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

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

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

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

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

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

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

We report a case of a 37-years-old man, affected by thalassemia major, hypogonadotropic hypogonadism, chronic HCV-hepatitis, diabetes mellitus, severe osteoporosis, prior septic pulmonary embolism and pulmonary artery hypertension was performed a long-term treatment with highdose of sildenafil (120 mg/die) with reduction of pulmonary arterial systolic pressure and of the dyspnea.

We report the case of an 81-year-old man who presented with chest pain after an adulterous intercourse with a young woman. At echocardiography a typical apical ballooning phenomenon was detectable and completely reversed after one week. Coronary angiography did not show significant coronary atherosclerosis.

We report a case of paroxysmal supraventricular tachycardia complicating Tako-Tsubo cardiomyopathy. We hypothesize that increased adrenergic tone supposedly underlying transient apical ballooning syndrome may facilitate the onset of paroxysmal supraventricular tachycardias in predisposed patients.

We report the case of a 41-year-old man with acute myocardial infarction showing first ST elevation in V1-V6-DI-aVL leads followed by a typical V2-V4 ST depression (concomitant occlusion of proximal diagonal branch with an incomplete left anterior descending occlusion) and DII-DIII-aVF ST elevation. At coronary angiography, a proximal left anterior descending coronary stenosis with right coronary artery thrombosis was found.

Cardiac troponin represents a sensitive and specific marker of ischemic myocardial damage in adult and neonatal populations. Cardiac function in neonates could be influenced by the severity of respiratory distress and its ventilatory management. This short review summarizes the experimental and clinical evidence regarding the role of cardiac troponin in assessment of cardiac function, in following findings: neonatal intensive care, respiratory distress syndrome, asphyxia, congenital heart disease and post cardiac surgery.

We report a case of a 51-year-old man with chest pain, sweating, and breathlessness for a few hours. He was a smoker, reporting neither history of heart disease nor other cardiovascular risk factors: he was not receiving any drug therapy. At emergency room, an electrocardiogram (ECG) showed an unusual type of ST-segment depression in V2-V6 leads, thus suggesting an involvement of left anterior descending (LAD) coronary artery (Fig. 1). Systolic arterial blood pressure at admission was 90/60 mm Hg, and physical examination was unremarkable. Chest radiography showed no sign of pulmonary congestion, with a normal cardiac transverse diameter. Suddenly, ventricular fibrillation appeared, necessitating a 250 Joule DC shock to restore sinus rhythm. After a while, a second ECG showed ST-segment elevation in V2-V6—DI leads associated with an intraventricular delay of conduction. The patient was immediately transferred into the coronary care unit where a third ECG unexpectedly showed ST-segment elevation in inferior leads (Fig. 2), mimicking an inferior acute myocardial infarction (AMI). The patient immediately underwent systemic fibrinolysis with tenecteplase, able to reverse any sign of ST-segment elevation (Fig. 3). Echocardiography showed anterior, septal, apical, and lateral akinesis, with mild mitral regurgitation and left ventricular ejection fraction b35%. A coronary angiography performed within 24 hours unexpectedly showed a severe narrowing at proximal LAD (Fig. 4): no other signs of severe coronary atherosclerosis were present. After coronary angioplasty with sirolimus-eluting stent, the patient was discharged with aspirin, clopidogrel, statins and β-blockers. Negative V2-V6–DI-aVLTwaves were

Alcoholic patients who consume >90 g of alcohol a day for >5 years are at risk of developing asymptomatic alcoholic cardiomyopathy (ACM). Those patients who continue to drink may become symptomatic and develop signs and symptoms of heart failure (HF). This distinct form of congestive HF is responsible for 21-36% of all cases of non-ischaemic dilated cardiomyopathy in Western Society. Without complete abstinence, the 4 year mortality for ACM is close to 50%. This short review summarizes the experimental and clinical evidence regarding the role of alcohol in the pathophysiology of ACM and HF.

The prognosis of Tako-Tsubo syndrome (TTS) is believed to be favorable. In most of the cases, there is a complete recovery of left ventricular (LV) function and of symptoms, but previous cases have been described with low-output syndrome, deaths within the first 24 h from acute heart failure, and some deaths due to LV free wall rupture. We describe a case of a patient with TTS who died after right ventricular (RV) free wall rupture. Furthermore, this report suggests that cardiac magnetic resonance imaging with echocardiography might be a useful integrated imaging diagnostic tool for the diagnosis of TTS, ruling out acute coronary syndrome.

