Prognostic Implications of Reductions in Heart Rates in Patients With Acute Heart Failure and Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia in patients with acute heart failure (AHF). Heart rate (HR) also changes significantly over time. However, the association between changes in HR in AF patients and prognosis is uncertain.Methods and Results:We investigated the association between HR reduction in AF achieved within 48 h of admission and 60-day mortality in patients with AHF from the REALITY-AHF study. The percentage HR (%HR) reduction was calculated as (baseline HR-HR at 48 h) / baseline HR × 100. The primary endpoint was 60-day all-cause mortality. In 468 patients with confirmed AF at both admission and 48 h after admission, the median HR at these time points was 105±31 and 84±18 beats/min, respectively. The median %HR reduction was 15.4% (interquartile range 2.2-31.4%). During the 60 days of admission, 39 deaths (8.3%) were recorded, and the %HR reduction within 48 h was significantly associated with 60-day mortality in the unadjusted model (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.77-0.95; P=0.005) and after adjusting for other covariates (HR 0.81; 95% CI 0.68-0.96; P=0.016).Furthermore, the %HR reduction was associated with a significant reduction in 60-day mortality in patients with higher baseline HR. CONCLUSIONS: %HR reduction is associated with a better short-term prognosis in patients with AHF presenting with AF, particularly in those with a rapid ventricular response.

Impact of Prosthesis-Patient Mismatch on Hemodynamics During Exercise in Patients With Aortic Stenosis After Transcatheter Aortic Valve Implantation With a Balloon-Expandable Valve.

BACKGROUND: There is no evidence of hemodynamic performance during exercise in patients with aortic stenosis (AS) after transcatheter aortic valve implantation (TAVI). This study aimed to investigate the changes in kinematic hemodynamics during exercise and determine the impact of prosthesis-patient mismatch (PPM) on the hemodynamics of transcatheter heart valves using exercise stress echocardiography (ESE) in AS patients after TAVI. METHODS AND RESULTS: This study enrolled 77 consecutive patients (mean age 82 ± 5 years, 50.6% male) who underwent ESE 3-6 months after TAVI with a balloon-expandable valve. The effective orifice area index at rest was significantly correlated with the mean pressure gradient (PG) during exercise (p <0.001). The patients were divided into two groups according to the presence of PPM (PPM and non-PPM groups). During exercise, the patients with PPM had a higher left ventricular ejection fraction (74.6 ± 6.1% vs. 69.7 ± 9.6%, p = 0.048), a lower stroke volume index (47.2 ± 14.0 ml/m2 vs. 55.6 ± 14.5 ml/m2, p = 0.037), a significantly higher mean transvalvular PG (21.9 ± 9.1 mmHg vs. 12.2 ± 4.9 mmHg, p = 0.01) and an increased mean PG from rest to exercise (5.7 ± 3.5 mmHg vs. 2.3 ± 2.8 mmHg, p <0.001) compared with patients without PPM. Patients with PPM had a higher pulmonary artery systolic pressure (SPAP) during exercise (57.3 ± 13.8 mmHg vs. 49.7 ± 10.9 mmHg, p = 0.021) and a higher incidence of exercise-induced pulmonary hypertension (43.8 vs. 15.0%, p = 0.037) than patients without PPM. PPM was strongly associated with exercise-induced pulmonary hypertension (hazard ratio: 3.570, p = 0.013). CONCLUSIONS: AS patients with PPM after TAVI showed a disproportionate increase in the transvalvular PG and SPAP during exercise, and PPM was associated with exercise-induced pulmonary hypertension.

Prognostic value of exercise stress echocardiography in patients with secondary mitral regurgitation: a long-term follow-up study.

