In-depth cardiovascular and pulmonary assessments in children with multisystem inflammatory syndrome after SARS-CoV-2 infection: a case series study

Objective To perform an in-depth assessment of cardiovascular and pulmonary outcomes in a series of 5 post discharged multisystem inflammatory syndrome (MIS-C) survivors. Methods Data were collected ≅1.9 month after hospital discharge at a tertiary hospital in São Paulo, Brazil. All patients (7-18 years; 3 females) fulfilled the MIS-C diagnosis according to CDC. The battery of tests included: 13 N-ammonia PET-CT imaging, standard echocardiography, brachial flow-mediated dilation using a Doppler ultrasound, cardiopulmonary exercise test, and blood markers. Results Upon PET-CT scans, two patients exhibited severe perfusion defect developed in the left ventricular cavity suggesting extensive myocardial ischemia, and one patient showed persistent mild pericardial effusion. Other two patients had endothelial dysfunction. All patients exhibited abnormal cardiopulmonary reserve during exercise (e.g., low VO2peak). Three patients had abnormal values for D-dimer and fibrinogen. Conclusion This study reveals novel pathological findings in MIS-C patients, which may help optimize treatment protocols in this condition.

The Role of a Cardiopulmonary Exercise Test as a Predictor of Survival in Patients With Hematologic Malignancies Who Underwent Hematopoietic Stem Cell Transplantation

Purpose: To evaluate the role of the cardiopulmonary exercise test (CPET) as a predictor of overall survival (OS) and non-relapse mortality (NRM) in patients with hematological malignancies who undergo allogeneic hematopoietic stem cell transplantation (HSCT).Methods: We retrospectively analyzed consecutive adult patients with hematological malignancies who underwent HLA-matched donor-HSCT at Chungnam National University Hospital (Daejeon, South Korea) between January 2014 and December 2020. Peak oxygen consumption (VO2max) was classified using the recommendations of the Mayo Clinic database.Results: Of 72 patients, 38 (52.8%) had VO2max values lower than the 25th percentile (VO2max < 25th) of an age- and sex-matched normal population. Patients with VO2max < 25th exhibited slightly lower OS and higher NRM (30-month OS 29.8% vs. 41%, p = 0.328; and 30-month NRM 16% vs. 3.3%, p = 0.222), compared with other patients. VO2max ≤ 25th was assigned a weight of 1 when added to the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) to form a composite comorbidity/CPET index (HCT-CI/CPET). Patients with HCT-CI/CPET scores of 0–1 demonstrated significantly better OS and NRM than did patients with HCT-CI/CPET scores ≥ 2 [median OS not reached vs. 6 months, p < 0.001 and 30-month NRM 7.4% vs. 33.3%, p = 0.006]. An HCT-CI/CPET score ≥ 2 was the only adverse risk factor for NRM on multivariate analysis [hazard ratio (HR) of NRM 10.36 (95% CI 1.486-2.25, p = 0.018)].Conclusion: The CPET may predict the survival and mortality of patients with hematological malignancies who undergo allogeneic HSCT.

The Efficacy of a Commercial Physical Activity Monitor in Longitudinal Tracking of Pulmonary Hypertension Patients

Patients with pulmonary arterial hypertension (PAH) have quality of life (QoL) limitations, decreased exercise capacity, and poor prognosis if left untreated. Standard exercise testing is routinely performed for the evaluation of patients with PAH but may be limited in its ability to monitor activity levels in daily living. We evaluated the validity of the commercial Fitbit Charge HR as a tool to assess real time exercise capacity as compared to standard exercise testing in patients with PAH. Ambulatory pediatric and adult PAH patients were enrolled and given a Fitbit with instructions to continuously wear during waking hours. Subjects underwent a 6-minute walk test (6MWT), cardiopulmonary exercise test (CPET) and an SF-36 QoL survey on the day of enrollment and follow-up. Twenty-seven ambulatory subjects with PH were enrolled and 21 had sufficient data for analyses (median age 25, range 13-59, 14 F) were enrolled. Daily steps measured by the Fitbit had a positive correlation with 6MWT distance (r = 0.72, p = 0.03) and an inverse correlation with WHO functional class. On the QoL survey, 77% reported improvement in energy/fatigue (p = 0.055). At follow up there was a strong correlation between Fitbit steps and role limitations due to physical problems (r = 0.88, p = 0.020) and weaker correlations with less related QoL markers. These findings suggest activity monitors may have potential as a simple/novel method of assessing longitudinal exercise capacity and activity levels in PAH patients. Further study in larger cohorts of patients is warranted to determine the best accelerometric correlates with outcomes.

