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Background and Importance: Chest pain is a frequent cause of patient admissions in emergency departments (EDs). Clinical scores can help in the management of chest pain patients with an undefined impact on the appropriateness of hospitalization or discharge when compared to usual care., Objectives: The aim of this study was to assess the performances of the HEART score to predict the 6-month prognostic of patients presenting to the ED of a tertiary referral university hospital with non-traumatic chest pain., Design, Settings, and Participants: From 7040 patients presenting with chest pain from 1 January 2015 to 31 December 2017, after applying exclusion criteria (ST-segment elevation >1 mm, shock, absence of telephone number) we selected a sample of 20% chosen randomly. We retrospectively assessed the clinical course, definitive diagnosis, and HEART score according to ED final report. Follow-up was made by telephone interview with discharged patients. In hospitalized patients, clinical records were analyzed to evaluate major adverse cardiac events (MACE) incidence., Outcome Measure and Analysis: The primary endpoint was MACE, comprising cardiovascular death, myocardial infarction, or unscheduled revascularization at 6 months. We assessed the diagnostic performance of the HEART score in ruling out MACE at 6 months. We also assessed the performance of ED usual care in the management of chest pain patients., Results: Of 1119 screened, 1099 were included for analysis after excluding patients lost to follow-up; 788 patients (71.70%) had been discharged and 311 (28.30%) were hospitalized. Incident MACE was 18.3% ( n  = 205). The HEART score was retrospectively calculated in 1047 patients showing increasing MACE incidence according to risk category (0.98% for low risk, 38.02% for intermediate risk, and 62.21% for high risk). Low-risk category allowed to safely exclude MACE at 6 months with a negative predictive value (NPV) of 99%. Usual care diagnostic performance showed 97.38% sensitivity, 98.24% specificity, 95.5% positive predictive value, and 99% NPV, with an overall accuracy of 98.00%., Conclusions: In ED patients with chest pain, a low HEART score is associated with a very low risk of MACE at 6 months., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Several electrocardiogram (ECG) criteria have been proposed to predict the location of the culprit occlusion in specific subsets of patients presenting with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to develop, through an independent validation of currently available criteria, a comprehensive and easy-to-use ECG algorithm, and to test its diagnostic performance in real-world clinical practice., Methods: We analyzed ECG and angiographic data from 419 consecutive STEMI patients submitted to primary percutaneous coronary intervention over a one-year period, dividing the overall population into derivation (314 patients) and validation (105 patients) cohorts. In the derivation cohort, we tested >60 previously published ECG criteria, using the decision-tree analysis to develop the algorithm that would best predict the infarct-related artery (IRA) and its occlusion level. We further assessed the new algorithm diagnostic performance in the validation cohort., Results: In the derivation cohort, the algorithm correctly predicted the IRA in 88% of cases and both the IRA and its occlusion level (proximal vs mid-distal) in 71% of cases. When applied to the validation cohort, the algorithm resulted in 88% and 67% diagnostic accuracies, respectively. In a real-world comparative test, the algorithm performed significantly better than expert physicians in identifying the site of the culprit occlusion (P = .026 vs best cardiologist and P < .001 vs best emergency medicine doctor)., Conclusions: Derived from an extensive literature review, this comprehensive and easy-to-use ECG algorithm can accurately predict the IRA and its occlusion level in all-comers STEMI patients., Competing Interests: Conflict of Interest None reported., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: Aim of this study was to evaluate the impact of cardiological and echocardiographic evaluation in addition to a standard clinical and instrumental approach on diagnostic and prognostic accuracy in patients presenting in the emergency department (ED) with chest pain (CP). Acute coronary syndromes, pulmonary embolism and acute aortic syndromes (AAS) (triple-rule-out/TRO) were considered., Methods: From 7040 patients presenting with CP from 1 January 2015 to 31 December 2017, we randomly selected a sample of 1119. We retrospectively evaluated the clinical course and definitive diagnosis according to the ED final report. A 6-month follow-up to assess incident acute cardiovascular events was made by telephone interview in discharged patients; in hospitalized patients, clinical records were analyzed to evaluate the appropriateness of admissions. Diagnostic and prognostic accuracy wasd estimated through sensitivity, specificity, positive (PPV) and negative (NPV) predictive values, according to the presence or absence of cardiological and echocardiographic consultation., Results: Complete information of 1099 patients out of 1119 was retrieved. Seven hundred and eighty-eight patients (71.70%) had been discharged, eight inappropriately (0.73%). Three hundred eleven (28.30%) had been hospitalized, 14 (1.27%) inappropriately. Diagnostic performance showed 97.38% sensitivity, 98.24% specificity, 95.5% PPV and 99% NPV, with an overall accuracy of 98.00%. In patients evaluated by the cardiologist in addition to the ED physician (n = 387) we observed an improvement of sensitivity and NPV at the expense of specificity. Among improperly discharged patients, 7/8 had normal troponin, 7/8 normal ECG and only 1 was evaluated by a cardiologist. Only one inappropriately hospitalized patient was not evaluated by a cardiologist., Conclusions: Early consultation with a cardiologist and echocardiography improves clinical judgment in doubtful cases of CP, increasing diagnostic performance mainly by reducing inappropriate patient discharge and guaranteeing a low rate of inappropriate hospitalizations., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background Acute chest pain with mild troponin rise and inconclusive diagnosis after clinical evaluation represents a diagnostic challenge. Triple-rule-out (TRO) CT may exclude coronary artery disease (CAD), as well as acute aortic syndrome and pulmonary embolism, but cannot help identify other causes of myocardial injury. Purpose To investigate the diagnostic value of a comprehensive CT protocol including both an angiographic and a late contrast enhancement (LCE) scan in participants with troponin-positive acute chest pain. Materials and Methods In this prospective study, consecutive patients with troponin-positive acute chest pain or anginal equivalent and inconclusive diagnosis after clinical evaluation (symptoms, markers, electrocardiography, and echocardiography) who underwent TRO CT between June 2018 and September 2020 were enrolled. TRO CT was performed to evaluate the presence of obstructive CAD (stenosis ≥50%), acute aortic syndrome, and pulmonary embolism. If the findings on the TRO CT scan were negative, an LCE CT scan was acquired after 10 minutes to assess the presence and pattern of scar and quantify the myocardial extracellular volume fraction. CT-based diagnoses were compared with diagnoses obtained with reference standard methods, including invasive coronary angiography, cardiac MRI, and endomyocardial biopsy. Results Eighty-four patients (median age, 69 years [interquartile range, 50-77 years]; 45 men) were enrolled. TRO CT helped identify obstructive CAD in 35 participants (42%), acute aortic syndrome in one (1.2%), and pulmonary embolism in six (7.1%). LCE CT scans were acquired in the remaining 42 participants. The following diagnoses were reached with use of LCE CT: myocarditis (22 of 42 participants [52%]), takotsubo cardiomyopathy (four of 42 [10%]), amyloidosis (three of 42 [7.1%]), myocardial infarction with nonobstructed coronary arteries (three of 42 [7.1%]), dilated cardiomyopathy (two of 42 [4.8%]), and negative or inconclusive findings (eight of 42 [19%]). The addition of LCE CT improved the diagnostic rate of TRO CT from 42 of 84 participants (50% [95% CI: 38.9, 61.1]) to 76 of 84 (90% [95% CI: 82.1, 95.8]) ( P < .001). Conclusion A CT protocol including triple-rule-out and late contrast enhancement CT scans improved diagnostic rate in participants presenting with acute chest pain syndrome. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Nagpal and Bluemke in this issue.

