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Background: Exercise stress echocardiography has not been recommended in the diagnostic workup of pulmonary hypertension because of insufficient certainty about feasibility and limits of normal.Methods: Doppler echocardiography pulmonary hemodynamic measurements were performed at a progressively increased workload in 56 healthy male and 57 healthy female volunteers aged 19 to 63 years. Mean pulmonary artery pressure (mPAP) was estimated from the maximal tricuspid regurgitation jet velocity. Cardiac index was calculated from the left ventricular outflow velocity-time integral. Pulmonary vascular distensibility a index, the percentage change of vessel diameter permm Hg of mPAP, was calculated from multipoint mPAP-cardiac output (CO) plots.Results: Peak exercise at 175 ±50 W was associated with an mPAP of 33±7 mm Hg and a CO of 18 ±5 L/min. The slope of mPAP-CO relationships was 1.5 ± 0.5 mm Hg/L/min, and the distensibility coefficient ( α ) was 1.3%± 1.0%/mm Hg. Maximal workload and cardiac index were higher in men than in women ( P , .05), but mPAP-cardiac index relationships were not different. However,women had a higher a (1.6%± 1.3%/mm Hg vs 1.1%± 0.6%/mm Hg, P < .05). The average mPAP-cardiac index slope was higher and a lower in subjects ≥50 years old. Upper limits of normal of mPAP at exercise were 34 mm Hg at a CO , 10 L/min, 45 mm Hg at a CO <20 L/min, and 52 mm Hg at a CO<30 L/min. These values are in keeping with previously reported invasive measurements.Conclusions: Exercise stress echocardiography of the pulmonary circulation is feasible and allows for fl ow-corrected definition of upper limits of normal. Women have a more distensible pulmonary circulation. [ABSTRACT FROM AUTHOR]

Background: Chronic mountain sickness (CMS) is characterized by a combination of excessive erythrocytosis,severe hypoxemia, and pulmonary hypertension, all of which affect exercise capacity.Methods: Thirteen patients with CMS and 15 healthy highlander and 15 newcomer lowlander control subjects were investigated at an altitude of 4,350 m (Cerro de Pasco, Peru). All of them underwent measurements of diffusing capacity of lung for nitric oxide and carbon monoxide at rest, echocardiography for estimation of mean pulmonary arterial pressure and cardiac output at rest and at exercise, and an incremental cycle ergometer cardiopulmonary exercise test.Results: The patients with CMS, the healthy highlanders, and the newcomer lowlanders reached a similar maximal oxygen uptake at 32 1, 32 2, and 33 2 mL/min/kg, respectively, mean SE( P 5 .8), with ventilatory equivalents for C O 2 vs end-tidal P CO 2 , measured at the anaerobic threshold,of 0.9 0.1, 1.2 0.1, and 1.4 0.1 mm Hg, respectively ( P , .001); arterial oxygen content of 26 1, 21 2, and 16 1 mL/dL, respectively ( P , .001); diffusing capacity for carbon monoxide corrected for alveolar volume of 155% 4%, 150% 5%, and 120% 3% predicted, respectively( P , .001), with diffusing capacity for nitric oxide and carbon monoxide ratios of 4.7 0.1 at sea level decreased to 3.6 0.1, 3.7 0.1, and 3.9 0.1, respectively ( P , .05) and a maximal exercise mean pulmonary arterial pressure at 56 4, 42 3, and 31 2 mm Hg, respectively ( P , .001).Conclusions: The aerobic exercise capacity of patients with CMS is preserved in spite of severe pulmonary hypertension and relative hypoventilation, probably by a combination of increased oxygen carrying capacity of the blood and lung diffusion, the latter being predominantly due to an increased capillary blood volume. [ABSTRACT FROM AUTHOR]

Objective. Cardiac catheterization (CC) is a life-threatening procedure in adult patients. Complicated by idiopathic arterial pulmonary hypertension (IPAH), there is a potential risk of central nervous system (CNS) damage. We measured serum levels of a well-established brain damage marker, namely S100B, collected before, during and after CC in adult patients in whom the nitric oxide (NO) test had been performed. Material and methods. In 12 adult patients who had undergone CC for IPAH diagnosis, we recorded clinical and standard monitoring procedures (laboratory variables and echocardiographic patterns) and serum concentrations of S100B before (time 0), during (time 1) and after the NO test (time 2) and at 24 h after (time 3) the procedure in samples obtained from the systemic and pulmonary circulation. Patients were subdivided into NO test responders (n = 6) and non-responders (n = 6). Neurological evaluation was performed at admission and at discharge from hospital. Results. Adult patients subjected to CC showed no overt neurological injury at discharge from hospital. No significant differences (p>0.05 for all) in S100B serum levels between groups at times 0, 1 and 3 have been shown independently from the sampling site. It was noteworthy that the concentration of protein in the responders group at time 2 was significantly decreased (p<0.05, for all) compared to the responder group and to baseline values. A significant correlation was found between arterial oxygen partial pressure and individual S100B concentration in the pulmonary and systemic bloodstream in the entire study group (R = -0.66 and R = -0.71, respectively; p<0.05, for both). Conclusions . The data suggest that S100B protein assessment, as well as the NO test, may be useful when monitoring possible CNS damage during CC in patients with IPAH, and may also be valuable in relation to brain functions, especially when performed as an emergency procedure in severely hypoxic patients. [ABSTRACT FROM AUTHOR]

