Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Congenital Heart Defects and Developmental and Other Psychiatric Disorders: A Danish Nationwide Cohort Study
- Peak Oxygen Uptake Correlates With Survival Without Clinical Deterioration in Ambulatory Children With Dilated Cardiomyopathy
- Intrathoracic Impedance Monitoring, Audible Patient Alerts, and Outcome in Patients With Heart Failure
- Blood Pressure Targets Recommended by Guidelines and Incidence of Cardiovascular and Renal Events in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET)
- Myocardial Structure, Function, and Scar in Patients With Type 1 Diabetes Mellitus
- Comparison of Transplacental Treatment of Fetal Supraventricular Tachyarrhythmias With Digoxin, Flecainide, and Sotalol: Results of a Nonrandomized Multicenter Study
- Pediatric Pulmonary Hypertension in the Netherlands: Epidemiology and Characterization During the Period 1991 to 2005
- Effect of Hypoxia-Inducible Factor-1α Gene Therapy on Walking Performance in Patients With Intermittent Claudication
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Congenital Heart Defects and Developmental and Other Psychiatric Disorders: A Danish Nationwide Cohort Study
Studies focusing on a wide range of congenital heart defects (CHDs) have reported associations with mild cognitive impairment, speech and language difficulties, impaired motor skills, attention deficit hyperactivity disorder, and autism-like disabilities. These disabilities may cross the boundaries of many clinical disciplines including neurology, pediatrics, and psychiatry, depending on referral practices. In this study we examined the incidence of psychiatric hospitalization or out-patient visits among Danish patients with CHD compared with a general population cohort. We focused on psychiatric admissions and out-patient contacts overall and on contacts for specific mental disorders in accordance with the overall pattern of neurobehavioral sequelae described in the CHD population, as well as relevant genetic risk factors. The overall risk of a first-time psychiatric diagnosis was elevated compared with the general population cohort, whether or not a cardiac therapeutic intervention had occurred. In the age range for potential pediatric cardiac follow-up (<15 years of age), the risk was increased for both male and female patients. Among those aged 15 to 30 years who receive treatment in an adult cardiac clinic, only males were at increased risk for a first-time psychiatric diagnosis compared with the general population cohort. Because our study only considered first-time psychiatric diagnoses, our results cannot exclude the possibility that more adult female CHD patients may have mental health issues at a given time (prevalent disease) compared with females in the general population. Our study indicates the importance of addressing mental health issues in optimal CHD follow-up and care. See p 1706.
Peak Oxygen Uptake Correlates With Survival Without Clinical Deterioration in Ambulatory Children With Dilated Cardiomyopathy
In adults, cardiopulmonary exercise testing is an integral part of the decision-making process for heart transplantation listing. However, experience with using cardiopulmonary exercise test as a prognostic tool in children is very limited. In the present study, using cardiopulmonary exercise testing, we studied 82 ambulatory children with dilated cardiomyopathy and found that lower peak oxygen uptake was associated with a higher rate of death (without transplantation) and clinical deterioration requiring urgent listing for transplantation. Children with a peak oxygen uptake ≤62% of the predicted value were at particularly high risk. The study provides supportive evidence for the use of cardiopulmonary exercise test for risk stratification of pediatric dilated cardiomyopathy and suggests that exercise test variables may become part of the standard clinical risk assessment of older children with dilated cardiomyopathy. See p 1713.
