Tibetan patients with hepatic hydatidosis can tolerate hypoxic environment without incident increase of pulmonary hypertension: an echocardiography study.

Use of echocardiography to evaluate the characteristics of right heart and pulmonary artery of Tibetans with hepatic hydatidosis living in a high plateau area. We recruited 222 Tibetan adults diagnosed with hydatidosis from June 2016 to June 2017 in Shiqu and Seda areas of Tibet; 40 healthy control from the same area, denoted as the high plateau group. We also include 755 Healthy adults of Han nationality living in the plain from the EMINCA study as the low altitude group. Compared to high plateau group, hydatidosis individuals showed decreased RVADed, RVTDed, increased E(T)/A(T) and reduced RVFAC and TAPSE (p < 0.05). The 2 groups did not differ in the incidence rate of tricuspid regurgitation (TR) and pulmonary regurgitation (PR) (63.9% vs. 55.0%, p = 0.281 and 15.3% vs. 5.0%, p = 0.135, respectively) or incidence of pulmonary hypertension (PH) (13.9% vs. 20.5%, p = 0.167). PH risk did not differ between hydatidosis individuals and high plateau controls (OR 0.559, 95% CI 0.243-1.287). The RVADed and TAPSE were higher and E(T)/A(T) was lower for high plateau group than low altitude group (p < 0.05). The decreased right ventricular size and reduced diastolic and systolic function were found in Tibetans with hydatidosis. Hepatic hydatidosis had no significant effect on the incidence of pulmonary hypertension in Tibetans. Healthy Tibetans showed increased right ventricular size, decreased diastolic function, and increased systolic function compared to the Han counterparts.

Gender Differences in Risk Factors Associated With Pulmonary Artery Systolic Pressure, Heart Failure, and Mortality in Blacks: Jackson Heart Study.

Background Pulmonary hypertension is prevalent in black individuals, especially women. Elevated pulmonary artery systolic pressure (PASP) is associated with significant morbidity and mortality. Methods and Results We developed linear and proportional hazards models to examine potential gender-related differences in risk factors for elevated PASP (estimated by transthoracic echocardiography) and PASP-associated clinical outcomes (incident heart failure admissions and mortality) in JHS (Jackson Heart Study) participants. JHS is a prospective observational cohort study of heart disease in blacks from the Jackson, Mississippi, metropolitan area. The study cohort included participants with measurable transtricuspid gradients (n=3286) at the time of first/baseline examination, 2000-2004. The median age (interquartile range) of patients at baseline was 57.8 years (18.6 years) with 67.5% being women. The median PASP at baseline was higher in women (men: 26 mm Hg [interquartile range 8], women: 27 mm Hg [interquartile range 9]. In multivariate linear regression analyses with PASP, significant gender interactions were noted for age, chronic lung disease, pulse pressure, and obstructive spirometry. In exploratory analyses stratified by gender, body mass index, and obstructive and restrictive spirometry patterns were associated with PASP in women, and chronic lung disease was associated with PASP in men. Age and pulse pressure had stronger associations with PASP in women compared with men. There was a significant interaction between gender and PASP for heart failure admissions but not mortality. Conclusions Specific cardiopulmonary risk factors are associated with elevated PASP in women and men. Women with elevated PASP have a higher risk of incident heart failure admissions. Future research is needed to understand associated gender-specific mechanisms that can help identify targeted prevention and management strategies for patients with elevated PASP.

Association of African-American ethnicity and smoking status with total and individual damage index in systemic lupus erythematosus.

