Background
The influence of right ventricular (RV) function on exercise capacity has been poorly explored in mitral stenosis (MS). The objective of this study was to assess the determinants of functional status with exercise echocardiography in MS.
Methods
Thirty-nine patients (55 ± 12 years, 29 female) with MS (1.3 ± 0.5 cm 2 ) underwent an exercise echocardiography (14 patients had previous balloon valvuloplasty). RV function was assessed by tricuspid annulus S-wave velocity (Tric-S) and tricuspid annular plane systolic excursion (TAPSE).
Results
Tric-S correlated with TAPSE ( P = . 03), cardiac output ( P = . 006), and mitral valve area ( P = . 009). With exercise, Tric-S and TAPSE increased significantly (11.3 ± 3.1 cm/s to 15.5 ± 3.4 cm/s and 21.2 ± 5.2 mm to 24.0 ± 5.8 mm, respectively, both P < .05). TAPSE was lower in patients in New York Heart Association class 3 or 4. In multivariate analysis, Tric-S at rest (β = 0.34, P = . 006) and mitral Δ mean diastolic gradient (β = 0.34, P = . 006) were the independent determinants of maximum workload.
Conclusion
Resting RV longitudinal function assessed through Tric-S is an important determinant of functional capacity in MS.
Mitral stenosis (MS) management is based on the assessment of patients’ symptoms and the severity of hemodynamic obstruction assessed by mitral valve orifice area. In patients with severe stenosis, symptoms lead to invasive treatment. Symptomatic patients with mild obstruction or asymptomatic patients with severe obstruction are more challenging. In this setting, functional and physiopathologic consequences of mitral valve obstruction should be evaluated carefully not only at rest but also with exercise. Patients with objective functional impairment and an increase in mitral mean diastolic gradient (MDG) ≥ 15 mm Hg or an increase in pulmonary artery systolic pressure (PASP) ≥ 60 mm Hg during exercise echocardiography are considered for a mitral valve procedure. Nevertheless, these recommendations are based on limited studies. Percutaneous balloon valvuloplasty is an efficient therapy in patients with MS. However, some patients remain symptomatic despite effective balloon valvuloplasty. Therefore, understanding the reasons of functional impairment, beyond mitral MDG and PASP, in patients with a history of MS, could in turn improve the clinical-decision making process and therapeutic management.
Therefore, we aimed at analyzing the cardiac determinants of functional impairment assessed by New York Heart Association (NYHA) class and maximal workload with exercise echocardiography in patients with mitral valve stenosis (either native MS or after balloon valvuloplasty).
Materials and Methods
Study Patients
A total of 63 consecutive patients with a history of rheumatic MS (mitral valve area [MVA] ≤ 2.5 cm 2 ) were examined by echocardiography from August 2002 to October 2009. Twenty-two patients were excluded for the following reasons: previous surgical valve replacement, aortic regurgitation (AR) or mitral regurgitation (MR) greater than mild (effective regurgitant orifice area > 10 mm 2 for AR and > 20 mm 2 for MR), cardiac stimulator, chronic obstructive pulmonary disease, poor echocardiographic windows, known coronary artery disease, or left ventricle systolic dysfunction (left ventricle ejection fraction ≤ 45%). The 41 remaining patients underwent comprehensive rest and exercise echocardiography. Two of them with inducible myocardial ischemia during exercise echocardiography were subsequently excluded, and 39 patients were finally included in the present study. Patients were classified in NYHA class according to the worst NYHA status within 3 months before exercise. Exercise was delayed after medical improvement in patients in NYHA class 4. All patients gave informed consent. The study was approved by the ethics committee of our institution (University Hospital, Lille, France).
