Severe Stenosis of Mitral Bioprosthetic Valve Thrombosis in a Patient with HCV-Related Cirrhosis and Duodenal Variceal Bleeding: The Deadly Triad

Round 1

Reviewer 1 Report

This is a case review regarding severe stenosis of mitral bioprosthetic valve thrombosis in a patient with HCV-related cirrhosis and duodenal variceal bleeding.

The cause of duodenal variceal bleeding is portal hypertension of HCV related liver cirrhosis. The thrombotic phenomenon of the mitral bioprosthetic valve is associated with asymptomatic bacteremia of reticuloendothelial dysfunction and systemic shunt or collaterals due to cirrhosis, because prothrombin time is significantly prolonged upon admission to the emergency department. Finally, the subject died of multi-organ failures. 

Major comment

What do you want to tell the readers in this case report?

Author Response

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Reviewer 2 Report

 

1. Abstract should be restructured- too much is written about bioprostetic valve and too little about cirrhosis, how patient was managed and what wat the outcome. 

2. Table 1- CMR is not compatible with some mechanical valves, particularly older ones

3. Lines 60-64- data are not informative or interesting, please rewrite or completely delete

4. Lines 69-71- should be deleted- already stated in the abstract

5. Discussion is awfully short. It needs to be expanded to increase the educational value, Typically for case reports discussion is the largest part of the case, here it is shorter than introduction. Please include what was the cause of death, was an autopsy performed. Please expend on the various treatment modalities of BPVT etc

Author Response

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Reviewer 3 Report

Thank you very much for the opportunity to read this interesting case.
The case has an unfortunate ending but lots of potential to learn from it.

But i am missing some clinical information about the patient at this point.
Apparently, the indication for primary valve replacement was endocarditis. The mitral valve is more involved in patients with drug abuse. Was that the case in this case? Was this continued, so that one can perhaps also assume a endocarditis and not thrombosis?
How was the initial endocarditis treated and for how long? What was the time interval to the current event?
The location of the bleeding varices is rather unusual. We find this constellation more frequently in patients with thrombosis of the splenic veins. Has this been ruled out in the Ct?
If there was no thrombosis, the possibility of one
Balloon-occluded retrograde transvenous obliteration discussed or a partial splenic artery embolization? These methods are all possible without TIPS.

Thank you for this great case.

Author Response

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Round 2

Reviewer 1 Report

The cause of unusual thrombus at prothetic tissue valve in heart is mainly bacteremia by gram positive or negative cocci, result in septic shock due to underlying liver cirrhosis, which is related to active duodenal variceal bleeding by worsening portal hypertension. From the view of the case, it would be helpful to have a chance to save him using very strong combination of intravenous antibiotics like vancomycin plus carbapenem antibiotics and visceral vasoconstrictor like terlipressin, before interventional procedure like BRTO, PARTO or CARTO, when TIPS is not good for him.

Duodenal varices can occur in intrahepatic or extrahepatic portal hypertension, and is a rare disease that accounts for 1 to 3% of varices due to cirrhosis and is a type of ectopic varices. It is known that duodenal variceal bleeding accounts for 25-33% of ectopic variceal bleeding and has a very high mortality rate of 40% during bleeding (1, 2, 3). In general, the first treatment to try when there is duodenal varicose veins is endoscopic treatment, and in case of failure, transjugular intrahepatic portosystemic shunt (TIPS) can be attempted. If the Liver disease (hereinafter referred to as MELD) score rises, the probability of complications increases, which limits the implementation (4, 5). In this case, balloon assisted retrograde transvenous obliteration (BRTO) can be performed as an alternative in this case, and cases of successful hemostasis through BRTO in duodenal varices have been reported (5). However, when it is difficult to use a balloon catheter or a vascular plug due to anatomical structure, it is difficult to perform plug assisted retrograde transvenous obliteration (PARTO) using BRTO and vascular plug. . In this case, Lee et al. (6) suggested the use of coil assisted retrograde transvenous obliteration (CARTO) as an alternative for retrograde jugular vein occlusion and demonstrated its effectiveness in patients with gastric varices bleeding.

