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Objectives The aim of this prospective study was to validate an echocardiographic protocol derived from 5 HeartWare left ventricular assist device (HVAD) patients for the noninvasive evaluation of right atrial pressure (RAP) and left atrial pressure (LAP) in HVAD patients. Background Echocardiography is an invaluable tool to optimize medical treatment and pump settings and also for troubleshooting residual heart failure. Little is known about the echocardiographic evaluation of hemodynamic status in HVAD patients. Methods Right heart catheterization and Doppler echocardiography were performed in 35 HVAD patients. Echocardiography-estimated RAP (eRAP) was assessed using inferior vena cava diameter, hepatic venous flow analysis, and tricuspid E/e′ ratio. Echocardiography-estimated LAP was assessed using E/A ratio, mitral E/e′ ratio, and deceleration time. Results eRAP and estimated LAP significantly correlated with invasive RAP and LAP (respectively, r = 0.839, p Conclusions Doppler echocardiography accurately estimated hemodynamic status in HVAD patients. This algorithm reliably detected high RAP and LAP. Notably, high RAP was associated with high wedge pressure and adverse outcome. The benefit of noninvasive estimation of hemodynamic status in the clinical management of patients with left ventricular assist devices needs further evaluation.

Left atrial appendage (LAA) morphology, investigated by computed tomography and magnetic resonance imaging, has proved to relate to the risk of cerebrovascular events in patients with atrial fibrillation (AF). The aim of the present study was to assess reproducibility of transesophageal echocardiography (TEE) imaging in describing LAA morphology.Two-hundred consecutive patients referred for TEE were enrolled. In the first group of 47 (23.5%) patients LAA morphology was analyzed by conventional TEE and described as ChickenWing, Windsock, Cactus or Cauliflower. In the second group of 153 (76.5%) patients, instead, a 3D-Xplane diagnostic algorithm was performed to stratify LAA morphology as linear (ChickenWing) or complex (Windsock/Cactus and Cauliflower). Interobserver variability within three independent readers was assessed in both groups of patients and stratified by operator's experience and training. In a subgroup of 19 (12.4%) patients, the agreement of LAA morphology description by 3D-Xplane diagnostic algorithm was compared to cardiac magnetic resonance.By conventional TEE the agreement among operators on LAA morphology classification was poor (ρ0.13). The 3D-XPlane diagnostic algorithm, significantly increased interobserver agreement up to ρ=0.32 within all readers and up to ρ=0.82 among the experienced and specifically trained operators. LAA morphology description in this latter group provided strong agreement with cardiac magnetic resonance (up to ρ=0.77).LAA morphology assessment is challenging by conventional TEE. To improve reproducibility, the use of the 3D-Xplane technique combined with a specific diagnostic algorithm and training of the operators is fundamental.

Background and Objectives: Surgical atrial fibrillation (AF) ablation concomitant to minimally invasive mitral valve repair has been proven to offer improved short- and long-term sinus rhythm (SR) maintenance compared to mitral valve surgery only. The objective of the present study was to explore, by thorough echocardiographic assessment, long-term morphological and functional left atrial (LA) outcomes after this combined surgical procedure. Materials and Methods: From October 2006 to November 2015, 48 patients underwent minimally invasive mitral valve repair and concomitant surgical AF cryoablation. Results: After 3.8 &plusmn, 2.2 years, 30 (71.4%) of those completing the follow-up (n = 42, 87.5%) presented SR. During follow-up, four (9.5%) patients suffered from cerebrovascular accidents and two of these subjects had a long-standing persistent AF relapse and were in AF at the time of the event, while the other two were in SR. An echocardiographic study focused on LA characteristics was performed in 29 patients (69.0%). Atrial morphology and function (e.g., maximal LA volume indexed to body surface area and total LA emptying fraction derived from volumes) in patients with stable SR (60.6 &plusmn, 13.1 mL/mq and 25.1 &plusmn, 7.3%) were significantly better than in those with AF relapses (76.8 &plusmn, 16.2 mL/mq and 17.5 &plusmn, 7.4%, respectively, p = 0.008 and p = 0.015). At follow-up, patients who suffered from ischemic cerebral events had maximal LA volume indexed to body surface area 61 &plusmn, 17.8 mL/mq, with total LA emptying fraction derived from volumes 23.6 &plusmn, 13.7%, patients with strokes in SR showed very enlarged LA volume (&gt, 70 mL/mq). Conclusions: AF cryoablation concomitant with minimally invasive mitral valve repair provides a high rate of SR maintenance and this relates to improved long-term morphological and functional LA outcomes. Further prospective studies are needed to define the cut-off values determining an increase in the risk for thromboembolic complications in patients with restored stable SR.

To assess the accuracy and reproducibly of cardiovascular magnetic resonance (CMR) in the measurement of the aortic annulus and in process of valve sizing as compared to intra-operative sizing, cardiovascular computed tomography (CCT) and transesophageal echocardiography (TEE). Retrospective study on 42 patients who underwent aortic valve replacement from September 2010 to September 2015, with available records of pre surgery annulus assessment by CMR, CCT and TEE and of peri-operative assessment. In CCT and CMR, the annular plane was considered a virtual ring formed by the lowest hinge points of the valvular attachments to the aorta. In TEE the annulus was measured at the base of leaflet insertion in the mid-esophageal long-axis view using the X-plane technique. Two double-blinded operators performed the assessments for each imaging technique. Intra-operative evaluation was performed using Hegar dilators. Continuous variables were studied with within-subject ANOVA, Bland-Altman (BA) plots, Wilcoxon's and Friedman's tests; trends were explored with scatter plots. Categorical variables were studied with Fisher's exact test. The intra- and inter-operator reliability was satisfying. There were no significant differences between the annulus dimensions measured by CMR and either one of the three references. Valve sizing for CoreValve by CMR had the same good agreement with CCT and TEE, with a 78 % match rate; for SAPIEN XT the agreement was slightly better (82 %) for CCT than for TEE (66 %). MR performs well when compared to the surgical reference of intra-operative sizing and stands up to the level of the most used imaging references (CCT and TEE).

