Quadriceps arthrogenic muscle inhibition: the effects of experimental knee joint effusion on motor cortex excitability

Introduction

Marked weakness of the quadriceps muscles is typically observed following injury, surgery or pathology affecting the knee joint. This is partly due to ongoing neural inhibition that prevents the central nervous system from fully activating the quadriceps, a process known as arthrogenic muscle inhibition (AMI). This study aimed to further investigate the mechanisms underlying AMI by exploring the effects of experimental knee joint effusion on quadriceps corticomotor and intracortical excitability.

Methods

Seventeen healthy volunteers participated in this study. Transcranial magnetic stimulation was used to measure quadriceps motor evoked potential area, short-interval intracortical inhibition, intracortical facilitation and cortical silent period duration before and after experimental knee joint effusion. Joint effusion was induced by the intraarticular infusion of dextrose saline into the knee.

Results

There was a significant increase in quadriceps motor evoked potential area following joint infusion, both at rest (P = 0.01) and during voluntary muscle contraction (P = 0.02). Cortical silent period duration was significantly reduced following joint infusion (P = 0.02). There were no changes in short interval intracortical inhibition or intracortical facilitation over time (all P > 0.05).

Conclusions

The results of this study provide no evidence for a supraspinal contribution to quadriceps AMI. Paradoxically, but consistent with previous observations in patients with chronic knee joint pathology, quadriceps corticomotor excitability increased after experimental knee joint effusion. The increase in quadriceps corticomotor excitability may be at least partly mediated by a decrease in gamma-aminobutyric acid (GABA)-ergic inhibition within the motor cortex.     

Association between individual quadriceps muscle volume/enthesis and patello femoral joint cartilage morphology

Introduction

The aim of this study was to determine the association between individual quadriceps muscle volumes and the quadriceps enthesis structures and cartilage morphology at the patellofemoral joint (PFJ).

Methods

We studied 12 cadavers (age 75 ± 5 years). For both legs, individual quadriceps muscles (vastus lateralis (VL), rectus femoris (RF), vastus intermedialis (VI) and vastus medialis (VM)) were dissected and their volumes measured. Cartilage areas at the PFJ were classified using the International Cartilage Repair Society (ICRS) score. Histological sections were evaluated at the quadriceps tendon enthesis (laterally, centrally and medially). Several variables were calculated on the binary images based on two-dimensional analysis. These were apparent bone area (BA) and apparent trabecular thickness (TH). A Spearman rank test was used to determine the strength of correlation between individual quadriceps muscles volume, the structure of the quadriceps tendon enthesis and the ICRS score.

Results

The thickness of calcified fibrocartilage tissue was significantly greater in the central part of the enthesis than both medially (P = 0.03) and laterally (P = 0.04). Uncalcified fibrocartilage was significantly thicker laterally (P = 0.04) and centrally (P = 0.02) than medially. Muscle volume was highest (P <0.05) for the VL, followed by the VI, VM and RF. There was no association between total and individual muscle volumes and ICRS or BA. However, there was a strong positive correlation (r = 0.81) between the VL/VM volume ratio and BA ratio (bone volume at the lateral part divided by bone volume at the medial part). There was a moderate positive correlation between VL/VM and ICRS (r = 0.65) and between ICRS and BA ratio (lateral/medial; r = 0.74).

Conclusions

Individual and total quadriceps volumes were not correlated with cartilage loss at the PFJ or fibrocartilage thickness. However, both VL/VM and BA ratio (lateral/medial) were positively correlated with ICRS scoring and therefore could be a tool for predicting degree of PFJ osteoarthritis severity.     

Peripheral blood derived mononuclear cells enhance osteoarthritic human chondrocyte migration

IntroductionA major problem in cartilage repair is the lack of chondrogenic cells migrating from healthy tissue into defects. Cartilage is essentially avascular and therefore its healing is not considered to involve mononuclear cells. Peripheral blood derived mononuclear cells (PBMC) offer a readily available autologous cell source for clinical use and therefore this study was designed to evaluate the effects of PBMCs on chondrocytes and cartilage.MethodsHuman primary chondrocytes and cartilage tissue explants were taken from patients undergoing total knee replacement (n = 17). Peripheral blood samples were obtained from healthy volunteers (n = 12) and mononuclear cells were isolated by density-gradient centrifugation. Cell migration and chemokinetic potential were measured using a scratch assay, xCELLigence and CyQuant assay. PCR array and quantitative PCR was used to evaluate mRNA expression of 87 cell motility and/or chondrogenic genes.ResultsThe chondrocyte migration rate was 2.6 times higher at 3 hour time point (p < 0.0001) and total number of migrating chondrocytes was 9.7 times higher (p < 0.0001) after three day indirect PBMC stimulus and 8.2 times higher (p < 0.0001) after three day direct co-culture with PBMCs. A cartilage explant model confirmed that PBMCs also exert a chemokinetic role on ex vivo tissue. PBMC stimulation was found to significantly upregulate the mRNA levels of 2 chondrogenic genes; collagen type II (COL2A1 600–fold, p < 0.0001) and SRY box 9 (SOX9 30–fold, p < 0.0001) and the mRNA levels of 7 genes central in cell motility and migration were differentially regulated by 24h PBMC stimulation.ConclusionThe results support the concept that PBMC treatment enhances chondrocyte migration without suppressing the chondrogenic phenotype possibly via mechanistic pathways involving MMP9 and IGF1. In the future, peripheral blood mononuclear cells could be used as an autologous point-ofcare treatment to attract native chondrocytes from the diseased tissue to aid in cartilage repair.     

