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The link between physical activity and the risk of atrial fibrillation (AF) remains controversial. We therefore sought to further assess by a meta-analysis whether increased levels of physical activity may increase the risk of AF. In October 2015, a PubMed research was conducted for studies that investigated this topic. We identified 11 relevant studies with a total of 81,787 participants. The pooled analysis did not show an increased risk of AF in subjects practicing physical activity (odds ratio (OR)=0.92, 95% C.I.=0.84-1.01, p=0.077, I(2)=90%). However, given the observed large heterogeneity among studies, a subgroup analysis was performed in order to identify possible variables influencing the risk of AF. Significantly higher risk of AF in subjects with reported physical activity was found in studies enrolling exclusively male participants (OR=7.49, 95% C.I.=3.12-19.01, p

Aims Obesity has been found to be protective in heart failure (HF), a finding leading to the concept of an obesity paradox. We hypothesized that a preserved cardiorespiratory fitness in obese HF patients may affect the relationship between survival and body mass index (BMI) and explain the obesity paradox in HF. Methods and results A total of 4623 systolic HF patients (LVEF 31.5 ± 9.5%, BMI 26.2 ± 3.6 kg/m2) were recruited and prospectively followed in 24 Italian HF centres belonging to the MECKI Score Research Group. Besides full clinical examination, patients underwent maximal cardiopulmonary exercise test at study enrolment. Median follow-up was 1113 (553–1803) days. The study population was divided according to BMI ( 30 to ≤35 kg/m2) and predicted peak oxygen consumption (peak VO2, 80%). Study endpoints were all-cause and cardiovascular deaths including urgent cardiac transplant. All-cause and cardiovascular deaths occurred in 951 (28.6%, 57.4 per person-years) and 802 cases (17.4%, 48.4 per 1000 person-years), respectively. In the high BMI groups, several prognostic parameters presented better values [LVEF, peak VO2, ventilation/carbon dioxide slope, renal function, and haemoglobin (P < 0.01)] compared with the lower BMI groups. Both BMI and peak VO2 were significant positive predictors of longer survival: both higher BMI and peak VO2 groups showed lower mortality (P < 0.001). At multivariable analysis and using a matching procedure (age, gender, LVEF, and peak VO2), the protective role of BMI disappeared. Conclusion Exercise tolerance affects the relationship between BMI and survival. Cardiorespiratory fitness mitigates the obesity paradox observed in HF patients.

Background In hypertrophic cardiomyopathy (HCM), most of the factors associated with the risk of sudden cardiac death (SCD) are also involved in the pathophysiology of exercise limitation. The present multicentre study investigated possible ability of cardiopulmonary exercise test in improving contemporary strategies for SCD risk stratification. Methods A total of 623 consecutive outpatients with HCM, from five tertiary Italian HCM centres, were recruited and prospectively followed, between September 2007 and April 2015. The study composite end point was SCD, aborted SCD and appropriate implantable cardioverter defibrillator (ICD) interventions. Results During a median follow-up of 3.7 years (25th–75th centile: 2.2–5.1 years), 25 patients reached the end point at 5 years (3 SCD, 4 aborted SCD, 18 appropriate ICD interventions). At multivariate analysis, ventilation versus carbon dioxide relation during exercise (VE/VCO 2 slope) remains independently associated to the study end point either when challenged with the 2011 American College of Cardiology Foundation/American Heart Association guidelines-derived score (C index 0.748) or with the 2014 European Society of Cardiology guidelines-derived score (C index 0.750). A VE/VCO 2 slope cut-off value of 31 showed the best accuracy in predicting the SCD end point within the entire HCM study cohort (sensitivity 64%, specificity 72%, area under the curve 0.72). Conclusions Our data suggest that the VE/VCO 2 slope might improve SCD risk stratification, particularly in those HCM categories classified at low-intermediate SCD risk according to contemporary guidelines. There is a need for further larger studies, possibly on independent cohorts, to confirm our preliminary findings.

Background: Several cardiopulmonary exercise test (CPET) parameters (peak VO2, PetCO2 and VE/VCO2) emerged as tools for the prediction of pulmonary arterial hypertension (PAH). Less is known on ventilatory power (VP) in patients with suspect PAH. Aim: To ascertain possible correlations between VP derived at CPET and hemodynamic parameters at right heart catheterization (RHC) indicative of PH. Methods: Forty-seven consecutive outpatients with suspect of PAH were assessed by CPET and RHC; VP was defined as peak SBP divided by the minute ventilation-CO2 production slope at CPET and Diastolic Pressure Gradient (DPG), Trans-pulmonary Pressure Gradient (TPG), mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) at RHC were also assessed and compared with VP. Results: VP values were inversely related to mPAP (r −0.427, p 0.003), DPG (r −0.36, p 0.019), TPG (r: −0.43, p 0.004), and PVR (r −0.52, p 0.001). Correlations remained significant even after correction at multivariate analysis for age and gender. VP values below median identified subjects with mPAP ≥ 25 mmHg with an odds ratio of 4.5 (95% confidence interval 1.05–19.36, p