Objectives: Aim of the study was to assess in-hospital survival rate and the degree of myocardial recovery after MCS treatment (IABP or IMPELLA) at discharge and at 6 months in patients with AMI-CS and planned early percutaneous revascularization., Background: All studies on MCS for acute myocardial infarction related cardiogenic shock (AMI-CS) focused on its impact on in-hospital mortality; however, few data about its role on myocardial recovery are available., Methods: Retrospective study on 64 patients: 36 patients (56%) received IABP and 28 (44%) Impella 2.5/CP., Results: Patients treated with Impella were sicker compared to those treated with IABP as shown by a higher need of catecholamines (93% Impella vs 57% IABP, P = 0.002) and higher inotropic score before procedure: 8 (5-15) versus 4.5 (0-9), P = 0.02. In-hospital survival and MCS-related complications were comparable; hemolysis was more frequent in the Impella group (32% vs 0%, P < 0.0001). Myocardial damage was lower in those patients who were implanted with IMPELLA before PCI: lower troponin peak [3831 ng/dL (1441-8436) vs 16 581 (7802-23 675), P = 0.004] and lower CPK peak [893 UI/L (584-4082) vs 5797 (2483-9292) P = 0.04]. Impella patients had higher LVEF at 6 months [45 (38-52) vs 40 (33-45)%, P = 0.04]. LVEF increase at 6 months was statistically significant in both groups (P < 0.0001), with higher myocardial recovery in patients supported with Impella (absolute delta-LVEF increase 20% vs 10% P = 0.005)., Conclusions: Cardiac unloading with IMPELLA in ACS-CS, especially if implanted before PCI, might provide lower myocardial damage and improved myocardial recovery which translates into significantly higher LVEF at 6 months., (© 2018 Wiley Periodicals, Inc.)

Aims: Renal dysfunction is common in heart failure. Recent evidence suggests a pivotal role for systemic venous congestion and functional tricuspid regurgitation (FTR) in the pathophysiology of renal dysfunction. We investigated the role of FTR as a determinant of renal dysfunction and a predictor of long-term prognosis in chronic systolic heart failure patients., Methods and Results: Four hundred and thirteen consecutive patients (mean age 74.2 ± 11 years) with chronic heart failure and left ventricular ejection fraction below 50% were enrolled. The FTR severity was quantified by transthoracic echocardiography. Renal function was evaluated with the estimated glomerular filtration rate measured by the simplified Modification of Diet in Renal Disease formula. The association between moderate/severe FTR and renal dysfunction, and its impact on heart failure episodes and overall mortality were also assessed. The median follow-up was 36 months (range 1-144 months). Through multivariate analysis, the interaction between moderate/severe FTR with tricuspid annular plane systolic excursion less than 16 mm was found to be an independent determinant of renal dysfunction [odds ratio 1.2, 95% confidence interval (CI) 1.1-1.5, P = 0.04]. Moderate/severe FTR (hazard ratio 1.3, 95% CI 1.2-2.7, P = 0.02) and tricuspid annular plane systolic excursion below 16 mm (hazard ratio 1.2, 95% CI 1.0-3.7, P = 0.01) were significantly related to the heart failure episodes. Moreover, the Kaplan-Meier analysis showed a worse outcome in patients with moderate/severe FTR (log-rank test 8.6, P = 0.003)., Conclusions: The combination of significant FTR and right ventricular dysfunction, but not FTR and right ventricular dysfunction alone, is independently associated with renal dysfunction. The presence of significant FTR is related to an excess event rate of heart failure and has significant impact on outcome.

Refractory angina pectoris (RAP) represents a clinical condition characterized by frequent episodes of chest pain despite therapy optimization. According to myocardial stunning and myocardial hibernation definitions, RAP should represent the ideal condition for systolic dysfunction development. We aim to investigate the evolution of left ventricular (LV) function in patients with RAP. A retrospective study which encompasses 144 patients with RAP referred to our institution from 1999 to December 2014 was performed. Of them, 88 met the inclusion criteria, and LV function was assessed by echocardiography. All of them had persistent angina episodes on top of optimal medical therapy and evidence of significant inducible myocardial ischemia and no further revascularization options. Nitrates consumption rate, time of angina duration, and the number of angina attacks were evaluated. In the whole population, ejection fraction (EF) was 44% ± 2. EF was significantly lower in patients with previous myocardial infarction (41% ± 1.5 vs 51% ± 1.8, p <0.0001). The duration time and the number of angina attacks did not correlate with EF in the whole population and in patients without previous myocardial infarction. In patients with previous myocardial infarction, the number of anginal attacks did not correlate with EF, but EF appeared higher in patients with angina duration >5 years (<5 years EF 37% ± 1 [n = 26]; >5 years 44% ± 2 [n = 44]; p 0.02). Long-term LV function in patients with RAP is generally preserved. A previous history of myocardial infarction is the only determinant in the development of systolic dysfunction. In conclusion, frequent angina attacks and a long-term history of angina are not apparently associated to worse LV function., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Right ventricular dysfunction (RVdysf) is a predictor of poor outcome in patients with heart failure and valvular disease. The aim of this study was to evaluate the evolution and the impact of RVdysf in patients with moderate-severe functional mitral regurgitation (FMR) successfully treated with MitraClip., Methods and Results: From October 2008 to July 2014, 60 consecutive high surgical risk FMR patients were evaluated and stratified into two groups: RVdysf group (TAPSE < 16 mm and/or S'TDI < 10 cm/s, 21 patients) and No-RVdysf group (38 patients). The overall mean age of patients was 73 ± 8 (83% male). Ischemic FMR etiology was present in 67%. Mean LVEF was 30 ± 10%. Overall mean time follow-up was 565 ± 310 days. The only significant difference between the two groups was a greater prevalence of stroke, ICD and use of aldosterone antagonist in RVdysf group. Acute procedural success was achieved in 90% of patients. At 6-month echo-matched analysis significant RV function improvement was observed in patients with baseline RVdysf (TAPSE 15 ± 3.0 vs. 19 ± 4.5, p = 0.007; S'TDI 7 ± 1.2 vs. 11 ± 2.8, p < 0.0001; baseline vs. 6-month, respectively). The mean improvement in the 6-min walking test was significant in both groups (120 and 143 m, RVdysf and No-RVdysf groups, respectively). At Kaplan-Meier analysis, the presence of RVdysf did not affect the outcome in terms of freedom from composite efficacy endpoint., Conclusions: This study shows that successful MitraClip implantation in patients with FMR and concomitant right ventricular dysfunction yields significant improvement of RV function at mid-term follow-up. Further data on larger population will be required to confirm our observations.

