A Case Report on Application of Multimodal Imaging to an Alcoholic Cardiomyopathic Patient Undergoing Heart Transplantation : Cardiology Discovery

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Special Issue for Coronary Bifurcation Lesions, Guest Editor, Shaoliang Chen: Case Report

A Case Report on Application of Multimodal Imaging to an Alcoholic Cardiomyopathic Patient Undergoing Heart Transplantation

Li, Zhiming1; Wang, Yu2; Duan, Bingsong3; Han, Dan1; Chen, Wei1,*

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doi: 10.1097/CD9.0000000000000062
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Abstract

Introduction

Following smoking and inactivity, alcohol consumption is the third-leading lifestyle-related cause of death in the United States. It is also responsible for 3.8% of all deaths worldwide.[1] Alcohol abuse is partly associated with approximately 30% to 50% of all non-ischemic cardiomyopathies, which is also called alcoholic cardiomyopathy (ACM).[2] For the treatment of ACM in its early stage, abstinence represents the most effective strategy according to some prior studies, while heart transplant is the last resort for the treatment of end-stage heart failure in ACM patients.[3] In this case report, we used multimodal imaging to diagnose ACM in a patient with refractory heart failure. The patient received a heart transplant with a good prognosis, and his pathological results after the transplant confirmed our suspected diagnosis. The patient has given his consent to publish his clinical data and images in the journal.

Case presentation

A 47-year-old-male patient was hospitalized for primary symptoms of exertional dyspnea and shortness of breath for 10 days. His physical examination showed a displaced apical impulse and systolic cardiac murmurs that could be heard in the mitral valve area and were conducted to the left axilla (A2 > P2). He had a history of refractory heart failure and heart palpitation for more than 2 years. He admitted to a 20-year history of consuming >200 g of alcohol per day, but denied having hypertension and diabetes. Based on the symptoms of his heart failure, the initial differential diagnosis remained general and vague, including ischemic cardiomyopathy, valvular disease, and pericardial disease. Dilated cardiomyopathy (DCM), including ACM, was also considered given his clinical manifestation.

An echocardiography was performed within 24 hours of admission, which demonstrated severe global left ventricular systolic dysfunction with an ejection fraction of 35%, left ventricle (LV) enlargement, and moderate mitral regurgitation; the right ventricular function was grossly normal [Table 1] [Figure 1A–C]. Laboratory examination revealed an increase in the levels of N-terminal pro-brain natriuretic peptide, C-reactive protein (CRP), and myocardial enzymes. To exclude ischemic cardiomyopathy, coronary computed tomography angiography was performed, but no significant coronary artery stenosis was found [Figure 1D–F]. To detect the cause of his heart failure, cardiac magnetic resonance (CMR) was performed, which revealed that both left atrium and LV dilated with LV systolic dysfunction, but the wall thickness was normal [Figure 1G–I]. Late gadolinium enhancement (LGE) occurred on the mid-wall of the septum, which was indicative of myocardial fibrosis [Table 2] [Figure 1J–L]. The patient was suspected of having ACM based on his history of alcoholism and our imaging findings. His congestive heart failure was treated with diuretics and angiotensin-converting enzyme inhibitor, and he was asked to completely abstain from alcohol consumption. After a period of treatment, his left ventricular ejection fraction (LVEF) improved from 35% to 45% before he was discharged. However, despite the moderate improvemen in cardiac function, he still had New York Heart Association (NYHA) class Ⅲ cardiac dysfunction and was unable to engage in any physical activity or even household activities, which seriously affected his quality of life. Given the prolonged and painful inactivity due to heart failure, the patient and his family were eager for further treatment. Thus, he was put on a waiting list for heart donation.

Table 1 - Patient’s echocardiography characteristics.
Variables Admission Pre-operation 3rd Postoperative days 15th Postoperative days 42nd Postoperative days 7th Postoperative months
LAD (mm) 54 40 32 40 46 46
LVEDD (mm) 82 66 46 34 41 44
RATD (mm) 42 31 28 29 29 38
RVD (mm) 30 28 18 22 26 31
IVST (mm) 10 11 8 10 8 11
LVPWT (mm) 10 11 9 9 6 8
LVEDV (mL) 465 262 85 157 109 91
LVESV (mL) 303 143 38 42 34 23
LVFS (%) 18 23 36 42 39 43
LVEF (%) 35 45 72 73 69 74
EROA (cm2) 0.37 0.18
Rvol (mL) 54 33
“–” indicates that data are not available.
EROA: Effective regurgitate orifice area; IVST: Interventricular septum thickness; LAD: Left atrial diameter; LVEDD: Left ventricular end diastolic diameter; LVEDV: Left ventricular end diastolic volume; LVEF: Left ventricular ejection fraction; LVESV: Left ventricular end systolic volume; LVFS: Left ventricular fraction shortening; LVPWT: Left ventricular posterior wall thickness; RATD: Right atrial transverse diameter; RVD: Right ventricular diameter; Rvol: Reflux volume.