Background: Previous studies and case-series showed improvement in left ventricular (LV) function and reverse remodeling after sacubitril/valsartan therapy in real-world studies. We therefore aimed to evaluate whether also right ventricular (RV) function may improve after sacubitril/valsartan therapy. Methods: Sixty consecutive patients with chronic heart failure and NYHA class II-III were followed up for 12 months after therapy with sacubitril/valsartan. Left and (RV) function was assessed at baseline and after 12 months of therapy. Results: At 12-month control, therapy with sacubitril/valsartan was associated with a significant improvement in a series of echo parameters: LVEF (p

Here we report the identification of two novel mutations in a previously asymptomatic young man who suffered an out-of-hospital sudden cardiac arrest. During following evaluation, diagnosis of early stage dilated cardiomyopathy was established, while electrocardiogram monitoring showed frequent complex ventricular arrhythmias, incomplete right bundle branch block and prolonged QT duration. No reversible causes explaining the clinical presentation were established and an automatic implantable cardioverter defibrillator was therefore implanted. Heterozygous mutations in human protein coding genes NKX2-5 and RBM20 are associated with a wide array of pathological phenotypes some of which are sudden cardiac death, unexplained syncope and either combined or isolated congenital heart diseases such as dilated cardiomyopathy.

Endocrine complications of haemochromatosis and heart failure mostly affect morbidity and mortality in polytransfused patients. This study analyzes endocrine dysfunctions and the impact of GH-IGF-1 axis alteration on cardiac performance in a population of 31 patients. A retrospective study on 31 Caucasian polytransfused outpatients, 27 adults and 4 pediatric, residing in Apulia, Italy, followed from 2005 to 2016, was conducted. Patients underwent basal and dynamic hormonal evaluation. GHRH plus arginine test was performed in 21 patients (19 adults and 2 children). Among them, 9 patients were affected by left ventricle diastolic dysfunction and/or atrial or ventricular dilatation (HD group) and 12 patients did not have cardiovascular disease (non-HD group). Twenty-nine out of 31 patients (94%) had at least one endocrinopathy. We found severe or mild GH deficit (GHD) in all HD patients versus 3 patients in the non-HD group (p=0.001). Mean IGF-1 levels were significantly lower in the HD group than in non-HD subjects (53±30 versus 122±91 μg/L, p=0.04). Our study confirms the need to perform a dynamic evaluation of the GH-IGF1 axis in polytransfused patients, especially when heart dysfunction emerges. An intervention study with GH replacement therapy in a larger randomized adult population will clarify the role of GH/IGF axis on cardiovascular outcomes in this patient population.

Dyslipidemia is one of the major cardiovascular risk factors, but beyond statin treatment-which represents the cornerstone of therapy-a relevant practical uncertainty regards the use of fibrate derivatives. In the lack of successful results from the main cardiovascular trials, guidelines recommend the use of peroxisome proliferator-activated receptor agonists in selected cases, i.e. patients with true atherogenic dyslipidemia. However, recent observations indicate that fenofibrate treatment may provide a reliable complementary support against residual cardiovascular risk. We therefore summarize current evidence on fenofibrate, seeking to provide an updated interpretation of recent studies in the field.

We report the case of an incomplete diagnosis of chronic thromboembolic pulmonary hypertension, with relevant prognostic implications, missing the presence of a primary pulmonary artery angiosarcoma. After the late neoplasm diagnosis, the patient, treated for months with riociguat, was considered inoperable and died soon after. This case highlights the need to manage patients with suspected pulmonary arterial hypertension by expert referral centers with specific and multi-professional expertise (heart and thoracic imaging) in order to avoid incomplete or delayed diagnoses.

Despite recent advances in chronic heart failure treatment, prognosis of acute heart failure patients remains poor with a heart failure rehospitalization rate or death reaching approximately 25% during the first 6 months after discharge. In addition, about half of these patients have preserved ejection fraction for which there are no evidence-based therapies. Disappointing results from heart failure clinical trials over the past 20 years emphasize the need for developing novel approaches and pathways for testing new heart failure drugs and devices. Indeed, many trials are being conducted without matching the mechanism and action of the drug with the clinical event. The implementation of these novel approaches should be coupled with the training of a new generation of heart failure physicians and scientists in the art and science of clinical trials. Currently, drug development is led by opinion leaders and experts who, despite their huge personal experience, were never trained systematically on drug development. The aim of this article is to propose a training program of 'drug development in Heart Failure'. A physician attending this course would have to be trained with a major emphasis on heart failure pathophysiology to better match mechanisms of death and rehospitalization with mechanism of action of the drug. Applicants will have to prove their qualifications and special interest in heart failure drug development before enrollment. This article should serve as a roadmap on how to apply emerging general principles in an innovative drug-development-in-heart-failure-process as well as the introduction of a new educational and mentorship program focusing on younger generations of researchers.