INTRODUCTION: Smoking has been associated with increased incidence, severity of cutaneous lupus, and lupus activity. We looked at the association of both smoking and ethnicity with the individual damage items from the SLICC/ACR Damage Index. METHODS: Poisson regression was used to model the total SLICC/ACR Damage Index score against ever smoking. Cox regression was used to assess the relationship between time to individual damage items and ever smoking. Furthermore, we compared SLICC/ACR Damage Index items among African-American and Caucasian ever smokers. RESULTS: The study included 2629 patients, 52.6% Caucasian and 39.3% African-American. The prevalence of ever smokers was 35.8%. There was no significant difference in total SLICC/ACR Damage Index score between ever smokers and never smokers after adjustment for ethnicity, gender, age at diagnosis, and years of education. Ever smokers had more atherosclerotic cardiovascular damage and skin damage compared to non-smokers. Caucasian SLE patients who ever smoked were more likely to have muscle atrophy and atherosclerosis compared to Caucasian non-smokers. African-American patients who ever smoked were more likely to have skin damage compared to African-American non-smokers. African-Americans who smoked were more likely to have many more damage items (cataract, renal damage, pulmonary hypertension, cardiomyopathy, deforming or erosive arthritis, avascular necrosis, skin damage, and diabetes) compared to Caucasians who smoked. CONCLUSION: Our analysis proved the major effect of smoking on cardiovascular and cutaneous damage. Surprisingly, cardiovascular damage items had higher hazard ratios in Caucasian smokers than non-smokers while skin damage items hazard ratios were higher in African-American smokers compared to non-smokers.Key Points• This study is the largest cohort study to date evaluating the effect of smoking on the cumulative SLICC/ACR Damage Index and its individual damage items.• It is the only study that examined the effect of smoking on individual items of the SLICC/ACR Damage Index in terms of Caucasians vs. African-American ethnicity.• Our analysis proved the major effect of smoking on cardiovascular and cutaneous damage. Compared to non-smokers, Caucasian smokers had higher risk of cardiovascular damage while African-American smokers had more skin damage.• African-Americans who smoked were more likely to have many more damage items (cataract, renal damage, pulmonary hypertension, cardiomyopathy, deforming or erosive arthritis, avascular necrosis, skin damage, and diabetes) compared to Caucasians who smoked.

Ethnicity in Pulmonary Arterial Hypertension: Possibilities for Novel Phenotypes in the Age of Personalized Medicine.

In the past decade and a half, the introduction of new therapeutic agents has revolutionized the management of pulmonary arterial hypertension (PAH). These new treatment options have improved the quality of life and survival in PAH. With an armamentarium of options available, the identification of unique phenotypes can help practitioners choose tailored treatment regimens. Experts in other cardiovascular diseases, such as congestive heart failure and hypertension, have recommended race-specific treatments in their fields based on data highlighting variations in response to therapies. With this perspective, we review evidence supporting the hypothesis that ethnicity or race plays an important role in the management of PAH. Preliminary research suggests that races/ethnicities have differences in the presentation and outcome of PAH and could respond to PAH-specific medications with varying efficacy. Genetic, physiological, and anatomic differences exist between races, particularly regarding the structure and function of the right ventricle. Unfortunately, clinical trials have not adequately included minorities, and registry data often omit inclusion of this demographic information. Further studies are needed to characterize the role that ethnicity plays in the prevalence, presentation, outcomes, and optimal treatment of PAH.

Health insurance and racial disparities in pulmonary hypertension outcomes.

OBJECTIVES: Pulmonary hypertension portends a poorer prognosis for blacks versus white populations, but the underlying reasons are poorly understood. We investigated associations of disease characteristics, insurance status, and race with clinical outcomes. STUDY DESIGN: Retrospective cohort study of patients presenting for initial pulmonary hypertension evaluation at 2 academic referral centers. METHODS: We recorded insurance status (Medicare, Medicaid, private, self-pay), echocardiographic, and hemodynamics data from 261 patients (79% whites, 17% blacks) with a new diagnosis of pulmonary hypertension. Subjects were followed for 2.3 years for survival. Adjustment for covariates was performed with Cox proportional hazards modeling. RESULTS: Compared with white patients, blacks were younger (50 ± 15 vs 53 ± 12 years; P = .04), with females representing a majority of patients in both groups (80% vs 66%; P = .08) and similar functional class distribution (class 2/3/4: 30%/52%/16% blacks vs 33%/48%/14% whites; P = .69). Blacks diagnosed with incident pulmonary hypertension were more frequently covered by Medicaid (12.5% vs 0.7%) and had less private insurance (50% vs 61%; P = .007) than whites. At presentation, blacks had more right ventricular dysfunction (P = .04), but similar mean pulmonary arterial pressure (46 vs 45 mm Hg, respectively; P = .66). After adjusting for age and functional class, blacks had greater mortality risk (hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.18-3.44), which did not differ by race after additional adjustment for insurance status (HR, 1.74; 95% CI, 0.84-3.32; P =.13). CONCLUSIONS: In a large cohort of patients with incident pulmonary hypertension, black patients had poorer right-side heart function and survival rates than white patients. However, adjustment for insurance status in our cohort removed differences in survival by race.

