Byung Won Yoo

Impact of pressure load caused by right ventricular outflow tract obstruction on right ventricular volume overload in patients with repaired tetralogy of Fallot

OBJECTIVES In correction of tetralogy of Fallot (TOF), surgical strategies to minimize right ventricular outflow tract (RVOT) enlargement have recently been preferred. However, we may be confronted with residual pulmonary stenosis (PS) combined with pulmonary regurgitation (PR), and how the pressure load affects these patients is not evident. METHODS We compared 51 patients with PR and significant PS (PR with PS group) with 87 patients with PR without significant PS (PR group) using echocardiography and cardiac magnetic imaging. We evaluated the differences in parameters derived by magnetic resonance imaging between the 2 groups and the influence of the pressure load on right ventricular (RV) volume and function. RESULTS Although the PR fraction was similar between the 2 groups, the PR with PS group showed significantly smaller RV end-diastolic volume (136.7 ± 26.5 mL/m(2) vs 151.2 ± 34.7 mL/m(2); P = .01), RV end-systolic volume (68.1 ± 23.7 mL/m(2) vs 80.2 ± 27.5 mL/m(2); P = .01), and slightly better RV ejection fraction (51.1% ± 9.8% vs 47.6% ± 8.9%; P = .03) than the PR group. For influence of the pressure load, PR fraction (r = -0.18, P = .03), RV end-diastolic volume (r = -0.25, P = .003), and RV end-systolic volume (r = -0.24, P = .005) were decreased as peak pressure gradient of PS was higher. Linear regression analysis revealed that both PR fraction and peak pressure gradient of PS were independent predictors for RV volume. CONCLUSIONS Our study demonstrated that the RV pressure load prevented RV dilatation from chronic PR without systolic dysfunction. It is suggested that a proper relief of RVOT obstruction with acceptable residual stenosis is more advantageous than aggressive RVOT enlargement in the long-term outcome of repaired TOF.

Congestive hepatopathy after Fontan operation and related factors assessed by transient elastography

OBJECTIVE Congestive hepatopathy after a Fontan operation can have a major effect on long-term morbidity. We evaluated congestive hepatopathy in patients with Fontan circulation using transient elastography to determine which risk factors for hepatopathy are related to liver stiffness (LS). METHODS We evaluated 46 patients with Fontan circulation and 26 with right side heart failure (RHF) and hepatic congestion using laboratory tests, the aspartate aminotransferase-to-platelet ratio index, ultrasonography, and transient elastography. RESULTS The LS value was significantly greater in the Fontan group (21.1±8.0 kPa) than in the RHF group (10.0±9.0 kPa). The total bilirubin and albumin serum levels, white blood cell count, and aspartate aminotransferase to platelet ratio index correlated significantly with LS in the Fontan group. Of the risk factors, age at evaluation (r=0.42, P=.004), age at Fontan completion (r=0.51, P<.001), inferior vena cava diameter (r=0.35, P=.02), and spleen size (r=0.53, P=.002) correlated significantly with LS. Nineteen patients in the Fontan group (41.3%) had abnormal ultrasound findings, and the frequency of abnormal findings increased with increasing LS (P=.002). In the subgroup with the greatest LS value (≥30 kPa), 88.9% had abnormal ultrasound findings and 44.4% liver cirrhosis. Multivariate analysis revealed that age at Fontan procedure completion and total bilirubin were independent risk factors for hepatopathy. CONCLUSIONS The present study revealed that congestive hepatopathy developed in a significant fraction of patients with long-term Fontan circulation and that transient elastography could be an easy and useful method to assess congestive hepatopathy in these patients.

Programmed death-1 (PD-1) gene polymorphisms lodged in the genetic predispositions of Kawasaki Disease

The purpose of this study is to investigate the association of programmed death-1 gene (PD-1) polymorphisms with genetic predispositions to Kawasaki disease (KD). A total of 73 patients with KD and 100 healthy controls were enrolled from 2007 to 2008. Two single nucleotide polymorphisms of the PD-1 gene, rs41386349 and rs2227981, were analyzed. Higher T allele frequency of rs41386349 was found in the patient group than the control group (p = 0.007, odds ratio (OR) = 1.9, 95% CI = 1.2–2.9). PD-1 rs2227981 polymorphism was not significant in patients with KD comparing with the control group (p = 0.4, OR = 1.2 (0.8–1.9)). Furthermore, no difference of PD-1 polymorphisms between patients with coronary artery dilatation (CAD) and those without CAD was found. Our data support the possibility that PD-1 gene polymorphism may be related with the genetic susceptibility of KD in Korean population.

