REVIEW For reprint orders, please contact: [email protected]
Individualized cardiovascular risk assessment by cardiovascular magnetic resonance
Rocio Hinojar1, Rene Botnar2, Juan Carlos Kaski3, Sanjay Prasad4, Eike Nagel1 & Valentina O Puntmann*,1
ABSTRACT: Cardiovascular magnetic resonance (CMR) is gaining clinical importance in preventive medicine. Evidence on diagnostic accuracy and prognostic value, in addition to the development of faster imaging, increased availability of equipment and imaging expertise have led to a wide-spread use of CMR in a growing number of clinical indications. The first part of this review summarizes the role of CMR biomarkers for risk assessment focusing on the patients groups that benefit from the use of CMR. In the second part, the future directions for CMR are discussed and their role in prevention of cardiovascular disease. Over the past decade, improved control of major risk factors and concerted efforts of primary and secondary prevention programs led to considerable reduction in morbidity and mortality due to cardiovascular (CV) disease in the western societies [1,2] . Yet, CV disease remains the leading cause of death and disability in developed countries despite substantial investment into public healthcare and the perceptibly improved CV health of the population as a whole. Current means of CV risk assessment rely on scoring systems based on traditional CV risk markers, such as age, gender, blood pressure, cholesterol and smoking history and target population as a whole. Nevertheless, a considerable number of subjects die suddenly or develop heart failure with no prior symptoms or identifiable CV risk factors [3–5] . Furthermore, detection and prevention of the subgroups at risk of due to inherited cardiomyopathies remain suboptimal despite the great advances in understanding of underlying pathophysiology and imaging technologies. Another example of a group at risk, are subjects suffering with accelerated CV disease at younger age due to comorbidities. Several potential plasma and imaging biomarkers have been proposed as adjunct to the CV riskscoring system, linking with the different phases in the evolution of disease, from risk factors to subclinical disease to overt disease [6,7] . These markers suffer with considerable limitations, because they are either associated with coronary disease indirectly (e.g., carotid intima media thickness) or only inform on the risk in patients with overt and expressed disease (e.g., maximal left ventricle; LV) wall thickness in hypertrophic cardiomyopathy; HCM). Many markers lack relationship with the underlying disease process or disease activity (e.g., calcium scoring) and evidence that the use of a biomarker leads to an improved outcome. Beyond the statin therapy, there is also a perceptible paucity of treatment options [8] especially when targeting risks early with the greatest opportunity for reversibility [9] . Most crucially, many of these markers suffer with significant limitations for the use in the young and asymptomatic subjects, including radiation, low diagnostic yield or reproducibility, and, as such, unlikely applicable for screening and exclusion of disease. The accurate identification of individuals at risk within the window of the greatest opportunity for targeted prevention is crucial
KEYWORDS
• cardiac magnetic
resonance imaging • cardiomyopathy • late gadolinium enhancement • noninvasive • prevention
Cardiovascular Imaging Department, Division of Imaging Sciences & Biomedical Engineering, King’s College London, London, UK Department of Medical Physics & Bioengineering, Division of Imaging Sciences & Biomedical Engineering, King’s College London, UK 3 Cardiac & Vascular Sciences, St George’s, University of London, UK 4 Royal Brompton & Harefield NHS Foundation Trust, UK *Author for correspondence: Tel.: +44 20 7188 7242; Fax: +44 20 7188 544; [email protected] 1 2
10.2217/FCA.13.102 © 2014 Future Medicine Ltd
Future Cardiol. (2014) 10(2), 273–289
part of
ISSN 1479-6678
273
