Search

The cause of dyspnea may remain uncertain even after a complete non-invasive clinical workup, and a right heart catheterization is performed to achieve a definitive diagnosis. Although pulmonary artery wedge pressure (PAWP) is key for the differential diagnosis between pulmonary arterial hypertension (PAH) and heart failure with preserved ejection fraction (HFpEF), the diagnosis may be challenging because PAWP may be normal after diuretic administration in HFpEF patients on optimal medical therapy. In order to avoid misdiagnosis, building a pre-test probability of pre- or post-capillary pulmonary hypertension is crucial. Current guidelines on pulmonary hypertension suggest to interpret hemodynamics in the context of clinical picture and imaging, mainly echocardiography. Indecisive measurements of PAWP in patients with an intermediate to high clinical probability of HFpEF can be repeated after a fluid challenge test with rapid infusion of 7 ml/kg or 500 ml of saline. The procedure is simple and does not take much catheterization laboratory time. A post-fluid challenge PAWP >18 mmHg strongly supports the diagnosis of occult HFpEF. A possible alternative to fluid challenge test is exercise or dobutamine stress test. However, exercise hemodynamics is not feasible in all catheterization laboratories and may be difficult to interpret due to wide swings in intrathoracic pressures. Otherwise, dobutamine infusion during right heart catheterization may be potentially more practical than exercise stress, but requires further validation studies to determine its utility. The aim of this case report is to provide a practical roadmap for challenging cases, when the differential diagnosis between PAH and HFpEF is uncertain.

Background: An acute vasodilator challenge is recommended in patients with heart failure and pulmonary hypertension during heart transplant evaluation. The aim of the study was to assess which hemodynamic parameters are associated with nonresponsiveness to the challenge., Methods and Results: This study is a retrospective analysis of 402 patients with heart failure with pulmonary hypertension who underwent right heart catheterization and a pulmonary vasodilator challenge. Among the 140 who fulfilled the transplant guidelines eligibility criteria for the vasodilator challenge, 38 were responders and 102 nonresponders. At multivariable analysis, a diastolic blood pressure of <70 mm Hg, pulmonary vascular resistance of >5 Woods units, and pulmonary artery compliance of <1.2 mL/mm Hg were independently associated with poor response to vasodilator challenge (all P < .001). The presence of any 2 of these 3 conditions was associated with a 90% probability of being a nonresponder. The covariate-adjusted hemodynamic predictors of death in the entire population were a low baseline systolic blood pressure (P = .0017) and a low baseline right ventricular stroke work index (P = .0395)., Conclusions: In patients with heart failure and pulmonary hypertension, low pulmonary arterial compliance, high pulmonary vascular resistance, and low diastolic blood pressure predict the nonresponsiveness to acute vasodilator challenge whilst a poor right ventricular function predicts a dismal prognosis., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This case report describes a procedure of retrieval of a leadless transcatheter pacemaker from the right pulmonary artery 3 days after device implantation. An 80-year-old man affected by ischemic cardiomyopathy and sinus node dysfunction was implanted with a leadless transcatheter pacemaker in the low septum of the right ventricle. Three days after the procedure, the leadless pacemaker migrated into a side branch of the right pulmonary artery. The device was successfully removed using two snares hooked to a tine via the proximal retrieval feature., (© 2020 Wiley Periodicals LLC.)

Background: During the COVID-19 pandemic, most of the health care systems suspended their non-urgent activities. This included the cancellation of consultations for patients with rare diseases, such as severe pulmonary hypertension (PH), resulting in potential medication shortage and loss of follow-up. Thus, the aim of the study was to evaluate PH patient health status evolution, access to health care and mental health experience during the early phase of the pandemic., Methods: We conducted an online patient survey, available in 16 languages, between 22/05/2020 and 28/06/2020. The survey included questions corresponding to demographic, COVID-19 and PH related information., Results: 1073 patients (or relatives, 27%) from 52 countries all over the world participated in the survey. Seventy-seven percent (77%) of responders reported a diagnosis of pulmonary arterial hypertension and 15% of chronic thromboembolic PH. The COVID-19 related events were few: only 1% of all responders reported a diagnosis of COVID-19. However, 8% of patients reported health deterioration possibly related to PH, and 4% hospitalization for PH. Besides, 11% of the patients reported difficulties to access their PH expert centre, and 3% interruption of treatment due to shortage of medication. Anxiety or depression was reported by 67% of the participants., Conclusion: Although COVID-19 incidence in PH patients was low, PH related problems occurred frequently as the pandemic progressed, including difficulties to have access to specialized care. The importance of primary health care was emphasized. Further studies are needed to evaluate the long-term consequences of COVID-related PH care disruption.

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.

A right heart catheterization with measurements of pulmonary artery wedge pressure (PAWP) may be necessary for the diagnosis of left heart failure as a cause of pulmonary hypertension or unexplained dyspnea. Diagnostic cutoff values are a PAWP of ≥ 15 mm Hg at rest or a PAWP of ≥ 25 mm Hg during exercise. However, accurate measurement of PAWP can be challenging and heart failure may be occult. Left heart catheterization, with measurement of left ventricular end-diastolic pressure, may also be indecisive. Measurements are then best repeated in stress conditions. Exercise is an option, but the equipment is not universally available, and interpretation can be difficult in patients with wide respiratory pressure swings. An alternative is offered by a fluid challenge. Studies have gathered data supporting infusion of 500 mL or 7 mL/kg saline and a PAWP of 18 mm Hg as a diagnostic cutoff. The procedure is simple and does not take much catheterization laboratory time. Combining echocardiography with invasive measurements may increase the diagnostic accuracy of diastolic dysfunction. Cardiac output after a fluid challenge may be of prognostic relevance., (Copyright © 2020. Published by Elsevier Inc.)

Over recent years, thanks to remarkable advances in pediatric cardiology, cardiac surgery and catheter interventions, survival of children with congenital heart disease has significantly increased with the majority of patients surviving into adulthood. Therefore, the prevalence of adult patients with congenital heart disease has dramatically increased, as well as the need for specific and dedicated programs. Acute heart failure, infective endocarditis and arrhythmias represent the most common causes of visit in the emergency department in this population. Our task force aimed at guiding physicians taking care of this peculiar cohort of patients in the emergency department.

