Mitral Annular and Left Ventricular Dynamics in Atrial Functional Mitral Regurgitation: A Three-Dimensional and Speckle-Tracking Echocardiographic Study.

BACKGROUND: Patients with atrial fibrillation (AF) and left atrial (LA) enlargement may develop functional, normal leaflet motion mitral regurgitation (MR) without left ventricular (LV) remodeling. Mitral annular dynamics and LV mechanics are important for preserving normal mitral valve function. The aim of this study was to assess the annular and LV dynamics in patients with AF and functional MR. METHODS: Twenty-one patients with AF with moderate or more MR (AFMR+ group), 46 matched patients with AF with no or mild MR (AFMR- group), and 19 normal patients were retrospectively studied. Mitral annular dynamics were quantitatively assessed using three-dimensional echocardiography. Systolic LV global longitudinal strain (GLS), global circumferential strain, and LA strain were measured using two-dimensional speckle-tracking echocardiography. RESULTS: The normal annulus displayed presystolic followed by systolic contraction and increase in saddle shape (P < .01 for all). Presystolic annular dynamics were abolished in both groups of patients with AF (P > .05 vs normal). In contrast, systolic and total annular dynamics during the cardiac cycle were preserved in AFMR- patients (P > .10 vs normal) but impaired in AFMR+ patients (P < .05 vs normal and AFMR-). LV GLS (P < .0001) and LA strain (P = .02), but not LV global circumferential strain (P = .97), were impaired in AFMR+ compared with AFMR- patients despite comparable LA and LV volumes. MR severity correlated with systolic annular contraction (r = 0.64, P < .0001), saddle deepening (r = 0.53, P = .003), and LV GLS (r = 0.46, P < .0001). Multivariate analysis identified that impaired systolic contraction (odds ratio, 2.18; P = .001) and saddle deepening (odds ratio, 2.68; P = .04) were independently associated with MR. Excluding annular dynamics from the model, less negative LV GLS, but not LA strain, became associated with MR (odds ratio, 1.93; P < .0001). CONCLUSIONS: In patients with AF and absent LA contraction, the normal predominantly "atriogenic" annular dynamics become "ventriculogenic." Isolated LA enlargement is insufficient to cause important MR without coexisting abnormal LV mechanics and annular dynamics during systole. "Atrial" functional MR may not be purely an atrial disorder.

Functional Implication of Mitral Annular Disjunction in Mitral Valve Prolapse: A Quantitative Dynamic 3D Echocardiographic Study.

OBJECTIVES: This study aimed to assess the hypothesis that mitral annular disjunction (MAD) is associated with abnormal annular dynamics due to decoupling of annular-ventricular function. BACKGROUND: MAD, defined as a separation between the atrial wall-mitral valve (MV) junction and left ventricular (LV) attachment, is a structural abnormality occurring in MV prolapse (MVP). Few data exist on the 3-dimensional (3D) geometry of MAD and its functional implication. METHODS: A total of 156 subjects including 101 MVP patients (58 ± 11 years), 30 subjects with normal MV (57 ± 15 years), and 25 heart failure patients with functional mitral regurgitation (66 ± 10 years) were studied using real-time 3D transesophageal echocardiography. The spatial relation between atrial wall, MV, and LV attachment was examined for MAD. The 3D extent of MAD and annular dynamics were quantitatively assessed. The LV global longitudinal strain and basal circumferential strains were measured by speckle tracking echocardiography. RESULTS: MAD was evident in 42 MVP patients (42%), measuring 8.9 mm (6.3 to 10.7 mm), circumferentially spanning 87 ± 41°. Dynamically, normal and nondisjunctive annulus contracted and increased in a saddle shape during systole. In heart failure patients with functional mitral regurgitation, mitral annulus was dilated and relatively adynamic, probably related to poor LV function. In contrast, disjunctive annulus displayed paradoxical systolic expansion and flattening (p < 0.0001), despite preserved and comparable LV strains with normal patients. The 3D extent of MAD correlated significantly with abnormal annular dynamics and larger regurgitant orifice (p < 0.0001). In MVP patients without MAD, the LV global longitudinal strain correlated inversely with change in height (r = -0.61; p < 0.0001), whereas LV basal circumferential strain correlated with change in area (r = 0.61; p < 0.0001), but not in patients with MAD (p > 0.05). CONCLUSIONS: MAD is a common anatomic abnormality in MVP. The disjunctive annulus is decoupled functionally from the ventricle, leading to paradoxical annular dynamics with systolic expansion and flattening, and may thus require specific intervention.

