The paradox of pulmonary arterial hypertension in Italy in the COVID-19 era: is risk of disease progression around the corner?

OBJECTIVE: The coronavirus disease 2019 (COVID-19) outbreak has led to significant restrictions on routine medical care. We conducted a multicentre nationwide survey of patients with pulmonary arterial hypertension (PAH) to determine the consequences of governance measures on PAH management and risk of poor outcome in patients with COVID-19. MATERIALS AND METHODS: The present study, which included 25 Italian centres, considered demographic data, the number of in-person visits, 6-min walk and echocardiographic test results, brain natriuretic peptide/N-terminal pro-brain natriuretic peptide test results, World Health Organization functional class assessment, presence of elective and non-elective hospitalisation, need for treatment escalation/initiation, newly diagnosed PAH, incidence of COVID-19 and mortality rates. Data were collected, double-checked and tracked by institutional records between March 1 and May 1, 2020, to coincide with the first peak of COVID-19 and compared with the same time period in 2019. RESULTS: Among 1922 PAH patients, the incidences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 were 1.0% and 0.46%, respectively, with the latter comparable to that in the overall Italian population (0.34%) but associated with 100% mortality. Less systematic activities were converted into more effective remote interfacing between clinicians and PAH patients, resulting in lower rates of hospitalisation (1.2% versus 1.9%) and related death (0.3% versus 0.5%) compared with 2019 (p<0.001). A high level of attention is needed to avoid the potential risk of disease progression related to less aggressive escalation of treatment and the reduction in new PAH diagnoses compared with 2019. CONCLUSION: A cohesive partnership between healthcare providers and regional public health officials is needed to prioritise PAH patients for remote monitoring by dedicated tools.

Risk Reduction and Hemodynamics with Initial Combination Therapy in Pulmonary Arterial Hypertension.

Rationale: An initial oral combination of drugs is being recommended in pulmonary arterial hypertension (PAH), but the effects of this approach on risk reduction and pulmonary vascular resistance (PVR) are not known.Objectives: To test the hypothesis that a low-risk status would be determined by the reduction of PVR in patients with PAH treated upfront with a combination of oral drugs.Methods: The study enrolled 181 treatment-naive patients with PAH (81% idiopathic) with a follow-up right heart catheterization at 6 months (interquartile range, 144-363 d) after the initial combination of endothelin receptor antagonist + phosphodiesterase-5 inhibitor drugs and clinical evaluation and risk assessments by European guidelines and Registry to Evaluate Early and Long-Term PAH Disease Management scores.Measurements and Main Results: Initial combination therapy improved functional class and 6-minute-walk distance and decreased PVR by an average of 35% (median, 40%). One-third of the patients had a decrease in PVR <25%. This poor hemodynamic response was independently predicted by age, male sex, pulmonary artery pressure and cardiac index, and at echocardiography, a right/left ventricular surface area ratio of greater than 1 associated with low tricuspid annular plane systolic excursion of less than 18 mm. A low-risk status at 6 months was achieved or maintained in only 34.8% (Registry to Evaluate Early and Long-Term PAH Disease Management score) to 43.1% (European score) of the patients. Adding criteria of poor hemodynamic response improved prediction of a low-risk status.Conclusions: A majority of patients with PAH still insufficiently improved after 6 months of initial combinations of oral drugs is identifiable at initial evaluation by hemodynamic response criteria added to risk scores.

Long-term clinical stabilization of scleroderma patients treated with a chronic and intensive IV iloprost regimen.

