In patients with carcinoid syndrome undergoing valve replacement: will a biological valve have acceptable durability?

Abstract

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was ‘In patients with carcinoid syndrome undergoing valve replacement, will a biological valve have acceptable durability?’ Altogether, more than 130 papers were found using the reported search, of which 17 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The pooled data from all papers represent 51 patients with carcinoid right heart disease who underwent tricuspid valve replacement. Two ‘outcomes’ studies reported a 30-day postoperative mortality of 16.7–18% and 2-year survival rates of 44 and 50%, respectively. Seventeen patients were detailed in case reports. Of these 17 patients, 7 died during the follow-up period. All but one of these patients had a normal bioprosthesis at echocardiography or at post-mortem. One patient with a plaque-covered valve had a functionally normal valve. We conclude that at present, the best available evidence suggests that although 30-day mortality approaches 20%, approximately half of patients with carcinoid syndrome undergoing tricuspid valve replacement can be expected to survive 2 years. Some patients survive considerably longer than this, beyond 10 years in some cases. Importantly, at autopsy, many replacement valves have been shown to be normal, with a few patients reported as having died of cardiac causes. This should be taken as cautious evidence that biological valves have an acceptable lifespan in patients with carcinoid syndrome and that the process of valve destruction seen in carcinoid patients does not continue to a significant level in the bioprosthesis. Caveats to this include the lack of any directly comparative trial and the predominance of case reports as opposed to higher-level evidence.

INTRODUCTION

A best evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1].

THREE-PART QUESTION

In [patients with carcinoid syndrome undergoing valve replacement] will a [biological valve] have acceptable [durability]?

CLINICAL SCENARIO

A 55-year old man presents with severe tricuspid valve regurgitation. He is known to have metastatic carcinoid syndrome, with evidence of disease in the liver. However, the oncologists tell you that he potentially has several years of good-quality life ahead of him as it is a slow-growing tumour. You tell him that you will be putting biological valves in him, but he asks whether his carcinoid syndrome will destroy the new valve just as it did his native valves. You had not thought about this so you resolve to check the literature.

SEARCH STRATEGY

Medline 1950 to February 2012 using MEDLINE interface [carcinoid.ti,ab] AND [tricuspid.ti,ab] AND [valve.ti,ab]. Reference lists were searched for further articles.

SEARCH OUTCOME

One hundred and thirty papers were found using the reported search. From these, 17 papers were identified that provided the best evidence to answer the question. These are presented in Table 1.

Table 1:

Best evidence papers

Author (date) journal, country Study type (level of evidence)	Patient group	Outcomes	Key results	Comments
Komoda et al. (2011), Gen Thorac Cardiovasc Surg, Japan [4] Case series (level 3)	Twelve patients with carcinoid heart diseases who underwent cardiac surgery. Valve operations for carcinoid heart disease comprised nine tricuspid valve replacements with bioprosthetic valves	Postoperative 30-day mortality Longest survival Two-year actuarial survival rate	16.7% 59 months 50%	This case review shows that although 30-day mortality is high, considering the mortality without treatment, there may be an acceptable 2-year survival rate with patients surviving up to 4.9 years
Bhattacharyya et al. (2011), Eur J Cardiothorac Surg, Germany [3] Case series (level 3)	Twenty-two patients with carcinoid heart disease who underwent cardiac valve surgery: 3 underwent tricuspid valve replacement alone, 15 tricuspid and pulmonary valve replacements, 2 tricuspid, pulmonary and mitral valve replacements and 2 patients underwent quadruple valve replacement	Postoperative 30-day mortality Longest survival 1-year survival 2-year survival	18% 42 months 56% 44%	This study showed that despite high initial postoperative mortality rates, patients who survive valve replacement in carcinoid heart disease significantly improve functionally. Most long-term complications were related to the tumour itself rather than cardiac complications
Takahashi et al. (2009), Circ J, Japan [11] Case report (level 4)	A patient with severe tricuspid and pulmonary regurgitation because of carcinoid syndrome successfully underwent double valve replacement using bioprostheses, the tricuspid valve was replaced by a size 27 mitral porcine heart valve	Status at the end of follow-up	Patient alive at the last follow-up 6 months postoperatively	This study did not investigate the echocardiographic features of the replacement bioprostheses after 6 months. Apart from showing that 6-month survival is possible, no other conclusions can be derived
Dworakowska et al. (2008), Pol J Endocrinol, UK [12] Case report (level 4)	A 46-year old woman with a symptomatic carcinoid who at the time of diagnosis had liver and abdominal lymph node metastases. The patient underwent tricuspid and pulmonary valve replacements using a bioprosthesis	Status at the end of follow-up	A patient alive at the last follow-up, 19 months postoperatively, is reported to be well, with good exercise tolerance and no further flushing or diarrhoea	This study did not investigate the echocardiographic features of the replacement bioprostheses after 1 year and 7 months. Apart from showing that 1-year and 7- month survivals are possible, no other conclusions can be derived
Voigt et al. (2005), Ann Thorac Surg, The Netherlands [13] Case report (level 4)	A 58-year old woman with tricuspid and pulmonary regurgitation due to carcinoid syndrome successfully underwent double bioprosthetic valve replacement. A size 29 mitral Carpentier Pericardiac Perimount bioprosthesis was used to replace the tricuspid valve	Status at the end of follow-up Echocardiographic examination of replacement valve form and function	Alive after 24 months post operatively No regurgitation or stenosis of either bioprosthesis. Right ventricular function was normal and the dimension had decreased to 41 mm	This case report shows that it is possible for patients with replacement of bioprosthetic tricuspid valves to survive for 2 years postoperatively with echocardiographically normal valves
Warner (2003), Endocr Relat Cancer, USA [14] Case report (level 4)	A 55-year old man underwent cardiac surgery consisting of replacement of both the tricuspid and pulmonic valves with bovine pericardial prostheses	Status at the end of follow-up	Alive after 13 months postoperatively	This study did not investigate the echocardiographic features of the replacement bioprostheses after 1 year and 1 month. Apart from showing that 1-year and 1-month survivals are possible, no other conclusions can be derived
Brunaud et al. (2001), Eur J Obstet Gynecol, France [15] Case report (level 4)	A 68-year old woman presented with severe tricuspid insufficiency due to carcinoid heart disease underwent the replacement of tricuspid valve with a bioprosthesis	Status at the end of follow-up	Alive 36 months postoperatively	This study did not investigate the echocardiographic features of the replacement bioprostheses after 1 year and 1 month. Apart from showing that 3-year survival is possible, no other conclusions can be derived
Robiolio et al. (1995), Am J Cardiol, USA [2] Case series (level 4)	Eight patients underwent tricuspid valve replacement with bioprostheses	30-day mortality rate Status at the end of follow-up	63% Of three alive after surgery, one was alive after 146 months. The other two died of noncardiac causes at 48 and 153 months. Cardiac catheterization of the latter at 107 months found a normal replacement of tricuspid valve and an abnormal native pulmonary valve	This case series shows that although immediate postoperative mortality was high, patients who survived could live up to 153 months after surgery. It was also shown that biological valves could be normally structured and functioning at catheterization 107 months after surgery
Ohri et al. (1994), Ann Thorac Surg, UK [5] Case series (level 4)	A 64-year old woman who underwent tricuspid valve replacement with a Carpentier-Edwards bioprosthesis	Status at the end of follow-up	Died after 3 months due to pulmonary regurgitation and hypertension Autopsy showed that bioprosthesis was normal
Lundin et al. (1990), J Thorac Cardiovasc Surg, Sweden [6] Case series (level 4)	Four female patients; three had a Carpentier-Edwards bioprostheses tricuspid replacement and one had a St Jude bioprosthesis tricuspid replacement	Status at the end of follow-up	One patient died on Day 5 of septicaemia Three other patients alive and well after 38, 12 and 10 months postoperatively	This study did not investigate the echocardiographic features of the replacement bioprostheses during the follow-up period. Apart from showing that up to 38 months survival is possible, no other conclusions can be derived
DiSesa et al. (1985), Chest, USA [7] Case report (level 4)	Two female patients with carcinoid heart disease, aged 56 and 32 years, underwent pulmonic valve resection surgery and tricuspid valve replacement with a porcine bioprosthesis	Status at the end of follow-up	One patient was alive 61 months postoperatively with a stable cardiac status and no signs or symptoms of right-side congestive heart failure One patient died after 49 months postoperatively. Post-mortem examination revealed that the tricuspid porcine bioprosthesis was not thickened, and it appeared to be functioning normally	This study provides post-mortem evidence showing that tricuspid bioprostheses can be normal after 49 months in vivo. Further evidence also shows symptom-free survival of 61 months is possible
Forman et al. (1984), Am Heart J, USA [8] Case report (level 4)	A 62-year old male who underwent TVR using a porcine heterograft	Status at the end of follow-up	Died after 4 months of renal failure Valve was functional at autopsy
Gutierrez et al. (1982), Chest, USA [16] Case report (level 4)	A 62-year old male who underwent TVR using a porcine heterograft	Status at the end of follow-up	Asymptomatic at 1 year Echocardiography normal at the end of follow-up
Schoen et al. (1981), J Thorac Cardiovasc Surg, USA [9] Case report (level 4)	A 53-year old man with carcinoid syndrome and tricuspid regurgitation had replacement with a Hancock glutaraldehyde-prepared porcine heterograft prosthesis	Status at the end of follow-up	Died of complications of the tumour 8 months postoperatively, both valves had clinically normal function Nevertheless, the bioprosthesis was coated with carcinoid plaque at post-mortem	This case report shows that patients can be clinically functional, while valves are coated with carcinoid plaque
Sworn et al. (1980), BMJ, UK [17] Case report (level 4)	A 60-year old woman with carcinoid-related severe tricuspid regurgitation had a replacement with a size 27 Carpentier-Edwards pig heterograft	Status at the end of follow-up	Remained well on mild diuretic therapy after 8 months	This study did not investigate the echocardiographic features of the replacement bioprostheses after 8 months. Apart from showing that 8-month survival is possible, no other conclusions can be derived
Okada et al. (1979), Cardiovasc Med, (USA) [18] Case report (level 4)	A 30-year old female who underwent TVR using a porcine heterograft	Status at the end of follow-up	Alive at 4 months
McGuire et al. (1978), J Kans Med Soc, (USA) [10] Case report (level 4)	A 24-year old female who underwent TVR using a porcine heterograft	Status at the end of follow-up	Survived 24 months, died of restrictive cardiomyopathy

