Downloaded from http://heart.bmj.com/ on July 26, 2015 - Published by group.bmj.com
Heart Online First, published on July 15, 2015 as 10.1136/heartjnl-2015-307907
Review
Systematic review of percutaneous interventions for malignant pericardial effusion Sohaib A Virk,1 David Chandrakumar,1 Claudia Villanueva,2 Hugh Wolfenden,3 Kevin Liou,4 Christopher Cao1 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ heartjnl-2015-307907). 1
The Systematic Review Unit, The Collaborative Research (CORE) Group, Sydney, Australia 2 Department of Cardiothoracic Surgery, St George Hospital, Sydney, Australia 3 Department of Cardiothoracic Surgery, Prince of Wales Hospital, Sydney, Australia 4 Department of Cardiology, Prince of Wales Hospital, Sydney, Australia 5 University of New South Wales, Sydney, Australia Correspondence to Dr Christopher Cao, The Systematic Review Unit, The Collaborative Research (CORE) Group, Sydney, Australia; [email protected] Received 28 March 2015 Revised 17 June 2015 Accepted 24 June 2015
ABSTRACT The present systematic review assessed the safety and efficacy of percutaneous interventions for malignant pericardial effusion (MPE), with primary endpoint of recurrence of pericardial effusion. Electronic searches of six databases identified thirty-one studies, reporting outcomes following isolated pericardiocentesis (n=305), pericardiocentesis followed by extended catheter drainage (n=486), pericardial instillation of sclerosing agents (n=392) or percutaneous balloon pericardiotomy (PBP) (n=157). Isolated pericardiocentesis demonstrated a pooled recurrence rate of 38.3%. Pooled recurrence rates for extended catheter drainage, pericardial sclerosis and PBP were 12.1%, 10.8% and 10.3%, respectively. Procedure-related mortality ranged from 0.5–1.0% across the percutaneous interventions. Although isolated pericardiocentesis can safely deliver immediate symptomatic relief, subsequent catheter drainage or sclerotherapy are required to minimize recurrence. PBP has been shown to be highly effective and may be particularly useful in managing recurrent effusions. Ultimately, the choice of intervention must be based on the clinical status of patients, their underlying malignancy and the expertise available.
INTRODUCTION
To cite: Virk SA, Chandrakumar D, Villanueva C, et al. Heart Published Online First: [please include Day Month Year] doi:10.1136/heartjnl2015-307907
Neoplastic involvement of the pericardium is found at autopsy in 10–20% of oncology patients.1 The development of malignant pericardial effusion (MPE) portends a poor prognosis and is the leading cause of cardiac tamponade in many tertiary hospitals.2 3 Successful management of MPE involves the relief of immediate symptoms and haemodynamic instability, as well as the prevention of fluid reaccumulation.4 Prevention of effusion recurrence can be particularly challenging in patients with MPE, with one series demonstrating a fivefold greater need for reintervention in this cohort compared with patients with non-neoplastic effusions.3 Traditionally, the definitive management of MPE has been associated with surgical procedures such as pericardial window formation through the subxiphoid or thoracotomy approach.5–7 However, recurrence rates reported following surgery for MPE vary widely, ranging from 4.5% to 27.3% across series.8–11 Moreover, patients with MPE are often poor surgical candidates with significant perioperative and anaesthetic risks due to multiple comorbidities and cancerous cachexia.6 7 As life expectancy is often very limited in patients with MPE, long-term treatment efficacy must be balanced with the need to minimise patient discomfort.3 12
In contrast to surgical intervention, pericardiocentesis is a minimally invasive approach in which pericardial fluid is percutaneously aspirated through the insertion of a needle into the anterior chest wall.13 Pericardiocentesis can be performed as an isolated intervention or in combination with an indwelling pericardial catheter to enable extended drainage.4 In some centres, percutaneous drainage is also accompanied by the instillation of sclerosing agents to induce an inflammatory reaction that promotes fibrosis of the pericardium and reduce reaccumulation of fluid.4 More recently, percutaneous balloon pericardiotomy (PBP) has emerged as an alternative percutaneous approach.14 During PBP, a dilating balloon catheter is advanced through the pericardial space and inflated to create a pericardial window, permitting the passage of pericardial fluid into the pleural or peritoneal space, where resorptive capacity is greater.15 Although various percutaneous approaches have been performed in the management of MPE, uncertainty persists regarding their relative safety and efficacy. As a result, the optimal management of MPE remains highly controversial. The aim of the present study was to systematically review the clinical outcomes of percutaneous interventions for MPE, with the primary endpoint of recurrence of pericardial effusion after treatment.
METHODS Search strategy and study selection Electronic searches were performed using Ovid Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), ACP Journal Club and Database of Abstracts of Review of Effects (DARE) from their dates of inception to December 2014. The search terms (“percutaneous” OR “pericardiocentesis” OR “pericardiostomy” OR “pericardiotomy” OR “drainage” OR “catheter” OR “sclerosis”) AND (“malignant” OR “malignancy” OR “neoplastic” OR “cancer”) AND (“pericardial effusion” OR “cardiac tamponade”) were combined as both keywords and MeSH terms. This was supplemented by hand searching the reference lists of reviews and all potentially relevant studies. Two reviewers (SAV and CC) independently screened the title and abstract of records identified in the search. Full-text publications were subsequently reviewed separately if either reviewer considered the manuscript as being potentially eligible. Disagreements regarding final study inclusion were resolved by discussion and consensus.