Purpose: This study was a quality-control study of resting and exercise Doppler echocardiography (EDE) variables measured by 19 echocardiography laboratories with proven experience participating in the RIGHT Heart International NETwork., Methods: All participating investigators reported the requested variables from ten randomly selected exercise stress tests. Intraclass correlation coefficients (ICC) were calculated to evaluate the inter-observer agreement with the core laboratory. Inter-observer variability of resting and peak exercise tricuspid regurgitation velocity (TRV), right ventricular outflow tract acceleration time (RVOT Act), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler tricuspid lateral annular systolic velocity (S'), right ventricular fractional area change (RV FAC), left ventricular outflow tract velocity time integral (LVOT VTI), mitral inflow pulsed wave Doppler velocity (E), diastolic mitral annular velocity by TDI (e') and left ventricular ejection fraction (LVEF) were measured., Results: The accuracy of 19 investigators for all variables ranged from 99.7 to 100%. ICC was > 0.90 for all observers. Inter-observer variability for resting and exercise variables was for TRV = 3.8 to 2.4%, E = 5.7 to 8.3%, e' = 6 to 6.5%, RVOT Act = 9.7 to 12, LVOT VTI = 7.4 to 9.6%, S' = 2.9 to 2.9% and TAPSE = 5.3 to 8%. Moderate inter-observer variability was found for resting and peak exercise RV FAC (15 to 16%). LVEF revealed lower resting and peak exercise variability of 7.6 and 9%., Conclusions: When performed in expert centers EDE is a reproducible tool for the assessment of the right heart and the pulmonary circulation.

Rationale: Despite well-established associations between alcohol use, poor mental health, and intimate partner violence (IPV), limited attention has been given to how psychological and behavioral interventions might prevent or treat IPV in low- and middle-income countries., Objective: In a recent randomized controlled trial in Lusaka, Zambia, transdiagnostic cognitive-behavioral psychotherapy (the Common Elements Treatment Approach; CETA) demonstrated significant treatment effects on men's alcohol use and women's IPV victimization in couples in which hazardous alcohol use by the male and intimate partner violence against the female was reported. In this study, we sought to gain a more in-depth understanding of mechanisms of behavior change among CETA participants., Methods: We conducted 50 semi-structured in-depth interviews and 4 focus groups with a purposeful sample of adult men and women who received CETA between April and October 2018. Transcripts were analyzed using an inductive constant comparison approach by a team of US- and Zambia-based coders., Results: Participants described interrelated mechanisms of change, including the use of safety strategies to not only avoid or prevent conflict but also to control anger; reductions in alcohol use that directly and indirectly reduced conflict; and, positive changes in trust and understanding of one's self and their partner. Several overarching themes also emerged from the data: how gender norms shaped participants' understanding of violence reduction strategies; the role of household economics in cycles of alcohol and violence; and, deleterious and virtuous intercouple dynamics that could perpetuate or diminish violence., Conclusions: Results suggest important avenues for future research including the potential for combining CETA with poverty reduction or gender norms focused interventions and for incorporating cognitivebehavioral skills into community level interventions., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Multidetector computed tomography (MDCT) is the gold standard in annulus sizing before transcatheter aortic valve replacement (TAVR). However, MDCT has limited applicability in specific subgroups of patients, such as those with atrial fibrillation and chronic kidney disease. Two-dimensional transesophageal echocardiography (2DTEE) has traditionally been limited to the long-axis measurement of the anteroposterior diameter of the aortic annulus. We describe a new 2DTEE approach for the measurement of the major diameter of the aortic annulus., Methods: Seventy-six patients with symptomatic severe aortic valve stenosis and high surgical risk underwent MDCT and 2DTEE before TAVR. A modified five-chamber view was used to measure the major aortic annulus diameter. This was obtained starting from a mid-esophageal four chamber and retracting the TEE probe up until the left ventricular outflow tract and the left and noncoronary aortic cusps were visualized: major aortic annulus diameter was measured as the distance between their insertion points in systole., Results: Major aortic annulus diameters measured at 2DTEE showed good correlation with MDCT diameter ( r = 0.79; P < 0.001) and perimeter ( r = 0.87; P < 0.0001). Using factsheet-derived sizing criteria, 2DTEE alone would have allowed accurate sizing in 75% of patients, with 21% of oversizing predominantly with smaller annuli., Conclusions: We describe a new method for 2DTEE measurement of the major aortic annulus diameter; this approach is simple, correlates with MDCT, and allows adequate TAVR sizing in most patients. These findings may help in the assessment of patients with contraindications to or inadequate MDCT images., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Cardiovascular Echography.)

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., Competing Interests: Disclosure statement M.D.A., R.B., C.D.V., S.G. received fees for participating in advisory boards and received benefits (travel and accommodation for scientific meetings) from Actelion, Bayer, Dompè, Ferrer, GlaxoSmithKline, and Merck Sharp & Dohme. P.A. received fees for participating in advisory boards and received benefits (travel and accommodation for scientific meetings) from Actelion, Dompè, GlaxoSmithKline, and Merck Sharp & Dohme. G.C. received fees for participating in advisory boards and received benefits (travel and accommodation for scientific meetings) from Actelion, Bayer, Dompè, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca, Boston Scient, Servier, Sanofi, Amgen, and Novartis. M.C. received grants for advisory board by GlaxoSmithKline and Janssen. R.P. received economical support for advisory boards and travel and accommodation for scientific meetings from Actelion, GlaxoSmithKline, and Bayer. E.R. received fees for participating in advisory boards and received benefits (travel and accommodation for scientific meetings) from Actelion, Dompè, GlaxoSmithKline, and Merck Sharp & Dohme. V.M. received a research fellowship grant from the European Respiratory Society. R.N. has relationships with AOP Orphan Pharmaceuticals, Actelion, Reata Pharmaceuticals, Lung Biotechnology Corporation, and United Therapeutics. The remaining authors have no conflict of interest to disclose., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an Acute Respiratory Distress Syndrome (ARDS)., Methods: Ninety-four consecutive patients (mean age 64 years) admitted for acute respiratory failure on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio RESULTS: The majority of patients needed ventilatory support, which was noninvasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62 ± 13 vs. 68 ± 12 years, p = 0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO 2 )/fraction of inspired O 2 (FIO 2 ) ratio (270 ± 104 vs. 117 ± 57 mmHg, p < 0.001). In the non-survivors, PASP was increased (42 ± 12 vs. 30 ± 7 mmHg, p < 0.001), while TAPSE was decreased (19 ± 4 vs. 25 ± 4 mm, p < 0.001). Accordingly, the TAPSE/PASP ratio was lower than in the survivors (0.51 ± 0.22 vs. 0.89 ± 0.29 mm/mmHg, p < 0.001). At univariate/multivariable analysis, the TAPSE/PASP (HR: 0.026; 95%CI 0.01-0.579; p: 0.019) and PaO 2 /FIO 2 (HR: 0.988; 95%CI 0.988-0.998; p: 0.018) ratios were the only independent predictors of mortality, with ROC-determined cutoff values of 159 mmHg and 0.635 mm/mmHg, respectively., Conclusions: COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO 2 /FIO 2 in ARDS on COVID-19.