Aims The purpose of this study was to evaluate the additional prognostic value of echocardiography in acute decompensation of advanced chronic heart failure (CHF), focusing on right ventricular (RV) dysfunction and its interaction with loading conditions. Few data are available on the prognostic role of echocardiography in acute HF and on the significance of pulmonary hypertension in patients with severe RV failure. Methods and results A total of 265 NYHA IV patients admitted for acute decompensation of advanced CHF (EF 22 ± 7%, systolic blood pressure 107 ± 20 mmHg) were prospectively enrolled. Fifty-nine patients met the primary composite endpoint of cardiac death, urgent heart transplantation, and urgent mechanical circulatory support implantation at 90 days. Pulmonary hypertension failed to predict events, while patients with a low transtricuspid systolic gradient (TR gradient

The onset of supraventricular arrhythmias (SVA) may be associated with clinical worsening in patients with pulmonary arterial hypertension (PAH). However, limited data have been reported, especially at long-term follow-up. Aim of this study was to investigate the incidence of SVA in our patients with PAH, the risk factors correlated to their onset and the prognostic impact. All consecutive patients with PAH without history of SVA were enrolled. Incidence of new SVA was investigated and also the risk factors for SVA. Primary end point of the study was the impact of SVA on a composite of all-cause mortality and re-hospitalization, whereas mortality was the secondary end point. Seventy-seven patients were enrolled. No significant differences in the clinical or instrumental baseline characteristics between the 2 study groups were reported. During a median follow-up of 35 months (interquartile range 21.5 to 53.5), 17 (22%) patients experienced SVA. Development of SVA was associated with worsening of prognostic parameters at the follow-up: increasing of World Health Organization (WHO) functional class (p = 0.005) and N-terminal-pro-brain natriuretic peptide (NT-proBNP) (p = 0.018) and reduction of 6-minute walking distance (p = 0.048), tricuspid annular plane systolic excursion (TAPSE) (p = 0.041), and diffusing capacity of the lung for carbon monoxide (p = 0.025). The primary end point occurred in 13 patients (76%) in the SVA group and in 22 patients (37%) in the group without SVA (p = 0.004), whereas 9 patients (53%) among those with SVA died during the follow-up compared with 8 (13%) among those without (p = 0.001). At multivariate analysis, development of SVA was independently associated with an increased risk to meet the both primary (hazard ratio 2.13; 95% confidence interval 1.07 to 4.34; p = 0.031) and secondary (hazard ratio 4.1; 95% confidence interval 1.6 to 10.6; p = 0.004) end points. In conclusion, during the 3-year follow-up period, 1/3 of patients with PAH developed SVA, which was related to worsening of hemodynamic and functional parameter and independently predicted adverse prognosis.

The aim of this prospective study was to validate an echocardiographic protocol derived from 5 HeartWare left ventricular assist device (HVAD) patients for the noninvasive evaluation of right atrial pressure (RAP) and left atrial pressure (LAP) in HVAD patients.Echocardiography is an invaluable tool to optimize medical treatment and pump settings and also for troubleshooting residual heart failure. Little is known about the echocardiographic evaluation of hemodynamic status in HVAD patients.Right heart catheterization and Doppler echocardiography were performed in 35 HVAD patients. Echocardiography-estimated RAP (eRAP) was assessed using inferior vena cava diameter, hepatic venous flow analysis, and tricuspid E/e' ratio. Echocardiography-estimated LAP was assessed using E/A ratio, mitral E/e' ratio, and deceleration time.eRAP and estimated LAP significantly correlated with invasive RAP and LAP (respectively, r = 0.839, p 0.001, and r = 0.889, p 0.001) and accurately detected high RAP and high LAP (respectively, area under the curve 0.94, p 0.001, and area under the curve 0.91, p 0.001). High eRAP was associated with high LAP (area under the curve 0.92, p 0.001) and correlated with death or hospitalization at 180 days (odds ratio: 8.2; 95% confidence interval: 1.1 to 21.0; p = 0.04). According to estimated LAP and eRAP, patients were categorized into 4 hemodynamic profiles. Fifteen patients (43%) showed the optimal unloading profile (normal eRAP and normal wedge pressure). This profile showed a trend toward a lower risk for adverse cardiac events at follow-up (odds ratio: 0.2; 95% confidence interval: 0.1 to 1.0; p = 0.05) compared with other hemodynamic profiles.Doppler echocardiography accurately estimated hemodynamic status in HVAD patients. This algorithm reliably detected high RAP and LAP. Notably, high RAP was associated with high wedge pressure and adverse outcome. The benefit of noninvasive estimation of hemodynamic status in the clinical management of patients with left ventricular assist devices needs further evaluation.

Oral anticoagulant therapy (OAT) patients have international normalized ratio (INR) safety windows for oral surgery, the lower limit of which is determined by the thromboembolic risk, with the upper limit typically 3.0. We sought to assess whether these limits will also be true with comorbidities that favor bleeding, such as diabetes, liver disease, and chronic renal failure.The study was designed for 500 consecutive extractions. Patients with an INR greater than 3.0 were switched to heparin and used as controls. The primary outcome was the incidence of bleeding with the need for reoperation, in connection with 3 principal predictors: the INR, reasons for OAT, and comorbidity type. Continuous variables were analyzed using the Mann-Whitney U test and categorical variables using χ2 or Fisher's exact test. Statistical significance was set at P.05. The reliability of the INR as a bleeding predictor was assessed using receiver operating characteristic (ROC) curves.Extractions in patients receiving OAT without comorbidities had a success rate of 99.7% against severe bleeding. Despite equivalent INR values, patients with comorbidities had a significantly lower rate (81.3%, P.001). For these patients, the ROC curve procedure indicated lower INR upper limits, 2.8 for mechanical heart prosthesis subjects and 2.3 for all others. Among the comorbidities, diabetes was associated with the greatest frequency of bleeding (31%) compared with liver disease (15%) and kidney failure (11%).Patients with comorbidities should be advised to bring their INR within narrower safety windows (upper limit of 2.5 to 2.8 for mechanical prosthesis and 2.0 to 2.3 otherwise) or be switched to heparin. Alternatively, we propose applying to the socket, a platelet-rich growth factor preparation to foster hemostasis.

Myocarditis, often triggered by viral infection, may lead to heart auto-immunity and dilated cardiomyopathy. What determines the switch between disease resolution and progression is however incompletely understood. We show that pharmacological inhibition of STAT3, the main mediator of IL-6 signalling and of Th17-cell differentiation, protects mice from the development of Experimental Auto-immune Myocarditis reducing liver production of the complement component C3, and can act therapeutically when administered at disease peak. Further, we demonstrate that STAT3 is sufficient when constitutively active for triggering the onset of immune-mediated myocarditis, involving enhanced complement C3 production and IL-6 signalling amplification in the liver. Disease development can be prevented by C3 depletion and IL-6 receptor neutralization. This appears to be relevant to disease pathogenesis in humans, since acute myocarditis patients display significantly elevated circulating IL-6 and C3 levels and activated heart STAT3. Thus, aberrant IL-6/STAT3-mediated induction of liver acute phase response genes including C3, which occurs as a consequence of pre-existing inflammatory conditions, might represent an important factor determining the degree of myocarditis and its clinical outcome.