Effect of dexamethasone prodrug on inflamed temporomandibular joints in juvenile rats

IntroductionJuvenile idiopathic arthritis (JIA) often causes inflammation of the temporomandibular joint (TMJ) and has been treated with both systemic and intra-articular steroids, with concerns about effects on growing bones. In this study, we evaluated the impact of a macromolecular prodrug of dexamethasone (P-DEX) with inflammation-targeting potential applied systemically or directly to the TMJ.MethodsJoint inflammation was initiated by injecting two doses of complete Freund’s adjuvant (CFA) at 1-month intervals into the right TMJs of 24 growing Sprague–Dawley male rats (controls on left side). Four additional rats were not manipulated. With the second CFA injection, animals received (1) 5 mg of P-DEX intra-articularly (n = 9), (2) 15 mg of P-DEX into the tail vein (n = 7), or (3) nothing in addition to CFA (n = 8). The rats were killed 28 days later and measured by radiography for ramus height (condylar superior to gonion inferior [CsGoInf]), by micro-computed tomography for condylar width (CW) and bone volume/standardized condylar volume (BV/CV), and by histology for retrodiscal inflammatory cells. Inflammation targeting of systemic P-DEX was confirmed by IVIS infrared dye imaging. Inflammation and bone growth were compared between groups using analysis of variance and Pearson’s correlations.ResultsCFA caused a significant reduction in CsGoInf (p < 0.05), but neither route of P-DEX administration had an effect on CsGoInf or CW at CFA injection sites. BV/CV was significantly reduced in both inflamed and control condyles as a result of either steroid application (p < 0.05). The inflammatory infiltrate was overwhelmingly lymphocytic, comprising 16.4 ± 1.3 % of the field in CFA alone vs. <0.01 % lymphocytes in contralateral controls (p < 0.0001). Both P-DEX TMJ (10.1 ± 1.2 %) and systemic P-DEX (8.9 ± 1.7 %) reduced lymphocytes (p < 0.002). The total area of inflammatory infiltrate was significantly less in the systemic injection group than in the group that received CFA injections alone (2.6 ± 1.5 mm² vs. 8.0 ± 1.3 mm²; p = 0.009), but not in the group that received intra-articular P-DEX (8.8 ± 1.2 mm²).ConclusionsHigh-dose systemic administration of inflammation-targeting P-DEX is more effective than an intra-articular injection in reducing TMJ inflammation, but both routes may affect TMJ bone density.     

Overexpression of MMP13 in human osteoarthritic cartilage is associated with the SMAD-independent TGF-β signalling pathway

IntroductionIn vitro and animal model of osteoarthritis (OA) studies suggest that TGF-β signalling is involved in OA, but human data is limited. We undertook this study to elucidate the role of TGF-β signalling pathway in OA by comparing the expression levels of TGFB1 and BMP2 as ligands, SMAD3 as an intracellular mediator, and MMP13 as a targeted gene between human osteoarthritic and healthy cartilage.MethodsHuman cartilage samples were collected from patients undergoing total hip/knee joint replacement surgery due to primary OA or hip fractures as controls. RNA was extracted from the cartilage tissues. Real-time quantitative PCR was performed to measure gene expression. Mann-Whitney test was utilized to compare the expression levels of TGFB1, BMP2, SMAD3 and MMP13 in human cartilage between OA cases and controls. Spearman’s rank correlation coefficient (rho) was calculated to examine the correlation between the expression levels of the four genes studied and non-parametric regression was used to adjust for covariates.ResultsA total of 32 OA cases (25 hip OA and 7 knee OA) and 21 healthy controls were included. The expression of TGFB1, SMAD3, and MMP13 were on average 70 %, 46 %, and 355 % higher, respectively, whereas the expression of BMP2 was 88 % lower, in OA-affected cartilage than that of controls (all p < 0.03), but no difference was observed between hip and knee OA (all p > 0.4). The expression of TGFB1 was correlated with the expression of SMAD3 (rho = 0.50, p = 0.003) and MMP13 (rho = 0.46, p = 0.007) in OA-affected cartilage and the significance became stronger after adjustment for age, sex, and BMI. The expression of BMP2 was negatively correlated with both TGFB1 (rho = −0.50, p = 0.02) and MMP13 (rho = −0.48, p = 0.02) in healthy cartilage, but the significance was altered after adjustment for the covariates. There was no correlation between the expression of SMAD3 and MMP13.ConclusionsOur results demonstrate that MMP13 expression is associated with an increased expression of TGFB1 in OA-affected cartilage, possibly through SMAD-independent TGF-β pathway. Furthermore, TGF-β/SMAD3 is overactivated in OA cartilage; yet, the consequence of this overactivation remains to be established.     

