Gaetano Rea

Clinical Relevance of Fluid Challenge in Patients Evaluated for Pulmonary Hypertension

Background Fluid challenge may help in the differential diagnosis between pre‐ and postcapillary pulmonary hypertension (PH). However, the test is still in need of standardization and better defined clinical relevance. Methods Two hundred twelve patients referred for PH underwent a right‐sided heart catheterization with measurements before and after rapid infusion of 7 mL/kg of saline. PH was defined as mean pulmonary artery pressure ≥ 25 mm Hg, and postcapillary PH was defined as pulmonary artery wedge pressure (PAWP) > 15 mm Hg. An increase in PAWP ≥ 18 mm Hg was considered diagnostic for postcapillary PH. At baseline, 66 patients received a diagnosis of no PH; 22, of postcapillary PH; and 124, of precapillary PH (mostly pulmonary arterial hypertension). Results After fluid challenge, five of 66 patients with no PH (8%) and eight of 124 with precapillary PH (6%) had the diagnosis reclassified as postcapillary PH. Fluid challenge was associated with an increase in PAWP by 7 ± 2 mm Hg in postcapillary PH and 3 ± 1 mm Hg in both precapillary PH and no‐PH groups. Between‐group differences were significant, but there was overlap. There were no adverse events related to fluid challenge. Prediction bands calculated from quadratic fits of the PAWP responses in pooled control subjects with no PH and patients with precapillary PH helped confirm 18 mm Hg as the cutoff for diagnosing postcapillary PH. Conclusions Fluid challenge with 7 mL/kg saline increases PAWP, more in postcapillary than in precapillary PH or in control subjects with no PH. A cutoff value of 18 mm Hg allows reclassification of 6% to 8% of patients with precapillary PH or normal hemodynamic characteristics at baseline.

Multimodality imaging in congenital heart disease-related pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) in adult patients with congenital heart disease (CHD) is associated with increased morbidity and mortality. The present review aims to discuss the clinical applications of invasive and non-invasive diagnostic modalities and to describe the strengths and weaknesses of each technique. Chest radiograph is an inexpensive investigation providing information on pulmonary arterial and hilar dilatation, pruning of peripheral pulmonary arteries and cardiomegaly. Transthoracic two-dimensional and Doppler echocardiography is the most widely used imaging tool. It provides information on cardiac anatomy and an estimate of haemodynamics and biventricular remodelling and function. In addition, echocardiography is valuable in assessing prognosis and monitoring the efficacy of therapy. Structural and functional changes associated with CHD-PAH, mainly affecting the right ventricle and pulmonary circulation, may represent an ideal target for evaluation with cardiac magnetic resonance. This non-invasive imaging modality has a low biological impact. CT plays an important role for patients with limited echocardiographic windows and those who are unable to undergo MRI (claustrophobia, poor compliance, presence of a pacemaker/implantable cardioverter defibrillator). It is the modality of choice for detailed assessment of pulmonary vessel obstruction or thrombosis. Finally, heart catheterisation remains the gold standard for diagnosing and confirming PAH in patients with CHD and for shunt evaluation. The diagnostic assessment of CHD-PAH requires great expertise and a deep knowledge of both CHD and PAH pathophysiology and should take place in a tertiary centre, where multiple data can be appropriately integrated and applied clinically.

A simple echocardiographic score for the diagnosis of pulmonary vascular disease in heart failure

Aims A simple echocardiographic score was designed for diagnosing precapillary vs postcapillary pulmonary hypertension and for discriminating between isolated postcapillary pulmonary hypertension (Ipc-PH) and combined precapillary and postcapillary pulmonary hypertension (Cpc-PH). Methods The score comprised 7 points (2 for E/e′ ratio ⩽10, 2 for a dilated non-collapsible inferior vena cava, 1 for a left ventricular eccentricity index ≥1.2, 1 for a right-to-left heart chamber dimension ratio >1 and 1 for the right ventricle forming the heart apex) and was applied to 230 consecutive patients referred for evaluation of pulmonary hypertension. Results Precapillary pulmonary hypertension and postcapillary pulmonary hypertension were diagnosed in 160 and 70 patients, respectively. In the latter, Ipc-PH was found in 51 and Cpc-PH in 19. The echo score was higher in precapillary vs postcapillary pulmonary hypertension patients (4.2 ± 1.7 vs 1.6 ± 1.7, P < 0.001) and in patients with Cpc-PH vs Ipc-PH (2.7 ± 2.1 vs 1.2 ± 1.3, P = 0.001). The sensitivity and specificity of the echo score at least 2 for precapillary pulmonary hypertension were 99 and 54%, respectively (area under the curve 0.85). In patients with postcapillary pulmonary hypertension, the sensitivity and specificity of the echo score at least 2 for Cpc-PH were 63 and 82% (area under the curve 0.73). Conclusion A simple echocardiographic score helps in the differential diagnosis between precapillary and postcapillary pulmonary hypertension, and between Ipc-PH and Cpc-PH.

