Clinical usefulness of gated technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography with phase analysis for the management of patients with isolated ventricular noncompaction

Abstract

Gated Tc-99m sestamibi myocardial perfusion single-photon emission computed tomography (GMPS) with phase analysis provides information on myocardial perfusion, left ventricular (LV) function, and LV dyssynchrony. We present a case of isolated left ventricular noncompaction (IVNC) cardiomyopathy in which GMPS with phase analysis proved to be beneficial and reliable to monitor the long-term response to cardiac resynchronization therapy with defibrillator (CRT-D). The patient was an 84-year-old man with shortness of breath on minimal exertion (New York Heart Association class III) who had severe drug-refractory heart failure with hypotension and ventricular tachycardia. He was diagnosed with IVNC using echocardiography. At baseline, GMPS with phase analysis revealed a reduced ejection fraction (EF, 21%), large perfusion defects in the inferior and inferolateral walls, and severe LV dyssynchrony [histogram bandwidth (HBW) 120°]. Combination therapy with CRT-D and a titrated beta-blocker was initiated to induce LV reverse remodeling and reduce LV dyssynchrony. Two years after CRT-D implantation, GMPS with phase analysis showed marked improvement in LV function and LV dyssynchrony (EF 28%, HBW 36°). This case demonstrates that GMPS with phase analysis is an important and useful modality to evaluate LV function and LV dyssynchrony in IVNC patients undergoing CRT-D.

<Learning objective: We experienced a rare case of heart failure with isolated left ventricular noncompaction (IVNC) treated with cardiac resynchronization therapy with defibrillator (CRT-D). We demonstrate that gated Tc-99m myocardial perfusion SPECT (GMPS) with phase analysis can simultaneously evaluate myocardial perfusion and left ventricular dyssynchrony to assess the indication and efficacy of CRT-D. This case demonstrates that GMPS with phase analysis is useful to monitor IVNC patients before and after CRT-D.>

Introduction

Isolated left ventricular noncompaction (IVNC) is a rare congenital genetic cardiomyopathy characterized by prominent trabeculations and deep intertrabecular recesses [1]. In patients with IVNC, left ventricular (LV) dyssynchrony is detected between the non-compacted and compacted myocardial layers by echocardiography. Several case reports used echocardiography to demonstrate that cardiac resynchronization therapy (CRT) with defibrillator (CRT-D) causes substantial improvements in clinical symptoms, functional outcome, and LV performance in IVNC patients [2]. However, echocardiography could not demonstrate the advantage in selecting appropriate candidates for CRT/CRT-D beyond current guidelines [3]. On the other hand, gated Tc-99m myocardial perfusion single-photon emission computed tomography (GMPS) with phase analysis can simultaneously evaluate myocardial perfusion, LV function, and LV dyssynchrony [4]. It has been demonstrated that phase analysis with GMPS may be superior to the echocardiographic techniques currently available in assessing LV dyssynchrony because of its high repeatability and reproducibility for follow-up protocols [5]. However, in IVNC patients, the potential of GMPS with phase analysis to monitor cardiac alterations before and after CRT/CRT-D has not been fully investigated. Herein, we report the case of a patient with IVNC in whom serial GMPS with phase analysis was performed to assess LV reverse remodeling and LV dyssynchrony over two years before and after CRT-D implantation.

Case report

An 84-year-old man, who had been diagnosed with chronic heart failure (HF), was admitted to our hospital after an exacerbation of congestive HF. He presented with shortness of breath on minimal exertion [New York Heart Association (NYHA) class III] and weight loss since one month. The initial chest X-ray revealed cardiomegaly [cardiothoracic ratio (CTR) of 66.1%, Fig. 1A] with bilateral pleural effusion. The 12-lead electrocardiogram (ECG) showed LV hypertrophy and non-specific intraventricular conduction disturbance with QRS duration of 128 ms (Fig. 1B). Two-dimensional echocardiography revealed reduced ejection fraction (EF, 22%), LV dilatation, and diffuse hypokinesis mimicking dilated cardiomyopathy. Additionally, multiple trabeculations and deep intertrabecular recesses were prominent in the inferior and inferolateral walls, with a thickness ratio of noncompaction over compaction layers (N/C ratio) > 2.0 (Fig. 1C, D) [1]. Coronary angiography was normal, whereas endomyocardial biopsy obtained from the inferior LV wall showed moderate myocyte hypertrophy with mild interstitial fibrosis.

Fig. 1.

At the time of admission, chest X-ray showed cardiomegaly with a cardiothoracic ratio (CTR) of 66.1% and lung congestion (A). The 12-lead electrocardiogram revealed a wide QRS duration of 128 ms (B). Two-dimensional echocardiography on the short-axis (C) and apical four-chamber (D) views showed prominent trabeculations and deep recesses in the inferior and inferolateral walls (white arrow). The ratio of noncompacted (N) over compacted (C) layers (N/C > 2.0) was calculated at the end-systole.

