Left ventricular heart failure and pulmonary hypertension

In patients with left ventricular heart failure (HF), the development of pulmonary hypertension (PH) and right ventricular (RV) dysfunction are frequent and have important impact on disease progression, morbidity, and mortality, and therefore warrant clinical attention. Pulmonary hypertension related to left heart disease (LHD) by far represents the most common form of PH, accounting for 65–80% of cases. The proper distinction between pulmonary arterial hypertension and PH-LHD may be challenging, yet it has direct therapeutic consequences. Despite recent advances in the pathophysiological understanding and clinical assessment, and adjustments in the haemodynamic definitions and classification of PH-LHD, the haemodynamic interrelations in combined post- and pre-capillary PH are complex, definitions and prognostic significance of haemodynamic variables characterizing the degree of pre-capillary PH in LHD remain suboptimal, and there are currently no evidence-based recommendations for the management of PH-LHD. Here, we highlight the prevalence and significance of PH and RV dysfunction in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), and provide insights into the complex pathophysiology of cardiopulmonary interaction in LHD, which may lead to the evolution from a ‘left ventricular phenotype’ to a ‘right ventricular phenotype’ across the natural history of HF. Furthermore, we propose to better define the individual phenotype of PH by integrating the clinical context, non-invasive assessment, and invasive haemodynamic variables in a structured diagnostic work-up. Finally, we challenge current definitions and diagnostic short falls, and discuss gaps in evidence, therapeutic options and the necessity for future developments in this context

Pulmonary endarterectomy normalizes interventricular dyssynchrony and right ventricular systolic wall stress

Background: Interventricular mechanical dyssynchrony is a characteristic of pulmonary hypertension. We studied the role of right ventricular (RV) wall stress in the recovery of interventricular dyssynchrony, after pulmonary endarterectomy (PEA) in chronic thromboembolic pulmonary hypertension (CTEPH). Methods: In 13 consecutive patients with CTEPH, before and 6 months after pulmonary endarterectomy, cardiovascular magnetic resonance myocardial tagging was applied. For the left ventricular (LV) and RV free walls, the time to peak (Tpeak) of circumferential shortening (strain) was calculated. Pulmonary Artery Pressure (PAP) was measured by right heart catheterization within 48 hours of PEA. Then the RV free wall systolic wall stress was calculated by the Laplace law. Results: After PEA, the left to right free wall delay (L-R delay) in Tpeak strain decreased from 97 +/- 49 ms to -4 +/- 51 ms (P <0.001), which was not different from normal reference values of -35 +/- 10 ms (P = 0.18). The RV wall stress decreased significantly from 15.2 +/- 6.4 kPa to 5.7 +/- 3.4 kPa (P <0.001), which was not different from normal reference values of 5.3 +/- 1.39 kPa (P = 0.78). The reduction of L-R delay in Tpeak was more strongly associated with the reduction in RV wall stress (r = 0.69, P = 0.007) than with the reduction in systolic PAP (r = 0.53, P = 0.07). The reduction of L-R delay in Tpeak was not associated with estimates of the reduction in RV radius (r = 0.37, P = 0.21) or increase in RV systolic wall thickness (r = 0.19, P = 0.53). Conclusion: After PEA for CTEPH, the RV and LV peak strains are resynchronized. The reduction in systolic RV wall stress plays a key role in this resynchronizatio

Smallest detectable change in volume differs between mass flow sensor and pneumotachograph

<p>Abstract</p> <p>Background</p> <p>To assess a pulmonary function change over time the mass flow sensor and the pneumotachograph are widely used in commercially available instruments. However, the smallest detectable change for both devices has never been compared. Therefore, the aim of this study is to determine the smallest detectable change in vital capacity (VC) and single-breath diffusion parameters measured by mass flow sensor and or pneumotachograph.</p> <p>Method</p> <p>In 28 healthy pulmonary function technicians VC, transfer factor for carbon monoxide (DLCO) and alveolar volume (VA) was repeatedly (10×) measured. The smallest detectable change was calculated by 1.96 x Standard Error of Measurement ×√2.</p> <p>Findings</p> <p>The mean (range) of the smallest detectable change measured by mass flow sensor and pneumotachograph respectively, were for VC (in Liter): 0.53 (0.46-0.65); 0.25 (0.17-0.36) (<it>p </it>= 0.04), DLCO (in mmol*kPa^-1*min^-1): 1.53 (1.26-1.7); 1.18 (0.84-1.39) (<it>p </it>= 0.07), VA (in Liter): 0.66. (0.53-0.82); 0.43 (0.34-0.53) (<it>p </it>= 0.04) and DLCO/VA (in mmol*kPa^-1*min^-1*L^-1): 0.22 (0.19-0.28); 0.19 (0.14-0.22) (<it>p </it>= 0.79).</p> <p>Conclusions</p> <p>Smallest detectable significant change in VC and VA as measured by pneumotachograph are smaller than by mass flow sensor. Therefore, the pneumotachograph is the preferred instrument to estimate lung volume change over time in individual patients.</p

