Results of Surgery for Ebstein Anomaly: a Multicenter Study from the European Congenital Heart Surgeons Association

OBJECTIVE: Since most centers' experience with Ebstein anomaly is limited, we sought to analyze the collective experience of participating institutions of the European Congenital Heart Surgeons Association with surgery for this rare malformation. METHODS: The records of all 150 patients (median age 6.4 years) who underwent surgery for Ebstein anomaly in the 13 participating Association centers between January 1992 and January 2005 were reviewed retrospectively. Patients with congenitally corrected transposition were excluded. RESULTS: Most patients (81%) had Ebstein disease type B or C and significant functional impairment (61% in New York Heart Association class III or IV) and 16% had prior operations. Surgical procedures (n = 179) included valve replacement (n = 60, 33.5%), valve repair (n = 49, 27.3%), 1(1/2) ventricle repair (n = 46, 25.6%), palliative shunt (n = 13, 7.26%), and other complex procedures (n = 11, 6.14%). There were 20 hospital deaths (operative mortality 13.3%) after valve replacement in 5 patients, valve repair in 3, 1(1/2) ventricle repair in 7, palliative procedures in 3, and miscellaneous procedures in 2. Younger age and palliative procedures were univariate risk factors for operative death, but only age was an independent predictor on multivariable analysis. CONCLUSIONS: Most patients coming to surgery presented in childhood and were significantly symptomatic. More than half underwent valve replacement or repair, but a considerable proportion had severe disease necessitating 1(1/2) ventricle repair or palliative procedures. Operative mortality did not differ significantly among repair, replacement, and 1(1/2) ventricle repair but was associated with palliative procedures for severe disease early in life, young age being the only independent predictor of operative death.

Acute Bivalvular Left-Sided Methicillin-Resistant Staphylococcus Aureus Endocarditis with Cardiac, Cerebral, Renal and Septic Complications

Infective endocarditis (IE) is now rare in developed countries, but its prevalence is higher in elderly patients with prosthetic valves, diabetes, renal impairment, or heart failure. An increase in health-care associated IE (HCAIE) has been observed due to invasive maneuvers (30% of cases). Methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus are the most common agents in HCAIE, causing high mortality and morbidity. We review complications of IE and its therapy, based on a patient with acute bivalvular left-sided MRSA IE and a prosthetic aortic valve, aggravated by congestive heart failure, stroke, acute immune complex glomerulonephritis, Candida parapsilosis fungémia and death probably due to Serratia marcescens sepsis. The HCAIE was assumed to be related to three temporally associated in-hospital interventions considered as possible initial etiological mechanisms: overcrowding in the hospital environment,iv quinolone therapy and red blood cell transfusion. Later in the clinical course,C. parapsilosis and S. marcescens septicemia were considered to be possible secondary etiological mechanisms of HCAIE.

Prognostic Value of a New Cardiopulmonary Exercise Testing Parameter in Chronic Heart Failure: Oxygen Uptake Efficiency at Peak Exercise - Comparison with Oxygen Uptake Efficiency Slope

INTRODUCTION: A growing body of evidence shows the prognostic value of oxygen uptake efficiency slope (OUES), a cardiopulmonary exercise test (CPET) parameter derived from the logarithmic relationship between O(2) consumption (VO(2)) and minute ventilation (VE) in patients with chronic heart failure (CHF). OBJECTIVE: To evaluate the prognostic value of a new CPET parameter - peak oxygen uptake efficiency (POUE) - and to compare it with OUES in patients with CHF. METHODS: We prospectively studied 206 consecutive patients with stable CHF due to dilated cardiomyopathy - 153 male, aged 53.3±13.0 years, 35.4% of ischemic etiology, left ventricular ejection fraction 27.7±8.0%, 81.1% in sinus rhythm, 97.1% receiving ACE-Is or ARBs, 78.2% beta-blockers and 60.2% spironolactone - who performed a first maximal symptom-limited treadmill CPET, using the modified Bruce protocol. In 33% of patients an cardioverter-defibrillator (ICD) or cardiac resynchronization therapy device (CRT-D) was implanted during follow-up. Peak VO(2), percentage of predicted peak VO(2), VE/VCO(2) slope, OUES and POUE were analyzed. OUES was calculated using the formula VO(2) (l/min) = OUES (log(10)VE) + b. POUE was calculated as pVO(2) (l/min) / log(10)peakVE (l/min). Correlation coefficients between the studied parameters were obtained. The prognosis of each variable adjusted for age was evaluated through Cox proportional hazard models and R2 percent (R2%) and V index (V6) were used as measures of the predictive accuracy of events of each of these variables. Receiver operating characteristic (ROC) curves from logistic regression models were used to determine the cut-offs for OUES and POUE. RESULTS: pVO(2): 20.5±5.9; percentage of predicted peak VO(2): 68.6±18.2; VE/VCO(2) slope: 30.6±8.3; OUES: 1.85±0.61; POUE: 0.88±0.27. During a mean follow-up of 33.1±14.8 months, 45 (21.8%) patients died, 10 (4.9%) underwent urgent heart transplantation and in three patients (1.5%) a left ventricular assist device was implanted. All variables proved to be independent predictors of this combined event; however, VE/VCO2 slope was most strongly associated with events (HR 11.14). In this population, POUE was associated with a higher risk of events than OUES (HR 9.61 vs. 7.01), and was also a better predictor of events (R2: 28.91 vs. 22.37). CONCLUSION: POUE was more strongly associated with death, urgent heart transplantation and implantation of a left ventricular assist device and proved to be a better predictor of events than OUES. These results suggest that this new parameter can increase the prognostic value of CPET in patients with CHF.