Review Hinojar, Botnar, Kaski, Prasad, Nagel & Puntmann and remains a major challenge. Increasing knowledge regarding the relevant subgroups where conventional population-targeting strategies fail to identify vulnerable subjects in time, may eventually also lead to improved screening and CV-risk assessment of these vulnerable subgroups. The increasing role of CV magnetic resonance (CMR) is due to its unique ability to provide insight into function and structure with high diagnostic accuracy, noninvasively and free from ionizing-radiation. As such, it is well suited to inform on the presence of subclinical or overt disease in an asymptomatic population. CMR is a technique that is sufficiently accurate and versatile to understand the complex pathophysiology in various CV conditions. A full CMR examination consists of different protocols that can be performed in various combinations during a single session. Faster imaging and increased availability of equipment and imaging expertise, now allow for the use of this modality early in the diagnostic cascade. High cost is commonly offset by the reduced need for other imaging to reach the diagnosis [10] . The number of overall clinical indications is increasing, and, as a result the evolving role of CMR is gaining importance, by virtue of exclusion of disease, secondary prevention and its ability to guide management. In the first part of this review, we will focus on the role of CMR biomarkers for risk assessment paying particular attention to the patients groups that benefit from the use of CMR. In the second part, we will summarize the future directions where CMR may contribute in prevention of CV disease. Role of CMR applications in risk assessment of focused patient groups There is increasing evidence that several patients groups benefit from the use of CMR, either by delivering an accurate diagnosis, not achieved with other modalities, or by the ability to guide their clinical management [11] . In Table 1 we outline the current clinical CMR applications and predictive outcome evidence in particular patient subgroups. ●●Assessment of myocardial ischemia in
subjects with recognized high risk
Assessment of myocardial ischemia by myocardial perfusion imaging offers incremental prognostic value in the prediction of cardiac death, new acute events and in assessing the benefit of revascularization in patients with
274
Future Cardiol. (2014) 10(2)
suspected or previously known coronary artery disease (CAD), allowing for clinical decisionmaking [24–26] . Ischemia imaging for detection of subclinical disease may be considered in asymptomatic adults with diabetes, strong family history of CAD or when previous risk assessment test suggests high risk of CAD, such as coronary artery calcium score of ≥400 [48] . In a large series of 2664 asymptomatic subjects referred to a stress perfusion imaging with single photon emission computerized tomography (SPECT), those with 7.5% myocardial ischemia had a higher annual event rate (3.2%), which was consistent with high risk [49] . Khandaker et al. summarized data from 260 asymptomatic adults at moderate risk and without diagnosis of CAD with a follow-up of almost 10 years [50] . Abnormal SPECT myocardial perfusion imaging scans were present in 142 patients (55%): low risk in 67% of patients, intermediate risk in 20% and high risk in 13%. Survival was 60% for patients with high-risk scans, 79% with intermediate-risk scans and 83% with low-risk scans. Adenosine stress perfusion imaging by CMR is a widely used application and bears low procedural risk [51] . Recent evidence confirmed that it is noninferior to SPECT in a multicenter, and even superior to SPECT in a single center setting [52–54] . This evidence is important as it supports the view that it is the most accurate available noninvasive technique of current clinical routine to rule out myocardial ischemia, which is also radiation-free and cost effective (Figure 1) [55] . Recent head-to-head comparison with SPECT has further demonstrated that in populations with similar disease prevalence, it is also more cost effective [10] . Dobutamine-stress CMR with or without stress perfusion is also highly sensitive and superior to dobutamine stress-echocardiography [27,56] . However, as it bears higher procedural risk and the required expertise, it is less widely available. ●●Myocardial structure & tissue
characterization in detection of ischemic & nonischemic cardiomyopathies
CMR provides a unique noninvasive morphological characterization at tissue level. Relevant to the diagnosis of cardiomyopathies, edema and scar imaging have become the mainstay CMR applications of clinical routine. T2-weighted imaging is sensitive for detection of tissue edema based on the long T2 signal of
future science group
Individualized cardiovascular risk assessment by cardiovascular magnetic resonance
Review
Table 1. Clinical cardiovascular magnetic resonance applications that link biomarker of risk with predictive outcomes. Biomarker of risk
Application
LV volumes General population and global systolic Nonischemic function (EF) cardiomyopathies Ischemic cardiomyopathies RV volumes Pulmonary and systolic hypertension function (RVEF) Ischemic/
Studies that link biomarker with prognosis
