Author + information
- Ganesan Karthikeyan, MD, DM, MSc∗ (, )
- Nagendra Boopathy Senguttuvan, MD, DM,
- Niveditha Devasenapathy, MBBS, MSc,
- Vinay K. Bahl, MD, DM and
- Balram Airan, MS, MCh
- ↵∗All India Institute of Medical Sciences, Room 24, Department of Cardiology, Ansari Nagar, New Delhi, 110029 India
Left-sided mechanical prosthetic valve thrombosis (PVT) is a life-threatening condition frequently seen in developing countries (1). Although urgent surgery is more effective (2,3), fibrinolytic therapy (FT) is the most commonly used treatment in these countries. About one-third of patients treated with FT do not have successful restoration of valve function (2–4). Although all such patients are considered for additional surgery, it is often delayed in resource-poor settings. It is our experience, supported by anecdotal reports (5), that residual valve dysfunction may normalize uneventfully while the patient receives oral anticoagulation. However, the rate of such an occurrence is unknown because there are no prospective studies of patients with residual valve dysfunction awaiting surgery.
In this single-center, prospective, observational study, we enrolled patients undergoing FT for left-sided PVT if they had either a failed or partial response (4). We excluded patients who were hemodynamically unstable or had a major complication requiring urgent intervention. All patients were referred for surgery and were followed up 1 month after discharge and subsequently at 3-month intervals. At each follow-up visit, patients underwent clinical, echocardiographic, and fluoroscopic evaluation. All patients gave written informed consent, and the institutional ethics committee approved the study protocol.
The primary outcome was the occurrence of spontaneous normalization of valve function, defined as complete normalization of valve leaflet motion on fluoroscopy and valve gradients on echocardiography. We determined the Kaplan-Meier rate of occurrence of the primary outcome and evaluated potential predictors by use of Cox regression. We also determined the rate of occurrence of major adverse events (a composite of death, stroke, transient ischemic attack, or non–central nervous system embolism, major bleeding, and recurrent PVT). All analyses were performed with the use of Stata 13 (StataCorp, College Station, Texas).
Of the 122 patients who received FT for left-sided PVT between February 1, 2010 and January 31, 2012, 31 patients were eligible for enrollment (Table 1). Streptokinase was the most commonly used agent for fibrinolysis. All except one patient received at least 72 h of streptokinase or a full dose of tissue plasminogen activator. All patients improved with FT, and nearly 90% (25 of 28) were in New York Heart Association functional class I or II at first follow-up.
Of the 31 patients, 1 died and 4 had restoration of valve function in-hospital, possibly as the result of delayed effects of the fibrinolytic infusion. Three patients (12.5%) underwent elective redo valve replacement, and 2 were lost to follow-up. Eleven of the remaining 24 patients (45.8%) showed spontaneous normalization of valve function over 15 person-years of follow-up (0.73/person-years; 95% confidence interval [CI]: 0.41 to 1.33). The mean time to valve opening was 3 months, with none opening beyond 6 months. Fewer patients had subtherapeutic international normalized ratios (INRs) at follow-up (21% vs. 65% at presentation, p = 0.006), and the average INR during follow-up was higher than at the time of presentation (3.1 ± 0.6 vs. 2.5 ± 1.6; p = 0.0059; n = 23). The percentage of reduction in transvalvular gradients with FT (hazard ratio, 4.80; 95% CI: 0.65 to 35.15; p = 0.12) and the average INR during follow-up (hazard ratio, 3.45; 95% CI: 0.84 to 14.19; p = 0.086) were associated with the occurrence of the primary outcome, but these associations were not statistically significant.
Seven patients had eight major adverse events. Four events occurred in the hospital (1 death, 2 non-fatal intracranial bleeds, and 1 stroke) and were attributable to fibrinolytic therapy. After discharge from the hospital, over a 27.8 person-year follow-up, 4 patients had 4 major adverse events (2 deaths, 1 recurrence of PVT, and 1 major bleed), at a rate of 0.14/person-years (95% CI: 0.05 to 0.38). The earliest event occurred at 1 month and the last at 4 months. There were no adverse events beyond 4 months of follow-up. Overall, 6 of 10 (60%) patients who did not improve by at least 1 New York Heart Association functional class had a major complication compared with one of 19 (5.3%) who did improve (p = 0.0026). Reduction in valve gradients with FT did not correlate with improvement in functional class and was not associated with the occurrence of adverse outcomes.
This is the first report to document the occurrence of spontaneous valve opening after failed FT. In a review of 243 patients in 17 retrospective studies with failed FT, Huang et al. (3) found that follow-up information was not available in more than 40% of patients even for assessment of 30-day outcomes. None of the studies followed up patients beyond 30 days. This information is relevant for developing countries because many patients with residual valve dysfunction do not undergo redo surgery.
Though spontaneous restoration of valve function was common, the rate of major adverse events during follow-up was high. However, these events occurred almost exclusively in patients (6 of 7) who were in New York Heart Association functional class III or those who had not improved in functional class with FT. The magnitude of reduction in transvalvular gradients, though predictive of spontaneous valve opening, was not associated with either improvement in functional class or the occurrence of adverse events. Transvalvular gradients are dynamic and are influenced by many variables, including heart rate, and may misrepresent the degree of valve dysfunction. However, these findings are based on a small number of patients and must be interpreted cautiously.
In conclusion, residual valve dysfunction after FT normalizes spontaneously in nearly one-half the patients, but the risk of major adverse events is prohibitively high, particularly among patients who do not show improvement in functional class after FT. Thus, these patients should be triaged for early redo surgery irrespective of the reduction in transvalvular gradients.
Please note: All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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