Anti-SmD1 antibodies are associated with renal disorder, seizures, and pulmonary arterial hypertension in Chinese patients with active SLE.

Detection of autoantibodies in systemic lupus erythematosus (SLE) plays an important role in timely diagnosis and earlier treatment of SLE. In this study, we used a SmD1 polypeptide-based ELISA to determine anti-SmD1 antibody in 269 SLE, including100 naïve (had not been treated with steroids or immunosuppressants at study inception) SLE patients and 169 non-naive SLE patients; 233 controls with other rheumatic diseases (RDC) (70 RA, 40 AS, 73SSc, and 50 SS), and 110 healthy controls (HC) group. The positive rate of anti-SmD1 among all SLE patients was 60.97%, higher than that in the RDC group (13.30%, P = 0.000) or the HC group (9.09%, P = 0.000). The positive rate of anti-SmD1 in non-naive SLE patients was higher than that for anti-dsDNA antibodies (44.97%, P = 0.03). Positivity for anti-SmD1 only was found in 14.00% of naive SLE patients and 16.00% of non-naive SLE patients. In naive SLE patients, the serum concentration of anti-SmD1 was lower after treatment than before treatment (P = 0.039). Active SLE patients positive for anti-SmD1 were more likely to have malar rash, rash, nonscarring alopecia, PAH and hypocomplementemia. High positivity for anti-SmD1 only in patients with SLE indicated the importance and necessity of detection of anti-SmD1 in patients with SLE.

Pulmonary Hypertension Is Associated With a Higher Risk of Heart Failure Hospitalization and Mortality in Patients With Chronic Kidney Disease: The Jackson Heart Study.

BACKGROUND: African Americans develop chronic kidney disease and pulmonary hypertension (PH) at disproportionately high rates. Little is known whether PH heightens the risk of heart failure (HF) admission or mortality among chronic kidney disease patients, including patients with non-end-stage renal disease. METHODS AND RESULTS: We analyzed African Americans participants with chronic kidney disease (estimated glomerular filtration rate <60 mL/min per 1.73 m2 or urine albumin/creatinine >30 mg/g) and available echocardiogram-derived pulmonary artery systolic pressure (PASP) from the Jackson Heart Study (N=408). We used Cox models to assess whether PH (PASP>35 mm Hg) was associated with higher rates of HF hospitalization and mortality. In a secondary, cross-sectional analysis, we examined the relationship between cystatin C (a marker of renal function) and PASP and potential mediators, including BNP (B-type natriuretic peptide) and endothelin-1. In our cohort, the mean age was 63±13 years, 70% were female, 78% had hypertension, and 22% had PH. Eighty-five percent of the participants had an estimated glomerular filtration rate >30 mL/min per 1.73 m2. During follow-up, 13% were hospitalized for HF and 27% died. After adjusting for potential confounders, including BNP, PH was found to be associated with HF hospitalization (hazard ratio, 2.37; 95% confidence interval, 1.15-4.86) and the combined outcome of HF hospitalization or mortality (hazard ratio, 1.84; confidence interval, 1.09-3.10). Log cystatin C was directly associated with PASP (adjusted ß =2.5 [95% confidence interval, 0.8-4.1] per standard deviation change in cystatin C). Mediation analysis showed that BNP and endothelin-1 explained 56% and 40%, respectively, of the indirect effects between cystatin C and PASP. CONCLUSIONS: Among African Americans with chronic kidney disease, PH, which is likely pulmonary venous hypertension, was associated with a higher risk of HF admission and mortality.

Echocardiographic Pulmonary Artery Systolic Pressure in the Coronary Artery Risk Development in Young Adults (CARDIA) Study: Associations With Race and Metabolic Dysregulation.