Echocardiography represents an essential tool for imagers and clinical cardiologists in the management of patients with heart failure. Advanced heart failure (AdHF) is a more severe and, typically, later stage of HF that exposes patients to a high risk of adverse outcomes, with a 1-year mortality rate of around 50%. Currently, several therapies are available to improve the outcomes of these patients, reduce their mortality rate, and, possibly, delay the need for advanced therapies such as heart transplant and long-term mechanical circulatory support. When accurately performed and interpreted, echocardiography provides crucial information to properly tailor medical and device therapy of patients with AdHF and to identify those at even higher risk. In this review, we present the state of the art of echocardiography applications in the clinical management of patients with AdHF. We will discuss the role of echocardiography chronologically, beginning with the prediction of AdHF, proceeding through diagnosis, and detailing how echocardiography informs clinical decision-making, before concluding with indications for advanced therapies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Sodium-glucose cotransporter inhibitors (SGLT2-i) improve outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF). However, evidence in patients with advanced HF is lacking. We aimed to determine the effect of SGLT2-i in advanced HFrEF compared to their effect on a non-advanced population., Methods: Consecutive HFrEF outpatients who started SGLT2-i were observed for 6-months. Patients were categorized as having advanced or non-advanced HFrEF. The primary outcome was the trend of NTproBNP in the two groups. Secondary outcomes included changes in New York Heart Association (NYHA) class, glomerular filtration rate (GFR), and ejection fraction (LVEF). The association between advanced HF diagnosis and including N-terminal pro-brain natriuretic peptide (NTproBNP) reduction was tested using multivariate analysis., Results: Overall, 105 patients (45 advanced, 60 non-advanced) were included. Mean age was 56 ± 10 years, 22 % were female, and 35 % had ischemic heart disease. Median NTproBNP at baseline for advanced and non-advanced patients was 1672pg/ml (IQR 520-3320) vs. 481 pg/ml (IQR 173-917), respectively (p < 0.001). At follow-up, only non-advanced patients reduced their NTproBNP (-32 % (95 % CI -51 to -3), p < 0.001), while advanced patients had an increase in NTproBNP. LVEF and NYHA class improved only in non-advanced patients. GFR was stable in both subgroups. At multivariate analysis a diagnosis of advanced HF was independently associated with a reduced probability of NTproBNP reduction (OR 0.041 (95 % CI 0.002-0.752), p = 0.031). Only one patient discontinued the drug due to side effects., Conclusion: In advanced HFrEF, SGLT2-i do not impact on NTproBNP, LVEF or NYHA class but are well tolerated., Competing Interests: Declaration of competing interest The authors have not any conflict of interest to declare, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools., Methods: Consecutive incident PAH patients aged ≥18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography. Simple echocardiographic variables were combined in order to define a priori four phenotypes representing different degrees of RV dilatation and RV-pulmonary arterial (PA) coupling: Phenotype 1 with mildy dilated right ventricle and preserved RV-PA coupling (n = 152 patients); phenotype 2 with mildly dilated right ventricle and poor RV-PA coupling (n = 143 patients); phenotype 3 with severely dilated right ventricle and preserved RV-PA coupling (n = 201 patients); phenotype 4 with severely dilated right ventricle and poor RV-PA coupling, with or without severe tricuspid regurgitation (n = 519 patients). Risk stratification was based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) 3-strata model and Registry to Evaluate Early and Long-Term PAH disease Management (REVEAL) 2.0 score., Results: These phenotypes were present in all risk groups. Notably, regardless of the ESC/ERS risk stratum assigned to the patient, phenotype 4 was associated with a 2-fold increase of the odds of death (HR 2.1, 95% CI 1.6-2.8, p < 0.001), while phenotype 1 was associated with a 71% reduction in the odds of dying (HR 0.29, 95% CI 0.18-0.47, p < 0.001)., Conclusions: Echocardiography-derived phenotypes describing RV remodeling and dysfunction may provide prognostic information which is independent of and additional to the clinically defined risk in incident PAH patients., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxanthin. This study investigated the impact of indicaxanthin on neuronal damage and gut microbiota dysbiosis induced by a high-fat diet in mice. The mice were divided into three groups according to different diets: the negative control group was fed a standard diet; the high-fat diet group was fed a high-fat diet; and the high-fat diet + indicaxanthin group was fed a high-fat diet and received indicaxanthin orally (0.86 mg/kg per day) for 4 weeks. Brain apoptosis, redox status, inflammation, and the gut microbiota composition were compared among the different animal groups. The results demonstrated that indicaxanthin treatment reduced neuronal apoptosis by downregulating the expression of proapoptotic genes and increasing the expression of antiapoptotic genes. Indicaxanthin also markedly decreased the expression of neuroinflammatory proteins and genes and inhibited high-fat diet-induced neuronal oxidative stress by reducing reactive oxygen and nitrogen species, malondialdehyde, and nitric oxide levels. In addition, indicaxanthin treatment improved the microflora composition by increasing the abundance of healthy bacterial genera, known as producers of short-chain fatty acids (Lachnospiraceae, Alloprovetella, and Lactobacillus), and by reducing bacteria related to unhealthy profiles (Blautia, Faecalibaculum, Romboutsia and Bilophila). In conclusion, indicaxanthin has a positive effect on high-fat diet-induced neuronal damage and on the gut microbiota composition in obese mice., (Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.)

A comprehensive evaluation of risk, using multiple indices, is necessary to provide reliable prognostic information and guide therapy in pulmonary arterial hypertension (PAH). The current ESC/ERS guidelines suggest using a three-strata model for incident (newly diagnosed) patients and a four-strata model for prevalent patients with PAH. The four-strata model serves as a fundamental risk-stratification tool and relies on a minimal dataset of indicators that must be considered during follow-up. Nevertheless, there are still areas of vagueness and ambiguity when classifying and managing patients in the intermediate-risk category. For these patients, considerations should include right heart imaging, hemodynamics, as well as individual factors such as age, sex, genetic profile, disease type, comorbidities, and kidney function. The aim of this report is to present case studies, with a specific focus on patients ultimately classified as intermediate risk. We aim to emphasize the challenges and complexities encountered in the realms of diagnosis, classification, and treatment for these particular patients., Competing Interests: Declaration of competing interest MD reports participation on a monitoring board or travel fee for Janssen, MSD, Dompè, AOP and Ferrer, outside the submitted work. SG reports personal fees from MSD and Ferrer, outside the submitted work. PA received speaker, advisory board and consultancy fees from Boehringer Ingelheim, Astra Zeneca, Bayer, Novartis, Janssen, MSD, and Gossamer Bio, and speaker and advisor fees and travel support from Daiichi Sankyo., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rationale: Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting., Methods: The study enrolled 181 treatment-naive PAH patients with a 6-month (IQR 144-363 days) right heart catheterisation and risk assessment after initial oral combination therapy., Results: Group A included 96 (53.0%) patients without cardiac comorbidities; Group B included 54 (29.8%) patients with one cardiac comorbidity; Group C included 31 (17.1%) patients with two cardiac comorbidities or more. Group C patients were older with a balanced sex distribution. There was a significant difference in PVR reduction moving from the absence to one or at least two cardiac comorbidities, respectively: median -45.0%, -30.3%, -24.3%. A European Respiratory Society/European Society of Cardiology low-risk status was present at first follow-up in 50 (52.0%) patients in Group A, 19 (35.1%) in Group B and 9 (29.0%) in Group C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group A, 15 (27.7%) in Group B and 7 (22.6%) in Group C. Group A patients were 2.3 times more likely to achieve/maintain a low-risk status compared with Group B and C (OR 2.27, 95% CI 1.15-4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities., Conclusion: Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment-induced decrease in PVR., Competing Interests: Conflict of interest: R. Badagliacca reports personal fees from UT, Dompè, Ferrer, Bayer, MSD and AOP Orphan Pharmaceuticals, outside the submitted work. M. D'Alto reports personal fees from Bayer, Dompè, GSK, MSD and Ferrer, outside the submitted work. C.D. Vizza reports personal fees from GSK, UT, Dompè, Bayer and MSD, outside the submitted work. The other authors have nothing to disclose., (Copyright ©The authors 2022.)

