Right ventricular myocardial biopsy with a guiding catheter for conduction system pacing during pacemaker implantation revealed transthyretin cardiac amyloidosis

Published: Jun 19, 2024

Introduction

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease that causes heart failure and arrhythmias, such as sinus node dysfunction, atrial fibrillation, and atrioventricular (AV) block. Disease suspicion usually arises during transthoracic echocardiography, which reveals significant left ventricular hypertrophy (LVH), followed by radionuclide bone scintigraphy with technetium-labeled bisphosphonates.

Effective drug therapies for ATTR-CM have emerged recently; however, their efficacy is limited to early-stage patients.¹ Therefore, early diagnosis is important but often challenging, especially when bone scintigraphy shows grade 0 (negative) or grade I results, as these cases require myocardial biopsy for a definitive diagnosis. Biopsy of subcutaneous fat as an alternative is less invasive but has a low sensitivity (≈15%).² In contrast, myocardial biopsy has a nearly definitive diagnostic power at the cost of a greater risk of severe complications.³ Hence, it is necessary to develop a safe and effective method for myocardial biopsy.

To address this unmet need, we report a case of ATTR-CM confirmed by a novel right ventricular biopsy technique during pacemaker implantation (PMI) using a guiding catheter (GC) for conduction system pacing (CSP).

Case report

An 85-year-old man presented to our department for a preoperative cardiac assessment before a prostate biopsy. Transthoracic echocardiography revealed severe LVH with preserved left ventricular ejection fraction (Figure 1A and 1B). Left ventricular global longitudinal strain showed an apical sparing pattern (Figure 1C). Electrocardiography exhibited complete right bundle branch block and left axis deviation with no further abnormalities, and ^99mTc-hydroxymethylene diphosphonate scintigraphy depicted the absence of cardiac accumulation (grade 0; Figure 1D), leading to a negative diagnosis of ATTR-CM. No further examinations, including biopsy, were performed, as apparent symptoms of heart failure were not observed.

Screening imaging studies. A, B: Left ventricular hypertrophy (interventricular septum / posterior wall = 17 / 16 mm) with a normal left ventricular ejection fractionexternal link, opens in a new tab (= 57%) on transthoracic echocardiogramexternal link, opens in a new tab. C: Apical sparing pattern of the left ventricular global longitudinal strain, a typical finding in cardiac amyloidosisexternal link, opens in a new tab. D: ^99mTc-hydroxymethylene diphosphonate scintigraphy shows no tracerexternal link, opens in a new tab accumulation to the heart (grade 0). E: Complete atrioventricular block with complete right bundle branch blockexternal link, opens in a new tab and left axis deviation on 12-lead electrocardiogram.

One year later, the patient was referred to our cardiology department owing to shortness of breath with complete atrioventricular block (CAVB) (Figure 1E) and required PMI. Although the previous bone scintigraphy was negative, the occurrence of CAVB prompted the reconsideration of further evaluation for ATTR-CM, including biopsy.

To minimize invasiveness, we performed biopsies of the right ventricular myocardium using a GC for CSP and subcutaneous fat of the pacemaker pocket during PMI. First, a pocket was created in the left subclavicular chest wall, and a 9 × 5 × 4 mm sample of subcutaneous fat was obtained from inside the pocket using a scalpel. Second, a guide wire was inserted into the left subclavian vein. Third, a preshaped GC (Selectra 3D 40 mm curve; Biotronik, Berlin, Germany), which is usually used for implanting a pacemaker lead for CSP, was threaded into the left subclavian vein over the guide wire and advanced to the right ventricle. Fourth, after removing the guidewire, a bioptome (5F Disposable Biopsy Forceps; Technowood, Tokyo, Japan) was inserted into the GC, which was used for myocardial biopsy. Finally, the bioptome was removed from the GC. The time required for fat biopsy was less than 1 minute and that required for myocardial biopsy was less than 2 minutes. After the biopsies, left bundle branch pacing was initially attempted but failed to penetrate the thick septum; therefore, right ventricular septum (RVS) pacing was finally chosen. The patient was discharged on postoperative day 9 without any complications.

ATTR-CM was confirmed in the myocardial sample following direct fast scarlet staining and apple-green birefringence examination under cross-polarized light microscopy and immunohistochemical staining (Figure 2A–2C). Amyloid deposits were also observed in fat samples using direct fast scarlet staining and apple-green birefringence examination (Figure 2D and 2E). Genetic sequencing of the TTR revealed no mutations, resulting in a definitive diagnosis of wild-type ATTR-CM. Following this confirmation, tafamidis was prescribed, and the patient experienced no further episodes of heart failure.

Authors

Kei Morishita MD, Katsuhito Fujiu MD, PhD, Kenichiro Yamagata MD, PhD, Eisuke Amiya MD, PhD, Norihiko Takeda MD, PhD