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Background: Prosthetic valve thrombosis (PVT) is a severe and life-threatening complication. Surgery and thrombolytic therapy (TT) carry a high risk, and in several circumstances, optimal anticoagulation with unfractionated heparin (UFH) infusion may be an alternative treatment. This study aimed to assess the results of UFH in patients diagnosed with both obstructive and non-obstructive PVT., Methods: This observational retrospective study enrolled patients who had contraindications for TT and surgery underwent UFH therapy., Results: A total of 136 patients were enrolled [male: 55 (40.4%), mean age: 50.3 ± 14.6 years] in the study. In the successful group, 66 patients (48,5%) showed >75% regression in the thrombus burden without facing death or major non-fatal complications.In the unsuccessful group, 56 had less than a 50% reduction in thrombus load and 14 (10.3%) suffered major complications. The presence of obstruction (27.1% vs. 12.1%; p = 0.028), thrombus area 1.1 cm 2 vs. 0.8 cm 2 ; p = 0.005] and the duration of UFH treatment (15.1 vs. 11.8 (days); p = 0.005) were significantly higher in the unsuccessful UFH group.In multivariate regression analyses the presence of obstruction (RR: 3.088, p = 0.020), increased thrombus area (RR: 2.400; p = 0.015), and increased duration of UFH therapy (RR: 1.073 95%, p = 0.012) were identified as independent predictive parameters for a failed UFH therapy., Conclusions: This study suggests that UFH therapy may be considered a relatively beneficial treatment strategy for some patients with PVT. The most significant factors affecting success are the obstructive nature and area of the thrombus., Competing Interests: Declaration of competing interest All of the authors have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Left ventricular apical thrombus ( LVAT) formation is a well-known complication of acute anterior myocardial infarction (AMI). The CHA2DS2VASc is a scoring system that has been used to estimate the risk of thromboembolism in patients with nonvalvular atrial fibrillation. This score has also been used for other clinical conditions. The aim of this study was to investigate the relationship between CHA2DS2VASc score and development of LVAT in patients with AMI., Method: The study population included 378 patients (mean age: 56.5 ± 12.3 years, male: 318) presenting with AMI between January 2016 and January 2020. Primary percutaneous coronary intervention procedure was performed in all patients. Initial echocardiogram was performed within 7 days of admission. All patients were evaluated with echocardiography at 3rd, 6th and 12th months. Patients were divided into two groups according to the presence of LVAT on echocardiography., Results: The incidence of the LVAT was 8.5% ( n  = 32) during a mean follow-up time of 233.1 ± 66.7 days. The mean CHA2DS2VASc score was notably higher in patients with LVAT compared to patients in the control group (3.1 ± 1.9 vs. 1.9 ± 1.2, p  < 0.001). In Cox regression analysis, high CHA2DS2VASc score, low left ventricular ejection fraction (LVEF) and the presence of LV apical akinesis/aneurysm were the independent predictors for LVAT formation. All of these parameters were associated with higher cumulative incidence of LVAT formation in Kaplan-Meier analyses ( p  < 0.001 for all)., Conclusion: High CHA2DS2VASc score, low LVEF and the presence of LV apical akinesis/aneurysm may be used for LVAT risk prediction among patients presenting with AMI.

Aim: This study aimed to evaluate the relationship between intracoronary thrombus burden and systemic immune-inflammation index (SII) and to compare the predictive capacity of SII together with the neutrophil-lymphocyte ratio (NLR), and the platelet-lymphocyte ratio (PLR) in patients with ST-elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PPCI)., Patient & Methods: A total of 425 patients were included in the study. The clinical, laboratory, and demographic characteristics of the patients were recorded. The thrombus classification "Thrombolysis in myocardial infarction (TIMI)" was used to assess the intracoronary thrombus burden. According to the TIMI thrombus classification, 229 (54%) patients with low thrombus burden (grade 0-3) and 196 (46%) patients with high thrombus burden (grade 4 and 5) were compared. SII was calculated as platelet × neutrophil/lymphocyte counts., Results: High NLR (OR: 1.068, 95% CI:1.023-1.404; p  = 0.031), PLR(OR: 1.012, 95% CI:1.002-1.018; p  = 0.043), SII(OR: 1.325, 95% CI: 1.156-1.879; p  = 0.015) and low left ventricle ejection fraction (LVEF) (OR: 0.957, 95% CI:0.924-0.990; p  = 0.012) were found to be independent predictors of high thrombus burden. SII values above 812 predicted a high thrombus burden with a sensitivity of 82% and specificity of 73% (AUC: 0.836; 95% CI:0.795-0.877; p  < 0.001). This predictiveness of SII was stronger as compared to NLR (0.836 vs. 0.818, p  = 0.043) and PLR (0.836 vs. 0.780, p  < 0.001)., Conclusion: SII is an independent predictor of high thrombus burden in patients with STEMI. In addition, SII is superior to NLR and PLR in this regard.