Objective: The coronavirus disease 2019 (COVID-19) outbreak has led to significant restrictions on routine medical care. We conducted a multicentre nationwide survey of patients with pulmonary arterial hypertension (PAH) to determine the consequences of governance measures on PAH management and risk of poor outcome in patients with COVID-19., Materials and Methods: The present study, which included 25 Italian centres, considered demographic data, the number of in-person visits, 6-min walk and echocardiographic test results, brain natriuretic peptide/N-terminal pro-brain natriuretic peptide test results, World Health Organization functional class assessment, presence of elective and non-elective hospitalisation, need for treatment escalation/initiation, newly diagnosed PAH, incidence of COVID-19 and mortality rates. Data were collected, double-checked and tracked by institutional records between March 1 and May 1, 2020, to coincide with the first peak of COVID-19 and compared with the same time period in 2019., Results: Among 1922 PAH patients, the incidences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 were 1.0% and 0.46%, respectively, with the latter comparable to that in the overall Italian population (0.34%) but associated with 100% mortality. Less systematic activities were converted into more effective remote interfacing between clinicians and PAH patients, resulting in lower rates of hospitalisation (1.2% versus 1.9%) and related death (0.3% versus 0.5%) compared with 2019 (p<0.001). A high level of attention is needed to avoid the potential risk of disease progression related to less aggressive escalation of treatment and the reduction in new PAH diagnoses compared with 2019., Conclusion: A cohesive partnership between healthcare providers and regional public health officials is needed to prioritise PAH patients for remote monitoring by dedicated tools., Competing Interests: Conflict of Interest: All authors have nothing to disclose., (Copyright ©The authors 2022.)

Rationale: An initial oral combination of drugs is being recommended in pulmonary arterial hypertension (PAH), but the effects of this approach on risk reduction and pulmonary vascular resistance (PVR) are not known. Objectives: To test the hypothesis that a low-risk status would be determined by the reduction of PVR in patients with PAH treated upfront with a combination of oral drugs. Methods: The study enrolled 181 treatment-naive patients with PAH (81% idiopathic) with a follow-up right heart catheterization at 6 months (interquartile range, 144-363 d) after the initial combination of endothelin receptor antagonist + phosphodiesterase-5 inhibitor drugs and clinical evaluation and risk assessments by European guidelines and Registry to Evaluate Early and Long-Term PAH Disease Management scores. Measurements and Main Results: Initial combination therapy improved functional class and 6-minute-walk distance and decreased PVR by an average of 35% (median, 40%). One-third of the patients had a decrease in PVR <25%. This poor hemodynamic response was independently predicted by age, male sex, pulmonary artery pressure and cardiac index, and at echocardiography, a right/left ventricular surface area ratio of greater than 1 associated with low tricuspid annular plane systolic excursion of less than 18 mm. A low-risk status at 6 months was achieved or maintained in only 34.8% (Registry to Evaluate Early and Long-Term PAH Disease Management score) to 43.1% (European score) of the patients. Adding criteria of poor hemodynamic response improved prediction of a low-risk status. Conclusions: A majority of patients with PAH still insufficiently improved after 6 months of initial combinations of oral drugs is identifiable at initial evaluation by hemodynamic response criteria added to risk scores.

Background: In idiopathic pulmonary arterial hypertension (IPAH) treatment goals include improving right ventricular (RV) function, hemodynamics and symptoms to move patients to a low-risk category for adverse clinical outcomes. No data are available on the effect of upfront combination therapy on RV improvement as compared with monotherapy. The aim of this study was to evaluate echocardiographic RV morphology and function in patients affected by IPAH and treated with different strategies., Methods: Sixty-nine consecutive, treatment-naive IPAH patients treated with first-line upfront combination therapy at 10 centers were retrospectively evaluated and compared with 2 matched cohorts treated with monotherapy after short-term follow-up. Evaluation included clinical, hemodynamic and echocardiographic parameters., Results: At 155 ± 65 days after baseline evaluation, patients in the oral+prostanoid group (Group 1) had the most clinical and hemodynamic improvement compared with the double oral group (Group 2), the oral monotherapy group (Group 3) and the prostanoid monotherapy group (Group 4). The more extensive reduction of pulmonary vascular resistance in Groups 1, 2 and 4 was associated with significant improvement in all RV echocardiographic parameters compared with Group 3. Considering the number of patients who reached the target goals suggested by established guidelines, 8 of 27 (29.6%) and 7 of 42 (16.7%) patients in Groups 1 and 2, respectively, achieved low-risk status, as compared with 2 of 69 (2.8%) and 6 of 27 (22.2%) in Groups 3 and 4, respectively., Conclusions: In advanced treatment-naive IPAH patients, an upfront combination therapy strategy seems to significantly improve hemodynamics and RV morphology and function compared with oral monotherapy. The most significant results seem to be achieved with prostanoids plus oral drug, whereas the use of the double oral combination and prostanoids as monotherapy seem to produce similar results., (Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Intravenous iloprost is a first-line option for the treatment of scleroderma-related digital vasculopathy, and some studies have suggested its favourable role on disease progression. The aim of our study is to evaluate the disease progression, specifically in terms of cardiopulmonary function, in a group of consecutive patients chronically treated with intravenous iloprost. Our retrospective study enrolled 68 scleroderma patients (68 F, 54.4 ± 12.3 years) treated with iloprost for 7.1 ± 2.9 years, with a schedule of 5-6 consecutive daily infusions per month (6 h/day, 0.5-2.0 ng/kg/min). In all patients, modified Rodnan skin score (4.7 ± 5.3 vs. 3.7 ± 5.3, p < 0.0001), systolic pulmonary arterial pressure (sPAP) (30.9 ± 6.4 vs. 24.0 ± 3.2 mmHg, p < 0.0001), tricuspid annular plane systolic excursion (22.1 ± 2.4 vs. 23.8 ± 3.5 mm, p = 0.0001), pro-brain natriuretic peptide (97.2 ± 69.3 vs. 65.8 ± 31.7 pg/ml, p = 0.0005) showed statistically significant improvement from baseline. In the subgroup of patients with baseline sPAP ≥36 mmHg (n = 17), a significant sPAP reduction was observed (from 39.5 ± 3.8 to 25.1 ± 4.5 mmHg, p < 0.0001) after 7.6 ± 2.5 years of follow-up. The number of patients with digital ulcers (DUs) at follow-up was reduced from baseline (42.6 vs. 11.8%, p < 0.001), and none of the free-DU patients at baseline presented DUs at follow-up. An intensive and chronic regimen of IV iloprost administration seems to stabilize and potentially improve the long-term development of disease in SSc patients, as suggested by stabilization or significant improvement of cardiopulmonary parameters and vasculopathy., Competing Interests: Alberto Farina is an employee of Italfarmaco S.p.A., and the other authors report no conflict of interest. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive parenchymal lung disease characterized by a median survival of 3-5 years following diagnosis. The diagnosis is based on clinical, radiological and histopathological evaluation. Therefore, a multidisciplinary team is needed to reach the correct diagnosis. For a long time, supportive care and lung transplantation in selected cases, have been considered the only possible treatments for IPF. In the last decade many studies have investigated IPF pathogenesis, leading to an improved knowledge of the mechanisms underlying the disease and to the approval of two new drugs for IPF treatment (pirfenidone and nintedanib). The therapeutic approach of IPF cannot be limited to the administration of antifibrotic drugs, but it is necessary for improving the quality of life of patients and for facilitating, as far as possible, the performance of normal daily activities and relationships. IPF patients are also afflicted by disease-related complications such as gastroesophageal reflux, pulmonary hypertension, acute exacerbations and an increased risk of developing lung cancer. The clinician who treats IPF patients, should also treat these possible complications to slow disease progression, thus maintaining the possibility of a pulmonary transplantation.

