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Improvement of global longitudinal strain following high-dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with amyloid light-chain cardiac amyloidosis: a case report

Improvement of global longitudinal strain following high-dose chemotherapy and autologous... Downloaded from https://academic.oup.com/ehjcr/article-abstract/3/4/1/5678686 by guest on 26 February 2020 CASE REPORT European Heart Journal - Case Reports (2019) 3, 1–6 doi:10.1093/ehjcr/ytz225 Cardiac imaging Improvement of global longitudinal strain following high-dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with amyloid light-chain cardiac amyloidosis: a case report 1 1 2 1 Yukina Hirata , Kenya Kusunose *, Hirokazu Miki , and Hirotsugu Yamada 1 2 Department of Cardiovascular Medicine, Ultrasound Examination Center, Tokushima University Hospital, 2-50-1 Kuramoto, Tokushima, Japan; and Division of Transfusion Medicine and Cell Therapy, Tokushima University Hospital, Tokushima, Japan Received 24 March 2019; first decision 10 June 2019; accepted 21 November 2019; online publish-ahead-of-print 16 December 2019 Background Cardiac amyloidosis (CA) is a secondary form of cardiomyopathy where abnormal accumulation of amyloid protein in the myocardial interstitium causes cardiac hypertrophy and myocardial fibrosis. If primary CA advances to heart failure, most patients do not survive for very long after the diagnosis. ............................................................................................................................................................................................................... Case summary A 40-year-old man was admitted to our hospital for dyspnoea, progressive anaemia, and decreased appetite. He has diag- nosed with amyloid light-chain (AL) amyloidosis. Although BD treatment (bortezomib þ dexamethasone) and medical treatment were started, there was no sign of improvement. Then, high-dose chemotherapy followed by autologous per- ipheral blood stem cell transplantation (auto-PBSCT) was initiated. Pretreatment echocardiography revealed typical find- ings of CA, such as ventricular wall thickening, valvular thickening, diastolic dysfunction, and pericardial effusion. Global longitudinal strain (GLS) was significantly reduced, and bull’s-eye mapping showed typical apical sparing. After auto- PBSCT, GLS gradually improved and was almost normal after 2 years. Other echocardiographic parameters, functional sta- tus, and laboratory data also showed that there was significant regression of CA. ............................................................................................................................................................................................................... Discussion Although the prognosis in primary CA is extremely poor, we achieved long-term survival in a patient with effective high- dose chemotherapy and auto-PBSCT. Global longitudinal strain may be a useful marker of prognosis, regression, and recovery. Keywords Cardiac amyloidosis Echocardiography Speckle tracking Global longitudinal strain Improvement • • • • Case report Learning points Global longitudinal strain (GLS) may be a useful marker of regression and recovery after auto peripheral blood stem cell transplantation in patients with cardiac amyloidosis (CA). Serial measurements of GLS may identify cardiac function improvement without demonstrable changes in standard echocardiographic parameters among light-chain CA patients. * Corresponding author. Tel: þ81 88 633 9311, Fax: þ81 88 633 7798, Email: kusunosek@tokushima-u.ac.jp Handling Editor: Matteo Cameli Peer-reviewers: Riccardo Liga and Savvas Loizos Compliance Editor: Mark Philip Cassar Supplementary Material Editor: Ross Thomson V The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Downloaded from https://academic.oup.com/ehjcr/article-abstract/3/4/1/5678686 by guest on 26 February 2020 2 Y. Hirata et al. brain natriuretic peptide (NT-proBNP) was markedly elevated to Introduction 12 994 pg/mL, and he was admitted to our hospital. At the first visit, Cardiac amyloidosis (CA) is part of a systemic disease characterized . his blood pressure was 84/46 mmHg and pulse rate was 65 b.p.m. by the deposition of amyloid in multiple tissues. Cardiac amyloidosis with a regular rhythm. Precordial examination revealed a third heart results in characteristic macroscopic structural and functional sound. Chest examination revealed bilateral diminished air entry 1 . changes on transthoracic echocardiography (TTE). Global longitu- . over both lung bases. He displayed oedema of the lower extremities. dinal strain (GLS) is significantly reduced, and bull’s-eye mapping typ- . A blood test indicated markedly elevated levels of BNP (1490 pg/ 2 . ically shows apical sparing. Cardiac amyloidosis is usually . mL). Complete blood count showed anaemia with haemoglobin of accompanied by refractory heart failure and conduction abnormal- 10.9 g/dL. ities; hence, most patients do not survive for very long after the diag- nosis. However, recent reports have demonstrated that select Diagnostic assessment