Case Report: Treatment of Hypertrophic Cardiomyopathy With Stereotactic Body Radiotherapy.

Patients with hypertrophic cardiomyopathy (HCM), which is characterized by left ventricular hypertrophy, is usually treated with medications such as calcium channel blockers or beta-blockers and invasive treatments such as transcatheter alcohol septal ablation, percutaneous radiofrequency ablation, or heart transplantation. However, non-invasive methods have not been employed for the management of patients with HCM. A 71-year-old male who presented with occasional chest pain for approximately 2 months and had been diagnosed with HCM since he was 39 years old due to occasional fainting was treated with a novel method for HCM using stereotactic body radiotherapy (SBRT). The administration of 25 Gy of radiation as one fraction led to an improvement in his quality of life. No toxicity occurred during or immediately after the treatment. Our observations suggest that SBRT may be a reasonable treatment approach for patients with HCM who are not suitable for surgery.

Introduction

Hypertrophic cardiomyopathy (HCM) is the most common type of genetic cardiomyopathy (1) often characterized by left ventricular hypertrophy, with a reported prevalence of 0.2% in the general population. Medications such as calcium channel blockers or beta-blockers are commonly used to control symptoms. Invasive treatments include transcatheter alcohol septal ablation, percutaneous radiofrequency ablation, and heart transplantation (2). However, some patients have no proper surgery indications so that they could only alleviate their symptoms by drugs. To the best of our knowledge, non-invasive methods have not been used in HCM treatment. Notably, SBRT can deliver a precise and high dose of radiation to targets, while ensuring decreased exposure to adjacent normal tissue. Moreover, SBRT can lead to better outcomes, fewer treatment times, and fewer side effects than conventional radiation therapy. In recent years, SBRT has been successful in the treatment of cardiac tumors and ventricular arrhythmias. In this study, we present a case of an elderly patient treated with SBRT and show the potential of treating HCM non-invasively. Figure 1 summarizes the timeline of the patient’s medical history.

FIGURE 1

Timeline of the patient’s medical history.

Case Description

A 71-year-old male presented with occasional chest pain for approximately 2 months, prompting admission to our hospital. The patient had been diagnosed with HCM when he was 39 years old due to occasional fainting. On interim since the initial diagnosis, he had six episodes of fainting. The patient’s medical history was unremarkable, with the exception of well-controlled hypertension and stable angina. Routine biochemical examination and symptomatic treatment were performed. Laboratory results showed high N-terminal prohormone brain natriuretic peptide levels (Nt-proBNP, 2430 pg/mL). Cardiac magnetic resonance imaging (MRI) and echocardiography further confirmed the diagnosis of HCM. Specifically, the left ventricular ejection fraction (LVEF) was 62%, left ventricular end-diastolic volume (LVEDV) was 120.4 ml/s, cardiac output (CO) was 5.5 L/min, and maximum ventricular septum thickness was 24 mm. Coronary arteriography and fractional flow reserve findings showed that the patient had no clinical indications for coronary intervention and no cardiac septal arteries appropriate for transcatheter surgery. However, ventriculography with pressure measurement indicated that the maximum pressure difference between the apex of the heart and the left ventricular outflow tract was over 100 mmHg.

After careful consideration by a multidisciplinary group, SBRT was planned. There were several consensuses: (1) The patient needs to be treated because his cardiac symptoms have worsened within 2 months; (2) The patient only accepted minimally invasive procedures, but he had contraindications for coronary intervention, thus considering the use of a novel therapy; and (3) SBRT had been used in the treatment of other cardiac diseases and might be a novel alternative treatment for HCM instead of coronary intervention or radiofrequency ablation. However, all procedures must be planned and performed under the full discussion of the multidisciplinary group. Thereafter, the patient and his family members were informed of the high risks involved and consented to our protocol.

Four-dimensional computed tomography (4D-CT) was performed during SBRT simulation to record respiratory and cardiac motions. We used an immobilization system with a vacuum cushion (CIVCO Vac-Lok™, Coralville, IA, United States) and a standard SBRT system (Klarity, Guangzhou, China). The target area (TA) was contoured on the contrast-enhanced 4D-CT series by two experienced radiologists. The planning gross target volume (PGTV) was calculated by adding a total expansion magnitude of 5 mm and 1 mm in the superior-inferior and left-right directions of the TA, respectively. The final PGTV for our SBRT was 8.35 cm3, and the organs at risk were contoured according to international guidelines. A volumetric modulated arc therapy technique was used to create a one-time treatment plan, with a prescription dose of 25 Gy delivered as 1 fraction covering at least 95% of the PGTV. Treatment was delivered using a linear accelerator (TRILOGY® SN5736 accelerator, Varian Medical Systems Inc., CA, United States) with 6-MV flattening filter-free photon beams. The dose distribution is shown in Figure 2 and Table 1.

