Pediatric Cardiology

Facility-Based and Virtual Cardiac Rehabilitation in Young Patients with Heart Disease During the COVID-19 Era. Aronoff EB, Chin C, Opotowsky AR, Mays WA, Knecht SK, Goessling J, Rice M, Shertzer J, Wittekind SG, Powell AW. Pediatr Cardiol. 2024 Oct;45(7):1533-1541. doi: 10.1007/s00246-023-03202-0. Epub 2023 Jun 9. PMID: 37294337 Commentary by:  Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch:  Take-home Points: Cardiac rehabilitation in younger patients can likely be successful even with virtual sessions, but improvements may be less robust than with in-person facility-based training. Hybrid models may solve some of the problems in facility-based or virtual (alone) programs, but further study is needed. Cardiac rehabilitation (CR) is considered an essential component of post-surgical care in adult cardiac patients. With data showing improved outcomes in pediatric and adult congenital heart patients who have higher exercise capacity (peak VO2) as measured on cardiopulmonary exercise testing (CPET), there has been a push to create rehabilitation and fitness programs for this population, especially given the often life-long, chronic nature of the cardiac disease. There have been a considerable number of publications showing better adherence to a rehabilitation program with virtual visits, but data in the pediatric population is minimal. Due to the COVID pandemic, facility-based sessions could not be performed for many patients at this single-center program. In younger patients, adherence for facility-based visits may be even more challenging due to school or longer distance of travel to the cardiac center. The goals of this study were to assess the physical and psychosocial outcomes in patients aged 19 +/- 7.3 years old undergoing virtual rehab session and to compare them to patients who received in-person visits.  Between 2020-2022, 73 patients were enrolled, but only 47 total patients completed CR (at least 2-3 sessions per week for 12 weeks). Virtual patients were more likely to complete the program, with 12/15 (80%) virtual and 33/55 (60%) facility-based (3 were hybrid and not included in the final analysis). Each session was 1 hour and included warm-up, 30 min aerobic (facility) or HIIT (virtual), 15 min of low resistance high repetition strength training, and cool-down. The aerobic training goal was sustaining 70-75% of the peak heart rate. Home exercise was encouraged but not tracked. There was a significant increase in peak VO2 (~8-9%), 6-min walk distance (76m), sit to stand repetitions, and arm curls, as well as an improvement in the psychosocial and activity test scores (PHQ-9, PCS, and DASI). When evaluating facility-based vs virtual groups, there was a 10% improvement in peak VO2 in the facility-based group, but no significant difference with the virtual group (see Figure 1). The other physical performance measurements were significantly improved in both groups (see Table 4). There were mixed results for the psychosocial measures (see Figure 2).  While small, this study did show that virtual CR was feasible and had better adherence than traditional facility-based CR. Many physical and emotional outcome measures were improved. It is possible that the type of aerobic training and lack of HR monitoring (and possibly less intensity) in the virtual group affected the findings. Emotional health improved overall but was not entirely significant in the virtual group. This may be due to smaller numbers but possibly could be influenced by the lack of 1:1 in person counseling that would occur in the traditional CR model. A hybrid approach may solve some of the problems seen in either model and should be studied further. 