Pulmonary arterial hypertension (PAH) is a complex disease with a poor prognosis. In recent years, great advances have occurred in our understanding of the pathophysiologic mechanisms underlying the characteristic vascular proliferative lesions, thus allowing the development of several specific drugs. Nevertheless, PAH still presents a high mortality; therefore, early diagnosis and prognostic stratification seem to be of paramount importance in order to choose the best therapeutic strategies. Circulating biomarkers have been proposed as potentially noninvasive and objective parameters for diagnosis, prognosis, and response to therapy. The molecules evaluated to date, including markers of dysfunction and neurohormonal activation, myocardial injury, inflammation and oxidative stress, vascular damage and remodelling, end-organ failure, and gene expression, reflect the complex pathophysiology of PAH. However, not one of these shows all the characteristics of the ideal biomarker; thus, a multiparameter approach is probably desirable. Moreover, future direction could be research of structural proteins specifically expressed in the pathologic tissue that act as disease-specific markers. This report presents an extensive review of circulating biomarkers in PAH and some consideration about potential future direction in this area., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Over the last two decades the development and analysis of a number of registries have enhanced the knowledge of the epidemiology, presentation, natural history, and pathophysiology of pulmonary arterial hypertension (PAH). The understanding of the effectiveness of available treatments has also been greatly improved. However, most of the registries present some methodological issues, such as differences in the classification of patients and presence of confounding factors or missing values, that can impact on the generalizability of the results., Objective: The aim of this study is to present the Italian Pulmonary Hypertension Network (iPHnet) Project, a database used to collect health records on patients with PAH that can also be used for research purposes to retrieve ad hoc information., Results: iPHnet presents various characteristics such as facilitated access, data sharing and interoperability, update, patient's anonymity and data integrity. The system also enables the creation of patients' electronic health records (EHRs), the exportation and personalization of data and the possibility to design clinical report forms (CRFs) and collect information usable in clinical trials. In addition, it is possible to analyze the information present in the registry, creating graphs or other immediately available charts to evaluate the trends of a specific data and perform therapeutic or clinic adjustments. Treatment of data in the iPHnet database complies with FDA requirements, backup and disaster recovery policies and patients' privacy., Conclusions: iPHnet is a flexible tool that integrates the capabilities of an EHR for PAH patients with those of a PAH registry. The ability to retrieve relevant information - although with all the limitations of any registry-based analysis - and to create appropriate CRFs will facilitate the development of prospective and retrospective trials aimed at providing new 'real-life' evidence on PAH.

Acute exposure to high altitude may induce changes in carbon monoxide (CO) membrane conductance (DmCO) and capillary lung volume (Vc). Measurements were performed in 25 lowlanders at Brussels (D0), at 4,300 m after a 2- or 3-day exposure (D2,3) without preceding climbing, and 5 days later (D7,8), before and after an exercise test, under a trial with two arterial pulmonary vasodilators or a placebo. The nitric oxide (NO)/CO transfer method was used, assuming both infinite and finite values to the NO blood conductance (θNO). Doppler echocardiography provided hemodynamic data. Compared with sea level, lung diffusing capacity for CO increased by 24% at D2,3 and is returned to control at D7,8. The acute increase in lung diffusing capacity for CO resulted from increases in DmCO and Vc with finite and infinite θNO assumptions. The alveolar volume increased by 16% at D2,3 and normalized at D7,8. The mean increase in systolic arterial pulmonary pressure at rest at D2,3 was minimal. In conclusion, the acute increase in Vc may be related to the increase in alveolar volume and to the increase in capillary pressure. Compared with the infinite θNO value, the use of a finite θNO value led to about a twofold increase in DmCO value and to a persistent increase in DmCO at D7,8 compared with D0. After exercise, DmCO decreased slightly less in subjects treated by the vasodilators, suggesting a beneficial effect on interstitial edema.

Aims: About 30 to 50% of patients undergoing cardiac resynchronization therapy (CRT) may not show clinical or echocardiographic improvement, despite fulfilling guidelines recommendations for CRT. For this reason, we need a more accurate method to assess CRT eligibility. The aims of this study were to verify, on a 12-month follow-up, the usefulness of QT corrected dispersion (QTcD) in a patient's selection for CRT., Methods: We stratified 53 patients who underwent CRT, into two groups based on the estimation of QTcD, that is, QTcD > 60 ms and QTcD ≤ 60 ms. In all patients were performed New York Heart Association (NYHA) class determination, six-minute walking test, QtcD, and QRS measurements, and complete echocardiographic assessment at 1, 3, 6, and 12 months after implantation., Results: At baseline, there were no significant differences in clinical, echocardiographic, and electrocardiographic parameters duration between two groups. At 12-month follow-up between the two groups, there were significant differences in NYHA (1.2 ± 0.4 vs 2 ± 0.6; P < 0.01), six-minute walking distance (422 ± 68 vs 364 ± 68; P < 0.01), left ventricular (LV) ejection fraction (34 ± 7% vs 28 ± 6%; P < 0.01), LV end-diastolic diameter (57 ± 7 vs 63 ± 8; P < 0.01), and LV intraventricular dyssynchrony (24 ± 14 vs 39 ± 23; P < 0.01)., Conclusion: This study suggests that QTc dispersion in addition to QRS duration could improve the sensitivity of electrocardiogram in a patient's selection for CRT., (©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.)