Table 2 - Patient’s cardiac magnetic resonance characteristics.
Ventricle EDV (mL) ESV (mL) SV (mL) EF (%) TD (mm) LD (mm) GLS (%) GRS (%) GCS (%) Myo-mass (g) LGE (%)
LV 440.2 352.2 88 19.9 50.2 65.1 −5.45 7.35 −4.72 213.7 21.2
RV 125.6 99.9 25.6 20.4 33.8 40.1
“–” indicates that data are not available.
EDV: End diastolic volume; EF: Ejection fraction; ESV: End systolic volume; GCS: Global circumferential strain; GLS: Global longitudinal strain; GRS: Global radial strain; LD: Long diameter; LGE: Late gadolinium enhancement; LV: Left ventricle; Myo-mass: Myocardial mass; RV: Right ventricular; SV: Stroke volume; TD: Transverse diameter.

F1
Figure 1::
Patient’s cardiac imaging. Transthoracic echocardiography (A–C), performed on the day of the first admission, showed left ventricle enlargement with systolic and diastolic dysfunction as well as moderate mitral regurgitation (white arrow). Coronary computed tomography angiography (D–F) showed no significant coronary artery stenosis. Cardiac magnetic resonance Cine imaging (G–I) showed that the left atrium and left ventricle were dilated, with left ventricle systolic dysfunction. Left ventricle wall thickness was normal (septum: 7.3–12.1 mm; free wall: 6.6–8.9 mm). Late gadolinium enhancement (J–L) showed enhancement in the mid-wall of the septum (red arrow). Transesophageal echocardiography (M–O) showed the donor heart performed well.

About 1 month after the discharge, the patient fortunately had a suitable donor, a young man who died in a car accident. The heart transplant was successfully performed. Intraoperative transesophageal echocardiography was performed immediately after the heart transplant, which revealed that the donor heart performed well in the patient’s body [Figure 1M–O]. Pathological features of the patient’s heart including cardiomyocyte necrosis, interstitial fibrosis, and lipid deposition ultimately confirmed our multimodal imaging-based diagnosis of ACM before the operation [Figure 2]. The patient underwent echocardiography examination every day during his 10-day stay in the critical care unit, and both the cardiac structure and function were good [Table 1]. The level of myocardial enzymes and CRP gradually returned to normal.

F2
Figure 2::
Patient’s pathology gross anatomy (A–C) showed heart enlargement and left ventricle chamber dilation, and left ventricle wall in normal range (septum: 6–11 mm; free wall: 7–9 mm; Red box). Myocardial sections of ventricular septum were used for HE staining and Masson staining, and examined by TEM (red dotted box). HE staining (×200) showed myocardial structural disorder, cardiomyocyte necrosis, apoptosis, and fat infiltration (D). Masson staining (×400) showed hyperplasia of the fibrous tissue (E). TEM showed myofibrillar disarray and lysis (Mf), cardiomyocyte necrosis (N), mitochondria degeneration (m), glycogen particles accumulation (g), lipid infiltration (black arrow), and accumulation of lysosomes and lipofuscin granules (white arrow) (F–I). HE: Hematoxylin-eosin; TEM: Transmission electron microscopy.

Upon discharge, there was no evidence of cardiac rejection reaction. Seven months after the heart transplant, his cardiac function evaluated by ultrasound was normal, and he had returned to normal life and was able to do physical activities [Table 1].

Discussion

This case report highlights the use of multimodal imaging, especially CMR, for diagnosing a patient with a prolonged history of alcohol abuse, who had refractory heart failure and underwent heart transplantation. Our initial suspected diagnosis of ACM was eventually confirmed by cardiac pathology. The patient recovered uneventfully after the transplantation.

