Management of Unoperated Tetralogy of Fallot in a 59-Year-Old Patient.

Tetralogy of Fallot is the most common cyanotic congenital heart defect consisting of an overriding aorta, right ventricular outflow obstruction, ventricular septal defect, and right ventricular hypertrophy. Without surgical management, approximately only 3% of patients survive past the age of 40 years. Cases of unoperated patients reaching adulthood have been reported; however, few studies describe treatment guidelines for surgical or therapeutic management. In this article, we report the case of a 59-year-old Hispanic male with unoperated tetralogy of Fallot presenting to our cardiology clinic for initial workup and management.

Brain diffusion changes in Eisenmenger syndrome.

OBJECTIVE: This preliminary study aimed to evaluate whether there are changes in the apparent diffusion coefficient (ADC) values of the brain in patients presenting with Eisenmenger syndrome (ES). METHODS: This cross-sectional study included 10 consecutively recruited patients with ES and 10 healthy control subjects. In the patients and controls, eight distinct neuroanatomical locations were selected for analysis. Quantitative measurements of ADC values of the frontal white matter (FWM), occipital white matter, lentiform nucleus (LN), thalamus, frontal cortex, anterior and posterior limbs of the internal capsule and caudate nucleus were measured. Statistical analysis was performed using SPSS® (IBM Corp., New York, NY; formerly SPSS Inc., Chicago, IL) for Windows v. 20. Data were presented as mean ± standard deviation values. The Kruskal-Wallis test was used to assess differences in the ADC values of each brain location between the ES group and the control group. Statistical significance was accepted at the level of p < 0.05. RESULTS: The ADC values of the FWM and LN were significantly higher in the ES group than that in the control group. The mean ADC levels of other brain regions were not significantly different between the groups. CONCLUSION: Chronic hypoxia in patients with ES may lead to diffusion changes in the brain tissue. There is a need for further studies to assess the clinical significance of cerebral ADC values in patients with ES. Advances in knowledge: The ratio of extracellular volume to intracellular volume in the FWM and LN can be considered to be increased in patients with ES.

Survival and outcomes of patients with unoperated single ventricle.

OBJECTIVE: Patients with unoperated single ventricle (SV) rarely survive into adulthood with good functional status and may develop Eisenmenger's syndrome (ES). We report outcomes of a 30-year cohort of such patients. METHODS: Adult patients with unoperated SV were identified by searching the Mayo Clinic medical record from 1984 to 2014. Clinical data were collected and compared between patients with pulmonary stenosis (PS) and ES. RESULTS: 24 patients were identified (median peak-age 56 (31-77) years (11 ES, 13 PS); 22 had left ventricular morphology. 50-year transplant-free survival was 65% (95% CI 43 to 81). Median age at death was 55 years (31-77 years); 15 deaths (62%) occurred before oral pulmonary vasodilators were commercially available. Two-thirds of the cohort demonstrated preserved New York Heart Association functional class and median EF was 60% (49% to 62%). The majority of patients to survive into the fifth decade exhibited anatomy of double-inlet LV (DILV) with PS. CONCLUSION: Selected patients with unoperated SV with PS and ES can survive with good functional class up to the eighth decade with good medical management. DILV/PS appears to be the ideal phenotype for advanced survival. Our outcomes may be considered when such patients with SV having 'balanced' physiology are evaluated for Fontan palliation. However, additional prospective study will be necessary to verify this assertion.

The Eisenmenger malformation: a morphologic study.

We studied 11 autopsied cases of the Eisenmenger malformation, comparing the findings with 11 hearts with intact ventricular septal structures, and nine hearts having perimembranous ventricular septal defects in the absence of aortic overriding. We found variable lengths for the subpulmonary infundibulum in the hearts with Eisenmenger defects. It was well developed in three hearts, of intermediate length in seven, and very short in one of the specimens. The muscular outlet septum was also of variable length compared with the free-standing subpulmonary infundibular sleeve. Except for one, all hearts had fibrous continuity between the aortic and tricuspid valvar leaflets, such that the ventricular septal defect was then perimembranous. In the remaining case, there was a completely subaortic muscular infundibulum, with the ventricular septal defect showing only muscular borders. The medial papillary muscle was absent in the majority of cases, but was well formed in three hearts, all with relatively short muscular outlet septums. We identified mild, intermediate, and severe degrees of rightward rotation of the aortic valve, and these findings correlated with the extent of aortic valvar overriding. In nine of the 11 hearts, the ventriculo-arterial connections were concordant, but there was double-outlet from the right ventricle in the other two specimens. Based on our anatomic and morphometric observations, we conclude that the hearts we have defined as having Eisenmenger defects show marked individual variation in their specific phenotypic anatomy.