Muscarinic antibodies and heart rate responses to dynamic exercise and to the Valsalva maneuver in chronic chagasic patients

We have studied the cardiac chronotropic responses to the Valsalva maneuver and to dynamic exercise of twenty chronic chagasic patients with normal left ventricular function and no segmental wall abnormalities by two-dimensional echocardiogram. The absolute increase in heart rate of the patients (Δ = 21.5 ± 10 bpm, M±SD) during the maneuver was significantly diminished when compared to controls (Δ = 31.30 ± 70, M±SD, p = 0.03). The minimum heart rate (58.24 ± 8.90 vs. 62.80 ± 10, p = 0.68) and the absolute decrease in heart rate at the end of the maneuver (Δ = 38.30 ± 13 vs. Δ = 31.47 ± 17, p = 0.10) were not different from controls. The initial heart rate acceleration during dynamic exercise (Δ = 12 ± 7.55 vs. Δ = 19 ± 7.27, M±SD, p = 0.01) was also diminished, but the heart rate recovery during the first ten seconds was more prominent in the sero-positive patients (Median: 14, Interquartile range: (9.75-17.50 vs. 5(0-8.75, p = 0.001). The serum levels of muscarinic cardiac auto-antibodies were significantly higher in the chagasic patients (Median: 34.58, Interquartile Range: 17-46.5, Optical Density) than in controls (Median: 0, Interquartile Range: 0-22.25, p = 0.001) and correlated significantly and directly (r = 0.68, p = 0.002) with early heart rate recovery during dynamic exercise. The results of this investigation indirectly suggest that, the cardiac muscarinic auto-antibodies may have positive agonist effects on parasympathetic heart rate control of chagasic patients.

PREDICTIVE FACTORS FOR THE PROGRESSION OF CHRONIC CHAGAS CARDIOMYOPATHY IN PATIENTS WITHOUT LEFT VENTRICULAR DYSFUNCTION

The identification of predictors for the progression of chronic Chagas cardiomyopathy (CCC) is essential to ensure adequate patient management. This study looked into a non-concurrent cohort of 165 CCC patients between 1985 and 2010 for independent predictors for CCC progression. The outcomes were worsening of the CCC scores and the onset of left ventricular dysfunction assessed by means of echo-Doppler cardiography. Patients were analyzed for social, demographic, epidemiologic, clinical and workup-related variables. A descriptive analysis was conducted, followed by survival curves based on univariate (Kaplan-Meier and Cox’s univariate model) and multivariate (Cox regression model) analysis. Patients were followed from two to 20 years (mean: 8.2). Their mean age was 44.8 years (20-77). Comparing both iterations of the study, in the second there was a statistically significant increase in the PR interval and in the QRS duration, despite a reduction in heart rates (Wilcoxon < 0.01). The predictors for CCC progression in the final regression model were male gender (HR = 2.81), Holter monitoring showing pauses equal to or greater than two seconds (HR = 3.02) increased cardiothoracic ratio (HR = 7.87) and time of use of digitalis (HR = 1.41). Patients with multiple predictive factors require stricter follow-up and treatment.

