Candice K. Silversides

ESC Guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC)

Table 1. Classes of recommendation Table 2. Levels of evidence Table 3. Estimated fetal and maternal effective doses for various diagnostic and interventional radiology procedures Table 4. Predictors of maternal cardiovascular events and risk score from the CARPREG study Table 5. Predictors of maternal cardiovascular events identified in congential heart diseases in the ZAHARA and Khairy study Table 6. Modified WHO classification of maternal cardiovascular risk: principles Table 7. Modified WHO classification of maternal cardiovascular risk: application Table 8. Maternal predictors of neonatal events in women with heart disease Table 9. General recommendations Table 10. Recommendations for the management of congenital heart disease Table 11. Recommendations for the management of aortic disease Table 12. Recommendations for the management of valvular heart disease Table 13. Recommendations for the management of coronary artery disease Table 14. Recommendations for the management of cardiomyopathies and heart failure Table 15. Recommendations for the management of arrhythmias Table 16. Recommendations for the management of hypertension Table 17. Check list for risk factors for venous thrombo-embolism Table 18. Prevalence of congenital thrombophilia and the associated risk of venous thrombo-embolism during pregnancy Table 19. Risk groups according to risk factors: definition and preventive measures Table 20. Recommendations for the prevention and management of venous thrombo-embolism in pregnancy and puerperium Table 21. Recommendations for drug use ABPM : ambulatory blood pressure monitoring ACC : American College of Cardiology ACE : angiotensin-converting enzyme ACS : acute coronary syndrome AF : atrial fibrillation AHA : American Heart Association aPTT : activated partial thromboplastin time ARB : angiotensin receptor blocker AS : aortic stenosis ASD : atrial septal defect AV : atrioventricular AVSD : atrioventricular septal defect BMI : body mass index BNP : B-type natriuretic peptide BP : blood pressure CDC : Centers for Disease Control CHADS : congestive heart failure, hypertension, age (>75 years), diabetes, stroke CI : confidence interval CO : cardiac output CoA : coarction of the aorta CT : computed tomography CVD : cardiovascular disease DBP : diastolic blood pressure DCM : dilated cardiomyopathy DVT : deep venous thrombosis ECG : electrocardiogram EF : ejection fraction ESC : European Society of Cardiology ESH : European Society of Hypertension ESICM : European Society of Intensive Care Medicine FDA : Food and Drug Administration HCM : hypertrophic cardiomyopathy ICD : implantable cardioverter-defibrillator INR : international normalized ratio i.v. : intravenous LMWH : low molecular weight heparin LV : left ventricular LVEF : left ventricular ejection fraction LVOTO : left ventricular outflow tract obstruction MRI : magnetic resonance imaging MS : mitral stenosis NT-proBNP : N-terminal pro B-type natriuretic peptide NYHA : New York Heart Association OAC : oral anticoagulant PAH : pulmonary arterial hypertension PAP : pulmonary artery pressure PCI : percutaneous coronary intervention PPCM : peripartum cardiomyopathy PS : pulmonary valve stenosis RV : right ventricular SBP : systolic blood pressure SVT : supraventricular tachycardia TGA : complete transposition of the great arteries TR : tricuspid regurgitation UFH : unfractionated heparin VSD : ventricular septal defect VT : ventricular tachycardia VTE : venous thrombo-embolism WHO : World Health Organization Guidelines summarize and evaluate all available evidence, at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes but are complements for textbooks and cover the European Society of Cardiology (ESC) Core Curriculum topics. Guidelines and recommendations should help the …

Bicuspid Aortic Valve Disease

Bicuspid aortic valve (BAV) disease is the most common congenital cardiac defect. While the BAV can be found in isolation, it is often associated with other congenital cardiac lesions. The most frequent associated finding is dilation of the proximal ascending aorta secondary to abnormalities of the aortic media. Changes in the aortic media are present independent of whether the valve is functionally normal, stenotic, or incompetent. Although symptoms often manifest in adulthood, there is a wide spectrum of presentations ranging from severe disease detected in utero to asymptomatic disease in old age. Complications can include aortic valve stenosis or incompetence, endocarditis, aortic aneurysm formation, and aortic dissection. Despite the potential complications, 2 large contemporary series have demonstrated that life expectancy in adults with BAV disease is not shortened when compared with the general population. Because BAV is a disease of both the valve and the aorta, surgical decision making is more complicated, and many undergoing aortic valve replacement will also need aortic root surgery. With or without surgery, patients with BAV require continued surveillance. Recent studies have improved our understanding of the genetics, the pathobiology, and the clinical course of the disease, but questions are still unanswered. In the future, medical treatment strategies and timing of interventions will likely be refined. This review summarizes our current understanding of the pathology, genetics, and clinical aspects of BAV disease with a focus on BAV disease in adulthood.