Intrathoracic Impedance Monitoring, Audible Patient Alerts, and Outcome in Patients With Heart Failure
Heart failure is associated with frequent hospitalizations, often because of volume overload. It is difficult, however, to identify patients at risk for hospitalization, and signs and symptoms are often unspecific. Measurement of intrathoracic impedance with an implanted device with an audible patient alert may detect increases in pulmonary fluid retention early. In the Diagnostic Outcome Trial in Heart Failure (DOT-HF), we studied patients with chronic heart failure who had undergone implantation of an implantable cardioverter-defibrillator alone or with cardiac resynchronization therapy. All devices featured a monitoring tool to track changes in intrathoracic impedance (OptiVol) and other diagnostic parameters. Patients were randomized to have information available to physicians and patients as an audible alert in case of preset threshold crossings (access arm) or not (control arm). The primary end point was a composite of all-cause mortality and heart failure hospitalizations. The study showed that the use of an implantable diagnostic tool to measure intrathoracic impedance with an audible patient alert did not improve outcome and in fact increased outpatient visits and heart failure hospitalizations in this population. These findings may have important implications. Although changes in intrathoracic impedance have been associated in a large number of studies with an increased risk for cardiovascular events in patients with heart failure, questions remain about its clinical use, sensitivity, and specificity. Moreover, the audible alert in particular seems to have played a role in the increased number of outpatient visits and heart failure hospitalizations. See p 1719.
Blood Pressure Targets Recommended by Guidelines and Incidence of Cardiovascular and Renal Events in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET)
In a large number of high-cardiovascular-risk patients of the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET), overall cardiovascular protection was achieved by more frequently lowering blood pressure to <140/90 mm Hg but that no overall beneficial effect was evident when the target blood pressure was set at <130/80 mm Hg. This study further shows that less tight and tighter blood pressure control may affect different vital organs, with renal and cerebral protection coexisting with much less effect or no effect at all on cardiac events such as myocardial infarction and heart failure. This portrays a situation in part different from that envisaged by current guidelines that recommend blood pressure be reduced to <130/80 mmHg when the cardiovascular risk is high. The ONTARGET data indicate that the effect of such a tight blood pressure target for treatment appears to be complex, and that an overall better result may be obtained by a more conservative approach. See p 1727.
Myocardial Structure, Function, and Scar in Patients With Type 1 Diabetes Mellitus
Type 1 diabetes mellitus is associated with a relatively high prevalence of cardiovascular disease and clinical and silent myocardial infarction compared with the nondiabetic population, leading to alterations in cardiac structure and function. In the present study, we evaluated the relationship of cardiovascular disease risk factors, including hemoglobin A1c levels and diabetic nephropathy, to myocardial structure, function, and scar by cardiac magnetic resonance imaging in 1017 patients of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. The DCCT/EDIC study is the first large-scale cohort of patients with type 1 diabetes mellitus. Patients had a mean clinical evaluation period of 22 years preceding cardiac magnetic resonance. We found that macroalbuminuria and mean hemoglobin A1c (over ≈22 years of follow-up) were significant risk factors for alterations in left ventricular structure and function and for having myocardial scar. The prevalence of myocardial scar by cardiac magnetic resonance was 4.3% compared with only 1.4% in patients with clinically recognized myocardial infarction. The concordance of scar and clinical history was relatively low. These findings suggest that modifiable cardiovascular disease risk factors and glycemic control play a significant role in relationship to cardiovascular morbidity and mortality in patients with type 1 diabetes mellitus. See p 1737.
Comparison of Transplacental Treatment of Fetal Supraventricular Tachyarrhythmias With Digoxin, Flecainide, and Sotalol: Results of a Nonrandomized Multicenter Study
Fetal atrial flutter and supraventricular tachycardia may result in low cardiac output and death. Consequently, maternal antiarrhythmic treatment is offered in most affected pregnancies. This retrospective multicenter study is the first to compare the efficacy and safety of transplacental digoxin, flecainide, and sotalol, the most commonly used drugs to treat fetal tachyarrhythmia. In the absence of fetal hydrops, arrhythmia-related mortality was 0%, suggesting that transplacental antiarrhythmic therapy is safe and effective regardless of the drug chosen. In fetal hydrops, however, when rapid heart rate control becomes a matter of urgency to improve the chances of survival, the rate of arrhythmia-mediated death was 17%. We found that the fetal response to drug therapy was significantly associated with the type of tachycardia, fetal state, and choice of antiarrhythmic. Atrial flutter, fetal hydrops, and an incessant arrhythmia pattern were independently associated with slower cardioversion rates. Flecainide and digoxin were associated with increased likelihood of conversion of fetal supraventricular tachycardia to a normal rhythm and significantly greater slowing of ventricular rates of persistent atrial flutter/supraventricular tachycardia than sotalol. The highest rate of prenatal atrial flutter termination was observed with sotalol, albeit this was achieved in only about half of the sotalol-treated patients. Flecainide or digoxin might therefore be considered first to treat significant fetal tachyarrhythmia, perhaps in combination with sotalol to treat poorly tolerated atrial flutter. Our results may also be useful in improving our understanding of the potentials and limitations of antiarrhythmic drug therapy and, in persistent arrhythmia, helping to define a treatment period after which an alternative management should be considered. See p 1747.
