Sildenafil is a drug used to successfully manage a variety of cardiopulmonary disorders in people and dogs, but there is limited information on its use in cats. The objective was to review the medical records of cats that received sildenafil as part of their clinical management. Medical records and pharmacy databases were searched for cats that received sildenafil for ≥24 h between 2009 and 2021, and data were collected from medical records. Fifty-five cats received sildenafil for ≥24 h and were included in the study: 43 with primary cardiac disease (acquired, n = 28; congenital, n = 15) and 12 with primary respiratory disease. Side effects possibly attributed to sildenafil were identified in two cats (systemic hypotension, n = 1; polydipsia, n = 1), and sildenafil was discontinued in the cat with hypotension. Sildenafil was discontinued in an additional three cats due to a lack of improvement in clinical signs. No cat was documented to develop worsening pulmonary edema within 72 h of starting sildenafil. Median duration of sildenafil administration was 87 days (range, 2-2362 days). Sildenafil administration in cats appeared to be generally well-tolerated. Studies are needed to determine whether sildenafil administration to cats with cardiopulmonary disease improves the quality of life or survival times.

UNASSIGNED: Computed tomography pulmonary angiography (CTPA) has been proposed to be diagnostic for pulmonary hypertension (PH) in multiple studies. However, the utility of the unenhanced CT measurements diagnosing PH has not been fully assessed. This study aimed to assess the diagnostic utility and reproducibility of cardiac and great vessel parameters on unenhanced computed tomography (CT) in suspected pulmonary hypertension (PH).
UNASSIGNED: In total, 42 patients with suspected PH who underwent unenhanced CT thorax and right heart catheterization (RHC) were included in the study. Three observers (a consultant radiologist, a specialist registrar in radiology, and a medical student) measured the parameters by using unenhanced CT. Diagnostic accuracy of the parameters was assessed by area under the receiver operating characteristic curve (AUC). Inter-observer variability between the consultant radiologist (primary observer) and the two secondary observers was determined by intra-class correlation analysis (ICC).
UNASSIGNED: Overall, 35 patients were diagnosed with PH by RHC while 7 patients were not. Main pulmonary arterial (MPA) diameter was the strongest (AUC 0.79 to 0.87) and the most reproducible great vessel parameter. ICC comparing the MPA diameter measurement of the consultant radiologist to the specialist registrar\'s and the medical student\'s were 0.96 and 0.92, respectively. Right atrial area was the cardiac measurement with highest accuracy and reproducibility (AUC 0.76 to 0.79; ICC 0.980, 0.950) followed by tricuspid annulus diameter (AUC 0.76 to 0.79; ICC 0.790, 0.800).
UNASSIGNED: MPA diameter and right atrial areas showed high reproducibility. Diagnostic accuracies of these were within the range of acceptable to excellent, and might have clinical value. Tricuspid annular diameter was less reliable and less diagnostic and was therefore not a recommended diagnostic measurement.
Pulmonary hypertension (PH) is a condition characterized by elevated pressure in the pulmonary artery and may lead to right heart failure. Several studies have demonstrated the diagnostic value of non-invasive techniques computed tomography (CT) with contrast in identifying PH. Therefore, we aim to investigate the diagnostic accuracy of non-contrast CT, which is commonly performed in patients with suspected lung diseases who are at risk of PH.

OBJECTIVE: To describe the safety and effectiveness of treating pediatric patients who have pulmonary arterial hypertension (PAH) with selexipag in a real-world, multi-center cohort, given that data supporting its use in pediatric PAH are sparse.
METHODS: We report a multi-center, retrospective, cohort study of children with PAH treated with selexipag. Demographic and clinical variables were extracted from the medical records. Clinical parameters were analyzed at 3 timepoints: pre-selexipag, 3-12 months post-selexipag, and >12 months follow-up.
RESULTS: Eighty-seven patients were included, 32 received selexipag as add-on to background therapy, and 55 transitioned from another prostanoid. Median starting and final doses were 4.7 and 28.5 μg/kg/dose BID, respectively. Add-on patients demonstrated improved indexed pulmonary to systemic vascular resistance ratio after selexipag initiation (PVRi/SVRi, 0.62v0.53, p=0.034) with a lower average mean pulmonary artery pressure (MPAP, 46v39 mmHg, p=NS), and oxygen consumption (VO2 max 27.8v30.9 mL/kg/min, p=NS). Transition patients demonstrated stable MPAP (47v45 mmHg, p=NS) and a lower mean PVRi (10.9v8.2 Wood units*m2, p=NS) but late functional worsening in some with VO2 max decreased at follow-up (26.0v19.5 ml/kg/min). Side effects were noted in 40% of the cohort but prompted discontinuation in only 2%.
CONCLUSIONS: In a large, multi-center cohort, the oral prostacyclin agonist selexipag demonstrates favorable tolerability and effectiveness. Add-on patients demonstrated early hemodynamic improvement. Transition patients demonstrated early stability with risk of late functional worsening, highlighting the importance of ongoing monitoring.

