bluuebunny/crossref_metadata_2025 huggingface dataset:
Admission serum magnesium levels associated with short- and long-term clinical outcomes in COVID-19 patients
Authors: Segev A , Sagir A , Matezky S , Segev A , Atar S , Shechter M
Published: October 2022

Introduction

In the face of the global pandemic coronavirus disease 2019 (COVID-19) has created, readily available prognostic markers may be of great use.

Purpose

To evaluate the association between serum magnesium levels (sMg) on admission and clinical outcomes in hospitalized COVID-19 patients.

Methods

We retrospectively analyzed all consecutive patients admitted to our medical center with a primary de novo diagnosis of COVID-19.Demographic, clinical and laboratory data were extracted from the electronic medical record. Clinical outcomes were compared between five groups of patients according to the quintiles of sMg on hospital admission.

Results

From 2,433 consecutive COVID-19 patients during the years 2020–2021, we included 1,522 patients with sMg on admission (1–3 day of hospitalization) (58% male, 69±17 years old). Patients were followed for a mean of 10±7 months. A low sMg level (1st quintile) was associated with higher rates of diabetes and steroid use, whereas a high sMg level (5th quintile) was associated with dyslipidemia, chronic kidney disease, andhigher levels of inflammatory markers (Table 1). Both low and high sMg levels were associated with lower oxygen saturation during hospitalization. All-cause in-hospital and long-term mortality was higher in patients with both low and high sMg levels, compared with mid-range sMg levels (2nd, 3rd and 4thquintiles; 19% and 30% vs. 9.5%, 10.7% and 17.8% and 35% and 45.3% vs. 23%, 26.8% and 27.3% respectively; p<0.001 for all) (Figure 1).

Conclusions

Both low and high sMg levels were associated with worse short- and long-term clinical outcomes and all-cause mortality in a large cohort of hospitalized COVID-19 patients. Thus, admission sMg levels may play a prognostic role in risk stratificationof COVID-19 patients.

Funding Acknowledgement

Type of funding sources: None.
Stress related neural activity: potential mechanism contributing to benefit of physical activity on heart failure incidence
Authors: Alhamam A , Gharios C , Zureigat H , Abohashem S , Osborne M , Tawakol A
Published: October 2022

Background

We previously observed that: 1) physical activity (PA) decreases stress-related neural activity (SNA) in a dose-dependent manner and 2) resting SNA predicts incident heart failure (HF). Thus, we hypothesize that PA may decrease the risk of incident HF in part through its beneficial effect on SNA.

Methods

Self-reported PA data were acquired from Partners Biobank participants. Metabolic equivalent of task-minutes per week (MET*minutes/week) were calculated and participants were categorized according to their adherence to current PA recommendations (<500 and ≥500 MET-min/wk). In a subset with clinically indicated 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging (n=744), SNA was measured as a ratio of amygdalar to ventromedial prefrontal cortical activity. Subsequent HF and baseline CVD risk factor data were obtained using International Classification of Diseases Codes. Kaplan-Meier and Cox regression analyses were used to evaluate the relationship between PA vs HF risk. Mediation analysis was used to test whether PA's impact on SNA significantly mediated the association between PA and HF.

Results

Among 50,363 participants (median age 59 years [IQR 42, 70], 40% male), 13,850 (11.6%) were diagnosed with HF over a median period of 3.1 years. PA within recommendations was associated with lower risk of subsequent HF (hazard ratio (HR) [95% confidence interval (CI)]: 0.849 [0.760, 0.948], p=0.004, Figure 1) in a model adjusted for CVD risk factors and history of myocardial infarction. As noted previously, higher SNA associated with higher risk of subsequent HF (HR [95% CI]: 1.34 [1.08, 1.66], p=0.007); and PA within guideline recommendations (vs.below) associated with lower SNA (Zscore ± SD: −0.14±0.92 vs 0.02±1, p=0.037). Moreover, mediation analysis shows that exercise reduces HF risk in part via reductions in SNA, accounting for 9% of the total relationship between exercise and HF risk (p<0.05, Figure 2).

Conclusion

PA associates with reductions in: A) stress-associated neural activity and B) subsequent HF risk. Moreover, the mechanism by which PA reduces HF risk may involve salutary effects on stress-related neural pathways.

Funding Acknowledgement

Type of funding sources: None.
Association of smartphone-recorded steps over years and change in cardiovascular risk factors among working aged adults
Authors: Hamaya R , Mori M , Miyake K , Lee I
Published: October 2022

Backgrounds

Evidence indicates a causal role of physical activity (PA), including steps, in decreasing cardiovascular disease (CVD) risk. However, few data exist on long-term steps and their relation to changes in CVD risk factors.

Objectives

To examine the associations of long-term smartphone-recorded steps and changes in CVD-related biomarkers in a large cohort of working aged adults.

Methods

The present analysis made use of data two national database and a commercial app database. Participants who underwent an annual health check-up between April 2015 and November 2020 and a second health check-up 24 to 35 months thereafter, and whose daily step data were available, were included. We evaluated the associations between smartphone-recorded daily steps over two years following the initial health check-up and two-year changes in the following CVD risk factors: weight, waist, blood pressure (BP), lipid and glucose metabolism biomarkers. Generalized additive models were used to investigate the non-linear relationships of steps and changes in CVD risks. Models were adjusted for baseline steps and other confounders. The present study design is summarized in Figure 1.