BACKGROUND: Secondary mitral regurgitation (MR) remains a challenging problem in the diagnosis and treatment of patients with heart failure. Although it is well known that secondary MR is dynamic, the impact of the severity of MR during exercise on long-term outcome has not been fully evaluated. The aim of the present study was to investigate the prognostic value of exercise stress echocardiography (ESE) in patients with secondary MR. METHODS: This prospective study included 118 consecutive patients with secondary MR and left ventricular dysfunction (mean ejection fraction at rest: 38 ± 14%) who underwent semi-supine ESE. Their major cardiovascular events (MACE) including cardiac death were followed up for a median of 41.7 (range: 6-128) months. RESULTS: MR significantly increased from rest to exercise (effective regurgitant orifice: 0.18 ± 0.09 vs. 0.25 ± 0.12 cm2, P < 0.001). The prevalence of severe MR was higher during exercise than those at rest (37% vs. 56%, P < 0.001). During follow-up, MACE occurred in 49 patients (41.5%) including 12 cardiac deaths. Cox proportional-hazard multivariate analysis revealed that older age and MR severity during exercise were significantly associated with increased risk of MACE (hazard ratio: 1.04 and 8.4, respectively, both P < 0.05). CONCLUSIONS: ESE provides prognostic information in patients with secondary MR that is useful for predicting long-term outcome.

Predictors of Exercise-Induced Pulmonary Hypertension in Patients with Asymptomatic Degenerative Mitral Regurgitation: Mechanistic Insights from 2D Speckle-Tracking Echocardiography.

Presence of exercise-induced pulmonary hypertension (EIPH) in asymptomatic degenerative mitral regurgitation (DMR) determines prognosis. This study aimed to elucidate the mechanism and predictors of EIPH in asymptomatic DMR. Ninety-one consecutive asymptomatic patients with DMR who underwent exercise stress echocardiography were prospectively included. We obtained various conventional echocardiographic parameters at rest and during peak exercise, as well as left atrial (LA) function at rest using 2-dimensional speckle-tracking analysis. The 25 patients (33.3%) with EIPH were significantly older and had a greater ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity during peak exercise than those without EIPH. LA strain (LAS)-s and LAS-e, indices of LA reservoir and conduit function, respectively, were significantly lower in those with EIPH than in those without EIPH. Multivariate analysis indicated that LAS-s was the only resting echocardiographic parameter that independently predicted EIPH, with a cut-off value of 26.9%. Furthermore, Kaplan-Meier curve analysis showed that symptom-free survival was markedly lower among those with reduced LAS-s. In conclusion, decreased LA reservoir function contributes to EIPH, and LAS-s at rest is a useful indicator for predicting EIPH in asymptomatic patients with DMR.

Two-dimensional transthoracic echocardiographic normal reference ranges for proximal aorta dimensions: results from the EACVI NORRE study.

AIMS: To report normal reference ranges for echocardiographic dimensions of the proximal aorta obtained in a large group of healthy volunteers recruited using state-of-the-art cardiac ultrasound equipment, considering different measurement conventions, and taking into account gender, age, and body size of individuals. METHODS AND RESULTS: A total of 704 (mean age: 46.0 ± 13.5 years) healthy volunteers (310 men and 394 women) were prospectively recruited from the collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. A comprehensive echocardiographic examination was obtained in all subjects following pre-defined protocols. Aortic dimensions were obtained in systole and diastole, following both the leading-edge to leading-edge and the inner-edge to inner-edge conventions. Diameters were measured at four levels: ventricular-arterial junction, sinuses of Valsalva, sino-tubular junction, and proximal tubular ascending aorta. Measures of aortic root in the short-axis view following the orientation of each of the three sinuses were also performed. Men had significantly larger body sizes when compared with women, and showed larger aortic dimensions independently of the measurement method used. Dimensions indexed by height and body surface area are provided, and stratification by age ranges is also displayed. In multivariable analysis, the independent predictors of aortic dimensions were age, gender, and height or body surface area. CONCLUSION: The NORRE study provides normal values of proximal aorta dimensions as assessed by echocardiography. Reference ranges for different anatomical levels using different (i) measurement conventions and (ii) at different times of the cardiac cycle (i.e. mid-systole and end-diastole) are provided. Age, gender, and body size were significant determinants of aortic dimensions.

Prognostic value of exercise left ventricular end-systolic volume index in patients with asymptomatic aortic regurgitation: an exercise echocardiography study.