Background Congenital heart disease (CHD) is a structural deformity of the heart present at birth. Pulmonary hypertension (PH) may arise from increased blood flow to the lungs, persistent pulmonary arterial pressure elevation, or the use of cardiopulmonary bypass (CPB) during surgical repair. Inhaled nitric oxide (iNO) selectively reduces high blood pressure in the pulmonary vessels without lowering systemic blood pressure, making it useful for treating children with postoperative PH due to heart disease. However, reducing or stopping iNO can exacerbate postoperative PH and hypoxemia, necessitating long-term administration and careful tapering. This study aimed to evaluate, using machine learning (ML), factors that predict the need for long-term iNO administration after open heart surgery in CHD patients in the postoperative ICU, primarily for PH management. Methods We used an ML approach to establish an algorithm to predict \'patients with long-term use of iNO\' and validate its accuracy in 34 pediatric postoperative open heart surgery patients who survived and were discharged from the ICU at Kagoshima University Hospital between April 2016 and March 2019. All patients were started on iNO therapy upon ICU admission. Overall, 16 features reflecting patient and surgical characteristics were utilized to predict the patients who needed iNO for over 168 hours using ML analysis with AutoGluon. The dataset was randomly classified into training and test cohorts, comprising 80% and 20% of the data, respectively. In the training cohort, the ML model was constructed using the important features selected by the decrease in Gini impurity and a synthetic oversampling technique. In the testing cohort, the prediction performance of the ML model was evaluated by calculating the area under the receiver operating characteristics curve (AUC) and accuracy. Results Among 28 patients in the training cohort, five needed iNO for over 168 hours; among six patients in the testing cohort, one needed iNO for over 168 hours. CPB, aortic clamp time, in-out balance, and lactate were the four most important features for predicting the need for iNO for over 168 hours. In the training cohorts, the ML model achieved perfect classification with an AUC of 1.00. In the testing cohort, the ML model also achieved perfect classification with an AUC of 1.00 and an accuracy of 1.00. Conclusion The ML approach identified that four factors (CPB, in-out balance, aortic cross-clamp time, and lactate) are strongly associated with the need for long-term iNO administration after open heart surgery in CHD patients. By understanding the outcomes of this study, we can more effectively manage iNO administration in postoperative open heart surgery in CHD patients with PH, potentially preventing the recurrence of postoperative PH and hypoxemia, thereby contributing to safer patient management.

BACKGROUND: Pulmonary arterial hypertension (PAH)-specific therapies are generally ineffective in patients with pulmonary hypertension associated with lung disease (PH-LD). The aim of this preliminary study was to evaluate the potential efficacy of selexipag, titrated according to individual tolerance, in patients with PH-LD.
METHODS: Consecutive patients diagnosed with PH-LD between October 2016 and March 2019, who received selexipag treatment, were retrospectively evaluated. Specific parameters, including changes in hemodynamic parameters, 6-min walk distance (6MWD), and partial pressure of atrial oxygen/fraction of inspiratory oxygen (PaO2/FiO2) were evaluated. Patients whose 6MWD improved ≥20 m were defined as responders.
RESULTS: Eight patients with PH-LD were included, comprising four with chronic obstructive pulmonary disease (COPD), two with interstitial lung disease (ILD) related to rheumatoid arthritis, one with ILD related to systemic sclerosis, and one with pulmonary Langerhans cell histiocytosis. No statistically significant improvements in hemodynamic parameters and 6MWD were noted following selexipag treatment. However, four patients showed improvements in 6MWD ≥20 m at follow-up and were considered responders. They had a higher body mass index (BMI) and lower PaO2/FiO2 at baseline than non-responders (p = 0.02 and p = 0.04, respectively). No Grade 3 or 4 adverse events were observed.
CONCLUSIONS: Selexipag was effective in half of the PH-LD cases, emphasizing higher BMI and lower PaO2/FiO2 as possible indicators for favorable response. Since selexipag starting at a low dose with subsequent titration may reduce the risk of early adverse events, it can be considered a treatment option for PH-LD. Further large-scale studies are warranted to confirm these findings.

