Sympathetic overactivity in patients with pulmonary stenosis and improvement after percutaneous balloon valvuloplasty.

OBJECTIVE: Percutaneous balloon valvulotomy (PBV) is the procedure of choice for the treatment of valvular pulmonary stenosis (PS) with similar results comparable to surgical valvotomy but less invasive. METHODS AND RESULTS: Twenty-seven consecutive patients with PS being evaluated for PBV were enrolled in the study. Peak instantaneous transvalvular gradient, right ventricle (RV) diameter, mean atrial pressures, RV systolic pressure (RVSP), pro-brain natriuretic peptide (proBNP) levels significantly decreased immediately after PBV. Regarding heart rate variability (HRV) parameters, mean HR (heart rate), LF (low frequency) day and night, LF/HF day and night significantly decreased and standard deviation of all NN intervals (SDNN), root mean square of successive differences (RMSSD), P number of NN intervals that differed by more than 50 ms from adjacent interval divided by the total number of all NN intervals (PNN50), HF (High frequency) day and night significantly increased 1 day after PBV and these changes were shown to be preserved at the first month. The increase in SDNN was correlated with the decrease in right atrial pressure (RAP) (r =-0.5, P = 0.04); the increase in standard deviation of the 5-minute mean RR intervals (SDANN) was correlated with the decrease in proBNP (r =-0.4, P = 0.03). CONCLUSIONS: Sympathetic overactivity and increased proBNP levels were associated with the symptomatic status of patients with PS. Associated with a decrease in atrial pressures and proBNP levels, PBV yielded a decrease in adrenergic overactivity in the patients with PS.

Effects of cigarette smoking on heart rate variability and plasma N-terminal pro-B-type natriuretic peptide in healthy subjects: is there the relationship between both markers?

BACKGROUND: Cigarette smoking increased the risk of acute cardiac events related with endothelial dysfunction and increased sympathetic activity. Impaired autonomic nervous activity is recognized as a considerable symptom of cardiac dysfunction and is strongly associated with increased risk overall mortality. METHODS: A total of 75 healthy habitual smokers (40 female, 35 male, mean age 36.5 +/- 8.5 years), and 73 non-smokers subjects (45 female, 28 male, mean age 34.6 +/- 7.2 years) were studied. LF and LF/HF ratio were significantly higher in smokers than in non-smokers. On the contrary, SDNN, SDANN, RMSSD, and HF values were lower in smokers compared to those in non-smokers. Not the duration of smoking but the number of cigarettes smoked per day was correlated with the HRV parameters and NT-pro BNP. Furthermore, the average levels of NT-pro BNP were found to be positively correlated with LF, LF/HF and inversely correlated with SDNN, SDANN, RMSSD and HF. RESULTS: As a result, smoking impaires sympathovagal balance and decreases the heart rate variability in healthy subjects. And even a one cigarette smoking leads to overt sympathetic excitation. Furthermore, smoking results in an increase in NT-proBNP levels and the changes in adrenergic nervous system and NT-proBNP levels are well correlated. CONCLUSION: These findings could contribute to the higher rate of cardiovascular events in smokers.

Evaluation of serum levels of solubilized adhesion molecules in patients with aortocoronary saphenous vein grafts.

OBJECTIVE: To assess the diagnostic importance of serum-solubilized adhesion molecules, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, sE-selectin and sP-selectin in aortocoronary saphenous vein graft disease. METHODS: The study population was composed of two groups consisting of 41 patients with saphenous vein graft stenosis (stenosis group) and 43 patients without saphenous vein graft stenosis (no-stenosis group) based on the results of coronary angiography. All patients underwent coronary artery bypass graft operation involving the use of at least one saphenous vein graft for bypass. At the time of cardiac catheterization, it had been more than 1 year since the operation. RESULTS: Serum level of sP-selectin was significantly higher in the stenosis group than in the no-stenosis group (72.9+/-21.7 versus 48.7+/-18.6 ng/ml, P<0.001). No differences were found between the two groups with respect to serum levels of sE-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Multivariate analysis revealed that only serum levels of sP-selectin, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were independently correlated with the stenosis of saphenous vein grafts. A cutoff value of serum sP-selectin >57.5 ng/ml yields a specificity of 79.5%, a sensitivity of 73.3% and a positive predictive value of 80.5% for saphenous vein graft stenosis. CONCLUSION: In this study, sP-selectin level was found to be significantly higher in the group that had late aortocoronary saphenous vein bypass graft disease. This result suggests that platelet activation may play a causal role in late graft disease.