Using Anatomic Intelligence to Localize Mitral Valve Prolapse on Three-Dimensional Echocardiography.

BACKGROUND: Accurate localization of mitral valve prolapse (MVP) is crucial for surgical planning. Despite improved visualization of the mitral valve by three-dimensional transesophageal echocardiography, image interpretation remains expertise dependent. Manual construction of mitral valve topographic maps improves diagnostic accuracy but is time-consuming and requires substantial manual input. A novel computer-learning technique called Anatomical Intelligence in ultrasound (AIUS) semiautomatically tracks the annulus and leaflet anatomy for parametric analysis. The aims of this study were to examine whether AIUS could improve accuracy and efficiency in localizing MVP among operators with different levels of experience. METHODS: Two experts and four intermediate-level echocardiographers (nonexperts) retrospectively performed analysis of three-dimensional transesophageal echocardiographic images to generate topographic mitral valve models in 90 patients with degenerative MVP. All echocardiographers performed both AIUS and manual segmentation in sequential weekly sessions. The results were compared with surgical findings. RESULTS: Manual segmentation by nonexperts had significantly lower sensitivity (60% vs 90%, P < .001), specificity (91% vs 97%, P = .001), and accuracy (83% vs 95%, P < .001) compared with experts. AIUS significantly improved the accuracy of nonexperts (from 83% to 89%, P = .003), particularly for lesions involving the A3 (from 81% to 94%, P = .006) and P1 (from 78% to 88%, P = .001) segments, presumably related to anatomic variants of the annulus that made tracking more challenging. AIUS required significantly less time for image analysis by both experts (1.9 ± 0.7 vs 9.9 ± 3.5 min, P < .0001) and nonexperts (5.0 ± 0.5 vs 13 ± 1.5 min, P < .0001), especially for complex lesions. CONCLUSIONS: Anatomic assessment of mitral valve pathology by three-dimensional transesophageal echocardiography is experience dependent. A semiautomated algorithm using AIUS improves accuracy and efficiency in localizing MVP by less experienced operators.

Automated quantification of mitral valve anatomy using anatomical intelligence in three-dimensional echocardiography.

BACKGROUND: Quantitative analysis of mitral valve morphology with three-dimensional (3D) transesophageal echocardiography (TEE) provides anatomic information that can assist clinical decision-making. However, routine use of mitral valve quantification has been hindered by tedious workflow and high operator-dependence. The purpose of this paper was to evaluate the feasibility, accuracy and efficiency of a novel computer-learning algorithm using anatomical intelligence in ultrasound (AIUS) to automatically detect and quantitatively assess the mitral valve anatomy. METHODS: A novice operator used AIUS to quantitatively assess mitral valve anatomy on the 3D TEE images of 55 patients (33 with mitral valve prolapse, 11 with functional mitral regurgitation, and 11 normal valves). The results were compared to that of manual mitral valve quantification by an experienced 3D echocardiographer and, in the 24 patients who underwent mitral valve repair, the surgical findings. Time consumption and reproducibility of AIUS were compared to the manual method. RESULTS: AIUS mitral valve quantification was feasible in 52 patients (95%). There were excellent agreements between AIUS and expert manual quantification for all mitral valve anatomic parameters (r=0.85-0.99, p<0.05). AIUS accurately classified surgically defined location of prolapse in 139 of 144 segments analyzed (97%). AIUS improved the intra- [intraclass-correlation coefficient (ICC)=0.91-0.99] and inter-observer (ICC=0.86-0.98) variability of novice users, surpassing the manual approach (intra-observer ICC=0.32-0.95; inter-observer ICC=0.45-0.93), yet requiring significantly less time (144±24s vs. 770±89s, p<0.0001). CONCLUSION: Anatomic intelligence in 3D TEE image can provide accurate, reproducible, and rapid quantification of the mitral valve anatomy.

Abnormal mitral-aortic intervalvular coupling in mitral valve diseases: a study using real-time three-dimensional transesophageal echocardiography.

