Determinants and Prognostic Implications of Left-Heart Filling Pressures in Tetralogy of Fallot.

BACKGROUND: Elevated pulmonary artery wedge pressure (PAWP) is the hallmark of left-heart failure and is responsible for heart failure symptoms and mortality. Although PAWP typically correlates with right atrial pressure (RAP), it is primarily dependent on left-heart myocardial properties and volume status. As right-heart disease can occur in the absence of left-heart disease in patients with tetralogy of Fallot (TOF), we hypothesized that RAP was the primary determinant of PAWP in this population. METHODS: A cohort study of adults with TOF that underwent right-heart catheterization at Mayo Clinic Rochester (1990 to 2017) to determine the relationship among RAP, PAWP, and mortality. RESULTS: Among 213 patients (male 105; age 37 ± 14 years), the mean PAWP was 14 ± 5 mm Hg, and RAP was 11 ± 5 mm Hg. RAP was the strongest predictor of PAWP (ß = 0.68, standard error = 0.06, P < 0.001), independent of left-heart disease and atherosclerotic cardiovascular risk factors. The patients with high PAWP also had normal tissue Doppler velocities, suggesting normal left-ventricular myocardial properties. PAWP was an independent predictor of death/transplant (hazard ration [HR] 1.11, 95% confidence interval [CI], 1.03-1.20, P = 0.004). However, when RAP was incorporated into the regression model, RAP (and not PAWP) became the independent predictor of outcomes (HR 1.14, 95% CI, 1.06-1.22, P = 0.001). CONCLUSIONS: The current study showed that RAP was the primary determinant of PAWP and accounts, to some extent, for the mortality in patients with TOF and high PAWP. The data provide new insight in the pathophysiology of disease progression for symptomatic patients with TOF.

Feasibility, reproducibility and accuracy of electrical velocimetry for cardiac output assessment in congenital heart disease.

BACKGROUND: Noninvasive cardiac output assessment is important for prognostication in patients with heart failure. Electrical velocimetry (EV), an impedance cardiography technique, can be used for noninvasive cardiac output assessment. The purpose of this study was to determine the feasibility, reproducibility and accuracy of cardiac output assessment by EV in adults with congenital heart disease (CHD). METHODS: Cross-sectional study of CHD patients that had simultaneous cardiac output assessment by Fick and EV (using Cardiotronic monitor, Osypka Medical). We divided the cohort into: Group 1 patients (n = 54) had hemodynamic assessment at rest only, while Group 2 patients (n = 7) had assessment both at rest and peak exercise. RESULTS: EV cardiac output assessment was feasible in 100% of the patients. There was good correlation between Fick-derived and EV-derived cardiac index (r = 0.89, p < 0.001) in Group 1. Among 26 patients in Group 1 that underwent cardiac output assessment pre- and post-intervention, there was no difference in the strength of correlation of Fick and EV cardiac output pre- and post-intervention (p-interaction 0.244) indicating good reproducibility of the technique. There was also modest correlation between Fick-derived and EV-derived cardiac index at rest (r = 0.68, p = 0.032), and peak exercise (r = 0.62, p = 0.055), in Group 2. CONCLUSION: In this study, we demonstrated the feasibility and accuracy of EV cardiac output assessment in adults with CHD. We also demonstrated, for the first time, that EV cardiac output assessment was reproducible under different loading conditions, and that EV can be used for the assessment of cardiac output augmentation at peak exercise.

Left ventricular filling pressure in Tetralogy of Fallot: Correlation between invasive and noninvasive indices.

BACKGROUND: Left heart filling pressures, as measured by pulmonary artery wedge pressure (PAWP), is associated with heart failure related mortality. Because of the prognostic importance of PAWP, several echocardiographic indices have been proposed for noninvasive assessment of PAWP. However, these indices have not been validated in the congenital heart disease population. The purpose of this study was to determine the correlation between echocardiographic indices of PAWP, and the effect of high PAWP on transplant-free survival in adults with tetralogy of Fallot (TOF). METHODS: Retrospective study of adult TOF patients that underwent cardiac catheterization at Mayo Clinic, 1990-2017. We selected these pre-defined set of echocardiographic indices of LV diastolic function: mitral valve early velocity (E), mitral valve early and late velocity ratio (E/A), mitral valve deceleration time (DT), mitral annular tissue Doppler early velocity (e'), and left atrial volume index (LAVI). RESULTS: Of the echocardiographic indices analyzed among 213 patients (age 37 ± 14 years), only E velocity (ß = 5.83, standard error = 1.52, p < 0.001) and LAVI (ß = 0.14, standard error = 0.05, p = 0.007) correlated with PAWP. LAVI > 28 ml/m2 had sensitivity of 79% and specificity of 63% (AUC 0.712), and E velocity > 1.0 m/s had sensitivity of 66% and specificity of 89% (AUC 0.692), for detecting PAWP > 15 mmHg. LAVI > 28 ml/m2 was associated with reduced 10-year transplant-free survival (49% vs 90%, p < 0.001). CONCLUSION: This study supports the use of LAVI for noninvasive assessment of PAWP and for prognostication. Further studies are required to validate these results in a different population.