Fluid challenge predicts clinical worsening in pulmonary arterial hypertension

AIM A fluid challenge with rapid saline infusion during right heart catheterization has been shown to be useful for the differential diagnosis between pre- and post-capillary pulmonary hypertension. The aim of this study was to evaluate the prognostic relevance of fluid challenge-induced changes in pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH). METHODS Overall, 118 PAH patients (mean age 57 ± 15 years, 80 female) underwent hemodynamic measurements before and after rapid saline infusion (7 mL/kg in 10 min) and were followed up for 19 ± 4 months. RESULTS Thirty-two patients (27%) had a clinical worsening event defined as the occurrence of one of the following: death, lung transplantation, initiation of parenteral prostanoids, or worsening of PAH (defined as the presence of all of the three following components: a decrease in the 6-minute walk distance of at least 15% from baseline, worsening of PAH symptoms, and need for new PAH treatment). Cardiac index (CI), stroke volume and pulmonary artery compliance were lower whereas right atrial pressure (RAP), the ratio of RAP to pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance were higher in patients with a clinical worsening event versus patients without events, both at baseline and after fluid challenge (all p < 0.01). At multivariable Cox proportional hazards regression analysis, a post-fluid challenge CI <2.8 L/min/m2 (hazard ratio 0.0143; 95% confidence interval 0.006-0.3383; p = 0.009) was the only independent predictor of outcome. CONCLUSIONS CI measured after a fluid challenge is an independent predictor of outcome in PAH.

Right heart and pulmonary thromboembolism from extensive splanchnic vein thrombosis after splenectomy for myeloproliferative disease.

BACKGROUND Splenectomy is a risk factor for both portal-vein and chronic thromboembolic pulmonary hypertension. The underlying mechanism is unclear, but may involve a hypercoagulable state. METHODS We describe 1 patient with polycythemia vera who developed extensive portal thrombosis of the portal, suprahepatic, and inferior cava veins, leading to right heart thromboembolism, with a resultant pulmonary embolism subsequent to splenectomy despite heparin prophylaxis. RESULTS In this patient, several mechanisms may have played a role, including perioperative stress, thrombocytosis, thrombophilia, and associated chronic liver disease. Nevertheless, combined treatment with intravenous heparin and thrombolysis and the myeloproliferative inhibitor hydroxyurea was associated with a favorable outcome. CONCLUSION The risk of pulmonary thromboembolic complications and their management after splenectomies for hematologic disease warrant further study.

Contrast-enhanced ultrasound does not discriminate between community acquired pneumonia and lung cancer

We investigated if contrast-enhanced ultrasound (CEUS) may differentiate community acquired pneumonia (CAP) from lung cancer (LC). Among 1374 patients admitted in a 5-year period for lung opacities, 728 (329 CAP and 399 LC) were investigated by CEUS, comparing the time of appearance, disappearance, duration and pattern of distribution of contrast enhancement (CE). The patients with CAP and LC did not differ in terms of age, time of CE appearance, disappearance and duration or CE distribution. Our data show that the timing and pattern of CE detected by chest CEUS does not distinguish between CAP and LC and overly optimistic beliefs on this matter should be abandoned.