Central American youth are at a high risk for experiencing trauma and related psychosocial problems. Despite this, few studies of evidence-based trauma-focused interventions with this population exist. The objective of this project was twofold: 1) to train providers in El Salvador in Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) as part of a clinical implementation project within a non-governmental organization, and 2) to conduct program evaluation to determine the feasibility of implementation and the effectiveness of the treatment. Fifteen Salvadoran psychologists were trained in TF-CBT who then provided TF-CBT to 121 children and adolescents ages 3-18 in community-based locations. The mean number of traumas reported by youth was 4.39. Results demonstrated large effect sizes for reduction in youth-reported trauma symptoms (Cohen's d  = 2.04), depressive symptoms (Cohen's d  = 1.68), and anxiety symptoms (Cohen's d  = 1.67). Our program evaluation results suggest that it was feasible to train providers in TF-CBT, that providers were in turn able to deliver TF-CBT in community-based settings, and that TF-CBT was an effective treatment option to address trauma-related concerns for youth in El Salvador. This project is an important first step in the dissemination and implementation of evidence-based trauma-focused treatment for youth in Latin American countries., (© Springer Nature Switzerland AG 2020.)

Right ventricular (RV) function is important for clinical status and outcomes in children and adults with congenital heart disease (CHD). In the normal RV, longitudinal systolic function is the major contributor to global RV systolic function. A variety of factors contribute to RV failure including increased pressure- or volume-loading, electromechanical dyssynchrony, increased myocardial fibrosis, abnormal coronary perfusion, restricted filling capacity and adverse interactions between left ventricle (LV) and RV. We discuss the different imaging techniques both at rest and during exercise to define and detect RV failure. We identify the most important biomarkers for risk stratification in RV dysfunction, including abnormal NYHA class, decreased exercise capacity, low blood pressure, and increased levels of NTproBNP, troponin T, galectin-3 and growth differentiation factor 15. In adults with CHD (ACHD), fragmented QRS is independently associated with heart failure (HF) symptoms and impaired ventricular function. Furthermore, we discuss the different HF therapies in CHD but given the broad clinical spectrum of CHD, it is important to treat RV failure in a disease-specific manner and based on the specific alterations in hemodynamics. Here, we discuss how to detect and treat RV dysfunction in CHD in order to prevent or postpone RV failure., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-370). The series “Right Ventricular Dysfunction” was commissioned by the editorial office without any funding or sponsorship. GH and MK served as the unpaid Guest Editors of the series. GH reports grants from German Research Foundation, Federal Ministry of Education and Research and from European Pediatric Pulmonary Vascular Disease Network, outside the submitted work. MD reports grants from Actelion/Johnson & Johnson, grants and personal fees from Merck Sharp & Dohme, grants and personal fees from Glaxo Smith Kline, grants from United Therapeutics, and grants from Ferrer group, outside the submitted work. WB reports other from Abbott and Occlutech, outside the submitted work. The authors have no other conflicts of interest to declare., (2020 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Noninvasive estimation of systolic pulmonary artery pressure (SPAP) during exercise stress echocardiography (ESE) is recommended for pulmonary hemodynamics evaluation but remains flow-dependent. Our aim was to assess the feasibility of pulmonary vascular reserve index (PVRI) estimation during ESE combining SPAP with cardiac output (CO) or exercise-time and compare its value in three group of patients: with invasively confirmed pulmonary hypertension (PH), at risk of PH development (PH risk) mainly with systemic sclerosis and in controls (C) without clinical risk factors for PH, age-matched with PH risk patients. We performed semisupine ESE in 171 subjects: 31 PH, 61 PH at risk and 50 controls as well as in 29 young, healthy normals. Rest and stress assessment included: tricuspid regurgitant flow velocity (TRV), pulmonary acceleration time (ACT), CO (Doppler-estimated). SPAP was calculated from TRV or ACT when TRV was not available. We estimated PVRI based on CO (peak CO/SPAP*0.1) or exercise-time (ESE time/SPAP*0.1). During stress, TRV was measurable in 44% patients ACT in 77%, either one in 95%. PVRI was feasible in 65% subjects with CO and 95% with exercise-time (p < 0.0001). PVRI was lower in PH compared to controls both for CO-based PVRI (group 1 = 1.0 ± 0.95 vs group 3 = 4.28 ± 2.3, p < 0.0001) or time-based PVRI estimation (0.66 ± 0.39 vs 3.95 ± 2.26, p < 0.0001). The proposed criteria for PH detection were for CO-based PVRI ≤ 1.29 and ESE-time based PVRI ≤ 1.0 and for PH risk ≤ 1.9 and ≤ 1.7 respectively. Noninvasive estimation of PVRI can be obtained in near all patients during ESE, without contrast administration, integrating TRV with ACT for SPAP assessment and using exercise time as a proxy of CO. These indices allow for comparison of pulmonary vascular dynamics in patients with varied exercise tolerance and clinical status.