Association Between Serial B-Type Natriuretic Peptide Levels, Vasoactive Drug Weaning, and Adverse Cardiovascular Outcomes in Pediatric Heart Failure. Loss KL, Su J, Menteer J, Weisert MA, Shaddy RE, Kantor PF.J Am Heart Assoc. 2024 Aug 20;13(16):e031132. doi: 10.1161/JAHA.123.031132. Epub 2024 Aug 9.PMID: 39119990 Take Home Points: More than 50% reduction in proBNP levels by six day was a valuable data piece helping in assisting the prognosis and adding a predictive value in management. Qualitatively RV systolic dysfunction baseline at admission, and persistent RV dysfunction is an independent factor in multivariate analysis for adverse cardiovascular outcomes. The severity of LV systolic dysfunction, LV dilation, presence of moderate or more mitral regurgitation, presence of qualitative RV systolic dysfunction, and a higher baseline BNP, BUN, and creatinine level are associated with higher intravenous vasoactive drugs support. Commentary from Dr. Vimal Jayswal (Indiana, USA), editor of Pediatric & Fetal Cardiology Journal Watch.                                                                                                                                                               Introduction: Pediatric heart failure is a complex pathophysiological disease with inherent challenges during inpatient management, this is due to limited cardiovascular reserve and severely ill patient population that makes it more difficult to predict its prognosis in a timely fashion before acute cardiovascular events such as death or listing for heart transplant occurred. Non-invasive biomarkers such as pro-B-type natriuretic peptide have been an active area of interest for researchers. This study provides a good insight into inpatient management by monitoring trend of pro BNP, percentage decrease from initial admission level, > 50 % drop in proBNP by 6th day of hospitalization could be a valuable tool for an eventual clinical composite score model for prognosis and prediction of ACV event outcomes.  Pro BNP levels are routinely monitored during inpatient hospitalization for pediatric heart failure patients; it is produced by ventricular myocytes in response to pressure and volume overload and wall tension. Daphne Hsu et al showed in children with moderately symptomatic HF, BNP ≥140 pg/mL and age >2 years identified subjects at higher risk for worse outcome. Price et al reported a positive association of a BNP level of 300 pg/mL with a 90-day composite outcome of HF-related hospitalization, HF-related death, or listing for transplantation.  Data collection and its clinical relevance: It’s a comprehensive retrospective chart review study from January, 2005 to July, 2021 with acute decompensated heart failure and with biventricular physiology with systemic left ventricular dysfunction. It's a robust study with emphasis on linear mixed-effects modeling to analyze BNP trends.   Results: Results were assessed either in the form of acute cardiovascular events, such as heart transplantation, death, or mechanical circulation. The secondary outcome such as successful weaning of inotropic support. Figure 1 The most commonly used drug for IV Vasoactive support during all hospitalizations was milrinone (N=81, 83.6%),  followed by dopamine (N=70, 72.2%), epinephrine (N=51, 52.6%), nicardipine (N=23, 23.7%), dobutamine (N=11, 11.3%), vasopressin (N=7, 7.2%), esmolol (N=6, 6.5%), and norepinephrine (N=4, 4.1%). Diuretics were used in 122 hospitalizations (93.1%), with IV intermittent or continuous furosemide being used in 92 (70.2%). 47% (N=62) of hospitalization reached ACV outcomes: 11 (8.4%) died, 11 8.4%) underwent HT, and 40 (30.5%) needed MCS. Of those patients who needed MCS, 10 (25%) received exclusively extracorporeal membrane oxygenation, 25 (62.5%) received exclusively VAD, and 5 (12.5%) received both extracorporeal membrane oxygenation and VAD during the hospitalization. Individuals who received IVV support (74/94) had a higher initial BNP level (1030 [542–1920] versus 572 [206–1630] pg/mL, P=0.038). None of the others baseline demographic, clinical, laboratory, or echocardiographic characteristics differentiated patients who failed weaning from those who weaned successfully from IVV support. Risk Factors for ACV Outcomes: The risk of ACV increased with a reduced baseline LVSF, LVEF, and the presence of qualitative RV systolic dysfunction. Limitation of study: It’s a single center retrospective study focusing on a biventricular pediatric heart failure patient with LV systolic dysfunction and results cannot be generalized on many single ventricle patients or other unrepaired complex congenital heart defects patients. Similarly, improvement in new modality for pediatric heart failure management, response to diuretics, improvement in ICU care, nursing care would also bring complexity in interpreting the data and extrapolating to current management.  Conclusion: In pediatric patients admitted with acute decompensated heart failure, baseline RV systolic dysfunction was independently associated with adverse CV outcomes. We identified a high prevalence of IV Vasoactive support that was associated with the severity of LV systolic dysfunction, LV dilation, presence of moderate or more mitral regurgitation, presence of qualitative RV systolic dysfunction, and a higher baseline BNP, BUN, and creatinine level. A serial decline in BNP levels reliably indicated patients unlikely to experience adverse CV outcome and likely to have successful weaning from IV vasoactive support.

