The Prescribing Practice for COPD: Relationship to Circadian Rhythm, Disease Severity, and Clinical Phenotype in the STORICO Observational Study.

INTRODUCTION: While selected clinical and laboratory findings are taken into account to find the best therapeutic strategies for chronic obstructive pulmonary disease (COPD), it is unknown whether the circadian rhythm of respiratory symptoms, a distinctive feature of COPD, affects the prescription pattern of pharmacological therapy. The main aim of this study was to verify whether the circadian rhythm of symptoms correlates with bronchodilating therapy prescribed to COPD patients as per clinical practice. A secondary objective was to assess the relationship between Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and circadian rhythm of symptoms and health status. METHODS: Five hundred sixty-six COPD patients were enrolled in the Italian multicenter STORICO study. Patients underwent a multidimensional assessment, and correlates of prescribed therapy were assessed through a multivariate multilevel model. RESULTS: As expected, patients in GOLD D stage were more likely to receive triple inhaled therapy than GOLD A-C patients, but the circadian rhythm of symptoms, assessed by the nighttime, morning, and daytime symptoms of the COPD questionnaire, was unrelated to the prescription pattern. The multivariate model showed that emphysematous (EM) patients had a 50% increased risk compared with patients affected by chronic bronchitis (CB) of being prescribed long-acting ß2-agonists (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combination (FDC) instead of triple therapy [relative risk (RR) EM versus CB 1.50, 95% CI 1.11, 2.03]. Symptoms, mainly in the early morning and daytime, were highly prevalent, even in GOLD B stage (76%). CONCLUSION: Even if we cannot infer about causality of the symptoms-therapy relationship, based on the structured recording of circadian symptoms clearly shows that symptoms are poorly controlled as the circadian rhythm of symptoms does not correlate with the prescription pattern, and many patients are symptomatic both at daytime and by nighttime. Thus, therapy should be better tailored to the individual needs, with special attention to control nocturnal symptoms. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03105999.

Operative Use of Thoracic Ultrasound in Respiratory Medicine: A Clinical Study.

For over 15 years, thoracic ultrasound has been applied in the evaluation of numerous lung diseases, demonstrating a variable diagnostic predictive power compared to traditional imaging techniques such as chest radiography and CT. However, in unselected pulmonary patients, there are no rigorous scientific demonstrations of the complementarity of thoracic ultrasound with traditional and standardized imaging techniques that use radiation. In this study 101 unselected pulmonary patients were evaluated blindly with ultrasound chest examinations during their hospital stay. Other instrumental examinations, carried out during hospitalization, were standard chest radiography, computed tomography (CT), and, when needed, radioisotopic investigation and cardiac catheterization. The operator who performed the ultrasound examinations was unaware of the anamnestic and clinical data of the patients. Diffuse fibrosing disease was detected with a sensitivity, specificity and diagnostic accuracy of 100%, 95% and 97%, respectively. In pleural effusions, ultrasound showed a sensitivity, specificity and diagnostic accuracy of 100%. In consolidations, the sensitivity, specificity and diagnostic accuracy were 83%, 98% and 93%, respectively. Low values of sensitivity were recorded for surface nodulations of less than one centimeter. Isolated subpleural ground glass densities were identified as White Lung with a sensitivity of 72% and a specificity of 86%. Only the associations Diffuse ultrasound findings/Definitive fibrosing disease, Ultrasound Consolidation/Definitive consolidation and non-diffuse ultrasound artefactual features/Definitive vascular pathology (pulmonary hypertension, embolism) were statistically significant with adjusted residuals of 7.9, 7 and 4.1, respectively. The obtained results show how chest ultrasound is an effective complementary diagnostic tool for the pulmonologist. When performed, as a complement to the patient's physical examination, it can restrict the diagnostic hypothesis in the case of pleural effusion, consolidation and diffuse fibrosing disease of the lung.

Epidemiology of systemic sclerosis: a multi-database population-based study in Tuscany (Italy).

