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Idiopathic pulmonary arterial hypertension is a rare condition, frequently complicated by pulmonary arteries' aneurysm. Aggressive medical therapy is often unsatisfactory and lung transplantation remains the only option. We report a unique case of severe idiopathic pulmonary arterial hypertension complicated by a giant pulmonary aneurism, massive pulmonary valve regurgitation, and right ventricle dysfunction. The patient was, as our first choice, listed for heart-lung transplantation and remained in emergency list for more than 7 months. Unfortunately, due to further clinical deterioration and the unavailability of a heart-lung bloc, plan B was mandatory. The patient underwent a combined procedure including: double lung transplant, pulmonary artery plasty, and sutureless pulmonary valve prosthesis with open deployment (first-in-man use in such scenario). Postoperative outcome was uneventful. Our thought is that double lung transplantation and conventional combined pulmonary artery/valve surgery should be considered as the first option avoiding excessive waiting times and potential further clinical deterioration.

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

Background and aims It is unknown whether the prognostic role of diabetes (T2DM) in outpatients with chronic heart failure (CHF) is independent of the most important echocardiographic markers of poor prognosis. The aims of this analysis were to evaluate whether T2DM modifies the risk of mortality in CHF patients stratified by etiology of disease or by right-ventricular to pulmonary arterial coupling at echocardiography and to evaluate how T2DM interacts with the prognostic role of cardiac plasma biomarkers. Methods and results This is a retrospective analysis of 1627 CHF outpatients who underwent a complete echocardiographic examination. During a median follow-up period of 63 months 255 patients died. Poor right-ventricular to pulmonary arterial coupling and reduced left ventricular ejection fraction were independent predictors of outcome, whereas ischemic etiology and T2DM were not. T2DM interacted with etiology increasing the risk of mortality by 32% among patients with ischemic disease (p = 0.003). Elevated hsTNI plasma levels were associated with poor survival in T2DM but not in non-diabetic patients. Conclusion T2DM signals a worse outcome in ischemic CHF patients regardless of the echocardiographic phenotype. High plasma levels of hsTNI are stronger predictors of mortality in CHF patients with T2DM than in patients without diabetes.

The correlation between myocardial injury and clinical outcome in COVID-19 patients is gaining attention in the literature. The aim of the present study was to evaluate the role of cardiac involvement and of respiratory failure in a cohort of COVID-19 patients hospitalized in an academic hospital in Lombardy, one of the most affected Italian (and worldwide) regions by the epidemic. The study included 405 consecutive patients with confirmed COVID-19 admitted to a medical ward from February 25th to March 31st, 2020. Follow-up of surviving patients ended either at hospital discharge or by July 30th, 2020. Myocardial injury was defined on the basis of the presence of blood levels of hs-TnI above the 99th percentile upper reference limit. Respiratory function was assessed as PaO2/FiO2 (P/F) ratio. The primary end-point was death for any cause. During hospitalization, 124 patients died. Death rate increased from 7.9% in patients with normal hs-TnI plasma levels and no cardiac comorbidity to 61.5% in patients with elevated hs-TnI and cardiac involvement (p

Background There is little evidence on the long-term effects of calcineurin inhibitor (CNI) withdrawal and substitution with everolimus and mycophenolate mofetil in maintenance therapy of patients who have received heart transplants and have concurrent CNI nephrotoxicity. Aims of this study were to evaluate the progression of renal dysfunction after discontinuation of CNIs and to monitor for major adverse events after therapy change. Methods Data from 41 patients who underwent heart transplant and have different degrees of renal dysfunction (estimated glomerular filtration rate [eGFR] Results In 52% of patients, there was a clear improvement in renal function (10.5 mL/min/1.73 m2 of extra eGFR on average). The former were characterized by less advanced age and a short time from the heart transplant. The echocardiographic parameters showed a significant reduction in septum thickness (11.58 ± 2 mm vs 10.29 ± 2 mm; P = .0001) and in left ventricle posterior wall thickness (10.74 ± 1 mm vs 9.74 ± 1 mm; P = .0004). The incidence of late acute rejection and cardiac allograft vasculopathy was similar in our population compared to literature data. Conclusions A therapeutic switch from CNIs to everolimus and mycophenolate mofetil can improve renal function in patients with CNI nephrotoxicity, especially in those with a shorter time period from transplantation, without exposing them to a higher incidence of late acute rejection and cardiac allograft vasculopathy.

Background: The aim of this study was to evaluate the prevalence of iron depletion in a prevalent population of patients with pulmonary arterial hypertension (PAH) and to gain preliminary insights on the possibility of its treatment with oral drugs.Methods: Iron status was determined in 31 consecutive prevalent idiopathic patients with PAH. Iron depletion was defined as serum iron

