Ultraslow thrombolytic therapy: A novel strategy in the management of PROsthetic MEchanical valve Thrombosis and the prEdictors of outcomE: The Ultra-slow PROMETEE trial.

BACKGROUND: Low-dose (25mg), slow infusion (6hours) of tissue-type plasminogen activator (t-PA) with repetition as needed has been shown to provide effective and safer thrombolysis in patients with prosthetic valve thrombosis (PVT). Further prolonging the infusion time may be rational with regard to reducing complication rates without reducing success rates. We aimed to investigate the efficacy and safety of ultraslow (25hours) infusion of low-dose (25mg) alteplase (t-PA) for PVT. METHODS AND RESULTS: Transesophageal echocardiography-guided thrombolytic therapy (TT) was administered to 114 patients with PVT in 120 different episodes between 2009 and 2013 in a single center. Prosthetic valve thrombosis was obstructive in 77 (64.2%) and nonobstructive in 43 (35.8%) episodes. Ultraslow infusion (25hours) of low-dose (25mg) t-PA, as the TT regimen, was used in all patients admitted with PVT. The end points were thrombolytic success, mortality, and complication rates. The overall success rate of TT was 90% (95% CI 0.85-0.95). The univariate predictors of an unsuccessful result were higher New York Heart Association (NYHA) class, thrombus cross-sectional area, duration of suboptimal anticoagulation, lower baseline valve area, and presence of atrial fibrillation. The NYHA class was the only independent predictor of TT failure by multiple variable analysis. The overall complication rate was 6.7% (3.3% nonfatal major, 2.5% minor, and 0.8% death). The predictors of complications were presence of atrial fibrillation, higher NYHA class, and thrombus area. CONCLUSION: Ultraslow (25hours) infusion of low-dose (25mg) t-PA without bolus appears to be associated with quite low nonfatal complications and mortality for PVT patients without loss of effectiveness, except for those with NYHA class IV.

Thrombolytic therapy for the treatment of prosthetic heart valve thrombosis in pregnancy with low-dose, slow infusion of tissue-type plasminogen activator.

BACKGROUND: Prosthetic valve thrombosis during pregnancy is life-threatening for mother and fetus, and the treatment of this complication is unclear. Cardiac surgery in pregnancy is associated with very high maternal and fetal mortality and morbidity. Thrombolytic therapy has rarely been used in these patients. The aim of this study is to evaluate the safety and efficacy of low-dose (25 mg), slow infusion (6 hours) of tissue-type plasminogen activator for the treatment of prosthetic valve thrombosis in pregnant women. METHODS AND RESULTS: Between 2004 and 2012, tissue-type plasminogen activator was administered to 24 consecutive women in 25 pregnancies with 28 prosthetic valve thrombosis episodes (obstructive, n=15; nonobstructive, n=13). Mean age of the patients was 29±6 years. Thrombolytic therapy sessions were performed under transesophageal echocardiography guidance. The mean dose of tissue-type plasminogen activator used was 48.7±29.5 mg (range, 25-100 mg). All episodes resulted in complete thrombus lysis after thrombolytic therapy. One patient had placental hemorrhage with preterm live birth at the 30th week, and 1 patient had minor bleeding. CONCLUSIONS: Low-dose, slow infusion of tissue-type plasminogen activator with repeated doses as needed is an effective therapy with an excellent thrombolytic success rate for the treatment of prosthetic valve thrombosis in pregnant women. This protocol also seems to be safer than cardiac surgery or any alternative medical strategies published to date. Thrombolytic therapy should be considered first-line therapy in pregnant patients with prosthetic valve thrombosis.

Thrombus attached to suture materials successfully thrombolysed with low-dose tissue plasminogen activator.

Mechanical prosthetic heart valve thrombosis is one of the most common complications of valve surgery. We herein describe an unusual clinical vignette. A 60-year-old man who underwent prosthetic mitral valve reoperation suffered from nonobstructive thrombus attached to the elongated suture materials in the postoperative sixth month. The thrombus was precisely depicted by two- and three-dimensional transesophageal echocardiography and was successfully lysed with low-dose slow infusion of tissue plasminogen activator after failed heparin treatment.

