P6318NT-proBNP indicates left ventricular impairment and adverse clinical outcome in patients with Tetralogy of Fallot and pulmonary regurgitation

Intracardiac hemodynamic forces have been proposed to influence remodeling and be a marker of ventricular dysfunction. We aimed to quantify the hemodynamic forces in patients with repaired tetralogy of Fallot (rToF) to further understand the pathophysiological mechanisms as this could be a potential marker for pulmonary valve replacement (PVR) in these patients. Patients with rToF and pulmonary regurgitation (PR) > 20% ( n = 18) and healthy control subjects ( n = 15) underwent MRI, including four-dimensional flow. A subset of patients ( n = 8) underwent PVR and MRI after surgery. Time-resolved hemodynamic forces were quantified using 4D-flow data and indexed to ventricular volume. Patients had higher systolic and diastolic left ventricular (LV) hemodynamic forces compared with control subjects in the lateral-septal/LV outflow tract ( P = 0.011 and P = 0.0031) and inferior-anterior ( P < 0.0001 and P < 0.0001) directions, which are forces not aligned with blood flow. Forces did not change after PVR. Patients had higher RV diastolic forces compared with control subjects in the diaphragm-right ventricular (RV) outflow tract (RVOT; P < 0.001) and apical-basal ( P = 0.0017) directions. After PVR, RV systolic forces in the diaphragm-RVOT direction decreased ( P = 0.039) to lower levels than in control subjects ( P = 0.0064). RV diastolic forces decreased in all directions ( P = 0.0078, P = 0.0078, and P = 0.039) but were still higher than in control subjects in the diaphragm-RVOT direction ( P = 0.046). In conclusion, patients with rToF and PR had LV hemodynamic forces less aligned with intraventricular blood flow compared with control subjects and higher diastolic RV forces along the regurgitant flow direction in the RVOT and that of tricuspid inflow. Remaining force differences in the LV and RV after PVR suggest that biventricular pumping does not normalize after surgery. NEW & NOTEWORTHY Biventricular hemodynamic forces in patients with repaired tetralogy of Fallot and pulmonary regurgitation were quantified for the first time. Left ventricular hemodynamic forces were less aligned to the main blood flow direction in patients compared with control subjects. Higher right ventricular forces were seen along the pulmonary regurgitant and tricuspid inflow directions. Differences in forces versus control subjects remain after pulmonary valve replacement, suggesting that altered biventricular pumping does not normalize after surgery.

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Study of the time-relationship of the mechano-electrical interaction in an animal model of tetralogy of Fallot: implications for the risk assessment of ventricular arrhythmias

Interactive CardioVascular and Thoracic Surgery ◽

10.1093/icvts/ivaa047 ◽

2020 ◽

Vol 31 (1) ◽

pp. 129-137

Author(s):

Thierry Bove ◽

Rahi Alipour Symakani ◽

Jonas Verbeke ◽

Anne Vral ◽

Milad El Haddad ◽

...

Keyword(s):