OBJECTIVE: Based on retrospective studies, the 2022 European guidelines changed the definition of post-capillary pulmonary hypertension (pcPH) in heart failure (HF) by lowering the level of mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR). However, the impact of this definition and its prognostic value has never been evaluated prospectively.
METHODS: Stable left HF patients with the need for right heart catheterization were enrolled from 2010 to 2018 and prospectively followed up in this multicentre study. The impact of the successive pcPH definitions on pcPH prevalence and subgroup [i.e. isolated (IpcPH) vs. combined pcPH (CpcPH)] was evaluated. Multivariable Cox regression analysis was used to assess the prognostic value of mPAP and PVR on all-cause death or hospitalization for HF (primary outcome).
RESULTS: Included were 662 HF patients were (median age 63 years, 60% male). Lowering mPAP from 25 to 20 mmHg resulted in +10% increase in pcPH prevalence, whereas lowering PVR from 3 to 2 resulted in +60% increase in CpcPH prevalence (with significant net reclassification improvement for the primary outcome). In multivariable analysis, both mPAP and PVR remained associated with the primary outcome [hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.00-1.03, P = .01; HR 1.07, 95% CI 1.00-1.14, P = .03]. The best PVR threshold associated with the primary outcome was around 2.2 WU. Using the 2022 definition, pcPH patients had worse survival compared with HF patients without pcPH (log-rank, P = .02) as well as CpcPH compared with IpcPH (log-rank, P = .003).
CONCLUSIONS: This study is the first emphasizing the impact of the new pcPH definition on CpcPH prevalence and validating the prognostic value of mPAP > 20 mmHg and PVR > 2 WU among HF patients.

Right ventricular assist devices (RVADs) have been extensively used to provide hemodynamic support for patients with end-stage right heart (RV) failure. However, conventional in-parallel RVADs can lead to an elevation of pulmonary artery (PA) pressure, consequently increasing the right ventricular (RV) afterload, which is unfavorable for the relaxation of cardiac muscles and reduction of valve complications. The aim of this study is to investigate the hemodynamic effects of the pulsatile frequency of the RVAD on pulmonary artery. Firstly, a mathematical model incorporating heart, systemic circulation, pulmonary circulation, and RVAD is developed to simulate the cardiovascular system. Subsequently, the frequency characteristics of the pulmonary circulation system are analyzed, and the calculated results demonstrate that the pulsatile frequency of the RVAD has a substantive impact on the pulmonary artery pressure. Finally, to verify the analysis results, the hemodynamic effects of the pulsatile frequency of the RVAD on pulmonary artery are compared under diffident support modes. It is found that the pulmonary artery pressure decreases by approximately 6% when the pulsatile frequency changes from 1 to 3 Hz. The increased pulsatile frequency of RA-PA support mode may facilitate the opening of the pulmonary valve, while the RV-PA support mode can more effectively reduce the load of RV. This work provides a useful method to decrease the pulmonary artery pressure during the RVAD supports and may be beneficial for improving myocardial function in patients with end-stage right heart failure, especially those with pulmonary hypertension.