Alternative causes of bioreaction to prosthetic heart valves: three cases with pannus formation.

Pannus formation is an infrequent but serious complication of prosthetic heart valve surgery. The cause of pannus is recognized as a bioreaction to the prostheses; histological investigations have shown that pannus comprises collagen and elastic tissues containing endothelial cells, chronic inflammatory cells, and myofibroblasts. However, the detailed mechanism of its formation has not been fully demonstrated. We aimed to evaluate the potential role of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in the pathogenesis of pannus formation in three patients with mechanical prosthetic heart valves. Pannus specimens removed from the prostheses were fixed in 10% neutral-buffered formalin for 24 hours after surgical removal and paraffin-embedded using standard procedures. Serial sections were cut at 4 µm for immunohistochemistry analysis. Hematoxylin and eosin (HE) was used in the histological analysis. VEGF and MMP-2 were studied in the immunohistochemistry analysis. Three patients with mechanical prosthetic obstruction due to pannus overgrowth underwent redo valve surgery. In the first and second patients, the mitral prosthesis was explanted along with the pannus overgrowth. The third patient had both aortic and mitral prostheses; the aortic prosthesis was explanted with obstructive pannus formation, whereas the mitral valve was spared with excision of the nonobstructive pannus. The immunohistochemical study demonstrated the expressions of MMP-2 and VEGF in all of the pannus specimens acquired from these cases. VEGF and MMP-2 may play a role in the mechanism of pannus formation as the elements of the chronic active inflammatory process.

A serial fluoroscopy-guided thrombolytic therapy of a mechanical tricuspid prosthetic valve thrombosis with low-dose and ultra-slow infusion of tissue-type plasminogen activator.

Prosthetic valve thrombosis is a life-threatening complication that is seen most commonly in patients with left-sided prosthetic valves. However, mechanical tricuspid valves carry the highest risk of thrombosis of any cardiac valve. Thrombolysis has been performed successfully in right-sided prosthetic valve thrombosis and has been recommended as the first-line treatment in these patients. Although two-dimensional and real-time three-dimensional transesophageal echocardiography are the gold standard imaging modalities for the diagnosis of prosthetic valve thrombosis, right-sided prosthetic valves may not be evaluated precisely. This is a serious problem during the follow-up of patients who receive thrombolytic therapy for tricuspid valve thrombosis. Fluoroscopy is an alternative noninvasive imaging method that provides valuable information about leaflet motion and may be used for such cases with restricted leaflets. Herein, we report a case of tricuspid valve thrombosis who was managed with low-dose (25 mg) and ultra-slow (25 hours) infusion of tissue-type plasminogen activator under the guidance of serial fluoroscopy.

The incremental value of RT three-dimensional TEE in the evaluation of prosthetic mitral valve ring thrombosis complicated with thromboembolism.

PURPOSE: Although nonobstructive prosthetic valve thrombosis (PVT) does not develop hemodynamic compromise, it carries potential risk for thromboembolism. Real time three-dimensional transesophageal echocardiography (RT-3DTEE), has emerged as a complementary tool in depicting "en face" views of prosthesis compared with two-dimensional transesophageal echocardiography (2DTEE). We aimed to evaluate the utility of RT-3DTEE in assessment of mitral ring-located thrombosis. METHOD: We present 3 cases of mechanical mitral valve thrombosis complicated by thromboembolism, who were all examined and followed-up by 2D transthoracic echocardiography (TTE), 2DTEE, and RT-3DTEE. RESULT: The consequencies of thromboembolism in the patients were coronary embolism, transient ischemic attack, and ischemic stroke, respectively. They were all inadequately anticoagulated at the time of admission. 2DTTE and TEE examination was unsatisfactory; RT-3DTEE depicted nonobstructive mitral ring thrombosis in each of the patients. The patients were followed up under effective anticoagulation and antiplatelet therapy. RT-3DTEE was able to demonstrate the evolution of thrombus size in each of the patients. CONCLUSION: Nonobstructive ring-located PVT which poses risk for thromboembolism, may be diagnosed with certainty and imaged with clarity utilizing RT-3DTEE.