BACKGROUND: The determinants of pulmonary artery systolic pressure (PASP) are not fully understood. It is unknown whether racial differences in PASP exist or if other population characteristics are associated with pulmonary pressure in humans. We examined echocardiographically estimated PASP in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a middle-aged, biracial community-based cohort. METHODS AND RESULTS: At the CARDIA year-25 examination, 3469 participants underwent echocardiography, including measurement of tricuspid regurgitant jet velocity to estimate PASP. Clinical features, laboratory values, pulmonary function tests, and measurement of adipose depot volume were analyzed for association with PASP. PASP was estimated in 1311 individuals (61% female, 51% white). Older age, higher blood pressure, and higher body mass index were associated with higher PASP. Black race was associated with higher PASP after adjustment for demographics and left and right ventricular function (ß 0.94, 95% CI 0.24-1.64; P=0.009), but this association was no longer significant after further adjustment for lung volume (ß 0.42, 95% CI -0.68 to 0.96; P=0.74). Insulin resistance, inflammation (C-reactive protein and interleukin-6), and visceral adipose volume were independently associated with higher PASP after adjustment for relevant covariates. PASP rose with worsening diastolic function (ratio of early transmitral Doppler velocity to average mitral annular tissue Doppler velocity [E/e'] and left atrial volume index). CONCLUSIONS: In a large biracial cohort of middle-aged adults, we identified associations among black race, insulin resistance, and diastolic dysfunction with higher echocardiographically estimated PASP. Further studies are needed to examine racial differences in PASP and whether insulin resistance directly contributes to pulmonary vascular disease in humans.

Managing adult Fontan patients: where do we stand?

The Fontan operation is performed as a palliative procedure to improve survival in infants born with a functionally univentricular circulation. The success of the operation is demonstrated by a growing adult Fontan population that exists with this unique physiology. Late follow-up has demonstrated expected and unexpected sequelae, and has shown multisystem effects of this circulation. This review discusses the challenges of managing the late complications in terms of understanding this unique physiology and the innovative therapeutic interventions that are being investigated. The challenge remains to maintain quality of life for adult survivors, as well as extending life expectancy.

TRPM8 genetic variations associated with COPD risk in the Chinese Han population.

TRPM8 plays a key role in COPD. The development of pulmonary hypertension (PH) in COPD adversely affects survival and exercise capacity. Thus, the aim of this study was to evaluate the possible association between single nucleotide polymorphisms (SNPs) in TRPM8 and COPD or PH in COPD among the Chinese Han population. A total of 513 COPD patients and 506 controls were enrolled in the study. Six tag SNPs (tSNPs) were genotyped. The relationship between COPD or PH in COPD and the six tSNPs was evaluated using the χ2 test and genetic model analysis. In the rs9789398 polymorphism, the T/C genotype was associated with an increased risk for COPD (P=0.005). Under the assumption of models of inheritance, there was an association between the rs9789398 polymorphism and COPD. In the rs9789675 polymorphism, the G/A genotype was associated with an increased risk for COPD (P=0.021). Furthermore, by the χ2 test, we found that the minor allele "A" of rs9789675 (odds ratio [OR] =0.63, 95% confidence interval [CI], 0.42-0.97, P=0.034) and the minor allele "C" of rs9789398 (OR =1.59, 95% CI, 1.03-2.44, P=0.034) were associated with a decreased risk of PH in COPD in allele models. In genetic models, the genotypes "GA" and "AA" of rs9789675 were associated with a decreased risk of PH in COPD. The genotypes "TC" and "CC" of rs9789398 were associated with a decreased risk of PH in COPD. Moreover, "CG" of rs1004478 was significantly associated with a decreased risk of PH in COPD. There was a significant association between the five SNPs (rs2362290, rs9789675, rs9789398, rs1003540, and rs104478) in the TRPM8 gene and the risk of PH in COPD. Our findings indicated that rs9789398 in the TRPM8 gene was significantly associated with the risk of COPD in the Chinese Han population. Moreover, rs9789675, rs9789398, and rs1004478 were significantly associated with the risk of PH in COPD. This study provides a novel insight into COPD and PH in the development of COPD.