BACKGROUND: Mitral and aortic valves are coupled via fibrous tissue. This coupling is considered to be important for cardiac function before and after mitral valve surgery. The relationship between mitral-aortic coupling and different types of mitral regurgitation (MR) is not completely understood. METHODS AND RESULTS: Real-time three-dimensional transesophageal echocardiography (RT3D-TEE) was performed in 133 subjects: 30 normal subjects, 15 patients with Carpentier type I MR (annular dilatation and congenital cleft), 40 type II (mitral valve prolapse), 20 type IIIa (rheumatic) and 28 type IIIb (ischemic mitral regurgitation). Custom software was used to track mitral (MA) and aortic annuli (AoA) in 3D space throughout cardiac cycle, allowing measurement of changes in mitral and aortic valve morphology. Normal mitral-aortic coupling is characterized by reciprocal changes in the annular areas throughout cardiac cycle, with systolic reduction of the angle between the two annular planes. In Carpentier type II patients, not only MA but also AoA areas were increased (P < 0.05 vs normal), but the reciprocal pattern of mitral-aortic coupling was preserved. In both type I IMR and IIIb patients, MA and AoA areas were both increased (P < 0.05 vs normal) and the reciprocal behavior of mitral-aortic coupling was lost. Only MA area was increased in type IIIa patients. The extent of mitral-aortic angle reduction during systole was diminished in all 4 Carpentier groups (P < 0.05 vs normal). CONCLUSIONS: Mitral valve diseases may affect normal mitral-aortic coupling and aortic valve function. Different patterns of abnormal mitral-aortic coupling are associated with different Carpentier types of MR.

The prevalence and prognosis of resistant hypertension in patients with heart failure.

BACKGROUND: Resistant hypertension is associated with adverse clinical outcome in hypertensive patients. However, the prognostic significance of resistant hypertension in patients with heart failure remains uncertain. METHODS AND RESULTS: The 1 year survival and heart failure re-hospitalization rate of 1288 consecutive patients admitted to a university hospital for either newly diagnosed heart failure or an exacerbation of prior chronic heart failure was analyzed. Resistant hypertension was defined as uncontrolled blood pressure (> 140/90 mmHg) despite being compliant with an antihypertensive regimen that includes 3 or more drugs (including a diuretic). A total of 176 (13.7%) heart failure patients had resistant hypertension. There was no difference in all cause mortality, cardiovascular mortality, and heart failure related re-hospitalization between patients with versus without resistant hypertension. Diabetes [hazard ratio = 1.62, 95% confidence interval = 1.13-2.34; P = 0.010] and serum sodium > 139 mmol/L (hazard ratio = 1.54, 95% confidence interval = 1.06-2.23; P = 0.024) were independently associated with resistant hypertension. Patients with resistant hypertension had a relatively higher survival rate (86.9% vs. 83.8%), although the difference was not significant (log-rank x2 = 1.00, P = 0.317). In patients with reduced ejection fraction, heart failure related re-hospitalization was significantly lower in patients with resistant hypertension (45.8% vs. 59.1%, P = 0.050). CONCLUSIONS: Resistant hypertension appears to be not associated with adverse clinical outcome in patients with heart failure, in fact may be a protective factor for reduced heart failure related re-hospitalization in patients with reduced ejection fraction.

Dynamic assessment of the changing geometry of the mitral apparatus in 3D could stratify abnormalities in functional mitral regurgitation and potentially guide therapy.

INTRODUCTION: In functional mitral regurgitation (FMR), effective regurgitant orifice area (EROA) displays a dynamic pattern. The impact of dynamic changes of annulus dysfunction and leaflets tenting on phasic EROA was explored with real-time three-dimensional transesophageal echocardiography (RT3D-TEE). METHODS: RT3D-TEE was performed in 52 FMR patients and 30 controls. Mitral annulus dimensions and leaflets tenting were measured throughout systole (TomTec, Germany). Phasic EROA was measured by proximal isovelocity surface area (PISA) method. RESULTS: Mitral annulus had the minimal area and an oval shape with saddle configuration during early systole in controls, which enlarged and became round and flattened towards mid and late systole (P<0.05). In contrast, annulus in FMR was significantly larger, rounder and flatter (P<0.001), which further dilated and became more flattened at late systole (P<0.05 vs control). Leaflet tenting height in FMR decreased in mid systole and remains unchanged towards late systole. The leaflet tenting volume peaked at early and late systole with a mid-systolic trough in both FMR and controls. But tenting volume of patients with FMR was significantly larger than that of controls (all P<0.001 vs control in whole systole). Further analysis demonstrated that early tenting volume (ß value=0.053, P<0.05) was a predictor of early EROA, whereas late tenting volume (ß value=0.031, P<0.05) and late annular displacement velocity were predictors of late EROA. CONCLUSIONS: The early and late peak EROAs of FMR was primarily contributed by tenting volume at early systole and late systole respectively. These findings would be of value to consider in interventions aimed at reducing the severity of FMR.

