Dr. Grapsa works at the Guys and St Thomas NHS Trust as a consultant cardiologist. Dr. Grapsa is an associate professor at King's College in London and is part of the UK's premier structural valve disease group. She also serves as the editor-in-chief of JACC Case Reports, the chair of the European Society of Cardiology's Women Task Force in Imaging, and the secretary of the ESC's Valvular Heart Disease Council.
In this video Dr. Grapsa discusses Staphylococcus Aureus Infective Endocarditis.
Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jaccas.2021.10.002
Abstract-
A 19-year-old female patient presented with Staphylococcus aureus infective endocarditis, with suspected subdural brain hemorrhage, disseminated intravascular coagulopathy, and septic renal as well as spleen infarcts. The patient had extensive vegetations on the mitral and tricuspid valves and underwent urgent mitral and tricuspid repair. This paper discusses the clinical case and current evidence regarding the management and treatment of Staphylococcus aureus endocarditis.
Take-Home Messages
• Echocardiography should be administered expeditiously as the optimal modality for the initial work-up of suspected IE and in the management of most patients with IE. TEE improves sensitivity and TTE improves specificity in detecting complications of IE, so both tests are necessary. TEE is superior for detecting small vegetations.
• CTA is highly sensitive for identifying complications of IE (eg, abscess or aneurysm) and complex IE (eg, PVE), in patients with suboptimal echo imaging and surgical planning in IE.
• 18F-FDG PET-CT: Although not sufficiently sensitive for diagnosing NVE, molecular imaging (mainly with 18F-FDG PET-CT) is an important advance in PVE and CIED-IE as well as in detecting systemic infective foci/septic emboli that often lead to changes in patient management. Use of 18F-FDG PET-CT influences outcomes and is recommended in European IE guidelines but not in the AHA statement.
• WBC scintigraphy is a specific whole-body test to locate infection in prosthetic valve and CIED IE but, currently, there is no clear recommendation in guidelines. It is quite useful in early PVE (where PET-CT, when done <3 months postsurgery, may pick up nonspecific sterile inflammation) and can best identify metastatic foci of infection.
• Surgery: Repair is the surgical method of choice when applicable. Main targets of surgery are the complete removal of infective tissue and reconstruction of affected tissue. In complex IE cases, bioprosthetic valves may be superior to metallic in terms of anticoagulation and have less bleeding risk.
• Antibiotic prophylaxis: There is harmony in the French, AHA, and ESC guidelines to limit prophylaxis to patients with the highest risk of a poor outcome with IE, including prosthetic heart valves, valve repair that includes annuloplasty rings or clips, left ventricular assist devices, complex congenital heart defect either repaired or unrepaired, and orthotopic transplanted hearts with valvulopathy. The United Kingdom’s NICE took the approach of recommending ABx prophylaxis for no group on a routine basis.
Introduction
JACC Patient Pathways is a new initiative from the JACC family to reflect the multidisciplinary collaboration that contributes to optimal patient care and decision-making. The Pathways will highlight the evidence-based discussions that are necessary to solve a clinical problem through an actual patient’s journey.
As clinicians are faced with challenging clinical cases, it is important to understand how current knowledge based on clinical guidelines and the published data can inform decisions. JACC Patient Pathways is a multiparametric approach to this patient journey that provides an interactive illustration, a paper that integrates the clinical case with current evidence, and a video discussion between expert clinicians.
This paper, which the authors are requesting to be copublished with JACC and JACC: Case Reports, begins with the clinical case and continues with mini reviews on the basic considerations of the case. The scope of the paper is not to provide an extensive review of the topic, but rather to act as guidance for clinicians who may encounter similar cases.
Case Presentation
A 19-year-old female patient presented to the emergency department with 5 days of vomiting, fever, intermittent abdominal pain, myalgia, and weakness. She arrived in the United Kingdom from Brazil 6 weeks ago during the coronavirus disease-2019 (COVID-19) pandemic. On presentation, the patient was in extremis: she was hypoxic, acidotic, and hypotensive with a blood pressure of 86/49 mm Hg, a heart rate of 140-150 beats/min, and a respiratory rate of 22 breaths/min. Electrocardiography (ECG) demonstrated sinus tachycardia (Figure 1). She was subsequently referred for extracorporeal membrane oxygenation (ECMO). Her chest x-ray (Figure 2) demonstrated opacified lungs. It was determined that she required a full-body computed tomography (CT) scan on her way to the intensive care unit. The patient was septic and had acute renal injury. She also tested negative for COVID-19, HIV, and hepatitis. Blood cultures proved to be positive for Staphylococcus aureus (Figure 3).
