Fetal echocardiography in pregnancies of women with congenital heart disease--clinical utility and limitations

Women with important cyanotic or uncyanotic, operated or unoperated congenital heart disease (CHD) have been shown to carry an inherent risk during pregnancy for themselves and for their fetus. Obstetrical and fetal echocardiography has recently been upgraded by new technical developments in ultrasound machines. These improvements have increased the detection rate of congenital malformations and cardiac anomalies which ranged in the past between 4 and 60% for significant anomalies. Obesity or an unfavourable position of the fetus may, however, obscure the imaging quality and cause limitations to visualise the fetal heart from different angles and thus prevent the detection of anomalies. In addition, several cardiac anomalies develop throughout pregnancy and may not yet be present at an early date of screening. While the risk for a congenital cardiac malformation (CCM) in a normal population is 0.8-1%, the recurrence rate for CCM increases to 2 to 3% when a previous child has been affected but will become significantly higher when genetically determined anomalies have affected a family member or when the pregnant woman (5.8%) has CHD. The aim of fetal screening in women with CCM is to ascertain normal intrauterine growth, to exclude fetal CHD and/or to ascertain a malformation or arrhythmia which has been suspected during an obstetrical screening. The acquired detailed echocardiographic knowledge of the malformation or arrhythmia allows the explanation of a CCM to the future parents, to present therapeutic options during pregnancy or after birth and to plan delivery in a tertiary center that provides early cardiovascular and/or catheter interventions and disposes of intensive care facilities for affected newborns. Under certain conditions, termination can be discussed in early pregnancy. Very recent publications have shown how important a prenatal diagnosis can become in a new-born with transposition of the great arteries and a very restrictive foramen ovale (Circulation 1999). Therapeutic measures in the fetus have been attempted with very limited success so far; successful life saving treatment does, however, exist for fetal arrhythmias. In conclusion: Fetal echocardiography has become an important analytical tool in high-risk pregnancies, especially when parents are affected by a CCM. The examination is safe and can be performed with a high predictive and sensitivity rate.     

彩色多普勒超声心动图诊断胎儿先天性心脏病的临床价值

目的:探讨彩色多普勒超声技术在诊断胎儿心脏异常中的应用价值。方法:对临床高度疑有胎儿先天性心脏病(CHD)的孕妇2600例行胎儿超声心动图检查。结果:检出胎儿心脏异常20例,检出率0.77%。其中CHD17例(0.65%),心脏肿瘤1例(0.038%),三尖瓣中量反流1例(0.038%),心包少量积液1例(0.038%)。经引产尸体解剖证实11例,产后彩色多普勒超声检查证实7例,失访2例。结论:胎儿超声心动图检查对产前检出胎儿心脏病具有重要的临床价值;胎儿心胸或心腔比率异常及胎儿心脏四腔观异常是胎儿CHD的最主要声像图表现。     

Fetal echocardiography and clinical genetics--a close correlation

Improving techniques in fetal echocardiography have important implications in the field of clinical genetics. 1) Fetal echocardiography in pregnancies with families with increased recurrence risks for congenital heart disease (CHD): In 473 pregnancies with increased recurrence risks for CHD second-trimester fetal echocardiography was performed. In 11 cases (2.3%) cardiac malformations were present that could be diagnosed in five cases prenatally (hypoplastic left heart, complete atrioventricular canal defect with hypoplastic left ventricle, preductal coarctation of aorta, tetralogy of Fallot, complete atrioventricular canal defect). In six cases the prenatal diagnosis could not be performed (total anomalous pulmonary venous connection [one case], secundum atrial septal defect [two cases], ventricular septal defect [three cases]). The recurrence risk in families with one previously affected child was 1.4% (5/364), and 17.6% (3/17) in families with two previously affected children. In two out of 44 cases with one affected parent a CHD could be diagnosed, in both cases one previous child was already affected. 2) Congenital heart defect as a common symptom in malformation syndromes: CHD is common as a symptom in malformation syndromes. The demonstration of a fetal CHD can lead to diagnosis of a complex malformation syndrome and it is integral in prenatal diagnosis in cases with increased recurrence risks for a complex malformation syndrome. The sonographic diagnosis of a CHD may signal associated chromosomal disorders. Between January 1986 and December 1988 in 433 cases with prenatally diagnosed congenital malformation and/or severe fetal growth retardation a prenatal chromosome analysis was performed. Within this group 77 fetuses demonstrated a CHD and 28 (36%) out of these revealed a chromosomal disorder. The genetic basis of CHD, the most common complex syndromes with CHD, and the principles of genetic counseling in families with CHD are summarized.     

