Incidence, predictors and outcomes of cardiac perforation during paediatric cardiac catheterization: A retrospective observational study from the Congenital Cardiac Interventional Study Consortium (CCISC)

Abstract

Introduction

Cardiac perforation is a rare life-threatening complication of cardiac catheterization. There is very little published literature detailing risk factors for cardiac perforation and outcomes from this complication in children.

Materials and Methods

This was a retrospective study analyzing the cardiac catheterization case registry of the Congenital Cardiovascular Interventional Study Consortium. Children aged <18 years were included during the study period of 9 years (January 2009- December 2017). The primary outcome measures were incidence of cardiac perforation, risk factors for and outcomes of patients who experience cardiac perforation during cardiac catheterization.

Results

Cardiac perforation occurred in 50 patients from a total of 36,986 (0.14%). Cardiac perforation was more likely to occur in younger, smaller patients undergoing urgent /emergent and interventional procedures (p<0.01). Cardiac peroration risk was significantly different across diagnostic and procedure categories (p<0.01). Higher CRISP score (Area Under Curve [AUC] =0.87), lower age and procedure category (radio-frequency perforation of pulmonary valve, AUC =0.84) were independent predictors of cardiac perforation. Cardiac perforation was associated with a significantly higher rate of mortality (14%), further emergency procedure (42%), ECMO (14%) and cardiac arrest (6%), p<0.01.

Conclusions

Cardiac perforation during cardiac catheterization is a life-threatening complication with a range of associated secondary complications. Higher CRISP score, lower age and radio-frequency perforation of pulmonary valve are independent predictors.

Introduction

Current literature has estimated major catheter-associated complication rates between 1.4-5% (1–5). As the range and complexity of catheter interventions increases so does the requirement for detailed, standardized outcome measures and risk modeling tools in order to plan procedures and give informed consent. Traditionally, risk-standardization and inter-institutional comparison have been difficult due to single centre publication and lack of standardization in reporting data. The recent development of specific registries, quality-improvement efforts and risk-prediction models have successfully described the breadth of procedures being performed, their outcomes and variables associated with increased risk (1,2,5,7).

Cardiac perforation is recognized as a potentially life-threatening complication. However, it is a rare complication requiring a large patient sample to achieve the necessary power for adequate analysis. This may explain the paucity of data modeling risk factors associated with cardiac perforation in paediatric patients. A large case registry having an ample sample size would be necessary to investigate on cardiac perforation in children. The Congenital Cardiac Interventional Study Consortium (CCISC) Risk Registry is an international multi-institutional registry which developed the predictive risk model using CRISP score as the first comprehensive, validated pre-procedural risk-calculator (1). The CCSIC Risk Registry was thought to be suitable to evaluate the incidence and risk factors of development of cardiac perforation in children. This study aims to describe the incidence of cardiac perforation in paediatric subjects, the variables associated with this complication and outcomes.

Materials And Methods

This retrospective observational study analyzed data from the CCISC risk registry database from 1st January 2009 to 31st December 2017 on patients less than 18 years old. Cases in which important demographic data were missing or incorrectly entered were excluded from further analysis. Patients were assumed to have an incorrectly entered weight if plotted greater than 5 kg outside the 0.4th and 99.8th centiles on the WHO growth chart (6). CCISC is an open, voluntary, multi-institutional registry receiving data from a large number of centres across North America, Europe and Latin America. Data is submitted via a secure, password protected website with no ability to link specific patient data back to the site from the CCISC database application. All participating centres have obtained approval to submit data to CCISC from local Institutional Review Boards or Research Ethics Committees.

Cardiac perforation/rupture during catheter procedure was the primary dependent variable. Independent variables included patient and procedural characteristics; age (years) weight (kg), ‘Cardiac diagnosis’, ‘Catheter procedure’, and Catheterization RISk Score for Pediatrics (CRISP) score. Other variables including procedure-type (diagnostic/interventional/hybrid), and gender were also reviewed. Due to the small number of cardiac perforations and the wide range of diagnoses and catheter procedures, categorizing these variables into groups was necessary in order to perform meaningful regression analyses. The raw-data for both ‘diagnosis’ and ‘procedure’ were recorded in prose. These categories were designed to avoid co-linearity but permit comprehensive multivariate analysis.