Incidence and outcomes of prosthetic valve endocarditis in adults with tetralogy of Fallot.

BACKGROUND: The risk of endocarditis varies with CHD complexity and the presence of prosthetic valves. The purpose of the study was therefore to describe incidence and outcomes of prosthetic valve endocarditis in adults with repair tetralogy of Fallot. METHODS: Retrospective review of adult tetralogy of Fallot patients who underwent prosthetic valve implantation, 1990-2017. We defined prosthetic valve endocarditis-related complications as prosthetic valve dysfunction, perivalvular extension of infection such abscess/aneurysm/fistula, heart block, pulmonary/systemic embolic events, recurrent endocarditis, and death due to sepsis. RESULTS: A total of 338 patients (age: 37 ± 15 years) received 352 prosthetic valves (pulmonary [n = 308, 88%], tricuspid [n = 13, 4%], mitral [n = 9, 3%], and aortic position [n = 22, 6%]). The annual incidence of prosthetic valve endocarditis was 0.4%. There were 12 prosthetic valve endocarditis-related complications in six patients, and these complications were prosthetic valve dysfunction (n = 4), systemic/pulmonary embolic events (n = 2), heart block (n = 1), aortic root abscess (n = 1), recurrent endocarditis (n = 2), and death due to sepsis (n = 1). Three (50%) patients required surgery at 2 days, 6 weeks, and 23 weeks from the time of prosthetic valve endocarditis diagnosis. Altogether three of the six (50%) patients died, and one of these deaths was due to sepsis. CONCLUSIONS: The incidence, complication rate, and outcomes of prosthetic valve endocarditis in tetralogy of Fallot patients underscore some of the risks of having a prosthetic valve. It is important to educate the patients on the need for early presentation if they develop systemic symptoms, have a high index of suspicion for prosthetic valve endocarditis, and adopt a multi-disciplinary care approach in this high-risk population.

Effect of right ventricular pacing on left ventricular systolic function in patients with Tetralogy of Fallot.

BACKGROUND: Prevalence of pacemaker-induced cardiomyopathy (PICM) in adults with congenital heart disease is unknown. Tetralogy of Fallot (TOF) is a common diagnosis in the adult congenital heart disease population, and the purpose of this study was to determine association between frequent right ventricular (RV) pacing and temporal decrease in left ventricular ejection fraction (LVEF) from pre-implantation to 2-years post-implantation (LVEFpost-pre) in TOF patients. METHODS: We studied TOF patients that received RV leads only (N = 51) and a reference group of 7 patients with atrial pacing or biventricular pacing. We defined PICM as a ≥10% decrease in LVEF resulting in LVEF <50%. Linear regression was used to assess relationship between frequent RV pacing (≤20%, 21-40%, >40%) and LVEFpost-pre. RESULTS: PICM occurred in 2 (4%) of 51 patients in RV pacing group. LVEFpost-pre was +3% (95% confidence interval [CI] 0% to +5%) in the reference group and -4% (95% CI -11% to +2%) in RV pacing group. No significant difference occured in LVEFpost-pre between the reference group (LVEFpost-pre +3%) vs RV pacing ≤20% (LVEFpost-pre +1%) vs RV pacing 21-40% (LVEFpost-pre -3%) vs RV pacing >40% (LVEFpost-pre -5%), p = 0.318. There was also no association between frequent RV pacing and LVEFpost-pre, R 2 = 0.307, p = 0.10. CONCLUSION: PICM occurred in 4% of TOF patients receiving RV pacing, and there was no association between frequent RV pacing and temporal decline in LVEF. Further studies are required to determine the long-term impact of RV pacing in the TOF population, and explore optimal treatment strategies.

The applications and potential limitations of right ventricular volumes as surrogate marker in tetralogy of fallot.

Cardiac magnetic resonance imaging derived right ventricular (RV) volumes are often necessary for optimal timing of pulmonary valve replacement in patients with tetralogy of Fallot (TOF). This practice is based on previous studies that reported preoperative RV volumetric thresholds that predicted postoperative RV remodeling. As a result, pulmonary valve replacements are being performed even in asymptomatic patients based on RV volumetric thresholds that predict complete postoperative RVOT remodeling. Hence, RV volumes are now being used as surrogate markers/endpoints for future cardiovascular outcomes. Unfortunately, there are no studies showing survival benefit for performing pulmonary valve replacement at smaller RV volumes. This review underscores some of the limitations of using RV volumes as surrogate markers for clinical outcomes, and also highlights knowledge gaps about the pathophysiologic mechanism of cardiovascular death in the TOF population.