Pediatric Pulmonary Hypertension in the Netherlands: Epidemiology and Characterization During the Period 1991 to 2005
In recent years, significant progress has been achieved in understanding the epidemiology and diagnosis of pulmonary hypertension (PH) in adults. In contrast, PH in children remains poorly understood because of a lack of epidemiological and clinical data. This study portrays epidemiological features, including incidence and prevalence, of pediatric PH and especially pulmonary arterial hypertension (PAH) based on nationwide data derived from 2 general medical registries (pediatric cardiology, national hospitalization) in the Netherlands during a 15-year period. This study demonstrates that pediatric PH is characterized by several age-specific diagnoses. Over 80% of these are transient forms of PAH not seen in adults. Progressive PAH in children includes idiopathic PAH (23%) but is mainly associated with congenital heart defects (PAH-CHD; 72%). Annual incidence for all PH diagnoses was 63.7 cases per million children. For iPAH and PAH-CHD, annual incidence and point prevalence averaged 0.7 and 4.4 (iPAH), and 2.2 and 15.6 (PAH-CHD) cases per million children. Incidence of pediatric iPAH was lower than reported in adults whereas incidence of pediatric PAH-CHD was higher. The group with pediatric PAH-CHD was more heterogeneous with highly variable clinical courses. Survival of Eisenmenger syndrome in children appeared to be worse than that reported in adults. Concomitant syndromes were frequent, especially in progressive PAH (39%). Notably, in the 15-year study period, only 71% of children with a diagnosis of PAH had confirmatory right heart catheterization as required by current guidelines, emphasizing the need for increasing specific clinical expertise. This can be reached by concentrating the care for pediatric PAH in specialized centers. See p 1755.
Effect of Hypoxia-Inducible Factor-1α Gene Therapy on Walking Performance in Patients With Intermittent Claudication
There are few medical therapies for patients with peripheral artery disease and intermittent claudication. Therapeutic angiogenesis has the potential to improve symptoms of claudication by forming new blood vessels and improving blood flow to affected limbs. Hypoxia-inducible factor 1α (HIF-1α) is an inducible transcriptional regulatory factor that plays a principal role in the cellular response to changes in oxygen tension and regulates genes involved in angiogenesis. This study tested the efficacy of intramuscular administration of AD2/HIF-1α/VP16, an engineered recombinant type 2 adenovirus vector encoding constitutively active HIF-1α, in improving walking time in patients with intermittent claudication. Compared with placebo, Ad2/HIF-1α/VP16 treatment did not improve peak walking time, claudication onset time, ankle-brachial index, or walking ability assessed by questionnaire. There are multiple reasons that should be considered to explain why this trial failed to improve walking time in patients with intermittent claudication. These include the biological activity of HIF-1α, the efficacy of gene transfer, the ability of intramuscular injection of HIF-1α at multiple sites to establish contiguous collateral vessels, the duration of effect after treatment on just 1 occasion, and the confounding effects of mechanisms other than blood supply that limit walking distance. To date, placebo-controlled clinical trials of angiogenic gene therapy have failed to demonstrate efficacy in patients with peripheral artery disease despite encouraging signals in preclinical models and preliminary human studies. These findings underscore the need to increase our understanding of the biology of angiogenesis and to develop effective and safe means to deliver gene therapy to patients with peripheral artery disease. See p 1765.
- © 2011 American Heart Association, Inc.
- Myocardial Structure, Function, and Scar in Patients With Type 1 Diabetes Mellitus
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