Effects of Sildenafil on spirometric pulmonary function parameters, pulmonary artery systolic pressure and BNP levels in patients with chronic obstructive pulmonary disease and erectile dysfunction

We aimed to investigate the effects of Sildenafil on pulmonary artery systolic pressure (PASP) as well as forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) and serum brain-type natriuretic peptide (BNP) levels in stable chronic obstructive pulmonary disease (COPD) patients with erectile dysfunction (ED). This was a prospective non-controlled interventional study that recruited COPD patients with ED between the ages of 49 and 79. International Index of Erectile Dysfunction Form (IIEF-5) was used for the evaluation of ED. Patients who had pulmonary artery systolic pressure >50 mmHg were included in the study. Single-dose Sildenafil 100 mg was administered orally to the patients. Before and after the drug ingestion, spirometry and echocardiographic measurements were performed, and serum BNP levels were measured as well. Forty-five male COPD patients with ED were included. Both percent predicted, and absolute FEV1 values increased significantly after the Sildenafil administration compared with baseline values (p<0.01). Similarly, the FEV1/FVC ratio also increased significantly with the Sildenafil administration compared to baseline values (p<0.01). Pulmonary artery systolic pressure significantly decreased from its baseline value with Sildenafil administration (p<0.01). Serum BNP values significantly reduced with Sildenafil administration compared to the pre-treatment values (p<0.01). This is the first study conducted in COPD patients with erectile dysfunction who had also pulmonary hypertension. The single-dose Sildenafil administration reduced PASP and serum BNP levels significantly. For the first time in the literature, we showed that the spirometric pulmonary function tests, namely FEV1 and FEV1/FVC ratio, improved significantly with the Sildenafil administration.

Measurement of Pulmonary Artery Wave Reflection Before and After Mitral Valvuloplasty in Canine Patients With Pulmonary Hypertension Caused by Myxomatous Mitral Valve Disease

Background: Pulmonary arterial wave reflection provides novel information about pulmonary artery hemodynamics in pulmonary hypertension (PH). PH is common in dogs with myxomatous mitral valve disease (MMVD), though research examining the relationship between pulmonary arterial wave reflection and MMVD with PH is lacking.Hypothesis/Objective: This study investigated conventional echocardiographic parameters and pulmonary artery wave reflection parameters before and after mitral valvuloplasty in canine patients with PH due to MMVD. The parameters were backward pressure (Pb), forward pressure (Pf), and the reflection coefficient calculated as the ratio of peak Pb to peak Pf (RC).Animals: The study subjects were 10 client-owned dogs receiving mitral valvuloplasty for MMVD with PH.Methods: Conventional echocardiographic parameters and pulmonary artery wave reflection parameters were measured before and after mitral valvuloplasty. The relationships between pulmonary artery wave reflection parameters and echocardiographic parameters, estimation of pulmonary artery systolic pressure, and right atrium pressure (RAP) gained by catheter in mitral valvuloplasty were also investigated. Post-operative echocardiography and the measurement of pulmonary arterial wave reflection were performed 2 weeks after mitral valvuloplasty.Results: The parameters of normalized left ventricular internal diameter at end-diastole (LVIDDN), E velocity, and the estimation of pulmonary artery systolic pressure were significantly reduced post-operatively compared with baseline measurements (p < 0.05). Post-operative Pb decreased significantly compared with pre-operative measurements (8.8 ± 5.9 to 5.0 ± 3.2 mmHg, p = 0.037) as did RC (0.37 ± 0.15 to 0.22 ± 0.11, p < 0.01). A statistically significant positive correlation existed between wave reflection parameters and RAP, an estimation of pulmonary artery systolic pressure.Conclusions: Results demonstrate that mitral valvuloplasty can be used to treat secondary PH caused by MMVD, resulting in the improvement of post-operative echocardiographic and wave reflection parameters and a decrease in the right afterload. In some patients, some degree of vascular admittance mismatch persisted, despite the improvement of left atrial pressure. This may be indicative of residual pulmonary arterial disease, which may continue to adversely affect interactions between the right ventricle and the vasculature.

