Medical Therapy for Systemic Right Ventricles: A Systematic Review (Part 1) for the 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Patients with systemic morphological right ventricles (RVs), including congenitally corrected transposition of the great arteries and dextro-transposition of the great arteries with a Mustard or Senning atrial baffle repair, have a high likelihood of developing systemic ventricular dysfunction. Unfortunately, there are a limited number of clinical studies on the efficacy of medical therapy for systemic RV dysfunction. We performed a systematic review and meta-analysis to assess the effect of angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), beta blockers, and aldosterone antagonists in adults with systemic RVs. The inclusion criteria included age ≥18 years, systemic RVs, and at least 3 months of treatment with ACE inhibitor, ARB, beta blocker, or aldosterone antagonist. The outcomes included RV end-diastolic and end-systolic dimensions, RV ejection fraction, functional class, and exercise capacity. EMBASE, PubMed, and Cochrane databases were searched. The selected data were pooled and analyzed with the DerSimonian-Laird random-effects meta-analysis model. Between-study heterogeneity was assessed with Cochran's Q test. A Bayesian meta-analysis model was also used in the event that heterogeneity was low. Bias assessment was performed with the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool, and statistical risk of bias was assessed with Begg and Mazumdar's test and Egger's test. Six studies met the inclusion criteria, contributing a total of 187 patients; treatment with beta blocker was the intervention that could not be analyzed because of the small number of patients and diversity of outcomes reported. After at least 3 months of treatment with ACE inhibitors, ARBs, or aldosterone antagonists, there was no statistically significant change in mean ejection fraction, ventricular dimensions, or peak ventilatory equivalent of oxygen. The methodological quality of the majority of included studies was low, mainly because of a lack of a randomized and controlled design, small sample size, and incomplete follow-up. In conclusion, pooled results across the limited available studies did not provide conclusive evidence with regard to a beneficial effect of medical therapy in adults with systemic RV dysfunction. Randomized controlled trials or comparative-effectiveness studies that are sufficiently powered to demonstrate effect are needed to elucidate the efficacy of ACE inhibitors, ARBs, beta blockers, and aldosterone antagonists in patients with systemic RVs.

Interventional Therapy Versus Medical Therapy for Secundum Atrial Septal Defect: A Systematic Review (Part 2) for the 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Secundum atrial septal defect (ASD) is the most common adult congenital heart defect and can present with wide variation in clinical findings. With the intention of preventing morbidity and mortality associated with late presentation of ASD, consensus guidelines have recommended surgical or percutaneous ASD closure in adults with right heart enlargement, with or without symptoms. The aim of the present analysis was to determine if the protective effect of secundum ASD closure in adults could be qualified by pooling data from published studies. A systematic review and meta-analysis were performed by using EMBASE, MEDLINE (through PubMed), and the Cochrane Library databases to assess the effect of secundum ASD percutaneous or surgical closure in unoperated adults ≥18 years of age. Data were pooled across studies with the DerSimonian-Laird random-effects model or a Bayesian meta-analysis model. Between-study heterogeneity was assessed with Cochran's Q test. Bias assessment was performed with the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool, and statistical risk of bias was assessed with Begg and Mazumdar's test and Egger's test. A total of 11 nonrandomized studies met the inclusion criteria, contributing 603 patients. Pooled analysis showed a protective effect of ASD closure on New York Heart Association functional class and on right ventricular systolic pressure, volumes, and dimensions. Two additional studies comprising 652 patients were reviewed separately for mortality outcome and primary outcome of interest because they did not meet the inclusion criteria. Those studies showed that ASD closure was associated with a weak protective effect on adjusted mortality rate but no significant impact on atrial arrhythmias in patients >50 years of age. Across all studies, there was significant heterogeneity between studies for nearly all clinical outcomes. The overall body of evidence was limited to observational cohort studies, the limitations of which make for low-strength evidence. Even within the parameters of the included studies, quality of evidence was further diminished by the lack of well-defined clinical outcomes. In conclusion, pooled data analysis on the impact of secundum ASD closure in adults was notably limited because of the lack of randomized controlled trials in patients with only secundum ASD. The few cohort studies in this population demonstrated improvement in functional status and right ventricular size and function as shown by echocardiogram. However, our findings suggest that at the time of this publication, insufficient data are available to determine the impact of ASD repair on mortality rate in adults.

