May

The Combined Usefulness of the Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Predicting Intravenous Immunoglobulin Resistance with Kawasaki Disease

The Combined Usefulness of the Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Predicting Intravenous Immunoglobulin Resistance with Kawasaki Disease.   Kawamura Y, Takeshita S, Kanai T, Yoshida Y, Nonoyama S.J Pediatr. 2016 Nov;178:281-284.e1. doi: 10.1016/j.jpeds.2016.07.035. Epub 2016 Aug 12.PMID: 27526622   Take-Home Points:   In patients with Kawasaki Disease, high Neutrophil to Lymphocyte ratio (NLR) and high Platelet to Lymphocyte ratio (PLR) before initiation of IVIG independently predicted IVIG resistance. The combination of NLR and ILR is a more reliable predictor than either of them used alone. The combination of these simple ratios calculated from the findings of standard blood test has the predictive ability of IVIG resistance almost equal to the traditional scoring systems     Commentary from Dr. Venugopal Amula (Salt Lake City UT), section editor of Pediatric Cardiology Journal Watch: In Kawasaki Disease, resistance to traditional therapy with IVIG and Aspirin occurs not infrequently and puts the patients at higher risk of developing coronary artery lesions.   Many scoring systems and laboratory biomarkers have been evaluated to predict IVIG resistance, as changes in treatment strategy may alter coronary artery involvement.   Kanai et al. report the utility of two blood cell type ratios, Neutrophil to Lymphocyte ratio( NLR) and Platelet to Lymphocyte Ratio, calculated before initiation of IVIG in predicting the ability of IVIG resistance in KD patients. The current report is an expansion of the same authors' pilot study that suggested the benefit of the combination of these ratios in predicting IVIG resistance. Small sample size limited the single-center pilot study.   . The current investigation is a retrospective, a multicenter cohort study of KD patients from seven hospitals in Japan admitted between March 2004 to Feb 2017. The datasets were divided into the development dataset (March 2004 to Mar 2014) and the validation cohort (April 2014 to Feb 2017).   Classic diagnostic criteria were applied, and IVIG resistance was defined as persistent fever lasting > 24 hrs. after IVIG completion or recrudescent fever after an afebrile period.   All patients were treated with a standard initial treatment regimen of 30mg/kg/d of Aspirin and 2g/kg/d of IVIG. Patients with incomplete KD, late diagnosis, coronary involvement before the initial treatment, and intensive nonstandard initial treatment regimen were excluded.   Receiver operating characteristic curves were constructed using the development dataset, and the most discriminating cut off values was used to assess sensitivity, specificity, PPV, and NPV when applied to NLR and PLR in predicting IVIG resistance. The predictive marker obtained was applied to the validation dataset to determine predictive accuracy.   A total of 852 patients were analyzed, with 520 representing the development dataset and the rest validation dataset. IN both the datasets, the NLR, PLR, cell count of neutrophils, ALT, AST, CRP Gunma score, and Kurume score were significantly higher in the IVIG resistant group than the active group. A ROC analysis showed the best cut off values of NLR and PLR were 4.11 and 119, respectively. Multiple regression analysis of the age at onset and other variables with a significant difference between the IVIG responsive and the resistant groups in the development dataset showed that both the NLR> or = 4.11 and PLR> or = 119 were independent predictors of IVIG resistance in KD with OR of 2.86 and 1.95 respectively. When combined the adjusted odds ratio was higher at 4.33 ( 95% CI 2.43-7.71; p<0.001).   The new predictive marker of the combination of NLR > 4.11 and PLR > 119 had a significant high adjusted OR of 2.6 in the validation set, suggesting it was as accurate in predicting IVIG resistance in a different dataset. The sensitivity and specificity of the new predictive in the validation data set were 0.54 and 0.72, almost the same in the development dataset. The marker also performed equally well, compared to the Gunma score and Kurume score in predicting IVIG resistance.   The authors present an easy-to-calculating predictive marker of a combination of NLR and PLR to predict IVIG resistance. Whether this novel and low-cost evaluation to predict IVIG resistance could be applied to different patient populations across the world is uncertain, but the authors opine that as these ratios simply focus on response to inflammation, they should work regardless of ethnicity.                                

