Phenotype and outcomes according to loop diuretic use in pulmonary arterial hypertension.

AIMS: The use of loop diuretics in pulmonary arterial hypertension (PAH) is less frequent compared with heart failure. The clinical and prognostic characteristics of PAH patients according to loop diuretic use remain unexplored. In this study, we retrospectively analysed the characteristics and survival of PAH patients requiring different doses of loop diuretics. METHODS AND RESULTS: Patients diagnosed with PAH between 2001 and 2022 at seven European centres for the management of PAH. According to the median equivalent dose of furosemide in the overall cohort, patients were divided into two subgroups: no/low-dose loop diuretic and high-dose loop diuretic. Primary outcome was 5 year all-cause mortality. Among the 397 patients included, 227 (57%) were treated with loop diuretics. Median daily furosemide equivalent dose was 25 mg, and accordingly patients were divided in no/low dose (i.e. ≤25 mg, n = 257, 65%) vs. high dose (i.e. >25 mg, n = 140, 35%). Patients in the high-dose group were older, more likely to have comorbidities, and had a more severe disease according to the ESC/ERS risk category. Crude 5 year survival was significantly shorter in patients in the high-dose group, but after adjustment for age, sex, and risk category, high loop diuretic dose was not significantly associated with the primary outcome. CONCLUSIONS: Use of high dose of loop diuretics in PAH is associated with a higher burden of comorbidities, more severe disease, and worse survival. However, in PAH, the need of high loop diuretic dose is a marker of disease severity and not an independent prognostic factor.

Frequency, characteristics and risk assessment of pulmonary arterial hypertension with a left heart disease phenotype.

AIM: To obtain real-world evidence about the features and risk stratification of pulmonary arterial hypertension (PAH) with a left heart disease (LHD) phenotype (PAH-LHD). METHODS AND RESULTS: By reviewing the records of consecutive incident PAH patients at 7 tertiary centers from 2001 to 2021, we selected 286 subjects with all parameters needed to determine risk of death at baseline and at first follow-up with COMPERA and COMPERA 2.0 scores. Fifty seven (20%) had PAH-LHD according to the AMBITION definition. Compared with no-LHD ones, they were older, had higher BMI, more cardiovascular comorbidities, higher E/e' ratio and left atrial area, but lower BNP concentrations and better right ventricular function and pulmonary hemodynamics. Survival was comparable between PAH-LHD and no-LHD patients, although the former were less commonly treated with dual PAH therapy. Both COMPERA and COMPERA 2.0 discriminated all-cause mortality risk of PAH-LHD at follow-up, but not at baseline. Risk profile significantly improved during follow-up only when assessed by COMPERA 2.0. At multivariable analysis with low-risk status as reference, intermediate-high and high-risk, but not LHD phenotype, were associated with higher hazard of all-cause mortality. Results were comparable in secondary analyses including patients in the last 10 years and atrial fibrillation and echocardiographic abnormalities as additional criteria for PAH-LHD. CONCLUSIONS: In real life, PAH-LHD patients are frequent, have less severe disease and are less likely treated with PAH drug combinations than no-LHD. The COMPERA 2.0 model may be more appropriate to evaluate their mortality risk during follow-up and how it is modulated by therapy.

The Fondazione Toscana Gabriele Monasterio app: a digital health system to improve wellbeing of inpatients with heart or lung disease.

BACKGROUND: An app providing material for education and entertaining is a possible way to support patients and healthcare providers in achieving person-centered care. METHODS: An app tailored on the Fondazione Toscana Gabriele Monasterio (FTGM), a research hospital treating cardiac and lung disorders, was created. A pilot evaluation project was conducted on consecutive patients hospitalized for heart or lung disorders. Patients were asked to complete an assessment questionnaire. RESULTS: The FTGM app provides information on diagnostic and therapeutic investigations, hospital and healthcare personnel, and includes content for entertainment and learning. It was tested on 215 consecutive patients (75% men, 66% aged >60 years, and 40% with a primary or middle school degree). Sixty-nine percentage of patients used the FTGM app, including 67% of patients aged >80 years and 65% of those with an elementary education (65%). Patients gave positive feedback on the app layout. Many (76%) looked for information on doctors and nurses in the 'People' section. Sixty-five percent of responders had used at least one of the sections called 'Music' and 'Museum visits'. The app helped many patients perceive the hospital as a more liveable place (68%), and to feel less anxious (76%), and more engaged in the diagnostic and therapeutic workup (65%). Overall, the majority of responders (87%) rated the app as 'excellent' or 'good', and almost all (95%) would have recommended other patients to use the app. CONCLUSIONS: The FTGM app is a possible tool to improve patient wellbeing during hospitalization.

