Abstract 19570: Diastolic Anterior Leaflet Tethering Contributes to Functional Mitral Stenosis after Restrictive Mitral Valve Annuloplasty

Introduction: Restrictive mitral valve annuloplasty (RMA) for secondary mitral regurgitation (MR) might cause functional (mitral) stenosis, yet underlying pathophysiological mechanisms remain debated. Hypothesis: Diastolic restriction of the anterior leaflet (AL) opening, due to papillary muscle tethering, plays a key role in the inflow obstruction after RMA. Increasing AL opening during exercise is associated with greater mitral valve area (MVA). Methods: Consecutive RMA patients (n=39, 63±11 years, 77% male) performed a symptom-limited (supine) bicycle exercise test with stepwise Doppler echocardiography and respiratory gas analysis. Diastolic AL opening angle (3-chamber view, Figure A), transmitral flow rate, mean transmitral gradient, and effective MVA were assessed at rest and during peak exercise. Results: At rest, effective MVA (1.5±0.4cm2) correlated moderately to the AL opening angle (68±10°) (r=0.4, p=0.014; Figure B). During exercise, effective MVA increased significantly to 2.0±0.5cm2 (p<0.001), with a stronger correlation to AL opening angle (r=0.6, p<0.001; Figure B). After stratification of the population into tertiles according to increase in AL opening angle during exercise (<=0°, 0-4° and >4° AL angle increase, respectively), a higher increase was significantly associated with greater effective MVA during exercise (p=0.013, Figure C). Patients with AL opening angle <69° at rest (median) and without dynamic AL angle increase of >4° (n=13) had a significantly lower maximal oxygen uptake compared to patients with AL opening angle at rest above the median or a greater dynamic AL angle increase with exercise (n=22) (VO2max 12.5±2.8 versus 16.4±4.7 mL/kg/min, p=0.005). Conclusions: Diastolic restriction of AL opening plays a key role in functional mitral stenosis after RMA for secondary MR. Increasing AL opening at rest, or better AL opening reserve during exercise, are associated with higher MVA and improved exercise capacity.

Human muscle net K+ release during exercise is unaffected by elevated anaerobic metabolism, but reduced after prolonged acclimatization to 4,100 m

It was investigated whether skeletal muscle K+ release is linked to the degree of anaerobic energy production. Six subjects performed an incremental bicycle exercise test in normoxic and hypoxic conditions prior to and after 2 and 8 wk of acclimatization to 4,100 m. The highest workload completed by all subjects in all trials was 260 W. With acute hypoxic exposure prior to acclimatization, venous plasma [K+] was lower ( P < 0.05) in normoxia (4.9 ± 0.1 mM) than hypoxia (5.2 ± 0.2 mM) at 260 W, but similar at exhaustion, which occurred at 400 ± 9 W and 307 ± 7 W ( P < 0.05), respectively. At the same absolute exercise intensity, leg net K+ release was unaffected by hypoxic exposure independent of acclimatization. After 8 wk of acclimatization, no difference existed in venous plasma [K+] between the normoxic and hypoxic trial, either at submaximal intensities or at exhaustion (360 ± 14 W vs. 313 ± 8 W; P < 0.05). At the same absolute exercise intensity, leg net K+ release was less ( P < 0.001) than prior to acclimatization and reached negative values in both hypoxic and normoxic conditions after acclimatization. Moreover, the reduction in plasma volume during exercise relative to rest was less ( P < 0.01) in normoxic than hypoxic conditions, irrespective of the degree of acclimatization (at 260 W prior to acclimatization: −4.9 ± 0.8% in normoxia and −10.0 ± 0.4% in hypoxia). It is concluded that leg net K+ release is unrelated to anaerobic energy production and that acclimatization reduces leg net K+ release during exercise.