Treatment Strategies for Prosthetic Valve Thrombosis in Pregnant Patients Bharti Joshi MBBS MD, DNB PII: DOI: Reference:
S0735-6757(15)00227-2 doi: 10.1016/j.ajem.2015.03.056 YAJEM 54899
To appear in:
American Journal of Emergency Medicine
Received date: Accepted date:
24 March 2015 26 March 2015
Please cite this article as: Joshi Bharti, Treatment Strategies for Prosthetic Valve Thrombosis in Pregnant Patients, American Journal of Emergency Medicine (2015), doi: 10.1016/j.ajem.2015.03.056
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title Page
RI P
T
Type of manuscript – Reviewer correspondence
Title - Treatment Strategies for Prosthetic Valve Thrombosis in Pregnant Patients
SC
Authors:
Dr Bharti Joshi, (MBBS, MD, DNB), Consultant WHO-NNPD Project, Department of Obstetrics
MA
NU
and Gynecology, Post Graduate Institute of Medical Education and Research Chandigarh, India.
Author for correspondence
PT
Consultant WHO-NNPD Project
ED
Dr Bharti Joshi
Department of Obstetrics and Gynecology
CE
Old Nehru hospital, 3rd Floor
AC
PGIMER Chandigarh, India +919915166210
[email protected]
ACCEPTED MANUSCRIPT The American Journal of Emergency Medicine Manuscript Draft Manuscript Number: AJEM10988
T
Title: Treatment Strategies for Prosthetic Valve Thrombosis in Pregnant Patients
AC
CE
PT
ED
MA
NU
SC
RI P
Article Type: Reviewer Recommendation
ACCEPTED MANUSCRIPT Manuscript Thrombotic occlusion of prosthetic valve during pregnancy is uncommon, but one of the
T
dreadful complication with unclear management strategies. In general, conservative approach,
RI P
re-replacement surgery, thrombectomy and thrombolytic therapy are the accepted treatment modalities for prosthetic valve thrombosis with their own pros and cons. Treatment modalities
SC
should be customized based upon clinical status, valve location, comorbidities and informed Conservative approach is suitable for stable patients or when there is any
NU
decision [1].
contraindication for surgery or thrombolytic therapy. As per available recommendations [2],
MA
outside pregnancy surgery remains preferred modality and thrombolysis is reserved as rescue treatment in critically ill or patients with high surgical risk (According to the 2007 European
ED
Society of Cardiology (ESC) and the 2008 American College of Cardiology/American Heart
PT
Association (ACC/ AHA). However, review of published reports on thrombolytic therapy has concluded that success rate ranging from 75%-88% can be achieved with this modality in
CE
prosthetic valve thrombosis (PVT) and has lower mortality for all NYHA classes as compared to
AC
re-do surgery [3, 4, 5]. There is no available evidence regarding safety of thrombolytic therapy in pregnancy [6] & fear of teratogenecity, risk of abortion and bleeding has hesitated clinicians to use this intervention. Nonetheless, for the past few years use of thrombolysis in pregnancy has shown promising results and complication rates does not seems to be higher than that of nonpregnant patient except when administered intrapartum or with concomitant use of anticoagulants. Various agents with numerous treatment protocols used for thrombolytic therapy are streptokinase, urokinase and tissue plasminogen activator (t-PA). All of them has similar efficacy and the choice of agent is influenced by various factors like cost, half-life and hemorrhagic
ACCEPTED MANUSCRIPT complications. Streptokinase is favored because it’s cheaper and has lower rate of cerebral hemorrhage. In contrast, t-PA is costly, has fastest reversion rate with shortest half-life [7]. So
T
far, there is no agreement on the ideal thrombolytic agent and treatment protocol, but most
RI P
experience has accumulated with streptokinase. Class 1 recommendation for prosthetic valve thrombosis in pregnancy is lacking in pregnancy due to the lack of randomized controlled trials
SC
and management guidelines are similar to that of non-pregnant women [2, 8]. Roudaut et al [9],
NU
in the largest nonrandomized retrospective study indicated that patients treated with streptokinase has better success rate compared to that of urokinase and t-PA (86%, 68% and 59%
