Sex and Race Differences in the Pathophysiology, Diagnosis, Treatment, and Outcomes of Valvular Heart Diseases.

Valvular heart diseases have long been considered to be similar in men and women and across races/ethnicities. Recently, studies have demonstrated major differences between sexes. Unfortunately, studies on valvular heart diseases, as on other cardiovascular diseases, are mostly performed in Caucasian men or in cohorts with a vast majority of Caucasian men. Therefore, our knowledge on valvular diseases in women and non-Caucasians remains limited. Nevertheless, aortic stenosis has been shown to be almost as prevalent in women as in men, and less prevalent in African Americans. Men appear to have a more calcified aortic valve lesion, and women tend to have a more fibrosed one. Primary mitral regurgitation is more frequent in women who have more rheumatic and Barlow etiologies, whereas men have more fibroelastic deficiency and posterior leaflet prolapse/flail. Left ventricular remodelling due to valvular heart diseases is sex related in terms of geometry and probably also in composition of the tissue. Outcomes seem to be worse in women after surgical interventions and better than or equivalent to men after transcatheter ones. Regarding other valvular heart diseases, very few studies are available: Aortic regurgitation is more frequent in men, isolated tricuspid regurgitation more frequent in women. Rheumatic valve diseases are more frequent in women and are mostly represented by mitral and aortic stenoses. Many other sex/gender- and race/ethnic-specific studies are still needed in epidemiology, pathophysiology, presentation, management, and outcomes. This review aims to report the available data on sex differences and race specificities in valvular heart diseases, with a primary focus on aortic stenosis and mitral regurgitation.

A nonsense variant in FBN1 caused autosomal dominant Marfan syndrome in a Chinese family: a case report.

BACKGROUND: Marfan syndrome (MFS) is a common autosomal dominant inherited disease, and the occurrence rate is around 0.1-0.2‰. The causative variant of FNB1 gene accounts for approximately 70-80% of all MFS cases. In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene. This finding extended the variant spectrum of the FBN1 gene and will provide a solution for patients to bear healthy offspring by preimplantation genetic testing or prenatal diagnosis. CASE PRESENTATION: The patient was treated due to tachycardia during excitement in a hospital. Echocardiography showed dilatation of the ascending aorta and main pulmonary artery, mitral regurgitation (mild), tricuspid regurgitation (mild), and abnormal left ventricular filling. Electrocardiograph showed sinus rhythm. In addition, flutters of shadows in front of his eyes and vitreous opacity were present in the patient. Genomic DNA was extracted from peripheral blood samples from members of the family and 100 unrelated controls. Potential variants were screened out by next-generation sequencing and confirmed by MLPA & Sanger sequencing. Real-time fluorescence quantitative PCR (RT-qPCR) was performed to detect the relative mRNA quantitation in the patient. A heterozygous nonsense variant c.3217G > T of the FBN1 gene, which resulted in p. Glu1073Term, was identified in both patients. Only wild type bases were found in the cDNA sequence of the patient. Real-time fluorogenic quantitative PCR results showed that the relative expression level of FBN1 cDNA in the patient was only about 21% compared to that of normal individuals. This variant c.3217G > T of the FBN1 gene introduces a Stop codon in the cb-EGF12 domain. We speculated that a premature translational-termination codon (PTC) was located in the mRNA and the target mRNA was disintegrated through a process known as nonsense-mediated mRNA decay (NMD), which led to a significant decrease of the fibrillin-1 protein, eventually causing clinical symptoms in the patient. CONCLUSIONS: In this study, we found a heterozygous c.3217G > T (p.Glu1073*) nonsense variant in the FBN1 gene, which eventually led to Marfan syndrome in a Chinese family.

Prevalence of rheumatic heart disease in young adults from New Caledonia.

BACKGROUND: Rheumatic heart disease (RHD) is an important public health issue, particularly in the Pacific region, but its true burden is unknown. OBJECTIVES: To evaluate the prevalence of rheumatic heart disease (RHD) in young adults from New Caledonia, based on echocardiography, and to evaluate the accuracy of dynamic criteria, focusing on mitral valve (MV) leaflet motion. METHODS: Blind analysis of echocardiography by three cardiologists; diagnosis of RHD required at least one dynamic criterion (exaggerated or restricted MV leaflet motion); subjects with morphological criteria (MV leaflet thickening), but without dynamic criteria, were considered as borderline. RESULTS: There were 834 subjects from three socioeconomic groups, aged 18-22 years: 699 had normal echocardiography; 93 (11.5%) had physiological regurgitation; nine (0.9%) had borderline RHD; and five (0.59%) had RHD. The prevalence of RHD in New Caledonia was thus estimated at 5.9 per 1000 (95% confidence interval 2.6-12.2). The RHD cases were of Pacific ethnicity. Physiological regurgitation was more frequent in Pacific subjects (13.7%) than in non-Pacific subjects (6.9%; P<0.0001). RHD was more prevalent in the lowest socioeconomic group. No disagreement occurred between the three reviewers concerning analysis of dynamic criteria; all disagreements were related to morphological criteria. CONCLUSIONS: The prevalence of echocardiographically diagnosed RHD in adults in New Caledonia is estimated at 5.9 per 1000; it occurs most frequently in Pacific subjects and those with low incomes. Dynamic criteria were more accurate and reproducible than standard morphological criteria.

