Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

The effect of pulmonary arterial hypertension specific treatment on the left ventricle in patients with pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is characterized by right ventricular (RV) pressure overload, leading to RV dilation, failure and death. In the course of the disease, the left ventricle (LV) is often impaired, due to interventricular interaction. Although the impact of PAH treatment on the RV has been well described, less is known on the LV.To examine effects of advanced PAH treatments on the volumes, function and strain of the left atrium and ventricle.This is a retrospective study. All patients underwent CMR and right heart catheterization, both at diagnosis and at 12-months follow up. Ventricular volumes and LV filling rate were calculated from the stack of short axis cine images using Simpsons method while left atrial (LA) volumes from the 4-chamber cine images using the area-length method. Tissue tracking was used for the evaluation of myocardial deformation. The LV endocardial and epicardial borders were manually delineated in all analysed sections with the initial contour set at end-diastole. All analyses were performed offline using dedicated software.In total, 66 patients (mean age 56.3±17.9 years, 67\ 77\ 23\ and 29 normal controls were included. The improvement in metrics of right and left heart size and function after the initiation of advanced PAH treatment, are presented in panel A. Of note, LV stroke volume was markedly increased (54.6±19.6ml at baseline vs 70.8±21.7ml at follow up, p\lt;0.0001) to reach controls. LV filling was markedly increased in latter two-thirds of the diastolic phase (panel B), especially at atrial kick point (arrow). Change in LA max volume was associated with changes in diastolic filling (r=0.354, p=0.004), LV end-diastolic and end-systolic volumes and stroke volume. These correlations were more robust in patients that increased LV filling compared to those that failed to increase LV filling (panels C-E). No association between changes in LV circumferential strain and LV volume load was observed. A weak correlation of change of LV peak longitudinal strain with stroke volume (r=−0.345, p=0.006), LV end diastolic volume (r=−0.284, p=0.027), LV ejection fraction (r=−0.337, p=0.008) and LA maximum area (r=−0.447, p\lt;0.0001) was observed. The changes of LV strain showed no correlation with the changes in patients' haemodynamics.Improvement in stroke volume after the initiation of advanced PAH treatment is associated with an increase in LA size, LV end diastolic volume and normalisation of strain. This reflects the improved filling state of the left ventricle and the potential of the left atrium to monitor treatment effects.Changes after PAH treatmentType of funding source: Non

A case of balloon pulmonary angioplasty as a palliative therapy in chronic thromboembolic pulmonary hypertension

[No abstract available

Relationship between right ventricular diastolic dysfunction, right atrial phasic function and ventricular filling in pulmonary arterial hypertension

In pulmonary arterial hypertension (PAH) patients, the right ventricle (RV) stiffens due to hypertrophy, fibrosis and intrinsic (sarcomeric) stiffness. In these patients, end-diastolic elastance (stiffness, Eed) is associated with parameters of disease severity and predicts mortality. However, the effect of RV stiffness on RV filling and the effect of increased filling pressures on right atrial (RA) function remain elusive.To examine the relationship between RV diastolic stiffness and RA phasic function and the effect of diastolic dysfunction on ventricular filling in PAH patients.Using single-beat pressure-volume analyses we determined Eed in controls (n=31) and baseline, treatment naive PAH patients (63 idiopathic, 9 hereditary and 25 connective tissue disease associated). We also measured RA reservoir, conduit and active strain by tissue tracking on cardiac magnetic resonance images. Furthermore, interventricular dyssynchrony was defined as a right to left difference in time to peak circumferential strain \gt;52ms (97.5th percentile in controls).End-diastolic pressure was higher in PAH patients (16±7 mmHg) than in controls (8±4 mmHg; p\lt;0.001). Median Eed in patients was 0.635 mmHg/mL (IQR: 0.40–0.99), while in controls it was 0.20 mmHg/mL (IQR: 0.15–0.24). In comparison with controls, patients had reduced RA reservoir (14.3±5.1\9.1±4.3\ p\lt;0.001) and conduit strain (−5.6±3.4\12.4±3.3\ p\lt;0.001), while RA active strain was enhanced (−9.0±4.0\7.5±2.8\ p=0.019). In patients with a stiff RV (Eed above median), RA conduit strain was worse than in patients with a more compliant RV as illustrated in figure A. However, no correlation between RA active strain and Eed was observed (Spearman rho 0.06; p=0.57).Passive filling time of the RV (end-systole until start of atrial contraction) was shorter in patients than in controls (244±136ms vs. 365±103ms; p\lt;0.001). Higher heart rate and ventricular dyssynchrony are causes of a shorter passive filling time in patients as illustrated in figure B. When comparing patients with short vs. long passive filling time (cutoff median of 220ms), the RV passive filling volume was lower (24±15ml vs. 42±19ml; p\lt;0.001). The active filling volume was slightly higher, although not significantly (25±17ml vs. 19±15ml; p=0.12).Stiffening of the RV in PAH patients is accompanied by increased filling pressures and decreased RA conduit strain, while there is no correlation between Eed and RA active strain. Higher heart rate and ventricular dyssynchrony lead to shorter passive filling time of the RV, which in turn leads to lower passive filling volume. In contrast, the active filling volume is preserved in these patients.Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Netherlands Organization for Scientific Researc

