Long-term outcomes of pulmonary embolism in children and adolescents.

ABSTRACT: Knowledge regarding the long-term consequences of pulmonary embolism (PE) in children is limited. This cohort study describes the long-term outcomes of PE in children who were followed-up at a single-center institution using a local protocol that included clinical evaluation, chest imaging, echocardiography, pulmonary function tests, and cardiopulmonary exercise tests at follow-up, starting 3 to 6 months after acute PE. Children objectively diagnosed with PE at age 0 to 18 years, who had ≥6 months of follow-up were included. Study outcomes consisted of PE resolution, PE recurrence, death, and functional outcomes (dyspnea, impaired pulmonary or cardiac function, impaired aerobic capacity, and post-PE syndrome). The frequency of outcomes was compared between patients with/without underlying conditions. In total, 150 patients were included; median age at PE was 16 years (25th-75th percentile, 14-17 years); 61% had underlying conditions. PE did not resolve in 29%, recurrence happened in 9%, and death in 5%. One-third of patients had at least 1 documented abnormal functional finding at follow-up (ventilatory impairments, 31%; impaired aerobic capacity, 31%; dyspnea, 26%; and abnormal diffusing capacity of the lungs to carbon monoxide, 22%). Most abnormalities were transient. When alternative explanations for the impairments were considered, the frequency of post-PE syndrome was lower, ranging between 0.7% and 8.5%. Patients with underlying conditions had significantly higher recurrence, more pulmonary function and ventilatory impairments, and poorer exercise capacity. Exercise intolerance was, in turn, most frequently because of deconditioning than to respiratory or cardiac limitation, highlighting the importance of physical activity promotion in children with PE.

Hemodynamic parameters at rest predicting exercise capacity in patients supported with left ventricular assist device.

Left ventricular assist devices improve prognosis and quality of life, but exercise capacity remains limited in most patients after device implantation. Left ventricular assist device optimization through right heart catheterization reduces device-related complications. However, hemodynamic parameters associated with exercise capacity under optimized conditions. The aim of this study was to elucidate the predictors of exercise capacity from hemodynamic parameters at rest after left ventricular assist device optimization. We retrospectively reviewed 24 patients who underwent a ramp test with right heart catheterization, echocardiography and cardiopulmonary exercise testing more than 6 months after left ventricular assist device implantation. Pump speed was optimized to a lower setting that achieved right atrial pressure < 12 mmHg, pulmonary capillary wedge pressure < 18 mmHg, and cardiac index > 2.2 L/min/m2, then exercise capacity was assessed by cardiopulmonary exercise testing. After left ventricular assist device optimization, the mean right atrial pressure, pulmonary capillary wedge pressure, cardiac index, and peak oxygen consumption were 7 ± 5 mmHg, 10 ± 7 mmHg, 2.7 ± 0.5 L/min/m2, and 13.2 ± 3.0 mL/min/kg, respectively. Pulse pressure, stroke volume, right atrial pressure, mean pulmonary artery pressure, and pulmonary capillary wedge pressure were significantly associated with peak oxygen consumption. Multivariate linear regression analysis of factors predicting peak oxygen consumption revealed that pulse pressure, right atrial pressure, and aortic insufficiency remained independent predictors (ß = 0.401, p = 0.007; ß = - 0.558, p < 0.001; ß = - 0.369, p = 0.010, respectively). Our findings suggests that cardiac reserve, volume status, right ventricular function, and aortic insufficiency predict exercise capacity in patients with a left ventricular assist device.

The electrocardiographic manifestations of pectus excavatum before and after surgical correction.

BACKGROUND: Pectus excavatum (PEx) can cause cardiopulmonary limitations due to cardiac compression and displacement. There is limited data on electrocardiogram (ECG) alterations before and after PEx surgical repair, and ECG findings suggesting cardiopulmonary limitations have not been reported. The aim of this study is to explore ECG manifestations of PEx before and after surgery including associations with exercise capacity. METHODS: A retrospective review of PEx patients who underwent primary repair was performed. ECGs before and after surgical correction were evaluated and the associations between preoperative ECG abnormalities and cardiopulmonary function were investigated. RESULTS: In total, 310 patients were included (mean age 35.1 ± 11.6 years). Preoperative ECG findings included a predominant negative P wave morphology in V1, and this abnormal pattern significantly decreased from 86.9% to 57.4% (p < 0.001) postoperatively. The presence of abnormal P wave amplitude in lead II (>2.5 mm) significantly decreased from 7.1% to 1.6% postoperatively (p < 0.001). Right bundle branch block (RBBB) (9.4% versus 3.9%, p < 0.001), rsr' patterns (40.6% versus 12.9%, p < 0.001), and T wave inversion in leads V1-V3 (62.3% vs 37.7%, p < 0.001) were observed less frequently after surgery. Preoperative presence of RBBB (OR = 4.8; 95%CI 1.1-21.6) and T wave inversion in leads V1-3 (OR = 2.3; 95%CI 1.3-4.2) were associated with abnormal results in cardiopulmonary exercise testings. CONCLUSION: Electrocardiographic abnormalities in PEx are frequent and can revert to normal following surgery. Preoperative RBBB and T wave inversion in leads V1-3 suggested a reduction in exercise capacity, serving as a marker for the need for further cardiovascular evaluation of these patients.

