Right ventricular dyssynchrony during hypoxic breathing but not during exercise in healthy subjects: a speckle tracking echocardiography study.

NEW FINDINGS: What is the central question of this study? Right ventricular dyssynchrony in severe pulmonary hypertension is associated with a poor prognosis. However, it has recently been observed in patients with lung or connective tissue disease and pulmonary artery pressure at the upper limits of normal. The mechanisms of right ventricular dyssynchrony in pulmonary hypertension remain uncertain. What is the main finding and its importance? Acute hypoxic breathing, but not normoxic exercise, induces an increase in right ventricular dyssynchrony detected by speckle tracking echocardiography in healthy subjects. These results add new insights into the determinants of right ventricular dyssynchrony, suggesting a role for systemic factors added to afterload in the pathophysiology of right ventricular inhomogeneity of contraction. ABSTRACT: Pulmonary hypertension (PH) has been shown to be associated with regional inhomogeneity (or dyssynchrony) of right ventricular (RV) contraction. Right ventricular dyssynchrony is an independent predictor of decreased survival in advanced PH, but has also been reported in patients with only mildly elevated pulmonary artery pressure (PAP). The mechanisms of RV dyssynchrony in PH remain uncertain. Our aim was to evaluate RV regional function in healthy subjects during acute hypoxia and during exercise. Seventeen healthy subjects (24 ± 6 years) underwent a speckle tracking echocardiography of the RV at rest in normoxia and every 15 min during a 60 min exposure to hypoxic breathing ( F I O 2 12%). Ten of the subjects also underwent an incremental cycle ergometry in normoxia to 100 W, with the same echocardiographic measurements. Dyssynchrony was measured as the SD of the times to peak systolic strain of the four basal and mid RV segments corrected for the heart rate (RV-SD4). RV-SD4 increased during hypoxia from 12 ± 7 to 22 ± 11 ms in spite of mild increases in mean PAP (mPAP) from 15 ± 2 to 20 ± 2 mmHg and pulmonary vascular resistance (PVR) from 1.18 ± 0.15 to 1.4 ± 0.15 Wood units (WU). During exercise RV-SD4 did not significantly change (from 12 ± 6 ms to 14 ± 6 ms), while mPAP increased to 25 ± 2 mmHg and PVR was unchanged. These data show that in healthy subjects, RV contraction is inhomogeneous in hypoxia but not during exercise. Since PAP increases more during exercise, RV dyssynchrony in hypoxia may be explained by a combination of mechanical (RV afterload) and systemic (hypoxia) factors.

Echocardiography during preload stress for evaluation of right ventricular contractile reserve and exercise capacity in pulmonary hypertension.

OBJECTIVES: Pulmonary hypertension (PH) is characterized by marked and sustained elevation of pulmonary vascular resistance and pulmonary artery pressure, and subsequent right-sided heart failure. Right ventricular (RV) function and exercise capacity have been recognized as important prognostic factors for PH. Our aim was to investigate RV contractile reserve and exercise capacity during a leg-positive pressure (LPP) maneuver. METHODS: The study population comprised 43 PH patients and 17 normal controls. All patients underwent echocardiography at rest and during LPP stress. Exercise capacity was assessed by 6-minute walk distance for PH patients. RV relative wall thickness was calculated from dividing by RV free wall thickness by basal RV linear dimensions at end-diastole. RV function was calculated by averaging peak speckle-tracking longitudinal strain from the RV free wall. RV contractile reserve was assessed as the difference in RV free wall strain at rest and during LPP stress. Changes in left ventricular stroke volume (ΔSV) during LPP stress were also calculated. RESULTS: ΔSV and RV contractile reserve of PH patients were significantly lower than of controls (3.6 ± 6.0 mL vs 8.5 ± 2.3 mL, and 8.2 ± 11.9% vs 14.5 ± 6.6%; both P < 0.01). RV contractile reserve of PH patients with ΔSV <3.3 mL was significantly lower than of PH patients with ΔSV >3.3 mL (3.9 ± 13.2% vs 12.3 ± 8.9%; P = 0.02). ΔSV had also significant correlation with 6-minute walk distance (r = 0.42, P = 0.006). Multivariate regression analysis showed that RV relative wall thickness was an independent determinant parameter of ΔSV during LPP stress for PH patients (ß = 3.2, P = 0.003). CONCLUSIONS: Preload stress echocardiography in response to LPP maneuver, a noninvasive and easy-to-use procedure for routine clinical use, proved to be useful for the assessment of RV contractile reserve and exercise capacity of PH patients.