Shortly after undergoing CT scanning, she received a transthoracic echocardiogram (TTE) (Videos 1, 2, 3, 4, 5, and 6), which demonstrated extensive vegetations on the mitral valve and right ventricular wall and good biventricular systolic functioning. She was therefore diagnosed with Staphylococcus aureus endocarditis of the mitral valve and right heart chambers.
After a multidisciplinary meeting with the surgeons, critical care clinicians, hematology, infectious disease, and cardiology, it was determined that the patient required urgent surgery within 24 hours of admission. She underwent mitral and tricuspid valve repair (Figure 6) and experienced mild residual mitral regurgitation immediately postoperatively (Videos 7, 8, 9, 10, 11, and 12). The ECGs were performed during the same day, with TTE taking place in the morning followed by the intraoperative transesophageal echocardiogram (TEE) in the afternoon.
In this video, Professor Leontien Kremer, MD of the Princess Máxima Center, along with PHd candidates Dr.Esmee C. de Baat of the Princess Máxima Center, Dr. Jan M. Leeink of the Amsterdam University Medical Centers, and Dr. Remy Merkx of the Radboud University Medical Center discuss Cardiac Disease in Childhood Cancer Survivors and Risk Prediction, Prevention, and Surveillance.
Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jaccao.2020.08.006
Abstract-
Cardiac disease is a key issue among the expanding population of pediatric cancer survivors. Cardiotoxicity caused by anthracyclines and chest irradiation is still a topic of discussion in today's medical world. Evidence on traditional cardiovascular risk factors in childhood cancer survivors is growing, and mitoxantrone has emerged as an important treatment-related risk factor. The goal of developing international monitoring recommendations is to detect and manage heart illnesses early and prevent symptomatic disease. Risk prediction algorithms are gaining popularity as a way to personalize prevention and surveillance. This State-of-the-Art Review compiles findings from a comprehensive PubMed search on cardiac problems following children cancer treatment. The prevalence, risk factors, prevention, risk prediction, and surveillance of cardiac disorders in pediatric cancer survivors are discussed here.
Highlights
• Anthracyclines, mitoxantrone, and the dose of chest-directed radiation are the key risk factors for heart illness in childhood cancer survivors.
• Using primary prevention techniques, the risk of anthracycline-induced cardiomyopathy may be reduced.
• Traditional cardiovascular risk factors are more prevalent in pediatric cancer survivors; screening and early care are critical to reducing risk.
• Multivariable risk prediction models could aid in the personalization of preventative and surveillance plans.
Introduction
Children's cancer survival rates have grown dramatically in recent decades, with 5-year survival rates now above 80%. (1). Long-term health repercussions in the expanding population of childhood cancer survivors (CCS) remain, nevertheless, a major source of concern (2). Cardiac disease caused by anthracyclines, mitoxantrone, and/or chest-directed radiotherapy (chest RT) can manifest as myocardial dysfunction and heart failure, but it can also manifest as valvular disease, coronary artery disease, arrhythmias, and pericardial disease, depending on the specific cardiotoxic agent (3).
We focus on long-term cardiac problems after children cancer therapy in this State-of-the-Art Review. In this population, we cover the prevalence, risk factors, prevention, prediction, and surveillance of heart illness (Central Illustration). We conducted a systematic search of PubMed for articles describing cardiac side effects in children receiving cardiotoxic cancer therapies. We restricted our search to full-text English-language papers published during the last ten years. We chose publications having a research cohort in which more than half of the participants had been treated for pediatric cancer before the age of 21. We looked for studies with a minimum of 500 CCS for studies describing the prevalence or cumulative incidence of heart failure, and a minimum of 100 CCS for the other outcomes. Previous Cochrane searches (4–6) turned up studies on primary preventive measures. 74 studies were selected to be described in this review based on these criteria (Figure 1). Supplementary Table 1 contains the whole search strategy.