Fistulous connection between internal mammary graft and pulmonary vasculature after coronary artery bypass grafting: a rare cause of continuous murmur.

A 58-year-old male who had undergone coronary artery bypass grafting (CABG) using left internal mammary artery and a sequential saphenous vein graft 2 years ago presented with new onset angina. His initial physical examination revealed an unexpected continuous murmur over the left sternal border, and two-dimensional echocardiography has failed to identy the cause. Cardiac catheterization then performed and revealed patent left internal mammary artery and saphenous vein grafts. Besides, selective injection of the left internal mammary artery graft also showed a fistula formation between left internal mammary artery graft and pulmonary vasculature of the left upper lobe. He was managed conservatively because of the severely diseased left anterior descending artery distal to internal mammary artery anastomosis and low pulmonary artery pressure. The development of fistulous connection between internal mammary artery and pulmonary vasculature is an extremely rare complication following CABG. Patients with such fistulae usually present with chest pain due to coronary steal syndrome. A new heart sound, especially a continuous murmur, may be detected during physical examination. Surgical correction is indicated in the event of refractory angina, growing fistula causing heart failure or endarteritis. Otherwise, a conservative approach with instruction of the patient for prophylactic precautions of subacute bacterial endocarditis may be recommended for asymptomatic patients.

Relationship between myocardial viability and the predischarge electrocardiographic pattern in patients with first anterior wall acute myocardial infarction.

BACKGROUND: The assessment of residual viability in the infarcted area after an acute myocardial infarction is relevant to subsequent management and prognosis. OBJECTIVE: The aim of this study was to investigate the correlation between myocardial viability after an acute anterior myocardial infarction (AMI) as assessed by low dose dobutamine stress echocardiography (LDDSE) and the electrocardiographic patterns of ST segment and T wave abnormalities at the end of the first week of the acute event. METHODS: Sixty-nine consecutive patients (51 men, 18 women, mean age+/-standard deviation=57+/-11 years) who admitted to our clinic due to a first episode of transmural AMI were included in this study. Two-dimensional echocardiography was performed to all patients during rest and low dose dobutamine administration at the end of the first week of admission (7+/-2 days). Patients were classified into four groups according to ST segment and T wave morphology: group A, ST elevation < or =0.1 mV and negative T waves; group B, ST elevation < or =0.1 mV and positive T waves; group C, ST elevation > or =0.1 mV and negative T waves and group D, ST elevation > or =0.1 mV and positive T waves. RESULTS: Myocardial viability was detected more often in patients with isoelectric ST segments (22/24, 92%) than those with elevated ST segments (21/45, 47%) (P<0.001). Similarly patients with negative T waves had myocardial viability more frequently compared to those with positive T waves (32/45, 71% vs. 11/24, 46%, P<0.01). Seventeen (94%) of 18 patients in group A and 5 (83%) of six patients in group B had viable myocardium (P>0.05). Myocardial viability was found in 15 (56%) of 27 patients in group C and six (33%) of 18 patients in group D (P<0.01). As a marker of viable myocardium, isoelectricity of ST segment was specific (92%) but only moderately sensitive (51%), with a 92% positive predictive accuracy and a poor (53%) negative predictive value. T wave negativity was less specific but more sensitive than isoelectricity of ST segment for myocardial viability. CONCLUSION: The presence of isoelectric ST segment and negative T wave indicates a high probability of myocardial viability. However, absence of these electrocardiographic patterns does not exclude the presence of viable myocardium.

The role of valvular and thoracic aortic calcifications in distinction between ischemic and nonischemic cardiomyopathy.