The Accuracy and Influencing Factors of Doppler Echocardiography in Estimating Pulmonary Artery Systolic Pressure: Comparison With Right Heart Catheterization : A Retrospective Cross-sectional Study

Background: Noninvasive assessment of pulmonary artery systolic pressure by Doppler echocardiography (sPAPECHO) has been widely adopted to screen for pulmonary hypertension (PH). But high proportion of overestimation or underestimation of sPAPECHO still remained. So we aimed to explore the accuracy and influencing factors of sPAPECHO with right heart catheterization (RHC) as reference. Methods: A total of 218 highly suspected pulmonary hypertension (PH) patients who underwent RHC and echocardiography within 7 days were included. The correlation and consistency between tricuspid regurgitation (TR) derived parameters and RHC results were tested by Pearson and Bland-Altaman methods. With mPAP ≥25mmHg measured by RHC as the standard diagnostic criteria of PH, ROC curve was used to compared the diagnostic efficacy of sPAPECHO with other TR related methods. The ratio of (sPAPECHO-sPAPRHC)/sPAPRHC was calculated and divided into three groups, namely, the underestimation group, accurate group and overestimation group by ±10% as the boundary. The influencing factors of sPAPECHO were analyzed by ordinal regression analysis.Results: sPAPECHO had the greatest correlation coefficient (r=0.781, P<0.001), best diagnostic efficiency (AUC=0.98) and lowest bias (mean bias= 0.07mmHg, 95% limits of agreement: -32.08 to +32.22mmHg) compared with other TR related methods. Ordinal regression analysis showed that TR signal quality, PAWP and sPAPRHC level affected the accuracy of sPAPECHO (P < 0.05). The OR value of PAWP was 0.94 (95%CI: 0.89, 0.99). Compared with high sPAPRHC level, the OR value of low and medium sPAPRHC level were 21.56 (95%CI: 9.57, 48.55) and 5.13 (95%CI: 2.55, 10.32) , respectively. Relative to the signal quality of type A, the OR value of type B and C signal quality were 0.26 (95%CI: 0.14, 0.48) and 0.23 (95%CI: 0.07, 0.73), respectively. While TR severity and right ventricular systolic function had no significant effect on the accuracy of sPAPECHO. Conclusions: sPAPECHO was superior to other TR-related methods in PH screening, and was often overestimated in patients with pre-capillary PH at low sPAPRHC level, even with good TR signal quality.Trial registration: This is a retrospectively registered study.

Unplanned Surgery After Transcatheter Closure of Ventricular Septal Defect in Children: Causes and Risk Factors

Objectives: To evaluate the causes and risk factors of unplanned surgery after transcatheter closure of ventricular septal defect (VSD) in children.Methods: A total of 773 patients with VSD who had the devices transcatheter released between January 2013 and December 2018 in our institution were retrospectively reviewed. Univariate and multivariate analyses were used to identify the risk factors for unplanned surgery.Results: Twenty four patients (3.1%) underwent unplanned surgery after transcatheter closure of VSD. The most common cause for unplanned surgery was new-onset or worsening aortic regurgitation (14/24; 58.3%), followed by occluder migration (4/24; 16.7%), complete atrioventricular block (2/24; 8.3%), severe hemolysis (2/24; 8.3%), residual shunt (1/24; 4.2%), and occluder edge near the tricuspid valve chordae (1/24; 4.2%). Logistic regression analysis revealed that primary aortic valve prolapse (OR: 5.507, 95%CI: 1.673–18.123, P = 0.005); intracristal VSD (OR: 8.731, 95%CI: 2.274–33.527, P = 0.002); eccentric occluder (OR: 4.191, 95%CI: 1.233–14.246, P = 0.022); larger occluder size (OR: 1.645, 95%CI: 1.331–2.033, P &lt; 0.001); and pulmonary artery systolic pressure ≥45 mmHg (OR: 4.003, 95%CI: 1.073–14.941, P = 0.039) were risk factors for unplanned surgery.Conclusions: New-onset or worsening aortic regurgitation was the primary cause for unplanned surgery after transcatheter closure of VSD in children. Primary aortic valve prolapse, intracristal VSD, eccentric occluder, larger occluder size, pulmonary artery systolic pressure ≥45 mmHg could increase the risk of unplanned surgery.

Type II Abernethy malformation in an adult male patient—a rare and reversible cause of pulmonary hypertension: a case report with review of literature

Background Co-occurrence of Type II Abernethy malformation (AM) with Type 1 pulmonary hypertension (PH) is extremely rare. In these patients, management of AM leads to reversal of PH. Case presentation We report a case of 24-year-old male that presented with fever and dyspnea of insidious-onset. Initial X-ray chest revealed pulmonary edema, prominent pulmonary knuckle, and dilated right descending pulmonary artery. Two-dimensional echocardiography suggested raised pulmonary artery systolic pressure (145 mmHg) and pulmonary angiogram revealed findings suggestive of Type 1 PH. Treatment with Tab. Tadalafil-Bosentan (20/5 mg, thrice daily) was initiated, but no major relief was obtained. On day 10, dyspnea worsened. Routine ultrasound revealed splenomegaly. Further evaluation with Doppler of the portal vein was suggestive of portal hypertension, and arterial ammonia was found to be raised. Contrast-enhanced computed tomography of abdomen and pelvis demonstrated a single dilated (1.3 cm) and torturous venous shunt between right internal iliac vein and superior mesenteric vein. Thus, a definitive diagnosis of Type II AM was reached. The patient was stabilized and subjected to the shunt closure with ASD Cocoon stent graft and recovered well. Conclusion Our case demonstrates a rare but reversible cause of PH. Type II AM should be included in the differential diagnosis of a patient presenting with dyspnea and provisionally diagnosed as a case of PH.