Left ventricular dispersion as a parameter for augmented left ventricular stroke volume in patients with atrial septal defect following transcatheter closure.

OBJECTIVES: The closure of atrial septal defect (ASD) results in normalized left ventricular (LV) and right ventricular (RV) geometry, and can increase LV stroke volume (LVSV), but the parameters associated with this increase after the closure of ASD remain uncertain. METHODS: Seventy ASD patients, who underwent transcatheter closure, were studied. Their mean age was 57.80 ± 16.88 years, 42 (60%) were female, and LV ejection fraction (LVEF) was 66.76% ± 7.91% (all ≥55%). Transthoracic echocardiography was performed before and 3 months after the procedure. Global longitudinal strain (GLS) was determined as the average peak speckle tracking strain of 18 segments from the 3 standard apical views, LV dispersion was defined as standard deviation of time-to-peak strain from the same views, and RV systolic function was calculated by averaging the 3-regional peak speckle tracking longitudinal strains from the RV free wall. A significant relative increase in LVSV between before and 3 months after the closure was defined as ∆LVSV ≥15%. Twenty age-, gender-, and LVEF-matched controls served as the control group. RESULTS: Global longitudinal strain (GLS) and RV free wall strain were similar for ASD patients and controls, but LV dispersion in ASD patients was significantly larger. Global longitudinal strain (GLS) remained unchanged after transcatheter closure, whereas RV free wall strain and LV dispersion decreased significantly. An important finding of the multivariate logistic regression analysis showed that ∆LV dispersion was the only independent determinant of increased LVSV after the closure (OR 1.023; 95% CI 1.001-1.046; P < .01). CONCLUSIONS: The assessment of LV dispersion may well have clinical implications for better management of ASD patients after transcatheter closure.

The Right Heart-Pulmonary Circulation Unit in Systemic Hypertension.

Systemic hypertension is a risk factor for left heart failure, mostly with preserved ejection fraction. Left heart failure is a cause of pulmonary hypertension and eventual right ventricular (RV) failure. There has been report of altered RV function in mild to moderate hypertension with preserved systolic as well as diastolic function of the left ventricle. The pathophysiology of this complication of hypertension is unclear. Preserving the RV and preventing the development of pulmonary vascular disease may be considered among the targets of optimized therapy for systemic hypertension.

Effects of a changeover from other angiotensin II receptor blockers to olmesartan on left ventricular hypertrophy in heart failure patients.

Left ventricular (LV) hypertrophy (LVH) is an independent cardiovascular risk factor for heart failure (HF) patients. The renin-angiotensin system plays a key role in LVH, and since olmesartan increases plasma angiotensin-(1-7) through an increase in angiotensin-converting enzyme-related carboxypeptidase (ACE2) expression, it was hypothesized to reduce LVH, unlike other angiotensin II receptor blockers (ARBs). The objective of this study was therefore to investigate the effects of a changeover from other ARBs to olmesartan on LVH in HF patients. Participants enrolled in this prospective trial were 64 outpatients with stable HF who had received ARBs other than olmesartan for more than 1 year (age: 59 ± 13 years). Transthoracic echocardiography and laboratory tests were performed before and 6 months after administration of olmesartan. Other drugs were not changed during follow-up. The primary end point was defined as a change in LV mass index (LVMI) from baseline up to 6 months after administration of olmesartan. No significant changes were observed in blood pressures and heart rate after administration of olmesartan. LVMI showed a significant decrease from 119 ± 38 to 110 ± 24 g/m2 (p = 0.007) 6 months after administration of olmesartan, and further decreased from 110 ± 24 to 103 ± 35 g/m2 (p = 0.0003) after 12 months. Moreover, this reduction tended to be more prominent in patients with LVH. In conclusions, LVH in HF patients was reduced by the changeover to olmesartan. This finding may well have clinical implications for better management of HF patients.

Risk Stratification of Future Left Ventricular Dysfunction for Patients with Indications for Right Ventricular Pacing due to Bradycardia.