Pharmacological or electrical cardioversion allows immediate symptoms improvement in the setting of paroxysmal or persistent atrial fibrillation (AF), although the periprocedural risk of systemic embolism should be considered. Recently, there was a great interest on the safety and efficacy of direct oral anticoagulants (DOACs) when used for the cardioversion of non-valvular AF. We performed a random-effects meta-analysis of patients undergoing both electrical and pharmacologic cardioversion for non-valvular AF in the RE-LY, ROCKET-AF, ARISTOTLE, ENGAGE AF-TIMI 48, X-VeRT, ENSURE-AF, and EMANATE trials. We assessed Mantel–Haenszel pooled estimates of risk ratios (RRs) and 95% confidence intervals (CIs) for stroke/systemic embolism (SSE) and major bleeding (MB) at follow-up. A total of 8564 patients have been included in the analysis. When compared with patients receiving vitamin-K antagonists (VKAs), patients receiving DOACs had a lower risk of SSE (RR 0.70, 95% CI 0.33–1.546, P = 0.34), as well as of MB (RR 0.86;,95% CI 0.47–1.58, P = 0.62), although both were non-significant. Funnel plot analysis showed, however, lower RRs with more recent ad hoc studies in comparison with registrational studies, even though statistical significance was not reached. DOACs are as effective and as safe as VKAs for thromboembolic prevention in non-valvular AF in the setting of cardioversion. There are differences, although non-significant, between registrational studies and studies enrolling exclusively patients undergoing cardioversion of AF.

The coexistence of coronary artery disease and atrial fibrillation (AF) in the same individuals raises great concern about the co-treatment with different antithrombotic agents in the case of percutaneous coronary interventions (PCI). The advent of direct oral anticoagulants (DOACs) revolutionised the therapy of AF; less is known, however, about the safety and efficacy of therapy with DOACs in combination with antiplatelet agents after PCI. We performed a meta-analysis of randomized controlled studies enrolling patients with nonvalvular AF undergoing PCI. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% CIs for any bleeding (AB), cardiovascular events (CVE), major bleeding (MB), myocardial infarction (MI), and stent thrombosis (ST) at follow-up: 4849 patients have been included in the analysis. When compared with patients receiving standard triple therapy (vitamin-K antagonists plus double antiplatelet therapy [VKAs plus DAPT]), patients receiving DOACs (rivaroxaban/dabigatran plus either one or two antiplatelet agents) had a statistically significant lower risk of AB (RR, 0.66; 95% CI, 0.59–0.75, p

Background: A blunted heart rate (HR) response is associated with an impaired peak oxygen uptake (pVO(2)), a powerful outcome predictor in hypertrophic cardiomyopathy (HCM). The present multicenter study sought to determine the prognostic role for exercise-induced HR response in HCM.Methods: A total of 681 consecutive HCM outpatients on optimized treatment were recruited. The heart failure (HF) end-pointwas death due to HF, cardiac transplantation, NYHA III-IV class progression, HF worsening leading to hospitalization and severe functional deterioration leading to septal reduction. The sudden cardiac death (SCD) end-point included SCD, aborted SCD and appropriate implantable cardioverter defibrillator discharges.Results: During a median follow-up of 4.2 years (25-75th centile: 3.9-5.2), 81 patients reached the HF and 23 the SCD end-point. Covariates with independent effects on the HF end-point were left atrial diameter, left ventricular ejection fraction, maximal left ventricular outflow tract gradient and exercise cardiac power (ECP=pVO(2)*systolic blood pressure) (C-Index= 0.807) whereas the HCM Risk-SCD score and the ECP remained associated with the SCD end-point (C-Index = 0.674). When the VO2-derived variables were not pursued, peak HR (pHR) re-entered in the multivariate HF model (C-Index= 0.777) and, marginally, in the SCD model (C-index= 0.656). A pHR= 70% of the maximum predicted resulted as the best cut-off value in predicting the HF-related events.Conclusions: The cardiopulmonary exercise test is pivotal in the HCM management, however the pHR remains a meaningful alternative parameter. A pHR < 70% identified a HCM population at high risk of HF-related events, thus calling for a reappraisal of the chronotropic incompetence threshold in HCM. (c) 2018 Elsevier B.V. All rights reserved.

Despite recent advances in the therapeutic management of patients affected by pulmonary arterial hypertension (PAH), survival remains poor. Prompt identification of the disease, especially in subjects at increased risk of developing PAH, and prognostic stratification of patients are a necessary target of clinical practice but remain challenging. Cardiopulmonary exercise test (CPET) parameters, particularly peak oxygen uptake, end-tidal carbon dioxide tension and the minute ventilation/carbon dioxide production relationship, emerged as new prognostic tools for PAH patients. Moreover, CPET provides a comprehensive pathophysiological evaluation of patients' exercise limitation and dyspnoea, which are the main and early symptoms of the disease. This review focuses on the role of CPET in the management of PAH patients, reporting guideline recommendations for CPET and discussing the pathophysiology of exercise limitation and the most recent use of CPET in the diagnosis, prognosis and therapeutic targeting of PAH.