Surgical aortic valve replacement in patients older than 75 years: is there really a quality of life benefit?

BackgroundTo evaluate the results of elective isolated surgical aortic valve replacement (SAVR) on quality of life (QoL) in patients > 75 years.Methods138 patients operated between January 2008 and December 2011 were included. The EuroQOL questionnaire (EQ-5D, EQ-VAS) was completed preoperatively, and 1- and 2-years postoperatively. The logistic EuroSCORE was used for risk stratification, the Corpus Christi Heart project criteria to assess physical activity.ResultsMean age was 79.5 ± 2.8 years, mean risk 9.7 ± 5.4, hospital mortality 2.8 %. For 115 patients (83.3 %) the preoperative QoL information was complete. Fifty patients were classified as sedentary. In the first postoperative year 13 patients died, mostly sedentary patients (p = 0.046) with a low EQ-5D (p = 0.017). There was no QoL information on 32 survivors, mostly sedentary patients (p = 0.001). The 70 patients with QoL information showed an increased QoL (NS). Two years postoperatively, 16 patients died, significantly more sedentary patients (p = 0.015) with a low EQ-5D (p = 0.006). For 42 survivors, there was no QoL information; these were mostly sedentary patients (p = 0.021). The 57 patients with 2-year QoL information had an increased EQ-5D (NS) and EQ-VAS (p = 0.024).ConclusionsQoL increases after SAVR. However, the patients lost to follow-up were mostly sedentary or had a low preoperative QoL, which can lead to biased results.     

Experimental knee pain impairs submaximal force steadiness in isometric,eccentric, and concentric muscle actions

IntroductionPopulations with knee joint damage, including arthritis, have noted impairments in the regulation of submaximal muscle force. It is difficult to determine the exact cause of such impairments given the joint pathology and associated neuromuscular adaptations. Experimental pain models that have been used to isolate the effects of pain on muscle force regulation have shown impaired force steadiness during acute pain. However, few studies have examined force regulation during dynamic contractions, and these findings have been inconsistent. The goal of the current study was to examine the effect of experimental knee joint pain on submaximal quadriceps force regulation during isometric and dynamic contractions.MethodsThe study involved fifteen healthy participants. Participants were seated in an isokinetic dynamometer. Knee extensor force matching tasks were completed in isometric, eccentric, and concentric muscle contraction conditions. The target force was set to 10 % of maximum for each contraction type. Hypertonic saline was then injected into the infrapatella fat pad to generate acute joint pain. The force matching tasks were repeated during pain and once more 5 min after pain had subsided.ResultsHypertonic saline resulted in knee pain with an average peak pain rating of 5.5 ± 2.1 (0–10 scale) that lasted for 18 ± 4 mins. Force steadiness significantly reduced during pain across all three muscle contraction conditions. There was a trend to increased force matching error during pain but this was not significant.ConclusionExperimental knee pain leads to impaired quadriceps force steadiness during isometric, eccentric, and concentric contractions, providing further evidence that joint pain directly affects motor performance. Given the established relationship between submaximal muscle force steadiness and function, such an effect may be detrimental to the performance of tasks in daily life. In order to restore motor performance in people with painful arthritic conditions of the knee, it may be important to first manage their pain more effectively.     

The presence of meniscal lesions is a strong predictor of neuropathic pain in symptomatic knee osteoarthritis: a cross-sectional pilot study

Introduction

Pain in osteoarthritis (OA) has been classically attributed to joint structural damage. Disparity between the degree of radiographic structural damage and the severity of symptoms implies that factors other than the joint pathology itself contribute to the pain. Peripheral and central sensitization have been suggested as two of the underlying mechanisms that contribute to pain in OA. The aim of this study was to explore in symptomatic knee OA patients, the structural changes assessed by magnetic resonance imaging (MRI) that could be used as markers of neuropathic pain (NP).