Background Mutations in the LMNA gene are associated with a high arrhythmic risk. The history of the disease in patients undergoing ICD implantation is poorly characterized. Purpose To evaluate the phenotype of patients with cardiolaminopathy at the time of first ICD implantation, the incidence, characteristics and timing of ventricular arrhythmias (VAs) during follow up and the predictive value of the European score (that assigns a point each to non-sustained VT (NSVT), left ventricular ejection fraction (LVEF) Methods Patients were identified retrospectively. Clinical and device data were collected at baseline and during follow-up. Results We identified 26 patients (54% male, 42±8 years, 31% with familial history of sudden cardiac death, 31% with non-missense mutation) undergoing ICD implantation, 96% in primary prevention, 47% with single chamber ICD, 38% with dual chamber ICD. At the time of implantation, 30% had skeletal muscle involvement, 15% history of syncope, 4% of cardiac arrest, 62% previous NSVT. Also, 38% had a history of supraventricular arrhythmias and 61% had AV conduction disturbances. LVEF was 41±11%, 35% were in NYHA class ≥2, the mean European and Wahbi scores were 2.1±0.8 and 18.2±8.9, respectively. During 8.3±5 years, 15% were transplanted, 8% died due to HF, 4% underwent LVAD implantation, despite 31% having received an upgrade to CRT-D. Appropriate device interventions occurred in 46% of patients with a median time to first event of 29 months (IQR 13–93), for a total of 137 ATP, 51% of which effective (median 3ATP/patient, IQR 1–8) and of 26 shocks, 96% of which effective (median 2 shocks/patient, IQR 1–3); 12% had an arrhythmic storm. The first treated arrhythmia was a polymorphic VT/VF in 17%, a monomorphic VT in the others (medium cycle length 293±37 msec). Survival free from appropriate ICD interventions at 1 and at 5 years was 75% and 19% respectively in case of a European score ≥3 vs 94% and 82% in case of a score Conclusions Patients with cardiolaminopathy are at a high risk of both arrhythmic and heart failure progression over the first decade after implantation of the first ICD. A European score ≥3 identifies patients with 5-year shock/ATP free survival of less than 20% but does not predict death/transplantation. The first arrhythmic event in these patients is more frequently a rapid monomorphic VT with modest ATP efficacy. Funding Acknowledgement Type of funding sources: None.

AIM To correlate 3-D Echo and CMR RV parameters and to verify whether they are similarly related to the clinical conditions of patients with pulmonary arterial hypertension (PAH), a disease in which the RV plays a crucial prognostic role. METHODS We enrolled 34 consecutive PAH patients followed by our PAH clinics. All patients underwent a 3-D Echo and CMR assessment of RV volumes and functions in the same day. The presence or absence of correlation between major findings was investigated; functional RV parameters were also analyzed in relation to 6-min walking test (6MWT) results and BNP/Nt-proBNP plasma levels. Twenty-four subjects served as controls. RESULTS Good agreement was found between 3-D Echo and CMR measures of RV volumes [RV-end-diastolic volume (r = 0.72, P

Background To evaluate if the positive effects recorded on glycaemic control with continuous subcutaneous insulin infusion (CSII) were maintained on the long-term compared with multiple daily injection (MDI). The secondary objective was to evaluate if there is a reduction of type and number of cardiovascular events (CV). Methods This retrospective, observational study evaluated glycaemic control and the number of CV in 104 patients with type 1 or 2 diabetes previously treated with MDI and initiating CSII therapy with tubed insulin pumps compared with 109 patients previously treated with MDI continuing MDI. Results After 8 years, the glycaemic control including glycated haemoglobin (HbA1c ), fasting plasma glucose (FPG), and prandial plasma glucose (PPG) improved with both CSII and MDI compared with baseline; however, HbA1c , FPG, and PPG recorded with CSII were lower than data recorded with MDI. During the 8 years, there were fewer CV events with CSII, compared with MDI, and in particular, there were fewer cases of atrial fibrillation, premature ventricular contractions, acute coronary infarction, angina pectoris, heart failure, and peripheral vascular ischemia. We did not record any reduction of ischemic stroke events. Conclusion Our preliminary data suggest that CSII treatment seems to reduce the rates of CV compared with MDI therapy. Moreover, CSII also improved glycaemic control, without increasing the number of hypoglycaemia. However, given the observational design of this trial, our data should be validated in a randomized clinical trial; if they will be confirmed, CSII could be chosen for fully informed and motivated patients at higher risk of developing CV.

Funding Acknowledgements Type of funding sources: None. Background and purpose Permanent pacemaker implantation (PPMi) is needed in about 5% of patients following heart transplant (HTx) primarily due to sinus node dysfunction (SND), which commonly occurs in an early phase, or to atrio-ventricular block (ABV), which is common later on. Currently, data on rate of ventricular pacing (VP) is lacking and little is known on long-term outcomes after PPMi. Methods This was a retrospective, monocentric study. Among 1123 patients treated with HTx, all with biatrial technique, from november 1985 to march 2019 at our institution, 61 (5.4%) patients needed PPMi. PM parameters, clinical and echocardiographic data were collected at 1 month and at 1-3-5-10 years follow-up. The primary aim was to analyse the percentage of right ventricular pacing in the overall population and in subgroups stratified by the timing of PPMi and by pacing indication. Secondary endpoints were to analyze long-term outcomes according to the percentage of ventricular pacing and to the type of implanted PM (single vs. dual chamber). Results Among patients treated with PPMi (68.9% single-chamber), 62.2% were implanted for SND and 36% for AVB. Early PPMi (< 3 months after HTx), occurred in 34.4% of patients, mainly due to SND, while late PPMi (> 3 months after HTx) occurred in 65,6% with an equal distribution between SND and AVB. Median follow-up time from HTx was 140 months and 82 months from PPMi. Overall mean rate of VP was 21%. Rate of VP was higher in patients implanted early rather than late after HTx, both at 1 month (91% vs 2%, P = 0,002) and at 1 year after the procedure (43 vs 1, P = 0,037). Patients with AVB had a greater rate of VP compared to those implanted for SND, irrespective of timing of implantation and these findings were still present at 3 and 5 years follow-up (62 vs 1%, P = 0,011 at 3 years and 80 vs 6%, P = 0,002 at 5 years). VP declined progressively after PPM implantation. No differences were observed in terms of 10-years mortality between early vs late PPMi, dual vs single-chamber and mean VP > 21% vs ≤ 21%. Conclusions Patients treated with PPMi after HTx show on average low percentage of VP over long-term follow-up. AV block indication and early implantation are associated with a higher percentage of VP. The rate of VP, the timing of PPMi and the use of single vs dual chamber PM do not affect overall prognosis or left ventricular systolic function. Our data may justify implantation of a single-chamber PPM, which bears less complications and procedural time, in the majority of HTx patients needing PPMi.