Background Mitral annular calcification (MAC) is a common echocardiographic finding. Caseous calcification of the mitral annulus (CCMA) is, on the other hand, a less known, rarely described variant, seen as a round mass with a central echolucent area composed of a puttylike admixture of fatty acids, cholesterol, and calcium. The aims of this study were to assess the prevalence of CCMA, assess its morphologic changes over the course of time, and evaluate the patients' characteristics and clinical outcome on follow-up. Methods Between January 2002 and December 2004, 20,468 consecutive patients, referred for transthoracic echocardiography, were included in the study. All patients underwent echocardiographic examinations. Four echocardiographic laboratories participated in the registry. CCMA was defined as a large, round, echodense mass with smooth borders located in annular region, without acoustic shadowing and with central areas of echolucencies resembling liquefaction. Results A total of 2169 (10.6%) patients were given the diagnosis of MAC by 2-dimensional echocardiography. A total of 14 patients (0.64% of all MACs, 0.068% of all studies) were given the diagnosis of echocardiographic findings compatible with CCMA. Six (43%) patients underwent transesophageal echocardiography (TEE) to better evaluate the nature of the mass. A complete TEE examination was performed using 2-dimensional and color flow Doppler, and the best visualizations of the mass were performed by midesophageal 4-chamber view, midesophageal 2-chamber view, and midesophageal long-axis view. More detailed imaging of the masses, above all a better visualization of the central areas of echolucency, the assessment of the posterior mitral leaflet motion, and the assessment of the correct location of the mass was achieved by TEE views. All calcifications were confined to the mitral annulus. The most common symptom was palpitation, which occurred in 43% of the patients. During a mean follow-up of 3.4 ± 1.2 years, one patient died. The cause was unrelated to the annular mass; it was the result of neoplasm. During the follow-up period, in 6 (43%) cases, the studies changed, in regard to the features of CCMA, in comparison with baseline studies, thus likely suggesting a changeable condition. Conclusions This study confirms prior observations that CCMA is a rare and benign condition. It illustrates the potential role of TEE in confirming the precise location of the lesion and in more clearly defining the extent of the involvement of the posterior mitral leaflet. There were no typical clinical characteristics in patients with CCMA although the absolute number of patients with CCMA was too small to be statistically significant. However, CCMA does tend to occur in older patients and all 14 patients with CCMA in this study had hypertension. CCMA may be a dynamic process based on the observation that 3 patients with MAC progressed to CCMA and 3 patients with CCMA reverted back to MAC during the study period. To avoid diagnostic mistakes such as tumor, abscess, or thrombus among echocardiographers, it is important for us to consider a more widespread knowledge of this rare lesion.

Real-time three-dimensional echocardiography (RT3DE) is the only on-line 3D method based on real-time volumetric scanning, as compared with other 3D imaging techniques such as computed tomography and magnetic resonance imaging, which are based on post-acquisition reconstruction and not on volumetric scanning. In recent years, several studies have revealed possible advantages of 3DE in daily clinical practice. The aim of this manuscript is to give a brief review of the development of the clinical applications of RT3DE.

Aim To investigate correlations between plasmatic concentrations of acute phase proteins (APPs) and left ventricular systolic function during the early phase of acute myocardial infarction. Methods Plasmatic concentrations of alpha-1-anti-trypsin (A1AT), alpha 1 glyco-protein (A1GP), haptoglobin (HG), caeruloplasmin (CP) and C-reactive protein (CRP) were evaluated in 123 patients with ST elevation acute myocardial infarction (STEMI) within 12 h after onset of chest pain. Systolic function was assessed with bi-dimensional echography and incidence of in-hospital adverse events was compared to APPs levels. Results A1AT, A1GP, HG and CP showed a statistically significant correlation with admission CRP concentrations (P < 0.001). Left ventricular ejection fraction inversely correlated with plasmatic concentrations of A1GP, A1AT, CP and HG. Incidence of acute heart failure correlated with values of APPs and, in a stepwise analysis, CP values were the most significant markers of acute heart failure. Conclusions Systolic dysfunction in STEMI patients seems to be associated with an inflammatory response featured by a rise in plasmatic concentration of APPs; increase in APPs concentrations seems to own a short-term prognostic relevance.

Aim:To investigate release of some inflammatory cytokines (Cys) after coronary angioplasty and its links with coronary atherosclerosis. Methods:Twenty-seven consecutive subjects with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) were enrolled in the study: serial blood samples were taken in order to evaluate plasma concentrations of Interleukin (IL)-2, IL-10, IL-18, TNFα, and IFNγ just before PCI at 12 and 24 hours. Patients were then divided, considering balance between each inflammatory Cy and IL-10, an antiinflammatory Cy, into four groups, ranging from a prevalent antiinflammatory response (stable inflammatory Cy–increasing IL-10 values) to a marked inflammatory imbalance (increasing inflammatory Cy–stable IL-10 values). Results:All Cys showed significant increases in plasma concentrations if compared with baseline values. Release curves were not significantly different when comparing subjects with ST-elevation myocardial infarction (STEMI) versus unstable angina–non-STEMI (UA-NSTEMI), diabetics versus controls. Subjects with marked inflammatory response showed a higher incidence of stenosis on left anterior descending (LAD) coronary artery (IL-2 χ2 and IFNγ P < 0.05); Cy release was higher in patients with multivessel coronary disease (IL-2 and IFNγ, ANOVA P < 0.01). Correlations were also referable between Cys and myocardial enzyme release. Subjects treated with sirolimus-eluting stents (SES) showed significantly lower Cy periprocedure ratio if compared with those treated with bare metal stents. Conclusions:A significant Cy release is detectable after PCI: inflammatory response seems to correlate with both PCI due to plaque instabilization and coronary atherosclerosis. A blunted inflammatory response is detectable in subjects treated with SES.