Exercises in anatomy: tetralogy of Fallot.

It is axiomatic that those performing surgery on the congenitally malformed heart require a thorough knowledge of the lesions they will be called upon to correct. The necessary anatomical knowledge is becoming increasingly difficult to obtain at first hand, since relatively few centres now hold archives of specimens obtained in an appropriately legal fashion from the patients unfortunately dying in previous years. One centre with such an archive is Ann and Robert H. Lurie Children's Hospital in Chicago, known previously as Chicago Memorial Children's Hospital. The archive was established by Farouk S. Idriss, and was subsequently enhanced and consolidated by his son, Rachid. It is now under the care of Carl L. Backer, the current chief of paediatric cardiothoracic surgery at Lurie Children's. With the support of Carl, the archive has been triaged and catalogued by Diane E. Spicer and Robert H. Anderson. It has now been used to create a series of video presentations, illustrating the salient features of surgical anatomy of selected entities, with the videoclips being edited and prepared for publication by Anne Sarwark. This video contains the fruits of the first of these exercises in anatomy, and is devoted to tetralogy of Fallot.We begin the exercise by making comparisons between the normal heart and the arrangement seen in typical tetralogy. We emphasize the need to recognize the 'building blocks' of the normal outflow tracts, and show how they come apart in tetralogy. We then show the variations to be found in the specific morphology of the borders of the hole between the ventricles, with the crest of the apical ventricular septum being overridden by the orifice of the aortic valve such that the latter structure has a biventricular connection. We emphasize that it is the squeeze between the deviated muscular outlet septum and septoparietal trabeculations that is the essential phenotypic feature of the lesion. We then proceed to demonstrate the further variation to be found in the length of the outlet septum, which in extreme cases can be fibrous and hypoplastic rather than muscular. We also show how the ventriculo-arterial connection can vary from being concordant to becoming double outlet from the right ventricle. We conclude by emphasizing that the anatomy of tetralogy can also be recognized when the subpulmonary outflow tract is atretic rather than stenotic.

Myocardial fibrosis in Eisenmenger syndrome: a descriptive cohort study exploring associations of late gadolinium enhancement with clinical status and survival.

BACKGROUND: A relationship between myocardial fibrosis and ventricular dysfunction has been demonstrated using late gadolinium enhancement (LGE) in the pressure-loaded right ventricle from congenital heart defects. In patients with Eisenmenger syndrome (ES), the presence of LGE has not been investigated. The aims of this study were to detect any myocardial fibrosis in ES and describe major clinical variables associated with the finding. METHODS: From 45 subjects screened, 30 subjects (age 43 ± 13 years, 20 female) underwent prospective cardiovascular magnetic resonance with LGE to quantify biventricular volume and function as well as maximal and submaximal exercise during a single visit. Standard cine acquisitions were obtained for ventricular volume and function. Further imaging was performed after administration of 0.1 mmol/kg gadolinium contrast. Regions of LGE were evaluated qualitatively and quantitatively by manual contouring of identified areas, with total area expressed as a percentage of mass. Patients were followed prospectively (mean follow up 7.4 ± 0.4 years) and any deaths recorded. Patients with LGE findings were compared to those without. RESULTS: LGE was present in 22/30 (73%) patients, specifically in RV myocardium (70%), RV trabeculae (60%), LV myocardium (33%) or LV papillary muscles (30%), though in small amounts (mean 1.4% of total ventricular mass, range 0.16 - 6.0%). Those with any LGE were not different in age, history of arrhythmia, desaturation, nor hemoglobin, nor ventricular size, mass, or function. Exercise capacity was low, but also not different between those with and without LGE. Similarly no significant associations were found with amount of fibrosis. There were five deaths among patients with LGE, versus two in patients without, but no difference in survival (log rank =0.03, P = 0.85). CONCLUSIONS: Myocardial fibrosis by LGE is common in ES, though not extensive. The presence and quantity of LGE did not correlate with ventricular size, function, degree of cyanosis, exercise capacity, or survival in this pilot study. More data are clearly required before recommendations for routine use of LGE in these patients can be made.