Intravenous iloprost is a first-line option for the treatment of scleroderma-related digital vasculopathy, and some studies have suggested its favourable role on disease progression. The aim of our study is to evaluate the disease progression, specifically in terms of cardiopulmonary function, in a group of consecutive patients chronically treated with intravenous iloprost. Our retrospective study enrolled 68 scleroderma patients (68 F, 54.4 ± 12.3 years) treated with iloprost for 7.1 ± 2.9 years, with a schedule of 5-6 consecutive daily infusions per month (6 h/day, 0.5-2.0 ng/kg/min). In all patients, modified Rodnan skin score (4.7 ± 5.3 vs. 3.7 ± 5.3, p < 0.0001), systolic pulmonary arterial pressure (sPAP) (30.9 ± 6.4 vs. 24.0 ± 3.2 mmHg, p < 0.0001), tricuspid annular plane systolic excursion (22.1 ± 2.4 vs. 23.8 ± 3.5 mm, p = 0.0001), pro-brain natriuretic peptide (97.2 ± 69.3 vs. 65.8 ± 31.7 pg/ml, p = 0.0005) showed statistically significant improvement from baseline. In the subgroup of patients with baseline sPAP ≥36 mmHg (n = 17), a significant sPAP reduction was observed (from 39.5 ± 3.8 to 25.1 ± 4.5 mmHg, p < 0.0001) after 7.6 ± 2.5 years of follow-up. The number of patients with digital ulcers (DUs) at follow-up was reduced from baseline (42.6 vs. 11.8%, p < 0.001), and none of the free-DU patients at baseline presented DUs at follow-up. An intensive and chronic regimen of IV iloprost administration seems to stabilize and potentially improve the long-term development of disease in SSc patients, as suggested by stabilization or significant improvement of cardiopulmonary parameters and vasculopathy.

Gaps in evidence in the management of patients with intermediate-risk pulmonary arterial hypertension: Considerations following the ESC/ERS 2022 guidelines.

A comprehensive evaluation of risk, using multiple indices, is necessary to provide reliable prognostic information and guide therapy in pulmonary arterial hypertension (PAH). The current ESC/ERS guidelines suggest using a three-strata model for incident (newly diagnosed) patients and a four-strata model for prevalent patients with PAH. The four-strata model serves as a fundamental risk-stratification tool and relies on a minimal dataset of indicators that must be considered during follow-up. Nevertheless, there are still areas of vagueness and ambiguity when classifying and managing patients in the intermediate-risk category. For these patients, considerations should include right heart imaging, hemodynamics, as well as individual factors such as age, sex, genetic profile, disease type, comorbidities, and kidney function. The aim of this report is to present case studies, with a specific focus on patients ultimately classified as intermediate risk. We aim to emphasize the challenges and complexities encountered in the realms of diagnosis, classification, and treatment for these particular patients.

Right ventricular phenotyping in incident patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools. METHODS: Consecutive incident PAH patients aged ≥18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography. Simple echocardiographic variables were combined in order to define a priori four phenotypes representing different degrees of RV dilatation and RV-pulmonary arterial (PA) coupling: Phenotype 1 with mildy dilated right ventricle and preserved RV-PA coupling (n = 152 patients); phenotype 2 with mildly dilated right ventricle and poor RV-PA coupling (n = 143 patients); phenotype 3 with severely dilated right ventricle and preserved RV-PA coupling (n = 201 patients); phenotype 4 with severely dilated right ventricle and poor RV-PA coupling, with or without severe tricuspid regurgitation (n = 519 patients). Risk stratification was based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) 3-strata model and Registry to Evaluate Early and Long-Term PAH disease Management (REVEAL) 2.0 score. RESULTS: These phenotypes were present in all risk groups. Notably, regardless of the ESC/ERS risk stratum assigned to the patient, phenotype 4 was associated with a 2-fold increase of the odds of death (HR 2.1, 95% CI 1.6-2.8, p < 0.001), while phenotype 1 was associated with a 71% reduction in the odds of dying (HR 0.29, 95% CI 0.18-0.47, p < 0.001). CONCLUSIONS: Echocardiography-derived phenotypes describing RV remodeling and dysfunction may provide prognostic information which is independent of and additional to the clinically defined risk in incident PAH patients.