MA
respectively) and advocated thrombolysis as first line therapy in critically ill patients .In a review by Aniteye et al, streptokinase as first line thrombolytic agent in management of prosthetic valve
ED
thrombosis is relatively safe and cheaper option [10]. In another study by Gupta et al, 108
PT
patients of prosthetic valve thrombosis out of 110 were treated with streptokinase and complete hemodynamic response was seen in 81.8%, partial in 10% and no response in 8.2% [11]. The
CE
overall response rate of 53.5% was found after thrombolysis with streptokinase in 86 patients of
AC
left sided thrombosis [12] which is closer to other Indian study of karthikeyan et.al with reported success of 59% [13]. However over recent era, thrombolytic therapy under the guidance of Transesophgeal Echocardiography (TEE) has shown high success rate with fewer complications. Thrombolysis with t-PA is an approved therapy for stroke, myocardial infarction and thrombosis. The TROIA trial consisting of largest cohort of 182 consecutive patients with prosthetic valve thrombosis, thrombolytic success rate was 83.2% with complication rate of 18.6%in whole series. The success rate did not differ among groups i.e. either t-PA or streptokinase using various treatment regimens and it was concluded that slow infusion regimen of t-PA without bolus seems to be the practicable & safest thrombolytic regimen [14] The subgroup analysis of
ACCEPTED MANUSCRIPT 24 pregnant women in this trial with prosthetic valve thrombosis, low dose slow infusion of t-PA showed complete lysis in all patients with lower maternal & fetal adverse events. All procedures
T
were done under TEE guidance and consensus statement is that this protocol seems better than
RI P
surgical or other medical therapy [15]. However, although this research included remarkable number of patients including pregnant women, its applicability may be questioned because of
SC
nonrandomized, single centered observational study, uneven numbers in few groups and due to
NU
high cost factor of t-PA. Furthermore, almost half of the patients had smaller, recent non obstructive thrombi and they in general have better prognosis. So, streptokinase still remains
MA
sustainable option mainly in developing countries until we have good randomized prospective studies with t-PA.
ED
Detailed clinical examination along with transthoracic echocardiography (TTE) is an
PT
initial and essential part of diagnostic assessment [16]. TTE provides direct visualization of prosthesis and accurately quantifies transvalvular gradient. Artifacts of prosthesis, quality of
CE
acoustic window, non-obstructive thrombosis are few limitations of TTE and it may be normal in
AC
case of low cardiac output despite valvular obstruction (silent Doppler PVT). Hence in these situations transesophgeal echocardiography (TEE) holds fundamental role as not only assess exact size and location of thrombus but also helps in making treatment decisions and can differentiate thrombus from vegetation or pannus [17]. So we do agree that transesophgeal echocardiography (TEE) is superior to transthoracic echocardiography (TTE).
NU
SC
RI P
T
ACCEPTED MANUSCRIPT
References
MA
1) Roudaut R, Serri K, Lafitte S. Thrombosis of prosthetic heart valves: diagnosis and therapeutic
ED
considerations. Heart 2007;93:137-142.
PT
2) Bonow RO, Carabello BA, Chatterjee K, et al. 2008 focused update incorporated into the ACC/AHA
AC
American
CE
2006 guidelines for the management of patients with valvular heart disease: a report of the
College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing
Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2008; 52: e1−e142
ACCEPTED MANUSCRIPT 3) Vidne H, Sagie A. Repeated thrombolysis in multiple episodes of obstructive thrombosis in prosthetic
T
Heart valves: a report of three cases and review of the literature.J Heart Valve Dis. 2000
RI P
Jan;9(l):146-9.
short- and
NU
Longterm results. Am Heart 1. 2000;140:906-916.