Echocardiographic Examination and Measurements
Two-dimensional images from parasternal long- and short-axis views, apical 2- and 4- chamber views, and Doppler data were obtained with a 2- to 4-Mhz probe interfaced to a commercially available echocardiograph (Sonos 5500, Hewlett-Packard, Palo Alto, CA; Vivid 7 System, GE Medical Systems, Horten, Norway). Left ventricular (LV) and right ventricular (RV) end-diastolic diameters were measured by M mode with the parasternal long-axis view. LV volumes and ejection fraction (EF) were assessed by the apical biplane Simpson disk method. Left atrial volume was assessed by the biplane area length method. Continuous-wave Doppler signal of mitral flow was used to assess mitral MDG by using a modified Bernoulli equation. MVA was measured with the continuity equation. Atrioventricular compliance was calculated as the ratio of MVA to mitral deceleration slope. Stroke volume was calculated as LV outflow tract area multiplied by the time velocity integral of the outflow tract, and the cardiac output was calculated as stroke volume multiplied by heart rate. The tricuspid peak pressure difference was estimated from the maximal tricuspid regurgitation using a modified Bernoulli equation. Noninvasive estimations of the right atrial pressure were based on the size and the collapse index of the inferior vena cava according to current recommendations. PASP was calculated as the sum of tricuspid peak pressure difference to estimated right atrial pressure. Pulmonary vascular resistance (PVR) was calculated as the corrected ratio of tricuspid peak pressure difference divided by RV outflow tract time velocity integral. Tricuspid annular plane systolic excursion (TAPSE) was measured with M mode in apical 4-chamber view (data available in 28/39 patients). Tissue Doppler images were acquired in apical 4-chamber view, with pulsed-Doppler sampling on the tricuspid annulus or basal segment of the RV free wall. Careful attention was taken to choose a high frame rate acquisition and to align the ultrasound beam parallel to the direction of wall motion. Echocardiography 2-dimensional and Doppler data obtained at rest and at peak exercise were stored on optical disk for off-line analysis. For each analysis, at least 3 consecutive cycles in sinus rhythm and 10 consecutive cycles in atrial fibrillation were averaged. All echocardiography data were collected by 2 experienced investigators (A.S.P. and T.L.T.), and these data were reviewed by the same physician (G.D.) blinded to clinical data. Intraobserver variability of exercise tricuspid annulus S-wave velocity (Tric-S) calculated as the average difference in 10 patients was 1.1 ± 0.5 cm/s.
Exercise Stress Echocardiography
A symptom-limited graded bicycle exercise test was performed until exhaustion in a semi-supine position with continuous 2-dimensional and Doppler echocardiography examination. Blood pressure and 12-lead electrocardiogram were recorded at rest and every 2 minutes during exercise and recovery periods. The exercise test was discontinued at exhaustion or if the following criteria were met: (1) target heart rate (≥85% of maximum predicted); (2) decrease in systolic blood pressure compared with baseline (≥20 mm Hg); (3) chest pain or dyspnea; and (4) significant arrhythmias. Patients received their routine medications (including beta-blockers) the morning of the study.
Statistical Analysis
Statistical analysis was performed using the Statistical Package for the Social Sciences Windows version 11.0 (SPSS Inc, Chicago, IL). Data were expressed as mean ± standard deviation or number and percentage. Comparisons between groups were performed by using the Student t test or chi-square test, as appropriate. Differences between rest and exercise results were assessed by a paired Student t test. To assess parameters associated with NYHA class (1-2 or 3-4), a multivariate logistic regression was performed. To assess parameters associated with maximal workload, univariate linear regression analyses were performed with Pearson’s correlation coefficient or Spearman’s rank-correlation test, as appropriate. Each variable with a P value ≤ .1 was entered in the stepwise linear multivariate regression analysis. Final multivariate linear regression analysis was performed with the Enter mode adjusted on age and gender. Variables included in the multivariate logistic or linear regression are shown in appropriate Tables in the Results section. A P value ≤ .05 was considered statistically significant.
Results
The study population comprised 39 patients (aged 55 ± 12 years, 29 female). Baseline characteristics are summarized in Table 1 . Twenty-five patients had MS without previous intervention (untreated MS group), and 14 patients had a history of percutaneous balloon valvuloplasty (treated MS group). Nine patients (23%) were in NYHA functional class I, 15 patients (38%) were in NYHA class II, 9 patients (23%) were in NYHA class III, and 6 patients (16%) were in NYHA class IV. The mean delay between balloon valvuloplasty and study enrollment averaged 20 ± 14 months in the treated MS group. MVA was less than 1.5 cm 2 in 2 of 14 patients in the treated MS group (1.35 cm 2 and 1.45 cm 2 ), and these patients presented the longer delay from valvuloplasty to study enrollment (41 and 37 months). Patients in the treated MS group had a lower NYHA class ( P = . 004) and a greater MVA ( P < .0001).
