Metabolomic Profiling of Adults with Congenital Heart Disease.

Metabolomic analysis may provide an integrated assessment in genetically and pathologically heterogeneous populations. We used metabolomic analysis to gain mechanistic insight into the small and diverse population of adults with congenital heart disease (ACHD). Consecutive ACHD patients seen at a single institution were enrolled. Clinical variables and whole blood were collected at regular clinical visits. Stored plasma samples were analyzed for the concentrations of 674 metabolites and metabolic markers using mass spectrometry with internal standards. These samples were compared to 28 simultaneously assessed healthy non-ACHD controls. Principal component analysis and multivariable regression modeling were used to identify metabolites associated with clinical outcomes in ACHD. Plasma from ACHD and healthy control patients differed in the concentrations of multiple metabolites. Differences between control and ACHD were greater in number and in degree than those between ACHD anatomic groups. A metabolite cluster containing amino acids and metabolites of amino acids correlated with negative clinical outcomes across all anatomic groups. Metabolites in the arginine metabolic pathway, betaine, dehydroepiandrosterone, cystine, 1-methylhistidine, serotonin and bile acids were associated with specific clinical outcomes. Metabolic markers of disease may both be useful as biomarkers for disease activity and suggest etiologically related pathways as possible targets for disease-modifying intervention.

Factors associated with a lower chance of having gaps in care in adult congenital heart disease.

BACKGROUND: To promote good health in patients with congenital heart disease (CHD), prevention of gaps in care is essential, as adverse prognosis is associated with care gaps. A well-organised, formal transition programme may help prevent loss to follow up after leaving paediatric care. To inform the development of a transition programme, we investigated factors associated with care gaps in adults with CHD. METHODS: Between 15 October 2018 and 15 November 2019 data on patient characteristics and patient experiences with transition-related education, difficulties, and gaps in care were collected and assessed in 87 adults with CHD. Two groups (with gaps in care versus without gaps) were compared to identify informative differences using chi-squared, Fisher's exact tests, or Wilcoxon rank-sum tests. To assess the relationship between care gaps and identified variables, factors with significant difference (p < 0.05) in bivariate analyses were employed as covariates in multivariable logistic regression analysis. RESULTS: About half of the study cohort reported having gaps in care. In a multivariate model, patients having thorough discussion about the importance of receiving adult care in paediatric care were 70% less likely to experience gaps (odds ratio 0.303, 95% CI 0.14, 0.66). Forty-seven percent of patient-perceived barriers to transitioning originated from negative feelings associated with transfer. CONCLUSION: Gaps in care are highly prevalent in adults with CHD. For a transition programme to be most effective, curriculum development may need to consider the differential impact of various factors and target areas to mitigate the psychological stress associated with transfer.

Development of a Novel Adult Congenital Heart Disease-Specific Patient-Reported Outcome Metric.

Background Patient-reported outcome metrics (PROs) quantify important outcomes in clinical trials and can be sensitive measures of patient experience in clinical practice. Currently, there is no validated disease-specific PRO for adults with congenital heart disease (ACHD). Methods and Results We conducted a preliminary psychometric validation of a novel ACHD PRO. ACHD patients were recruited prospectively from 2 institutions and completed a series of questionnaires, a physician health assessment, and a 6-minute walk test. Participants returned to complete the same questionnaires and assessment 3 months±2 weeks later. We tested the internal consistency and test-retest reliability by comparing responses among clinically stable patients at the 2 study visits. We assessed convergent and divergent validity by comparison of ACHD PRO responses to existing validated questionnaires. We assessed responsiveness by comparison with patient-reported clinical change. One hundred three patients completed 1 study visit and 81 completed both. The ACHD PRO demonstrated good internal consistency in each of its 5 domains (Cronbach's α: 0.87; 0.74; 0.74; 0.90; and 0.89, respectively) and in the overall summary score (0.92). Test-retest reliability was good with an intraclass correlation ≥0.73 for all domains and 0.78 for the Summary Score. The ACHD PRO accurately assessed domain concepts based on comparison with validated standards. Preliminary estimates of responsiveness suggest sensitivity to clinical status. Conclusions These studies provide initial support for the validity and reliability of the ACHD PRO. Further studies are needed to assess its sensitivity to changes in clinical status.