Is there any role for thoracic ultrasound for interstitial lung disease underlying rheumatologic conditions? Comment

We read the commentary of Sambataro et al. [1] which focused on a possible role for thoracic ultrasound (TUS) to identify interstitial lung disease (ILD) through the count of ‘‘B lines‘‘. In our opinion, this raises some concerns: TUS, in optimal conditions, assesses only 70% of the lung surface, due to the anatomical constraints of the thoracic cage, and only the alterations closely related to the pleural surface may be visualized [2]. There is no correlation, contrary to what the authors report [1], between the number of B lines (C4 as cut-off value) and pathology of connective tissue diseases (CTD): in fact, in all those pathological pleuro-pulmonary conditions where the proportion of air/liquid film varies with respect to normal, such as occurs in the majority of diffuse lung diseases, you may have an increase in artifacts (ring down/B line) [2]. The evaluation process of B lines is at best semiquantitative, because the method is more of a subjective overview than an actual ‘‘measurement,’’ and this is contrary to efforts to improve the reliability and objectivity of imaging. Moreover, there is no sufficient information about the ultrasound devices employed and their respective settings (TGC, tissue harmonic, and electronic focus), and elements can result in a significant difference in sonographic pattern. There is a great difference between linear or convex probes and phased-array transducers, for example, the use of phased-array transducers provides a greater risk of artifacts, particularly at lower frequencies [3]. Based on our experience over the last 20 years, we believe that thoracic US can provide potentially useful information regarding the structural and functional changes provoked by ILD, even in the early stages of the disease. We find that morphological imaging of pleural–subpleural lung nodules or thickening of the pleural line by TUS [4] is a more rewarding way for a reproducible assessment of pulmonary fibrosis severity, as it is recognized. Although the US features are not always specific for ILD, they show good correlation with the degree of fibrosis: in fact, in patients with clinically severe disease, the abnormalities observed on US are more numerous and more evident. In a recent study [4], our group compared the findings of thoracic US to those of HRCT in 175 consecutive patients with systemic sclerosis (SSc). The pleural line thickness is 3.0 mm in all patients without signs of interstitial involvement on HRCT [4]. The sensitivity of pleural line thickness (Fig. 1) to identify interstitial lesions HRCTdetected ranges from 74.3% for reticulo-nodular involvement if the width is 3.5 mm to 80.0% for a reticular pattern with a width of 3.0 to [-5 mm, and to 90.1% for honeycombing if the width is[5.0 mm, and the specificity is 99% in all cases [4]. This very high specificity allows the exclusion of interstitial involvement in patients with systemic sclerosis without clinical evidence of lung disease. Thoracic ultrasonography is also easy to repeat, and this makes it an ideal complementary method for monitoring the evolution of the disease and the patients’ responses to treatment. & Maria Giulia Tinti mariagiulia.tinti@gmail.com

Chest ultrasound findings in pulmonary alveolar microlithiasis

Pulmonary alveolar microlithiasis (PAM) is a rare disorder of unknown etiology affecting people at any age. It is characterized by multiple and microscopic calcium deposits diffusely localized within the alveoli. Thorax high-resolution computed tomography is considered the gold standard for PAM imaging. Herein we report for the first time the use of trans-thoracic ultrasound (TUS) examination in a young severely obese PAM female patient, diagnosed at the age of 10, and referred to our clinic for re-staging purposes at the age of 36. Unlike expected, no reverberation or additional artifacts were appreciated on TUS examination despite the severity of the interstitial/alveolar involvement seen on conventional CT imaging. To date, no ring-down or comet-tail artifacts were detected. The only TUS finding was an increased thickness and irregular profile, more evident in the dorsal lower lung regions, of the hyper-echoic pleural line. TUS has recently aroused increasing interest among clinicians and radiologists as a useful noninvasive diagnostic tool for studying pleuro-pulmonary diseases, including interstitial lung diseases (ILDs). The peculiarity of our case is represented by the discrepancy between TUS and CT findings. Further efforts to address the usefulness and US patterns in diffuse ILDs, with the inclusion of rare disorders, are needed.

Idiopathic pleuroparenchymal fibroelastosis: incidental findings in a patient with suspected pneumonia

