Petrescu, Ioana

Introduction: Bioprosthetic valve thrombosis (BPVT) is a well-recognized cause of prosthetic dysfunction. Anticoagulation restores prosthetic valve gradients, but long term outcomes and complications from therapy are unknown. Objectives: To define the complications and long-term outcomes of anticoagulant therapy for BPVT. Methods: Retrospective matched cohort study of patients treated with warfarin for presumed BPVT at a single center from 1999 to 2016. Controls with normal bioprostheses by echocardiography were matched 2:1 for age at implantation, gender, prosthetic valve position, and type of prosthesis (porcine / pericardial). Results: A total of 83 presumed BPVT patients (40 aortic, 21 mitral, 18 tricuspid, and 4 pulmonary) and 166 controls were included. Age at BPVT diagnosis was 60±19 yrs (41±41 months post implantation); 45 (54%) were male. Transvalvular gradients returned to baseline in 63 (76%) of the patients, after 5±4 months of warfarin; 60 (72%) patients were maintained on warfarin indefinitely. Recurrent BPVT was seen in 13 (16%) patients, 33±31 months after initial therapy. When compared to controls, warfarin-treated BPVT patients had similar incidence of stroke [4(5%) vs 5 (3%), p=0.49], peripheral embolic events [4(5%) vs 10 (6%), p=0.78)], and death [12 (14%) vs 28 (17%), p= 0.72] (Figure, left panel), but more bleeding requiring transfusion [18 (22%) vs 3 (2%), p<0.0001]. Presumed BPVT patients more often required surgical or percutaneous valve re-replacement (Figure, center panel); this difference persisted even when comparing only patients with confirmed BPVT (those who responded to anticoagulant therapy) vs. their matched controls (Figure, right panel). Conclusion: Warfarin anticoagulation for presumed BPVT is successful in the majority of patients, without increase in stroke, peripheral embolism or death, but at the cost of excess bleeding. Recurrent BPVT occured in 16% of patients. Importantly, patients with BPVT required more often valve re-replacement. This finding suggests that anticoagulant therapy does not fully restore prosthetic valve durability, and that BPVT patients should be closely monitored.

Introduction: Intrinsic wave propagation is a novel approach to measure myocardial stiffness (MS) as validated in animal studies. Aims and Hypothesis: 1) To compare MS measured by the wave method with chamber stiffness (CS) derived from noninvasively estimated end-diastolic pressure-volume relationship (EDPVR) in patients; 2) To test the hypothesis that MS is superior to CS for predicting outcomes in patients with cardiac amyloidosis (CA). Methods: Prospective study in 56 patients with amyloidosis (CA: 38, noncardiac amyloidosis, NCA: 18; 90% AL-type; age 63 ± 10 yrs; ejection fraction 57 ± 11%) and 36 normal subjects (age 49 ± 13 years). Intrinsic velocity propagation of myocardial stretch (iVP), a measure of MS, was measured by ultra-high frame rate (250-465Hz) tissue Doppler imaging. Left ventricular (LV) EDPVR were reconstructed using the noninvasive single-beat method (Fig.A). Stiffness coefficients (α, β, load-independent) and CS (dP/dV) were calculated. End-diastolic pressure (EDP) was estimated from E/e’. Adverse events at follow-up (death, heart failure, stroke, significant arrhythmia) were recorded. Results: iVP was higher in CA compared to NCA and controls, indicating higher MS (Fig. B). This was confirmed by EDPVR, which were steeper and shifted leftward (Fig. A). The slope (β) of EDPVR and CS (dP/dV) were higher and LV capacitance (V 30 , volume at 30 mmHg) was lower in CA (Fig. A) and correlated with iVP (β: r = 0.59; CS dP/dV, r = 0.43; EDP, r = 0.61; all p<0.0001). Patients with higher LV thickness (r = 0.66), lower LV longitudinal strain (r = -0.57) and elevated NT-proBNP (r = 0.69) had higher iVP. At follow-up (median 2.5 years), after adjusting for relevant confounders, an iVP >2.7 m/s was strongly associated with excess events (p<0.0001; Fig. C) and was superior to measures of CS (dP/dV: p = 0.28; β >6.5: p = 0.03; Fig. D). Conclusions: Myocardial stiffness by intrinsic wave method shows similar findings to chamber stiffness by EDVPR, but is more strongly related to outcomes in patients with amyloidosis.

