Changes in left atrial deformation in hypertrophic cardiomyopathy: Evaluation by vector velocity imaging.

OBJECTIVES: Hypertrophic cardiomyopathy (HCM) represents a generalized myopathic process affecting both ventricular and atrial myocardium. We assessed the global and regional left atrial (LA) function and its relation to left ventricular (LV) mechanics and clinical status in patients with HCM using Vector Velocity Imaging (VVI). METHODS: VVI of the LA and LV was acquired from apical four- and two-chamber views of 108 HCM patients (age 40 ± 19years, 56.5% men) and 33 healthy subjects, all had normal LV systolic function. The LA subendocardium was traced to obtain atrial volumes, ejection fraction, velocities, and strain (ϵ)/strain rate (SR) measurements. RESULTS: Left atrial reservoir (ϵsys,SRsys) and conduit (early diastolic SRe) function were significantly reduced in HCM compared to controls (P  - 1.8s(- 1) was 81% sensitive and 30% specific, SRa> - 1.5s(- 1) was 73% sensitive and 40% specific. By multivariate analysis global LVϵsys and LV septal thickness are independent predictors for LAϵsys, while end systolic diameter is the only independent predictor for SRsys, P < .001. CONCLUSION: Left atrial reservoir and conduit function as measured by VVI were significantly impaired while contractile function was preserved among HCM patients. Left atrial deformation was greatly influenced by LV mechanics and correlated to severity of phenotype

Left ventricular remodeling and function in ischemic heart disease and aortic valve disease

Background: Cardiac remodeling is a broad term that refers to structural and functional alterations of the heart in response to chronic changes in loading conditions or left ventricular (LV) contractile performance. Different loading conditions will affect the heart in different ways, some leading to impaired heart function, symptoms of heart failure, or even death. However, the process of remodeling may not be permanent. If the heart is relieved of the underlying cause of the remodeling, the heart function and structure may normalize in a process referred to as reverse remodeling. The complex interplay of factors that determine the process of reverse remodeling is not fully elucidated. Cardiac remodeling can be evaluated by many different diagnostic modalities, but the most widely used diagnostic tool is two-dimensional echocardiography (2DE). In recent years, three-dimensional echocardiography (3DE) has emerged with possible advantages in the assessment of LV volume and function. The thesis aimed to evaluate 3DE in the assessment of LV function and remodeling, and to study different aspects of remodeling in response to pressure and volume overload in patients with aortic stenosis (AS) and aortic regurgitation (AR), respectively. Methods: Studies I and II investigated patients with ischemic heart disease (n = 15 and n = 32, respectively). In Study I, the assessments of LV volume and ejection fraction (EF) were compared using 3DE, cardiac magnetic resonance (CMR), and single-photon emission computer tomography (SPECT). Study II compared the performance of 2DE, contrast-enhanced 2DE, 3DE, and contrast-enhanced 3DE in the assessment LV volumes and EF, using CMR as a reference standard. In Studies III and IV, 65 patients with severe AR and 120 patients with severe AS, respectively, were examined using 2DE and 3DE before and at one year after aortic valve replacement (AVR). In Study III, LV volumes, systolic and diastolic LV function, and left atrial strain (LAS) were analyzed to identify predictors of impaired LV reverse remodeling in AR. Study IV assessed LV functional indices, including 2D global longitudinal strain (GLS) and 3D strain, to assess predictors of incomplete reverse remodeling in AS. Results and conclusions: There were significant differences among 3DE, SPECT and CMR regarding the measurement of LV volumes. However, the estimation of EF showed good agreement. 3DE was more accurate and showed more favorable reproducibility than 2DE for the assessment of EF and LV volumes. Contrast enhancement improved accuracy and reproducibility for both 2DE and 3DE. One-third of patients with AR had signs of impaired LV diastolic function. After AVR, diastolic LV functional indices improved, LV and left atrial (LA) volumes decreased, and indices of LA function increased. LA conduit strain had an incremental prognostic value for the prediction of impaired LV functional and structural recovery. In patients with AS, AVR was associated with a decrease in LV mass, an improvement in 2D GLS, and a decrease in LV twist. 2D GLS and left ventricular mass index were predictive of incomplete reverse remodeling during the follow-up period. 3D GLS did not add discriminatory or predictive information over 2D GLS