OBJECTIVE: To test the inter-reader agreement in classifying pulmonary hypertension (PH) on chest contrast-enhanced computed tomography (CECT) between a consensus of two cardio-pulmonary-devoted radiologists (CRc) and inexperienced readers (radiology residents, RRs) when using a CECT-based quick hands-on tool built upon PH imaging literature, i.e., the \"Rapid Access and Practical Information Digest on Computed Tomography for PH-RAPID-CT-PH\".
METHODS: The observational study retrospectively included 60 PH patients who underwent CECT between 2015 and 2022. Four RRs independently reviewed all CECTs and classified each case into one of the five PH groups per the 2022 ESC/ERS guidelines. While RR3 and RR4 (RAPID-CT-PH group) used RAPID-CT-PH, RR1 and RR2 (control group) did not. RAPID-CT-PH and control groups\' reports were compared with CRc using unweighted Cohen\'s Kappa (k) statistics. RRs\' report completeness and reporting time were also compared using the Wilcoxon-Mann-Whitney test.
RESULTS: The inter-reader agreement in classifying PH between the RAPID-CT-PH group and CRc was substantial (k = 0.75 for RR3 and k = 0.65 for RR4); while, it was only moderate for the control group (k = 0.57 for RR1 and k = 0.49 for RR2). Using RAPID-CT-PH resulted in significantly higher report completeness (all p < 0.0001) and significantly lower reporting time (p < 0.0001) compared to the control group.
CONCLUSIONS: RRs using RAPID-CT-PH showed a substantial agreement with CRc on CECT-based PH classification. RAPID-CT-PH improved report completeness and reduced reporting time. A quick hands-on tool for classifying PH on chest CECT may help inexperienced radiologists effectively contribute to the PH multidisciplinary team.

BACKGROUND: The SPHERe (Supervised Pulmonary Hypertension Exercise Rehabilitation) trial is a multi-centre, pragmatic, randomised controlled trial assessing the clinical and cost-effectiveness of supervised exercise rehabilitation with psychosocial and motivational support compared to best-practice usual care for people with pulmonary hypertension (PH). The original protocol was published in BMC Pulmonary Medicine (accessible online). We randomised our first participant in January 2020. In response to the COVID-19 pandemic, the trial was stopped in March 2020. In person delivery of the SPHERe intervention to a vulnerable population was not possible during the COVID-19 pandemic. We describe here how trial procedures and intervention delivery were adapted in response to the COVID-19 pandemic.
METHODS: Restrictions imposed by the COVID-19 pandemic on the clinically vulnerable PH population meant that trial delivery was changed from a centre-based rehabilitation programme to remotely delivered group online sessions. This led to minor alterations to the eligibility criteria. These changes followed a consultation process with stakeholders and people with PH and were approved by the funder and independent trial committees.
CONCLUSIONS: We describe the modified SPHERe trial protocol in response to restrictions imposed by the COVID-19 pandemic. SPHERe is the first randomised controlled trial to assess the clinical and cost-effectiveness of an online group rehabilitation programme for people with PH compared to usual care.
BACKGROUND: ISRCTN no. 10608766. Prospectively registered on 18th March 2019, updated 16th August 2023.

UNASSIGNED: To investigate the ventilatory and circulatory differences between eccentric (ECC) and concentric (CON) cycling exercise at submaximal, low-dose intensity from onset to end-exercise in healthy middle-aged participants.
UNASSIGNED: Randomized controlled crossover trial.
UNASSIGNED: The participants underwent 1 ECC and 1 CON test according to stepwise incremental exercise protocols at identical, submaximal intensities. Breath-by-breath analyses of ventilatory gas exchange and echocardiography were used to assess cardiopulmonary function during exercise.
UNASSIGNED: 24 healthy middle-aged, untrained participants (14 women, 10 men, 50±14 years) were included.
UNASSIGNED: 1 ECC and 1 CON test at submaximal intensities.
UNASSIGNED: The main outcome was oxygen uptake (V\'O2).
UNASSIGNED: The V\'O2 increase was reduced by -422 mL/min (-52%, 95% confidence interval: -513 to -292, P<.001) during ECC, as well as the ventilatory drive. Echocardiographic parameters, heart rate (-14%), cardiac output (-21%), stroke volume (-15%), and pulmonary artery pressure by tricuspid regurgitation pressure gradient (TRPG) (-26%) were also significantly reduced during ECC compared with CON at identical intensities. Participants reported significantly less dyspnea and unchanged perceived leg fatigue in ECC.
UNASSIGNED: ECC was well tolerated, and significant reductions were observed in V\'O2, ventilation, and right ventricular load compared with CON, even at low intensity levels. This study, conducted on healthy middle-aged participants, did not raise concerns that would hinder further investigation of the effects of ECC in patients with severely limited cardiopulmonary disease, and it calls for further research on this topic.