Amyloid Deposition Mainly Localized in the Basal Area of the Left Ventricle in a Patient with Amyloid Transthyretin Cardiac Amyloidosis

Abstract

A 74-year-old Japanese man was admitted to our hospital for catheter ablation of paroxysmal atrial fibrillation. Transthoracic echocardiography revealed basal interventricular septal hypertrophy without apical sparing. Cardiac magnetic resonance imaging revealed late gadolinium enhancement in the hypertrophic lesions. The Kumamoto criteria was one point, and the patient had no carpal tunnel syndrome. However, technetium-99m pyrophosphate scintigraphy revealed an accumulation in the basal region of the left ventricle. A skin biopsy revealed transthyretin (TTR) amyloid deposition. A TTR gene examination revealed no variants. This case suggests that amyloid deposition in TTR may occur in the basal area of the interventricular septum.

Introduction

Amyloid transthyretin cardiac amyloidosis (ATTR-CA) is a progressive and fatal cardiomyopathy caused by extracellular deposition of TTR amyloid fibrils in the myocardium (1,2). An early diagnosis is important for these patients, and diagnostic criteria and algorithms have been proposed in Japan (3,4).

We herein report a patient with wild-type ATTR-CA (ATTRwt-CA) who had a sigmoid septum on echocardiography and amyloid deposition mainly in the basal region of the left ventricle.

Case Report

A 74-year-old man was admitted to our ward for catheter ablation of atrial fibrillation (AF). The patient experienced dyspnea on exertion, associated with paroxysmal AF. The patient was treated with bepridil (50 mg, twice daily), apixaban (5 mg, twice daily), and prednisone (3 mg, once daily) for polymyalgia rheumatica. He had suffered a cerebral infarction three years prior, although he had no carpal tunnel syndrome or spinal canal stenosis. The patient's father had died of myocardial infarction. The patient had a history of smoking 20 cigarettes per day for 20 years but had no history of alcohol consumption.

A physical examination on admission revealed the following findings: blood pressure, 138/72 mmHg; regular pulse rate, 42 beats/min; body temperature, 36.0°C; height, 171 cm; body weight, 67.5 kg; body mass index, 23.1 kg/m²; and no abnormal findings. Laboratory data revealed slightly high levels of high-sensitivity troponin T (0.016 ng/mL) and N-terminal pro-brain natriuretic peptide (237 pg/mL) but a normal estimated glomerular filtration rate (74.3 mL/min/1.73 m²), thyroid function, and free light chain.

Chest radiography revealed cardiomegaly (cardiothoracic ratio 62%). Electrocardiography (ECG) six months prior had shown atrial fibrillation, left-axis deviation, and poor R-wave progression. ECG on admission revealed sinus bradycardia with a wide QRS after treatment with bepridil (50 mg twice daily) (Fig. 1). Transthoracic echocardiography (TTE) on admission revealed a thickened basal interventricular septum (IVS) (12 mm), normal left ventricular function (ejection fraction, 69%), and mildly reduced global longitudinal strain (GLS) in the basal anteroseptal and lateral walls of the left ventricle (LV) without apical sparing (Fig. 2A-C). Contrast-enhanced cardiac computed tomography revealed a thickened basal IVS and posterior wall of the LV (Fig. 2D).

Figure 1.

Electrocardiography (ECG) revealing atrial fibrillation, left axis deviation, and poor R-wave progression six months prior (A). ECG on admission revealing sinus bradycardia with wide QRS (120 ms) (B).

Figure 2.

Transthoracic echocardiography revealing basal hypertrophy of the left ventricle and mild pericardial effusion (A: parasternal long-axis view, B: apical four-chamber view), and mildly reduced global longitudinal strain without apical sparing (C). Enhanced cardiac computed tomography revealed thickened basal IVS and posterior wall of the left ventricle.

Cardiac magnetic resonance imaging (CMRI) revealed delayed gadolinium enhancement mainly in the basal anteroseptal and lateral walls of the LV (Fig. 3A-F), along with T1 elevation of native T1 mapping in the basal IVS and basal posterior wall of the LV (Fig. 3G, H) and a dark blood pool suggesting CA (Fig. 3A-F). Thus, ^99mtechnetium-pyrophosphate (^99mTC-PYP) scintigraphy was performed. ^99mTC-PYP did not suggest ATTR cardiac amyloidosis, although it revealed an accumulation in the basal IVS and high posterior wall of the LV with a grade 2 myocardial uptake (visual assessment, grades 2 and 3 classified as positive) and a heart/contralateral lung (H/CL) ratio of 1.39 (quantitative assessment; H/CL ratio ＞1.5 is considered positive) (Fig. 4).

Figure 3.

