Prosthetic valve thrombosis: predisposition and diagnosis

Transcription

1 European Heart Journal Supplements (2001) 3 (Supplement Q), Q16 Q21 Prosthetic valve thrombosis: predisposition and diagnosis C. Piper, D. Hering and D. Horstkotte Department of Cardiology, Heart Center North Rhine-Westphalia, University Hospital of the Ruhr University of Bochum, Bad Oeynhausen, Germany Prosthetic valve thrombosis (PVT) is an obstruction of a prosthesis by non-infective thrombotic material. The interaction of a variety of prosthesis- and patient-related factors account for risk for PVT. The typical clinical finding in PVT is diminution of occluder clicks, which may be detected using sound spectroscopy. Fluoroscopy facilitates prompt and reliable assessment of occluder movements. Interpretation of echocardiographic findings is not so simple. Echo-Doppler derived gradients that are twice as high as those found in Introduction Thrombotic and thromboembolic complications remain an important cause of morbidity and mortality following valve replacement surgery. Efforts to reduce the thrombogenicity of valve substitutes have prompted new designs that allow for better transprosthetic flow conditions and that have surfaces with improved biocompatibility in comparison with older designs [1]. A reduction in thrombogenicity after covering synthetic material with colloidal graphite solution was reported as early as 1961 [2]. Valve housings and/or occluders of modern prostheses are manufactured from or coated with pyrolite. The biocompatibility of pyrolite is primarily due to the fact that the molecular structure of plasma proteins does not alter significantly when they are adsorbed on the surface of the prosthesis [3]. The total thromboembolic hazard after valve replacement is accounted for not only by the device itself, but also by interactions between a variety of factors that relate both to prosthesis and patient (e.g. coagulability, cardiac physiology, cardiac morphology). In most cases of thromboembolism, the heart had been affected for many years by chronic volume or pressure overload, resulting in endocardial damage and eventually chamber enlargement, impaired cardiac function and concomitant arrhythmias. normal prostheses are suspicious and indicate PVT. Early diagnosis and prompt therapeutic intervention are required for successful management of PVT. (Eur Heart J Supplements 2001; 3 (Suppl Q): Q16 Q21) 2001 The European Society of Cardiology Key Words: Anticoagulation, fluoroscopy, hypercoagulability, prosthetic valve thrombosis, sound spectroscopy. Those aspects and their relationship to prosthetic valve thrombosis (PVT) are addressed in detail in this supplement by Horstkotte et al. Definition PVT is an obstruction of a prosthesis by non-infective thrombotic material. In contrast, entrapment of the occluder, and obstruction of the blood-stream by pannus (tissue ingrowth), sutures or cardiac structures (e.g. following inappropriate sizing of the prosthesis), and infective vegetations are considered non-structural dysfunction [4]. Valve thrombosis is a subcategory of thromboembolic events. This category includes all new, permanent or transient events, unless the non-thrombotic nature is evident from intraoperative/autopsy findings or clinical investigations [4]. All clinically documented thromboses are reported in accordance with this definition, which tends to result in excessive reporting, because non-thrombotic obstructions are also regarded as PVT if the aetiology cannot be differentiated accurately. Pathogenesis Correspondence: Cornelia Piper, MD, Heart Center North Rhine- Westphalia, Department of Cardiology, Georgstrasse 11, D Bad Oeynhausen, Germany X/01/0Q $35.00/0 The pathogenesis of intra-cardiac thrombus formation, irrespective of whether it occurs with or without the 2001 The European Society of Cardiology