Impact of atrial arrhythmia on survival in adults with tetralogy of Fallot.

BACKGROUND: Atrial arrhythmia is a late complication after tetralogy of Fallot (TOF) repair, but arrhythmia outcomes data are limited. OBJECTIVES: The purpose of the study was to describe atrial arrhythmia presentations, outcomes of antiarrhythmic therapy, and impact of arrhythmia on transplant-free survival. METHODS: We reviewed the MACHD (Mayo Adult Congenital Heart Disease) Registry and identified 113 patients (age 49 ±â€¯13 years) with documented arrhythmia, and 302 patients without history of arrhythmia, 1990-2017. We classified arrhythmias into atrial fibrillation and atrial flutter/tachycardia based on the rhythm on the first abnormal electrocardiogram. RESULTS: At the time of first documented arrhythmia, 58(51%) had atrial fibrillation while 55(49%) had atrial flutter/tachycardia. Of the 113 patients, 14(12%) received rhythm control with class I/III antiarrhythmic drugs (AAD), 79(70%) had direct current cardioversion, 9(8%) received rate control with class II/IV AAD, and 11(10%) received only anticoagulation. Successful cardioversion occurred in 100(89%) patients, and arrhythmia recurrence rate was 16 per 100 patient-years. The multivariate risk factors for death and/or heart transplant were atrial fibrillation (HR 1.94, CI 1.10-3.15, P = .031) and older age (HR 1.63, CI 1.12-2.43, P = .019) per 5 year increment. CONCLUSIONS: Atrial fibrillation, but not atrial flutter, was associated with reduced survival in our repaired TOF cohort. Further studies are required to determine if more aggressive antiarrhythmic therapy will improve survival in patients with atrial fibrillation.

Assessment and Implications of Right Ventricular Afterload in Tetralogy of Fallot.

Patients with tetralogy of Fallot (TOF) have abnormal right ventricular (RV) afterload because of residual or recurrent outflow tract obstruction, often with abnormal pulmonary artery (PA) vascular function. The purpose of this study was to determine if RV afterload was independently associated with death and/or heart transplant in patients with TOF. This is a retrospective study of TOF patients that underwent cardiac catheterization for clinical indications at Mayo clinic between 1990 and 2015. Invasively measured RV systolic pressure (RVSP) was used to define RV afterload. To explore clinical utility for echocardiographic estimates of invasive data, correlations between invasive and Doppler-derived indices of RV afterload were examined. Among 266 patients with TOF (age 35 ± 14 years, TOF-pulmonary atresia 117 [44%]), RVSP was 72 ± 28 mm Hg, PA systolic pressure 45 ± 19 mm Hg, mean PA pressure 27 ± 10 mm Hg, pulmonary vascular resistance 4.2 ± 3.1 WU, and PA wedge pressure 14 ± 5 mm Hg. Over a mean follow up of 12.9 years, there were 35 deaths and 4 heart transplants. Invasively measured RVSP (hazard ratio 1.25, 95% confidence interval 1.12 to 1.37; p <0.001) and TOF-pulmonary atresia (hazard ratio 1.18, 95% confidence interval 1.08 to 1.41; p = 0.023) were independent risk factors for death and/or transplant. Doppler-derived RVSP was well-correlated with invasive RVSP (r = 0.92, p <0.001), and was also independently associated with the combined end point. RVSP, a composite measure of RV afterload, is independently prognostic in patients with TOF, and can be reliably assessed using Doppler echocardiography. Further study is required to test whether interventions to reduce RVSP can improve outcomes in patients with TOF.

Prevalence and in-hospital mortality during arrhythmia-related admissions in adults with tetralogy of Fallot.