Although right ventricular (RV) pacing is the only effective treatment for patients with symptomatic bradycardia, it creates left ventricular (LV) dyssynchrony, which can induce LV dysfunction and heart failure. The current criterion for consideration of cardiac resynchronization therapy (CRT) is LV ejection fraction (LVEF) ≤ 35%, but indication for CRT in patients required for RV pacing with LVEF > 35% remains unclear.We studied 40 patients, all LVEF ≥ 35%, who had undergone implantable cardioverter-defibrillator implantation with RV pacing < 5%. Echocardiography was performed at baseline and during RV pacing. LV dyssynchrony was defined as anteroseptal-to-posterior wall delay from the mid-LV short-axis view using two-dimensional speckle-tracking radial strain (significant: ≥ 130 ms). Patients were divided into two groups based on baseline LVEF: normal LVEF ( ≥ 50%; n = 20) and mildly reduced LVEF (35-50%; n = 20).LVEF and LV dyssynchrony in patients with mildly reduced LVEF deteriorated significantly during RV pacing compared to those in patients with normal LVEF. Moreover, changes in LV dyssynchrony during RV pacing significantly correlated with changes in LVEF (r = -0.44, P < 0.01). Multivariate logistic regression analysis showed that baseline LVEF was the only independent predictor and baseline LVEF < 48% predictive of significant LV dyssynchrony during RV pacing.The extent of RV pacing-induced LV dysfunction may be associated with baseline LV function. These adverse effects on patients with mildly reduced LVEF of 35-50% and indications for RV pacing due to bradycardia can thus be prevented by CRT.

Association of Apical Longitudinal Rotation with Right Ventricular Performance in Patients with Pulmonary Hypertension: Insights into Overestimation of Tricuspid Annular Plane Systolic Excursion.

BACKGROUND: Current guidelines recommend the routine use of tricuspid annular plane systolic excursion (TAPSE) as a simple method for estimating right ventricular (RV) function. However, when ventricular apical longitudinal rotation (apical-LR) occurs in pulmonary hypertension (PH) patients, it may result in overestimated TAPSE. METHODS: We studied 105 patients with PH defined as mean pulmonary artery pressure >25 mmHg at rest measured by right heart cardiac catheterization. TAPSE was defined as the maximum displacement during systole in the RV-focused apical four-chamber view. RV free-wall longitudinal speckle tracking strain (RV-free) was calculated by averaging 3 regional peak systolic strains. The apical-LR was measured at the peak rotation in the apical region including both left and right ventricle. The eccentricity index (EI) was defined as the ratio of the length of 2 perpendicular minor-axis diameters, one of which bisected and was perpendicular to the interventricular septum, and was obtained at end-systole (EI-sys) and end-diastole (EI-dia). Twenty age-, gender-, and left ventricular ejection fraction-matched normal controls were studied for comparison. RESULTS: The apical-LR in PH patients was significantly lower than that in normal controls (-3.4 ± 2.7° vs. -1.3 ± 1.9°, P = 0.001). Simple linear regression analysis showed that gender, TAPSE, EI-sys, and EI-dia/EI-sys were associated with apical-LR, but RV-free was not. Multiple regression analysis demonstrated that gender, EI-dia/EI-sys, and TAPSE were independent determinants of apical-LR. CONCLUSIONS: TAPSE may be overestimated in PH patients with clockwise rotation resulting from left ventricular compression. TAPSE should thus be evaluated carefully in PH patients with marked apical rotation.

Utility of Isovolumic Contraction Peak Velocity for Evaluation of Adult Patient Status after Transcatheter Closure of Atrial Septal Defect.

BACKGROUND: Transcatheter closure is a well-established treatment for patients with atrial septal defect (ASD), but long-term outcome prognostic factors for adults have not been fully identified yet. METHODS: Forty-nine consecutive patients (age 57 ± 17 years, 59% female), who underwent transcatheter closure of ASD, were the subjects of this study. Transthoracic echocardiography was performed before and midterm after the procedure (6 ± 1 months). Isovolumic contraction peak velocity (IVV) was measured at the lateral site of the tricuspid annulus using spectral tissue Doppler imaging, and ΔIVV was determined as the absolute change at midterm follow-up. Long-term unfavorable outcome events, tracked for 19 ± 9 months, were prespecified as primary end points comprising newly developed atrial fibrillation, cerebral infarction, and heart failure. RESULTS: Symptomatic improvement, defined as an improvement in New York Heart Association functional class by one grade or more at midterm after the procedure, was observed in 24 patients (49%), and the remaining 25 (51%) were classified as not symptomatically improved. ΔIVV was significantly larger for patients with symptomatic improvement than for those without (from 11.5 ± 4.3 cm/s to 14.2 ± 3.7 cm/s vs. from 11.8 ± 4.1 cm/s to 12.5 ± 2.9 cm/s; P = 0.045). An important finding of the multivariate Cox proportional-hazards analysis was that only ΔIVV was independently associated with cardiovascular events (HR: 0.701; 95% CI 0.537-0.916; P = 0.01). Kaplan-Meier analysis showed that more patients with enhanced ΔIVV presented with favorable long-term outcome than those with diminished ΔIVV (log-rank P = 0.0001). CONCLUSIONS: IVV, which is a less volume-sensitive parameter, can be useful for comprehensive evaluation of ASD patients referred for transcatheter closure.