2 Prosthetic valve thrombosis Q17 implantation of prosthetic material, is complex. Three basic mechanisms should be defined. Molecular interactions The first mechanism involves the molecular interaction between corpuscular blood components, plasma and artificial surfaces. The initial adsorption of plasma proteins (fibrinogen) on the artificial surface is generally followed by platelet adhesion [5]. Influence of transprosthetic blood flow The second mechanism is dependent on the influence of the transprosthetic blood flow on local thrombus formation. This can occur in three ways. First, unphysiological flow that involves rapidly changing flow directions ( turbulent flow ) may result in a blood-borne increase in shear stress (>5 10 dyn cm 2 ) and consequently in a structurally and metabolically damaged endocardium, causing it to lose its resistance to thrombosis (see review by Horstkotte et al. in this supplement). Second, the thrombogenic role played by blood stasis in recirculation areas downstream from the prosthesis after valve replacement surgery is beyond doubt. Clot formation starts almost exclusively in the area subject to peri-prosthetic recirculation (i.e. on the outflow side of the prosthesis) [6,7]. Because the velocity of the transprosthetic flow near the valve housing is low, most mechanical prostheses are designed to allow for mild leakage while the occluders are closed, in order to prevent clot formation in these areas. Finally, chronic, subclinical haemolysis may occur as a consequence of the accelerated destruction of thrombocytes and erythrocytes with shortened intravascular lifespans. The subsequent release of adenosine diphosphatase, platelet factor 4, beta-thromboglobulin and other proteins is closely related to the increase in blood-borne shear stress to which these blood elements are exposed [6]. Local hypercoagulability The impact of local hypercoagulability is often underestimated; it is important to appreciate that all factors that promote clotting or platelet aggregation, permanently or temporarily, increase the risk for local thrombosis. Among these factors are inadequate or unstable anticoagulation, loss of atrial contraction (atrial fibrillation), sporadic use of a variety of drugs, malignancies or systemic diseases, defects on the prosthetic surface, incomplete endothelialization of the sewing ring, inflammation with or without an increase in fibrinogen, and other hypercoagulable states [5,8,9]. The non-linearized hazard for thrombotic/ thromboembolic complications, which peaks during the first months following valve replacement, can thus easily be explained by a temporary increase in local hypercoagulability caused by the highly activated intrinsic clotting system that results from exposure to the sewing cuff (which is yet to be endothelialized), intraoperative tissue damage and the unstable anticoagulation [10]. Incidence The incidence of PVT has been reported to average 0 2% per patient-year after aortic and 1 8% per patient-year after mitral valve replacement, within a broad range from less than 0 1 to more than 6% per patient-year [11,12]. These significant differences are probably a consequence of under-reporting in studies because of inadequate follow-up techniques [13,14] and non-standardized postoperative anticoagulation regimens [10]. The risk for PVT appears to be twice as high in mitral as in aortic valve replacement, and is more than three times higher for a tricuspid valve prosthesis (Fig. 1). Predisposing factors If we report on the results in our institution, we documented 67 PVTs. Incidence by prosthesis type and position is provided in Fig. 2. For 32 of those patients detailed information regarding the anticoagulation status at least for the 12 months before the occurrence of PVE is presented (group A; Fig. 3a); for the remaining 35 patients, sufficient but less precise data are available (group B, Fig. 3b). Anticoagulation status Anticoagulation status during the 12 months before the occurrence of PVT in 32 patients is provided in Fig. 3. Patients can be grouped as follows. Ten of the patients of group A (31 2%) had documented optimal anticoagulation during the 12 months before the occurrence of PVT (patients 2, 6, 10, 11, 14, 17, 20, 24, 25 and 29; Fig. 3a). The median International Normalized Ratio (INR) in those patients was 3 6 ± 0 2. Of all measurements, 95% were within the target therapeutic INR range and there were no significant variations between two consecutive measurements. Six of the patients of group A (18 8%) had received inappropriately low anticoagulation, with median INR levels below the accepted therapeutic range (patients 4, 8, 9, 16, 22 and 27; Fig. 3a). They also had large fluctuations in consecutive INR measurements, indicating frequent interruption or incorrect intake of their medication. Thirteen patients of group A (40 6%; patients 1, 3, 5, 12, 13, 18, 21, 23, 26, 28 and 30 32; Fig. 3a) and all patients of group B (Fig. 3b) had unstable anticoagulation, with large variations between consecutive INR measurements. The median INRs in group A (3 6 ± 0 3, ranging from 3 2 to 4 0) were within the recommended therapeutic range (INR ). The unstable anticoagulation (mean INR 3 8 ± 2 3,