Mortality following an admission for acute decompensated heart failure (ADHF) is high and risk stratification in this context remains a challenge. The objective of the present study was to assess whether a simple echocardiographic assessment of pulmonary hypertension (PH) and/or of right ventricular (RV) dysfunction is associated with cardiovascular events in a 1-year follow-up after hospital discharge.The present prospective longitudinal study included 214 patients admitted to hospital with a cardiologist-adjudicated diagnosis of ADHF and a left ventricular ejection fraction (LVEF) at echocardiography 40%. Echocardiography was performed at admission and at discharge and included pulmonary artery systolic pressure (PASP) and RV function as defined by the tricuspid annular plane systolic displacement (TAPSE). The primary end-point was the combination of all-cause mortality and re-hospitalization for worsening heart failure at 1 year after hospital discharge. During an average follow-up period of 230 ± 130 days, 40 patients died and 41 patients underwent re-hospitalization due to ADHF. At multivariate analysis the independent predictors were LVEF, PASP at discharge and creatinine plasma levels (all p 0.001). At ROC analysis the best threshold of PASP to discriminate low-risk from high-risk patients was 40 mm Hg.In ADHF patients with reduced LVEF, PH at discharge is a pivotal prognostic feature to predict morbidity/mortality within the first year after the acute episode.

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.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.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.Initial combination therapy with ambrisentan and tadalafil offers clinical benefits and significant haemodynamic improvement in newly diagnosed PAH patients.

Background Tissue Doppler imaging (TDI) is used to improve risk stratification in patients with chronic heart failure (CHF). So far, few studies have used this method to investigate the characteristics of subjects with CHF and Cheyne–Stokes breathing (CSB). The aim of this study was therefore to evaluate whether TDI assessment may predict the presence of CSB in patients with CHF. Materials and methods A total of 41 consecutive patients with CHF enrolled in the Daunia Heart Failure Registry underwent echocardiography assessment and nocturnal polygraphy to evaluate the presence of sleep apnea and CSB. Conventional echocardiography and TDI parameters were calculated. We have also quantified by TDI a combined index (EAS index) of diastolic and systolic performance: E'/(A' × S'). Results Subjects with evidence of CSB (N = 8) were characterized by lower values of A' (5·03 ± 2·64 vs. 7·88 ± 2·64 cm/s, P < 0·01). A' and EAS index values were related to Cheyne–Stokes episode rates (r = −0·49 and 0·52, P < 0·05 and

Tissue Doppler imaging (TDI) may be useful in identifying subjects at higher risk among patients with chronic heart failure (CHF). The clinical role of newly developed TDI parameters, however, still needs to be documented.A total of 287 consecutive patients with CHF enrolled in the Daunia Heart Failure Registry underwent echocardiography assessment and were followed prospectively for a median 255 (204-316) days. Conventional echocardiography and TDI parameters were calculated. We also quantified by TDI a combined index (EAS index) of diastolic and systolic performance E'/(A'xS') and assessed its possible additional prognostic role in combination with 'traditional' parameters such as left ventricular ejection fraction (LVEF) and myocardial performance index (MPI).Subjects readmitted for worsening HF were characterized by higher levels of EAS index (median 0·14 (95% C.I. 0·12-0·21) vs. 0·11 (0·10-0·12, P 0·05)). Increased rates of rehospitalization were found in subjects with EAS indexmedian (0·115) (21% vs. 10%, P 0·05); higher EAS index values predicted the incidence of readmissions for worsening HF during follow-up, even at multivariable analysis. The assessment of EAS index in addition to LVEF and MPI showed an adjunctive prognostic value (log-rank P 0·001 and P 0·05, respectively).EAS index assessed by TDI may be helpful in predicting the risk of rehospitalizations in subjects with CHF. EAS index may represent an independent adjunctive tool for the risk stratification of patients with CHF in addition to 'traditional' tools such as LVEF or MPI.

Pulmonary arterial hypertension (PAH) is a life-threatening complication of HIV infection. The prevalence of HIV-associated PAH (HIV-PAH) seems not to be changed over time, regardless of the introduction of highly active antiretroviral therapy (HAART). In comparison with the incidence of idiopathic PAH in the general population (1-2 per million), HIV-infected patients have a 2500-fold increased risk of developing PAH. HIV-PAH treatment is similar to that for all PAH conditions and includes lifestyle changes, general treatments and specific treatments.

Background In a recent paper Singh et al. analyzed the effect of drug treatment on recurrence of takotsubo cardiomyopathy (TTC) in a comprehensive meta-analysis. The study found that recurrence rates were independent of clinic utilization of BB prescription, but inversely correlated with ACEi/ARB prescription: authors therefore conclude that ACEi/ARB rather than BB may reduce risk of recurrence. Methods We aimed to re-analyze data reported in the study, now weighted for populations' size, in a meta-regression analysis. Results After multiple meta-regression analysis, we found a significant regression between rates of prescription of ACEi and rates of recurrence of TTC; regression was not statistically significant for BBs. Conclusions On the bases of our re-analysis, we confirm that rates of recurrence of TTC are lower in populations of patients with higher rates of treatment with ACEi/ARB. That could not necessarily imply that ACEi may prevent recurrence of TTC, but barely that, for example, rates of recurrence are lower in cohorts more compliant with therapy or more prescribed with ACEi because more carefully followed. Randomized prospective studies are surely warranted.