Tetralogy Of Fallot ◽

Ventricular Arrhythmias ◽

Pulmonary Regurgitation ◽

Left Ventricular ◽

Monophasic Action Potential ◽

Control Group ◽

Stroke Work ◽

Long Term Outcome ◽

Intraventricular Conduction ◽

Qrs Prolongation

Abstract OBJECTIVES The long-term outcome of tetralogy of Fallot (TOF) is determined by progressive right ventricular (RV) dysfunction through pulmonary regurgitation (PR) and the risk of malignant arrhythmia. Although mechano-electrical coupling in TOF is well-known, its time effect on the inducibility of arrhythmia remains ill-defined. The goal of this study was to investigate the mechano-electrical properties at different times in animals with chronic PR. METHODS PR was induced by a transannular patch with limited RV scarring in infant pigs. Haemodynamic assessment included biventricular pressure–volume loops after 3 (n = 8) and 6 months (n = 7) compared to controls (n = 5). The electrophysiological study included endocardial monophasic action potential registration, intraventricular conduction velocity and induction of ventricular arrhythmia by burst pacing. RESULTS Progressive RV dilation was achieved at 6 months (RV end-diastolic volume 143 ± 13 ml/m2—RV end-systolic volume 96 ± 7 ml/m2; P < 0.001), in association with depressed RV contractility (preload recruitable stroke work-slope: 19 ± 1 and 11 ± 3 Mw.ml−1.s−1 for control and 6 m; P < 0.001) and left ventricular contractility (preload recruitable stroke work-slope: 60 ± 13 and 40 ± 11 Mw.ml−1.s−1 for control and 6 m; P = 0.005). Concomitant to QRS prolongation, monophasic action potential90-duration and dispersion at the RV and left ventricle were increased at 6 months. Intraventricular conduction was delayed only in the RV at 6 months (1.8 ± 0.2 and 2.4 ± 0.6 m/s for group 6M and the control group; P = 0.035). Sustained ventricular arrhythmias were not inducible. CONCLUSIONS In animals yielding the sequelae of a contemporary operation for TOF, mechano-electrical alterations are progressive and affect predominantly the RV after midterm exposure of PR. Because ventricular arrhythmias were not inducible despite significant RV dilation, the data suggest that the haemodynamic RV deterioration effectively precedes the risk of inducing sustained arrhythmia after TOF repair and opens a window for renewed stratification of contemporary risk factors of ventricular arrhythmias in patients operated on with currently used pulmonary valve- and RV-related techniques.

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Left ventricular outflow obstruction resulting from insertion of mitral prostheses leaving the native leaflets intact: Adverse clinical outcome in seven patients

American Heart Journal ◽

10.1016/0002-8703(91)91005-8 ◽

1991 ◽

Vol 122 (2) ◽

pp. 483-488 ◽

Cited By ~ 18

Author(s):

Alan D. Waggoner ◽

Julio E. Pérez ◽

Benico Barzilai ◽

Michael Rosenbloom ◽

Mark H. Eaton ◽

...

Keyword(s):

Clinical Outcome ◽

Left Ventricular ◽

Adverse Clinical Outcome ◽

Outflow Obstruction ◽

Left Ventricular Outflow Obstruction ◽

Ventricular Outflow Obstruction ◽

Left Ventricular Outflow

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Right ventricular systolic dysfunction but not dilatation correlates with prognostically significant reductions in exercise capacity in repaired Tetralogy of Fallot

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez245 ◽

2019 ◽

Vol 21 (8) ◽

pp. 906-913 ◽

Cited By ~ 1

Author(s):

Imran Rashid ◽

Adil Mahmood ◽

Tevfik F Ismail ◽

Shamus O’Meagher ◽

Shelby Kutty ◽

...

Keyword(s):

Right Ventricular ◽

Tetralogy Of Fallot ◽

Exercise Capacity ◽

Multivariable Analysis ◽

Cardiopulmonary Exercise Testing ◽

Pulmonary Regurgitation ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Peak Vo2 ◽

Repaired Tetralogy Of Fallot

Abstract Aims The optimal timing for pulmonary valve replacement in asymptomatic patients with repaired Tetralogy of Fallot (rTOF) and pulmonary regurgitation remains uncertain but is often guided by increases in right ventricular (RV) end-diastolic volume. As cardiopulmonary exercise testing (CPET) performance is a strong prognostic indicator, we assessed which cardiovascular magnetic resonance (CMR) parameters correlate with reductions in exercise capacity to potentially improve identification of high-risk patients. Methods and results In all, 163 patients with rTOF (mean age 24.5 ± 10.2 years) who had previously undergone CMR and standardized CPET protocols were included. The indexed right and left ventricular end-diastolic volumes (RVEDVi, LVEDVi), right and left ventricular ejection fractions (RVEF, LVEF), indexed RV stroke volume (RVSVi), and pulmonary regurgitant fraction (PRF) were quantified by CMR and correlated with CPET-determined peak oxygen consumption (VO2) or peak work. On univariable analysis, there was no significant correlation between RVEDVi and PRF with peak VO2 or peak work (% Jones-predicted). In contrast, RVEF and RVSVi had significant correlations with both peak VO2 and peak work that remained significant on multivariable analysis. For a previously established prognostic peak VO2 threshold of <27 mL/kg/min, receiver-operating characteristic curve analysis demonstrated a Harrell’s c of 0.70 for RVEF (95% confidence interval 0.61–0.79) with a sensitivity of 88% for RVEF <40%. Conclusion In rTOF, CMR indices of RV systolic function are better predictors of CPET performance than RV size. An RVEF <40% may be useful to identify prognostically significant reductions in exercise capacity in patients with varying degrees of RV dilatation.