Maternal cardiovascular impairment in pregnancies complicated by severe fetal growth restriction

Fetal growth restriction and preeclampsia are both conditions of placental etiology and associated to increased risk for the long-term development of cardiovascular disease in the mother. At presentation, preeclampsia is associated with maternal global diastolic dysfunction, which is determined, at least in part, by increased afterload and myocardial stiffness. The aim of this study is to test the hypothesis that women with normotensive fetal growth-restricted pregnancies also exhibit global diastolic dysfunction. This was a prospective case-control study conducted over a 3-year period involving 29 preterm fetal growth-restricted pregnancies, 25 preeclamptic with fetal growth restriction pregnancies, and 58 matched control pregnancies. Women were assessed by conventional echocardiography and tissue Doppler imaging at diagnosis of the complication and followed-up at 12 weeks postpartum. Fetal growth-restricted pregnancies are characterized by a lower cardiac index and higher total vascular resistance index than expected for gestation. Compared with controls, fetal growth-restricted pregnancy was associated with significantly increased prevalence (P<0.001) of asymptomatic left ventricular diastolic dysfunction (28% versus 4%) and widespread impaired myocardial relaxation (59% versus 21%). Unlike preeclampsia, cardiac geometry and intrinsic myocardial contractility were preserved in fetal growth-restricted pregnancy. Fetal growth-restricted pregnancies are characterized by a low output, high resistance circulatory state, as well as a higher prevalence of asymptomatic global diastolic dysfunction and poor cardiac reserve. These findings may explain the increased long-term cardiovascular risk in these women who have had fetal growth-restricted pregnancies. Further studies are needed to clarify the postnatal natural history of cardiac dysfunction in these women.     

Fetal Brain Development in Congenital Heart Disease

Neurodevelopmental impairments are the most common extracardiac morbidities among patients with complex congenital heart disease (CHD) across the lifespan. Robust clinical research in this area has revealed several cardiac, medical, and social factors that can contribute to neurodevelopmental outcome in the context of CHD. Studies using brain magnetic resonance imaging (MRI) have been instrumental in identifying quantitative and qualitative difference in brain structure and maturation in this patient population. Full-term newborns with complex CHD are known to have abnormal microstructural and metabolic brain development with patterns similar to those seen in premature infants at approximately 34 to 36 weeks’ gestation. With the advent of fetal brain MRI, these brain abnormalities are now documented as they begin in utero, as early as the third trimester. Importantly, disturbed brain development in utero is now known to be independently associated with neurodevelopmental outcome in early childhood, making the prenatal period an important timeframe for potential interventions. Advances in fetal brain MRI provide a robust imaging tool to use in future neuroprotective clinical trials. The causes of abnormal fetal brain development are multifactorial and include cardiovascular physiology, genetic abnormalities, placental impairment, and other environmental and social factors. This review provides an overview of current knowledge of brain development in the context of CHD, common prenatal imaging tools to evaluate the developing fetal brain in CHD, and known risk factors contributing to brain immaturity.     

Introduction: From fetal echocardiography to fetal cardiology: A journey of over half a century

In this Special Issue of the Journal, 8 review articles that represent the new developments and applications of fetal echocardiography and fetal cardiology for diagnosis, prognosis, and treatment of fetal cardiovascular disease are included. The goal was to provide an updated review of the evidence for the current and emerging use of fetal echocardiography and cardiac magnetic resonance, improved diagnosis of challenging congenital heart disease, new tools for evaluation of fetal systolic and diastolic function, better prognosis and risk stratification of newborns with congenital heart diseases, and new and promising therapies for fetuses with cardiovascular disease.     