Background: Multislice computed tomography (MSCT) has generally been accepted as the most accurate modality fulfilling this purpose with good reproducibility. A major drawback of MSCT consists in the use of contrast dye, which may be unsafe in transcatheter aortic valve implantation (TAVI) patients who frequently are affected by renal failure. We sought to appraise the accuracy of intracardiac echocardiography (ICE) in measurements of structures in the aortic root in patients undergoing TAVI., Methods: Aortic annulus and sinus of Valsalva diameters were measured using ICE, performed during standard invasive preprocedural assessment in 30 consecutive patients with severe aortic stenosis referred for TAVI. Multislice computed tomography was performed in all patients afterward, and aortic root measurements were made by an independent radiologist., Results: Effective ICE measurements were obtained in all patients, easily and without any complication. Mean aortic annulus diameters were 21.9 ± 1.8 mm using ICE, 22.0 ± 1.9 mm using MSCT (3-chamber [3-C] view) and 22.8 ± 1.8 mm using the mean of long-axis and short-axis (L-ax/S-ax) view MSCT (P = .192, ICE vs 3-C MSCT; P < .001, ICE vs L-ax/S-ax MSCT, respectively). Correlation between ICE and both MSCT measurements was good (r(2) = 0.83, P < .001; r(2) = 0.80, P < .001, respectively). Mean sinus of Valsalva diameters were 32.3 ± 3.3 mm using ICE and 32.5 ± 3.1 mm using 3-C MSCT view (P = .141). Even in this case, correlation between ICE and both MSCT measurements was excellent (r(2) = 0.96, P < .001)., Conclusions: In patients referred for TAVI, measurements of the aortic annulus and the sinus of Valsalva using ICE compare favorably with those made at MSCT. This approach might be a useful and reproducible strategy in patients with severe renal impairment to avoid the administration of contrast dye during MSCT., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Percutaneous valve repair with MitraClip System is an emerging alternative for high surgical risk patients with severe mitral regurgitation (MR). QoL is a critical measure of effectiveness of this procedure. We sought to evaluate quality of life (QoL) and NYHA class following this novel procedure., Methods: The study included 39 consecutive patients who underwent mitral valve repair with the MitraClip System, both for functional (64%) and degenerative (36%) MR. All patients received the SF-12v2 questionnaire pre-procedure and at 6 months follow-up to assess the physical and mental health., Results: Acute procedural success was obtained in 100%. Three patients experienced minor procedural complications. At follow-up 86% of patients had MR ≤ 1+ and 14% experienced a moderate MR. Mean pre-procedural SF-12v2 scores of our patients showed a severe impairment of perceived QoL, both for physical and mental scores; after six months a striking improvement in physical (PCS 35.44 vs 44.67, p<0.0001) and mental (MCS 38.07 vs 46.94, p<0.0001) aspect of QoL was observed. Furthermore, physical and mental status upgrading was higher in patients with functional MR. NYHA functional class improved in all patients., Conclusion: Our results show an early marked improvement in functional status and physical and mental health in patients underwent percutaneous mitral valve repair with the MitraClip System., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aims: Prosthesis dislocation during transcatheter aortic valve implantation (TAVI) is a rare but important complication. There is scarce data on the performance of prosthesis in the aorta that have become dislocated from their intended anatomical position in the aortic annulus. We investigated the causes of dislocation during TAVI of the self-expanding CoreValve ReValving™ System (CRS) (Medtronic Inc., Minneapolis, MN, USA). This included midterm follow-up of patients experiencing this acute complication., Methods and Results: Among 176 consecutive patients undergoing TAVI with the CRS prosthesis, seven (3.9%) experienced acute valve dislocation. A comprehensive analysis of the mechanism of dislocation and clinical outcomes of patients experiencing this complication was performed. Based on the underlying mechanism, all cases of prosthesis displacement were classified into the following three groups: 1) accidental dislocation immediately after valve implantation (n=1; 14.3%); 2) dislocation during the snaring manoeuvre to reposition a low deployment of the CRS prosthesis (lower edge >10 mm) below the aortic annulus accompanied with haemodynamically significant regurgitation (n=4; 57.1%); 3) intentional dislocation performed with the snaring manoeuvre as a bailout in cases of coronary ostia impairment or severe prosthetic leak due to higher deployment for a suboptimal sealing of the device with valve calcifications (n=2; 28.6%). The majority of cases occurred during early experiences with the new Accutrak™ (Medtronic Inc., Minneapolis, MN, USA) delivery system. In six patients a second CRS was implanted in the appropriate position. The dislodged CRS functioned normally, without any evidence of structural deterioration, thrombosis or further distal migration and showed complete apposition against the aortic wall. No thromboembolic events were reported in any patient., Conclusions: Dislocation of a CRS device can be managed effectively with the implantation of a second device in a standard fashion leaving the dislocated device safely in the aorta. Intentional repositioning of a CRS device in the aorta can be accomplished by experienced operators without any serious neurologic or vascular events in the post-procedure period or at midterm follow-up.

Background: Transcatheter aortic valve implantation (TAVI) is an emerging alternative to medical therapy reserved to a limited population with severe aortic stenosis. The European consensus document recommended TAVI for prohibitive-risk patients not eligible for conventional surgery (prohibitive risk defined as expected mortality ≥ 20% calculated with the Logistic EuroScore (LES) in association with clinical judgment). To date, there is lack of clarity on data about outcomes of TAVI in lower risk patients. We sought to evaluate the outcomes of patients undergoing TAVI with LES ≥ 20% in comparison with patients with LES < 20%., Method: Of 165 patients who underwent TAVI using the 18-French Medtronic CoreValve (N = 153) and the Sapien Edwards™ (N = 12) at our Institution between June 2007 and September 2010, we identified those with LES < 20%, with prosthesis implantation (n = 84), and reported on their clinical outcome compared with patients with LES ≥ 20% (n = 78). The primary endpoint was the incidence of overall death and major adverse cerebrovascular and cardiac events (MACCE) at 30-day and midterm follow-up stratifying patients by clinical characteristics., Results: At 30-day, a significant higher incidence of MACCE (20.8% vs. 6.0%, odds ratio [OR] 4.08 95% confidence interval [CI] 1.42-11.74, P = 0.009) and death (15.6% vs. 2.4%, OR 7.45 95% CI 1.61-34.48, P = 0.010) was reported in the LES ≥ 20% group as compared with the LES < 20% group, respectively. The 12-month MACCE rates was (27.1% vs. 11.4%, hazard ratio [HR] 2.47 95% CI 0.93-6.63, P = 0. 071) for LES ≥ 20% and LES < 20% patients, respectively (mortality rates was 25.7% vs. 6.8% HR 4.21 95% CI 1.24-14.30, P = 0.021)., Conclusion: This study tends to suggest that current mortality reported after TAVI could be significantly affected by the very-high risk profile of the population which currently undergoes this procedure, making comparison with surgical series rather unreliable., (Copyright © 2011 Wiley Periodicals, Inc.)