BACKGROUND: Surgical timing of chronic aortic regurgitation (AR) remains a matter of debate because of limited data. This study assessed the prognostic value of exercise echocardiography in asymptomatic AR. METHODS: This prospective study included 60 consecutive asymptomatic patients with isolated moderate or severe AR (mean regurgitant volume 56.7 ± 11.8 ml) and preserved ejection fraction who underwent exercise echocardiography. The clinical outcomes were defined by the presence of major adverse cardiovascular events (MACE) and the indication for aortic valve replacement (AVR) with class I or IIa classification in the current guidelines. RESULTS: During the average follow-up of 731 days, 12 patients suffered from the clinical events, including two patients developing MACE (3%) and ten patients indicating for AVR (17%). No difference in left ventricular (LV) ejection fraction at rest was found between the patients with and without the clinical events. The indexed LV diameters and LV volumes were significantly dilated in the patients with the clinical events. The Cox proportional hazards regression analysis resulted that the exercise LV end-systolic volume index (LVESVi) was significantly associated with the clinical outcomes [hazard ratio, 1.116; 95% CI (1.032-1.205); p = 0.006]. The Kaplan-Meier analysis showed that exercise LVESVi was clearly stratified the event-free survival. CONCLUSIONS: Exercise LVESVi might be an independent predictor of prognosis in patients with asymptomatic moderate or severe AR.

Prediction of new onset of resting pulmonary arterial hypertension in systemic sclerosis.

BACKGROUND: Early detection of pulmonary arterial hypertension (PH) is crucial in systemic scleroderma. However, predictors of new onset of resting PH during follow-up (FUPH) have been poorly explored. AIM: To determine whether nailfold videocapillaroscopy (NVC) grade and exercise echocardiographic variables are predictors of FUPH. METHODS: We prospectively enrolled 40 patients with systemic sclerosis (age 54±13 years; 68% women). All patients underwent graded semisupine exercise echocardiography and NVC. Baseline resting PH and FUPH were defined as systolic pulmonary arterial pressure (sPAP)>35 mmHg, and exercise-induced PH (EIPH) as exercise sPAP>50 mmHg. RESULTS: Seventeen patients developed EIPH (43%). During follow-up (FU) (25±15 months), 11 patients without baseline PH developed FUPH (28%), all from the EIPH group. Patients with FUPH were significantly older (60±14 vs 50±12 years; P=0.04), had higher resting and exercise sPAP (30±4 vs 22±5 and 60±12 vs 40±11 mmHg, respectively; P<0.0001) and a higher exercise E/e' ratio (9.4±0.7 vs 5.8±0.4; P=0.0003) and presented more frequently NVC grade>2 (90% vs 35%; P=0.0009). After adjustment for age, resting sPAP, exercise sPAP and NVC grade>2 were associated with maximal resting sPAP during follow-up and FUPH (P<0.05). Patients with both EIPH and NVC grade>2 had a very high incidence of FUPH (82%), and both variables remained strongly associated with FUPH after adjustment for age (hazard ratio 11.6, 95% confidence interval 2.4-55.3; P=0.002). CONCLUSION: Exercise echocardiography and NVC can identify a subgroup of patients with systemic sclerosis who are at risk of developing FUPH.

Impact of Serial B-Type Natriuretic Peptide Changes for Predicting Outcome in Asymptomatic Patients With Aortic Stenosis.

BACKGROUND: The aim of this study was to determine the impact on the outcome of serial B-type natriuretic peptide (BNP) changes during follow-up in asymptomatic patients with ≥ moderate aortic stenosis (AS) and preserved left ventricular ejection fraction. METHODS: We prospectively screened 69 patients who underwent comprehensive transthoracic echocardiography, BNP level measurement at baseline and after every 6 or 12 months. Annualized BNP changes were calculated as the difference between the last and baseline BNP measurements divided by the duration of follow-up. The primary endpoint was the occurrence of symptoms, aortic valve replacement, or cardiovascular death. RESULTS: During a follow-up of 30 ± 19 months, 43 patients experienced a cardiac event. These patients were significantly older (73 ± 9 vs 65 ± 16 years; P = 0.010), had more often dyslipidemia (79% vs 42%; P = 0.038), more severe AS (peak velocity: 3.9 ± 0.6 vs 3.5 ± 0.6 m/s; P = 0.002), larger indexed left atrial area (10.2 ± 2.5 vs 8.7 ± 1.9 cm(2)/m(2); P = 0.006), and a higher increase in annualized BNP (+90 ± 155 vs +7 ± 49 pg/mL/y; P = 0.010). Patients with higher annualized BNP changes (> 20 pg/mL/y) had a significantly lower cardiac event-free survival (1 year: 63 ± 8% vs 97 ± 3%; 3 years: 31 ± 8% vs 68 ± 8%; P < 0.001). Using the multivariate Cox proportional hazards model, higher annualized BNP changes were significantly associated with increased risk of cardiac events (hazard ratio: 2.73, 95% confidence interval: 1.27-5.86; P = 0.010) after adjustment for age, dyslipidemia, and echocardiographic parameters. CONCLUSIONS: In asymptomatic patients with AS and preserved left ventricular ejection fraction, the use of serial BNP changes may help to anticipate development of class I indication for aortic valve replacement.