patients who achieve haematologic remission after high-dose chemo- Electrocardiography displayed a low-amplitude R-wave on the limb therapy and autologous peripheral blood stem cell transplantation leads and a QS pattern on leads V1–V3 (Figure 1A). Transthoracic 4,5 . (auto-PBSCT) may regress these cardiac features. We report a pa- . echocardiography revealed moderately increased left ventricular tient with light-chain (AL)-CA who showed significant improvement . (LV) wall thickness (septal wall, 14 mm; posterior wall, 14 mm) with a in the anatomic features associated with CA, including GLS. . small pericardial effusion (Figure 1B). Thickening of the right ventricu- lar (RV) wall was also shown. Left ventricular systolic function was preserved, with an ejection fraction (EF) of 63%, as measured by the Timeline . modified Simpson method. Longitudinal myocardial systolic strain based on two-dimensional speckle-tracking echocardiography showed far more significant LV dysfunction. Global longitudinal strain was markedly reduced to -6.2%, and bull’s eye mapping revealed the Events . ................................................................................................. . characteristic apical sparing pattern (Figure 1C). The regional values of 2 months prior to Patient admitted to our hospital for dyspnoea, . the RV free wall longitudinal strain (RV free wall LS) were reduced to autologousperip- progressive anaemia, and decreased appetite -7.0% (Figure 1D). Left atrial (LA) strain was also reduced to -14%. heral blood stem Transthoracic echocardiography led us to The mitral inflow profile showed a restricted pattern such that the cell transplant- strongly suspect cardiac amyloidosis (CA) patient’s peak early filling (E) and late diastolic filling (A)velocityratio ation (auto- with heart failure was 3.2. Furthermore, the septal and lateral tissue Doppler e‘values PBSCT) were low, with an E/e’ ratio >15. Pulmonary artery systolic pressure 1 month prior to Diagnosed with light-chain CA could not be estimated due to absence of tricuspid regurgitation. auto-PBSCT BD treatment (bortezomib þ dexamethasone) Inferior vena cava (IVC) was dilated and showed decreased respira- and medical treatment was started . tory variability. These findings led us to strongly suspect CA with February 2014 High-dose chemotherapy (melphalan, . heart failure. Cardiac magnetic resonance imaging (MRI) showed dif- 140 mg/m ) with auto-PBSCT was started . fuse subendocardial mild enhancement of the biventricular myocar- Brain natriuretic peptide (BNP) = 1194 pg/mL, . dium. Subsequently, the patient was diagnosed with primary systemic global longitudinal strain (GLS) = -6.2%, and . AL amyloidosis by cardiac muscle, duodenum, and bone marrow bi- left ventricular (LV) wall = 14 mm . opsy (Supplementary material online, Figure S1). 4 months after Symptoms were getting relieved and discharged . auto-PBSCT hospital . Interventions and outcomes BNP levels declined to the 700s pg/mL . Although BD treatment (bortezomib þ dexamethasone) and medic- 6 months after BNP levels declined to the 200s pg/mL . al treatment were started, the patient’s condition gradually wors- auto-PBSCT GLS showed only a slight change (-8.3%) ened. Then, high-dose chemotherapy (melphalan, 140 mg/m )with 11 months after BNP levels declined to the 80s pg/mL . auto-PBSCT was started. The clinical course of auto-PBSCT is shown auto-PBSCT GLS improved to a value of -12.2% . in Figure 2. Brain natriuretic peptide levels declined to the 200 s pg/ LV wall showed only a slight change (12 mm) . mL at 6 months after auto-PBSCT and continued to decrease. Left 22 months after BNP levels normalized. . ventricular diastolic function measurements corresponded to pro- auto-PBSCT GLS improved to a value of -16.2% gressive improvement in the BNP level. Doppler demonstrated a re- LV wall improved to 10 mm laxation abnormality pattern with an E/A <0.8, and an IVC diameter 60 months after Patient has been no relapse and continues to <15 mm at 6 months after auto-PBSCT. These improvements were auto-PBSCT visit the outpatient clinic. accompanied by an improvement in biventricular LS. While GLS showed a slight change at 6 months after auto-PBSCT was started, it . significantly improved thereafter. Twenty-two months after auto- . PBSCT, GLS improved to a value of -16.2%, and bull’s-eye mapping Case presentation . . showed a more normal pattern. Right ventricular free wall LS and LA A 40-year-old man presented to a local clinic complaining of dys- . strain were also improved to -17% and -27%, respectively. Left ven- pnoea, progressive anaemia, and decreased appetite. N-terminal pro- tricular EF did not change significantly from pretreatment levels. The Downloaded from https://academic.oup.com/ehjcr/article-abstract/3/4/1/5678686 by guest on 26 February 2020 GLS following high-dose chemotherapy 3 Figure 1 Imaging examinations before treatment. (A) Electrocardiogram. (B) Parasternal echocardiographic view demonstrated biventricular hypertrophy and a small pericardial effusion. (C) Bull’s-eye mapping. Regional values of the left ventricle longitudinal strain decreased markedly in the base even though the apex remained unchanged, indicating an apical sparing pattern. (D) Regional values of the right ventricle free wall longitudinal strain. These changes are considered to exhibit high sensitivity and specificity for the diagnosis of cardiac amyloidosis. anatomic changes in ventricular wall thickness occurred at a slower rate than the changes in GLS. Left ventricular wall thickness improved Furosemide (20mg) to 10 mm at 22 months after auto-PBSCT (Figure 3, Supplementary Bortezomib+ Dexamethasome material online, Videos S1 and S2). Interestingly, the subendocardial Auto-PBSCT+ Melphalan 140mg/m enhancement disappeared on cardiac MRI after auto-PBSCT. 