Exercise ventilatory response after COVID-19: comparison between ambulatory and hospitalized patients.

Inefficient ventilatory response during cardiopulmonary exercise testing (CPET) has been suggested as a cause of post-COVID-19 dyspnea. It has been described in hospitalized patients (HOSP) with lung parenchymal sequelae but also after mild infection in ambulatory patients (AMBU). We hypothesize that AMBU and HOSP have different ventilatory responses to exercise, due to different etiologies. We analyzed CPET realized between July 2020 and May 2022 of patients with persisting respiratory symptoms 3 mo after COVID-19. Chest computed tomography (CT) scan, pulmonary function tests, quality of life, and respiratory questionnaires were collected. CPET data were specifically explored as a function of ventilation (V̇e) and time. Seventy-nine consecutive patients were included (42 AMBU and 37 HOSP, median: 54 [44-60] yr old, 57% female). Patients were hospitalized for a median of 20 [8-34] days, with pneumonia (41%) or acute respiratory distress syndrome (ARDS; 30%). Among HOSP, 12(32%) patients had abnormal values for spirometry and 18(51%) for carbon monoxide diffusing capacity (P < 0.001). CPET showed no differences between AMBU and HOSP in peak absolute O2 uptake (V̇o2) (1.59 [1.22-2.11] mL·min-1; P = 0.65). Tidal volume (VT) as a function of V̇e, was lower in AMBU than in HOSP (P < 0.01) toward the end of exercise. The slope of the V̇e-CO2 production was higher than normal in both groups (30.9 [26.1-34.3]; P = 0.96). In conclusion, the severity of COVID-19 did not influence the exercise capacity, but AMBU demonstrated a less efficient ventilatory response to exercise as compared with HOSP. CPET with exploration of data as a function of V̇e and throughout the exercise better unveil ventilatory inefficiency.NEW & NOTEWORTHY We evaluated the exercise ventilatory response in patients with persisting dyspnea after severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. We found that despite similar peak power and peak absolute O2 uptake, tidal volume as a function of ventilation was lower in ambulatory than in hospitalized patients toward the end of exercise, reflecting ventilatory inefficiency. We call for evaluation of minute ventilation with the exploration of data throughout the exercise and not only peak data to better unveil ventilatory inefficiency.

Predicting the Development of Renal Replacement Therapy Indications by Combining the Furosemide Stress Test and Chemokine (C-C Motif) Ligand 14 in a Cohort of Postsurgical Patients.

OBJECTIVES: Optimal timing of renal replacement therapy (RRT) initiation in severe acute kidney injury (AKI) remains controversial. Initiation of treatment early in the course of AKI may lead to some patients undergoing unnecessary RRT, whereas delayed treatment is associated with increased mortality. This study aims to investigate whether the combination of the furosemide stress test (FST) and AKI-associated biomarkers can predict the development of indications for RRT. DESIGN: Single-center, prospective, observational study. SETTING: University Hospital of Muenster, Germany. PATIENTS: Critically ill, postoperative patients with moderate AKI (Kidney Disease: Improving Global Outcomes stage 2) and risk factors for further progression (vasopressors and/or mechanical ventilation) receiving an FST. INTERVENTIONS: Sample collection and measurement of different biomarkers (chemokine [C-C motif] ligand 14 [CCL14], neutrophil gelatinase-associated lipocalin, dipeptidyl peptidase 3). MEASUREMENT AND MAIN RESULTS: The primary endpoint was the development of greater than or equal to one predefined RRT indications (hyperkalemia [≥ 6 mmol/L], diuretic-resistant hypervolemia, high urea serum levels [≥ 150 mg/dL], severe metabolic acidosis [pH ≤ 7.15], oliguria [urinary output < 200 mL/12 hr], or anuria). Two hundred eight patients were available for the primary analysis with 108 having a negative FST (urine output < 200 mL in 2 hr following FST). Ninety-eight patients (47%) met the primary endpoint, 82% in the FST negative cohort. At the time of inclusion, the combination of a negative FST test and high urinary CCL14 levels had a significantly higher predictive value for the primary endpoint with an area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI, 0.82-0.92) compared with FST or CCL14 alone (AUC, 0.79; 95% CI, 0.74-0.85 and AUC, 0.83; 95% CI, 0.77-0.89; p < 0.001, respectively). Other biomarkers showed lower AUCs. CONCLUSIONS: The combination of the FST with the renal biomarker CCL14 predicts the development of indications for RRT.