SC
4) Gupta D, Kothara SS, Bahl VK, et al. Thrombolytic therapy for prosthetic valve thrombosis:
5) Ozkan c., Kaymaz c., Kirma K. Intravenous thrombolytic treatment of mechanical prosthetic
MA
valve
thrombo¬sis: a study using seriaI transesophageal echocardiography. Am. Coll. Cardiol., June
ED
l, 2000;
PT
35(7): 1881 - 1889.
6) Sahnoun-Trabelsi I, Jimenez M, Choussat A, Roudaut R. [Prosthetic valve thrombosis in
CE
pregnancy. A
AC
single-center study of 12 cases]. Arch Mal Coeur Vaiss2004; 97:305-10 7) Caceres-Loriga FM, Perez-Lopez H, Santos-Gracia J, Morlans- Hernandez K. Prosthetic heart valve
thrombosis: pathogenesis, diagnosis and management. Int J Cardiol 2006;110:1-6. 8) Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Barón-Esquivias G,. Guidelines on the management of valvular heart disease (version 2012): The Joint Task Force on the Management of Valvular Heart
ACCEPTED MANUSCRIPT Disease of the European Society of Cardiology and the European Association for CardioThoracic
T
Surgery. Eur Heart J.2012; 33:2451-2496.
RI P
9) Roudaut R, Lafitte S, Roudaut MF, Courtault C, Perron JM, Jaïs C, Pillois X, Coste P, DeMaria A.
SC
Fibrinolysis of mechanical prosthetic valve thrombosis: a single-center study of 127 cases. J
NU
Am Coll Cardiol 2003; 41:653-658.
10) E.A. Aniteye, M. Tettey, L. Sereboe, D. Kotei, F. Edwin et al. Thrombolysis for prosthetic
MA
valve
thrombosis: a report of 6 cases and review of the literature. Ann. Afr. Chir. Thor.
ED
Cardiovasc. 2007;
PT
2(1): 38-41
short- and
CE
11) Gupta D, Kothara SS, Bahl VK, et al. Thrombolytic therapy for prosthetic valve thrombosis:
AC
long-term results. Am Heart J 2000; 140:906–16. 2007; 2(1): 38-41 12) Singh A K & Agarwal S, Satyarthi S, Kunal, Satsangi DK. Comparison of thrombolytic therapy for
prosthetic valve thrombosis at the mitral and aortic position. Indian J Thorac Cardiovasc Surg (July- September 2011) 27(3):114–118. 13) Karthikeyan G, Ravi S. Math, Navin Mathew, Bhima Shankar, MD, DM; Mani Kalaivani, MSc; Sandeep Singh . Accelerated Infusion of Streptokinase for the Treatment of Left-Sided Prosthetic Valve
ACCEPTED MANUSCRIPT Thrombosis A Randomized Controlled Trial. 2009 American Heart Association 14) Özkan M, Gunduz S, Biteker M, et al: Comparison of different TEE-guided thrombolytic
T
regimens for
RI P
prosthetic valve thrombosis: The TROIA Trial. JACC Cardiovasc Imaging 2013; 6:206-216. 15) Özkan M, Gunduz S, Biteker M,; Karakoyun S, Gürsoy OM, Çevik C. Thrombolytic
SC
Therapy for the
NU
Treatment of Prosthetic Heart Valve Thrombosis in Pregnancy with Low-Dose, Slow Infusion of
MA
Tissue-Type Plasminogen Activator. Circulation. 2013; 128:532-540. 16) Zoghbi WA, Chambers JB, Dumesnil JG, et al. Recommendations for evaluation of
ED
prosthetic valves
PT
with echocardiography and doppler ultrasound. J Am Soc Echocardiogr 2009; 22: 975−1014 17) Muratori M, Montorsi P, Teruzzi G, Celeste F, Doria E, Alamanni F, Pepi M. Feasibility and
CE
diagnostic
AC
accuracy of quantitative assessment of mechanical prostheses leaflet motion by transthoracic and transesophageal echocardiography in suspected prosthetic valve dysfunction. Am J Cardiol
2006;97:94-100.