Quantification of mitral valve morphology with three-dimensional echocardiography--can measurement lead to better management?

The mitral valve (MV) has complex 3-dimensional (3D) morphology and motion. Advance in real-time 3D echocardiography (RT3DE) has revolutionized clinical imaging of the MV by providing clinicians with realistic visualization of the valve. Thus far, RT3DE of the MV structure and dynamics has adopted an approach that depends largely on subjective and qualitative interpretation of the 3D images of the valve, rather than objective and reproducible measurement. RT3DE combined with image-processing computer techniques provides precise segmentation and reliable quantification of the complex 3D morphology and rapid motion of the MV. This new approach to imaging may provide additional quantitative descriptions that are useful in diagnostic and therapeutic decision-making. Quantitative analysis of the MV using RT3DE has increased our understanding of the pathologic mechanism of degenerative, ischemic, functional, and rheumatic MV disease. Most recently, 3D morphologic quantification has entered into clinical use to provide more accurate diagnosis of MV disease and for planning surgery and transcatheter interventions. Current limitations of this quantitative approach to MV imaging include labor-intensiveness during image segmentation and lack of a clear definition of the clinical significance of many of the morphologic parameters. This review summarizes the current development and applications of quantitative analysis of the MV morphology using RT3DE.

Beyond auscultation: acoustic cardiography in clinical practice.

Cardiac auscultation by stethoscope is widely used but limited by low sensitivity and accuracy. Phonocardiogram was developed in an attempt to provide quantitative and qualitative information of heart sounds and murmurs by transforming acoustic signal into visual wavelet. Although phonocardiogram provides objective heart sound information and holds diagnostic potentials of different heart problems, its examination procedure is time-consuming and it requires specially trained technicians to operate the device. Acoustic cardiography (AUDICOR, Inovise Medical, Inc., Portland, OR, USA) is a major recent advance in the evolution of cardiac auscultation technology. The technique is more efficient and less operator-dependent. It synchronizes cardiac auscultation with ECG recording and provides a comprehensive assessment of both mechanical and electronic function of the heart. The application of acoustic cardiography is far beyond auscultation only. It generates various parameters which have been proven to correlate with gold standards in heart failure diagnosis and ischemic heart disease detection. Its application can be extended to other diseases, including LV hypertrophy, constrictive pericarditis, sleep apnea and ventricular fibrillation. The newly developed ambulatory acoustic cardiography is potentially used in heart failure follow-up in both home and hospital setting. This review comprehensively summarizes acoustic cardiographic research, including the most recent development.

Cathepsin S-mediated fibroblast trans-differentiation contributes to left ventricular remodelling after myocardial infarction.

BACKGROUND: Extracellular matrix (ECM) turnover plays an important role in left ventricular (LV) remodelling following myocardial infarction (MI). Cysteinyl cathepsins contribute to ECM catabolism in arterial diseases, suggesting their participation in post-MI remodelling. METHODS AND RESULTS: Left anterior descending artery ligation-induced MI in mice showed increased expression and activity of cathepsin S (CatS). Administration of a non-selective cathepsin inhibitor, E64d, aggravated LV dysfunction at 7 and 28 days post-MI. Mechanistic studies showed that E64d increased post-MI inflammatory cell accumulation and cytokine expression, but did not affect apoptosis or angiogenesis in infarcted myocardium. Furthermore, E64d suppressed TGF-ß1-induced Smad2 and Smad3 activation and expression of fibronectin extra domain A (ED-A), an alternatively spliced fibronectin variant, and subsequently prevented cardiac fibroblast trans-differentiation into myofibroblast, which contributed to post-MI collagen and fibronectin synthesis and deposition. Consistently, selective inhibition or genetically determined deficiency of CatS also reduced myocardial Smad2 and Smad3 activation and ED-A fibronectin expression, thus suppressing fibroblast trans-differentiation and resulting in adverse collagen turnover and impaired cardiac function-recapitulating the findings in mice treated with E64d. CONCLUSION: Along with its established activities in ECM degradation, CatS plays novel roles in TGF-ß1 signalling, myofibroblast trans-differentiation, and ECM protein synthesis, thereby regulating scar formation in the infarcted myocardium and preserving LV function after experimental MI.