Atrial fibrillation (AF) is the most common clinically relevant cardiac arrhythmia. AF poses patients at increased risk of thromboembolism, in particular ischemic stroke. The CHADS2 and CHA2DS2-VASc scores are useful in the assessment of thromboembolic risk in nonvalvular AF and are utilized in decision-making about treatment with oral anticoagulation (OAC). However, OAC is underutilized due to poor patient compliance and contraindications, especially major bleedings. The Virchow triad synthesizes the pathogenesis of thrombogenesis in AF: endocardial dysfunction, abnormal blood stasis, and altered hemostasis. This is especially prominent in the left atrial appendage (LAA), where the low flow reaches its minimum. The LAA is the remnant of the embryonic left atrium, with a complex and variable morphology predisposing to stasis, especially during AF. In patients with nonvalvular AF, 90% of thrombi are located in the LAA. So, left atrial appendage occlusion could be an interesting and effective procedure in thromboembolism prevention in AF. After exclusion of LAA as an embolic source, the remaining risk of thromboembolism does not longer justify the use of oral anticoagulants. Various surgical and catheter-based methods have been developed to exclude the LAA. This paper reviews the physiological and pathophysiological role of the LAA and catheter-based methods of LAA exclusion.

Background: This observational study was designed to evaluate the prevalence of coronary microvascular dysfunction (CMD) in asymptomatic patients affected by systemic sclerosis (SSc), stratifying the results according to the limited (lcSSc) and the diffuse (dcSSc) forms of the disease., Methods and Results: We enrolled 19 consecutive asymptomatic patients with dcSSc (n=7) or lcSSc (n=12). In all subjects, coronary flow reserve (CFR) was assessed by measuring diastolic coronary flow velocities in the left anterior descending artery by pulsed wave Doppler at baseline and after dipyridamole infusion (0.84 mg·kg(-1)·6 min(-1)). Wall motion score index was evaluated at baseline and during stress. We enrolled 20 healthy subjects as controls. Mean CFR was 1.96±0.62 in patients and 2.69±0.47 in controls (P<0.001). Abnormal values of CFR (≤2) were significantly more prevalent in patients than in controls (10/19 vs. 0/20; P<0.001) and in the dcSSc subgroup than in the lcSSc subgroup (6/7 vs. 4/12; P=0.05). An inverse relationship between disease duration (from time of onset of Raynaud's phenomenon) and CFR value was observed in the lcSSc group (correlation coefficient -0.583; P=0.046). Neither patients nor controls had wall motion abnormalities during dipyridamole administration., Conclusions: A blunted CFR, most likely because of CMD, is more frequent in patients affected by the dcSSc form in the early stages of the disease, whereas it seems to appear later in lcSSc.

Background and Aim of the Study: The study aim was to evaluate whether, in patients with severe mitral regurgitation (MR), tricuspid valve remodeling was independent of the degree of functional tricuspid regurgitation (FTR) present. Whether any differences in the analysis remodeling, as assessed by two-dimensional (2D) and three-dimensional (3D) echocardiography, can be demonstrated was also addressed., Methods: A total of 188 patients (mean age 63.5 +/- 16.0 years) with severe organic or functional MR with or without associated FTR, and 30 normal controls (mean age 59.2 +/- 15 years) were enrolled in the study. Subsequently, both 2D and 3D transthoracic anatomic and functional parameters of the tricuspid valve were analyzed., Results: Patients and controls differed in all 2D and 3D parameters of tricuspid valve remodeling, except for the 2D end-diastolic annular diameter and circularity indices. The patients were then allocated to either group A (trivial/mild FTR) or group B (moderate/severe FTR). Significant differences were identified between groups A and B compared to controls in all tricuspid valve remodeling indices, except for the diastolic 2D annular diameter and circularity indices. Groups A and B had similar 2D and 3D parameters of tricuspid valve remodeling. The right ventricular end-diastolic diameter (RVEDD) (beta = 0.24, 95% CI: 0.11 to 0.22, p = 0.02) and fractional area change (beta = -0.48, 95% CI: -0.24 to 0.09, p = 0.0001, R2 = 0.22) were independent predictors of the tenting area, whereas the RVEDD was the only independent predictor of the diastolic 3D tricuspid annular area (beta = 0.53, 95% CI: 1.2 to 2.7, p = 0.0001, R2 = 0.28)., Conclusion: In patients with severe MR, tricuspid valve remodeling was also demonstrated in those with trivial/mild FTR, but was better characterized by 3D echocardiography. Tricuspid valve remodeling and right ventricular dilation were the main determinants of tricuspid valve regurgitation.

The aim of this study is to evaluate the role of contrast transesophageal echocardiography (cTEE) in the diagnostic characterization of acute aortic syndromes (AAS) [aortic dissection, intramural hematoma, penetrating ulcer]. We enrolled 66 non-consecutive patients with clinical suspicion of AAS. Standard transesophageal echocardiography and cTEE were performed prior to gated-CT angiography, which has been assumed as reference standard. cTEE was obtained with a single bolus of contrast agent injection. The definitive diagnosis of AAS was made in 48 patients by gated-CT angiography: 22 aortic dissections, 15 intramural hematomas and 11 penetrating aortic ulcers. Standard TEE and cTEE correctly diagnosed AAS in 87 and 100% (P = 0.03) cases respectively. Standard TEE correctly diagnosed aortic dissection in 20/22 (91%) and cTEE in 22/22 (100 %) (P = 0.5) cases. cTEE was superior than standard TEE in the visualization of false lumen entry tear (22/22 vs. 16/22, P = 0.03). Standard TEE correctly diagnosed intramural hematoma in 11/15 and cTEE 15/15 (P = 0.12) cases. Microtears were identified in 3 patients by cTEE an in 1 patient by standard TEE (P = 0.4). The presence of focal contrast enhancement was identified in 4 and 0 patients by cTEE and standard TEE respectively (P = 0.06). Both standard and cTEE correctly diagnosed penetrating aortic ulcer in 11/11 (100%) (P = 1.0) cases. cTEE provides additional value over standard TEE in the diagnosis and in the anatomic and functional characterization of AAS.

We describe the case of a young pregnant woman with moderate mitral regurgitation who was admitted to our department for dyspnea. The patient was treated with low-dose diuretic therapy and ventilatory support. At follow-up echocardiographic evaluation, a progressive improvement of mitral regurgitation and pulmonary artery pressure was observed. The most significant hemodynamic changes occurring during pregnancy are reviewed and discussed in the setting of associated mitral regurgitation.