Ectopic variceal bleeding is varicose veins in which the splanchnic veins are stretched or portosystemic shunts that are not normally where varicose veins occur. It can occur throughout the gastrointestinal tract, accounting for 2-5% of all variceal bleeding. Among these, duodenal variceal bleeding accounts for 25-33%. Duodenal varices are mainly observed in the first and second parts of the duodenum, and rarely in the third and fourth parts of the duodenum (1, 2). Afferent veins include superior or inferior pancreaticoduodenal vein, cystic branch of superior mesenteric vein, gastroduodenal vein, and pyloric vein. veins) are present. Efferent veins include the right gonadal vein and the renal capsular vein, and are discharged into the inferior vena cava. The left gonadal vein can become an exporting vein in rare cases when varicose veins develop in the third or fourth part of the duodenum (2). In this way, RTO can be performed because a passage is formed through the hepatic portal vein or gastrointestinal mesenteric vein to the inferior vena cava (3). In general, endoscopic treatment is tried first, but if the size of the duodenal varices is large or located in the submucosal layer or deep, there is a high risk of duodenal perforation and it is difficult to access with an endoscope, so try an intervention such as TIPS or BRTO (5). TIPS is known to be an effective and safe treatment for varicose bleeding, including duodenal varices, by lowering portal hypertension (4). reported cases treated with However, TIPS is limited in implementation in cases of elevated MELD score, hepatic encephalopathy, abnormal vein anatomy, portal vein thrombosis, and low hepatic venous pressure gradient. There are (4, 5). In this case, BRTO can be performed as an alternative, and cases of successful hemostasis through BRTO in duodenal varices have been reported (5).

BRTO is a treatment method by injecting a curing agent for several hours while the balloon is inflated, and the procedure takes a long time and requires long-term monitoring. In addition, the inflated balloon may burst, and complications such as pulmonary edema, disseminated intravascular coagulation, portal vein thrombosis, renal failure and anaphylaxis due to curing agents may occur. In order to compensate for such shortcomings of BRTO, PARTO was newly introduced as a modified BRTO using a blood vessel stopper as an alternative, and complications could be minimized. However, if the diameter of the shunt is large and blood flow is fast, it cannot be completely blocked with a vascular plug, and the vascular plug has a size of up to 22 mm, so only shunts with a diameter of 16 to 18 mm or less can be used. In addition, since the conduit of 6~8F must be able to enter, there is a limitation in the case of small or tortuous vessels. A new CARTO has been proposed to block a large and fast-flowing shunt, and it can effectively stop varicose bleeding with a 30 mm shunt (6, 8). It has also been reported that effective hemostasis was achieved even when the shunt was small and tortuous (7). CARTO is technically easier and safer than BRTO and PARTO when it is difficult to perform TIPS in patients with duodenal variceal bleeding who have failed endoscopic treatment. In particular, it is considered a procedure that can replace BRTO and PARTO in the case of large shunt diameter or steep and tortuous vessels.

 

1.     Weishaupt D, Pfammatter T, Hilfiker PR, Wolfensberger U, Marincek B. Detecting bleeding duodenal varices with multislice helical CT. AJR Am J Roentgenol 2002;178:399–401.

2.     Saad WE, Lippert A, Saad NE, Caldwell S. Ectopic varices: anatomical classification, hemodynamic classification, and hemodynamic-based management. Tech Vasc Interv Radiol 2013;16:158–175.

3.     Henry Z, Uppal D, Saad W, Caldwell S. Gastric and ectopic varices. Clin Liver Dis 2014;18:371–388.

4.     Boyer TD, Haskal ZJ, American Association. The role of transjugular intrahepatic portosystemic shunt in the management of portal hypertension. Hepatology 2005;41:386–400.

5.     Copelan A, Chehab M, Dixit P, Cappell MS. Safety and efficacy of angiographic occlusion of duodenal varices as an alternative to TIPS: review of 32 cases. Ann Hepatol 2015;14:369–379.

6.     Lee EW, Saab S, Gomes AS, Busuttil R, McWilliams J, Durazo F, et al. Coil-assisted retrograde transvenous obliteration (CARTO) for the treatment of portal hypertensive variceal bleeding: preliminary results. Clin Transl Gastroenterol 2014;5:e61.

7.     Lee SJ, Jeon GS. Coil-assisted retrograde transvenous obliteration for the treatment of duodenal varix. Diagn Interv Radiol 2018;24:292–294.

8.     Kim DJ, Darcy MD, Mani NB, Park AW, Akinwande O, Ramaswamy RS, et al. Modified balloon-occluded retrograde transvenous obliteration (BRTO) techniques for the treatment of gastric varices: vascular plug-assisted retrograde transvenous obliteration (PARTO)/coil-assisted retrograde transvenous obliteration (CARTO)/balloon-occluded antegrade transvenous obliteration (BATO). Cardiovasc Intervent Radiol 2018;41:835–847.

Author Response

Response to Reviewer 1 Comments (Round 2)

 

Point 1: The cause of unusual thrombus at prothetic tissue valve in heart is mainly bacteremia by gram positive or negative cocci, result in septic shock due to underlying liver cirrhosis, which is related to active duodenal variceal bleeding by worsening portal hypertension. From the view of the case, it would be helpful to have a chance to save him using very strong combination of intravenous antibiotics like vancomycin plus carbapenem antibiotics and visceral vasoconstrictor like terlipressin, before interventional procedure like BRTO, PARTO or CARTO, when TIPS is not good for him.