Association between psychological resilience and subjective well-being in older adults living with chronic illness.

We aimed to determine the impact of resilience on well-being in chronically ill adults, hypothesizing that resilient participants would have higher quality of life, life satisfaction, and happiness and less psychological distress than those with low resilience. Patients who received treatment for a chronic illness at Baylor Scott & White Health and self-identified an informal caregiver (nonpaid friend/family member who provides regular care) were eligible. After the Center for Community Research and Development administered a phone survey from March to June 2017, we built linear and ordinal logistic regression models to assess the effect of resilience on well-being while adjusting for health, finances, marital status, and gender. Forty-one participants completed the study. The average age was 67 ± 10 years; the most common illness was heart failure (39%). Participants had high resilience (median 4 [quartile 1 = 3, quartile 3 = 5], scale: 1-5), low psychological distress (4 [2, 7], scale: 0-24), high quality of life (8 [5, 9], scale: 0-10) and life satisfaction (5 ± 2, scale: 1-7), and 81% were pretty/very happy. The effect of resilience was significant in the expected directions in unadjusted analyses. After accounting for demographic, social, and clinical factors, resilience remained highly significant for psychological distress and happiness (b = -1.91, P = 0.002; odds ratio = 4.71, P = 0.003, respectively). Psychological resilience may be a resource to preserve well-being for chronically ill individuals.

Differential impact of physical activity type on depression in adults with congenital heart disease: A multi-center international study.

OBJECTIVE: This study aimed to examine the association between physical activity (PA) and depression in a large international cohort of adults with congenital heart disease (ACHD) as data about the differential impact of PA type on depression in this population are lacking. METHODS: In 2018, we conducted a cross-sectional assessment of 3908 ACHD recruited from 24 ACHD-specialized centers in 15 countries between April 2013 to March 2015. The Hospital Anxiety and Depression Scale was used to assess self-reported depressive symptoms and the Health-Behavior Scale-Congenital Heart Disease was used to collect PA information. Cochran-Armitage tests were performed to assess trends between depressive symptom levels and PA participation. Chi-Square and Wilcoxon Rank Sum tests were utilized to examine relations between depressive symptom levels and patient characteristics. Stepwise multivariable models were then constructed to understand the independent impact of PA on depressive symptoms. RESULTS: The overall prevalence of elevated depressive symptoms in this sample was 12% with significant differences in rates between countries (p < .001). Physically active individuals were less likely to be depressed than those who were sedentary. Of the 2 PA domains examined, sport participation rather than active commute was significantly associated with reduced symptoms of depression. After adjustment in multivariable analysis, sport participation was still significantly associated with 38% decreased probability of depressive symptoms (p < .001). CONCLUSIONS: Sport participation is independently associated with reduced depressive symptoms. The development and promotion of sport-related exercise prescriptions uniquely designed for ACHD may improve depression status in this unique population.

Cardiac Denial and Expectations Associated With Depression in Adults With Congenital Heart Disease.

Depression in adults with congenital heart disease is highly prevalent and strongly associated with adverse prognosis. Better management of risk factors for depression may improve clinical outcomes in this population. We conducted a single-site, cross-sectional study of 78 adults with congenital heart disease followed at Washington University School of Medicine. Data considered in the analyses included retrospectively obtained clinical information and patients' self-assessed psychosocial functioning and health status. To identify the clinical and psychosocial variables associated with depression, we built a stepwise multivariate model to measure the relative contribution of these variables to depression status. The prevalence of depression in our sample was 26%. Our model accounted for approximately 67% of the variability in depression scores. The final model consisted of the Cardiac Denial of Impact Scale, expectations domain of Barriers to Care, and the energy and social domains of the Rand 36-Item Short Form Health Survey. Clinical variables did not predict variability in depression scores. In conclusion, greater cardiac denial and negative expectations of the healthcare team were associated with increased depression symptoms in ACHD.