Echocardiographic Features in Canine Myxomatous Mitral Valve Disease: An Animal Model for Human Mitral Valve Prolapse

Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs and has many similarities to human mitral valve prolapse (MVP). Transthoracic echocardiography is a non-invasive method for making a diagnosis and predicting the progression of heart failure (HF) in dogs and humans with mitral regurgitation (MR). It enables clinicians to detect the mitral valve (MV) lesions, to evaluate MR severity, and to assess its impact on cardiac remodeling, myocardial function, left ventricular (LV) filling pressures, as well as pulmonary arterial pressure. Furthermore, advanced ultrasound technologies such as tissue Doppler imaging (TDI), strain and strain rate imaging, and two-dimensional (2D) speckle tracking echocardiography (STE) provide a better assessment of global and regional myocardial function. Although the severity of MR and HF in dogs with MMVD is being evaluated as similar to human cardiology, the veterinary cardiologists are more focused on the severity of cardiac remodeling and cardiac dysfunction caused by MR, because surgical restoration of defected mitral apparatus is rarely done in dogs. The chapter will review conventional echocardiographic features of MMVD in dogs to provide a better understanding of the similarities and discrepancies between canine MMVD and human MVP to veterinary and human cardiologists and researchers

Shear wave echocardiography

In this thesis we demonstrate that the assessment of the diastolic function of the left ventricle withclassical echocardiography remain

Assessment of myocardial mechanics in chronic rheumatic mitral regurgitation

A thesis submitted to the Faculty of Medicine, University of the Witwatersrand, for the degree of Doctor of Philosophy Johannesburg 2016Chronic rheumatic mitral regurgitation (CRMR) is a commonly encountered lesion in the developing world, yet it remains an understudied disease in comparison to degenerative MR. There are several unresolved issues in CRMR ranging from limited data on the current demographic and clinical profile of the contemporary patient with CRMR, to the evaluation of this lesion with sophisticated techniques utilising strain (Ɛ), magnetic resonance imaging (MRI) and biomarkers. Furthermore, the role of medical therapy has been mainly restricted to studies pertaining to degenerative MR. Thus, in this thesis the aim was to address some of the aforementioned deficiencies in the field of CRMR. In the process of studying the atrioventricular functional parameters in CRMR, we established age and vendor-specific (Philips QLAB 9) normative data for left atrial (LA) functional and volumetric parameters in a normal black population. Eighty four subjects with CRMR were studied at Chris Hani Baragwanath Hospital (CHBAH) and compared with a prior landmark study by Marcus et al conducted at this institution. Mean age was 44.0±15.3 years, compared to 19 years in the study by Marcus et al. Acute rheumatic fever (ARF) was rare compared to the previous study. Hypertension and human immunodeficiency virus (HIV) were present in 52% and 26% respectively. Echocardiography showed leaflet thickening and calcification, restricted motion and sub-valvular disease, as opposed to pliable leaflets with predominant prolapse and chordal rupture in the study by Marcus et al. One hundred and twenty normal black subjects from 18 and 70 years of age were studied. Maximum LA volume indexed (LAVi) was 19.7±5.9 mL/m2. LA pump function increased with age (r=0.2, p=0.02), and the conduit function decreased with age (r=-0.3, p< 0.001). LA Ɛ in the reservoir phase was 39.0±8.3%. LA Ɛ in the reservoir phase declined with age (p<0.001). Two studies were conducted using speckle tracking in 77 patients with CRMR. The first study found that 86% had decreased LA peak reservoir Ɛ and 58% had depressed left ventricular (LV) peak systolic Ɛ. In the second study, right ventricle (RV) peak systolic Ɛ was lower in the MR group compared to controls (-16.8±4.5% vs -19.2±3.4%, p=0.003). LV peak systolic Ɛ was an independent predictor of RV peak systolic Ɛ (r=0.46, p<0.004). CRMR is a disease characterised by eccentric jets due to distorted leaflet architecture. Thus, the echocardiographic proximal isovelocity surface area (PISA) method, to assess MR severity, is suboptimal. In CRMR there may be involvement of the LV by the rheumatic process especially in the postero basal region. To study these issues, 22 patients without comorbidities underwent MRI. On comparison of MR severity assessment by echocardiography (using an integrated approach) and MRI, there was concordance between the two techniques in all but seven patients. Six patients were reclassified as severe MR after MRI and one patient was re-categorised as moderate MR. Only four patients had fibrosis on late gadolinium enhancement. No particular regional involvement was noted. We also studied markers of collagen degradation and synthesis in CRMR and their relation with MRI parameters. Matrix metalloproteinase-1 was increased compared to controls (log MMP-1 3.5±0.68 vs 2.7±0.9, p=0.02), implying increased collagen degradation rather than synthesis in CRMR. This supports the paucity of fibrosis found on MRI. Effects of combination medical therapy in heart failure (HF) secondary to severe CRMR in 31 patients was studied. On optimal therapy no HF-related admissions or deaths were noted. There was improvement in LA peak systolic strain. LV and RV functional indices remained unchanged on maximal therapy. In conclusion, the contemporary CRMR patients are older, have comorbidities and less ARF. Upper limits of maximum LAVi are lower in the black population compared to Caucasians, and age needs to be considered when interpreting abnormalities of LA function. LA dysfunction was noted with or without involvement of the LV, therefore perhaps in CRMR, LA dysfunction precedes LV dysfunction. RV peak systolic Ɛ was useful for assessment of subclinical RV dysfunction in CRMR, therefore quantitative measurement of RV systolic function should not rely solely on conventional indices. Cardiac MRI was a useful adjunctive tool for MR severity assessment in 32% of CRMR patients when echocardiography alone was insufficient. CRMR is characterised by predominant collagen degradation and is associated with low prevalence of fibrosis. Finally, there may be a role for combination anti-remodelling therapy in HF secondary to MR. Finally, we have provided normal reference ranges for LA volume and strain parameters that would serve as platform for future studies in this population. Our findings pertaining to imaging, biomarkers and role of combination anti-remodelling therapy in CRMR may aid in the clinical assessment and management of patients with CRMR, and serve as a base for further research in these fields.MT201