Red blood cell distribution width predicts survival in patients with Eisenmenger syndrome.

BACKGROUND: Previous studies identified an independent relationship between red blood cell distribution width (RDW) and prognosis in patients with pulmonary hypertension of mixed etiologies and idiopathic pulmonary arterial hypertension. This study aimed to investigate the significance of RDW for predicting survival in patients with Eisenmenger syndrome (ES). METHODS: We retrospectively reviewed the clinical records and collected baseline data for patients newly diagnosed with ES in our hospital between January 2005 and October 2009. Follow-up data were collected periodically using a specifically designed network database until December 31, 2012. The end point was all-cause death. RESULTS: A total of 109 patients with ES were included in the study. Twenty-one patients (19.3%) died during a median follow-up period of 4.2 years (interquartile range 3.7-5.0 years). Baseline RDW was significantly correlated with mixed venous oxygen saturation (r=-0.286, p=0.003), arterial oxygen saturation (r=-0.423, p<0.001), mean pulmonary arterial pressure (r=0.271, p=0.004) and total pulmonary resistance (r=0.465, p<0.001). The 1-, 3- and 5-year survival rates for all 109 patients were 94%, 87% and 78%, respectively. Kaplan-Meier analysis showed that patients with RDW ≥13.9% had a lower survival rate than patients with RDW <13.9% (p=0.001). Multivariate Cox regression analysis showed that RDW was an independent prognostic marker in ES, with a hazard ratio of 1.162 (95% CI 1.036-1.302; p=0.010). CONCLUSIONS: Baseline RDW correlates with hemodynamics and is an independent prognostic marker in ES.

Patent ductus arteriosus with Eisenmenger syndrome.

Herein we report a 21 year-old woman with a previously documented patent ductus arteriosus and Eisenmenger physiology. She presented with increasing cyanosis and exercise intolerance which could be explained by a new finding of right to left shunting through an interatrial communication. She was started on Bosentan therapy aiming to reduce the pulmonary pressure with consideration for heart-lung transplantation should any further deterioration occur.

Histopathology of the great vessels in patients with pulmonary arterial hypertension in association with congenital heart disease: large pulmonary arteries matter too.

BACKGROUND: Pulmonary arterial hypertension (PAH) is considered primarily a disease of the distal pulmonary arteries whereas little is known on the effect of long-standing pulmonary hypertension on the larger proximal pulmonary arteries. This study aims to investigate the structural changes in the great arteries of adults who developed PAH in association with congenital heart disease (CHD), with severe cases termed Eisenmenger syndrome. METHODS: We performed macroscopic and light microscopy analyses on the great arteries of 10 formalin-fixed human hearts from patients with PAH/CHD and compared them to age-matched healthy controls. A detailed histology grading score was used to assess the severity of medial wall abnormalities. RESULTS: Severe atherosclerotic lesions were found macroscopically in the elastic pulmonary arteries of 4 PAH/CHD specimens and organised thrombi in 3; none were present in the controls. Significant medial wall abnormalities were present in the pulmonary trunk (PT), including fibrosis (80%), and atypical elastic pattern (80%). Cyst-like formations were present in less than one third of patients and were severe in a single case leading to wall rupture. The cumulative PT histology grading score was significantly higher in PAH/CHD cases compared to controls (p<0.0001) and correlated positively with larger PT diameters (ρ=0.812, p<0.0001) and the degree of medial wall hypertrophy (ρ=0.749, p<0.0001). CONCLUSIONS: Chronic PAH in association with CHD results in marked macroscopic and histological abnormalities in the large pulmonary arteries. These abnormalities are likely to affect haemodynamics and contribute to morbidity and mortality in this cohort.

[Clinical and hemodynamic features of Eisenmenger syndrome patients at the time of first admission: a tertiary referral-center experience]. / Eisenmenger sendromlu hastalarin ilk basvuru anindaki klinik ve hemodinamik özellikleri: Tersiyer merkez deneyimi.