Aims: Transcatheter aortic valve implantation (TAVI) is an emerging alternative to medical therapy reserved to a limited population with severe aortic stenosis. Quality-of-life (QoL) is a critical measure of effectiveness of TAVI in this patient population. In this prospective study, we sought to assess one year changes in QoL in patients who underwent TAVI., Methods and Results: From June 2007 to July 2010, 149 consecutive patients underwent TAVI using the 18 Fr CoreValve (Medtronic Inc, Minneapolis, MN, USA) or the Edwards SAPIEN XT heart valve (Edwards Lifescience, Irvine, CA, USA) at our institution. Of these, 143 patients with successful prosthesis implantation comprised the study population. The SF-12v2 Health-Survey questionnaire provides scales for physical (physical component summary [PCS]) and mental (mental component summary [MCS]) health. Among patients included in the present analysis, device success was obtained in 138 patients (96.5%). Mean preprocedural SF-12v2 scores showed an important upgrading after TAVI: PCS improved from 28.3 to 44.0 at five months and 42.4 at 12 months (p<0.001). MCS increased from 38.0 to 47.3 at five months and 48.2 at 12 months (p<0.001). Both the physical and mental score summaries at follow-up of these post-TAVI patients were not significantly different from the anticipated thresholds of the general Italian population over the age of 75 years. NYHA functional class improvement was reported in all patients., Conclusions: Our results showed a marked mid-term improvement in functional status and physical and mental health in patients who underwent TAVI.

Pulmonary arterial hypertension (PAH) is a rare, but serious condition which, if untreated, is associated with a poor survival. Currently, even if several trials have led to the approval of many drugs for PAH, there is no established cure for this disease. However, approved drugs for PAH have contributed to significantly improve symptoms, exercise capacity, quality of life and survival of these patients. The aim of this review is to overview the standard treatment of PAH and to give some insights about new treatments that are currently under investigation along with the discussion of recent patents.

Aims: To compare functional and structural changes of the left ventricle and long-term clinical outcomes in diabetic and nondiabetic patients with heart failure undergoing cardiac resynchronization therapy (CRT)., Methods: Sixty-eight patients with heart failure undergoing CRT were included: 18 were diabetic patients and 50 nondiabetic patients. The CRT eligibility was established by echocardiographic assessments., Results: CRT improved ventricular geometry and dyssynchrony in both diabetic and nondiabetic patients, with no significant difference in the magnitude of the effects on the left ventricular function. Over a median follow-up of 30.6 ± 6.2 months, there were no significant differences in the rates of any cause death (16.7 vs. 14.0%, P = 0.72), cardiac death (11.1 vs. 8.0%, P = 0.65) and heart rehospitalization (5.6 vs. 6.0%, P = 1.0), between diabetic and nondiabetic patients, respectively. Diabetes was not found to be an independent factor associated with worse clinical outcome., Conclusion: Resynchronization therapy provided significant functional and hemodynamic improvements in both diabetic and nondiabetic patients. Long-term prognosis in heart failure patients with diabetes was comparable with that in those without diabetes.

Background: Transcatheter aortic valve implantation (TAVI) carries higher risk of post-procedural adverse events than conventional percutaneous cardiovascular interventions. We report our experience about postoperative management protocol adopted in our Division., Methods: One hundred and ten patients underwent TAVI and 108 were transferred to the cardiac intensive care unit (CICU) after procedure. During the first 48 hours, vital parameters were monitored continuously. Close attention was given to rhythm and atrio-ventricular conduction disturbances, systemic blood pressure, fluid balance and vascular accesses., Results: The most common complications were renal impairment (21.3%), femoral artery pseudo-aneurysms (FAP) (11%), new complete atrioventricular block (20.3 %), cerebral vascular accident (4.5%) and cardiac perforation due to temporary pacemaker lead (1.8%). Ultrasound-guided compression repair was considered the first line treatment for FAP, but in 6 cases surgical treatment was immediately performed due to the rapid expansion of FAP. Complete atrio-ventricular block occurred in 22 patients (20.3 %) within the first 24 hours after TAVI and a permanent pacemaker was implanted in 21 patients (19.1%). Acute kidney injury occurred in 18 patients (35%) with pre-procedural chronic renal failure and in 5 patients (9%) without preoperative renal dysfunction., Conclusions: After TAVI, cardiovascular complications are common and therefore accurate standardized management of patients in CICU during the first 48 hours is mandatory to early detect and manage complications and to decrease the rate of adverse events and the length of in-hospital stay. © 2010 Wiley-Liss, Inc.

Mitral regurgitation (MR) is the second most common heart valve disease worldwide and the current gold-standard treatment is surgical repair or replacement. Nevertheless, many patients do not undergo surgical intervention due to several comorbidities. Percutaneous "edge-to-edge" mitral valve repair using the MitraClip System is an emerging and effective option to this subset of patients. This device has been used to treat both functional and degenerative mitral valve regurgitation and has been compared to surgery in the Endovascular Valve Edge-to-Edge Repair Study II (EVEREST II) randomized trial. Although the field of percutaneous management of MR is at an early stage, it has been demonstrated that percutaneous approaches can reduce MR, suggesting there is a great deal of potential for clinical benefit to patients with MR.