Background Transesophageal echocardiography (TEE) is routinely performed before atrial fibrillation (AF) transcatheter ablation to exclude the presence of left atrial (LA) or LA appendage (LAA) thrombi. The aim of the study is to evaluate if easily accessible clinical parameters may relate to the presence of LA or LAA thrombi to identify patients who could potentially avoid TEE. Methods and results Between January 2012 and September 2014, data from 1539 consecutive patients undergoing TEE, as a work-up before AF transcatheter ablation, in six large volume centers were collected. Baseline clinical features, CHA 2 DS 2 -VASc score, transthoracic echocardiography and presence of thrombi at TEE were recorded. Exclusion criteria were valvular, hypertrophic or dilated cardiomyopathy, previous heart surgery or an ejection fraction ≤35%. Mean age was 59.6±10.4years, 1215 (78.9%) were males; 951 (62.9%) presented in sinus rhythm (SR) on admission, 324 (21.1%) had undergone at least one previous ablation and 900 (58.5%) had CHA 2 DS 2 -VASc score 0–1. Thrombi were encountered in 12 patients (0.8%). SR at TEE independently related to the absence of thrombi (OR 5.15, 95% CI 1.38–19.02, p =0.015); in addition to this, no patient with a CHA 2 DS 2 -VASc score 0–1 and SR on admission presented thrombi at TEE (specificity 100%, p =0.011). Conclusion In a selected population of patients referred for AF ablation, LA/LAA thrombi prevalence is low. No patients in SR with CHA 2 DS 2 -VASc score 0–1 presented LAA thrombi at TEE, identifying a significant subset of patients who could potentially safely be spared from pre-procedural TEE.

Background Aim of this study was to evaluate whether asymptomatic recurrent (≥ 2) antibody-mediated rejection (pAMR1+), defined as diffuse capillary C4d immunostaining (rAMR) on endomyocardial biopsies (EMB), during the first year after heart transplantation impairs left ventricular (LV) function. Methods 54 consecutive heart transplant patients who survived well (NYHA ≤ 2 and EF ≥ 55%) the first month after transplantation were enrolled and prospectively underwent 490 echocardiographies and EMB. Asymptomatic rAMR without histopathologic findings was evaluated as a risk factor for deterioration of graft function. Primary endpoint, assessed one year after transplantation, was development of LV dysfunction and/or adverse remodeling according to prespecified echo parameters. Results During the first year from transplantation rAMR occurred in 5 patients. Recurrent AMR was associated with a significant higher risk to develop LV concentric hypertrophy (OR 3.6, 95% CI: 1.8-7.0, p .02) or reduced lateral S’ peak velocity (OR 2.3, 95% CI: 1.5-3.6, p .03). Patients with rAMR showed significative adverse graft remodeling (ΔLV end-diastolic volume: +16 ± 12.3 vs. - 0.2 ± 14.4 ml; p .02) and deterioration of graft function (Δlateral S’ peak velocity: -3.3 ± 3 vs. -0.4 ± 2.9 cm/s; p .03). Conclusions Recurrent asymptomatic diffuse capillary C4d immunostaining may play a role in the early development of cardiac allograft adverse remodeling and dysfunction. This article is protected by copyright. All rights reserved.

Interest in minimally invasive video-assisted mitral valve surgery (MIMVS) is rapidly growing. Data on concomitant atrial fibrillation (AF) ablation to MIMVS are still lacking. The present study investigates the long-term results of AF cryoablation concomitant to MIMVS. From October 2006-September 2014, 68 patients with mitral valve disease (age 65.9 ± 11.1 years, 34 men out of 68 patients, Euroscore log 5.4 ± 4.5) and drug-resistant AF underwent MIMVS via right minithoracotomy and concomitant left-sided AF endocardial cryoablation (Cryoflex Medtronic, Minneapolis, MN). Patients were independently followed up by cardiological outpatient visits and underwent electrophysiological study when indicated. In total, 44 out of 68 patients (64.7%) underwent mitral valve repair and 8 patients (11.8%) also received concomitant tricuspid valve surgery. One procedure was electively converted to full sternotomy (1.5%). Total clamp time was 97.6 ± 22.8 minutes. In March 2015, 60 patients were alive and completed the follow-up after a mean of 3.4 ± 2.0 years following the procedure. In all, 48 patients (80%) presented sinus rhythm throughout the whole follow-up. Freedom from AF was respectively 95%, 87%, and 72% at 1, 3, and 5 years, respectively. We recorded 2 pacemaker implants (3.3%). A total of 3 patients suffered symptomatic recurrences (2 atypical atrial flutter and 1 atrial fibrillation) and underwent transcatheter ablation—all the 3 patients remained in stable sinus rhythm for the remaining follow-up. In conclusions, given the favorable long-term sinus rhythm maintenance rates of concomitant cryoablation, MIMVS can also be offered to patients with symptomatic AF. AF transcatheter ablation may easily avoid further symptomatic recurrences.

Objective: This study aims to assess changes in mitral regurgitation (MR) severity after transcatheter aortic valve implantation (TAVI). Background: Existing data on MR after TAVI are contradictory. Methods: Thirty-five patients with MR graded 2+ were followed after undergoing TAVI with either the Edwards Sapien or CoreValve device. Echocardiography was performed the week before and 3 months after the procedure. MR was graded on a scale of 0 to 4+, classified as organic or functional, and the effective regurgitant orifice area (EROA) and MR index were calculated. Results: At baseline, MR was graded 4+ in 4 (11.4%) patients, 3+ in 10 (28.6%), and 2+ in 21 (60%). At follow-up, MR was graded at 3+ in 4 (11.4%) patients, 2+ in 8 (22.9%), and 1+ in 19 (54.3%); 4 (11.4%) exhibited no MR. EROA (24.4 ± 11.5 mm 2 pre-TAVI vs. 11.2 ± 10.3 mm 2 post-TAVI, P < 0.001) and MR index (1.9 ± 0.3 preTAVI vs. 1.3 ± 0.7 post-TAVI, P < 0.001) were reduced with TAVI, independent of the etiology. MR decreased by at least 1 grade in 28 (80%) patients, with a reduction 2 grades in 10 (28.6%) patients; no patient showed a worsened condition. Subgroup analyses showed that the reduction in MR was significant in patients treated with the Edwards Sapien device but not in patients treated with the CoreValve device. Conclusions: This multiparametric echocardiographic evaluation showed that MR improved significantly after TAVI and that this result may be related to the type of valve implanted. (Echocardiography 2013;30:250-257)

Aims Actual rates of lead vegetations (LVs) in cardiovascular device infections (CDI) are debated in this study. The aim of this study is to characterize prevalence and risk factors of LV in patients with CDI treated with lead extraction (LE). Methods and results Between 2003 and 2011, 293 leads were extracted from 136 patients (age 70.5 ± 14.5 years, 109 male) with infective indications: 39.2% chronic draining sinus, 20.9% pocket infections, and 28.8% systemic infections/sepsis. All patients underwent transesophageal echocardiography (TEE) before LE. Lead vegetation prevalence was 40.4%: 62.2% in systemic infection, but noteworthy in local infection/chronic draining sinus (21.9/36.4%). Younger age, renal disease, ad dialysis were associated with systemic infection. Fever after last intervention, revision, previous reparative procedure, infection at wound/device site and infection >6 months were associated with local infection/chronic draining sinus. Cardiac resynchronization therapy device, fever after last intervention, infection