Background: Intermittent malfunction is a rare but potentially serious complication of prosthetic heart valve replacement. This study aimed to describe the clinical features and etiologic causes of patients with intermittent mechanical prosthetic heart valve dysfunction., Methods: Between 2010 and 2021, 16 patients who were evaluated in the echocardiography laboratory of Koşuyolu Training and Research Hospital with the diagnosis of intermittent malfunction of prosthetic valves were included in the study., Results: The evaluated patients consisted of 12 bi-leaflet mitral valve replacements and 2 mono-leaflet mitral valve replacements. The underlying causes of intermittent malfunction were classified as follows: residual chord (n=4), obstructive thrombus (n=2), non-obstructive thrombus (n=2), vegetation (n=2), pannus and obstructive thrombus coexistence (n=1), and solely pannus (n=1). One of the patients with mono-leaflet mitral valve replacements had pannus and obstructive thrombus. In the other patient with mono-leaflet mitral valve replacement, a stuck valve was observed in 1 of 12 beats secondary to arrhythmia. There were also 2 patients with aortic valve replacements. One patient had moderate aortic regurgitation due to prominent calcification and the other had moderate obstruction due to pannus. In the patient with pannus, a stuck leaflet was observed in 1 of 6 beats and moderate aortic regurgitation arose in 1 of 2 beats in the patient with calcification., Conclusions: The intermittent stuck valve may have catastrophic outcomes. When making a treatment decision in these patients, assessing the degree of regurgitation or stenosis is essential. In particular, the frequency of entrapment should be taken into consideration when deciding the optimal therapy for intermittent prosthetic heart valve dysfunction.

Background: Prosthetic valve thrombosis (PVT) is one of the life-threatening complications of prosthetic heart valve replacement. Due to the lack of randomized controlled trials, the optimal treatment of PVT remains controversial between thrombolytic therapy (TT) and surgery., Objectives: This study aimed to prospectively evaluate the outcomes of TT and surgery as the first-line treatment strategy in patients with obstructive PVT., Methods: A total of 158 obstructive PVT patients (women: 103 [65.2%]; median age 49 years [IQR: 39-60 years]) were enrolled in this multicenter observational prospective study. TT was performed using slow (6 hours) and/or ultraslow (25 hours) infusion of low-dose tissue plasminogen activator (t-PA) (25 mg) mostly in repeated sessions. The primary endpoint of the study was 3-month mortality following TT or surgery., Results: The initial management strategy was TT in 83 (52.5%) patients and surgery in 75 (47.5%) cases. The success rate of TT was 90.4% with a median t-PA dose of 59 mg (IQR: 37.5-100 mg). The incidences of outcomes in surgery and TT groups were as follows: minor complications (29 [38.7%] and 7 [8.4%], respectively), major complications (31 [41.3%] and 5 [6%], respectively), and the 3-month mortality rate (14 [18.7%] and 2 [2.4%], respectively)., Conclusions: Low-dose and slow/ultraslow infusion of t-PA were associated with low complications and mortality and high success rates and should be considered as a viable treatment in patients with obstructive PVT., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Prosthetic valve thrombosis (PVT) is a serious complication among patients with prosthetic heart valves. Thrombolytic therapy (TT) is now widely used as first-line treatment for PVT. Endothelial dysfunction has previously been reported in patients with PVT. The aim of this study was to investigate the changes in endothelial function soon after TT in PVT patients., Methods: The study group included 85 patients with PVT [female: 53 (62.3%); age: 48.7±13.9 years] who were evaluated prospectively before and shortly after TT. All of the patients were evaluated using transthoracic and transesophageal echocardiography. TT was administered in all cases with a low-dose, ultra-slow infusion regimen. Endothelial function was evaluated using a noninvasive measurement of flow-mediated dilatation (FMD) of the brachial artery during reactive hyperemia., Results: The study population included 38 (44.7%) obstructive and 47 (55.3%) non-obstructive PVT patients. The obstructive PVT patients had lower baseline FMD values than the non-obstructive PVT group (5.31±0.76% vs. 5.87±0.84%; p=0.003). TT was successful in 79 patients (92.9%). FMD was significantly increased in the successfully thrombolyzed patients after TT (5.65±0.86% vs. 7.13±1.26%; p<0.001). There was no significant difference in the FMD values after TT in patients who were unresponsive to TT (5.07±0.61% vs. 5.38±0.95%; p=0.371). There was a significant increase in FMD values after TT in patients with obstructive PVT (5.31±0.76% vs. 8.22±1.15%; p<0.001). However, this difference was not statistically significant for patients with non-obstructive PVT (5.87±0.84% vs. 6.11±0.95%; p=0.276)., Conclusion: This study demonstrated that successful TT may contribute to improvement of impaired endothelial function in patients with obstructive PVT.

