Clinical Importance of Fontan Circuit Thrombus in the Adult Population: Significant Association With Increased Risk of Cardiovascular Events

BackgroundThe impact of Fontan circuit thrombus is poorly understood. The objectives of this study were to determine (1) the incidence of Fontan circuit thrombus and proportion of silent thrombus; (2) any association between Fontan circuit thrombus and markers of Fontan circulatory dysfunction; and (3) the association of Fontan circuit thrombus with adverse cardiac outcomes.MethodsWe conducted a retrospective review of adult patients who underwent the Fontan procedure (aged > 18 years) followed at St. Paul’s Hospital who underwent cardiac computed tomography or magnetic resonance imaging assessment (n = 67). Fontan circulatory dysfunction markers included clinical heart failure, N-terminal pro-brain natriuretic peptide, ventricular dysfunction, atrioventricular valvular regurgitation, refractory arrhythmias, declining exercise capacity, and hepatic/renal dysfunction. Adverse cardiac outcomes were death, heart transplantation, or surgery for Fontan revision or atrioventricular valve replacement.ResultsFontan circuit thrombus was present in 15 of 67 patients (22%): 41% (7/17) classic/modified Fontan and 16% (8/50) total cavopulmonary connection. Incidence was 36% among those suspected to have Fontan circuit thrombus; 14% in those with no clinical/echocardiographic suspicion; and clinically silent in 40% diagnosed with Fontan thrombus. The time from Fontan surgery to Fontan circuit thrombus diagnosis was 22 ± 6 years in the classic/modified group vs 14 ± 8 years in the total cavopulmonary connection group (P = 0.03. Fontan circuit thrombus was associated with adverse cardiac outcomes (27% [4/15] vs 8% [4/52], P = 0.02), but there was no difference in Fontan circulatory dysfunction markers.ConclusionGiven the incidence of Fontan circuit thrombus and association with adverse cardiac outcomes, routine surveillance of the Fontan circuit should strongly be considered. The identification of thrombus should lead to anticoagulation implementation/optimization, along with screening/intervention for reversible Fontan circulatory issues in an attempt to prevent adverse cardiac outcomes.     

Cardiorenal Syndrome and Heart Failure—Challenges and Opportunities

Cardiorenal syndromes (CRS) describe concomitant bidirectional dysfunction of the heart and kidneys in which 1 organ initiates, perpetuates, and/or accelerates decline of the other. CRS are common in heart failure and universally portend worsened prognosis. Despite this heavy disease burden, the appropriate diagnosis and classification of CRS remains problematic. In addition to the hemodynamic drivers of decreased renal perfusion and increased renal vein pressure, induction of the renin-angiotensin-aldosterone system, stimulation of the sympathetic nervous system, disruption of balance between nitric oxide and reactive oxygen species, and inflammation are implicated in the pathogenesis of CRS. Medical therapy of heart failure including renin-angiotensin-aldosterone system inhibition and β-adrenergic blockade can blunt these deleterious processes. Renovascular disease can accelerate the progression of CRS. Volume overload and diuretic resistance are common and complicate the management of CRS. In heart failure and CRS being treated with diuretics, worsening creatinine is not associated with worsened outcome if clinical decongestion is achieved. Adjunctive therapy is often required in the management of volume overload in CRS, but evidence for these therapies is limited. Anemia and iron deficiency are importantly associated with CRS and might amplify decline of cardiac and renal function. End-stage cardiac and/or renal disease represents an especially poor prognosis with limited therapeutic options. Overall, worsening renal function is associated with significantly increased mortality. Despite progress in the area of CRS, there are still multiple pathophysiological and clinical aspects of CRS that need further research to eventually develop effective therapeutic options.     

Insights on Atrial Fibrillation in Congenital Heart Disease

Patients with congenital heart disease (CHD) have been surviving late into adulthood, with atrial arrhythmias being the most common long-term complication. In recent reports, atrial fibrillation (AF) tended to be the most common form of arrhythmias among groups of patients with adult CHD (ACHD) older than 50 years of age. When compared with their adult counterparts without CHD, AF in patients with ACHD has been characterized by a higher incidence and prevalence, younger age of onset, and a greater risk of progression to persistent AF. Risk factors for the development of AF are not well known but include older age, left atrial dilation, systemic hypertension, and multiple cardiac surgeries. Data on management options such as optimal antiarrhythmic drug therapy, indications for anticoagulation, and efficacy and safety of catheter ablation are limited. There is a crucial need for further research exploring management, prevention, and monitoring strategies for the growing ACHD patient population with AF. This report will provide a contemporary review of the epidemiology, pathophysiology, and management options for AF in this complex patient population.     