Cardiac hypertrophy is a major risk factor for heart failure. Hence, its attenuation represents an important clinical goal. Erk1,2 signalling is pivotal in the cardiac response to stress, suggesting that its inhibition may be a good strategy to revert heart hypertrophy. In this work, we unveiled the events associated with cardiac hypertrophy by means of a transgenic model expressing activated Met receptor. c-Met proto-oncogene encodes for the tyrosine kinase receptor of Hepatocyte growth factor and is a strong inducer of Ras-Raf-Mek-Erk1,2 pathway. We showed that three weeks after the induction of activated Met, the heart presents a remarkable concentric hypertrophy, with no signs of congestive failure and preserved contractility. Cardiac enlargement is accompanied by upregulation of growth-regulating transcription factors, natriuretic peptides, cytoskeletal proteins, and Extracellular Matrix remodelling factors (Timp1 and Pai1). At a later stage, cardiac hypertrophic remodelling results into heart failure with preserved systolic function. Prevention trial by suppressing activated Met showed that cardiac hypertrophy is reversible, and progression to heart failure is prevented. Notably, treatment with Pimasertib, Mek1 inhibitor, attenuates cardiac hypertrophy and remodelling. Our results suggest that modulation of Erk1.2 signalling may constitute a new therapeutic approach for treating cardiac hypertrophies.

Objectives: Evaluate echocardiographic predictors of pulmonary artery hypertension (PAH) in a prospective cohort of patients with systemic sclerosis (SSc). Methods: 38 patients with SSc who did not have PAH and significant left heart disease, with peak tricuspid regurgitant velocity (TRV) ≤ 2.8 m/sec and systolic pulmonary artery pressure (sPAP) < 40 mmHg on echo Doppler were enrolled. Patients underwent: clinical assessment, NT-proBNP, and DLco measurements. Echo Doppler evaluation included right ventricular (RV) dimensions, tricuspid annular plan systolic excursion, fractional area change, tricuspid DTI systolic velocity, Tei index, pulmonary flow acceleration time (AcT), ratio of TRV to RV outflow tract time–velocity integral (TVI) and a parameter of disturbed RV ejection (TRV/AcT). After a planned 12-month follow-up we evaluated the predictive value of these parameters for the development of PAH, as demonstrated by right heart catheterization (RHC). Criteria for RHC were TRV ≥ 3 m/sec or sPAP ≥ 40 mmHg. Results: Four patients developed PAH. Only TRV/TVI and TRV/AcT ratios significantly predicted PAH development (TRV/TVI ratio ≥ 0.16 [predefined and ROC confirmed]: OR 99, CI 95%: 4.865–2015, P = 0.004; TRV/AcT ratio ≥ 0.022 [predefined and ROC confirmed]: OR 12.68, CI 95% 1.163–379.3, P = 0.036). Both parameters showed a good diagnostic power (TRV/TVI ratio: ROC area 79%, sensitivity 75%, specificity 97% and diagnostic accuracy 94.74% for cutoff value of 0.16; TRV/AcT ratio: ROC area 75%, sensitivity 75%, specificity 71% and diagnostic accuracy 72% for cutoff value of 0.022). Conclusions: This prospective study identified increased values of the two ratios TRV/TVI and TRV/AcT as predictors of PAH in SSc. (Echocardiography 2011;28:860-869)

BACKGROUND Data are lacking on the effect of radiofrequency catheter ablation (RFCA) on atrial function. The aim of this study was to determine a cut-off of pre-ablation left atrial (LA) function in order to predict atrial functional recovery after RFCA. METHODS AND RESULTS A total of 64 atrial fibrillation (AF) patients who underwent RFCA were enrolled (age, 59.05±12.09 years; 36% persistent AF; LA volume 37.8±13.6 ml/m(2)). LA emptying fraction (LAEF), LA active fraction (LAAEF), LA passive emptying fraction (LAPEF) and LA expansion index (LAEI) were evaluated in sinus rhythm before and 48 h, 15 days, 1, 2, 3 and 9 months after ablation. LA function improvement was defined as any positive increase in LAEF compared with baseline. On univariate and multivariate analysis only baseline atrial function proved to be an independent predictor of LA function improvement after ablation (P=0.002; OR=0.001; 95% CI: 0.000-0.099). On receiver operating characteristic analysis (AUC=0.70), cut-off for baseline LAEF was 40%. At 9 months, patients with LAEF

The purpose of this study was to evaluate the additional prognostic value of echocardiography in acute decompensation of advanced chronic heart failure (CHF), focusing on right ventricular (RV) dysfunction and its interaction with loading conditions. Few data are available on the prognostic role of echocardiography in acute HF and on the significance of pulmonary hypertension in patients with severe RV failure.A total of 265 NYHA IV patients admitted for acute decompensation of advanced CHF (EF 22 ± 7%, systolic blood pressure 107 ± 20 mmHg) were prospectively enrolled. Fifty-nine patients met the primary composite endpoint of cardiac death, urgent heart transplantation, and urgent mechanical circulatory support implantation at 90 days. Pulmonary hypertension failed to predict events, while patients with a low transtricuspid systolic gradient (TR gradient20 mmHg) showed a worse outcome [hazard ratio (HR) 2.37, 95% confidence interval (CI) 1.12-5.00, P = 0.02]. RV dysfunction [tricuspid annular plane systolic excursion (TAPSE) ≤14 mm] in the presence of a low TR gradient identified patients at higher risk of events (HR 2.97, 95% CI 1.19-7.41, P = 0.02). Multivariate analysis showed as best predictors of outcome low RV contraction pressure index (RVCPI), defined as TAPSE × TR gradient, and high estimated right atrial pressure (eRAP). Adding RVCPI (400 mm*mmHg) and eRAP (≥20 mmHg) to conventional clinical (ADHERE risk tree and NT-proBNP) and echocardiographic risk evaluation resulted in an increase in net reclassification improvement of +19.1% and +20.1%, respectively (P = 0.01) and in c-statistic from 0.59 to 0.73 (P0.01).In acute decompensation of advanced CHF, pulmonary hypertension failed to predict events. The in-hospital and short-term prognosis can be better predicted by eRAP and RVCPI.