: The recent outbreak of 2019 severe acute respiratory syndrome coronavirus-2 is having major repercussions on healthcare services provision in Italy and worldwide. Data suggest the virus has a strong impact on the cardiovascular system, and cardiac imaging will play an important role in patients affected by coronavirus disease-2019. Although paediatric patients are mildly affected, they represent a clear accelerator in spreading the virus, and healthcare workers are at higher risk of infection. The aim of this position paper is to provide clinical recommendation regarding the execution of imaging investigations for the cardiac diagnostic work-up of paediatric patients with suspected or confirmed infection.

Introduction: Pulmonary hypertension (PH) is a common complication in patients with congenital heart disease (CHD), aggravating the natural, post-operative, or post-interventional course of the underlying anomaly. The various CHDs differ substantially in characteristics, functionality, and clinical outcomes among each other and compared with other diseases with pulmonary hypertension., Objective: To describe current management strategies and outcomes for adults with PH in relation to different types of CHD based on real-world data., Methods and Results: COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) is a prospective, international PH registry comprising, at the time of data analysis, >8200 patients with various forms of PH. Here, we analyzed a subgroup of 680 patients with PH due to CHD, who were included between 2007 and 2018 in 49 specialized centers for PH and/or CHD located in 11 European countries. At enrollment, the patients´ median age was 44 years (67% female), and patients had either pre-tricuspid shunts, post-tricuspid shunts, complex CHD, congenital left heart or aortic disease, or miscellaneous other types of CHD. Upon inclusion, targeted therapies for pulmonary arterial hypertension (PAH) included endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin analogues, and soluble guanylate cyclase stimulators. Eighty patients with Eisenmenger syndrome were treatment-naïve. While at inclusion the primary PAH treatment for the cohort was monotherapy (70% of patients), with 30% of the patients on combination therapy, after a median observation time of 45.3 months, the number of patients on combination therapy had increased significantly, to 50%. The use of oral anticoagulants or antiplatelets was dependent on the underlying diagnosis or comorbidities. In the entire COMPERA-CHD cohort, after follow-up and receiving targeted PAH therapy ( n = 511), 91 patients died over the course of a 5-year follow up. The 5-year Kaplan-Meier survival estimate for CHD associated PH was significantly better than that for idiopathic PAH (76% vs. 54%; p < 0.001). Within the CHD associated PH group, survival estimates differed particularly depending on the underlying diagnosis and treatment status., Conclusions: In COMPERA-CHD, the overall survival of patients with CHD associated PH was dependent on the underlying diagnosis and treatment status, but was significantly better as than that for idiopathic PAH. Nevertheless, overall survival of patients with PAH due to CHD was still markedly reduced compared with survival of patients with other types of CHD, despite an increasing number of patients on PAH-targeted combination therapy., Competing Interests: COMPERA is supported by an educational grant from Bayer, GSK, OMT and Actelion. The authors declare no conflicts of interest in relation to the study.

Background: Combinations of therapies are currently recommended for patients with severe pulmonary arterial hypertension (PAH), and excellent results have been reported with triple upfront combination of these drugs. We evaluated the effects of this approach on right ventricular (RV) function and outcome in patients with severe PAH., Methods: Twenty-one patients (age, 44 ± 15 years) with newly diagnosed high-risk idiopathic PAH that was nonreversible by the inhalation of nitric oxide were treated upfront with a combination of ambrisentan, tadalafil, and subcutaneous treprostinil between 2014 and 2018. Clinical evaluation, World Health Organization functional class, 6-min walk distance, biomarkers, echocardiography, and right-sided heart catheterization data were recorded at baseline and during follow-up., Results: At a median follow-up of 2 years, all patients were still alive. The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management score decreased from 10 ± 1 to 5 ± 1, right-sided atrial pressure decreased from 13 ± 3 to 5 ± 2 mm Hg, mean pulmonary artery pressure decreased from 60 ± 9 to 42 ± 5 mm Hg, pulmonary vascular resistance (PVR) decreased from 16.4 ± 4.4 to 5.5 ± 1.3 Wood units, N-terminal pro-brain natriuretic peptide decreased from 3,379 ± 1,921 to 498 ± 223 pg/mL, and World Health Organization functional class decreased from 3.4 ± 0.5 to 2.0 ± 0.4 (all P < .001). Cardiac index increased from 1.8 ± 0.3 to 3.5 ± 0.8 L/min/m 2 and 6-min walk distance increased from 158 ± 130 to 431 ± 66 m (both P < .001). Echocardiography showed decreased right-sided atrial and RV areas, improved left ventricular eccentricity index, and increased fractional area change (all P < .001) in proportion to treatment-induced decrease in PVR., Conclusions: Triple upfront combination therapy with ambrisentan, tadalafil, and subcutaneous treprostinil in severe nonreversible PAH is associated with considerable clinical and hemodynamic improvement and right-sided heart reverse remodeling., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The right heart has been traditionally considered a passive conduit between the venous system and the lungs. Today, we know that a close hemodynamic interdependence exists between right ventricle, pulmonary circulation, and left ventricle, and that the right ventricle plays a key role in the ability to adapt to many super-physiological and pathological conditions. Dynamic exercise is a considerable stress for the "right heart-pulmonary circulation unit", which responds, in healthy subjects, with an increase of right ventricular contractility and cardiac output, a decrease of pulmonary vascular resistance, and a non-significant rise in pulmonary pressures. In patients affected by cardiac and/or pulmonary diseases (e.g. ischemic heart disease, heart failure, severe valvular stenosis or regurgitation, systemic sclerosis, chronic obstructive pulmonary disease, etc.) right ventricular contractile reserve may be impaired, and pulmonary artery systolic pressure may abnormally increase during exercise. From this perspective, stress echocardiography is a primary tool to evaluate right ventricle and pulmonary circulation during exercise, and can be useful in setting diagnosis, prognosis, and therapeutic timing of many cardiopulmonary diseases.