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Treatment strategies for protein-losing enteropathy in Fontan-palliated patients

Treatment strategies for protein-losing enteropathy in Fontan-palliated patients. Schleiger A, Ovroutski S, Peters B, Schubert S, Photiadis J, Berger F, Kramer P. Cardiol Young. 2020 May;30(5):698-709. doi: 10.1017/S1047951120000864. Epub 2020 May 4.PMID: 32364090   Take-Home Points:   Protein-losing enteropathy (PLE) occurred in 30 out of 439 (6.8%) Fontan patients managed at a single institution during the study period of 1986-2019, and it developed at the median of 2.9 years after Fontan operation. Cardiopulmonary perturbations in the form of unilateral diaphragmatic paralysis or central PA stenosis or Fontan pathway obstruction or bradyarrhythmia were present at manifestation or during the disease in 25 of 30 patients (83%). The factors significantly associated with the development of PLE in this cohort were bradyarrhythmia, phrenic nerve palsy, and stenosis within the Fontan pathway. Patency of Fontan fenestration was associated with decreased odds of PLE. The treatment strategies were varied, including surgical management of phrenic palsy with diaphragm plication, pacemaker implantation for bradyarrhythmia, and percutaneous cath interventions aimed at relieving the Fontan pathway obstruction. Medical therapies were predominantly a combination of pulmonary vasodilator therapy and anti-inflammatory therapy with budesonide and diuretics and heart failure therapy. Between all the treatment strategies, stable remission, defined as regression of symptoms and elevated serum albumin levels >3.5g/dl over 12 months, was seen among 15 patients (50%) at the time of the study. The somatic growth and physical development was significantly delayed in Fontan patients associated with PLE than non-PLE cohort as compared by z-scores for height and body weight. The sexual development was also delayed but not statistically significant. The mortality in this cohort was 33.3% and occurred after a median of 7.2 years from the onset of the disease. The survival estimates declined from 96.1% at five years to 70.5 % at 10 and 50.1% at 20 years. Nonsurvivors had lower serum albumin and total protein levels, higher pulmonary artery pressure, and impaired ventricular function, at last follow-up compared to survivors. Lack of indications for surgical or cath-based interventions and failure to respond to medical treatment with no significant improvement or remission within 6-12 months should prompt cardiac transplantation evaluation.     Commentary from Dr. Venugopal Amula (Salt Lake City UT), section editor of Pediatric Cardiology Journal Watch: Protein Losing Enteropathy is an infrequent but critical complication that limits survival in Fontan patients – the exact pathophysiological mechanism of which remains unknown. This current report by A. Schleiger et al. is a retrospective, observational study of Fontan patients followed up at a single institution between 1986 and 2019. The authors identified a cohort of 439 patients, of which 327 were operated in their institution. They retrospectively applied a proposed universal diagnostic definition of protein-losing enteropathy in Fontan patients and identified 30 patients with the disease condition. PLE was defined by the criteria of the combination of persistent diarrhea or recurring edema or pleural effusions or ascites, decreased serum albumin levels, and total serum protein levels and confirmation of intestinal protein loss with increased fecal alpha antitrypsin levels.   Demographic, clinical, laboratory, and echocardiographic data were abstracted from institutional medical records. Surgical and hemodynamic data detailing the Fontan surgery was also retrieved. Standard descriptive statistics were applied survival, and freedom from PLE was assessed using Kaplan Meier Survival analysis.   The PLE patients had a long median follow up of 13.1 years. The long follow up helped them chronicle the anthropometric, clinical, hemodynamic, and laboratory parameters of these patients since the onset of PLE. Extracardiac total cavopulmonary connection was a common type of Fontan modification in 20 of 30 patients, and 60% had a single left ventricle. Patents who eventually developed PLE had significantly prolonged ICU and hospital lengths of stay, however ventricular morphology was unrelated to disease manifestation.   Around 80% of patients had cardiopulmonary perturbations that were heterogeneous, ranging from diaphragm paralysis, obstruction of Fontan pathway, bradyarrhythmia, and central PA stenosis. Significant risk factors associated with PLE were phrenic nerve palsy, bradyarrhythmia, and Fontan pathway obstruction.   The treatment strategies for PLE were analyzed in detail and involved surgical and catheter-based interventions for those indicated. Medical therapy was targeted towards pulmonary vasodilation, anti-inflammatory therapy with budesonide, diuretic, and heart failure therapy. Surgical indications were discrete such as phrenic nerve palsy and PM placement for bradyarrhythmias. A total of 64 percutaneous catheter-based procedures were performed in 25 patients directed towards relieving Fontan pathway obstruction.   Overall, 15 patients were in remission at the time of study with surgical or interventional or medical or combination of therapies.   During the follow up there was a progressive decline in ventricular function, although the degree of Av valve regurgitation did not change. One-third of the patients died after a median interval of 7.2 years, with an estimated ten-year survival of 70.5% and 20-year survival of 50.1%. Overall, four patients were listed for transplant with two patients receiving it while two died on the waiting list. Among those transplanted, one died in the postoperative period.   Although the authors evaluated a large cohort of patients with a reasonable long follow up period, the study is limited by being a single institutional experience. It may not apply to other centers with different populations and variations in surgical and postoperative management strategies. The extended study period lends itself to era effect on disease manifestation with improved current era surgical and anesthetic techniques. Significant advances in the understanding of the abdominal lymphatic system and drainage in the setting of central venous congestion have occurred recently and are paramount to the latest interventions of redirecting lymphatic drainage to prevent and treat PLE.            