Short QT syndrome (SQTS) is a congenital ion channel disease characterized by an increased risk of sudden cardiac death. Little is known about the possibility that accelerated repolarization alters mechanical function in SQTS.The study investigated the presence of left ventricular dysfunction and mechanical dispersion, assessed by tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE), and their correlation with QT interval duration and genetics.Fifteen SQTS patients (7 with HERG and 3 with KCNQ1 mutation) were studied. Electrocardiographic and echocardiographic parameters were compared with age- and sex-matched healthy controls.When compared to the control group, SQTS patients showed reduced left ventricular contraction (global longitudinal strain: -16.0% ± 3.4% vs -22.6% ± 1.7%, P.001; myocardial performance index 0.59 ± 0.17 vs 0.34 ± 0.08, P.001) and a higher incidence of ejection fraction55% (odds ratio 11, 95% confidence interval 1.045-374, P = .04). Mechanical dispersion assessed by TDI (P.01) and STE (P.001) was higher in the SQTS group than in controls; each parameter showed a significant inverse correlation with QT interval but not with QT dispersion.This study showed that in SQTS systolic function may also be affected. SQTS patients presented a significant dispersion of myocardial contraction. TDI and STE could become part of the evaluation of this rare disease.

collagen deposition. The cytokine profiles indicate an increased production of pro-inflammatory molecules in presence of PM. The levels of DNA adducts were significantly increased in HFD groups and,interestingly, the effects of HFD and PMwere synergistic in fact the DNA adducts were about thirty fold greater in HFD mice compared to controls treated with the same amounts of air particulate matters. Conclusions: Our data suggest that in subjects with steatosis due to a western style of life, the association with a chronic exposition to urban particulate matter plays an important role in the pathogenesis of NASH and its evolution to cirrhosis and also to cancer.

Little is known about the impact of left-ventricular (LV) diastolic dysfunction on risk of atrial fibrillation (AF) recurrence in patients with left-atrial (LA) dilation. To evaluate, in patients with symptomatic persistent AF and LA dilation, the incremental role of LV diastolic dysfunction in predicting early AF recurrence after cardioversion (CV).From July 2011 to July 2013, 175 patients with persistent AF referred to our centre for CV were screened. Inclusion criteria were: European Heart Rhythm Association (EHRA) class ≥2 despite optimal medical treatment and heart rate at rest ≤80 bpm, LA volume ≥34 mL/m(2), EF35%, absence of untreated ischaemic disease and significant valvular disease, successful CV. Finally, 127 patients (age 64 ± 10 years, 60% EHRA ≥3, LA volume 42 ± 15 mL/m(2)) were enrolled. At 3 months, 37 (29%) patients presented AF recurrence. At univariate analysis, AF duration90 days before CV (P0.01), septal e'8 cm/s (P 0.03), and septal E/e' ratio ≥11 (P0.001) but no LA dimensions significantly correlated with AF recurrence. Logistic regression analysis confirmed septal E/e' ratio ≥11 as the best predictor of recurrence (OR 3.25 95% CI 1.19-8.86 P 0.001) together with an AF duration90 days before the CV (OR 2.69 95% CI 1.01-7.53 P 0.04). At ROC curve analysis, the septal E/e' ratio ≥11 showed the best diagnostic accuracy (AUC 0.66, 95% CI 0.55-0.76, P 0.007).In this population with symptomatic persistent AF and LA enlargement, septal E/e' ratio ≥11 and AF duration90 days predicted AF recurrence at 3 months.

We studied the records of 175 consecutive patients referred to our neurologic ward between January 1994 and February 2000 with a diagnosis of ischaemic cerebrovascular disease (ICVD) (stroke or transient ischaemic attack – TIA) who underwent transoesophageal echocardiography (TEE). We excluded patients with large vessel disease, high-risk embolic cardiopathies and other rare causes of stroke. According to clinical and neuroimaging findings, patients were divided into two groups. The lacunar (LAC) group (69/175 (39.4%)) and the nonlacunar (N-LAC) one (106/175 (60.6%)). The control population consisted of 78 consecutive patients, referred to the echocardiography laboratory for TEE without history of ICVD and known heart disorders. Patent foramen ovale (PFO) frequency was significantly higher in case patients than in control subjects (55/175 (31.4%) vs. 13/78 (16.6%); p = 0.02). Among case patients, PFO was more prevalent in the N-LAC group than in the LAC one (43/106 (40.6%) vs. 12/69 (17.4%); p = 0.0005). A large degree of shunt occurred in 53.5% of N-LAC patients and in 16.7% of LAC ones (p = 0.04). Atrial septal aneurysm (ASA) was detected in 12% of case patients and 1.3% of control subjects (p = 0.003) and was more frequent in the N-LAC group than in the LAC one (16 vs. 5.8%; p = 0.05). Mitral prolapse (MP) was present in 6/175 (3.4%) ICVD patients (vs. 1/78 among controls) in most cases associated with myxomatous valve redundancy. Aortic arch atheromas (AA) were detected in 12% of ICVD patients and in 10.2% of controls. The frequency was 9.4% in N-LAC and 15.9 in LAC. No complicated AA (plaque thickness >4 mm, ulcerated atheroma, superimposed thrombus) were detected. After multivariate analysis, PFO (OR = 3.8; 95% CI = 2.7–7.9) and ASA (OR = 8.01; 95% CI = 3.0–16.1) appeared to be independent predictors of ICVD. PFO (OR = 2.24; 95% CI = 1.24–4.92) was also independently associated with N-LAC stroke subtype and its importance was even higher in younger patients. Our study provides further evidence that TEE is a helpful diagnostic tool in stroke patients without arterial and major cardiac sources of embolism. However, its utility differs according to type and localization of the ischaemic lesion being more relevant in patient with N-LAC infarctions.

OBJECTIVE There is evidence showing that GH and IGF-I have specific receptors in the heart and that these hormones are able to promote cardiac remodelling and inotropism. It has been reported that patients with dilated cardiomyopathy (DCM) benefit from treatment with rhGH showing a striking increase in cardiac contractility. However, until now, the activity of GH/IGF-I axis in DCM has never been clearly assessed. PATIENTS To clarify this point, we enrolled 39 patients with idiopathic or post-ischaemic DCM (36 M/3 F; age (mean ± S.D.) 55.3 ± 9.0 years; BMI: 25.3 ± 3.2 kg/m2; New York Heart Association class (NYHA) I/2, II/19, III/15, IV/3) and 42 age-matched controls (CS, 38 M/4 F; age 56.0 ± 7.8 years; BMI: 24.9 ± 1.5 kg/m2). DCM patients were characterized by a left-ventricular diastolic diameter of 73.8 ± 8.3 mm, a shortening fraction of 15.9 ± 6.4% and a left ventricular ejection fraction of 25.1 ± 8.7%. In all subjects clinical and biochemical indices of renal and hepatic function as well as nutritional parameters were in the normal range. MEASUREMENTS In both groups we studied: a) IGF-I levels in basal conditions and after administration of low rhGH doses for 4 days (5.0 or 10.0 μ/kg/day × 4 days); b) the acute GH-response to GHRH (1.0 μ/kg i.v.) or hexarelin (HEX, 2.0 μ/kg i.v.), a peptidyl GH secretagogue (GHRP); c) mean GH concentration (mGHc) over 10 h sampling (every 20 min) from 2200 h to 0800 h. RESULTS Basal IGF-I levels in DCM were lower (P = 0.000039) than in CS (135.2 ± 46.8 vs. 193.7 ± 63.7 μ/l), whereas, basal IGFBP-3 and GHBP2 levels in DCM and CS were similar (2.5 ± 1.3 vs. 2.6 ± 0.5 mg/l and 25.3 ± 3.6 vs. 28.3 ± 5.0%; P = 0.95 and P = 0.085, respectively). After 4 days of 5.0 μ/kg/day rhGH administration, IGF-I levels in DCM (215.4 ± 82.0 μ/l; P = 0.0023 vs. baseline) remained lower (P = 0.027) than those in CS (280.0 ± 80.7 μ/l; P = 0.000080 vs. baseline). After 10.0 μ/kg/day for 4 days, IGF-I levels in DCM (297.2 ± 109.2 μ/l; P = 0.0033 vs. baseline) were similar (P = 0.76) to those in CS (310.9 ± 81.7 μ/l; P = 0.000060 vs. baseline). The GH response to GHRH in DCM was lower (P = 0.0022) than that in CS (hAUC0 →120: 192.0 ± 177.3 vs. 345.3 ± 191.1 μ/l/h) whereas that to HEX in DCM and CS was similar (611.0 ± 437.5 vs. 535.4 ± 302.8 μ/l/h; P = 0.95). Within the DCM group, basal and rhGH-stimulated IGF-Ievels as wel as the GH response to GHRH or HEX were not different among NYHA classes and did not show any correlation with ECHO parameters. The mGHc in DCM (1.0 ± 0.5 μ/l) was similar (P = 0.57) to that in CS (0.9=0.7 μ/l). CONCLUSIONS Our present data demonstrate that in dilated cardiomyopathy patients with severe left ventricular dysfunction basal IGF-I levels are reduced whereas the IGF-I response to low rhGH doses is preserved. These findings suggest a normal peripheral GH sensitivity in dilated cardiomyopathy. On the other hand, though nocturnal mean GH concentration in dilated cardiomyopathy patients is similar to that in normal subjects, the somatotroph responsiveness to GHRH, but not that to hexarelin, is reduced. Thus, subtle alterations in the activity of GH/IGF-I axis are present in dilated cardiomyopathy.