Background Identification of occult diastolic dysfunction often requires invasive right heart catheterization with provocative maneuvers such as fluid challenge. Non-invasive predictors of occult diastolic dysfunction have not been identified. We hypothesized that echocardiographic measures of diastolic function are associated with occult diastolic dysfunction identified at catheterization. Methods and Results We retrospectively examined hemodynamic and echocardiographic data from consecutive patients referred for right heart catheterization with fluid challenge from 2009 to 2017. A replication cohort of 52 patients who prospectively underwent simultaneous echocardiography and right heart catheterization before and after fluid challenge at Monaldi Hospital, Naples, Italy. In the retrospective cohort of 126 patients (83% female, 56+14 years), 27/126 (21%) had occult diastolic dysfunction. After adjusting for tricuspid regurgitant velocity and left atrial volume index, E velocity (odds ratio 1.8, 95% CI 1.1-2.9, P=0.01) and E/e' (odds ratio 1.9, 95% CI 1.1-3, P=0.005) were associated with occult diastolic dysfunction with an optimal threshold of E/e' >8.6 for occult diastolic dysfunction (sensitivity 70%, specificity 64%). In the prospective cohort, 5/52 (10%) patients had diastolic dysfunction after fluid challenge. Resting E/e' (odds ratio 8.75, 95% CI 2.3-33, P=0.001) and E velocity (odds ratio 7.7, 95% CI 2-29, P=0.003) remained associated with occult diastolic dysfunction with optimal threshold of E/e' >8 (sensitivity 73%, specificity 90%). Conclusions Among patients referred for right heart catheterization with fluid challenge, E velocity and E/e' are associated with occult diastolic dysfunction after fluid challenge. These findings suggest that routine echocardiographic measurements may help identify patients like to have occult diastolic dysfunction non-invasively.

Gender differences in the outcome of acquired cardiovascular disease are well known, but available literature on the influence of gender in congenital heart disease (CHD) is limited. Registries have provided valuable, albeit at times conflicting data. Higher mortality rates have been reported in older males with CHD, while sudden cardiac death is more prevalent in young males. However, mortality around surgery for CHD is higher in girls compared to boys, likely due to smaller body size. Women are at higher risk of developing pulmonary arterial hypertension, but at lower risk of adverse aortic outcomes, even though they are less likely to receive aortic surgery. Finally, women have a lower risk of presenting with infective endocarditis compared to men. The underlying reasons for gender differences in CHD can be attributed to genetic, hormonal, behavioural and other causes. The aim of the present paper is to provide an overview of available evidence on gender differences in CHD and their impact on outcome., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Quantitative high resolution computed tomography (HRCT) may objectively assess systemic sclerosis (SSc)-interstitial lung disease (ILD) extent, using three basic densitometric measures: mean lung attenuation (MLA), skewness, and kurtosis. This prospective study aimed to develop a composite index - computerized integrated index (CII) - that accounted for MLA, skewness, and kurtosis by means of Principal Component Analysis over HRCTs of 83 consecutive SSc subjects, thus eliminating redundancies. Correlations among CII, cardiopulmonary function and immune-inflammatory biomarkers (e.g. sIL-2Rα and CCL18 serum levels) were explored. ILD was detected in 47% of patients at visual HRCT assessment. These patients had worse CII values than patients without ILD. The CII correlated with lung function at both baseline and follow-up, and with sIL-2Rα and CCL18 serum levels. The best discriminating CII value for ILD was 0.1966 (AUC = 0.77; sensitivity = 0.81 [95%CI:0.68-0.92]; specificity = 0.66 [95%CI:0.52-0.80]). Thirty-four percent of patients without visual trace of ILD had a CII lower than 0.1966, and 67% of them had a diffusing lung capacity for CO <80% of predicted. We showed that this new composite CT index for SSc-ILD assessment correlates with both lung function and immune-inflammatory parameters and could be sufficiently sensitive for capturing early lung density changes in visually ILD-free patients.

Objectives of this European Respiratory Society task force were to summarise current studies, to develop strategies for future research and to increase availability and awareness of exercise training for pulmonary hypertension (PH) patients.An evidence-based approach with clinical expertise of the task force members, based on both literature search and face-to-face meetings was conducted. The statement summarises current knowledge and open questions regarding clinical effects of exercise training in PH, training modalities, implementation strategies and pathophysiological mechanisms.In studies (784 PH patients in total, including six randomised controlled trials, three controlled trials, 10 prospective cohort studies and four meta-analyses), exercise training has been shown to improve exercise capacity, muscular function, quality of life and possibly right ventricular function and pulmonary haemodynamics. Nevertheless, further studies are needed to confirm these data, to investigate the impact on risk profiles and to identify the most advantageous training methodology and underlying pathophysiological mechanisms.As exercise training appears to be effective, cost-efficient and safe, but is scarcely reimbursed, support from healthcare institutions, commissioners of healthcare and research funding institutions is greatly needed. There is a strong need to establish specialised rehabilitation programmes for PH patients to enhance patient access to this treatment intervention., Competing Interests: Conflict of interest: E. Grünig reports grants and personal fees from Actelion and Bayer/MSD, grants from GSK, United Therapeutics and Novartis, and personal fees from SCOPE, OrPha Swiss GmbH and Zurich Heart House, outside the submitted work. Conflict of interest: C. Eichstaedt has nothing to disclose. Conflict of interest: J-A. Barberà has nothing to disclose. Conflict of interest: N. Benjamin reports personal fees for speaking from Bayer and Actelion, outside the submitted work. Conflict of interest: I. Blanco has nothing to disclose. Conflict of interest: E. Bossone has nothing to disclose. Conflict of interest: A. Cittadini has nothing to disclose. Conflict of interest: G. Coghlan has nothing to disclose. Conflict of interest: P. Corris reports grants and personal fees from Actelion and Bayer, and personal fees from MSD, outside the submitted work. Conflict of interest: M. D'Alto has nothing to disclose. Conflict of interest: A. D'Andrea has nothing to disclose. Conflict of interest: M. Delcroix has nothing to disclose. Conflict of interest: F. de Man has nothing to disclose. Conflict of interest: S. Gaine reports personal fees from Actelion, United Therapeutics, MSD and GSK, outside the submitted work. Conflict of interest: S. Ghio has nothing to disclose. Conflict of interest: S. Gibbs reports grants and personal fees from Actelion, Bayer and MSD, personal fees from Arena, Bellopheron, Acceleron, Complexa and Pfizer, and grants from GSK, Amco and United Therapeutics, during the conduct of the study. Conflict of interest: L. Gumbiene has nothing to disclose. Conflict of interest: L.S. Howard has nothing to disclose. Conflict of interest: M. Johnson reports research grants and personal fees for attendance at meeting and speaking from Actelion, Bayer, GSK and MSD, outside the submitted work. Conflict of interest: E. Jurevičienė has nothing to disclose. Conflict of interest: D.G. Kiely reports grants, personal fees and non-financial support from Actelion, Bayer and GSK, and personal fees and non-financial support from MSD, outside the submitted work. Conflict of interest: G. Kovacs reports personal fees for lecturing, travel support and advisory board work from Actelion and MSD, personal fees for lecturing and advisory board work from GSK, personal fees for lecturing, consultancy and advisory board work from Boehringer Ingelheim and Chiesi, personal fees for lecturing and travel support from Bayer, and personal fees for lecturing from Pfizer and Novartis, outside the submitted work. Conflict of interest: A. MacKenzie has nothing to disclose. Conflict of interest: A.M. Marra reports a grant for Young Researcher (Principal Investigator “Ricerca Finalizzata under 40” n. GR-2016-02364727) from the Italian Healthcare Ministry, and personal fees for lecturing from Bayer Healthcare, during the conduct of the study. Conflict of interest: N. McCaffrey has nothing to disclose. Conflict of interest: P. McCaughey has nothing to disclose. Conflict of interest: R. Naeije has nothing to disclose. Conflict of interest: H. Olschewski reports personal fees and non-financial support from Bayer, MSD, Pfizer and Novartis, grants, personal fees and non-financial support from Actelion, grants from Inventiva, and personal fees from Bellerophon, outside the submitted work; and is a part time employee of Ludwig Boltzmann Insitute for Lung Vascular Research. Conflict of interest: J. Pepke-Zaba or her institution have received educational/research grants and J. Pepke-Zaba serves on advisory boards for Actelion, Merck, Bayer and GSK. Conflict of interest: A. Reis has nothing to disclose. Conflict of interest: M. Santos has nothing to disclose. Conflict of interest: S. Saxer has nothing to disclose. Conflict of interest: R.M. Tulloh has received honoraria and speaker fees from Actelion, Pfizer, Bayer and GSK. Conflict of interest: S. Ulrich reports grants from Swiss National Science Foundation and Zurich Lung, grants and personal fees from Actelion SA and Orpha Swiss, and personal fees from MSD SA, outside the submitted work. Conflict of interest: A. Vonk Noordegraaf reports speaker fees from Actelion, and grants from MSD, Actelion and GSK, outside the submitted work. Conflict of interest: A.J. Peacock reports grants from Actelion, Bayer and GSK, and personal fees from MSD and Arena, outside the submitted work., (Copyright ©ERS 2019.)