Percutaneous closure of paravalvular mitral regurgitation with Vascular Plug III under the guidance of real-time three-dimensional transesophageal echocardiography.

Transcatheter closure of mitral prosthetic paravalvular leak (PVL) has been hampered by technical challenges and the lack of closure devices specifically designed for this purpose. The oblong cross-sectional shape of the Amplatzer Vascular Plug III device (AVP) may be a more appropriate choice to be deployed for mitral PVL's. Real-time three-dimensional transesophageal echocardiography (RT-3D TEE) has emerged as an efficient tool that provides essential information concerning leakage size, location, and shape as well as navigation of catheters and wires. We assessed the feasibility and short, mid, and long-term efficacy of transcatheter mitral PVL closure using AVP-III under the guidance of RT-3D TEE. Three patients with severe symptomatic mitral PVL at high risk for repeat surgery underwent transcatheter leak closure with AVP III. Transfemoral approaches were used under RT-3D TEE guidance. Transcatheter closure of mitral PVLs was performed successfully in 3 patients using 5 devices. The first patient with 2 devices deployed had residual mitral regurgitation resulting in re-operation at the sixth month. The second patient had improved normally with a functioning prosthesis after the deployment of two devices, but had progressively worsening mitral regurgitation for which re-operation at the sixteenth month of follow-up was necessary. The third patient had no residual leak, with normal prosthetic function. At 24 months follow-up, all patients were in satisfactory clinical status. Although RT-3D TEE plays an essential role in guidance of transcatheter closure of mitral PVLs with AVP III, the absence of a specific closure device limits mid and long-term success rates.

Normal echocardiographic measurements in a Turkish population: The Healthy Heart ECHO-TR Trial.

OBJECTIVE: Normal reference values for the cardiac chambers are widely based on cohorts from European or American populations. In this study, we aimed to obtain normal echocardiographic measurements of healthy Turkish volunteers to reveal the age, gender, and geographical region dependent differences between Turkish populations and other populations. METHODS: Among 31 collaborating institutions from all regions of Turkey, 1154 healthy volunteers were enrolled in this study. Predefined protocols were used for all participants during echocardiographic examination. Blood biochemical parameters were also obtained for all patients on admission. The American Society of Echocardiography and European Association of Cardiovascular Imaging recommendations were used to assess the echocardiographic cardiac chamber quantification. RESULTS: The study included 1154 volunteers (men: 609; women: 545), with a mean age of 33.5±11 years. Compared to men, women had a smaller body surface area, lower blood pressure and heart rate, lower hemoglobin, total cholesterol, lower low-density lipoprotein (LDL) levels, and higher high density lipoprotein (HDL) levels. Cardiac chambers were also smaller in women and their size varied with age. When we compared the regions in Turkey, the lowest values of left cardiac chamber indices were seen in the Marmara region and the highest values were observed in the Mediterranean region. Regarding the right cardiac indices, the Mediterranean region reported the lowest values, while the Black Sea region and the Eastern Anatolia region reported the highest values. CONCLUSION: This is the first study that evaluates the normal echocardiographic reference values for a healthy Turkish population. These results may provide important reference values that could be useful in routine clinical practice as well as in further clinical trials. (.

Ambulatory arterial stiffness index is associated with impaired left atrial mechanical functions in hypertensive diabetic patients: A speckle tracking study.