BACKGROUND: Systemic Sclerosis (SSc) is a chronic autoimmune disease with a complex pathogenesis that includes vascular injury, abnormal immune activation, and tissue fibrosis. We provided a complete epidemiological characterization of SSc in the Tuscany region (Italy), considering prevalence and incidence, survival, comorbidities and drug prescriptions, by using a multi-database population-based approach. Cases of SSc diagnosed between 1st January 2003 and 31st December 2017 among residents in Tuscany were collected from the population-based Rare Diseases Registry of Tuscany. All cases were linked to regional health and demographic databases to obtain information about vital statistics, principal causes of hospitalization, complications and comorbidities, and drug prescriptions. RESULTS: The prevalence of SSc in Tuscany population resulted to be 22.2 per 100,000, with the highest prevalence observed for the cases aged ≥ 65 years (33.2 per 100,000, CI 95% 29.6-37.3). In females, SSc was predominant (86.7% on the total) with an overall sex ratio F/M of 6.5. Nevertheless, males presented a more severe disease, with a lower survival and significant differences in respiratory complications and metabolic comorbidities. Complications and comorbidities such as pulmonary involvement (HR = 1.66, CI 95% 1.17-2.35), congestive heart failure (HR = 2.76, CI 95% 1.80-4.25), subarachnoid and intracerebral haemorrhage (HR = 2.33, CI 95% 1.21-4.48) and malignant neoplasms (HR = 1.63, CI 95% 1.06-2.52), were significantly associated to a lower survival, also after adjustment for age, sex and other SSc-related complications. Disease-modifying antirheumatic drugs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors were the drugs with the more increasing prevalence of use in the 2008-2017 period. CONCLUSIONS: The multi-database approach is important in the investigation of rare diseases where it is often difficult to provide accurate epidemiological indicators. A population-based registry can be exploited in synergy with health databases, to provide evidence related to disease outcomes and therapies and to assess the burden of disease, relying on a large cohort of cases. Building an integrated archive of data from multiple databases linking a cohort of patients to their comorbidities, clinical outcomes and survival, is important both in terms of treatment and prevention.

A novel echocardiographic method for estimation of pulmonary artery wedge pressure and pulmonary vascular resistance.

AIMS: This study aimed to evaluate a novel echocardiographic algorithm for quantitative estimation of pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance (PVR) in patients with heart failure and pulmonary hypertension (PH) scheduled to right heart catheterization (RHC). METHODS AND RESULTS: In this monocentric study, 795 consecutive patients (427 men; age 68.4 ± 12.1 years) undergoing echocardiography and RHC were evaluated. Multiple regression analysis was performed to identify echocardiographic predictors of PAWP and PVR measured by RHC in the derivation group (the first 200 patients). The diagnostic accuracy of the model was then tested in the validation group (the remaining 595 patients). PH was confirmed by RHC in 507 (63.8%) patients, with 192 (24.2%) cases of precapillary PH, 248 (31.2%) of postcapillary PH, and 67 (8.4%) of combined PH. At regression analysis, tricuspid regurgitation maximal velocity, mitral E/e' ratio, left ventricular ejection fraction, right ventricular fractional area change, inferior vena cava diameter, and left atrial volume index were included in the model (R = 0.8, P < 0.001). The model showed a high diagnostic accuracy in estimating elevated PAWP (area under the receiver operating characteristic curve = 0.97, 92% sensitivity, and 93% specificity, P < 0.001) and PVR (area under the receiver operating characteristic curve = 0.96, 89% sensitivity, and 92% specificity, P < 0.001), outperforming 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations (P < 0.001) and Abbas' equation (P < 0.001). Bland-Altman analysis showed satisfactory limits of agreement between echocardiography and RHC for PAWP (bias 0.7, 95% confidence interval -7.3 to 8.7) and PVR (bias -0.1, 95% confidence interval -2.2 to 1.9 Wood units), without indeterminate cases. CONCLUSIONS: A novel quantitative echocardiographic approach for the estimation of PAWP and PVR has high diagnostic accuracy in patients with heart failure and PH.