Inhibition of the prolyl isomerase Pin1 improves endothelial function and attenuates vascular remodelling in pulmonary hypertension by inhibiting TGF-β signalling

Pulmonary arterial hypertension (PAH) is a devastating disease, characterized by obstructive pulmonary vascular remodelling ultimately leading to right ventricular (RV) failure and death. Disturbed transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) signalling, endothelial cell dysfunction, increased proliferation of smooth muscle cells and fibroblasts, and inflammation contribute to this abnormal remodelling. Peptidyl-prolyl isomerase Pin1 has been identified as a critical driver of proliferation and inflammation in vascular cells, but its role in the disturbed TGF-β/BMP signalling, endothelial cell dysfunction, and vascular remodelling in PAH is unknown. Here, we report that Pin1 expression is increased in cultured pulmonary microvascular endothelial cells (MVECs) and lung tissue of PAH patients. Pin1 inhibitor, juglone significantly decreased TGF-β signalling, increased BMP signalling, normalized their hyper-proliferative, and inflammatory phenotype. Juglone treatment reversed vascular remodelling through reducing TGF-β signalling in monocrotaline + shunt-PAH rat model. Juglone treatment decreased Fulton index, but did not affect or harm cardiac function and remodelling in rats with RV pressure load induced by pulmonary artery banding. Our study demonstrates that inhibition of Pin1 reversed the PAH phenotype in PAH MVECs in vitro and in PAH rats in vivo, potentially through modulation of TGF-β/BMP signalling pathways. Selective inhibition of Pin1 could be a novel therapeutic option for the treatment of PAH. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10456-021-09812-7

Right ventricular recovery after bilateral lung transplantation for pulmonary arterial hypertension

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a progressive and often fatal disease characterized by increased pulmonary vascular resistance (PVR) and right ventricular (RV) failure. End-stage PAH is often an indication for a lung transplant (LTX). Our goal was to study ventricular recovery using cardiac magnetic resonance imaging late after LTX. METHODS: We studied 10 patients with PAH who underwent isolated bilateral LTX. RV and left ventricular (LV) volumes, function and mass were measured. In addition, the RV stroke volume/end-systolic ratio (SV/ESV), the LV eccentricity index, the RV/LV volume ratio, the area of the tricuspid valve annulus and the severity of tricuspid regurgitation (TR) were calculated. RESULTS: The median age was 44 [30-54] years and the mean PVR was 1020 ± 435 dynes·s·cm â ' 5. Six patients had ≥ moderate TR. After LTX, the RV ejection fraction increased from 32 to 64% (P < 0.001) and both RV volume (from 118 to 51 ml/m 2, P < 0.001) and RV mass (from 69 to 33 g/m 2, P < 0.001) decreased. The mean SV/ESV ratio increased from 0.5 to 1.9 (P < 0.001) and the LV mass increased from 55 to 61 g/m 2 (P = 0.005). There was a decrease in both the LV eccentricity index (from 2.8 to 1.1, P < 0.001) and the RV/LV volume ratio (from 2.3 to 0.8, P < 0.001). The area of the tricuspid valve annulus also decreased (from 9.8 to 4.6 cm 2 /m 2, P < 0.001); no patient had ≥ mild TR post-LTX. CONCLUSIONS: Cardiac magnetic resonance imaging confirms ventricular recovery after isolated bilateral LTX for end-stage PAH

Management strategy after diagnosis of Abernethy malformation: a case report

<p>Abstract</p> <p>Introduction</p> <p>The Abernethy malformation is a rare anomaly with a widely variable clinical presentation. Many diagnostic dilemmas have been reported. Nowadays, with the evolution of medical imaging, diagnosis can be made more easily, but management of patients with an Abernethy malformation is still open for discussion.</p> <p>Case presentation</p> <p>In this case study, we describe a 34-year-old Caucasian man who presented with a large hepatocellular carcinoma in the presence of an Abernethy malformation, which was complicated by the development of pulmonary arterial hypertension.</p> <p>Conclusion</p> <p>This case underlines the importance of regular examination of patients with an Abernethy malformation, even in older patients, to prevent complications and to detect liver lesions at an early stage.</p