Cardiovascular Imaging for Ischemic Heart Disease in Women: Time for a Paradigm Shift

Heart disease is the leading cause of death among men and women. Women have a unique phenotype of ischemic heart disease with less calcified lesions, more nonobstructive plaques, and a higher prevalence of microvascular disease compared with men, which may explain in part why current risk models to detect obstructive coronary artery disease (CAD) may not work as well in women. This paper summarizes the sex differences in the functional and anatomical assessment of CAD in women presenting with stable chest pain and provides an approach for using multimodality imaging for the evaluation of suspected ischemic heart disease in women in accordance to the recently published American Heart Association/American College of Cardiology guidelines for the evaluation and diagnosis of chest pain. A paradigm shift in the approach to imaging ischemic heart disease women is needed including updated risk models, a more profound understanding of CAD in women where nonobstructive disease is more prevalent, and algorithms focused on the evaluation of ischemia with nonobstructive CAD and myocardial infarction with nonobstructive CAD.     

Vulnerable plaque intervention: State of the art

Progressive atherosclerotic disease is responsible for many of the late adverse clinical events that detract from the high procedural and clinical success of percutaneous coronary intervention. Despite recent advances in catheter based technology for the treatment of obstructive coronary artery disease, the greater risk to the patient over time may in fact come from the significant rate of acute coronary events triggered by nonculprit and/or nonobstructive coronary artery lesions. These areas of vulnerability within the epicardial coronary tree have generated a great deal of interest surrounding the concepts of vulnerable plaque (VP), vulnerable blood and the vulnerable patient. This ‘state of the art’ review discusses the limitations of coronary angiography alone in providing risk assessment; reviews the underlying biological concepts of VP; discusses evolving noninvasive and invasive imaging technologies for the detection of VP; and finally provides a futuristic look at how the field of interventional cardiology may transcend the traditional angiogram and move toward a more comprehensive treatment approach that benefits the patients' overall coronary health. © 2008 Wiley‐Liss, Inc.     

Cholesterol management in women and the elderly

Women, like men, die mostly of coronary atherosclerosis, although atherosclerotic death in women occurs 5–10 years later than in men. Major risk factors predict coronary risk in women and men. What evidence is available suggests that women, similar to men, benefit from cholesterol lowering. Older individuals with symptomatic coronary disease but a relatively good prognosis should be offered the same benefits from secondary prevention as younger individuals.     

Echocardiography and Coronary CT Angiography Imaging of Variations in Coronary Anatomy and Coronary Abnormalities in Athletic Children: Detection of Coronary Abnormalities that Create a Risk for Sudden Death

In a recent publication, Maron et al. reported the causes of sudden death in athletes from data collected in the US National Registry of Sudden Death in Athletes at the Minneapolis Heart Institute Registry. It is not surprising that in this study, cardiovascular disease is reported as the most common cause of sudden death in athletes (56%). The most frequently encountered cardiac pathology was hypertrophic cardiomyopathy (36% of the population who died of cardiac disease). Coronary artery anomalies of wrong sinus origin were next in frequency (17%). Less common causes attributed to coronary pathology were Kawasaki disease, origin of the left coronary artery from the pulmonary artery, atherosclerotic coronary artery disease, and myocardial bridging of the left anterior descending artery. Echocardiographic imaging along with color and pulsed‐wave Doppler has been widely employed to visualize the anatomy and function of the heart and proves to be a valuable instrument in the identification of coronary artery abnormalities. Moreover, coronary CT angiography provides additional confirmatory information. This article will discuss the scope, importance, and implications of echocardiographic and coronary CT angiography imaging of the major coronary anomalies and abnormalities in young athletes who are at risk of sudden death and who otherwise have a structurally normal heart.     

雄激素与绝经后女性冠状动脉粥样硬化性心脏病相关研究进展

冠状动脉粥样硬化性心脏病发病率存在着明显的年龄差异,女性在绝经前发病率较低,绝经后迅速增加,几乎达到绝经前的4倍.这种现象提示绝经后女性冠状动脉粥样硬化性心脏病的发生可能与性激素水平的改变有关.近期关于绝经后雄激素水平改变与冠状动脉粥样硬化性心脏病的关系已成为研究的热点,但由于雄激素的确切作用机制较为复杂,所以其对冠状动脉粥样硬化性心脏病的作用仍未完全明确.现就目前雄激素与绝经后女性冠状动脉粥样硬化性心脏病关系的研究进展做一综述,并对雄激素能否用于绝经后女性冠状动脉粥样硬化性心脏病的治疗进行展望.     

