Changes in BNP and cardiac troponin I after high-intensity interval and endurance exercise in heart failure patients and healthy controls

Exercise training represents a cornerstone of contemporary cardiac rehabilitation. Recently, high-intensity interval training (HIT) has been popularized for heart failure (HF) patients (1) and may serve as a superior mode of exercise compared to traditional endurance exercise training. However, there is controversy regarding the safety (2) and the direct effects of HIT on the heart. Previous studies have demonstrated that an acute bout of exercise leads to an increase in cardiac troponin (cTn), a biomarker for cardiac injury, and B-type natriuretic peptide (BNP), a marker for cardiomyocyte stress (3,4). Exercise-induced elevation in these biomarkers is related to exercise intensity and duration (4,5), and may occur to a larger extend in patients with cardiovascular risk factors (6). To date, no previous study: 1. compared changes in cTn and BNP between endurance exercise and HIT, and 2. explored differences in exercise-induced changes in cTn and BNP between HF patients and controls

Heart failure is associated with exaggerated endothelial ischaemia-reperfusion injury and attenuated effect of ischaemic preconditioning

Background Reperfusion is mandatory after ischaemia, but it also triggers ischaemia–reperfusion (IR)-injury. It is currently unknown whether heart failure alters the magnitude of IR-injury. Ischaemic preconditioning can limit IR-injury. Since ischaemic preconditioning is typically applied in subjects at risk for cardiovascular complications, it is of clinical importance to understand its efficacy in heart failure patients. Objective To examine the magnitude of endothelial IR-injury, and the ability of ischaemic preconditioning to protect against endothelial IR-injury in heart failure. Methods We included 15 subjects with heart failure (67 ± 10 years, New York Heart Association class II/III) and 15 healthy, age- and sex-matched controls (65 ± 9 years). We examined brachial artery endothelial function using flow-mediated dilation before and after arm IR (induced by 5-min ischaemic handgrip exercise +15 min reperfusion). IR was preceded by ischaemic preconditioning (consisting in three cycles of 5-min upper arm cuff inflation to 220 mmHg) or no inflation. Results A significant interaction-effect was found for the change in flow-mediated dilation after IR between groups (two-way ANOVA interaction-effect: p = 0.01). Whilst post-hoc analysis revealed a significantly decline in flow-mediated dilation in both groups (p < 0.05), the decline in flow-mediated dilation in heart failure patients (6.2 ± 3.6% to 3.3 ± 1.8%) was significantly larger than that observed in controls (4.9 ± 2.1 to 4.1 ± 2.0). Neither in heart failure patients nor controls was the decrease in flow-mediated dilation after IR altered by ischaemic preconditioning (three-way ANOVA interaction: p = 0.87). Conclusion We found that patients with heart failure are associated with exaggerated endothelial IR-injury compared with age- and sex-matched, healthy controls, which may contribute to the poor clinical prognosis in heart failure. Furthermore, we found no protective effect of ischaemic preconditioning (3 × 5-min forearm ischaemia) against endothelial IR-injury in heart failure patients

Effects of preload manipulation on right ventricular contractility: invasive pressure-area loop versus non-invasive strain-area loop.

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The Acute Impact of Changes to Haemodynamic Load on the Left Ventricular Strain-Volume Relationship in Young and Older Men.

OBJECTIVES: Chronic changes in left ventricular (LV) haemodynamics, for example induced by increased afterload (i.e., hypertension), mediate changes in LV function. This study examined the proof-of-concept that: 1. the LV longitudinal strain (ԑ)-volume loop is sensitive to detect an acute increase in afterload, and 2. these effects differ between healthy young versus older men. METHODS: Thirty-five healthy male volunteers were recruited including 19 young (24±2 yr) and 16 older participants (67±5 yr). Tests were performed prior to, during and after 10-min recovery from acute manipulation of afterload. Real-time haemodynamic data was obtained and LV longitudinal ԑ-volume loops were calculated from 4-chamber images using 2D-echocardiography. RESULTS: Inflation of the anti-G-suit resulted in an immediate increase in heart rate, blood pressure and systemic vascular resistance, and a decrease in stroke volume (all P0.05). Manipulation of cardiac haemodynamics caused comparable effects in young versus older men (all P>0.05). CONCLUSIONS: Acute increases in afterload immediately change the diastolic phase of the LV longitudinal ԑ-volume loop in young and older men. This supports the potency of the LV longitudinal ԑ-volume loop to provide novel insights into dynamic cardiac function in humans in vivo