Results

A total of 15,708 participants with mean (SD) age of 44.1 (9.5) and 23.5% women were included. Differences in weight were almost linearly associated with two-year steps in men (estimate [SE] per 1000 steps/day: −0.33 [0.029] kg), and inversely related only above 5,000 steps/day in women (−0.18 [0.054] kg) (Figure 2). Similar trends were observed in waist. An inverse linear association with systolic BP was observed in men (−0.34 [0.097] mmHg) but not in women. Greater steps were associated with favorable change in HDL cholesterol and triglycerides (0.61 [0.068] and −3.4 [0.61] mg/dL in men; 0.64 [0.17] and −2.3 [0.67] mg/dL in women), while negative changes in LDL cholesterol was evident in men only (−0.59 [0.17] mg/dL). A significant negative association with HbA1c was observed only in women (−0.012 [0.0043] %). In the secondary analyses of the associations between one-year steps and one-year (i.e., 12 to 23 months) changes in CVD related biomarkers (N=26,884), the relationships were weaker and less robust compared with those in two-year analyses.

Conclusions

In a large cohort of Japanese adults, smartphone-recorded steps over years were associated with beneficial changes in CVD risk factors, with some differences between men and women in the associational patterns. The sex differences might highlight the undercount of steps among women who may be less likely to always carry their phone [1], or true sex differences in the effects of steps. The findings support the benefit of long-term PA for CVD health and suggest a useful role of smartphone-recorded steps for monitoring CVD risk over the long term.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): DeSC Healthcare Inc., Tokyo, Japan
Protective effect of N-acetyl cysteine on vascular function of young individuals after a bout of resistance exercise: a randomized placebo-controlled study
Authors: Mavraganis G , Georgiopoulos G , Sakelliou A , Delialis D , Patras R , Sianis A , Dimopoulou A M , Oikonomou E , Athanasopoulos S , Kanakakis I , Fatouros I , Mitrakou A , Stamatelopoulos K
Published: October 2022

Background

High intensity resistance exercise may temporarily induce vascular dysfunction mediated by pro-oxidant and pro-inflammatory pathways. Whether antioxidant supplements ameliorate this dysfunction has not been clarified.

Purpose

In the present study we aimed to evaluate the effect of the antioxidant N-acetyl cysteine (NAC) on vascular function after a bout of high-intensity resistance exercise in healthy young individuals.

Methods

In this randomized, cross-over, placebo-controlled study, ten healthy male volunteers (mean age 24.2±2.1 years) who exercised regularly were randomized to a daily oral administration of NAC or placebo during an 8-day recovery after an acute intense eccentric exercise protocol. In order to estimate changes in vascular parameters of interest -pulse wave velocity (PWV) and flow-mediated dilation (FMD)-, measurements were performed pre-exercise and across 6 pre-specified time points post-exercise (from 2 to 120 hours) in both arms. Blood samples were collected at baseline, immediately after exercise, 2 hours after exercise, and daily for eight consecutive days thereafter for the measurement of cellular components of the immune system.

Results

Muscle exercise induced a significant decrease in FMD in the placebo arm (F=2.74, p=0.017). This phenomenon was evident until 48 hours after exercise while FMD progressively returned to baseline values thereafter. In contrast, in the NAC arm, FMD did not decrease significantly (p>0.05 for all time-points). By linear mixed model analysis, a higher increase in CD4 cells levels correlated with preserved FMD (coefficient=0.025, p=0.046) in the placebo arm whereas this association was not significant (coefficient=0.004, p=0.811) in the NAC arm. PWV did not present significant fluctuations before and after exercise in either arm (p>0.05 for all comparisons).

Conclusion

A bout of eccentric exercise in young regularly training individuals induced endothelial dysfunction peaking at 48 hours, possibly partly mediated by an attenuated CD4 response. NAC exerted protective action on FMD, indicating that oxidative stress may be implicated in vivo in this setting.

Funding Acknowledgement

Type of funding sources: None.
Peak oxygen uptake in cardiopulmonary exercise testing was associated with left ventricular diastolic dysfunction in patients with preserved ejection fraction
Authors: Ojima S , Kubozono T , Kawasoe S , Kawabata T , Salim A A , Ikeda Y , Ohishi M
Published: October 2022

Background

Heart failure with preserved ejection fraction (EF) remains a poor prognosis as same as heart failure with reduced EF. Peak oxygen uptake (VO2) by cardiopulmonary exercise testing (CPET) is a useful parameter for predicting cardiovascular diseases prognosis. Furthermore, though there are some reports that CPET parameters are associated with indicators of diastolic dysfunction, each of these indicators has some limitations. Recently, recommendations for the evaluation of left ventricular diastolic function by echocardiography were reported from the ASE/EACVI. However, no reports have examined the association between exercise tolerance indices and diastolic dysfunction based on these recommended variables.

Purpose

To examine the relationship between peak VO2 and diastolic dysfunction using the recommendation from ASE/EACVI in cardiovascular diseases patients with preserved EF

Methods

We recruited 214 patients who were performed both CPX and echocardiography. EF ≥50% was 99 patients. All patients underwent 0W warm-up and 10W ramp on an upright electrical bicycle ergometer. Diastolic dysfunction was assessed using the recommendations for the evaluation of diastolic function by ASE/EACVI. We used abnormal cutoff values are annular e' velocity: septal e' <7 cm/s, lateral e' <10 cm/s, average E/e' ratio >14, left atrial volume index >34 ml/m2, and peak tricuspid regurgitation (TR) velocity >2.8 m/s. Diastolic dysfunction is present if more than half of the available parameters meet these cutoff values.

Results

Mean age was 57±14 years old, the portion of women was 69%. The portion of diastolic dysfunction was 16%. In univariable logistic regression analysis, age, log BNP, septal e' <7 cm/s or lateral e' <10 cm/s, peak TR velocity >2.8 m/s, and the presence of diastolic dysfunction were significantly associated with peakVO2 <14 ml/min/kg. In multivariable logistic regression analysis, the presence of diastolic dysfunction was an independent risk factor for peak VO2 <14 ml/min/kg (OR 5.03 CI 1.32–19.2, p=0.018). Furthermore, we investigated the association between each variable of diastolic dysfunction and peak VO2 and found that low septal and lateral e'velocity and high TR peak flow velocity were significantly associated with peak VO2 <14 ml/min/kg.