2000 -16 BNP LV GLS RV free wall LS Currently, the patient has had no relapse over 60 months (Figure 4). 1500 -12 1000 --8 Discussion 500 --4 Amyloid light-chain-CA is an infiltrative cardiomyopathy beginning with subclinical myocardial deposition of fibrils, LV and RV wall thick- 0 0 -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12 ening, and impairment of diastolic function. Cardiac involvement Month occurs in 50% of amyloidosis cases. As the volume of infiltration Figure 2 Transthoracic echocardiography. Left ventricular car- increases, patients develop clinical heart failure with preserved EF. diac apex (upper), M mode view (middle), and speckle tracking Prognosis is poor, with survival reported as 48 months, dropping to (lower). Although the left ventricular ejection fraction remained un- 5–8 months with cardiac involvement. changed at 60–65%, global longitudinal strain gradually improved. Our patient had a rapid reduction in BNP and has maintained a Gradual alleviation of left ventricular wall hypertrophy was noted, good condition over a period of 5 years. This improvement may 1 year after therapy. have been due to shifting the treatment to high-dose melphalan and BNP(pg/ml) LS (%) Downloaded from https://academic.oup.com/ehjcr/article-abstract/3/4/1/5678686 by guest on 26 February 2020 4 Y. Hirata et al. 6 months after 11 months after 18 months after Pre 22 months after auto-PBSCT auto-PBSCT auto-PBSCT auto-PBSCT auto-PBSCT EF: 61% 63% 64% 65% 64% 10mm LV wall: 14mm 14mm 12mm 12mm LV GLS: -6.2% -8.3% -12.2% -16.0% -16.2% Figure 3 Clinical course of the patient on high-dose chemotherapy with auto-PBSCT. After autologous peripheral blood stem cell transplantation, the brain natriuretic peptide spiked to 1700 pg/mL, but declined to 200 pg/mL after 6 months. These improvements were accompanied by a reduc- tion in the global longitudinal strain levels. auto-PBSCT. Plasma levels of the natriuretic peptides (BNP and NT- showed a tendency for higher levels of myocardial amyloid depos- proBNP) tend to be high in CA independent of the severity of heart ition by histopathology of myocardial biopsies. A further analysis is failure and have prognostic value as an index of response to therapy. needed to determine whether or not our findings can be generalized In contrast, a recent study showed patients who achieve haemato- to other cases. logic remission after auto-PBSCT have significant regression of the classical echocardiographic changes in CA. However, several studies Conclusion have reported that serial assessments of wall thickness and EF do in- deed improve in association with a maintained complete haemato- . Our report provides detailed echocardiography follow-up of a pa- logic response, and these changes typically require many years (three . tient throughout the clinical course of CA. or more) to observe; they are rarely, if ever, observed in the short term. Speckle-tracking echocardiography has been widely reported to Lead author biography be useful in the diagnosis and prognosis of CA. Global longitudinal Yukina Hirata is the sonographer at strain and an apical sparing pattern have been widely reported to dis- Tokushima University Hospital. She criminate between AL-CA and other wall thickening processes, and majored in cardiovascular Medicine predict survival associated with heart failure development in a cohort 2,10,11 and received her PhD degree from of AL amyloidosis patients (cardiac and non-cardiac). Graduate School of Medical Furthermore, several studies have reported that GLS may unmask Sciences, Tokushima University, early cardiac recovery following chemotherapy in patients with CA. Japan in March 2016. Her main re- Fitzgerald et al. reported a case of an AL-CA patient who showed search theme is examine the clinical complete remission with normalization of GLS 2 years after PBSCT. In this previous case, the anatomic changes (regression in utility of epicardial adipose tissue wall thickness) occurred at a slower rate than the changes in GLS. using echocardiography. Recently, These findings are consistent with our case. Improvement in GLS she is interested in artificial intelli- may be related to a reduction in the amount of myocardial amyloid gence and supervised by Dr Kenya deposition. Ternacle et al. reported that areas with low strain Kusunose. Downloaded from https://academic.oup.com/ehjcr/article-abstract/3/4/1/5678686 by guest on 26 February 2020 GLS following high-dose chemotherapy 5 Figure 4 Imaging examinations 60 months after treatment. (A) Electrocardiogram. Electrocardiography demonstrated a R-wave improvement on the limb leads. (B) Parasternal echocardiographic. (C)Bull’s-eye mapping. (D) Regional values of the right ventricle free wall longitudinal strain. Consent: The author/s confirm that written consent for submission and Supplementary material publication of this case report including image(s) and associated text has . been obtained from the patient in line with COPE guidance. Supplementary material is available at European Heart Journal - Case Reports online. Conflict of interest: none declared. References . 