A Population-Based Study of Adherence to Guideline Recommendations and Appropriate-Use Criteria for Implantable Cardioverter Defibrillators

Studies evaluating physician adherence to guideline recommendations for implantable cardioverter defibrillator (ICD) therapy are sparse, and none exist for the application of appropriate-use criteria (AUC) in clinical practice. As part of a quality improvement initiative, a review of all ICD procedures was performed from January 1, 2015 to December 31, 2016 in Alberta, Canada, to evaluate the proportion of patients receiving appropriate ICD therapy and to identify reasons for nonadherence. Our device-implant process involves an electrophysiologist or implanting cardiologist evaluation, reminders of ICD eligibility criteria on the device requisition, and peer-review consensus. Implants were classified according to the 2008 American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) ICD guidelines, 2013 Canadian Cardiovascular Society (CCS) Cardiac Resynchronization Therapy (CRT) guidelines, and 2013 AUC. There were 1,300 ICD procedures performed, and the mean age was 63.8 ± 12.9 years; 79% were male; the mean ejection fraction was 0.32 ± 0.13, and 69% were for primary prevention. Among all implants, < 1% were discordant with American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) recommendations. Among CRT implants, 10% were inconsistent with Canadian Cardiovascular Society (CCS) recommendations. According to AUC, 92% of implants were appropriate. Reasons for nonadherence to ACC/AHA/HRS recommendations included QRS width < 120 msec (n = 3), LVEF > 0.35 (n = 2) and recent myocardial infarction (MI) (n = 1). The most common reason for nonadherence to AUC was the absence of criteria for classification (n = 57, 4%). In this population-based study, we found that a process of specialist evaluation, eligibility reminders on device forms, and peer-review consensus may improve adherence to guideline recommendations and AUC for ICD therapy.     

The Multiple Causes of Stroke in Atrial Fibrillation: Thinking Broadly

Atrial fibrillation (AF) is numerically the most important risk factor for stroke. It is well established that patients with AF have a 5-fold increased risk of stroke relative to those without and that anticoagulation reduces the risk of stroke by approximately two-thirds. Definitively attributing the mechanism of an individual stroke to AF is more problematic, however. In fact, there is no way to reliably establish the etiology of any ischemic infarction. This necessitates screening for all potential stroke risk factors and treating accordingly. The pattern of infarction is often used to classify the presumed mechanism of infarction as thrombotic or embolic, although even this is approach is based on association and increasingly is recognized as not completely reliable. Furthermore, it should not dictate management—patients with perforating arterial territory infarcts with AF also require and benefit from anticoagulation. Likewise, if other potential embolic sources beyond AF are identified, anticoagulation remains the standard of care. The traditional conceptual model of the mechanistic link between AF and cardioembolic infarction is likely oversimplified. Long-term cardiac rhythm recording studies indicate an inconsistent temporal relationship between AF and infarction. This suggests that cardioembolic stroke in patients with AF may result from the underlying atrial cardiopathy, rather than the rhythm disturbance leading to atrial stasis and thromboembolism. We reviewed traditional and current concepts, as well as evidence for the role of AF in ischemic stroke.     

Variables Associated With Cardiac Surgical Waitlist Mortality From a Population-Based Cohort

Background

Cardiac surgery waitlist recommendations, which were developed based on expert opinion, poorly predict preoperative mortality. Studies reporting risk factors for waitlist mortality have not evaluated the risks including nonadherence to waitlist benchmarks.