| Variables | Overall (n = 39) | Untreated MS (n = 25) | Treated MS (n = 14) | P |
|---|---|---|---|---|
| Female, n (%) | 29 (74) | 19 (76) | 10 (71) | .76 |
| Age, y | 55 ± 12 | 56 ± 12 | 52 ± 11 | .24 |
| Atrial fibrillation, n (%) | 15 (39) | 11 (44) | 4 (29) | .44 |
| NYHA class | 2.3 ± 1 | 2.6 ± 1 | 1.7 ± 0.7 | .004 |
| Max workload, Watts | 85 ± 25 | 79 ± 27 | 95 ± 19 | .07 |
| MVA, cm 2 | 1.3 ± 0.5 | 1.1 ± 0.4 | 1.7 ± 0.2 | <.0001 |
| Beta-blocker, n (%) | 15 (39) | 9 (36) | 6 (43) | .41 |
| Beta-blocker dose, % | 52 ± 25 | 58 ± 34 | 46 ± 10 | .41 |
Baseline Echocardiographic Characteristics
At rest, LV volumes and ejection fraction were normal ( Table 2 ). Mitral MDG correlated negatively with MVA ( P < .0001) and positively with PASP ( P < .001) and PVR ( P = . 04). Calculated atrioventricular compliance was 5.2 ± 3.1 mL/mm Hg (1.6-13.4 mL/mm Hg) and correlated positively with MVA ( P = . 005) and cardiac output ( P = . 002) and negatively with mitral MDG ( P = . 03) and exercise PASP ( P = . 05). RV diameter was 27 ± 5 mm (range: 19-36 mm). Tric-S ( Figures 1 and 2 ) averaged 11.3 ± 3.1 cm/s (4.0 to 17.3 cm/s), and PVR averaged 2.2 ± 0.9 Wood units (1.5-4.8 Wood units). Tric-S correlated with cardiac output ( P = . 006) and MVA ( P = . 009). TAPSE averaged 21.2 ± 5.2 mm (11-32 mm) and correlated weakly to Tric-S ( r = 0.40, P = . 05) and baseline heart rate ( r = −0.41, P = . 03).
| Whole population (n = 39) | |||
|---|---|---|---|
| Variables | Rest | Peak exercise | P |
| Heart rate, beats/min | 76 ± 16 | 140 ± 25 | <.0001 |
| Systolic blood pressure, mm Hg | 128 ± 16 | 149 ± 2 | <.0001 |
| LVEF,% | 59 ± 9 | 64 ± 14 | <.0001 |
| LV end-diastolic volume, mL | 86 ± 18 | 86 ± 30 | .9 |
| LV end-systolic volume, mL | 35 ± 12 | 27 ± 10 | .005 |
| Mitral MDG, mm Hg | 7.4 ± 3.9 | 21.0 ± 7.6 | <.0001 |
| Cardiac output, L/min | 4.5 ± 1.8 | 8.5 ± 3.5 | <.0001 |
| PASP, mm Hg | 39 ± 14 | 74 ± 20 | <.0001 |
| Tricuspid S-wave velocity, cm/s | 11.3 ± 3.1 | 15.5 ± 3.4 | <.0001 |
| TAPSE, mm | 21.2 ± 5.2 | 24.0 ± 5.8 | .01 |
| Variables | NYHA 1-2 (n = 24) | NYHA 3-4 (n = 15) | P |
|---|---|---|---|
| Clinical | |||
| Atrial fibrillation, n (%) | 24 (61) | 15 (39) | .005 |
| Rest | |||
| Mitral valve area, cm 2 | 1.46 ± 0.42 | 1.09 ± 0.55 | .03 |
| MDG, mm Hg | 6.3 ± 2.8 | 9.1 ± 4.7 | .03 |
| Left atrial volume, mL | 108 ± 40 | 163 ± 148 | .15 |
| Pulmonary vascular resistance, Wood Units | 1.8 ± 0.2 | 3.2 ± 1.0 | .001 |
| PASP, mm Hg | 35 ± 10 | 44 ± 18 | .05 |
| Tricuspid S-wave velocity, cm/s | 11.8 ± 2.7 | 10.4 ± 3.5 | .17 |
| TAPSE, mm | 22 ± 5 | 18 ± 6 | .04 |
| Peak exercise | |||
| Mitral Δ MDG,% | 251 ± 132 | 146 ± 92 | .011 |
| PASP, mm Hg | 68 ± 18 | 84 ± 19 | .012 |
| Max workload, Watts | 91 ± 26 | 76 ± 23 | .071 |
| Univariate | Multivariate | |||
|---|---|---|---|---|
| Variables | R | P | β | P |
| Rest | ||||
| Cardiac output | 0.39 | .015 | ||
| Mitral valve area | 0.36 | .03 | ||
| Atrioventricular compliance | 0.31 | .08 | ||
| Tricuspid S-wave velocity | 0.52 | .001 | 0.34 | .006 |
| PASP | −0.38 | .02 | ||
| Peak exercise | ||||
| Mitral Δ MDG | 0.53 | .001 | 0.34 | .006 |
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