1. Falk RH, Comenzo RL, Skinner M. The systemic amyloidosis. N Engl J Med 1997; Acknowledgements . 337:898–909. Theauthors aredeeplygratefultostaffsand DrsHisanoriUeharaat 2. Phelan D, Collier P, Thavendiranathan P, Popovi c ZB, Hanna M, Plana JC, Marwick TH, Thomas JD. Relative apical sparing of longitudinal strain Department of Pathology of Tokushima University Hospital for data . using two-dimensional speckle-tracking echocardiography is both sensitive acquisitions of Pathological specimen and to all staffs at Ultrasound and specific for the diagnosis of cardiac amyloidosis. Heart 2012;98: 1442–1448. Examination Center, Tokushima University Hospital for acquisitions . . 3. Dubrey SW, Cha K, Anderson J, Chamarthi B, Reisinger J, Skinner M, Falk RH. of echocardiographic parameters. Finally, we are gratefully acknow- The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart ledge to Masataka Sata at Department of Cardiovascular Medicine of involvement. QJM 1998;91:141–157. 4. Fitzgerald BT, Bashford J, Scalia GM. The return of the normal heart: resolution Tokushima University Hospital for advice with this paper. . of cardiac amyloidosis after chemotherapy and bone marrow transplantation. Heart Lung Circ 2013;22:655–660. 5. Fitzgerald BT, Bashford J, Scalia GM. Regression of the anatomic cardiac features Funding . . of amyloid light chain cardiac amyloidosis accompanied by normalization of glo- This work was supported by JSPS Kakenhi Grants [17K13037 to Y.H., bal longitudinal strain. CASE (Phila) 2017;1:46–48. 15K19381/17K09506 to K.K.]. . 6. Falk RH. Cardiac amyloidosis: a treatable disease, often overlooked. Circulation 2011;124:1079–1085. Slide sets: A fully edited slide set detailing this case and suitable for local . 7. Merlini G, Lousada I, Ando Y, Dispenzieri A, Gertz MA, Grogan M, Maurer MS, presentation is available online as Supplementary data. Sanchorawala V, Wechalekar A, Palladini G, Comenzo RL. Rationale, application Downloaded from https://academic.oup.com/ehjcr/article-abstract/3/4/1/5678686 by guest on 26 February 2020 6 Y. Hirata et al. and clinical qualification for NT-proBNP as a surrogate end point in pivotal clinic- 11. Liu D, Hu K, Niemann M, Herrmann S, Cikes M, Sto ¨ rk S, Gaudron PD, Knop S, al trials in patients with al amyloidosis. Leukemia 2016;30:1979–1986. Ertl G, Bijnens B, Weidemann F. Effect of combined systolic and diastolic func- 8. Salinaro F, Meier-Ewert HK, Miller EJ, Pandey S, Sanchorawala V, Berk JL, Seldin . tional parameter assessment for differentiation of cardiac amyloidosis from other DC, Ruberg FL. Longitudinal systolic strain, cardiac function improvement, and causes of concentric left ventricular hypertrophy. Circ Cardiovasc Imaging 2013;6: survival following treatment of light-chain (AL) cardiac amyloidosis. Eur Heart J 1066–1072. Cardiovasc Imaging 2017;18:1057–1064. 12. Tuzovic M, Kobayashi Y, Wheeler M, Barrett C, Liedtke M, Lafayette R, Schrier 9. Meier-Ewert HK, Sanchorawala V, Berk J, Finn KT, Skinner M, Seldin DC, Ruberg . S, Haddad F, Witteles R. Functional cardiac recovery and hematologic response FL. Regression of cardiac wall thickness following chemotherapy and stem cell to chemotherapy in patients with light-chain amyloidosis (from the Stanford transplantation for light chain (AL) amyloidosis. Amyloid 2011;18 Suppl 1:130–131. University Amyloidosis Registry). Am J Cardiol 2017;120:1381–1386. 10. Buss SJ, Emami M, Mereles D, Korosoglou G, Kristen AV, Voss A, Schellberg D, 13. Ternacle J, Bodez D, Guellich A, Audureau E, Rappeneau S, Lim P, Radu C, Zugck C, Galuschky C, Giannitsis E, Hegenbart U, Ho AD, Katus HA, Schonland Guendouz S, Couetil J-P, Benhaiem N, Hittinger L, Dubois-Rande ´ J-L, Plante- SO, Hardt SE. Longitudinal left ventricular function for prediction of survival in Bordeneuve V, Mohty D, Deux J-F, Damy T. Causes and consequences of longi- systemic light-chain amyloidosis: incremental value compared with clinical and tudinal LV dysfunction assessed by 2D strain echocardiography in cardiac amyl- biochemical markers. J Am Coll Cardiol 2012;60:1067–1076. . oidosis. JACC Cardiovasc Imaging 2016;9:126–138. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal - Case Reports Oxford University Press

Improvement of global longitudinal strain following high-dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with amyloid light-chain cardiac amyloidosis: a case report

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© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.