A new efficient tool for non-invasive diagnosis of fetomaternal platelet antigen incompatibility

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the consequence of platelet destruction by maternal alloantibodies against fetal human platelet antigens (HPA). This may result in intracranial haemorrhages (ICH) or even fetal death. Currently, fetal HPA genotyping is performed using invasive procedures. Here, we carried out a proof-of-concept study for non-invasive prenatal diagnosis of fetal platelet genotyping in four HPA systems (HPA-1, -3, -5 and-15) by droplet digital polymerase chain reaction (ddPCR) using cell-free DNA extracts from the plasma of 47 pregnant women with suspected, or history of, FNAIT. Results showed that 74% (35/47) of pregnant women presented incompatibility in at least one HPA system, and 38% (18/47) of cases presented HPA-1 incompatibility, including nine women with multiple incompatibilities. ICH occurred in one case of profound fetal thrombocytopenia with HPA-15 incompatibility, confirming the need for non-invasive prenatal genotyping in systems other than HPA-1. Fetal HPA genotypes predicted by ddPCR were confirmed in all FNAIT cases after amniocentesis or delivery. Fetal HPA genotyping on maternal plasma based on ddPCR is a fast, safe and reliable non-invasive method. This technique will be useful for the early identification of pregnancies at high risk of FNAIT requiring antenatal management to minimize the risk of fetal/neonatal haemorrhage.     

产前彩色多普勒超声检查在胎儿先天性心脏病诊断中的应用

目的 探讨胎儿先天性心脏病（先心病）的有效诊断方法及依据。方法 随机选择孕24～42周的孕妇12000例,用彩色多普勒超声（彩超）及胎儿心电记录技术进行胎儿心脏四腔观、胎心率（律）及胎心各腔血流检测。对由此诊断为先心病的胎儿进行随访,其中引产者进行尸解,分娩出生者进行彩超复查。结果 产前共检出胎儿先心病69例,其中28例经引产后尸解证实,41例出生后经彩超复查证实。69例均见胎心异常血流,其中伴胎心四腔观异常57例,无四腔观异常12例。检出心律失常胎儿136例,其中确诊先心病5例。彩超检查无异常发现的胎儿中,产后发现先心病5例。结论 产前彩超检查是诊断胎儿先心病的有效方法,胎儿心脏四腔观是诊断胎儿先心病的重要依据,配合胎儿心腔血流及心律的检测,更有利于发现胎儿先心病。     

Identification of fetal gender in maternal blood is a helpful tool in the prenatal diagnosis of haemophilia

Fetal DNA identification in maternal circulation has provided a new approach for non-invasive prenatal diagnosis. However, fetal DNA can persist in maternal blood long after the delivery, severely hampering this possibility. We addressed the issue of fetal DNA persistence in maternal blood. Thus, we investigated cell-free fetal DNA as a reliable approach in prenatal diagnosis of haemophilia. Forty non-pregnant women, who had had at least a male fetus, 29 control pregnant women, and 14 pregnant women, carriers of hemophilia A or B. The assessment of Y-chromosomal sequences was performed by analysing SRY and amelogenin genes using PCR-based techniques. A protocol consisting of double centrifugation at full speed followed by plasma filtration hampered the detection of Y chromosome-specific sequence in non-pregnant women. In 29 control pregnant women, blinded determination of fetal sex confirmed the specificity and sensitivity of the method applied. In 14 pregnant carriers of hemophilia, the investigation revealed a male fetus in nine pregnancies. Excluding the three cases in which a spontaneous miscarriage occurred, the sensitivity and specificity of fetal sex prediction by SRY and amelogenin gene analyses were both 100% as compared with the invasive approach and the fetal sex outcome at birth (six males and five females). Because of its high accuracy in prediction, fetal gender determination with cell-free fetal DNA in maternal plasma may be a useful tool in prenatal diagnosis of haemophilia allowing for the avoidance of invasive procedures for female fetuses.     

Fetal arrhythmias: Surveillance and management

Fetal arrhythmias warrant sophisticated surveillance and management, especially for the high-risk pregnancies. Clinically, fetal arrhythmias can be categorized into 3 types: premature contractions, tachyarrhythmias, and bradyarrhythmias. Fetal arrhythmias include electrocardiography, cardiotocography, echocardiography and magnetocardiography. Oxygen saturation monitoring can be an effective way of fetal surveillance for congenital complete AV block or SVT during labor. Genetic surveillance of fetal arrhythmias may facilitate the understanding of the mechanisms of the arrhythmias and provide theoretical basis for diagnosis and treatment. For fetal benign arrhythmias, usually no treatment but a close follow-up is need, while persistant fetal arrhythmias with congestive heart dysfunction or hydrops fetalis, intrauterine or postnatal treatments are required. The prognoses of fetal arrhythmias depend on the type and severity of fetal arrhythmias and the associated fetal conditions. Responses of fetal arrhythmias to individual treatments and clinical schemes are heterogeneous, and the prognoses are poor particularly under such circumstances.     