Objective: Spontaneous echo contrast (SEC) is defined as dynamic, smoke-like echoes within the cardiac cavities with a characteristic swirling motion seen on echocardiography. Clinical studies have demonstrated that SEC is a risk factor for left atrial thrombus formation and an important indicator for potential systemic embolism. Platelet indices have been associated with the presence of SEC in patients with mitral stenosis. The aim of this study was to investigate the relationship between platelet indices and SEC in patients with prosthetic heart valves., Methods: A total of 89 patients [female: 38 (42.4%); median age: 52 years (range: 36-67 years)] with SEC formation in the left atrium, and 257 control subjects [female: 123 (47.5%); median age: 56 years (range: 45-65 years)] without SEC formation were enrolled. All of the patients were evaluated by using transthoracic and transesophageal echocardiography. Laboratory tests including complete blood count and biochemical parameters were analyzed., Results: Patients with SEC formation had more frequent atrial fibrillation, higher left atrial diameter (LAD) and lower left ventriular ejection fraction values. Platelet indices including platelet count, platelet distribution width, mean platelet volume, and plateletcrit did not differ between the groups. Increased LAD was detected as the only independent predictor of SEC development., Conclusion: Platelet indices were not found to be associated with the presence of SEC formation in the left atrium among patients with mitral prosthetic valves. Therefore, the use of platelet indices alongside known echocardiographic and clinical risk factors to predict SEC development in patients with a mitral prosthesis is debatable.

Introduction : Prosthetic heart valve thrombosis is a life-threatening complication after valve replacement surgery. Although subtherapeutic anticoagulation is the main cause, there are many other conventional and esoteric predisposing factors. Areas covered : The etiopathogenesis, diagnosis, and management of prosthetic heart valve thrombosis with particular focus on conventional and esoteric predisposing factors, diagnosis with multimodality imaging and current therapeutic approaches were covered. Expert opinion : Subtherapeutic anticoagulation remains the key driving force for the development of prosthetic valve thrombosis. However, cardiologists should be cognizant of other frequent or rare conventional and esoteric causes. The diagnosis is now more straightforward with the use of multimodality imaging. Transthoracic and transesophageal echocardiography with or without real-time three-dimensional imaging are the current gold standard modalities. Multidetector computed tomography is now a major complementary tool. The favorable clinical outcomes with recently introduced slow or ultra-slow infusions of alteplase, as compared to relatively poor surgical results, have rendered thrombolytic therapy the first-line treatment option in most eligible patients with prosthetic valve thrombosis. Surgical treatment could be reserved in whom thrombolytic therapy is contraindicated or has already failed. The efficacy and safety of thrombolytic therapy as compared to surgery should be confirmed with large observational cohorts, and ideally randomized trials.

Introduction: Procoagulant activity of heparanase has been recently described in several arterial and venous thrombotic disorders. In this study, we aimed to investigate the role of heparanase with regard to thrombus burden, thromboembolism, and treatment success with unfractionated heparin (UFH) in patients with prosthetic valve thrombosis (PVT)., Methods: This study enrolled 79 PVT patients who received UFH for PVT and 82 controls. Plasma samples which were collected from patients both at baseline and after the UFH treatment and from controls at baseline only, were tested for heparanase levels by heparanase enzyme-linked immunosorbent assay., Results: The PVT group included 18 obstructive and 61 non-obstructive PVT patients who received UFH infusions for a median duration of 15 (7-20) days. The UFH treatment was successful in 37 (46.8%) patients. Baseline heparanase levels were significantly higher in the patient group than in the controls [0.29 (0.21-0.71) vs. 0.25 (0.17-0.33) ng/mL; p = 0.002]. Baseline heparanase levels were significantly higher in obstructive PVT patients. There was a significant increase in heparanase levels after UFH treatment. Post-UFH heparanase levels were higher in patients who experienced treatment failure compared to successfully treated group. Baseline and post-UFH heparanase levels were significantly higher in patients with a thrombus area ≥1 cm 2 and with a recent history of thromboembolism., Conclusions: Increased heparanase levels may be one of the esoteric causes for PVT. UFH treatment may trigger an increase in heparanase levels which may affect the treatment success. Increased heparanase levels may be associated with high risk of thromboembolism and increased thrombus burden in PVT patients., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