Background: The most important determinant of long-term survival in patients with idiopathic pulmonary fibrosis is the right ventricular (RV) adaptation to the increased pulmonary vascular resistance. Our aim was to explore RV contractile reserve during stress echocardiography in early-stage IPF., Methods: Fifty early-stage patients with IPF and 50 healthy control patients underwent rest and stress echocardiography, including RV two-dimensional speckle tracking echocardiography. At peak exertion, blood gas analysis and spirometry were also assessed., Results: At rest, RV diameters were mildly increased in IPF; however, although RV conventional systolic function indexes were similar between the IPF and control groups, RV global longitudinal strain and RV lateral wall longitudinal strain (LWLS) were significantly reduced in the IPF cohort. During physical exercise, patients with IPF showed a reduced exercise tolerance with lower maximal workload (P < .01), level of oxygen saturation (P < .001), and peak heart rate (P < .01). Systolic and diastolic BP values were similar in both groups. Systolic pulmonary artery pressure (PAPs) increase (ΔPAPs) during exertion was higher in IPF vs healthy subjects (P < .0001); RV LWLS increase (ΔRV LWLS) during exercise was lower in patients with IPF vs control patients (P < .00001). By multivariable analysis, RV LWLS at rest and ΔRV LWLS were directly related to peak exertion capacity, PAPs, and blood oxygen saturation level (Spo 2 ; P < .0001). Δ RV LWLS was directly related to diffusion lung carbon monoxide (P < .0001)., Conclusions: RV myocardial dysfunction is already present at rest in early-stage IPF and worsens during exertion as detected by two-dimensional speckle-tracking echocardiography. The RV altered contractile reserve appears to be related to reduced exercise tolerability and impaired pulmonary hemodynamic., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

A fluid challenge with a rapid infusion of saline helps to discriminate between pre- and post-capillary pulmonary hypertension (PH) and allows unmasking hidden post-capillary PH. Systemic sclerosis (SSc) patients may present with biventricular systolic and diastolic dysfunction. The aim of this study was to evaluate the hemodynamic changes of the pulmonary circulation in SSc patients without PH after a fluid challenge. Twenty-five SSc patients and 25 controls underwent right heart catheterization in basal conditions and after volume loading with saline infusion of 7 mL/kg over 5-10 min. At baseline, there was no difference in hemodynamics between SSc patients and controls. Rapid volume loading resulted in a significant increase in pressures and flows in both groups. Increases in right atrial pressure (3 ± 1 vs. 2 ± 1 mmHg, P = 0.03), mean pulmonary artery pressure (5 ± 1 vs. 3 ± 1 mmHg, P < 0.001), and pulmonary artery wedge pressure (PAWP; 5 ± 2 vs. 3 ± 1 mmHg, P < 0.001) were larger in SSc patients than in controls. Conversely, cardiac index (0.4 ± 0.2 vs. 0.6 ± 0.3 L/min/m 2 , P = 0.005) increased less in SSc patients than in controls. Pulmonary vascular resistance did not differ between groups before and after volume loading. Four SSc patients and only one of the controls reached a PAWP > 18 mmHg suggesting latent left heart failure. Even if differences are small and not diagnostic for heart failure, SSc patients without PH have a larger increase in pulmonary vascular pressures and a smaller increase in cardiac output than controls after an acute volume loading, probably due to subclinical left ventricular diastolic dysfunction.

In the original publication of the article, the seventh author name "Giampaolo Tocci" has been misspelt. The correct name is given in this.

