Hypertension and heart failure are intimately related with the incidence of heart failure among hypertensive subjects between 1% and 2% per year. Structural and functional myocardial abnormalities identified in hypertensive patients contribute to the progression of myocardial dysfunction. Systolic abnormalities in hypertension begin to develop in the early stages of the disease despite normal left ventricular (LV) ejection fraction (EF) and contribute to the progressive deterioration of LV systolic performance. However, these systolic abnormalities are initially not detectable by conventional echocardiographic methods. Speckle tracking echocardiography (STE) is a sensitive quantitative technique for assessing LV function. LV twist is an important contributing factor to the systolic function of the LV in health and disease and may be a better index of systolic function than ejection fraction (EF) in hypertensive patients (HTP).
The remodelling process of the left ventricle in hypertension entails a complex interplay between myocyte hypertrophy and dysfunction, with qualitative changes in the extracellular matrix contributing to progressive dysfunction. Adverse LV remodeling in HTP is associated with an imbalance in collagen degradation and may contribute to the remodelling phenotype and systolic dysfunction in hypertension. Increased matrix metalloproteinase-1 (MMP1) levels contribute to development of LV dilatation and failure with higher levels of MMP1 in the myocardium of hypertensive patients with low EF than those with normal EF.
Hypertension can cause systolic dysfunction as a consequence of adverse remodelling and LV hypertrophy, but given the multitude of factors involved in LV decompensation mediated by mechanical, neurohormonal and cytokine routes, the exact mechanisms that contribute to the adverse remodelling and EF deterioration are not fully elucidated. LV twist may be a contributing factor to systolic dysfunction independent of other factors, thus, a focus on abnormalities in the cardiac mechanics of twist in the left ventricle may be helpful in understanding the pathogenesis behind the transition from compensated to decompensated heart failure. Furthermore, the changes in the extracellular matrix may account for the varying morphology, EF and LV twist in HTP.
The purpose of this thesis was to 1) determine LV twist in healthy adults of different age groups (n=127), 2) evaluate LV twist changes in African HTP with low (EF<50%) and preserved EF (EF ≥ 50%) (n=82) and 3) examine the relationship between LV twist and biomarkers of collagen degradation in HTP with preserved and low EF.
Parasternal short-axis images of three consecutive end-expiratory cardiac cycles at LV basal and apical levels were obtained. Apical rotation (AR) and basal rotation (BR) during ejection and instantaneous LV peak systolic twist (net twist, defined as maximal value of instantaneous AR minus BR) were measured. 127 normal subjects were divided into four age groups: 20-29 (n=34); 30-39 (n=33); 40-49 (n=29); and 50-65 (n=31) years. LV twist and markers of collagen turnover (serum concentrations of matrix metalloproteinase -1 (MMP1), tissue inhibitor of MMP1 (TIMP1) and ratio of MMP1:TIMP1) were measured in 82 hypertensive patients, 41 with EF < 50% (HTLEF) and 41 with EF ≥ 50% (HTNEF). Rigid body rotation (RBR) was defined as AR and BR occurring in the same direction. Serum biomarkers were log transformed before analysis.
LV twist increased with age in normal subjects. Multivariate linear regression analysis showed age as the main predictor of net LV twist (R2=0.82, P<0.0001) in normal subjects. Net LV twist was lower in HTLEF compared with HTNEF (3.34 + 1.10 vs. 11.70 + 0.67, p < 0.0001). Of 41 HTLEF patients, 28 (68%) had normal twist pattern while 13 (32%) exhibited RBR. The subgroup with RBR showed greater LV dysfunction (EF: 27.9±5.8% vs. 35±7.5%; p=0.005) and more spherical LV geometry (p=0.0009) compared with those who had normal pattern of twist. Log TIMP1, Log MMP1 and Log MMP1:TIMP1 ratio levels were higher in HTLEF compared with HTNEF (12.32 ± 0.25 vs. 11.81 ± 0.13, p<0.0001; 9.08 ± 0.32 vs. 8.00 ± 0.18, p<0.0001; -3.25 ± 0.30 vs. -3.81 ± 0.18, p<0.0001; respectively). There was an inverse correlation between Log MMP1:TIMP1 and net LV twist after adjusting for EF (r = -0.41, p <0.0001).
This study established normative data and patterns for myocardial deformation (strain and LV twist) in a normal black-African adult population across different age groups and can be used as a
baseline for future studies. Age was the major determinant of increased LV twist in a normal black population. LV twist may be a compensatory mechanism to preserve EF and maintain normal systolic function with advancing age and in hypertension. LV twist varies with the degree of remodeling and systolic function in hypertension. RBR represents a novel assessment of more severe LV remodeling and LV systolic dysfunction in hypertensive patients. Alterations in collagen turnover not only accompanies more adverse remodelling but also contributes to LV twist differences observed between HTLEF and HTNEF patients. The inverse relation between LV twist and loss of myocardial collagen scaffolding suggests that integrity of the extracellular matrix may play an important role in preservation of LV twist. These findings highlight the value of LV twist as a sensitive global parameter of LV systolic myocardial performance. Longitudinal studies assessing LV twist may provide significant value in clinical practice as an early marker for risk stratification in hypertensive patients who may benefit from aggressive medical therapy to prevent LV remodelling and heart failure.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/15430 |
| Date | 08 September 2014 |
| Creators | Maharaj, Nirvarthi |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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