Introduction: Bioprosthetic valve thrombosis (BPVT) is increasingly being recognized as a cause of prosthetic valve dysfunction within the first years after surgical implantation. However, in the absence of changes in clinical status, current guidelines recommend cardiac imaging only after 10 years post bioprosthetic valve implantation . Hypothesis: We hypothesized that an increase in prosthetic valve gradient is detectable months before a formal diagnosis of symptomatic BPVT. Methods: Eighty-three patients diagnosed with BPVT and treated medically at our institution between 2002 and 2017 were retrospectively identified. Transvalvular gradients recorded on TTE immediately post implantation, at time of clinical BPVT diagnosis, and within a 12-month period prior to BPVT diagnosis were available in 45 patients: 18 for the aortic position, 11 for mitral, and 16 for tricuspid. When more than one study was conducted in the 12 months’ timeframe, the latest value was used in the analysis. Data are reported as mean (95% CI). Results: For all valve positions, an increased gradient was detectable within 12 months prior to formal BPVT diagnosis: mean increase vs. baseline of 17 (10-23) mmHg, p < 0.0001 for aortic prostheses; 5 (2-8) mmHg, p = 0.004 for mitral prostheses, and 2 mm Hg (1-3) mmHg, p = 0.003 for tricuspid prostheses. The figure presents the evolution of prosthetic valve gradients (normalized to the baseline, immediately post-implantation value) in patients with aortic (left), mitral (middle), and tricuspid (right) valve . Conclusions: Elevated gradients precede formal clinical diagnosis of BPVT. Closer monitoring of transvalvular gradients may prove useful for BPVT diagnosis before patients become symptomatic. With recent evidence supporting the efficacy of anticoagulant therapy in BPVT, earlier diagnosis may lead to an increased rate of response and better clinical outcomes.

Objective Bioprosthetic valve thrombosis (BPVT) is increasingly recognised as a major cause of prosthetic dysfunction in the first years postimplantation. How early abnormal gradients can be detected prior to diagnosis and how fast they normalise with anticoagulant therapy is unknown. We set forth to (1) evaluate patterns of increase in gradients prior to BPVT diagnosis and (2) characterise time-course of response to anticoagulation. Methods Patients treated with warfarin for BPVT (1999–2019) with clinically significant reduction of mean gradients (≥25%) were identified retrospectively. Recovery was defined as gradient decrease ≥50%, to postimplantation or to normal-range gradients per position, model and size. Time-to-BPVT (implantation—BPVT diagnosis), potential diagnostic delay (first abnormal gradient by position, model and size—BPVT diagnosis) and time-to-recovery (BPVT diagnosis—complete resolution) were recorded. Results 77 patients were identified; 32 (42%) aortic (23 surgical—12 porcine, 11 pericardial; 9 transcatheter); 24 (31%) mitral; 21 (27%) tricuspid. Median time-to-BPVT was 24, 21 and 10 months, respectively. Potential diagnostic delay was median 21 months for aortic, 4 months for mitral, but 0 for tricuspid. Recovery was significantly faster in mitral than aortic (median 2.5 vs 4.8 months, p=0.038) and tricuspid (median 5.9 months, p=0.025) positions. Porcine aortic valves responded faster than pericardial aortic valves (median 2.9 vs 20.3 months, p=0.004). Conclusion Gradients start to increase months before the clinical BPVT diagnosis. Recovery is faster in mitral and surgical aortic porcine valves; a longer warfarin trial seems indicated in tricuspid and surgical aortic pericardial valves.

Background: Warfarin is known to be effective in the treatment of bioprosthetic valve thrombosis (BPVT). However, the time-course of response to anticoagulation has not been fully characterized. Hypothesis: We hypothesized that response to warfarin can differ depending on valve position. Methods: We retrospectively identified 45 patients with BPVT diagnosis between 2002 and 2019 that involved either the mitral (MV) or the aortic valve (AV) prostheses, all with eventual echocardiographic resolution with warfarin. BPVT involved AV in 26 (57.8%) patients and MV in 19 (42.2%). Mean gradients (MGs) were tracked starting from BPVT diagnosis until recovery, which was defined as MGs decreasing to initial post-implantation MGs, to 50% below MGs at BPVT diagnosis, or to < 20 mmHg in AV and < 5 mmHg in MV. Kaplan Meier analysis was used to compare recovery time between MV and AV. Duration is reported relative to the time of BPVT diagnosis. Results: Recovery was faster in MV than in AV patients treated with warfarin, with median time of 3.8 months in the AV and 1.8 months in the MV group, p < 0.001 (Figure 1). At 1 month follow up, 15.4% recovered in AV group and 21.1% in MV, p = 0.605. At 3 months, 38.5% recovered in the AV and 78.9% in the MV, p = 0.009. At 6 months, 57.7% of AV group recovered while 100% recovered in the MV group, p = 0.001. The longest time for recovery was 30 months in 1 AV patient. Conclusion: Recovery using warfarin tended to be faster in BPVT involving the MV compared with the AV. In our study, all patients with MV BPVT recovered by 6 months, while this only happened in half the patients with AV BPVT. This suggests that a longer duration of warfarin trial may be needed in the case of AV disease. This might also suggest that the pathogenesis may differ between the two valves.