HR/OR for all-cause mortality (95% CI); p
Individualized cardiovascular risk assessment by cardiovascular magnetic resonance
Rocio Hinojar1, Rene Botnar2, Juan Carlos Kaski3, Sanjay Prasad4, Eike Nagel1 & Valentina O Puntmann*,1
ABSTRACT: Cardiovascular magnetic resonance (CMR) is gaining clinical importance in preventive medicine. Evidence on diagnostic accuracy and prognostic value, in addition to the development of faster imaging, increased availability of equipment and imaging expertise have led to a wide-spread use of CMR in a growing number of clinical indications. The first part of this review summarizes the role of CMR biomarkers for risk assessment focusing on the patients groups that benefit from the use of CMR. In the second part, the future directions for CMR are discussed and their role in prevention of cardiovascular disease. Over the past decade, improved control of major risk factors and concerted efforts of primary and secondary prevention programs led to considerable reduction in morbidity and mortality due to cardiovascular (CV) disease in the western societies [1,2] . Yet, CV disease remains the leading cause of death and disability in developed countries despite substantial investment into public healthcare and the perceptibly improved CV health of the population as a whole. Current means of CV risk assessment rely on scoring systems based on traditional CV risk markers, such as age, gender, blood pressure, cholesterol and smoking history and target population as a whole. Nevertheless, a considerable number of subjects die suddenly or develop heart failure with no prior symptoms or identifiable CV risk factors [3–5] . Furthermore, detection and prevention of the subgroups at risk of due to inherited cardiomyopathies remain suboptimal despite the great advances in understanding of underlying pathophysiology and imaging technologies. Another example of a group at risk, are subjects suffering with accelerated CV disease at younger age due to comorbidities. Several potential plasma and imaging biomarkers have been proposed as adjunct to the CV riskscoring system, linking with the different phases in the evolution of disease, from risk factors to subclinical disease to overt disease [6,7] . These markers suffer with considerable limitations, because they are either associated with coronary disease indirectly (e.g., carotid intima media thickness) or only inform on the risk in patients with overt and expressed disease (e.g., maximal left ventricle; LV) wall thickness in hypertrophic cardiomyopathy; HCM). Many markers lack relationship with the underlying disease process or disease activity (e.g., calcium scoring) and evidence that the use of a biomarker leads to an improved outcome. Beyond the statin therapy, there is also a perceptible paucity of treatment options [8] especially when targeting risks early with the greatest opportunity for reversibility [9] . Most crucially, many of these markers suffer with significant limitations for the use in the young and asymptomatic subjects, including radiation, low diagnostic yield or reproducibility, and, as such, unlikely applicable for screening and exclusion of disease. The accurate identification of individuals at risk within the window of the greatest opportunity for targeted prevention is crucial
KEYWORDS
• cardiac magnetic
resonance imaging • cardiomyopathy • late gadolinium enhancement • noninvasive • prevention
Cardiovascular Imaging Department, Division of Imaging Sciences & Biomedical Engineering, King’s College London, London, UK Department of Medical Physics & Bioengineering, Division of Imaging Sciences & Biomedical Engineering, King’s College London, UK 3 Cardiac & Vascular Sciences, St George’s, University of London, UK 4 Royal Brompton & Harefield NHS Foundation Trust, UK *Author for correspondence: Tel.: +44 20 7188 7242; Fax: +44 20 7188 544; [email protected] 1 2
10.2217/FCA.13.102 © 2014 Future Medicine Ltd
Future Cardiol. (2014) 10(2), 273–289
part of
ISSN 1479-6678
273