BACKGROUND: The majority of studies demonstrating the diagnostic potential of three-dimensional (3-D) echocardiography have been conducted on selected series of patients in research laboratories. AIM: To investigate the feasibility and usefulness of real-time 3-D transthoracic echocardiography in daily routine practice. METHODS: Two hundred consecutive patients underwent standard two-dimensional (2-D) transthoracic echocardiography (TTE) and real-time (RT) 3-D TTE with a commercially available ultrasound system (Sonos 7500 LIVE 3D, Philips Medical Systems). The quality of 3-D acquisitions and post-processed images was graded as: bad, satisfactory, good and demo. In each case, the results of 3-D TTE were compared with 2-D images to disclose additional qualitative information provided by 3-D examination. An additional qualitative information score was given for each cardiac structure. RESULTS: The mean time of the 3-D examination was 11+/-4 min. The mean time of 2-D transthoracic studies in our laboratory is 25 min and the total time in this series was therefore approximately 36 min. The mean number of acquisitions in our series was 11.5 per patient. The quality was evaluated as bad/insufficient in 7.0%, satisfactory/sufficient in 29.6%, good in 40.2% and demo in 23.2% of all datasets and reconstructions. The structures with greater additional qualitative information scores comprise the anterior and posterior mitralic leaflets, antero-lateral and postero-medial papillary muscles and leaflets of tricuspid valve. The intra- and interobserver reproducibility of quality grading was good and there are few interobserver discrepancies, which were resolved by two physicians, experienced in 3-D echocardiography, not involved in the study. CONCLUSIONS: RT 3-D TTE may be used in clinical settings with high feasibility rate and may provide additional, clinically quite relevant qualitative information. This technique may expand the abilities of non-invasive cardiology and open new doors for the evaluation of cardiac disease.

Background C-reactive protein (CRP) plasma levels increase in patients with acute coronary syndrome (ACS). The role and implications of increased plasma concentrations of other acute phase proteins (APPs), such as alpha-1-antitrypsin (A1AT), alpha-1 glycoprotein (A1GP), haptoglobin (HG), ceruloplasmin (CP), and C3c and C4 complement fraction, in patients with ACS are still not completely defined. Methods A total of 218 consecutive patients with ACS were included in the study, 185 with acute myocardial infarction (AMI) and 33 with unstable angina (UA). In all patients, A1AT, A1GP, HG, CP, C3c and C4 complement fraction, and CRP were evaluated within 12 h after the onset of symptoms. Sixty-two patients with AMI underwent coronary angiography. Results APPs showed a significant correlation with CRP concentrations. Patients with AMI had higher concentrations of A1AT and HG than UA patients. Cholesterol levels were correlated with APPs in patients with AMI. Patients with three coronary vessel disease or LAD disease had significantly higher C3c concentrations. Coronary collateral flow was associated with higher A1GP and CP concentrations, and total coronary occlusion with A1AT and CP. Conclusions APPs were correlated with CRP concentrations in subjects with ACS. The increase in APPs in patients with ACS seems to be linked to the entity of myocardial damage and coronary atherosclerotic burden.

Introduction: There are some evidences that in patients with systemic sclerosis the ratio between Forced Vital Capacity (FVC) and diffusing capacity of carbon monoxide (DLCO) could be, with others data, a good predictor of Pulmonary Hypertension (PH) when it is higher than 1.5. The aims of this study was to evaluate if also in patients without scleroderma this index could be used. Methods: Patients afferent to Pulmonary Hypertension ambulatory of University of Foggia with suspect of PH, underwent to spirometry and DLCO test before right heart catheterization (RHC), FVC%/DLCO% was then calculated. In accord with the results of RHC, sensibility and specificity was then calculated. Results: 71 patients were enrolled and according Mean Pulmonary Arterial Pressure (PAPm) divided in two groups: 27 were PH negative (PAPm= 18,96 ± 4,78 mmHg) while 44 were PH positive (PAPm= 40,43 ± 14,18). Patients were matched for age, sex and BMI. Any difference rose between FVC%/DLCO% in two groups (1,71±0,69 vs 2,20±1,16; p=0,27). Even if there was a slight correlation between FVC%/DLCO% with PAPm and Cardiac Index (IC) the results were not significant (R=0.21; p 0.35; R=-32; p=0.2 respectively). At cut-off value of 1.5 this index was quite sensible (0.72) and very low specific (0.22). Conclusion: In patients without systemic sclerosis, FVC%/DLCO% cannot be used routinely to screening patients with suspect Pulmonary Hypertension.