Virk SA, et al. Heart 2015;0:1–8. doi:10.1136/heartjnl-2015-307907
1
Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd (& BCS) under licence.
Downloaded from http://heart.bmj.com/ on July 26, 2015 - Published by group.bmj.com
Review Eligibility criteria Studies on percutaneous interventions for MPE were eligible for inclusion in the present systematic review if they reported on the incidence of recurrence requiring reintervention. Percutaneous interventions were categorised into (i) isolated pericardiocentesis, (ii) pericardiocentesis followed by extended catheter drainage, (iii) pericardiocentesis followed by intrapericardial instillation of sclerosing agents and (iv) PBP. Studies involving patients with effusions of combined aetiology were excluded unless recurrence rates for the MPE cohort could be extracted separately. When studies reported on multiple percutaneous interventions, data were extracted separately for each intervention where possible. All publications were limited to those involving human subjects and written in English. Abstracts, case reports, conference presentations, editorials and expert opinions were excluded. Only studies reporting on a minimum of 10 patients were eligible for inclusion. Review articles were omitted because of potential publication bias and duplication of results. When institutions published duplicated studies with accumulating numbers of patients or increased lengths of follow-up, only the most complete reports were included for assessment.
Data extraction All data were independently extracted from text, tables and figures by two investigators (CV and DC). Discrepancies between the reviewers were resolved by discussion and consensus with a third reviewer (SAV). The predetermined primary endpoint was recurrence of pericardial effusion. This was defined as the accumulation of pericardial fluid resulting in relapse of symptoms and/or necessitating secondary intervention directed at the pericardium.
Secondary endpoints included procedure-related mortality and morbidity, and overall survival following intervention.
Statistical analysis The primary endpoint of MPE recurrence was pooled for each intervention using the random-effects model.16 For all studies, overall survival referred to freedom from death of any cause, and was presented from the time of intervention. Publication bias was assessed using funnel plots comparing logit recurrence rates with their SE. The Egger regression test was used to detect funnel plot asymmetry and the Trim-and-Fill method was used to explore the impact of studies potentially missing due to publication bias.17 18 All statistical analyses were performed using Comprehensive Meta-analysis V.2.2 (Biostat, Englewood, New Jersey, USA). All p values were two-sided, and values
Heart Online First, published on July 15, 2015 as 10.1136/heartjnl-2015-307907
Review
Systematic review of percutaneous interventions for malignant pericardial effusion Sohaib A Virk,1 David Chandrakumar,1 Claudia Villanueva,2 Hugh Wolfenden,3 Kevin Liou,4 Christopher Cao1 ▸ Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ heartjnl-2015-307907). 1
The Systematic Review Unit, The Collaborative Research (CORE) Group, Sydney, Australia 2 Department of Cardiothoracic Surgery, St George Hospital, Sydney, Australia 3 Department of Cardiothoracic Surgery, Prince of Wales Hospital, Sydney, Australia 4 Department of Cardiology, Prince of Wales Hospital, Sydney, Australia 5 University of New South Wales, Sydney, Australia Correspondence to Dr Christopher Cao, The Systematic Review Unit, The Collaborative Research (CORE) Group, Sydney, Australia; [email protected] Received 28 March 2015 Revised 17 June 2015 Accepted 24 June 2015
ABSTRACT The present systematic review assessed the safety and efficacy of percutaneous interventions for malignant pericardial effusion (MPE), with primary endpoint of recurrence of pericardial effusion. Electronic searches of six databases identified thirty-one studies, reporting outcomes following isolated pericardiocentesis (n=305), pericardiocentesis followed by extended catheter drainage (n=486), pericardial instillation of sclerosing agents (n=392) or percutaneous balloon pericardiotomy (PBP) (n=157). Isolated pericardiocentesis demonstrated a pooled recurrence rate of 38.3%. Pooled recurrence rates for extended catheter drainage, pericardial sclerosis and PBP were 12.1%, 10.8% and 10.3%, respectively. Procedure-related mortality ranged from 0.5–1.0% across the percutaneous interventions. Although isolated pericardiocentesis can safely deliver immediate symptomatic relief, subsequent catheter drainage or sclerotherapy are required to minimize recurrence. PBP has been shown to be highly effective and may be particularly useful in managing recurrent effusions. Ultimately, the choice of intervention must be based on the clinical status of patients, their underlying malignancy and the expertise available.