The safety of carotid stenosis during vasodilator pharmacologic stress testing.

BACKGROUND: While thousands of patients undergo stress testing annually, the risk of exercise and pharmacologic stress in patients with carotid artery disease has not been fully defined but is of concern as patients are at risk for cerebrovascular accidents and transient ischemic attacks. METHODS: All patients with either ultrasound or CTA evaluation of their carotid arteries from over a 10 year period who underwent stress testing within 180 days without intervening carotid intervention were reviewed for any adverse events within 24 hours of their stress test. The primary end point was any cerebrovascular event or syncope while the secondary endpoints included death, myocardial infarction, urgent angiography, urgent revascularization, or exaggerated hemodynamic response (systolic BP drop > 20 mmHg or systolic BP > 180 mmHg at peak stress). Patients were stratified into categories based on their level of carotid disease. Patients with severe carotid stenosis were propensity matched to those with mild or no stenosis. RESULTS: A total of 4457 patients underwent carotid ultrasound, 10,644 CTA, and 16,011 had stress testing during this time period with 514 having both a carotid evaluation and a stress test within 6 months. After propensity matching, 62 patients with severe carotid stenosis were matched to 170 patients with mild or no carotid stenosis. Incidentally, all patients with severe carotid stenosis underwent pharmacologic stress. There were no primary endpoints and only three secondary endpoints in two patients in the mild or no carotid stenosis group. The proportion of exaggerated hemodynamic response to stress was similar in both groups-21.0% in the carotid stenosis group vs 31.2% without (P = .17) having a significant drop in systolic BP, and 3.2% vs 4.7% (P = 1.0) having a significantly elevated systolic BP. CONCLUSION: In this study cohort there were few primary and secondary outcome events with no events occurring in patients with significant carotid stenosis. Additionally, there was no difference in exaggerated hemodynamic responses. While these results suggest that stress testing entails no demonstrable increased risk in patients with significant carotid stenosis, continued care should be taken given the limitations of the small size of this study.

Increasing frequency of dyspnea among patients referred for cardiac stress testing.

OBJECTIVE: To assess the frequency, change in prevalence, and prognostic significance of dyspnea among contemporary patients referred for cardiac stress testing. PATIENTS AND METHODS: We evaluated the prevalence of dyspnea and its relationship to all-cause mortality among 33,564 patients undergoing stress/rest SPECT-MPI between January 1, 2002 and December 31, 2017. Dyspnea was assessed as a single-item question. Patients were divided into three temporal groups. RESULTS: The overall prevalence of dyspnea in our cohort was 30.2%. However, there was a stepwise increase in the temporal prevalence of dyspnea, which was present in 25.6% of patients studied between 2002 and 2006, 30.5% of patients studied between 2007 and 2011, and 38.7% of patients studied between 2012 and 2017. There was a temporal increase in the prevalence of dyspnea in each age, symptom, and risk factor subgroup. The adjusted hazard ratio for mortality was higher among patients with dyspnea vs those without dyspnea both among all patients, and within each chest pain subgroup. CONCLUSIONS: Dyspnea has become increasingly prevalent among patients referred for cardiac stress testing and is now present among nearly two-fifths of contemporary cohorts referred for stress-rest SPECT-MPI. Prospective study is needed to standardize the assessment of dyspnea and evaluate the reasons for its increasing prevalence.

[Anatomical resection for non-small cell lung cancer: cardiopulmonary exercise testing in assessing the risk of respiratory complications]. / Anatomicheskie rezektsii po povodu nemelkokletochnogo raka legkogo: kardiorespiratornoe nagruzochnoe testirovanie v otsenke riska respiratornykh oslozhnenii.

