This study was conducted following the principles of the Declaration of Helsinki and its later amendments. In this single-center retrospective observational study, between January 2018 and February 2021, medical and family history was obtained, along with current drug therapy and assessment of heart failure symptoms using the New York Heart Association (NYHA) classification.

NYHA classification, echocardiographic data, serum brain natriuretic peptide (BNP) level, and LV or LV-intra-aortic blood flow were evaluated before and after the intervention in eight patients (five patients with HOCM and three patients with AS) using 4D flow MRI. Post-procedural data, except for MRI, were obtained after 3 months of treatment and MRI was obtained within 6 months.

We performed two-dimensional, M-mode, and Doppler TTE studies before and after ASA or SAVR using PHILIPS IE 33 (Philips Healthcare, Best, The Netherlands) or GE Vivid E 9 ultrasound systems (GE Healthcare, Boston, MA, USA). TTE was performed preoperatively within a week before surgery and postoperatively approximately 30 days after surgery. We measured the LV dimensions in both diastole and systole, the left atrium (LA) dimensions, and the thickness of the intraventricular septum (IVS) and LV posterior wall (LVPW) using M-mode. We also measured the LV ejection fraction (LVEF) using a modified Simpson's method. Peak velocity in the aortic valve or the LVOT and pressure gradient (PG) between the aorta and LV were calculated using LVOT Doppler waveforms, LVOT diameter, heart rate, and the continuity equation as per standard techniques. We also measured LV diastolic function [the E/A (peak early transmitral filling velocity/peak late transmitral filling velocity) and the E/e' (peak early transmitral filling velocity/peak early diastolic mitral annulus velocity) of the septal side or lateral side on tissue Doppler imaging].

We performed ASA and assessed serial MRI in five patients with HOCM. Indication for HOCM was determined according to the following criteria: (1) symptoms were life-limiting after optimization of medication, (2) resting or provoked gradient >50 mmHg that was confirmed by at least one method during simultaneous pressure recordings, and (3) appropriate target branch(es) leading to the septal myocardium were responsible for intra-LV obstruction. ASA was performed as previously described (4, 10).

AS was diagnosed by TTE and all the patients had clinical symptoms such as shortness of breath and/or chest pain. We performed SAVR with a bioprosthetic valve (INSPIRIS RESILIA 19 mm, Edwards Lifesciences, Irvine, CA, USA) and assessed serial MRI in three symptomatic patients with severe AS.

All patients underwent cardiac MRI before and after ASA or SAVR, along with 4D flow MRI, on a 1.5T MRI system (MR SIGNA HDxt, GE Healthcare, Waukesha, WI, USA), with a maximum gradient strength of 33 mT/m and a maximum slew rate of 120 T/m/s. The postoperative MRI was performed within 6 months, and the average time interval for all cases was 5.6 months after the procedure. The standard-of-care cardiac MRI included electrocardiogram-gated steady-state free procession cine cardiac MRI and late gadolinium enhancement (LGE) if renal function was preserved (11). A commercially available eight-channel phased array body coil was applied. For the clinical purposes of assessment of chamber size and extent of scarring, two-dimensional (2D) fast imaging employing steady-state acquisition (FIESTA) based on a steady-state free precession sequence for cine images was conducted and an inversion recovery prepared fast gradient echo sequence for LGE images was acquired in the short, vertical long-axis, and horizontal long-axis orientations with a slice thickness gap of 9 mm/0 mm.

The LV end-diastolic and LV end-systolic volume indexes (LVEDVI and LVESVI), LV stroke volume index (LVSVI) and LVEF, and LV mass index (LVMI) were quantified using short-axis images from 2D FIESTA. The field of view was adjusted for each subject to fully encompass the heart.

Time-resolved two-dimensional phase-contrast MRI of the three-chamber plane with three-directional velocity encoding was implemented during breath-holding with prospective electrocardiogram gating. The imaging parameters for 4D flow MRI were as follows: voxel size: 6.000 mm³ × 1.5625 mm³ × 1.5625 mm³, repetition time (TR): 2.955–9.932 ms, echo time (TE): 1.232–4.516 ms, flip angle (FA): 20°–60°, number of excitations (NEX): 0.75–1.9, and view per cardiac phase 12–20. Post-processing and quantitative analysis of 4D flow MRI were performed using commercially available post-processing software (iT Flow version 1.8.7; Cardio Flow Design Inc., Japan). We described the region of interest (ROI) as the area surrounded by the LV endocardium, sinotubular junction, and mitral annulus within the three-chamber plane. The ROI was traced manually in each single phase of the cine MRI, allowing the software to automatically calculate the viscous energy loss (mW/m) within the region in each phase based on a previously established formula (8, 12). Intra-cardiac energy loss (EL) can be calculated as follows: Energyloss=∫μ∑ıj(∂μj∂χı+∂μı∂χj)2dvwhere µ represents blood viscosity, i and j are arbitrary directions on the Cartesian axes, and dv is the volume increment of the segmented lumen. Energy loss inside the LV and energy loss from the LV to the ascending thoracic aorta during one cardiac cycle were calculated from the extracted lumen of the LV and from the LV to the ascending aorta, respectively. Artifacts caused by the bioprosthetic valve were removed to calculate the actual energy loss because they disturb energy loss. This energy loss was integrated by one cardiac cycle, and TKE loss was calculated backward from this energy loss.