Prognostic Role of Subclinical Congestion in Heart Failure Outpatients: Focus on Right Ventricular Dysfunction

Background: subclinical pulmonary and peripheral congestion is an emerging concept in heart failure, correlated with a worse prognosis. Very few studies have evaluated its prognostic impact in an outpatient setting and its relationship with right-ventricular dysfunction. The study aims to investigate subclinical congestion in chronic heart failure outpatients, exploring the close relationship between the right heart-pulmonary unit and peripheral congestion. Materials and methods: in this observational study, 104 chronic HF outpatients were enrolled. The degree of congestion and signs of elevated filling pressures of the right ventricle were evaluated by physical examination and a transthoracic ultrasound to define multiparametric right ventricular dysfunction, estimate the right atrial pressure and the pulmonary artery systolic pressure. Outcome data were obtained by scheduled visits and phone calls. Results: ultrasound signs of congestion were found in 26% of patients and, among this cohort, half of them presented as subclinical, affecting their prognosis, revealing a linear correlation between right ventricular/arterial coupling, the right-chambers size and ultrasound congestion. Right ventricular dysfunction, TAPSE/PAPS ratio, clinical and ultrasound signs of congestion have been confirmed to be useful predictors of outcome. Conclusions: subclinical congestion is widespread in the heart failure outpatient population, significantly affecting prognosis, especially when right ventricular dysfunction also occurs, suggesting a strict correlation between the heart-pulmonary unit and volume overload.

Preoperative Evaluation of Pulmonary Hypertension in Lung Transplant Candidates: Echocardiography Versus Right Heart Catheterization

Background - Right heart catheterization (RHC) and echocardiography are both routinely used for pulmonary artery systolic pressure (PASP) assessment in lung transplantation (LT) candidates, although this is not mandated by current guidelines. We aimed to explore the correlation between PASP estimated by echocardiography to that measured by RHC, in this population in order to assess the necessity of RHC. Methods - From a retrospective registry of 393 LT candidates undergoing RHC and echocardiography during 2015-2019, patients were assessed for the presence of pulmonary hypertension (PH), defined as mean pulmonary artery pressure (mPAP) above 20 mmHg, according to two methods – echocardiography and RHC. The primary outcome was the correlation between the PASP estimated by echocardiography to that measured by RHC. Secondary outcomes were the prediction value of the echocardiographic evaluation and its accuracy. Results - The mean value of PASP estimated by echocardiography was 49.5±20.0 mmHg, compared to 42.5±18.0 mmHg measured by RHC. The correlation between the two measurements was moderate (Pearson’s correlation: r=0.609, p<0.01). Echocardiography PASP measurements were moderately discriminative to diagnose PH, with an area under the curve (AUC) of 0.72 (95% CI 0.66-0.76). Echocardiographic overestimation of PASP of more than 10 mmHg was found in 35.0% of the patients, and underestimation was found in 11.6% of the patients.Conclusion - In the pre-surgical evaluation of LT candidates, echocardiographic estimation of PASP had moderate correlation and limited accuracy compared to the PASP measured by RHC. We thus recommend performing routine RHC to all LT candidates, regardless of the echocardiographic estimation of PASP.

Preventing the Increase in Lysophosphatidic Acids: A New Therapeutic Target in Pulmonary Hypertension?

Cardiovascular diseases (CVD) are the leading cause of premature death and disability in humans that are closely related to lipid metabolism and signaling. This study aimed to assess whether circulating lysophospholipids (LPL), lysophosphatidic acids (LPA) and monoacylglycerols (MAG) may be considered as potential therapeutic targets in CVD. For this objective, plasma levels of 22 compounds (13 LPL, 6 LPA and 3 MAG) were monitored by liquid chromatography coupled with tandem mass spectrometry (HPLC/MS2) in different rat models of CVD, i.e., angiotensin-II-induced hypertension (HTN), ischemic chronic heart failure (CHF) and sugen/hypoxia(SuHx)-induced pulmonary hypertension (PH). On one hand, there were modest changes on the monitored compounds in HTN (LPA 16:0, 18:1 and 20:4, LPC 16:1) and CHF (LPA 16:0, LPC 18:1 and LPE 16:0 and 18:0) models compared to control rats but these changes were no longer significant after multiple testing corrections. On the other hand, PH was associated with important changes in plasma LPA with a significant increase in LPA 16:0, 18:1, 18:2, 20:4 and 22:6 species. A deleterious impact of LPA was confirmed on cultured human pulmonary smooth muscle cells (PA-SMCs) with an increase in their proliferation. Finally, plasma level of LPA(16:0) was positively associated with the increase in pulmonary artery systolic pressure in patients with cardiac dysfunction. This study demonstrates that circulating LPA may contribute to the pathophysiology of PH. Additional experiments are needed to assess whether the modulation of LPA signaling in PH may be of interest.