Performance of risk stratification scores and role of comorbidities in older vs younger patients with pulmonary arterial hypertension.

BACKGROUND: Risk scores are important tools for the prognostic stratification of pulmonary arterial hypertension (PAH). Their performance and the additional impact of comorbidities across age groups is unknown. METHODS: Patients with PAH enrolled from 2001 to 2021 were divided in ≥65 years old vs <65 years old patients. Study outcome was 5-year all-cause mortality. French Pulmonary Hypertension Network (FPHN), FPHN noninvasive, Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL 2.0) risk scores were calculated and patients categorized at low, intermediate and high risk. Number of comorbidities was calculated. RESULTS: Among 383 patients, 152 (40%) were ≥65 years old. They had more comorbidities (number of comorbidities 2, IQR 1-3, vs 1, IQR 0-2 in <65 years patients). Five-year survival was 63% in ≥65 vs 90% in <65 years. Risk scores correctly discriminated the different classes of risk in the overall cohort and in the older and younger groups. REVEAL 2.0 showed the best accuracy in the total cohort (C-index 0.74, standard error-SE- 0.03) and older (C-index 0.69, SE 0.03) patients, whereas COMPERA 2.0 performed better in younger patients (C-index 0.75, SE 0.08). Number of comorbidities was associated with higher 5-year mortality, and consistently increased the accuracy of risk scores, in younger but not in older patients. CONCLUSIONS: Risk scores have similar accuracy in the prognostic stratification of older vs younger PAH patients. REVEAL 2.0 had the best performance in older patients and COMPERA 2.0 had it in younger patients. Comorbidities increased the accuracy of risk scores only in younger patients.

[Pulmonary hypertension clinical pathway: ANMCO Tuscany Board model]. / Clinical pathway per l'ipertensione polmonare: la proposta di ANMCO Toscana.

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure >20 mmHg at rest during right heart catheterization. PH prevalence is about 1% of the global population. The PH clinical classification includes five groups: pulmonary arterial hypertension, PH associated with left heart disease, PH associated with lung disease, PH associated with pulmonary artery obstructions, PH with unclear and/or multifactorial mechanisms. In case of clinical suspicion, echocardiography is the first-line tool to start the diagnostic process. Right heart catheterization is the gold standard for diagnosis of PH, requires great experience and should be performed in expert centers. The classification of the PH patient in a specific subgroup requires multidisciplinary clinical and instrumental skills that only a reference center can provide. This document proposes a clinical pathway for the management of PH patients in the Tuscany region in order to standardize access to specialized care.

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.

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.

Impact of residual pulmonary obstruction on the long-term outcome of patients with pulmonary embolism.

The impact of residual pulmonary obstruction on the outcome of patients with pulmonary embolism is uncertain.We recruited 647 consecutive symptomatic patients with a first episode of pulmonary embolism, with or without concomitant deep venous thrombosis. They received conventional anticoagulation, were assessed for residual pulmonary obstruction through perfusion lung scanning after 6 months and then were followed up for up to 3 years. Recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension were assessed according to widely accepted criteria.Residual pulmonary obstruction was detected in 324 patients (50.1%, 95% CI 46.2-54.0%). Patients with residual pulmonary obstruction were more likely to be older and to have an unprovoked episode. After a 3-year follow-up, recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension developed in 34 out of the 324 patients (10.5%) with residual pulmonary obstruction and in 15 out of the 323 patients (4.6%) without residual pulmonary obstruction, leading to an adjusted hazard ratio of 2.26 (95% CI 1.23-4.16).Residual pulmonary obstruction, as detected with perfusion lung scanning at 6 months after a first episode of pulmonary embolism, is an independent predictor of recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension.

