Impaired Myocardial Blood Flow and Contractile Function in Increased Left Ventricular Wall Thickness- A Quantitative Perfusion Cardiovascular Magnetic Resonance Study

Background: Increased left ventricular (LV) wall thickness, resulting from hypertrophy or remodeling, has been linked to metabolic stress and susceptibility to coronary microvascular dysfunction. Global Thickness (GT), derived LV mass (LVM) and left ventricular end-diastolic volume (LVEDV), has been proposed as a prognostic marker with high clinical potential. However, the relationship of GT and LVM to myocardial perfusion and contractile function remains largely unknown. This study aimed to: (I) evaluate the relationship between increased LV GT, LVM, and (subendocardial and epicardial) myocardial perfusion; and (II) examine the impact of increased LV GT and LVM on myocardial systolic function, using quantitative perfusion cardiac magnetic resonance (QP-CMR) and feature-tracking strain analysis, respectively.

Methods: This study retrospectively analyzed patients without presence of obstructive coronary artery disease and myocardial infarction, who underwent dual-bolus adenosine stress perfusion CMR including rest and stress first-pass perfusion for detection of myocardial ischemia. GT was calculated based on the LV mass and LVEDV. Increased GT was defined as >7.1 mm in females and >8.5 mm in males, and increased LVM was defined as > 103 gram (g) in females and >152 g in males [1, 2]. Patients with presence of late gadolinium enhancement and visual perfusion defects at both rest and stress were excluded from analysis. All CMR images were post-processed using cvi42 software.

Results: Among the sixty-six patients included, the mean GT was 7.0 ± 1.2 mm and the mean LVM was 111 ± 37 g (Table 1). Increased GT and LVM were observed in 11 (17%) and 14 (21%), respectively. Stress myocardial blood flow (MBF) was inversely correlated with GT (r= -0.299; p=0.015). Global longitudinal and circumferential strain (GLS & GCS), retrieved from feature-tracking strain analysis, showed significant positive correlations with GT (r=0.454; p< 0.001 and r= 0.427; p< 0.001) and LVM (r= 0.551; p< 0.001 and r= 0.620; p< 0.001) (Figure 1). Transmural stress MBF was significantly lower in patients with increased GT (p= 0.050) and increased LVM (p= 0.028) (Figure 2). In addition, the subendocardial-to-epicardial MBF ratio at rest was significantly increased in patients with increased GT (p= 0.004) and increased LVM (p< 0.001), whereas the stress gradient did not differ significantly. GT was a significant independent predictor of stress MBF (β= -0.518; p= 0.048) and GCS (β= -1.368; p=0.037), while LV mass was a significant independent predictor of both GLS (β= 0.063; p< 0.001) and GCS (β= 0.082; p< 0.001).

Conclusion: Increased myocardial GT and LVM are associated with impaired stress perfusion and reduced myocardial systolic strain, even in the absence of visual perfusion defects and late gadolinium enhancement. These findings suggest that GT and LVM may reflect early structural and functional myocardial remodeling and may serve as markers of subclinical myocardial perfusion impairment and contractile dysfunction.

Baseline Characteristics

Baseline characteristics	N=66
Demographic data
Age, years	61 ± 12
Male, %	33 [50%]
BMI, kg/m2	26 ± 5
Medical history and risk factors
Previous history of CAD, %	16 [24%]
History of PCI, %	11 [17%]
Obesity (BMI≥30), %	10 [15%]
Hypertension, %	27 [41%]
Dyslipidemia, %	16 [24%]
Diabetes, %	8 [12%]
History of smoking, %	26 [39%]
Anatomical measurements
LV mass, g	111 ± 37
LV mass index, g/m2	56 ± 15
LV Global Thickness, mm	7 ± 1.2
LV  Global Thickness index, mm/m2	3.6 ± 0.5
Functional measurements
LV GLS, %	-15.8 ± 3.1
LV GCS, %	-16.8 ± 3.5
Myocardial Perfusion
LV Transmural Rest MBF, ml/g/min	1.1 ± 0.3
Sub-endocardial rest MBF, ml/g/min	1.47 ± 0.5
Epicardial rest MBF, ml/g/min	1.03 ± 0.3
LV Transmural stress MBF, ml/g/min	2.7 ± 0.8
Sub-endocardial stress MBF, ml/g/min	2.87 ± 0.8
Epicardial stress MBF, ml/g/min	2.59 ± 0.7
LV Global MPR	2.7 ± 1.1

Figure 1. Correlations of Global thickness and LV mass with stress MBF, GLS, and GCS. This figure illustrates the correlations of GT (mm) and LVM (g) with (A.) stress MBF (ml/g/min), (B.) GLS (%) and (C.) GCS (%), with significant negative correlations with stress MBF and GT, and significant negative correlations of both GT and LVM with GLS and GCS. GT- Global thickness, LVM- left ventricular mass; MBF- myocardial blood flow; GLS- Global longitudinal strain; GCS- Global circumferential strain.
Figure 2. Myocardial perfusion between increased and normal Global thickness and LV mass. A. Comparison of increased and normal GT in rest MBF and stress MBF, indicating for a significant decrease in stress MBF when GT is increased. B. Comparison of increased and normal LVM in rest and stress MBF, indicating for a significant decrease in stress MBF when LVM is increased. MBF- Myocardial blood flow; GT- Global thickness; LVM- Left ventricular mass.