OBJECTIVE: To assess the role of cardiopulmonary exercise testing in examination of patients with high risk of respiratory complications in anatomical resections for non-small cell lung cancer. MATERIAL AND METHODS: A non-randomized retrospective single-center study was devoted to immediate results of surgical treatment of patients with NSCLC between December 2020 and April 2021. Median age of patients was 65 (84; 30) years, male-to-female ratio - 129 (57%)/98 (43%). All patients were examined according to a unified algorithm recommended by the American (ATS) and European (ESTS) societies of thoracic surgeons. At the first stage, we analyzed airflow rate and performed non-invasive exercise tests (6-minute walk and/or stair test). Resections of lungs were performed in 231 patients, anatomic lung resections - in 227 patients (lobectomy - 199, bilobectomy - 4, segmentectomy - 17, pneumonectomy - 7). We excluded 4 patients who underwent non-anatomic lung resections (marginal resections). RESULTS: Among 236 patients referred for anatomical lung resections, 34 (14.4%) ones were selected for cardiopulmonary testing. Selection was based on low exercise tolerance and/or severe decrease in predictive respiratory parameters (FEV<50%). Patients were divided into 4 groups depending on peak oxygen consumption. There were 5 (2%), 10 (29.4%), 11 (32.3%) and 8 (23.5%) patients with extremely high, high, moderate and low risk of respiratory complications, respectively. Surgeries were performed for IA1 (n=6), IA2 (n=50), IA3 (n=37), IB (n=31), IIA (n=19), IIB (n=37), IIIA (n=25) and IIIB (n=4) stages. The overall incidence of postoperative complications was 23% (95% CI: 18-28.8). Complications Clavien-Dindo grade I, IIIA, IIIB, IVA, IVB and V prevailed in both groups. Median postoperative hospital-stay (6 (6; 8) vs. 7 (6; 8) days) and time of pleural drainage (4 (2; 5) vs. 3 (3; 4) days) were similar. Organ-sparing procedures prevailed in the main group (5 (26%) out of 19 (95% CI: 11.81-48.8) vs. 12 (6.7%) out of 180 (95% CI: 3.8-11.3)). Overall mortality (n=231) was 1.7% (95% CI: 0.7-4.4). Mortality throughout the first postoperative year was 24% (95% CI: 12.2-42.1) and 7.4% (95% CI: 4.2-11.3), respectively. CONCLUSION: Cardiopulmonary exercise testing makes it possible to objectively assess exercise tolerance and identify high-risk patients for respiratory complications. These data are valuable when planning the treatment of patients with non-small cell lung cancer.

Physical and physiological effects of dobutamine stress echocardiography in low-gradient aortic stenosis.

Dobutamine stress echocardiography (DSE) is a useful tool for assessing low-gradient significant aortic stenosis (AS) and contractile reserve (CR), but its prognostic utility has become controversial in recent studies. We evaluated the impact of DSE on aortic valve physiological, structural, and left ventricular parameters in low-gradient AS. Consecutive patients undergoing DSE for low-gradient AS evaluation from September 2010 to July 2016 were retrospectively studied, and DSE findings were divided into four groups: with and without severe AS and/or CR. Relationships between left ventricular chamber quantification, CR, aortic valve Doppler during DSE, and calcium score [by computerized tomography (CT)] were analyzed. There were 258 DSE studies performed on 243 patients, mean age 77.6 ± 10.8 yr and 183 (70.1%) were males. With increasing dobutamine dose, apart from systolic blood pressure, left ventricular ejection fraction, flow, cardiac power output, and longitudinal strain magnitude, along with aortic valve area and mean aortic gradient were all significantly increased (P < 0.05). Flow and mean gradient increased in both the presence and absence of CR, whereas stroke volume and aortic valve area increased mainly in those with CR only. The aortic valve area increased in both patients with low and high calcium scores; however, the baseline area was lower in those with a higher calcium score. During DSE, aortic valve area increases with increase in aortic valve gradient. Higher calcium score is associated with lower baseline aortic valve area, but the aortic valve area still increases with dobutamine even in presence of a high calcium score.NEW & NOTEWORTHY We show that even in most severe aortic stenosis, there is some residual valve pliability. This suggests that a complete loss of pliability is not compatible with survival.

Variation of PetCO2 during incremental exercise and severity of IPAH and CTEPH.