Duodenal varices can occur in intrahepatic or extrahepatic portal hypertension, and is a rare disease that accounts for 1 to 3% of varices due to cirrhosis and is a type of ectopic varices. It is known that duodenal variceal bleeding accounts for 25-33% of ectopic variceal bleeding and has a very high mortality rate of 40% during bleeding (1, 2, 3). In general, the first treatment to try when there is duodenal varicose veins is endoscopic treatment, and in case of failure, transjugular intrahepatic portosystemic shunt (TIPS) can be attempted. If the Liver disease (hereinafter referred to as MELD) score rises, the probability of complications increases, which limits the implementation (4, 5). In this case, balloon assisted retrograde transvenous obliteration (BRTO) can be performed as an alternative in this case, and cases of successful hemostasis through BRTO in duodenal varices have been reported (5). However, when it is difficult to use a balloon catheter or a vascular plug due to anatomical structure, it is difficult to perform plug assisted retrograde transvenous obliteration (PARTO) using BRTO and vascular plug. . In this case, Lee et al. (6) suggested the use of coil assisted retrograde transvenous obliteration (CARTO) as an alternative for retrograde jugular vein occlusion and demonstrated its effectiveness in patients with gastric varices bleeding.

Ectopic variceal bleeding is varicose veins in which the splanchnic veins are stretched or portosystemic shunts that are not normally where varicose veins occur. It can occur throughout the gastrointestinal tract, accounting for 2-5% of all variceal bleeding. Among these, duodenal variceal bleeding accounts for 25-33%. Duodenal varices are mainly observed in the first and second parts of the duodenum, and rarely in the third and fourth parts of the duodenum (1, 2). Afferent veins include superior or inferior pancreaticoduodenal vein, cystic branch of superior mesenteric vein, gastroduodenal vein, and pyloric vein. veins) are present. Efferent veins include the right gonadal vein and the renal capsular vein, and are discharged into the inferior vena cava. The left gonadal vein can become an exporting vein in rare cases when varicose veins develop in the third or fourth part of the duodenum (2). In this way, RTO can be performed because a passage is formed through the hepatic portal vein or gastrointestinal mesenteric vein to the inferior vena cava (3). In general, endoscopic treatment is tried first, but if the size of the duodenal varices is large or located in the submucosal layer or deep, there is a high risk of duodenal perforation and it is difficult to access with an endoscope, so try an intervention such as TIPS or BRTO (5). TIPS is known to be an effective and safe treatment for varicose bleeding, including duodenal varices, by lowering portal hypertension (4). reported cases treated with However, TIPS is limited in implementation in cases of elevated MELD score, hepatic encephalopathy, abnormal vein anatomy, portal vein thrombosis, and low hepatic venous pressure gradient. There are (4, 5). In this case, BRTO can be performed as an alternative, and cases of successful hemostasis through BRTO in duodenal varices have been reported (5).

BRTO is a treatment method by injecting a curing agent for several hours while the balloon is inflated, and the procedure takes a long time and requires long-term monitoring. In addition, the inflated balloon may burst, and complications such as pulmonary edema, disseminated intravascular coagulation, portal vein thrombosis, renal failure and anaphylaxis due to curing agents may occur. In order to compensate for such shortcomings of BRTO, PARTO was newly introduced as a modified BRTO using a blood vessel stopper as an alternative, and complications could be minimized. However, if the diameter of the shunt is large and blood flow is fast, it cannot be completely blocked with a vascular plug, and the vascular plug has a size of up to 22 mm, so only shunts with a diameter of 16 to 18 mm or less can be used. In addition, since the conduit of 6~8F must be able to enter, there is a limitation in the case of small or tortuous vessels. A new CARTO has been proposed to block a large and fast-flowing shunt, and it can effectively stop varicose bleeding with a 30 mm shunt (6, 8). It has also been reported that effective hemostasis was achieved even when the shunt was small and tortuous (7). CARTO is technically easier and safer than BRTO and PARTO when it is difficult to perform TIPS in patients with duodenal variceal bleeding who have failed endoscopic treatment. In particular, it is considered a procedure that can replace BRTO and PARTO in the case of large shunt diameter or steep and tortuous vessels.