Cardiovascular outcome in systemic sclerosis.

OBJECTIVES: Cardiovascular involvement is recognized as a poor prognostic factor in systemic sclerosis (SSc). The aim of this study was to evaluate the usefulness of nailfold video-capillaroscopy (NVC), brain natriuretic peptide (BNP) blood level and exercise echocardiography to predict the occurrence of cardiovascular events in SSc. METHODS: We prospectively enrolled 65 patients with SSc (age 54±14 years, 30% female) followed in CHU Sart-Tilman, Liège, Belgium. All patients underwent graded semi-supine exercise echocardiography. Both baseline resting pulmonary hypertension (PH) and PH during follow-up (FUPH) were defined as systolic pulmonary arterial pressure (sPAP)>35 mmHg, and exercise-induced PH (EIPH) as sPAP>50 mmHg during exercise. RESULTS: EIPH was present in 21 patients. During FU (27±18 months), 13 patients developed FUPH and 9 presented cardiovascular complications. Patients with cardiovascular events were significantly older (63±14 vs 52±13 years; P=0.03), presented more frequently NVC grade>2 (89 vs 43%; P=0.009), had higher resting and exercise sPAP (30±6 vs 24±6; P=0.007 and 57±13 vs 44±13 vs mmHg; P=0.01, respectively), and higher BNP blood level (112±106 vs 26±19 pg/ml; P=0.0001). After adjustment for age and gender, NVC grade>2 (ß=2.4±1.1; P=0.03), EIPH (ß=2.30±1.13; P=0.04), FUPH (ß=0.24±0.09; P=0.01 and ß=3.52±1.16; P=0.002, respectively;) and BNP (ß=0.08±0.04; P=0.02) were independent predictors of CV events. Beyond age, an incremental value of EIPH, BNP and NVC grade>2 was predictive of cardiovascular events (P<0.001). CONCLUSION: Cardiovascular complications are not rare in SSc (18%). NVC, BNP blood level assessment and exercise echocardiography could be useful tools to identify patients at risk of SSc.

Echocardiographic reference ranges for normal cardiac Doppler data: results from the NORRE Study.

AIMS: Reference values for Doppler parameters according to age and gender are recommended for the assessment of heart physiology, specifically for left ventricular (LV) diastolic function. In this study, we report normal reference ranges for Doppler parameters obtained in a large group of healthy volunteers. Echocardiographic data were acquired using state-of-the-art cardiac ultrasound equipment following Doppler acquisition and measurement protocols approved by the European Association of Cardiovascular Imaging. METHODS AND RESULTS: A total of 449 (mean age: 45.8 ± 13.7 years) healthy volunteers (198 men and 251 women) were enrolled at the collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. A comprehensive echocardiographic examination was obtained from all subjects following predefined protocols. The majority of the Doppler diastolic parameters (e', E/e') as well as right ventricle systolic s' wave velocity were similar in men and women. Left ventricle s' wave velocity was higher in men than in women. E wave and e' were higher in younger subjects and decreased progressively in the older ones. E/e' ratio increased with ageing. Septal e' <8 cm/s was present in 19.7% of the subjects in the 40-60 year group and in 55% of those in the ≥60 year group. However, the cut-off value of average E/e' or lateral E/e' remained <15 or 13, respectively, in the majority of patients. CONCLUSION: The NORRE study provides the reference values for the most useful Doppler parameters in the evaluation of heart physiology. These data highlight the need of using age-specific reference values especially for the diagnosis of LV systolic and diastolic dysfunction and for the estimation of LV filling pressures.

Influence of exercise-induced pulmonary hypertension on exercise capacity in asymptomatic degenerative mitral regurgitation.