Dr. Christine Albert, MD works in the Department of Cardiology at the Smidt Heart Institute at Cedars-Sinai Medical Center in Los Angeles, California. In This video Dr. Albert discusses Diabetes and the Risk of Sudden Death in Coronary Artery Disease Patients Without Severe Systolic Dysfunction.
Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jacep.2021.05.014
Abstract
In patients with coronary artery disease (CAD) who do not qualify for implantable cardioverter-defibrillators, this study sought to determine the absolute and relative associations of diabetes mellitus (DM) and hemoglobin A1c (HbA1c) with sudden and/or arrhythmic death (SAD) versus other modes of death.
Background
Patients with CAD and diabetes are at an increased risk of SAD; however, given competing causes of death, it is unclear whether these patients would benefit from implantable cardioverter-defibrillators and/or whether HbA1c could help with SAD risk stratification.
Methods
Competing risk analyses were used to compare the absolute and relative risks of SAD versus non-SAD by DM status and HbA1c level in the PRE-DETERMINE study of 5,764 patients with CAD with left ventricular ejection fraction (LVEF) of >30% to 35 percent and to identify risk factors for SAD among 1,782 patients with DM.
Results
DM and HbA1c were significantly associated with SAD and non-SAD over a median follow-up of 6.8 years (P 0.05 for all comparisons); however, the cumulative incidence of non-SAD (19.2 percent; 95 percent CI: 17.3 percent -21.2 percent) in DM patients was nearly 4 times higher than SAD (4.8 percent; 95 percent CI: 3.8 percent -5.9 percent). Absolute risk followed a similar pattern across HbA1c groups. HbA1c was not connected with SAD in studies limited to diabetic patients, although decreased LVEF, atrial fibrillation, and ECG measures were all linked to a higher risk of SAD.
Conclusions
Patients with CAD and LVEF of >30% to 35% who had DM and/or increased HbA1c have a considerably higher absolute risk of dying from non-SAD than from SAD. Clinical risk factors, not HbA1c, were linked to the incidence of SAD in diabetic individuals. (NCT01114269; PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study)
Dr. Christine Albert, MD works in the Department of Cardiology at the Smidt Heart Institute at Cedars-Sinai Medical Center in Los Angeles, California. In This video Dr. Albert discusses Diabetes and the Risk of Sudden Death in Coronary Artery Disease Patients Without Severe Systolic Dysfunction.
Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jacep.2021.05.014
Abstract
In patients with coronary artery disease (CAD) who do not qualify for implantable cardioverter-defibrillators, this study sought to determine the absolute and relative associations of diabetes mellitus (DM) and hemoglobin A1c (HbA1c) with sudden and/or arrhythmic death (SAD) versus other modes of death.
Background
Patients with CAD and diabetes are at an increased risk of SAD; however, given competing causes of death, it is unclear whether these patients would benefit from implantable cardioverter-defibrillators and/or whether HbA1c could help with SAD risk stratification.
Methods
Competing risk analyses were used to compare the absolute and relative risks of SAD versus non-SAD by DM status and HbA1c level in the PRE-DETERMINE study of 5,764 patients with CAD with left ventricular ejection fraction (LVEF) of >30% to 35 percent and to identify risk factors for SAD among 1,782 patients with DM.
Results
DM and HbA1c were significantly associated with SAD and non-SAD over a median follow-up of 6.8 years (P 0.05 for all comparisons); however, the cumulative incidence of non-SAD (19.2 percent; 95 percent CI: 17.3 percent -21.2 percent) in DM patients was nearly 4 times higher than SAD (4.8 percent; 95 percent CI: 3.8 percent -5.9 percent). Absolute risk followed a similar pattern across HbA1c groups. HbA1c was not connected with SAD in studies limited to diabetic patients, although decreased LVEF, atrial fibrillation, and ECG measures were all linked to a higher risk of SAD.
Conclusions
Patients with CAD and LVEF of >30% to 35% who had DM and/or increased HbA1c have a considerably higher absolute risk of dying from non-SAD than from SAD. Clinical risk factors, not HbA1c, were linked to the incidence of SAD in diabetic individuals. (NCT01114269; PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study)
Dr. Pavel Osmanick works at the University Hospital Kralovske Vinohrady, Third Faculty of Medicine, along with Charles University, in Prague, Czech Republic. In this video Dr. Osmanick discusses The Efficacy and Safety of Hybrid Ablations for Atrial Fibrillation.
Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jacep.2021.04.013
Abstract
Objectives
This study sought to comprehensively determine the procedural safety and midterm efficacy of hybrid ablations.
Background
Hybrid ablation of atrial fibrillation (AF) (thoracoscopic ablation followed by catheter ablation) has been used for patients with nonparoxysmal AF; however, accurate data regarding efficacy and safety are still limited.
Methods
Patients with nonparoxysmal AF underwent thoracoscopic, off-pump ablation using the COBRA Fusion radiofrequency system (Estech) followed by a catheter ablation 3 months afterward. The safety of the procedure was assessed using sequential brain magnetic resonance and neuropsychological examinations at baseline (1 day before), postoperatively (2-4 days for brain magnetic resonance imaging or 1 month for neuropsychological examination), and at 9 months after the surgical procedure. Implantable loop recorders were used to detect arrhythmia recurrence. Arrhythmia-free survival (the primary efficacy endpoint) was defined as no episodes of AF or atrial tachycardia while off antiarrhythmic drugs, redo ablations or cardioversions.
Results
Fifty-nine patients (age: 62.5 ± 10.5 years) were enrolled, 37 (62.7%) were men, and the mean follow-up was 30.3 ± 10.8 months. Thoracoscopic ablation was successfully performed in 55 (93.2%) patients. On baseline magnetic resonance imaging, chronic ischemic brain lesions were present in 60.0% of patients. New ischemic lesions on postoperative magnetic resonance imaging were present in 44.4%. Major postoperative cognitive dysfunction was present in 27.0% and 17.6% at 1 and 9 months postoperatively, respectively. The probability of arrhythmia-free survival was 54.0% (95% CI: 41.3-66.8) at 1 year and 43.8% (95% CI: 30.7–57.0) at 2 years.
Conclusions
The thoracoscopic ablation is associated with a high risk of silent cerebral ischemia. The midterm efficacy of hybrid ablations is moderate.
Dr. Pavel Osmanick works at the University Hospital Kralovske Vinohrady, Third Faculty of Medicine, along with Charles University, in Prague, Czech Republic. In this video Dr. Osmanick discusses The Efficacy and Safety of Hybrid Ablations for Atrial Fibrillation.
Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jacep.2021.04.013
Abstract
Objectives
This study sought to comprehensively determine the procedural safety and midterm efficacy of hybrid ablations.
Background
Hybrid ablation of atrial fibrillation (AF) (thoracoscopic ablation followed by catheter ablation) has been used for patients with nonparoxysmal AF; however, accurate data regarding efficacy and safety are still limited.
Methods
Patients with nonparoxysmal AF underwent thoracoscopic, off-pump ablation using the COBRA Fusion radiofrequency system (Estech) followed by a catheter ablation 3 months afterward. The safety of the procedure was assessed using sequential brain magnetic resonance and neuropsychological examinations at baseline (1 day before), postoperatively (2-4 days for brain magnetic resonance imaging or 1 month for neuropsychological examination), and at 9 months after the surgical procedure. Implantable loop recorders were used to detect arrhythmia recurrence. Arrhythmia-free survival (the primary efficacy endpoint) was defined as no episodes of AF or atrial tachycardia while off antiarrhythmic drugs, redo ablations or cardioversions.
Results
Fifty-nine patients (age: 62.5 ± 10.5 years) were enrolled, 37 (62.7%) were men, and the mean follow-up was 30.3 ± 10.8 months. Thoracoscopic ablation was successfully performed in 55 (93.2%) patients. On baseline magnetic resonance imaging, chronic ischemic brain lesions were present in 60.0% of patients. New ischemic lesions on postoperative magnetic resonance imaging were present in 44.4%. Major postoperative cognitive dysfunction was present in 27.0% and 17.6% at 1 and 9 months postoperatively, respectively. The probability of arrhythmia-free survival was 54.0% (95% CI: 41.3-66.8) at 1 year and 43.8% (95% CI: 30.7–57.0) at 2 years.
Conclusions
The thoracoscopic ablation is associated with a high risk of silent cerebral ischemia. The midterm efficacy of hybrid ablations is moderate.