Right ventricular function has long been neglected by heart failure specialists. We have now learnt that it is strongly associated with morbidity and mortality in all patients with heart failure, regardless of the degree of left ventricular dysfunction. Importantly, right ventricular function is tightly linked with pulmonary hypertension, and only a thorough understanding of how the right ventricle couples with the pulmonary circulation can provide an improved knowledge of the pathophysiology and possibly a more efficient treatment and a better prognosis in patients with heart failure.

Aim To evaluate canrenone effects compared to other therapies on cardiovascular mortality in patients with chronic heart failure (CHF) and preserved systolic function after 10 years of evaluation. Methods We enrolled 532 patients with CHF and preserved systolic function. Patients were followed with a mean follow-up of 10 years: 166 patients were in therapy with canrenone, while 336 patients were in conventional therapy. We re-evaluated these data after 10 years, together with the rate of death and survival. Results Systolic and diastolic blood pressure were lower with canrenone compared to the group not treated with canrenone, both in supine and orthostatism. In the group treated with canrenone we recorded a lower value of fasting plasma glucose and glycated hemoglobin. Uric acid was lower in the group treated with canrenone, no differences were observed regarding creatinine, sodium, potassium, brain natriuretic peptide (BNP), pro-BNP or plasma renin activity (PRA), while aldosterone levels were reduced in canrenone group compared to control. After 10 years, left ventricular mass was lower in canrenone group. We recorded a more pronounced progression of NYHA class in controls compared to patients treated with canrenone, with also a higher number of deaths. A higher number of deaths was recorded in control group in the 68–83 years range compared to canrenone. A higher incidence of death was reported among patients without hypercholesterolemia in control group; this was not significant in patients treated with canrenone. A longer survival was observed in patients treated with canrenone. Conclusion Administered to patients with CHF and preserved systolic fraction, reduced mortality and extended the life.

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.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 of70 mm Hg, pulmonary vascular resistance of5 Woods units, and pulmonary artery compliance of1.2 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).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.

BACKGROUND: Pulmonary arterial hypertension (PAH) is common in congenital heart disease (CHD). Because clinical-trial data on PAH associated with CHD (PAH-CHD) remain limited, registry data on the long-term course are essential. This analysis aimed to update information from the COMPERA-CHD registry on management strategies based on real-world data. METHODS: The prospective international pulmonary hypertension registry COMPERA has since 2007 enrolled more than 10,000 patients. COMPERA-CHD is a sub-registry for patients with PAH-CHD. RESULTS: A total of 769 patients with PAH-CHD from 62 specialized centers in 12 countries were included into COMPERA-CHD from January 2007 through September 2020. At the last follow-up in 09/2020, patients [mean age 45.3±16.8 years; 512 (66%) female] had either post-tricuspid shunts (n=359; 46.7%), pre-tricuspid shunts (n=249; 32.4%), complex CHD (n=132; 17.2%), congenital left heart or aortic valve or aortic disease (n=9; 1.3%), or miscellaneous CHD (n=20; 2.6%). The mean 6-minute walking distance was 369±121 m, and 28.2%, 56.0%, and 3.8% were in WHO functional class I/II, III or IV, respectively (12.0% unknown). Compared with the previously published COMPERA-CHD data, after 21 months of follow-up, the number of included PAH-CHD patients increased by 91 (13.4%). Within this group the number of Eisenmenger patients rose by 39 (16.3%), the number of "Non-Eisenmenger PAH" patients by 45 (26.9%). Currently, among the 674 patients from the PAH-CHD group with at least one follow-up, 450 (66.8%) received endothelin receptor antagonists (ERA), 416 (61.7%) PDE-5 inhibitors, 85 (12.6%) prostacyclin analogues, and 36 (5.3%) the sGC stimulator riociguat. While at first inclusion in the COMPERA-CHD registry, treatment was predominantly monotherapy (69.3%), this has shifted to favoring combination therapy in the current group (53%). For the first time, the nature, frequency, and treatment of significant comorbidities requiring supportive care and medication are described. CONCLUSIONS: Analyzing "real life data" from the international COMPERA-CHD registry, we present a comprehensive overview about current management modalities and treatment concepts in PAH-CHD. There was an trend towards more aggressive treatment strategies and combination therapies. In the future, particular attention must be directed to the "Non-Eisenmenger PAH" group and to patients with complex CHD, including Fontan patients. TRIAL REGISTRATION: www.clinicaltrials.gov, study identifier: Clinicaltrials.gov NCT01347216. ispartof: CARDIOVASCULAR DIAGNOSIS AND THERAPY vol:11 issue:6 pages:1255-1268 ispartof: location:China status: published

Background Few studies addressed the issue of risk stratification in patients with residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). This study tested the potential added value of parameters that have not been included in existing risk models. Methods We evaluated 546 consecutive patients with chronic thromboembolic pulmonary hypertension who underwent PEA and were followed-up for a median period of 58 months. Results Among the 242 with residual PH, 27 died and had 127 a clinical worsening event. At univariable analysis, the parameters associated with poor survival were pulmonary vascular resistance (PVR) ≥425 dyn·s·cm−5 (p ≤ 0.001), mean pulmonary artery pressure (mPAP) ≥38 mmHg (p = 0.003) and pulmonary artery compliance (CPA) ≤1.8 ml/mmHg (p = 0.014). In the bivariable models including either PVR or mPAP as first parameter, the addition of CPA was not statistically significant. The parameters associated with poor clinical worsening were CPA ≤1.8 ml/mmHg (p Conclusions Risk stratification in residual PH can be refined if CPA and PaO2 are considered in association with standard hemodynamic parameters.

The term idiopathic pulmonary arterial hypertension (IPAH) is used to categorize patients with pre-capillary pulmonary hypertension of unknown origin. There is considerable variability in the clinical presentation of these patients. Using data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension, we performed a cluster analysis of 841 patients with IPAH based on age, sex, diffusion capacity of the lung for carbon monoxide (DLCO

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, &gt, 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&acute, 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-na&iuml, ve. 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&ndash, Meier survival estimate for CHD associated PH was significantly better than that for idiopathic PAH (76% vs. 54%, p &lt, 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.