Evaluation of Suspected Ischemic Heart Disease in Symptomatic Women

There is a wealth of evidence about the role of a variety of diagnostic testing modalities to define coronary artery disease (CAD) risk in women presenting for evaluation of suspected myocardial ischemia. The exercise electrocardiogram (ECG) is the core index procedure, which can define risk in women capable of performing maximal exercise. Stress imaging, using echocardiography or myocardial perfusion single-photon emission computed tomography/positron emission tomography, is useful for symptomatic women with an abnormal resting ECG or for those who are functionally disabled. For women with low-risk stress imaging findings, there is a very low risk of CAD events, usually < 1%. There is a gradient relationship between the extent and severity of inducible abnormalities and CAD event risk. Women at high risk are those defined as having moderate to severely abnormal wall motion or abnormal perfusion imaging findings. In addition to stress imaging, the evidence of the relationship between CAD extent and severity and prognosis has been clearly defined with coronary computed tomographic angiography. In women, prognosis for those with mild but nonobstructive CAD is higher when compared with those without any CAD. The current evidence base clearly supports that women presenting with chest pain can benefit from one of the commonly applied diagnostic testing modalities.     

Coronary artery imaging in the new millennium

Atherosclerotic disease and its thrombotic complications remain the leading causes of mortality and morbidity in Western society. In Australia, cardiovascular disease is responsible for one in every 2.4 (41%) deaths and is the leading single cause of mortality. The crucial final common process for the conversion of a non-occlusive, often clinically silent, atherosclerotic lesion to a potentially fatal condition is plaque disruption. The mortality associated with atherosclerotic disease relates to the acute coronary syndromes, including acute myocardial infarction, unstable angina pectoris and sudden cardiac death. There is substantial clinical, experimental and postmortem evidence demonstrating the role acute thrombosis upon a disrupted atherosclerotic plaque plays in the onset of acute coronary syndromes. Atherosclerotic plaque composition, rather than the stenotic severity, appears to be central in determining risk of both plaque rupture and subsequent thrombogenicity. In particular, a large lipid core and a thin fibrous cap render an atherosclerotic lesion susceptible or vulnerable to these complications. We are currently limited in our ability to accurately identify patients at risk for an acute coronary event. The armamentarium of diagnostic investigations, both non-invasive and invasive, currently clinically available is only able to provide us with data related to the stenotic severity of a coronary artery. The non-invasive testing includes stress-induced (exercise or pharmacological) ischaemic changes in electrical repolarisation, wall motion or myocardial radioactive-tracer uptake. The invasive test of coronary angiography, although the current 'gold standard' for the detection of coronary atherosclerotic disease, provides us with no data about the composition of the atherosclerotic lesion. However, the vast majority of acute coronary events involve a non-critically stenosed atherosclerotic lesion, and thus with currently available means of identification, these lesions would be undetected by stress testing/imaging techniques. Given the critical role that atherosclerotic lesion composition has been shown to play in the risk of both plaque rupture and subsequent thrombogenicity and, consequently, an acute coronary event, new detection techniques need to be investigated for the task of documenting atherosclerotic lesion composition. In the present review we will focus on the status of imaging modalities available for coronary artery imaging and how they may advance our understanding and management of patients with and at risk of coronary artery disease in the new millennium.     

Bilateral congenital coronary ostial obstruction: Exertional syncope in an otherwise healthy 8‐year‐old

Congenital stenosis/atresia of a coronary artery is an exquisitely rare anomaly (Congenit Heart Dis, 2, 2007, 347) with increased risk of sudden death. Bilateral coronary obstruction is even more unusual but has been reported in conjunction with aortic valve disease, syphilis, and Takayasu's arteritis. To the best of our knowledge, obstruction of both coronaries in a pediatric patient has only been reported once (Ann Thorac Surg, 55, 1993, 1564). We present a patient with an intramural, anomalous aortic origin of the right coronary artery from the contralateral sinus (AAORCA) with near atresia of the left main coronary ostium. The diagnosis was made by echocardiogram and confirmed by catheterization and magnetic resonance imaging.     