Left ventricular deformation and myocardial fibrosis in pediatric patients with Duchenne muscular dystrophy

Background: Left ventricular (LV) strain and rotation are emerging functional markers for early detection of LV dysfunction and have been associated with the burden of myocardial fibrosis in several disease states. This study examined the association between LV deformation (i.e., LV strain and rotation) and extent and location of LV myocardial fibrosis in pediatric patients with Duchenne muscular dystrophy (DMD). Methods and results: 34 pediatric patients with DMD underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) to assess LV myocardial fibrosis. Offline CMR feature-tracking analysis was used to assess global and segmental longitudinal and circumferential LV strain, and LV rotation. Patients with fibrosis (n = 18, 52.9%) were older than those without fibrosis (14 ± 3 years (yrs) vs 11 ± 2 yrs., p = 0.01). There was no significant difference in LV ejection fraction (LVEF) between subjects with and without fibrosis (54 ± 6% vs 56 ± 4%, p = 0.18). However, lower endocardial global circumferential strain (GCS), but not LV rotation, was associated with presence of fibrosis (adjusted Odds Ratio 1.25 [95% CI 1.01–1.56], p = 0.04). Both GCS and global longitudinal strain correlated with the extent of fibrosis (r =.52, p = 0.03 and r =.75, p < 0.01, respectively). Importantly, segmental strain did not seem to correspond to location of fibrosis. Conclusion: A lower global, but not segmental, strain is associated with presence and extent of LV myocardial fibrosis in pediatric DMD patients. Therefore, strain parameters might detect structural myocardial alterations, however currently more research is needed to evaluate its value (e.g., prognostic) in clinical practice

Association of left ventricular strain-volume loop characteristics with adverse events in patients with heart failure with preserved ejection fraction.

Aims: Patients with heart failure with preserved ejection fraction (HFpEF) are characterized by impaired diastolic function. Left ventricular (LV) strain–volume loops (SVL) represent the relation between strain and volume during the cardiac cycle and provide insight into systolic and diastolic function characteristics. In this study, we examined the association of SVL parameters and adverse events in HFpEF. Methods and results: In 235 patients diagnosed with HFpEF, LV-SVL were constructed based on echocardiography images. The endpoint was a composite of all-cause mortality and Heart Failure (HF)-related hospitalization, which was extracted from electronic medical records. Cox-regression analysis was used to assess the association of SVL parameters and the composite endpoint, while adjusting for age, sex, and NYHA class. HFpEF patients (72.3% female) were 75.8 ± 6.9 years old, had a BMI of 29.9 ± 5.4 kg/m2, and a left ventricular ejection fraction of 60.3 ± 7.0%. Across 2.9 years (1.8–4.1) of follow-up, 73 Patients (31%) experienced an event. Early diastolic slope was significantly associated with adverse events [second quartile vs. first quartile: adjusted hazards ratio (HR) 0.42 (95%CI 0.20–0.88)] after adjusting for age, sex, and NYHA class. The association between LV peak strain and adverse events disappeared upon correction for potential confounders [adjusted HR 1.02 (95% CI 0.96–1.08)]. Conclusion: Early diastolic slope, representing the relationship between changes in LV volume and strain during early diastole, but not other SVL-parameters, was associated with adverse events in patients with HFpEF during 2.9 years of follow-up

Exercised-based cardiac rehabilitation associates with lower all-cause mortality in patients with primary pulmonary hypertension

Background: Despite pharmacological therapies to improve outcomes of pulmonary hypertension (PH), poor long-term survival remains. Exercised-based cardiac rehabilitation (ExCR) may be an alternative strategy to improve prognosis. Therefore, using an electronic medical record (EMR) database, the objective of this study was to compare mortality between patients with primary PH with ExCR vs. propensity-matched PH patients without ExCR. Methods: The retrospective analysis was conducted on February 15, 2023 using anonymized data within TriNetX, a global federated health research network. All patients were aged ≥18 years with primary PH recorded in EMRs with at least 1-year follow-up from ExCR. Using logistic regression models, patients with PH with an EMR of ExCR were 1:1 propensity score-matched with PH patients without ExCR for age, sex, race, and comorbidities, and cardiovascular care. Results: In total, 109,736 patients with primary PH met the inclusion criteria for the control group and 784 patients with primary PH met the inclusion criteria for the ExCR cohort. Using the propensity score-matched cohorts, 1-year mortality from ExCR was proportionally lower with 13.6% (n = 101 of 744 patients) in the ExCR cohort compared to 23.3% (n = 174 of 747 patients) in the controls (OR 0.52, 95% CI 0.40–0.68).Conclusion: The present study of 1,514 patients with primary PH suggests that ExCR is associated with 48% lower odds of 1-year mortality, when compared to propensity score-matched patients without ExCR

Exercise-induced cardiac fatigue after a 45-minute bout of high-intensity running exercise is not altered under hypoxia.