S0735-6757(15)00227-2 doi: 10.1016/j.ajem.2015.03.056 YAJEM 54899
To appear in:
American Journal of Emergency Medicine
Received date: Accepted date:
24 March 2015 26 March 2015
Please cite this article as: Joshi Bharti, Treatment Strategies for Prosthetic Valve Thrombosis in Pregnant Patients, American Journal of Emergency Medicine (2015), doi: 10.1016/j.ajem.2015.03.056
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title Page
RI P
T
Type of manuscript – Reviewer correspondence
Title - Treatment Strategies for Prosthetic Valve Thrombosis in Pregnant Patients
SC
Authors:
Dr Bharti Joshi, (MBBS, MD, DNB), Consultant WHO-NNPD Project, Department of Obstetrics
MA
NU
and Gynecology, Post Graduate Institute of Medical Education and Research Chandigarh, India.
Author for correspondence
PT
Consultant WHO-NNPD Project
ED
Dr Bharti Joshi
Department of Obstetrics and Gynecology
CE
Old Nehru hospital, 3rd Floor
AC
PGIMER Chandigarh, India +919915166210
[email protected]
ACCEPTED MANUSCRIPT The American Journal of Emergency Medicine Manuscript Draft Manuscript Number: AJEM10988
T
Title: Treatment Strategies for Prosthetic Valve Thrombosis in Pregnant Patients
AC
CE
PT
ED
MA
NU
SC
RI P
Article Type: Reviewer Recommendation
ACCEPTED MANUSCRIPT Manuscript Thrombotic occlusion of prosthetic valve during pregnancy is uncommon, but one of the
T
dreadful complication with unclear management strategies. In general, conservative approach,
RI P
re-replacement surgery, thrombectomy and thrombolytic therapy are the accepted treatment modalities for prosthetic valve thrombosis with their own pros and cons. Treatment modalities
SC
should be customized based upon clinical status, valve location, comorbidities and informed Conservative approach is suitable for stable patients or when there is any
NU
decision [1].
contraindication for surgery or thrombolytic therapy. As per available recommendations [2],
MA
outside pregnancy surgery remains preferred modality and thrombolysis is reserved as rescue treatment in critically ill or patients with high surgical risk (According to the 2007 European
ED
Society of Cardiology (ESC) and the 2008 American College of Cardiology/American Heart
PT
Association (ACC/ AHA). However, review of published reports on thrombolytic therapy has concluded that success rate ranging from 75%-88% can be achieved with this modality in
CE
prosthetic valve thrombosis (PVT) and has lower mortality for all NYHA classes as compared to
AC
re-do surgery [3, 4, 5]. There is no available evidence regarding safety of thrombolytic therapy in pregnancy [6] & fear of teratogenecity, risk of abortion and bleeding has hesitated clinicians to use this intervention. Nonetheless, for the past few years use of thrombolysis in pregnancy has shown promising results and complication rates does not seems to be higher than that of nonpregnant patient except when administered intrapartum or with concomitant use of anticoagulants. Various agents with numerous treatment protocols used for thrombolytic therapy are streptokinase, urokinase and tissue plasminogen activator (t-PA). All of them has similar efficacy and the choice of agent is influenced by various factors like cost, half-life and hemorrhagic
ACCEPTED MANUSCRIPT complications. Streptokinase is favored because it’s cheaper and has lower rate of cerebral hemorrhage. In contrast, t-PA is costly, has fastest reversion rate with shortest half-life [7]. So
T
far, there is no agreement on the ideal thrombolytic agent and treatment protocol, but most
RI P
experience has accumulated with streptokinase. Class 1 recommendation for prosthetic valve thrombosis in pregnancy is lacking in pregnancy due to the lack of randomized controlled trials
SC
and management guidelines are similar to that of non-pregnant women [2, 8]. Roudaut et al [9],
NU
in the largest nonrandomized retrospective study indicated that patients treated with streptokinase has better success rate compared to that of urokinase and t-PA (86%, 68% and 59%