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Ramipril for left ventricular diastolic function in patients with pulmonary regurgitation after repair of tetralogy of Fallot

International Journal of Cardiology ◽

10.1016/j.ijcard.2018.11.006 ◽

2019 ◽

Vol 278 ◽

pp. 95

Author(s):

Lin Xie ◽

Ke Lin

Keyword(s):

Diastolic Function ◽

Tetralogy Of Fallot ◽

Pulmonary Regurgitation ◽

Left Ventricular Diastolic Function ◽

Left Ventricular ◽

Ventricular Diastolic Function

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Right-left ventricular shape variations in tetralogy of Fallot: associations with pulmonary regurgitation

Journal of Cardiovascular Magnetic Resonance ◽

10.1186/s12968-021-00780-x ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Charlène A. Mauger ◽

Sachin Govil ◽

Radomir Chabiniok ◽

Kathleen Gilbert ◽

Sanjeet Hegde ◽

...

Keyword(s):

Right Ventricular ◽

Tetralogy Of Fallot ◽

Pulmonary Regurgitation ◽

Principal Component ◽

Pulmonary Valve Replacement ◽

Left Ventricular ◽

Optimal Timing ◽

Shape Variation ◽

Regurgitant Volume ◽

Cross Sectional

Abstract Background Relationships between right ventricular (RV) and left ventricular (LV) shape and function may be useful in determining optimal timing for pulmonary valve replacement in patients with repaired tetralogy of Fallot (rTOF). However, these are multivariate and difficult to quantify. We aimed to quantify variations in biventricular shape associated with pulmonary regurgitant volume (PRV) in rTOF using a biventricular atlas. Methods In this cross-sectional retrospective study, a biventricular shape model was customized to cardiovascular magnetic resonance (CMR) images from 88 rTOF patients (median age 16, inter-quartile range 11.8–24.3 years). Morphometric scores quantifying biventricular shape at end-diastole and end-systole were computed using principal component analysis. Multivariate linear regression was used to quantify biventricular shape associations with PRV, corrected for age, sex, height, and weight. Regional associations were confirmed by univariate correlations with distances and angles computed from the models, as well as global systolic strains computed from changes in arc length from end-diastole to end-systole. Results PRV was significantly associated with 5 biventricular morphometric scores, independent of covariates, and accounted for 12.3% of total shape variation (p < 0.05). Increasing PRV was associated with RV dilation and basal bulging, in conjunction with decreased LV septal-lateral dimension (LV flattening) and systolic septal motion towards the RV (all p < 0.05). Increased global RV radial, longitudinal, circumferential and LV radial systolic strains were significantly associated with increased PRV (all p < 0.05). Conclusion A biventricular atlas of rTOF patients quantified multivariate relationships between left–right ventricular morphometry and wall motion with pulmonary regurgitation. Regional RV dilation, LV reduction, LV septal-lateral flattening and increased RV strain were all associated with increased pulmonary regurgitant volume. Morphometric scores provide simple metrics linking mechanisms for structural and functional alteration with important clinical indices.