BACKGROUND: Acute exercise promotes transient exercise-induced cardiac fatigue (EICF), which affects the right ventricle (RV) and to a lesser extent the left ventricle (LV). Hypoxic exposure induces an additional increase in RV afterload. Therefore, exercise in hypoxia may differently affect both ventricles. AIM: Investigate the acute effects of a bout of high-intensity exercise under hypoxia versus normoxia in healthy individuals on right- and left-sided cardiac function and mechanics. METHODS: 21 healthy individuals (22.2±3.0 years, fourteen men) performed a 45-minute high-intensity running exercise, under hypoxia (fraction of inspired oxygen [FiO2] 14.5%) and normoxia (FiO2 20.9%) in a randomized order. Pre- and post-exercise echocardiography, at rest and during low-to-moderate intensity recumbent exercise ('stress'), was performed to assess RV and LV cardiac function and mechanics. RV structure, function and mechanics were assessed using conventional 2D, Doppler, tissue Doppler, speckle tracking echocardiography and novel strain-area loops. RESULTS: Indices for RV systolic function (RVFAC, TAPSE, RVS', RV free wall strain) as well as LV function (LV ejection fraction, LV global longitudinal strain)) significantly reduced after high-intensity running exercise (p0.05). CONCLUSION: There was no impact of hypoxia on the magnitude of EICF in the RV and LV after a bout of 45-minute high-intensity exercise. This finding suggests that any potential increase in loading conditions does not automatically exacerbate EICF in this setting

Common genetic variants contribute to risk of transposition of the great arteries

Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. Objective: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. Methods and Results: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10-10, OR=0.69 per C allele). SNP-based heritability analysis showed that 25% of variance in susceptibility to D-TGA may be explained by common variants. A genome-wide polygenic risk score derived from the discovery set was significantly associated to D-TGA in the replication set (P=4x10-5). The genome-wide significant locus (3p14.3) co-localizes with a putative regulatory element that interacts with the promoter of WNT5A, which encodes the Wnt Family Member 5A protein known for its role in cardiac development in mice. We show that this element drives reporter gene activity in the developing heart of mice and zebrafish and is bound by the developmental transcription factor TBX20. We further demonstrate that TBX20 attenuates Wnt5a expression levels in the developing mouse heart. Conclusions: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 near WNT5A. Genomic and functional data support a causal role of WNT5A at the locus

Effect of Exercise Training on Sports Enjoyment and Leisure-time Spending in Adolescents with Complex Congenital Heart Disease: The Moderating Effect of Health Behavior and Disease Knowledge

ObjectiveThe aim of this study was to evaluate the effects of a standardized exercise program on sports enjoyment and leisure-time spending in adolescents with congenital heart disease and to know what the moderating impact of their baseline health behavior and disease knowledge is. MethodsIncluded were 93 patients, aged 10 to 25, with surgical repair for tetralogy of Fallot or with a Fontan circulation for single-ventricle physiology, of 5 participating centers of pediatric cardiology in The Netherlands. They were randomly allocated, stratified for age, gender, and type of congenital heart disease to a 12-week period with either: (1) three times per week standardized exercise training or (2) care as usual (randomization ratio 2:1). At baseline and after 12 weeks, participants completed Web-based questionnaires and were interviewed by phone. Outcome MeasuresPrimary analyses tested changes from baseline to follow-up in sports enjoyment and leisure-time spending in the exercise group vs. control group. Secondary analyses concerned the moderating influence of baseline health behavior and disease knowledge on changes from baseline to follow-up, and comparison with normative data. ResultsAt follow-up, the exercise group reported a decrease in passive leisure-time spending (watching television and computer usage) compared with controls. Exercise training had no effect on sports enjoyment and active leisure-time spending. Disease knowledge had a moderating effect on improvement in sports enjoyment, whereas health behavior did not. Compared with normative data, patients obtained similar leisure time scores and lower frequencies as to drinking alcohol and smoking. ConclusionsExercise training decreased passive, but not active, leisure-time spending. It did not influence sports enjoyment