Traumatic ventricular septal defect in a 4-year-old boy after blunt chest injury

Traumatic ventricular septal defect (VSD) resulting from blunt chest injury is a very rare event. The mechanisms of traumatic VSD have been of little concern to dateuntil now, but two dominant theories have been described. In one, the rupture occurs due to acute compression of the heart; in the other, it is due to myocardial infarction of the septum. The clinical symptoms and timing of presentation are variable, so appropriate diagnosis can be difficult or delayed. Closure of traumatic VSD has been based on a combination of heart failure symptoms, hemodynamics, and defect size. Here, we present a case of a 4-year-old boy who presented with a traumatic VSD following a car accident. He showed normal cardiac structure at the time of injury, but after 8 days, his repeated echocardiography revealed a VSD. He was successfully treated by surgical closure of the VSD, and has been doing well up to the present. This report suggests that the clinician should pay great close attention to the patients injured by blunt chest trauma, keeping in mind the possibility of cardiac injury.

Pulmonary stenosis and pulmonary regurgitation: both ends of the spectrum in residual hemodynamic impairment after tetralogy of Fallot repair

Repair of tetralogy of Fallot (TOF) has shown excellent outcomes. However it leaves varying degrees of residual hemodynamic impairment, with severe pulmonary stenosis (PS) and free pulmonary regurgitation (PR) at both ends of the spectrum. Since the 1980s, studies evaluating late outcomes after TOF repair revealed the adverse impacts of residual chronic PR on RV volume and function; thus, a turnaround of operational strategies has occurred from aggressive RV outflow tract (RVOT) reconstruction for complete relief of RVOT obstruction to conservative RVOT reconstruction for limiting PR. This transformation has raised the question of how much residual PS after conservative RVOT reconstruction is acceptable. Besides, as pulmonary valve replacement (PVR) increases in patients with RV deterioration from residual PR, there is concern regarding when it should be performed. Regarding residual PS, several studies revealed that PS in addition to PR was associated with less PR and a small RV volume. This suggests that PS combined with PR makes RV diastolic property to protect against dilatation through RV hypertrophy and supports conservative RVOT enlargement despite residual PS. Also, several studies have revealed the pre-PVR threshold of RV parameters for the normalization of RV volume and function after PVR, and based on these results, the indications for PVR have been revised. Although there is no established strategy, better understanding of RV mechanics, development of new surgical and interventional techniques, and evidence for the effect of PVR on RV reverse remodeling and its late outcome will aid us to optimize the management of TOF.

The Pythagorean theorem reveals the inherent companion of cardiac ejection fraction

BACKGROUND Quantification of ventricular performance requires a comprehensive metric which is manageable for patient care and clinical trials. Ejection fraction (EF) has been embraced as an attractive candidate. However, being a dimensionless ratio, EF has serious limitations. METHODS We aim to identify what information is not recognized when limiting the volume-related analysis by exclusively relying on EF. This investigation applies the volume domain concept, relating end-systolic volume (ESV) to end-diastolic volume (EDV). This approach allows graphical identification of the information not covered by EF. Implications for atria, left ventricle (LV) and right ventricle (RV) are investigated in healthy individuals, and cardiac patient groups using various imaging modalities. RESULTS The Pythagorean theorem indicates that the hypotenuse which relates any {EDV, ESV} combination to EF corresponds with the information not covered by the single metric EF. The impact of the recovered EF companion (EFC) is illustrated in healthy adults (N = 410, LV 2D echocardiography), heart transplant patients (N = 101, LV CT), individuals with heart failure (N = 197, biplane angiocardiography), for the RV with corrected Fallot (N = 124, MRI), diameters for left atrium (N = 49, MRI) and area for right atrium (N = 51, MRI). For any limited EF range we find a spectrum of EFC values, showing that the two metrics contain (partly) independent information, and emphasizing that the sole use of EF only partially conveys the full information available. CONCLUSIONS The EFC is a neglected companion, containing information which is additive to EF. Analysis based on ESV and EDV is preferred over the use of EF.

Comparison of biosimilar filgrastim with a reference product: pharmacokinetics, pharmacodynamics, and safety profiles in healthy volunteers

Purpose Filgrastim, a granulocyte-colony stimulating factor, is used to treat patients with neutropenia, including neutropenic fever. Leucostim® is a recombinant filgrastim product tested for biosimilarity with its reference product, Neupogen®. We conducted a comparative clinical trial of the 2 products. Patients and methods A randomized, open-label, 2-way crossover, single-dose Phase I study was conducted for 56 healthy subjects. After a 5 and 10 μg/kg single subcutaneous administration of test and reference product, pharmacokinetic and pharmacodynamic parameters (absolute neutrophil count and CD34+ cell count) were compared. During the study, safety tests and adverse event monitoring were performed. Results The test and the reference products had a comparable pharmacokinetic, pharmacodynamic, and safety profile. In both 5 and 10 μg/kg dosing, the 90% CIs of the test to reference ratio for primary parameters (peak plasma concentration and area under the plasma concentration vs time curve from time 0 extrapolated to the infinite time for plasma filgrastim concentration; maximal effect and area under the time-effect curve from time 0 to time of the last quantifiable effect for absolute neutrophil count) were within the 0.8–1.25 range. In addition, safety profiles between the 2 products were similar without any serious adverse events. Conclusion This study has provided firm clinical evidence that the test filgrastim product is similar to its reference filgrastim product.