Conclusions

In preserved EF, low peak VO2 was significantly associated with diastolic dysfunction assessed by the recommendations from the ASE/EACVI.

Funding Acknowledgement

Type of funding sources: None.
Oxidative stress was significantly associated with peak oxygen uptake in patients with dilated cardiomyopathy
Authors: Ojima S , Kubozono T , Kawasoe S , Kawabata T , Salim A A , Ikeda Y , Ohishi M
Published: October 2022

Background

Systemic oxidative stress is known to be associated with the severity and prognosis in patients with cardiovascular diseases (CVD), including chronic heart failure. On the other hand, exercise tolerance is closely related to the prognosis in heart failure patients. However, no report has examined how oxidative stress is involved in each parameter evaluated by cardiopulmonary exercise testing (CPET) in patients with dilated cardiomyopathy (DCM).

Purpose

To examine the relationship between oxidative stress and CPET parameters such as peak VO2 and VE/VCO2 slope in patients with DCM

Methods

We recruited 214 patients with CVD who were performed CPET and measured brain natriuretic peptide (BNP) and haemoglobin (Hb). Finally, we enrolled 96 patients with DCM who have dilated dimensions of the left ventricular lumen by echocardiography and are diagnosed by endomyocardial biopsy. All patients underwent CPET using 0W warm-up and 10W ramp protocol on an upright electrical bicycle ergometer. We defined low peak VO2 as peak VO2<14 ml/min/kg and high VE/VCO2 slope as VE/VCO2 slope>34. The oxidative stress level was evaluated by a d-ROMs test, in which the amount of organic hydroperoxide converted into radicals oxidizing N, N-diethyl-p-phenylenediamine hydroperoxide is measured. The high level of d-ROMs was defined as d-ROMs≥401 U.CARR.

Results

Mean age was 56±15 years old. Mean ejection fraction, peak VO2 and VE/VCO2 slope were 37±15%, 16.3±5.0 ml/min/kg, and 31.0±11.8, respectively. The percentage of the high level of d-ROMs was 25%. In univariable logistic regression analysis, Hb, log BNP, and the high level of oxidative stress were significantly associated with low peak VO2, whereas, in multivariable logistic regression analysis, age, Hb, and log BNP were significant factors for high VE/VCO2 slope. In multivariable logistic regression analysis, only the high level of d-ROMs was independently associated with low peak VO2 (OR 3.18, CI 1.12–9.04, p=0.030). While, in multivariable logistic regression analysis, Hb (OR 0.51, CI 0.32–0.81, p=0.004) and log BNP (OR 2.77, CI 1.33–5.76, p=0.006) were significantly related to high VE/VCO2 slope.

Conclusions

In patients with DCM, low peak VO2 was associated with the high level of d-ROMs, and high VE/VCO2 slope was associated with BNP. These results suggested that oxidative stress was only related to peak VO2.

Funding Acknowledgement

Type of funding sources: None.
Low chronotropic index predicts rehospitalization in post-acute myocardial infarction patients with preserved or mildly reduced left ventricular ejection fraction
Authors: Smarz K , Tysarowski M , Ziolo J , Jaxa-Chamiec T , Zaborska B , Budaj A
Published: October 2022

Background

There are limited data about the clinical utility of combined stress echocardiography and cardiopulmonary exercise testing (CPET-ESE) in predicting prognosis in patients after acute myocardial infarction (AMI) with preserved left ventricular ejection fraction (LVEF).

Aim

To assess prognostic parameters using CPET-ESE in post-AMI patients with preserved or mildly reduced LVEF.

Methods

Eighty-seven patients after the first AMI with LVEF >40% were followed for 2 years (median 1.93 years IQR 1.16–2.41). The composite end-point was all-cause mortality or rehospitalization due to ischaemic heart disease (AMI, unstable angina, percutaneous coronary intervention/coronary artery bypass grafting) or heart failure exacerbation. All patients underwent symptom-limited CPET-ESE on a semi-supine cycle ergometer 3 to 5 weeks after AMI. The chronotropic index was calculated as the percent of heart rate reserve. Six patients refused to complete the survey and they were not included in the analysis.

Results

Follow-up was conducted in 81 consecutive patients (mean age 59±10 years, 62% males, 50% AMI with ST-segment elevation, 85% on beta-blockers). Mean LVEF was 56±9% and peak VO2 18.5±5.0 mL/kg/min. There were no deaths during follow-up. The composite end-point occurred in 13 patients. In multivariate Cox regression analysis after correction for demographic and clinical variables, only chronotropic index correlated with the composite end-point (HR 0.93, 95% CI 0.87–0.99, p=0.026). A positive predictive value of 33.3% and a negative predictive value of 91.3% (sensitivity 61.5%, specificity 76.5%, area under the curve, AUC 71%) for predicting the composite end-point was established for the chronotropic index ≤36.8% (Fig. 1). There was a statistically significant difference in the composite end-point occurrence (p<0.01) between subgroups with the chronotropic index above and below that threshold (Fig. 2).