: Plasma D-dimer level is an indicator of thrombosis and endogenous fibrinolytic activity. We investigated the association between the D-dimer levels and thrombus burden and cerebrovascular events in patients with obstructive prosthetic valve thrombosis (PVT). This retrospective study included 47 patients with obstructive left-sided PVT and 32 controls in whom PVT was excluded with comprehensive transthoracic and transesophageal echocardiography (TEE). The patient group included 11 aortic, 27 mitral, and 9 aortic and mitral valve PVT patients and the control group included 2 aortic, 25 mitral, and 5 aortic and mitral valve patients. Laboratory analysis including plasma D-dimer levels was performed at the time of admission in all patients. The baseline characteristics were similar between the two groups. The plasma D-dimer levels were significantly higher in patients with obstructive PVT compared with controls [680 (110-3590) vs. 310 (80-380) μg/l; P < 0.001]. By multivariate logistic regression analysis high D-dimer level, low-INR value on admission, high NYHA functional class and recent history of cerebrovascular accident (CVA), and transient ischemic attack (TIA) were the independent predictors of obstructive PVT. A plasma D-dimer level of greater than 365 μg/l predicted the presence of PVT with a sensitivity of 81% and a specificity of 69% (AUC= 0.781, P < 0.001). Plasma D-dimer levels were significantly higher in patients with a recent history of CVA/TIA [2140 (470-2980) vs. 590 (380-830) μg/l; P = 0.021]. In addition to the so-called indicators of PVT including subtherapeutic anticoagulation, increased D-Dimer levels may strengthen the suspicion of PVT. Moreover, higher plasma D-dimer levels were associated with higher thrombus burden and higher prevalence of recent CVA/TIA.

Background: Prosthetic valve thrombosis (PVT) may impair pulmonary venous flow (PVF) and left atrial appendage (LAA) functions. An investigation was conducted to determine the association between left superior PVF and LAA functions and mitral PVT., Methods: This observational case-control study included 100 consecutive patients (87 females, 13 males; mean age 59 years; range 35-71 years) with mechanical mitral PVT, and 50 age- and gender-matched otherwise healthy controls with normally functioning mitral prostheses. All patients were included after comprehensive transesophageal echocardiography (TEE) examinations for the presence and quantification of PVT, the left atrial diameter, and LAA length. Peak systolic velocity (PSV), velocity-time integral of systolic flow (VTI-s), peak diastolic velocity (PDV), velocity-time integral of diastolic flow (VTI-d), systolic fraction (SFr) of the left upper PVF and the flow of the LAA orifice were each recorded using color-guided pulsed-wave Doppler imaging during TEE., Results: The PSV [30 cm/s (range: 13-77 cm/s) versus 44 cm/s (range: 16-71 cm/s)], respectively (p = 0.002), VTI-s [(2.85 cm (range: 0.5-10.7 cm) versus 5 cm (range: 1.3-12.7 cm)], respectively (p <0.001), VTI-d [(3 cm (range: 0.6-9.7 cm) versus 4.2 cm (range: 1.5-8.3 cm)], respectively (p <0.001), SFr (45.5% (range: 15.66-67.44%) versus 50 % (range: 21.11-82.61%)], respectively (p = 0.008), and LAA orifice velocity [(23 cm/s (range: 11-75 cm/s) versus 34 cm/s (range: 10-112 cm/s)], respectively (p = 0.011) were each significantly lower in patients with PVT compared to controls. The PDV was similar between groups. Patients with obstructive PVT (n = 21) had a lower PDV and a higher VTI-d compared to those with non-obstructive PVT., Conclusions: Mitral mechanical PVT is associated with decreased systolic PVF and LAA function. The presence of obstructive PVT is associated with further limitations of diastolic flow velocity, and a compensatory prolongation of diastolic flow of the left upper pulmonary vein.