Fibromatosis, a benign breast disease mimicking carcinoma. A case report.

INTRODUCTION: Fibromatosis is an uncommon breast lesion that can mimic breast carcinoma in its clinical presentation. CASE SUMMARY: We present a clinical case in which a diagnosis and treatment dilemma existed, in terms of ultrasound findings that were not clear and suspicious, as well as results of Fine needle aspiration cytology. Our findings are compared with previous published cases. Also, literature review regarding fibromatosis presentation and diagnosis has been discussed, as well as treatment options. CONCLUSION: Management of breast fibromatosis remains controversial because of the low incidence and further efforts needed to establish evidence-based treatment guidelines.

Body height as risk factor for emphysema in COPD.

Pulmonary emphysema is a phenotypic component of chronic obstructive pulmonary disease (COPD) which carries substantial morbidity and mortality. We explored the association between emphysema and body height in 726 patients with COPD using computed tomography as the reference diagnostic standard for emphysema. We applied univariate analysis to look for differences between patients with emphysema and those without, and multivariate logistic regression to identify significant predictors of the risk of emphysema. As covariates we included age, sex, body height, body mass index, pack-years of smoking, and forced expiratory volume in one second (FEV1) as percent predicted. The overall prevalence of emphysema was 52%. Emphysemic patients were significantly taller and thinner than non-emphysemic ones, and featured significantly higher pack-years of smoking and lower FEV1 (P < 0.001). The prevalence of emphysema rose linearly by 10-cm increase in body height (r2 = 0.96). In multivariate analysis, the odds of emphysema increased by 5% (95% confidence interval, 3 to 7%) along with one-centimeter increase in body height, and remained unchanged after adjusting for all the potential confounders considered (P < 0.001). The odds of emphysema were not statistically different between males and females. In conclusion, body height is a strong, independent risk factor for emphysema in COPD.

Predictors of Pulmonary Infarction.

In the setting of acute pulmonary embolism (PE), pulmonary infarction is deemed to occur primarily in individuals with compromised cardiac function.The current study was undertaken to establish the prevalence of pulmonary infarction in patients with acute PE, and the relationship between infarction and: age, body height, body mass index (BMI), smoking habits, clot burden, and comorbidities.The authors studied prospectively 335 patients with acute PE diagnosed by computed tomographic angiography (CT) in 18 hospitals throughout central Italy. The diagnosis of pulmonary infarction on CT was based on Hampton and Castleman's criteria (cushion-like or hemispherical consolidation lying along the visceral pleura). Multivariable logistic regression was used to model the relationship between covariates and the probability of pulmonary infarction.The prevalence of pulmonary infarction was 31%. Patients with infarction were significantly younger and with significantly lower prevalence of cardiovascular disease than those without (P < 0.001). The frequency of infarction increased linearly with increasing height, and decreased with increasing BMI. In logistic regression, the covariates significantly associated with the probability of infarction were age, body height, BMI, and current smoking. The risk of infarction grew with age, peaked at approximately age 40, and decreased afterwards. Increasing body height and current smoking were significant amplifiers of the risk of infarction, whereas increasing BMI appeared to confer some protection.Our data indicate that pulmonary infarction occurs in nearly one-third of the patients with acute PE. Those with infarction are often young and otherwise healthy. Increasing body height and active smoking are predisposing risk factors.