Methods

This cross-sectional observational pilot study included 50 knee OA patients with moderate to severe pain (VAS ≥40) in the target knee. The presence of NP was determined based on the PainDETECT questionnaire. Among the 50 patients included, 25 had PainDETECT score ≤12 (unlikely NP), 9 had PainDETECT score between 13 and 18 (uncertain NP) and 16 had PainDETECT score ≥19 (likely NP). WOMAC, PainDETECT, and VAS pain scores as well as knee MRI were assessed.

Results

Data showed no significant difference in demographic characteristics between the three groups. However, a positive and statistically significant association was found between the WOMAC pain (P <0.001), function (P <0.001), stiffness (P = 0.007) and total (P <0.001) scores as well as higher VAS pain score (P = 0.023), and PainDETECT scores. Although no difference was found in the cartilage volume between groups, the presence of meniscal extrusion in both medial (P = 0.006) and lateral (P = 0.023) compartments, and presence of meniscal tears in the lateral compartment (P = 0.011), were significantly associated with increasing PainDETECT score. Moreover, the presence of bone marrow lesions in the lateral plateau and the extent of the synovial membrane thickness in the lateral recess were associated with increasing PainDETECT scores (P = 0.032, P = 0.027, respectively).

Conclusions

In this study, meniscal lesions, particularly extrusion, were found to be among the strongest risk factors for NP in knee OA patients.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01733277","term_id":"NCT01733277"}}NCT01733277. Registered 16 November 2012.     

Coronary CT angiography for suspected acute coronary syndrome: sex-associated differences

AimThe optimal diagnostic test in the work-up of suspected acute coronary syndrome (ACS) may differ between men and women. The aim of this study was to compare sex-associated differences between using a diagnostic strategy including early coronary computed tomography angiography (CCTA) and standard of care (SOC).MethodsIn total, 500 patients who presented with symptoms suggestive of ACS at the emergency department were randomised between a diagnostic strategy supplemented with early CCTA and SOC.ResultsWomen were generally older than men (mean ± standard deviation 56 ± 10 vs 53 ± 10 years, p < 0.01) and were less often admitted to hospital (33% vs 44%, p = 0.02). Obstructive coronary artery disease on CCTA (> 50% luminal narrowing) was less frequently seen in women (14% vs 26%, p = 0.02), and ACS was diagnosed less often in women (5% vs 10%, p = 0.03). Women underwent less outpatient testing when early CCTA was used in the emergency department evaluation of suspected ACS (p = 0.008).ConclusionWomen had a lower incidence of obstructive CAD on CCTA and were less often admitted to hospital than men. They were subjected to less outpatient testing when early CCTA was used in the emergency department evaluation of suspected ACS.Supplementary InformationThe online version of this article (10.1007/s12471-021-01607-1) contains supplementary material, which is available to authorized users.     

In vivo patellar tracking induced by individual quadriceps components in individuals with patellofemoral pain

Patellofemoral pain is a common knee disorder with a multi-factorial etiology related to abnormal patellar tracking. Our hypothesis was that the pattern of three-dimensional rotation and translation of the patella induced by selective activation of individual quadriceps components would differ between subjects with patellofemoral pain and healthy subjects. Nine female subjects with patellofemoral pain and seven healthy female subjects underwent electrical stimulation to selectively activate individual quadriceps components (vastus medialis obliquus, VMO; vastus medialis lateralis, VML; vastus lateralis, VL) with the knee at 0° and 20° flexion, while three-dimensional patellar tracking was recorded. Normalized direction of rotation and direction of translation characterized the relative amplitudes of each component of patellar movement. VMO activation in patellofemoral pain caused greater medial patellar rotation (distal patellar pole rotates medially in frontal plane) at both knee positions (p<0.01), and both VMO and VML activation caused increased anterior patellar translation (p<0.001) in patellofemoral pain compared to healthy subjects at 20° knee flexion. VL activation caused more lateral patellar translation (p<0.001) in patellofemoral pain compared to healthy subjects. In healthy subjects the 3-D mechanical action of the VMO is actively modulated with knee flexion angle while such modulation was not observed in PFP subjects. This could be due to anatomical differences in the VMO insertion on the patella and medial quadriceps weakness. Quantitative evaluation of the influence of individual quadriceps components on patellar tracking will aid understanding of the knee extensor mechanism and provide insight into the etiology of patellofemoral pain.     

