Myocardial Work Appraisal in Transthyretin Cardiac Amyloidosis and Nonobstructive Hypertrophic Cardiomyopathy

Abstract

Global left ventricular (LV) myocardial work (MW) indexes can be recognized at ultrasound imaging from the LV pressure/global longitudinal strain (GLS) loop analysis. A total of 4 indexes, global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), have been demonstrated to overcome the methodological limitations of GLS and provide useful information on myocardial dysfunction in some clinical settings. Although impaired MW indexes have been demonstrated in patients with transthyretin cardiac amyloidosis (ATTR) or with nonobstructive hypertrophic cardiomyopathy (HCM), there are no comparative studies at present. This study aimed to describe the characteristics of MW in both these clinical settings compared with patients with well-controlled hypertension (HTN). A total of 83 patients, 32 with ATTR (aged 70 ± 11 years, 32% mutated, 68% wild-type, 72% men), 29 with HCM (aged 57 ± 17 years), and 22 HTN controls (aged 56 ± 5.6 years, 59% men) were prospectively enrolled at 2 clinical centers. All participants had New York Heart Association class I or II. Overall, the LV mass index was greater in both study groups than in HTN, whereas the LV ejection fraction (EF) was significantly lower in ATTR compared with other groups. Based on this finding, patients with ATTR were further divided into 2 subgroups: ATTR1 (LVEF ≤0.50), n = 14 (44%) and ATTR2 (LVEF >0.50), n = 18 (56%). Overall, the GWI and GCW were lower in all ATTR patients (mostly in ATTR1) than in the other groups (p <0.001), whereas only small differences in GWE and none in GWW were found among the groups. Of interest, the pairwise comparison and receiver operating characteristic analysis in preserved LVEF patients showed that GWI was a better discriminator of ATTR2 from HCM patients than GLS, with the cut-off value ≤1,419 mm Hg% (89% sensitivity; 55% specificity; p = 0.013). In conclusion, MW analysis was confirmed to be a modern way to investigate myocardial function in patients with hypertrophic phenocopies. GWI and GCW were more impaired in patients with ATTR compared with HCM and HTN controls. Furthermore, this study likely revealed an additional discriminative value of GWI over GLS alone in preserved LVEF settings. Global left ventricular (LV) myocardial work (MW) indexes can be recognized at ultrasound imaging from the LV pressure/global longitudinal strain (GLS) loop analysis. A total of 4 indexes, global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE), have been demonstrated to overcome the methodological limitations of GLS and provide useful information on myocardial dysfunction in some clinical settings. Although impaired MW indexes have been demonstrated in patients with transthyretin cardiac amyloidosis (ATTR) or with nonobstructive hypertrophic cardiomyopathy (HCM), there are no comparative studies at present. This study aimed to describe the characteristics of MW in both these clinical settings compared with patients with well-controlled hypertension (HTN). A total of 83 patients, 32 with ATTR (aged 70 ± 11 years, 32% mutated, 68% wild-type, 72% men), 29 with HCM (aged 57 ± 17 years), and 22 HTN controls (aged 56 ± 5.6 years, 59% men) were prospectively enrolled at 2 clinical centers. All participants had New York Heart Association class I or II. Overall, the LV mass index was greater in both study groups than in HTN, whereas the LV ejection fraction (EF) was significantly lower in ATTR compared with other groups. Based on this finding, patients with ATTR were further divided into 2 subgroups: ATTR1 (LVEF ≤0.50), n = 14 (44%) and ATTR2 (LVEF >0.50), n = 18 (56%). Overall, the GWI and GCW were lower in all ATTR