Physical Activity-Related Drivers of Perceived Health Status in Adults With Congenital Heart Disease.

Data on the differential impact of physical activity on perceived health status (PHS) in a large adult congenital heart disease (ACHD) patient population are lacking. We conducted a cross-sectional assessment of 4,028 ACHD patients recruited from 24 ACHD-specialized centers in 15 countries across 5 continents to examine the association between physical activity and PHS in a large international cohort of ACHD patients. A linear analog scale of the EuroQol-5D 3 level version and the 12-item Short Form Health Survey-version 2 were used to assess self-reported health status and the Health-Behavior Scale-Congenital Heart Disease was used as a subjective measurement of physical activity type, participation, and level. Correlation analyses and Wilcoxon Rank Sum tests examined bivariate relations between sample characteristics and PHS scores. Then, multivariable models were constructed to understand the impact of physical activity on PHS. Only 30% of our sample achieved recommended physical activity levels. Physically active patients reported better PHS than sedentary patients; however, the amount of physical activity was not associated with PHS. Further statistical analyses demonstrated that specifically sport participation regardless of physical activity level was a predictor of PHS. In conclusion, the majority of ACHD patients across the world are physically inactive. Sport participation appears to be the primary physical activity-related driver of PHS. By promoting sport-related exercise ACHD specialists thus may improve PHS in ACHD patients.

Clinical and Psychological Drivers of Perceived Health Status in Adults With Congenital Heart Disease.

The factors having the greatest impact on self-reported health status in adults with congenital heart disease (ACHD) remain incompletely studied. We conducted a single-site, cross-sectional study of ACHD patients followed at the Center for ACHD at Washington University School of Medicine, including retrospectively gathered clinical data and psychometric and health status assessments completed at the time of enrollment. To identify primary drivers of perceived health status, we investigated the impact of the demographic, clinical, and psychological variables on self-reported health status as assessed using the Rand 36-Item Short Form Health Survey. Variables with significant associations within each domain were considered jointly in multivariable models constructed via stepwise selection. There was domain-specific heterogeneity in the variables having the greatest effect on self-reported health status. Depression was responsible for the greatest amount of variability in health status in all domains except physical functioning. In the physical functioning domain, depression remained responsible for 5% of total variability, the third most significant variable in the model. In every domain, depression more strongly influenced health status than did any cardiac-specific variable. In conclusion, depression was responsible for a significant amount of heterogeneity in all domains of self-perceived health status. Psychological variables were better predictors of health status than clinical variables.

Comparison of Characteristics of Patients Undergoing Heart Transplantation at the Same Hospital in Two Different Time Periods (1997-2012 and 2013-2015).

Heart transplantation (HT) increases at some centers each year and decreases at others. We examined characteristics of patients having HT at the same hospital in 2 different time periods (1997-2012 and 2013-2015) by 2 different surgical groups. We compared certain clinical and morphological finding in 291 patients having HT 1997 to 2012 to finding in 228 other patients having HT from 2013 to 2015. Several significant (p <0.05) differences were found: in the most recent time period (2013-2015) compared to the earlier time period (1997-2012), the mean ages of the men were older (57 years -vs- 55 years); diabetes mellitus was more frequent (37% -vs- 21%); systemic hypertension (by history) was more frequent (59% -vs- 32%); the mean body mass index was higher (29.2 kg/m(2) -vs- 26.5 kg/m(2)), and mean heart weight was lower in both men (509 g -vs- 549 g) and women (422 g -vs- 454 g). There were insignificant (p >0.05) differences in gender, frequency of massive cardiac adiposity, underlying cardiac condition, frequency of coronary heart disease, and frequency of previous insertion of a left ventricular assist device. In conclusion, certain characteristics of patients having HT at one Texas hospital changed in several respects in 2 time periods corresponding to changes in surgeons doing the HTs.

Mitral Valve Replacement After Failed Mitral Ring Insertion With or Without Leaflet/Chordal Repair for Pure Mitral Regurgitation.