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Abstract

Downloaded from https://academic.oup.com/ehjcr/article-abstract/3/4/1/5678686 by guest on 26 February 2020 CASE REPORT European Heart Journal - Case Reports (2019) 3, 1–6 doi:10.1093/ehjcr/ytz225 Cardiac imaging Improvement of global longitudinal strain following high-dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with amyloid light-chain cardiac amyloidosis: a case report 1 1 2 1 Yukina Hirata , Kenya Kusunose *, Hirokazu Miki , and Hirotsugu Yamada 1 2 Department of Cardiovascular Medicine, Ultrasound Examination Center, Tokushima University Hospital, 2-50-1 Kuramoto, Tokushima, Japan; and Division of Transfusion Medicine and Cell Therapy, Tokushima University Hospital, Tokushima, Japan Received 24 March 2019; first decision 10 June 2019; accepted 21 November 2019; online publish-ahead-of-print 16 December 2019 Background Cardiac amyloidosis (CA) is a secondary form of cardiomyopathy where abnormal accumulation of amyloid protein in the myocardial interstitium causes cardiac hypertrophy and myocardial fibrosis. If primary CA advances to heart failure, most patients do not survive for very long after the diagnosis. ............................................................................................................................................................................................................... Case summary A 40-year-old man was admitted to our hospital for dyspnoea, progressive anaemia, and decreased appetite. He has diag- nosed with amyloid light-chain (AL) amyloidosis. Although BD treatment (bortezomib þ dexamethasone) and medical treatment were started, there was no sign of improvement. Then, high-dose chemotherapy followed by autologous per- ipheral blood stem cell transplantation (auto-PBSCT) was initiated. Pretreatment echocardiography revealed typical find- ings of CA, such as ventricular wall thickening, valvular thickening, diastolic dysfunction, and pericardial effusion. Global longitudinal strain (GLS) was significantly reduced, and bull’s-eye mapping showed typical apical sparing. After auto- PBSCT, GLS gradually improved and was almost normal after 2 years. Other echocardiographic parameters, functional sta- tus, and laboratory data also showed that there was significant regression of CA. ............................................................................................................................................................................................................... Discussion Although the prognosis in primary CA is extremely poor, we achieved long-term survival in a patient with effective high- dose chemotherapy and auto-PBSCT. Global longitudinal strain may be a useful marker of prognosis, regression, and recovery. Keywords Cardiac amyloidosis Echocardiography Speckle tracking Global longitudinal strain Improvement • • • • Case report Learning points Global longitudinal strain (GLS) may be a useful marker of regression and recovery after auto peripheral blood stem cell transplantation in patients with cardiac amyloidosis (CA). Serial measurements of GLS may identify cardiac function improvement without demonstrable changes in standard echocardiographic parameters among light-chain CA patients. * Corresponding author. Tel: þ81 88 633 9311, Fax: þ81 88 633 7798, Email: kusunosek@tokushima-u.ac.jp Handling Editor: Matteo Cameli Peer-reviewers: Riccardo Liga and Savvas Loizos Compliance Editor: Mark Philip Cassar Supplementary Material Editor: Ross Thomson V The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com Downloaded from https://academic.oup.com/ehjcr/article-abstract/3/4/1/5678686 by guest on 26 February 2020 2 Y. Hirata et al. brain natriuretic peptide (NT-proBNP) was markedly elevated to Introduction 12 994 pg/mL, and he was admitted to our hospital. At the first visit, Cardiac amyloidosis (CA) is part of a systemic disease characterized . his blood pressure was 84/46 mmHg and pulse rate was 65 b.p.m. by the deposition of amyloid in multiple tissues. Cardiac amyloidosis with a regular rhythm. Precordial examination revealed a third heart results in characteristic macroscopic structural and functional sound. Chest examination revealed bilateral diminished air entry 1 . changes on transthoracic echocardiography (TTE). Global longitu- . over both lung bases. He displayed oedema of the lower extremities. dinal strain (GLS) is significantly reduced, and bull’s-eye mapping typ- . A blood test indicated markedly elevated levels of BNP (1490 pg/ 2 . ically shows apical sparing. Cardiac amyloidosis is usually . mL). Complete blood count showed anaemia with haemoglobin of accompanied by refractory heart failure and conduction abnormal- 10.9 g/dL. ities; hence, most patients do not survive for very long after the diag- nosis. However, recent reports have demonstrated that select Diagnostic assessment patients who achieve haematologic remission after high-dose chemo- Electrocardiography displayed a low-amplitude R-wave on the limb