Transition and Transfer From Pediatric to Adult Congenital Heart Disease Care in Canada: Call For Strategic Implementation

Dramatic increases in survival to adulthood for persons born with congenital heart disease (CHD) have led rise to a corresponding need to provide age-appropriate and developmentally appropriate care across the lifespan. Health care transition is a multidimensional process that ideally begins in early adolescence in the pediatric setting and continues through young adulthood with input from both pediatric and adult CHD providers. Preparation for transition includes the fostering of adolescents' knowledge of their CHD and of self-management and self-advocacy skills needed for lifelong management of chronic disease. Transfer is the event in time when a patient’s care and ownership of health records is taken over by the adult health care team; this is just one element of the broader transition process. Transfer typically occurs by age 18 throughout much of Canada. Successful transition is a shared responsibility, requiring engaged pediatric and adult providers and partnership with both young adults and their parents, all of whom may struggle with this process. An interdisciplinary approach to transition is recommended, given that health care transition is a complex process that occurs within the broader context of young adults’ lives. This review summarizes existing evidence regarding transition and transfer, offers perspectives from multiple stakeholders, and proposes a transition curriculum of development of CHD education and self-management and self-advocacy skills. Specific recommendations to improve implementation of transition and transfer care within the Canadian context are provided. This review sheds light on the current capacity and challenges of adult CHD providers and proposes directions to move this field forward.     

Challenges With Severe Coronary Artery Calcification in Percutaneous Coronary Intervention: A Narrative Review of Therapeutic Options

Coronary calcification often complicates atherosclerosis. With an aging population, coinciding with lower thresholds for coronary angiography and percutaneous coronary intervention (PCI), severe calcific coronary stenoses remain a challenge for interventional cardiologists. Although advances in coronary guidewires, percutaneous balloons, and adjunctive procedural devices have improved success of PCI, recalcitrant calcified lesions not amenable to the conventional technique frequently occur. Coronary atherectomy with plaque modification provides a therapeutic alternative. As such, various modalities such as rotational, orbital or laser atherectomy, and more recently shockwave lithoplasty have become therapeutic options for PCI. We provide a summary of the principles, technique, and contemporary evidence for these currently approved devices designed to treat severe coronary calcific lesions.     

Transcatheter Mitral Valve Intervention for Chronic Mitral Regurgitation: A Plethora of Different Technologies

Chronic mitral regurgitation (MR) remains a common cardiovascular condition resulting in significant morbidity and mortality. With an aging population, increasing trends for both primary (degenerative) and secondary (functional) MR have become apparent. Although the gold standard remains surgical intervention with mitral valve repair/replacement, comorbid conditions have steered the development of less invasive technologies to mitigate perioperative surgical risk. Transcatheter mitral valve repair using a percutaneous edge-to-edge technique is the most widely available choice at present. However, other transcatheter mitral valve repair techniques such as annuloplasty and chordal implantation are notable alternatives. Moreover, emerging technologies in transcatheter mitral valve replacement are rapidly establishing their roles in the field of chronic severe MR therapy. Hence, it is imperative to understand the indications and limitations of these various transcatheter mitral valve interventions to provide the best and most up-to-date clinical care for patients. This review will outline current evidence and patient selection criteria for such device-based therapies.     

Fontan-Associated Liver Disease: Evidence for Early Surveillance of Liver Health in Pediatric Fontan Patients

The growing awareness of Fontan-associated liver disease (FALD) in adults with Fontan physiology has provided the impetus to better understand the natural history of FALD and develop a reliable noninvasive method to diagnose and monitor liver health in this population. Biochemical and imaging tests have been investigated to determine their association with liver pathology. The congestive hepatopathy that develops after the Fontan procedure has made interpreting these tests challenging. We have reviewed and summarized the current understanding and ongoing challenges with respect noninvasive measures of liver health in Fontan patients including biochemical tests, elastography, hepatic ultrasound, cross-sectional imaging, and hemodynamics and how they relate to liver pathology. It has been demonstrated from biopsy data that liver disease is universal and progressive in Fontan patients. Traditional biochemical tests, elastography, and imaging methods are often abnormal in Fontan patients but do not reliably indicate significant liver pathology. Although a reliable means for surveillance of FALD remains elusive, this continues to be an active area of investigation, with promising recent developments. Therapeutic options for FALD are limited, with cardiac transplant as the only option that can stabilize FALD pathology and improve symptomatology. Given the limited therapeutic options and the prevalence of liver disease in Fontan patients, there is a compelling case for early routine surveillance of liver health and promotion of global liver health.     