Question addressedEchocardiography is not currently considered as providing sufficient prognostic information to serve as an integral part of treatment goals in pulmonary arterial hypertension (PAH). We tested the hypothesis that incorporation of multiple parameters reflecting right heart function would improve the prognostic value of this imaging modality.Methods and main resultsWe pooled individual patient data from a total of 517 patients (mean age 52±15 years, 64.8% females) included in seven observational studies conducted at five European and United States academic centres. Patients were subdivided into three groups representing progressive degrees of right ventricular dysfunction based on a combination of echocardiographic measurements, as follows. Group 1 (low risk): normal tricuspid annular plane systolic excursion (TAPSE) and nonsignificant tricuspid regurgitation (TR) (n=129); group 2 (intermediate risk): normal TAPSE and significant TR or impaired TAPSE and nondilated inferior vena cava (IVC) (n=256); group 3 (high risk): impaired TAPSE and dilated IVC (n=132). The 5-year cumulative survival rate was 82% in group 1, 63% in group 2 and 43% in group 3. Low-risk patients had better survival rates than intermediate-risk patients (log-rank Chi-squared 12.25; pAnswer to the questionThe proposed echocardiographic approach integrating the evaluation of TAPSE, TR grade and IVC is effective in stratifying the risk for all-cause mortality in PAH patients, outperforming the prognostic parameters suggested by current guidelines.

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.\ud \ud Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.\ud \ud Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.\ud \ud Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56–0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro–brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil–assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12–60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.\ud \ud Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.\ud \ud Clinical trial registered with www.clinicaltrials.gov (NCT01560624).

International audience; Rationale: Recently, rare heterozygous mutations in GDF2 were identified in patients with pulmonary arterial hypertension (PAH). GDF2 encodes the circulating BMP (bone morphogenetic protein) type 9, which is a ligand for the BMP2 receptor.Objectives: Here we determined the functional impact of GDF2 mutations and characterized plasma BMP9 and BMP10 levels in patients with idiopathic PAH.Methods: Missense BMP9 mutant proteins were expressed in vitro and the impact on BMP9 protein processing and secretion, endothelial signaling, and functional activity was assessed. Plasma BMP9 and BMP10 levels and activity were assayed in patients with PAH with GDF2 variants and in control subjects. Levels were also measured in a larger cohort of control subjects (n = 120) and patients with idiopathic PAH (n = 260).Measurements and Main Results: We identified a novel rare variation at the GDF2 and BMP10 loci, including copy number variation. In vitro, BMP9 missense proteins demonstrated impaired cellular processing and secretion. Patients with PAH who carried these mutations exhibited reduced plasma levels of BMP9 and reduced BMP activity. Unexpectedly, plasma BMP10 levels were also markedly reduced in these individuals. Although overall BMP9 and BMP10 levels did not differ between patients with PAH and control subjects, BMP10 levels were lower in PAH females. A subset of patients with PAH had markedly reduced plasma levels of BMP9 and BMP10 in the absence of GDF2 mutations.Conclusions: Our findings demonstrate that GDF2 mutations result in BMP9 loss of function and are likely causal. These mutations lead to reduced circulating levels of both BMP9 and BMP10. These findings support therapeutic strategies to enhance BMP9 or BMP10 signaling in PAH.

Patients with end-stage heart failure (HF), pulmonary hypertension and elevated pulmonary vascular resistance (PVR) despite medical therapy are not eligible for heart transplantation (HTx). In this ‘proof of concept’ case series, we demonstrate the feasibility and efficacy of the MitraClip procedure as ‘bridge to list’ in end-stage HF patients not eligible for HTx. In fact, in the three patients reported, who were initially excluded from the HTx list because of elevated PVR, the MitraClip procedure was followed by a sustained improvement of PVR, allowing the patients’ risk to be reclassified, and they were then considered eligible for HTx.

Hereditary hemorrhagic telangiectasia (HTT) is an autosomal dominant disease, most frequently caused by a mutation in either ENG or ACVRL1 , which can be associated with pulmonary arterial hypertension (PAH). In this report, we describe a new unpublished ACVRL1 mutation segregating in three members of the same family, showing three different types of pulmonary hypertension (PH) in the absence of BMPR2 mutations. The first patient has a form of heritable PAH (HPAH) in the absence of hepatic arteriovenous malformations (AVMs); the second one has a severe form of portopulmonary hypertension (PoPAH) associated with multiple hepatic AVMs; the third one has hepatopulmonary syndrome (HPS) with numerous hepatic arteriovenous fistulas and a form of post-capillary PH due to high cardiac output. In summary, a single mutation in the ACVRL1 gene can be associated, in the same family, with an extreme phenotypic variability regarding not only the clinical presentation of HHT but also the type of PH in the absence of BMPR2 mutations. More studies are needed to evaluate if this variability can be explained by the presence of additional variants in other genes relevant for the pathogenesis of HHT.

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.

Aims The most recent European guidelines have proposed new definitions of pulmonary hypertension (PH) in left heart disease, to better approach the characteristics required to reflect the presence of pulmonary vascular disease. The purpose of this study was to assess whether different haemodynamic definitions of post-capillary PH imply a different reversibility of PH in response to acute vasodilator administration in heart failure patients with reduced ejection fraction and PH (HFrEF-PH). Methods and results Right heart catheterization and reversibility testing was performed in 156 HFrEF-PH patients. Patients were classified as combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH) vs. isolated post-capillary pulmonary hypertension (Ipc-PH) and on the basis of diastolic pulmonary gradient (DPG) ≥ 7 vs. 12 vs. ≤12 mmHg. After vasodilator administration, Cpc-PH patients showed a greater per cent improvement in pulmonary vascular resistance (PVR), DPG and TPG as compared with Ipc-PH patients (all Pint 12 mmHg groups (28.3, 26.7 and 18.9%, respectively). Conclusion Although substantial improvements in PVR, DPG and TPG were observed in Cpc-PH patients after acute vasodilator administration, this response was associated with persistent abnormalities in the PVR vs. PCa relationship. The link between baseline right heart haemodynamics and pulmonary vascular disease remains elusive.