Aims: The prognostic role of tricuspid regurgitation (TR) associated with organic left-sided valvular heart disease is well known. However, no data are available regarding the prognostic value of functional TR (FTR) in patients with functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction. The purpose of this study was to evaluate the prognostic role of FTR for occurrence of heart failure (HF) and mortality in patients with FMR., Methods and Results: We enrolled 373 consecutive patients (mean age 68±11 years) with LV dysfunction and at least mild FMR and with or without FTR, both quantitated by echocardiography. The median follow-up was 32 months (range 1-120 months); 132 (35.4%) and 97 patients developed HF or died, respectively. The incidence of HF at 3 and 6 years was 36±2% and 55±4%, respectively. Moderate to severe FTR [hazard ratio (HR) 1.4, 95% confidence interval (CI) 1.1-2.1, P = 0.01) was an independent determinant of HF. The incidence of HF was 41±5, 46±7, 57±7, and 65±8% for patients without, and with mild, moderate, and severe FTR respectively (P = 0.03). At 3 and 6 years the survival free of all-cause mortality was 77.5±2% and 60±3%, respectively. Moderate to severe FTR (HR 1.6, 95% CI 1.2-2.1, P = 0.01) was an independent determinant of overall mortality. At 6 years, survival free of all-cause mortality was 69±2.5, 67±2.1, 51±2.5, and 40±4.8% for patients without, and with mild, moderate, and severe FTR, respectively (P = 0.004)., Conclusions: Moderate or more FTR is independently associated with worse survival and a high incidence of HF episodes in patients with FMR.

Background: Although the prognostic impact of a moderate degree of ischemic mitral regurgitation (IMR) is well known, there are no data regarding the potential role of a mild degree of IMR. The aim of this study was to evaluate the impact of a mild degree (effective regurgitant orifice area < 20 mm(2)) of IMR on left ventricular (LV) remodeling and heart failure (HF)., Methods: A retrospective study was conducted in 35 patients with mild IMR that were propensity matched with 35 patients without IMR (controls). The population was evaluated between 3 and 6 months after first myocardial infarction and at 6 and 12 months, measuring LV volumes, ejection fraction, and the degree of mitral regurgitation. HF events requiring hospitalization were recorded., Results: The two groups were similar at baseline. During follow-up, patients with IMR showed significant increases in LV end-diastolic and end-systolic volumes and no change in ejection fractions, whereas controls did not show significant changes in volumes but did show increases in ejection fractions. Patients with IMR showed significantly higher end-systolic volumes at 6 months (P = .003) and 12 months (P = .007) and significantly higher end-diastolic volumes at 6 months (P = .048) and 12 months (P = .03) and lower ejection fractions at 6 months (P = .0001) and 12 months (P = .002) compared with controls. Patients with IMR experienced a significantly higher incidence of HF than controls (62% vs 23%, P = .001). At 6 months, in six patients mitral regurgitation degree changed from mild to moderate, and in one patient from mild to severe. Interestingly, 71.5% of patients who experienced increases in mitral regurgitation degree had no coronary revascularization (P = .04)., Conclusions: Mild IMR affects the LV remodeling process, increases its degree over time, and determines a higher rate of HF., (Copyright © 2011 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: Cardiac stem cell therapy is a field of scientific research with the goal to translate into clinical benefit the initial findings obtained in basic research laboratories. We have moved into clinical trials in different disease categories: acute myocardial infarction, chronic stable angina refractory to conventional therapy and heart failure. So far we have faced with contradictory results. Some previous studies suggested that bone marrow cell injection may improve myocardial perfusion and left ventricular function in patients with chronic myocardial ischemia., Methods: In this paper we present a brief review about stem cell use in clinical cardiology and describe our research protocol evaluating the effects of direct intramyocardial injection of autologous bone marrow cells (CD34+ selected cells versus all mononuclear cells) in patients with chronic myocardial ischemia., Results: Preliminary results show that this procedure seems to be safe and generally well tolerated by patients. An improvement in symptoms, in the first 6 months, appears to be achieved in approximately 50% of patients, with concomitant improvement of quantitative scintigraphic stress test imaging., Conclusions: Before drawing any definitive conclusions, we need to wait for the end of enrollment and unblinding of study randomization.

The introduction of three-dimensional echocardiography and its evolution from time-consuming and cumbersome off-line reconstruction to real-time volumetric technique (real-time three-dimensional echocardiography) are one of the most significant advances in ultrasound imaging of the heart of the past decade. This imaging modality currently provides realistic views of cardiac valves capable of demonstrating the anatomy of various heart valve diseases in a unique, noninvasive manner. In addition, real-time three-dimensional echocardiography offers completely new views of the valves and surrounding structures, and allows accurate quantification of severity of valve disease. This article reviews the advantages of real-time three-dimensional echocardiography in assessing heart valves and shows also technological limitations in order to provide the scientific basis for its clinical use.

Aims: To assess long-term prognosis in patients with functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction, receiving current standard pharmacological therapy., Methods and Results: We prospectively enrolled 404 consecutive patients (mean age 70.2 +/- 10 years) with ischaemic (76.5%) and non-ischaemic (23.5%) LV dysfunction (ejection fraction 34.4 +/- 10.8%) and at least mild MR. Results are reported at 4 years' follow-up. Survival free of all-cause mortality was 53% and cardiac death was 74%. Survival free of all-cause mortality was 50% (95% CI 35-72) for patients with moderate MR, 49% (95% CI 27-65) for severe MR, and 64% (95% CI 47-78) for mild MR (P = 0.03). Survival free of cardiac death was 57% (95% CI 38-74) for patients with moderate MR, 55% (95% CI 30-77) for severe MR, and 94% (95% CI 59-98) for mild MR (P = 0.003). Moderate-to-severe MR [relative risk (RR) 2.7, 95% CI 1.2-6.1, P = 0.003] was an independent predictor of cardiac death but not of all-cause mortality. Survival free of heart failure (HF) was 32%. Survival free of HF was 20% (95% CI 17-35) for patients with moderate MR, 18% (95% CI 15-32) for severe MR, and 62% (95% CI 45-72) for mild MR (P = 0.0001). Moderate-to-severe MR (RR 3.2, 95% CI 1.9-5.2, P = 0.0001) was an independent predictor of HF., Conclusion: The mortality and morbidity of patients with LV dysfunction and FMR remain high despite current standard pharmacological therapy. Moderate-to-severe MR is an independent predictor of cardiac death and HF.

The perioperative management of patients with aortic stenosis is influenced by preoperative echocardiographic findings. This paper explains how to read and interpret key echocardiografic findings and suggests how to optimize monitoring and pharmacological treatment of patients with aortic stenosis undergoing cardiac or non-cardiac surgery.