During the acute and sub-acute stages, the standard therapy with a beta-blocker (carvedilol 2.5 mg/day) and angiotensin-converting enzyme inhibitors was limited by symptomatic hypotension and adverse effects. Moreover, ventricular tachycardia and paroxysmal atrial fibrillation were documented by 24-h Holter monitoring. Therefore, CRT-D was considered clinically indicated, based on the current guidelines [6]. Recently it has been reported that myocardial viability is essential for CRT/CRT-D pacing site [7] and can also be evaluated by GMPS [8]. Therefore, GMPS with phase analysis using the quantitative gated single-photon emission computed tomography (SPECT) (QGS) software was performed to assess the LV dyssynchrony and determine the appropriate pacing site. A dose of approximately 740 MBq of Tc-99m sestamibi was administered intravenously with the patient at rest. Resting SPECT image acquisition was initiated 60 min thereafter. GMPS with phase analysis showed severe perfusion defects in the inferior and inferolateral walls (Fig. 2A), increased ventricular volume with reduced systolic function [end-systolic volume (ESV) 155 ml, EF 21%], and marked LV dyssynchrony with histogram bandwidth (HBW) of 120° (Fig. 2B). On M-mode echocardiography, the septal-to-posterior wall motion delay (SPWMD) was 105 ms. He successfully received a CRT-D device with appropriate lead position according to the result of myocardial perfusion derived from GMPS.

Fig. 2.

Baseline imaging characteristics of a patient with isolated left ventricular noncompaction (IVNC) before cardiac resynchronization therapy with defibrillator (CRT-D). Gated Tc-99m myocardial perfusion single-photon emission computed tomography (GMPS) with phase analysis showed a large defect in the inferior and inferolateral walls on the polar map (A) and histogram bandwidth (HBW) of 120° on the phase distribution map (white arrow, B). Impact of CRT-D on cardiac functions in a patient diagnosed with IVNC. Two years after CRT-D implantation, chest X-ray showed marked reduction in CTR (54.5%) without congestion (C). Serial GMPS with phase analysis also revealed improvement in HBW (36°) on the phase distribution map (white arrow, D).

After CRT-D implantation, there was a steady improvement in clinical symptoms and LV function with titration of carvedilol up to 20 mg/day. Two years after CRT-D implantation, chest X-ray showed improved cardiomegaly and pleural effusion (CTR of 54.5%, Fig. 2C). Serial GMPS with phase analysis also revealed LV reverse remodeling (ESV 93 ml, EF 28%) and a reduction in LV dyssynchrony (HBW of 36°, Fig. 2D). Similarly, M-mode echocardiography revealed improvement in SPWMD (17 ms).

These findings highlight the clinical usefulness of GMPS with phase analysis to evaluate the indication and efficacy of CRT-D in IVNC patients.

Discussion

GMPS is the most widely used nuclear imaging procedure because of superb standardization and reproducibility. Electrocardiographic gating enhances the diagnostic and prognostic capability of nuclear cardiology, providing incremental information on perfusion data [9]. Functional assessments by GMPS include systolic and diastolic functions, wall motion, and thickening. A phase analysis technique has been developed to allow GMPS to assess LV dyssynchrony [5]. A histogram derived from the phase analysis was constructed to display the phase angle distribution of all sample points in the left ventricle, providing quantitative measures of LV dyssynchrony, including HBW. This technique has been shown to improve the prediction of CRT-D responders and prognosis [4].

IVNC is an idiopathic cardiomyopathy characterized by prominent trabeculations and deep intertrabecular recesses due to the interruption of compaction of the loose interwoven meshwork in the absence of coexisting congenital lesions. In adult HF, IVNC was reported to be rare, with a prevalence of 3% [1]. Recently, multimodal imaging, especially echocardiography and cardiovascular magnetic resonance imaging, have been essential for the diagnosis of IVNC [1]. The appropriate diagnosis and management of IVNC are important because of the high mortality and morbidity rates due to HF, arrhythmia, and thromboembolism. However, there is currently no specific treatment for IVNC that includes medication for HF and anticoagulation for thromboembolism. In cases of severe drug-refractory HF, CRT/CRT-D has been considered as an important adjunct therapy. Several reports showed that CRT/CRT-D considerably improves the symptomatic status and LV function of IVNC patients [2].

In our patient, ECG showed no remarkable changes in QRS duration and morphology over two years after CRT-D implantation. Gold et al. reported that the change in QRS duration induced by CRT was not an independent predictor of outcome after correction for baseline variables [10]. Therefore, another modality is required to precisely assess the efficacy of CRT/CRT-D during follow-up periods. So, we demonstrate herein that GMPS with phase analysis can monitor improvements in LV function and LV dyssynchrony in IVNC patients before and after CRT-D. These responses might be caused by CRT-D and/or the increasing beta-blocker dose. However, there is currently no evidence of beta-blocker efficacy for IVNC. In contrast, CRT/CRT-D was recently shown to improve cardiac functions in IVNC patients [2]. In addition, using GMPS, we had the crucial information to find the appropriate pacing site where myocardial viability was demonstrated.

Taken together, these findings suggest that the improvements in clinical symptoms and LV function in our patient were mainly due to CRT-D. Thus, GMPS with phase analysis provided us with information to monitor the severity of LV dyssynchrony and to find the appropriate LV pacing location for CRT/CRT-D implantation [7].

Serial GMPS with phase analysis is particularly useful given the requirements to keep radiation exposure as low as reasonably achievable. This integrated assessment of myocardial perfusion, LV function, and dyssynchrony would be useful to monitor IVNC patients before and after CRT/CRT-D implantation. Further studies are needed to clarify the clinical significance of CRT/CRT-D using GMPS with phase analysis to improve the outcome of IVNC patients.

Conflict of interest

The authors have no conflict of interest to declare.