BACKGROUND: Exercise capacity is helpful in the management of patients with mitral regurgitation (MR). However, the determinants of exercise capacity reduction in MR have remained unclear. This study was designed to objectively assess exercise capacity, identify the echocardiographic predictors of exercise capacity, and investigate its impact on development of symptoms in asymptomatic degenerative MR. METHODS: A total of 49 consecutive asymptomatic patients (age, 58.9±13.1 years; 82% males) with at least moderate degenerative MR (effective regurgitant orifice area=0.40±0.14cm(2); regurgitant volume=60.9±19.6mL) underwent the symptom-limited cardiopulmonary exercise testing for assessing exercise capacity (peak oxygen uptake, peak V˙O2; the minute ventilation/carbon dioxide production, V˙E/V˙CO2 slope). All patients also underwent exercise stress echocardiography for detecting exercise-induced pulmonary hypertension (EIPH) defined by systolic pulmonary arterial pressure (SPAP) ≥60mmHg. RESULTS: The mean peak V˙O2 was 22.6±5.1mL/kg/min (86.7±14.1% of age, gender-predicted); peak V˙O2 widely varied (48-121% of predicted), and was markedly reduced (<80.4% of predicted) in 24% of the study patients. The patients with EIPH had lower 2-year symptom-free survival than those without EIPH (p=0.003). The multivariable analysis demonstrated that EIPH was an independent echocardiographic determinant of peak V˙O2 (p=0.001) and V˙E/V˙CO2 slope (p=0.021). Furthermore, the area under curve of age- and gender-adjusted exercise SPAP was 0.88 (95% confidence interval: 0.78-0.97) for reduced exercise capacity. CONCLUSIONS: In asymptomatic moderate to severe degenerative MR, EIPH was independently associated with exercise capacity and predicted the occurrence of symptoms. Exercise stress echocardiography is an important tool in managing patients with asymptomatic degenerative MR.

Usefulness of serial B-type natriuretic peptide assessment in asymptomatic aortic stenosis.

B-type natriuretic peptide (BNP) level may be a useful prognostic marker for the management of asymptomatic patients with aortic stenosis (AS). The aim of this study was to identify the echocardiographic determinants of BNP changes during follow-up in AS. We studied 61 asymptomatic patients with greater than moderate AS and preserved left ventricular (LV) ejection fraction who underwent rest and exercise Doppler echocardiography with concomitant BNP level measurement at baseline. BNP measurement was repeated after inclusion every 6 months. Patients were divided into 2 groups according to the median of BNP changes during follow-up. According to parameters at rest, patients in the high BNP changes group had significantly higher E/e' ratio. Statistically significant correlations were found between BNP changes and E/e' ratio and indexed left atrial area. According to exercise parameters, patients in the high BNP changes group had significantly lower exercise-induced increase in LV ejection fraction. Statistically significant correlations were found between BNP changes and exercise-induced changes in LV ejection fraction. After adjustment for age, mean aortic pressure gradient, and BNP level at baseline, multivariate analysis identified indexed left atrial area, E/e' at rest, and exercise-induced increase in ejection fraction as independent determinants of BNP changes during follow-up. In conclusion, this study shows that, in asymptomatic patients with preserved LV function and moderate AS, serial BNP measurements may widely vary. Subclinical LV diastolic and systolic dysfunctions are frequently present in patients with higher serial BNP changes.

Determinants of exercise-induced pulmonary arterial hypertension in systemic sclerosis.