先天性心脏病筛查治疗和监测网络平台建立与规范化管理的研究

目的:探索北京市先天性心脏病(先心病)筛查、治疗及监测网络模式,以提高先心病管理水平,降低北京市复杂先心病出生率及死亡率。方法:2007年1月至2009年6月,对北京6家二级妇幼保健院医生进行先心病知识、胎儿超声心动图技术培训。前瞻性研究胎儿先心病产前筛查,复杂先心病终止妊娠后尸检与诊断符合率,活产新生儿72h内超声心动图结果。同期开发网络直报及监测系统。结果:1.入组孕妇17721例,平均孕周23.2(16～28周)。产前筛查出先心病121例(6.83‰),其中复杂先心病100例,97例引产,59例尸检诊断符合率96.7%;2.先心病产前筛查技术培训使基层医生筛查水平整体提高。3.成功开发并试用"先心病母婴数据采集系统"网络直报。结论:建立北京市先心病筛查、治疗及监测网络,对降低复杂先心病的出生率及死亡率,规范先心病治疗及随访的科学化管理有积极临床意义和社会价值。     

产前重复超声检查在发现胎儿复杂型先天性心脏病中的作用

目的探讨产前重复超声检查在发现胎儿复杂型先天性心脏病(先心病)中的作用。方法回顾性分析5例孕中期初次超声检查胎儿心脏正常而孕晚期超声复查发现复杂型先心病的病例资料,分析初次检查漏诊原因和重复超声复查的作用。结果初查发现胎儿复杂型先心病17例,初查胎儿心脏正常而超声复查发现复杂型先心病5例,两次超声检查共发现胎儿复杂型先心病22例,占我院产检病例的0.6%。结论产前诊断胎儿先心病受多因素影响,有一定的漏诊率,要提高产前诊断的准确率,需同时重视孕中期的初次超声检查及孕晚期的重复超声检查,多次的超声检查可使先心病在产前的检出率达到最大。     

Prenatal ultrasound diagnosis in Thailand

Ultrasound technology has been extensively employed in obstetric and gynecologic practice for several decades. It has been used not only in gestational age estimation, placental location, amniotic fluid assessment but also in antenatal diagnosis of fetal abnormalities of various systems. The incidence of Congenital Heart Disease (CHD) is currently estimated to be 8 to 9 out of every 1,000 live births. Congenital heart disease is thought to be a multifactorial disorder in over 90% of the cases. Pioneer studies on the ultrasound investigation of the heart were reported in the early 1970s. Since the introduction of high resolution real-time ultrasound in the late 1970s, reports on ultrasound assessment of fetal cardiac anatomy and function have been appearing with increasing frequency in both the obstetric and cardiologic literature. At present, fetal echocardiography is a well established technique for the prenatal diagnosis of CHD. However, the distribution of the technique is still limited as it requires both a very experienced operator and meticulous scanning. Screening the entire obstetric population does not appear possible at present. Therefore fetal echocardiography is as necessarily directed toward selected pregnancies carrying a higher-than-normal risk of fetal cardiac anomalies. The progressive developments in cardiac ultrasound during the past two decades have substantially altered the practice of perinatologists, obstetricians and cardiologists. Total cardiac ultrasound studies are now becoming the primary armamentarium in the diagnosis of fetal congenital heart diseases. Since a 92% sensitivity of 4-chamber view in screening fetal heart diseases was first reported in 1987, 4-chamber view has been widely recommended for routine use in fetal sonographic examinations. Recent studies have demonstrated somewhat variable results and have suggested incorporation of the out flow should thoroughly understand the advantages and limitations of fetal cardiac scanning especially the 4-chamber view in order that the appropriate information and management plan can be offered to the patients. Fetal cardiac scanning is well recognized as one of the most tedious scanning of all fetal organ systems. With a tremendous advancement in ultrasound resolution including color imaging capacity several kinds of fetal cardiac anomalies could be diagnosed antenatally which inevitably allows more proper management plan for couples engaged in these.     