Physical Fitness as a Prognostic Marker for Infectious Events in Kidney Transplant Recipients

<b><i>Introduction:</i></b> Infectious events are one of the leading causes of death in kidney transplant recipients (KTRs). KTRs have reduced cardiorespiratory fitness (CRF), a predictor for infections in other populations. The aim of this study was to investigate whether CRF and muscle strength are prognostic markers for infectious events in KTRs. <b><i>Methods:</i></b> In this retrospective cohort study, 155 KTRs underwent an incremental, maximal cardiopulmonary exercise test (CPET) 3 months after transplantation. CRF was analyzed with peak oxygen consumption (VO₂ peak) while muscle strength with isometric handgrip (HG) test. Laboratory blood samples and drug therapy were collected. The median follow-up period was 54 (interquartile range 38–62) months. Cox regression analyses were performed to evaluate predictors of infectious events adjusting for potential confounders. <b><i>Results:</i></b> During this study, severe infectious events occurred in 41 subjects (26.5%). 15.5% (<i>n</i> = 24) of patients had a severely reduced CRF, defined as a VO₂ peak below the 5th percentile of the reference values reported for a matched healthy population. The hazard ratio for infectious events in this subgroup was 2.389 (95% CI = 1.188–4.801, <i>p</i> = 0.014), independently of gender, age, BMI, time on dialysis, hemoglobin concentration, eGFR, diabetes, and immunosuppressive regimen. On the contrary, no significant association of HG strength and infections was found. <b><i>Conclusion:</i></b> Therefore, low CRF may be considered as a modifiable predictor of severe infectious events in KTRs. A CPET should thus be recommended for cardiovascular screening, evaluation of CRF, and tailored exercise prescription to reduce the risk of infections and potentially improve long-term outcomes of transplantation.

Noninvasive Scale Measurement of Stroke Volume and Cardiac Output Compared With the Direct Fick Method: A Feasibility Study

Background Objective markers of cardiac function are limited in the outpatient setting and may be beneficial for monitoring patients with chronic cardiac conditions. We assess the accuracy of a scale, with the ability to capture ballistocardiography, electrocardiography, and impedance plethysmography signals from a patient’s feet while standing on the scale, in measuring stroke volume and cardiac output compared with the gold‐standard direct Fick method. Methods and Results Thirty‐two patients with unexplained dyspnea undergoing level 3 invasive cardiopulmonary exercise test at a tertiary medical center were included in the final analysis. We obtained scale and direct Fick measurements of stroke volume and cardiac output before and immediately after invasive cardiopulmonary exercise test. Stroke volume and cardiac output from a cardiac scale and the direct Fick method correlated with r =0.81 and r =0.85, respectively ( P <0.001 each). The mean absolute error of the scale estimated stroke volume was −1.58 mL, with a 95% limits of agreement of −21.97 to 18.81 mL. The mean error for the scale estimated cardiac output was −0.31 L/min, with a 95% limits of agreement of −2.62 to 2.00 L/min. The changes in stroke volume and cardiac output before and after exercise were 78.9% and 96.7% concordant, respectively, between the 2 measuring methods. Conclusions In a proof‐of‐concept study, this novel scale with cardiac monitoring abilities may allow for noninvasive, longitudinal measures of cardiac function. Using the widely accepted form factor of a bathroom scale, this method of monitoring can be easily integrated into a patient’s lifestyle.