EVALUATION OF LEFT VENTRICULAR AND ATRIAL-APPENDAGE FUNCTION IN NORMAL AND ISCHEMIC MOUSE MODELS BY CARDIAC IMAGING TECHNIQUES: A PHARMACOLOGICAL VALIDATION

Despite progress in diagnosis and treatment lead to a significant reduction of the rate of death attributable to cardiovascular disease (CVD), many efforts must to be done to modify the pathological process and enhance protection. Thus the development of new technologies for diagnosis and novel therapeutic agents is fundamental for clinicians and researcher. In the last decade, murine model had become a useful tool to study CVDs mechanism and to test new pharmacological treatments. Noninvasive imaging technique, specific for laboratory animals, provide the opportunity to image longitudinally the same animal, investigating the follow-up of pathologies and assessing the effect of pharmacological treatments. Aims of this work are to set up an animal model of myocardial infarction (MI) and cardiac imaging (cardiac magnetic resonance imaging and echocardiography) of left ventricle (LV), left atrium (LA) and appendage (LAA) in healthy mice, and then evaluate the global and regional functional-structural changes and remodeling occurring on LV, LA and LAA after MI, with or without pharmacological treatment. The in vivo imaging data were supported by morphological, histological and gene expression analysis. Results from this study described the regional area changes occurring on LV after MI with a progressive loss of contractility also in remote non-infarcted tissue; the presence of only three pulmonary veins entering LA and the presence of the large LAA which, working together with LA, plays an important role in LV filling. After MI not only LV but also LA and LAA remodel in order to maintain, with their enlargement, LV stroke volume. The pharmacological treatment with valsartan, a selective inhibitor of AT1 receptor of Ang II, influenced LV remodeling by reducing LV enlargement, infarct size, ECM gene expression (in particular collagen VIII, fibulin-2 involved in fibrosis and hypertrophy), preserving LV SV without affecting LAA and LA increase in dimension

Left Atrial Velocity Vector Imaging Can Assess Early Diastolic Dysfunction in Left Ventricular Hypertrophy and Hypertrophic Cardiomyopathy

