Impact of the 2022 pulmonary hypertension definition on haemodynamic classification and mortality in patients with aortic stenosis undergoing valve replacement.

Aims: With the 2022 pulmonary hypertension (PH) definition, the mean pulmonary artery pressure (mPAP) threshold for any PH was lowered from ≥25 to >20 mmHg, and the pulmonary vascular resistance (PVR) value to differentiate between isolated post-capillary PH (IpcPH) and combined pre- and post-capillary PH (CpcPH) was reduced from >3 Wood units (WU) to >2 WU. We assessed the impact of this change in the PH definition in aortic stenosis (AS) patients undergoing aortic valve replacement (AVR). Methods and results: Severe AS patients (n = 503) undergoing pre-AVR cardiac heart catheterization were classified according to both the 2015 and 2022 definitions. The post-AVR mortality [median follow-up 1348 (interquartile range 948-1885) days] was assessed. According to the 2015 definition, 219 (44% of the entire population) patients had PH: 63 (29%) CpcPH, 125 (57%) IpcPH, and 31 (14%) pre-capillary PH. According to the 2022 definition, 321 (+47%) patients were diagnosed with PH, and 156 patients (31%) were re-classified: 26 patients from no PH to IpcPH, 38 from no PH to pre-capillary PH, 38 from no PH to unclassified PH, 4 from pre-capillary PH to unclassified PH, and 50 from IpcPH to CpcPH (CpcPH: +79%). With both definitions, only the CpcPH patients displayed increased mortality (hazard ratios ≈ 4). Among the PH-defining haemodynamic components, PVR was the strongest predictor of death. Conclusion: In severe AS, the application of the 2022 PH definition results in a substantially higher number of patients with any PH as well as CpcPH. With either definition, CpcPH patients have a significantly increased post-AVR mortality.

Age-related differences in hemodynamics and functional status in pulmonary arterial hypertension: Baseline results from the Pulmonary Hypertension Association Registry.

BACKGROUND: The age of patients with pulmonary arterial hypertension (PAH) has increased, with registries now reporting mean ages of 50 to 65 years old. Limited data exist on age-related differences in hemodynamic and functional assessments in PAH. METHODS: Adults with PAH in the Pulmonary Hypertension Association Registry were divided into 3 groups (18-50, 51-65, and >65 years old). Analysis of variance and chi-square testing were used to assess for baseline differences. Linear regression was used to examine the association of age with continuous hemodynamic and functional variables. RESULTS: A total of 769 patients with mean age of 56 ± 16 years were included. Older patients had more connective tissue disease-associated PAH and less drug-associated PAH. In linear regression models, each year of increased age was associated with shorter 6-minute walk distance (-3.37 meters; 95% CI, -3.97 to -2.76), lower mean pulmonary arterial pressure (-0.21 mm Hg; 95% CI, -0.27 to -0.15), and lower pulmonary vascular resistance (-0.06 Wood units; 95% CI, -0.09 to -0.04). Pulmonary arterial compliance, cardiac index, right ventricular stroke work index, and percent predicted 6-minute walk distance were unrelated to age; resistance-compliance time was negatively related to age (-3 milliseconds per year; 95% CI, -4 to -2). CONCLUSIONS: Relative to their pulmonary vascular resistance, older patients have lower pulmonary artery compliance and worse right ventricular performance. Based on these findings, we suspect that age influences right ventricular loading conditions and the response of the right ventricle to increased afterload.

Therapeutic potential of phosphodiesterase type 5 inhibitors in heart failure with preserved ejection fraction and combined post- and pre-capillary pulmonary hypertension.

OBJECTIVE: Heart failure with preserved ejection fraction (HFpEF) is frequently associated with pulmonary hypertension (PH), which substantially impacts survival. Based on pulmonary vascular resistance (PVR) and the diastolic pressure gradient (DPG), current guidelines distinguish between isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH). However, the therapeutic consequences of this sub-classification remain entirely unclear. We specifically investigated the efficacy and safety of PDE5i in patients with HFpEF and CpcPH. METHODS: In 40 hemodynamically precisely characterized patients with HFpEF and Cpc-PH who were treated with a PDE5i for at least 12 months, the therapeutic effect on 6-minute walk distance (6MWD), WHO functional class (FC), NTproBNP levels, right ventricular function, and hospitalization rates was evaluated. RESULTS: Patients' mean age was 73 ±â€¯9 years, and comorbidities were frequent (78% hypertension, 58% atrial fibrillation, 35% diabetes). Initially, 38 patients (95%) were in WHO-FC III and 2 patients (5%) in WHO-FC II. Prior to PDE5i initiation, mean PAPm was 46.2 ±â€¯10.3 mmHg, PAWP 21.2 ±â€¯4.7 mmHg, DPG 5.5 ±â€¯7.2 mmHg, and PVR 6.2 ±â€¯3.0 WU. After 12 months of PDE5i therapy, the 6MWD increased from initially 277 ±â€¯17 to 340 ±â€¯18 m (p < 0.001), and the proportion of patients in WHO-FC I/II increased from 5% to 37.5%. NTproBNP levels decreased by 33% (p = 0.004), and TAPSE improved from 16.8 ±â€¯0.7 mm at baseline to 18.2 ±â€¯0.6 mm (p = 0.01). The rate of HF-associated hospitalizations was substantially lower in the 12 months post PDE5i initiation compared to the prior 12 months. The DPG had no impact on the response to therapy. No deaths occurred, and typical side effects of PDE5i were observed. CONCLUSION: These data indicate that at least a subset of precisely characterized patients with HFpEF and CpcPH who tolerate PDE5i may benefit from targeted therapy. A randomized study in this particular sub-population is warranted.

The resistance-compliance product of the pulmonary circulation varies in health and pulmonary vascular disease.

Pulmonary vascular resistance (PVR) is traditionally used to describe pulmonary hemodynamic characteristics. However, it does not take into account pulmonary artery compliance (Ca) or pulsatile flow. The product of PVR and Ca is known as RC time. Previous studies assert that the PVR-Ca relationship is fixed and RC time is constant between health and disease states. We hypothesized that RC time was not constant in health and pulmonary vascular disease. Right heart catheterizations performed in Papworth Hospital over a 6 year period were analyzed. Subjects were divided into those with normal pulmonary hemodynamics (NPH group; n = 156) and pulmonary arterial hypertension (PAH group; n = 717). RC time and the right ventricle (RV) oscillatory power fraction were calculated. RC time for the NPH group (0.47 ± 0.13 sec) is significantly lower than the PAH group (0.56 ± 0.16 sec; P < 0.0001). The RV oscillatory power fraction is lower in the NPH group (P < 0.0001). RC time correlates inversely with the RV oscillatory power fraction in each group. We conclude, there is an inverse relationship between PVR and Ca, however, this relationship is not always fixed. Consequently, RC time is significantly lower in health compared to disease with elevated pulmonary artery pressures. PAH leads to a decrease in cardiac efficiency.