587 Exercise induced pulmonary hypertension in hypertrophic cardiomyopathy: a combined cardiopulmonary exercise test-echocardiographic study

Aims Pulmonary arterial hypertension (PAH) has been described in patients with hypertrophic cardiomyopathy (HCM) and it was associated with a worse prognosis. Nevertheless in most HCM patients, despite normal pulmonary pressures at rest, congestive symptoms are elicited by exercise. In the present study, combining cardiopulmonary exercise test (CPET) with echocardiography, we aimed to evaluate the presence of exercise-induced pulmonary hypertension (EiPAH) its role in functional limitation and its prognostic significance in a cohort of patients with obstructive and non-obstructive HCM. Methods and results 182 HCM patients (35% females, mean age 47.5 ± 15.9) undergoing CPET. During CPET, LVOT velocities and trans-tricuspid gradient were measured. Thirty-seven patients (20%) developed sPAP &gt; 40 mmHg at peak exercise (EiPAH). EiPAH was associated with an lower exercise performance, larger left atrial volumes, higher left ventricular gradient and higher VE/VCO2 slope .At multivariable model baseline sPAP (P &lt; 0.0001) and baseline left ventricular obstruction (LVOT) (P = 0.028) were significantly associated with EiPAH .Kaplan-Meier curve analysis showed EiPAH was a significant predictor of HCM –related morbidity (hazards ratio: 6.21, 95% CI: 1.47–26.19; P = 0.05; 4.21, 95% CI: 1.94–9.12; P &lt; 0.001) for the primary and the secondary endpoint respectively. Conclusions EiPAH was present in about one fifth of HCM patients without evidence of elevated pulmonary pressures at rest, and was associated with adverse clinical outcome. Diagnosing EiPAH by exercise echo/CPET may help physicians to detect early stage of PAH requiring a closer clinical monitoring and individualized treatment strategies.

333 Phrenic nerve neuropathy discovered with cardiopulmonary exercise test in long-COVID-19 syndrome

Corona virus disease of 2019 (COVID19) is an ongoing global pandemic caused by SARS-CoV-2 virus. COVID-19 typically involves the respiratory tract with a wide spectrum of disease severity. Long-Covid19 syndrome refers to a series of symptoms that sometimes persist after COVID-19 infection. We describe a case of unilateral phrenic nerve palsy in a young woman with Long-COVID-19 syndrome. a 28-year-old woman admitted for COVID-19 presented persistent exertional dyspnoea. All the examinations performed were normal. At Cardiopulmonary exercise test (CPET) however, the ventilation plot was characterized by a lack of increase of the tidal volume compensated with a premature and continuous rise in respiratory frequency. Suspecting a ventilation abnormality, an electroneurography of the diaphragmatic nerves was conducted showing a right phrenic nerve palsy. Long-COVID-19 syndrome is a growing entity in clinical practice and dyspnoea is one of the most common symptoms. In this setting, phrenic nerve palsy should be ruled out, especially in patients with unexplained dyspnoea. CPET is a complete technique that assesses both pulmonary and cardiac performance. Since it might give important clues in the recognition of the cause of persistent symptoms after COVID-19 it should be extensively performed in these patients.

Compound Mutation in Cardiac Sarcomere Proteins Is Associated with Increased Risk for Major Arrhythmic Events in Pediatric Onset Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is associated with adverse left ventricular (LV) remodeling causing dysfunction and malignant arrhythmias. Severely affected patients present with disease onset during childhood and sudden cardiac death risk (SCD) stratification is of the highest importance in this cohort. This study aimed to investigate genotype–phenotype association regarding clinical outcome and disease progression in pediatric onset HCM. Medical charts from forty-nine patients with pediatric HCM who had undergone genetic testing were reviewed for retrospective analysis. Demographic, clinical, transthoracic echocardiographic, electrocardiographic, long-term electrocardiogram, cardiopulmonary exercise test, cardiac magnetic resonance, and medication data were recorded. Childhood onset HCM was diagnosed in 29 males and 20 females. Median age at last follow-up was 18.7 years (range 2.6–51.7 years) with a median follow-up time since diagnosis of 8.5 years (range 0.2–38.0 years). Comparison of patients carrying mutations in distinct genes and comparison of genotype-negative with genotype-positive individuals, revealed no differences in functional classification, LV morphology, hypertrophy, systolic and diastolic function, fibrosis and cardiac medication. Patients with compound mutations had a significantly higher risk for major arrhythmic events than a single-mutation carrier. No association between affected genes and disease severity or progression was identified in this cohort.