The Brugada electrocardiogram pattern is characterized by coved-type ST-elevation (>2 mm) in the right precordial leads. We report the case of a 62-year-old man, with bipolar disorder, admitted to the emergency department because of dyspnea and chest discomfort. The patient was on treatment with pregabalin and quetiapine. Unexpectedly, electrocardiogram at admission showed diffuse ST-elevation, more evident in inferior leads, where a Brugada-like pattern was present. The patient underwent coronary angiography with a diagnosis of suspected acute coronary syndrome. Coronary angiography, however, showed mild coronary artery disease not requiring coronary angioplasty. Echocardiography did not reveal left ventricular dysfunction or pericardial effusion. Troponin levels remained normal over serial controls. Eventually, chest radiography showed lung opacities and consolidation suggestive for pneumonia. To the best of our knowledge, this is one of the first cases showing a transient Brugada-like electrocardiogram pattern in inferior leads, probably amplified by the administration of pregabalin and quetiapine.

WereadwithgreatinterestthepaperbyShaoet al.highlightingthepossible shared mechanism underlying McConnell's phenomenon andreverseTakotsubocardiomyopathy(TTC)[1].Theauthorsbrilliantlyre-late ventricular wall overstretching induced by abrupt increase inafterload and transient ventricular dyskinesis observable in pulmonaryembolism (McConnell's sign [2]) with basal dyskinesis characterizingreverse TTC [3]. The authors also remarked that myocardial ischemiapossibly induced by increased local wall stress may further precipitatemyocardial stunning observable in both conditions, usually featuredby local dyskinesis and generally related to catecholamine toxicity inTTC. Tricuspid regurgitation, another condition potentially generatedby the right ventricular overload in pulmonary embolism, may be alsofound in the right ventricular TTC [4].We surely agree that abrupt increase in afterload may represent apossible link between McConnell's phenomenon and reverse TTC.Shao & colleagues, however, do hesitate to correlate McConnell's phe-nomenonalsowithapicalballooningobservedintypicalTTC,which,in-stead, the authors associate with lower ventricular afterload forms ofstress cardiomyopathy.Notwithstanding, some points should be considered for a completeassessment of the left ventricular afterload.First, catecholamine surge observed in TTC may be associated withperipheral vaso-constriction: apparently lower peripheral blood pres-sure values may therefore result deceptive and conceal rather highercentral arterial blood pressure values, which eventually determine theeffective left ventricular afterload [5].Second, dehydration, a condition often observed in TTC [6,7],mayprecipitatelatentleft intra-ventriculargradients,leadingtoleftventric-ularoutflowtractobstruction[8],intra-ventriculargradientsandfinallyextremely higher left ventricularapical afterloads,potentially responsi-ble for apical stretching and bulging found in TTC apical ballooning.Even in suchcase,peripheralarterialpressure levelsmaybeapparentlynormal and deceptively lower than the actual pressure burden on theleftventricularapex.Leftventricularwallstretchingmaycauseexternalcompression of coronary vessel in overstretched areas, thus leading tomyocardial ischemia and stunning, and further precipitating apical bal-looning.Themechanism,however,isusuallyselflimiting:leftventricu-lar dilation lowers ventricular pressure and after-load, and systolicfunction of dyskinetic areas gradually recovers.Third, left ventricular basal hyperkinesis may (sometimes?) pre-cede apical ballooning; given this event, the first ‘victims’ of the leftventricular overload may be represented by apical segments, whichare eventually overstretched and display characteristic apical bal-looning [5].In conclusion, shared underlying mechanisms linking McConnell'sphenomenon observable in pulmonary embolism and reverse basalTTC could not be actually excluded even in typical TTC with apicaldysfunction, just because of the presence of several conditionswhich can induce abrupt increase in the left ventricular apex afterload.Further studies and brilliant interpretative views, like those fromShao et al. [1], are surely deserved for the future to better address thisissue.Conflict of interestThe authors have no potential conflict of interest to disclose.