Contemporary Application of Point-of-Care Echocardiography in the Emergency Department

Point-of-care echocardiography is revolutionizing the management of patients presenting with undifferentiated shock and cardiac arrest in the emergency department (ED). Its primary purpose is to aid the clinician in rapidly ruling in and ruling out life-threatening diagnoses at the bedside. In addition, it has become an important component of the clinical examination for stable patients seen in the ED with nonspecific signs and symptoms such as shortness of breath or syncope. Although first described to facilitate the diagnosis of pericardial effusions and cardiac standstill, ED echocardiography has since evolved and is now widely used by emergency physicians to help diagnose other important cardiovascular pathologic conditions that may be contributing to undifferentiated shock, such as left ventricular failure and right ventricular dilatation resulting from pulmonary embolism. The use of echocardiography in the ED continues to expand, with advanced applications that include valvular assessment, diastolic dysfunction, and regional wall motion abnormalities, as well as the use of point-of-care transesophageal echocardiography. As the diffusion of these new skills continues and becomes routine, it will alter the practice of emergency medicine and the interaction with consulting cardiologists.     

Geographical Differences in Comorbidity Burden and Outcomes in Adults With Syncope Hospitalizations in Canada

A recent study found that rates of hospitalization for syncope vary across provinces; however, it is unknown whether differences in comorbidity burden and outcomes also exist. The Canadian Institute for Health Information Discharge Abstract Database was used to identify primary syncope hospitalizations (ICD-10 code R55) from 2004 to 2013 for all provinces (except Quebec). Charlson comorbidity score was calculated from comorbidities at the time of hospitalization. Outcomes were defined as in-hospital mortality, 30-day readmission for any cause, and syncope. Logistic regression models were constructed for odds ratios (ORs) and 95% confidence intervals (CIs) to estimate interprovincial differences in outcomes. The interprovincial range (IPR) for mean age was 61.1 ± 17.5 to 73.7 ± 16.3 years, and at least half were male patients. There were significant differences in comorbidity burden across provinces (P < 0.01); however, the majority of patients had a Charlson comorbidity score = 0 (IPR, 53.9%- 71.9%). In multivariable analysis, compared with Ontario, in-hospital mortality was higher for British Columbia (OR, 1.59; 95% CI, 1.22-2.06), Nova Scotia (OR, 1.67; 95% CI, 1.05-2.65), and Newfoundland (OR, 2.27; 95% CI, 1.29-4.00); 30-day readmission for any cause was higher for British Columbia (OR, 1.15; 95% CI, 1.06-1.26), Alberta (OR, 1.19; 95% CI, 1.07-1.31), Manitoba (OR, 1.36; 95% CI, 1.18-1.56), and Prince Edward Island (OR, 1.38; 95% CI, 1.0-1.89), and all outcomes were higher in Saskatchewan. There is significant interprovincial heterogeneity in comorbidity burden and outcomes for hospitalizations for syncope. Future research evaluating whether standardized practices for management of syncope reduce variability and improve healthcare utilization and costs is needed.     

Decision Support Tools: Realizing the Potential to Improve Quality of Care

Delivering evidence-based, personalized care that engages patients requires profound changes in the structure, process, and organization of care, along with revised incentives to support such changes. Health care providers must absorb and apply a vast, usually overwhelming, amount of scientific information to provide high-quality patient care. Accordingly, care remains inconsistent, with unintentional adverse consequences. Decision support tools can provide patient-specific assessments that support clinical decisions, improve prescribing practices, reduce medication errors, improve the delivery of primary as well as secondary prevention, and improve adherence to standards of care. Decision support tools are created using an individual patient’s genetic, sociodemographic, and clinical characteristics to improve the delivery of precise, personalized care. Implementation requires ease of use for busy clinicians; uptake improves with active education, and gradual adoption of a tool integrated into care processes without disrupting clinical work flow. As health care systems continue to evolve and computerized support increases, increased implementation of decision support tools that are provided automatically as part of usual work flow, with clinically actionable recommendations at the point of care, requiring accountability for deviations from recommended therapy, represent an important opportunity to enhance quality of care by tailoring treatment to risk, improving the consistency of health care delivery, increasing patient knowledge and engagement, and avoiding specific therapeutic interventions in patients who will receive no benefit. However, successful implementation also requires strategies to engage providers in accepting and using these tools to improve care.     