Determination of underlying etiology in patients with dilated and globally hypokinetic left ventricles may sometimes be difficult even after detailed history and complete clinical evaluation. Cardiac valvular and thoracic aortic calcifications have previously been reported to be used as a window to diffuse atherosclerosis of the vascular system. The authors prospectively examined the predictive value of mitral annular calcification (MAC), aortic valve calcification (AVC), and thoracic aortic calcification (TAC) in diagnosis of coronary artery disease as the underlying cause of diffuse left ventricular dilatation and systolic dysfunction. The study included 98 consecutive patients (male/female = 76/22, mean age = 58.9 +/- 10.7 years, range: 33 to 75 years) over the age of 30 years admitted to their clinics between October 1999 and December 2001 with signs and symptoms of congestive heart failure associated with documented cardiomegaly. Transthoracic echocardiography and coronary angiography were performed in all patients for the evaluation of valvular calcifications and coronary status. Although there was no significant difference between the groups with and without coronary artery stenosis (CAS), with regard to presence of MAC, patients with CAS tended to have MAC more frequently (12/61, 20% vs 4/37, 11%, p > 0.05). AVC and TAC were found to be significantly more frequent in patients with CAS compared to those without CAS (AVC, 35/61, 57% vs 4/37, 11%, p < 0.001 and TAC, 28/61, 46% vs 2/37, 5%, p < 0.001). While all 3 calcifications had sensitivity under 60%, and specificity and positive predictive value over 75% individually, the presence of any of them had a sensitivity of 80%, specificity of 86%, positive predictive value of 91%, and negative predictive value of 73%. Thus the presence of any of these calcifications distinguished patients with coronary artery disease with a sensitivity of 80% and specificity of 86%. The presence of aortic valvular valve and thoracic aortic calcifications seems to be associated with significant coronary arterial stenosis; however, with relatively low negative predictive values these cannot be used in clinical practice for diagnosis of underlying coronary artery disease in patients with dilated left ventricles and impaired systolic functions.

Double mitral valve imaging.

Double-orifice mitral valve is an uncommon anomaly of the mitral valve with a single fibrous annulus with 2 orifices opening into the left ventricle. Three major types of this anomaly are recognized: (1) the eccentric or hole type (accounting for about 85%), (2) the central or bridge type (about 15%), and (3) duplicate mitral valve, which involves 2 mitral valve annuli and valves, each with its own set of leaflets, commissures, chordae, and papillary muscles. However, some echocardiographic artifacts also may lead to interesting appearances. The duplicating of cardiac valves by refraction of the ultrasound beam or mirror images has rarely been reported. The authors present the duplication of a moving mitral valve associated with an echocardiographic refraction artifact.

Assessment of the relationship between functional capacity and right ventricular ultrasound tissue characterization by integrated backscatter in patients with isolated mitral stenosis.

AIM: The aim of the present study was to investigate right ventricular (RV) myocardial textural properties in asymptomatic and symptomatic mitral stenosis (MS) patients with normal RV systolic function using integrated backscatter (IBS). METHODS: The study included 40 patients with MS of moderate or severe degree. Patients were classified into 2 groups according to NYHA class (asymptomatic group, NYHA class I, symptomatic group, NYHA class II-III). RV pulsed-wave tissue Doppler imaging (TDI) and IBS analyses were performed in all patients. Isovolumic contraction time (IVCT), systolic wave velocity (S), isovolumic relaxation time (IVRT), early diastolic wave velocity (E), and late diastolic wave velocity (A) were measured by TDI. IBS amplitude (IB) and cyclic variation (CV) of the RV lateral wall in the parasternal long-axis view were measured by IBS. CV was calculated by subtracting systolic IB from diastolic IB. RESULTS: IVRT (54.2 +/- 11.9 ms versus 86.2 +/- 16.2 ms, P < 0.001) and A wave amplitude (10.2 +/- 2.1 cm/s versus 13.6 +/- 1.8 cm/s, P < 0.05) were higher whereas E wave amplitude (11.7 +/- 1.6 cm/s and 10.3 +/- 1.5 cm/s, P < 0.05) and E/A ratio (1.3 +/- 0.3 versus 0.7 +/- 0.1, P < 0.001) were lower in group 2. Symptomatic patients had a lower CV value of RV (9.5 +/- 3.4 dB versus 6.7 +/- 1.9 dB, P = 0.004). There was a positive correlation between CV and E/A (r = 0.964, P < 0.001) CONCLUSION: Symptomatic isolated MS patients had RV echo texture changes and diastolic dysfunction in comparison to asymptomatic ones with similar mitral valve areas in the presence of normal RV systolic function. In isolated MS, both pulsed-wave TDI and IBS may aid in the detection of RV diastolic pathology.