Cardio-pulmonary involvement in pulmonary arterial hypertension: A perfusion and innervation scintigraphic evaluation.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by the right ventricle (RV) remodeling and pulmonary endothelial dysfunction. We studied cardiac perfusion and innervation in PAH with a cadmium-zinc-telluride (CZT) scanner and lung uptake impairment of 123I-metaiodobenzylguanidine (123I-MIBG). METHODS: In 13 patients with newly diagnosed PAH and 11 dilated cardiomyopathies (DCM, for comparative purposes), we assessed early and delayed 123I-MIBG uptake ratios of lung-to-mediastinum (L/M) and heart-to-mediastinum (H/M) on anterior planar images. A quantitative myocardial innervation with 123I-MIBG and perfusion with 99mTc-tetrofosmin using CZT-SPECT was performed. All patients underwent right heart catheterization. RESULTS: Early and delayed L/M ratios in PAH were lower than DCM (1.47 ± 0.14 vs 1.98 ± 0.11 and 1.40 ± 0.13 vs 1.83 ± 0.09; P < .001), while early and delayed H/M were impaired but not different (1.73 ± 0.20 vs 1.65 ± 0.18 and 1.73 ± 0.27 vs 1.58 ± 0.19). RV perfusion and early innervation were significantly higher in PAH compared to DCM (68.4 ± 13.4 vs 28.6 ± 4.1 and 58.8 ± 9.3 vs 27 ± 2.2; P < .001); delayed RV innervation was not evaluable. RV/LV perfusion and innervation ratios were significantly related (R = 0.74; P < .0001) and had a significant correlation with clinical, hemodynamic, and morpho-functional parameters, including L/M ratios. CONCLUSION: Cardio-pulmonary scintigraphy through a perfusion and innervation study is feasible and may identify pulmonary vascular and RV remodeling, as in PAH.

Real-time multi-frequency ultrasound imaging for quantitative lung ultrasound - first clinical results.

Lung ultrasound imaging is a fast-evolving field of application for ultrasound technologies. However, most diagnoses are currently performed with imaging protocols that assume a quasi-homogeneous speed of sound in the volume of interest. When applied to the lung, due to the presence of air, this assumption is unrealistic. Consequently, diagnoses are often based on imaging artifacts and thus qualitative and subjective. In this paper, we present an image formation protocol that is capable of capturing the frequency dependence of well-known artifacts (B-lines) and visualizing it in real time, ultimately providing a quantitative assessment of the signals received from the lung. Previous in vitro studies have shown the potential of B-lines native-frequency for the characterization of bubbly medium, but this paper presents the first results on clinical data. The image formation process has been designed to work on lung tissue, and ultrasound images generated with four orthogonal bands centered at 3, 4, 5 and 6 MHz can be acquired and displayed in real time. Results show that B-lines can be characterized on the basis of their native frequency in vivo and open the way toward real-time quantitative lung ultrasound imaging.

Hemodynamics and risk assessment 2 years after the initiation of upfront ambrisentan‒tadalafil in pulmonary arterial hypertension.

BACKGROUND: Upfront combination therapy with ambrisentan and tadalafil has been reported to improve the condition of patients with pulmonary arterial hypertension (PAH) more than with either drug alone. However, little is known about the long-term associated changes in hemodynamics and risk assessment scores. METHODS: This was a multicenter, retrospective analysis of clinical data in 106 patients with newly diagnosed PAH. Clinical evaluations, including demographics, medical history, World Health Organization (WHO) functional class (FC) and 6-minute walk distance (6MWD), right heart catheterization, and Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk score 2.0, were assessed over 48 months of ambrisentan‒tadalafil therapy. RESULTS: At baseline, 9 patients (9%) showed a low (<7), 48 patients (45%) showed an intermediate (7-8), and 49 patients (46%) showed a high (>8) REVEAL risk score. At a median follow-up of 2 years, 45 patients (43%) showed a low, 47 patients (44%) showed an intermediate, and 14 patients (13%) showed a high REVEAL score, along with improvements in WHO FC, 6MWD and a decrease in mean pulmonary artery pressure and N-terminal pro brain natriuretic peptide (all p < 0.001). Pulmonary vascular resistance (PVR) decreased by 37% from 11.5 ± 6.5 to 7.2 ± 4.1 Wood units (p < 0.001). A total of 61 patients (57%) remained in intermediate-risk or high-risk categories. Low-risk patients had either a decrease in PVR of >50% or a stroke volume within the limits of normal. CONCLUSIONS: Initial combination therapy with ambrisentan and tadalafil in PAH improves the REVEAL risk score in proportion to decreased PVR and preserved stroke volume but still insufficiently so in approximately 50% of the patients.