 

1. Weishaupt D, Pfammatter T, Hilfiker PR, Wolfensberger U, Marincek B. Detecting bleeding duodenal varices with multislice helical CT. AJR Am J Roentgenol 2002;178:399–401.
2. Saad WE, Lippert A, Saad NE, Caldwell S. Ectopic varices: anatomical classification, hemodynamic classification, and hemodynamic-based management. Tech Vasc Interv Radiol 2013;16:158–175.
3. Henry Z, Uppal D, Saad W, Caldwell S. Gastric and ectopic varices. Clin Liver Dis 2014;18:371–388.
4. Boyer TD, Haskal ZJ, American Association. The role of transjugular intrahepatic portosystemic shunt in the management of portal hypertension. Hepatology 2005;41:386–400.
5. Copelan A, Chehab M, Dixit P, Cappell MS. Safety and efficacy of angiographic occlusion of duodenal varices as an alternative to TIPS: review of 32 cases. Ann Hepatol 2015;14:369–379.
6. Lee EW, Saab S, Gomes AS, Busuttil R, McWilliams J, Durazo F, et al. Coil-assisted retrograde transvenous obliteration (CARTO) for the treatment of portal hypertensive variceal bleeding: preliminary results. Clin Transl Gastroenterol 2014;5:e61.
7. Lee SJ, Jeon GS. Coil-assisted retrograde transvenous obliteration for the treatment of duodenal varix. Diagn Interv Radiol 2018;24:292–294.
8. Kim DJ, Darcy MD, Mani NB, Park AW, Akinwande O, Ramaswamy RS, et al. Modified balloon-occluded retrograde transvenous obliteration (BRTO) techniques for the treatment of gastric varices: vascular plug-assisted retrograde transvenous obliteration (PARTO)/coil-assisted retrograde transvenous obliteration (CARTO)/balloon-occluded antegrade transvenous obliteration (BATO). Cardiovasc Intervent Radiol 2018;41:835–847.

 

Response 1:

We thank the reviewer for his/her comments. Following changes have been included in the test:

 

Pag. 2, lines 44-45

"one-third of patients with varices develop bleeding with a mortality rate of approximately 40% [6, 7, 8]."

 

Pag. 6, lines 133-134

"The management of a patient with M-BPVT and HCV-related cirrhosis complicated by duodenal variceal bleeding is high risk, whatever the option taken."

Pag. 6-7, lines 134-145

"In general, the first therapeutic option to try in case of duodenal varicose veins is the endoscopic treatment. However, if the duodenal varices are large in size and/or located in the submucosal layer, there is a high risk of duodenal perforation and it is difficult to access with an endoscope, so an intervention such as TIPS should be evaluated (17). TIPS is known to be an effective and safe treatment for varicose bleeding, including duodenal varices, by lowering portal hypertension (17). However, in this specific case TIPS was limited by the high risk of pulmonary oedema as direct consequence of volume overload [9]. Thus, a balloon assisted retrograde transvenous obliteration (BRTO), or plug assisted retrograde transvenous obliteration (PARTO), or coil assisted retrograde transvenous obliteration (CARTO) could have been performed (if specific expertise present) as an alternative to TIPS considering patient clinical status (18, 19, 20, 21)."

 

References added

6. Weishaupt D.; Pfammatter T.; Hilfiker PR.; Wolfensberger U.; Marincek B. Detecting bleeding duodenal varices with mul-tislice helical CT. AJR Am J Roentgenol 2002;178:399–401.
7. Saad WE.; Lippert A.; Saad NE.; Caldwell S. Ectopic varices: anatomical classification, hemodynamic classification, and hemodynamic-based management. Tech Vasc Interv Radiol 2013;16:158–175.
8. Henry Z.; Uppal D.; Saad W.; Caldwell S. Gastric and ectopic varices. Clin Liver Dis 2014;18:371–388.
9. Boyer TD.; Haskal ZJ. American Association. The role of transjugular intrahepatic portosystemic shunt in the management of portal hypertension. Hepatology 2005;41:386–400.
10. Copelan A.; Chehab M.; Dixit P.; Cappell MS. Safety and efficacy of angiographic occlusion of duodenal varices as an alter-native to TIPS: review of 32 cases. Ann Hepatol 2015;14:369–379.
11. Lee EW.; Saab S.; Gomes AS.; Busuttil R.; McWilliams J.; Durazo F.; Han SH.; Goldstein L.; Tafti BA.; Moriarty J.; et al. Coil-assisted retrograde transvenous obliteration (CARTO) for the treatment of portal hypertensive variceal bleeding: pre-liminary results. Clin Transl Gastroenterol 2014;5:e61.
12. Lee SJ.; Jeon GS. Coil-assisted retrograde transvenous obliteration for the treatment of duodenal varix. Diagn Interv Radiol 2018;24:292–294.
13. Kim DJ.; Darcy MD.; Mani NB.; Park AW.; Akinwande O.; Ramaswamy RS.; Kim SK. Modified balloon-occluded retrograde transvenous obliteration (BRTO) techniques for the treatment of gastric varices: vascular plug-assisted retrograde trans-venous obliteration (PARTO)/coil-assisted retrograde transvenous obliteration (CARTO)/balloon-occluded antegrade transvenous obliteration (BATO). Cardiovasc Intervent Radiol 2018;41:835–847.

Author Response File: Author Response.docx