Dr. Grapsa works at the Guys and St Thomas NHS Trust as a consultant cardiologist. Dr. Grapsa is an associate professor at King's College in London and is part of the UK's premier structural valve disease group. She also serves as the editor-in-chief of JACC Case Reports, the chair of the European Society of Cardiology's Women Task Force in Imaging, and the secretary of the ESC's Valvular Heart Disease Council.
In this podcast Dr. Grapsa discusses Staphylococcus Aureus Infective Endocarditis.
Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jaccas.2021.10.002
Abstract-
A 19-year-old female patient presented with Staphylococcus aureus infective endocarditis, with suspected subdural brain hemorrhage, disseminated intravascular coagulopathy, and septic renal as well as spleen infarcts. The patient had extensive vegetations on the mitral and tricuspid valves and underwent urgent mitral and tricuspid repair. This paper discusses the clinical case and current evidence regarding the management and treatment of Staphylococcus aureus endocarditis.
Take-Home Messages
• Echocardiography should be administered expeditiously as the optimal modality for the initial work-up of suspected IE and in the management of most patients with IE. TEE improves sensitivity and TTE improves specificity in detecting complications of IE, so both tests are necessary. TEE is superior for detecting small vegetations.
• CTA is highly sensitive for identifying complications of IE (eg, abscess or aneurysm) and complex IE (eg, PVE), in patients with suboptimal echo imaging and surgical planning in IE.
• 18F-FDG PET-CT: Although not sufficiently sensitive for diagnosing NVE, molecular imaging (mainly with 18F-FDG PET-CT) is an important advance in PVE and CIED-IE as well as in detecting systemic infective foci/septic emboli that often lead to changes in patient management. Use of 18F-FDG PET-CT influences outcomes and is recommended in European IE guidelines but not in the AHA statement.
• WBC scintigraphy is a specific whole-body test to locate infection in prosthetic valve and CIED IE but, currently, there is no clear recommendation in guidelines. It is quite useful in early PVE (where PET-CT, when done <3 months postsurgery, may pick up nonspecific sterile inflammation) and can best identify metastatic foci of infection.
• Surgery: Repair is the surgical method of choice when applicable. Main targets of surgery are the complete removal of infective tissue and reconstruction of affected tissue. In complex IE cases, bioprosthetic valves may be superior to metallic in terms of anticoagulation and have less bleeding risk.
• Antibiotic prophylaxis: There is harmony in the French, AHA, and ESC guidelines to limit prophylaxis to patients with the highest risk of a poor outcome with IE, including prosthetic heart valves, valve repair that includes annuloplasty rings or clips, left ventricular assist devices, complex congenital heart defect either repaired or unrepaired, and orthotopic transplanted hearts with valvulopathy. The United Kingdom’s NICE took the approach of recommending ABx prophylaxis for no group on a routine basis.
Introduction
JACC Patient Pathways is a new initiative from the JACC family to reflect the multidisciplinary collaboration that contributes to optimal patient care and decision-making. The Pathways will highlight the evidence-based discussions that are necessary to solve a clinical problem through an actual patient’s journey.
As clinicians are faced with challenging clinical cases, it is important to understand how current knowledge based on clinical guidelines and the published data can inform decisions. JACC Patient Pathways is a multiparametric approach to this patient journey that provides an interactive illustration, a paper that integrates the clinical case with current evidence, and a video discussion between expert clinicians.
This paper, which the authors are requesting to be copublished with JACC and JACC: Case Reports, begins with the clinical case and continues with mini reviews on the basic considerations of the case. The scope of the paper is not to provide an extensive review of the topic, but rather to act as guidance for clinicians who may encounter similar cases.
Case Presentation
A 19-year-old female patient presented to the emergency department with 5 days of vomiting, fever, intermittent abdominal pain, myalgia, and weakness. She arrived in the United Kingdom from Brazil 6 weeks ago during the coronavirus disease-2019 (COVID-19) pandemic. On presentation, the patient was in extremis: she was hypoxic, acidotic, and hypotensive with a blood pressure of 86/49 mm Hg, a heart rate of 140-150 beats/min, and a respiratory rate of 22 breaths/min. Electrocardiography (ECG) demonstrated sinus tachycardia (Figure 1). She was subsequently referred for extracorporeal membrane oxygenation (ECMO). Her chest x-ray (Figure 2) demonstrated opacified lungs. It was determined that she required a full-body computed tomography (CT) scan on her way to the intensive care unit. The patient was septic and had acute renal injury. She also tested negative for COVID-19, HIV, and hepatitis. Blood cultures proved to be positive for Staphylococcus aureus (Figure 3).