Background: The function of left atrium (LA) is difficult to assess because of its ventricle-dependent, dynamic movement. The aim of this study was to assess LA function using velocity vector imaging (VVI) and compare LA function in patients with hypertrophic cardiomyopathy (HCMP) and left ventricular hypertrophy (LVH) with normal controls. Methods: Fourteen patients with HCMP (72% male, mean age of 52.6 ± 9.8), 15 hypertensive patients with LVH (88% male, mean age of 54.0 ± 15.3), and 10 age-matched controls (83% male, mean age of 50.0 ± 4.6) were prospectively studied. Echocardiographic images of the LA were analyzed with VVI, and strain rate (SR) was compared among the 3 groups. Results: The e' velocity (7.7 ± 1.1; 5.1 ± 0.8; 4.5 ± 1.3 cm/sec, p = 0.013), E/e' (6.8 ± 1.6; 12.4 ± 3.3; 14.7 ± 4.2, p = 0.035), and late diastolic SR at mid LA (-1.65 ± 0.51; -0.97 ± 0.55; -0.82 ± 0.32, p = 0.002) were significantly different among the groups (normal; LVH; HCMP, respectively). The e' velocity, E/e', and late diastolic SR at mid LA were significantly different between normal and LVH (p = 0.001; 0.022; 0.018), whereas LA size was similar between normal and LVH (p = 0.592). The mean late diastolic peak SR of mid LA was significantly correlated with indices of diastolic function (E/e', e', and LA size). Conclusions: The SR is a useful tool for detailed evaluation of LA function, especially early dysfunction of LA in groups with normal LA size.ope

Age- and gender-specific reference values for cardiac chamber geometry and function using three-dimensional echocardiography