therapy and autologous peripheral blood stem cell transplantation leads and a QS pattern on leads V1–V3 (Figure 1A). Transthoracic 4,5 . (auto-PBSCT) may regress these cardiac features. We report a pa- . echocardiography revealed moderately increased left ventricular tient with light-chain (AL)-CA who showed significant improvement . (LV) wall thickness (septal wall, 14 mm; posterior wall, 14 mm) with a in the anatomic features associated with CA, including GLS. . small pericardial effusion (Figure 1B). Thickening of the right ventricu- lar (RV) wall was also shown. Left ventricular systolic function was preserved, with an ejection fraction (EF) of 63%, as measured by the Timeline . modified Simpson method. Longitudinal myocardial systolic strain based on two-dimensional speckle-tracking echocardiography showed far more significant LV dysfunction. Global longitudinal strain was markedly reduced to -6.2%, and bull’s eye mapping revealed the Events . ................................................................................................. . characteristic apical sparing pattern (Figure 1C). The regional values of 2 months prior to Patient admitted to our hospital for dyspnoea, . the RV free wall longitudinal strain (RV free wall LS) were reduced to autologousperip- progressive anaemia, and decreased appetite -7.0% (Figure 1D). Left atrial (LA) strain was also reduced to -14%. heral blood stem Transthoracic echocardiography led us to The mitral inflow profile showed a restricted pattern such that the cell transplant- strongly suspect cardiac amyloidosis (CA) patient’s peak early filling (E) and late diastolic filling (A)velocityratio ation (auto- with heart failure was 3.2. Furthermore, the septal and lateral tissue Doppler e‘values PBSCT) were low, with an E/e’ ratio >15. Pulmonary artery systolic pressure 1 month prior to Diagnosed with light-chain CA could not be estimated due to absence of tricuspid regurgitation. auto-PBSCT BD treatment (bortezomib þ dexamethasone) Inferior vena cava (IVC) was dilated and showed decreased respira- and medical treatment was started . tory variability. These findings led us to strongly suspect CA with February 2014 High-dose chemotherapy (melphalan, . heart failure. Cardiac magnetic resonance imaging (MRI) showed dif- 140 mg/m ) with auto-PBSCT was started . fuse subendocardial mild enhancement of the biventricular myocar- Brain natriuretic peptide (BNP) = 1194 pg/mL, . dium. Subsequently, the patient was diagnosed with primary systemic global longitudinal strain (GLS) = -6.2%, and . AL amyloidosis by cardiac muscle, duodenum, and bone marrow bi- left ventricular (LV) wall = 14 mm . opsy (Supplementary material online, Figure S1). 4 months after Symptoms were getting relieved and discharged . auto-PBSCT hospital . Interventions and outcomes BNP levels declined to the 700s pg/mL . Although BD treatment (bortezomib þ dexamethasone) and medic- 6 months after BNP levels declined to the 200s pg/mL . al treatment were started, the patient’s condition gradually wors- auto-PBSCT GLS showed only a slight change (-8.3%) ened. Then, high-dose chemotherapy (melphalan, 140 mg/m )with 11 months after BNP levels declined to the 80s pg/mL . auto-PBSCT was started. The clinical course of auto-PBSCT is shown auto-PBSCT GLS improved to a value of -12.2% . in Figure 2. Brain natriuretic peptide levels declined to the 200 s pg/ LV wall showed only a slight change (12 mm) . mL at 6 months after auto-PBSCT and continued to decrease. Left 22 months after BNP levels normalized. . ventricular diastolic function measurements corresponded to pro- auto-PBSCT GLS improved to a value of -16.2% gressive improvement in the BNP level. Doppler demonstrated a re- LV wall improved to 10 mm laxation abnormality pattern with an E/A <0.8, and an IVC diameter 60 months after Patient has been no relapse and continues to <15 mm at 6 months after auto-PBSCT. These improvements were auto-PBSCT visit the outpatient clinic. accompanied by an improvement in biventricular LS. While GLS showed a slight change at 6 months after auto-PBSCT was started, it . significantly improved thereafter. Twenty-two months after auto- . PBSCT, GLS improved to a value of -16.2%, and bull’s-eye mapping Case presentation . . showed a more normal pattern. Right ventricular free wall LS and LA A 40-year-old man presented to a local clinic complaining of dys- . strain were also improved to -17% and -27%, respectively. Left ven- pnoea, progressive anaemia, and decreased appetite. N-terminal pro- tricular EF did not change significantly from pretreatment levels. The Downloaded from https://academic.oup.com/ehjcr/article-abstract/3/4/1/5678686 by guest on 26 February 2020 GLS following high-dose chemotherapy 3 Figure 1 Imaging examinations before treatment. (A) Electrocardiogram. (B) Parasternal echocardiographic view demonstrated biventricular hypertrophy and a small pericardial effusion. (C) Bull’s-eye mapping. Regional values of the left ventricle longitudinal strain decreased markedly in the base even though the apex remained unchanged, indicating an apical sparing pattern. (D) Regional values of the right ventricle free wall longitudinal strain. These changes are considered to exhibit high sensitivity and specificity for the diagnosis of cardiac amyloidosis. anatomic changes in ventricular wall thickness occurred at a slower rate than the changes in GLS. Left ventricular wall thickness improved Furosemide (20mg) to 10 mm at 22 months after auto-PBSCT (Figure 3, Supplementary Bortezomib+ Dexamethasome material online, Videos S1 and S2). Interestingly, the subendocardial Auto-PBSCT+ Melphalan 140mg/m enhancement disappeared on cardiac MRI after auto-PBSCT. 