide levels in patients with hypertrophic cardiomyopathy: insights from cardiac magnetic resonance imaging.Int J Cardiovasc Imaging. 2012; 28: 763-772Crossref PubMed Scopus (16) Google Scholar, 17Munch J Avanesov M Bannas P Saring D Kramer E Mearini G Carrier L Suling A Lund G Patten M Serum matrix metalloproteinases as quantitative biomarkers for myocardial fibrosis and sudden cardiac death risk stratification in patients with hypertrophic cardiomyopathy.J Card Fail. 2016; 22: 845-850Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar, 18Hasler S Manka R Greutmann M Gamperli O Schmied C Tanner FC Biaggi P Luscher TF Keller DI Gruner C Elevated high-sensitivity troponin T levels are associated with adverse cardiac remodelling and myocardial fibrosis in hypertrophic cardiomyopathy.Swiss Med Wkly. 2016; 146: w14285PubMed Google Scholar, 19Weng Z Yao J Chan RH He J Yang X Zhou Y He Y Prognostic value of LGE-CMR in HCM: a meta-analysis.JACC Cardiovasc Imaging. 2016; 9: 1392-1402Crossref PubMed Scopus (245) Google Scholar In the previously mentioned clinical context, we aimed to identify predictors of extensive LGE between routinely assessed clinical variables and a broad panel of biomarkers in nonhigh risk HC patients. In addition, we demonstrate the predictive value of the addition of biomarkers in comparison to a prediction model with clinical variables only. For this analysis, we selected nonhigh risk patients from a large cohort of HC patients who participated in a Dutch multicenter study on CMR imaging and biomarkers.20Gommans DF Cramer GE Bakker J Michels M Dieker HJ Timmermans J Fouraux MA Marcelis CL Verheugt FW Brouwer MA Kofflard MJ High T2-weighted signal intensity is associated with elevated troponin T in hypertrophic cardiomyopathy.Heart. 2017; 103: 293-299Crossref PubMed Scopus (16) Google Scholar In short, adult HC patients from different hospitals were enrolled at 2 outpatient clinics (Radboud University Medical Center, Nijmegen and Albert Schweitzer Hospital, Dordrecht, The Netherlands) from 2008 to 2014. Patients had to fulfill the diagnostic criteria for HC according to the prevailing guidelines at the time of inclusion and should not have a history of coronary artery disease or septal reduction therapy. For this analysis, data on the extent of LGE had to be available. Furthermore, we selected HC patients who are considered not to be at high SCD risk based on the American Heart Association (AHA)/American College of Cardiology (ACC) guidelines (i.e., low to intermediate risk HC patients). Accordingly, we excluded patients with a family history of SCD, extreme hypertrophy (≥30 mm) or a recent unexplained syncope (i.e., patients in whom ICD implantation is considered reasonable according to the latest AHA/ACC guidelines).2Gersh BJ Maron BJ Bonow RO Dearani JA Fifer MA Link MS Naidu SS Nishimura RA Ommen SR Rakowski H Seidman CE Towbin JA Udelson JE Yancy CW ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.Circulation. 2011; 124: 783-831Crossref PubMed Scopus (666) Google Scholar The study complies with the Declaration of Helsinki and the protocol was approved by the local ethical committees and conducted accordingly. All participants provided written informed consent. CMR imaging was performed on 1.5 T 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 in more detail.20Gommans DF Cramer GE Bakker J Michels M Dieker HJ Timmermans J Fouraux MA Marcelis CL Verheugt FW Brouwer MA Kofflard MJ High T2-weighted signal intensity is associated with elevated troponin T in hypertrophic cardiomyopathy.Heart. 2017; 103: 293-299Crossref PubMed Scopus (16) Google Scholar T1-weighted inversion-recovery imaging was performed to assess LGE 10 minutes after the administration of 0.2 mmol/kg contrast medium (Dotarem; Guerbet, Gorinchem, The Netherlands). Images were analyzed with commercially available software (QMass 7.5, Medis, Leiden, The Netherlands) by three observers (FG, JB, and HD) unaware of the subjects' clinical information. The extent of LGE was scored visually according to a semi-quantitative score, previously validated in HC.21Doesch C Huck S Bohm CK Michaely H Fluechter S Haghi D Dinter D Borggrefe M Papavassiliu T Visual estimation of the extent of myocardial hyperenhancement on late gadolinium-enhanced CMR in patients with hypertrophic cardiomyopathy.Magn Reson Imaging. 