胎儿超声心动图产前诊断先天性心脏病准确性评价

目的 评价胎儿超声心动图产前诊断先天性心脏病的准确性.方法 回顾2001年1月至2007年12月诊断为先天性心脏病胎儿的超声心动图资料,将产前诊断与胎儿心脏病理诊断或出生后新生儿超声心动图诊断结果进行比较.结果 研究期间共诊断胎儿先天性心脏病113例,初次检查时平均孕周为26.8周.79例(70%)行胎儿心脏病理检查或新生儿超声心动图检查确诊,其中68例产前诊断与产后诊断相符,产前诊断准确率86%.锥干畸形诊断准确率77%(24/31),间隔缺损96%(26/27),瓣膜畸形90%(9/10),单心室畸形83%(5/6).产前假阳性诊断4例,阳性预测值95%(75/79).结论 胎儿超声心动图检查是先天性心脏病产前诊断的有效方法,能够对各种常见类型的先天性心脏病进行准确诊断.完整的分段诊断是降低漏诊及误诊率,提高诊断准确性的关键.     

Blood smears and prenatal diagnosis

Fetal blood sampling is a widely used technique for both diagnostic and therapeutic purposes. However, despite the fact that examination of blood smears is a critical step in the study of a large variety of disorders, the place of fetal blood smears analysis has been overshadowed by more sophisticated diagnostic tools such as those offered by molecular biology. Nevertheless, as highlighted by four cases presented in this paper, the role of fetal blood smears examination must be re-emphasized. The recognition of abnormal cytological findings limits the number of possible aetiologies, thus elegantly contributing to the diagnosis without multiplying unnecessary test techniques.     

“3+1”复合超声切面培训在先天性心脏病产前筛查中的作用

目的:评价"3+1"复合超声切面(标准胎儿四腔心切面,左、右心室流出道切面+三血管切面)培训在先心病产前筛查中的作用。方法:自2006年7月始对北京地区6家妇幼保健院超声医生采取集中授课,观摩见习,指导实践等多种形式进行胎儿心脏超声"3+1"复合切面培训,并以2007年1月至2009年6月入组的17721例孕妇为研究对象,应用"3+1"复合超声切面行先天性心脏病(先心病)产前筛查,所有筛查过程均录像并保存电子图像,以生后超声或尸检结果验证产前超声结果并评价"3+1"切面培训成果。结果:17721例中,诊断胎儿先心病121例,其中复杂胎儿先心病100例,产前及生后超声心动图检查共确诊复杂先心病109例,产前漏诊10例,误诊1例,复杂先心病的产前诊断率为91%(99/109)。简单先心病病种以室间隔缺损(室缺)为主,存在假阳性和假阴性结果。小型膜周部室缺和肌部室缺漏诊较多。结论:"3+1"复合超声切面的培训和应用有效提高了复杂先心病产前诊断率,对降低复杂先心病出生率,进而降低新生儿及婴幼儿病死率意义重要。     

Analysis of fetal blood using capillary electrophoresis system: a simple method for prenatal diagnosis of severe thalassemia diseases

Introduction: Prenatal diagnosis of severe α‐ and β‐thalasssemia diseases is usually performed by DNA analysis. Objective: To establish a simple method, we have evaluated the reliability of prenatal diagnosis by fetal blood analysis using automated capillary electrophoresis system. Methods: Forty‐seven fetal blood specimens collected by cordocentesis at 18–28 wk of gestation were analyzed by the capillary electrophoresis system (Sebia). Fetal DNA was analyzed for respective thalassemia alleles by PCR. Results: Among 47 fetuses, 20 were at risk for the Hb Bart’s hydrops fetalis. DNA analysis identified four cases of homozygous α°‐thalassemia (SEA type). Hb analysis by the capillary electrophoresis demonstrated a major peak of Hb Bart’s (78.4–81.3%), Hb H (0.8–1.4%) and minor peaks of presumably embryonic Hbs. No Hb F and Hb A was observed. The level of Hb Bart’s was found to be 3.4–5.8% in unaffected heterozygote whereas normal fetus had no Hb Bart’s. Among the remaining 27 fetuses at risk for Hb E‐β‐thalassemia, DNA analysis identified 12 affected fetuses. Hb analysis showed Hb F (94.9–98.9%) and Hb E (1.1–1.8%) without Hb A in all cases. The levels of Hb A were found to be (4.3–7.2%), (1.0–5.5%) and (2.1–3.9%) in normal, heterozygous Hb E and heterozygous β‐thalassemia fetuses, respectively. Affected and unaffected fetuses could be easily distinguished. Conclusion: Capillary electrophoresis system is a simple and automated procedure for accurate prenatal diagnosis of severe thalassemia diseases which could readily be performed in routine setting.     