Effects of ß-adrenergic blockade on left ventricular remodeling among Hispanics and African Americans with chronic heart failure.

BACKGROUND: Although ß-blockers (BBs) have been shown to improve cardiac function, there is individual and ethnic variation in BB clinical response. We examined the effects of BBs on left ventricular remodeling among African Americans (AAs), Hispanics, and Caucasians with systolic heart failure. HYPOTHESIS: There is ethnic variability in the effects of BBs on cardiac remodeling. METHODS: There were 185 AAs, 159 Hispanics, and 74 Caucasians selected with ejection fraction ≤ 40% from any etiology. Change in left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimensions (LVEDD), and degree of mitral regurgitation (MR) in response to 1 year of BBs was evaluated retrospectively. RESULTS: Overall, there was a significant improvement in LVEF, LVEDD, and degree of MR in AAs and Caucasians after 1 year of BBs (P < 0.001 vs baseline). Compared with other races, Hispanics (%) had no significant improvement in LVEDD and degree of MR, and had fewer patients with reverse remodeling: LVEF (42.77%), LVEDD (5.03%), and MR (16.35%). In multivariable analysis, Hispanic and AA race were important predictors of LVEF and LVEDD (P < 0.01) but not MR response. CONCLUSIONS: Although most patients demonstrated improvement of LVEF, there seems to be ethnic variability in the effects of BBs on cardiac remodeling. Degree of MR and LVEDD failed to show improvement among Hispanics.

Pregnancy outcomes in women with mitral valve prolapse and mitral valve regurgitation.

PURPOSE: To examine pregnancy and perinatal outcomes in patients with mitral valve disorders [mitral valve prolapse and/or mitral regurgitation; mitral valve disorders (MVD)]. METHODS: A retrospective comparative study was conducted comparing all singleton deliveries, during the years 1988-2010, of women with and without known MVD. Women lacking prenatal care were excluded. Stratified analysis using logistic regression was performed to control for confounds. RESULTS: Out of 233,194 singleton deliveries that occurred during the study period, 390 deliveries occurred in women with MVD. Using a multivariate analysis, advanced maternal age (OR = 1.06; 95 % CI 1.05-1.08; P < 0.001), recurrent abortions (OR = 1.62; 95 % CI 1.15-2.28; P = 0.005), hypertensive disorders (OR = 1.62; 95 % CI 1.17-2.26; P = 0.004) and Jewish ethnicity (OR = 2.21; 95 % CI 1.76-2.79; P < 0.001) were found to be significantly associated with MVD. Since cesarean sections (CS) were significantly higher in deliveries of patients with MVD (17.9 vs. 14 %; P = 0.025), another multivariate analysis was constructed, with CS as the outcome variable. MVD was not found to be an independent risk factor for CS (OR = 1.05; 95 % CI 0.79-1.37; P = 0.74). CONCLUSIONS: MVD associated with advanced maternal age, recurrent abortions, Jewish ethnicity and hypertensive disorders were not found to be an independent risk factor for CS.

Mitral valve repair: past, present, and future.

Mitral valve repair is the operation of choice for mitral valve regurgitation, with appropriate selection. Studies have shown that mitral repair is associated with a decrease in both long-term thromboembolic complications and mortality. Since its initial description, various selection criteria and techniques of mitral valve repair have been discussed in the literature. This review serves as a synopsis of the previous achievements, present status, and possible future directions of mitral valve repair, specifically from an Asian perspective. Vast experience has been amassed in understanding mitral valve pathophysiology, and excellent surgical treatments for mitral regurgitation have been developed. With the efforts of pioneers in the field of mitral valve repair, standard surgical treatment strategies have been proven to restore the life-expectancy of patients with degenerative mitral regurgitation to that of the age-adjusted population. Minimally invasive techniques of mitral valve repair further reduce access trauma, and could potentially benefit patients previously excluded from conventional surgery.