Background Atrial fibrillation (AF) is common in heart failure (HF). It is unclear whether AF has an independent prognostic role in HF. The aim of the present study was to assess the prognostic role of AF in HF patients with reduced ejection fraction (EF). Methods HF patients were followed in 17 centers for 3.15 years (1.51–5.24). Study endpoints were the composite of cardiovascular (CV) death and heart transplant (HTX) and all-cause death. Data analysis was performed considering the entire population and a 1 to 1 match between sinus rhythm (SR) and AF patients. Match process was done for age ± 5, gender, left ventricle EF ± 5, peakVO 2 ± 3 (ml/min/kg) and recruiting center. Results A total of 3447 patients (SR = 2882, AF = 565) were included in the study. Considering the entire population, CV death and HTX occurred in 114 (20%) AF vs. 471 (16%) SR (p = 0.026) and all-cause death in 130 (23%) AF vs. 554 (19.2%) SR patients (p = 0.039). At univariable Cox analysis, AF was significantly related to prognosis. Applying a multivariable model based on all variables significant at univariable analysis (EF, peakVO 2 , ventilation/carbon dioxide relationship slope, sodium, kidney function, hemoglobin, beta-blockers and digoxin) AF was no longer associated with adverse outcomes. Matching procedure resulted in 338 couples. CV death and HTX occurred in 63 (18.6%) AF vs. 74 (21.9%) SR (p = 0.293) and all-cause death in 71 (21%) AF vs. 80 (23.6%) SR (p = 0.406), with no survival differences between groups. Conclusion In systolic HF AF is a marker of disease severity but not an independent prognostic indicator.

Background: Oxygen uptake at the anaerobic threshold (VO 2 AT), a submaximal exercise-derived variable, independent of patients' motivation, is a marker of outcome in heart failure (HF). However, previous evidence of VO 2 AT values paradoxically higher in HF patients with permanent atrial fibrillation (AF) than in those with sinus rhythm (SR) raised uncertainties. Design: We tested the prognostic role of VO 2 AT in a large cohort of systolic HF patients, focusing on possible differences between SR and AF. Methods: Altogether 2976 HF patients (2578 with SR and 398 with AF) were prospectively followed. Besides a clinical examination, each patient underwent a maximal cardiopulmonary exercise test (CPET). Results: The follow-up was analysed for up to 1500 days. Cardiovascular death or urgent cardiac transplantation occurred in 303 patients (250 (9.6%) patients with SR and 53 (13.3%) patients with AF, p=0.023). In the entire population, multivariate analysis including peak oxygen uptake (VO 2 ) showed a prognostic capacity (C-index) similar to that obtained including VO 2 AT (0.76 vs 0.72). Also, left ventricular ejection fraction, ventilation vs carbon dioxide production slope, β-blocker and digoxin therapy proved to be significant prognostic indexes. The receiver-operating characteristic (ROC) curves analysis showed that the best predictive VO 2 AT cut-off for the SR group was 11.7 ml/kg/min, while it was 12.8 ml/kg/min for the AF group. Conclusions: VO 2 AT, a submaximal CPET-derived parameter, is reliable for long-term cardiovascular mortality prognostication in stable systolic HF. However, different VO 2 AT cut-off values between SR and AF HF patients should be adopted.

Background:In patients with chronic heart failure (HF) the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score, is a predictor of cardiovascular death and urgent heart transplantation. We investigated the relationship between age, exercise tolerance and the prognostic value of the MECKI score.Methods and Results:We analyzed data from 3,794 patients with chronic systolic HF. The primary endpoint was a composite of cardiovascular death and urgent heart transplantation. Older patients had higher prevalence of comorbidities and lower exercise performance compared with younger subjects (peak V̇O2, 925 vs. 1,351 L/min; P#x003C;0.0001; V̇E/V̇CO2slope, 33.2 vs. 28.3; P>0.0001). The rate of the primary endpoint was 19% in the highest age quartile and 14% in the lowest quartile. At multivariable analysis, the independent predictors of the primary endpoint were left ventricular ejection fraction (LVEF), eGFR, peak V̇O2, serum Na+and the use of β-blockers in patients aged ≥70 years, and LVEF, eGFR and peak V̇O2in younger subjects. The MECKI risk score increased across age subgroups, but on receiver operating characteristic curve analysis its prognostic power was similar in both patients aged ≥70 and #x003C;70 years.Conclusions:Older patients with HF are a high-risk population with lower exercise performance. The MECKI score increased according to age and maintained its prognostic value also in older patients.

Most patients with pulmonary arterial hypertension (PAH) in combination therapy suffer from depression or live alone, in absence of any at home assistance or caregiver; so, their compliance in the case of therapy with continuous infusion with epoprostenol, is actually limited. An alternative therapeutic approach for the treatment of severe PAH is therefore needed. Ivabradine, a selective inhibitor of the sinus node If channels, may be of help in improving the hemodynamics of patients with PAH and higher sinus rates. We therefore sought to verify the safety and feasibility of ivabradine and high-dose sildenafil in such patients, who often refuse continuous infusion with prostanoids.