Conclusions

In patients after the first AMI with preserved or mildly reduced left ventricular systolic function, a lower chronotropic index is a predictor of rehospitalization in 2-year follow-up.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Centre of Postgraduate Medical Education, Warsaw, Poland
“Innocent” ventricular arrhythmia – can cardiovascular magnetic resonance augment diagnosis of structural heart disease?
Authors: Costa C , Calvao J , Amador J , Proenca T , Carvalho M , Pinto R , Cabrita A , Marques C , Oliveira C , Santos L , Pinho A , Madureira A J , Lebreiro A , Pinho T , Macedo F
Published: October 2022

Background

Ventricular arrhythmias (VA) include a spectrum that ranges from premature ventricular beats (VPBs) to ventricular fibrillation (VF) and account for approximately 50% of all cardiovascular deaths. Echocardiography is commonly used to identify structural heart disease (SHD), the most frequent substrate of VA. Cardiovascular magnetic resonance (CMR) is recommended to complement echocardiography when image quality is suboptimal.

Purpose

This study sought to determine whether CMR may identify SHD in patients (pts) with VA, who had normal baseline ECGs and whose echocardiogram with fair technical conditions, ruled out pathological findings.

Methods

We included consecutive pts followed in arrythmia outpatient clinic of one clinical center from June 2014 to June 2021 for significant VA; this was categorized as >1,000 but <10,000 VPBs/24 h; ≥10,000 VPBs/24 h; nonsustained ventricular tachycardia (NSVT), sustained VT, or a history of resuscitated cardiac arrest, and no pathological findings at echocardiography, requiring a clinically indicated CMR. Primary endpoint was CMR detection of SHD. Data were collected at the end of the study.

Results

A total of 75 pts were included (no SHD: N=59; 45±15 years old; SHD: N=16, 53±15 years). All pts performed CMR, and Table 1 shows pts' baseline characteristics, VA diagnosis and CMR measurements. Definite SHD was diagnosed in 8 patients (11%): ischemic cardiopathy (three pts), myocarditis (1 pt), hypertrophic cardiomyopathy (1 pt), right ventricle arrhythmogenic disease (1 pt), non-compaction cardiomyopathy (1 pt); 1 patient presented higher myocardial T2 signal and was later diagnosed with sarcoidosis. Furthermore, abnormal findings not specific for a definite SHD diagnosis were found in other 8 pts (10%) who showed unspecific intra-myocardium enhancement.

Discussion and conclusion

CMR imaging identified SHD in around 20% of patients with normal ECG and echocardiogram. Among patients with identified SHD, ischemic cardiopathy was the most common finding, differently from the largest study that showed myocarditis as the main diagnosis. This may be associated to higher age in the SHD group. In conclusion, CMR allowed diagnosis of clinically relevant SHD even when echocardiography excluded it.

Funding Acknowledgement

Type of funding sources: None.
Exercise intensity domains determined by heart rate at ventilatory threshold: a comparison of the guideline-directed exercise intensity domains for cardiovascular rehabilitation prescription
Authors: Goulart Prata Oliveira Milani J , Milani M , Cipriano G F B , Hansen D , Cipriano Junior G
Published: October 2022

Background

Appropriate exercise prescription for cardiovascular diseases patients is a keystone for efficient and safe cardiovascular rehabilitation (CR). Exercise intensity prescribed according to the first and second ventilatory threshold (VT1 and VT2), identified by cardiopulmonary exercise testing (CPET), is considered the gold-standard method. However, because CPET is often not available, percentages of peak heart rate (%HRpeak) or heart rate reserve (%HRR), according to heart rate (HR) response during a conventional exercise test, are very commonly used.

Purpose

To compare the HR at VT1 and VT2 identified by CPET with the recommended exercise intensity prescription domains according to the Brazilian, American, and European CR guidelines/recommendations.

Methods

This retrospective cohort study assessed 1,465 treadmill CPETs from adult patients with stable cardiovascular diseases. Inclusion criteria were available VT1 and VT2 identification, sinus rhythm during exercise, and had reached maximal effort (respiratory exchange rate ≥1.10). HR at VT1 and VT2 were compared with the exercise intensity prescription domains recommended by Brazilian CR Guideline 2020, European Position Statement 2022, and the American College of Sports Medicine Guideline 2017, according to the obtained %HRpeak and %HRR.

Results

After applying the inclusions criteria, a sample of 972 CPETs were included (mean age 57.7±12.0 years, 80.8% males, 81.4% with coronary artery disease, and 26.6% with heart failure). VT1 and VT2 were identified, respectively, at 68.8% (63.8, 74.7) and 89.1 (85.8, 92.2) of the peak HR, and 39.0 (32.9, 45.8) and 78.0 (71.6, 84.5) of the HR reserve, indicating a greater heterogeneity of the latter (Figure 1). We found substantial heterogeneity between the measured %HRpeak and %HRR correspondent to the VT1 and VT2 and the estimated HR exercise intensity domains by compared international recommendations (Figure 2).

Conclusion

The disparities among currently established guideline-directed exercise domains limits the clinical validity of the use of %HRR and %HRpeak, and further strengthens the importance of performing CPET for an accurate exercise intensity prescription in CR. In the absence of CPET, HR values identified in our study at VT1 and VT2 could be used for guiding moderate-intensity exercise prescription for CVD patients, and the suggested range would be 69 to 89% of %HRpeak or 40 to 78% of %HRR. Current established exercise domains limits should be revised to improve HR-based prescription efficiency and safety.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).Conselho Nacional de Desenvolvimento Científico e Tecnolόgico (CNPq).
Athlete status and gender strongly influence CMR T1 mapping times: an athlete-control study
Authors: Daems J J N , Verwijs S M , Van Luijk-Snoeks R D , Van Hattum J C , Ercan A , Moen M H , Nederveen A J , Planken R N , Van Randen A , Pinto Y M , Groenink M , Jorstad H T
Published: October 2022

Background/Introduction

In the general population, cardiac magnetic resonance imaging (CMR) T1 mapping is an established tool used for cardiac tissue characterisation. Such characterisation is of particular interest in athletes, as differentiation of the “grey zone” between physiological adaptation to sports and myocardial pathology can be highly challenging. To correctly interpret individual T1 times, T1 times are conventionally compared with normal values derived from healthy controls. However, whether these normative T1 values can be applied to elite athletes, who commonly demonstrate the most extreme cardiac adaptation, is unknown.