Venous thromboembolism (VTE), including pulmonary embolism and deep venous thrombosis, is the third most common cause of cardiovascular death. The management of the acute phase of VTE has already been described in several guidelines. However, the management of the follow-up (FU) of these patients has been poorly defined. This consensus document, created by the Italian cardiologists, wants to clarify this issue using the currently available evidence in VTE. Clinical and instrumental data acquired during the acute phase of the disease are the cornerstone for planning the FU. Acquired or congenital thrombophilic disorders could be identified in apparently unprovoked VTE during the FU. In other cases, an occult cancer could be discovered after a VTE. The main targets of the post-acute management are to prevent recurrence of VTE and to identify the patients who can develop a chronic thromboembolic pulmonary hypertension. Knowledge of pathophysiology and therapeutic approaches is fundamental to decide the most appropriate long-term treatment. Moreover, prognostic stratification during the FU should be constantly updated on the basis of the new evidence acquired. Currently, the cornerstone of VTE treatment is represented by both the oral and the parenteral anticoagulation. Novel oral anticoagulants should be an interesting alternative in the long-term treatment.

Background Heart Transplantation is still the gold standard therapy for patients suffering from end-stage cardiomyopathy and has been successfully performed in our center since 1985. Over this 30 years period there has been a significant evolution in patients characteristics and in candidate selection (either as a donor and as recipient) as shown by the recent benchmark from International Society of Heart and Lung Transplantation (ISHLT). Here we analyze the evolution of patients profile in our population and we correlated such evolution to the clinical outcomes and to the overall data from ISHLT. Materials and methods Overall 1122 patients underwent heart transplantation at our center from November 19th1985 to date. To analyze the evolution patients profile and donor criteria, patient population was divided in 4 groups according era of transplantation following ISHLT model (Group A from 1985 to 1991; Group B from 1992 to 2003; Group C from 2004 to 2008 and Group D from 2009 to date). Patients characteristics at time of transplantation, donor criteria ad clinical outcomes were analyzed and compared within 4 groups. An overall comparison of our results to the data from ISHLT was also performed. Results Overall Kaplan-Meier survival curve correlates favourably with ISHLT data showing a 20 years survival approaching 40%. Patients age at transplantation changed significantly among 4 groups from a median of 49 years (95% CI 47 to 51) in Group A to 54 years (95% CI 50 to 57) in Group D (p Figure 1 Conclusions The significant changing characteristics of both recipients and donors, over 30 years of activity, had a significant impact in early (1 year) postoperative survival following heart transplantation. Although medium/long term outcomes are still satisfactory in patients surviving at least 1 year, these data clearly suggest a more accurate patients selection and the need of alternative treatment before patients conditions deteriorate while on waiting list for heart transplantation

Background and aim Hypertrophic cardiomyopathy (HCM) is a genetic based cardiomyopathy with heterogeneous phenotypic expression. Since it is one of the most common cause of sudden cardiac death (SCD) in the young different risk score have been proposed to properly identify the patients that would benefit from a primary prevention with an implantable cardioverter-defibrillator (ICD). ESC guidelines on HCM suggest to estimate the risk of SCD considering clinical and echocardiographic parameters and mention the use of cardiac magnetic resonance (CMR) only in the case of poor echo windows. The aim of the present study-level meta-analysis was to explore the prognostic value of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) for adverse fatal events. Methods We searched PubMed and EMBASE for studies that investigated the prognostic value of LGE in patients with HCM. The outcomes of interest were SCD or aborted SCD, all-cause mortality and cardiovascular (CV) mortality. Random-effects Odds Ratios (ORs) were estimated using a DerSimonian-Laird method with a person-year approach. Moreover, an univariate meta-regression was performed to assess the moderator effect of mean age, LGE % of left ventricle (LV) and gender (expressed as male percentage). Results A total of 7 studies (n=3351) were included in the analysis. Mean follow-up was 3±0.63 years. Mean age was 47.7±14.6 years and 56.9% were male. LGE was detected in 1845 (55%) patients with a mean LGE percentage of LV of 7%. The presence of LGE was associated with an increased incidence of SCD or aborted SCD (OR 3.44; 95% CI 2.02–5.86; p Prognostic value of LGE for SCD Conclusions The presence of LGE at CMR in patients with HCM exhibited a substantial prognostic value in fatal events and, in particular, in the prediction of SCD. LGE assessment is an effective tool to stratify the arrhythmic risk in HCM. Therefore, it should be considered, especially in borderline cases, to improve the identification of HCM patients who could benefit from ICD implantation.

Background: RESPITE evaluated patients with pulmonary arterial hypertension and an inadequate response to phosphodiesterase type 5 inhibitors (PDE5i) who switched to riociguat. This post hoc analysis assessed response to this switch in parameters associated with clinical improvement. Methods: RESPITE was a 24-week, uncontrolled pilot study (n = 61). Differences in functional, hemodynamic, and cardiac function parameters, REVEAL risk score (RRS), and biomarkers were compared between responders (free from clinical worsening, World Health Organization functional class I/II, and ≥30 m improvement in 6-min walking distance at Week 24) and non-responders. Results: Of 51 patients (84%) completing RESPITE, 16 (31%) met the responder endpoint. At baseline, there were significant differences between responders and non-responders in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), growth/differentiation factor 15 (GDF-15), and RRS, whereas there were no differences in hemodynamics or cardiac function. At Week 24, responders had significant improvements in pulmonary arterial compliance, pulmonary vascular resistance, and mean pulmonary arterial pressure, while non-responders showed no significant change. Cardiac efficiency and stroke volume index significantly improved irrespective of responder status. Conclusions: NT-proBNP, GDF-15, and RRS were identified as potential predictors of response in patients switching from PDE5i to riociguat. Further prospective controlled studies are needed to confirm the association of these parameters with response., SCOPUS: ar.j, info:eu-repo/semantics/published