Evaluation of the relationship between functional capacity and right ventricular diastolic function in patients with isolated mitral stenosis and sinus rhythm: a tissue Doppler study.

AIM: The right ventricular (RV) systolic function is an important determinant of clinical symptoms and exercise capacity in patients with mitral stenosis. No sufficient data are available concerning the effect of RV diastolic function on symptoms of patients with mitral stenosis. In the presence of normal RV systolic function, RV diastolic functions of asymptomatic patients with mitral stenosis of moderate or severe degree were compared to symptomatic ones by pulsed-wave tissue Doppler echocardiography in this study. MATERIALS AND METHODS: The study included 40 patients with mitral stenosis. Patients were classified into two groups according to New York Heart Association (NYHA) class (asymptomatic group NYHA class I, symptomatic group NYHA class II-III). RV diastolic functions were evaluated via pulsed-wave tissue Doppler in terms of isovolumic contraction time (IVCT), systolic wave velocity (S), isovolumic relaxation time (IVRT), early diastolic wave velocity (E'), and late diastolic wave velocity (A'). RESULTS: Statistical difference was not determined in systolic parameters (S, IVCT) between the two groups. However, IVRT (54.21 +/- 11.93 msec vs 86.19 +/- 16.23 msec, P < 0.0001) and A' wave amplitude (10.16 +/- 2.14 cm/sec vs 13.55 +/- 3.35 cm/sec, P < 0.0001) were higher whereas E' wave amplitude (11.68 +/- 1.60 cm/sec and 10.25 +/- 2.73 cm/sec, P = 0.009) and E'/A' ratio (1.18 +/- 0.23 vs 0.76 +/- 0.17, P < 0.0001) were lower in group 2. CONCLUSION: In isolated mitral stenosis, pulsed-wave tissue Doppler may be used for the detection of RV diastolic pathology. Diastolic functions of RV may deteriorate in the presence of normal systolic functions in symptomatic patients with isolated mitral stenosis.

Evaluation of effects of intra aortic balloon counterpulsation on autonomic nervous system functions by heart rate variability analysis.

BACKGROUND: In patients with acute myocardial infarction (AMI), intraaortic balloon counterpulsation (IABC) may improve cardiac performance, decrease the incidence of recurrent ischemia, and improve survival. Although there have been several reports concerning circulatory maintenance with the IABC, response of the autonomic nervous system to these hemodynamic changes is not clear. Heart rate variability (HRV) analysis has been extensively used to evaluate autonomic modulation of sinus node and to identify patients at risk for an increased cardiac mortality. In this study, we evaluated effects of the IABC on autonomic nervous system functions by HRV analysis. METHODS: The study group was composed of 32 consecutive patients (13 female, 19 male aged 61.8 +/- 8.8 years) undergoing IABC. Transthoracic echocardiography and 1-hour Holter recordings for HRV analysis in each IAB pumping mode were obtained. RESULTS: The IABC improved left ventricular diastolic and systolic functions as well as caused an increase in SDNN1, PNN50(1), RMSSD1, and HF1 and a decrease in LF1, LF/HF1, mean heart rate, and the number of ventricular extrasystoles. The improvements in HRV parameters were correlated with some hemodynamic changes such as the increase in MAP and CO during counterpulsation. The only independent factors affecting in-hospital mortality were the change in LF/HF1 ratio (DeltaLF/HF1) and the change in the number of ventricular extrasystole (DeltaVES). The decrease in LF/HF1 > or = 4.9 decreased the mortality by 1.7-folds (RR = 0.6, P = 0.04, 95% CI: 0.1-2.3). The decrease in VES > or = 27/15 minutes resulted in mortality reduction by 16-folds (RR = 0.06, P = 0.02, 95% CI: 0.01-0.4). CONCLUSIONS: As a result, the IABC, especially in 1:1 support, causes an increase in HRV, decrease in sympathetic overactivity, and improvement in sympathovagal balance besides the favorable hemodynamic changes, and these electrophysiologic changes may explain the role of the IABC in the treatment of ventricular arrhythmias.

Electrocardiographic changes after coronary artery surgery.