Anabolic-androgenic steroids (AAS) are used by power athletes to improve performance. However, the real effects of the chronic consumption of AAS on cardiovascular structures are subjects of intense debate. To detect by speckle tracking echocardiography (STE) underlying left atrial (LA) dysfunction in athletes abusing AAS and assess possible correlation between LA myocardial function and exercise capacity during cardiopulmonary stress test. 65 top-level competitive bodybuilders were selected (45 males), including 35 athletes misusing AAS for at least 5 years (users), 30 anabolic-free bodybuilders (non-users), compared to 40 age- and sex-matched healthy sedentary controls. Standard Doppler echocardiography, STE analysis and bicycle ergometric test were performed to assess LA myocardial function and exercise capacity. Athletes showed increased left ventricular (LV) mass index, wall thickness and stroke volume compared with controls, whereas LV ejection fraction, LV end-diastolic diameter and transmitral Doppler indexes were comparable between the three groups. Conversely, LA volume index, LV and LA strain and LV E/Em were significantly increased in AAS users. By multivariate analyses, LV E/Em (beta = - 0.30, p < 0.01), LA volume index (- 0.42, p < 0.001) and number of weeks of AAS use per year (- 0.54, p < 0.001) emerged as the only independent determinants of LA lateral wall peak STE. In addition, a close association between LA myocardial function and VO 2 peak during cardiopulmonary exercise testing was evidenced (p < 0.001), showing a powerful incremental value with respect to clinical and standard echocardiographic data. STE represents a promising technique to assess LA myocardial function in athletes abusing steroids. AAS users showed a more impaired LA deformation, associated with reduced functional capacity during physical effort.

Transvenous pacemaker (PM) catheters can be unintentionally placed in the left ventricle (LV) during the implantation procedure. An 8-year-old girl was discovered with a malpositioned pm wire, seven years after the implant. Trans-thoracic echocardiogram revealed the lead traversing the inter-atrial septum, crossing the mitral valve and embedded in the basal lateral wall of the LV. This is a report of a 14-year long follow-up after the surgical extraction of the malpositioned PM lead.

Doppler echocardiography is extensively used in clinical practice for the screening and detection of pulmonary hypertension (PH). It allows for accurate estimates of pulmonary artery pressures, but with moderate precision, which explains why it is more appropriate for population studies than for definitive diagnosis of PH in individual patients. Moreover, echocardiography allows one to distinguish different patterns of right ventricular remodelling in various forms of PH and enables clinically satisfactory differentiation between pre- and post-capillary PH. This article will review the methods for evaluating PH by echocardiography, while also providing an insight into specific strengths and weaknesses., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The Right Heart International Network is a multicenter international study aiming to prospectively collect exercise Doppler echocardiography tests of the right heart pulmonary circulation unit (RHPCU) in large cohorts of healthy subjects, elite athletes, and individuals at risk of or with overt pulmonary hypertension. It is going to provide standardization of exercise stress echocardiography of RHPCU and explore the full physiopathologic response., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The etiologic diagnosis of pulmonary hypertension (PH) may be very challenging. Right-heart catheterization (RHC) in isolation cannot classify a precapillary PH patient into group 1, 3, 4, or 5. Moreover, RHC may be not sufficient for reaching a definitive differential diagnosis of precapillary or postcapillary PH if hemodynamic data are not integrated in clinical context and combined with information gleaned from noninvasive imaging. Therefore, only the integration of risk factors, clinical evaluation, invasive and noninvasive tests allows the physician to distinguish between different forms of PH., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Cardiomyopathies (CM) are a heterogeneous group of muscle heart diseases, divided into 3 main categories (dilated, hypertrophic, and restrictive). In addition to these subgroups, athlete's heart and hypertensive cardiopathy are both the result of heart adaptation to increased loading conditions, making it possible to include them in the CM group. Right heart involvement is clear in some CM as arrhythmogenic CM, carcinoid syndrome, and endomyocardial fibrosis, whereas in others, like hypertrophic or dilated CM, it is known that the right heart has a prognostic impact but less clear is its pathogenic role., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Exercise stress testing of the pulmonary circulation for the diagnosis of latent or early-stage pulmonary hypertension (PH) is gaining acceptance. There is emerging consensus to define exercise-induced PH by a mean pulmonary artery pressure > 30 mm Hg at a cardiac output < 10 L/min and a total pulmonary vascular resistance> 3 Wood units at maximum exercise, in the absence of PH at rest. Exercise-induced PH has been reported in association with a bone morphogenetic receptor-2 gene mutation, in systemic sclerosis, in left heart conditions, in chronic lung diseases, and in chronic pulmonary thromboembolism. Exercise-induced PH is a cause of decreased exercise capacity, may precede the development of manifest PH in a proportion of patients, and is associated with a decreased life expectancy. Exercise stress testing of the pulmonary circulation has to be dynamic and rely on measurements of the components of the pulmonary vascular equation during, not after exercise. Noninvasive imaging measurements may be sufficiently accurate in experienced hands, but suffer from lack of precision, so that invasive measurements are required for individual decision-making. Exercise-induced PH is caused either by pulmonary vasoconstriction, pulmonary vascular remodeling, or by increased upstream transmission of pulmonary venous pressure. This differential diagnosis is clinical. Left heart disease as a cause of exercise-induced PH can be further ascertained by a pulmonary artery wedge pressure above or below 20 mm Hg at a cardiac output < 10 L/min or a pulmonary artery wedge pressure-flow relationship above or below 2 mm Hg/L/min during exercise., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Right heart catheterization (RHC) is the gold standard for the diagnosis and classification of pulmonary hypertension. Significant expertise is required for safely performing a full RHC and for the acquisition of reliable and reproducible information. Physicians performing an RHC should have adequate training not only in vascular access, catheter insertion, and manipulation but also in the interpretation of waveforms, potential pitfalls, and strict quality control. This article describes the essential technical aspects of RHC as applied to the pulmonary circulation, the potential pitfalls, and areas of major controversy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Involvement of the right heart-pulmonary circulation system in systemic sclerosis is a typical feature, with critical prognostic implications. Pulmonary hypertension may occur in association with interstitial lung disease or as a result of an isolated pulmonary vascular disease that may affect both the precapillary arterioles and the postcapillary venules, as well as a consequence of left heart involvement. These apparently different phenotypes often underlie a significant pathophysiologic overlap, which makes the diagnosis and management of these patients highly complex and uncertain., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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/m 2 (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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Undifferentiated connective tissue disease at risk for systemic sclerosis (UCTD-risk-SSc), otherwise referred to as very early-early SSc, is a condition characterized by Raynaud's phenomenon with serum SSc marker autoantibodies and/or typical capillaroscopic findings and unsatisfying classification criteria for the disease. The aim of the present study was to assess the prevalence of right (RV) or left ventricular (LV) systolic and/or diastolic dysfunction by standard echocardiography and tissue Doppler imaging (TDI). Thirty patients with UCTD-risk-SSc (28 female, mean age 47 ± 13 years, range 21-70) and 30 age- and sex-matched controls underwent cardiac assessment by standard echocardiography and TDI. UCTD-risk-SSc patients and controls did not show any difference at standard echocardiography. Despite results falling within the respective normal ranges, TDI pointed out a mild impairment of LV and RV diastolic (E m 15 ± 4 vs. 19 ± 5, p = 0.0004; E/E m 6.1 ± 1.7 vs. 4.8 ± 1.2, p = 0.001; E t 14 ± 3 vs. 16 ± 2, p = 0.02; E t /A t 0.9 ± 0.4 vs. 1.3 ± 0.3, p = 0.002; E/E t 3.5 ± 1.2 vs. 4.2 ± 0.9, p = 0.02) and systolic function (S m 13 ± 3 vs. 15 ± 2 cm/s, p < 0.0003; S t 14 ± 2 vs. 16 ± 3 cm/s, p < 0.0001) and increased estimated pulmonary artery wedge pressure (9 ± 2 vs. 8 ± 1, p = 0.001) in UCTD-risk-SSc patients as compared to controls. Notably, a statistically significant difference also emerged in the prevalence of TDI detected E'/A' t , (71% of UCTD-risk-SSc patients vs. 19% of controls; p < 0.0001). Our study shows that UCTD-risk-SSc patients show a previously unrecognized, mild biventricular systolic and diastolic dysfunction as compared to controls. The pathophysiologic meaning as well the predictive value of developing overt SSc await to be elucidated.

