CARDIAC FUNCTION OF BASKETBALL PLAYERS UNDER STRESS TRAINING

ABSTRACT Introduction: Basketball can enhance the physical fitness of young people, promote the growth and development of their bodies, and improve health and athletic ability. Objective: To explore the characteristics of basketball players’ cardiac response to increasing load training. Methods: By analyzing 12 juvenile male amateur basketball training athletes, when performing incremental load exercises on the treadmill, using a 12-lead electrocardiograph to record the electrocardiogram, HR, and blood pressure responses for each level of exercise. Results: The mean heart rate of the basketball players before movement was 82.45± 11.44 bpm, slightly higher than the heart rate at rest. Depending on the exercise load, the blood pressure should increase by 5 to 12 mmHg. Under different load training conditions, each level of blood pressure in the Bruce treadmill test procedure should increase 12.5 ~ 44mmHg. The basketball player’s systolic pressure increased by 2.25 ~ 15.7mmHg, diastolic pressure increased by 0.43 to 11.37 mmHg. Conclusions: In basketball players, the psychological stress is less than that of the average person performing the same exercise. The strong ability to adapt to exercise under incremental load training, the contractility of the ventricular muscles and the development of the heart are good. Level of evidence II; Therapeutic studies - investigation of treatment results.

Cardiac Startle Response and Clinical Outcomes in Preschool Children With Fragile X Syndrome and Autism Spectrum Disorder

Objective: Poor physiological regulation in response to threat is linked to multiple negative developmental outcomes including anxiety, which is highly prevalent and impairing in young children with neurodevelopmental disabilities like fragile X syndrome (FXS) and autism spectrum disorder (ASD). The present study contrasted cardiac startle response in pre-school-aged children with FXS, with and without ASD, to children with non-syndromic ASD (nsASD) and neurotypical controls (NT). The relationship of cardiac startle to non-verbal mental age (NVMA), ASD severity, and parent-reported anxiety was also examined.Method: Four age-matched groups of pre-school children participated including those with FXS without ASD (FXS-Only, n = 21), FXS with ASD (FXS+ASD, n = 17), nsASD (n = 42), and NT children (n = 27). Participants viewed a silent movie during which a single 200 ms 98-decibel white noise burst occurred. Cardiac activity was analyzed for pre-stimulus respiratory sinus arrhythmia (RSA) and the inter-beat intervals (IBI) at the auditory stimulus and 10 s post-stimulus. The Spence Pre-school Anxiety Scale, Autism Diagnostic Observation Schedule-2nd Edition, and Mullen Scales of Early Learning were examined in relation to startle response.Results: The nsASD group demonstrated heightened cardiac activity at the auditory stimulus and 10 s post-stimulus compared to the NT controls. Neither of the FXS groups showed differences from any other group. Higher pre-stimulus RSA was associated with reduced cardiac response across groups, while the relationship between cognitive ability and ASD severity to cardiac response varied between groups. Parent-reported anxiety was not associated with cardiac response for any group.Conclusion: These findings demonstrate group distinctions in cardiac responses to auditory startle. Although FXS and ASD share behavioral characteristics, the nsASD group showed a heightened cardiac startle response compared to the NT group that was not present in the FXS groups with or without ASD. Non-verbal mental age was associated with greater stimulus or post-stimulus reactivity for all groups except the FXS+ASD group, which showed no association between startle response and any clinical outcomes. Increased understanding of the relationship between physiological regulation and clinical outcomes will assist in identifying the timing and targets for effective interventions for individuals with neurodevelopmental disabilities.