Congenital Heart Disease and Women’s Health Across the Life Span: Focus on Reproductive Issues

From adolescence to older age, women with congenital heart disease (CHD) face unique challenges. In this review we explore the ways in which CHD affects women’s sexual and reproductive health and, in turn, how their sexual and reproductive history affects the course of their CHD. In adolescence, special attention must be paid to menstrual irregularities and concerns of developing sexuality and self-image. Discussions about sexuality and reproduction are an important part of transition planning and must be done with an awareness of the adolescent’s developing understanding and maturity. Pregnancy imposes a hemodynamic load on the heart which may lead to cardiac, obstetric, and fetal/neonatal complications in women with CHD. Prepregnancy counselling must include an assessment of maternal and fetal risk according to several well developed models. Counselling should also include discussions about fertility and alternatives to pregnancy when appropriate. Recommendations for contraception must be made according to the patient’s cardiac lesion. In caring for women with CHD during pregnancy, a multidisciplinary cardio-obstetrics team is recommended to optimize care. More research is needed into the long-term impact of pregnancy on the prognosis of patients with CHD. As women with CHD increasingly survive into old age, more attention will need to be directed toward the treatment of menopause and acquired heart disease in this population.     

Acute Decompensated Heart Failure After Initiation of Amiodarone in a Patient With Anderson-Fabry Disease

A 54-year-old man with the lysosomal storage disorder Anderson-Fabry disease (AFD) and cardiac involvement was placed on amiodarone for treatment of symptomatic paroxysmal atrial fibrillation. Shortly thereafter, he developed symptoms of acute decompensated heart failure, requiring hospital admission. Endomyocardial biopsy demonstrated findings consistent with AFD and possible amiodarone toxicity. Amiodarone was discontinued, and the patient’s heart failure resolved with return to baseline status. Amiodarone is known to alter lysosomal pH and enzyme activity, and this case illustrates how it should be used with considerable caution in patients with AFD.     

Reversal of protein losing enteropathy with prednisone in adults with modified Fontan operations: long term palliation or bridge to cardiac transplantation?

Protein losing enteropathy (PLE), defined as severe loss of serum protein into the intestine, occurs in 4-13% of patients after the Fontan procedure and carries a dismal prognosis with a five year survival between 46% and 59%. Chronically raised systemic venous pressure is thought to be responsible for the development of PLE in these patients, with perhaps superimposed immunological or inflammatory factors. The success rate of contemporary medical, transcatheter, and surgical treatments attempting to reduce systemic venous pressure ranges from 19% to 40%. Prednisone treatment for PLE has been tried, with variable success rates reported in children. The effect of prednisone in adult patients with PLE after the Fontan procedure is largely unknown. Two cases of PLE in adults (a 39 year old woman and a 25 year old man) after modified Fontan procedure who responded dramatically to oral prednisone treatment are reported, suggesting that a trial of this "non-invasive" treatment should be considered as long term palliation or bridge to cardiac transplantation.     

Acute Coronary Syndromes and Heart Failure Critical Care Units Utilization and Outcomes in Teaching and Community Hospitals: A National Population-Based Analysis

Acute coronary syndromes (ACS) and heart failure (HF) are the leading diagnoses in patients admitted to critical care units (CCUs). Little is known about the differences between CCU resource use and outcomes across hospital types. The Canadian Institute for Health Information was used to identify patients hospitalized with primary diagnoses of ACS or HF. CCUs were categorized as teaching, large community, medium community, and small community hospitals. Outcomes included CCU rates of admission, use of critical care therapy/procedures, and in-hospital mortality. Among 204,900 patients hospitalized with ACS or HF, 73,338 (35.8%, hospital range 0% to 81.4%) were admitted to CCUs, and it varied across hospital types: 41.0% in teaching, 30.0% in large, 45.4% in medium, and 30.9% in small community hospitals (P < 0.001). The percentage of patients admitted to CCUs who received critical care therapies in teaching, large, medium, and small hospitals were as follows: 73.6%, 50.9%, 24.6%, and 8.8% (P < 0.0001). Compared with the in-hospital mortality rate for patients admitted to CCUs in teaching hospitals (8.2%), outcomes were worse for CCU patients in large (11.0%, adjusted odds ratio [aOR] 1.50; 95% CI, 1.19-1.90), medium (10.5%, aOR 1.56; 95% CI, 1.27-1.92), and small community hospitals (9.2%, aOR 1.59; 95% CI, 1.20-2.10). Patients admitted with ACS or HF to teaching hospital CCUs had a higher observed use of critical care therapies and lower mortality compared with community hospitals. These differences highlight the need to examine differences in CCU admission thresholds, resource utilization, and outcomes across hospitals types.     