BACKGROUND AND OBJECTIVE: End-tidal PCO2 (PetCO2) patterns during exercise testing as well as ventilatory equivalents for CO2 have been reported for different pulmonary vascular diseases but seldomly for the significant differences in exercise response depending on the etiology of pulmonary hypertension. We aimed to compare PetCO2 change pattern in IPAH and CTEPH with varying severity during incremental cardiopulmonary exercise testing (CPET). METHODS: 164 IPAH patients and 135 CTEPH patients referred to Shanghai Pulmonary Hospital between 2012 and 2019 were retrospectively recruited into the study. All patients performed CPET and also underwent right-heart catheterization (RHC). Forty-four healthy subjects also performed CPET and were included as controls. RESULTS: PetCO2 was significantly lower in IPAH and CTEPH patients as compared to normal subjects. Moreover, the PetCO2 did not rise, in fact fell from rest to anaerobic threshold (AT), then further decreased until peak in both IPAH and CTEPH. PetCO2 value at rest, unloaded, AT and peak were proportionately reduced as the World Health Organization functional class (WHO-Fc) increased in both IPAH and CTEPH patients. The PETCO2 in IPAH patients had significant differences during all phases of exercise between WHO-Fc I-II and III-IV subgroup. CTEPH also demonstrated significant difference except for PetCO2 at peak. PetCO2 values were significantly higher in IPAH during all phases of exercise as compared to CTEPH patients (all P < 0.001). PeakVO2%pred correlated significantly with PetCO2 at rest (r = 0.477, P < 0.001), AT (r = 0.609, P < 0.001) and peak exercise (r = 0.576, P < 0.001) in IPAH. N-terminal natriuretic peptide type-B (NT-proBNP) also correlated markedly with PetCO2, with a correlation coefficient of - 0.326 to - 0.427 (all P < 0.001). Additionally, PetCO2 at rest, at AT and at peak correlated positively with peakVO2%pred and showed an inverse correlation with NT-proBNP in CTEPH patients (all P < 0.05). CONCLUSIONS: PetCO2 during exercise in IPAH and CTEPH patients was significantly different from normal subjects. Moreover, PetCO2 values were significantly higher in IPAH during all phases of exercise as compared to CTEPH patients (all P < 0.001). PetCO2 was progressively more abnormal with increasing disease severity according to peakVO2%pred and WHO-Fc.

Identifying the limitations of cardiopulmonary exercise testing prior to esophagectomy using a pooled analysis of patient-level data.

Preoperative cardiopulmonary exercise testing (CPET) provides an objective assessment of aerobic fitness in patients undergoing surgery. While peak oxygen uptake during exercise (VO2peak) and anaerobic threshold have demonstrated a moderate correlation with the development of complications following esophagectomy, no clinically useful threshold values have been defined. By pooling patient level data from existing studies, we aimed to define optimal thresholds for preoperative CPET parameters to predict patients at high risk of postoperative complications. Studies reporting on the relationship between preoperative CPET variables and post-esophagectomy complications were determined from a comprehensive literature search. Patient-level data were obtained from six contributing centers for pooled-analyses. Outcomes of interest included cardiopulmonary and non-cardiopulmonary complications, unplanned intensive care unit readmission, and 90-day and 12-month all-cause mortality. Receiver operating characteristic curves and logistic regression models estimated the predictive value of CPET parameters for each individual outcome of interest. This analysis comprised of 621 patients who underwent CPET prior to esophagectomy during the period from January 2004 to March 2017. For both anaerobic threshold and VO2peak, none of the receiver operating characteristic curves achieved an area under the curve value > 0.66 for the outcomes of interest. The discriminatory ability of CPET for determining high-risk patients was found to be poor in patients undergoing an esophagectomy. CPET may only carry an adjunct role to clinical decision-making.

Tidal volume expandability affected by flow, dynamic hyperinflation, and quasi-fixed inspiratory time in patients with COPD and healthy individuals.