A 29-year-old woman with two mechanical valve prostheses was referred to our institution for sudden and self-resolved diplopia 2 weeks after childbirth. From the beginning of pregnancy, nadroparin was started instead of warfarin. The echocardiogram performed at hospital admission revealed a severe aortic prosthesis regurgitation due to incomplete leaflet apposition with a prosthetic aortic transvalvular gradient increase. Three-dimensional transoesophageal echocardiography revealed a thrombus located between the two prostheses, causing intermittent aortic valve malfunction. Intravenous heparin was started. Three days later, a second transoesophageal echocardiogram revealed a decreased aortic transvalvular gradient, but an oval thrombus adhered to the mitral prosthesis and fluctuating through the prosthetic valve was detected. Tissue plasminogen activator infusion was started. To reduce cerebral embolization, carotid filters used during artery angioplasty were placed in common carotid arteries, left and right. No complication occurred during and after the procedure. With thrombus absence at 30-min transoesophageal echocardiography, filters were removed. The patient continued intravenous heparin until achievement of a therapeutic international normalized ratio range and she was asymptomatic on discharge.

Right ventricular (RV) function plays a pivotal role in advanced heart failure patients, especially for screening those who may benefit from left ventricular assist device (LVAD) implantation. We introduce RV contraction pressure index (RVCPI) as a new echo-Doppler parameter of RV function. The accuracy of RVCPI in detecting RV failure was compared with the criterion standard, the RV stroke work index (RVSWI) obtained through right heart catheterization in advanced heart failure patients referred for heart transplantation or LVAD implantation.Right heart catheterization and echo-Doppler were simultaneously performed in 94 consecutive patients referred to our center for advanced heart failure (ejection fraction (EF) 24 ± 8.8%, 40% NYHA functional class IV). RV stroke volume and invasive pulmonary pressures were used to obtain RVSWI. Simplified RVCPI (sRVCPI) was derived as TAPSE × (RV - right atrial pressure gradient). Close positive correlation between sRVCPI and RVSWI was found (r = 0.68; P .001). With logistic regression, we found that increased sRVCPI showed an independent reduced risk (odds ratio 0.98, 95% confidence interval [CI] 0.97-0.99; P = .016) for patients to present a depressed RVSWI (0.25 mm Hg/L·m(2)). Simplified RVCPI showed high diagnostic accuracy (area under the receiver operating characteristic curve 0.94, 95% CI 0.89-0.99) and good sensitivity and specificity (92% and 85%, respectively) to predict depressed RVSWI with the use of a cutoff value of400 mm·mm Hg.In patients with advanced heart failure, the new simple bedside sRVCPI closely correlated with RVSWI, providing an independent, noninvasive, and easy tool for the evaluation of RV function.

Evaluate echocardiographic predictors of pulmonary artery hypertension (PAH) in a prospective cohort of patients with systemic sclerosis (SSc).38 patients with SSc who did not have PAH and significant left heart disease, with peak tricuspid regurgitant velocity (TRV) ≤ 2.8 m/sec and systolic pulmonary artery pressure (sPAP)40 mmHg on echo Doppler were enrolled. Patients underwent: clinical assessment, NT-proBNP, and DLco measurements. Echo Doppler evaluation included right ventricular (RV) dimensions, tricuspid annular plan systolic excursion, fractional area change, tricuspid DTI systolic velocity, Tei index, pulmonary flow acceleration time (AcT), ratio of TRV to RV outflow tract time-velocity integral (TVI) and a parameter of disturbed RV ejection (TRV/AcT). After a planned 12-month follow-up we evaluated the predictive value of these parameters for the development of PAH, as demonstrated by right heart catheterization (RHC). Criteria for RHC were TRV ≥ 3 m/sec or sPAP ≥ 40 mmHg.Four patients developed PAH. Only TRV/TVI and TRV/AcT ratios significantly predicted PAH development (TRV/TVI ratio ≥ 0.16 [predefined and ROC confirmed]: OR 99, CI 95%: 4.865-2015, P = 0.004; TRV/AcT ratio ≥ 0.022 [predefined and ROC confirmed]: OR 12.68, CI 95% 1.163-379.3, P = 0.036). Both parameters showed a good diagnostic power (TRV/TVI ratio: ROC area 79%, sensitivity 75%, specificity 97% and diagnostic accuracy 94.74% for cutoff value of 0.16; TRV/AcT ratio: ROC area 75%, sensitivity 75%, specificity 71% and diagnostic accuracy 72% for cutoff value of 0.022).This prospective study identified increased values of the two ratios TRV/TVI and TRV/AcT as predictors of PAH in SSc.