patients (mostly in ATTR1) than in the other groups (p <0.001), whereas only small differences in GWE and none in GWW were found among the groups. Of interest, the pairwise comparison and receiver operating characteristic analysis in preserved LVEF patients showed that GWI was a better discriminator of ATTR2 from HCM patients than GLS, with the cut-off value ≤1,419 mm Hg% (89% sensitivity; 55% specificity; p = 0.013). In conclusion, MW analysis was confirmed to be a modern way to investigate myocardial function in patients with hypertrophic phenocopies. GWI and GCW were more impaired in patients with ATTR compared with HCM and HTN controls. Furthermore, this study likely revealed an additional discriminative value of GWI over GLS alone in preserved LVEF settings. The pathophysiology and management of cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) are unceasingly under investigation. Despite similarities in left ventricular (LV) chamber size and wall thickness on standard echocardiography investigation, discrepancies on LV function are detected by advanced imaging.1Mor-Avi V Lang RM Badano LP Belohlavek M Cardim NM Derumeaux G Galderisi M Marwick T Nagueh SF SenGupta PP Sicari R Smiseth OA Smulevitz B Takeuchi M Thomas JD Vannan M Voigt JU Zamorano JL. Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography.Eur J Echocardiogr. 2011; 12: 167-205Crossref PubMed Scopus (748) Google Scholar,2Di Bella G Pizzino F Donato R Di Nunzio D de Gregorio C. Advanced non-invasive imaging techniques in chronic heart failure and cardiomyopathies: focus on cardiac magnetic resonance imaging and computed tomographic.Adv Exp Med Biol. 2018; 1067: 183-196Crossref PubMed Scopus (2) Google Scholar HCM is a genetic sarcomere disorder of the myocytes, often resulting in a variable tissue fibrosis, whereas CA is an interstitial disease caused by misfolded amyloid fibril deposit, with ensuing ceaseless electromechanical dysfunction. Amyloid disease is the consequence of a disorder involving the carrier protein called transthyretin, either genetically determined (transthyretin CA [ATTR] mutated [ATTRv]) or acquired (ATTR wild-type [ATTRwt]), as well as due to hematologic dyscrasia (amyloid light chain [AL] form). Typically, cardiac involvement is more frequent in the ATTRwt variant, largely affecting older male patients.3Maron BJ Desai MY Nishimura RA Spirito P Rakowski H Towbin JA Dearani JA Rowin EJ Maron MS Sherrid MV. Management of hypertrophic cardiomyopathy: JACC State-of-the-Art Review.J Am Coll Cardiol. 2022; 79: 390-414Crossref PubMed Scopus (97) Google Scholar,4Garcia-Pavia P Rapezzi C Adler Y Arad M Basso C Brucato A Burazor I Caforio ALP Damy T Eriksson U Fontana M Gillmore JD Gonzalez-Lopez E Grogan M Heymans S Imazio M Kindermann I Kristen AV Maurer MS Merlini G Pantazis A Pankuweit S Rigopoulos AG Linhart A. Diagnosis and treatment of cardiac amyloidosis. A position statement of the Society of on and J Heart PubMed Scopus Google Scholar with or HCM often to for and or for clinical in the echocardiographic be patients LV mass and LV ejection fraction a greater in LV and function be found in Bella G Pizzino F Donato R Di Nunzio D de Gregorio C. Advanced non-invasive imaging techniques in chronic heart failure and cardiomyopathies: focus on cardiac magnetic resonance imaging and computed tomographic.Adv Exp Med Biol. 2018; 1067: 183-196Crossref PubMed Scopus (2) Google BJ Desai MY Nishimura RA Spirito P Rakowski H Towbin JA Dearani JA Rowin EJ Maron MS Sherrid MV. Management of hypertrophic cardiomyopathy: JACC State-of-the-Art Review.J Am Coll Cardiol. 