Accuracy of intracardiac echocardiography for aortic root assessment in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Multislice computed tomography (MSCT) has generally been accepted as the most accurate modality fulfilling this purpose with good reproducibility. A major drawback of MSCT consists in the use of contrast dye, which may be unsafe in transcatheter aortic valve implantation (TAVI) patients who frequently are affected by renal failure. We sought to appraise the accuracy of intracardiac echocardiography (ICE) in measurements of structures in the aortic root in patients undergoing TAVI. METHODS: Aortic annulus and sinus of Valsalva diameters were measured using ICE, performed during standard invasive preprocedural assessment in 30 consecutive patients with severe aortic stenosis referred for TAVI. Multislice computed tomography was performed in all patients afterward, and aortic root measurements were made by an independent radiologist. RESULTS: Effective ICE measurements were obtained in all patients, easily and without any complication. Mean aortic annulus diameters were 21.9 ± 1.8 mm using ICE, 22.0 ± 1.9 mm using MSCT (3-chamber [3-C] view) and 22.8 ± 1.8 mm using the mean of long-axis and short-axis (L-ax/S-ax) view MSCT (P = .192, ICE vs 3-C MSCT; P < .001, ICE vs L-ax/S-ax MSCT, respectively). Correlation between ICE and both MSCT measurements was good (r(2) = 0.83, P < .001; r(2) = 0.80, P < .001, respectively). Mean sinus of Valsalva diameters were 32.3 ± 3.3 mm using ICE and 32.5 ± 3.1 mm using 3-C MSCT view (P = .141). Even in this case, correlation between ICE and both MSCT measurements was excellent (r(2) = 0.96, P < .001). CONCLUSIONS: In patients referred for TAVI, measurements of the aortic annulus and the sinus of Valsalva using ICE compare favorably with those made at MSCT. This approach might be a useful and reproducible strategy in patients with severe renal impairment to avoid the administration of contrast dye during MSCT.

Early- and mid-term outcomes of transcatheter aortic valve implantation in patients with logistic EuroSCORE less than 20%: a comparative analysis between different risk strata.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an emerging alternative to medical therapy reserved to a limited population with severe aortic stenosis. The European consensus document recommended TAVI for prohibitive-risk patients not eligible for conventional surgery (prohibitive risk defined as expected mortality ≥ 20% calculated with the Logistic EuroScore (LES) in association with clinical judgment). To date, there is lack of clarity on data about outcomes of TAVI in lower risk patients. We sought to evaluate the outcomes of patients undergoing TAVI with LES ≥ 20% in comparison with patients with LES < 20%. METHOD: Of 165 patients who underwent TAVI using the 18-French Medtronic CoreValve (N = 153) and the Sapien Edwards™ (N = 12) at our Institution between June 2007 and September 2010, we identified those with LES < 20%, with prosthesis implantation (n = 84), and reported on their clinical outcome compared with patients with LES ≥ 20% (n = 78). The primary endpoint was the incidence of overall death and major adverse cerebrovascular and cardiac events (MACCE) at 30-day and midterm follow-up stratifying patients by clinical characteristics. RESULTS: At 30-day, a significant higher incidence of MACCE (20.8% vs. 6.0%, odds ratio [OR] 4.08 95% confidence interval [CI] 1.42-11.74, P = 0.009) and death (15.6% vs. 2.4%, OR 7.45 95% CI 1.61-34.48, P = 0.010) was reported in the LES ≥ 20% group as compared with the LES < 20% group, respectively. The 12-month MACCE rates was (27.1% vs. 11.4%, hazard ratio [HR] 2.47 95% CI 0.93-6.63, P = 0. 071) for LES ≥ 20% and LES < 20% patients, respectively (mortality rates was 25.7% vs. 6.8% HR 4.21 95% CI 1.24-14.30, P = 0.021). CONCLUSION: This study tends to suggest that current mortality reported after TAVI could be significantly affected by the very-high risk profile of the population which currently undergoes this procedure, making comparison with surgical series rather unreliable.

Selection of patient for cardiac resynchronization therapy: role of QT corrected dispersion.