Telomere length-related gene ACYP2 polymorphism is associated with the risk of HAPE in Chinese Han population.

BACKGROUND: High altitude pulmonary edema (HAPE) is a type of pneumonedema that mostly occurs under conditions such as high altitude, rapid ascent and hypoxia, amongst others. The ACYP2 polymorphism is suggested to be associated with mean telomere length, and telomere length is significantly longer at a moderate attitude than at sea-level or at simulated high attitude. The present study aimed to determine whethher there is any association between ACYP2 polymorphism and the risk of HAPE. METHODS: A total of 265 patients and 303 healthy controls were enrolled in our case-control study. Six SNPs were selected and genotyped using the Sequenom MassARRAY method. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by unconditional logistic regression with adjustment for gender and age. RESULTS: Using chi-squared tests, we found that the minor allele G of rs11896604 is significantly associated with a decreased risk of HAPE [odds ratio (OR) = 0.87, 95% confidence interval (CI) = 0.65-1.16, p = 0.048]. We also found that the 'A/A' genotype of rs12615793 is associated with a decreased risk of HAPE based on the recessive model (OR =0.28; 95% CI = 0.09-0.88; p = 0.017). Additionally, the 'G/G' genotype of rs11896604 was found to be associated with a decreased risk of HAPE based on the codominant model (OR =0.26; 95% CI = 0.08-0.79; p = 0.025) and recessive model (OR =0.25; 95% CI = 0.08-0.77; p = 0.007). However, only rs11896604 remained significant after Bonferroni correction (p < 0.0083). CONCLUSIONS: The present study found that the ACYP2 gene polymorphism significantly decreased the risk of HAPE. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Association of Elevated Plasma Endothelin-1 Levels With Pulmonary Hypertension, Mortality, and Heart Failure in African American Individuals: The Jackson Heart Study.

IMPORTANCE: Despite pathophysiological links between endothelin-1 and pulmonary vascular remodeling, to our knowledge, the association between plasma endothelin-1 levels and pulmonary hypertension has not been studied in the general population. Also, whether endothelin-1 can predict future heart failure and mortality, outcomes that are associated with pulmonary hypertension, in a population cohort is unclear. OBJECTIVE: To determine whether elevated plasma endothelin-1 levels are associated with pulmonary hypertension, mortality, and heart failure. DESIGN, SETTING, AND PARTICIPANTS: Data from the Jackson Heart Study, a longitudinal, prospective observational cohort study of heart disease in African American individuals from Jackson, Mississippi, were analyzed. The community population sample was limited to participants with detectable tricuspid regurgitation on echocardiography. The study participants included self-identified African American individuals with plasma endothelin-1 levels and tricuspid regurgitation on echocardiogram (n = 3223) at the time of first examination (2000-2004). The analysis of the data began on April 14, 2014, and was completed on February 23, 2016. EXPOSURE: Log-transformed plasma endothelin-1 level. MAIN OUTCOMES AND MEASURES: Cross-sectional analysis: presence of pulmonary hypertension (defined as an elevated pulmonary artery systolic pressure >40 mm Hg on echocardiogram). Longitudinal outcomes were all-cause mortality (median follow-up, 7.75 years) and heart failure admissions (median follow-up, 5.32 years). RESULTS: Of the 3223 participants enrolled in the study, 1051 were men (32.6%). Mean (SD) endothelin-1 levels were 1.36 (0.64) pg/mL; 217 of 3223 cohort members (6.7%) had pulmonary hypertension. After adjusting for potential confounders, log-transformed endothelin-1 levels were associated with increased odds of pulmonary hypertension (adjusted odds ratio per log increment in endothelin-1, 1.66; 95% CI, 1.16-2.37). Log-transformed endothelin-1 levels were associated with mortality (adjusted hazard ratio per log increment in endothelin-1, 1.69; 95% CI, 1.27-2.25; median follow-up, 7.75 years) and heart failure (adjusted hazard ratio per log increment in endothelin-1, 1.57, 95% CI, 1.05-2.37; median follow-up, 5.32 years) in the study cohort. Phenotyping by pulmonary hypertension and endothelin-1 level showed mortality decreasing in order from subgroup with pulmonary hypertension and high endothelin-1 (high endothelin-1: ≥1.7 pg/mL; upper quartile); pulmonary hypertension and low endothelin-1 <1.7 pg/mL; lower 3 quartiles); no pulmonary hypertension and high endothelin-1; and no pulmonary hypertension and low endothelin-1 (log-rank χ2 = 77.16; P < .01 ). CONCLUSIONS AND RELEVANCE: Elevated plasma endothelin-1 levels, especially associated with an elevated pulmonary artery systolic pressure on echocardiogram, may identify an at-risk population that could be evaluated for targeted prevention and management strategies in future studies.