2022; 79: 390-414Crossref PubMed Scopus (97) Google P Rapezzi C Adler Y Arad M Basso C Brucato A Burazor I Caforio ALP Damy T Eriksson U Fontana M Gillmore JD Gonzalez-Lopez E Grogan M Heymans S Imazio M Kindermann I Kristen AV Maurer MS Merlini G Pantazis A Pankuweit S Rigopoulos AG Linhart A. Diagnosis and treatment of cardiac amyloidosis. A position statement of the Society of on and J Heart PubMed Scopus Google Scholar ultrasound techniques provide as tissue and global longitudinal strain that can in a and treatment in the cardiac S J in heart PubMed Scopus Google M H A T Smiseth A clinical for of left ventricular loop a non-invasive index of myocardial Heart PubMed Scopus Google Scholar Although GLS well LV dysfunction in patients with hypertrophic from the analysis of loop myocardial work (MW) been as an advanced for myocardial function the GLS M H A T Smiseth A clinical for of left ventricular loop a non-invasive index of myocardial Heart PubMed Scopus Google Scholar MW a of myocardial the and and the as in J S B R A to myocardial work by non-invasive left ventricular in hypertension and Heart J PubMed Scopus Google S A D M R The of myocardial work in clinical Am Echocardiogr. PubMed Scopus Google value of global myocardial work over ejection fraction and global longitudinal strain in patients with heart failure and ejection Heart J PubMed Scopus Google Scholar Although studies on MW are from hypertrophic patients, comparative studies in patients with ATTR HCM are This study aimed to describe the characteristics of the MW indexes in both clinical settings and compared with patients with well-controlled to all patients to the heart failure at and for clinical or with ATTR or HCM were enrolled in this to the Society of the was on The of either or ATTRwt imaging at ultrasound or cardiac magnetic resonance and was confirmed by total 2 or genetic P Rapezzi C Adler Y Arad M Basso C Brucato A Burazor I Caforio ALP Damy T Eriksson U Fontana M Gillmore JD Gonzalez-Lopez E Grogan M Heymans S Imazio M Kindermann I Kristen AV Maurer MS Merlini G Pantazis A Pankuweit S Rigopoulos AG Linhart A. Diagnosis and treatment of cardiac amyloidosis. 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Management of hypertrophic cardiomyopathy: JACC State-of-the-Art Review.J Am Coll Cardiol. 2022; 79: 390-414Crossref PubMed Scopus (97) Google Scholar,4Garcia-Pavia P Rapezzi C Adler Y Arad M Basso C Brucato A Burazor I Caforio ALP Damy T Eriksson U Fontana M Gillmore JD Gonzalez-Lopez E Grogan M Heymans S Imazio M Kindermann I Kristen AV Maurer MS Merlini G Pantazis A Pankuweit S Rigopoulos AG Linhart A. Diagnosis and treatment of cardiac amyloidosis. A position statement of the Society of on and J Heart PubMed Scopus Google Scholar In these patients, the analysis that GWI value ≤1,419 mm Hg% can from sarcomere cardiomyopathy with with likely of the characteristics of Bella G Pizzino F Donato R Di Nunzio D de Gregorio C. Advanced non-invasive imaging techniques in chronic heart failure and cardiomyopathies: focus on cardiac magnetic resonance imaging and computed tomographic.Adv Exp Med Biol. 2018; 1067: 183-196Crossref PubMed Scopus (2) Google BJ Desai MY Nishimura RA Spirito P Rakowski H Towbin JA Dearani JA Rowin EJ Maron MS Sherrid MV. Management of hypertrophic cardiomyopathy: JACC State-of-the-Art Review.J Am Coll Cardiol. 2022; 79: 390-414Crossref PubMed Scopus (97) Google P Rapezzi C Adler Y Arad M Basso C Brucato A Burazor I Caforio ALP Damy T Eriksson U Fontana M Gillmore JD Gonzalez-Lopez E Grogan M Heymans S Imazio M Kindermann I Kristen AV Maurer MS Merlini G Pantazis A Pankuweit S Rigopoulos AG Linhart A. Diagnosis and treatment of cardiac amyloidosis. A position statement of the Society of on and J Heart PubMed Scopus Google P M V work in nonobstructive hypertrophic cardiomyopathy: for Am Echocardiogr. 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