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Retrospective Analysis of Clinical Genetic Testing in Pediatric Primary Dilated Cardiomyopathy: Testing Outcomes and the Effects of Variant Reclassification

Retrospective Analysis of Clinical Genetic Testing in Pediatric Primary Dilated Cardiomyopathy: Testing Outcomes and the Effects of Variant Reclassification.   Quiat D, Witkowski L, Zouk H, Daly KP, Roberts AE.J Am Heart Assoc. 2020 Jun 2;9(11):e016195. doi: 10.1161/JAHA.120.016195. Epub 2020 May 27.PMID: 32458740   Take Home Points:   Clinical genetic testing identifies about ⅓ of patients with a primary dilated cardiomyopathy (DCM) with many variants of unknown significance (VUS). Reevaluation/reclassification of prior genetic testing decreased the number of VUS but a large number still remained. Familial genetic testing may help with interpretation of the results.     Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch: Only ~ 30-50% of DCM cases have an identifiable etiology, with neuromuscular and myocarditis being the most common. With the improvement in genetic testing, many of the “idiopathic” cases have shown pathogenic variants. However, the amount of VUS has been quite high, and in some regards, this could be considered almost as a “worst case scenario” since it remains unclear if this is the pathogenic etiology or a benign variant. This can markedly affect future family planning or determine prognosis in genotypic carriers. In 2015, the American College of Medical Genetics and Genomics established a 5-tier classification system for VUS (pathogenic, likely pathogenic, uncertain significance, likely benign, benign). This, along with an increase in testing panel content and availability of allele databases, people with a VUS on testing in the past may be able to be reclassified, allowing for improved diagnosis, prognosis, and family counseling.   In this paper, a cohort of 63 patients over a 10 year period (2008-2018) with DCM was evaluated. 18% had a family history of cardiomyopathy or sudden death. 30% had a disease causing variant identified with nearly half occurring de novo. 116 variants were found on initial gene testing, 8 classified as pathogenic, 11 likely pathogenic, 90 VUS, 3 likely benign, and 2 benign (and an additional 2 as unclassified). Reclassification was performed which resulted in the downgrading of 29% (26/90) of VUS to either likely benign or benign and an absolute decrease in the number of BUS from 60% to 52% and an increase in likely benign/benign from 14% to 24%. See table 2. In those with a positive family history (9), 3 variants were inherited and 6 were de novo mutations. In 6 patients with potentially disease causing VUS, familial testing showed 3 occurring de novo and 3 inherited. Interestingly though, they did not find a difference in rates of positive cardiomyopathy genetic testing in patients with (27%) or without (33%) a family history cardiomyopathy or sudden death. With regards to testing, larger gene panels (> 50) found 27% with pathogenic variants vs. 20% in smaller panels (< 50). Of their cohort, 29/63 (46%) underwent heart transplantation or died during the follow up period.   This study shows that periodic reclassification and familial cascade genetic testing can reduce the number of VUS to allow for better diagnosis and future screening for DCM. Unfortunately, the percentage of VUS remains high, so hopefully with further reevaluation as larger panels and other advances are made (or use of whole genome testing is done), this can be improved. Since there are no clear guidelines for how to undergo this process, the authors recommend a review of genetic testing any time there is a VUS, more than a year has passed, and the parents are planning to have more children.          