BACKGROUND: Exercise-induced pulmonary arterial hypertension (EIPH) in systemic sclerosis (SSc) has already been observed but its determinants remain unclear. The aim of this study was to determine the incidence and the determinants of EIPH in SSc. METHODS AND RESULTS: We prospectively enrolled 63 patients with SSc (age 54±3years, 76% female) followed in CHU Sart-Tilman in Liège. All patients underwent graded semi-supine exercise echocardiography. Systolic pulmonary arterial pressure (sPAP) was derived from the peak velocity of the tricuspid regurgitation jet and adding the estimation of right atrial pressure, both at rest and during exercise. Resting pulmonary arterial hypertension (PH) was defined as sPAP > 35 mmHg and EIPH as sPAP > 50 mmHg during exercise. The following formulas were used: mean PAP (mPAP) = 0.61 × sPAP + 2, left atrial pressure (LAP)=1.9+1.24 × left ventricular (LV) E/e' and pulmonary vascular resistance (PVR)=(mPAP-LAP)/LV cardiac output (CO) and slope of mPAP-LVCO relationship=changes in mPAP/changes in LVCO. Resting PH was present in 3 patients (7%) and 21 patients developed EIPH (47%). Patients with EIPH had higher resting LAP (10.3 ± 2.2 versus 8.8 ± 2.3 mmHg; p = 0.03), resting PVR (2.6 ± 0.8 vs. 1.4 ± 1.1 Woods units; p=0.004), exercise LAP (13.3 ± 2.3 vs. 9 ± 1.7 mmHg; p < 0.0001), exercise PVR (3.6 ± 0.7 vs. 2.1 ± 0.9 Woods units; p = 0.02) and slope of mPAP-LVCO (5.8 ± 2.4 vs. 2.9 ± 2.1 mmHg/L/min; p < 0.0001). After adjustment for age and gender, exercise LAP (ß=3.1 ± 0.8; p=0.001) and exercise PVR (ß=7.9 ± 1.7; p=0.0001) were independent determinants of exercise sPAP. CONCLUSION: EIPH is frequent in SSc patients and is mainly related to both increased exercise LV filling pressure and exercise PVR.

Echocardiographic reference ranges for normal cardiac chamber size: results from the NORRE study.

AIMS: Availability of normative reference values for cardiac chamber quantitation is a prerequisite for accurate clinical application of echocardiography. In this study, we report normal reference ranges for cardiac chambers size obtained in a large group of healthy volunteers accounting for gender and age. Echocardiographic data were acquired using state-of-the-art cardiac ultrasound equipment following chamber quantitation protocols approved by the European Association of Cardiovascular Imaging. METHODS: A total of 734 (mean age: 45.8 ± 13.3 years) healthy volunteers (320 men and 414 women) were enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. A comprehensive echocardiographic examination was performed on all subjects following pre-defined protocols. There were no gender differences in age or cholesterol levels. Compared with men, women had significantly smaller body surface areas, and lower blood pressure. Quality of echocardiographic data sets was good to excellent in the majority of patients. Upper and lower reference limits were higher in men than in women. The reference values varied with age. These age-related changes persisted for most parameters after normalization for the body surface area. CONCLUSION: The NORRE study provides useful two-dimensional echocardiographic reference ranges for cardiac chamber quantification. These data highlight the need for body size normalization that should be performed together with age-and gender-specific assessment for the most echocardiographic parameters.

Simple exercise echocardiography using a Master's two-step test for early detection of pulmonary arterial hypertension.

BACKGROUND: Early detection of pulmonary arterial hypertension (PAH) is indispensable, although, echocardiography at rest alone does not provide sufficient evidence for it. Here, this study aimed to investigate the usefulness of simple exercise echocardiography using a Master's two-step test for detecting early PAH. METHODS: This study included 52 connective tissue disease patients who had mild symptoms in World Health Organization functional classification 2, suspected as having early PAH, and underwent exercise echocardiography and right heart catheterization. Echocardiography was performed before and after the Master's two-step exercise test; the study patients were classified into the non-PAH (mean pulmonary arterial pressure <25 mmHg, n=37) or PAH (mean pulmonary arterial pressure ≥25 mmHg, n=15) groups. RESULTS: Rest systolic pulmonary artery pressure estimated using echocardiography did not significantly differ between the two groups; however, a significant difference in post-exercise systolic pulmonary artery pressure was found (non-PAH, 58.8±10.8 mmHg; PAH, 80.2±14.3 mmHg, p<0.0001). The multiple logistic regression analysis indicated post-exercise systolic pulmonary artery pressure as an independent predictor of PAH (p=0.013). The area under the curve by post-exercise systolic pulmonary artery pressure was 0.91 for PAH. Post-exercise systolic pulmonary artery pressure ≥69.6 mmHg predicted PAH with the sensitivity of 93% and the specificity of 90%. CONCLUSIONS: Simple exercise echocardiography using the Master's two-step test could detect PAH in mildly symptomatic connective tissue disease patients. The usefulness of this method should be verified for the early detection of PAH.

Normal Reference Ranges for Echocardiography: rationale, study design, and methodology (NORRE Study).

