We studied 85 patients (mean age 60±11 years, 75% female) with HFpEF (LVEF ≥45%) and New York Heart Association (NYHA) functional class I–III. Based on the mean normal value of MAPSE derived from previous studies, patients were classified as having HFpEF with impaired MAPSE (≤1.2 cm, n=42), or with normal MAPSE (>1.2 cm, n=43).19,20

Patients were referred to the Service of Cardiology, Internal Medicine Clinic, University Clinical Centre of Kosovo, between February 2013 and November 2013. At the time of the study all patients were on conventional medical treatment, optimized at least two weeks prior to enrollment, based on symptoms and renal function: 76% were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, 58% beta-blockers, 34% diuretics, 66% aspirin and 20% calcium channel blockers. Patients with clinical evidence of cardiac decompensation, limited physical activity due to factors other than cardiac symptoms (e.g. arthritis), stage >2 chronic renal failure (glomerular filtration rate ≤89 ml/min), chronic obstructive pulmonary disease (COPD) or recent acute coronary syndrome, stroke or anemia, were excluded. Patients gave written informed consent to participate in the study, which was approved by the local Ethics Committee.

Detailed history and clinical assessment were obtained in all patients, and routine biochemical tests were also performed including lipid profile, blood glucose level, and kidney function tests. Body mass index was calculated from weight and height measurements. Waist and hip measurements were also recorded and waist/hip ratio calculated.

A single operator performed all echocardiographic examinations using a Philips iE33 system with a multi-frequency transducer, and harmonic imaging as appropriate. Images were obtained with the patient in left lateral decubitus position and during quiet expiration. LV end-systolic and end-diastolic dimension (LVESD and LVEDD) were measured in left parasternal long-axis view with the M-mode cursor positioned by the tips of the mitral valve leaflets. LV volumes and ejection fraction (EF) were calculated from apical 2- and 4-chamber views using the modified Simpson's method. MAPSE and tricuspid annular plane systolic excursion (TAPSE) were assessed by placing the M-mode cursor at the lateral and septal angles of the mitral annulus and the lateral angle of the tricuspid annulus.

Total amplitude of long-axis motion (MAPSE or TAPSE) was measured as previously described21 from peak inward to peak outward points. LV and right ventricular (RV) long-axis myocardial velocities were also assessed using Doppler myocardial imaging. From apical 4-chamber view, longitudinal velocities were recorded with the pulsed wave Doppler sample volume placed at the basal part of the LV lateral and septal segments as well as the RV free wall. Systolic (s′) and early and late (e′ and a′) diastolic myocardial velocities were measured with the gain optimally adjusted. Mean lateral and septal LV velocities were calculated.

LV and RV diastolic function was assessed from filling velocities using spectral pulsed wave Doppler with the sample volume positioned at the tips of the mitral and tricuspid valve leaflets, respectively, during short breath-hold. Peak LV and RV early (E wave) and late (A wave) diastolic velocities were measured and E/A ratios were calculated. The E/e′ ratio was calculated as the ratio between the transmitral E wave and mean lateral and septal e′ wave velocities. Isovolumic relaxation time was also measured from aortic valve closure to mitral valve opening on pulsed wave Doppler recording. The LV filling pattern was considered restrictive when the E/A ratio was >2.0, E wave deceleration time <140 ms and the left atrium dilated more than 40 mm in transverse diameter.22

Mitral regurgitation severity was assessed by color and continuous wave Doppler and was graded as mild, moderate, or severe according to the jet area relative to that of the left atrium as well as the flow velocity profile, in line with the recommendations of the American Society of Echocardiography (ASE).23 Likewise, tricuspid regurgitation was assessed by color Doppler and continuous-wave Doppler. A retrograde transtricuspid pressure drop of >35 mmHg was taken as evidence of pulmonary hypertension.24 All M-mode and Doppler recordings were performed at a high speed of 100 mm/s with superimposed ECG (lead II).