OBJECTIVE: The ambulatory arterial stiffness index has been proposed as an indicator of arterial stiffness. The aim of this study was to test the hypothesis that increased ambulatory arterial stiffness index might be related with impaired left atrial function in hypertensive diabetic patients with no previous history of cardiovascular disease. METHODS: Inclusion criteria included office systolic BP> 130 mm Hg or diastolic BP> 80 mm Hg and absence of secondary causes of HT, whereas exclusion criteria LV ejection fraction <50%, history of significant coronary artery disease, chronic renal failure, atrial fibrillation/ flutter, second or third-degree atrioventricular block, moderate to severe valvular heart disease, history of cerebrovascular disease, non-dipper hypertensive pattern and sleep apnea. The study was composed of 121 hypertensive diabetic patients. Twenty-four-hour ambulatory blood pressure monitoring and echocardiography were performed in each patient. The relationship between ambulatory arterial stiffness index and left atrial functions was analyzed. AASI was calculated as 1 minus the regression slope of diastolic BP plotted against systolic BP obtained through individual 24-h ABPM. RESULTS: The univariate analysis showed that ambulatory arterial stiffness index was positively correlated with age (r=:0.287, p=:0.001), hypertension duration (r=:0.388, p<0.001), fasting plasma glucose (r=:0.224, p=:0.014), HbA1c (r=:0.206, p=:0.023), LDL cholesterol (r=:0.254, p=:0.005), and also overall pulse pressure (r=:0.195, p=:0.002), office- pulse pressure (r=:0.188, p=:0.039), carotid intima-media thickness (r=:0.198, p=:0.029), E/E' (r=:0.248, p=:0.006), and left atrial volume index (r=:0.237, p=:0.009). Moreover, ambulatory arterial stiffness index was negatively correlated with eGFR (r=:(-) 0.242, p=:0.008), peak left atrial strain during ventricular systole [S-LAs (r=:(-) 0.654, p<0.001)], peak left atrial strain at early diastole [S-LAe (r=:(-)0.215, p=:0.018)], and peak left atrial strain rate during ventricular systole [SR-LAs (r=:(-) 0.607, p<0.001)]. The multiple linear regression analysis showed that ambulatory arterial stiffness index was independently associated with peak left atrial strain rate during ventricular systole (SR-LAs) (p<0.001). CONCLUSION: In hypertensive diabetic patients, increased ambulatory arterial stiffness index is associated with impaired left atrial functions, independent of left ventricular diastolic dysfunction.

Sixty-Four-Section Cardiac Computed Tomography in Mechanical Prosthetic Heart Valve Dysfunction: Thrombus or Pannus.

BACKGROUND: Distinguishing pannus and thrombus in patients with prosthetic valve dysfunction is essential for the selection of proper treatment. We have investigated the utility of 64-slice multidetector computed tomography (MDCT) in distinguishing between pannus and thrombus, the latter amenable to thrombolysis. METHODS AND RESULTS: Sixty-two (23 men, mean age 44±14 years) patients with suspected mechanical prosthetic valve dysfunction assessed by transesophageal echocardiography were included in this prospective observational trial. Subsequently, MDCT was performed before any treatment was started. Periprosthetic masses were detected by MDCT in 46 patients, and their attenuation values were measured as Hounsfield Units (HU). Patients underwent thrombolysis unless contraindicated, and those with a contraindication or failed thrombolysis underwent surgery. A mass which was completely lysed or surgically detected as a clot was classified as thrombus, whereas a mass which was surgically detected as tissue overgrowth was classified as pannus. A definitive diagnosis could be achieved in 37 patients with 39 MDCT masses (22 thrombus and 17 pannus). The mean attenuation value of 22 thrombotic masses was significantly lower than that in 17 pannus (87±59 versus 322±122; P<0.001). Area under the receiver operating characteristic curve was 0.96 (95% confidence interval: 0.91-0.99; P<0.001), and a cutoff point of HU≥145 provided high sensitivity (87.5%) and specificity (95.5%) in discriminating pannus from thrombus. Complete lysis was more common for masses with HU<90 compared with those with HU 90 to 145 (100% versus 42.1%; P=0.007). CONCLUSIONS: Sixty-four slice MDCT is helpful in identifying masses amenable to thrombolysis in patients with prosthetic valve dysfunction. A high (HU≥145) attenuation suggests pannus overgrowth, whereas a lower value is associated with thrombus formation. A higher attenuation (HU>90) is associated with reduced lysis rates.