Background: Initial combination treatment with ambrisentan and tadalafil (up-front therapy) offers clinical benefits in pulmonary arterial hypertension (PAH) and reduces the risk of clinical failure compared with monotherapy in naive patients. Aims: To assess the efficacy of 12 month up-front therapy with ambrisentan and tadalafil to improve hemodynamic changes 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 evaluation, including demographics, medical history, World Health Organization (WHO) functional class, 6-minutes walk distance (6MWD), and right heart catheterization (RHC) were collected from medical records at baseline and 12 month of follow up. Results: WHO functional class at baseline was: II in 12 patients, III in 38 and IV in 6. Over a median follow-up period of 12 months, 53 (95%) patients are still alive, 6 (11%) of whom received parenteral prostanoids. Ambrisentan-tadalafil association was a associated with significant improvements in WHO-functional class (2.2±0.8 vs 2.8±0.6, p Conclusion: This study shows that initial combination with oral medications ambrisentan and tadalafil offers clinical benefits, and significant haemodynamic improvement in newly diagnosed PAH patients.

Background Pulmonary arterial hypertension (PAH) represents one of the main clinical expression of the vascular changes in Systemic Sclerosis (SSc). Many clinical and experimental evidences suggest that lung microvascular changes play a role in the pathogenesis of idiopathic PAH (IPAH) also. Objectives The aim of this study is to investigate the presence of capillaroscopic abnormalities in patients with idiopathic PAH and to evaluate the differences in capillary naifold changes between patients with IPAH and SSc patients with and without PAH. Methods 37 subjects with SSc (of whom 17 with PAH), 21 subjects with IPAH and 20 healthy subjects were recruited. PAH was diagnosed by right heart chateterization. Periungual capillaroscopy was performed in all recruited subjects, considering the following parameters: loops length and width, capillary density, microhemorrhages, avascular areas, neoangiogenesis. To define the pattern of capillary changes in IPAH and healthy subjects a semiquantitative scoring (normal, minor abnormalities, major abnormalities) was used, whereas in SSc subjects the capillary changes were defined as early, active and late pattern. Results In all SSc subjects a capillaroscopic scleroderma pattern was found. Particularly, comparing SSc-PAH vs SSc-nonPAH we found an early pattern in 26,7% vs 50%, an active pattern in 66,6% vs 33,3% and a late pattern in a 6,6 vs 16,7% of subjects. None of IPAH subject presented a capillaroscopic scleroderma pattern, but interestingly in 36,4% of minor or major capillaroscopic changes were found. Analysing the single capillarocopic parameters, capillary density was lower in SSc subjects compared to the other groups; in SSc-PAH was lower than in SSc-nonPAH; in IPAH capillary density was lower compared to healthy control. Capillary width was higher in SSc patients compared to healthy and IPAH subjects, being higher in SSc-PAH compared to SSc-nonPAH. The number of megacapillaries, bushy capillaries and microhemorrages was significantly higher in patients with SSc-PAH compared to SSc-nonPAH patients. Interestingly, compared to healthy controls, the IPAH subjects presented a significantly lower capillary density and a significantly higher mean capillary width. Further, IPAH subjects presented a significant increase of number of microhemorrages and ectasic capillaries compared to healthy controls. Conclusions Microcirculation alterations, and particularly the reduction of capillary density and the increase od capillary width appears to be more severe in SSc subjects with PAH compared to SSc subjects without PAH. Capillaroscopic changes can be present in IPAH subjects also. These data support the hypothesis that in SSc peripheral microcirculation changes can be related to the entity of pulmonary microcirculation changes and that an altered vascular lung remodelling could play a role in IPAH also. References Cutolo M et al. The contribution ofcapillaroscopy to the differential diagnosis of connective autoimmune diseases. Best Pract Res Clin Rheumatol. 2007 Dec;21(6):1093–108. Riccieri V. Systemic sclerosis patients with and without pulmonary arterial hypertension: a nailfoldcapillaroscopy study. Rheumatology (Oxford). 2013 Aug;52(8):1525–8. Disclosure of Interest None declared

Background Right heart catheterization (RHC) is usually required to confirm the diagnosis of pulmonary artery hypertension (PAH). As an invasive test, RHC may be associated with possible complications; so, non-invasive parameters able to predict PAH at RHC would be extremely useful. Aim To ascertain possible correlations between cardiopulmonary exercise testing (CPET) and hemodynamic parameters at RHC indicative of PH. Methods Thirty-six consecutive outpatients with suspect of PAH underwent CPET and RHC; the intercept of ventilation (VEint) on the VE vs. carbon dioxide production (VE/VCO2) and VE/VCO2 slope at CPET and Diastolic Pressure Gradient (DPG), Trans-pulmonary Pressure Gradient (TPG), mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) at RHC were assessed and compared. Results VE/VCO2 slope were directly related to DPG (r 0.41, p 0.019), TPG (r 0.45, p 0.01), mean pulmonary arterial pressure (mPAP, r 0.36, p 0.031), PVR (r 0.41, p 0.029), VEint and VE/VCO2 slope inversely related to DPG (r -0.63, p