Shortly after undergoing CT scanning, she received a transthoracic echocardiogram (TTE) (Videos 1, 2, 3, 4, 5, and 6), which demonstrated extensive vegetations on the mitral valve and right ventricular wall and good biventricular systolic functioning. She was therefore diagnosed with Staphylococcus aureus endocarditis of the mitral valve and right heart chambers.
After a multidisciplinary meeting with the surgeons, critical care clinicians, hematology, infectious disease, and cardiology, it was determined that the patient required urgent surgery within 24 hours of admission. She underwent mitral and tricuspid valve repair (Figure 6) and experienced mild residual mitral regurgitation immediately postoperatively (Videos 7, 8, 9, 10, 11, and 12). The ECGs were performed during the same day, with TTE taking place in the morning followed by the intraoperative transesophageal echocardiogram (TEE) in the afternoon.
In this Podcast, Professor Leontien Kremer, MD of the Princess Máxima Center, along with PHd candidates Dr.Esmee C. de Baat of the Princess Máxima Center, Dr. Jan M. Leeink of the Amsterdam University Medical Centers, and Dr. Remy Merkx of the Radboud University Medical Center discuss Cardiac Disease in Childhood Cancer Survivors and Risk Prediction, Prevention, and Surveillance.
Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jaccao.2020.08.006
Abstract-
Cardiac disease is a key issue among the expanding population of pediatric cancer survivors. Cardiotoxicity caused by anthracyclines and chest irradiation is still a topic of discussion in today's medical world. Evidence on traditional cardiovascular risk factors in childhood cancer survivors is growing, and mitoxantrone has emerged as an important treatment-related risk factor. The goal of developing international monitoring recommendations is to detect and manage heart illnesses early and prevent symptomatic disease. Risk prediction algorithms are gaining popularity as a way to personalize prevention and surveillance. This State-of-the-Art Review compiles findings from a comprehensive PubMed search on cardiac problems following children cancer treatment. The prevalence, risk factors, prevention, risk prediction, and surveillance of cardiac disorders in pediatric cancer survivors are discussed here.
Highlights
• Anthracyclines, mitoxantrone, and the dose of chest-directed radiation are the key risk factors for heart illness in childhood cancer survivors.
• Using primary prevention techniques, the risk of anthracycline-induced cardiomyopathy may be reduced.
• Traditional cardiovascular risk factors are more prevalent in pediatric cancer survivors; screening and early care are critical to reducing risk.
• Multivariable risk prediction models could aid in the personalization of preventative and surveillance plans.
Introduction
Children's cancer survival rates have grown dramatically in recent decades, with 5-year survival rates now above 80%. (1). Long-term health repercussions in the expanding population of childhood cancer survivors (CCS) remain, nevertheless, a major source of concern (2). Cardiac disease caused by anthracyclines, mitoxantrone, and/or chest-directed radiotherapy (chest RT) can manifest as myocardial dysfunction and heart failure, but it can also manifest as valvular disease, coronary artery disease, arrhythmias, and pericardial disease, depending on the specific cardiotoxic agent (3).
We focus on long-term cardiac problems after children cancer therapy in this State-of-the-Art Review. In this population, we cover the prevalence, risk factors, prevention, prediction, and surveillance of heart illness (Central Illustration). We conducted a systematic search of PubMed for articles describing cardiac side effects in children receiving cardiotoxic cancer therapies. We restricted our search to full-text English-language papers published during the last ten years. We chose publications having a research cohort in which more than half of the participants had been treated for pediatric cancer before the age of 21. We looked for studies with a minimum of 500 CCS for studies describing the prevalence or cumulative incidence of heart failure, and a minimum of 100 CCS for the other outcomes. Previous Cochrane searches (4–6) turned up studies on primary preventive measures. 74 studies were selected to be described in this review based on these criteria (Figure 1). Supplementary Table 1 contains the whole search strategy.
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