Interventional Therapy Versus Medical Therapy for Secundum Atrial Septal Defect: A Systematic Review (Part 2) for the 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Secundum atrial septal defect (ASD) is the most common adult congenital heart defect and can present with wide variation in clinical findings. With the intention of preventing morbidity and mortality associated with late presentation of ASD, consensus guidelines have recommended surgical or percutaneous ASD closure in adults with right heart enlargement, with or without symptoms. The aim of the present analysis was to determine if the protective effect of secundum ASD closure in adults could be qualified by pooling data from published studies. A systematic review and meta-analysis were performed by using EMBASE, MEDLINE (through PubMed), and the Cochrane Library databases to assess the effect of secundum ASD percutaneous or surgical closure in unoperated adults ≥18 years of age. Data were pooled across studies with the DerSimonian-Laird random-effects model or a Bayesian meta-analysis model. Between-study heterogeneity was assessed with Cochran's Q test. Bias assessment was performed with the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool, and statistical risk of bias was assessed with Begg and Mazumdar's test and Egger's test. A total of 11 nonrandomized studies met the inclusion criteria, contributing 603 patients. Pooled analysis showed a protective effect of ASD closure on New York Heart Association functional class and on right ventricular systolic pressure, volumes, and dimensions. Two additional studies comprising 652 patients were reviewed separately for mortality outcome and primary outcome of interest because they did not meet the inclusion criteria. Those studies showed that ASD closure was associated with a weak protective effect on adjusted mortality rate but no significant impact on atrial arrhythmias in patients >50 years of age. Across all studies, there was significant heterogeneity between studies for nearly all clinical outcomes. The overall body of evidence was limited to observational cohort studies, the limitations of which make for low-strength evidence. Even within the parameters of the included studies, quality of evidence was further diminished by the lack of well-defined clinical outcomes. In conclusion, pooled data analysis on the impact of secundum ASD closure in adults was notably limited because of the lack of randomized controlled trials in patients with only secundum ASD. The few cohort studies in this population demonstrated improvement in functional status and right ventricular size and function as shown by echocardiogram. However, our findings suggest that at the time of this publication, insufficient data are available to determine the impact of ASD repair on mortality rate in adults.

Medical Therapy for Systemic Right Ventricles: A Systematic Review (Part 1) for the 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Patients with systemic morphological right ventricles (RVs), including congenitally corrected transposition of the great arteries and dextro-transposition of the great arteries with a Mustard or Senning atrial baffle repair, have a high likelihood of developing systemic ventricular dysfunction. Unfortunately, there are a limited number of clinical studies on the efficacy of medical therapy for systemic RV dysfunction. We performed a systematic review and meta-analysis to assess the effect of angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), beta blockers, and aldosterone antagonists in adults with systemic RVs. The inclusion criteria included age ≥18 years, systemic RVs, and at least 3 months of treatment with ACE inhibitor, ARB, beta blocker, or aldosterone antagonist. The outcomes included RV end-diastolic and end-systolic dimensions, RV ejection fraction, functional class, and exercise capacity. EMBASE, PubMed, and Cochrane databases were searched. The selected data were pooled and analyzed with the DerSimonian-Laird random-effects meta-analysis model. Between-study heterogeneity was assessed with Cochran's Q test. A Bayesian meta-analysis model was also used in the event that heterogeneity was low. Bias assessment was performed with the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool, and statistical risk of bias was assessed with Begg and Mazumdar's test and Egger's test. Six studies met the inclusion criteria, contributing a total of 187 patients; treatment with beta blocker was the intervention that could not be analyzed because of the small number of patients and diversity of outcomes reported. After at least 3 months of treatment with ACE inhibitors, ARBs, or aldosterone antagonists, there was no statistically significant change in mean ejection fraction, ventricular dimensions, or peak ventilatory equivalent of oxygen. The methodological quality of the majority of included studies was low, mainly because of a lack of a randomized and controlled design, small sample size, and incomplete follow-up. In conclusion, pooled results across the limited available studies did not provide conclusive evidence with regard to a beneficial effect of medical therapy in adults with systemic RV dysfunction. Randomized controlled trials or comparative-effectiveness studies that are sufficiently powered to demonstrate effect are needed to elucidate the efficacy of ACE inhibitors, ARBs, beta blockers, and aldosterone antagonists in patients with systemic RVs.