The influence of dipper/nondipper blood pressure patterns on global left ventricular systolic function in hypertensive diabetic patients: a speckle tracking study.

OBJECTIVE: This study was designed to investigate the effects of dipper and nondipper patterns on global longitudinal systolic functions of left ventricle (LV) by means of two-dimensional speckle tracking echocardiography in treated hypertensive diabetic patients with preserved left ventricular ejection fraction. PATIENTS AND METHODS: We enrolled 86 hypertensive diabetic patients. Twenty-four hour ambulatory blood pressure monitoring and echocardiography were performed in each patient. The relationship between dipper/nondipper patterns and global longitudinal strain (GLS) was analyzed. RESULTS: Fifty-one (59.3%) patients had a nondipper pattern. GLS and average global longitudinal strain rate systolic (GLSRs) were significantly decreased (-17.8±1.5, -19.6±1.9; P<0.001 vs. -1.01±0.171, -1.18±0.19; P<0.001) and E/E' was significantly increased (9.7±4.3, 7.7±3.8; P=0.033) in nondippers compared with dippers. Multivariate linear regression analysis showed that the difference between mean arterial pressure (MAP)-asleep and MAP-awake and left ventricular mass index (LVMI) was associated independently with GLS and GLSRs (MAP-asleep-MAP-awake ß=-0.292, P=0.004; ß=-0.305, P=0.001 and LVMI ß=-0.373, P=0.001, ß=-0.517, P<0.001; respectively). E/E' was associated independently with MAP-asleep-MAP-awake (ß=0.241, P=0.022), age (ß=-0.272, P=0.012), male sex (ß=0.351, P=0.001), and LVMI (ß=0.236, P=0.038). Also, SBP-asleep and LVMI were found to be associated independently with GLS and GLSRs (SBP-asleep ß=-0.405, P<0.001; ß=-0.271, P=0.004 and LVMI ß=-0.339, P=0.002; ß=-0.517, P<0.001; respectively). CONCLUSION: This study shows that the nondipper pattern is associated with subclinical LV systolic dysfunction in treated hypertensive diabetic patients with preserved left ventricular ejection fraction. Also, elevated night-time SBP was found to be related to impaired LV systolic functions.

Usefulness of novel hematologic inflammatory parameters to predict prosthetic mitral valve thrombosis.

Prosthetic valve thrombosis (PVT) is a life-threatening complication. Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) have been studied as inflammatory biomarkers in atherosclerosis, but data regarding valvular disease are lacking. The study population included patients with mitral PVT (n = 152) versus control subjects (n = 164) with functional mitral prosthesis. Transesophageal echocardiography was performed to diagnose PVT. NLR and PLR were calculated using complete blood count. C-reactive protein (CRP) levels were also analyzed. Neutrophil and platelet levels did not differ between the groups (4.9 ± 2.0 vs 4.7 ± 1.5, p = 0.84 and 254.8 ± 89.7 vs 241.5 ± 62.8 p = 0.36, respectively), but lymphocyte levels were significantly lower in patients with PVT than the controls (1.8 ± 0.7 vs 2.2 ± 0.6, p <0.001). NLR, PLR, and CRP levels were significantly higher in patients with PVT than in controls (3.2 ± 2.1 vs 2.2 ± 0.8, p <0.001; 163 ± 77.5 vs 114.9 ± 37.3, p <0.001; and 1.97 ± 3.02 vs 1.02 ± 1.22, p = 0.01, respectively). A positive correlation was observed between NLR and PLR (r = 528, p <0.001). NLR level of >2.23, measured on admission, yielded an area under the curve value of 0.659 (95% confidence interval 0.582 to 0.736, sensitivity 66%, specificity 60%, p <0.001) and PLR level of >117.78 yielded an area under the curve value of 0.707 (95% confidence interval 0.636 to 0.777, sensitivity 70%, specificity 58%, p <0.001). Multivariate analysis showed that increased PLR and inadequate anticoagulation were independent predictors of thrombosis in patients with PVT. In conclusion, patients with PVT had increased NLR, PLR, and CRP levels compared with subjects with normofunctional prosthesis, and increased PLR was an independent predictor of mitral PVT.