Time to Left Ventricular Reverse Remodeling after Cardiac Resynchronization Therapy: Better Late than Never

INTRODUCTION: Left ventricular reverse remodeling (LVRR), defined as reduction of end-diastolic and end-systolic dimensions and improvement of ejection fraction, is associated with the prognostic implications of cardiac resynchronization therapy (CRT). The time course of LVRR remains poorly characterized. Nevertheless, it has been suggested that it occurs ≤6 months after CRT. OBJECTIVE: To characterize the long-term echocardiographic and clinical evolution of patients with LVRR occurring >6 months after CRT and to identify predictors of a delayed LVRR response. METHODS: A total of 127 consecutive patients after successful CRT implantation were divided into three groups according to LVRR response: Group A, 19 patients (15%) with LVRR after >6 months (late LVRR); Group B, 58 patients (46%) with LVRR before 6 months (early LVRR); and Group C, 50 patients (39%) without LVRR during follow-up (no LVRR). RESULTS: The late LVRR group was older, more often had ischemic etiology and fewer patients were in NYHA class ≤II. Overall, group A presented LVRR between group B and C. This was also the case with the percentage of clinical response (68.4% vs. 94.8% vs. 38.3%, respectively, p<0.001), and hospital readmissions due to decompensated heart failure (31.6% vs. 12.1% vs. 57.1%, respectively, p<0.001). Ischemic etiology (OR 0.044; p=0.013) and NYHA functional class

Molecular tools to dissect the role of Dmrt2a and Dmrt2b in the left-right axis formation in zebrafish

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Digoxin serum levels in patients with Chagas' cardiomyopathy and heart failure

INTRODUCTION: The purpose of this study was to determine digoxin serum concentrations in patients with Chagas' cardiomyopathy with chronic heart failure, because little is known concerning this laboratory test in patients with this condition. METHODS: This study focuses on 29 (29%) out of 101 patients with chronic heart failure secondary to Chagas' cardiomyopathy receiving digoxin therapy. Digoxin was measured by the immune-enzymatic method. RESULTS: New York Heart Association Functional Class III/IV was noted in 13 (45%) patients. The mean potassium serum level was 4.3± 0.5mEq/L, mean creatinine serum levels 1.4± 0.3dg/100ml, and left ventricular ejection fraction 34.7± 13.8%. The median digoxin serum level was 1.27 (0.55; 1.79)ng/ml. Sixteen (55%) patients had digoxin serum levels higher than 1.0ng/ml. Abnormal digoxin serum levels were verified in 13 (45%) patients. Digoxin serum levels correlated moderately with creatinine serum levels (r = 0.39; p< 0.03) and negatively with sodium serum levels (r= -0.38; p= 0.03). CONCLUSIONS: Digoxin serum concentration should be measured in patients with Chagas' cardiomyopathy with chronic heart failure receiving digoxin therapy due to the potential for digoxin toxicity.

Prevalence of Trypanosoma cruzi antibodies and inflammatory markers in uncompensated heart failure

INTRODUCTION: Heart failure (HF) represents the final stage of chronic chagasic cardiomyopathy (CChC). The diagnosis of CChC is based on the demonstration of anti-Trypanosoma cruzi antibodies (aTcAg) and clinical and epidemiological data. In Venezuela, there are no data about the prevalence of chagasic HF. The aim of this study was to determine the epidemiological, clinical, and inflammatory risk factors associated with seronegative or seropositive HF patients. METHODS: We performed a cross-sectional study in the Venezuelan central-west states among a healthy rural population and in patients admitted to the emergency room with uncompensated HF. RESULTS: The seroprevalence rates of Trypanosoma cruzi antibodies were 11.2% and 40.1% in the healthy population and in HF patients, respectively. Seropositivity in healthy individuals was associated with age, knowledge on triatomine vectors, and having seen wild reservoirs in the house; in HF patients, with contact with the vector and previous clinical diagnosis of Chagas' disease; and in both groups taken together, with age, knowledge on triatomines, and HF. Seropositive patients had prolonged QRS, decreased ejection fraction, and high serum magnesium, all significant as compared with HF seronegative cases. Left atrium enlargement and ventricular hypertrophy were most frequently observed in HF seronegative patients. CRP, IL6, ILβ1, IL2, and FNTα were elevated in 94.5%, 48%, 17.8%, 13.7%, and 6.9% of HF patients, respectively, but only IL2 levels were associated with chagasic HF. CONCLUSIONS: There is a high prevalence of aTcAg in HF patients from the central-west region of Venezuela, and their epidemiological, clinical, and inflammatory features are discreetly different as compared with those of seronegative cases.