MA
respectively) and advocated thrombolysis as first line therapy in critically ill patients .In a review by Aniteye et al, streptokinase as first line thrombolytic agent in management of prosthetic valve
ED
thrombosis is relatively safe and cheaper option [10]. In another study by Gupta et al, 108
PT
patients of prosthetic valve thrombosis out of 110 were treated with streptokinase and complete hemodynamic response was seen in 81.8%, partial in 10% and no response in 8.2% [11]. The
CE
overall response rate of 53.5% was found after thrombolysis with streptokinase in 86 patients of
AC
left sided thrombosis [12] which is closer to other Indian study of karthikeyan et.al with reported success of 59% [13]. However over recent era, thrombolytic therapy under the guidance of Transesophgeal Echocardiography (TEE) has shown high success rate with fewer complications. Thrombolysis with t-PA is an approved therapy for stroke, myocardial infarction and thrombosis. The TROIA trial consisting of largest cohort of 182 consecutive patients with prosthetic valve thrombosis, thrombolytic success rate was 83.2% with complication rate of 18.6%in whole series. The success rate did not differ among groups i.e. either t-PA or streptokinase using various treatment regimens and it was concluded that slow infusion regimen of t-PA without bolus seems to be the practicable & safest thrombolytic regimen [14] The subgroup analysis of
ACCEPTED MANUSCRIPT 24 pregnant women in this trial with prosthetic valve thrombosis, low dose slow infusion of t-PA showed complete lysis in all patients with lower maternal & fetal adverse events. All procedures
T
were done under TEE guidance and consensus statement is that this protocol seems better than
RI P
surgical or other medical therapy [15]. However, although this research included remarkable number of patients including pregnant women, its applicability may be questioned because of
SC
nonrandomized, single centered observational study, uneven numbers in few groups and due to
NU
high cost factor of t-PA. Furthermore, almost half of the patients had smaller, recent non obstructive thrombi and they in general have better prognosis. So, streptokinase still remains
MA
sustainable option mainly in developing countries until we have good randomized prospective studies with t-PA.
ED
Detailed clinical examination along with transthoracic echocardiography (TTE) is an
PT
initial and essential part of diagnostic assessment [16]. TTE provides direct visualization of prosthesis and accurately quantifies transvalvular gradient. Artifacts of prosthesis, quality of
CE
acoustic window, non-obstructive thrombosis are few limitations of TTE and it may be normal in
AC
case of low cardiac output despite valvular obstruction (silent Doppler PVT). Hence in these situations transesophgeal echocardiography (TEE) holds fundamental role as not only assess exact size and location of thrombus but also helps in making treatment decisions and can differentiate thrombus from vegetation or pannus [17]. So we do agree that transesophgeal echocardiography (TEE) is superior to transthoracic echocardiography (TTE).
NU
SC
RI P
T
ACCEPTED MANUSCRIPT
References
MA
1) Roudaut R, Serri K, Lafitte S. Thrombosis of prosthetic heart valves: diagnosis and therapeutic
ED
considerations. Heart 2007;93:137-142.
PT
2) Bonow RO, Carabello BA, Chatterjee K, et al. 2008 focused update incorporated into the ACC/AHA
AC
American
CE
2006 guidelines for the management of patients with valvular heart disease: a report of the
College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing
Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2008; 52: e1−e142
ACCEPTED MANUSCRIPT 3) Vidne H, Sagie A. Repeated thrombolysis in multiple episodes of obstructive thrombosis in prosthetic
T
Heart valves: a report of three cases and review of the literature.J Heart Valve Dis. 2000
RI P
Jan;9(l):146-9.
short- and
NU
Longterm results. Am Heart 1. 2000;140:906-916.