Prevalence of mitral annulus calcification in African Americans: comparison with non-Hispanic whites and Hispanics.

BACKGROUND: The association of ethnic ancestry with coronary artery calcifications suggests that mitral annulus calcification may also vary with ethnicity. We sought to compare prevalence and clinical correlates of mitral annulus calcification in non-Hispanic Whites, Hispanics, and African Americans. DESIGN: This was a retrospective study of 857 patients age 40-75 years that included 217 (25%) African Americans, 349 (41%) Hispanics, and 291 (34%) non-Hispanic Whites referred for echocardiography. Multiple logistic regression was used to determine the interrelationships between mitral annulus calcification, risk factors, and ethnicity. RESULTS: Mitral annulus calcification was detected in 181 (21.1%) patients including 35 (16.1%) African Americans, 80 (22.9%) Hispanics, and 66 (22.7%) non-Hispanic whites. In univariate analysis, patients with mitral annulus calcification were older and more likely to have hypertension, diabetes, dyslipidemia, smoking history, and two or more risk factors than were those without calcification. In multivariate analysis, age and smoking history were independent predictors of mitral annulus calcification; dyslipidemia and diabetes were borderline significant predictors; and after adjusting for the remaining variables in the model, ethnicity was not an independent significant predictor of mitral annulus calcification. CONCLUSION: In a retrospective study of middle-aged and elderly African Americans, non-Hispanic Whites, and Hispanics referred for echocardiography, mitral annulus calcification is common in all three major ethnic groups but not significantly associated with ethnic ancestry.

Mitral valve disease presentation and surgical outcome in African-American patients compared with white patients.

BACKGROUND: Disparities associated with race, particularly African-American race, in access to medical and surgical care for patients with cardiac disease have previously been documented. The purpose of this study was to determine the presentation, etiology, and hospital outcome differences between African-American patients and white patients with regard to surgically corrected mitral valve disease. METHODS: All 1,425 adult patients who underwent first time, isolated mitral valvuloplasty or mitral valve replacement by the same group of surgeons at New York University Medical Center and Bellevue Hospital Center between 1993 and 2003 were studied. RESULTS: African Americans (n = 123, 8.6%) were significantly younger (45.6 +/- 14.4 versus 60.5 +/- 15.3 years) and had significantly higher incidences of diabetes mellitus, renal failure, congestive heart failure, endocarditis, and rheumatic mitral disease; whereas whites (n = 1,302, 91.4%) more commonly had degenerative mitral disease. African Americans were less likely to undergo mitral valvuloplasty. There were no significant differences in the incidences of postoperative complications or hospital mortality (2.4% African American versus 5.1% white, p = 0.19). CONCLUSIONS: African Americans present for mitral valve surgery at a significantly younger age than whites and with higher incidences of many risk factors. Whether presentation at a significantly earlier age in African Americans is a result of failures in primary care or an enhanced susceptibility to the process of mitral disease and comorbidities remains to be determined. African Americans were less likely to undergo mitral valvuloplasty, which may have an effect on long-term outcome. Improved screening in this racial group will facilitate earlier referral, increasing the potential for mitral valvuloplasty.

Epidemiology of pure valvular regurgitation in the large middle-aged African American cohort of the Atherosclerosis Risk in Communities study.

BACKGROUND: There are limited data on the prevalence and the clinical and echocardiographic correlates of pure valvular regurgitation in African Americans despite the higher rates of cardiovascular disease in this group. PURPOSE: The Jackson, Mississippi, site of the Atherosclerosis Risk in Communities study provides a unique opportunity to study mitral regurgitation (MR), tricuspid regurgitation (TR), and aortic regurgitation (AR) in this population. METHODS: There were 2285 participants who were available for analysis. The prevalence rates of MR, TR, and AR by severity were calculated for participants aged 50 to 59, 60 to 69, and > or = 70 years. Multivariable regression analyses were conducted to determine clinical and echo variables associated with the presence of MR, TR, and AR. RESULTS: Mild or greater MR and TR were present in 14.7% and 17.2% of participants, respectively. Aortic regurgitation was present in 15.6% of participants. In the multivariable regression model, MR was independently associated with age, sex, lower body mass index (BMI), systolic blood pressure, left atrial size, left ventricular (LV) diastolic diameter, and low LV ejection fraction. Tricuspid regurgitation was independently associated with age, sex, lower BMI, high-density lipid, left atrial size, and lower relative wall thickness. Aortic regurgitation was independently associated with age, sex, lower BMI, systolic blood pressure, LV diastolic diameter, LV hypertrophy, and low LV ejection fraction. CONCLUSION: In this middle-aged African Americans cohort, the prevalence of mild to greater MR and TR was similar to that seen in other cohorts; however, AR was more prevalent. Several cardiovascular risk factors and echo parameters were identified as independent correlates of valvular regurgitation.