Spontaneous coronary artery dissection (SCAD): The underdiagnosed cardiac condition that plagues women

Coronary heart disease (CHD) continues to be understudied, underdiagnosed, and undertreated in women. Gender and age bias complicate the evaluation of women with acute coronary syndrome (ACS). As a result, conditions like spontaneous coronary artery dissection (SCAD) are often missed. SCAD is an infrequent yet important cause of myocardial infarction (MI) with a predilection for young to middle aged women. The condition is thought to be under-reported, likely a result of both low index of suspicion as well as an unfamiliarity with SCAD’s angiographic variants. Recently, the European Society of Cardiology (ESC) detailed an assessment pathway for patients with myocardial infarction with non-obstructive coronary arteries (MINOCA), a subset of which includes patients with SCAD. The pathway highlights the role of cardiac magnetic resonance (CMR) in addition to intracoronary imaging for increased diagnostic yield. Early and proper diagnosis is crucial in SCAD given the potential for sudden cardiac death, as well as the increased risk for future cardiac events including recurrent dissection. In addition, SCAD has frequently been associated with underlying connective tissue disease and/or arteriopathy, most commonly fibromuscular dysplasia (FMD), which requires careful screening. The lack of consensus on investigation or treatment highlights the need for increased awareness and further research to better understand this challenging entity.     

女性急性冠状动脉综合征患者危险因素及住院期间不良事件的分析

目的:探讨女性急性冠状动脉综合征(ACS)患者的危险因素及住院期间不良事件的分析。方法:分析急性冠状动脉事件全球注册(GRACE)研究中登记的明确诊断为ACS的住院313例女性患者的病例资料,与857例男性患者的危险因素及预后进行比较。结果:1.女性ACS患者合并糖尿病、高血压的比例大,2组比较差异有统计学意义(P<0.05)。2.女性患者并发症多,预后较男性差,2组比较差异有统计学意义(P<0.05)。3.应用Logistic回归分析影响女性ACS患者住院期间不良预后的危险因素为发病年龄、糖尿病及高血压,而男性住院期间不良预后的危险因素为发病年龄及体质量指数。结论:女性ACS患者较男性ACS患者危险因素多,预后差。     

Italian Chapter of the International Society of Cardiovascular Ultrasound expert consensus document on coronary computed tomography angiography: overview and new insights

Coronary computed tomography angiography is a noninvasive heart imaging test currently undergoing rapid development and advancement. The high resolution of the three‐dimensional pictures of the moving heart and great vessels is performed during a coronary computed tomography to identify coronary artery disease and classify patient risk for atherosclerotic cardiovascular disease. The technique provides useful information about the coronary tree and atherosclerotic plaques beyond simple luminal narrowing and plaque type defined by calcium content. This application will improve image‐guided prevention, medical therapy, and coronary interventions. The ability to interpret coronary computed tomography images is of utmost importance as we develop personalized medical care to enable therapeutic interventions stratified on the bases of plaque characteristics. This overview provides available data and expert's recommendations in the utilization of coronary computed tomography findings. We focus on the use of coronary computed tomography to detect coronary artery disease and stratify patients at risk, illustrating the implications of this test on patient management. We describe its diagnostic power in identifying patients at higher risk to develop acute coronary syndrome and its prognostic significance. Finally, we highlight the features of the vulnerable plaques imaged by coronary computed tomography angiography.     

An angiographic and intravascular ultrasound study of the left anterior descending coronary artery in takotsubo cardiomyopathy

The precise cause of takotsubo cardiomyopathy (TC) remains controversial. Plaque rupture with transient thrombotic occlusion of a transapical left anterior descending coronary artery (LAD) has been advanced as a potential mechanism. To explore this hypothesis, the investigators analyzed data from 11 patients prospectively enrolled in the Rhode Island Takotsubo Cardiomyopathy Registry who underwent coronary angiography and intravascular ultrasound evaluation of the LAD during their initial presentation. Despite the presence of nonobstructive coronary artery disease, no culprit lesion was identified in any patient. Similarly, the course of the LAD failed to account for the characteristic left ventricular apical ballooning seen in TC. In conclusion, an atherosclerotic coronary lesion in the LAD causing an aborted myocardial infarction may not be the primary underlying cause of TC, and nonobstructive coronary artery disease and TC may coexist without a direct causal association.     

