Meta-analysis: Incidence of cirrhosis and hepatocellular carcinoma in patients with Fontan palliation.

BACKGROUND AND AIMS: The Fontan palliation is the final stage of surgery for many children born with univentricular physiology. Almost all Fontan patients develop liver fibrosis which may eventually lead to cirrhosis and hepatocellular carcinoma (HCC). These are important causes of morbidity and mortality in these patients. We performed a systematic review and meta-analysis to assess the incidence of cirrhosis and HCC in Fontan patients and stratify it based on time since surgery. METHODS: A literature search of seven databases identified 1158 records. Studies reporting the number of cirrhosis and HCC cases in Fontan patients and time since Fontan surgery were included. In the cirrhosis cohort, we included only those studies where all patients underwent liver biopsy. RESULTS: A total of 23 studies were included: 12 and 13 studies in the cirrhosis and HCC cohorts, respectively, with two studies included in both cohorts. The incidence of cirrhosis was 0.97 per 100 patient-years (95% CI 0.57-1.63), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 1.61 per 100 patient-years (95% CI 1.24-2.08) and 32.2% (95% CI 25.8%-39.4%), respectively. The incidence of HCC was 0.12 per 100 patient-years (95% CI 0.07-0.21), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 0.20 per 100 patient-years (95% CI 0.12-0.35) and 3.9% (95% CI 2.2%-6.8%), respectively. Only about 70% of patients with HCC (20/28) had underlying cirrhosis. CONCLUSION: The incidence of cirrhosis and HCC increases over time, especially at ≥20 years post Fontan surgery. Studies are needed to further identify at-risk patients in order to streamline surveillance for these highly morbid conditions.

Aggregate risk of cardiovascular disease among adolescents perinatally infected with the human immunodeficiency virus.

BACKGROUND: Perinatally HIV-infected adolescents may be susceptible to aggregate atherosclerotic cardiovascular disease risk, as measured by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries and abdominal aorta risk scores, as a result of prolonged exposure to HIV and antiretroviral therapy. METHODS AND RESULTS: Coronary arteries and abdominal aorta PDAY scores were calculated for 165 perinatally HIV-infected adolescents, using a weighted combination of modifiable risk factors: dyslipidemia, cigarette smoking, hypertension, obesity, and hyperglycemia. Demographic and HIV-specific predictors of scores ≥1 were identified, and trends in scores over time were assessed. Forty-eight percent and 24% of the perinatally HIV-infected adolescents had coronary arteries and abdominal aorta scores ≥1, representing increased cardiovascular disease risk factor burden. Significant predictors of coronary arteries scores ≥1 included male sex, history of an AIDS-defining condition, longer duration of use of a ritonavir-boosted protease inhibitor, and no prior use of tenofovir. Significant predictors of abdominal aorta scores ≥1 included suppressed viral load, history of an AIDS-defining condition, and longer duration of boosted protease inhibitor use. No significant changes in coronary arteries and abdominal aorta risk scores were observed over the 4-year study period. CONCLUSIONS: A substantial proportion of perinatally HIV-infected youth have high PDAY scores, reflecting increased aggregate atherosclerotic cardiovascular disease risk factor burden. High scores were predicted by HIV disease severity and boosted protease inhibitor use. PDAY scores may be useful in identifying high-risk youth who may benefit from early lifestyle or clinical interventions.

Cardiac effects in perinatally HIV-infected and HIV-exposed but uninfected children and adolescents: a view from the United States of America.