Nomogram Model for Dynamic and Individual Prediction of Cardiac Response and Survival for Light Chain Amyloidosis in 737 Patients With Cardiac Involvement

ObjectiveLight chain amyloidosis (AL) with cardiac involvement is associated with poor prognosis. The existing prognostic assessment system does not consider treatment-related factors, and there is currently no effective system for predicting the response. The purpose of this study was to build an individualized, dynamic assessment model for cardiac response and overall survival (OS) for AL patients with cardiac involvement.MethodsThe records of 737 AL patients with cardiac involvement were collected through cooperation with 18 hospitals in the Chinese Registration Network for Light-chain Amyloidosis (CRENLA). We used univariate and multivariate analyses to evaluate the prognostic factors for OS and cardiac response. Then, two nomogram models were developed to predict OS and cardiac response in AL patients with cardiac involvement.ResultsA nomogram including four independent factors from the multivariate Cox proportional hazards analysis—Mayo staging, courses of treatment, hematologic response, and cardiac response—was constructed to calculate the possibility of achieving survival by adding all the points associated with four variables. The higher the score, the more likely death would occur. The other nomogram model included the courses of treatment, hematological response, and different treatment regimens, and was correlated with cardiac response. The higher the score, the more likely a cardiac response would occur.ConclusionIn conclusion, based on the large Chinese cohort of patients with AL and cardiac involvement, we identified nomogram models to predict cardiac response and OS. These models are more individualized and dynamic, and therefore, they have important clinical application value.

Chronotropic Incompetence in Non-Hospitalized Patients with Post-COVID-19 Syndrome

Patients recovering from COVID-19 commonly report persistence of dyspnea, exertional fatigue, and difficulties in carrying out their daily activities. However, the nature of these symptoms is still unknown. The purpose of the study was to identify limiting causes of cardiopulmonary origin for the performance of physical exercise in post-COVID-19 condition that could explain the symptomatic persistence of dyspnea or fatigue-related symptoms. Thirty-two non-hospitalized patients with post-COVID-19 condition (i.e., still presenting a chronic symptomatic phase lasting >90 days since debut of symptoms that lasted for at least 2 months and cannot be explained by an alternative diagnosis) completed a clinical examination including echocardiography, submaximal and maximal cardiorespiratory fitness tests (Ekblom-Bak and Bruce’s protocols), and a battery of validated questionnaires about fatigue and exercise intolerance. Four participants (12.5%) reported an abnormal cardiac response to exercise during the submaximal test, which aroused suspicion of the presence of chronotropic incompetence. All of them were confirmed with a positive diagnosis maximal exercise test after cardiology screening, even with a comprehensive clinical examination, resting ECG, and echocardiogram, without other findings. No statistical differences were found in any physiological variables or questionnaire values, between patients with positive and negative diagnoses. Chronotropic incompetence and other autonomic disorders may appear in patients with mild forms of COVID-19 presentation and may persist in the long term, being responsible for exercise intolerance after resolution of acute infection. Clinicians should be aware that chronotropic incompetence and other autonomic disorders may be a complication of COVID-19 and should consider appropriate diagnostic and therapeutic interventions in these patients, especially when early exercise-related fatigability is reported.

Cardiac Rehabilitation Early after Sternotomy Using New Assistive VR-Enhanced Robotic Exoskeleton—Study Protocol for a Randomised Controlled Trial

(1) Background and objective: Cardiac rehabilitation (CR) means delivering health education by structured exercises with the means of risk reduction, in a cost-effective manner. Well-conducted CR improves functional capacity, decreases re-hospitalization, and reduces mortality up to 25%. We bring to attention the protocol of a randomised control trial with the aim of validating the prototype of an assistive upper-body robotic exoskeleton system enhanced with a non-immersive virtual reality exergame (CardioVR-ReTone) in patients who undergone cardiac surgery. (2) Methods: Description of the CardioVR-ReTone system and the technical specification, followed by the group selection, randomization and evaluated variables. (3) Expected results: The primary outcome measurement is the modification of life quality at the end of the CR exercise training program. Secondary outcomes will encompass measurements of sternal stability, muscular activity, cardiac response to exercise, pain level and compliance/adherence to CR. (4) Conclusions: Implementing these novel features of the CardioVR-ReTone system, addressability, and efficacy of CR, so problematic in certain situations and especially in cardiac surgery, will be greatly facilitated, being independent of the skills and availability of the rehabilitation therapist.