Projected growth of the adult congenital heart disease population in the United States to 2050: an integrative systems modeling approach.

BACKGROUND: Mortality for children with congenital heart disease (CHD) has declined with improved surgical techniques and neonatal screening; however, as these patients live longer, accurate estimates of the prevalence of adults with CHD are lacking. METHODS: To determine the prevalence and mortality trends of adults with CHD, we combined National Vital Statistics System data and National Health Interview Survey data using an integrative systems model to determine the prevalence of recalled CHD as a function of age, sex, and year (by recalled CHD, we mean positive response to the question "has a doctor told you that (name) has congenital heart disease?", which is a conservative lower-bound estimate of CHD prevalence). We used Human Mortality Database estimates and US Census Department projections of the US population to calculate the CHD-prevalent population by age, sex, and year. The primary outcome was prevalence of recalled CHD in adults from 1970 to 2050; the secondary outcomes were birth prevalence and mortality rates by sex and women of childbearing age (15-49 years). RESULTS: The birth prevalence of recalled CHD in 2010 for males was 3.29 per 1,000 (95 % uncertainty interval (UI) 2.8-3.6), and for females was 3.23 per 1,000 (95 % UI 2.3-3.6). From 1968 to 2010, mortality among zero to 51-week-olds declined from 170 to 53 per 100,000 person years. The estimated number of adults (age 20-64 years) with recalled CHD in 1968 was 118,000 (95 % UI 72,000-150,000). By 2010, there was an increase by a factor of 2.3 (95 % UI 2.2-2.6), to 273,000 (95 % UI 190,000-330,000). There will be an estimated 510,000 (95 % UI: 400,000-580,000) in 2050. The prevalence of adults with recalled CHD will begin to plateau around the year 2050. In 2010, there were 134,000 (95 % UI 69,000-160,000) reproductive-age females (age 15-49 years) with recalled CHD in the United States. CONCLUSION: Mortality rates have decreased in infants and the prevalence of adults with CHD has increased but will slow down around 2050. This population requires adult medical systems with providers experienced in the care of adult CHD patients, including those familiar with reproduction in women with CHD.

Transcatheter closure of atrial septal communication during pregnancy in women with Ebstein's anomaly of the tricuspid valve and cyanosis.

Transcatheter atrial septal defect occlusion is described in three pregnant patients with Ebstein's anomaly and exercise-induced cyanosis. Procedures took place in the second and third trimester. Careful hemodynamic testing was performed prior to permanent atrial septal occlusion to confirm the capacity of the right ventricle to accept the entirety of systemic venous return in the volume-expanded state of pregnancy. Outcomes for mother and fetus were favorable in all patients with significant reduction in maternal symptoms and resolution of cyanosis.

Echocardiographic evaluation of univentricular physiology and cavopulmonary shunts.

The term univentricular heart (UH) defines complex congenital heart disease that lacks a pulmonic ventricular chamber either in the original anatomy or the final palliation. The prevalence of patients with this type of physiology continues to increase due to improved surgical palliative procedures. This review will outline the physiology, complications, and echocardiographic approach to image patients with palliated UH.

Sex and age differences in the association of depression with obstructive coronary artery disease and adverse cardiovascular events.