BACKGROUND: Although outcomes of arrhythmia diagnosis have been described in ambulatory tetralogy of Fallot (TOF) patients, these have not been studied in hospitalized patients. The purpose of this study was to determine the prevalence and in-hospital mortality due to arrhythmias in TOF patients based on a review of the National Inpatient Sample database. METHODS: Admissions in adult TOF patients (2000-2014) were categorized as arrhythmia-related admission (ARA) or non-arrhythmia-related admission (NRA) based on arrhythmia diagnostic codes. RESULTS: Of 18,353 admissions, 5071 (27.6%) were ARA. The most common arrhythmias were atrial fibrillation (15.5%), atrial flutter (8.4%) and ventricular tachycardia (8.2%), and the prevalence of overall ARA as well as specific arrhythmia types increased over time. In-hospital mortality for ARA was 5.4%, and decreased over time. Arrhythmia diagnosis was an independent predictor of in-hospital mortality (odds ratio [OR] 1.63, 1.34-2.01, p = 0.001). Similarly, atrial fibrillation (OR 1.49, 1.18-1.89, p = 0.001) and ventricular tachycardia (OR: 2.01, 1.55-2.98, p = 0.001) were independent predictors of in-hospital mortality. Compared to small bed-size hospital, ARA in large hospital bed-size hospital was associated with a lower in-hospital mortality (OR 0.71, 0.53-0.96, p = 0.03). CONCLUSION: Atrial fibrillation was the most common arrhythmia in hospitalized TOF patients, and arrhythmia diagnosis (specifically atrial fibrillation and ventricular tachycardia) was an independent predictor of in-hospital mortality, while admission to a large bed-size hospital was associated with a lower risk of in-hospital mortality. Further studies are required to determine if a more proactive approach to arrhythmia management in the ambulatory TOF population will reduce hospitalizations and mortality.

Usefulness of Right Ventricular Volumetric and Afterload Indices for Risk Stratification in Patients With Tetralogy of Fallot.

Right ventricular (RV) volume overload due to chronic pulmonary regurgitation is the common mechanism for hemodynamic deterioration after tetralogy of Fallot (TOF) repair. As a result, RV volumetric indices are used for clinical risk stratification in this population. Since RV afterload is a determinant of RV hemodynamic performance, we hypothesized that afterload-adjusted RV volumetric indices will have a better correlation with disease severity compared with RV volumetric indices alone in patients with TOF. Cross-sectional study of adults with previous TOF repair that received care at Mayo Clinic, 2002-2015. We defined disease severity as atrial arrhythmia and/or impaired exercise capacity. We created afterload-adjusted RV volumetric indices by indexing these indices to RV systolic pressure (RVSP) as follows: RV end-diastolic volume (RVEDVi)/RVSP, RV end-systolic volume (RVESVi)/RVSP, and RV ejection fraction (RVEF)/RVSP. The RV volumetric indices were: RVEDVi 141 ± 43 ml/m2, RVESVi 79 ± 38 ml/m2, and RVEF 44 ± 10%, and RVSP was 48 ± 9 mm Hg. RVESVi was the only RV volumetric parameter that was associated with disease severity (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.01 to 1.32, p = 0.041) with area under the curve (AUC) of 0.612. In contrast RVEF/RVSP (OR 0.73, 95% CI 0.38 to 0.92, p = 0.037, AUC 0.649), and RVESVi/RVSP (OR 1.28, 95% CI 1.14-1.55, p = 0.008, AUC 0.798) were associated with disease severity. Compared with RV volumetric indices alone, the combined RV volumetric and afterload indices had better correlation with disease severity as measured by AUC. Afterload-adjusted RV volumetric indices had better correlation with disease severity, and may potentially improve risk stratification in this population.

Long-term outcomes in adults with repaired tetralogy of Fallot and pulmonary atresia.

BACKGROUND: There are limited outcome data in adults with tetralogy of Fallot and pulmonary atresia. The purpose of this study was to describe re-operations and all-cause mortality in adults with tetralogy of Fallot and pulmonary atresia. METHODS: Retrospective review of adults with repaired tetralogy of Fallot and pulmonary atresia who received care at the Mayo Adult Congenital Heart Disease Clinic, 1990-2016. All-cause mortality was calculated as events per 100 patient-years from the time of first presentation to the Adult Congenital Heart Disease Clinic. RESULTS: Of the 221 patients, the age at initial tetralogy of Fallot repair was 6 (5-13) years, and the age at first presentation to the clinic was 27 - 8 years. All patients had at least one right ventricular to pulmonary artery conduit re-operation. There were 31 deaths (14%) at mean age of 41 - 14 years. The causes of death were end-stage heart failure (n = 17), sudden cardiac death (n=9), post-operative death after cardiac surgery (n = 2), sepsis with multi-system organ failure (n = 2), and unknown (n = 1). All-cause mortality rate was 1.7 per 100 patient-years. The risk factors for all-cause mortality were older age (>12 years) at the time of repair (hazard ratio 1.41, 95 confidence interval 1.06-2.02, p = 0.033), non-sustained ventricular tachycardia (hazard ratio 1.36, 95 confidence interval 1.17-2.47, p = 0.015), and left ventricular ejection fraction <50% (hazard ratio 1.39, 95 confidence interval 1.08-2.31, p = 0.031). CONCLUSION: Based on a review of 221 adults with repaired tetralogy of Fallot and pulmonary atresia, all patients had re-operations and all-cause mortality rate was 1.7 events per 100 patient-years. The current study provides important outcomes data for risk stratification in adults with tetralogy of Fallot and pulmonary atresia.