title: Ultraslow thrombolytic therapy: A novel strategy in the management of PROsthetic MEchanical valve Thrombosis and the prEdictors of outcomE: The Ultra-slow PROMETEE trial.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Cardiology, Faculty of Medicine, Kars Kafkas University, Kars, Turkey; Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey.
authors: Mehmet
authors: M
authors: Özkan
authors: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey. Electronic address: sabahattingunduz@yahoo.com.
authors: Sabahattin
authors: S
authors: Gündüz
authors: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey.
authors: Ozan Mustafa
authors: OM
authors: Gürsoy
authors: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey.
authors: Süleyman
authors: S
authors: Karakoyun
authors: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey.
authors: Mehmet Ali
authors: MA
authors: Astarcıoğlu
authors: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey.
authors: Macit
authors: M
authors: Kalçık
authors: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey.
authors: Ahmet Çağrı
authors: AÇ
authors: Aykan
authors: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey.
authors: Beytullah
authors: B
authors: Çakal
authors: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey.
authors: Zübeyde
authors: Z
authors: Bayram
authors: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey.
authors: Ali Emrah
authors: AE
authors: Oğuz
authors: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey.
authors: Emre
authors: E
authors: Ertürk
authors: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey.
authors: Mahmut
authors: M
authors: Yesin
authors: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey.
authors: Tayyar
authors: T
authors: Gökdeniz
authors: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey.
authors: Nilüfer Ekşi
authors: NE
authors: Duran
authors: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey.
authors: Mustafa
authors: M
authors: Yıldız
authors: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, Istanbul, Turkey.
authors: Ali Metin
authors: AM
authors: Esen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D017548:Echocardiography, Transesophageal; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D006349:Heart Valve Diseases / Q000150:complications / Q000601:surgery; D006350:Heart Valve Prosthesis / Q000009:adverse effects*; D006352:Heart Ventricles; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D017410:Practice Guidelines as Topic; D011475:Prosthesis Failure; D012189:Retrospective Studies; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005343:Fibrinolytic Agents