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Pediatric Cardiology Specialist’s Opinions Toward the Acceptability of Comfort Care for Congenital Heart Disease

Pediatric Cardiology Specialist's Opinions Toward the Acceptability of Comfort Care for Congenital Heart Disease. Swanson TM, Patel A, Baxter AJ, Morris SA, Maskatia SA, Lantos JD. Pediatr Cardiol. 2020 May 18. doi: 10.1007/s00246-020-02367-2. Online ahead of print. PMID: 32419096   Take Home Points: There is consensus amongst pediatric cardiologists and CV surgeons to seek legal action and mandate surgery for low surgical mortality risk lesions. There was less likelihood of seeking legal action for Shone complex, single ventricle lesions or CHD associated with trisomy 13 or 18.     Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch: As survival has improved dramatically for CHD over the past 40 years, decisions regarding the acceptability of comfort care would seemingly change. Balancing short term and long term mortality data along with morbidities, whether cardiac or neurodevelopmental, is necessary for physicians to help counsel families appropriately. Given the complexity of CHD, it can be difficult for families to truly understand the risks, and defaulting to parental decision-making may not be the most ethical course of action. This paper describes an interesting and basic survey of pediatric cardiologists and CV surgeons at 4 sites to determine the acceptability of overriding parental refusal of surgery for various forms of isolated CHD or associated with various genetic syndromes. 4 choices were provided: (1) agree and support parents who choose not to pursue surgical intervention; (2) disagree but support parental decision; (3) disagree, would not support parental decision, but would not interfere with the decision; and (4) disagree and would seek legal action to pursue surgery. Opinions were cross referenced with STS data regarding surgical mortality for each lesion.   135 physicians were surveyed and there were no statistically significant differences between site location. Table 2 shows physician choice for each lesion. Table 3 shows the percentage of physicians who would seek legal action along with published mortality rates. Figure 1 shows a regression line to demonstrate the strength of correlation between surgical mortality and willingness to pursue legal action. For mortality less than 4.5%, most physicians would seek legal action. Associated genetic syndrome, especially trisomy 13 or 18 strongly decreased the likelihood of recommending surgery.   There are a few interesting points brought in the discussion. First, STS data alone is not always enough to make a decision regarding care. Especially for a single ventricle lesion, this does not capture survival to the following stages of palliation or include life expectancy and morbidity, which can strongly influence decision making. Additionally, ductal dependent lesions, in which non-intervention would lead to “quick” demise may be different than those that could lead to a shorter life expectancy but have profound and progressive future cardiac symptoms and medical problems. Additionally, genetic syndromes influence opinion, and interestingly, the presence of Down syndrome with an AVSD resulted in a lower number of physicians who would seek legal action, even though published mortality rates are lower than those without Down syndrome. The authors also conject that lesions such as Shone syndrome that have uncertainty with future outcomes could influence physician opinion. Fetal counseling or discussion regarding termination was not addressed in this survey, and could be confounded by politics or religious beliefs.          

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Accessing Femoral Arteries Less than 3 mm in Diameter is Associated with Increased Incidence of Loss of Pulse Following Cardiac Catheterization in Infants

Accessing Femoral Arteries Less than 3 mm in Diameter is Associated with Increased Incidence of Loss of Pulse Following Cardiac Catheterization in Infants Sachin Tadphale 1, Thomas Yohannan 2, Travis Kauffmann 2, Vinod Maller 3, Vijaykumar Agrawal 3, Hannah Lloyd 4, B...

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Skeletal muscle index determined by bioelectrical impedance analysis is a determinant of exercise capacity and a prognostic predictor in patients with congenital heart disease

Skeletal muscle index determined by bioelectrical impedance analysis is a determinant of exercise capacity and a prognostic predictor in patients with congenital heart disease.   Sato M, Inai K, Asagai S, Harada G, Shimada E, Sugiyama H.J Cardiol. 2020 May...

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Modified Lung Ultrasound Examinations in Assessment and Monitoring of Positive End-Expiratory Pressure-Induced Lung Reaeration in Young Children With Congenital Heart Disease Under General Anesthesia.

Wu L, Hou Q, Bai J, Zhang J, Sun L, Tan R, Zhang M, Zheng J. Pediatr Crit Care Med. 2019 May;20(5):442-449. doi: 10.1097/PCC.0000000000001865. PMID:  31058784 Similar articles   Take Home Points: The most prevalent region of post-intubation atelectasis in...

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