Mitral repair operations for correction of pure mitral regurgitation (MR) are generally quite successful. Occasionally, however, the reparative procedure incompletely corrects the MR or the MR recurs. From March 1993 to January 2016, twenty nine patients had mitral valve replacement after the initial mitral repair operation, and observations in them were analyzed. All 29 patients at the repair operation had an annular ring inserted and later (<1 year in 6 and >1 year in 21) mitral valve replacement. The cause of the MR before the repair operation appears to have been prolapse in 16 patients (55%), secondary (functional) in 12 (41%) (ischemic in 5), and infective endocarditis which healed in 1 (3%). At the replacement operation the excised anterior mitral leaflet was thickened in all 29 patients. Some degree of stenosis appeared to have been present in 16 of the 29 patients before the replacement operation, although only 10 had an echocardiographic or hemodynamic recording of a transvalvular gradient; at least 11 patients had restricted motion of the posterior mitral leaflet; 10, ring dehiscence; 2, severe hemolysis; and 2, left ventricular outflow obstruction. In conclusion, there are multiple reasons for valve replacement after earlier mitral repair. Uniformly, at the time of the replacement, the mitral leaflets were thickened by fibrous tissue. Measurement of the area enclosed by the 360° rings and study of the excised leaflet suggest that the ring itself may have contributed to the leaflet scarring and development of some transmitral stenosis.

Frequency of Massive Cardiac Adiposity (Floating Heart) in the Native Hearts of Patients Having Heart Transplantation at a Single Texas Hospital (2013 to 2015) and Comparison of Various Clinical and Morphologic Variables in the Patients With Massive Versus Nonmassive Cardiac Adiposity.

Body weight continues to increase worldwide due primarily to the increase in body fat. This study analyzes the frequency of massive adiposity at hearts of patients who underwent heart transplantation (HT) determined by the ability of the heart to float in a container of 10% formaldehyde (because adipose tissue is lighter than myocardium) and compares certain characteristics of those patients with and without floating hearts. The hearts studied at HT during a 3-year period (2013 to 2015) at Baylor University Medical Center were carefully "cleaned" and weighed by the same individual and tested as to their ability to float in a container of formaldehyde, an indication of severe cardiac adiposity. Of the 220 hearts studied, 84 (38%) floated in a container of formaldehyde and 136 (62%) did not. Comparison of the 84 patients with floating hearts to the 136 with nonfloating hearts showed a significant difference in ages, but a nonsignificant difference in gender, body mass index, frequency of systemic hypertension, or diabetes mellitus. The odds of a heart being a floating one was increased in patients with a diagnosis of ischemic cardiomyopathy (unadjusted odds ratio 2.12, 95% CI 1.21 to 3.70). The frequency of massive cardiac adiposity in the native hearts of patients having HT (38%) is striking and appears to have increased in frequency in the recent decades.

Frequency of Massive Cardiac Adiposity (Floating Heart) at Necropsy and Comparison of Clinical and Morphologic Variables With Cases With Nonmassive Cardiac Adiposity at a Single Texas Hospital, 2013 to 2014.

Body weight continues to increase worldwide primarily because of the increase in body fat. This study analyzes the frequency of massive adiposity at autopsy determined by the ability of the heart to float in a container of 10% formaldehyde (because adipose tissue is lighter than myocardium) and compares certain findings in the patients with floating to those with nonfloating hearts. The hearts studied at necropsy during a 2-year period (2013 to 2014) at Baylor University Medical Center were carefully "cleaned" and weighed by the same person and tested as to their ability to float in a container of formaldehyde, an indication of severe cardiac adiposity. Of the 146 hearts studied, 76 (52%) floated in a container of formaldehyde and 70 (48%) did not. Comparison of the 76 patients with floating hearts with the 70 with nonfloating hearts showed significant differences in ages (62 ± 13 vs 58 ± 14 years). No significant differences between the 2 groups were found in gender, body mass index, frequency of systemic hypertension or diabetes mellitus, either acute or healed myocardial infarction, or whether death was due to a coronary or a noncoronary condition. A weak correlation was found between body mass index and heart weight in both men and women and in both floating and nonfloating hearts. The massive quantity of cardiac adipose tissue (floating heart) appears to have increased enormously in recent decades in the United States.