Survival in COPD: impact of lung dysfunction and comorbidities.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in industrialized countries. Recent studies investigated the impact of comorbidities on the survival in COPD, but most of them lacked a referent group of comorbidity-matched, nonobstructed individuals.We examined the 10-year mortality in a sample of 200 COPD patients and 201 nonobstructed controls. They were part of a larger cohort enrolled in a European case-control study aimed at assessing genetic susceptibility to COPD. By design, the COPD group included patients with a forced expiratory volume in 1 second (FEV1) ≤70% predicted. Cases and controls were matched on age, sex, and cumulative smoking history, and shared a nearly identical prevalence of cardiovascular and metabolic disorders. We estimated the hazard of death with Cox regression and percentiles of survival with Laplace regression. COPD was the main exposure variable of interest. Five comorbidities (hypertension, coronary artery disease, prior myocardial infarction, chronic heart failure, and diabetes) were included as covariates in multiple regression models.The all-cause mortality rate was significantly higher in cases than in controls (43% vs 16%, P < 0.001). The unadjusted hazard of death for COPD was 3-fold higher than the referent category (P < 0.001), and remained nearly unchanged after introducing the 5 comorbidities in multiple regression. Patients with COPD had significantly shorter survival percentiles than comorbidity-matched controls (P < 0.001). Notably, 15% of the nonobstructed controls died by 10.3 years into the study; the same proportion of COPD patients had died some 6 years earlier, at 4.6 years.In a separate analysis, we split the whole sample into 2 groups based on the lower tertile of FEV1 and carbon monoxide lung diffusing capacity (DLCO). The hazard of death for COPD patients with low FEV1 and DLCO was nearly 3.5-fold higher than in all the others (P < 0.001), and decreased only slightly after introducing age and chronic heart failure as relevant covariates.COPD is a strong predictor of reduced survival independently of coexisting cardiovascular and metabolic disorders. Efforts should be made to identify patients at risk and to ensure adherence to prescribed therapeutic regimens.

Accuracy of chest radiography in predicting pulmonary hypertension: a case-control study.

OBJECTIVE: To assess the accuracy of chest radiography (CXR) in predicting pulmonary hypertension (PH). METHODS: We studied 108 consecutive patients with suspected PH who underwent right heart catheterization (RHC). All were PH treatment naives. Hemodynamic criteria included a mean pulmonary artery pressure >25 mmHg at rest, and a mean pulmonary wedge pressure <15 mmHg. Postero-anterior and lateral CXR were obtained shortly before RHC. To avoid a selection bias which could be introduced by examining only patients with suspected PH, we included in the analysis the CXR of 454 additional patients with different diagnosis: 57 with left heart failure (LHF) and pulmonary venous hypertension at RHC, 197 with chronic obstructive pulmonary disease, and 200 non-obstructed controls. CXR were examined independently by 4 raters, who were blinded to clinical, hemodynamic, and spirometric data. The diagnosis of PH was made if a prominent main pulmonary artery was associated with anyone of: isolated enlargement of right ventricle, right descending pulmonary artery >16 mm in diameter, pruning of peripheral pulmonary vessels. RESULTS: Eighty-two patients had PH confirmed at RHC. Weighted sensitivity of CXR was 96.9% (95% confidence interval, 94.9 to 98.2%), and weighted specificity 99.8% (95% confidence interval, 99.6 to 99.9%). By considering the 165 patients who underwent RHC, weighted sensitivity of CXR was unchanged, and weighted specificity decreased to 99.1%. None of the patients with PH were misclassified as having LHF, and vice versa. CONCLUSIONS: CXR is accurate in predicting PH. It may aid clinicians in selecting patients with suspected PH for hemodynamic ascertainment.

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.

Prognostic value of alveolar volume in systolic heart failure: a prospective observational study.