Efficacy of cardiac rehabilitation after balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

OBJECTIVE: To determine safety and efficacy of cardiac rehabilitation (CR) initiated immediately following balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) who presented with continuing exercise intolerance and symptoms on effort even after a course of BPA; 2-8 sessions/patient. METHODS: Forty-one consecutive patients with inoperable CTEPH who underwent their final BPA with improved resting mean pulmonary arterial pressure of 24.7±5.5 mm Hg and who suffered remaining exercise intolerance were prospectively studied. Participants were divided into two groups just after the final BPA (6.8±2.3 days): patients with (CR group, n=17) or without (non-CR group, n=24) participation in a 12-week CR of 1-week inhospital training followed by an 11-week outpatient programme. Cardiopulmonary exercise testing, haemodynamics, and quality of life (QOL) were assessed before and after CR. RESULTS: No significant between-group differences were found for any baseline characteristics. At week 12, peak oxygen uptake (VO2), per cent predicted peak VO2 (70.7±9.4% to 78.2±12.8%, p<0.01), peak workload, and oxygen pulse significantly improved in the CR group compared with the non-CR group, with a tendency towards improvement in mental health-related QOL. Quadriceps strength and heart failure (HF) symptoms (WHO functional class, 2.2-1.8, p=0.01) significantly improved within the CR group. During the CR, no patient experienced adverse events or deterioration of right-sided HF or haemodynamics as confirmed via catheterisation. CONCLUSIONS: The combination of BPA and subsequent CR is a new treatment strategy for inoperable CTEPH to improve exercise capacity to near-normal levels and HF symptoms, with a good safety profile.

Mitochondrial Haplogroups and Risk of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a serious and often fatal disease. It is a panvasculopathy of the pulmonary microcirculation characterized by vasoconstriction and arterial obstruction due to vascular proliferation and remodeling and ultimately right ventricular failure. Mitochondrial dysfunction is a universal finding in pulmonary vascular cells of patients with PAH, and is mechanistically linked to disease origins in animal models of pulmonary hypertension. Mitochondria have their own circular DNA (mtDNA), which can be subgrouped into polymorphic haplogroup variants, some of which have been identified as at-risk or protective from cardiovascular and/or neurodegenerative diseases. Here, we hypothesized that mitochondrial haplogroups may be associated with PAH. To test this, mitochondrial haplogroups were determined in a cohort of PAH patients and controls [N = 204 Caucasians (125 PAH and 79 controls) and N = 46 African Americans (13 PAH and 33 controls)]. Haplogroup L was associated with a lower rate of PAH as compared to macrohaplogroups N and M. When haplogroups were nested based on ancestral inheritance and controlled for age, gender and race, haplogroups M and HV, JT and UK of the N macro-haplogroup had significantly higher rates of PAH compared to the ancestral L (L0/1/2 and L3) (all p ≤ 0.05). Overall, the findings suggest that mitochondrial haplogroups influence risk of PAH and that a vulnerability to PAH may have emerged under the selective enrichment of specific haplogroups that occurred with the migration of populations out of Africa.

Exercise Training in Group 2 Pulmonary Hypertension: Which Intensity and What Modality.