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Predictive Value of Coagulation Markers Concerning Clinical Outcome 90 Days after Anterior Myocardial Infarction

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614557 ◽

1999 ◽

Vol 81 (05) ◽

pp. 701-704 ◽

Cited By ~ 11

Author(s):

Frederic Kontny ◽

Ulrich Abildgaard ◽

Carl-Erik Dempfle

Keyword(s):

Myocardial Infarction ◽

Clinical Outcome ◽

Predictive Value ◽

Thrombus Formation ◽

Left Ventricular ◽

Adverse Clinical Outcome ◽

Coagulation Activation ◽

Activation Markers ◽

Increased Risk ◽

D Dimer

SummaryTo study the predictive value of coagulation markers concerning clinical outcome, prothrombin fragment F1.2 (F1.2), fibrin monomer antigen (FM), D-Dimer (DD), and fibrinogen were measured in plasma samples drawn 2 and 7 days after acute myocardial infarction (AMI) in 314 consecutive patients randomized in a clinical trial of low molecular weight heparin (Dalteparin) (the FRAMI trial). Placebo-treated patients suffering death or new AMI within 90 days had significantly higher levels at day 2 of FM (Enzymun-Test FM), and DD (TINAquant D-dimer) (p = 0.001 and 0.02, respectively), but not F1.2 (Enzygnost F1.2 micro), relative to those without serious clinical events. At day 7 all three coagulation activation markers were significantly higher in patients with subsequent adverse clinical outcome. The Dalteparin group had significantly lower levels of these markers as compared to the placebo group. Left ventricular (LV) thrombus formation was not associated with changes in coagulation activation. However, patients with thrombus had significantly higher fibrinogen levels than those without thrombus (p = 0.004 day 2), independent of treatment group. Thus, markers of coagulation activation may be useful in stratification of patients when estimating risk for adverse clinical outcome after AMI. Furthermore, elevated fibrinogen levels are associated with increased risk of LV thrombus formation.

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The value of right ventricular longitudinal strain in the evaluation of adult patients with repaired tetralogy of Fallot: a new tool for a contemporary challenge

Cardiology in the Young ◽

10.1017/s1047951116000810 ◽

2016 ◽

Vol 27 (3) ◽

pp. 498-506 ◽

Cited By ~ 8

Author(s):

Luís Almeida-Morais ◽

Tiago Pereira-da-Silva ◽

Luísa Branco ◽

Ana T. Timóteo ◽

Ana Agapito ◽

...

Keyword(s):

Ejection Fraction ◽

Right Ventricular ◽

Tetralogy Of Fallot ◽

Longitudinal Strain ◽

Pulmonary Regurgitation ◽

Right Ventricular Ejection Fraction ◽

Left Ventricular ◽

Ventricular Ejection ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction

AbstractObjectiveThe role of right ventricular longitudinal strain for assessing patients with repaired tetralogy of Fallot is not fully understood. In this study, we aimed to evaluate its relation with other structural and functional parameters in these patients.MethodsPatients followed-up in a grown-up CHD unit, assessed by transthoracic echocardiography, cardiac MRI, and treadmill exercise testing, were retrospectively evaluated. Right ventricular size and function and pulmonary regurgitation severity were assessed by echocardiography and MRI. Right ventricular longitudinal strain was evaluated in the four-chamber view using the standard semiautomatic method.ResultsIn total, 42 patients were included (61% male, 32±8 years). The mean right ventricular longitudinal strain was −16.2±3.7%, and the right ventricular ejection fraction, measured by MRI, was 42.9±7.2%. Longitudinal strain showed linear correlation with tricuspid annular systolic excursion (r=−0.40) and right ventricular ejection fraction (r=−0.45) (all p<0.05), which in turn showed linear correlation with right ventricular fractional area change (r=0.50), pulmonary regurgitation colour length (r=0.35), right ventricular end-systolic volume (r=−0.60), and left ventricular ejection fraction (r=0.36) (all p<0.05). Longitudinal strain (β=−0.72, 95% confidence interval −1.41, −0.15) and left ventricular ejection fraction (β=0.39, 95% confidence interval 0.11, 0.67) were independently associated with right ventricular ejection fraction. The best threshold of longitudinal strain for predicting a right ventricular ejection fraction of <40% was −17.0%.ConclusionsRight ventricular longitudinal strain is a powerful method for evaluating patients with tetralogy of Fallot. It correlated with echocardiographic right ventricular function parameters and was independently associated with right ventricular ejection fraction derived by MRI.

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