Studies report that alcoholic patient who consume more than 90 g of alcohol per day for more than 5 years are at the high risk of developing ACM, which may involve left ventricular dilation, reduce cardiac output, and eventually lead to heart failure.[4]

In the early stage of ACM, with abstinence, more than 80% patients can survive for >12 years after the diagnosis.[5] In the advanced stage of ACM, patients often suffer from refractory heart failure. Therefore, heart transplantation is recommended given the deterioration of cardiac structure and dysfunction.[3] Despite the symptoms of refractory heart failure having mildly improved in our patient after drug therapy and abstinence, he was still unable to perform daily physical activities and had NYHA class Ⅲ cardiac dysfunction. The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation suggest that alcoholics should abstain from alcohol for a year before they can be considered for a heart transplant.[6] In our patient, the heart transplant was carried out because of the rarity of a suitable donor and the patient’s strong desire for further treatment and heart transplantation. In addition, after the heart transplant, the patient showed good prognosis and lived a significantly improved quality of life. Therefore, this case suggests that ACM patients who have improved cardiac function after abstinence and drug therapy but retain heart failure (eg, NYHA class Ⅲ) may have a better prognosis if the heart transplant is performed using a suitable available donor.

Chronic exposure to ethanol may trigger cardiac apoptosis because of the activation of the mitochondrial permeability transition pore by physiological calcium oscillations. Myocyte apoptosis has been demonstrated to be an active phenomenon leading to myocyte loss in people with chronic high-dosed consumption of ethanol both in experimental and clinical models.[7,8] Dysregulated excessive autophagy, together with other factors such as oxidative stress, neurohormonal activation, and altered fatty acid metabolism can contribute to cardiac structural and functional damages and may worsen ACM.[4] A recent study used full-thickness cardiac specimens to compare the histologic characteristics of ACM patients with that of idiopathic DCM patients and found a reduction in myocytes in ACM patients as compared to idiopathic DCM patients.[9]

Echocardiography is one of the most commonly used techniques for initial detection and follow-up study of cardiomyopathy.[10] The ultrasonic manifestations of ACM patients are basically consistent with those of DCM patients, which is characterized by an enlarged heart chamber, thinned ventricular wall, and decreased ejection fraction. While it is difficult for echocardiography to determine the causes of heart failure, CMR has been widely accepted as an imaging modality for all heart failure patients with an uncertain diagnosis.[11]

In addition to accurately evaluating cardiac function and structure, tissue characteristic imaging of CMR can help distinguish DCM from ACM for the following reasons. First, CMR imaging shows typical characteristics of ACM, which are similar to those of DCM. As the ventricular wall thickness of ACM patients is usually normal, it may be used to help narrow the scope for differential diagnosis.[9] Second, LGE localization is significantly different for ACM and DCM, with LGE mostly located in the septum of ACM patients and LGE in DCM mostly located in the LV lateral wall.[12] The thickness of the ventricular wall of this patient was normal and his LGE was mainly located on the myocardial middle layer of the interventricular septum. His septal myocardial pathology showed obvious myocardial fibrosis. These CMR and pathological changes were consistent with those reported by prior studies on ACM. Moreover, LGE can be used to predict the prognosis of ACM. As recently demonstrated by Halliday et al,[13] the presence of a mid-wall LGE can help identify a subgroup of patients with DCM and an LVEF ≥40% who might be at increased risk of sudden cardiac death. In the previous studies, subjects with moderate-to-heavy alcohol consumption showed significantly shorter native T1 and greater extracellular volume fraction than controls, with the former possibly indicative of a myocardial fat deposition and the latter possibly indicative of myocardial fibrosis or an abnormal deposition of metabolites into the myocardium of alcoholics.[14,15] This report reveals that further studies are needed to validate whether T1 mapping can be used to differentiate ACM from DCM and to evaluate the prognosis of ACM patients.

Conclusion

End-stage ACM may lead to refractory heart failure, and multimodal imaging may play an important role in the diagnosis, prognosis prediction, and follow-up study of suspected ACM.

Acknowledgments

The authors thank Guomiao Su from the Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, China; Qiying Guo from Kunming Institute of Zoology, CAS, Kunming, China; and Yue Jiang from Xi’an Jiaotong University School of Foreign Studies, Xi’an, China, for their outstanding technical assistance.