We report the case of a 65-year-old woman with complete atrio-ventricular block who underwent orciprenaline administration and pacemaker implantation. The intervention was complicated by pneumothorax and acute left ventricular systolic dysfunction with typical apical ballooning (Tako-Tsubo like syndrome). The patient was treated with diuretics and calcium-sensitizers and completely recovered. We speculate that both external and internal catecholamine triggered an acute left ventricular impairment with typical Tako-Tsubo features.

AIMS Heart failure is a widespread syndrome involving several organs, still characterized by high mortality and morbidity, and whose clinical course is heterogeneous and hardly predictable.In this scenario, the assessment of heart failure prognosis represents a fundamental step in clinical practice. A single parameter is always unable to provide a very precise prognosis. Therefore, risk scores based on multiple parameters have been introduced, but their clinical utility is still modest. METHODS In this review, we evaluated several prognostic models for acute, right, chronic, and end-stage heart failure based on multiple parameters. In particular, for chronic heart failure we considered risk scores essentially based on clinical evaluation, comorbidities analysis, baroreflex sensitivity, heart rate variability, sleep disorders, laboratory tests, echocardiographic imaging, and cardiopulmonary exercise test parameters. RESULTS What is at present established is that a single parameter is not sufficient for an accurate prediction of prognosis in heart failure because of the complex nature of the disease. However, none of the scoring systems available is widely used, being in some cases complex, not user-friendly, or based on expensive or not easily available parameters. CONCLUSION We believe that multiparametric scores for risk assessment in heart failure are promising but their widespread use needs to be experienced.

Statins are effective in the prevention of coronary events and the treatment of acute coronary syndromes. However, their efficacy and safety in patients with heart failure (HF) is still a matter of debate. On the basis of literature evidence from subgroup analysis, retrospective, prospective cohort studies, and randomized controlled trials, in this review we try to answer the following question: Is statin therapy in HF patients for good, for bad, or indifferent? Some studies showed a negative impact of low cholesterol levels in patients with severe HF (endotoxin-lipoprotein hypothesis and coenzyme Q10 hypothesis). On the other hand, a large amount of literature demonstrates that in patients with HF, statins have a positive impact on survival and other outcomes, regardless of whether the HF was of ischemic or nonischemic origin, which is related to a combination of mechanisms (pleiotropic effects and cholesterol reduction). Much of this evidence, however, comes from observational and retrospective studies and subgroup analyses of statin use in patients with HF. Randomized clinical trials examining the efficacy of statins in HF (GISSI-HF and CORONA) did not show a benefit in mortality for patients with HF randomized to receive statins. Nevertheless, a meta-analysis found that statin therapy does not decrease all-cause or cardiovascular mortality but significantly decreases the rate of hospitalization for worsening HF and increased left ventricular ejection fraction compared with placebo.