2010; 28: 812-819Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar The definition of extensive LGE was met in case the LGE extent comprised ≥15% of the LV mass. Blood samples were obtained by trained personnel and processed within 60 minutes after phlebotomy, and stored at −80°C until further analysis. Serum samples were used for the determination of the biomarkers (1) cardiac troponin T using the highly sensitive assay (hs-cTnT), (2) N-terminal-pro-B-type-natriuretic peptide (NTproBNP), (3) Galectin-3 (Gal-3), (4) soluble tumorigenicity suppressor2 (sST2), (5) growth differentiation factor-15 (GDF-15), and (6) C-terminal propeptide of type I collagen (CICP). Variability and performance in healthy controls and patients with heart failure have been published.22Meijers WC van der Velde AR Muller Kobold AC Dijck-Brouwer J Wu AH Jaffe A de Boer RA Variability of biomarkers in patients with chronic heart failure and healthy controls.Eur J Heart Fail. 2017; 19: 357-365Crossref PubMed Scopus (93) Google Scholar We refer to Appendix A for a detailed description of the assays. Continuous variables are presented as means (±standard deviations) or medians (interquartile ranges) and were compared between patients with and without extensive LGE using a Student's t or Mann–Whitney U test, whichever is appropriate. Dichotomous variables were compared using a chi-square or Fisher's exact test, whichever appropriate. A p value of <0.05 was considered significant (two-sided). Then, multivariable regression analysis was performed. A stepwise forward approach was adopted to predict extensive LGE based on the likelihood-ratio-test (P-in, 0.05; P-out, 0.10). First, we constructed a model for prediction of extensive LGE with the clinical variables that differed between patients with and without extensive LGE (p <0.10; model 1). Second, we constructed model 2 for prediction of extensive LGE with the addition of the biomarkers that differed between patients with and without extensive LGE (p <0.10). To assess the calibration of the models, we used the Hosmer–Lemeshow goodness-of-fit statistical method. Receiver operating characteristic (ROC) analysis using c-statistics was performed to determine the area under the curve of both models, and of each biomarker variable included in model 2 separately. The cut-off value for the continuous variables was determined using the Youden index. Statistical analysis was performed with IBM SPSS Statistics 22 (IBM Corp, Armonk, New York). For the present analysis, 98 nonhigh HC patients selected from our total HC cohort of 141 HC patients were studied (61% male, age 55 ± 14 years) (Figure 1 and Table 1).20Gommans DF Cramer GE Bakker J Michels M Dieker HJ Timmermans J Fouraux MA Marcelis CL Verheugt FW Brouwer MA Kofflard MJ High T2-weighted signal intensity is associated with elevated troponin T in hypertrophic cardiomyopathy.Heart. 2017; 103: 293-299Crossref PubMed Scopus (16) Google Scholar Most patients were a- or mildly symptomatic with 96 (98%) in New York Heart Association class I to II. The presence of LGE was demonstrated in 56 (57%) patients. In these 56 patients, the extent of LGE comprised 8% (interquartile ranges 3 to 13%) of the LV mass. In 10 (10%) patients the extent of LGE was ≥15%.Table 1Baseline characteristics stratified according to extensive late gadolinium enhancementVariableLGE extentp valueTotal 6.5 mmol/l.29 (30%)24 (27%)5 (50%)0.16Diabetes mellitus5 (5%)4 (5%)1 (10%)0.42Creatinine (μmol/l)84 ± 1684 ± 1689 ± 200.37Systolic blood pressure (mm Hg)131 ± 22131 ± 22133 ± 200.76Heart rate (beats/minute)73 ± 1273 ± 1276 ± 150.36Framingham 10-year heart risk (%)15 (5-26)15 (5-25)23 (7-31)0.37 Risk factors for SCD History of nonsustained VT*These variables were used for multivariate logistic regression analysis.14 (15%)10 (12%)4 (40%)0.04Abnormal BP response*These variables were used for multivariate logistic regression analysis.11 (12%)8 (9%)3 (30%)0.09Symptoms Chest pain18 (18%)18 (21%)-0.20 Dyspnea (NYHA class ≥II)43 (44%)40 (46%)3 (30%)0.51Echocardiography Maximal LV wall thickness (mm)*These