2000 -16 BNP LV GLS RV free wall LS Currently, the patient has had no relapse over 60 months (Figure 4). 1500 -12 1000 --8 Discussion 500 --4 Amyloid light-chain-CA is an infiltrative cardiomyopathy beginning with subclinical myocardial deposition of fibrils, LV and RV wall thick- 0 0 -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12 ening, and impairment of diastolic function. Cardiac involvement Month occurs in 50% of amyloidosis cases. As the volume of infiltration Figure 2 Transthoracic echocardiography. Left ventricular car- increases, patients develop clinical heart failure with preserved EF. diac apex (upper), M mode view (middle), and speckle tracking Prognosis is poor, with survival reported as 48 months, dropping to (lower). Although the left ventricular ejection fraction remained un- 5–8 months with cardiac involvement. changed at 60–65%, global longitudinal strain gradually improved. Our patient had a rapid reduction in BNP and has maintained a Gradual alleviation of left ventricular wall hypertrophy was noted, good condition over a period of 5 years. This improvement may 1 year after therapy. have been due to shifting the treatment to high-dose melphalan and BNP(pg/ml) LS (%) Downloaded from https://academic.oup.com/ehjcr/article-abstract/3/4/1/5678686 by guest on 26 February 2020 4 Y. Hirata et al. 6 months after 11 months after 18 months after Pre 22 months after auto-PBSCT auto-PBSCT auto-PBSCT auto-PBSCT auto-PBSCT EF: 61% 63% 64% 65% 64% 10mm LV wall: 14mm 14mm 12mm 12mm LV GLS: -6.2% -8.3% -12.2% -16.0% -16.2% Figure 3 Clinical course of the patient on high-dose chemotherapy with auto-PBSCT. After autologous peripheral blood stem cell transplantation, the brain natriuretic peptide spiked to 1700 pg/mL, but declined to 200 pg/mL after 6 months. These improvements were accompanied by a reduc- tion in the global longitudinal strain levels. auto-PBSCT. Plasma levels of the natriuretic peptides (BNP and NT- showed a tendency for higher levels of myocardial amyloid depos- proBNP) tend to be high in CA independent of the severity of heart ition by histopathology of myocardial biopsies. A further analysis is failure and have prognostic value as an index of response to therapy. needed to determine whether or not our findings can be generalized In contrast, a recent study showed patients who achieve haemato- to other cases. logic remission after auto-PBSCT have significant regression of the classical echocardiographic changes in CA. However, several studies Conclusion have reported that serial assessments of wall thickness and EF do in- deed improve in association with a maintained complete haemato- . Our report provides detailed echocardiography follow-up of a pa- logic response, and these changes typically require many years (three . tient throughout the clinical course of CA. or more) to observe; they are rarely, if ever, observed in the short term. Speckle-tracking echocardiography has been widely reported to Lead author biography be useful in the diagnosis and prognosis of CA. Global longitudinal Yukina Hirata is the sonographer at strain and an apical sparing pattern have been widely reported to dis- Tokushima University Hospital. She criminate between AL-CA and other wall thickening processes, and majored in cardiovascular Medicine predict survival associated with heart failure development in a cohort 2,10,11 and received her PhD degree from of AL amyloidosis patients (cardiac and non-cardiac). Graduate School of Medical Furthermore, several studies have reported that GLS may unmask Sciences, Tokushima University, early cardiac recovery following chemotherapy in patients with CA. Japan in March 2016. Her main re- Fitzgerald et al. reported a case of an AL-CA patient who showed search theme is examine the clinical complete remission with normalization of GLS 2 years after PBSCT. In this previous case, the anatomic changes (regression in utility of epicardial adipose tissue wall thickness) occurred at a slower rate than the changes in GLS. using echocardiography. Recently, These findings are consistent with our case. Improvement in GLS she is interested in artificial intelli- may be related to a reduction in the amount of myocardial amyloid gence and supervised by Dr Kenya deposition. Ternacle et al. reported that areas with low strain Kusunose. Downloaded from https://academic.oup.com/ehjcr/article-abstract/3/4/1/5678686 by guest on 26 February 2020 GLS following high-dose chemotherapy 5 Figure 4 Imaging examinations 60 months after treatment. (A) Electrocardiogram. Electrocardiography demonstrated a R-wave improvement on the limb leads. (B) Parasternal echocardiographic. (C)Bull’s-eye mapping. (D) Regional values of the right ventricle free wall longitudinal strain. Consent: The author/s confirm that written consent for submission and Supplementary material publication of this case report including image(s) and associated text has . been obtained from the patient in line with COPE guidance. Supplementary material is available at European Heart Journal - Case Reports online. Conflict of interest: none declared. References . 