Objective: To evaluate the feasibility of mitral valve (MV) reconstruction protocol by real-time 3D echocardiography (RT3DE) in the assessment mitral regurgitant (MR) lesions, and to determine the accuracy of RT3DE compared with transthoracic (TTE) and transesophageal (TEE) echocardiographies using surgical findings as gold standard., Patients and Methods: Sixty-three consecutive patients (mean age 61.7+/-12.5 years, 35 men and 28 women) with severe organic MR were enrolled. Data were acquired in zoom and in full-volume modes from apical and/or parasternal windows. A volume rendered en-face view of MV and five serial longitudinal cut planes were reconstructed to visualize all segments of both leaflets., Results: The feasibility of RT3D reconstruction was 94%. Compared with surgical diagnosis, the accuracy of RT3D was 91% for aetiology, 92% for mechanisms, 94% for prolapse, 88% for flail and 94% for defect location. Diagnostic accuracy was significant higher for RT3D than TTE for all end points except for flail lesion and similar to TEE but inferior to this for flail lesion. The accuracy, sensitivity and specificity were higher in patients with good-excellent than those with poor image quality regarding aetiology, mechanisms and defect location (all p=0.0001)., Conclusions: RT3D imaging of MV is feasible and accurate in defining aetiology, mechanism and defect location in patients with MR and has incremental diagnostic value if TTE is inconclusive and similar diagnostic value of TEE except for flail lesion. RT3D, at least in patients with good acoustic window, may obviate the need for subsequent TEE and/or can be considered a complementary technique to study MV in patients with MR.

Chronic ischemic mitral regurgitation (IMR) is a common complication of myocardial infarction and severely affects cardiovascular mortality and morbidity. Multiple pathophysiologic mechanisms, such as left ventricular (LV) remodeling and dysfunction, annular dilation/dysfunction, and mechanical dyssynchrony, are involved in generating IMR, each of them having different weight. However, the prerequisite to initially creating regurgitation is the presence of local or global LV remodeling that alters the geometrical relationship between the ventricle and valve apparatus. In the wide spectrum of patients with chronic IMR, the assessment of some echocardiographic parameters, such as tethering pattern, leaflet motion, origin and direction of the regurgitant jets, allows one to identify different specific subgroups of patients subjected to different therapeutic approaches. The aim of medical and/or surgical therapy is to ameliorate heart failure symptoms, and improve LV remodeling and function and the intermediate/long-term outcome. The targets of surgical MV repair involve annulus, leaflets, chordae and ventricles. The restricted annuloplasty is the most commonly adopted surgical procedure that improves heart failure symptoms but not survival when compared to medical therapy and is also subject to a high incidence of late failure (approximately 30%). There are some preoperative echocardiographic predictors of failure that include valve (degree of valve remodeling, jet characteristics), ventricular (degree of remodeling, diastolic dysfunction) and surgical factors.

Objective: To assess regional mechanical dyssynchrony as a determinant of the degree of functional mitral regurgitation (FMR)., Setting: Tertiary cardiology clinic., Patients: 74 consecutive patients with left ventricular (LV) dysfunction (ejection fraction < 40%, mean 32.2 (SD 7.3)%) were evaluated., Methods: Effective regurgitant orifice (ERO) area, indices of mitral deformation (systolic valvular tenting, mitral annular contraction) and of global LV function and remodelling (ejection fraction, end systolic volume, sphericity index) and local remodelling (papillary-fibrosa distance, regional wall motion score index), and tissue Doppler-derived dyssynchrony index (DI) (regional DI, defined as the standard deviation of time to peak myocardial systolic contraction of eight LV segments supporting the papillary muscles attachment) were measured., Results: All the assessed variables correlated significantly with ERO. By multivariate analysis, systolic valvular tenting was the strongest independent predictor of ERO (R(2) = 0.77, p = 0.0001), with a minor influence of papillary-fibrosa distance (R(2) = 0.77, p = 0.01) and regional DI (R(2) = 0.77, p = 0.03). Local LV remodelling (regional wall motion score index: R(2) = 0.58, p = 0.001; papillary-fibrosa distance: R(2) = 0.58, p = 0.002) and global remodelling indices (sphericity index: R(2) = 0.58, p = 0.003) were the main determinants of systolic valvular tenting, whereas regional DI did not enter into the model. Regional DI was an independent predictor of ERO (R(2) = 0.56, p = 0.005) in patients with non-ischaemic LV dysfunction but not in patients with ischaemic LV dysfunction when these groups were analysed separately., Conclusions: The degree of FMR is associated mainly with mitral deformation indices. The regional dyssynchrony also has an independent association with ERO but with a minor influence; however, it is not a determinant of FMR in patients with ischaemic LV dysfunction.

Ultrasound lung comet images (ULC) are useful for the noninvasive assessment of extravascular lung water (EVLW). We investigated the modification of EVLW, its relation to indices of left ventricular systolic and diastolic function, and noninvasively determined pulmonary capillary wedge pressure (PCWP) (PCWP = 1.24 ratio of early diastolic mitral inflow velocity to early diastolic velocity of the mitral annulus [E/Em] + 1.9) at rest and its variation during exercise echocardiography. A total of 72 patients (mean age 66.4 +/- 8.4 years) with mean ejection fraction of 41.2 +/- 14.4% underwent symptoms-limited exercise echocardiography. The sum of the ULC yielded a score of EVLW. The ULC increased significantly from baseline to postexercise (5.9 +/- 14.9 vs 11 +/- 20.7, P = .0001). Positive linear correlations were found between baseline ULC score and baseline ejection fraction (r = -0.37, P = .002), systolic pulmonary artery pressure (r = 0.69, P = .0001), E/Em (r = 0.70, P = .0001), and estimated PCWP (r = 0.69, P = .0001). The variation between postexercise and baseline ULC score correlated significantly with the variation between peak stress and rest PCWP (r = 0.62, P = .0001), systolic pulmonary artery pressure (r = 0.44, P = .0001), wall-motion score index (r = 0.30, P = .01), and peak stress E/Em (r = 0.71, P = .0001), whereas no significant correlations were found between variations of ULC score and ejection fraction. This study shows that ULC represents a simple way to assess the presence of excess EVLW. Increased EVLW is associated with estimated PCWP and indices of left ventricular systolic and diastolic dysfunction. The additional exercise-induced increase of PCWP, the worsening of left ventricular diastolic function, and extensive wall-motion abnormalities correlate with variations of EVLW.