variables were used for multivariate logistic regression analysis.16 (13-19)16 (13-19)18 (16-21)0.08 LVMI (g/m2)*These variables were used for multivariate logistic regression analysis.125 (103-162)124 (102-155)160 (127-179)0.05 Reduced LV systolic function*These variables were used for multivariate logistic regression analysis.8 (8%)5 (6%)3 (30%)0.03 LV outflow tract gradient at rest ≥30 mm Hg18 (19%)18 (21%)-0.20 Left atrial diameter (mm)44 (39-50)44 (39-48)45 (42-58)0.26Therapy Beta-blocker50 (51%)43 (49%)7 (70%)0.32 Calcium antagonist12 (12%)10 (11%)2 (20%)0.35Data are presented as means ± standard deviations, medians (interquartile ranges) or numbers (percentages). BP = blood pressure; LGE = late gadolinium enhancement; LV = left ventricle; LVMI = left ventricle mass indexed to body surface area; NYHA = New York heart association; SCD = sudden cardiac death; VT = ventricular tachycardia. These variables were used for multivariate logistic regression analysis.† Dyslipidemia was defined as a total cholesterol > 6.5 mmol/l. Open table in a new tab Data are presented as means ± standard deviations, medians (interquartile ranges) or numbers (percentages). BP = blood pressure; LGE = late gadolinium enhancement; LV = left ventricle; LVMI = left ventricle mass indexed to body surface area; NYHA = New York heart association; SCD = sudden cardiac death; VT = ventricular tachycardia. Patients with extensive LGE tended to be younger at the time of diagnosis compared with patients without extensive LGE (Table 1). Atrial fibrillation tended to be more often present in patients with extensive LGE. A history of NSVTs was more often present in these patients. With regard to echocardiographic parameters, patients with extensive LGE had a higher LV mass indexed to BSA and had a numerically higher maximal LV wall thickness. Lastly, 3 of 10 patients with extensive LGE had a reduced LV systolic function compared with 5 of 88 patients without extensive LGE. The median hs-cTnT concentration was twice as high in patients with extensive LGE (Table 2). No significant differences were observed for NTproBNP or any of the other biomarkers.Table 2Biomarkers stratified according to extensive late gadolinium enhancementBiomarkersLGE extentp valueTotal 0.05). For model 1, ROC analysis demonstrated a high discriminative ability (area under the curve, c-statistic: 0.868 [95% confidence interval [CI] 0.780 to 0.956, p <0.001]). For model 2, the discriminative ability was even slightly higher (area under the curve, c-statistic: 0.900 [95% CI 0.836 to 0.964], p <0.001) (Figure 2). As a single variable, none of the clinical characteristics (history of NSVT, abnormal LV function, and LV wall thickness) demonstrated valuable discriminative ability for prediction of extensive LGE (c-statistics, p = N.S.). In contrast, ROC analysis of hs-cTnT as a single variable demonstrated good discriminative value (area under the curve, c-statistic of 0.818 [95% CI 0.716 to 0.920], p = 0.001) (Figure 3). Based on the Youden index, the optimal cut-off value for hs-cTnT was 8 ng/L. Of note, this was also the median concentration of our cohort. Using this cutoff, the sensitivity and specificity of hs-cTnT for extensive LGE were 100% and 54%, respectively. Consequently, the negative and positive predictive values for extensive LGE were 100% and 19% in our population.Table 3Models 1 and 2 for prediction for extensive late gadolinium enhancementModel 1: Routine clinical variablesAdjusted OR95% CIp valueHistory of non-sustained VT6.801.32-35.200.022Maximal LV wall thickness (mm)1.231.03-1.480.023Reduced LV systolic function9.311.48-58.400.017Model 2: Routine clinical variables + biomarkersAdjusted OR95% CIp valueHistory of non-sustained VT10.001.54-64.780.016Maximal LV wall thickness (mm)1.231.012-1.4970.037Reduced LV systolic function9.571.33-68.860.025Hs-cTnT (ng/L)1.071.001-1.132.046CI = confidence interval; LGE = late gadolinium enhancement; LV = left ventricle; OR = odds ratio; VT = ventricular tachycardia. Open table in a new tab Figure 3ROC curve of hs-cTnT for the prediction of extensive LGE.Show full captionThis figure demonstrates the discriminative ability of hs-cTnT for extensive LGE in our cohort of low