BACKGROUND: Availability of normative reference values for cardiac chamber dimensions, volumes, mass, and function is a prerequisite for the accurate application of echocardiography for both clinical and research purposes. However, due to the lack of consistency in current echocardiographic 'reference values', their use for clinical decision-making remains questionable. AIMS: The aim of the 'Normal Reference Ranges for Echocardiography Study (NORRE Study)' is to obtain a set of 'normal values' for cardiac chamber geometry and function in a large cohort of healthy Caucasian individuals aged over a wide range of ages (25-75 years) using both conventional and advanced echocardiographic techniques. METHODS: The NORRE Study is a large prospective, observational multicentre study in which transthoracic echocardiographic studies will be acquired in 22 laboratories accredited by the European Association of Cardiovascular Imaging and in one laboratory in the USA accredited by ICAEL. The final sample size has been estimated in 1100 normal subjects in whom M-mode, 2D, and 3D imaging, colour Doppler, pulsed-wave Doppler, pulsed-wave tissue Doppler, and colour tissue Doppler imaging data will be obtained. All studies will be sent to a central echocardiographic core laboratory for quantitative analysis. Multiple studies will be performed for reproducibility analysis. CONCLUSION: After completion of the NORRE Study, uniform reference limits according to age, gender, and anthropometric parameters will be available to standardize the quantitative interpretation of echocardiography.

Early diastolic function during exertion influences exercise intolerance in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) patients with preserved left ventricular ejection fraction (LVEF) often develop dyspnea and exercise intolerance. Diastolic dysfunction may contribute to exercise intolerance in these patients. This study aimed to clarify our hypothesis as to whether diastolic function rather than systolic function would be associated with exercise intolerance in HCM using two-dimensional (2D) speckle tracking echocardiography during exercise. METHODS: Thirty-three HCM patients (mean age 59.3 ± 15.7 years) underwent 2D speckle tracking echocardiography at rest and during submaximal semi-supine bicycle exercise. Global longitudinal strain (LS), LS rate during systole (LSRs), early diastole (LSRe), and late diastole (LSRa) were measured. The symptom-limited cardiopulmonary exercise testing was performed using a cycle ergometer for measuring the peak oxygen consumption (peak [Formula: see text]). RESULTS: In the multivariate linear regression analysis, peak [Formula: see text] did not associate with strain or strain rate at rest. However, peak [Formula: see text] correlated with LS (ß = -0.403, p = 0.007), LSRe (ß = 6.041, p = 0.001), and LSRa (ß = 5.117, p = 0.021) during exercise after adjustment for age, gender, and heart rate. The first quartile peak [Formula: see text] (14.2 mL/min/kg) was assessed to predict exercise intolerance. The C-statistic of delta LSRe was 0.74, which was relatively greater than that of delta LS (0.70) and delta LSRa (0.58), indicating that early diastolic function rather than systolic and late diastolic function affects exercise intolerance. CONCLUSIONS: LSRe during exercise is closely associated with the peak [Formula: see text]. Early diastolic function during exercise is an important determinant of exercise capacity in patients with HCM.

Relationship between left ventricular ejection fraction and mitral annular displacement derived by speckle tracking echocardiography in patients with different heart diseases.

BACKGROUND: Speckle tracking echocardiography (STE)-derived mitral annular displacement (MAD) utilizes the speckle tracking technique to measure strain vectors, which provides accurate estimates of left ventricular ejection fraction (LVEF). Here, we investigated a link between STE-derived MAD and LVEF in patients with different heart diseases and evaluated its clinical usefulness. METHODS: This study included 266 outpatients and 84 controls. Of the study patients, 52 patients had ischemic heart disease (IHD), 37 patients had dilated cardiomyopathy (DCM), 34 patients had hypertrophic cardiomyopathy (HCM), 74 patients had valvular heart disease (VHD), and 69 patients had hypertensive heart disease (HHD). STE continuously tracked annular motion throughout the cardiac cycle in the apical 4- and 2-chamber views. RESULTS: In all participants, the curvilinear relationship was found between STE-derived MAD and LVEF (R(2)=0.642). The strong correlation between STE-derived MAD and LVEF was also found in the patients with IHD (R(2)=0.733, p=0.001) and in those with DCM (R(2)=0.614, p=0.008). However, such a correlation was not found in the patients with HCM, VHD, or HHD. CONCLUSION: The specificity in the correlation between STE-derived MAD and LVEF was found in patients with each heart disease, which should be taken into account when assessing these parameters.