TVR: tricuspid valve replacement.

RESULTS

The 17 papers all provide either Level 3 (n = 2) or Level 4 (n = 15) evidence describing case experiences and none provide a comparison between bioprostheses and mechanical prostheses. The generalisability of the evidence found is limited by low power and varying treatment protocols in different centres. The pooled data from all papers represent 51 patients with carcinoid right heart disease who underwent tricuspid valve replacement.

The papers are also limited by variable lengths of the follow-up periods. Of the papers that reported the length of the follow-up period, the mean length was 34.1 months (range 3–153 months). The longest survival reported after tricuspid replacement was 153 months [2]. Two outcome studies reported a 30-day postoperative mortality of 16.7–18% [3, 4]. The 2-year survival rates from these studies were 44 and 50%, respectively. Important to note, is that one series reported the longest survival and follow-up periods of 146 and 153 months [2]. Excluding these, the average length of the follow-up, regardless of the patient's status at the end of the follow-up, was 21 months.

Of the 51 patients, 34 were reported in the two-level three-outcome analyses in which the individual status of each patient was not detailed [3, 4]. The remaining 17 patients were detailed in case reports. Of these 17 patients, 7 died during the follow-up period. Of the three patients alive at the end of the Robiolio et al.'s [2] follow-up period, two died of noncardiac causes and one of these, who died after 153 months, had undergone cardiac catheterization at 107 months, demonstrating a normal replacement of tricuspid valve but a failing native pulmonary valve. Ohri et al. [5] reported that the case of a 64-year old woman who underwent tricuspid replacement with a Carpentier-Edwards bioprosthesis but died after 3 months due to pulmonary regurgitation and hypertension. Autopsy showed that the replacement of bioprosthesis was normal. In Lundin et al.'s [6] series, one patient died 5 days postoperatively of septicaemia. DiSesa et al. [7] reported that the case of a patient who died after 49 months. Post-mortem examination revealed that the replacement of bioprosthesis was not thickened and was functioning normally. Forman et al.'s [8] patient died of renal failure 4 months postoperatively with a functional bioprosthesis. Schoen et al. [9] treated a 53-year old man with carcinoid syndrome and tricuspid regurgitation by replacing it with a Hancock glutaraldehyde-prepared porcine heterograft prosthesis. When the patient died of complications of the tumour 8 months postoperatively, both valves had a clinically normal function. Nevertheless, the bioprosthesis was coated with carcinoid plaque at post-mortem, suggesting that this could have caused clinical problems with time. McGuire et al.'s [10] patient survived 24 months and died of restrictive cardiomyopathy, but the state of the prostheses was not revealed.

CLINICAL BOTTOM LINE

At present, the best available evidence suggests that although 30-day mortality approaches 20%, approximately half of patients with carcinoid syndrome undergoing tricuspid valve replacement can be expected to survive 2 years. Some patients survive considerably longer than this, beyond 10 years in some cases. Importantly, at autopsy many replacement valves have been shown to be normal, with few patients being reported to die of cardiac causes. This should be taken as cautious evidence that biological valves have an acceptable lifespan in patients with carcinoid syndrome and that the process of valve destruction seen in carcinoid patients does not continue to a significant level in the bioprosthesis. Caveats to this include the lack of any directly comparative trial and the predominance of case reports as opposed to higher-level evidence.

Conflict of interest: none declared.