BackgroundThe Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine involved in many physiological processes, including skeletal muscle, placenta and liver development. Little is known about its role and that of Met tyrosine kinase receptor in cardiac development.Methodology/principal findingsIn this study, we generated two transgenic mice with cardiac-specific, tetracycline-suppressible expression of either Hepatocyte Growth Factor (HGF) or the constitutively activated Tpr-Met kinase to explore: i) the effect of stimulation of the endogenous Met receptor by autocrine production of HGF and ii) the consequence of sustained activation of Met signalling in the heart. We first showed that Met is present in the neonatal cardiomyocytes and is responsive to exogenous HGF. Exogenous HGF starting from prenatal stage enhanced cardiac proliferation and reduced sarcomeric proteins and Connexin43 (Cx43) in newborn mice. As adults, these transgenics developed systolic contractile dysfunction. Conversely, prenatal Tpr-Met expression was lethal after birth. Inducing Tpr-Met expression during postnatal life caused early-onset heart failure, characterized by decreased Cx43, upregulation of fetal genes and hypertrophy.Conclusions/significanceTaken together, our data show that excessive activation of the HGF/Met system in development may result in cardiac damage and suggest that Met signalling may be implicated in the pathogenesis of cardiac disease.

Aims To compare in a randomized and prospective fashion the outcome of atrial fibrillation (AF) ablation either after one procedure or after two procedures using the Carto-XP vs. the Carto-Merge mapping system in two different AF populations. Methods and results Two hundred and ninety-nine patients with paroxysmal and persistent AF were enrolled in the study. One hundred and fifty patients with paroxysmal or persistent AF were randomly assigned to the Carto-Merge group and 149 patients to the Carto-XP group. The Carto-Merge patients underwent magnetic resonance imaging (MRI) of left atrium (LA) the day before the ablation. The ablation scheme included electrical disconnection of the pulmonary veins plus linear lesions. In the Carto-Merge patients, the three-dimensional MRI of the LA reconstruction merged with the electroanatomical map, and in the Carto-XP patients, the electroanatomical map guided the procedure. Considering the overall population with paroxysmal AF, 54% maintained sinus rhythm (SR), whereas in the persistent AF population, SR was present in 43% of the patients at the 12-month follow-up. In patients with paroxysmal AF, 52% in the Carto-XP group and 55% in the Carto-Merge group maintained SR without drugs. Procedure durations and exposure to X-ray in the Carto-XP group were 94.6 ± 17.5 and 40.4 ± 13.5 min, respectively. In the Carto-Merge group, duration and X-ray exposure were 89 ± 41.6 and 22.1 ± 11.4 min, respectively. Considering the patients with persistent AF at the12-month follow-up, 44% in the Carto-XP group and 42% in the Carto-Merge group maintained SR without drugs. Procedure durations and X-ray exposure in the Carto-XP group were 102.9 ± 22.9 and 58 ± 8.7 min, respectively. In the Carto-Merge group, both duration and X-ray exposure were 114.4 ± 50.9 and 28.8 ± 14.3 min, respectively. Conclusion Image integration using Carto-Merge in patients undergoing catheter ablation for paroxysmal and persistent AF does not significantly improve the clinical outcome, but shortens the X-ray exposure.

Exhaled nitric oxide (NO) levels may be elevated in patients with liver cirrhosis and autoimmune diseases. Primary biliary cirrhosis (PBC) is often associated with keratoconjunctivitis sicca (Sjogren syndrome [SS]), an extrahepatic autoimmune manifestation. The aim of this study was to evaluate the source of increased exhaled NO (ie, alveolar vs airway) in patients with PBC, whether associated with SS or not, and to evaluate its impact on oxygenation abnormalities.Observational controlled study.University hospital.The fractional alveolar NO concentration (FANO) and airway flux of NO (QbrNO) were measured by the multiple flows technique in 34 patients with PBC, 12 with associated SS, and were compared to 20 control subjects and 12 patients with primary SS.FANO was significantly higher in patients with PBC, associated with SS (mean [+/- SEM], 8.9 +/- 0.8 parts per billion [ppb]) or not (mean, 7.7 +/- 0.7 ppb) compared to healthy control subjects (mean, 4.6 +/- 0.5 ppb; p0.001) and to patients with primary SS (mean, 4.3 +/- 0.5 ppb; p0.001). FANO was significantly higher in cirrhotic patients with increased alveolar-arterial oxygen pressure difference (P[A-a]O(2)) compared to patients with normal P(A-a)O(2) values (9.8 +/- 0.8 vs 7.3 +/- 0.7, respectively; p = 0.018). When compared with control subjects and with patients with PBC not associated with SS, QbrNO was significantly increased in patients with both primary SS and SS associated with PBC.Increased exhaled NO levels found in PBC are from both alveolar and airway sources in patients with associated SS, but only FANO is associated with oxygenation impairment.

BACKGROUND: Pulmonary hypertension (PH) is an important limiting factor of exercise tolerance in patients with mitral stenosis (MS). We wished to investigate the relationship between respiratory nitric oxide (NO), a potent vasodilator, and exercise tolerance in patients with moderate MS. In the same patients, we wondered whether acute change in pulmonary hemodynamics could affect respiratory NO. METHODS: Ten patients with moderate MS (valve area 1.4+/-0.2 cm(2)) were studied at rest, during incremental cycle ergometry exercise, and during dobutamine stress echocardiography (DSE). The concentration of NO in exhaled air (FE(NO)) and NO output (V'(NO)) were measured at baseline, at the end of exercise, and at the end of DSE. Eight healthy subjects served as normal controls for NO output during exercise. RESULTS: During exercise, FE(NO) decreased both in patients and in controls, while V'(NO) increased in both. At the end of exercise, both VO(2) max and V'(NO) were significantly higher in controls than in patients. The increase in V'(NO) during exercise was significantly correlated with VO(2) max, both in patients and in controls. During DSE, cardiac output (CO), pulmonary artery pressure (PAP), and mitral valve gradient increased. No changes in mean FE(NO), V'(NO), or ventilation were observed during DSE. There was a significant inverse correlation between FE(NO) and mitral valve gradient at the end of DSE. CONCLUSIONS: In patients with moderate MS, exercise performance is correlated with respiratory NO output. In the same patients, during DSE, the increase in CO, which is not accompanied by an increase in ventilation, is not associated with an increase in respiratory V'(NO).

Hepatopulmonary syndrome--a complication of chronic liver disease-is characterised by hypoxaemia, which results from widespread intrapulmonary vascular dilatations. Amplified production of pulmonary nitric oxide is thought to be important in development of this disorder in patients with liver cirrhosis. Here, we report a 64-year-old man with hepatopulmonary syndrome associated with hepatitis-C-virus-related cirrhosis. We gave the patient nebulised N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, which enhanced oxygenation (arterial oxygen pressure increased from 6.98 to 9.45 kPa). After L-NAME, the distance the patient could walk in 6 min rose by 92 m. Administration of L-NAME by aerosol might offer a new approach to treatment of hepatopulmonary syndrome.

