LV fractional shortening and ejection fraction were selected as a marker for systolic function. LV end-diastolic (LV-EDD) and end-systolic (LV-ESD) dimensions were measured using M-mode from parasternal long axis view and thus LV fractional shortening were calculated by the traditional formula: Fractional shortening (%)?=?[LV-EDD???LV-ESD]/LV-EDD%. LV end-diastolic (LV-EDV) and end-systolic (LV-ESV) volumes were measured by 2D biplane modified Simpson?s method and then ejection fraction was calculated by the formula: Ejection fraction?=?[LV-EDV?LV-ESV]/LV-EDV. Transmitral E/A ratio was defined by pulsed wave Doppler and used as a marker of LV diastolic function.

Mitral regurgitation was defined by colour Doppler and graded according to the maximum regurgitant jet area as mild (jet area <4?cm²), moderate (jet area 4?8?cm²), and severe (jet area >8?cm²) [¹²]

Maximum LAD was measured at three planes: antero-posterior from parasternal long axis view, medial-lateral and superior-inferior from apical four-chamber view. Then mean LAD (mean LAD) was defined as the average of the three LAD (See Fig.?1)

LA mass was calculated with the same formula applied for left ventricular mass [¹³] {(mean LAD?+?anterior LA wall?+?posterior LA wall)³???mean LAD³}???0.8?+?0.6. Thickness of anterior and posterior LA walls was measured from parasternal long axis view. Zooming was used to discriminate between posterior LA wall and pericardium (See Fig.?2)

LAV was assessed according to the formula [⁶] 8/3???L???A_1???A₂ where (L) is the LA longitudinal axis and (A₁) is LA area at apical four-chamber and (A₂) at apical two-chamber views. (L) was defined as the perpendicular line from mid point of the mitral valve plane to the tip of LA apex (See Fig.?3). LA area was obtained by manual tracing of LA endocardial border excluding LA appendage and the pulmonary veins when visualized. The superior border of atrial outline was a straight line connecting both sides of the leaflet base attachment points. LAV was calculated at three phases of ventricular cardiac cycle: maximum LAV (V_max) at the end-systole just before mitral valve opening, minimum LAV (V_min) at end-diastole just before mitral valve closure, and LAV before atrial contraction (V_Pre-A): the last frame before mitral valve reopening. From the three LAV, the following measurements were selected as indices of LA function and calculated according to previous studies [¹⁴, ¹⁵]:

(1) Total Atrial Stroke Volume (TA-SV) defined as V_max???V_min, 2) Total Atrial Emptying Fraction (TA-EF) defined as TA-SV/V_max???100%, 3) Active Atrial Stroke Volume (AA-SV) defined as V_Pre?A???V_min, 4) Active Atrial Emptying Fraction (AA-EF) defined as AA-SV/V_{Pre A}???100%, 5) Atrial Expansion Index (AEI) defined as TA-SV/V_min???100%, 6) Passive Atrial Stroke Volume (PA-SV) defined as V_max???V_{Pre A}, and 7) Passive Atrial Emptying Fraction (PA-EF) defined as (V_max???V_{Pre A})/V_max???100%.

LA-KE [¹⁶] was calculated according to the formula ????AA-SV???P???V², where P?=?1.06?g?cm^?3 (blood density), and (V) is the peak velocity of transmitral A wave was measured by pulsed wave Doppler.

To characterize the three phases of LA activity, PA-SV and PA-EF were defined as indices for LA conduit function, AA-SV, AA-EF, and LA-KE for LA pump function, and AEI for LA reservoir function.