3 Q18 C. Piper et al. % per patient-year Figure 1 The incidence of prosthetic valve thrombosis (PVT) in 67 cases shown by position and different observation periods from 1981 to 2000 reveal a significant reduction in PVT over the years. The risk for PVT remains twice as high in mitral than in aortic valve prostheses, and risk for PVT in tricuspid protheses remains far higher. % per patient-year Tricuspid Mitral Aortic old TD CM SJM bio Figure 2 Comparison of the incidence of prosthetic valve thrombosis (PVT) in mitral, aortic and tricuspid position for prostheses of prior generations (old=starr-edwards, Smeloff-Cutter, Lillelei-Kaster), various tilting disc prostheses (TD), Carbomedics (CM), St. Jude Medical (SJM), and bioprostheses (bio) is shown in 67 patients with proven PVT. range ) in group B patients was predominantly due to long intervals between consecutive INR controls. Eight patients had <4, 17 patients had 4 8, and 10 patients had 9 15 INR controls during the 12 months prior to the diagnosis of PVT (Fig. 3b). Morerover, 33 of the 249 INR measurements (13 3%) documented in group B showed an INR below 2.0. Three patients of group A (9 4%) had not had any anticoagulation for 14, 48 and 72 months, respectively (patients 7, 15 and 19). (a) International Normalized Ratio (b) International Normalized Ratio consecutive patients, group A 35 patients, group B Mitral position (n = 33) Aortic position (n = 23) Tricuspid position (n = 11) Figure 3 (a) For 32 of the patients detailed information regarding the anticoagulation status at least for the 12 months before the occurrence of prosthetic valve thrombosis (PVT) is presented (group A). (b) For the remaining 35 patients, sufficient but less precise data are available (group B). The box represents 66% of parameters, the bar ( whisker ) 95% of measurements. From these findings it appears that unstable anticoagulation may be the major risk factor predisposing to clot formation after mechanical valve replacement. Other contributory factors Seasonal variations in fibrinogen levels during the winter months have been correlated with an increased risk for stroke and acute myocardial infarction [15 17]. In our patient cohort we were able to confirm earlier observations of a seasonal increase in incidence of PVT during the winter months (Fig. 4). The higher fibrinogen levels (Fig. 5) and the increase in plasma viscosity (Fig. 6) may be considered additional indicators of a potential influence of hypercoagulability on the occurrence of PVT. Diagnosis Patients with rapid progression of obstruction present with acute and progressive dyspnoea/orthopnoea or lung oedema. Cerebral, coronary or peripheral embolization

4 Prosthetic valve thrombosis Q19 % per patient-year Mitral valve prostheses Aortic valve prostheses I II III IV V VI VII VIII IX X XI Calendar months Figure 4 Seasonal incidence of prosthetic valve thrombosis in patients with mitral or aortic valve protheses demonstrates a seasonal increase during the winter months for both implantation sites. 1 Fibrinogen (mg. dl ) P < Patients with proven PVT Figure 5 Plasma fibrinogen levels in 52 patients with proven prosthetic valve thrombosis (PVT) were significantly greater than in 31 patients being reoperated for periprosthetic leaks during the same time period. manifests in up to 25% of patients before the diagnosis is made [12]. The typical clinical finding in PVT is diminution of the occluder clicks that are characteristic of that particular prosthesis. A sound pressure analysis is very sensitive in detecting clot formation at a very early stage [18,19]. In patients with bileaflet prostheses the high resolution of sound spectrography makes it possible, for instance, to distinguish between two different closing clicks (one for each leaflet), with such a short time interval between them that they cannot be differentiated by auscultation. A typical finding in thrombosed bileaflet prostheses is a delayed click with reduced amplitude (Fig. 7). Because sophisticated sound analysis is available in only a few centres, fluoroscopy is the diagnostic tool of choice if XII Patients being reoperated for periprosthetic leaks Plasma viscosity (mpa) P < Patients with proven PVT Patients being reoperated for periprosthetic leaks Figure 6 Plasma viscosity in 14 patients reoperated for prosthetic valve thrombosis (PVT) and 31 patients reoperated for periprosthetic leaks during the same time period. Significantly higher plasma viscosity, mostly above the empirical normal value (1.35 mpa), was measured in patients with proven PVT. PVT is suspected. It allows prompt and reliable assessment of inadequate opening or faulty closure of the occluder, provided that the radiological characteristics and the design specifications of the respective prostheses are known and suitable fluoroscopic planes are chosen. Interpretation of echocardiographic findings in PVT are not so simple. Reduced opening amplitude, or non-homogeneous or rounded opening movement of the disc may indicate valve thrombosis or an obstruction of some other origin. However, these indications can also be found in cases of low cardiac output or during long diastole, especially in bradyarrythmias [19 21]. Prosthetic valve obstruction may be suspected if the Doppler-derived gradients are twice as high as empirically found in normal prostheses [12]. Valve malfunction should be also considered if the prototypic haemolysis parameter lactate dehydrogenase is higher than 400 U. l 1, especially if this parameter was not increased at earlier examinations [6,22]. Early diagnosis and prompt initiation of adequate therapeutic procedures are required for successful management of PVT (see review by Hering et al. in this supplement). If PVT is suspected then a diagnostic flow chart (Fig. 8) should be followed in order to prove or to exclude PVT rapidly. In emergency situations with acute backward failure, pulmonary oedema, acute pump failure (low cardiac output failure), life-threatening arrhythmias or syncope, the diagnostic procedures should be reduced to the bare essentials to save time. Frequently, clinical examination by an experienced cardiologist with up-to-date knowledge of