Purpose

To determine whether there are gender-specific differences in normative T1 times between elite athletes and healthy controls.

Methods

This study is a cross-sectional assessment of healthy athletes included the ELITE-cohort. ELITE includes athletes at national, international, and Olympic level in the Netherlands, aged sixteen years or older and without a history of cardiovascular disease. All athletes undergo standard periodic preparticipation screening with cardiovascular magnetic resonance imaging (Phillips 1.5 Tesla), including native T1 mapping. For the current study, we compared athletes to healthy controls per gender group. T1 inversion times were calculated in Circle Cardiovascular software (v5.12); means for global and segmented myocardium, according to the AHA 16-segment model, were determined using R (v4.1.4).

Results

A total of 81 elite athletes (35 women, 43.2%) with a median (IQR) age of 26 (22.0–29.55) years and 55 healthy controls (27 women, 49.1%), with a mean age of 38.4±15 years were included (Table 1). Overall, mean global T1 times were markedly shorter in athletes compared with controls (959±21.1ms vs. 984±26.6ms, P<0.001). This difference was also present in both women (athletes 968±18.5ms vs controls 999±26.5ms, P<0.001) and men (athletes 952±20.3ms vs controls 970±18.0ms, P<0.001). We observed gender differences in T1 times within both the athlete (men 952±20.3ms vs women 968±18.5ms, P<0.001) and the control group (men 984±26.6ms vs women 999±26.5ms, P<0.001). Gender specific differences in T1 times were consistent between athletes and controls in the basal-, mid- and apical slices, as well as across all 16 segments (Figure panels A and B).

Conclusion(s)

Athletes demonstrate markedly shorter T1 times as compared with healthy controls, both in women and men. Sex-specific, athlete-normative T1 times should be taken into account when interpreting T1 times in athletes undergoing cardiac evaluation.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Amsterdam Movement Sciences and the Dutch Olympic Committee*Dutch Sports Federation
Extracellular inflammasome specks are released after marathon running and induce proinflammatory effects in endothelial cells
Authors: Kogel A K , Fikenzer S F , Uhlmann L U , Opitz L O , Kneuer J M K , Haeusler K G H , Endres M E , Kratzsch J K , Schwarz V S , Werner C W , Kalwa H K , Gaul S G , Laufs U L
Published: October 2022

Objectives

The intracellular NLRP3 inflammasome is an important regulator of sterile inflammation. Recent data suggest that inflammasome particles can be released into the circulation. The effects of exercise on circulating extracellular apoptosis-associated speck-like protein (ASC) particles and their effects on endothelial cells are not known.

Methods

We established a flow cytometric method to quantitate extracellular ASC specks in human serum. ASC specks were quantitated in 52 marathon runners 24–72 hours before, immediately after, and again 24–58 hours after the run. For mechanistic characterization, NLRP3 inflammasome particles were isolated from a stable mutant NLRP3 (p.D303N)-YFP HEK cell line and used to treat primary human coronary artery endothelial cells (HCAEC).

Results

Athletes showed a significant increase in serum concentration of circulating ASC specks immediately after the marathon (t1, +52% compared to baseline, p<0.05) and a decrease during follow-up after 24–58 hours (t2, 12% reduction compared to immediately after the run, p<0.01). Confocal microscopy revealed that HCAEC can internalize extracellular NLRP3 inflammasome specks. After internalization, endothelial cells showed an inflammatory response with higher expression of the cell adhesion molecule ICAM1 (6.9-fold, p<0.05) and increased adhesion of monocytes (1.5-fold, p<0.05).

Conclusion

These findings identify extracellular inflammasome specks as novel systemic mediators of cell-cell communication that are transiently increased after acute high-intensity exercise.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): University Hospital Leipzig
Coronary inflammation by computed tomography pericoronary fat attenuation in young male anabolic androgenic steroid users
Authors: Souza F , Rochitte C E , Silva D C , Gomes A M R , Santos M R , Fonseca G W P , Battaglia A C B F , Correa K T S , Yonamine M , Pereira R M R , Negrao C E , Alves M J N N
Published: October 2022

Background

The illicit use of anabolic androgenic steroids (AAS) has been associated with diminished cholesterol efflux mediated by HDL, remarkable decrease in high-density lipoprotein (HDL) plasma concentration and subclinical coronary artery disease (CAD). Inflammation is the key to the atherogenic process associated with atherosclerotic plaque vulnerability. The pericoronary mean fat attenuation (pFAM) has emerged as a marker of coronary inflammation and can predict future cardiovascular events, which is measurable from standard coronary computed tomography angiography (CCTA). However, whether AAS abuse has a role in pFAM in young male AAS users is unknown.

Purpose

The aim of this study was to evaluate whether AAS abuse could leads to higher pFAM and premature coronary inflammation in young male AAS users.

Methods

Twenty strength-trained AAS users (AASU) age 29±5 yr, 20 age-matched strength-trained AAS nonusers (AASNU), and 10 sedentary controls (SC) were enrolled in this study. Coronary inflammation was assessed by pFAM-CCTA in the right coronary artery (RCA), left anterior descending artery (LDA) and left circumflex coronary artery (Cx).