Comprehensive Functional Assessment of Right-Sided Heart Using Speckle Tracking Strain for Patients with Pulmonary Hypertension.

BACKGROUND: Right ventricular (RV) systolic function is one of the most important determinants of outcome for pulmonary hypertension (PH) patients, but the factors influencing prognosis vary widely. Elevated right atrial (RA) pressure is reported to be one of these prognostic factors, but its functional importance has scarcely been assessed. METHODS: Eighty-two PH patients, all of whom underwent echocardiography and right heart catheterization, were recruited. RV function was assessed by two-dimensional speckle tracking longitudinal strain from RV-focused apical four-chamber view and calculated by averaging the three regional peak strains from the RV free wall (RV-free). RA function was determined as the sum of three peak strain values comprising reservoir, conduit, and contractile function (sum of RA strain). RESULTS: Sum of RA strain correlated significantly with hemodynamic parameters such as mean right atrial pressure (r = -0.35, P = 0.002) and end-diastolic RV pressure (r = -0.29, P = 0.008). Patients with sum of RA strain ≥30.2% experienced more favorable outcomes than those with sum of RA strain <30.2% (log-rank P = 0.001). Furthermore, patients with impaired RV systolic function (RV-free <20%) and RA function (sum of RA strain <30.2%) showed the worst outcome (P = 0.001). A sequential Cox model based on clinical variables (χ(2) = 5.8) was improved by addition of RV-free (χ(2) = 8.7; P < 0.05) and further improved by addition of sum of RA strain (χ(2) = 12.0; P < 0.01). CONCLUSION: Right atrial strain appears to be a valuable additive factor for predicting outcomes for PH patients, and comprehensive functional assessment of right-sided heart using speckle tracking strain may have potential clinical implications for better management of PH patients.

Clinical features of subclinical left ventricular systolic dysfunction in patients with diabetes mellitus.

BACKGROUND: Left ventricular (LV) longitudinal systolic dysfunction has been identified even in asymptomatic patients with diabetes mellitus (DM) and preserved LV ejection fraction (LVEF). However, its relevant clinical features have not been fully evaluated. METHODS: We studied 144 asymptomatic DM patients without coronary artery disease. Their mean age was 57 ± 15 years, 79 (55%) were female, and mean LVEF was 66 ± 4% (all ≥50%). Global longitudinal strain (GLS) was determined as the average peak strain of 18 segments from the three standard apical views, and was expressed as an absolute value. With the pre-defined cutoff for subclinical LV systolic dysfunction in DM patients with preserved LVEF set at GLS < 18%, this dysfunction was detected in 53 patients (37%). RESULTS: Multivariate logistic regression analysis revealed that type 2 DM, hypertriglyceridemia, overweight/obesity, nephropathy and neuropathy were independently associated with GLS < 18%, with nephropathy being the highest risk factor (OR: 5.26; 95% CI 2.111-13.12, p < 0.001). For sequential logistic regression models, a model based on clinical variables including gender, type 2 DM and DM duration (χ(2) = 24.1) was improved by addition of overweight/obesity and hypertriglyceridemia (χ(2) = 45.6, p < 0.001), and further improved by addition of nephropathy and neuropathy (χ(2) = 70.2, p < 0.001) as variables. Furthermore, albuminuria significantly correlated with GLS (r = -0.51, p < 0.001), and a multivariate regression model showed it to be the factor most closely associated with GLS (ß = -0.33, p < 0.001). CONCLUSIONS: Diabetic complications, hypertriglyceridemia and overweight/obesity were closely associated with early stage of LV systolic longitudinal myocardial dysfunction in asymptomatic DM patients with preserved LVEF. Our findings can be clinically noticeable for the management of DM patients.