Exertional dyspnea (ED) and impaired exercise performance (EP) are mainly caused by dynamic hyperinflation (DH) in chronic obstructive pulmonary disease (COPD) patients by constraining tidal volume expansion at peak exercise (VTpeak). As VTpeak is the product of inspiratory time (TIpeak) and flow (VT/TIpeak), it was hypothesized that VTpeak and VTpeak/total lung capacity (VTpeak/TLC) may be affected by TIpeak and VT/TIpeak. Hence, the study investigated the (1) effect of TIpeak and VT/TIpeak on VTpeak expansion, (2) factors associated with TIpeak, expiratory time (TEpeak), VT/TIpeak, and VTpeak/TLC, and (3) relationships between VT/TIpeak and VTpeak/TLC with ED and EP in COPD patients and controls. The study enrolled 126 male stable COPD patients and 33 sex-matched controls. At peak exercise, TIpeak was similar in all subjects (COPD versus controls, mean ± SD: 0.78 ± 0.17 s versus 0.81 ± 0.20 s, p = NS), whereas the COPD group had lower VT/TIpeak (1.71 ± 0.49 L/s versus 2.58 ± 0.69 L/s, p < .0001) and thus the COPD group had smaller VTpeak (1.31 ± 0.34 L versus 2.01 ± 0.45 L,p < .0001) and VTpeak/TLC (0.22 ± 0.06 vs 0.33 ± 0.05, p < .0001). TIpeak, TEpeak, and VT/TIpeak were mainly affected by exercise effort, whereas VTpeak/TLC was not. TEpeak, VT/TIpeak, and VTpeak/TLC were inversely changed by impaired lung function. TIpeak was not affected by lung function. Dynamic hyperinflation did not occur in the controls, however, VTpeak/TLC was strongly inversely related to DH (r = -0.79) and moderately to strongly related to lung function, ED, and EP in the COPD group. There was a slightly stronger correlation between VTpeak/TLC with ED and EP than VT/TIpeak in the COPD group (|r| = 0.55-0.56 vs 0.38-0.43). In summary, TIpeak was similar in both groups and the key to understanding how flow affects lung expansion. However, the DH volume effect was more important than the flow effect on ED and EP in the COPD group.

Obesity is associated with higher heart rate and excessive dyspnea with fatigue in the six-minute walk test.

According to the World Health Organization, obesity is the fifth most important risk factor responsible for cardiovascular mortality. The Six- Minute Walk Test (6MWT) is a very useful assessment of patients' exercise tolerance in clinical circumstances. Owing to submaximal exercise during the test, its results reflect patients' ability to perform daily activities. AIM: Assessment of cardiorespiratory functions in obese patients using the 6MWT. MATERIALS AND METHODS: The study group included 234 patients, divided into 3 groups depending on their BMI: Group 1 - BMI<30kg/m2, Group 2 - BMI≥30<40kg/m2, Group 3 - BMI≥40kg/m2. Laboratory tests were performed for all patients. Cardiorespiratory fitness was assessed with the 6MWT. Pulse rate, blood pressure (BP) and oxygen saturation, the degree of dyspnea and perceived exertion, the total distance walked, and the percent of the predicted mean value for the walked distance were recorded and analyzed. RESULTS: Pre and post the 6MWT test BP and pulse rate increased significantly with the higher BMI and were highest in Group 3. Patients with the highest BMI felt more fatigue after the test than those with the lowest BMI. Patients in Group 1 walked a significantly longer total distance compared to Group 3, However, a significantly higher pulse rate and degree of dyspnea and exertion were observed in more obese patients. CONCLUSIONS: Morbidly obese patients covered the same walking distance as adjusted according to Enright's reference equations in the 6MWT as patients with a lower BMI. They required more effort as evidenced by the increased pulse rate and BP, and they complained of a higher degree of dyspnea and perceived exertion. Resting higher heart rates in this patient group may be an issue of concern in the context of subsequent morbidity and all-cause mortality.

Anxiety and hemodynamic reactivity during cardiac stress testing: The role of gender and age in myocardial ischemia.

BACKGROUND: The prevalence of myocardial ischemia is associated with anxiety. State and trait anxiety are more common in younger women compared to men, and high anxiety levels could affect hemodynamic reactivity during cardiac stress testing. The aim is to examine whether anxiety plays a role in gender differences in patients ≤ 65 and > 65 years in hemodynamic reactivity and ischemia during cardiac stress testing. METHODS AND RESULTS: Included were 291 patients (66.8 ± 8.7 years, 45% women) with suspect ischemia undergoing myocardial perfusion single-photon emission computed tomography (MPI-SPECT). Primary outcomes were semi-quantitative summed difference score (SDS) and summed stress score (SSS), as continuous indicators of myocardial ischemia. Analyses were stratified by age. Trait anxiety was measured using a validated questionnaire (GAD-7) and state anxiety using facial expression analyses software. Overall, trait and state anxiety were not associated with the prevalence of ischemia (N = 107, 36%). A significant interaction was found between gender and trait anxiety in women ≤ 65 years for SDS (F(1,4) = 5.73, P = .019) and SSS (F(1,10) = 6.50, P = .012). This was not found for state anxiety. CONCLUSION: SDS and SSS were significantly higher in women younger than 65 years with high trait anxiety. This interaction was not found in men and women over 65 years.

Asystole following Regadenoson administration: Review of literature, risk factors and management.