Belantamab Mafadotin in Patients with Relapsed/Refractory AL Amyloidosis with Myeloma

Introduction: Daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone (Dara/CyBorD) is the only FDA approved therapy for newly diagnosed systemic light-chain (AL) amyloidosis (N Engl J Med 2021;385:46). Belantamab mafodotin is a novel anti-BCMA immunoconjugate with humanized IgG1 anti-BCMA monoclonal antibody conjugated to a microtubule-disrupting agent, monomehtyl auristatin F (MMAF) via a non-cleavable linker (Blood 2014;123:3128). Phase I/II studies in heavily pre-treated multiple myeloma patients showed single agent clinical activity with overall response rates ranging from 30-60%, with majority of responses being durable at 13 months of follow-up. Toxicity profile included keratopathy, thrombocytopenia and anemia (Blood Cancer J 2019;9:37; Lancet Oncol 2020;21:207). Based on these results, belantamab mafadotin (BLM; Blenrep) was FDA approved for relapsed myeloma. A role for new agents such as BLM in AL has not been previously reported. Here we report outcomes of six patients who received BLM at different centers for relapsed refractory (RR) AL associated with myeloma. Methods: In this retrospective study we identified AL patients with RR disease who received at least one dose of BLM. In a multi-institutional collaboration we collected demographic, medical history, laboratory, pathologic and treatment/response data on patients with myeloma and biopsy-proven AL who had received BLM. Laboratory assessment including evaluations for hematologic and organ response was done as per standard criteria and toxicity assessed as per CTCAE v6.0. Results: We identified 6 patients, 3M/3F, from 4 centers; baseline characteristics and treatment data are provided in Table 1. Baseline median age was 61 years (range, 51-74) and median marrow plasmacytosis and iFLC were 40% (10-90) and 868mg/L (145-5324). Four patients had AL λ-type and 2 κ-type, and 5 of 6 had cardiac involvement while 3 had additional organ involvement (renal, GI, nervous system). Prior to initiating BLM the median number of lines of prior therapy was 6 (range, 5-10), including daratumumab, bortezomib and lenalidomide, and prior to initiating BLM marrow assessment showed a median plasmacytosis of 23%. BLM at 2.5 mg/kg was given as an intravenous infusion over the course of 30 minutes every three weeks after ophthalmologic exam clearance until discontinuation for progression or toxicity. At a median follow-up of 4.5 months, 5 patients (83%) achieved hematological responses (HR) with 3 (50%) achieving complete hematological responses (CR) by standard criteria (J Clin Oncol 2012;30:4541). Time to HR ranged from 3 to 150 days. Cardiac response was seen in all but 1 patient, with time to response ranging from 11 to 96 days. One patient had a renal response; response assessment is not yet available for 2 other patients with renal involvement. The most common toxicity was keratopathy (grade 1-2). BLM was held after the first dose in one patient who had been heavily pre-treated and had extensive cardiac and pulmonary AL and multiple sites of FDG-avid progressive myeloma bone disease. Two days after administration of the first dose of BLM, this 51-year-old man was admitted to hospital for dyspnea, developed atrial fibrillation and ventricular tachycardia, and briefly required cardiac resuscitation without intubation with return of spontaneous circulation after 6 minutes. This patient achieved a CR after one dose of BLM that has been stable for over 5 months with marked clinical improvement. A 62 year-old woman with cardiac and renal AL has achieved a CR durable for over 16 months with cardiac and renal responses. Conclusions: In this group of 6 patients with RR AL with myeloma, HR and cardiac response rates were impressive at 83% and 80%, respectively. One patient who had 24-hour urine protein evaluation also achieved a renal response. Time to response was rapid with 2 patients achieving HR within a week of starting treatment, and the rest within five months. Additionally, 3 of 6 patients achieved CR, 1 had no clonal plasma cells in the marrow and another clonal disease detectable only by MRD. In this retrospective multi-institutional cohort BLM resulted in rapid reduction of iFLC and induced critical organ responses. These data provide preliminary evidence for the clinical activity of BLM in RR AL. Results of the on-going phase 2 clinical trial in the European Myeloma Network (EMN27; NCT04617925) are awaited with great interest. Figure 1 Figure 1. Disclosures Sborov: Sanofi: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy; SkylineDx: Consultancy. Comenzo: Karyopharm: Research Funding; Prothena Biosciences: Consultancy, Research Funding; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Unum: Membership on an entity's Board of Directors or advisory committees, Research Funding; Caelum: Consultancy, Research Funding; Janssen: Patents & Royalties: WO2016187546A1, Research Funding. Kansagra: Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Cota Health: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Alynylam: Membership on an entity's Board of Directors or advisory committees.