AIMS: About 30 to 50% of patients undergoing cardiac resynchronization therapy (CRT) may not show clinical or echocardiographic improvement, despite fulfilling guidelines recommendations for CRT. For this reason, we need a more accurate method to assess CRT eligibility. The aims of this study were to verify, on a 12-month follow-up, the usefulness of QT corrected dispersion (QTcD) in a patient's selection for CRT. METHODS: We stratified 53 patients who underwent CRT, into two groups based on the estimation of QTcD, that is, QTcD > 60 ms and QTcD ≤ 60 ms. In all patients were performed New York Heart Association (NYHA) class determination, six-minute walking test, QtcD, and QRS measurements, and complete echocardiographic assessment at 1, 3, 6, and 12 months after implantation. RESULTS: At baseline, there were no significant differences in clinical, echocardiographic, and electrocardiographic parameters duration between two groups. At 12-month follow-up between the two groups, there were significant differences in NYHA (1.2 ± 0.4 vs 2 ± 0.6; P < 0.01), six-minute walking distance (422 ± 68 vs 364 ± 68; P < 0.01), left ventricular (LV) ejection fraction (34 ± 7% vs 28 ± 6%; P < 0.01), LV end-diastolic diameter (57 ± 7 vs 63 ± 8; P < 0.01), and LV intraventricular dyssynchrony (24 ± 14 vs 39 ± 23; P < 0.01). CONCLUSION: This study suggests that QTc dispersion in addition to QRS duration could improve the sensitivity of electrocardiogram in a patient's selection for CRT.

Relevance of comorbidities on initial combination therapy in pulmonary arterial hypertension.

Rationale: Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting. Methods: The study enrolled 181 treatment-naive PAH patients with a 6-month (IQR 144-363 days) right heart catheterisation and risk assessment after initial oral combination therapy. Results: Group A included 96 (53.0%) patients without cardiac comorbidities; Group B included 54 (29.8%) patients with one cardiac comorbidity; Group C included 31 (17.1%) patients with two cardiac comorbidities or more. Group C patients were older with a balanced sex distribution. There was a significant difference in PVR reduction moving from the absence to one or at least two cardiac comorbidities, respectively: median -45.0%, -30.3%, -24.3%. A European Respiratory Society/European Society of Cardiology low-risk status was present at first follow-up in 50 (52.0%) patients in Group A, 19 (35.1%) in Group B and 9 (29.0%) in Group C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group A, 15 (27.7%) in Group B and 7 (22.6%) in Group C. Group A patients were 2.3 times more likely to achieve/maintain a low-risk status compared with Group B and C (OR 2.27, 95% CI 1.15-4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities. Conclusion: Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment-induced decrease in PVR.

Management of implant failure during transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an emerging alternative to palliative medical therapy for nonsurgical patients with severe aortic stenosis. There is a paucity of detailed data on the management and outcome of complications related to the sub-optimal deployment of the prosthesis. We appraised the incidence and management of early implant failure occurring during TAVI. METHODS: Of 110 patients who underwent TAVI using the third generation 18-French CoreValve ReValving System (Medtronic, MN) in our Institution between June 2007 and January 2010, we identified those experiencing early implant failure and reported on their management and clinical outcome. The primary endpoint was the incidence of major adverse cardiovascular and cerebrovascular event (MACCE) at 30 days and mid-term follow up. RESULTS: Early implant failure occurred in 18 of 110 patients (16.3%). The most common cause was prosthesis under-expansion conditioning moderate to severe peri-valvular leak (44.4%). Prosthesis deployment too low or too high with respect to the aortic annulus leading to severe peri-valvular leak occurred in 22.2% and 5.5% of patients, respectively. Need of valve retrieve after the first attempt of deployment occurred in four cases (22.2%). Prosthesis embolization in the ascending aorta occurred in 5.5% of patients who experienced early implant failure. All implant failure cases were managed percutaneously with gain in aortic valve area from 0.44 ± 0.17 to 1.28 ± 0.27 cm(2) (P < 0.001), decrease of mean transaortic gradient from 55.00 ± 19.51 to 11.58 ± 5.91 mmHg (P < 0.001) and no MACCE at 30 days. After 11 ± 6 months, MACCE occurred cumulatively in two patients (11.1%). CONCLUSIONS: Early implant failure can complicate the TAVI procedure with the CoreValve system, but it can be managed safely and effectively with bailout transcatheter techniques, avoiding surgery, with good early and mid-term clinical and echocardiographic results.