Pulmonary arterial hypertension (PAH) represents one of the main clinical expressions of the vascular changes in systemic sclerosis (SSc). Lung microvascular changes can play a role in the pathogenesis of idiopathic PAH (IPAH) also. The aim of this study is to investigate the presence of capillaroscopic abnormalities in patients with IPAH and to evaluate the differences in capillary nailfold changes between patients with IPAH and patients with SSc with and without PAH.39 SSc patients (19 with PAH - SSc-PAH and 20 without - SSc-noPAH), 21 subjects with IPAH and 20 healthy subjects were recruited. PAH was diagnosed by right heart catheterization. Nailfold videocapillaroscopy was performed (NVC) in all recruited subjects; capillary quantitative parameters (loops length and width, capillary density, neoangiogenesis) were evaluated and a semiquantitative scoring was used (normal, minor or major abnormalities for healthy controls and IPAH subjects and specific patterns - early, active and late - for SSc subjects) to define microvascular alterations.The presence of capillaroscopic abnormalities was detected in 38,1% subjects with IPAH; particularly, compared to healthy controls, capillary density was significantly lower (7,5±1,65loops/mm vs 9±1,37loops/mm p0,05) and mean capillary width was significantly higher (21±13μm vs 17±3μm p0,05). A more severe NVC pattern (active/late) was described. SSc-PAH patients compared to SSc-noPAH patients (73,2% vs 50% respectively, p0,05), with a significantly lower capillary density (5,64±1,9loops/mm vs 6,5±1,3loops/mm p0,05) and a significantly higher capillary width (55±7μm vs 35±8μm - p0,05) and mean number of neoangiogenesis (N/mm) (1±0,33 vs 0,2±0,22 respectively p0,05).These data, beyond to confirm the role of microvascular damage in SSc-related PAH, support the hypothesis of systemic microvascular involvement in IPAH also, which can be detected by NVC, although further studies are needed to establish whether the changes in the systemic microcirculation are causal or consequential to PAH.

Background: Anemia is frequent in heart failure (HF), and it is associated with higher mortality. The predictive power of established HF prognostic parameters in anemic HF patients is unknown. Methods: Clinical, laboratory, echocardiographic and cardiopulmonary-exercise-test (CPET) data were analyzed in 3913 HF patients grouped according to hemoglobin (Hb) values. 248 (6%), 857 (22%), 2160 (55%) and 648 (17%) patients had very low (b11 g/dL), low (11–12 for females, 11–13 for males), normal (12–15 for females, 13–15 for males) and high (N15) Hb, respectively. Results: Median follow-up was 1363 days (606–1883). CPETs were always performed safely. Hb was related to prognosis (Hazard ratio (HR) = 0.864). No prognostic difference was observed between normal and high Hb groups. Peak oxygen consumption (VO2), ventilatory efficiency (VE/VCO2 slope), plasma sodium concentration, ejection fraction (LVEF), kidney function and Hb were independently related to prognosis in the entire popula- tion. Considering Hb groups separately, peakVO2 (very low Hb HR = 0.549, low Hb HR = 0.613, normal Hb HR = 0.618, high Hb HR = 0.542) and LVEF (very low Hb HR = 0.49, low Hb HR = 0.692, normal Hb HR = 0.697, high Hb HR = 0.694) maintained their prognostic roles. High VE/VCO2 slope was associated with poor prognosis only in patients with low and normal Hb. Conclusions: Anemic HF patients have a worse prognosis, but CPET can be safely performed. PeakVO2 and LVEF, but not VE/VCO2 slope, maintain their prognostic power also in HF patients with Hb b 11 g/dL, suggesting CPET use and a multiparametric approach in HF patients with low Hb. However, the prognostic effect of an anemia-oriented follow-up is unknown.

Aim To compare inflammatory response accompanying acute coronary syndrome (ACS) with that following coronary plaque rupture caused by coronary angioplasty (PCI). Methods Twenty-seven consecutive subjects with either ACS or treated with PCI in the subacute phase of ACS underwent serial evaluation of circulating interleukin (IL)-2, IL-8, IL-10, interferon (IFN)-γ and tumor-necrosis-factor (TNF)-α levels. Blood samples were drawn immediately before angioplasty ( T 0 ) in the PCI group or at admission in the ACS group, 12 h ( T 1 ) and 24 h later ( T 2 ). Results Differences between cytokine levels were substantially not statistically significant when comparing PCI, non-ST-elevation-ACS, and ST-elevation-ACS groups, especially 24 h after plaque rupture ( T 2 , Type-II error 85–94%). Conclusions Inflammatory activation during the first 24 h of ACS or after PCI is comparable, regardless of myocardial damage in terms of troponin levels. Coronary plaque rupture may be presumed as being the main responsible for increased circulating cytokine levels in this early phase.

Idiopathic pulmonary fibrosis (IPF) is a chronic condition of unknown etiology with deteriorating respiratory function leading to respiratory failure. Corticosteroids, alone or in combination with immunosuppressive drugs such as azathioprine, colchicine, and cyclophosphamide, have been used with limited success. Interferon-gamma-1b showed a significant improvement in pulmonary function only in one study. Pirfenidone, cyclosporine and acetylcysteine may also be of benefit but data from studies are limited. Novel drugs, mainly antifibrotic, anticytokine and immunoregulatory, are currently being investigated in various trial phases. Endothelin receptor antagonists have been shown to have possible beneficial effects in early stages of IPF. However, most recently, the so-called triple combination therapy, anticoagulation therapy and endothelin receptor antagonists, especially ambrisentan, are either harmful or ineffective in IPF and are not recommended. We report a brief review on the present and possible future therapeutic options in IPF.