Association of peripheral nerve conduction in diabetic neuropathy with subclinical left ventricular systolic dysfunction.

BACKGROUND: Subclinical left ventricular (LV) longitudinal myocardial systolic dysfunction occurs in patients with diabetes mellitus (DM) and preserved LV ejection fraction (LVEF), and is closely related to DM-related complications. However, the association of diabetic neuropathy (DN) with subclinical LV systolic longitudinal dysfunction in such patients has not been fully clarified. METHODS: The subjects of this study were 112 consecutive DM patients with preserved LVEF (all ≥50%) without coronary artery disease and overt heart failure (aged 59 ± 14 years; 60 women, 52 men). Global longitudinal strain (GLS) was determined as the average peak strain of 18 segments from the three standard apical views, and was expressed as an absolute value. DN was diagnosed by experienced diabetologists. Median, ulnar, and sural nerves were subjected to motor and sensory nerve conduction studies. F-wave latency was defined as the minimum F-wave latency after a total of 16 stimulations of the tibial nerve. RESULTS: Forty-one (37%) patients were clinically diagnosed with DN. LV functions of DM patients with and without DN were similar except for GLS being significantly smaller in patients with than in patients without DN (18 ± 2% vs. 20 ± 2%, p < 0.001). It was noteworthy that, of the parameters for the nerve conduction study, only F-wave latency correlated with GLS (r = -0.34, p < 0.001), and also was identified as an independent determinative value of GLS in a multivariate linear regression model (ß = -0.25, p = 0.001) even after adjustment for other closely related GLS factors. CONCLUSIONS: Monitoring of F-wave latency may aid early detection of not only DN but also subclinical LV dysfunction. Joint planning of assessment by diabetologists and cardiologists is therefore advisable for better management of DM patients.

Association of left atrial booster-pump function with heart failure symptoms in patients with severe aortic stenosis and preserved left ventricular ejection fraction.

BACKGROUND: Identification of heart failure (HF) symptoms in patients with severe aortic stenosis (AS) and preserved left ventricular (LV) ejection fraction (EF) is clinically important, but assessment of HF symptoms is challenging. It was recently reported that resting left atrium (LA) functions are related to exercise performance and are also important prognostic markers for patients with HF. The aim of this study was to assess the association of the HF symptoms with LA function in patients with severe AS and preserved LVEF. METHODS: We retrospectively studied 40 patients with severe AS and preserved LVEF (all ≥50%) who were referred for aortic valve replacement (AVR). LA reservoir (SR-LAs), conduit (SR-LAe), and booster-pump (SR-LAa) functions were determined as the averaged global LA speckle tracking longitudinal strain rate from apical four- and two-chamber views. Twenty patients were symptomatic and 20 asymptomatic. RESULTS: Aortic stenosis severity was similar for the 2 groups. Symptomatic status was associated with age, LV mass index, hemoglobin, B-type natriuretic peptide, LV end-systolic volume index, LVEF, LA volume index, SR-LAs, SR-LAe, and SR-LAa. Importantly, multivariate logistic regression analysis revealed that SR-LAa was the only independent determinant of symptomatic status (OR = 0.242, P = 0.002). Furthermore, significant improvement of SR-LAa was observed along with the reduction in LA volume index and LV mass index after AVR. CONCLUSIONS: SR-LAa was found to be associated with the HF symptoms. Characterization of LA booster-pump function may be useful for the assessment of the symptomatic status in patients with severe AS patients and limited physical activity.

Impact of Right Ventricular Geometry on Mitral Regurgitation After Transcatheter Closure of Atrial Septal Defect.