INTRODUCTION: Human immunodeficiency virus (HIV) infection is a primary cause of acquired heart disease, particularly of accelerated atherosclerosis, symptomatic heart failure, and pulmonary arterial hypertension. Cardiac complications often occur in late-stage HIV infections as prolonged viral infection is becoming more relevant as longevity improves. Thus, multi-agent HIV therapies that help sustain life may also increase the risk of cardiovascular events and accelerated atherosclerosis. DISCUSSION: Before highly active antiretroviral therapy (HAART), the two-to-five-year incidence of symptomatic heart failure ranged from 4 to 28% in HIV patients. Patients both before and after HAART also frequently have asymptomatic abnormalities in cardiovascular structure. Echocardiographic measurements indicate left ventricular (LV) systolic dysfunction in 18%, LV hypertrophy in 6.5%, and left atrial dilation in 40% of patients followed on HAART therapy. Diastolic dysfunction is also common in long-term survivors of HIV infection. Accelerated atherosclerosis has been found in HIV-infected young adults and children without traditional coronary risk factors. Infective endocarditis, although rare in children, has high mortality in late-stage AIDS patients with poor nutritional status and severely compromised immune systems. Although lymphomas have been found in HIV-infected children, the incidence is low and cardiac malignancy is rare. Rates of congenital cardiovascular malformations range from 5.6 to 8.9% in cohorts of HIV-uninfected and HIV-infected children with HIV-infected mothers. In non-HIV-infected infants born to HIV-infected mothers, foetal exposure to ART is associated with reduced LV dimension, LV mass, and septal wall thickness and with higher LV fractional shortening and contractility during the first two years of life. CONCLUSIONS: Routine, systematic, and comprehensive cardiac evaluation, including a thorough history and directed laboratory assays, is essential for the care of HIV-infected adults and children as cardiovascular illness has become a part of care for long-term survivors of HIV infection. The history should include traditional risk factors for atherosclerosis, prior opportunistic infections, environmental exposures, and therapeutic and illicit drug use. Laboratory tests should include a lipid profile, fasting glucose, and HIV viral load. Asymptomatic cardiac disease related to HIV can be fatal, and secondary effects of HIV infection often disguise cardiac symptoms, so systematic echocardiographic monitoring is warranted.

Cardiovascular disease and therapeutic drug-related cardiovascular consequences in HIV-infected patients.

The incidence of cardiovascular disease is greatly increased in the HIV-infected population compared with people of the same age without HIV. Cardiovascular manifestations of HIV/AIDS include, but are not limited to, accelerated atherosclerosis, pulmonary arterial hypertension, vasculitis, myocarditis, cardiomyopathy, pericardial diseases, malignancy (myocardial Kaposi sarcoma and B-cell immunoblastic lymphoma), and endocarditis. Drug effects and interactions that challenge the cardiovascular system are even more prevalent in this population, and careful review and surveillance of medication effects is crucial as is careful selection of highly active antiretroviral therapy. A focused assessment and understanding of disease prevalence and presentation is needed as symptoms may be non-specific and cardiovascular physical examination findings indeterminate due to co-morbid conditions in the patient population now living with chronic HIV infection.

Heart failure and "inoperable" aortic stenosis: staged balloon aortic valvuloplasty and aortic valve bypass.

The prognosis for patients with symptomatic aortic stenosis is poor but is improved significantly by surgical aortic valve replacement. Unfortunately, many patients are refused surgery because of age, comorbidities, and hemodynamic instability. This report describes the successful use of balloon aortic valvuloplasty as a bridge to aortic valve bypass surgery (apicoaortic conduit) in an elderly patient with class IV congestive heart failure and severe left ventricular systolic dysfunction as a consequence of aortic stenosis who was not a candidate for traditional surgical valve replacement.

Impact of HIV and highly active antiretroviral therapy on leukocyte adhesion molecules, arterial inflammation, dyslipidemia, and atherosclerosis.

Highly active antiretroviral therapy (HAART) has greatly extended the lives of people infected with the human immunodeficiency virus (HIV). This reduced risk of early death from opportunistic infections or other sequelae of HIV infection, however, means that other possible causes of death emerge. Myocardial infarction has become a matter of particular concern. Two of the main sources of cardiovascular disease in this population are believed to be vascular inflammation and dyslipidemia. We review the evidence for this hypothesis and discuss the relationship of HIV to vascular inflammation. Current treatment guidelines do not recommend the immediate initiation of HAART unless warranted, potentially allowing long-term, unchecked viral impact on the development of atherosclerosis. Finally, we consider the protease inhibitors traditionally included in HAART regimens and their relationship to the development of dyslipidemia, as well as other classes of antiretrovirals, such as the non-nucleoside reverse transcriptase inhibitors, which might be a better choice for patients with cardiovascular risks. Other strategies, such as pharmacologic, nutritional, and physical activity interventions are discussed. The patients who might benefit most are those in whom the precursors of vascular plaques, such as fatty streak, smooth muscle cell, macrophage, and T-lymphocyte aggregation not yet identified by echocardiographic and biopsy findings have already developed as a result of unchecked viral inflammation and replication.

HIV-related cardiovascular disease and drug interactions.