BACKGROUND Acute coronary syndrome is characterized by an acute inflammatory systemic response. We investigated whether timely reperfusion could reduce the inflammatory response in patients with ST-elevation acute myocardial infarction (STEMI). METHODS Forty-seven consecutive patients with STEMI eligible for fibrinolysis and admitted to a coronary care unit were enrolled in the study and reperfused with tenecteplase; 33 patients admitted 6 h after the onset of chest pain (late comers), who therefore underwent delayed coronary angioplasty, acted as controls. All patients underwent serial blood sampling in order to evaluate plasma concentrations of C-reactive protein (CRP), fibrinogen and erythrocyte sedimentation rate (ESR) for 4 days. Patients treated with primary (

Background Tissue Doppler imaging (TDI) may be useful in identifying subjects at higher risk among patients with chronic heart failure (CHF). The clinical role of new developed TDI parameters, however, still needs to be documented. Methods A total of 113 consecutive patients with CHF enrolled in the Daunia heart failure registry underwent echocardiography assessment and were followed prospectively for 234 ± 262 days. Conventional echocardiography and TDI parameters were calculated. We also calculated peak myocardial acceleration during isovolumic relaxation time (pIVA[r]) derived from TDI (pIVV(r)/AT). Results Subjects readmitted for worsening HF were characterized by lower levels of pIVA(r) (0.8 ± 0.3 vs. 1.3 ± 0.5 m/s2, P

Background Few works have evaluated the effect of statins on left ventricular dysfunction in patients with chronic heart failure (CHF), by using tissue Doppler imaging (TDI). We therefore aimed to investigate whether atorvastatin treatment may influence prognosis and myocardial performance evaluated by TDI in subjects with CHF. Methods Five hundred thirty-two consecutive CHF outpatients enrolled in a local registry, the Daunia Heart Failure Registry, were prospectively analysed. 195 patients with CHF and left ventricular ejection fraction (LVEF) ≤40 %, either in treatment with atorvastatin (N: 114) or without statins (N: 81), underwent TDI examination. Adverse events were evaluated during follow-up. Results The atorvastatin group showed a lower incidence of adverse events (cardiac death: 0 % vs 7 %, p

Clinical trials demonstrated that statin therapy is associated with a significant reduction in cardiovascular morbidity and mortality when used for either primary or secondary prevention of cardiovascular events. Several studies have shown that statins, having an important effect in the prevention of acute coronary syndromes, are also able to prevent heart failure (HF) in patients with coronary artery disease. This review summarizes the experimental and clinical evidence regarding the role of statins in the management of HF.

Introduction: In patients with systemic sclerosis a ratio between Forced-Vital-Capacity (FVC) and diffusing capacity of carbon-monoxide (DLCO, FCV%/DLCO%) >1.5 could be a predictor of pulmonary hypertension (PH). The aim of this study was therefore to evaluate whether this index could be used in patients with PH, regardless of etiology. Methods: 83 consecutive outpatients with suspected PH at non-invasive work-up underwent spirometry and DLCO test before right heart catheterization (RHC); FVC%/DLCO% ratio was then calculated and compared with mean pulmonary-artery-pressure (mPAP) and mortality at 5-year follow up. Results: Significant correlations between FVC%/DLCO% and PAsP and mPAP levels were found (p 3, p 25 mmHg, increased FVC%/DLCO% values predicted a worse outcome (p Conclusions: FVC%/DLCO% values are related to mPAP in subjects with suspected PH and may further stratify the risk of mortality in addition to PAP.

Several therapeutic options are available for the treatment of the acute phase of stress cardiomyopathy, pharmacological (β-blockers, diuretics, anticoagulants, antiarrhythmics, noncatecholamine inotropics [levosimendan]), and nonpharmacological (intra-aortic balloon pumping, extracorporeal membrane oxygenation), according to the wide possible clinical presentation and course of the disease. However, there is a gap in evidence, and very few data come from randomized and adequately powered studies. Some evidence supports the use of β-blockers, in particular with a short half-life, in the case of left ventricular outflow tract obstruction, and angiotensin-converting enzyme inhibitors in secondary prevention. Future perspectives include the study of genetic basis of stress cardiomyopathy, role of miRNA and neurovegetative modulation. Randomized studies, however, are surely warranted.

Background Prior meta-analysis studies showed that direct oral anticoagulants (DOAs) are as effective and safe as warfarin for the prevention of recurrences in patients with venous thrombo-embolism(VTE) and cancer. However, randomized studies also showed that low-molecular-weight-heparin (LMWH) performs better than warfarin in subjects with cancer. We therefore aimed to assess whether, even after pooling data with warfarin and LMWH, the use of DOAs remains safe and effective. Methods We performed a meta-analysis of randomized controlled trials with the aim of assessing the efficacy and safety of DOAs in patients with VTE and cancer. Data on recurrent VTE and major and clinically relevant nonmajor bleeding were analyzed. Data were pooled and compared by ORs and 95% CIs. Results Nine studies were included in the meta-analysis, seven in comparison with VKI, 2 with LMWH, accounting for a total of 1952 patients. VTE recurred in 5.4% and in 5.9% of patients with cancer treated with DOAs and conventional treatment, respectively (OR 0.79; 95% CI, 0.53–1.17; I 2 0%). Bleeding occurred in 10.8% and 11% of patients receiving DOAs and conventional treatment, respectively (OR 0.96; 95% CI, 0.71–1.30; I 2 , 44%). Higher bleeding rates were found when DOAs are compared with LMWH (OR 2.72, 95% CI, 1.05–7.01). Conclusions DOAs seem to be as effective and safe as conventional treatment for the prevention of VTE in patients with cancer in comparison with VKI. Higher bleeding rates were found when DOAs are compared with LMWH.