A fibroelastose pleuroparenquimatosa idiopatica (FEPPI) e uma doenca rara que afeta a pleura e os pulmoes. Em 2013, a FEPPI foi considerada uma doenca pulmonar intersticial (DPI) rara em uma declaracao conjunta da American Thoracic Society/European Respiratory Society sobre a classificacao das pneumonias intersticiais idiopaticas.(1) Caracterizada por fibrose e espessamento do tecido pleural e subpleural (fibroelastose subpleural), a FEPPI afeta predominantemente a periferia dos lobos pulmonares superiores, com perda de volume, como inicialmente descreveram Frankel et al. em 2004.(2) Ate o momento, nao mais de quarenta casos de FEPPI foram descritos na literatura em ingles. Atualmente, alem de nao haver consenso a respeito dos criterios diagnosticos usados para classificar a FEPPI, nao se sabe se a doenca e de fato uma entidade especifica nova. Embora a etiologia seja desconhecida, a FEPPI esta relacionada com infeccoes, transplante de medula ossea, autoimunidade e, possivelmente, predisposicao genetica. Clinicamente, pacientes com FEPPI geralmente apresentam sintomas respiratorios cronicos como dispneia e tosse seca. O diagnostico de FEPPI baseia-se em achados clinicos, radiologicos e histopatologicos. A TCAR de torax mostra consolidacoes subpleurais pronunciadas com espessamento irregular; distorcao, geralmente nos lobos pulmonares superiores (“capa pleural”); bronquiolectasias subpleurais; opacidades reticulares e, em alguns casos, faveolamento leve. Essas caracteristicas sao semelhantes as de outras formas de fibrose pulmonar idiopatica. No entanto, na FEPPI, elas sao vistas principalmente nos lobos superiores, e sao raras ou ausentes nos lobos inferiores.(3,4) As caracteristicas histologicas da FEPPI sao fibrose subpleural homogenea e fibras elasticas abundantes (vistas por meio de tecnicas de coloracao de fibras elasticas).(5)

The imaging spectrum of pulmonary tuberculosis: a critical appraisal.

The article by Cardinale et al. (1) is greatly welcome for the considerable interest and the great clinical relevance of the chosen topic, pulmonary tuberculosis, which, nonetheless, is currently a quite neglected disease. The migratory flows, the HIV epidemics and the fallout on the general population enhance interest and research on the usefulness and potential of different diagnostic tools suitable for the evaluation of patients with tuberculosis. In our institution, the Monaldi Hospital of Naples, there is a trend toward the increase of hospital admissions, from approximately 130 new cases of tubercular infection in 2011 to approximately 160 new cases in 2013. Sixty percent of them came from the East (Europe and Asia) or North Africa (Morocco). All cases were evaluated by X-ray, multidetector computed tomography (MDCT), and thoracic ultrasound (TUS). Few statements of this review deserve, in our opinion, to be managed with a greater care, in order to improve the information without misleading concepts or recommendation. First: ‘‘the radiologic signs of the disease are often misleading. Indeed, tuberculosis may be diagnosed in about 25% of cases initially misinterpreted as lung cancer’’ (1). This is not exactly correct, since in the quoted original article it is reported: ‘‘The overwhelming majority of patients (93.3%) referred to ‘‘rule out’’ lung cancer were documented as having a neoplastic process, and only 1.3% had an infection. Fungal infections (histoplasmosis, cryptococcosis, coccidiomycosis) accounted for 46%, mycobacteria for 27%, bacteria for 22%, and parasitic lesions (dirofilariasis) for 5% of these infections’’. In other words, we understand that only a minority of patients – 1.3% – in that case series of almost 20 years ago, even referred for lung cancer investigation were, actually, patients with pulmonary infectious disease: of them, 27% were patients with tuberculosis (2). In our experience only a minority of patients with tuberculosis are referred erroneously to further investigation for cancer or to intervention procedures; and this is true not only for a specialized institution like we are, but also for the referral from non-specialized institutions or outpatients clinics, as confirmed in more recent reviews (3). The misunderstanding of the quoted article can be misleading for many readers since seemingly is displaying concerns on the actual expertise of radiologists. Second: we perform regularly TUS in tuberculosis patients and we wonder why the authors (1) quote only a very old report (4) simply writing ‘‘Tuberculous effusions contain high quantity of proteins and often show fibrin strands and septa on thoracic ultrasound imaging. Very often septa that have been imaged by ultrasound are not detected by CT’’ (4). This description does not fully correspond to what we actually see (loculated pleural effusions are a feature of a part of such conditions) and, more important, no comment is provided for pleural thickness and nodularity, described in that report, 20 years ago, and that we also often see (4). A comment on the reliability for monitoring pleural effusions by TUS and for FNAB under appropriate TUS guidance (5) should be added to this otherwise constructive review on pulmonary tuberculosis.