BACKGROUND: Young women with coronary heart disease have high rates of depression and a higher risk of adverse events than men of similar age. Whether depression has a higher prognostic value in this group than in men and older women is not known. Our objective was to assess whether depression in young women is associated with higher risk of coronary artery disease (CAD) and adverse outcomes compared with similarly aged men and older women. METHODS AND RESULTS: We examined 3237 patients undergoing coronary angiography for evaluation of CAD and followed them for 2.9 years (median). Depressive symptoms were assessed with the Patient Health Questionnaire (PHQ)-9, and CAD burden was dichotomized based on its presence or absence. After multivariable adjustment for CAD risk factors, depressive symptoms predicted CAD presence in women aged ≤ 55 years (odds ratio=1.07 95% confidence interval [CI] 1.02 to 1.13 per 1 point increase in PHQ-9 score), but not in men aged ≤ 55 years or women aged >55 years. Depressive symptoms also predicted increased risk of death in women aged ≤ 55 years (adjusted hazard ratio=1.07, 95% CI 1.02 to 1.14, per 1 point increase in PHQ-9 score), but not in men aged ≤ 55 years and women aged >55 years, with P=0.02 for the depression-sex interaction and P=0.02 for depression-sex-age interaction. CONCLUSIONS: Among patients with suspected or established CAD, depressive symptoms are associated with increased risk of death, particularly in young women. This group may be especially vulnerable to the adverse cardiovascular effects of depression.

Management of pulmonic regurgitation and right ventricular dysfunction in the adult with repaired tetralogy of fallot.

OPINION STATEMENT: With surgical repair most children with Tetralogy of Fallot survive into adulthood. The main complications seen after Tetralogy of Fallot repair include arrhythmias, sudden cardiac death, pulmonary regurgitation, and right ventricular dysfunction/heart failure. Pulmonary regurgitation over time may lead to right ventricular dilation and failure. In this article, we will review the literature regarding management of pulmonary regurgitation with specific focus on timing for pulmonary valve replacement and prevention of right ventricular dysfunction.

Real time three-dimensional echocardiography evaluation of intracardiac masses.

The evaluation of cardiac masses is often a challenge for cardiac imaging techniques. The traditional standby has been two-dimensional echocardiography (2DE). Real time three-dimensional echocardiography (RT3DE) offers incremental value for the evaluation of intracardiac masses by providing more accurate assessment of the size and shape of the mass as well as in some cases, composition of the mass. RT3DE aids with the relationship between the mass and adjacent structures. Therefore, here we discuss the subject of RT3DE evaluation of cardiac masses is reviewed and discussed in detail.

Quality improvement of tuberculosis screening in foreign-born patients.

In the United States, a disproportionate percentage of tuberculosis (TB) cases occur in foreign-born persons. We implemented a performance improvement project to improve rates of screening for latent tuberculosis infection in a medical clinic. A questionnaire was developed to identify patients for tuberculosis screening, which was performed as a Tuberculin Skin Test (TST). Patients with positive skin tests underwent further testing. One hundred and sixty-five patients were screened, with 58 TSTs ordered and 36 placed. Twenty-seven patients returned to have the TST read with 12 positive. Eleven of these patients had chest X-rays, 2 revealing findings suggestive of active TB. This project identifies the importance of a standardized TB screening process for high-risk patients and identifies barriers to such a process.

Predictors of success with highly active antiretroviral therapy in an antiretroviral-naive urban population.