Quantitative Lung Ultrasound Spectroscopy Applied to the Diagnosis of Pulmonary Fibrosis: The First Clinical Study.

The application of ultrasound imaging to the diagnosis of lung diseases is nowadays receiving growing interest. However, lung ultrasound (LUS) is mainly limited to the analysis of imaging artifacts, such as B-lines, which correlate with a wide variety of diseases. Therefore, the results of LUS investigations remain qualitative and subjective, and specificity is obviously suboptimal. Focusing on the development of a quantitative method dedicated to the lung, in this work, we present the first clinical results obtained with quantitative LUS spectroscopy when applied to the differentiation of pulmonary fibrosis. A previously developed specific multifrequency ultrasound imaging technique was utilized to acquire ultrasound images from 26 selected patients. The multifrequency imaging technique was implemented on the ULtrasound Advanced Open Platform (ULA-OP) platform and an LA533 (Esaote, Florence, Italy) linear-array probe was utilized. RF data obtained at different imaging frequencies (3, 4, 5, and 6 MHz) were acquired and processed in order to characterize B-lines based on their frequency content. In particular, B-line native frequencies (the frequency at which a B-line exhibits the highest intensity) and bandwidth (the range of frequencies over which a B-line shows intensities within -6 dB from its highest intensity), as well as B-line intensity, were analyzed. The results show how the analysis of these features allows (in this group of patients) the differentiation of fibrosis with a sensitivity and specificity equal to 92% and 92%, respectively. These promising results strongly motivate toward the extension of the clinical study, aiming at analyzing a larger cohort of patients and including a broader range of pathologies.

Respiratory Symptoms in Relation to Living near a Crude Oil First Treatment Plant in Italy: A Cross-Sectional Study.

Exposure to air pollution has been shown to increase the risk of developing chronic respiratory diseases. The largest crude oil first treatment plant in Italy emits harmful polluting substances. This cross-sectional study assesses the occurrence of respiratory symptoms in a sample of the adult population living near the plant. A proximal and a reference area were defined in order to recruit 200 subjects. Each subject performed a spirometry test and completed a questionnaire. Associations between the distance from the plant and selected respiratory outcomes were assessed (distance-based approach). The prevalence of outcomes between a proximal and a reference area (area-based approach) were also compared. Odds ratios were adjusted for potential confounders. Living near the plant was associated with a higher prevalence of respiratory symptoms, with significant associations for severe dyspnoea equivalent to the halving of risk as the distance of residence from the plant increased by 1 km (adjusted odds ratio (OR) 0.48, confidence interval at the 95% probability level (95% CI): 0.25⁻0.92). Several signals emerged for respiratory allergic symptoms. The area-based approach generally confirmed the results obtained with the distance-based approach. This is the first study to be carried out on a crude oil first treatment plant aimed at assessing the association with the occurrence of respiratory symptoms. These findings contribute to the evidence supporting the need for a space⁻time surveillance system in the investigated area.

Initial tadalafil and ambrisentan combination therapy in pulmonary arterial hypertension: cLinical and haemodYnamic long-term efficacy (ITALY study).