The Pattern of Organ Responses Varies in Patients with Systemic Light-Chain Amyloidosis and Heart or Kidney or Heart and Kidney Involvement Who Achieve Deep Hematologic Responses

Introduction: In systemic light-chain amyloidosis (AL) aberrant clonal free immunoglobulin light chains (FLC) misfold and deposit in vital organs causing severe dysfunction (Nat Rev Dis Primers 2018;4:38). With anti-plasma cell therapy that reduces or eliminates the involved FLC (iFLC), defined organ responses can occur (N Engl J Med 2021;385:46, Blood Rev 2019;37:100581, Leukemia 2017;31:136, Blood 2014;124:2325). We asked whether the timing of individual organ responses may be influenced by the number of organs involved at diagnosis; therefore we evaluated the pattern of responses in patients with the two most commonly involved organs (heart, kidney) who achieved deep hematologic responses to therapy (CR=complete response, VGPR=very good partial response)(J Clin Oncol 2012;30:4541). We examined whether the rate of and time to organ response varied in patients with only heart or kidney or heart and kidney involvement, and whether the depth of hematologic response impacted the pattern of organ response. Methods: We performed a retrospective analysis AL patients diagnosed by tissue biopsy between 2007-2019 who had heart and/or kidney involvement at diagnosis and achieved hematologic CR/VGPR with treatment. Mann-Whitney was used to compare rates of organ responses and log-rank tests were applied to compare times to organ response among the subgroups as well as overall survival (OS) differences based on iFLC responses and on organ responses. Results were considered to be significant if two-sided P-value was less than or equal to 0.05. Results: We identified 111 patients with a median age of 62.5 years (range, 40-80) who met these criteria, 65 of whom (59%) were male. Cardiac involvement only was present in 34 (30.6%), renal involvement only in 31 (28.0%), and both cardiac and renal involvement in 46 (41.4%). Table 1 highlights patient characteristics. The median OS for the entire cohort was 112 months (95% CI 100-NA). The overall cardiac response rate was 62.5%, with a median time to response of 8 months (range, 1-73 months). Overall renal response rate was 67.1% with a median time to response of 10 months (range, 1-57 months). Log-rank analysis showed a significant difference in the OS based on post treatment iFLC levels (<10 vs. 10-20 vs. >20 mg/L) as we have previously described (Am J Hematol 2021;96:E20). Patients with kidney involvement only had significantly improved overall survival (OS) compared to those with cardiac involvement only (p=0.05), as expected. However, there was no difference in the OS of patients with cardiac only vs. cardiac and renal involvement (p=0.58), while there was a trend towards shorter OS in patients with cardiac and renal vs renal (p=0.09). The lower iFLC levels achieved post-treatment influenced cardiac response rate (p=0.07), and significantly impacted renal response rate (p<0.01). For patients with cardiac involvement, iFLC responses did not have a significant impact on time to cardiac response, whereas for patients with renal involvement, faster responses were noted in those achieving lower iFLC levels (p=0.017) (Figure 1). There was no significant difference in time to cardiac response between patients with cardiac only vs. cardiac and renal involvement (p=0.93) whereas patients with renal only vs cardiac and renal involvement had a faster time to renal response (medians 14 (range, 10-29) vs 43 (13-not reached) months, p=0.018) (Figure 2). Conclusion: In AL patients with renal involvement who achieve CR/VGPR with treatment, post-treatment iFLC levels and co-presence of cardiac involvement play significant roles in the timing of renal responses. In AL patients with cardiac involvement who achieve CR/VGPR, post-treatment iFLC levels but not the co-presence of renal involvement influences the rate of cardiac response but neither influences the timing. These differences may be due to organ-specific factors such as proteomic adaptations or relative iFLC toxicity or complex cardio-renal hormonal interactions. Further hypothesis-driven study of these differences is warranted in this era of new and effective anti-plasma cell therapies. Figure 1 Figure 1. Disclosures Comenzo: Prothena Biosciences: Consultancy, Research Funding; Karyopharm: Research Funding; Takeda: Research Funding; Unum: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Caelum: Consultancy, Research Funding; Janssen: Patents & Royalties: WO2016187546A1, Research Funding.