Postprocedural management of patients after transcatheter aortic valve implantation procedure with self-expanding bioprosthesis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) carries higher risk of post-procedural adverse events than conventional percutaneous cardiovascular interventions. We report our experience about postoperative management protocol adopted in our Division. METHODS: One hundred and ten patients underwent TAVI and 108 were transferred to the cardiac intensive care unit (CICU) after procedure. During the first 48 hours, vital parameters were monitored continuously. Close attention was given to rhythm and atrio-ventricular conduction disturbances, systemic blood pressure, fluid balance and vascular accesses. RESULTS: The most common complications were renal impairment (21.3%), femoral artery pseudo-aneurysms (FAP) (11%), new complete atrioventricular block (20.3 %), cerebral vascular accident (4.5%) and cardiac perforation due to temporary pacemaker lead (1.8%). Ultrasound-guided compression repair was considered the first line treatment for FAP, but in 6 cases surgical treatment was immediately performed due to the rapid expansion of FAP. Complete atrio-ventricular block occurred in 22 patients (20.3 %) within the first 24 hours after TAVI and a permanent pacemaker was implanted in 21 patients (19.1%). Acute kidney injury occurred in 18 patients (35%) with pre-procedural chronic renal failure and in 5 patients (9%) without preoperative renal dysfunction. CONCLUSIONS: After TAVI, cardiovascular complications are common and therefore accurate standardized management of patients in CICU during the first 48 hours is mandatory to early detect and manage complications and to decrease the rate of adverse events and the length of in-hospital stay. © 2010 Wiley-Liss, Inc.

Quality of life assessment after percutaneous aortic valve implantation.

AIMS: To assess the NYHA class and the quality of life (QoL) scores after percutaneous aortic valve implantation (PAVI) with the 18-Fr CoreValve prosthesis. METHODS AND RESULTS: From April 2007 until August 2008, 57 consecutive patients with aortic stenosis were evaluated for PAVI. Of these, 30 patients with successfully prosthesis implantation had more than 5-month follow-up. QoL assessment was realized with the SF-12v2 Health-Survey, a simple questionnaire designed for self-administration that provides easily interpretable scales for physical [physical component summary (PCS)] and mental [mental component summary (MCS)] health. The questionnaire was administered before and 5 months after PAVI. All 30 patients had a marked upgrading in haemodynamic and echocardiographic parameters (peak-to-peak gradient from 64 +/- 23 to 2 +/- 0.4; P < 0.001; aortic valve area index from 0.3 +/- 0.1 to 0.9 +/- 0.3; P < 0.001), with an improvement in New York Heart Association (NYHA) class at discharge and after 5 months. Mean pre-operative SF-12v2 scores showed a severe impairment of perceived quality of life compared with general Italian population >75 years, both for physical (PCS-baseline 28.5 vs. 37.9, P < 0.001) and mental scores (MCS-baseline 37.8 vs. 45.4, P < 0.001). After 5 months, a striking improvement in both scores (PCS 41.3-MCS 48.3; P < 0.001) was observed. CONCLUSION: Our preliminary results show a marked short-term improvement in functional status and physical and mental health in patients underwent PAVI.

The valve-in-valve technique: transcatheter treatment of aortic bioprothesis malposition.

Percutaneous aortic valve replacement is an emerging alternative to palliative medical therapy for nonsurgical patients with severe aortic valve stenosis. The impossibility of repositioning of the current transcatheter prosthesis in case of suboptimal placement is the main limit of these devices. Here, we report on a case of an 84-year-old woman successfully treated with implantation of two 18-Fr CoreValve prosthesis (CoreValve, Irvine, California), because of the suboptimal deployment of the first one, analyzing the procedural technique and the immediate and short-term clinical and hemodynamic results.

Percutaneous closure of patent foramen ovale with a bioabsorbable occluder device: single-centre experience.