The electrocardiographic changes early after uncomplicated coronary artery bypass with complete revascularization were examined preoperatively and on the 1st and 3rd postoperative days in 53 patients. Heart rate, PR index, corrected PR interval, corrected P dispersion, corrected duration of QRS complex, corrected QT dispersion, corrected QT interval, rhythm, QRS axis, ST-segment changes, and blocks were determined. Changes in new parameters obtained by different combinations of R, S, and T waves were also studied. On the 1st postoperative day, atrial fibrillation was significantly less prevalent, right bundle branch block increased significantly, and QRS axis was significantly more positive but returned to baseline on the 3rd postoperative day. Postoperative heart rate and PR index were significantly higher than preoperative values. In the postoperative period, corrected PR interval was significantly lower, corrected QRS complex duration was significantly shorter, corrected QT interval was significantly longer, and corrected QT dispersion showed a significant increase on the 1st postoperative day. This study defines electrocardiographic changes in uncomplicated patients with complete revascularization. Any deviations from these findings may alert us to the need for further evaluation of an undesired event.

Relation between sympathetic overactivity and left atrial spontaneous echo contrast in patients with mitral stenosis and sinus rhythm.

BACKGROUND: Spontaneous echo contrast (SEC) is common in patients with mitral stenosis (MS) and presence of SEC in left atrium (LA) is associated with a higher risk of thromboembolism. Recently, an increase in activation of platelets was demonstrated in patients with SEC raising the hypothesis that platelets are involved in the pathogenesis of SEC. In this study, we evaluated effects of autonomic nervous system activity on SEC formation in patients with rheumatic MS and sinus rhythm by heart rate variability analysis. METHODS AND RESULTS: Twenty-six patients with LASEC were compared with 28 patients without LASEC. Mean heart rate, low frequency (LF) and low frequency/high frequency (LF/HF) ratio were significantly higher, standard deviation of all NN (SDNN), root mean square of successive differences (RMSSD), number of NN intervals that differed by more than 50 ms from adjacent interval divided by the total number of all NN intervals (PNN50) and high frequency (HF) values were lower in the patients with LASEC. A standard deviation of all NN intervals <90ms separated the patients with LASEC from control subjects with a sensitivity of 77% and specificity of 90%; a low frequency >79.5 with a sensitivity of 92% and specificity of 90; a low frequency/high frequency ratio >3.7 with a sensitivity of 96% and specificity of 90%. A left atrial diameter >4.3 cm increased the LASEC formation by 3.0 folds, HR >78 beats/min by 6.4 folds, standard deviation of all NN intervals <90 ms by 9.2 folds, a low frequency/high frequency ratio >3.7 by 6.4 folds, sP-selectin>142 by 5.8 folds. Variables affecting sP-selectin levels were LA diameter, mitral valve area, transmitral mean gradient, left ventricular ejection fraction, the presence of mitral regurgitation, HR, standard deviation of all NN intervals, low frequency, high frequency and low frequency/high frequency ratio. CONCLUSION: Sympathetic overactivity and reduced heart rate variability are important determinants for LASEC formation and increased s-P selectin levels. Therefore, platelet activation via increased sympathetic activity may play an important role in pathogenesis of LASEC.

Right bundle branch block: a new parameter revealing the progression rate of mitral stenosis.

BACKGROUND: Mitral stenosis has a generally slow but often variable clinical course. However, the factors that influence the rate of stenosis progression have not been completely identified. The aim of this study was to evaluate whether right bundle branch block (RBBB) may be related to the rapid progression of pure mitral stenosis besides echocardiographic parameters. METHODS: Four hundred and thirty-six patients (300 females) were reviewed retrospectively. The patients were classified according to RBBB existence in electrocardiography: group A included 83 patients with RBBB existence, and group B contained 353 patients without RBBB. The patients were further classified as subjects who had an echocardiographic valve score < or =8 (325 patients, group 1) and those with a valve score >8 (111 patients, group 2). RESULTS: The mean age of the patients was similar in groups A and B. In group A, the mean mitral valve gradient was higher (12.63 +/- 4.43 vs. 10.58 +/- 3.37 mm Hg; p < 0.0001), the mitral valve area smaller (1.05 +/- 0.2 vs. 1.14 +/- 0.52 cm2; p = 0.011), and the systolic pulmonary artery pressure higher (53.5 +/- 16.2 vs. 46.9 +/- 13.2 mm Hg; p = 0.001) than in group B. The mean age and mitral valve area were similar in groups 1 and 2. The mean mitral valve gradient (10.5 +/- 3.7 vs. 12.3 +/- 3.0 mm Hg; p < 0.0001) and systolic pulmonary artery pressure were higher in group 2 (46.7 +/- 13.3 vs. 52.5 +/- 15 mm Hg; p < 0.0001). CONCLUSION: These findings indicate that RBBB existence correlates with the severity of the disease and the grade of valve calcification in moderate and severe pure mitral stenosis.