Results

pFAM in the RCA was significantly higher in AASU compared with AASNU and SC (−64.59±9.45 vs. −79.21±6.67 vs. −80.97±7,91 Hounsfield Units (HU), respectively, p<0.001]. Also, the pFAM in the LAD was higher in AASU compared with AASNU and SC (−72.83±7.21 vs. −79.41±6.72 vs. −80.97±7.72 HU, p=0.006). However, no difference to pFAM in the Cx between AASU, AASNU and SC (−74.30±5.85 vs. −79.77±7.13 vs. −78.19±5.82 HU, respectively, p=0.069) was found.

Conclusion

This study indicates that AAS abuse may be associated with higher pFAM and premature coronary inflammation in the RCA and LAD. The higher pFAM may be linked to early development of CAD in young AAS users.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Fundação Zerbini
Evaluation of the Marburg Heart Score and INTERCHEST score compared to current telephone triage for chest pain in out-of-hours primary care
Authors: Manten A , De Clercq L , Rietveld R P , Lucassen W A M , Moll Van Charante E P , Harskamp R E
Published: October 2022

Background/Introduction

Chest pain is a common and challenging symptom for telephone triage in urgent primary care. Existing chest pain-specific risk scores originally developed for diagnostic purposes may perhaps outperform current, expert-based and unvalidated telephone triage protocols.

Purpose

To evaluate the performance of the Marburg Heart Score (MHS) and INTERCHEST as stand-alone triage tools, and to compare their performance with the current “Netherlands Triage Standard (NTS) protocol on differentiating major events”.

Methods

This study involved a retrospective, observational cohort of consecutive patients evaluated for chest pain at a large-scale out-of-hours primary care facility in the Netherlands. We evaluated the performance of the MHS and INTERCHEST score as stand-alone triage tools and compared them with the current decision support tool (NTS). The outcomes of interest were; C-statistics, calibration and diagnostic accuracy for optimized thresholds with major events as reference standard. Major events are a composite of all-cause mortality and both cardiovascular and non-cardiovascular urgent conditions requiring in-hospital treatment, occurring within 6 weeks of initial contact.

Results

We included 1,433 patients, 57.6% women, with a median age of 55.0 years. Major events occurred in 16.4% (n=235), of which acute coronary syndrome (ACS) accounted for 6.8% (n=98). For predicting major events, C-statistics for MHS and INTERCHEST were 0.74 [95%-CI: 0.70–0.77] and 0.76 [0.73–0.80], respectively. In comparison, NTS had a C-statistic of 0.66 [0.62–0.69]. All had appropriate calibration. Both scores (at threshold ≥2) reduced the number of referrals (with lower false positive rates) and maintained equal safety compared with NTS.

Conclusion

Diagnostic risk stratification scores for chest pain may also improve telephone triage for major events in out-of-hours primary care, by reducing the number of unnecessary referrals without compromising on triage safety. Further validation is warranted.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Amsterdam Cardiovascular Research InstituteZonMw-HGOG
The effects of human papillomavirus vaccination on cardiovascular diseases. The United States National Health and Nutrition Examination Survey
Authors: Chou O H I , Liang X , Cheung B M Y
Published: October 2022

Aims

We investigated the association between HPV and CVDs in women with and without HPV vaccination.

Methods and results

We studied 9353 women aged between 18 to 59 years old who were tested for vaginal HPV DNA in the National Health and Nutrition Examination Survey (NHANES) 2003–2016. The CVDs were defined as the self-reported coronary heart diseases, heart attack, angina pectoris and stroke. The HPV vaccination status was extracted from the NHANES 2007–2016 database. The association between HPV and CVDs was studied using logistic regression, with adjustment for the potential confounders.

Among the participants, 40.8% (95% CI, 39.4–42.4) were HPV DNA positive, and 3.0% (95% CI, 2.6–3.5) had CVDs. 9.0% (95% CI, 8.0–10.0) of women received the HPV vaccine. The presence of vaginal HPV infection was associated with CVD [OR=1.66, 95% CI (1.28–2.16), P<0.01], which remained significant [OR=1.53, (95% CI 1.13–2.07), P<0.01] after adjustment for sociodemographic characteristics, smoking, alcohol use, number of sexual partners, cervical cancer, BMI, hypertension, diabetes, and hyperlipidemia. Women younger than 38 years old showed a stronger association between HPV and CVDs [OR=2.15, 95% CI (1.01–4.77), P<0.01]. The association was absent among those who wereHPV vaccinated [OR= 0.44, 95% CI (0.07–2.79), P=0.83], but only present among those who were not [OR=1.60, 95% CI (1.15–2.24), P<0.01].

Conclusions

In this large nationally representative survey, HPV infection was associated with CVDs. The association was absent in women vaccinated against HPV. Our findings regarding early HPV vaccinations may pave the way for new strategies for CVD prevention.

Funding Acknowledgement

Type of funding sources: None.
Gender-sensitive analysis of resynchronization therapy indications in 2021 European heart failure guidelines
Authors: Rilo I , Beramendi Calero J , Quintas Ovejero L , Rengel Jimenez A , Cea Primo D , Nunez Rodriguez A , Hernandez De Alba L , Calvo Chumillas S , Aldave Zabaleta P , Querejeta Iraola R
Published: October 2022

Introduction

Although there is evidence that women benefit very much more than men from resynchronization therapies even with narrower QRSs, the clinical practice guidelines for heart failure do not contemplate a different attitude taking into account gender.

Objective

The aim of this study is to analyze the clinical trials and registries on which the recommendations of the guidelines are based.

Methods

We selected in the bibliography of the 2021 European heart failure guidelines the registries and clinical essays and analyzed them attending to gender perspective according to the following questions:

Is gender treated as a primary variable? Is gender treated as a secondary variable?

Is there a differentiated analysis by sex? Are side effects described differently by sex?

What is the proportion of women in the study?