to intermediate risk HC patients.Hs-cTnT = cardiac troponin T assessed with a highly sensitive assay; LGE = late gadolinium enhancement.View Large Image Figure ViewerDownload Hi-res image Download (PPT) CI = confidence interval; LGE = late gadolinium enhancement; LV = left ventricle; OR = odds ratio; VT = ventricular tachycardia. This figure demonstrates the discriminative ability of hs-cTnT for extensive LGE in our cohort of low to intermediate risk HC patients. Hs-cTnT = cardiac troponin T assessed with a highly sensitive assay; LGE = late gadolinium enhancement. In an era of increasing interest in CMR imaging as part of the workup to assess whether nonhigh risk HC patients qualify for ICD implantation, we herein describe predictors of extensive LGE. We found that a set of three clinical variables had a high discriminative value, with a significant improvement in diagnostic accuracy after addition of hs-cTnT. Even without accounting for the history of NSVT, reduced LV systolic function, and maximal LV wall thickness on echocardiography, a strategy based on the use of hs-cTnT by itself showed remarkable results. Based on the optimal cutoff for hs-cTnT, extensive LGE could reliably be excluded in half of the cohort. Previous reports have associated various clinical variables with the presence of LGE, such as a history of NSVT and measures of LV hypertrophy.9Olivotto I Maron MS Autore C Lesser JR Rega L Casolo G De Santis M Quarta G Nistri S Cecchi F Salton CJ Udelson JE Manning WJ Maron BJ Assessment and significance of left ventricular mass by cardiovascular magnetic resonance in hypertrophic cardiomyopathy.J Am Coll Cardiol. 2008; 52: 559-566Crossref PubMed Scopus (225) Google Scholar, 10Hen Y Iguchi N Utanohara Y Takada K Machida H Takara A Teraoka K Sumiyoshi T Takamisawa I Takayama M Yoshikawa T Extent of late gadolinium enhancement on cardiac magnetic resonance imaging in Japanese hypertrophic cardiomyopathy patients.Circ J. 2016; 80: 950-957Crossref PubMed Scopus (11) Google Scholar, 11Adabag AS Maron BJ Appelbaum E Harrigan CJ Buros JL Gibson CM Lesser JR Hanna CA Udelson JE Manning WJ Maron MS Occurrence and frequency of arrhythmias in hypertrophic cardiomyopathy in relation to delayed enhancement on cardiovascular magnetic resonance.J Am Coll Cardiol. 2008; 51: 1369-1374Crossref PubMed Scopus (545) Google Scholar Moreover, maximal wall thickness on CMR imaging was reported to be independently predictive of the presence of LGE.13Zhang C Liu R Yuan J Cui J Hu F Yang W Zhang Y Chen Y Qiao S Predictive values of N-terminal Pro-B-type natriuretic peptide and cardiac troponin I for myocardial fibrosis in hypertrophic obstructive cardiomyopathy.PLoS ONE. 2016; 11e0146572PubMed Google Scholar As the clinical importance of the mere presence of LGE is limited, we focused on the prediction of extensive LGE and only with variables available before CMR imaging. Our findings that a history of NSVT and a reduced LV systolic function on echocardiography were associated with extensive LGE corroborates with previous findings. Clearly, myocardial scar, which is suggested by the presence of extensive LGE, is a substrate for ventricular arrhythmias and leads to adverse remodeling.11Adabag AS Maron BJ Appelbaum E Harrigan CJ Buros JL Gibson CM Lesser JR Hanna CA Udelson JE Manning WJ Maron MS Occurrence and frequency of arrhythmias in hypertrophic cardiomyopathy in relation to delayed enhancement on cardiovascular magnetic resonance.J Am Coll Cardiol. 2008; 51: 1369-1374Crossref PubMed Scopus (545) Google Scholar The association between maximal LV wall thickness and extensive LGE corresponds with previous observations that HC patients with more hypertrophy more often have LGE.9Olivotto I Maron MS Autore C Lesser JR Rega L Casolo G De Santis M Quarta G Nistri S Cecchi F Salton CJ Udelson JE Manning WJ Maron BJ Assessment and significance of left ventricular mass by cardiovascular magnetic resonance in hypertrophic cardiomyopathy.J Am Coll Cardiol. 2008; 52: 559-566Crossref PubMed Scopus (225) Google Scholar, 10Hen Y Iguchi N Utanohara Y Takada K Machida H Takara A Teraoka K Sumiyoshi T Takamisawa I Takayama M Yoshikaw
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