Continuous variables are presented as means ± standard deviations. Categorical variables are presented as numbers (percentages). All statistical analyses were performed using IBM SPSS Statistics software (version 21 for Windows, SPSS Inc., Chicago, IL, USA). Both continuous and categorical variables were compared between pre-ASA/SAVR and post-ASA/SAVR using paired tests (Wilcoxon signed rank and McNemar tests). Statistical significance was defined as a p-value of <0.05.

4D flow MRI parameters were compared between patients with HOCM (n = 5) or AS (n = 3) before and after ASA or SAVR from between January 2018 and February 2021.

The baseline characteristics of the patients enrolled in our study are listed in Table 1. The average ages of the patients with HOCM and AS were 76.6 ± 6.1 and 75.7 ± 8.1 years, respectively. Comorbidities such as hypertension, dyslipidemia, diabetes mellitus, and smoking history were not statistically significantly different between the groups.

The LV-aortic PG was significantly improved from 79.4 ± 3.9 to 23.0 ± 2.0 mmHg (p < 0.001) and the NYHA functional class was also significantly improved from 2.7 ± 0.6 to 1.3 ± 0.6 by SAVR in the patients with severe AS (p < 0.001) (Table 2). In contrast, TKE loss in LV was not significantly improved by AVR in the AS group (TKE: from 6.7 ± 2.5 to 4.5 ± 3.3 mW, p = 0.22) (Figure 1A).

The intra-LV PG was improved from 79.0 ± 54.2 to 8.7 ± 4.0 mmHg (p < 0.05) and SAM in all the patients with HOCM was resolved by ASA (Table 2). TKE loss was significantly improved from 7.0 ± 2.0 to 5.0 ± 0.1 mW (p < 0.05) (Figure 1B).

A 72-year-old man with anginal symptoms was diagnosed with severe AS by TTE, and the decision was made to perform SAVR. SAVR with a bioprosthetic valve (INSPIRIS RESILIA 19 mm, Edwards Lifesciences, Irvine, CA, USA) was performed; cardiac MRI was performed 3 months after SAVR to compare with preoperative results. LV streamline images of 4D Flow MRI in the long-axis image showed that, unlike HOCM, there were relatively large vortex flows in the LV. Moreover, its position, size, and number in the LV did not change after SAVR (Figure 2A-a). The value of TKE loss did not change (Figure 2A-b). However, its pattern changed and the peak of TKE loss was shifted forward (Figure 2A-c).

A 69-year-old woman had been diagnosed with HOCM and LVOTO by TTE and catheterization. She had no history of sudden cardiac death in her family, and her genetic background of HCM was unclear; however, it was a familiar form of HOCM with asymmetrical septal hypertrophy. She had heart failure of NYHA functional classification II and an intra-LV PG of 62.5 mm Hg. Despite administration of a β-blocker (bisoprolol, 5 mg) and a class Ia drug (cibenzoline, 150 mg), her symptoms were not well controlled. Her chest discomfort and dyspnea on exertion gradually worsened with NYHA functional class II with moderate limitation (class IIm). Thus, she had drug-resistant HOCM and ASA was performed. ASA was performed by injecting 1.5 ml of ethanol into the second septal branch. The PG in the LV improved from 62.5 to 19.8 mmHg, and SAM disappeared postoperatively (Figure 2B-a). CK (CKMB) was 661 (81) U/L. Cardiac MRI was performed 3 months after ASA to compare with preoperative results. LV streamline images of 4D flow MRI in the long-axis image showed vortex flows toward the posterior mitral leaflet (PML) and posterior LV wall before ASA, and these vortex flows disappeared after ASA. Besides the vortex flows in the LV, the small vortex flows in the left atrium found before ASA improved after ASA (Figure 2B-b). TKE loss was also improved both in the pattern and value (Figure 2B-c). The graph of energy loss over time shows that the peak after ASA improved markedly, and its integral value, TKE, also improved from 8.83 to 5.09 mW (Figure 2B-d).

The peak velocity of blood flow was faster and steeper in AS than in HOCM. A larger number and various forms of vortices were more frequently found in HOCM than in AS, especially in the LV under the mitral valve in HOCM. Intra-LV flows showed differences between valvular and muscular stenosis. In HOCM, a large number and various forms of vortex flows were formed. The release of LVOTO by ASA improved vortex flows both in the LV and LA, and the TKE loss also improved accordingly. The reduction of the LV pressure load resulted in a change in the intra-LV blood flow, especially in HOCM.

Our study has several limitations. First, it is a single-center, retrospective study. The study includes the small number of patients enrolled due to the limited capacity for patient selection at our hospital. Second, although the post-procedure evaluations were performed after a certain period, it is undeniable that the different levels of invasiveness of the procedures (open heart surgery for AS and catheter intervention for HOCM) may have influenced the results. Third, especially in SAVR for AS, we used the same type and size of bioprosthetic valve, but the bioprosthetic valve might have an impact on the evaluation of blood flow on MRI. Finally, the reconstructed voxel resolution of the 4D flow MRI was anisotropic voxels, which may have affected the accuracy of the results. Finally, tracing the region of interest in each phase of the cardiac cycle was done manually and was time-consuming to analyze.