The cardiopulmonary vascular system represents a key determinant of prognosis in several cardiorespiratory diseases. Although right heart catheterization is considered the gold standard for assessing pulmonary hemodynamics, a comprehensive noninvasive evaluation including left and right ventricular reserve and function and cardiopulmonary interactions remains highly attractive. Stress echocardiography is crucial in the evaluation of many cardiac conditions, typically coronary artery disease but also heart failure and valvular heart disease. In stress echocardiographic applications beyond coronary artery disease, the assessment of the cardiopulmonary vascular system is a cornerstone. The possibility of coupling the left and right ventricles with the pulmonary circuit during stress can provide significant insight into cardiopulmonary physiology in healthy and diseased subjects, can support the diagnosis of the etiology of pulmonary hypertension and other conditions, and can offer valuable prognostic information. In this state-of-the-art document, the topic of stress echocardiography applied to the cardiopulmonary vascular system is thoroughly addressed, from pathophysiology to different stress modalities and echocardiographic parameters, from clinical applications to limitations and future directions., (Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Childhood maltreatment negatively impacts the development of maternal and peer relationships and may put adolescents at risk for depression. The present study examined gender differences in maternal relationship quality and peer social acceptance as mediators of the association between childhood maltreatment and adolescent depressive symptoms in 342 (151 female, 191 male) maltreated (n = 198) and nonmaltreated (n = 144) youth in the USA. An observer report Q-Scale measure of depressive symptoms was developed and received preliminary support. Social acceptance was a significant mediator for both genders. The significant association between maltreatment and maternal relationship quality was unique to females, and the association between maternal relationship quality and depressive symptoms was significantly stronger for females. Lower maternal relationship quality marginally significantly mediated the association between maltreatment and depressive symptoms for females only. Results have implications for the prevention and intervention of depression in adolescents with a history of childhood maltreatment., (Copyright © 2017 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

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 ± 0.8 vs. 2.8 ± 0.6, P < 0.001, improved in 29 patients), exercise capacity (395 ± 123 vs. 353 ± 101 m, P = 0.039), N-terminal probrain natriuretic peptide (528 ± 493 vs. 829 ± 620 pg/ml; P = 0.009), and haemodynamics (right atrial pressure 7 ± 4 vs. 9 ± 5 mmHg, P = 0.02; mean pulmonary artery pressure 45 ± 15 vs. 50 ± 13 mmHg, P = 0.03; cardiac index 3.0 ± 1.0 vs. 2.5 ± 0.9 l/min/m, P = 0.001; pulmonary vascular resistance 8 ± 4 vs. 11 ± 6 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.

Background: Tricuspid regurgitation velocity (TRV) is the most widely used parameter by transthoracic echocardiography (TTE) in the evaluation of patients with suspected pulmonary hypertension (PH)., Objectives: To explore the physiologic range of TRV in healthy adults and to investigate its clinical determinants., Methods: In the first part of the study, 614 healthy individuals (age 45.7± 14.7 years, 60.26% women) were prospectively assessed by TTE. In the second part, a pooled meta-analysis of 16 already published studies with TRV values in healthy subjects (n = 981) was performed. Statistical analysis included the calculation of 95% quantiles for defining reference ranges., Results: In the prospectively enrolled cohort, mean TRV was 2.01 ± 0.29 m/s (5-95% CI 1.987-2.033 m/s). It was significantly but weakly positively correlated with age, body mass index, systolic blood pressure, diastolic blood pressure, left atrial volume and negative with mitral inflow E/A ratio. No significant differences were found between males and females. The prospectively enrolled data revealed similar values to the literature-based datasets resulting in a mean TRV of 1.96 m/s (95% CI 1.91-2.02 m/s) and a 95% quantile of 2.55 m/s., Conclusions: To the best of our knowledge, this is the largest dataset to describe reference ranges of TRV and their clinical determinants in healthy adults years. The determined cut-off value of 2.55 m/s of this study has to be confirmed in specific pathologies such as patients at risk of PH., (© 2018 S. Karger AG, Basel.)