Transcatheter aortic valve implantation amid the COVID-19 pandemic: a nationwide analysis of the first COVID-19 wave in the Netherlands

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic has put tremendous pressure on healthcare systems. Most transcatheter aortic valve implantation (TAVI) centres have adopted different triage systems and procedural strategies to serve highest-risk patients first and to minimise the burden on hospital logistics and personnel. We therefore assessed the impact of the COVID-19 pandemic on patient selection, type of anaesthesia and outcomes after TAVI.MethodsWe used data from the Netherlands Heart Registration to examine all patients who underwent TAVI between March 2020 and July 2020 (COVID cohort), and between March 2019 and July 2019 (pre-COVID cohort). We compared patient characteristics, procedural characteristics and clinical outcomes.ResultsWe examined 2131 patients who underwent TAVI (1020 patients in COVID cohort, 1111 patients in pre-COVID cohort). EuroSCORE II was comparable between cohorts (COVID 4.5 ± 4.0 vs pre-COVID 4.6 ± 4.2, p = 0.356). The number of TAVI procedures under general anaesthesia was lower in the COVID cohort (35.2% vs 46.5%, p < 0.001). Incidences of stroke (COVID 2.7% vs pre-COVID 1.7%, p = 0.134), major vascular complications (2.3% vs 3.4%, p = 0.170) and permanent pacemaker implantation (10.0% vs 9.4%, p = 0.634) did not differ between cohorts. Thirty-day and 150-day mortality were comparable (2.8% vs 2.2%, p = 0.359 and 5.2% vs 5.2%, p = 0.993, respectively).ConclusionsDuring the COVID-19 pandemic, patient characteristics and outcomes after TAVI were not different than before the pandemic. This highlights the fact that TAVI procedures can be safely performed during the COVID-19 pandemic, without an increased risk of complications or mortality.Supplementary InformationThe online version of this article (10.1007/s12471-022-01704-9) contains supplementary material, which is available to authorized users.     

High mobility group box 1 levels in large vessel vasculitis are not associated with disease activity but are influenced by age and statins

IntroductionTakayasu arteritis (TA) and giant cell arteritis (GCA) are large vessel vasculitides (LVV) that usually present as granulomatous inflammation in arterial walls. High mobility group box 1 (HMGB1) is a nuclear protein that acts as an alarmin when released by dying or activated cells. This study aims to evaluate whether serum HMGB1 can be used as a biomarker in LVV.MethodsTwenty-nine consecutive TA patients with 29 healthy controls (HC) were evaluated in a cross-sectional study. Eighteen consecutive GCA patients with 16 HC were evaluated at the onset of disease and some of them during follow-up. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay.ResultsIn GCA patients at disease onset mean serum HMGB1 levels did not differ from HC (5.74 ± 4.19 ng/ml vs. 4.17 ± 3.14 ng/ml; p = 0.230). No differences in HMGB1 levels were found between GCA patients with and without polymyalgia rheumatica (p = 0.167), ischemic manifestations (p = 0.873), systemic manifestations (p = 0.474) or relapsing disease (p = 0.608). During follow-up, no significant fluctuations on serum HMGB1 levels were observed from baseline to 3 months (n = 13) (p = 0.075), 12 months (n = 6) (p = 0.093) and at the first relapse (n = 4) (p = 0.202). Serum HMGB1 levels did not differ between TA patients and HC [1.19 (0.45–2.10) ng/ml vs. 1.46 (0.89–3.34) ng/ml; p = 0.181] and no difference was found between TA patients with active disease and in remission [1.31 (0.63–2.16) ng/ml vs. 0.75 (0.39–2.05) ng/ml; p = 0.281]. HMGB1 levels were significantly lower in 16 TA patients on statins compared with 13 patients without statins [0.59 (0.29–1.46) ng/ml vs. 1.93 (0.88–3.34) ng/ml; p = 0.019]. Age was independently associated with higher HMGB1 levels regardless of LVV or control status.ConclusionsPatients with TA and GCA present similar serum HMGB1 levels compared with HC. Serum HMGB1 is not useful to discriminate between active disease and remission. In TA, use of statins was associated with lower HMGB1 levels. HMGB1 is not a biomarker for LVV.     

CMR-derived TAPSE measurement: a semi-quantitative method of right ventricular function assessment in patients with hypertrophic cardiomyopathy

Aim

To compare cardiovascular magnetic resonance (CMR)-derived right ventricular fractional shortening (RVFS), tricuspid annular plane systolic excursion with a reference point within the right ventricular apex (TAPSE_in) and with one outside the ventricle (TAPSE_out) with the standard volumetric approach in patients with hypertrophic cardiomyopathy (HCM).