Background and Aim of the Study: Protein Z (PZ) is a vitamin K-dependent factor that is synthesized mainly by the liver. It acts as an activator of serpin, the protein Z-dependent inhibitor (ZPI), which inhibits factor Xa. The potential role of alterations in protein Z and/or ZPI levels in the pathogenesis of thrombotic and/or hemorrhagic diseases has been previously investigated, but results have been conflicting. The study aim was to evaluate the role of PZ/ZPI polymorphisms in the development of prosthetic valve thrombosis (PVT)., Methods: This prospective, observational cross-sectional study included 50 consecutive patients with PVT [non-obstructive thrombosis (NOT) in 35 patients; obstructive thrombosis (OT) in 15] and 50 consecutive healthy subjects with normally functioning prostheses. gDNA was extracted from ca. 5 × 106 leukocytes, using the QIAamp DNA Mini Kit (Qiagen), according to the manufacturer's recommendations. For mutational analysis, a minisequencing method was employed. Results of the analyses were compared between the PVT and control groups, and also between the OT and NOT subgroups., Results: The frequency of A allele (mutant type) of PZG79A was equal in all PVT patients and in controls. With regards to PZ-A13G polymorphisms, frequency of the mutant G allele was 22% in PVT patients and 19% in controls. Serpina-R67X polymorphism was observed in 8% of PVT patients and 6% of controls. Normal variant CC was present in 47 controls (94%), whereas a heterozygotic mutation (CT) was detected in four PVT patients (8%). Frequency of the ZPI-R67X mutation was significantly higher in patients with OT than in those with NOT (p = 0.041)., Conclusions: The present study was the first to evaluate the potential impact of PZ (PZ-A13G, PZG79A) and ZPI (R-67X, W303X) polymorphisms in the development of PVT. Based on the results of this small observational case-control study, PZ/ZPI polymorphisms do not appear to play an active role in the development of PVT. Hence, further extensive studies are necessary.

Background: The outcomes of thrombolytic therapy (TT) in elderly patients with prosthetic valve thrombosis (PVT) have not been evaluated previously. We investigated the outcomes of low-dose and slow infusion TT strategies in elderly patients with PVT., Methods: Twenty-seven (19 female) patients aged ≥65 years (median: 70 years, range: 65-82 years) were treated with repeated TT agents for PVT. The TT regimens included 24-hour infusion of 1.5 million units of streptokinase in 2 patients, 6-hour infusion of 25 mg recombinant tissue plasminogen activator (t-PA) in 12 patients, and 25-hour infusion of 25 mg t-PA in 13 patients. Treatment success and adverse event rates were assessed., Results: The initial and cumulative success rates were 40.7% and 85.2%, respectively. Adverse events occurred in 6 (22.2%) patients including 4 (14.8%) major (1 death, 1 rethrombosis, and 2 failed TT) and 2 (7.4%) minor (1 transient ischemic attack and 1 access site hematoma) events. Higher thrombus burden (thrombus area ≥1.1 cm 2 by receiver operating characteristics analysis, sensitivity: 83.3%, specificity: 85%, area under the curve: 0.86, P = .008) and New York Heart Association class (0% vs 15.4% vs 25% vs 100% for classes I-IV, respectively, P = .02) predicted adverse events. By multiple variable analysis, thrombus area was the only independent predictor of adverse events (odds ratio: 13.8, 95% confidence interval: 1.02-185, P = .04)., Conclusion: Slow infusion of low doses of TT agents (mostly t-PA) with repetition is successful and safe in elderly patients with PVT. However, excessive thrombus burden may predict adverse events.

Prosthetic valve thrombosis is one of the major causes of primary valve failure, which can be life-threatening. Multimodality imaging is necessary for determination of leaflet immobilization, cause of underlying pathology (thrombus versus pannus or both), and whether thrombolytic therapy attempt in the patient would be successful or surgery is needed. Current guidelines for the management of prosthetic valve thrombosis lack definitive class I recommendations due to lack of randomized controlled trials, and usually leave the choice of treatment to the clinician's experience. In this review, we aimed to summarize the pathogenesis, diagnosis, and management of mechanical prosthetic valve thrombosis.