Multimarker approach for assessing efficiency of cardiac resynchronization therapy in patients with sinus rhythm

Purpose. To design a mathematical model, that can predict a positive response to cardiac resynchronization therapy (CRT) in patients with congestive heart failure (CHF) and sinus rhythm, according to complex analysis of neurohumoral and immune activation biomarkers, fibrosis, renal dysfunction, echocardiography.Methods. Parameters of echocardiography, plasma levels of NT-proBNP, interleukins-1β, 6, 10, tumor necrosis factor α, С-reactive protein (СRP), matrix metalloproteinase-9 (ММР-9), tissue inhibitors of metalloproteinase 1 and 4, cystatin С (CYSTATIN) were studied in 40 CHF patients with sinus rhythm (65% coronary artery disease patients, 75% males, mean age 54.8±10.6 years old) during the period of maximum decrease of left ventricular end-systolic volume (LVESV) (mean duration 27.5 [11.1; 46.3] months). Responders (decrease in LVESV ≥15%) and non-responders (decrease in LVESV <15%) were identified.Results. The number of responders was 26 (65%). The initial set of variables included: age, left ventricular ejection fraction (EF), pulmonary artery systolic pressure, right ventricle size and NT-proBNP, СRP, ММР-9, CYSTATIN. According to logistic regression analysis, a prediction model of positive CRT response was created. The specificity of the model was 92.9%, sensitivity - 83.3%, AUC=0.952 (р˂0.001).Conclusion. The proposed model, based on the assessment of left ventricle EF and circulating biomarkers of inflammation, fibrosis, and renal function, strongly suggests a higher possibility of response to CRT.

Cardiovascular status and echocardiographic changes in survivors of COVID-19 pneumonia three months after hospital discharge

Coronavirus disease 2019 (COVID-19) affects the function of all organs and systems. Today, studying the effect of COVID-19 on cardiovascular system, including on echocardiographic characteristics, is relevant.Aim. To study the prevalence of symptoms, cardiovascular disease and changes in echocardiographic data in persons after documented COVID-19 pneumonia 3 months after discharge from the hospital.Material and methods. The study included 106 patients after documented COVID-19 pneumonia. The patients underwent a comprehensive examination during hospitalization and 3 months±2 weeks after discharge from the hospital. The mean age of participants was 47±16 years (19-84 years); 49% of subjects were women.Results. Three months after hospital discharge, the symptoms persisted in 86% of examined patients. There were significant echocardiographic changes as follows: a decrease in LV end-diastolic, end-systolic and stroke volume (113,8±26,8 ml vs 93,5±29,4 ml; 37,7±13,0 ml vs 31,3±14,2 ml; 77,2±17,8 ml vs 62,2±18,7 ml, respectively, p<0,001 for all). The right ventricular anteroposterior dimension and the pulmonary trunk diameter decreased over time (26,0 [24,0-29,3] mm vs 25,0 [23,0-27,0] mm, p=0,004; 21,7±3,6 mm vs 18,7±2,5 mm, p<0,001), the same as the pulmonary artery systolic pressure, estimated by tricuspid regurgitation gradient (28,0 [25,0-32,25] mm Hg vs 21,5 [17,0-25,0] mm Hg). The right atrial volume (42,0 [37,0-50,0] m><0,001), the same as the pulmonary artery systolic pressure, estimated by tricuspid regurgitation gradient (28,0 [25,0-32,25] mm Hg vs 21,5 [17,0-25,0] mm Hg). The right atrial volume (42,0 [37,0-50,0] ml vs 31,0 [22,0-36,5] ml, p<0,001) a><0,001) and maximum width (36,1±4,6 mm vs 34,5±6,5 mm, p=0,023) decreased, while the right atrial maximum length increased (46,7±6,8 mm vs 48,6±7,1 mm, p=0,021).Conclusion. In survivors of COVID-19 pneumonia three months after hospital discharge, complaints persisted in 86% of cases. Cardiovascular diseases were detected in 52% of participants, including hypertension in 48,1% and coronary artery disease in 15,1%. Compared with in-hospital data, the echocardiographic characteristics improved, which was expressed mainly in a decrease in right heart load.