BACKGROUND: Percutaneous closure of patent foramen ovale (PFO) is routinely performed with nonbiological devices, characterized by a persistent low-grade inflammatory response. We report our experience about PFO closure with a bioabsorbable device, BioSTAR (NMT Inc, USA). METHODS: From September 2007 to September 2008, 14 patients with migraine (eight with aura) and cerebral magnetic resonance positive for silent ischemia and nine patients with prior cardiovascular accident (CVA) underwent closure of PFO using BioSTAR. One patient had heterozygosis for sickle-cell-anaemia. Nickel allergy was present in eight patients. Echocardiogram was performed at 24 hr, one and 6 months. At 6 and 12 months a contrast-transcranial-doppler (c-TCD) and a trans-oesophageal echocardiogram (TOE) were scheduled, respectively. RESULTS: BioSTAR was successfully implanted in 22 patients (96%). The mean procedural time and the mean fluoroscopy time were 22 +/- 6 and 4 +/- 2 minutes, respectively. The mean in-hospital stay was 3 +/- 0.5 days. After a mean follow-up of 7.8 +/- 3.5 months there was an hemorrhagic stroke related to double antiaggregation. No other CVA or allergic reactions were registered. There were two cases of atrial arrhythmia. Fifteen patients had not residual shunts at c-TCD, while in four patients we observed a trivial microbubbles passage. The TOE, achieved in nine patients without contrast, showed the device well positioned, with a low profile and without thrombus. CONCLUSIONS: In our experience PFO closure with BioSTAR is safe and efficacious in preventing recurrent CVA. Its use could be advantageous in patients with nickel allergy and haematological disorders. The potential benefits of this device need to be certified in a larger cohort of patients with a longer follow-up.

Percutaneous closure of left atrial appendage to prevent embolic events in high-risk patients with chronic atrial fibrillation.

BACKGROUND: Percutaneous closure of the left atrial appendage (LAA) is a novel alternative for the treatment of patients with atrial fibrillation (AF) and with a high risk of stroke who are not eligible for long-term anticoagulation therapy. The aim of this study was to asses the safety, feasibility, and long-term efficacy of this procedure. METHODS: From July 2004 to June 2007, 20 patients (13 male, mean age 69 +/- 8 years) with non-valvular AF (NV-AF) underwent LAA percutaneous closure using the PLAATO system, implanted through a transeptal access. All patients had contraindications to anticoagulant therapy and were at high risk for cardioembolic stroke (mean CHADS(2) score 3 +/- 1.2). A trans-thoracic echocardiogram was performed at 1, 3, and every 6 months after the procedure, whereas a trans-oesophageal echocardiogram (TOE) was scheduled at 6 months. After 24 months, a phone interview was obtained. RESULTS: All procedures were successfully performed in 18 patients. In two patients, LAA closure was not feasible for the presence of a multilobed LAA. Two patients underwent percutaneous closure of patent foramen ovale in the same session. In one patient, the procedure was complicated by cardiac perforation with pericardial effusion, treated with pericardiocentesis. At a mean follow up of 40 +/- 10 months, no embolic events occurred. One patient died, after 36 months, for gastric cancer. TOE examination showed the complete exclusion of the LAA in all patients. CONCLUSIONS: Percutaneous closure of LAA is safe and efficacious to prevent stroke in patients with NV-AF at high risk for cardioembolic events, with contraindications to anticoagulant therapy.

Influence of various therapeutic strategies on right ventricular morphology, function and hemodynamics in pulmonary arterial hypertension.

BACKGROUND: In idiopathic pulmonary arterial hypertension (IPAH) treatment goals include improving right ventricular (RV) function, hemodynamics and symptoms to move patients to a low-risk category for adverse clinical outcomes. No data are available on the effect of upfront combination therapy on RV improvement as compared with monotherapy. The aim of this study was to evaluate echocardiographic RV morphology and function in patients affected by IPAH and treated with different strategies. METHODS: Sixty-nine consecutive, treatment-naive IPAH patients treated with first-line upfront combination therapy at 10 centers were retrospectively evaluated and compared with 2 matched cohorts treated with monotherapy after short-term follow-up. Evaluation included clinical, hemodynamic and echocardiographic parameters. RESULTS: At 155 ± 65 days after baseline evaluation, patients in the oral+prostanoid group (Group 1) had the most clinical and hemodynamic improvement compared with the double oral group (Group 2), the oral monotherapy group (Group 3) and the prostanoid monotherapy group (Group 4). The more extensive reduction of pulmonary vascular resistance in Groups 1, 2 and 4 was associated with significant improvement in all RV echocardiographic parameters compared with Group 3. Considering the number of patients who reached the target goals suggested by established guidelines, 8 of 27 (29.6%) and 7 of 42 (16.7%) patients in Groups 1 and 2, respectively, achieved low-risk status, as compared with 2 of 69 (2.8%) and 6 of 27 (22.2%) in Groups 3 and 4, respectively. CONCLUSIONS: In advanced treatment-naive IPAH patients, an upfront combination therapy strategy seems to significantly improve hemodynamics and RV morphology and function compared with oral monotherapy. The most significant results seem to be achieved with prostanoids plus oral drug, whereas the use of the double oral combination and prostanoids as monotherapy seem to produce similar results.