Left ventricular dysfunction is a risk factor for sudden cardiac death in adults late after repair of tetralogy of fallot

OBJECTIVES The purpose of this study was to determine if left ventricular (LV) systolic dysfunction was also a predictor of sudden cardiac death (SCD) in adults late after repair of tetralogy of Fallot (TOF). BACKGROUND Previous studies looking at risk factors for SCD in adults with repair of TOF have focused on the right ventricle (RV). METHODS A retrospective chart review of patients assessed at the Toronto Congenital Cardiac Centre for Adults was performed. Twelve adult patients with repaired TOF and SCD were identified (SCD group). A total of 125 living adult patients with repaired TOF were randomly selected for comparison (control group). RESULTS Patients with SCD were more likely to exhibit moderate or severe pulmonary regurgitation (92% vs. 51%, p = 0.02), have a history of sustained ventricular tachycardia (42% vs. 6%, p < 0.01), and have a QRS > or =180 ms (56% vs. 13%, p = 0.02). Moderate or severe LV systolic dysfunction was also significantly more common in patients with SCD than in the control group (42% vs. 9%, p < 0.01) with a positive predictive value of 29%. The combination of moderate or severe LV systolic dysfunction and QRS > or =180 ms had a positive and negative predictive value for SCD of 66% and 93%, respectively. CONCLUSIONS Moderate or severe LV systolic dysfunction is significantly more common in adult patients with repaired TOF and SCD. The combination of QRS > or =180 ms and significant LV systolic dysfunction has high positive and negative predictive value for SCD. The implication of the role of prophylactic antiarrhythmic implantable cardiac defibrillator insertion in these patients needs further elucidating.

Sudden Cardiac Death in Adult Congenital Heart Disease

Background— Sudden cardiac death (SCD) is a major cause of mortality in adults with congenital heart disease (CHD). The aim of this study was to determine the adult CHD population at risk of SCD and the clinical parameters associated with SCD. Methods and Results— We performed a multicenter case-control study. Patients who died suddenly as a result of proven or presumed arrhythmia were included (cases). For each case, 2 controls matched on diagnosis, type of surgical intervention, age, and gender were included. From 3 databases including 25 790 adults with CHD, 1189 deaths (5%) were identified, of whom 213 patients (19%) died suddenly. Arrhythmic death occurred in 171 of 1189 patients. The underlying cardiac lesions were mild, moderate, and severe CHD in 12%, 33%, and 55% of the SCD cases, respectively. Clinical variables associated with SCD were supraventricular tachycardia (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.5–7.9; P=0.004), moderate to severe systemic ventricular dysfunction (OR, 3.4; 95% CI, 1.1–10.4; P=0.034), moderate to severe subpulmonary ventricular dysfunction (OR, 3.4; 95% CI, 1.1–10.2; P=0.030), increased QRS duration (OR, 1.34 [per 10-ms increase]; 95% CI, 1.10–1.34; P=0.008), and QT dispersion (OR, 1.22 [per 10-ms increase]; 95% CI, 1.22–1.48; P=0.008). Conclusions— The clinical parameters found to be associated with SCD in adults with a broad spectrum of CHD, including systemic right ventricles, are similar to those in ischemic heart disease. Moreover, even those patients with mild cardiac lesions are potentially at risk for SCD. This highlights the need for further prospective studies as well as vigilant ongoing follow-up of the adult with CHD.