Cardiac diagnosis was subdivided into 5 categories; ‘atrial septal defect’, ‘semi-lunar valve stenosis/ atresia, ‘single ventricle’, ‘arrhythmia’ and ‘other’. Catheter procedure was subdivided into 7 categories; ‘atrial septostomy/atrial septal stent’, ‘pulmonary valve radio-frequency ablation’, ‘cardiac biopsy’, ‘aortic/pulmonary valvuloplasty’, ‘Stent insertion in right ventricular outflow tract or main pulmonary artery (includes percutaneous pulmonary valve), ‘electrophysiology study/ablation’, and ‘other procedure’.

The outcome measures included ‘extended length of stay in hospital due to complication’, ‘serious adverse incident’, ‘pericardial effusion’, ‘hemopericardium’, ‘second emergency procedure’, ‘cardiac arrest within 24 hours’, ‘further procedure’ and ‘death due to complication during catheterization’.

Results

Over a 9-year period, 1st January 2009 to 31st December 2017 inclusive, 38,103 cardiac catheterizations were submitted to the CCISC registry on patients under 18 years old. Due to missing or incorrectly entered demographic data, 1,117 cases (2.9%) were excluded from further analysis leaving a study cohort = 36,986. The median (IQR) age of the study cohort was 3.3 years (0.6–9.9 years). Two-third (69%) of cases were performed beyond the first birthday and 5.9% during the neonatal period. The median (IQR) weight was 14.0kg (6.7–30.6 kg). The number (%) patients weighing < 2.5kg = 1,171 (3.1%), between 2.5-5 kg = 5,377 (14.5%) and > 5 kg = 30,448 (82%). Elective procedures comprised 90.3% of cases with a further 6.7% as emergency procedures and post-operative cases accounting for 3% (1.7% elective, 1.3% urgent).

There were 50 cases (0.14%) of cardiac perforation. A comparison of the baseline demographics, diagnostic category and procedure type are presented in Table 1. Patients who experienced a cardiac perforation during the catheterization are more likely to be younger, of lower weight, and undergoing a non-elective intervention. As the diagnostic and procedure categories are nominal data and some of the data entries would be very small with very large differences in the sample sizes, it is not possible to perform further analysis as to which category is most significant. However, a simple review of the data highlights “Radio-frequency perforation of the pulmonary valve” as being a potential outlier.

Table 1: Comparison of demographics, diagnosis and procedural types of patient with cardiac perforation and those with no cardiac perforation.

Risk Factors

The total CRISP score is significantly different between those patients who had a cardiac perforation compared with those without. A simple logistic regression analysis confirmed that a higher total CRISP score was predictive of cardiac perforation (OR = 0.73 per unit increase in CRISP score, and 819 over entire range, p < 0.01, Receiver Operating characteristic area under the curve [AUC] = 0.84). Multiple logistic regression analysis was performed using three factors (procedure type, age and diagnostic category). An effective likelihood ratio test demonstrated that procedure type and age (p < 0.01, OR per unit = 1.1, 4.3 over entire range) independently contributed to risk of perforation. Radiofrequency perforation of pulmonary valve was identified as the only significantly different procedure associated with greater risk of cardiac perforation (p < 0.01, AUC = 0.84). Further multiple logistic regression analysis using procedure type, diagnostic category and weight again demonstrated that only procedure type was independently predictive of cardiac perforation (p < 0.01, AUC = 0.87). Table 2 presents the Odds Ratio of cardiac perforation for each procedural category using the lowest risk category as a control group (“Other”). Radiofrequency perforation of pulmonary stands out as having an OR = 443 whilst cardiac biopsy has no significant observed increased risk.

Table 2: Incidence of cardiac perforation for specific procedure categories

Outcomes

Cardiac perforation is associated with a much higher risk of a further serious adverse event including hemopericardium (40%), prolongation of hospital admission (32%), cardiac arrest (6%), second organ damage (4%), requirement of haemodynamic support (30%) or blood transfusion (28%) (Table 3). Cardiac perforation was also associated with an increased requirement of unplanned ECMO (14%) and a significantly higher risk of death from a complication occurring during cardiac catheterization (14%). In total 28/50 (56%) patients required a further procedure following cardiac perforation – 5 emergency pericardioentesis, 1 non-emergency pericardiocentesis, 9 emergency surgical interventions, 6 non-emergency surgical interventions and 7 emergency unspecified procedures.