Methods and results

105 patients with HCM and 20 healthy subjects underwent CMR. In patients with HCM, TAPSE_in (r = 0.31, p = 0.001) and RVFS (r = 0.35, p = 0.0002) revealed a significant but weak correlation with right ventricular ejection fraction (RVEF), whereas TAPSE_out (r = 0.57, p < 0.0001) showed a moderate correlation with RVEF. The ability to predict RVEF < 45 % in HCM patients was best for TAPSE_out. In patients with hypertrophic obstructive cardiomyopathy (HOCM), RVEF showed a significant but weak correlation with TAPSE_out (r = 0.36, p = 0.02) and no correlation with TAPSE_in (r = 0.05, p = 0.07) and RVFS (r = 0.02, p = 0.2). In patients with hypertrophic non-obstructive cardiomyopathy (HNCM), there was a moderate correlation between RVEF and TAPSE_out (r = 0.57, p < 0.0001) and a weak correlation with TAPSE_in (r = 0.39, p = 0.001) and RVFS (r = 0.38, p = 0.002). In the 20 healthy controls, there was a strong correlation between RVEF and all semi-quantitative measurements.

Conclusion

CMR-derived TAPSE_in is not suitable to determine right ventricular function in HCM patients. TAPSE_out showed a good correlation with RVEF in HNCM patients but only a weak correlation in HOCM patients. TAPSE_out might be used for screening but the detection of subtle changes in RV function requires the 3D volumetric approach.     

Prognostic significance of incident atrial fibrillation following STEMI depends on the timing of atrial fibrillation

Atrial fibrillation (AF) is associated with short-term mortality after ST-elevation myocardial infarction (STEMI), but there is limited data on the temporal association between AF and mortality after STEMI. A total of 830 patients were included (age: 62 ± 12 years, 76 % male). Patients with new-onset AF < 30 days after STEMI were divided among three subgroups: AF on the day of admission, AF 24–72 h and AF > 72 h after admission. Thirty-day mortality was assessed by telephone and via the municipal population registry. Twenty patients died < 30 days after admission. In 41 patients, AF was detected on the day of admission, in 14 patients 24–72 h after admission and in 18 patients > 72 h after admission. Mortality was higher in patients with AF on the day of admission (7.3 vs 2.2 %, p = 0.036) and 24–72 h after admission (14.3 vs 1.4 %, p < 0.001), but not in patients with AF > 72 h after admission (0 vs 1.1 %, p > 0.999). Age (odds ratio (OR) 1.123, p < 0.001), Killip class (adjusted OR 8.341, p < 0.001), AF on the day of admission (OR 3.585, p = 0.049) and 24–72 h after admission (OR 11.515, p = 0.003) were, amongst other variables, associated with an increased 30-day mortality. In conclusion, only new-onset incident AF during the first 72 h after admission was associated with 30-day mortality in STEMI patients.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-015-0709-2) contains supplementary material, which is available to authorized users.     

Right ventricular function in dilated cardiomyopathy and ischemic heart disease: assessment with non-invasive imaging

Background

Dilated cardiomyopathy and ischaemic heart disease can both lead to right ventricular (RV) dysfunction. Direct comparisons of the two entities regarding RV size and function using state-of-the-art imaging techniques have not yet been performed. We aimed to determine RV function and volume in dilated cardiomyopathy and ischaemic heart disease in relation to left ventricular (LV) systolic and diastolic function and systolic pulmonary artery pressure.

Methods and results

A well-characterised group (cardiac magnetic resonance imaging, echocardiography, coronary angiography and endomyocardial biopsy) of 46 patients with dilated cardiomyopathy was compared with LV ejection fraction (EF)-matched patients (n = 23) with ischaemic heart disease. Volumes and EF were determined with magnetic resonance imaging, diastolic LV function and pulmonary artery pressure with echocardiography.After multivariable linear regression, four factors independently influenced RVEF (R² = 0.51, p < 0.001): LVEF (r = 0.54, p < 0.001), ratio of peak early and peak atrial transmitral Doppler flow velocity as measure of LV filling pressure (r = − 0.52, p < 0.001) and tricuspid regurgitation flow velocity as measure of pulmonary artery pressure (r = − 0.38, p = 0.001). RVEF was significantly worse in patients with dilated cardiomyopathy compared with ischaemic heart disease: median 48 % (interquartile range (IQR) 37–55 %) versus 56 % (IQR 48–63 %), p < 0.05.

Conclusions

In patients with dilated cardiomyopathy and ischaemic heart disease, RV function is determined by LV systolic and diastolic function, the underlying cause of LV dysfunction, and pulmonary artery pressure. It was demonstrated that RV function is more impaired in dilated cardiomyopathy.     