Objective: The non-O alleles of the ABO genotype have been associated with an increased risk of thrombosis. We aimed to assess the association between blood group status and prosthetic valve thrombosis., Methods: The association between AB0 blood group status and prosthetic valve thrombosis was assessed in this retrospective study. Transesophageal echocardiography was performed in 149 patients with a diagnosis of prosthetic valve thrombosis and in 192 control subjects., Results: Non-0 blood group type (p<0.001), presence of NYHA class III-IV status (p<0.001), and central nervous system (p<0.001) and non-central nervous system (p<0.001) emboli were significantly more prevalent in prosthetic valve thrombosis patients than in the control subjects. The incidence of ineffective anticoagulation was higher in patients with prosthetic valve thrombosis than in controls (p<0.001), as was the presence of moderate to severe left atrial spontaneous echo contrast (p<0.001). The non-0 blood prosthetic valve thrombosis subgroup had a higher incidence of obstructive thrombi and central nervous system thrombotic events than having 0 blood prosthetic valve thrombosis subgroup. Non-0 blood group, ineffective anticoagulation, left atrial spontaneous echo contrast, and a poor NYHA functional capacity were identified to be the predictors of prosthetic valve thrombosis., Conclusion: Our data demonstrate that patients with non-0 compared with 0 blood groups have higher incidence of prosthetic valve thrombosis and central nervous system embolism and similar rates of non-central nervous system embolism at presentation compared with 0 blood group type. Thus, non-O blood group may be a risk factor that may be prone to the development of prosthetic valve thrombosis in patients with prosthetic heart valves.

Background: Thrombolysis is an effective treatment strategy for prosthetic valve thrombosis (PVT). Recombinant tissue-type plasminogen activator (rt-PA) is widely used as a thrombolytic agent. Infusion of rt-PA may trigger the production of anti-tissue plasminogen activator (tPA) antibodies (ATAs). We aimed to evaluate the possible relationship between ATA levels and PVT formation, and the role of baseline ATA levels on outcomes of thrombolytic therapy in patients with PVT., Methods: This prospective, single-center cohort study included 28 patients with PVT undergoing thrombolysis and 31 controls with normal prostheses. Plasma samples were collected from patients with PVT at baseline and at 15th, 30th, 90th, and 180th days after thrombolysis and from controls at baseline only. The ATA levels were assessed in human plasma by an enzyme-linked immunosorbent assay., Results: Baseline ATA-immunoglobulin (Ig) G and IgM were significantly higher in patients with PVT than in controls. The levels of IgM and IgG peaked at 15th and 30th days after rt-PA infusion, respectively. Subtherapeutic international normalized ratio and baseline ATA-IgM were independent predictors of PVT. Thrombolysis failed in 6 patients (21%) in whom baseline IgM levels were significantly higher than successfully lysed patients. Rethrombosis occurred in 9 patients (32%) in whom baseline IgG levels were significantly higher than those without rethrombosis. There was a moderate positive correlation between baseline and 15th-day IgM levels and the dose of rt-PA needed for successful lysis., Conclusion: The ATA levels tended to be higher in patients with PVT at the time of initial diagnosis compared to controls without PVT. In addition, such patients with PVT and high ATA levels may be at high risk for failed thrombolysis or rethrombosis., (© The Author(s) 2015.)

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Coronary thromboembolism is a rare cause of acute coronary syndromes (ACS). The information regarding ACS in patients with prosthetic heart valves is scarce and based mainly on case reports. Although plaque rupture is the most common cause of acute myocardial infarction, coronary embolism (CE) is not a rare cause of acute myocardial infarction. There is no consensus regarding the treatment in such a situation. We present three cases of prosthetic valve thrombosis complicated with CE causing non-ST elevation ACS, who were successfully treated with thrombolytic therapy (TT). We administered low-dose (25 mg), slow-infusion (6 hours) tissue plasminogen activator (t-PA), which was shown to be safe and effective in our group in a large study. The patients benefited from TT with respect to the coronary flow, as shown by the lysis of thrombi in all three patients on coronary angiogram.

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.

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.

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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., (© 2013, Wiley Periodicals, Inc.)

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.

Intermittent malfunction is a rare but potentially serious complication of prosthetic heart valve (PHV) replacement. It may be observed in both mitral and aortic valve prosthesis and may lead to either paroxysmal obstruction or regurgitation, depending on the valve location and on the phase of the cardiac cycle during which the leaflet is entrapped. The most frequently encountered causes of intermittent valve malfunction are pannus formation, prosthetic valve thrombosis, vegetations, and remnants of subvalvular apparatus such as chordae tendineae and suture material. Intermittent severe regurgitation of PHV due to residual chordae tendineae is very rare clinical entity, and transesophageal echocardiography is an indispensable guide in the differential diagnosis. Here, we represent an interesting case of intermittent regurgitation of a mitral prosthetic valve due to entrapment by a residual subvalvular apparatus. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]