An asymptomatic 76-year-old woman with a prior history of mitral annular calcification underwent a transthoracic echocardiographic examination for evaluation. Her risk factor for atherothrombotic disease was hypertension, and she had no prior medical history of hyperlipidemia or diabetes. She was given the following pharmacologic treatments: an angiotensin-converting enzyme (ACE) inhibitor (quinapril 5 mg), a calcium antagonist (lercanidipine 10 mg), a loop diuretic (furosemide 25 mg), and an antiplatelet agent (acetylsalicylic acid 150 mg). A round, echo-dense structure was visualized in the left atrioventricular groove region (Fig. 1, upper panels). A transesophageal echocardiographic examination (TEE) was performed to better evaluate this intracardiac mass (Fig. 1, lower panels). A large (2.14 × 1.82 cm), round, echo-dense mass containing central areas of echolucencies (central liquefaction) was revealed by TEE. No acoustic shadowing could be detected behind the mass, suggesting an absence of dense calcium deposition. The mass had sharp and distinct borders, with an echogenicity distinct from that of the adjacent myocardium (Fig. 2, left panel). The echocardiographic findings were consistent with the diagnosis of Caseous Calcification of the Mitral Annulus (CCMA). The patient was asymptomatic and was treated conservatively. A TEE conducted nine months later revealed the disappearance of the mass (Fig. 2, right panel). Figure 1 Transthoracic two-dimensional visualization of the mass: parasternal long axis view and apical four-chamber view (upper panels). Transesophageal visualization of the mass (lower panels) Figure 2 Transesophageal visualization of the mass (left panel) and trans-esophageal examination repeated nine months later, showing the disappearance of the mass (right panel). LV: left ventricle; LA: left atrium; RA: right atrium; Ao: Aorta; *: Caseous calcification ... DISCUSSION Mitral Annular Calcification (MAC) is a chronic degeneration of the mitral valve fibrous ring involving the posterior annulus. This disorder is common in the elderly, particularly in women.1 It may also occur in younger patients with advanced renal disease or other metabolic disorders that result in abnormal calcium metabolism. MAC is a consequence of atherosclerosis, with risk factors identical to those of cardiovascular disease. CCMA is a less-known and rarely described entity. This condition is an extensive “soft” periannular calcification, resembling a tumor, that is composed of an admixture of calcium, fatty acids, and cholesterol with a “toothpaste-like texture.” CCMA is often misdiagnosed as a myocardial abscess,2,3 a tumor,4,5,6 or a thrombus,7 in some cases2 leading to unnecessary explorative cardiotomy. Differential diagnosis of round echogenic structures adjacent to the left atrioventricular groove should also include infected mitral calcification, lipomatosis of the atrioventricular groove, and enlarged lymph nodes.8 In this case, a correct diagnosis was made according to clinical presentation and echocardiographic findings. Generally, valvular endocarditis is unlikely in the absence of mitral valve regurgitation, fever, or positive blood cultures or laboratory examinations for infectious disease. Clinical signs of malignancy were absent. The round, echodense lobular aspect and mobility of the mass favored the diagnosis of myxoma; however, myxomas seldom originate from valves and are often found attached to the inter-atrial septum in the fossa ovalis region. Instead, specific echocardiographic features of CCMA favor the diagnosis: a large, round echodense mass in the posterior periannular mitral region that is heterogeneous and contains central echolucent areas of necrosis. The density of the mass suggested calcification and ruled out a thrombus diagnosis. Harpaz and colleagues conducted a prospective series of echocardiographic examinations to define the echocardiographic appearance, prevalence, and prognosis of CCMA.9 They described the typical echocardiographic appearance of CCMA as a large, round, echo-dense mass with smooth borders situated in the periannular region, lacking acoustic shadowing artifacts, and containing central areas of echolucencies resembling liquefaction. They emphasized that it is possible to make a correct diagnosis by transthoracic examination alone, since no additional significant information was obtained by TEE in the 19 cases they examined. In this patient, however, TEE gave a more precise and detailed image of the mass and a better definition of the motion of the posterior mitral leaflet. Recently, we10 have confirmed that CCMA is a rare and benign condition (14 patients with CCMA, 0.64% of all mitral annular calcifications, 0.068% of all studies). This study revealed no clinical characteristics typical of patients with CCMA. However, CCMA did tend to occur in older patients, and all 14 patients with CCMA had hypertension. We suggested that CCMA may be a dynamic process based on the observation that three patients with MAC progressed to CCMA and three patients with CCMA reverted back to MAC during the study period. It is important to differentiate between CCMA and MAC; the former is a larger, well-delineated structure surrounded by clear borders with a distinct echolucency and a “softer” appearance that is less reflective and does not have acoustic shadowing. When a CCMA is perforated, a large amount of toothpaste-like, milky, caseous material is exuded from the mass. This material it is not truly calcific, but rather consists of caseous, putty-like material. After the material is removed, only a calcified envelope remains. In the case of large dense deposits of calcifications in the left atrioventricular groove, significant acoustic shadowing artifacts may rule out the diagnosis of CCMA. However, if the calcified envelope of the CCMA is very large, acoustic shadowing could result in an erroneous non-diagnosis of CCMA.10 The mechanisms involved in the liquefaction necrosis of CCMA are not well understood. Hypercholesterolemia and dissolution of lipid-laden macrophages might be implicated; high serum cholesterol is associated with MAC and may be responsible for liquefaction necrosis. The peculiarity of this case is in its spontaneous resolution ten months later. A previous similar case11 in the literature showed a spontaneous resolution of a CCMA. In this previous case, the patient had a prior history of hemodialysis treatment, but no change was made in the hemodialysis regimen. In another similar case12 with a prior history of hemodialysis treatment, the reduction of the mass was observed after treatment with low calcium hemodialysis, so the authors suggested that the acute change in the serum calcium level might have contributed to the dissolution of the mass. In our case, we hypothesize that central liquefaction and dissolution of the material through a rupture of external wall occurred without evident clinical consequences. In order to avoid misdiagnoses of CCMA as tumors, abscesses, or thrombi by echocardiographers, it is important that knowledge of this rare lesion becomes more widespread.

We report the case of a 79-year-old woman with transient left ventricular systolic dysfunction with apical ballooning (tako-tsubo like syndrome, TTS) showing an alternative newly reported "onion" shape. The patient was also characterized by atrial fibrillation and marked spontaneous echo-contrast: possible precipitating role for these conditions in TTS are discussed.

The membranes of left atrial appendage (LAA) cavity are very rare entity. To date, only five cases of a membrane involving LAA have been described. In this report, we describe two different cases: in Case 1, we show image of a "real" nonobstructive membrane within the body of LAA, but in Case 2 we show a linear image, mimicking a membrane within the body of LAA. It really is a "pitfall" of transesophageal echocardiography (TEE).