Background: Transcatheter aortic valve implantation (TAVI) is an emerging alternative to palliative medical therapy for nonsurgical patients with severe aortic stenosis. There is a paucity of detailed data on the management and outcome of complications related to the sub-optimal deployment of the prosthesis. We appraised the incidence and management of early implant failure occurring during TAVI., Methods: Of 110 patients who underwent TAVI using the third generation 18-French CoreValve ReValving System (Medtronic, MN) in our Institution between June 2007 and January 2010, we identified those experiencing early implant failure and reported on their management and clinical outcome. The primary endpoint was the incidence of major adverse cardiovascular and cerebrovascular event (MACCE) at 30 days and mid-term follow up., Results: Early implant failure occurred in 18 of 110 patients (16.3%). The most common cause was prosthesis under-expansion conditioning moderate to severe peri-valvular leak (44.4%). Prosthesis deployment too low or too high with respect to the aortic annulus leading to severe peri-valvular leak occurred in 22.2% and 5.5% of patients, respectively. Need of valve retrieve after the first attempt of deployment occurred in four cases (22.2%). Prosthesis embolization in the ascending aorta occurred in 5.5% of patients who experienced early implant failure. All implant failure cases were managed percutaneously with gain in aortic valve area from 0.44 ± 0.17 to 1.28 ± 0.27 cm(2) (P < 0.001), decrease of mean transaortic gradient from 55.00 ± 19.51 to 11.58 ± 5.91 mmHg (P < 0.001) and no MACCE at 30 days. After 11 ± 6 months, MACCE occurred cumulatively in two patients (11.1%)., Conclusions: Early implant failure can complicate the TAVI procedure with the CoreValve system, but it can be managed safely and effectively with bailout transcatheter techniques, avoiding surgery, with good early and mid-term clinical and echocardiographic results.

Exercise stress tests have been used for the diagnosis of pulmonary hypertension, but with variable protocols and uncertain limits of normal. The pulmonary haemodynamic response to progressively increased workload and recovery was investigated by Doppler echocardiography in 25 healthy volunteers aged 19-62 yrs (mean 36 yrs). Mean pulmonary artery pressure ((Ppa)) was estimated from the maximum velocity of tricuspid regurgitation. Cardiac output (Q) was calculated from the aortic velocity-time integral. Slopes and extrapolated pressure intercepts of (Ppa)-Q plots were calculated after using the adjustment of Poon for individual variability. A pulmonary vascular distensibility alpha was calculated from each (Ppa)-Q plot to estimate compliance. (Ppa) increased from 14+/-3 mmHg to 30+/-7 mmHg, and decreased to 19+/-4 mmHg after 5 min recovery. The slope of (Ppa)-Q was 1.37+/-0.65 mmHg x min(-1) x L(-1) with an extrapolated pressure intercept of 8.2+/-3.6 mmHg and an alpha of 0.017+/-0.018 mmHg(-1). These results agree with those of previous invasive studies. Multipoint (pa)-Q plots were well described by a linear approximation, from which resistance can be calulated. We conclude that exercise echocardiography of the pulmonary circulation is feasible and provides realistic resistance and compliance estimations. Measurements during recovery are unreliable because of rapid return to baseline.

Background: Percutaneous closure of patent foramen ovale (PFO) is routinely performed with nonbiological devices, characterized by a persistent low-grade inflammatory response. We report our experience about PFO closure with a bioabsorbable device, BioSTAR (NMT Inc, USA)., Methods: From September 2007 to September 2008, 14 patients with migraine (eight with aura) and cerebral magnetic resonance positive for silent ischemia and nine patients with prior cardiovascular accident (CVA) underwent closure of PFO using BioSTAR. One patient had heterozygosis for sickle-cell-anaemia. Nickel allergy was present in eight patients. Echocardiogram was performed at 24 hr, one and 6 months. At 6 and 12 months a contrast-transcranial-doppler (c-TCD) and a trans-oesophageal echocardiogram (TOE) were scheduled, respectively., Results: BioSTAR was successfully implanted in 22 patients (96%). The mean procedural time and the mean fluoroscopy time were 22 +/- 6 and 4 +/- 2 minutes, respectively. The mean in-hospital stay was 3 +/- 0.5 days. After a mean follow-up of 7.8 +/- 3.5 months there was an hemorrhagic stroke related to double antiaggregation. No other CVA or allergic reactions were registered. There were two cases of atrial arrhythmia. Fifteen patients had not residual shunts at c-TCD, while in four patients we observed a trivial microbubbles passage. The TOE, achieved in nine patients without contrast, showed the device well positioned, with a low profile and without thrombus., Conclusions: In our experience PFO closure with BioSTAR is safe and efficacious in preventing recurrent CVA. Its use could be advantageous in patients with nickel allergy and haematological disorders. The potential benefits of this device need to be certified in a larger cohort of patients with a longer follow-up.

Background: Percutaneous closure of the left atrial appendage (LAA) is a novel alternative for the treatment of patients with atrial fibrillation (AF) and with a high risk of stroke who are not eligible for long-term anticoagulation therapy. The aim of this study was to asses the safety, feasibility, and long-term efficacy of this procedure., Methods: From July 2004 to June 2007, 20 patients (13 male, mean age 69 +/- 8 years) with non-valvular AF (NV-AF) underwent LAA percutaneous closure using the PLAATO system, implanted through a transeptal access. All patients had contraindications to anticoagulant therapy and were at high risk for cardioembolic stroke (mean CHADS(2) score 3 +/- 1.2). A trans-thoracic echocardiogram was performed at 1, 3, and every 6 months after the procedure, whereas a trans-oesophageal echocardiogram (TOE) was scheduled at 6 months. After 24 months, a phone interview was obtained., Results: All procedures were successfully performed in 18 patients. In two patients, LAA closure was not feasible for the presence of a multilobed LAA. Two patients underwent percutaneous closure of patent foramen ovale in the same session. In one patient, the procedure was complicated by cardiac perforation with pericardial effusion, treated with pericardiocentesis. At a mean follow up of 40 +/- 10 months, no embolic events occurred. One patient died, after 36 months, for gastric cancer. TOE examination showed the complete exclusion of the LAA in all patients., Conclusions: Percutaneous closure of LAA is safe and efficacious to prevent stroke in patients with NV-AF at high risk for cardioembolic events, with contraindications to anticoagulant therapy., ((c) 2009 Wiley-Liss, Inc.)