Worsening of mitral regurgitation (MR) is sometimes observed after closure of an atrial septal defect (ASD). However, since the mechanism of this deterioration remains unclear, the aim of our study was to investigate the effect of left (LV) and right ventricular (RV) geometry on MR after transcatheter closure of ASD.We studied 27 patients with ASD who underwent transcatheter closure. Echocardiography was performed before and 6 ± 2 months after the procedure. In addition to conventional echocardiographic parameters, full volume data of the whole LV and RV heart was obtained with 3-dimensional echocardiography. MR was quantified by measuring the width of the vena contracta, and was graded as mild (< 3.0 mm), moderate (3.0 to 6.9 mm), or severe (≥ 7.0 mm).Ten patients (37%) were classified as having worsening MR and the remaining 17 (63%) as not having worsening MR. The two groups showed similar baseline characteristics, except for patients with worsening MR being more likely to be older (P = 0.009) and having a larger left-to-right shunt of pulmonary and systemic blood flow ratio (P = 0.02). It is noteworthy that the horizontal-to-vertical ratio of basal-RV at end-systole for patients with worsening MR was significantly smaller than that for patients without worsening MR (1.0 ± 0.2 versus 1.4 ± 0.2, P < 0.0001). Furthermore, multivariate analysis showed that the horizontal-to-vertical ratio of basal-RV at end-systole was the independent predictor of worsening MR during follow-up (P < 0.001).RV geometry may affect MR after closure of ASD. The pre-operative horizontal-to-vertical ratio of basal-RV is considered useful for predicting worsening of MR after closure of ASD.

Efficacy of right ventricular free-wall longitudinal speckle-tracking strain for predicting long-term outcome in patients with pulmonary hypertension.

BACKGROUND: The development of right ventricular (RV) dysfunction in pulmonary hypertension (PH) patients is associated with adverse outcome, so that the assessment of RV function has become increasingly important in the management of such patients. The present objective was to test the hypothesis that RV free-wall longitudinal speckle-tracking strain (RV-free), an independent echocardiographic predictor of hemodynamic RV performance, can predict long-term outcome. METHODS AND RESULTS: Forty-two PH patients were studied. RV-free was calculated by averaging the 3 regional peak systolic strains for the RV free wall. For comparison, tricuspid annular plane systolic excursion (TAPSE), RV fractional area change, RV index of myocardial performance, and tissue Doppler-derived tricuspid lateral annular systolic velocity were also studied. Long-term follow-up was performed for 4 years after adding PH-specific drugs. Receiver operating characteristic curve analysis identified RV-free ≤ 19.4% as the best predictor of cardiovascular events with 90% sensitivity, 69% specificity, and area under the curve of 0.819 (P=0.0001). Furthermore, the Kaplan-Meier curve indicated that patients with RV-free >19.4% experienced fewer cardiovascular events than those with RV-free ≤ 19.4% (log-rank P=0.0008). Importantly, the co-occurrence of RV-free ≤ 19.4% and TAPSE <16 mm was associated with the highest frequency of cardiovascular events. CONCLUSIONS: RV-free may serve as a non-invasive predictor of cardiovascular events for PH patients. Combining RV-free with TAPSE may be more effective for predicting long-term cardiovascular events.

Right ventricular-pulmonary arterial coupling impairment and exercise capacity in obese adults.

Background: Obesity-related exercise intolerance may be associated with pulmonary vascular and right ventricular dysfunction. This study tested the hypothesis that decreased pulmonary vascular reserve and right ventricular (RV)-pulmonary arterial (PA) uncoupling contributes to exercise limitation in subjects with obesity. Methods: Seventeen subjects with obesity were matched to normo-weighted healthy controls. All subjects underwent; exercise echocardiography, lung diffusing capacity (DL) for nitric oxide (NO) and carbon monoxide (CO) and an incremental cardiopulmonary exercise test. Cardiac output (Q), PA pressure (PAP) and tricuspid annular plane systolic excursion (TAPSE) were recorded at increasing exercise intensities. Pulmonary vascular reserve was assessed by multipoint mean PAP (mPAP)/Q relationships with more reserve defined by lesser increase in mPAP at increased Q, and RV-PA coupling was assessed by the TAPSE/systolic PAP (sPAP) ratio. Results: At rest, subjects with obesity displayed lower TAPSE/sPAP ratios (1.00 ± 0.26 vs. 1.19 ± 0.22 ml/mmHg, P < 0.05), DLCO and pulmonary capillary blood volume (52 ± 11 vs. 64 ± 13 ml, P < 0.01) compared to controls. Exercise was associated with steeper mPAP-Q slopes, decreased TAPSE/sPAP and lower peak O2 uptake (VO2peak). The changes in TAPSE/sPAP at exercise were correlated to the body fat mass (R = 0.39, P = 0.01) and VO2peak (R = 0.44, P < 0.01). Conclusion: Obesity is associated with a decreased pulmonary vascular and RV-PA coupling reserve which may impair exercise capacity.