SC
4) Gupta D, Kothara SS, Bahl VK, et al. Thrombolytic therapy for prosthetic valve thrombosis:
5) Ozkan c., Kaymaz c., Kirma K. Intravenous thrombolytic treatment of mechanical prosthetic
MA
valve
thrombo¬sis: a study using seriaI transesophageal echocardiography. Am. Coll. Cardiol., June
ED
l, 2000;
PT
35(7): 1881 - 1889.
6) Sahnoun-Trabelsi I, Jimenez M, Choussat A, Roudaut R. [Prosthetic valve thrombosis in
CE
pregnancy. A
AC
single-center study of 12 cases]. Arch Mal Coeur Vaiss2004; 97:305-10 7) Caceres-Loriga FM, Perez-Lopez H, Santos-Gracia J, Morlans- Hernandez K. Prosthetic heart valve
thrombosis: pathogenesis, diagnosis and management. Int J Cardiol 2006;110:1-6. 8) Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Barón-Esquivias G,. Guidelines on the management of valvular heart disease (version 2012): The Joint Task Force on the Management of Valvular Heart
ACCEPTED MANUSCRIPT Disease of the European Society of Cardiology and the European Association for CardioThoracic
T
Surgery. Eur Heart J.2012; 33:2451-2496.
RI P
9) Roudaut R, Lafitte S, Roudaut MF, Courtault C, Perron JM, Jaïs C, Pillois X, Coste P, DeMaria A.
SC
Fibrinolysis of mechanical prosthetic valve thrombosis: a single-center study of 127 cases. J
NU
Am Coll Cardiol 2003; 41:653-658.
10) E.A. Aniteye, M. Tettey, L. Sereboe, D. Kotei, F. Edwin et al. Thrombolysis for prosthetic
MA
valve
thrombosis: a report of 6 cases and review of the literature. Ann. Afr. Chir. Thor.
ED
Cardiovasc. 2007;
PT
2(1): 38-41
short- and
CE
11) Gupta D, Kothara SS, Bahl VK, et al. Thrombolytic therapy for prosthetic valve thrombosis:
AC
long-term results. Am Heart J 2000; 140:906–16. 2007; 2(1): 38-41 12) Singh A K & Agarwal S, Satyarthi S, Kunal, Satsangi DK. Comparison of thrombolytic therapy for
prosthetic valve thrombosis at the mitral and aortic position. Indian J Thorac Cardiovasc Surg (July- September 2011) 27(3):114–118. 13) Karthikeyan G, Ravi S. Math, Navin Mathew, Bhima Shankar, MD, DM; Mani Kalaivani, MSc; Sandeep Singh . Accelerated Infusion of Streptokinase for the Treatment of Left-Sided Prosthetic Valve
ACCEPTED MANUSCRIPT Thrombosis A Randomized Controlled Trial. 2009 American Heart Association 14) Özkan M, Gunduz S, Biteker M, et al: Comparison of different TEE-guided thrombolytic
T
regimens for
RI P
prosthetic valve thrombosis: The TROIA Trial. JACC Cardiovasc Imaging 2013; 6:206-216. 15) Özkan M, Gunduz S, Biteker M,; Karakoyun S, Gürsoy OM, Çevik C. Thrombolytic
SC
Therapy for the
NU
Treatment of Prosthetic Heart Valve Thrombosis in Pregnancy with Low-Dose, Slow Infusion of
MA
Tissue-Type Plasminogen Activator. Circulation. 2013; 128:532-540. 16) Zoghbi WA, Chambers JB, Dumesnil JG, et al. Recommendations for evaluation of
ED
prosthetic valves
PT
with echocardiography and doppler ultrasound. J Am Soc Echocardiogr 2009; 22: 975−1014 17) Muratori M, Montorsi P, Teruzzi G, Celeste F, Doria E, Alamanni F, Pepi M. Feasibility and
CE
diagnostic
AC
accuracy of quantitative assessment of mechanical prostheses leaflet motion by transthoracic and transesophageal echocardiography in suspected prosthetic valve dysfunction. Am J Cardiol
2006;97:94-100.