Cardiac magnetic resonance imaging revealed delayed gadolinium enhancement mainly in the basal anteroseptal and lateral walls of the LV (arrows) and atrial wall (arrowhead) (A-F; A to E, from basal to apical transverse sections), and T1 elevation of native T1 mapping in the basal IVS and basal posterior wall of the LV (G and H), and a dark blood pool suggesting CA (A-F).

Figure 4.

(A) ^99mTechnetium-pyrophosphate scintigraphy revealing a heart/contralateral lung (H/CL) ratio of 1.39 (A, planner anterior view) and an accumulation in the basal interventricular septum and high posterior wall of the left ventricle with a grade 2 myocardial uptake (arrows). (B) Transaxial view of single-photon emission computed tomography (SPECT image) (left-ventricle level), (C) transaxial view of SPECT/CT fusion image (left ventricle level) before tafamidis, (D) coronal view of SPECT/CT fusion image.

Radiofrequency catheter ablation was successfully performed after coronary angiography confirmed the presence of normal coronary arteries. The voltage map obtained during ablation revealed severe myocardial damage to the anterior wall of the left atrium (Fig. 5). One month later, a pacemaker was implanted because of severe sinus bradycardia (heart rate 20 beats/min).

Figure 5.

Left atrial voltage mapping created during sinus rhythm using the mapping catheter (Advisor^TM HD Grid Mapping Catheter; Abbott Medical Japan, Tokyo, Japan). Low-voltage areas <0.5 mV (arrows) were observed in the anterior wall, the inferior wall, and the septum of the left atrium. Left: anteroposterior (AP) orientation; Right: posteroanterior (PA) orientation.

In our patient, wild-type ATTR amyloidosis was diagnosed by a skin biopsy and immunostaining (Fig. 6), and ATTR gene testing showed no variants. Subsequently, tafamidis (80 mg/day) was initiated in addition to amiodarone, instead of bepridil and sacubitril/valsartan (50 mg twice daily), and the patient's condition stabilized.

Figure 6.

A skin biopsy revealing transthyretin (TTR) type amyloid deposition. A: Congo red staining, B: apple-green birefringence of the Congo red-stained deposits under polarized light, C: TTR immunostaining.

Discussion

We encountered a patient with ATTRwt-CA who had amyloid deposition mainly in the basal hypertrophic region of the left ventricle, as seen on several modalities, including TTE, CMRI, and ^99mTC-PYP scintigraphy. Furthermore, TTE revealed mildly reduced GLS in the basal anteroseptal and lateral walls of the LV, and LGE on CMRI indicated amyloid deposition mainly in that area.

Martinez-Naharro et al. (5) reported asymmetrical septal left ventricular hypertrophy (LVH) in 79% of patients with ATTR (70% sigmoid septum and 30% reverse septal contour) studied using CMRI. However, they did not mention the differences in LGE distribution or amyloid deposition in patients with ATTR-CA and did not examine amyloid deposition using bone scintigraphy.

Sperry et al. (6) reported an increased ^99mTC-PYP uptake in the basal and mid regions relative to the apical LV segments, as well as an apical-sparing LS pattern on echocardiography. They did not evaluate the LVH pattern or amyloid deposition using TTE or CMRI.

Ternacle et al. (7) reported that LV LGE was most common in the basal section and was correlated with LS abnormalities. They also noted increased amyloid deposition in the basal and mid segments of explanted hearts with diffuse LVH in three patients who underwent heart transplantation without ATTRwt-CA (two with AL amyloidosis and one with variant-type ATTR-CA) (7).

Sawada et al. (8) reported that amyloid protein deposition increased from the apex to the base in an autopsy case of ATTR-CA. The patient had severe heart failure (New York Heart Association classification III), and transesophageal echocardiography revealed LVH, an impaired LV systolic function (ejection fraction, 38%), and apical sparing of the GLS. These findings suggest that ATTR-CA was at the end stage in that patient.

In our patient, TTE showed a normal LV systolic function without apical sparing of the GLS, a low Kumamoto score (3,9), and National Amyloidosis Center Stage I (10). These findings suggest that our patient had early-phase ATTR-CA. Given these findings, TTR amyloid deposition may have been initiated in the basal interventricular septum, which is related to asymmetrical basal septal hypertrophy and reduced GLS in the basal region of the LV. AF and a pseudo-infarct pattern were the most common ECG findings in patients with ATTRwt-CA (11,12). In our patient, voltage mapping and CMRI revealed atrial myocardial damage due to amyloidosis. Furthermore, Syed et al. (13) reported that ECG findings including a pseudo-infarction pattern were associated with the presence of LGE in patients without echocardiographic evidence of CA. Thus, the combination of the basal hypertrophy of the LV and these ECG findings may be a characteristic of the early phase of ATTRwt-CA.

In conclusion, the early phase of ATTRwt-CA must be considered in elderly patients with basal hypertrophy and ECG findings that suggest CA, such as AF and/or pseudoinfarct pattern (poor R-wave progression).

The authors state that they have no Conflict of Interest (COI).