INTRODUCTION
To cite: Virk SA, Chandrakumar D, Villanueva C, et al. Heart Published Online First: [please include Day Month Year] doi:10.1136/heartjnl2015-307907
Neoplastic involvement of the pericardium is found at autopsy in 10–20% of oncology patients.1 The development of malignant pericardial effusion (MPE) portends a poor prognosis and is the leading cause of cardiac tamponade in many tertiary hospitals.2 3 Successful management of MPE involves the relief of immediate symptoms and haemodynamic instability, as well as the prevention of fluid reaccumulation.4 Prevention of effusion recurrence can be particularly challenging in patients with MPE, with one series demonstrating a fivefold greater need for reintervention in this cohort compared with patients with non-neoplastic effusions.3 Traditionally, the definitive management of MPE has been associated with surgical procedures such as pericardial window formation through the subxiphoid or thoracotomy approach.5–7 However, recurrence rates reported following surgery for MPE vary widely, ranging from 4.5% to 27.3% across series.8–11 Moreover, patients with MPE are often poor surgical candidates with significant perioperative and anaesthetic risks due to multiple comorbidities and cancerous cachexia.6 7 As life expectancy is often very limited in patients with MPE, long-term treatment efficacy must be balanced with the need to minimise patient discomfort.3 12
In contrast to surgical intervention, pericardiocentesis is a minimally invasive approach in which pericardial fluid is percutaneously aspirated through the insertion of a needle into the anterior chest wall.13 Pericardiocentesis can be performed as an isolated intervention or in combination with an indwelling pericardial catheter to enable extended drainage.4 In some centres, percutaneous drainage is also accompanied by the instillation of sclerosing agents to induce an inflammatory reaction that promotes fibrosis of the pericardium and reduce reaccumulation of fluid.4 More recently, percutaneous balloon pericardiotomy (PBP) has emerged as an alternative percutaneous approach.14 During PBP, a dilating balloon catheter is advanced through the pericardial space and inflated to create a pericardial window, permitting the passage of pericardial fluid into the pleural or peritoneal space, where resorptive capacity is greater.15 Although various percutaneous approaches have been performed in the management of MPE, uncertainty persists regarding their relative safety and efficacy. As a result, the optimal management of MPE remains highly controversial. The aim of the present study was to systematically review the clinical outcomes of percutaneous interventions for MPE, with the primary endpoint of recurrence of pericardial effusion after treatment.
METHODS Search strategy and study selection Electronic searches were performed using Ovid Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), ACP Journal Club and Database of Abstracts of Review of Effects (DARE) from their dates of inception to December 2014. The search terms (“percutaneous” OR “pericardiocentesis” OR “pericardiostomy” OR “pericardiotomy” OR “drainage” OR “catheter” OR “sclerosis”) AND (“malignant” OR “malignancy” OR “neoplastic” OR “cancer”) AND (“pericardial effusion” OR “cardiac tamponade”) were combined as both keywords and MeSH terms. This was supplemented by hand searching the reference lists of reviews and all potentially relevant studies. Two reviewers (SAV and CC) independently screened the title and abstract of records identified in the search. Full-text publications were subsequently reviewed separately if either reviewer considered the manuscript as being potentially eligible. Disagreements regarding final study inclusion were resolved by discussion and consensus.
Virk SA, et al. Heart 2015;0:1–8. doi:10.1136/heartjnl-2015-307907
1
Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd (& BCS) under licence.
Downloaded from http://heart.bmj.com/ on July 26, 2015 - Published by group.bmj.com
Review Eligibility criteria Studies on percutaneous interventions for MPE were eligible for inclusion in the present systematic review if they reported on the incidence of recurrence requiring reintervention. Percutaneous interventions were categorised into (i) isolated pericardiocentesis, (ii) pericardiocentesis followed by extended catheter drainage, (iii) pericardiocentesis followed by intrapericardial instillation of sclerosing agents and (iv) PBP. Studies involving patients with effusions of combined aetiology were excluded unless recurrence rates for the MPE cohort could be extracted separately. When studies reported on multiple percutaneous interventions, data were extracted separately for each intervention where possible. All publications were limited to those involving human subjects and written in English. Abstracts, case reports, conference presentations, editorials and expert opinions were excluded. Only studies reporting on a minimum of 10 patients were eligible for inclusion. Review articles were omitted because of potential publication bias and duplication of results. When institutions published duplicated studies with accumulating numbers of patients or increased lengths of follow-up, only the most complete reports were included for assessment.
Data extraction All data were independently extracted from text, tables and figures by two investigators (CV and DC). Discrepancies between the reviewers were resolved by discussion and consensus with a third reviewer (SAV). The predetermined primary endpoint was recurrence of pericardial effusion. This was defined as the accumulation of pericardial fluid resulting in relapse of symptoms and/or necessitating secondary intervention directed at the pericardium.
Secondary endpoints included procedure-related mortality and morbidity, and overall survival following intervention.
Statistical analysis The primary endpoint of MPE recurrence was pooled for each intervention using the random-effects model.16 For all studies, overall survival referred to freedom from death of any cause, and was presented from the time of intervention. Publication bias was assessed using funnel plots comparing logit recurrence rates with their SE. The Egger regression test was used to detect funnel plot asymmetry and the Trim-and-Fill method was used to explore the impact of studies potentially missing due to publication bias.17 18 All statistical analyses were performed using Comprehensive Meta-analysis V.2.2 (Biostat, Englewood, New Jersey, USA). All p values were two-sided, and values