Abstract Predictors of successful virologic, immunologic, and clinical response with combined antiretroviral therapy (cART) containing a boosted protease inhibitor or a nonnucleoside reverse transcriptase inhibitor were analyzed among an antiretroviral naive (ARV-naive) urban cohort. Measures of success included virologic suppression [HIV-1 viral load (VL) <400 copies/ml], an increase in CD4(+) T cells from baseline of >100 cells/microl, and lack of development of an AIDS-defining illness at 24 and 48 weeks after cART initiation. Two hundred and eighty-seven ARV-naive patients were included in this cohort, of which 76.7% were male and 86.8% were nonwhite. At the time of cART initiation their median age was 39 years, the geometric mean CD4(+) count was 42 cells/microl, and the mean viral load was 5.3 log(10) copies/ml. At 48 weeks, 72% of patients achieved virologic suppression, with > or =90% adherence and high school graduation predicting viral undetectability at 48 weeks. Baseline VL < or =100,000 copies/ml and a CD4(+) cell count >100 cells/microl were associated with viral suppression at 24 weeks [OR (95% CI) = 3.55 (1.29-9.81) and 3.96 (1.19-13.15), respectively]; female gender was associated with a greater increase in CD4(+) cell counts [OR (95% CI) = 7.41 (2.48-22.1)]. CDC stage A1-C2 at baseline predicted lack of clinical progression at 48 weeks. The results of this analysis of an ARV-naive cohort comprised predominantly of indigent, minority patients suggest that men who did not have a high school education and who had advanced HIV infection are less likely to have therapeutic success after cART initiation.

Adenosine stress magnetic resonance imaging in women with low risk chest pain: the Emory University experience.

OBJECTIVES: The purpose of this study was to evaluate the accuracy of adenosine stress magnetic resonance imaging (ASMRI) for the evaluation of women with low-risk chest pain (CP). BACKGROUND: Coronary artery disease (CAD) can present differently among women than among men. There is increased interest in the use of ASMRI for lower risk patients in the emergency department to rule out CAD, and it would be valuable to assess its performance specifically in women. METHODS: This study included 82 women with low-risk CP who presented to the emergency department during a 2-year period at our institution and were evaluated by ASMRI. Clinical events were followed by review of medical records. RESULTS: The specificity of ASMRI for ischemia detection in this small cohort of patients was 100%. Sensitivity was 94.9%, negative predictive value 100%, and positive predictive value 42.9%. CONCLUSIONS: ASMRI may be used as the initial imaging modality for ruling out CAD in women with low-risk CP because of its very high sensitivity, specificity, and negative predictive value for the detection of ischemia. Further randomized controlled trials comparing ASMRI with established noninvasive nuclear and echocardiographic stress modalities are needed.

Prognostic value of adenosine stress cardiovascular magnetic resonance in patients with low-risk chest pain.

BACKGROUND: Approximately 5% of patients with an acute coronary syndrome are discharged from the emergency room with an erroneous diagnosis of non-cardiac chest pain. Highly accurate non-invasive stress imaging is valuable for assessment of low-risk chest pain patients to prevent these errors. Adenosine stress cardiovascular magnetic resonance (AS-CMR) is an imaging modality with increasing application. The goal of this study was to evaluate the negative prognostic value of AS-CMR among low-risk acute chest pain patients. METHODS: We studied 103 patients, mean 56.7 + or - 12.3 years of age, with chest pain and no electrocardiographic evidence of ischemia and negative cardiac biomarkers of necrosis, who were admitted to the Cardiac Decision Unit of our institution. All patients underwent AS-CMR. A negative AS-CMR was defined as absence of all the following: regional wall motion abnormalities at rest; perfusion defects during stress (adenosine) and rest; and myocardial scar on late gadolinium enhancement images. The patients were followed for a mean of 277 (range 161-462) days. The primary end point was defined as the combination of cardiac death, nonfatal acute myocardial infarction, re-hospitalization for chest pain, obstructive coronary artery disease (>50% coronary stenosis on invasive angiography) and coronary revascularization. RESULTS: In 14 patients (13.6%), AS-CMR was positive. The remaining 89 patients (86.4%), who had negative AS-CMR, were discharged. No patient with negative AS-CMR reached the primary end-point during follow-up. The negative predictive value of AS-CMR was 100%. CONCLUSION: AS-CMR holds promise as a useful tool to rule out significant coronary artery disease in patients with low-risk chest pain. Patients with negative AS-CMR have an excellent short and mid-term prognosis.