Morphologic demonstration of spontaneous and surgical closure of membranous ventricular septal defect.

This report demonstrates morphologic features of membranous ventricular septal defect that was closed spontaneously in one patient and operatively in the other.

A review of spontaneous closure of ventricular septal defect.

Ventricular septal defect (VSD) is the most common congenital heart malformation and can be detected during the prenatal and postnatal period, in childhood, and in adulthood. Spontaneous closure of VSD can be determined through a variety of methods-echocardiography, Doppler color flow imaging, angiography, auscultation, and cardiac catheterization-and can be proven by pathological evidence at necropsy. There are two major types of VSD, membranous and muscular, as well as the perimembranous variety, which comprises variable portions of the adjacent muscular septum but lacks the membranous septum. VSD appears either as an isolated cardiac defect without other abnormalities or with several complex malformations. It has long been recognized that VSD can close spontaneously, but the incidence of spontaneous VSD closure is still uncertain. Since necropsy study of the hearts with VSD has rarely been reported, information on morphological features of spontaneous VSD closure remains limited. In addition, the mechanisms for spontaneous VSD closure are not fully understood. Herein, we present a brief review of the incidence of spontaneous VSD closure, morphological characteristics of the closure, and the main mechanisms responsible for the closure.

Clinical and morphologic features of acute, subacute and chronic cor pulmonale (pulmonary heart disease).

Described are certain clinical and morphologic features of one patient with acute, another with subacute, and one with chronic cor pulmonale. All 3 had evidence of severe pulmonary hypertension. The patient with acute cor pulmonale 4 days after coronary bypass for unstable angina pectoris suddenly developed severe breathlessness with cyanosis and had fatal cardiac arrest and necropsy disclosed massive pulmonary embolism. The patient with subacute cor pulmonale had severe right-sided heart failure for 5 weeks and necropsy disclosed microscopic-sized neoplastic pulmonary emboli from a gastric carcinoma without parenchymal pulmonary metastases. The patient with chronic cor pulmonale had evidence of right-sided heart failure for years, the result of primary or idiopathic pulmonary hypertension almost certainly present from birth because the pattern of elastic fibers in the pulmonary trunk was that seen in newborns where the pressure in the pulmonary trunk and ascending aorta are similar. The patient with chronic cor pulmonale had plexiform pulmonary lesions indicative of irreversible pulmonary hypertension. Neither the acute nor the subacute patient had chronic pulmonary vascular changes. All 3 patients had dilated right ventricular cavities and non-dilated left ventricular cavities and only the patient with chronic cor pulmonale had right ventricular hypertrophy.

Commonalities of cardiac rupture (left ventricular free wall or ventricular septum or papillary muscle) during acute myocardial infarction secondary to atherosclerotic coronary artery disease.

Although mortality rates during acute myocardial infarction (AMI) continue to drop, cardiac rupture (left ventricular free wall [LVFW] or ventricular septum [VS] or papillary muscle [PM] or combination) remains relatively common. The aim was to identify commonalities among patients with AMI complicated by cardiac rupture. During a 22-year period (1993-2014) 64 patients hospitalized for AMI were studied and clinical and morphologic variables in those with (25 patients) - vs - those without (39 patients) cardiac rupture were compared, and previous reports on this topic were reviewed. Compared to the non-rupture cases, the rupture group was significantly older (71 years - vs - 60 years); had a much higher frequency of huge deposits of adipose tissue in the heart (floated in formaldehyde) (88% - vs - 20%) but a lower mean body mass index (28.2 Kg/m(2) - vs - 33.2 Kg/m(2)); a much lower frequency of healed myocardial infarct (scar) (4% - vs - 28%); a lower frequency of diabetes mellitus (24% - vs - 47%), and a higher frequency of thrombolytic therapy during the fatal AMI (32% - vs - 10%). None of the rupture cases had evidence of dilated left ventricular cavities or evidence of heart failure before the AMI complicated by rupture. In conclusion, cardiac rupture appears to account for a high percent of deaths during a first AMI. It most commonly occurs in patients with extremely fatty hearts and in those without evidence of prior heart failure.