Heart hypoplasia in an animal model of congenital diaphragmatic hernia

PURPOSE: In previous papers, we described a new experimental model of congenital diaphragmatic hernia in rabbits, and we also reported noninvasive therapeutic strategies for prevention of the functional and structural immaturity of the lungs associated with this defect. In addition to lung hypoplasia, pulmonary hypertension, biochemical, and structural immaturity of the lungs, the hemodynamics of infants and animals with congenital diaphragmatic hernia are markedly altered. Hence, cardiac hypoplasia has been implicated as a possible cause of death in patients with congenital diaphragmatic hernia, and it is hypothesized to be a probable consequence of fetal mediastinal compression by the herniated viscera. Cardiac hypoplasia has also been reported in lamb and rat models of congenital diaphragmatic hernia. The purpose of the present experiment was to verify the occurrence of heart hypoplasia in our new model of surgically produced congenital diaphragmatic hernia in fetal rabbits. METHODS: Twelve pregnant New Zealand rabbits underwent surgery on gestational day 24 or 25 (normal full gestational time - 31 to 32 days) to create left-sided diaphragmatic hernias in 1 or 2 fetuses per each doe. On gestational day 30, all does again underwent surgery, and the delivered fetuses were weighed and divided into 2 groups: control (non-surgically treated fetuses) (n = 12) and congenital diaphragmatic hernia (n = 9). The hearts were collected, weighed, and submitted for histologic and histomorphometric studies. RESULTS: During necropsy, it was noted that in all congenital diaphragmatic hernia fetuses, the left lobe of the liver herniated throughout the surgically created defect and occupied the left side of the thorax, with the deviation of the heart to the right side, compressing the left lung; consequently, this lung was smaller than the right one. The body weights of the animals were not altered by congenital diaphragmatic hernia, but heart weights were decreased in comparison to control fetuses. The histomorphometric analysis demonstrated that congenital diaphragmatic hernia promoted a significant decrease in the ventricular wall thickness and an increase in the interventricular septum thickness. CONCLUSION: Heart hypoplasia occurs in a rabbit experimental model of congenital diaphragmatic hernia. This model may be utilized for investigations in therapeutic strategies that aim towards the prevention or the treatment of heart hypoplasia caused by congenital diaphragmatic hernia.

Assessment of inotropic and vasodilating effects of milrinone lactate in patients with dilated cardiomyopathy and severe heart failure

OBJECTIVE: To assess the hemodynamic and vasodilating effects of milrinone lactate (ML) in patients with dilated cardiomyopathy (DCM) and New York Heart Association (NYHA) class III and IV heart failure. METHODS: Twenty patients with DCM and NYHA class III and IV heart failure were studied. The hemodynamic and vasodilating effects of ML, administered intravenously, were evaluated. The following variables were compared before and during drug infusion: cardiac output (CO) and cardiac index (CI); pulmonary capillary wedge pressure (PCWP); mean aortic pressure (MAP); mean pulmonary artery pressure (MPAP); mean right atrial pressure (MRAP); left ventricular systolic and end-diastolic pressures (LVSP and LVEDP, respectively); peak rate of left ventricular pressure rise (dP/dt); systemic vascular resistance (SVR); pulmonary vascular resistance (PVR); and heart rate (HR). RESULTS: All patients showed a significant improvement of the analysed parameters of cardiac performance with an increase of CO and CI; a significant improvement in myocardial contractility (dP/dt) and reduction of the LVEDP; PCWP; PAP; MAP; MRAP; SVR; PVR. Were observed no significant increase in HR occurred. CONCLUSION: Milrinone lactate is an inotropic dilating drug that, when administered intravenously, has beneficial effects on cardiac performance and myocardial contractility. It also promotes reduction of SVR and PVR in patients with DCM and NYHA class III and IV of heart failure.

Anomalous origin of the left coronary artery from the pulmonary trunk. Clinical features and midterm results after surgical treatment

OBJECTIVE: To report the authors' experience with the anomalous origin of the left coronary artery (AOLCA) from the pulmonary trunk, emphasizing preoperative data, surgical aspects and midterm results of the follow-up. METHODS: Retrospective analysis of 11 patients operated upon at the Royal Brompton Hospital from October, 84 to April, 97. RESULTS: Nine infants had heart failure (HF) and two other children presented with dyspnea and chest pain. All had ECG changes. The echocardiogram identified the anomalous origin of the coronary artery in 7 (64%) patients and hemodynamic studies were performed in 7 patients. All infants were operated upon between the 2nd and 10th month of life. Six patients were treated with aortic reimplantation of the left coronary artery, whereas five were operated upon according to the Takeuchi technique. All patients are alive, with clear improvement of the ECG changes and ventricular function, as evaluated by echocardiography. Two patients operated upon according to the Takeuchi technique required additional surgery due to severe supravalvular pulmonary stenosis. CONCLUSION: AOLCA is a rare disease. Most patients show early signs of severe HF associated with ECG findings. Surgical therapy must be instituted early in the disease, preferentially through aortic implantation of the anomalous coronary artery, with a high possibility of success. Shortly after surgery, clinical and ECG improvement, as well as normalization of left ventricular function, should be expected.