5 Q20 C. Piper et al. Figure 7 Real-time sound spectrography reveals two similar closing clicks (one for each leaflet) of a normal bileaflet prosthesis (left) and the typical finding in a thrombosed bileaflet prosthesis, exhibiting a delayed second click with a reduced amplitude (right). Case history (anticoagulation) the case history is sufficient to make a tentative diagnosis. Supplementary examinations should be restricted to those that are required for planning the emergency operation. Conclusion Auscultation (sound spectroscopy) + Echo and fluoroscopy (coronary angiography) PVT suspected Acute decompensation/lung oedema Fluoroscopy Figure 8 Diagnostic flow chart to rapidly prove or exclude suspected prosthetic valve thrombosis (PVT). PVT is an obstruction of a prosthesis by non-infective thrombotic material. The pathogenesis of PVT is complex but mainly relies on molecular interactions between corpuscular blood components, plasma and artificial surfaces, on the influence of transprosthetic blood flow on local thrombus formation, and on the impact of local hypercoagulability. Unstable anticoagulation appears to be the major risk factor predisposing to clot formation after mechanical valve replacement. Seasonal elevation of fibrinogen levels and the increase in plasma viscosity may influence the occurrence of PVT. The typical clinical finding in PVT is diminution of the occluder clicks. Because sophisticated sound spectrography is only available in a few centres, fluoroscopy is the diagnostic tool of choice if PVT is suspected. Interpretation of echocardiographic findings are not so simple. PVT may be suspected if the Doppler-derived gradients are twice as high as empirically found in normal prostheses. Early diagnosis and prompt initiation of adequate therapeutic procedures are required for successful management of PVT. References [1] Roe B. Extinct cardiac valve prostheses. In: Bodnar E, Frater RWM, eds. Replacement Cardiac Valves, 1st Edition. New York, Pergamon press, 1991: [2] Gott VL, Koepke DE, Dagget RL. The coating of intravascular plastic prostheses with colloidal graphite. Surgery 1961; 50: [3] Bokros JC, La Grange LD, Schoen FJ. Control of structure of carbon for use in bioengineering. In: Walker PL, ed. Chemistry and Physics of Carbon. New York, Dekker, 1973: [4] Edmunds LH, Clark RE, Cohn LH, Grunkemeier GL, Miller DC, Weisel RD. Guidelines for reporting morbidity and mortality after cardiac valvular operations. J Thorac Cardiovasc Surg 1996; 112: [5] Anderson JM, Schoen EJ. Interaction of blood with artificial surfaces. In: Butchart E, Bodnar E, eds. Thrombosis, Embolism and Bleeding. London, ICR Publishers, 1992: [6] Horstkotte D, Aul C, Seipel L et al. Influence of valve type and valve function on chronic intravascular hemolysis following mitral and aortic valve replacement using alloprostheses. Z Kardiol 1983; 72: [7] Horstkotte D, Haerten K, Herzer JA. Five year results after randomised mitral valve replacement with Björk-Shiley, Lillehei- Kaster and Starr-Edwards prostheses. Thorac Cardiovasc Surg 1983; 31:

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