BACKGROUND: Ventilatory impairment is known to occur in patients with heart failure (HF). Alveolar volume (VA) is measured by the dilution of an inert gas during a single breath-hold maneuver. Such measurement is sensitive to ventilatory disturbances. We conducted a prospective, observational study to establish the prognostic value of VA in systolic HF. METHODS: We studied 260 consecutive patients who were hospitalized for systolic HF. All patients were evaluated under stable clinical conditions, before hospital discharge. Lung function studies included spirometry and determination of the lung diffusing capacity for carbon monoxide (DLCO) by the single-breath method. We also measured the cardiothoracic ratio on frontal chest radiographs, and the circulating levels of N-terminal pro-hormone of B-type natriuretic peptide (NT-proBNP). The hazard ratio (HR) of death was estimated with Cox regression, and the percentiles of survival time with Laplace regression. For survival analysis, VA was categorized as < 80% (n = 135), or ≥ 80% of the predicted value (n = 125). RESULTS: Follow-up had a median duration of 2.7 years (interquartile range, 1.1 to 4.2 years). The crude mortality rate was 27% in the whole sample, 36% in patients with VA < 80%, and 16% in those with VA ≥ 80%. The HR of death was 2.3-fold higher in patients with VA < 80% than in those with VA ≥80% (p = 0.002). After adjusting for age, New York Heart Association class III-IV, cardiothoracic ratio >0.5, NT-proBNP, persistent atrial fibrillation, DLCO, COPD comorbidity, use of beta-blockers and angiotensin converting enzyme inhibitors, the HR decreased to 1.9 but remained statistically significant (p = 0.039). Two percent of the patients with VA < 80% died about 0.9 years earlier than those with VA ≥ 80% (p = 0.033). The difference in survival time at the 20th percentile was 0.8 years. CONCLUSIONS: VA is a significant, independent predictor of reduced survival in patients with systolic HF.

DCIS and LCIS are confusing and outdated terms. They should be abandoned in favor of ductal intraepithelial neoplasia (DIN) and lobular intraepithelial neoplasia (LIN).

The terms ductal and lobular intraepithelial neoplasia (DIN and LIN) were introduced by Tavossoli 15 years ago, who proposed they should replace, respectively, ductal and lobular carcinoma in situ (DCIS and LCIS). This proposal has been slowly gaining ground. We argue that DCIS and LCIS should now be definitively abandoned. Bringing together 'in situ' and other entities into the simpler and more logical DIN/LIN framework--as has been done with intraepithelial neoplasias of cervix, vagina, vulva, prostate, and pancreas--would eliminate the artificial and illogical distinctions between 'not cancers' (e.g. flat epithelial atypia, atypical ductal hyperplasia--now classified as low grade DIN) and 'cancers' (e.g. DCIS--now considered medium-high grade DIN). Elimination of the term 'carcinoma' from entities that cannot metastasize will reduce confusion among health professionals and patients, and contribute to reducing the risk of overtreatment, as well as reducing adverse psychological reactions in patients.

A computer-aided diagnosis approach for emphysema recognition in chest radiography.

The purpose of this work is twofold: (i) to develop a CAD system for the assessment of emphysema by digital chest radiography and (ii) to test it against CT imaging. The system is based on the analysis of the shape of lung silhouette as imaged in standard chest examination. Postero-anterior and lateral views are processed to extract the contours of the lung fields automatically. Subsequently, the shape of lung silhouettes is described by polyline approximation and the computed feature-set processed by a neural network to estimate the probability of emphysema. Images of radiographic studies from 225 patients were collected and properly annotated to build an experimental dataset named EMPH. Each patient had undergone a standard two-views chest radiography and CT for diagnostic purposes. In addition, the images (247) from JSRT dataset were used to evaluate lung segmentation in postero-anterior view. System performances were assessed by: (i) analyzing the quality of the automatic segmentation of the lung silhouette against manual tracing and (ii) measuring the capabilities of emphysema recognition. As to step i, on JSRT dataset, we obtained overlap percentage (Ω) 92.7±3.3%, Dice Similarity Coefficient (DSC) 95.5±3.7% and average contour distance (ACD) 1.73±0.87 mm. On EMPH dataset we had Ω=93.1±2.9%, DSC=96.1±3.5% and ACD=1.62±0.92 mm, for the postero-anterior view, while we had Ω=94.5±4.6%, DSC=91.0±6.3% and ACD=2.22±0.86 mm, for the lateral view. As to step ii, accuracy of emphysema recognition was 95.4%, with sensitivity and specificity 94.5% and 96.1% respectively. According to experimental results our system allows reliable and inexpensive recognition of emphysema on digital chest radiography.