Influence of the elevation of the left ventricular diastolic pressure on the values of the first temporal derivative of the ventricular pressure (dP/dt)

PURPOSE: To assess the effects of the elevation of the left ventricular end-diastolic pressure (LVEDP) on the value of the 1st temporal derivative of the ventricular pressure (dP/dt). METHODS: Nineteen anesthetized dogs were studied. The dogs were mechanically ventilated and underwent thoracotomy with parasympathetic nervous system block. The LVEDP was controlled with the use of a perfusion circuit connected to the left atrium and adjusted to the height of a reservoir. The elevation of the LVEDP was achieved by a sudden increase in the height of a reservoir filled with blood. Continuous recordings of the electrocardiogram, the aortic and ventricular pressures and the dP/dt were performed. RESULTS: Elevation of the LVEDP did not result in any variation of the heart rate (167±16.0bpm, before the procedure; 167±15.5bpm, after the procedure). All the other variables assessed, including systolic blood pressure (128±18.3mmHg and 150±21.5mmHg), diastolic blood pressure (98±16.9mmHg and 115±19.8mmHg), LVEDP (5.5±2.49 and 9.3±3.60mmHg), and dP/dt (4,855 ± 1,082 mmHg/s and 5,149±1,242mmHg/s) showed significant increases following the expansion of the ventricular cavity. Although the elevation of the dP/dt was statistically significant, 6 dogs curiously showed a decrease in the values of dP/dt. CONCLUSION: Sudden elevation of the LVEDP resulted in increased values of dP/dt; however, in some dogs, this response was not uniform.

Anomalous origin of the left coronary artery from the right pulmonary artery with intramural aortic trajectory. Clinicosurgical diagnostic implications

OBJECTIVE: Anomalous origin of the left coronary artery from the right pulmonary artery (AOLCARPA), is a rare entity that is usually associated with other defects. Of the 20 cases of AOLCARPA reported in the literature, 14 (70%) had associations. We describe four patients with AOLCARPA without associated defects, but with a peculiar intramural aortic trajectory. METHODS: Fifty-five patients with anomalous origin of the left coronary artery were operated upon at INCOR-FMUSP. Four of the patients had the anomalous origin from the right pulmonary artery (RPA) without associated defects but with intramural aortic trajectory. Clinical and laboratory examinations were analyzed, as well as surgical findings. RESULTS: All patients had congestive heart failure (CHF) and 3 also had angina pectoris. Two patients had a murmur of mitral regurgitation, signs of myocardial infarction on the ECG and cardiomegaly. The shortening fraction varied from 9% to 23%. The hemodynamic study confirmed the diagnosis of anomalous origin of the coronary artery, but the intramural trajectory and the origin from the RPA were established only at surgery. In 3 patients, the technique of side-to-side anastomosis was performed with a good outcome. One patient, who underwent end-to-side anastomosis, died 6 months after the surgery. CONCLUSION: Association with other defects usually occurs in the AOLCARPA, and the intramural aortic trajectory is difficult to clinically diagnose but easy to surgically correct.

Growth hormone for optimization of refractory heart failure treatment

It has been reported that growth hormone may benefit selected patients with congestive heart failure. A 63-year-old man with refractory congestive heart failure waiting for heart transplantation, depending on intravenous drugs (dobutamine) and presenting with progressive worsening of the clinical status and cachexia, despite standard treatment, received growth hormone replacement (8 units per day) for optimization of congestive heart failure management. Increase in both serum growth hormone levels (from 0.3 to 0.8 mg/l) and serum IGF-1 levels (from 130 to 300ng/ml) was noted, in association with clinical status improvement, better optimization of heart failure treatment and discontinuation of dobutamine infusion. Left ventricular ejection fraction (by MUGA) increased from 13 % to 18 % and to 28 % later, in association with reduction of pulmonary pressures and increase in exercise capacity (rise in peak VO2 to 13.4 and to 16.2ml/kg/min later). The patient was "de-listed" for heart transplantation. Growth hormone may benefit selected patients with refractory heart failure.