Left atrial appendage morphology at transesophageal echocardiography: how to improve reproducibility?

BACKGROUND: 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. METHODS: 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. RESULTS: By conventional TEE the agreement among operators on LAA morphology classification was poor (ρ<0.13). 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). CONCLUSIONS: 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.

Left Atrial Function after Atrial Fibrillation Cryoablation Concomitant to Minimally Invasive Mitral Valve Repair: A Pilot Study on Long-Term Results and Clinical Implications.

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 ± 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 ± 13.1 mL/mq and 25.1 ± 7.3%) were significantly better than in those with AF relapses (76.8 ± 16.2 mL/mq and 17.5 ± 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 ± 17.8 mL/mq, with total LA emptying fraction derived from volumes 23.6 ± 13.7%; patients with strokes in SR showed very enlarged LA volume (>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.

Noninvasive Assessment of Hemodynamic Status in HeartWare Left Ventricular Assist Device Patients: Validation of an Echocardiographic Approach.

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 < 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. 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 thrombi relate to easily accessible clinical parameters in patients undergoing atrial fibrillation transcatheter ablation: A multicenter study.

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, CHA2DS2-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 CHA2DS2-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 CHA2DS2-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 CHA2DS2-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.

Does asymptomatic recurrent diffuse capillary C4d complement deposition impair cardiac allograft function?

BACKGROUND: The aim of this study was to evaluate whether asymptomatic recurrent (≥2) antibody-mediated rejection (pAMR 1+), defined as diffuse capillary C4d immunostaining (rAMR) on endomyocardial biopsies (EMBs), during the first year after heart transplantation impairs left ventricular (LV) function. METHODS: Fifty-four consecutive heart transplant patients who survived well (New York Heart Association ≤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 1 year after transplantation, was development of LV dysfunction and/or adverse remodeling according to pre-specified echo parameters. RESULTS: During the first year from transplantation, rAMR occurred in five 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.

Cardiovascular magnetic resonance as a reliable alternative to cardiovascular computed tomography and transesophageal echocardiography for aortic annulus valve sizing.

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).

Cardiac concentric hypertrophy promoted by activated Met receptor is mitigated in vivo by inhibition of Erk1,2 signalling with Pimasertib.

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.

Prognostic incremental role of right ventricular function in acute decompensation of advanced chronic heart failure.

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 <20 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 (P < 0.01). CONCLUSIONS: 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.

Results of Cryoablation for Atrial Fibrillation Concomitant With Video-Assisted Minimally Invasive Mitral Valve Surgery.

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.

Supraventricular Arrhythmias in Patients With Pulmonary Arterial Hypertension.

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.

Left Atrial Function After Radiofrequency Catheter Ablation of Atrial Fibrillation--Can Pre-Ablation Function Predict Contractile Improvement During Follow-up?

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 <40% had significant improvement in atrial performance (LAEF, P=0.01; LAAEF, P=0.036; LAEI, P=0.004); a significant negative correlation between baseline LAEF and LA function improvement was observed (r=-0.62; 95% CI: -0.83 to -0.26; P(r=0)<0.002). CONCLUSIONS: Baseline LAEF is an independent predictor of LA function recovery after RFCA. The beneficial effect of AF ablation is most evident in patients with LAEF<40%.

New echocardiographic insights in short QT syndrome: More than a channelopathy?

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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 fraction <55% (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. CONCLUSION: 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.

Prediction of atrial fibrillation recurrence after cardioversion in patients with left-atrial dilation.

AIMS: 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). METHODS AND RESULTS: 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), EF > 35%, 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 duration >90 days before CV (P < 0.01), septal e' <8 cm/s (P 0.03), and septal E/e' ratio ≥11 (P < 0.001) 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 duration >90 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). CONCLUSION: In this population with symptomatic persistent AF and LA enlargement, septal E/e' ratio ≥11 and AF duration >90 days predicted AF recurrence at 3 months.

Postpartum valve thrombosis: a happy ending thriller.

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.

Bleeding rate during oral surgery of oral anticoagulant therapy patients with associated systemic pathologic entities: a prospective study of more than 500 extractions.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Prognostic role of myocardial performance index on long-term survival after heart transplantation: a prospective study.

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 patients >1 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; P < 0.001) and higher MPI (0.45 ± 0.19 vs. 0.31 ± 0.13; P < 0.001) 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 EF > 50% and MPI < 0.45 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.

STAT3 activity is necessary and sufficient for the development of immune-mediated myocarditis in mice and promotes progression to dilated cardiomyopathy.

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.

Lead vegetations in patients with local and systemic cardiac device infections: prevalence, risk factors, and therapeutic effects.

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 <6 months, renal disease, dialysis, abnormal chest X-ray, fever at admission, pulmonary symptoms, white blood cell (WBC) count, erythrocyte sedimentation rate, C-reactive protein increase and positive blood samples were related to LV. Risk of vegetations was reduced by antibiotic prophylaxis. Multivariate analysis indicated that renal failure and increased WBC count were related to LV. CONCLUSION: Lead vegetations were frequently observed in patients with only local symptoms. Therefore, TEE should be mandatory in all patients undergoing LE for infective indications.

Impact of TAVI on mitral regurgitation: a prospective echocardiographic study.

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 pre-TAVI 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.

Echocardiographic evaluation of right ventricular stroke work index in advanced heart failure: a new index?

BACKGROUND: 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. METHODS AND RESULTS: 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 of <400 mm·mm Hg. CONCLUSIONS: 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.