Funding

This work was supported by the National Natural Science Foundation of China (82060312), Yunnan Applied Basic Research Projects (2018FE001(-039), 202101AT070249), Fund of Yunnan Province Clinical Research Center for Interventional Medicine (202102AA100067) and Graduate Innovation Fund of Kunming Medical University (2021S185).

Conflicts of interest

None.

References

[1]. Walls H, Cook S, Matzopoulos R, et al. Advancing alcohol research in low-income and middle-income countries: a global alcohol environment framework. BMJ Glob Health. 2020;5(4):e001958. doi:10.1136/bmjgh-2019-001958.
[2]. Guzzo-Merello G, Cobo-Marcos M, Gallego-Delgado M, et al. Alcoholic cardiomyopathy. World J Cardiol. 2014;6(8):771–781. doi:10.4330/wjc.v6.i8.771.
[3]. Bozkurt B, Colvin M, Cook J, et al. Current diagnostic and treatment strategies for specific dilated cardiomyopathies: a scientific statement from the American Heart Association. Circulation. 2016;134(23):e579–e646. doi:10.1161/CIR.0000000000000455.
[4]. Fernández-Solà J. The effects of ethanol on the heart: alcoholic cardiomyopathy. Nutrients. 2020;12(2):572. doi:10.3390/nu12020572.
[5]. Shield KD, Rylett M, Gmel G, et al. Global alcohol exposure estimates by country, territory and region for 2005—a contribution to the comparative risk assessment for the 2010 global burden of disease study. Addiction. 2013;108(5):912–922. doi:10.1111/add.12112.
[6]. Mehra MR, Canter CE, Hannan MM, et al. The 2016 international society for heart lung transplantation listing criteria for heart transplantation: a 10-year update. J Heart Lung Transplant. 2016;35(1):1–23. doi:10.1016/j.healun.2015.10.023.
[7]. Rodrigues P, Santos-Ribeiro S, Teodoro T, et al. Association between alcohol intake and cardiac remodeling. J Am Coll Cardiol. 2018;72(13):1452–1462. doi:10.1016/j.jacc.2018.07.050.
[8]. Steiner JL, Lang CH. Etiology of alcoholic cardiomyopathy: mitochondria, oxidative stress and apoptosis. Int J Biochem Cell Biol. 2017;89:125–135. doi:10.1016/j.biocel.2017.06.009.
[9]. Li X, Nie Y, Lian H, et al. Histopathologic features of alcoholic cardiomyopathy compared with idiopathic dilated cardiomyopathy. Medicine (Baltim). 2018;97(39):e12259. doi:10.1097/MD.0000000000012259.
[10]. Ederhy S, Mansencal N, Réant P, et al. Role of multimodality imaging in the diagnosis and management of cardiomyopathies. Arch Cardiovasc Dis. 2019;112(10):615–629. doi:10.1016/j.acvd.2019.07.004.
[11]. Donal E, Delgado V, Bucciarelli-Ducci C, et al. Multimodality imaging in the diagnosis, risk stratification, and management of patients with dilated cardiomyopathies: an expert consensus document from the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2019;20(10):1075–1093. doi:10.1093/ehjci/jez178.
[12]. Artico J, Merlo M, Asher C, et al. The alcohol-induced cardiomyopathy: a cardiovascular magnetic resonance characterization. Int J Cardiol. 2021;331:131–137. doi:10.1016/j.ijcard.2021.01.067.
[13]. Halliday BP, Gulati A, Ali A, et al. Association between midwall late gadolinium enhancement and sudden cardiac death in patients with dilated cardiomyopathy and mild and moderate left ventricular systolic dysfunction. Circulation. 2017;135(22):2106–2115. doi:10.1161/CIRCULATIONAHA.116.026910.
[14]. Liu S, Lin X, Shi X, et al. Myocardial tissue and metabolism characterization in men with alcohol consumption by cardiovascular magnetic resonance and 11C-acetate PET/CT. J Cardiovasc Magn Reson. 2020;22(1):23. doi:10.1186/s12968-020-00614-2.
[15]. da Silva R, de Mello R. Fat deposition in the left ventricle: descriptive and observational study in autopsy. Lipids Health Dis. 2017;16(1):86. doi:10.1186/s12944-017-0475-9.
Keywords:

Cardiomyopathy, alcoholic; Chronic heart failure; Cardiac magnetic resonance; Coronary angiography; Echocardiography; Case report

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