OBJECTIVE: In this study, patients admitted with the diagnosis of Eisenmenger syndrome (ES) in a tertiary referral center were analyzed. METHODS: The data of 20 consecutive patients (mean age: 27.6+1.8 years, 7 male and mean follow-up time: 35.6 ± 9.1 months) with ES were retrospectively analyzed. Demographic characteristics, symptoms, physical examination, laboratory and hemodynamic parameters were analyzed at the time of first admission. RESULTS: The most frequent underlying heart diseases were ventricular septal defect (VSD) with complex congenital disease (n:8, 40%) and isolated VSD (n:7, 35%). 6-minute walking test distance was 347.9 ± 33.7 meters and 15 patients (75%) had a functional capacity of NYHA Class III, at the time of admission. ES was diagnosed with catheterization in all patients and mean systolic pulmonary arterial pressure measured by catheterization was 112 ± 6.8 mmHg. Pulmonary function tests, FVC (forced vital capacity), FEV1 (forced expiratory volume), FEV1/FVC values were respectively, 3.1 ± 0.4, 2.5 ± 0.4 L and 76.7 ± 3.3%. Metabolic tests were performed in all patients at the first visit. Mean VO2 max was 16.7 ± 1.0 ml / kg/min and VE/VCO2 rate was 53.9 ± 3.2%. Although PH and partial pressure of carbon dioxide levels were within normal range in blood gas analysis, oxygen saturation and partial pressure of oxygen levels were low. CONCLUSION: The most common underlying heart disease of ES patients is VSD. In this cases exercise capacity is restricted and this restriction is reflected in laboratory parameters.

Comparative efficacy of sildenafil in Eisenmenger's syndrome secondary to atrial septal defect versus ventricular septal defect: a cardiac catheterisation follow-up study.

OBJECTIVES: This study evaluates the efficacy and safety of sildenafil in patients with Eisenmenger's syndrome with special emphasis on haemodynamic parameters and its comparative efficacy in atrial septal defect versus ventricular septal defect patients. METHODS: Oral sildenafil was given to 22 patients with Eisenmenger's syndrome - eight with atrial septal defect and 14 with ventricular septal defect - after detailed baseline evaluation including a six-minute walk test, echocardiography, and cardiac catheterisation. Patients were followed up for a period of 6 months for functional class assessment and six-minute walk distance. Cardiac catheterisation was repeated in all patients. RESULTS: A significant improvement in the World Health Organization functional class, six-minute walk distance, mean pulmonary arterial pressure, and pulmonary vascular resistance was noticed. Systemic arterial and mixed venous oxygen saturations were also significantly improved along with improvement in pulmonary blood flow. None showed any significant side effects or worsening of systemic arterial saturation. At baseline, mean pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary/systemic vascular resistance ratios were significantly higher in ventricular septal defect patients than in atrial septal defect patients. Atrial septal defect patients showed better response in clinical as well as haemodynamic parameters. CONCLUSIONS: Sildenafil is an effective and safe agent for patients with Eisenmenger's syndrome. It improves their functional capacity as well as haemodynamic parameters. The beneficial effects are greater in patients with Eisenmenger's syndrome secondary to atrial septal defect than ventricular septal defect.

Eisenmenger ventricular septal defect: classification, morphology, and indications for surgery.

This study aimed to examine the definition and indications for surgery, to elucidate the morphologic substrate of aortic regurgitation, and to extrapolate the pathologic mechanisms of subpulmonary stenosis in Eisenmenger ventricular septal defect (EVSD). The study enrolled 160 patients. Preoperative respiratory symptoms and poor growth were present in 41 patients (26%), and 21 patients (13%) required mechanical ventilation. Perimembranous ventricular septal defect (pVSD) had been diagnosed previously for 136 of the patients (85%) at other institutions. Of the 160 patients, 51 (32%) had muscular posteroinferior rims. Aortic regurgitation was experienced by 36 patients (23%), found to be mild in 31 cases (19%) and moderate in 5 cases (3%). None of the patients had severe regurgitation. No aortic valvuloplasty was performed. The significant risk factors for aortic regurgitation were subpulmonary stenosis (p = 0.001) and a muscular posteroinferior rim (p = 0.000). Subpulmonary stenosis was seen in 57 patients (35%), found to be mild to moderate in 42 cases (26%) and severe in 15 cases (9%). Adequacy of the stenosis band was repaired through the tricuspid valve for 57 of these patients. The definition of EVSD should identify it as a subgroup different from pVSD, and it should be closed as soon as it is identified in developing countries. Aortic regurgitation occurs rarely, and aortic valvoplasty should be performed if it exceeds a moderate level. The subpulmonary stenosis can be repaired through the tricuspid valve.