Anatomic-ultrasound correlations for intraoperative open chest imaging of coronary artery atherosclerotic lesions in human beings

This study was performed to further validate a method for intraoperative ultrasound imaging of coronary arteries. Ultrasound images of coronary atherosclerotic lesions were compared with anatomic specimens of the coronary arteries obtained from open chest human subjects. The anatomic specimens were derived from four cardiac transplant recipients, accepted as candidates for transplantation because they had severe diffuse atherosclerotic disease, and one patient who died in the early postoperative period after a coronary artery bypass procedure. Twenty-six ultrasonically imaged atherosclerotic areas of the coronary arteries in these patients were compared with formalin-fixed and decalcified anatomic specimens. Specific ultrasound appearances for atherosclerotic lesions were observed, including 1) discrete (focal) stenosing fibrous/atheromatous plaques; 2) diffuse nonobstructive fibrous/atheromatous disease (detectable even in anatomically small vessels); 3) complete occlusion by fibrous/atheromatous lesions or organizing thrombus; and 4) "shadowing," an ultrasound pattern characteristic of significant calcification within atherosclerotic plaques. As part of this study, a new 12 MHz water path probe was evaluated for coronary artery scanning. The new probe allowed improved access to coronary arteries and increased detail of anatomic visualization. Both the performance of the new high resolution probe and the knowledge gained by the anatomic correlations obtained in this study should aid the development of intraoperative coronary artery scanning for surgical localization of atherosclerotic disease during coronary bypass surgery.     

Acute Coronary Syndromes: Differences in Men and Women

Purpose of Review

Increased awareness of cardiovascular disease in women has prompted studies to investigate gender-related disparities in acute coronary syndromes (ACSs). In this review, we discuss findings from current literature on the clinical presentation, pathophysiology, diagnosis, and management of ACS in women as compared to men.

Recent Findings

Emerging data show that cardiovascular disease (CVD) continues to be the leading cause of death in women and the annual mortality rate from CVD remains higher in women compared to men. Recent studies demonstrate sex-specific differences in patients presenting with ACS. Comorbidities, especially diabetes, are more common in young women compared with age-matched men who develop acute myocardial infarction (AMI). Women are more likely to have atypical symptoms and nonobstructive coronary disease on angiography. Women are less likely to receive guideline-based therapies. They have higher rates of peri-procedural complications with PCI and are less likely to be referred to cardiac rehabilitation.

Summary

Awareness of differences in the underlying pathophysiology of coronary disease in women compared to men may lead to improved gender-based diagnostic and treatment modalities. However, until more studies are performed, efforts should be directed toward improving delivery of current, gender-neutral guidelines in women just as in men.

     

Subclinical atherosclerosis in multiple vascular beds: an index of atherosclerotic burden evaluated in postmenopausal women

The Healthy Women Study has evaluated risk factor changes as women go through the menopause. In 274 women, measures of atherosclerosis in the coronary, aorta and carotid arteries were obtained at 8 years postmenopause using electron beam tomography and carotid ultrasound. The purpose of this study was to evaluate the association between baseline premenopausal risk factors and subclinical disease in various vascular beds and with an aggregate atherosclerosis index based on all subclinical measures. The prevalence of measurable disease for the coronaries, carotids and aorta was 45, 55 and 72%, respectively. Disease measures across these three locations were significantly correlated (P<0.001). Premenopausal LDL, triglycerides, blood pressure (BP) and smoking were associated with each measure of subclinical atherosclerosis, and were strikingly associated with the number of elevated disease measures. Among 126 women taking hormone replacement therapy (HRT), there was a strong positive association between systolic BP and subclinical atherosclerosis (P<0.001). No such relationship was seen among women not on HRT and this interaction was significant (P=0.048). An index of subclinical atherosclerosis rather than measurement at a single arterial site may be the best estimate of disease risk. Such a measure should be evaluated for its prognostic value along with individual measures of subclinical disease. Women with lower premenopausal risk factors did not develop high levels of subclinical atherosclerosis, suggesting that atherosclerosis is a preventable disease in women.     