Depression and anxiety in adult congenital heart disease: Predictors and prevalence

BACKGROUND Adult congenital heart disease (ACHD) patients face unique medical and social challenges that may contribute to psychological difficulties. The goals of this study were to identify predictors of symptoms of depression and anxiety and evaluate the prevalence of mood and anxiety disorders among North American ACHD patients. METHODS In this cross-sectional study, consecutive patients were recruited from two ACHD outpatient clinics. All patients completed self-report psychosocial measures and a subset was randomly selected to participate in structured clinical interviews. Linear regression models were used to predict symptoms of depression and anxiety. RESULTS A total of 280 patients (mean age=32 years; 52% female) completed self-report measures. Sixty percent had defects of moderate complexity and 31% had defects of great complexity. Significant predictors of depressive symptoms were loneliness (p<0.001), perceived health status (p<0.001), and fear of negative evaluation (p=0.02). Predictors of anxiety symptoms were loneliness (p<0.001) and fear of negative evaluation (p<0.001). Disease severity and functional class did not predict mood or anxiety symptoms. Fifty percent of interviewed patients (29/58) met diagnostic criteria for at least one lifetime mood or anxiety disorder, of whom 39% had never received any mental health treatment. CONCLUSIONS The results confirm an increased risk and under-treatment of mood and anxiety disorders in ACHD patients. Social adjustment and patient-perceived health status were more predictive of depression and anxiety than medical variables. These factors are modifiable and therefore a potential focus of intervention.

Canadian Cardiovascular Society 2009 Consensus Conference on the management of adults with congenital heart disease: Outflow tract obstruction, coarctation of the aorta, tetralogy of Fallot, Ebstein anomaly and Marfan’s syndrome

With advances in pediatric cardiology and cardiac surgery, the population of adults with congenital heart disease (CHD) has increased. In the current era, there are more adults with CHD than children. This population has many unique issues and needs. Since the 2001 Canadian Cardiovascular Society Consensus Conference report on the management of adults with CHD, there have been significant advances in the field of adult CHD. Therefore, new clinical guidelines have been written by Canadian adult CHD physicians in collaboration with an international panel of experts in the field. Part II of the guidelines includes recommendations for the care of patients with left ventricular outflow tract obstruction and bicuspid aortic valve disease, coarctation of the aorta, right ventricular outflow tract obstruction, tetralogy of Fallot, Ebstein anomaly and Marfans syndrome. Topics addressed include genetics, clinical outcomes, recommended diagnostic workup, surgical and interventional options, treatment of arrhythmias, assessment of pregnancy risk and follow-up requirements. The complete document consists of four manuscripts that are published online in the present issue of The Canadian Journal of Cardiology. The complete document and references can also be found at www.ccs.ca or www.cachnet.org.

Ventricular arrhythmias and sudden death in adults after a Mustard operation for transposition of the great arteries

AIMS To examine the prevalence of sustained ventricular tachycardia (VT) and sudden death (SD) in adults with atrial repair of transposition of the great arteries (TGA) and to determine associated risk factors. METHODS AND RESULTS In a single-centre review, we studied the outcome of 149 adults (mean age 28 +/- 7 years) who had undergone a Mustard operation for TGA. During a mean follow-up of 9 +/- 6 years, sustained VT and/or SD occurred in 9% (13/149) of the cohort. Sustained VT/SD was more likely to occur in patients with associated anatomic lesions [hazard ratio (HR) 4.9, 95% CI 1.5-16.0], with NYHA class >or=III (HR 9.8, 95% CI 3.0-31.6) and with an impaired subaortic right ventricular (RV) ejection fraction (EF) (HR 2.2, 95% CI 1.2-4.0 per 10% decrease in EF). There was an inverse correlation between the RV-EF and both age and QRS duration. Patients with a QRS duration >or=140 ms were at highest risk of sustained VT/SD (HR 13.6, 95% CI 2.9-63.4). Atrial tachyarrhythmia was detected in 66 (44%) patients, but was not a statistically significant predictor of sustained VT/SD in our adult population (HR 2.7, 95% CI 0.6-13.0). CONCLUSION Sustained VT/SD in adults after a Mustard operation for TGA are more common than previously described. Age, systemic ventricular function, and QRS duration are interrelated and are associated with VT/SD. A QRS duration >or=140 ms helps to identify the high risk patient.