Results

We analyzed 16 articles. The proportion of women is between 15 and 25%. Only 6 in 16 articles reported a differentiated analysis by sex and there was only one article that differentiated side effects according to sex.

Conclusions

Gender analysis should be mandatory in all the clinical essays carried out in the future. Guidelines should consider different recommendations according to gender. Being excluded or infrarrepresented in studies could conditionate a discrimination to women not only now but also in the future when the algorithms of artificial intelligence condition the decisions we make in the different pathologies

Funding Acknowledgement

Type of funding sources: None.
The impact of dominant ventricle morphology and accessory ventricle size on clinical outcomes after Fontan procedure
Authors: Padalino M , Azzolina D , Puricelli F , Reffo E , Cabrelle G , Cavaliere A C , Guariento A , Castaldi B , Biffanti R , Vida V , Disalvo G
Published: October 2022

Objectives

the physio-pathological role of the morphological ventricular dominance (left, FSLV; right, FSRV), and the hemodynamic contribute of an accessory ventricular chamber (AVC), in patients with functional single ventricle (FSV) after Fontan operation are still uncertain due to conflicting data. We analyzed a cohort of Fontan patients to assess and correlate such anatomical features to late clinical outcomes.

Methods

We enrolled all patients after a Fontan procedure who underwent a cardiac magnetic resonance (CMR) and a cardiopulmonary exercise test (CPET) in the previous 3 years. Clinical, CMR and CPET data from the last follow-up visit were retrieved to analyze whether the size of any AVC and the morphological ventricular dominance (FSLV vs FSRV) were correlated with clinical outcomes (NYHA, need for reinterventions or cardiac transplantation, mortality, arrhythmias, liver disease and protein-losing enteropathy) and functional parameters (including FSV ejection fraction and presence of late gadolinium enhancement, LGE, on CMR and peak metabolic equivalents, pMETs, and peak oxygen consumption, pVO2, at CPET). All statistical tests were two tailed and significance was set at 0.05.

Results

we enrolled 50 patients: 29 had FSLV (58%), FSRV in 21 (42%). Median age at evaluation was 19.5 years [IQR 15–26]; median follow-up was 16 years [4–42]. NYHA class III or IV was present in 6%, while 4 (8%) underwent a re-do Fontan, 2 (4%) entered transplantation waiting list and one of these received a transplant. 2 patients (4%) died at follow-up. Statistical analysis showed that the accessory chamber was larger (>20 cc/m2) in FSLV than in FSRV (p=0.01). In the post-operative period, FSRV was associated with higher incidence of low-cardiac output syndrome (p=0.043). In the long-term, there was no statistically significant difference in major clinical outcomes or NYHA class between the two groups. FSLV was associated with a better cardiac function (median FSV ejection fraction 56% vs 52%; p=0.041), less extent of LGE [p = 0.022], better functional capacity expressed by METs (14.1 vs 12.3; p=0.01) and pVO2 (1.625 ml/min vs 1.233 ml/min; p=0.033). An AVC was detected in all: its size was <5 ml/m2 in 31%, 5–20 ml/m2 in 47%, and >20 ml/m2 in 22%. A larger AVC was associated with higher need for postoperative ECMO support (p=0.007), while size of AVC was not associated to any statistically difference in clinical outcomes, cardiac function and functional capacity.

Conclusions

In Fontan circulation, a FSLV is correlated to better clinical and functional outcomes when compared to FSRV. On the other side, an AVC appears to be not significantly related to any clinical disadvantage. However, the immediate postoperative course may be influenced negatively by the presence of a larger AVC.

Funding Acknowledgement

Type of funding sources: None.
Advanced microstructural substrate detection in pre-hypertrophic HCM and its relationship to arrhythmogenesis; a hybrid CMR-ECG-Imaging study
Authors: Joy G , Webber M , Kelly C I , Pierce I , Teh I , Schneider J , Nguyen C , Kellman P , Orini M , Lambiase P , Rudy Y , Captur G , Dall'armellina E , Moon J C , Lopes L R
Published: October 2022

Background

Hypertrophic cardiomyopathy is defined in three domains; clinically by unexplained hypertrophy, genetically by sarcomeric gene mutations and histologically by disarray, small vessel disease and fibrosis. Both ischaemia and myocyte disarray have been implicated in arrhythmogenesis and sudden cardiac death but whether disarray occurs before hypertrophy and its relationship to ischaemia is unknown.

Diffusion-tensor CMR, perfusion mapping & ECG Imaging (ECGI) can measure disarray, ischaemia and electrical aberrance respectively in vivo. We aimed to investigate these in genotype positive (G+) subjects without hypertrophy (LVH−) to identify further subclinical manifestations of gene expression and whether these relate to ventricular arrhythmia formation.

Methods

Diffusion-tensor CMR (3-Tesla) using a motion-compensated spin-echo sequence was acquired in 3 short-axis slices. Quantitative adenosine stress perfusion mapping was performed using standard clinical protocols. A novel ECGI vest, containing 256 unipolar electrodes acquired a 5-minute recording of body-surface potentials to quantify conduction and repolarisation dynamics intervals.

Results

ECGI/CMR was performed on 68 mutation carriers from 64 families and 24 age sex and ethnicity matched healthy controls. Of the mutation carriers, median age was 33 (24–41 years), 57% (39) were female, and 79% (54) were white. Mutations were 39 (57%) MYBPC3, 19 (28%) MYH7, 1 (1%) MYL2 and 9 (12%) were thin filament/non-sarcomeric mutations. There was no significant difference in ejection fraction or LV mass, however G+LVH− had a higher maximum wall thickness (9 (9–10) vs 8 (7–9) mm p=0.003).