Acute coronary syndromes in patients with angiographically normal or near normal (non-obstructive) coronary arteries

Patients with acute coronary syndrome (ACS) with normal or near-normal (non-obstructive) coronary arteries (ACSNNOCA) constitute an important, albeit heterogeneous, patient subset of younger patients, more commonly females, who may have lower risk of cardiovascular events compared to patients with obstructive coronary artery disease; however this risk remains substantial, hence needing further investigation to identify the underlying cause and devise a proper therapeutic strategy. A diagnostic algorithm starts during coronary angiography with some essential additional diagnostic steps, such as a left ventricular angiogram that may readily identify the underlying cause, e.g. Takotsubo syndrome, while intravascular imaging and vascular reactivity testing may need to be considered for assessing other diagnostic possibilities (e.g. occult atherosclerotic plaque rupture, spontaneous coronary dissection or microvascular dysfunction). Nevertheless, pursuing further investigation with less risky noninvasive tests, such as echocardiography and cardiac magnetic resonance imaging, may effectively identify the cause of ACSNNOCA (e.g. myocarditis or Takotsubo syndrome), and guide management.     

Advances in Coronary Computed Tomographic Angiographic Imaging of Atherosclerosis for Risk Stratification and Preventive Care

The diagnostic evaluation of coronary artery disease is undergoing a dramatic transformation with a new focus on atherosclerotic plaque. This review details the evidence needed for effective risk stratification and targeted preventive care based on recent advances in automated measurement of atherosclerosis from coronary computed tomography angiography (CTA). To date, research findings support that automated stenosis measurement is reasonably accurate, but evidence on variability by location, artery size, or image quality is unknown. The evidence for quantification of atherosclerotic plaque is unfolding, with strong concordance reported between coronary CTA and intravascular ultrasound measurement of total plaque volume (r >0.90). Statistical variance is higher for smaller plaque volumes. Limited data are available on how technical or patient-specific factors result in measurement variability by compositional subgroups. Coronary artery dimensions vary by age, sex, heart size, coronary dominance, and race and ethnicity. Accordingly, quantification programs excluding smaller arteries affect accuracy for women, patients with diabetes, and other patient subsets. Evidence is unfolding that quantification of atherosclerotic plaque is useful to enhance risk prediction, yet more evidence is required to define high-risk patients across varied populations and to determine whether such information is incremental to risk factors or currently used coronary computed tomography techniques (eg, coronary artery calcium scoring or visual assessment of plaque burden or stenosis). In summary, there is promise for the utility of coronary CTA quantification of atherosclerosis, especially if it can lead to targeted and more intensive cardiovascular prevention, notably for those patients with nonobstructive coronary artery disease and high-risk plaque features. The new quantification techniques available to imagers must not only provide sufficient added value to improve patient care, but also add minimal and reasonable cost to alleviate the financial burden on our patients and the health care system.     

Sex differences in nonobstructive coronary artery disease: Recent insights and substantial knowledge gaps

The existence of sex differences in the epidemiology, presentation, diagnosis, and management of coronary artery disease (CAD) has been a subject of growing inquiry for the past several decades. The prevailing paradigm is that the prevalence of anatomically obstructive disease of the epicardial coronary arteries is less common in women than similarly aged men, while nonobstructive and microvascular ischemic disease is more prevalent in women. Although both “patterns” of coronary atherosclerosis are associated with angina and cardiovascular events, the dominant diagnostic and therapeutic tools used in cardiology have focused on the male-predominant pattern of anatomically obstructive epicardial CAD. This has raised justified concerns about the under-diagnosis and under-treatment of symptomatic women with nonobstructive CAD. However, as recent research has begun to highlight the importance of nonobstructive CAD and coronary physiology in men as well as women, adjustments to this paradigm and greater attention to nonobstructive CAD are necessary. The present article seeks to review key insights as well as substantial knowledge gaps regarding sex differences and nonobstructive CAD.     

Myocardial Infarction with Nonobstructive Coronary Arteries: The Importance of Achieving Secondary Prevention Targets

Background

Approximately 5% to 10% of all patients with myocardial infarction have nonobstructive coronary arteries. Studies investigating the importance of follow-up and achievement of conventional secondary prevention targets in these patients are lacking.

他汀类药物与冠状动脉钙化关系的研究进展

冠状动脉钙化在冠状动脉粥样硬化、糖尿病血管病变和慢性肾脏病等多种疾病中普遍存在,他汀类药物是冠状动脉粥样硬化性心脏病等血脂代谢紊乱患者的常用药物。既往研究显示,他汀类药物可能具有抑制冠状动脉钙化的作用,而新近研究则提出相反意见。鉴于目前他汀类药物与冠状动脉钙化关系存在一定争议,故本文就冠状动脉钙化发生机制,他汀类药物与冠状动脉钙化关系及两者关系矛盾性结论成因作一分析。