Spontaneous coronary artery dissection (SCAD) causing acute myocardial infarction is a rare event. It occurs mostly in young women without traditional risk factors for coronary artery disease, particularly during the peripartum period. We describe two occurrences of SCAD in young women in whom coronary atherosclerosis was also present. In both cases, angiography showed extended coronary dissection on the left anterior descending coronary artery (LAD), starting from an atheromasic stenosis on the middle LAD segment. Coronary dissection could complicate an unstable atheromasic plaque, especially in young women presenting with acute coronary syndrome.

A patient with bicuspid aortic valve was evaluated in our echocardiography laboratory over serial follow-up controls. Echocardiography showed trivial mitral valve regurgitation and the already known bicuspid aortic valve (Fig. 1a) with a mild regurgitation. An abnormal origin of the subclavian right artery, deriving from the distal aortic arch (Fig. 1b), was unexpectedly found. The patient underwent CT imaging of the thoracic aorta and supraaortic vessels, which confirmed the right subclavian originating from a lusory artery after a retroesophageal course (Fig. 1c–f). No further vascular abnormalities were found. The caliber of the thoracic aorta was normal as well. Lusory artery is an uncommon congenital vascular abnormality, whose incidence varies between 0.2–2.5 % [1], resulting from interruption of the fourth right aortic arch between the common carotid artery and subclavian artery and the persistence of the retroesophageal aortic arch [2]. The right subclavian artery thus originates as the last branch of the aortic arch. The condition is usually asymptomatic, even if it may cause dysphagia due to esophageal compression [1]. Complications are described, ranging from atherosclerotic disease and thrombosis [3], potentially eased by the abnormal retroesophageal course, to aneurysma [4] and arterioesophageal fistulae, and other possible serious events usually precipitated by the placement of nasogastric tubes in patients where the erosion of the esophagus was already present [5]. Despite the potentially dangerous implications, this anatomical variant does not usually require surgery, although restoring a normal course of the right subclavian artery by aortic arch repair is feasible and often recommended [1]. The lusory artery is known to be associated with other congenital abnormalities, especially Down syndrome [2]. The association with bicuspid aortic valve appears new. One of the most consistent findings in bicuspid aortic valve is dilatation of the ascending aorta, even in the absence of clinically significant valvular dysfunction. Dilatation of the ascending aorta represents a key risk factor for dissection and rupture. So, all patients with a bicuspid valve and dilatation of the ascending aorta should have evaluation of the aorta with an MRI or CT angiography. Cardiac MRI is preferred because it also provides the added benefit of information regarding LV function, LV dimensions, and assessment of valve stenosis/regurgitation severity. For those with no aortic dilatation, we tend to use only echocardiography for follow-up. To our knowledge, there is no any association between lusory artery and persistent branchial cleft cysts. Further attention should be placed in screening of paucisymptomatic vascular abnormalities in patients found to bear bicuspid aortic valve, so that the need for repair can be determined, according to the risk of potential complications and clinical conditions. L. D. Martino M. Correale (&) D. Cocco M. D. Biase N. D. Brunetti Department of Cardiology, ‘‘Ospedali Riuniti’’ OO.RR, University of Foggia, viale L Pinto, 1, 71100 Foggia, Italy e-mail: opsfco@tin.it

Patients with chronic heart failure (HF) are often rehospitalized; rehospitalization identifies subjects with a poorer quality of life and a worse prognosis. Estimates of the time intervals by tissue Doppler imaging (TDI) in patients with chronic HF has not been fully investigated, despite recent studies having explored the prognostic role of TDI-derived parameters in major cardiac diseases, such as HF. We, therefore, aimed to assess the prognostic value of time intervals evaluated by TDI in patients with chronic HF.A total of 249 patients with chronic HF enrolled in the Daunia Heart Failure Registry underwent echocardiography assessment and were followed prospectively for a mean 284 ± 210 days. Conventional echocardiography and TDI parameters were calculated; time intervals were calculated by TDI: ST (systolic time), ET (ejection time), FT (filling time), and ICT (isovolumic contraction time). We also have calculated ICT/ET and tissue myocardial performance index ([ICT+IRT]/ET).At univariate analysis, ET (RR: 0.80, 95% confidence interval [CI] 0.71-0.90, P0.001), ST (RR: 0.88, 95% CI 0.78-0.99, P0.05), FT (RR: 0.88, 95% CI 0.78-0.99, P0.05), ICT/ET (RR: 1.21, 95% CI 1.07-1.37, P0.01) were related to the occurrence of rehospitalization during follow-up. At multivariate Cox regression analysis, correlations remained significant for ET and ST (P0.05 and P0.01, respectively).Time intervals assessed by TDI may be helpful in predicting the risk of rehospitalization in subjects with chronic HF.