Prolonged Infusions of Low-Dose Thrombolytics in Elderly Patients With Prosthetic Heart Valve Thrombosis.

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 cm2 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.

Primary cardiac hydatid cyst presenting as noncompaction cardiomyopathy.

We report a case of cyst was initially labeled as left ventricular noncompaction cardiomyopathy. An accurate diagnosis is essential to establish the most effective treatment strategy. In particular, echocardiographic examination assists in identifying the correct diagnosis. In this case, two-dimensional and three-dimensional echocardiography and computed tomography were used for definitive diagnosis of cardiac hydatid cyst.

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.

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.

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.

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.

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).

Acute ST-elevation inferior myocardial infarction in a patient with a non-obstructive mechanical mitral valve thrombosis.

The risk of systemic embolisation in patients with prosthetic heart valves who are receiving anticoagulation therapy is 0.5 to 1.7% per patient year and most cases present with cerebrovascular events. Here we report the case of a 42-year-old woman who was uneventfully treated with a low dose, prolonged infusion of tissue plasminogen activator because of non-obstructive prosthetic mitral valve thrombosis. It presented as coronary embolism and resulted in acute ST-elevation inferior myocardial infarction.

Effect of levosimendan and predictors of recovery in patients with peripartum cardiomyopathy, a randomized clinical trial.

BACKGROUND: Levosimendan is a promising new inodilator agent but its effectiveness in peripartum cardiomyopathy (PPCM) has not been tested in a clinical trial. The authors sought to evaluate the effect of levosimendan therapy and to determine the predictors of clinical outcome in patients with PPCM. METHODS AND RESULTS: The authors prospectively randomized 24 consecutive women with PPCM. Twelve patients (control group) were randomized to conventional heart failure therapy and 12 patients (levosimendan group) were randomized to levosimendan in addition to the conventional therapy. Mean follow-up period was 20.9 ± 9 months (ranged 12-38 months). The two groups did not differ in baseline demographic and echocardiographic characteristics. Eleven patients (45.8%) recovered completely (6 in control group and 5 in levosimendan group, p > 0.05), 6 died (25%) (3 in control group and 3 in levosimendan group), and 7 (29.1%) were left with persistent left ventricular dysfunction (PLVD) (3 in control group and 4 in levosimendan group, p > 0.05). There were significant differences in baseline characteristics between deceased patients and survivors including left ventricular end-diastolic diameter (7.1 ± 0.6 vs. 6.4 ± 0.5 cm, p = 0.031), left ventricular end-systolic diameter (LVESD) (6.4 ± 0.8 vs. 5.5 ± 0.6 cm, p = 0.027), left ventricular ejection fraction (LVEF) (19.7 vs. 27.4%, p = 0.025), and left atrial diameter (4.9 ± 0.3 vs. 4.3 ± 0.4 cm, p = 0.011). CONCLUSIONS: Addition of levosimendan to conventional therapy did not improve outcome in patients with PPCM. In patients with PLVD or patients who died, LVEF, LVESD and left atrial diameter were worse than those with complete resolution.

Acute myocardial infarction during thrombolysis of mechanical aortic valve thrombosis associated with heparin-induced thrombocytopenia.

We report a case of a 60-year-old man with obstructive aortic prosthetic valve thrombosis (APVT). He was treated with low-dose (25 mg) slow infusion (6 hours) of intravenous tissue plasminogen activator (t-PA), and he suffered acute anterior myocardial infarction (MI) at the fourth hour of t-PA infusion. Infusion was kept on, and coronary reperfusion and successful lysis of APVT were achieved. Intravenous unfractionated heparin (UFH) was then started, however, on the third day following heparin treatment, heparin-induced thrombocytopenia (HIT) was recognized by a drop in the platelet count and rethrombosis of the prosthetic valve. Although no nonheparin anticoagulant was available, intravenous continuous infusion of streptokinase (SKZ) 250,000 U per day was administered for 5 days followed by transition to warfarin therapy. Successful lysis of the APVT was again achieved with this regimen and the patient was discharged after uneventful recovery. The patient remained well at 6 months and 1 year follow-up.

Multiple spontaneous coronary artery dissection associated with Trousseau's syndrome.