Pulmonary hypertension (PH) due to left-sided heart disease (LSHD) is a common and disconcerting occurrence. For example, both heart failure (HF) with preserved and reduced ejection fraction (HFpEF and HFrEF) often lead to PH as a consequence of a chronic elevation in left atrial filling pressure. A wealth of literature demonstrates the value of exercise training (ET) in patients with LSHD, which is particularly robust in patients with HFrEF and growing in patients with HFpEF. While the effects of ET have not been specifically explored in the LSHD-PH phenotype (i.e., composite pathophysiologic characteristics of patients in this advanced disease state), the overall body of evidence supports clinical application in this subgroup. Moderate intensity aerobic ET significantly improves peak oxygen consumption, quality of life and prognosis in patients with HF. Resistance ET significantly improves muscle strength and endurance in patients with HF, which further enhance functional capacity. When warranted, inspiratory muscle training and neuromuscular electrical stimulation are becoming recognized as important components of a comprehensive rehabilitation program. This review will provide a detailed account of ET programing considerations in patients with LSHD with a particular focus on those concomitantly diagnosed with PH.

Severity of systemic sclerosis-associated pulmonary arterial hypertension in African Americans.

African Americans (AA) with systemic sclerosis (SSc) have a worse prognosis compared to Americans of European descent (EA). We conducted the current study to test the hypothesis that AA patients with SSc have more severe disease and poorer outcomes compared to EA patients when afflicted with pulmonary arterial hypertension (PAH). We studied 160 consecutive SSc patients with PAH diagnosed by right heart catheterization, comparing demographics, hemodynamics, and outcomes between AA and EA patients. The cohort included 29 AA and 131 EA patients with similar baseline characteristics except for increased prevalence of diffuse SSc in AA. AA patients had worse functional class (FC) (80% FC III-IV vs 53%; p = 0.02), higher brain natriuretic peptide (NT-pro-BNP) (5729 ± 9730 pg/mL vs 1892 ± 2417 pg/mL; p = 0.02), more depressed right ventricular function, a trend toward lower 6-minute walk distance (263 ± 111  m vs 333 ± 110  m; p = 0.07), and worse hemodynamics (cardiac index 1.95 ± 0.58 L/min/m vs 2.62 ± 0.80 L/min/m; pulmonary vascular resistance 10.3 ± 6.2 WU vs 7.6 ± 5.0 WU; p  < 0.05) compared with EA patients. Kaplan-Meier survival estimates for AA and EA patients, respectively, were 62% vs 73% at 2 years and 26% vs 44% at 5 years (p  > 0.05). In conclusion, AA patients with SSc-PAH are more likely to have diffuse SSc and to present with significantly more severe PAH compared with EA patients. AA patients also appear to have poorer survival, though larger studies are needed to investigate this association definitively.

Elevated pulmonary artery systolic pressure predicts heart failure admissions in African Americans: Jackson Heart Study.

BACKGROUND: Although elevated pulmonary artery systolic pressure (PASP) is associated with heart failure (HF), whether PASP measurement can help predict future HF admissions is not known, especially in African Americans who are at increased risk for HF. We hypothesized that elevated PASP is associated with increased risk of HF admission and improves HF prediction in African American population. METHODS AND RESULTS: We conducted a longitudinal analysis using the Jackson Heart Study cohort (n=3125; 32.2% men) with baseline echocardiography-derived PASP and follow-up for HF admissions. Hazard ratio for HF admission was estimated using Cox proportional hazard model adjusted for variables in the Atherosclerosis Risk in Community (ARIC) HF prediction model. During a median follow-up of 3.46 years, 3.42% of the cohort was admitted for HF. Subjects with HF had a higher PASP (35.6±11.4 versus 27.6±6.9 mm Hg; P<0.001). The hazard of HF admission increased with higher baseline PASP (adjusted hazard ratio per 10 mm Hg increase in PASP: 2.03; 95% confidence interval, 1.67-2.48; adjusted hazard ratio for highest [≥33 mm Hg] versus lowest quartile [<24 mm Hg] of PASP: 2.69; 95% confidence interval, 1.43-5.06) and remained significant irrespective of history of HF or preserved/reduced ejection fraction. Addition of PASP to the ARIC model resulted in a significant improvement in model discrimination (area under the curve=0.82 before versus 0.84 after; P=0.03) and improved net reclassification index (11-15%) using PASP as a continuous or dichotomous (cutoff=33 mm Hg) variable. CONCLUSIONS: Elevated PASP predicts HF admissions in African Americans and may aid in early identification of at-risk subjects for aggressive risk factor modification.