Comparison of neutrophil to lymphocyte ratio in patients with coronary artery ectasia versus patients with obstructive coronary artery disease.

BACKGROUND: Previous studies have demonstrated that inflammation, neurohormonal process and cardiovascular risk factors are associated with the development of coronary artery ectasia (CAE). However, the underlying mechanisms responsible for ectasia formation are not fully understood. The neutrophil to lymphocyte (N/L) ratio has recently emerged as a new inflammation marker for cardiovascular disease. AIM: In this study, we hypothesised that CAE could be associated with more severe inflammation compared to obstructive coronary artery disease (O-CAD) with regard to N/L ratio values. METHODS: A total of 405 patients with isolated CAE, O-CAD and insignificant CAD (controls) were enrolled. Severity of isolated CAE was determined according to the Markis classification. N/L ratio values were compared between the three groups. RESULTS: We determined that the patients with isolated CAE had significantly elevated N/L ratio values compared to O-CAD and control groups (2.5 vs. 1.9, p < 0.001 and vs. 1.6, p < 0.001, respectively). In multivariate analysis adjusted for age, sex, diabetes mellitus (DM) and hypertension, N/L ratio was independently associated with the presence (N/L ratio, OR = 2.48, 95% CI 2.03-3.02, p < 0. 001) and severity (DM, OR = 2.90, 95% CI 1.02-8.18, p = 0.044, N/L ratio, OR = 1.88, 95% CI 1.47-2.41, p = 0.004) of isolated CAE. ROC curve analysis revealed that a N/L ratio value of > 2.06 identified the patients with isolated CAE. CONCLUSIONS: We showed that patients with isolated CAE had a significantly higher N/L ratio than patients with O-CAD and control groups. This finding suggests that a more severe inflammatory process could be involved in the development of CAE.

Severe mitral paravalvular leakage: echo-morphologic description of 47 patients from real-time three-dimensional transesophageal echocardiography perspective.

OBJECTIVE: Paravalvular leaks (PVLs) commonly occur in mitral prostheses. Real-time 3-dimensional transesophageal echocardiography (RT-3D TEE) may provide invaluable information about complex 3D anatomy of mitral PVLs compared to two-dimensional (2D) TEE findings. We, herein, aimed to evaluate the detailed description of anatomical characteristics of severe mitral PVLs using RT-3D TEE. METHODS: Patients with diagnosis of severe mitral PVLs were simultaneously examined with 2D transthoracic echocardiography (TTE), 2D TEE, and RT-3D TEE. 3D characteristics of PVLs (localization, number, size, shape, etc.) were recorded and compared to 2D findings. Results were also compared with surgical findings. RESULTS: The study comprised 47 cases (3 bioprosthesis, 44 mechanical) with 61 severe mitral PVLs. The most common PVL localizations were anterolateral commissure, posteromedial commissures and posterolateral region. The mean PVL width measured by 2D TEE was 3.1±1.3 (range; 2-7) mm and the mean width of defect measured by 3D TEE was 3.1±1.1 (range; 2-7) mm (p=0.7). The mean length of defect measured by 3D TEE was 11.1±6.5 mm. The most common defect type was 'oval/round' shaped (n=29; 48%). There were also 19 'crescentic' (31%), 9 'slit like' (15%), and 2 tunnel-like shaped defects. In 22 patients, the site and dimension of the PVLs were all confirmed surgically. CONCLUSION: RT-3D TEE permits detailed structural evaluation of the prosthesis and description of paravalvular leak morphology compared to 2D TEE. It may provide more accurate information to the clinician in decision making and may contribute to the success of the potential corrective procedures.

Real-time three-dimensional transesophageal echocardiography in the assessment of mechanical prosthetic mitral valve ring thrombosis.