Both HCM patient group and controls were comparable with respect to age and sex distribution. All patients and controls were in sinus rhythm (mean heart rate 72???13 beat per minute) and had normal LV systolic function. All HCM patients had type I diastolic dysfunction (increased A velocity, with an E/A ratio <1) [¹⁷]. Twenty patients (80%) were under medications (10 patients under Verapamil, six under ?-blockers, four under Amiodarone). LV-ESD and LV-ESV were significantly smaller in HCM patients than controls, while LV-EDD and LV-EDV showed no difference. LV-FS and LV-EF were significantly higher in HCM patients than controls (P?=?0.001). HCM patients had a higher mean transmitral peak A velocity (61.5???20.3 vs. 39.7???9.9?cm/s, P?<?0.01). The prevalence and severity of mitral regurgitation were significantly higher in HCM patients compared to controls as 80% of HCM patients had mitral regurgitation (60% mild and 20% moderate to severe), while 20% of controls had mild mitral regurgitation (P?<?0.0001). Both HCM patient subgroups (obstructive and non-obstructive) showed no significant differences in LV dimensions, volumes and function. Also, no significant difference in the prevalence and severity of mitral regurgitation was present.

The maximum LAD at the three planes and the mean LAD were significantly larger in HCM patients than controls (P?<?0.001). Thickness of anterior and posterior LA walls showed no significant differences between HCM patients and controls. LA mass was significantly higher in HCM patients than controls (89.8???37.2 vs. 32.3???12.0?g, P?<?0.0001). No significant differences were found between HCM patient subgroups in the mean LAD, wall thickness and LA mass.

LAV at the three phases of cardiac cycle (V_max, V_min, and V_Pre-A) was significantly higher in both HCM patient subgroups than control group. TA-SV, TA-EF showed no significant differences between both HCM patient subgroups and control group. V_max was well correlated with the mean LAD (r?=?0.89, P?<?0.0001).

AA-EF showed no significant differences between both HCM patient subgroups and control group, while AA-SV was significantly higher in both HCM patient subgroups than control group (12.0???6.2?ml, 11.4???6.5?ml vs. 7.3???4.0?ml, P?<?0.001). No significant differences were found between HCM patient subgroups in AA-EF and AA-SV. LA-KE was significantly higher in HCM patients than controls (24.3???18.9 vs. 11.9???7.4?kdynes?cm, P?=?0.002). LA-KE was significantly higher in obstructive HCM patients than non-obstructive patients (32.5???23.3 vs. 18.3???12.5?kdynes?cm, P?<?0.001).

PA-SV was significantly increased in HCM patients than controls (18.9???9.2 vs. 13.4???5.7?ml, P?=?0.01). PA-SV was significantly higher in non-obstructive HCM patients than controls (20.0???8.8 vs. 13.4???5.7?ml, P?=?0.02), while in obstructive HCM patients; it was comparable to controls (17.5???9.8 vs.13.4???5.7?ml). PA-EF showed no significant difference between HCM patients and controls. PA-EF was significantly lower in obstructive HCM patients than controls (27.1???7.0 vs. 33.9???10.1, P?=?0.02), while in non-obstructive HCM patients; it was comparable to controls (34.0???14.8 vs. 33.9???10.1).

AEI showed no significant difference between HCM patients and controls. AEI was comparable in non-obstructive HCM patients and controls (134.8???74.4% vs. 141.7???74.0%, P=NS) but it was significantly lower in obstructive HCM patients than controls (91.1???39.7% vs. 141.7???74.0%, P?=?0.02).

The study had some limitations. The sample size of HCM patients (25 patients) is small but due to low prevalence of HCM (0.2%). The assessment of LA mass is a new idea not discussed before by any imaging modalities. Of course it needs validation by autopsy or magnetic resonance imaging but at least it can pave a way for thinking about in further studies either by the same or another formula. Assessment of diastolic dysfunction was relied on transmitral flow by pulsed wave Doppler and other parameters by tissue Doppler imaging were not available. There are no data about prognostic value of atrial remodelling as a predictor for development of atrial fibrillation because it need long time follow up for large sample of patients. However data from previous studies could be relied on [¹⁸, ¹⁹].

Abbreviations: FS fractional shortening, EF ejection fraction, and LAD left atrial diameter

Abbreviations: see text

^*P value between non-obstructive HCM patients and controls

^**P value between obstructive HCM patients and controls

^aP value?<?0.001 between obstructive and non-obstructive HCM patients