The healthcare burden of hypertension in Asia.

As the leading global risk for mortality, hypertension (HT) is a common healthcare problem in the world. The total number of patients with HT is likely to grow in the next few decades as the population age and the prevalence of obesity and diabetes increase. HT, as a major modifiable risk factor for cardiovascular disease, results in more deaths than any other risk factors, including diabetes and cigarette smoking. High prevalence, inadequate awareness, suboptimal treatment and low rate of achieving guideline-recommended target blood pressure control are key factors leading to severe cardiovascular complications that impose a heavy socioeconomic burden, especially in developing countries. Asia is the world's largest and most populous continent with approximately 4.3 billion people, hosting 60% of the world's current human population, and has a high growth rate. Asia differs very widely from the West with regard to ethnic groups, cultures, environments, economics, historical ties and government systems. Therefore, the purpose of this review is to comprehensively summarise the epidemiology, treatment practice and the status of control of HT in different Asian countries in order to guide the future prevention and management in this part of the world.

Tea consumption and risk of stroke: a dose-response meta-analysis of prospective studies.

OBJECTIVE: To determine the association between tea consumption and the risk of stroke. METHODS: We searched the PubMed database from January 1966 to March 2012 and reviewed reference lists of retrieved articles to identify relevant studies. Studies were included if they reported relative risks (RRs) and corresponding 95% confidence intervals (CIs) of stroke with respect to three or more categories of tea consumption. A random-effects model was used to combine the study-specific risk estimates. RESULTS: Fourteen studies, consisting of 513,804 participants with a median follow-up of 11.5 years, were included in this meta-analysis. We observed a modest but statistically significant inverse association between tea consumption and risk of stroke. An increase of three cups/d in tea consumption was associated with a 13% decreased risk of stroke (RR 0.87; 95% CI, 0.81-0.94). The decreased risk of stroke with tea consumption was consistent among most subgroups. Based on the three studies that provided results for stroke subtypes, tea consumption was also inversely associated with the risk of ischemic stroke (RR 0.76; 95% CI, 0.69-0.84), but not cerebral hemorrhage (RR 0.96; 95% CI, 0.82-1.11) or subarachnoid hemorrhage (RR 0.81; 95% CI, 0.57-1.16). CONCLUSIONS: Tea consumption is associated with a decreased risk of stroke, particularly ischemic stroke. More well-designed, rigorously conducted studies are needed in order to make confident conclusions about the association between tea consumption and stroke subtypes.

Association between SNP rs1800875, serum chymase and immunoglobulin E levels in patients with coronary heart disease.

OBJECTIVE: The gene for mast cell chymase (CMA1) is an ideal candidate for investigating the genetic predisposition to coronary heart disease (CHD), as activated mast cells have been found to be present in a greater proportion in the shoulder region of atheroma than in normal coronary intimae. Previous studies have indicated that CMA1 promoter polymorphism rs1800875 may be involved in regulating immunoglobulin E (IgE) levels in patients with eczema, and it is associated with the progression of immunoglobulin A nephropathy. METHODS: The association between single nucleotide polymorphism (SNP) rs1800875, serum chymase, and serum IgE levels was examined in 175 CHD subjects and 95 non-CHD subjects. RESULTS: Statistical analysis indicated no significant difference in allele frequency between CHD and non-CHD. However, a significant association was found between CMA1 genotypes and total IgE levels in CHD subjects. Meanwhile, crossover analysis revealed that, in GG homozygotes, CHD risk was nearly six times higher in those with IgE (U/ml) level <2.58 (natural logarithm conversion), while no association was found with chymase level. CONCLUSIONS: Polymorphism rs1800875 of CMA1 may be associated with serum IgE level in CHD subjects, but not with chymase level in both groups. In GG homozygotes, high IgE level is a protective factor against coronary disease.