Regadenoson, a selective A2A receptor agonist, is widely used for vasodilator stress myocardial perfusion imaging and has a superior adverse effect profile when compared with other agents. However, with widespread use, there have been several reported cases of Regadenoson induced bradyarrhythmias and even asystole in patients with no known conduction system disease. In this article, we report a case of asystole following Regadenoson administration, evaluate mechanisms and risk factors for Regadenoson induced bradyarrhythmias to better identify patients at risk. We also review the available treatment options and propose recommendations for limiting its risk.

Exercise-induced ventricular tachycardia in a case with hypertrophic cardiomyopathy taking cibenzoline.

We report a 17-year-old woman with hypertrophic cardiomyopathy (HCM) successfully resuscitated from ventricular fibrillation while taking cibenzoline. During exercise-stress testing before implanting an implantable cardioverter-defibrillator, ventricular tachycardia was induced and thought to be a proarrhythmia due to the use-dependent effect of the Na channel blockade with cibenzoline. In patients with arrhythmogenic substrates such as HCM, it is critical to pay attention to the proarrhythmic effects of class I antiarrhythmic drugs while increasing heart rate.

Changes in plasma hydroxyproline and plasma cell-free DNA concentrations after higher- versus lower-intensity eccentric cycling.

PURPOSE: We examined changes in plasma creatine kinase (CK) activity, hydroxyproline and cell-free DNA (cfDNA) concentrations in relation to changes in maximum voluntary isometric contraction (MVIC) torque and delayed-onset muscle soreness (DOMS) following a session of volume-matched higher- (HI) versus lower-intensity (LI) eccentric cycling exercise. METHODS: Healthy young men performed either 5 × 1-min HI at 20% of peak power output (n = 11) or 5 × 4-min LI eccentric cycling at 5% of peak power output (n = 9). Changes in knee extensor MVIC torque, DOMS, plasma CK activity, and hydroxyproline and cfDNA concentrations before, immediately after, and 24-72 h post-exercise were compared between groups. RESULTS: Plasma CK activity increased post-exercise (141 ± 73.5%) and MVIC torque decreased from immediately (13.3 ± 7.8%) to 48 h (6.7 ± 13.5%) post-exercise (P < 0.05), without significant differences between groups. DOMS was greater after HI (peak: 4.5 ± 3.0 on a 10-point scale) than LI (1.2 ± 1.0). Hydroxyproline concentration increased 40-53% at 24-72 h after both LI and HI (P < 0.05). cfDNA concentration increased immediately after HI only (2.3 ± 0.9-fold, P < 0.001), with a significant difference between groups (P = 0.002). Lack of detectable methylated HOXD4 indicated that the cfDNA was not derived from skeletal muscle. No significant correlations were evident between the magnitude of change in the measures, but the cfDNA increase immediately post-exercise was correlated with the maximal change in heart rate during exercise (r = 0.513, P = 0.025). CONCLUSION: Changes in plasma hydroxyproline and cfDNA concentrations were not associated with muscle fiber damage, but the increased hydroxyproline in both groups suggests increased collagen turnover. cfDNA may be a useful metabolic-intensity exercise marker.

Forced treadmill running reduces systemic inflammation yet worsens upper limb discomfort in a rat model of work-related musculoskeletal disorders.

BACKGROUND: Musculoskeletal disorders can result from prolonged repetitive and/or forceful movements. Performance of an upper extremity high repetition high force task increases serum pro-inflammatory cytokines and upper extremity sensorimotor declines in a rat model of work-related musculoskeletal disorders. Since one of the most efficacious treatments for musculoskeletal pain is exercise, this study investigated the effectiveness of treadmill running in preventing these responses. METHODS: Twenty-nine young adult female Sprague-Dawley rats were used. Nineteen were trained for 5 weeks to pull a lever bar at high force (15 min/day). Thirteen went on to perform a high repetition high force reaching and lever-pulling task for 10 weeks (10-wk HRHF; 2 h/day, 3 days/wk). From this group, five were randomly selected to undergo forced treadmill running exercise (TM) during the last 6 weeks of task performance (10-wk HRHF+TM, 1 h/day, 5 days/wk). Results were compared to 10 control rats and 6 rats that underwent 6 weeks of treadmill running following training only (TR-then-TM). Voluntary task and reflexive sensorimotor behavioral outcomes were assessed. Serum was assayed for inflammatory cytokines and corticosterone, reach limb median nerves for CD68+ macrophages and extraneural thickening, and reach limb flexor digitorum muscles and tendons for pathological changes. RESULTS: 10-wk HRHF rats had higher serum levels of IL-1α, IL-1ß and TNFα, than control rats. In the 10-wk HRHF+TM group, IL-1ß and TNFα were lower, whereas IL-10 and corticosterone were higher, compared to 10-wk HRHF only rats. Unexpectedly, several voluntary task performance outcomes (grasp force, reach success, and participation) worsened in rats that underwent treadmill running, compared to untreated 10-wk HRHF rats. Examination of forelimb tissues revealed lower cellularity within the flexor digitorum epitendon but higher numbers of CD68+ macrophages within and extraneural fibrosis around median nerves in 10-wk HRHF+TM than 10-wk HRHF rats. CONCLUSIONS: Treadmill running was associated with lower systemic inflammation and moderate tendinosis, yet higher median nerve inflammation/fibrosis and worse task performance and sensorimotor behaviors. Continued loading of the injured tissues in addition to stress-related factors associated with forced running/exercise likely contributed to our findings.