Aortic dissection with diastolic prolapse of intimal flap into left ventricle.

Ascending aortic dissection is often a catastrophic condition. Dissection into the commissures or into an aortic valve leaflet may lead to leaflet avulsion and valvular insufficiency due to a flail valve. We present an image report describing an important and life-threatening complication due to the movement of a partially dehisced intimal aortic flap into the left ventricle causing aortic valve insufficiency in a patient with acute dissection of the ascending aorta.

Evaluation of the early hemodynamic changes in carotid arteries during ventricular and dual chamber pacing.

In spite of a wide choice of pacemakers, there are some problems in making more rational clinical decisions for individual patients since mode selection and programming is usually performed on the basis of a clinical hunch. The aim of this study was to measure the differences in carotid flow in patients with a pacemaker programmed in the dual chamber and in the single chamber pacing modes. Sixty patients with implanted bipolar DDD pacemakers were enrolled in this study. Blood peak systolic velocity (PSV) and end-diastolic velocity (EDV), cross-sectional area, resistive index (RI), and pulsatility index (PI) were measured in the common (CCA), internal (ICA), and external (ECA) carotid arteries before pacemaker implantation and after dual chamber and ventricular pacing at 60 beats/min. PSVs in the left CCA (79.3 +/- 24.9 cm/s) and right CCA (84.1 +/- 18.7) were shown to significantly decrease after VVI pacing (60.1 +/- 16.6 and 62.1 +/- 20.0, respectively). There was also a similar significant decrease in PSV in the left and right ICAs and ECAs. Besides PSV, RI, and PI in the left and right CCAs, ICAs, and ECAs significantly decreased after VVI pacing. There was no similar decrease after DDD pacing. Cross-sectional area and flow volume in the CCA, ICA, and ECA were similar after DDD and VVI pacing and before pacemaker implantation suggesting that cardiac output was similar when the measurements were recorded. Carotid artery PSVs, pulsatility, and RIs were found to be significantly decreased during VVI pacing compared to baseline and DDD pacing. The greater incidence of adverse cerebral outcomes in patients with VVI rather than DDD pacing may be partly due to decreased carotid PSVs.

Sympathetic overactivity in patients with rheumatic mitral stenosis.

BACKGROUND: Mitral stenosis may increase sympathetic nervous activity by increasing left atrial pressure and reducing cardiac output. And elevated sympathetic nerve activity may be a risk factor for the development of clinical manifestations of mitral stenosis. In this study, we assessed the autonomic nervous system activity in patients with mitral stenosis by heart rate variability analysis and defined factors affecting autonomic functions. METHODS AND RESULTS: Fifty-four patients with rheumatic mitral stenosis were compared with an age- and gender-matched control group composed of 42 healthy individuals. SDNN, RMSSD, PNN50, and HF were lower; mean heart rate (HR), LF and LF/HF ratio were higher in the patients with mitral stenosis compared to the control group. SDNN was correlated positively with left ventricle ejection fraction (LVEF), negatively with mitral valve area, left atrial (LA) diameter, and duration of symptoms. RMSSD was correlated positively with mean transmitral gradient, negatively correlated with age; PNN50 was correlated negatively with mitral valve area and positively correlated with transmitral gradient. LF was positively and HF was negatively correlated with LA diameter; LF was correlated positively, and HF was negatively correlated with duration of symptoms. LF/HF ratio was positively correlated with LA diameter and duration of symptoms, negatively with LVEF and mean valve area. CONCLUSION: As a result, sympathetic nervous system activity is increased in patients with mitral stenosis and sympathetic overactivity worsens their symptoms. Most significant factors that affect autonomic functions in these patients are left atrial dilatation and mitral valve area.