Spontaneous coronary artery dissection (SCAD) remains a rare cause of acute coronary syndrome. SCAD has been observed in three groups of patients: those with coronary atherosclerosis, women in the peripartum period, and an idiopathic group. SCAD may also be associated with some other conditions. Herein, we present a 57 year-old man who developed SCAD concomitant with Trousseau's syndrome secondary to colon adenocarcinoma.

Sinus arrest due to sertraline.

Sertraline is a selective serotonin reuptake inhibitor with established safety for the treatment of depression. Among the common adverse effects associated with sertraline are nausea, insomnia, diarrhea, somnolence, and dizziness. Cardiac arrest had not been reported in the literature, although tachycardia was frequently seen. In this case report, a patient was presented who had adverse reactions such as nausea, dizziness, insomnia under citalopram treatment, and after his drug was changed to sertraline, developed sinus arrest on the fourth day of treatment.

Depicting of a cleft mitral valve by real time three-dimensional transesophageal echocardiography.

We report the usefulness of real time three-dimensional transesophageal echocardiography in comprehensive delineation of cleft mitral valve. This new technique may be a useful supplement to two-dimensional and three-dimensional transthoracic echocardiography in the assessment of this pathology.

Successful treatment of massive pulmonary embolism in a pregnant woman, with low-dose, slow infusion of tissue plasminogen activator.

Pulmonary embolism (PE) is an important cause of morbidity and mortality during pregnancy. A 21-year-old pregnant woman presented with chest pain and progressive shortness of breath at 35 weeks of gestation. Her respiratory rate was 26 breaths/min. Electrocardiography showed sinus tachycardia and nonspecific ST-T changes. Her plasma D-dimer level was elevated (1,325 ng/ml). Transthoracic echocardiography revealed enlargement of the right ventricle and a large, highly mobile thrombus in the right atrium moving during diastole into the right ventricle. Doppler ultrasonography of the lower extremities showed bilateral acute deep femoral vein thrombosis. Following the diagnosis of right heart thrombosis with massive PE, low-dose and prolonged infusion of tissue-type plasminogen activator (25 mg in three hours) was administered. Echocardiography performed six hours after thrombolysis showed a significant decrease in the right ventricular size and complete lysis of the thrombus in the right heart. Thrombosis risk panel studies showed factor V Leiden homozygote mutation. A live newborn was delivered by cesarean section at 37 weeks of gestation. No complications were seen during a 6-month follow-up.

Coronary artery disease in patients with peripheral artery disease.

OBJECTIVES: Peripheral artery disease (PAD) is an atherosclerotic disease associated with cardiovascular risk factors, and with high cardiovascular morbidity and mortality. This study sought to assess the prevalence of angiographic coronary artery disease (CAD), and to determine the predictive value of traditional cardiovascular risk factors on the presence of CAD in patients with PAD of the lower extremities. METHODS: In total, 231 patients who presented at hospital complaining of intermittent claudication were included. All patients underwent simultaneous peripheral and cardiac angiography. Age, gender, hypertension, diabetes, smoking, and lipid values were recorded. RESULTS: The coronary angiograms of 64 (28%) patients were within normal limits, and 167 (72%) patients manifested CAD. Logistic regression analysis revealed that hypertension and diabetes were independent predictors for the presence of CAD or PAD. CONCLUSION: Aggressive treatment of cardiovascular risk factors, especially hypertension and diabetes, in PAD is critically important in reducing mortality and morbidity.

Diagnosis of the prosthetic heart valve pannus formation with real-time three-dimensional transoesophageal echocardiography.

Prosthetic heart valve obstruction (PHVO) caused by pannus formation is an uncommon but serious complication. Although two-dimensional transesophageal echocardiography (2D-TEE) is the method of choice in the evaluation of PHVO, visualization of pannus is almost impossible with 2D-TEE. While demonstrating the precise aetiology of PHVO is essential for guiding the therapy, either thrombolysis for valve thrombosis or surgery for pannus formation, more sophisticated imaging techniques are needed in patients with suspected pannus formation. We present real-time 3D-TEE imaging in a patient with mechanical mitral PHVO, clearly demonstrating pannus overgrowth.