HIV infection is a global public health issue that is frequently associated with cardiovascular involvement. These HIV-associated cardiovascular manifestations are often clinically occult or attributed incorrectly to other non-cardiac disease processes. A heightened awareness and routine screening for cardiovascular involvement in HIV-infected patients leads to earlier detection and the hope for a reduction in associated morbidity and mortality. Left ventricular dysfunction, an independent predictor of mortality in HIV-infected patients, is the result of many causes in this population and may result in dilated cardiomyopathy and congestive heart failure in about 10% of patients. Other HIV-associated cardiovascular problems include infective endocarditis, cardiovascular malignancy, pulmonary arterial hypertension, vasculitis, pericardial effusion, premature atherosclerosis, and arrhythmias. HIV-associated cardiovascular emergencies include congestive heart failure, pulmonary edema, supraventricular and ventricular arrhythmias, endocarditis, and tamponade. Anti-infective and immunomodulatory therapies may be particularly helpful in this population to reduce associated cardiovascular disease. Highly active antiretroviral therapy may result in lipodystrophy, hyperlipidemia, truncal adiposity, and insulin resistance that can be improved by physical activity and training programs. Cardiovascular complications of therapeutic drugs in HIV-infected patients include torsade de pointes, congestive heart failure, dyslipidemia, accelerated atherosclerosis, and myocardial infarction. In summary, cardiovascular complications are important contributors to morbidity and mortality in HIV-infected patients that can be detected early in many cases and treated effectively.

Cardiovascular risk factors, monitoring, and therapy for HIV-infected patients.

Cardiovascular complications are important contributors to morbidity and mortality in HIV-infected patients. These complications can usually be detected at subclinical levels with monitoring, which can help guide targeted interventions. This article reviews available data on types and frequency of cardiovascular manifestations in HIV-infected patients and proposes monitoring strategies aimed at early subclinical detection. In particular, we recommend routine echocardiography for HIV-infected patients, even those with no evidence of cardiovascular disease. We also review preventive and therapeutic cardiovascular interventions. For procedures that have not been studied in HIV-infected patients, we extrapolate from evidence-based guidelines for the general population.

Myocardial and Pericardial Disease in HIV.

Cardiovascular complications are frequently encountered in the HIV-infected population. Cardiac care providers should implement appropriate preventive, screening, and therapeutic strategies to maximize survival and quality of life in this increasingly treatable, chronic disease. All HIV-infected individuals should undergo periodic cardiac evaluation, including echocardiography, in order to identify subclinical cardiac dysfunction. Left ventricular (LV) dysfunction can result from, or be exacerbated by, a variety of treatable infectious, endocrine, nutritional, and immunologic disorders. Aggressive diagnosis and treatment of these conditions may lead to improvement or even normalization of myocardial function. Endomyocardial biopsy should be considered to direct etiology-specific therapy. Standard measures for the prevention and treatment of congestive heart failure are recommended for HIV-infected patients. Afterload reduction with angiotensin-converting enzyme inhibitors may be indicated for patients with elevated afterload and preclinical LV dysfunction diagnosed by echocardiogram. However, judicious drug selection and titration are necessary in this cohort of patients with frequent autonomic dysfunction, at risk for a number of potentially lethal drug interactions. Carnitine, selenium, and multivitamin supplementation should be considered, especially in those with wasting or diarrhea syndromes. Monthly intravenous immunoglobulin (IVIG) infusions have been demonstrated to preserve LV parameters in HIV-infected children; ventricular recovery has been documented in some children with recalcitrant HIV-related cardiomyopathy following IVIG infusion. We support the use of immunomodulatory therapy in the pediatric population, and look forward to further study into the efficacy and broader application of this approach. Highly active antiretroviral therapy (HAART) may be associated with dyslipidemia and the metabolic syndrome. This should be treated with dietary and possibly with pharmacologic interventions. Drug interactions need to be considered when instituting pharmacologic therapies. Pericardial effusions are often seen in patients with advanced HIV infection. Asymptomatic effusions are most often nonspecific in nature, related to the proinflammatory milieu found in advanced AIDS. Nonspecific effusions are a marker of advanced disease and do not require exhaustive etiologic evaluation. In contrast, large or symptomatic effusions are often associated with infection or malignancy, and warrant thorough investigation and etiology-specific treatment.