Familial recurrence of congenital heart disease in a prospective series of mothers referred for fetal echocardiography

Fetal echocardiography can ascertain, at an early stage in pregnancy, recurrences of congenital heart disease (CHD) in mothers with a family history of CHD. In 1,021 mothers referred for this reason, 20 recurrences were found; 17 occurred when there had been 1 previously affected child, and 3 when there had been 2 previously affected children. No recurrences were found in the 41 cases in which a parent had CHD. The overall recurrence rate was 1 in 52 with a previously affected child and 1 in 10 with 2 previously affected children. However, certain forms of CHD recurred much more frequently than others. Aortic valve atresia was associated with a recurrence rate of 1 in 28, coarctation of the aorta at a rate of 1 in 15, complex CHD at a rate of 1 in 11 and truncus arteriosus at 1 in 13. These findings are inconsistent with previous family studies; this may be due to more complete ascertainment, particularly of major lesions, possibly overlooked by postnatal family studies because of fetal loss. Alternatively, the availability of prenatal diagnosis may be producing an increase in family size after major CHD. The results support current doubts on the polygenic theory of inheritance for all forms of CHD.     

Percutaneous Closure of Aortic and Mitral Paravalvular Leaks—Diagnostic and Therapeutic Considerations

Purpose of review

Prenatal diagnosis of congenital heart disease (CHD) is continuously evolving with each passing decade. Early efforts in fetal cardiology focused on identifying CHD in mid-gestation and understanding of fetal circulation in pathologic conditions. Improving prenatal detection rates for CHD remains an ongoing challenge and increasingly the field of fetal cardiology is moving to not only diagnosing CHD prenatally but also assessing the impact of prenatal diagnosis of CHD outcomes. Future directions include earlier diagnosis of fetal CHD, improved diagnostic rates, widespread sonographer education, and a better understanding of antenatal factors that impact outcomes. Our goal in this review is to describe the past, present, and future of prenatal diagnosis of CHD.

Recent findings

There has been a steady improvement in the prenatal diagnosis rate for CHD; however, there remains a significant variation between countries and within the USA. Prenatal diagnosis of CHD allows for counseling and delivery planning in those fetuses with critical CHD, thereby providing parents with resources and important tools while dealing with a challenging situation of carrying a child with heart disease and helping them with important decisions for their family and their future. There are several specific conditions which continue to pose a challenge from a diagnostic standpoint as they may appear mild at the time of initial diagnosis and may be missed but progress through the pregnancy and lead to significant CHD in the neonatal period.

Summary

In summary, continued efforts aimed at collaborative research and education are needed in order to be able to improve CHD detection rates. We need to cautiously assess lesions that appear minor in mid-gestation but have the potential to progress in late gestation. Earlier detection of CHD by means of a transvaginal or a first-trimester fetal echocardiogram may further help families with delivery planning and decision-making.

     

Poor glycemic control predicts coronary heart disease events in patients with type 1 diabetes without nephropathy

Patients with type 1 diabetes mellitus, especially those with nephropathy, are at increased risk for coronary heart disease (CHD). However, information on the predictive value of cardiovascular risk factors and the degree of hyperglycemia with respect to CHD events in patients with type 1 diabetes without nephropathy is still incomplete. Therefore, we performed a prospective study on risk factors for CHD in patients with type 1 diabetes free of clinical nephropathy. At baseline examination, cardiovascular risk factor levels of CHD were determined in 177 patients with type 1 diabetes (87 men and 90 women), age 45 to 64 years at baseline and >/=30 years at the time of diagnosis of diabetes. These patients were followed up to 7 years with respect to CHD events. Altogether, 20 patients with type 1 diabetes (13 men [7.3%] and 7 women [3.9%]) died of CHD and 28 patients with type 1 diabetes (17 men [9.6%] and 11 women [6.2%]) had a serious CHD event (death from CHD or nonfatal myocardial infarction). In multivariate Cox regression analysis, a previous history of myocardial infarction (hazard ratio [HR] and its 95% confidence interval, 8.0 [3.1 to 21.0], P<0.001), high glycohemoglobin A1 (>10.4%, the highest tertile, HR 5.4 [1.4 to 20.4], P=0.013), and the duration of diabetes (>16 years, the highest tertile, HR 4.2 [1.3 to 12.9], P=0.013) were the only variables associated with CHD death even after adjustment for other cardiovascular risk factors. These variables also predicted the incidence of all CHD events. Our results indicate that poor metabolic control is a strong predictor of CHD events in patients with late-onset type 1 diabetes without nephropathy, independently of other cardiovascular risk factors.