Pulmonary Atresia with Intact Ventricular Septum: Midterm Outcomes from a Multicenter Cohort. Iliopoulos I, Mastropietro CW, Flores S, Cheung E, Amula V, Radman M, Kwiatkowski D, Puente BN, Buckley JR, Allen KY, Loomba R, Karki KB, Chiwane S, Cashen K, Piggott K, Kapileshwarkar Y, Gowda KMN, Badheka A, Raman R, Zang H, Costello JM; Collaborative Research from the Pediatric Cardiac Intensive Care Society Investigators. Pediatr Cardiol. 2024 Apr;45(4):847-857. doi: 10.1007/s00246-022-02954-5. Epub 2022 Jun 25. PMID: 35751685 Commentary from Dr. Anna Tsirka (Hartford, CT, USA), section editor of Pediatric and Fetal Cardiology Journal Watch Take Home Message This multi-center, retrospective study reviewed outcomes of neonates with PA-IVS treated between 2009 and 2019 in 19 major US hospitals. They found that mortality remains high (close to 20% at 5 years). TV Z-score is significantly associated with increased probabilities of biventricular repair, while right ventricular coronary dependency and left, but not right, coronary atresia significantly worsens transplant-free survival.  Introduction Pulmonary atresia with intact ventricular septum (PAIVS) is a rare congenital heart lesion with substantial morphologic heterogeneity, which drives widely variable management strategies and subsequent outcomes. Treatment is individualized, dependent on coronary anatomy, and size of right sided structures. Potential final end-states for patients with PAIVS include a biventricular repair, a one-and-a half ventricular repair, a Fontan, cardiac transplantation, or death.  The primary objective of this study was to describe medium-term outcomes for a contemporary multicenter cohort of patients with PAIVS, and identify factors associated with attainment of each end-state and evaluate the effect of RVDCC and coronary atresia on transplant-free survival. Methods This was a multicenter retrospective cohort study across 19 United States hospitals affiliated with Collaborative Research from the Pediatric Cardiac Intensive Care Society (CoRe-PCICS). All neonates (age less than 30 days) with PAIVS admitted in one of the participating centers from 01.01.2009 until 01.01.2019 were included. Patients with any blood flow across the pulmonary valve and those with any size ventricular septal defects were excluded. Additionally, patients with Ebstein’s anomaly or severely dysplastic tricuspid valve were also excluded. Right ventricular dependent coronary circulation (RVDCC) was based on the assessment of the local team. The primary endpoint was the cumulative risk of the five mutually exclusive end-states (biventricular, one-and-a half ventricular, Fontan, transplant, and death). The secondary end point was transplant-free survival. Results N of 295 neonates were included, 11% of which had a chromosomal anomaly. 46% had normal coronaries, while 54% had RV to coronary artery fistulas. 29% were deemed to have RV dependent coronary circulation and 6.6% had coronary atresia.   Median duration of follow up was 4.9 years. At the end of the follow-up, 76 patients (26%) remained in mixed circulation. Mortality occurred in 54 patients (18.3%): 16 patients (5.4%) died prior to any intervention, 23 patients (8.2%) died post-procedure prior to hospital discharge, and 15 patients (5.1%) died after discharge following their initial neonatal hospitalization. The cumulative risk of death was 16.9%, 17.2%, 18.8%, and 19.5% at 1, 2, 5 years, and end of study period, respectively.  Figure one demonstrates the incidence of the five competing outcomes over time.  A sub-distribution hazard model analysis indicated that increase in TV Z-score was associated with a greater chance of achieving a biventricular repair [hazard ratio (HR) 2.03, (95% CI 1.68, 2.46) per unit increase of TV Z-score], whereas the presence of RVDCC was associated with a higher likelihood of heart transplantation [HR 9.15 (95% CI 2.76, 30.27)]  A TV z score below -1.6 was more likely to result in a Fontan circulation while a TV z score over -1.6 was more likely to result in a biventricular circulation.  Similarly, higher TV Z-score decreases the odds of death or transplantation [OR 0.46, (95%CI  0.29, 0.75)], whereas the presence of coronary atresia increases the odds of death or transplantation [OR 3.75, (95%CI 1.46, 9.61)]. The table below depicts the risk factors for death or transplantation:  Finally, figure 5 describes the effect of coronary dependent circulation and coronary atresia on transplant free survival. Transplant-free survival at 25 months after the initial neonatal procedure was 84.5% (95% CI 79.2%, 90.1%) for patients without RVDCC, 49.0% (95% CI 37.6%, 63.9%) for patients with RVDCC and normal coronary ostia, 57.1% (95% CI 36.3%, 89.9%) for patients with RVDCC and right atresia, and 20.0% (95% CI 7.3%, 55.0%) for those with RVDCC and left coronary atresia (log-rank p among groups < 0.001).  Conclusions:  In this contemporary cohort of neonates with PA/IVS, overall survival is improving, surpassing 80% at 5 years, however RVDCC and left coronary atresia have a significant negative impact on transplant-free survival.   In this cohort, only 15% of patients achieved biventricular repair. A TV z-score of − 1.6 is the crossing point above which a biventricular circulation is more likely to be achievable, but not guaranteed.  The study is limited by its retrospective and multi center nature, as each center had different practice biases and procedures. 