Background The hemodynamic definitions of pulmonary hypertension (PH) in left heart disease have recently been refined to better match the characteristics required to reflect the presence of pulmonary vascular disease. Accordingly, we tested the hypothesis that abnormalities in the stiffness of pulmonary circulation would persist after heart transplantation in patients with combined post-capillary and pre-capillary PH (Cpc-PH) in contrast to those with isolated post-capillary PH (Ipc-PH). Methods We retrospectively analyzed right heart hemodynamics in a cohort of 295 consecutive patients with heart failure and advanced left ventricular systolic dysfunction (LVSD) before and 1 year after heart transplantation. Results According to their baseline hemodynamic profile, patients were classified as: 75 Cpc-PH, 111 Ipc-PH, and 98 without PH (no-PH), and 11 pre-capillary PH. One year after heart transplantation, pulmonary artery pressures, pulmonary vascular resistance and cardiac index normalized in all patients regardless of the baseline hemodynamic profile. However, pulmonary arterial compliance remained lower in Cpc-PH patients (from 1.6±1.2 at baseline to 3.7±1.4 ml/mmHg at 1 year) than in Ipc-PH (from 1.2±2.0 to 4.4±2.3 ml/mmHg) and no-PH patients (from 3.7±2.0 to 4.5±1.8 ml/mmHg); (adjusted p = 0.03 Ipc-PH vs. Cpc-PH INT

AIMS A compromised tricuspid annular plane systolic excursion (TAPSE) is associated with worse survival in patients with chronic heart failure with reduced ejection fraction (HFrEF). However, it is not known whether a reversible abnormal TAPSE at follow-up predicts survival. Our aim was to evaluate whether a reversible abnormal TAPSE is associated with a better survival in patients with chronic HFrEF. METHODS AND RESULTS A complete echocardiography was performed in 706 patients with chronic HFrEF (LVEF ≤45%) at baseline and after 6 ± 3 months. Right ventricular (RV) systolic function was evaluated using TAPSE. The study endpoint was all-cause mortality. At baseline, TAPSE was severely reduced (≤14 mm) in 89 (13%) patients, and slightly reduced (>14 but

Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease, caused by defects of the alpha-galactosidase A (GLA) gene. AFD can affect the heart, brain, kidney, eye, skin, peripheral nerves, and gastrointestinal tract. Cardiology (hypertrophic cardiomyopathy), neurology (cryptogenic stroke), and nephrology (end-stage renal failure) screening studies suggest the prevalence of GLA variants is 0.62%, with diagnosis confirmation in 0.12%. OBJECTIVES: This study sought to expand screening from these settings to include ophthalmology, dermatology, gastroenterology, internal medicine, pediatrics, and medical genetics to increase diagnostic yield and comprehensively evaluate organ involvement in AFD patients. METHODS: In a 10-year prospective multidisciplinary, multicenter study, we expanded clinical, genetic, and biochemical screening to consecutive patients enrolled from all aforementioned clinical settings. We tested the GLA gene and α-galactosidase A activity in plasma and leukocytes. Inclusion criteria comprised phenotypical traits and absence of male-to-male transmission. Screening was extended to relatives of probands harboring GLA mutations. RESULTS: Of 2,034 probands fulfilling inclusion criteria, 37 (1.8%) were carriers of GLA mutations. Cascade family screening identified 60 affected relatives; clinical data were available for 4 affected obligate carriers. Activity of α-galactosidase A in plasma and leukocytes was diagnostic in male subjects, but not in female subjects. Of the 101 family members harboring mutations, 86 were affected, 10 were young healthy carriers, and 5 refused clinical evaluation. In the 86 patients, involved organs or organ systems included the heart (69%), peripheral nerves (46%), kidney (45%), eye (37%), brain (34%), skin (32%), gastrointestinal tract (31%), and auditory system (19%). Globotriaosylceramide accumulated in organ-specific and non-organ-specific cells in atypical and classic variants, respectively. CONCLUSIONS: Screening probands with clinically suspected AFD significantly increased diagnostic yield. The heart was the organ most commonly involved, independent of the clinical setting in which the patient was first evaluated. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

In CTEPH patients who have undergone pulmonary endarterectomy, exercise capacity is better associated with changes in invasively measured pulmonary arterial compliance than with changes in magnetic resonance imaging of pulmonary artery stiffnesshttp://bit.ly/30DAWUj

Background: There is controversy about the outcome of patients with acute myocarditis (AM), and data are lacking on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management, and long-term outcome of patients with AM based on a retrospective multicenter registry from 19 Italian hospitals. Methods: A total of 684 patients with suspected AM and recent onset of symptoms (70 years of age and those >50 years of age without coronary angiography were excluded. The final study population comprised 443 patients (median age, 34 years; 19.4% female) with AM diagnosed by either endomyocardial biopsy or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance. Results: At presentation, 118 patients (26.6%) had left ventricular ejection fraction P P P =0.18). After a median time of 196 days, 200 patients had follow-up cardiac magnetic resonance, and 8 of 55 (14.5%) with complications at presentation had left ventricular ejection fraction Conclusions: In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction

Background: The relation between systolic pulmonary pressure (sPAP) and left atrium in patients with heart failure (HF) is unclear. Diastolic dysfunction, expressed as restrictive mitral filling pattern (RMP), and functional mitral regurgitation (FMR) are associated with both LA enlargement and increased sPAP. We aimed to evaluate whether atrial dilation might modulate the consequences of RMP and FMR on the pulmonary circulation of patients with HF with reduced ejection fraction (HFrEF). Methods: 1256 HFrEF patients were retrospectively recruited in four Italian centers. Left ventricular (LVD) and atrial (LAD) diameters were measure by m-mode, and EF were measured. RMP was defined as E-wave deceleration time lower than 140 ms. FMR was quantitatively measured. sPAP was evaluated based on maximal tricuspid regurgitant velocity and estimated right atrial pressure. Results: Final study population was formed by 1005 patients because of unavailability of sPAP in 252 patients. Mean EF was 33 ± 3, 35% had RMP, 67% had mild, and 26% moderate-to-severe FMR. 69% of patients had increased sPAP. A significant association was observed between sPAP and EF, RMP, FMR, and LAD (p

Background There is a growing interest in exploring the concept of right ventricular functional reserve in patients with pulmonary arterial hypertension. However, it is still unclear how it should be assessed. Aim of the study was to investigate the determinants of the changes in cardiac output and in pulmonary pressure during dobutamine stress echocardiography in pulmonary arterial hypertension. Methods Low-dose dobutamine stress echocardiography was performed in 55 patients and 28 controls. Tricuspid annular plane systolic excursion, its ratio to systolic pulmonary artery pressure, right ventricular area change, degree of tricuspid regurgitation, right ventricular end-systolic pressure-area ratio, cardiac output were assessed at rest and at peak stress. Results According to the stress induced increase in cardiac output, patients were classified into 2 groups: above/equal to the median of 2.8 L/min (high cardiac output) or below the median (low cardiac output). High cardiac output patients were characterized by a greater increase in heart rate (+45.1 ± 17.5 vs +21.3 ± 17.7 bpm), a greater improvement in tricuspid annular plane systolic excursion (+4.2 ± 3.3 vs +1.9 ± 2.6 mm, P = 0.005) and a decrease in tricuspid regurgitation (P = 0.010) as compared to low cardiac output patients. Changes in pulmonary pressure were not associated with changes in indicators of right ventricular function but only with changes in heart rate. Conclusions The increase in cardiac output during dobutamine is associated with an improvement in longitudinal right ventricular function, a decrease in tricuspid regurgitation and an increase in heart rate. Changes in pulmonary pressure only reflect the changes in heart rate.

The impact of incident sudden cardiac death (SCD) on the predictive accuracy of prognostic risk scores for patients with chronic heart failure (HF) has rarely been examined. We assessed the relationship between estimated probability of death and modes of death in this population, as well as the predictors of death and survival in prognostic outliers.The MAGGIC 3-year probability of death was estimated in 6,859 participants of the GISSI-HF trial (mean age 67±11 years, 78% men, 91% with ejection fraction40%, mean follow-up 3.5±1.3 years, observed mortality 28.4%). The incidence of SCD progressively decreased with increased probability of death, and occurred in 52.5% of patients estimated at low-risk (N = 61 with probability14%) vs. in 23.5% of the high-risk ones (N = 375 with probability56%, P.0001). On the contrary, death from worsening HF was significantly more frequent in the latter group (19.7% vs. 46.1%, P.0001). The overall predictive accuracy of the MAGGIC model improved after excluding deaths from SCD (AUC from 0.731 to 0.760, P = .0034). Among patients estimated at low-risk (N = 61 dead, 743 alive), independent predictors of death were older age, longer history of HF, higher serum uric acid and chronic obstructive pulmonary disease. The only predictor of survival in patients estimated at high-risk (N = 210 alive, 375 dead) was higher systolic blood pressure.The MAGGIC risk score demonstrated its scarce ability to capture SCD, particularly in chronic HF patients estimated at low risk of death. Newer and better prognostic tools in the evolving horizon of HF are needed.

Background: Pulmonary arterial compliance (PAC), defined as stroke volume/(systolic pulmonary arterial pressure–diastolic pulmonary arterial pressure), is a measure of pulmonary artery stiffness and is a physiological sign of ventricular afterload. Aim: This post hoc analysis assessed the effect on PAC of switching from phosphodiesterase type 5 inhibitors (PDE5is) to riociguat in patients with PAH in the RESPITE study. Methods: RESPITE was a prospective, multicenter, uncontrolled, open-label, single-arm, Phase IIIb trial. Patients with PAH (n=61) were enrolled based on prespecified criteria indicating an insufficient response to PDE5i therapy. Following PDE5i washout, riociguat was adjusted to the optimal dose (maximum 2.5 mg three times daily). Right heart catheterization was performed at baseline and after 24 weeks. Results: Mean (SD) PAC at baseline was 1.22 (0.62) mL/mmHg (n=59), and had increased by 0.22 (0.64) mL/mmHg at Week 24 (n=48). PAC increased from baseline by 0.41 (0.68) mL/mmHg in the 26 patients who achieved WHO FC I/II at Week 24; however, no change was seen in the 22 patients who remained in WHO FC III (+0.002 [0.51] mL/mmHg). Similarly, patients who were free of clinical worsening at Week 24, and achieved WHO FC I/II and a ≥30 m improvement in 6MWD (n=16), had a greater increase in PAC (+0.55 [0.81] mL/mmHg) than patients not achieving this endpoint (n=32; +0.06 [0.46] mL/mmHg). Conclusion: In RESPITE, riociguat improved PAC in patients with PAH who had transitioned from PDE5i. The increase in PAC was more pronounced in patients whose exercise and functional capacity had also improved by Week 24.