Review Hinojar, Botnar, Kaski, Prasad, Nagel & Puntmann and remains a major challenge. Increasing knowledge regarding the relevant subgroups where conventional population-targeting strategies fail to identify vulnerable subjects in time, may eventually also lead to improved screening and CV-risk assessment of these vulnerable subgroups. The increasing role of CV magnetic resonance (CMR) is due to its unique ability to provide insight into function and structure with high diagnostic accuracy, noninvasively and free from ionizing-radiation. As such, it is well suited to inform on the presence of subclinical or overt disease in an asymptomatic population. CMR is a technique that is sufficiently accurate and versatile to understand the complex pathophysiology in various CV conditions. A full CMR examination consists of different protocols that can be performed in various combinations during a single session. Faster imaging and increased availability of equipment and imaging expertise, now allow for the use of this modality early in the diagnostic cascade. High cost is commonly offset by the reduced need for other imaging to reach the diagnosis [10] . The number of overall clinical indications is increasing, and, as a result the evolving role of CMR is gaining importance, by virtue of exclusion of disease, secondary prevention and its ability to guide management. In the first part of this review, we will focus on the role of CMR biomarkers for risk assessment paying particular attention to the patients groups that benefit from the use of CMR. In the second part, we will summarize the future directions where CMR may contribute in prevention of CV disease. Role of CMR applications in risk assessment of focused patient groups There is increasing evidence that several patients groups benefit from the use of CMR, either by delivering an accurate diagnosis, not achieved with other modalities, or by the ability to guide their clinical management [11] . In Table 1 we outline the current clinical CMR applications and predictive outcome evidence in particular patient subgroups. ●●Assessment of myocardial ischemia in
subjects with recognized high risk
Assessment of myocardial ischemia by myocardial perfusion imaging offers incremental prognostic value in the prediction of cardiac death, new acute events and in assessing the benefit of revascularization in patients with
274
Future Cardiol. (2014) 10(2)
suspected or previously known coronary artery disease (CAD), allowing for clinical decisionmaking [24–26] . Ischemia imaging for detection of subclinical disease may be considered in asymptomatic adults with diabetes, strong family history of CAD or when previous risk assessment test suggests high risk of CAD, such as coronary artery calcium score of ≥400 [48] . In a large series of 2664 asymptomatic subjects referred to a stress perfusion imaging with single photon emission computerized tomography (SPECT), those with 7.5% myocardial ischemia had a higher annual event rate (3.2%), which was consistent with high risk [49] . Khandaker et al. summarized data from 260 asymptomatic adults at moderate risk and without diagnosis of CAD with a follow-up of almost 10 years [50] . Abnormal SPECT myocardial perfusion imaging scans were present in 142 patients (55%): low risk in 67% of patients, intermediate risk in 20% and high risk in 13%. Survival was 60% for patients with high-risk scans, 79% with intermediate-risk scans and 83% with low-risk scans. Adenosine stress perfusion imaging by CMR is a widely used application and bears low procedural risk [51] . Recent evidence confirmed that it is noninferior to SPECT in a multicenter, and even superior to SPECT in a single center setting [52–54] . This evidence is important as it supports the view that it is the most accurate available noninvasive technique of current clinical routine to rule out myocardial ischemia, which is also radiation-free and cost effective (Figure 1) [55] . Recent head-to-head comparison with SPECT has further demonstrated that in populations with similar disease prevalence, it is also more cost effective [10] . Dobutamine-stress CMR with or without stress perfusion is also highly sensitive and superior to dobutamine stress-echocardiography [27,56] . However, as it bears higher procedural risk and the required expertise, it is less widely available. ●●Myocardial structure & tissue
characterization in detection of ischemic & nonischemic cardiomyopathies
CMR provides a unique noninvasive morphological characterization at tissue level. Relevant to the diagnosis of cardiomyopathies, edema and scar imaging have become the mainstay CMR applications of clinical routine. T2-weighted imaging is sensitive for detection of tissue edema based on the long T2 signal of
future science group
Individualized cardiovascular risk assessment by cardiovascular magnetic resonance
Review
Table 1. Clinical cardiovascular magnetic resonance applications that link biomarker of risk with predictive outcomes. Biomarker of risk
Application
LV volumes General population and global systolic Nonischemic function (EF) cardiomyopathies Ischemic cardiomyopathies RV volumes Pulmonary and systolic hypertension function (RVEF) Ischemic/
Studies that link biomarker with prognosis
HR/OR for all-cause mortality (95% CI); p