Heart Failure With Preserved Ejection Fraction in Diabetes: Mechanisms and Management

Diabetes mellitus (DM) is a major cause of heart failure in the Western world, either secondary to coronary artery disease or from a distinct entity known as “diabetic cardiomyopathy.” Furthermore, heart failure with preserved ejection fraction (HFpEF) is emerging as a significant clinical problem for patients with DM. Current clinical data suggest that between 30% and 40% of patients with HFpEF suffer from DM. The typical structural phenotype of the HFpEF heart consists of endothelial dysfunction, increased interstitial and perivascular fibrosis, cardiomyocyte stiffness, and hypertrophy along with advanced glycation end products deposition. There is a myriad of mechanisms that result in the phenotypical HFpEF heart including impaired cardiac metabolism and substrate utilization, altered insulin signalling leading to protein kinase C activation, advanced glycated end products deposition, prosclerotic cytokine activation (eg, transforming growth factor-β activation), along with impaired nitric oxide production from the endothelium. Moreover, recent investigations have focused on the role of endothelial-myocyte interactions. Despite intense research, current therapeutic strategies have had little effect on improving morbidity and mortality in patients with DM and HFpEF. Possible explanations for this include a limited understanding of the role that direct cell-cell communication or indirect cell-cell paracrine signalling plays in the pathogenesis of DM and HFpEF. Additionally, integrins remain another important mediator of signals from the extracellular matrix to cells within the failing heart and might play a significant role in cell-cell cross-talk. In this review we discuss the characteristics and mechanisms of DM and HFpEF to stimulate potential future research for patients with this common, and morbid condition.     

Cardiovascular Efficacy and Safety of PCSK9 Inhibitors: Systematic Review and Meta-analysis Including the ODYSSEY OUTCOMES Trial

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are efficacious lipid-lowering agents, but more precise estimates of their effects on major adverse cardiovascular events (MACE), mortality, and safety are needed. We systematically reviewed and meta-analyzed randomized controlled trials with durations ≥ 6 months comparing MACE, mortality, and safety with PCSK9 inhibitors vs control. We searched CENTRAL, Embase, MedLine and the grey literature to November 7, 2018. From 2048 articles, we included 23 trials (n = 60,723). PCSK9 inhibitors reduced MACE (relative risk, 0.83; 95% confidence interval, 0.78-0.88), but did not clearly reduce mortality (relative risk, 0.93; 95% confidence interval, 0.85-1.02) or increase adverse events. In conclusion, PCSK9 inhibitors reduce nonfatal MACE, are well tolerated, but effects on mortality remain unclear.     

Eisenmenger Syndrome: A Multisystem Disorder—Do Not Destabilize the Balanced but Fragile Physiology

Eisenmenger syndrome is the most severe and extreme phenotype of pulmonary arterial hypertension associated with congenital heart disease. A large nonrestrictive systemic left-to-right shunt triggers the development of pulmonary vascular disease, progressive pulmonary arterial hypertension, and increasing pulmonary vascular resistance at the systemic level, which ultimately results in shunt reversal. Herein, we review the changing epidemiological patterns and pathophysiology of Eisenmenger syndrome. Multiorgan disease is an integral manifestation of Eisenmenger syndrome and includes involvement of the cardiac, hematological, neurological, respiratory, gastrointestinal, urinary, immunological, musculoskeletal, and endocrinological systems. Standardized practical guidelines for the assessment, management, risk stratification, and follow-up of this very fragile and vulnerable population are discussed. Multidisciplinary care is the best clinical practice. An approach to the prevention and management of a broad spectrum of complications is provided. Relevant therapeutic questions are discussed, including anticoagulation, noncardiac surgery, physical activity, transplantation, and advanced-care planning (palliative care). Advanced pulmonary arterial hypertension therapies are indicated in patients with Eisenmenger syndrome and World Health Organization functional class II or higher symptoms to improve functional capacity, quality of life, and—less well documented—survival. Specific recommendations regarding monotherapy or combination therapy are provided according to functional class and clinical response. The ultimate challenge for all care providers remains early detection and management of intracardiac and extracardiac shunts, considering that Eisenmenger syndrome is a preventable condition.