1. Falk RH, Comenzo RL, Skinner M. The systemic amyloidosis. N Engl J Med 1997; Acknowledgements . 337:898–909. Theauthors aredeeplygratefultostaffsand DrsHisanoriUeharaat 2. Phelan D, Collier P, Thavendiranathan P, Popovi c ZB, Hanna M, Plana JC, Marwick TH, Thomas JD. Relative apical sparing of longitudinal strain Department of Pathology of Tokushima University Hospital for data . using two-dimensional speckle-tracking echocardiography is both sensitive acquisitions of Pathological specimen and to all staffs at Ultrasound and specific for the diagnosis of cardiac amyloidosis. Heart 2012;98: 1442–1448. Examination Center, Tokushima University Hospital for acquisitions . . 3. Dubrey SW, Cha K, Anderson J, Chamarthi B, Reisinger J, Skinner M, Falk RH. of echocardiographic parameters. Finally, we are gratefully acknow- The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart ledge to Masataka Sata at Department of Cardiovascular Medicine of involvement. QJM 1998;91:141–157. 4. Fitzgerald BT, Bashford J, Scalia GM. The return of the normal heart: resolution Tokushima University Hospital for advice with this paper. . of cardiac amyloidosis after chemotherapy and bone marrow transplantation. Heart Lung Circ 2013;22:655–660. 5. Fitzgerald BT, Bashford J, Scalia GM. Regression of the anatomic cardiac features Funding . . of amyloid light chain cardiac amyloidosis accompanied by normalization of glo- This work was supported by JSPS Kakenhi Grants [17K13037 to Y.H., bal longitudinal strain. CASE (Phila) 2017;1:46–48. 15K19381/17K09506 to K.K.]. . 6. Falk RH. Cardiac amyloidosis: a treatable disease, often overlooked. Circulation 2011;124:1079–1085. Slide sets: A fully edited slide set detailing this case and suitable for local . 7. Merlini G, Lousada I, Ando Y, Dispenzieri A, Gertz MA, Grogan M, Maurer MS, presentation is available online as Supplementary data. Sanchorawala V, Wechalekar A, Palladini G, Comenzo RL. Rationale, application Downloaded from https://academic.oup.com/ehjcr/article-abstract/3/4/1/5678686 by guest on 26 February 2020 6 Y. Hirata et al. and clinical qualification for NT-proBNP as a surrogate end point in pivotal clinic- 11. Liu D, Hu K, Niemann M, Herrmann S, Cikes M, Sto ¨ rk S, Gaudron PD, Knop S, al trials in patients with al amyloidosis. Leukemia 2016;30:1979–1986. Ertl G, Bijnens B, Weidemann F. Effect of combined systolic and diastolic func- 8. Salinaro F, Meier-Ewert HK, Miller EJ, Pandey S, Sanchorawala V, Berk JL, Seldin . tional parameter assessment for differentiation of cardiac amyloidosis from other DC, Ruberg FL. Longitudinal systolic strain, cardiac function improvement, and causes of concentric left ventricular hypertrophy. Circ Cardiovasc Imaging 2013;6: survival following treatment of light-chain (AL) cardiac amyloidosis. Eur Heart J 1066–1072. Cardiovasc Imaging 2017;18:1057–1064. 12. Tuzovic M, Kobayashi Y, Wheeler M, Barrett C, Liedtke M, Lafayette R, Schrier 9. Meier-Ewert HK, Sanchorawala V, Berk J, Finn KT, Skinner M, Seldin DC, Ruberg . S, Haddad F, Witteles R. Functional cardiac recovery and hematologic response FL. Regression of cardiac wall thickness following chemotherapy and stem cell to chemotherapy in patients with light-chain amyloidosis (from the Stanford transplantation for light chain (AL) amyloidosis. Amyloid 2011;18 Suppl 1:130–131. University Amyloidosis Registry). Am J Cardiol 2017;120:1381–1386. 10. Buss SJ, Emami M, Mereles D, Korosoglou G, Kristen AV, Voss A, Schellberg D, 13. Ternacle J, Bodez D, Guellich A, Audureau E, Rappeneau S, Lim P, Radu C, Zugck C, Galuschky C, Giannitsis E, Hegenbart U, Ho AD, Katus HA, Schonland Guendouz S, Couetil J-P, Benhaiem N, Hittinger L, Dubois-Rande ´ J-L, Plante- SO, Hardt SE. Longitudinal left ventricular function for prediction of survival in Bordeneuve V, Mohty D, Deux J-F, Damy T. Causes and consequences of longi- systemic light-chain amyloidosis: incremental value compared with clinical and tudinal LV dysfunction assessed by 2D strain echocardiography in cardiac amyl- biochemical markers. J Am Coll Cardiol 2012;60:1067–1076. . oidosis. JACC Cardiovasc Imaging 2016;9:126–138.

Journal

European Heart Journal - Case Reports – Oxford University Press

Published: Dec 1, 2019

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