Subjective and objective levels of physical activity and their association with cardiorespiratory fitness in rheumatoid arthritis patients

IntroductionThe aims of the present study were: (a) to examine the agreement between subjective (assessed via the International Physical Activity Questionnaire; IPAQ) and objective (accelerometry; GT3X) physical activity (PA) levels in patients with rheumatoid arthritis (RA), and (b) to evaluate the associations of RA patients’ subjective and objective PA to their scores on the maximal oxygen uptake test (VO2max).MethodsThe participants wore the GT3X for seven days before completing the IPAQ and VO2max test. The Bland-Altman plot was used to illustrate the agreement between the objective and subjective PA data, and the Wilcoxon test was employed to examine the differences. The association between the PA measurement and VO2max test was examined via the correlations and the magnitude was presented by the Steiger’s Z value.ResultsSixty-eight RA patients (age = 55 ± 13 years, body mass index: 27.8 ± 5.4 kg/m2, median of disease duration = 5 (2–8) yrs) were recruited. Smaller differences between the subjective and objective measures were found when PA was assessed at the moderate level. Wilcoxon tests revealed that patients reported less time spent engaged in sedentary behaviours (Z = −6.80, P < 0.01) and light PA (Z = −6.89, P < 0.01) and more moderate PA (Z = −6.26, P < 0.01) than was objectively indicated. Significant positive correlations were revealed between VO2max with all PA levels derived from accelerometry (light PA rho = .35, P < .01; moderate PA rho = .34, P = .01; moderate and vigorous PA, (MVPA) rho = .33, P = .01), and a negative association to sedentary time (ST) emerged (rho = −.27, P = .04). IPAQ-reported moderate PA and MVPA positively correlated with maxV02 (rho = .25, P = .01, rho = .27, P = .01, respectively). Differences between the magnitude of correlations between the IPAQ-VO2 max and GT3X-VO2 max were only significant for ST (Z = 3.43, P < .01).ConclusionsVia responses to the IPAQ, RA patients reported that they were less sedentary and engaged in more higher intensity PA than what was objectively assessed. Accelerometry data correlated with VO2max at all PA levels. Only subjective moderate and MPVA correlated with VO2max. Findings suggest that self-reported PA and ST should be interpreted with caution in people with RA and complemented with accelerometry when possible.

Trial registration

Trial registration: ClinicalTrials.gov ISRCTN04121489. Registered 5 September 2012.     

Impact of COVID-19 outbreak on hospital admissions and outcome of acute coronary syndromes in a single high-volume centre in southeastern Europe

BackgroundAs coronavirus disease 2019 (COVID-19) has reached pandemic status, authors from the most severely affected countries have reported reduced rates of hospital admissions for patients with acute coronary syndrome (ACS).AimThe aim of the present study was to investigate the influence of the COVID-19 outbreak on hospital admissions and outcomes in ACS patients in a single high-volume centre in southeastern Europe.MethodsThis retrospective observational study aimed to investigate the number of hospital admissions for ACS, clinical findings at admission, length of hospitalisation, major complications and in-hospital mortality during the COVID-19 outbreak and to compare the data with the same parameters during an equivalent time frame in 2019. For the ST-elevated myocardial infarction (STEMI) subgroup of patients, changes in ischaemic times were analysed as well.ResultsThere was a significant reduction of 44.3% in the number of patients admitted for ACS during the COVID-19 outbreak when compared with the same period in 2019 (151 vs 271; 95% confidence interval 38.4–50.2, p < 0.01) with a higher mortality rate (13.2% vs 7.2%, p = 0.03). In 2020, patients with non-ST-elevated myocardial infarction presented more often with acute heart failure (3.3% vs 0.7%, p = 0.04). During the COVID-19 outbreak, we observed increases in the total ischaemic time (303 ± 163.4 vs 200.8 ± 156.8 min, p < 0.05) and door-to-balloon time (69.2 ± 58.4 vs 50.5 ± 31.3 min, p < 0.01) in STEMI patients.ConclusionsThese findings should increase the awareness of morbidity and mortality related to missed or delayed treatment of ACS among the public and the healthcare services.     

Impact of heart rate variability,a marker for cardiac health,on lupus disease activity