Use of Low Molecular Weight Heparin in Pregnant Women With Mechanical Heart Valves

There are a number of different anticoagulation options for pregnant women with mechanical heart valves. The purpose of this study was to examine maternal thromboembolic complications in women with mechanical valves treated with low-molecular weight heparin (LMWH) throughout pregnancy. This was a substudy of a larger prospective cohort study of pregnant women with heart disease followed from 1998 to 2008. All pregnant women with mechanical left-sided valves who were treated with LMWH throughout pregnancy were included. Maternal thromboembolic events were defined as valve thrombosis, need for valve replacement, or stroke during pregnancy or postpartum (up to 6 months). Twenty-three pregnancies (17 women) occurred in women treated with LMWH and low-dose aspirin: 15 in women with mechanical mitral valves, 9 in women with mechanical aortic valves, and 1 in a woman with both. There was 1 maternal thromboembolic event (4%), which resulted in maternal and fetal death. Five women (22%) developed other adverse cardiac events during pregnancy. Nine pregnancies (43%) had fetal or neonatal adverse events, 5 of which had favorable outcomes. Three pregnancies were complicated by postpartum hemorrhage. In conclusion, carefully monitored LMWH may be a suitable anticoagulation strategy in pregnant women with mechanical heart valves who are unwilling to use warfarin. However, this group of women remains at risk for maternal cardiac and fetal complications. The occurrence of valve thrombosis resulting in maternal death despite therapeutic anti-Xa levels highlights current limitations with anticoagulation in this population.

Rare Copy Number Variations in Adults with Tetralogy of Fallot Implicate Novel Risk Gene Pathways

Structural genetic changes, especially copy number variants (CNVs), represent a major source of genetic variation contributing to human disease. Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease, but to date little is known about the role of CNVs in the etiology of TOF. Using high-resolution genome-wide microarrays and stringent calling methods, we investigated rare CNVs in a prospectively recruited cohort of 433 unrelated adults with TOF and/or pulmonary atresia at a single centre. We excluded those with recognized syndromes, including 22q11.2 deletion syndrome. We identified candidate genes for TOF based on converging evidence between rare CNVs that overlapped the same gene in unrelated individuals and from pathway analyses comparing rare CNVs in TOF cases to those in epidemiologic controls. Even after excluding the 53 (10.7%) subjects with 22q11.2 deletions, we found that adults with TOF had a greater burden of large rare genic CNVs compared to controls (8.82% vs. 4.33%, p = 0.0117). Six loci showed evidence for recurrence in TOF or related congenital heart disease, including typical 1q21.1 duplications in four (1.18%) of 340 Caucasian probands. The rare CNVs implicated novel candidate genes of interest for TOF, including PLXNA2, a gene involved in semaphorin signaling. Independent pathway analyses highlighted developmental processes as potential contributors to the pathogenesis of TOF. These results indicate that individually rare CNVs are collectively significant contributors to the genetic burden of TOF. Further, the data provide new evidence for dosage sensitive genes in PLXNA2-semaphorin signaling and related developmental processes in human cardiovascular development, consistent with previous animal models.

Cardiac outcomes in young adult survivors of the arterial switch operation for transposition of the great arteries.

OBJECTIVES We sought to determine cardiac outcomes in young adults with complete transposition of the great arteries (TGA) after the arterial switch operation (ASO). BACKGROUND Although cardiac outcomes in the pediatric population with TGA after ASO have been well described, outcomes in the adult population have not to our knowledge been studied. METHODS We determined late survival in all operative survivors with TGA after ASO performed before 1991 at our local pediatric referring hospital. In the subset of adults (n = 65) followed in our adult congenital cardiac clinic, we examined cardiac outcomes in adulthood. RESULTS Survival of the 132 infants discharged from hospital after ASO was 97% (70% confidence interval [CI]: 95.0% to 98.1%) at 20 years. In the 65 patients (mean age 21 +/- 3 years, 62% male) followed at our institution, 17% (11 of 65) had at least 1 clinically significant cardiac lesion, including ventricular dysfunction, valvular dysfunction, or arrhythmias. Residual lesions were more common in those who had had cardiac reinterventions in childhood (odds ratio: 10.7, 95% CI: 2.1 to 55). In adulthood, 5 patients (8%) had arrhythmia requiring treatment and 7 patients (11%) required reinterventions (5 reoperations and 2 pacemaker implantations). Intervention for aortic valve regurgitation and aortic root dilation were not observed. Exercise capacity was reduced in most adults (82%) after ASO. CONCLUSIONS Although most adults after ASO are well, and few have residual defects, there are subgroups, particularly those who needed further cardiac intervention in childhood, who are at higher risk for ventricular and valve dysfunction and arrhythmias.