Table 3: Comparison of patient outcomes between patients with cardiac perforation and those with no cardiac perforation.

Discussion

This is the first study to evaluate risk factors associated with cardiac perforation during cardiac catheterization in children. The CCISC registry is one of the largest worldwide congenital cardiac catheterization database compiling detailed demographic, procedural and outcome data. (8) Cardiac perforation was found to be a very rare but very serious complication (0.13%) in this cohort. This study confirms that it is associated with a very high risk of requiring further invasive, intervention (56%) and a high risk of further complications (ECMO 14%, cardiac arrest 6%, haemodynamic support 30%), prolongation of hospital admission (32%) and high mortality rate (14%). As such an evidence-based approach to identify pre-procedure risk factors could be very useful when planning and consenting for particular procedures. This study suggests that younger age, higher CRISP score and radiofrequency perforation of the pulmonary valve are independent risk factors for cardiac perforation. The risk factor most strongly associated with cardiac perforation is total CRISP score.

The CRISP score is an empirically based risk score developed specifically for paediatric cardiac catheterization from the CCISC registry which has been refined to utilize only pre-procedure data. (8) It has been externally validated and confirms accurate prediction of risk of SAE. Cardiac perforation is one of the SAEs included in the CCISC data set but comprises a very small proportion of the total (2.7%). (7) This is the first study to specifically address a single SAE from the CCISC database. The results of this study provide further evidence that the total CRISP score is a powerful tool in predicting a potentially lethal complication (AUC = 0.84, p < 0.01).

The CCISC registry is voluntary and as such there is some risk of under reporting of complications and failure to capture cases/ data points. As cardiac perforation is a very rare event, multiple logistical regression analysis to identify independent risk factors is difficult despite the facility of a very large, detailed database. Many variables are co-dependent such as age/ weight and diagnosis/ procedure. These frustrations are well recognized and were one of the key drivers in the development of risk scores. In this study it was necessary to group diagnoses and procedures into a small number of categories to facilitate statistical analysis.

Risk scores are well established in adult coronary artery disease. GRACE and TIMI are externally validated scoring systems to predict outcomes in acute coronary syndrome. (8,9) However, they are not designed to predict SAEs/ outcomes associated with particular procedures. There are a number of studies examining the risk of cardiac perforation during coronary catheterization/ intervention. A systematic review and meta-analysis conducted by Shimony et al in 2011 involving approximately 200,000 cases reported an incidence of 0.43%. Risk factors for coronary perforation included complexity of coronary lesion and use of atheroma obliterative devices. (10)

The vast majority of published data relating to procedural complications/ outcomes is viewed from the other end of the telescope. Studies evaluating a wide spectrum of procedures are available with detailed procedural, mid and long-term outcome data, including complications (11–14). Despite a full chapter dedicated to cardiac perforation appearing in 1968 in Circulation (15), there is comparatively little in the literature describing factors associated with specific complications. The Toronto group published a detailed overview of procedural complications experienced at their institution over a 22-year period. Complications were grouped into Death, Cardiac Arrest, Arrhythmia, Vascular, Perforation and Other. Cardiac perforation occurred in 13/ 11,073 cases (0.11%). Most perforations occurred during myocardial biopsy, nine resolved spontaneously and four required surgical repair. It was beyond the scope of that particular study to examine risk factors associated with individual complications.(3)

A small number of studies report specific complications relating to paediatric cardiac catheterization. Kim et al. reported the incidence, risk factors and outcomes associated with femoral arterial thrombosis in children undergoing cardiac catheterization providing a valuable addition to the literature (16). Rizzi et al. conducted a systematic review of all catheter related arterial thrombosis. Five studies reported an 11% pooled incidence of arterial thrombosis associated with cardiac catheterization but were unable to produce specific risk factors (17).

Conclusion

Cardiac perforation during paediatric cardiac catheterization is a rare but very serious, life threatening complications. Risk factors predicting cardiac perforation include younger age, radiofrequency perforation of the pulmonary valve but most reliably higher CRISP score.

Declarations

Conflicts: None

References

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