We report the case of an 81-year-old woman referred for dizziness andsuspectedatrial fibrillationandhospitalizedfor bronchopneumonia and fever. The woman was diabetic in treatment with insulin; she also had history of chronic obstructive pulmonary disease, gastrointestinal bleeding after treatment with warfarin, and hypothyroidism.

The cardiopulmonary exercise test (CPX) is an affordable tool for risk prediction in patients with chronic heart failure (CHF). We aimed to determine the role of CPX parameters in predicting the risk of incidence of sustained ventricular arrhythmias (SVA) in CHF.Sixty-one consecutive patients with CHF enrolled in the Daunia Heart Failure Registry underwent CPX and were followed for 327 ± 247 days. Clinical follow-up was performed every month and anticipated in case of re-hospitalisation for cardiac disease. Incidence of SVA was evaluated by direct clinical examination (ECG, ambulatory ECG).Patients with episodes of SVA (N 14) showed lower values of pVO2 and PetCO2, and higher values of VE/VCO2, VE/VCO2 slope, and VE%. After correction for age, gender, diabetes, ischaemic heart disease and left ventricular ejection fraction, peak VO2 (hazard ratio (HR) 0.68, 95 % confidence interval (CI) 0.51-0.91, p 0.05), VE% (HR 1.38, 95 % CI 1.04-1.84, p 0.05), VE/VCO2 (HR 1.38, 95 % CI 1.04-1.82, p 0.05), VE/VCO2 slope (HR 1.77, 95 % CI 1.31-2.39, p 0.01), PetCO2 (HR 0.66, 95 % CI 0.50-0.88, p 0.01) were found as predictors of SVA. At Kaplan-Meier analysis, lower event-free rates were found in subjects with peak VO2 values below median (log rank p 0.05), values of VE/VCO2 above mean (p 0.05), higher VE/VCO2 slope tertiles (p0.05), and values of PetCO2 below median (p 0.05).CPX provides prognostic independent information for risk of SVA in subjects with CHF.

We report the case of a woman who presented with ST elevation and episodes of chest pain, mimicking an acute myocardial infarction. At coronary angiography no sign of coronary stenosis was found and ECG anomalies were related to asymmetric left ventricular hypertrophy and aortic stenosis.

Recent studies have explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as coronary artery disease (CAD) and heart failure (HF). In these conditions, myocardial mitral annular systolic (S’) and early diastolic (E’) velocities have been shown to predict mortality or cardiovascular events. In heart failure non invasive assessment of LV diastolic pressure by transmitral to mitral annular early diastolic velocity ratio (E/E’) is a strong prognosticator, especially when E/E’ is > or =15. Moreover, other parameters derived by TDI, as cardiac time intervals and Myocardial Performance Index, might play a role in the prognostic stratification in CAD and HF. Recently, a three-dimensional (3-D) TDI imaging modality, triplane TDI, has become available, and this allows calculation of 3-Dvolumes and LV ejection fraction. We present a brief update of TDI.

Background: Patients with chronic heart failure (HF) are often rehospitalized; rehospitalization identifies subjects with a poorer quality of life and a worse prognosis. Estimates of the time intervals by tissue Doppler imaging (TDI) in patients with chronic HF has not been fully investigated, despite recent studies having explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as HF. We, therefore, aimed to assess the prognostic value of time intervals evaluated by TDI in patients with chronic HF. Methods: A total of 249 patients with chronic HF enrolled in the Daunia Heart Failure Registry underwent echocardiography assessment and were followed prospectively for a mean 284 ± 210 days. Conventional echocardiography and TDI parameters were calculated; time intervals were calculated by TDI: ST (systolic time), ET (ejection time), FT (filling time), and ICT (isovolumic contraction time). We also have calculated ICT/ET and tissue myocardial performance index ([ICT+IRT]/ET). Results: At univariate analysis, ET (RR: 0.80, 95% confidence interval [CI] 0.71–0.90, P < 0.001), ST (RR: 0.88, 95% CI 0.78–0.99, P < 0.05), FT (RR: 0.88, 95% CI 0.78–0.99, P < 0.05), ICT/ET (RR: 1.21, 95% CI 1.07–1.37, P < 0.01) were related to the occurrence of rehospitalization during follow-up. At multivariate Cox regression analysis, correlations remained significant for ET and ST (P < 0.05 and P < 0.01, respectively). Conclusions: Time intervals assessed by TDI may be helpful in predicting the risk of rehospitalization in subjects with chronic HF.