The ratio of mitral deceleration time to E-wave velocity and mitral deceleration slope outperform deceleration time alone in predicting cardiovascular outcomes: the Strong Heart Study.

BACKGROUND: The deceleration time of early mitral inflow (E) is shortened by left ventricular chamber stiffening and prolonged by impaired relaxation. For any given rate of deceleration of early mitral inflow, a higher E-wave velocity (E) is associated with a longer deceleration time. It is not known whether deceleration time normalized for E-velocity or its inverse (deceleration slope) better predicts cardiovascular (CV) events compared with deceleration time or E-velocity alone. METHODS: We compared the prognostic value of deceleration time, E-velocity, deceleration time/E-velocity, and deceleration slope in 3102 American Indian participants in the Strong Heart Study, free of clinical CV disease and documented atrial fibrillation, in predicting fatal and nonfatal CV events. RESULTS: During a mean of 8.5 +/- 2.4 years, there were 637 fatal and nonfatal CV events. After adjustment for traditional CV risk factors, deceleration time/E-velocity (adjusted hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.00-1.18; P = .04 for every 0.89 msec/[cm/s] [1 + standard deviation {SD}] increase) and deceleration slope (HR, 0.91; 95% CI, 0.82-1.00; P = .01 for every 91 msec [1 + SD] increase) predicted CV events, whereas deceleration time and E-velocity did not. When participants with restrictive-type filling (n = 74) were removed from the analysis, deceleration time/E-velocity (HR, 1.10; 95% CI, 1.01-1.20; P = .03 for every 0.89 msec/[cm/s] [1 + SD] increase) and deceleration slope (HR, 0.64; 95% CI, 0.36-0.91; P = .01 for every 91 msec [1 + SD] increase) predicted CV events even more strongly. CONCLUSION: In a large population-based sample with high prevalences of hypertension and diabetes, free of prevalent CV disease, deceleration time/E-velocity and deceleration slope predict CV events, whereas their components (deceleration time and E-velocity) do not. This suggests normalization of deceleration time for E-velocity or using its inverse (deceleration slope) more precisely captures prognostically significant prolongation of deceleration than does deceleration time alone.

Association between transforming growth factor-beta1 gene C-509T and T869C polymorphisms and rheumatic heart disease.

BACKGROUND: Scarring and collagen deposition in the valves and destruction of myocytes may result from the combined effects of a smoldering rheumatic process and a constant trauma to the mitral valve or aortic valve by the turbulent flow in rheumatic heart disease (RHD). Transforming growth factor-beta1 (TGF-beta1) may be responsible for the increased valvular fibrosis and calcification in the pathogenesis of RHD. However, the role of TGF-beta1 genetic variant in RHD has not been studied. This case-controlled study was carried out to investigate the possible relationship between the TGF-beta1 gene C-509T and T869C polymorphisms and RHD among the Chinese population in Taiwan. METHODS: A group of 115 patients with RHD documented by using echocardiography and 100 age- and sex-matched healthy control patients were studied. TGF-beta1 gene C-509T and T869C polymorphisms were identified with polymerase chain reaction-based restriction analysis. RESULTS: A significant difference was seen in the distribution of genotypes between patients with RHD and control patients for either TGF-beta1 C-509T polymorphism (P <.0001) or T869C polymorphism (P <.0001). The frequency of TGF-beta1 C-509T CC genotype was lower in the RHD group than in the control group (chi2 = 19.05, P <.0001), which suggests that this genotype may confer protective effects against RHD. A significant difference was seen in the distribution of allelic frequency between patients with RHD and control patients for TGF-beta1 T869C polymorphism (P =.04). The odds ratio (OR) for risk of RHD associated with TGF-beta1 T869C T allele was 1.49 (95% CI, 1.02-2.19). Further categorization of patients with RHD into mitral valve disease and combined valve disease subgroups revealed no statistical difference in these gene polymorphisms when compared with the 2 subgroups. CONCLUSIONS: Patients with RHD have a lower frequency of TGF-beta1 C-509T CC genotype and a higher frequency of T869C T allele, which supports a role for the TGF-beta1 gene C-509T and T869C polymorphisms in determining the risk/protection of RHD in Taiwan Chinese patients.