BACKGROUND The hemodynamic definitions of pulmonary hypertension (PH) in left heart disease have recently been refined to better match the characteristics required to reflect the presence of pulmonary vascular disease. Accordingly, we tested the hypothesis that abnormalities in the stiffness of pulmonary circulation would persist after heart transplantation in patients with combined post-capillary and pre-capillary PH (Cpc-PH) in contrast to those with isolated post-capillary PH (Ipc-PH). METHODS We retrospectively analyzed right heart hemodynamics in a cohort of 295 consecutive patients with heart failure and advanced left ventricular systolic dysfunction (LVSD) before and 1 year after heart transplantation. RESULTS According to their baseline hemodynamic profile, patients were classified as: 75 Cpc-PH, 111 Ipc-PH, and 98 without PH (no-PH), and 11 pre-capillary PH. One year after heart transplantation, pulmonary artery pressures, pulmonary vascular resistance and cardiac index normalized in all patients regardless of the baseline hemodynamic profile. However, pulmonary arterial compliance remained lower in Cpc-PH patients (from 1.6±1.2 at baseline to 3.7±1.4 ml/mmHg at 1 year) than in Ipc-PH (from 1.2±2.0 to 4.4±2.3 ml/mmHg) and no-PH patients (from 3.7±2.0 to 4.5±1.8 ml/mmHg); (adjusted p = 0.03 Ipc-PH vs. Cpc-PH INT

We tested the hypothesis that analysis of longitudinal right ventricular (RV) function and analysis of transverse RV function by echocardiography provide different clinical information in patients with pulmonary hypertension (PH). Indices of longitudinal and transverse RV function were obtained with different echocardiographic techniques in 30 patients with idiopathic pulmonary arterial hypertension, 28 patients with systolic left ventricular dysfunction and PH (sLVD PH), 27 patients with sLVD and normal pulmonary pressure (sLVD no PH) undergoing right heart catheterization and 20 healthy patients. Indices of RV transverse function were significantly worse in patients with PH than in patients without PH and did not statistically differ between patients with normal and those with reduced cardiac index; RV diameter shortening at mid-segment correlated best with mean pulmonary artery pressure (h = 0.63, p0.001). Indices of longitudinal function were poorly related to severity of PH, but a tricuspid annular plane systolic excursion15 mm predicted a cardiac index2.5 L/min/m(2) with 80% sensitivity and 93% specificity (area under curve = 0.85). In conclusion, in patients with PH, reduced transverse RV function is a reliable indicator of the presence of high pulmonary artery pressure, whereas reduced RV longitudinal function is associated with impairment of cardiac function.

Background— For almost 30 years, anticoagulation has been recommended for patients with idiopathic pulmonary arterial hypertension (IPAH). Supporting evidence, however, is limited, and it is unclear whether this recommendation is still justified in the modern management era and whether it should be extended to patients with other forms of pulmonary arterial hypertension (PAH). Methods and Results— We analyzed data from Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), an ongoing European pulmonary hypertension registry. Survival rates of patients with IPAH and other forms of PAH were compared by the use of anticoagulation. The sample consisted of 1283 consecutively enrolled patients with newly diagnosed PAH. Anticoagulation was used in 66% of 800 patients with IPAH and in 43% of 483 patients with other forms of PAH. In patients with IPAH, there was a significantly better 3-year survival ( P =0.006) in patients on anticoagulation compared with patients who never received anticoagulation, albeit the patients in the anticoagulation group had more severe disease at baseline. The survival difference at 3 years remained statistically significant ( P =0.017) in a matched-pair analysis of n=336 IPAH patients. The beneficial effect of anticoagulation on survival of IPAH patients was confirmed by Cox multivariable regression analysis (hazard ratio, 0.79; 95% confidence interval, 0.66–0.94). In contrast, the use of anticoagulants was not associated with a survival benefit in patients with other forms of PAH. Conclusions— The present data suggest that the use of anticoagulation is associated with a survival benefit in patients with IPAH, supporting current treatment recommendations. The evidence remains inconclusive for other forms of PAH. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01347216.

Among different subgroups of pulmonary arterial hypertension (PAH), those associated with connective tissue diseases (CTDs) have distinct hemodynamic and prognostic features; a correct etiologic diagnosis is thus mandatory. To estimate frequency and prognosis of previously undiagnosed CTDs in a suspect idiopathic (i) PAH cohort. Consecutive patients with PAH confirmed by right heart catheterization referred at the Cardiology Division of our Hospital without a previous rheumatological assessment or the occurrence of other conditions explaining PAH were checked for CTD by a clinical, laboratory, and instrumental evaluation. Survival in each group has also been analyzed. In our study 17 of 49 patients were classified as CTD-PAH, corresponding to a prevalence (95% CI) of 34.7% (21.7–49.6%). ANA positivity had 94% (71.3–99.9%) sensitivity and 78.1% (60–90.7%) specificity for a diagnosis of CTD-PAH; Raynaud phenomenon (RP) showed 83.3% (51.6–97.9%) sensitivity and 100% (90.5–100%) specificity for the diagnosis of Systemic Sclerosis (SSc)-PAH. At diagnosis, SSc patients were older and had a lower creatinine clearance compared with iPAH and other CTD-PAH. After a median follow-up of 44 (2–132) months, 18 of 49 (36.7%) patients died: 31.2% in the iPAH group, 20% in the CTD-, and 58.3% in the SSc-PAH group. Mortality was significantly higher in SSc-PAH (HR 3.32, 1.11–9.95, P

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

Group 2 pulmonary hypertension is most frequently caused by left heart disease, a heterogeneous set of disorders. These processes include left ventricular systolic dysfunction, left ventricular dysfunction with preserved ejection fraction and valvular (mitral and/or aortic) diseases. Left heart disease may cause passive backward transmission of pressure leading to elevated left atrial and pulmonary arterial pressures due to a myriad of processes. Increasingly, it has been recognized that some patients may develop pulmonary arterial pressure out of proportion from what is expected. This is believed to be due to increases in vasomotor tone and/or vascular remodeling. Over time patients may go on to develop progressive right ventricular dysfunction, a marker for poor prognosis. This review will explore the different characteristics of these conditions including the incidence, pathophysiology, clinical implications, prognosis and current state of available medical therapies.