AIMS: Initial combination therapy with ambrisentan and tadalafil (upfront therapy) offers clinical benefits in pulmonary arterial hypertension (PAH) and reduces the risk of clinical failure compared with monotherapy in naïve patients. The aim of study is to assess the efficacy of a 12-month upfront therapy with ambrisentan and tadalafil in improving haemodynamics in incident PAH patients. METHODS: This is a multicentre retrospective analysis of real-world Italian clinical data in 56 patients with newly diagnosed PAH. Clinical evaluations, including demographics, medical history, WHO functional class, 6-min walk distance, and right heart catheterization, were collected from the patients' medical records at baseline and at 12-month follow-up. RESULTS: At baseline, there were 16, 34, and 6 patients in WHO functional class II, III, and IV, respectively. Over a median follow-up of 12 months, 54 (96%) patients were still alive, 6 (11%) of whom received parenteral prostanoids. Ambrisentan-tadalafil combination was associated with significant improvements in WHO functional class (2.2 ±â€Š0.8 vs. 2.8 ±â€Š0.6, P < 0.001, improved in 29 patients), exercise capacity (395 ±â€Š123 vs. 353 ±â€Š101 m, P = 0.039), N-terminal probrain natriuretic peptide (528 ±â€Š493 vs. 829 ±â€Š620 pg/ml; P = 0.009), and haemodynamics (right atrial pressure 7 ±â€Š4 vs. 9 ±â€Š5 mmHg, P = 0.02; mean pulmonary artery pressure 45 ±â€Š15 vs. 50 ±â€Š13 mmHg, P = 0.03; cardiac index 3.0 ±â€Š1.0 vs. 2.5 ±â€Š0.9 l/min/m, P = 0.001; pulmonary vascular resistance 8 ±â€Š4 vs. 11 ±â€Š6 Wood units, P = 0.001) compared with baseline. CONCLUSIONS: Initial combination therapy with ambrisentan and tadalafil offers clinical benefits and significant haemodynamic improvement in newly diagnosed PAH patients.

Cardiovascular and respiratory effects of the neoprene wetsuit in non-immersed divers.

A neoprene wetsuit is widely used to reduce thermal dispersion during diving. Recent observations have pointed out that elastic recoil of the wetsuit might have significant compressive effects, able to affect water and electrolyte homeostasis during both dry and immersed conditions. The aim of this study was to evaluate the possible cardiovascular and respiratory effects of the neoprene wetsuit in dry conditions in a sample of experienced divers. Twenty-four (24) healthy divers were evaluated by Doppler-echocardiography and by spirometry in basal conditions and while wearing a full neoprene wetsuit. During wetsuit conditions, we observed a significant decrease in heart rate (-5%; p ⟨ 0.05) and cardiac output (-12%; p ⟨ 0.05), and a significant increase in total peripheral resistances (15%; p ⟨ 0.05). Moreover, a significant reduction of right ventricular early diastolic filling was observed (-15%; p ⟨ 0.05). As concerns pulmonary function, a significant reduction of vital capacity (-2%; p ⟨ 0.001) and expiratory reserve volume (-25%; p ⟨ 0.001), and a significant increase of inspiratory capacity (9%; p ⟨ 0.001) and tidal volume (25%; p ⟨ 0.05) were observed. These data support the hypothesis that neoprene elastic recoil, possibly due to a compression exerted on chest, might affect systemic circulation (decreasing cardiac output and impairing right ventricular filling) and respiratory function.

Correction: How Reliable Are Current Data for Assessing the Actual Prevalence of Chronic Obstructive Pulmonary Disease?

[This corrects the article DOI: 10.1371/journal.pone.0149302.].

How Reliable Are Current Data for Assessing the Actual Prevalence of Chronic Obstructive Pulmonary Disease?

BACKGROUND: Estimating COPD occurrence is perceived by the scientific community as a matter of increasing interest because of the worldwide diffusion of the disease. We aimed to estimate COPD prevalence by using administrative databases from a city in central Italy for 2002-2006, improving both the sensitivity and the reliability of the estimate. METHODS: Multiple sources were used, integrating the hospital discharge register (HDR), clinical charts, spirometry and the cause-specific mortality register (CMR) in a longitudinal algorithm, to reduce underestimation of COPD prevalence. Prevalence was also estimated on the basis of COPD cases confirmed through spirometry, to correct misclassification. Estimating such prevalence relied on using coefficients of validation, derived as the positive predictive value (PPV) for being an actual COPD case from clinical and spirometric data at the Institute of Clinical Physiology of the National Research Council. RESULTS: We found that sensitivity of COPD prevalence increased by 37%. The highest estimate (4.43 per 100 residents) was observed in the 5-year period, using a 3-year longitudinal approach and combined data from three sources. We found that 17% of COPD cases were misclassified. The above estimate of COPD prevalence decreased (3.66 per 100 residents) when coefficients of validation were applied. The PPV was 80% for the HDR, 82% for clinical diagnoses and 91% for the CMR. CONCLUSIONS: Adjusting the COPD prevalence for both underestimation and misclassification of the cases makes administrative data more reliable for epidemiological purposes.