The two extremes of cardiac sarcoidosis and the effect of Prednisone therapy.

Described herein are clinical and morphologic findings in 2 patients who underwent heart transplantation because of severe heart failure resulting from cardiac sarcoidosis. Although the explanted hearts in each patient had characteristic gross changes of cardiac sarcoidosis, one patient who had been treated with prednisone, had no residual sarcoid granulomas in the myocardium, whereas the other patient, in whom diagnosis was not made until heart transplantation, had innumerable sarcoid granulomas in her heart. This report suggests that prednisone can eliminate sarcoid granulomas in the heart but that their replacement is by dense fibrous tissue, something also likely the result of the granulomas themselves, creating a situation where the treated (prednisone) and the non-treated sarcoid heart may appear similar by gross examination.

Nontraumatic intracerebral hemorrhage unassociated with arterial aneurysmal rupture as a cause of sudden unexpected death.

Sudden death from intracerebral hemorrhage was observed in two patients admitted to Baylor University Medical Center at Dallas in a single month. Each had been drinking alcohol at the time of onset of first symptoms. Intracerebral hemorrhage was diagnosed in one patient by computed tomography, but not in the second patient who clinically was diagnosed as having acute coronary syndrome. Both died within 24 hours of onset of symptoms, and autopsy in both disclosed intracerebral hemorrhage, an infrequent cause of sudden death. This report calls attention to intracerebral hemorrhage as a cause of sudden death.

Clues to diagnosing carcinoid heart disease as the cause of isolated right-sided heart failure.

Described herein is a 67-year-old woman who underwent replacement of both tricuspid and pulmonic valves because of severe isolated right-sided systolic heart failure. The cause of the heart failure preoperatively was believed to be the result of left breast radiation a year earlier. At operation, however, the pulmonic valve was excised and a biopsy of the stiff-walled right atrium was performed, and histologic examination of each was classic of carcinoid heart disease. She never awoke postoperatively. Postoperatively, computed tomography disclosed numerous masses in the liver. Retrospectively, clues to the presence of carcinoid heart disease include thickening of both the tricuspid and pulmonic valve leaflets by echocardiogram, a pressure gradient, albeit small, across the pulmonic valve, the plastering of the septal tricuspid-valve leaflet to the ventricular septum, the total absence of left-sided heart disease, and the presence of extremely low 12-lead QRS electrocardiographic voltage.

Morphologic features of the recipient heart in patients having cardiac transplantation and analysis of the congruence or incongruence between the clinical and morphologic diagnoses.

Cardiac transplantation (CT) has been one of the great medical advances of the last nearly 50 years. We studied the explanted hearts of 314 patients having CT at Baylor University Medical Center Dallas from 1993 to 2012, and compared the morphologic diagnoses to the clinical diagnoses before CT. Among the 314 patients the morphologic and clinical diagnoses were congruent in 272 (87%) and incongruent in 42 (13%). Most of the incongruity occurred among the 166 patients with non-ischemic cardiomyopathy (non-IC) (36/166 [22%]), and of that group the major incongruity occurred among the patients with hypertrophic cardiomyopathy (7/17 [41%]), non-compaction left ventricular cardiomyopathy (NCLVC) (3/3 [100%]), mononuclear myocarditis (3/3 [100%]), arrhythmogenic right ventricular cardiomyopathy (ARVC) (4/4 [100%]), and cardiac sarcoidosis (8/8 [100%]). The phrase "non-IC" is a general term that includes several subsets of cardiac diseases and simply means "insignificant narrowing of 1 or more of the epicardial coronary arteries," but it does not specify the specific cause of the heart failure leading to CT. A number of cardiac illustrations are provided to demonstrate the morphologic variability occurring among the patients with IC and non-IC.