FIGURE 2

Dose distribution is shown with representative computed tomography (CT) simulation scans in the axial (A), coronal (B), and sagittal (C) planes.

TABLE 1

Dose statistics of the target area and OARs.

Region of interest	Volume (cm3)	Parameter	Value
PGTV	8.35	R100%*	0.99
		R50%#	4.62
		D2cm+	43.40%
Bilateral Lung	3064.9	V5	<1%
		Dmax	5.94 Gy
		Dmean	0.56 Gy
Spinal Cord PRV	71.8	Dmax	2.07 Gy
		Dmean	0.28 Gy
Esophagus	30.5	Dmax	3.01 Gy
		Dmean	0.41 Gy
Trachea	32	Dmax	0.09 Gy
		Dmean	0.04 Gy
Heart	958.2	Dmax	28.67 Gy
		Dmean	26.65 Gy

*R100% represents the ratio of the 100% isodose volume to the volume of the PGTV.

OARs, organs at risk; PGTV, planning gross target volume.

No acute symptoms and physical signs, such as chest pain, chest tightness, shortness of breath, pericardial effusion, and radiation dermatitis, were observed during or immediately after the treatment. However, a slight increase in the Nt-proBNP levels from 1571 pg/mL preoperatively to 2522 pg/mL on postoperative day 1 was noted, followed by a gradual decrease to approximately 1500 pg/mL on postoperative day 7. Similarly, LVEF, LVEDV, and CO gradually decreased on the same postoperative day, which was followed by an increase during the follow-up period. Finally, LVEF, LVEDV, and CO had increased from 62 to 69%, 120.4 to 140.3 mL/s, and 5.5 to 6.1 L/min from preoperative to postoperative month 3, respectively. In addition, septum thickness continuously decreased from 24 mm preoperatively to 19 mm on postoperative month 3. As for the MRI examinations, gradually decreasing T1 values on T1 mappings and steadily increasing percentages on bull’s eye figures showed gradual myocardial improvement from the preoperative stage to postoperative month 3 (Figure 3). This indicated that partial myocardial contraction gradually recovered, especially in the apical and middle regions of the heart.

FIGURE 3

Preoperative and postoperative magnetic resonance images of T1 mapping and bull’s eye.

Discussion

To the best of our knowledge, this is the first case of a patient with HCM and no proper surgery indication who received SBRT for symptom alleviation. SBRT treatment was employed in this case because it targeted the myocardium with a high conformal dose distribution and a significant margin from adjacent structures. It also has other benefits, such as its non-invasiveness, faster duration, and not requiring the induction of anesthesia. Furthermore, the MRI protocol can be tailored for differential diagnoses and functional assessments, such as the myocardial T1-value, using advanced sequences and quantitative analysis (3, 4). Moreover, cine MRI can precisely determine the region of injury by calculating the normalized path length of the critical points on the borders of the myocardium.

However, there were many challenges during the SBRT treatment. Primarily, although SBRT is indicated for the treatment of ventricular arrhythmias (5), there is limited and low-quality clinical evidence regarding the efficacy and safety of radiofrequency ablation for cardiac disease. In our case, the minimum effective dose, i.e., a single-fraction treatment of 25 Gy, was applied as reported by Robinson et al. (6). Additionally, cardiac SBRT can fail because of its non-uniform radiation dose (7). To reduce the influence of respiratory and cardiac motions on dosing, we performed 4D-CT. Fortunately, SBRT caused no acute symptoms in our patient, and his cardiac function improved, as determined using cardiac MRI and echocardiography. Three months after SBRT, the patient had not experienced chest pain, dizziness, faintness, palpitations, or shortness of breath. Any other abnormal signs, including pericardial effusion and radiation dermatitis, were also not found.

Although we have overcome some difficulties in SBRT treatment of HCM, there are limitations in our study. On the one hand, the time of follow-up is not enough and a longer term monitoring is necessary. On the other hand, an new application of clinical technology should be widely verified by more cases in the further investigation.

In conclusion, this case report shows how HCM can be treated non-invasively with SBRT, suggesting that SBRT may be a reasonable treatment approach for patients with HCM who are contraindicated for surgery.

Data Availability Statement

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

Ethics Statement

Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Author Contributions

TC and EX: conceptualization. JL and YT: data curation. MZ and ZD: formal analysis. LX: methodology, supervision, validation, and writing – original draft. LX, YL, and YZ: project administration. EX and YT: resources. TC: writing – review and editing. All authors contributed to the article and approved the submitted version.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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