Background: Doppler of mitral and pulmonary vein flows are used to estimate left ventricular (LV) filling pressure. Mitral regurgitation (MR) makes unreliable these parameters by inducing changes of both mitral inflow and pulmonary vein flow., Objectives: To evaluate whether Doppler tissue imaging (DTI) diastolic indices obtained at the level of LV lateral mitral annulus can provide accurate estimation of LV filling pressure in patients with MR., Methods: Forty-three patients (age 55 +/- 11 years) with severe MR and mean LV ejection fraction (EF) 58 +/- 13 were enrolled, 10 (23%) with LV EF < 50% and 33 (77%) with LV EF > 50%. Doppler signals from the mitral inflow, pulmonary venous flow, and DTI indices of the lateral mitral annulus were obtained. LV end-diastolic pressure (LVEDP) was measured invasively with fluid-filled catheter., Results: In the overall population, the majority of standard Doppler and DTI indices correlated with LVEDP, but the multivariate analysis showed that the ratio of mitral velocity to early diastolic velocity of the mitral annulus (E/Em ratio) (beta = .87, P = .0001) was independent predictor of LVEDP (R2 = 0.74, SE = 4, P = .0001). An E/Em ratio > 10 predicted an LVEDP > 15 mm Hg (sensitivity 90%, specificity 83%). In both groups with LV EF > 50% (beta = .77, P = .005; cumulative R2 = 0.73, SE = 2.5, P = .0001) and < 50% (beta = .89, P = .002; cumulative R2 = 0.77, SE = 2.1, P = .002), multivariate analysis underscored again only E/Em ratio as independent predictor of LVEDP., Conclusions: The combination of DTI indices of the mitral annulus and mitral inflow velocities provides reliable parameters to predict LV filling pressure in patients with MR both in patients with LV EF > 50% and < 50%.

Background: Echographic examination of the lung surface may reveal multiple "comet-tail images" originating from water-thickened interlobular septa. These images could be useful for noninvasive assessment of interstitial pulmonary edema., Study Objective: The purpose of this study was to assess the diagnostic accuracy of lung comet-tail images compared with chest radiography, wedge pressure, and extravascular lung water (EVLW) quantified by the indicator dilution method (PiCCO System, version 4.1; Pulsion Medical Systems; Munich, Germany)., Methods and Patients: We enrolled 20 patients (mean age, 62.6 +/- 11.5 years [+/- SD]). Patients were studied before, immediately after, and 24 h following cardiac surgery with chest ultrasound, chest radiography, pulmonary artery catheterization, and the PiCCO system. Performing echo scanning (right and left hemithorax, from second to fourth intercostal space, from parasternal to midaxillary line), an individual patient comet score was obtained by summing the number of comets in each scanned space., Results: A total of 60 comparisons were obtained. Significant positive linear correlations were found between comet score and EVLW determined by the PiCCO System (r = 0.42, p = 0.001), between comet score and wedge pressure (r = 0.48, p = 0.01), and between comet score and radiologic lung water score (r = 0.60, p = 0.0001)., Conclusions: The presence and the number of comet-tail images provide reliable information on interstitial pulmonary edema. Therefore, ultrasonography represent an attractive, easy-to-use, bedside diagnostic tool for assessing cardiac function and pulmonary congestion.

Pregnancy exacerbates heart diseases. The aim of this clinical report is to review the different anesthesiological management of emergent cesarean section in 2 patients with heart failure. The pathophysiology of heart failure is described according to the primary cause of disease, as well as the impact of 2 different anesthetic techniques. Two case reports of a university referral hospital are presented. Both patients left the hospital in good general conditions. Case 1: a pregnant patient with severe aortic regurgitation who received epidural anesthesia. Case 2: a pregnant patient with peripartum cardiomyopathy who was given general anesthesia. Medical and surgical therapies for aortic regurgitation and peripartum dilated cardiomyopathy are evolving. Adequate knowledge of anesthesiology is required to appropriately manage these cases. We tailored the anesthetic technique to the specific characteristics of our 2 patients. The beneficial effects of sympathectomy were observed in the postoperative period of case 1; the use of high doses opiates minimised dangerous cardiovascular changes in case 2, but rapid resuscitation of the baby should be available. Selection of the anesthetic technique in obstetrics is the most challenging issue for the anesthesiologist: extensive knowledge of the pathophysiology of heart disease is required for an optimal choice.

We assessed whether the presence of latent myocardial dysfunction, evaluated by echocardiographic derived force-frequency relationship (FFR) during exercise, predicts the appearance of stress-induced pulmonary hypertension in minimally symptomatic patients with severe mitral regurgitation (MR). Two groups of patients were identified: group I with normal (40 mm Hg) peak stress systemic pulmonary artery pressure. Group I had normal and upsloping FFR and group II had abnormal flat or biphasic FFR. Therefore, in patients with severe MR and apparently normal left ventricular function, the stress-induced pulmonary hypertension seems to be related to the presence of latent left ventricular dysfunction.

Although the mechanism of ischemic mitral regurgitation (MR) is understood, the echocardiographic picture of ischemic MR is not homogeneous. Ninety-two consecutive patients with chronic ischemic MR due to restricted motion were divided into two groups according to tethering pattern: the asymmetric group with predominant posterior tethering of both leaflets (54 patients) and the symmetric one with predominant apical tethering of both leaflets (38 patients). The mitral deformation indexes, LV global (volume, function and sphericity) and local (papillary muscle displacements and regional wall motion score index) remodeling were evaluated. All indexes of global LV remodeling were significantly higher in the symmetric than asymmetric group (all p < 0.0001), such as the posterior and lateral displacement of the anterior papillary muscle (both p < 0.04), the papillary muscle separation and the anterior papillary muscle wall motion index (both p < 0.0001). The origin as well as the direction of the jet was central in all patients of the symmetric group. In the asymmetric one the origin was central in 78% of the cases and arising from the medial commissure in 22% whereas the jet direction was posterior and central in 83% and 17% of patients, respectively. Therefore, it is possible to distinguish at least two subgroups of patients with ischemic MR due to restricted motion on the basis of tethering pattern, different degree of local and global LV remodeling and characteristics of the regurgitant jet.

Echocardiography has the ability to noninvasively explore hemodynamic variables during pharmacologic or exercise stress test in patients with heart failure. In this review, we detail some important potential applications of stress echocardiography in patients with heart failure. In patients with coronary artery disease and chronic LV dysfunction, dobutamine stress echocardiography is able to distinguish between viable and fibrotic tissue to make adequate clinical decisions. Exercise testing, in combination with echocardiographic monitoring, is a method of obtaining accurate information in the assessment of functional capacity and prognosis. Functional mitral regurgitation is a common finding in patients with dilated and ischaemic cardiomyopathy and stress echocardiography in the form of exercise or pharmacologic protocols can be useful to evaluate the behaviour of mitral regurgitation. It is clinical useful to search the presence of contractile reserve in non ischemic dilated cardiomyopathy such as to screen or monitor the presence of latent myocardial dysfunction in patients who had exposure to cardiotoxic agents. Moreover, in patients with suspected diastolic heart failure and normal systolic function, exercise echocardiography could be able to demonstrate the existence of such dysfunction and determine that it is sufficient to limit exercise tolerance. Finally, in the aortic stenosis dobutamine echocardiography can distinguish severe from non-severe stenosis in patients with low transvalvular gradients and depressed left ventricular function.