Anthracycline-free tumor elimination in mice leads to functional and molecular cardiac recovery from cancer-induced alterations in contrast to long-lasting doxorubicin treatment effects

Systemic effects of advanced cancer impact on the heart leading to cardiac atrophy and functional impairment. Using a murine melanoma cancer model (B16F10 melanoma cells stably transduced with a Ganciclovir (GCV)-inducible suicide gene), the present study analysed the recovery potential of cancer-induced cardiomyopathy with or without use of doxorubicin (Dox). After Dox-free tumor elimination and recovery for 70 ± 5 days, cancer-induced morphologic, functional, metabolic and molecular changes were largely reversible in mice previously bearing tumors. Moreover, grip strength and cardiac response to angiotensin II-induced high blood pressure were comparable with healthy control mice. In turn, addition of Dox (12 mg/kg BW) to melanoma-bearing mice reduced survival in the acute phase compared to GCV-alone induced recovery, while long-term effects on cardiac morphologic and functional recovery were similar. However, Dox treatment was associated with permanent changes in the cardiac gene expression pattern, especially the circadian rhythm pathway associated with the DNA damage repair system. Thus, the heart can recover from cancer-induced damage after chemotherapy-free tumor elimination. In contrast, treatment with the cardiotoxic drug Dox induces, besides well-known adverse acute effects, long-term subclinical changes in the heart, especially of circadian clock genes. Since the circadian clock is known to impact on cardiac repair mechanisms, these changes may render the heart more sensitive to additional stress during lifetime, which, at least in part, could contribute to late cardiac toxicity.

Frank-Starling mechanism, fluid responsiveness, and length-dependent activation: Unravelling the multiscale behaviors with an in silico analysis

The Frank-Starling mechanism is a fundamental regulatory property which underlies the cardiac output adaptation to venous filling. Length-dependent activation is generally assumed to be the cellular origin of this mechanism. At the heart scale, it is commonly admitted that an increase in preload (ventricular filling) leads to an increased cellular force and an increased volume of ejected blood. This explanation also forms the basis for vascular filling therapy. It is actually difficult to unravel the exact nature of the relationship between length-dependent activation and the Frank-Starling mechanism, as three different scales (cellular, ventricular and cardiovascular) are involved. Mathematical models are powerful tools to overcome these limitations. In this study, we use a multiscale model of the cardiovascular system to untangle the three concepts (length-dependent activation, Frank-Starling, and vascular filling). We first show that length-dependent activation is required to observe both the Frank-Starling mechanism and a positive response to high vascular fillings. Our results reveal a dynamical length dependent activation-driven response to changes in preload, which involves interactions between the cellular, ventricular and cardiovascular levels and thus highlights fundamentally multiscale behaviors. We show however that the cellular force increase is not enough to explain the cardiac response to rapid changes in preload. We also show that the absence of fluid responsiveness is not related to a saturating Frank-Starling effect. As it is challenging to study those multiscale phenomena experimentally, this computational approach contributes to a more comprehensive knowledge of the sophisticated length-dependent properties of cardiac muscle.

Experimental high thoracic spinal cord injury impairs the cardiac and cerebrovascular response to orthostatic challenge in rats

This is the first use of LBNP to interrogate the cardiac and cerebrovascular responses to simulated OH in a preclinical study of SCI. Here, we demonstrate the utility of our simulated OH model and use it to demonstrate that SCI impairs the cardiac response to simulated OH and disrupts dynamic cerebrovascular autoregulation.