Date Published: July 30, 2019
Publisher: Public Library of Science
Author(s): Nicolaj Lyhne Christensen, Jordi Sanchez Dahl, Rasmus Carter-Storch, Kurt Jensen, Redi Pecini, Flemming Hald Steffensen, Eva Vad Søndergaard, Lars Melgaard Videbæk, Jacob Eifer Møller, Tim Lahm.
Aortic stenosis (AS) is a progressive disease in which left ventricular (LV) diastolic dysfunction is common. However, the association between diastolic dysfunction and right ventricular (RV) loading conditions and function has not been investigated in asymptomatic AS patients.
A total of 41 patients underwent right heart catheterization and simultaneous echocardiography at rest and during maximal supine exercise, stratified according to resting diastolic function. Cardiac chamber size and morphology was assessed using cardiac magnetic resonance imaging (cMRI). RV stroke work index, pulmonary artery (PA) compliance, PA elastance, PA pulsatility index, and right atrial pressure (RAP) were calculated at rest and maximal exercise. Ten patients (24%) had normal LV filling pattern, 20 patients (49%) had grade 1, and 11 patients (27%) had grade 2 diastolic dysfunction. Compared to patients with normal diastolic filling pattern, patients with diastolic dysfunction had lower RV end-diastolic volume (66 ± 11 ml/m2 vs. 79 ± 15 ml/m2, p = 0.02) and end-systolic volume (25 ± 7 ml/m2 vs. 32 ± 9 ml/m2, p = 0.04). An increase in mean RAP to ≥15 mmHg following exercise was not seen in patients with normal LV filling, compared to 4 patients (20%) with mild and 7 patients (63%) with moderate diastolic dysfunction (p = 0.003). PA pressure and PA elastance was increased in grade 2 diastolic dysfunction and correlated with RV volume and maximal oxygen consumption (r = -0.71, p < 0.001). Moderate diastolic dysfunction is associated with increased RV afterload (elastance), which is compensated at rest, but is associated with increased RAP and inversely related to maximal oxygen consumption during maximal exercise.
Calcified aortic stenosis (AS) is a chronic, slowly progressing disorder where pressure overload can lead to heart failure symptoms warranting aortic valve replacement . However, some patients remain asymptomatic for years with gradual adaptation to pressure overload. Typically, the adaptive response will counterbalance pressure overload, in which left ventricular (LV) hypertrophy will help maintain end-systolic wall stress and preserve adequate cardiac output. However, adaptive concentric remodeling over time is associated with diffuse fibrosis and impaired coronary flow reserve, leading to increased myocardial stiffness and diastolic dysfunction [2–4]. The filling pressure increases during diastolic dysfunction especially during exertion, thereby exposing the right ventricle (RV) to increased afterload through the pulmonary vascular bed . Prior hemodynamic studies have shown that loading conditions on the left side of the heart inevitably affects RV diastolic properties and pressure, possibly through ventricular interdependence . Further, previous studies have demonstrated that exercise in symptomatic as well as asymptomatic patients with AS inflicts severe post-capillary pulmonary artery hypertension, thus exposing the RV to increased afterload [7, 8].
A total of 41 patients with significant AS defined as aortic valve area (AVA) < 1cm2, aortic peak velocity > 3.5 m/s and LV ejection fraction > 50% were prospectively enrolled from January 2014 to January 2016.
All 41 patients completed the exercise protocol and 1 patient did not complete cMRI due to claustrophobia. Patients were classified into 3 groups according to LV diastolic filling pattern: 10 patients (24%) had normal diastolic filling pattern, 20 patients (49%) had grade 1 diastolic dysfunction, and 11 patients (27%) had grade 2 diastolic dysfunction. Grade 3 diastolic dysfunction was not observed in this cohort. Patients with diastolic dysfunction were older compared to those with a normal filling pattern (p<0.001) (Table 1). Further, during Valsalva maneuver, E/A ratio decreased significantly in patients with moderate diastolic dysfunction (0.71 ± 0.21 vs. 0.59 ± 0.17, p<0.001). The severity of AS in terms of AVA (p = 0.76), mean aortic gradient (p = 0.73), or aortic peak gradient (p = 0.77) was unrelated to LV diastolic function. Resting Zva was significantly higher in patients with diastolic dysfunction compared to those with a normal diastolic filling pattern (3.98 ± 0.61 vs. 4.62 ± 0.88 mmHg*ml-1*m-2, p = 0.04), which was driven by patients with grade 1 diastolic dysfunction (Table 1). Although TAPSE (tricuspid annular plane systolic excursion) was numerically higher in patients with grade 2 diastolic dysfunction, no significant difference was observed between groups (p = 0.19). However, S’ measured in the basal RV free wall was higher in patients with moderate diastolic dysfunction compared to those with normal diastolic function (Table 1). The present study confirms the following two findings: (1) abnormal LV diastolic function is a common finding in asymptomatic patients with significant AS; (2) right ventricular afterload is increased when diastolic dysfunction is moderate. The increase in RV afterload is compensated at rest but is associated with increased right atrial pressure and inversely related to oxygen consumption during exercise. Morphologically, RV remodeling in patients with diastolic dysfunction was characterized by smaller chamber size suggesting reduced RV compliance in these patients. The present study demonstrates that abnormal LV diastolic function is a common finding in asymptomatic significant AS, and when diastolic dysfunction is moderate, right ventricular afterload is increased. The increase in RV afterload is compensated at rest with no signs of right heart failure but is associated with increased right atrial pressure and inversely related to oxygen consumption during exercise. Morphologically, RV remodeling in patients with diastolic dysfunction was characterized by smaller chamber size suggesting reduced RV compliance. Source: http://doi.org/10.1371/journal.pone.0215364