Association of European Pediatric and Congenital Cardiology practical recommendations for surveillance and prevention of cardiac disease in childhood cancer survivors: the importance of physical activity and lifestyle changes From the Association of European Pediatric and Congenital Cardiology Working Group Sports Cardiology, Physical Activity and Prevention, Working Group Adult Congenital Heart Disease, Working Group Imaging and Working Group Heart Failure. Kesting S, Giordano U, Weil J, McMahon CJ, Albert DC, Berger C, Budts W, Fritsch P, Hidvégi EV, Oberhoffer-Fritz R, Milano GM, Wacker-Gußmann A, Herceg-Čavrak V. Cardiol Young. 2024 Feb;34(2):250-261. doi: 10.1017/S1047951123004213. Epub 2024 Jan 4. PMID: 38174736 Review.  Take home points: Regular cardiac screening is necessary in long-term pediatric cancer survivors Modifiable lifestyle factors should be addressed Exercise assessment and exercise training are underappreciated and likely very helpful for these patients Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch: With the improved survival of pediatric cancer patients, the long-term health effects are becoming increasingly important. Besides secondary malignancies, many known adverse cardiac issues can develop due to cardiotoxicity from chemotherapy and radiation therapy to the chest, such as cardiomyopathies, valve dysfunction, arrhythmias, peripheral vascular disease, pericardial disease, and early coronary artery disease. See Table 1. This article is a consensus guidelines statement from the European Paediatric and Congenital Cardiology Working group. Summary as follows: Primary prevention includes dexrazoxane, liposomal anthracyclines, and a longer duration of infusions. Secondary prevention was discussed in much more detail. Those with high and moderate risk should have lifelong surveillance, usually recommended every few years; see Table 4. Given that many patients may have subclinical dysfunction, standard testing may not detect changes. Global longitudinal strain should be added to echocardiography and MRI considered if there is insufficient information on myocardial performance. Additionally, provocative testing such as cardiopulmonary exercise testing (CPET) +/- stress imaging may be helpful in the detection of early myocardial changes. Hypertension and metabolic syndrome are also common. Decreased physical fitness is possibly a modifiable risk factor in long-term survivors. Many survivors likely have decreased peak VO2 and if they have subclinical cardiomyopathies, may not be able to increase cardiac output appropriately. Exercise therapy may be a critical component of long-term health and reductions in morbidity and mortality, but research is in its early stages. While physical activity recommendations are provided for the general population, those with a history of chronic illness and a higher risk of CVD may have greater benefits.

The Child Opportunity Index 2.0 and Disparities in Pediatric Cardiorespiratory Fitness. Wang AP, Griffith G, Otto-Meyer S, Ward K.J Pediatr. 2024 May;268:113964. doi: 10.1016/j.jpeds.2024.113964. Epub 2024 Feb 17.PMID: 38369240  Take home points: Cardiac Opportunity Index 2.0 (COI) is being increasingly used to assess neighborhood-level characteristics that may affect pediatric medical disparities Lower COI was associated with lower cardiorespiratory fitness (CRF) Racial differences were not significant when adjusting for COI Commentary from Dr. Jared Hershenson (Greater Washington DC), section editor of Pediatric Cardiology Journal Watch: CRF as measured by peak oxygen consumption (pVO2) on cardiopulmonary exercise testing (CPET) is a known predictor of morbidity and mortality in many adult and pediatric studies. There have been some studies suggesting a racial disparity, with some biologic factors that may have contributed (eg. less aerobic muscle fibers or lower Hg), along with higher sedentary time. However, CRF can also be influenced by community level factors such as access to safe exercise and nutrition and whether these factors may be more significant than racial differences have not been well studied. The COI is a publicly available index of 29 domains that include education, health, environment, and socioeconomic factors that may impact health and child development. This study attempted to determine if lower COI is associated with lower CRF. This was a retrospective review of CPET data from 2004-2022 in 1735 patients referred for cardiac symptoms that did not have any underlying congenital or acquired cardiac disease. All had maximal tests (defined as RER > 1.10). Demographic data and COI based on zip codes were collected. COI was categorized into quintiles. Table 1 shows the full demographics. CPET data showed statistically significantly lower peak VO2 and exercise duration in the lower COI groups. White and Latinx patients had a higher peak VO2 than black patients, but with multivariate analysis when COI was included, no difference in race was present. See Figure 1. Given the neighborhood and socioeconomic factors contributing to decreased CRF and likely other risk factors for adult cardiac disease, it will be important from a provider and system level to address the barriers to regular and safe physical activity.