The haemodynamic basis of lung congestion during exercise in heart failure with preserved ejection fraction.

AIMS: Increases in extravascular lung water (EVLW) during exercise contribute to symptoms, morbidity, and mortality in patients with heart failure and preserved ejection fraction (HFpEF), but the mechanisms leading to pulmonary congestion during exercise are not well-understood. METHODS AND RESULTS: Compensated, ambulatory patients with HFpEF (n = 61) underwent invasive haemodynamic exercise testing using high-fidelity micromanometers with simultaneous lung ultrasound, echocardiography, and expired gas analysis at rest and during submaximal exercise. The presence or absence of EVLW was determined by lung ultrasound to evaluate for sonographic B-line artefacts. An increase in EVLW during exercise was observed in 33 patients (HFpEFLW+, 54%), while 28 (46%) did not develop EVLW (HFpEFLW-). Resting left ventricular function was similar in the groups, but right ventricular (RV) dysfunction was two-fold more common in HFpEFLW+ (64 vs. 31%), with lower RV systolic velocity and RV fractional area change. As compared to HFpEFLW-, the HFpEFLW+ group displayed higher pulmonary capillary wedge pressure (PCWP), higher pulmonary artery (PA) pressures, worse RV-PA coupling, and higher right atrial (RA) pressures during exercise, with increased haemoconcentration indicating greater loss of water from the vascular space. The development of lung congestion during exercise was significantly associated with elevations in PCWP and RA pressure as well as impairments in RV-PA coupling (area under the curve values 0.76-0.84). CONCLUSION: Over half of stable outpatients with HFpEF develop increases in interstitial lung water, even during submaximal exercise. The acute development of lung congestion is correlated with increases in pulmonary capillary hydrostatic pressure that favours fluid filtration, and systemic venous hypertension due to altered RV-PA coupling, which may interfere with fluid clearance. CLINICAL TRIAL REGISTRATION: NCT02885636.

Exercise-Induced Elevated BDNF Level Does Not Prevent Cognitive Impairment Due to Acute Exposure to Moderate Hypoxia in Well-Trained Athletes.

Exposure to acute hypoxia causes a detrimental effect on the brain which is also manifested by a decrease in the ability to perform psychomotor tasks. Conversely, brain-derived neurotrophic factor (BDNF), whose levels are elevated in response to exercise, is a well-known factor in improving cognitive function. Therefore, the aim of our study was to investigate whether the exercise under hypoxic conditions affects psychomotor performance. For this purpose, 11 healthy young athletes performed a graded cycloergometer exercise test to volitional exhaustion under normoxia and acute mild hypoxia (FiO2 = 14.7%). Before, immediately after exercise and after a period of recovery, choice reaction time (CRT) and number of correct reactions (NCR) in relation to changes in serum BDNF were examined. Additionally, other selected factors which may modify BDNF production, i.e., cortisol (C), nitrite, catecholamines (adrenalin-A, noradrenaline-NA, dopamine-DA, serotonin-5-HT) and endothelin-1 (ET-1), were also measured. Exercise in hypoxic conditions extended CRT by 13.8% (p < 0.01) and decreased NCR (by 11.5%) compared to rest (p < 0.05). During maximal workload, NCR was lower by 9% in hypoxia compared to normoxia (p < 0.05). BDNF increased immediately after exercise in normoxia (by 29.3%; p < 0.01), as well as in hypoxia (by 50.0%; p < 0.001). There were no differences in BDNF between normoxia and hypoxia. Considering the fact that similar levels of BDNF were seen in both conditions but cognitive performance was suppressed in hypoxia, acute elevation of BDNF did not compensate for hypoxia-induced cognition impairment. Moreover, neither potentially negative effects of C nor positive effects of A, DA and NO on the brain were observed in our study.