Improved survival in limited scleroderma-related pulmonary artery hypertension.

Reportedly, patients with scleroderma-related pulmonary hypertension (SSc-PAH) respond poorly to new vasoactive drugs (NVD). Forty-nine SSc-PAH patients underwent right heart catheterization (RHC) and, according to NVD availability, divided as follows: Group 1 (n = 23, from 1999 to 2004, poor availability), and Group 2 (n = 26, from 2005 to 2010, good availability). Before diagnostic RHC, NVD had been given to 30 % of the patients in Group 1, and 58 % of those in Group 2 (p = 0.049). At diagnosis, patients in Group 1 had greater heart dilatation (p < 0.01), higher mean pulmonary artery pressure (p < 0.05), lower pulmonary artery capacitance (p < 0.05), and lower carbon monoxide lung diffusing capacity (DLco, p < 0.05) than those in Group 2. At a median follow-up time of 15.5 months, DLco further decreased in Group 1 (p < 0.05), whereas cardiac index increased in Group 2 (p < 0.05). At 36 months of follow-up, 72.4 % of the patients in Group 2 were still alive as opposed to 30.4 % in Group 1 (p = 0.02). In multivariate analysis, DLco and mixed venous oxygen saturation (SvO2) were independent predictors of survival. A value of DLco <7.2 mL/mmHg/min was associated with a hazard ratio (HR) of 5.3 (p < 0.001); for SvO2 <63.8 %, the HR was 3.7 (p < 0.01).NVD have beneficial effects in patients with SSc-PAH. Both DLco and SvO2 are predictors of survival and may assist in planning treatment.

Inappropriateness of cardiovascular radiological imaging testing; a tertiary care referral center study.

AIMS: Radiological inappropriateness in medical imaging leads to loss of resources and accumulation of avoidable population cancer risk. Aim of the study was to audit the appropriateness rate of different cardiac radiological examinations. METHODS AND PRINCIPAL FINDINGS: With a retrospective, observational study we reviewed clinical records of 818 consecutive patients (67 ± 12 years, 75% males) admitted from January 1-May 31, 2010 to the National Research Council - Tuscany Region Gabriele Monasterio Foundation cardiology division. A total of 940 procedures were audited: 250 chest x-rays (CXR); 240 coronary computed tomographies (CCT); 250 coronary angiographies (CA); 200 percutaneous coronary interventions (PCI). For each test, indications were rated on the basis of guidelines class of recommendation and level of evidence: definitely appropriate (A, including class I, appropriate, and class IIa, probably appropriate), uncertain (U, class IIb, probably inappropriate), or inappropriate (I, class III, definitely inappropriate). Appropriateness was suboptimal for all tests: CXR (A = 48%, U = 10%, I = 42%); CCT (A = 58%, U = 24%, I = 18%); CA (A = 45%, U = 25%, I = 30%); PCI (A = 63%, U = 15%, I = 22%). Top reasons for inappropriateness were: routine on hospital admission (70% of inappropriate CXR); first line application in asymptomatic low-risk patients (42% of CCT) or in patients with unchanged clinical status post-revascularization (20% of CA); PCI in patients either asymptomatic or with miscellaneous symptoms and without inducible ischemia on non-invasive testing (36% of inappropriate PCI). CONCLUSION AND SIGNIFICANCE: Public healthcare system--with universal access paid for with public money--is haemorrhaging significant resources and accumulating avoidable long-term cancer risk with inappropriate cardiovascular imaging prevention.

Improved survival in patients with inoperable chronic thromboembolic pulmonary hypertension.