Prognostic relevance of pulmonary arterial compliance after therapy initiation or escalation in patients with pulmonary arterial hypertension.

BACKGROUND: Conventional hemodynamic parameters are considered to be the gold standard indices of outcome in pulmonary arterial hypertension (PAH); on the contrary, few data support the hypothesis that the pulsatile component of right ventricular afterload provides important prognostic information. The aim of the study was to investigate the prognostic significance of pulmonary arterial compliance (PCa) after therapy initiation or escalation in PAH patients. METHODS: A cohort of 419 consecutive PAH patients (308 naive and 111 prevalent) underwent right heart catheterisation (RHC) prior to initiating or escalating PAH-targeted therapy. RHC was repeated in 255 patients (61%) after 4 to 12months of therapy as 62 patients (15%) died and 102 (24%) did not undergo a follow-up RHC within the first year. RESULTS: After the follow-up RHC, 63 patients died over a median follow-up period of 39months. At multivariate analysis, age>50years old, male gender, etiology associated with systemic sclerosis, persistence of WHO class III/IV, and reduced PCa at follow-up RHC were the independent parameters significantly associated with poor prognosis. At ROC analysis, the optimal cut-off point of PCa to predict survival was 1.4mL/mmHg (AUC 0.73, sensitivity 81.8%, specificity 58.8%). CONCLUSIONS: In PAH patients hospitalized to initiate or to escalate PAH-specific therapy, failure to improve PCa after therapy is a strong hemodynamic predictor of poor prognosis.

New perspectives on management of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive parenchymal lung disease characterized by a median survival of 3-5 years following diagnosis. The diagnosis is based on clinical, radiological and histopathological evaluation. Therefore, a multidisciplinary team is needed to reach the correct diagnosis. For a long time, supportive care and lung transplantation in selected cases, have been considered the only possible treatments for IPF. In the last decade many studies have investigated IPF pathogenesis, leading to an improved knowledge of the mechanisms underlying the disease and to the approval of two new drugs for IPF treatment (pirfenidone and nintedanib). The therapeutic approach of IPF cannot be limited to the administration of antifibrotic drugs, but it is necessary for improving the quality of life of patients and for facilitating, as far as possible, the performance of normal daily activities and relationships. IPF patients are also afflicted by disease-related complications such as gastroesophageal reflux, pulmonary hypertension, acute exacerbations and an increased risk of developing lung cancer. The clinician who treats IPF patients, should also treat these possible complications to slow disease progression, thus maintaining the possibility of a pulmonary transplantation.

Lung membrane conductance and capillary volume derived from the NO and CO transfer in high-altitude newcomers.

Acute exposure to high altitude may induce changes in carbon monoxide (CO) membrane conductance (DmCO) and capillary lung volume (Vc). Measurements were performed in 25 lowlanders at Brussels (D0), at 4,300 m after a 2- or 3-day exposure (D2,3) without preceding climbing, and 5 days later (D7,8), before and after an exercise test, under a trial with two arterial pulmonary vasodilators or a placebo. The nitric oxide (NO)/CO transfer method was used, assuming both infinite and finite values to the NO blood conductance (θNO). Doppler echocardiography provided hemodynamic data. Compared with sea level, lung diffusing capacity for CO increased by 24% at D2,3 and is returned to control at D7,8. The acute increase in lung diffusing capacity for CO resulted from increases in DmCO and Vc with finite and infinite θNO assumptions. The alveolar volume increased by 16% at D2,3 and normalized at D7,8. The mean increase in systolic arterial pulmonary pressure at rest at D2,3 was minimal. In conclusion, the acute increase in Vc may be related to the increase in alveolar volume and to the increase in capillary pressure. Compared with the infinite θNO value, the use of a finite θNO value led to about a twofold increase in DmCO value and to a persistent increase in DmCO at D7,8 compared with D0. After exercise, DmCO decreased slightly less in subjects treated by the vasodilators, suggesting a beneficial effect on interstitial edema.