Right Ventricular and Right Atrial Function Are Less Compromised in Pulmonary Hypertension Secondary to Heart Failure With Preserved Ejection Fraction: A Comparison With Pulmonary Arterial Hypertension With Similar Pressure Overload

Background: Heart failure with preserved ejection fraction (HFpEF) is a prevalent disorder for which no effective treatment yet exists. Pulmonary hypertension (PH) and right atrial (RA) and ventricular (RV) dysfunction are frequently observed. The question remains whether the PH with the associated RV/RA dysfunction in HFpEF are markers of disease severity. Methods: To obtain insight in the relative importance of pressure-overload and left-to-right interaction, we compared RA and RV function in 3 groups: 1. HFpEF (n=13); 2. HFpEF-PH (n=33), and; 3. pulmonary arterial hypertension (PAH) matched to pulmonary artery pressures of HFpEF-PH (PH limited to mPAP >= 30 and <= 50 mmHg) (n=47). Patients underwent right heart catheterization and cardiac magnetic resonance imaging. Results: The right ventricle in HFpEF-PH was less dilated and hypertrophied than in PAH. In addition, RV ejection fraction was more preserved (HFpEF-PH: 52 +/- 11 versus PAH: 36 +/- 12%). RV filling patterns differed: vena cava backflow during RA contraction was observed in PAH only. In HFpEF-PH, RA pressure was elevated throughout the cardiac cycle (HFpEF-PH: 10 [8-14] versus PAH: 7 [5-10] mm Hg), while RA volume was smaller, reflecting excessive RA stiffness (HFpEF-PH: 0.14 [0.10-0.17] versus PAH: 0.08 [0.06-0.11] mm Hg/mL). RA stiffness was associated with an increased eccentricity index (HFpEF-PH: 1.3 +/- 0.2 versus PAH: 1.2 +/- 0.1) and interatrial pressure gradient (9 [5 to 12] versus 2 [-2 to 5] mm Hg). Conclusions: RV/RA function was less compromised in HFpEF-PH than in PAH, despite similar pressure-overload. Increased RA pressure and stiffness in HFpEF-PH were explained by left atrial/RA-interaction. Therefore, our results indicate that increased RA pressure is not a sign of overt RV failure but rather a reflection of HFpEF-severity

Right Ventricular and Right Atrial Function Are Less Compromised in Pulmonary Hypertension Secondary to Heart Failure With Preserved Ejection Fraction: A Comparison With Pulmonary Arterial Hypertension With Similar Pressure Overload

Background: Heart failure with preserved ejection fraction (HFpEF) is a prevalent disorder for which no effective treatment yet exists. Pulmonary hypertension (PH) and right atrial (RA) and ventricular (RV) dysfunction are frequently observed. The question remains whether the PH with the associated RV/RA dysfunction in HFpEF are markers of disease severity. Methods: To obtain insight in the relative importance of pressure-overload and left-to-right interaction, we compared RA and RV function in 3 groups: 1. HFpEF (n=13); 2. HFpEF-PH (n=33), and; 3. pulmonary arterial hypertension (PAH) matched to pulmonary artery pressures of HFpEF-PH (PH limited to mPAP >= 30 and <= 50 mmHg) (n=47). Patients underwent right heart catheterization and cardiac magnetic resonance imaging. Results: The right ventricle in HFpEF-PH was less dilated and hypertrophied than in PAH. In addition, RV ejection fraction was more preserved (HFpEF-PH: 52 +/- 11 versus PAH: 36 +/- 12%). RV filling patterns differed: vena cava backflow during RA contraction was observed in PAH only. In HFpEF-PH, RA pressure was elevated throughout the cardiac cycle (HFpEF-PH: 10 [8-14] versus PAH: 7 [5-10] mm Hg), while RA volume was smaller, reflecting excessive RA stiffness (HFpEF-PH: 0.14 [0.10-0.17] versus PAH: 0.08 [0.06-0.11] mm Hg/mL). RA stiffness was associated with an increased eccentricity index (HFpEF-PH: 1.3 +/- 0.2 versus PAH: 1.2 +/- 0.1) and interatrial pressure gradient (9 [5 to 12] versus 2 [-2 to 5] mm Hg). Conclusions: RV/RA function was less compromised in HFpEF-PH than in PAH, despite similar pressure-overload. Increased RA pressure and stiffness in HFpEF-PH were explained by left atrial/RA-interaction. Therefore, our results indicate that increased RA pressure is not a sign of overt RV failure but rather a reflection of HFpEF-severity.Therapeutic cell differentiatio