LA diameter was measured from aortic root recordings with the M-mode cursor positioned at the level of the aortic valve leaflets. LA volumes were measured using the area-length method from apical 4- and 2-chamber views, according to the ASE guidelines.25 Left atrial maximum volume (LAVmax) was measured at LV end-systole, just before the opening of the mitral valve, LA minimum volume (LAVmin) was measured at end-diastole, immediately after closure of the mitral valve, and left atrial ejection fraction (LAEF) was calculated automatically.25,26

The time from the onset of the P wave on the ECG to the beginning of the A′ wave on TDI (PA′-TDI interval) was calculated from the lateral (PA′ lateral) and septal (PA′ septal) mitral annuli as well as the lateral tricuspid annulus (PA′ tricuspid) (Figure 1).10,11 Values for the PA′-TDI interval were averaged over three consecutive beats. The difference between PA′ lateral and PA′ septal was taken as the left atrial (LA) dyssynchrony. The difference between PA′ septal and PA′ tricuspid was taken as right atrial (RA) dyssynchrony and the difference between PA′ lateral and PA′ tricuspid as interatrial dyssynchrony.12,27

Figure 1.

Measurement of the time from the onset of the P wave on the ECG to the beginning of the A′ wave on tissue Doppler imaging (PA′-TDI interval).

(0.18MB).

Data are presented as mean ± SD or proportions (percentage of patients). Continuous data were compared with the two-tailed unpaired Student's t test and discrete data with the chi-square test. Correlations were tested with Pearson coefficients. A significant difference was defined as p<0.05 (two-tailed).

Patients were divided according to MAPSE into those with HFpEF and impaired MAPSE (≤1.2 cm), and those with HFpEF and normal MAPSE (>1.2 cm) were compared using the unpaired Student's t test.

Forty-three patients had normal longitudinal LV systolic function and the other 42 had reduced longitudinal function. Patients with reduced longitudinal LV systolic function (MAPSE ≤1.2 cm) were older (p<0.001) and had higher body surface area (BSA) (p=0.004). All other clinical and biochemical data did not differ between the groups (Table 2).

Patients with HFpEF and reduced MAPSE had higher LV mass index (p<0.001), thicker interventricular septum (p=0.003), larger LAVmin (p=0.007) and reduced LAEF (p<0.001) compared with normal MAPSE, but LA diameters and LV dimensions and volumes did not differ between groups. Patients with reduced MAPSE also had higher E/e′ ratio (p=0.002), reduced lateral and septal e′ (p=0.005 and p=0.006, respectively), and reduced TAPSE (r=0.40, p<0.001) and right e′ and tricuspid E (p=0.02 and p=0.03, respectively) compared to patients with normal MAPSE (Table 3).

Furthermore, tricuspid annulus electromechanical time (PA′ tricuspid) was longer (p=0.03), and RA dyssynchrony was increased (p=0.001), compared with patients with normal MAPSE. In contrast, LA dyssynchrony and interatrial asynchrony did not differ between groups (Table 4).

Of the biochemical and clinical findings only age (r=−0.34, p=0.003), NYHA class (r=−0.35, p=0.004), waist/hip ratio (r=−0.24, p=0.05) and BSA (r=0.33, p=0.004) correlated with MAPSE (Table 5).

MAPSE correlated with RA dyssynchrony (r=−0.40, p<0.0001, Figure 2), LV mass index (r=−0.56, <0.001), LVEDD (r=−0.22, p=0.04) and LVESD (r=−0.27, p=0.01), as well as with LAVmin (r=−0.22, p<0.001) and LAEF (r=0.44, p<0.001), but not with LA or interatrial dyssynchrony.

Figure 2.

Correlation between mitral annular plane systolic excursion and right atrial dyssynchrony. MAPSE: mitral annular plane systolic excursion; RA: right atrial.

(0.08MB).

MAPSE also showed significant correlation with TDI indices such as a′ wave (lateral a′, r=0.24, p=0.02 and septal a′, r=0.22, p=0.03, respectively) and e′ wave (lateral e′ and septal e′, r=0.26, p=0.01 for both). Among right ventricular echocardiographic indices, TAPSE (r=0.40, p<0.001), right e′ (r=0.22, p=0.03) and tricuspid E (r=0.28, p=0.009) also correlated with MAPSE (Table 5).

The authors declare that no experiments were performed on humans or animals for this study.

The authors declare that they have followed the protocols of their work center on the publication of patient data.

The authors declare that no patient data appear in this article.