Background: TAVI is by now a valid therapeutic option in elderly patients (pts) with severe symptomatic aortic stenosis considered at high risk or with contraindication to aortic valve replacement (AVR). The impact of postprocedural leaks on mortality is still debated. Methods: Since May 2008 to July 2011, 100 consecutive pts underwent TAVI (60 Edwards Sapien Valve, 40 CoreValve). Transthoracic echocardiogram (TTE) was performed before discharge and after 3 months. Prosthesis insufficiency (PI) was considered significant if at least mild according to ASE and EAE recommendations. The aim of the study is to evaluate the effect of postprocedural periprosthetic and intraprosthetic leaks on mortality. Results: Retrograde approach was performed in 67 pts, while 33 pts benefited from the transapical access. Predischarge TTE was performed in all pts, and 24 had at least mild PI: 17 (70.8%) periprosthetic, 3 (12.5%) intraprosthetic, and 4 (16.7%) mixed. VARC mortality was 15%. At 3-month follow-up (range 36–126 days), all 85 alive pts underwent a TTE at our institution. Significant leaks were found in 24 (28.2%) pts: 18 (75%) periprosthetic, 1 (4.2%) intraprosthetic, and 5 (20.4%) mixed. The univariate analysis with Yatescorrected χ showed that postprocedural PI affects 1-year mortality (RR 2.68, IC 1.39–5.18, P=.009). Subgroups analysis showed an increased incidence of leaks in CoreValve group compared to the Edwards Sapien group (28/36 vs. 24/49, P=.02). Conclusion: Periprosthesis leaks, affected also by prosthesis choice, increase 1-year mortality in patients undergoing TAVI. These data confirm the actual limits of this procedure compared to AVR. In the near future, new technologies and devices could help to improve results.

This study was planned to investigate the effect of ischemic dysfunction of the free wall of the right ventricle on right and left ventricular performance in the presence of a normally contracting interventricular septum. The experiments were performed in 6 anesthetized dogs in which echocardiogram, electrocardiogram, aortic blood pressure and left and right ventricular pressure were recorded. In the dog, the contractility of the septum is not affected by the occlusion of the right coronary artery which does not perfuse this part of the myocardium. Complete occlusion of the major individual ventricular branches and partial occlusion of the main right coronary artery did not impair right ventricular performance. Only complete occlusion of the main artery affected right and left ventricular function as revealed by echocardiogram. Reduced output by the ischemic right ventricle caused a reduction in left ventricular diastolic and systolic dimensions and in left ventricular developed pressure without any effect on left ventricular end-diastolic pressure.

Nitric oxide may be involved in the impaired oxygenation of cirrhotic patients, a condition that improves in most patients after liver transplantation.To compare oxygenation and nitric oxide concentrations before and after liver transplantation.Before-and-after observational study.Academic medical center.18 patients with cirrhosis and no obvious cardiopulmonary disease who underwent successful orthotopic liver transplantation.Orthotopic liver transplantation.Blood gas analysis, measurement of exhaled nitric oxide, contrast-enhanced echocardiography, and pulmonary function tests.Before transplantation, the mean (+/- SD) exhaled nitric oxide concentration was higher in patients than in normal controls (13 +/- 4.9 parts per billion [ppb] compared with 5.75 +/- 1.9 ppb; P0.001). After transplantation, the alveolar-arterial oxygen gradient significantly decreased (from 17.3 +/- 7.1 mm Hg to 9 +/- 5.2 mm Hg; P0.001), as did the exhaled nitric oxide concentration (from 13 +/- 4.9 ppb to 6.2 +/- 2.8 ppb; P0.001). The decrease in the exhaled nitric oxide concentration was significantly correlated with the decrease in the alveolar-arterial oxygen gradient (r = 0.56; P = 0.014). Five patients met the criteria for the diagnosis of the hepatopulmonary syndrome before transplantation; the syndrome was cured by transplantation.The correlation between the decrease in exhaled nitric oxide concentration after liver transplantation and the improvement in oxygenation reinforces the hypothesis that nitric oxide is an important mediator of impaired oxygenation in patients with cirrhosis.

Impaired arterial oxygenation, ranging from increased alveolar-arterial oxygen gradient (AaDo2) to hypoxemia, is commonly present in patients with cirrhosis. Nitric oxide (NO), through pulmonary vasodilatation, may play a major role in the oxygen abnormalities of cirrhosis. Our aim was to study the relationship between NO production and O2 abnormalities in 45 nonsmoking patients with cirrhosis and without major cardiovascular and respiratory diseases. Intrapulmonary shunting was detected by contrast-enhanced (CE) echocardiography. Lung volumes and diffusion, arterial blood gas analysis, serum NO2-/NO3-, NO output in the exhaled air, and cardiac index by the echocardiographic method were determined in all patients. Twenty-seven (60%) patients had an abnormally increased (15 mm Hg) AaDo2. The mean values of exhaled NO output and serum NO2-/NO3- were significantly higher in cirrhotic patients than in controls (252 +/- 117 vs. 75.2 +/- 19 nL/min/m2, P.0001; and 47.5 +/- 29.4 vs. 32.9 +/- 10.1 micromol/L, P.02, respectively). In all patients, there was a significant correlation between exhaled NO and AaDo2 (r = .78, P.0001). Twelve patients (26.6%) were found to have CE-echocardiographic evidence of intrapulmonary shunting (positive CE-echo). Nine patients were considered to have hepatopulmonary syndrome (HPS) on the basis of an AaDo215 mm Hg and positive CE-echo. These 9 patients had a mean value of exhaled NO significantly higher than patients without HPS (331 +/- 73.2 vs. 223 +/- 118.4 nL/min/m2, P.05). In all patients, cardiac index was positively correlated with exhaled NO (r = .47, P.001) and with serum NO2-/NO3- (r = .43, P.01). The results suggest an important role of NO in the oxygenation and circulatory abnormalities of patients with cirrhosis.

The survival rate of heart transplant patients is increasing, underlying the need for accurate predictors of adverse events during clinical follow-up. Myocardial performance index (MPI) is a Doppler-derived index of combined systolic and diastolic function: we assessed the prognostic role of MPI in survival of patients1 year after heart transplantation (HT). A total of 152 consecutive HT patients referred to our institution were enrolled in this prospective study. Primary endpoints were cardiac death and a composite of major adverse cardiac events (MACE). During follow-up (69 ± 22 months), 68 (44.7%) patients had an adverse event and 20 (13.15%) patients died. Patients with MACE during follow-up showed lower EF (57.3 ± 9.3 vs. 63 ± 6.1; P0.001) and higher MPI (0.45 ± 0.19 vs. 0.31 ± 0.13; P0.001) at enrolment. MPI and EF were independently related to MACE (OR = 2.2; 95% confidence interval [CI] = 1.01-5.1; and OR = 6.6; 95% CI = 3.5-11.2, respectively) and showed strong diagnostic power (MPI: receiver operating characteristic [ROC] area = 79%, with 79% sensitivity and 81% specificity; EF: ROC area = 77%, with 54% sensitivity and 91% specificity) in the subsequent year. Patients with EF50% and MPI0.45 at enrolment showed 75% event-free survival 5 years after HT. In HT patients, MPI combined with EF was an accurate means of predicting long-term adverse events.