Patients with inoperable chronic thromboembolic pulmonary hypertension (Inop-CTEPH) treated with conventional therapy have a poor survival. We compare the 3-year survival between those treated with conventional therapy and those treated with conventional therapy and a combination of novel drugs. We also evaluate the clinical course. A total of 34 Inop-CTEPH consecutive patients were evaluated from 1991 to 2009 including right heart catheterization (RHC) and perfusion lung scan (PLS): 7 underwent surgical treatment while 27 were confirmed inoperable. Of these 27 patients, 12 evaluated from 1991 to 2003 (Group 1) were treated with conventional therapy and 15 evaluated from 2004 to 2009 (Group 2) were treated with conventional and novel therapies. At baseline, no group difference emerged at RHC. Based on clinical course, novel drugs and oxygen supplementation were given to patients of Group 2. Seven of these who had worse clinical course repeated RHC and four of them also PLS during therapy. Those without repeat RHC had baseline pulmonary artery mean pressure and brain natriuretic peptide (NT-proBNP) lower and mixed venous saturation (SvO2) and exercise test higher (p = 0.022, 0.015, 0.044 and 0.003, respectively). During therapy, those with repeat RHC had total pulmonary vascular resistance reduced (p = 0.012), base excess increased (p = 0.002) and significant redistribution of pulmonary blood flow at PLS. At the 3-year follow-up, survival was 86% in Group 2 and 31% in Group 1 (p = 0.031). In Inop-CTEPH patients, the clinical course may help to select drugs and the level of oxygen supply that can improve hemodynamics, gas exchange and long-term survival.

Routine Chest X-ray: Still Valuable for the Assessment of Left Ventricular Size and Function in the Era of Super Machines?

OBJECTIVES: The development of technologically advanced, expensive techniques has progressively reduced the value of chest X-ray in clinical practice for the assessment of left ventricular (LV) dilatation and dysfunction. Although controversial data are reported on the role of this widely available technique in cardiac assessment, it is known that the cardio-thoracic ratio is predictive of risk of progression in the NYHA Class, hospitalization, and outcome in patients with LV dysfunction. This study aimed to evaluate the reliability of the transverse diameter of heart shadow [TDH] by chest X-ray for detecting LV dilatation and dysfunction as compared to Magnetic Resonance Imaging (MRI) performed for different clinical reasons. MATERIALS AND METHODS: In 101 patients, TDH was measured in digital chest X-ray and LV volumes and ejection fraction (EF) by MRI, both exams performed within 2 days. RESULTS: A direct correlation between TDH and end-diastolic volumes (r = .75, P<0.0001) was reported. TDH cut-off values of 14.5 mm in females identified LV end-diastolic volumes >150 mL (sensitivity: 82%, specificity: 69%); in males a cut-off value of 15.5 mm identified LV end-diastolic volumes >210 mL (sensitivity: 84%; specificity: 72%). A negative relation was found between TDH and LVEF (r = -.54, P<0.0001). The above cut-off values of TDH discriminated patients with LV systolic dysfunction - LVEF <35% (sensitivity and specificity: 67% and 57% in females; 76% and 59% in males, respectively). CONCLUSIONS: Chest X-ray may still be considered a reliable technique in predicting LV dilatation by the accurate measurement of TDH as compared to cardiac MRI. Technologically advanced, expensive, and less available imaging techniques should be performed on the basis of sound clinical requests.

Preliminary observations on the effect of hypoxic and hyperbaric stress on pulmonary gas exchange in breath-hold divers.

AIM: To evaluate pulmonary alveolar-capillary membrane integrity and ventilation/perfusion mismatch after breath-hold diving. METHODS: Pulmonary diffusing capacity to carbon monoxide (DLCO) and nitric oxide (DLNO), haemoglobin (Hb) and haematocrit (Hct) were measured in six elite divers before and at 2, 10 and 25 minutes after a maximal breath-hold dive to a depth of 10 metres' sea water. RESULTS: Compared to pre-dive, DLCO showed a slight increase at 2 minutes in five subjects and a tendency to decrease at 25 minutes (P < 0.001) in all subjects. DLNO showed an increase at 10 minutes in three divers and a slight decrease at 25 minutes in five subjects. There was a small but significant (P < 0.001) increase in Hb and Hct at 2 minutes, possibly affecting the DLCO measurements. CONCLUSIONS: An early but transient increase in DLCO in five divers may reflect the central shift in blood volume during a breath-hold dive. The late parallel decrease in DLCO and DLNO likely reflects alveolar-capillary distress (interstitial oedema). The DLNO increase in three subjects at 10 minutes may suggest ventilation/perfusion mismatch.