Objective: To assess whether tissue Doppler myocardial imaging (TDI) indices can predict postoperative left ventricular function in patients with mitral regurgitation (MR) after surgical correction., Methods: 84 patients (mean (SD) age 54.3 (10.8) years) with asymptomatic severe MR, an end systolic diameter < 45 mm, and an ejection fraction (EF) > 60% were subdivided in two groups: 43 patients with a postoperative EF reduction < 10% (group 1) and 41 patients with a postoperative EF reduction > or = 10% (group 2).TDI systolic indices of the lateral annulus were analysed preoperatively to assess myocardial systolic wave (Sm) velocity, myocardial precontraction time (PCTm), myocardial contraction time (CTm), and the PCTm:CTm ratio., Results: Postoperative EF decreased significantly (from 67 (5)% to 60 (5.5)%, p = 0.0001). Group 2 had a higher PCTm, CTm, and PCTm:CTm ratio and a lower Sm velocity than group 1 (PCTm 100.4 (19) ms v 82 (21.8) ms, p = 0.004; CTm 222 (3.1) ms v 215 (2.3) ms, p = 0.01; PCTm:CTm 0.45 (0.08) v 0.38 (0.09), p = 0.001; Sm velocity 10.4 (1.1) cm/s v 13 (1.3) cm/s, p = 0.0001). Multivariate regression analysis showed that the combination of PCTm:CTm ratio > or = 40 ms and Sm velocity < or = 10.5 cm/s was the main independent predictor of postoperative EF reduction > or = 10% (sensitivity 78%, specificity 95%)., Conclusions: TDI systolic indices can predict postoperative left ventricular function in patients with asymptomatic MR undergoing surgical correction.

Transesophageal echocardiography has been widely used as a diagnostic tool during the past two decades to detect cardiac abnormalities that are not visible or poorly visible with transthoracic echocardiography. At present, transesophageal echocardiography is a cornerstone of modern diagnosis of several cardiac diseases, providing diagnostic, prognostic and therapeutic information. In this review, the present status of transesophageal echocardiography not only as a diagnostic tool, underlining its effects on clinical decision making, but also as a monitoring adjunct for many interventional cardiac procedures is examined.

Residual mitral regurgitation (MR) after repair is a risk factor for late reoperation. The use of intraoperative transesophageal echocardiography (IOTEE) decreases the incidence of immediate repair failure. This study identifies the mechanisms of immediate failure by IOTEE in the quadrangular resection technique, a well-standardized mitral valve repair procedure to guide further repair procedures. Two hundred five consecutive patients underwent quadrangular resection due to prolapse or flail posterior leaflet. Twenty-four patients (11%) had immediate failure. Immediate reinstitution of cardiopulmonary bypass ("second pump run") was needed in 21 patients (10%) for further repair. The identified mechanisms of failure were residual cleft provoking interscallop malcoaptation into the posterior leaflet in 8 patients, residual prolapse of the anterior or posterior leaflets in 1 and 4 patients, respectively, residual annular dilation in 3, left ventricular outflow obstruction in 2, suture dehiscence in 2, and other mechanisms in another 2 patients. In 20 patients (95%), IOTEE guided further repair with resolution of the residual MR, whereas 1 patient underwent valve replacement due to pharmacologically untreatable left ventricular outflow obstruction. In conclusion, even if this type of valve repair technique is well standardized, the incidence of immediate failure is not negligible. IOTEE identified the mechanisms of the immediate failure and guided further repair procedures, thus reducing the incidence of valve replacement (0.5%) without increasing perioperative mortality and morbility.

Multiplane transesophageal echocardiography is a useful tool to study mitral regurgitation. We evaluated the diagnostic accuracy of multiplane transesophageal echocardiography performed according to the guidelines of the American Society of Echocardiography. We used 4 midesophageal and 2 transgastric views in 313 patients with degenerative lesions, endocarditic lesions, or both to identify regurgitant defects, comparing transesophageal echocardiography results with surgical findings. The overall diagnostic accuracy using individual scallops was 97.2% (P <.00001) with a sensitivity of 96.6% and a specificity of 97.6%. Considering the single sections of the mitral valve, an accuracy of 98%, 97.1%, and 98%, was found, respectively, for the lateral, middle, and medial third of the anterior leaflet. For the posterior leaflet, the accuracy was 98% for the lateral scallop, 98.4% for the middle, and 96.1% for the medial. This strategy provides good accuracy in diagnosing both simple and challenging mitral-valve lesions and its widespread use should be recommended.

Yra1p and Sub2p are components of the TREX complex, which couples transcription elongation with nuclear export of mRNAs. Here, we report a genetic interaction between Yra1p and a conserved protein Sac3p, which previously was found to interact with Sub2p. In vivo, Sac3p forms a stable complex with Thp1p, which was reported to function in transcription elongation. In addition, Sac3p binds to the mRNA exporter Mex67p-Mtr2p and requires the nucleoporin Nup1p to dock at the nuclear side of the nuclear pore complex (NPC). Significantly, mutations in Sac3p or Thp1p lead to strong mRNA export defects. Taken together, our data suggest that the novel Sac3p-Thp1p complex functions by docking the mRNP to specific nucleoporins at the nuclear entrance of the NPC.

Background: The minor technical and time requirements with respect to the maze operation combined with a comparable efficacy has led to an increasing popularity of left atrial approaches to treat atrial fibrillation. We report our experience with a left atrial procedure based on extensive use of epicardial radiofrequency ablation in an effort to minimize cardiac arrest time., Methods: A total of 132 consecutive patients with atrial fibrillation (121 chronic, 11 paroxysmal) undergoing open heart surgery had combined intraoperative ablation. An original set of left atrial lesions was performed using a radiofrequency linear catheter. Most of the ablations were performed epicardially before aortic cross-damping. Patients with contraindications to the epicardial approach had the whole lesion set performed endocardially., Results: The mean cardiac arrest time spent for open heart ablations was significantly shorter (5.2 +/- 0.9 minutes with modem catheters) when the epicardial approach was used (107 of 132 patients, 81%). Hospital mortality was 0.8%. Freedom from atrial fibrillation was 77% 3 years after the operation. Of all the variables analyzed, only age at surgery and early postoperative arrhythmias increased the risk of recurrent atrial fibrillation. Overall 3-year survival was 94%. The 3-year actuarial freedom from stroke was 98%. No patient required implantation of a permanent pacemaker. Atrial contractility was recovered in all patients with stable sinus rhythm., Conclusions: Left atrial radiofrequency ablation allows recovery of sinus rhythm and atrial function in the great majority of patients with atrial fibrillation who undergo open heart surgery. The epicardial radiofrequency approach is a safe and effective means to cure atrial fibrillation with negligible technical and time requirements.