BackgroundDecreased heart rate variability (HRV) is associated with adverse outcomes in cardiovascular diseases and has been observed in patients with systemic lupus erythematosus (SLE). We examined the relationship of HRV with SLE disease activity and selected cytokine pathways.MethodsFifty-three patients from the Oklahoma Lupus Cohort were evaluated at two visits each. Clinical assessments included the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), British Isles Lupus Assessment Group (BILAG) index, physician global assessment (PGA), and Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI Flare Index. HRV was assessed with a 5-minute electrocardiogram, and the following HRV parameters were calculated: square root of the mean of the squares of differences between adjacent NN intervals (RMSSD), percentage of pairs of adjacent NN intervals differing by more than 50 milliseconds (pNN50), high-frequency power (HF power), and low frequency to high frequency (LF/HF) ratio, which reflects sympathetic/vagal balance. Plasma cytokine levels were measured with a multiplex, bead-based immunoassay. Serum B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) were measured with an enzyme-linked immunosorbent assay. Linear regression analysis was applied.ResultsBaseline HRV (pNN50, HF power, LF/HF ratio) was inversely related to disease activity (BILAG, PGA) and flare. Changes in RMSSD between visits were inversely related to changes in SLEDAI (p = 0.007). Age, caffeine, tobacco and medication use had no impact on HRV. Plasma soluble tumor necrosis factor receptor II (sTNFRII) and monokine induced by interferon gamma (MIG) were inversely related with all baseline measures of HRV (p = 0.039 to <0.001). Plasma stem cell factor (SCF), interleukin (IL)-1 receptor antagonist (IL-1RA), and IL-15 showed similar inverse relationships with baseline HRV, and weaker trends were observed for interferon (IFN)-α, interferon gamma-induced protein (IP)-10, and serum BLyS. Changes in the LF/HF ratio between visits were also associated with changes in sTNFRII (p = 0.021), MIG (p = 0.003), IFN-α (p = 0.012), SCF (p = 0.001), IL-1RA (p = 0.023), and IL-15 (p = 0.010). On the basis of multivariate linear regression, MIG was an independent predictor of baseline HRV after adjusting for plasma IL-1RA, SCF, IFN-α, IP-10, and serum BLyS. In a similar model, the sTNFRII impact remained significant after adjusting for the same variables.ConclusionsImpaired HRV, particularly the LF/HF ratio, is associated with lupus disease activity and several cytokines related to IFN type II and TNF pathways. The strongest association was with MIG and sTNFRII, expanding previous immune connections of vagal signaling.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-016-1087-x) contains supplementary material, which is available to authorized users.     

Neuromuscular activation of quadriceps bellies during tasks performed in the same biomechanical condition in patients undergoing total knee arthroplasty

ObjectiveTo investigate neuromuscular activation of quadriceps bellies during different tasks in patients before and after total knee arthroplasty (TKA).MethodsTwenty-six patients scheduled for TKA and 16 control subjects performed three isometric tasks: knee extension (KE), hip flexion (HF), hip flexion with contralateral hip extension (HFE). Surface electromyography signals of rectus femoris, vastus medialis and vastus lateralis were collected the day before (T0), at one (T1) and three (T2) days after surgery, whereas control subjects underwent a single evaluation. The Root Mean Square peak normalized for its highest value during the three tasks (nRMS-peak) was used as index of maximum neuromuscular activation for each belly. Sixteen patients performed the postoperative assessment, due to the placement of an elastomeric pump aimed at reducing pain in 10 patients.ResultsPatients showed lower rectus femoris nRMS-peak during KE compared to HF and HFE before and after surgery (p < 0.001), as occurred in control subjects. Differently from control subjects, patients showed higher vastus medialis and vastus lateralis nRMS-peak during HF compared to KE at T1 (p = 0.008) and T2 (p = 0.039).ConclusionTKA modified quadriceps neuromuscular activation during different tasks performed the same biomechanical condition. These findings may be considered in planning physiotherapy interventions after TKA.     

Performance of a simplified HEART score and HEART-GP score for evaluating chest pain in urgent primary care

BackgroundChest pain is a common symptom in urgent primary care. The distinction between urgent and non-urgent causes can be challenging. A modified version of the HEART score, in which troponin is omitted (‘simplified HEART’) or replaced by the so-called ‘sense of alarm’ (HEART-GP), may aid in risk stratification.MethodThis study involved a retrospective, observational cohort of consecutive patients evaluated for chest pain at a large-scale, out-of-hours, regional primary care facility in the Netherlands, with 6‑week follow-up for major adverse cardiac events (MACEs). The outcome of interest is diagnostic accuracy, including positive predictive value (PPV) and negative predictive value (NPV).ResultsWe included 664 patients; MACEs occurred in 4.8% (n = 32). For  simplified HEART and HEART-GP, we found C‑statistics of 0.86 (95% confidence interval (CI) 0.80–0.91) and 0.90 (95% CI 0.85–0.95), respectively. Optimal diagnostic accuracy was found for a simplified HEART score ≥2 (PPV 9%, NPV 99.7%), HEART-GP score ≥3 (PPV 11%, NPV 99.7%) and HEART-GP score ≥4 (PPV 16%, NPV 99.4%). Physicians referred 157 patients (23.6%) and missed 6 MACEs. A simplified HEART score ≥2 would have picked up 5 cases, at the expense of 332 referrals (50.0%, p < 0.001). A HEART-GP score of ≥3 and ≥4 would have detected 5 and 3 MACEs and led to 293 (44.1%, p < 0.001) and 186 (28.0%, p = 0.18) referrals, respectively.ConclusionHEART-score modifications including the physicians’ ‘sense of alarm’ may be used as a risk stratification tool for chest pain in primary care in the absence of routine access to troponin assays. Further validation is warranted.Supplementary InformationThe online version of this article (10.1007/s12471-020-01529-4) contains supplementary material, which is available to authorized users.