Background. Three-dimensional echocardiography (3DE) enables a comprehensive, accurate and reproducible quantification of cardiac chamber size and function without any geometric assumption about their shape. Superior accuracy and reproducibility of 3DE over stabdard two-dimensional (2DE) approach for cardiac chamber volume measurements in comparison to cardiac magnetic resonance (CMR) has been well documented in a number of studies. Both the European Association of Cardiovascular Imaging and the American Society of Echocardiography recommend 3DE, rather than 2DE, for routine clinical assessment of cardiac chamber volumes. However, both Societes also acknowledge that the application of 3DE into routine clinical practice has been hindered by the limited availability of reference values, and particularly the lack of gender- and anthropometric-based analysis. Therefore, identification of reference values for cardiac chamber size, geometry and function has become a prerequisite for the routine clinical application of quantitative 3DE. Research Project Single-centre, prospective, observational cohort study aimed to: (i). comprehensively analyze the four cardiac chamber geometry and function using state-of-the-art 3DE equipment in a large cohort of healthy volunteers; (ii). assess the effects of age, body size and gender on these parameters; and (iii). compare the values measured using 3DE with those obtained by conventional echocardiography in the same subjects and with other cohorts of healthy subjects from published 3DE studies. Methods. 263 healthy volunteers (43±14 years, range 18-75; 58% women) whose data sets have been acquired from October 2011 to July 2013 using a commercially available 3D echo scanner (Vivid E9, GE Vingmed, Horten, NO) equipped with 4V matrix array probe. Data sets were analyzed with different commercially available (EchoPac BT 12, GEVingmed Horten, NO; 4D RV function, TomTec Imaging system, Unterschleissheim, D ) and prototype (EchoPac BT 13, GEVingmed Horten, NO; 4D LA Tomtec Imaging systems, Unterschleissheim, D) analysis softwares. The study was approved by the University of Padua Ethics Committee (protocol # 2380 P approved on 06/10/2011) and signed informed consent has been obtained in all volunteers before the screening for eligibility in the study. Results Study #1: Analysis of left ventricular (LV) size, geometry and function. In 226 consecutive healthy volunteers (125 women, aged 18-76 years), we performed a comprehensive 3DE analysis of LV parameters and compared them with values obtained by conventional echocardiography. Upper reference values (mean+2 standard deviatons) for 3D LV end-diastolic (EDV) and end-systolic (ESV) volumes were 85 ml/m2 and 34 ml/m2 in men, and 72 ml/m2 and 28 ml/m2 in women, respectively. Indexing LV volumes by body surface area did not eliminate gender differences. Lower reference values (mean-2 standard deviations) for ejection fraction (EF) were 54% in men and 57% in women, while for stroke volume (SV) were 25 ml/m2 and 24 ml/m2, respectively. Upper reference values for LV mass were 97 g/m2 in men and 90 g/m2 in women, while for end-diastolic sphericity index were 0.49 and 0.48, respectively. Significant age-dependency of LV parameters was identified and reported across age groups. 3DE LV volumes were larger, EF was similar, SV and mass were significantly smaller in comparison with the corresponding values obtained by conventional echocardiography. Study #2: Analysis of right ventricular (RV) size and function. RV volumes, SV and EF were measured by 3DE in 540 healthy adult volunteers, prospectively enrolled, evenly distributed across age and gender. The relation of age, gender and body size parameters with RV volumes and EF were investigated using bivariate and multiple linear regressions. Analysis was feasible in 507 (94%) subjects (260 women, age 45±16 years, range 18-90). Age, gender, height and weight significantly influenced RV volumes and EF. Gender effect was significant (p<0.01), with RV volumes larger and EF smaller in men than in women. Older age was associated with smaller volumes (EDV, -5 ml/decade; ESV, -3 ml/decade; SV, -2 ml/decade), and higher EF (+1%/decade). Inclusion of body size parameters in the statistical models resulted in improved overall explained variance for volumes (EDV, R2=0.43; ESV, R2=0.35; SV, R2=0.30), while EF was unaffected. Ratiometric and allometric indexing for age, gender and body size resulted in no significant residual correlation between RV geometry measures and height or weight. Study #3: Analysis left atrial size and function. 244 healthy volunteers (43±14 years, range 18-75; 58% women) underwent 3DE and 2DE to measure maximal (Vmax), minimal (Vmin) and preA (VpreA) LA volumes to calculate total, passive and active LA emptying volumes (TotEV, PassEV, ActEV) and fractions (TotEmptFr, PassEmptFr, ActEemptFr). Feasibility of 3DE and 2DE LA volumes was 91% and 96% (p=0.59 ). 3DE LA volumes were larger than 2DE ones (Vmax: 48±11 ml vs. 43±11 ml; Vmin: 18±5 vs. 14±6, respectively, p<0.001). LA TotEmptFr (61±6% vs. 68±9%) and ActEmptFr (30±7% vs. 47±10%) were lower by 3DE than 2DE (p<0.001), whereas PassEmptFr (44±10% vs. 41±11%) was higher by 3DE than 2DE (p= 0.002). 3DE LA volumes indexed by body surface area were similar in both genders and increased with ageing (p=0.002). Study #4: Analysis of right atrial (RA) size and function. 200 healthy volunteers (43±15 years; 44% men) underwent 2DE and 3DE to measure maximal (Vmax), minimal (Vmin) and preA (VpreA) volumes to derive total (TotEV), passive (PassEV) and true (TrueEV) emptying volumes and emptying fractions (TotEmptFr, PassEmptFr, TrueEmptFr). 3DE volumes (Vmax, 52±15 ml vs 41±14 ml, p<0.0001), EVs (TotSV, 33±10 ml vs. 24±9 ml, p<0.0001) and EmptFrs (TotEmptFr, 63±9% vs. 58±9%, p<0.0001) were larger than 2DE ones. Indexed 3D RA volumes were significantly larger in men than in women. Aging was associated with a significant decrease in passive RA function (PassEV, r= -0.26; PassEmptFr, r= -0.38; all p<0.0001) and an increase in active RA function (TrueEV, r= 0.25; p<0.0001; and TrueEmptFr, r= 0.15; p= 0.035) in order to maintain TotEV (r= -0.14, p= 0.05). Conclusions The present research project provides a comprehensive quantitative analysis of the four cardiac chamber geometry and function using 3DE in a relatively large cohort of Caucasian healthy volunteers with a wide age range. The main results can be summarized as follows: (i). Cardiac chamber quantification with 3DE is feasible and reproducible; (ii) Reference values for cardiac chamber size and function by 3DE were found to be significantly different from those obtained with conventional echocardiography, highlighting the importance of applying method-specific reference values for a reliable identification of remodeling and/or dysfunction of cardiac chambers; (iii). Cardiac chamber parameters measured by 3DE showed excellent reproducibility, and were more robust than 2DE indices at repeated measurements; (iii). Most parameters describing cardiac chamber size should be defined according to age and gender, since indexing them only for BSA does not account for all the physiologic variations in geometry and function. Availability of reference values and age- and gender-specific cut-off values should facilitate the implementation of 3DE to identify cardiac chamber remodelling and dysfunction in both clinical routine and research