Although 2-dimensional (2D) transesophageal echocardiography (TEE) is the gold standard for the diagnosis of prosthetic valve thrombosis, nonobstructive clots located on mitral valve rings can be missed. Real-time 3-dimensional (3D) TEE has incremental value in the visualization of mitral prosthesis. The aim of this study was to investigate the utility of real-time 3D TEE in the diagnosis of mitral prosthetic ring thrombosis. The clinical outcomes of these patients in relation to real-time 3D transesophageal echocardiographic findings were analyzed. Of 1,263 patients who underwent echocardiographic studies, 174 patients (37 men, 137 women) with mitral ring thrombosis detected by real-time 3D TEE constituted the main study population. Patients were followed prospectively on oral anticoagulation for 25 ± 7 months. Eighty-nine patients (51%) had thrombi that were missed on 2D TEE and depicted only on real-time 3D TEE. The remaining cases were partially visualized with 2D TEE but completely visualized with real-time 3D TEE. Thirty-seven patients (21%) had thromboembolism. The mean thickness of the ring thrombosis in patients with thromboembolism was greater than that in patients without thromboembolism (3.8 ± 0.9 vs 2.8 ± 0.7 mm, p <0.001). One hundred fifty-five patients (89%) underwent real-time 3D TEE during follow-up. There were no thrombi in 39 patients (25%); 45 (29%) had regression of thrombi, and there was no change in thrombus size in 68 patients (44%). Thrombus size increased in 3 patients (2%). Thrombosis was confirmed surgically and histopathologically in 12 patients (7%). In conclusion, real-time 3D TEE can detect prosthetic mitral ring thrombosis that could be missed on 2D TEE and cause thromboembolic events.

Comparison of different TEE-guided thrombolytic regimens for prosthetic valve thrombosis: the TROIA trial.

OBJECTIVES: The aim of this prospective study was to identify the most effective and safest regimen among different thrombolytic treatment strategies. BACKGROUND: The best treatment strategies for prosthetic valve thrombosis have been controversial. METHODS: Transesophageal echocardiography-guided thrombolytic treatment was administered to 182 consecutive patients with prosthetic valve thrombosis in 220 different episodes (156 women; mean age, 43.2 ± 13.06 years) between 1993 and 2009 at a single center. These regimens chronologically included rapid (Group I), slow (Group II) streptokinase, high-dose (100 mg) tissue plasminogen activator (t-PA) (Group III), a half-dose (50 mg) and slow infusion (6 h) of t-PA without bolus (Group IV), and a low dose (25 mg) and slow infusion (6 h) of t-PA without bolus (Group V). The endpoints were thrombolytic success, in-hospital mortality, and nonfatal complication rates. RESULTS: The overall success rate in the whole series was 83.2%; it did not differ significantly among Groups I through V (68.8%, 85.4%, 75%, 81.5%, and 85.5%, respectively; p = 0.46). The overall complication rate in the whole series was 18.6%. Although the overall complication rate was similar among Groups I through IV (37.5%, 24.4 %, 33.3%, and 29.6%, respectively; p > 0.05 for each comparison), it was significantly lower in Group V (10.5%, p < 0.05 for each). The combined rates of mortality and nonfatal major complications were also lower in Group V than in the other groups, with all differences significant except for comparison of Groups IV and V. By multivariate analysis, the predictors of combined mortality plus nonfatal major complications were any thrombolytic therapy regimen other than Group V (odds ratios for Groups I through IV: 8.2, 3.8, 8.1, and 4.1, respectively; p < 0.05 for each) and a history of stroke/transient ischemic attack (odds ratio: 3.5, p = 0.011). In addition, there was no mortality in Group V. CONCLUSIONS: Low-dose slow infusion of t-PA repeated as needed without a bolus provides effective and safe thrombolysis in patients with prosthetic valve thrombosis. (Comparison of Different TRansesophageal Echocardiography Guided thrOmbolytic Regimens for prosthetIc vAlve Thrombosis; NCT01451320).