Exercise stress echocardiography of the pulmonary circulation and right ventricular-arterial coupling in healthy adolescents.

AIMS: To explore the effects of age and sex in adolescents vs. young or middle-aged adults on pulmonary vascular function and right ventricular-arterial (RV-PA) coupling as assessed by exercise stress echocardiography. METHODS AND RESULTS: Forty healthy adolescents aged 12-15 years were compared with 40 young adults aged 17-22 years and 40 middle-aged adults aged 30-50 years. Sex distribution was equal in the three groups. All the subjects underwent an exercise stress echocardiography. A pulmonary vascular distensibility coefficient α was determined from multipoint pulmonary vascular pressure-flow relationships. RV-PA coupling was assessed by the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio, who has been previously validated by invasive study. While cardiac index and mean PAP were not different, adolescents compared to young and middle-aged adults, respectively had higher pulmonary vascular distensibility coefficients α (1.60 ± 0.31%/mmHg vs. 1.39 ± 0.29%/mmHg vs. 1.20 ± 0.35%/mmHg, P < 0.00001). Adolescents and young adults compared to middle-aged adults, respectively had higher TAPSE/PASP ratios at rest (1.24 ± 0.18 mm/mmHg and 1.22 ± 0.17 mm/mmHg vs. 1.07 ± 0.18 mm/mmHg, P < 0.008) and during exercise (0.86 ± 0.24, 0.80 ± 0.15 and 0.72 ± 0.15 mm/mmHg, P < 0.04). The TAPSE/PASP ratio decreased with exercise. There were no sex differences in α or TAPSE/PASP. CONCLUSION: Compared to adults, adolescents present with a sex-independent more distensible pulmonary circulation. Resting and exercise RV-PA coupling is decreased in middle-aged adults.

Fluid challenge predicts clinical worsening in pulmonary arterial hypertension.

AIM: A fluid challenge with rapid saline infusion during right heart catheterization has been shown to be useful for the differential diagnosis between pre- and post-capillary pulmonary hypertension. The aim of this study was to evaluate the prognostic relevance of fluid challenge-induced changes in pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH). METHODS: Overall, 118 PAH patients (mean age 57 ±â€¯15 years, 80 female) underwent hemodynamic measurements before and after rapid saline infusion (7 mL/kg in 10 min) and were followed up for 19 ±â€¯4 months. RESULTS: Thirty-two patients (27%) had a clinical worsening event defined as the occurrence of one of the following: death, lung transplantation, initiation of parenteral prostanoids, or worsening of PAH (defined as the presence of all of the three following components: a decrease in the 6-minute walk distance of at least 15% from baseline, worsening of PAH symptoms, and need for new PAH treatment). Cardiac index (CI), stroke volume and pulmonary artery compliance were lower whereas right atrial pressure (RAP), the ratio of RAP to pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance were higher in patients with a clinical worsening event versus patients without events, both at baseline and after fluid challenge (all p < 0.01). At multivariable Cox proportional hazards regression analysis, a post-fluid challenge CI <2.8 L/min/m2 (hazard ratio 0.0143; 95% confidence interval 0.006-0.3383; p = 0.009) was the only independent predictor of outcome. CONCLUSIONS: CI measured after a fluid challenge is an independent predictor of outcome in PAH.

Lung diffusing capacity in sub-Saharan Africans versus European Caucasians.

Single breath measurements of lung diffusing capacity (DL) for carbon monoxide (CO) and nitric oxide (NO) were performed in age-, sex-, weight- and height-matched 32 sub-Saharan Africans (13 women) and 32 Caucasian Europeans, and repeated in 14 of each group at 80% of maximum exercise capacity. In Africans versus Caucasians respectively, DLNO was 153±31 vs 176±38ml/mmHg/min at rest (P<0.001) and 210±48 vs 241±52ml/mmHg/min at exercise (P<0.01) while hemoglobin-adjusted DLCO was 29±6 vs 34±6ml/mmHg/min at rest (P<0.001), and 46±11 vs 51±13ml/mmHg/min at exercise (P<0.01). However there were no differences in DLCO/alveolar volume(VA) (KCO) and DLNO/VA(KNO). The sitting-to-standing height ratio was lower in the Africans. Differences in lung volume with respect to body height explain lower DLNO and DLCO in sub-Saharan Africans as compared to Caucasian Europeans.