Aims: To assess the NYHA class and the quality of life (QoL) scores after percutaneous aortic valve implantation (PAVI) with the 18-Fr CoreValve prosthesis., Methods and Results: From April 2007 until August 2008, 57 consecutive patients with aortic stenosis were evaluated for PAVI. Of these, 30 patients with successfully prosthesis implantation had more than 5-month follow-up. QoL assessment was realized with the SF-12v2 Health-Survey, a simple questionnaire designed for self-administration that provides easily interpretable scales for physical [physical component summary (PCS)] and mental [mental component summary (MCS)] health. The questionnaire was administered before and 5 months after PAVI. All 30 patients had a marked upgrading in haemodynamic and echocardiographic parameters (peak-to-peak gradient from 64 +/- 23 to 2 +/- 0.4; P < 0.001; aortic valve area index from 0.3 +/- 0.1 to 0.9 +/- 0.3; P < 0.001), with an improvement in New York Heart Association (NYHA) class at discharge and after 5 months. Mean pre-operative SF-12v2 scores showed a severe impairment of perceived quality of life compared with general Italian population >75 years, both for physical (PCS-baseline 28.5 vs. 37.9, P < 0.001) and mental scores (MCS-baseline 37.8 vs. 45.4, P < 0.001). After 5 months, a striking improvement in both scores (PCS 41.3-MCS 48.3; P < 0.001) was observed., Conclusion: Our preliminary results show a marked short-term improvement in functional status and physical and mental health in patients underwent PAVI.

Percutaneous aortic valve replacement is an emerging alternative to palliative medical therapy for nonsurgical patients with severe aortic valve stenosis. The impossibility of repositioning of the current transcatheter prosthesis in case of suboptimal placement is the main limit of these devices. Here, we report on a case of an 84-year-old woman successfully treated with implantation of two 18-Fr CoreValve prosthesis (CoreValve, Irvine, California), because of the suboptimal deployment of the first one, analyzing the procedural technique and the immediate and short-term clinical and hemodynamic results., (Copyright 2009 Wiley-Liss, Inc.)

Background: Percutaneous aortic valve replacement (PAVR) is an emerging alternative for high-risk patients with severe aortic stenosis. The aim of this study was to report acute and short-term outcomes of PAVR with the 18 Fr CoreValve Revalving System., Methods: From January 2007 to July 2008, 69 high-risk symptomatic patients with severe aortic stenosis were screened to assess their eligibility criteria for PAVR. All candidates were evaluated by a cardiac surgeon and a cardiologist. Thirty patients (13 men, 17 women, ages 82 +/- 5 years, range 73-88 years) met all the eligibility criteria and were enrolled in the study., Results: Twenty-nine patients (97%) underwent successful valve implantation by a retrograde approach, with improvement in valve area (0.61 +/- 0.18 cm(2) to 1.49 +/- 0.39 cm(2); p < 0.001) and transvalvular gradient (58.1 +/- 17.6 mmHg to 9.2 +/- 4.0; p < 0.001). Paravalvular leakages were 1+ (n = 12) and 2+ (n = 2). Procedural success was achieved in 93% of patients, with 1 case of pericardial tamponade occurred during the first 48 hours after implantation. At 30-day mortality was 7%. The mean NYHA Functional Class declined from 2.72 +/- 0.59 to 1.31 +/- 0.47 (p < 0.001). No other major adverse events occurred at a mean follow up of 4.9 +/- 4.0 months (range 1-13 months)., Conclusions: Our initial experience of PAVR in a cohort of older and high-risk surgical patients has been positive, with excellent acute and encouraging short-term results in terms of safety and efficacy.

Aim: The clinical and prognostic role of cardiac natriuretic peptides (CNP) in patients with heart failure is well known; recently, several studies have evaluated the possibility of using CNP to evaluate their potential prognostic role in patients with acute coronary syndromes (ACS). The aim of this study was to evaluate the short term prognostic value of NT-proBNP in 70 patients admitted for ACS., Methods: The authors studied 70 patients with ACS, evaluating, at admission, clinical-anamnestic, instrumental and laboratory characteristics including NT-proBNP plasma levels. Patients were monitored in a 6-month-follow-up to record adverse fatal events and their possible correlation with baseline characteristics., Results: The incidence of adverse events during the follow-up period was 28% (10 patients). In patients with adverse events, the authors observed lower left ventricle ejection fraction (P=0.01), higher prevalence of ST elevation myocardial infarction (P=0.03) and higher NT-proBNP levels (P=0.03), compared to those without adverse events. Moreover, the logistic regression analysis underlined how ST elevation myocardial infarction (P=0.05) and higher NT-proBNP levels (P=0.05) were the only predictive variables for adverse events during the follow up period., Conclusions: This study demonstrates the short term prognostic role of NT-pro BNP in patients admitted for ACS.

Objective: The percutaneous left atrial appendage transcatheter occlusion system (PLAATO, ev3 Inc., Plymouth, Minnesota, USA) is a novel technique of interventional cardiology, which has recently been proposed for the nonpharmacological prophylaxis of thromboembolic events in patients with chronic nonvalvular atrial fibrillation ineligible for oral anticoagulation therapy with vitamin K antagonists. The aim of this study was to assess the safety, feasibility and mid-term efficacy of this procedure., Methods: We conducted a preliminary institutional experience on a selected population of seven patients (two male, five female, mean age 64 +/- 7 years) with chronic nonvalvular atrial fibrillation at high risk for thromboembolic events with contraindications for oral anticoagulation therapy with vitamin K antagonists., Results: All procedures were successfully performed without any complications at a mean follow-up of 7 +/- 4 months and no thromboembolic or adverse cardiac events occurred., Conclusions: Percutaneous left atrial appendage transcatheter occlusion is safe and feasible, without any complications at mid-term follow-up.

Background and Purpose: The present study evaluated the concurrent validity of the NK hand dexterity test (NKHDT) by use of three separate analyses: (1) the correlation between the NKHDT and a criterion comparator (Jebson's Hand Function Test (JHFT)); (2) the correlation between both dexterity tests and a patient-rated function questionnaire; and (3) the ability of subscales to differentiate between subjects with and without upper extremity pathology., Method: The study population included 40 individuals with a variety of musculoskeletal problems affecting the upper extremity and 10 individuals without any history of upper extremity problems. Both dexterity tests were administered on a single occasion according to a standard protocol. Subjects also completed a rating scale which evaluated self-care, household work, work and recreation on an 0-10-point scale., Results: The validity of the NKHDT was supported in all three analyses because: (1) the correlation between the NKHDT and JHFT subtests was moderate to strong (Pearson's r = 0.47-0.87) and stronger when the objects were more similar in size; (2) both scales correlated to a similar extent with patient-rated function (Pearson's r = 0.34-0.67); and (3) all subscales were statistically different between subjects with and without upper extremity pathology (p < 0.01)., Conclusions: The present study supports the use of the NKHDT as a measure of hand dexterity.

The case is described of a 6 1/2-year-old child with pseudohyperaldosteronism due to excessive and prolonged liquorice ingestion. The authors debate its differential diagnosis, its physiopathological mechanism (glycyrrhetinic acid, the active metabolite of liquorice, inhibits the conversion of cortisol in cortisone) and its unusual association with haemorrhagic gastritis never observed in the course of liquorice intoxication.