Background and Aim of the Study: The edge-to-edge technique is used to restore valvular competence in mitral insufficiency. The efficacy of the method is under debate due to the potential for creating functional mitral stenosis. An exercise echocardiographic study was carried out to investigate valve function and hemodynamics in patients who had undergone double-orifice mitral valve repair., Methods: Thirty patients (mean age 49.1 +/- 12.7 years) with previous double-orifice mitral valve repair underwent exercise echocardiography (10 W/min). An annular prosthesis was present in 28 patients (93%). The mean and maximum mitral valve gradient, planimetric valve area, stroke volume, systolic pulmonary artery pressure, heart rate and systolic blood pressure were measured at baseline and at peak stress., Results: At peak stress, heart rate (77.7 +/- 12.2 versus 118.6 +/- 26.0 beats/min, p < 0.00001), systolic blood pressure (124.1 +/- 10.9 versus 146.6 +/- 22.8 mmHg, p < 0.00001) and stroke volume (78.0 +/- 10.2 versus 97.0 +/- 15.1 ml, p < 0.00001) were significantly increased, showing a physiological behavior of the mitral valve. The mean mitral valve gradient (2.8 +/- 1.3 versus 4.6 +/- 1.9 mmHg, p < 0.00001), maximum mitral valve gradient (6.4 +/- 2.8 versus 10.5 +/- 4.6 mmHg, p < 0.00002) and systolic pulmonary artery pressure (22.8 +/- 6.1 versus 28.2 +/- 9.9 mmHg, p < 0.001) were increased, but not to pathologic levels. Planimetric valve area increased significantly (3.2 +/- 0.6 versus 4.3 +/- 0.7 cm2, p < 0.00001). A significant negative linear correlation was found between the relative change in mitral valve area and planimetric valve area at rest (r = -0.51, p < 0.05)., Conclusion: The double-orifice repair, even with concomitant ring annuloplasty, does not cause mitral valve obstruction, either at baseline or during physical exercise, and does not affect valve hemodynamic and valve reserve.

The essential yeast proteins Yra1 and Sub2 are messenger RNA export factors that have conserved counterparts in metazoans, designated Aly and UAP56, respectively. These factors couple the machineries that function in splicing and export of mRNA. Here we show that both Yra1 and Sub2 are stoichiometrically associated with the heterotetrameric THO complex, which functions in transcription in yeast. We also show that Sub2 and Yra1 interact genetically with all four components of the THO complex (Tho2, Hpr1, Mft1 and Thp2). Moreover, these components operate in the export of bulk poly(A)(+) RNA as well as of mRNA derived from intronless genes. Both Aly and UAP56 associate with human counterparts of the THO complex. Together, these data define a conserved complex, designated the TREX ('transcription/export') complex. The TREX complex is specifically recruited to activated genes during transcription and travels the entire length of the gene with RNA polymerase II. Our data indicate that the TREX complex has a conserved role in coupling transcription to mRNA export.

Prophylactic valve replacement in asymptomatic patients with severe aortic stenosis is controversial. Most authors consider that patients could be managed without surgery until symptoms develop. The incidence of sudden death in patients without symptoms is low, < 1%/year and valve replacement is complicated by an operative mortality up to 5 and 1-2% of incidence of valve-related major events. Early surgical approach is suggested by several observations. The first one is the unpredictable risk of myocardial fibrosis after long standing left ventricular hypertrophy and pressure overload, with associated systolic and diastolic dysfunction. Left ventricular impairment can persist after valve replacement influencing exercise capacity and survival in selected patients. On the other hand, major improvement in myocardial protection techniques, intraoperative monitoring with transesophageal echocardiography, prosthetic design (stentless, supra-annular), all have reduced in-hospital mortality and morbidity. More precise recommendations can be made according to an improved characterization of the patients from fast to slow evolution, according to age, type of aortic stenosis, degree of calcification, changes in transaortic gradients over time, tolerance to exercise test and response of aortic valve area to dobutamine. In patients with high risk of progression (severely calcified valve, Doppler velocity > 4 m/s, rapidly increasing with time), indirect evidence of myocardial fibrosis (excessive left ventricular hypertrophy, systolic or diastolic dysfunction), and need of myocardial revascularization, an early surgical approach should be considered.

Objective: The aim of this study is to report our results with the central double-orifice technique used for the treatment of complex mitral valve lesions., Methods: The central double-orifice repair has been used in 260 patients (mean age, 56 +/- 14.3 years) over a period of 7 years. The mechanism responsible for mitral regurgitation was prolapse of both leaflets in 148 patients, prolapse of the anterior leaflet in 68, prolapse of the posterior leaflet with annular calcification or other unfavorable features in 31, and lack of leaflet coaptation for restricted motion or erosion of the free edge in 13. Degenerative disease was the cause of mitral regurgitation in 80.8% of the patients, rheumatic disease was the cause in 9.6%, endocarditis was the cause in 6.1%, and ischemic disease was the cause in 2.3%., Results: Hospital mortality was 0.7%, and the overall survival at 5 years was 94.4% +/- 2.59%. Thirteen patients required a reoperation (2 early postoperatively and 11 late during the follow-up), for an overall freedom from reoperation of 90.0% +/- 3.37% at 5 years. Freedom from reoperation was lower in patients with rheumatic valve disease and in patients who did not undergo an annuloplasty procedure., Conclusions: The effectiveness and durability of the central double-orifice technique were assessed in this study. This type of repair can be a useful addition to the surgical armamentarium in mitral valve reconstruction.

Background: Many different doses and administration schemes have been proposed for the use of the antifibrinolytic drug tranexamic acid during cardiac surgery. This study evaluated the effects of the treatment using tranexamic acid during the intraoperative period only and compared the results with the effects of the treatment continued into the postoperative period., Methods: Patients undergoing elective cardiac surgery with use of cardiopulmonary bypass (N = 510) were treated intraoperatively with tranexamic acid and then were randomized in a double-blind fashion to one of three postoperative treatment groups: group A: 169 patients, infusion of saline for 12 h; group B: 171 patients, infusion of tranexamic acid, 1 mg x kg(-1) x h(-1) for 12 h; group C: 170 patients, infusion of tranexamic acid, 2 mg x kg(-1) x h(-1) for 12 h. Bleeding was considered to be a primary outcome variable. Hematologic data, allogeneic transfusions, thrombotic complications, intubation time, and intensive care unit and hospital stay duration also were evaluated., Results: No differences were found among groups regarding postoperative bleeding and outcomes; however, the group treated with 1 mg x kg(-1) x h(-1) tranexamic acid required more units of packed red blood cells because of a significantly lower basal value of hematocrit, as shown by multivariate analysis., Conclusions: Prolongation of treatment with tranexamic acid after cardiac surgery is not advantageous with respect to intraoperative administration alone in reducing bleeding and number of allogeneic transfusions. Although the prevalence of postoperative complications was similar among groups, there is an increased risk of procoagulant response because of antifibrinolytic treatment. Therefore, the use of tranexamic acid during the postoperative period should be limited to patients with excessive bleeding as a result of primary fibrinolysis.