Chinese SLE Treatment and Research group (CSTAR) registry: II. Prevalence and risk factors of pulmonary arterial hypertension in Chinese patients with systemic lupus erythematosus.

OBJECTIVES: To estimate the prevalence of pulmonary arterial hypertension (PAH) and risk factors for PAH in patients registered in the Chinese SLE Treatment and Research group (CSTAR) database, the first online registry of Chinese patients with systemic lupus erythematosus (SLE). METHODS: A prospective cross-sectional study of patients with SLE was conducted using the CSTAR registry. Resting transthoracic echocardiography was used to estimate pulmonary artery pressure (PAP); PAH was defined as systolic PAP (PASP)≥40 mmHg. Patients with interstitial lung disease, valvular disease or cardiomyopathy were excluded because of disease influence on PAP. We explored potential risk factors for PAH including patient characteristics, organ involvement, laboratory findings and SLE disease activity. RESULTS: Of 1934 patients with SLE, 74 had PASP with 54.2±17.1 (40,106) mmHg and were diagnosed with probable PAH. The incidences of lupus nephritis, pleuritis, pericarditis, hypocomplementemia, anti-SSA, and anti-ribonucleoprotein (RNP) were significantly higher in patients with PAH than in those without (p<0.05). SLE disease activity was significantly higher in patients with PAH than in unaffected patients (p<0.05). Multivariate analysis indicated that pericarditis (odds ratio (OR)=4.248), pleuritis (OR=3.061) and anti-RNP (OR=2.559) were independent risk factors for PAH in patients with SLE (p<0.05). CONCLUSIONS: The possible prevalence of PAH was 3.8% in Chinese patients with SLE in the CSTAR registry. The significant association of pericarditis, pleuritis and anti-RNP positivity with PAH suggests that higher disease activity and vasculopathy may both contribute to the development of PAH in SLE, which need be treated aggressively to improve prognosis.

Pulmonary circulation and gas exchange at exercise in Sherpas at high altitude.

Tibetans have been reported to present with a unique phenotypic adaptation to high altitude characterized by higher resting ventilation and arterial oxygen saturation, no excessive polycythemia, and lower pulmonary arterial pressures (Ppa) compared with other high-altitude populations. How this affects exercise capacity is not exactly known. We measured aerobic exercise capacity during an incremental cardiopulmonary exercise test, lung diffusing capacity for carbon monoxide (DL(CO)) and nitric oxide (DL(NO)) at rest, and mean Ppa (mPpa) and cardiac output by echocardiography at rest and at exercise in 13 Sherpas and in 13 acclimatized lowlander controls at the altitude of 5,050 m in Nepal. In Sherpas vs. lowlanders, arterial oxygen saturation was 86 ± 1 vs. 83 ± 2% (mean ± SE; P = nonsignificant), mPpa at rest 19 ± 1 vs. 23 ± 1 mmHg (P < 0.05), DL(CO) corrected for hemoglobin 61 ± 4 vs. 37 ± 2 ml · min(-1) · mmHg(-1) (P < 0.001), DL(NO) 226 ± 18 vs. 153 ± 9 ml · min(-1) · mmHg(-1) (P < 0.001), maximum oxygen uptake 32 ± 3 vs. 28 ± 1 ml · kg(-1) · min(-1) (P = nonsignificant), and ventilatory equivalent for carbon dioxide at anaerobic threshold 40 ± 2 vs. 48 ± 2 (P < 0.001). Maximum oxygen uptake was correlated directly to DL(CO) and inversely to the slope of mPpa-cardiac index relationships in both Sherpas and acclimatized lowlanders. We conclude that Sherpas compared with acclimatized lowlanders have an unremarkable aerobic exercise capacity, but with less pronounced pulmonary hypertension, lower ventilatory responses, and higher lung diffusing capacity.