Compared to healthy volunteers, G+LVH− individuals had more perfusion defects (18/64 (30%) vs 0, p=0.004), lower Fractional Anisotropy (FA) (suggestive of more disarray) (0.32±0.02 vs 0.34±0.02, p<0.0001) and more prolonged Activation–Recovery Intervals (ARI, a surrogate for action potential duration (259±40 vs 240±31 ms, p=0.03).

In G+LVH−, patients with perfusion defects had more prolonged ARI (263 (248 vs 292) vs 246 (225–283) ms, p=0.03) and lower FA suggestive of more disarray (0.32±0.2 vs 0.31±0.1, p=0.04).

Conclusion

Ischaemia, myocyte disarray and electrical abnormalities occur even in the absence of hypertrophy in HCM. These abnormalities associate to form a complex a clinical phenotype.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): British Heart FoundationBarts Charity
Exercise capacity and imaging for the prediction of cardiovascular, cancer and noncardiovascular noncancer death in senior people
Authors: Peteiro Vazquez J C , Bouzas-Mosquera A , Barbeito-Caamano C , Vazquez-Rodriguez J M
Published: October 2022

Exercise echocardiography (ExE) can predict overall and cardiovascular mortality. We aimed to assess the value of imaging and functional capacity by ExE for the prediction of cardiovascular (CV), cancer (CA) and non-cardiovascular non-cancer (NCV-NCA) death in senior people.

Methods

Retrospective analysis of prospectively collected data on 1,826 patients aged ≥75 years (79±3 years, 44% women) with a first treadmill ExE performed in our center for known/suspected coronary artery disease. Exclusion criteria were significant valve disease, cardiomyopathy, and congenital heart disease. Ischemia was defined as new wall motion abnormalities (WMAs) with exercise; abnormal ExE as ischemia or resting WMAs. A good functional capacity was defined as a maximal workload of 10 metabolic equivalents (METs). The end point was death (CV, CA or NCV-NCA).

Results

During a median follow-up of 2.7 years (interquartil range 0.3–6.2 years) there were 642 deaths: 306 CV, 143 CA, and 174 NCV-NCA deaths. Multivariate analysis included clinical characteristics, resting echocardiography, exercise testing and peak exercise echocardiography. Different clinical characteristics including age, sex, and coronary risk factors predicted CV death, along with maximal achieved workload in Metabolic Equivalents (METs: Hazard Ratio [HR]=0.98, 95% Confidence Interval [CI]=0.96–0.99, p<0.001) and ExE variables. CA death was independently predicted by gender as well as for achieved METs (HR=0.91, 95% CI =0.85–0.97, p=0.003). Similarly NCV-NCA death was predicted by clinical characteristics (age, diabetes mellitus, dyspnea, peak double product) and also by the achieved METs (HR=0.93, 95% CI: 0.89–0.97, p<0.001). Nor ischemia nor abnormal ExE were predictors of CA or NCV-NCA death. Annualized CV, CA and NCV-NCA deaths according to ExE results and functional capacity are depicted in Figure 1.

In conclusion, the “exercise part” of an ExE study predicts not only CV death, but death due to CA or to NCV-NCA in elder patients. Senior but fitness patients based on the achievement of 10 METs during exercise testing, have less chance of death of any cause.

Funding Acknowledgement

Type of funding sources: None.
Outcomes of sodium-glucose co-transporter type 2 inhibitors use in elderly patients with heart failure with reduced ejection fraction
Authors: Balaguer German J , Cortes Garcia M , Rodriguez Lopez C , Romero Otero J M , Esteban Chapel J A , Nieto Roca L , Martinez Milla J , Taibo Urquia M , Pello Lazaro A M , Tunon Fernandez J
Published: October 2022

Background

Heart failure is a highly prevalent condition, especially in patients over 75 years. In recent years, new therapeutic lines have emerged for the management of heart failure with reduced ejection fraction (HFrEF), most notably sodium-glucose co-transporter type 2 inhibitors (iSGLT2). However, there are currently low evidence of the benefit in this subgroup.

Methods

A retrospective study was conducted from January 2016 to December 2020 in our hospital. All patients aged ≥75 years, diagnosed with HFrEF (defined by left ventricular ejection fraction <40%), and current guidelines recommendations for iSGLT2 were included. Clinical, electrocardiographic and echocardiographic data were collected.

Results

A total of 616 patients were included, with a mean age at the inclusion of 83.3 years (standard deviation, SD, ± 5); 65.6% of the patients included were male. 81.2% were hypertensive, 35.4% were diabetic. 46.2% had chronic kidney disease (defined as glomerular filtrate <60mL/min/1.73 m2). Chronic lung disease was present in 14.8% of the patients, 16.2% had a history of cerebrovascular events and 12.7% suffered from peripheral vascular disease. The most frequent cause of HFrEF was ischemic, with 53.9%. A total of 86.8% presented a NYHA I-II; in 60.3% of the subjects, the rhythm at inclusion was sinus rhythm. The percentage of patients with BB was 76.9%, with ACEI / ARB 69.8%, 14.3% with ARNI and with anti-aldosterone agents 40.4%. The percentage of patients with SGLT2i was only 4.2%. The median follow-up was 34.5 months, during which 50.4% of the population died and 62.5% had a cardiovascular event (death or hospitalization for heart failure). A survival analysis using Cox regression showed that SGLT2i in this subgroup of patients was a protective factor against mortality (HR 0.124; 95% CI 0.031–0.497) and cardiovascular events (HR 0.428; 95% CI 0.221–0.830)

Conclusion

Despite current recommendations in the guidelines, there is marked underuse in elderly patients of SGLT2i. This could be related to greater intolerance or contraindication, but also to a lesser application of the clinical evidence in this population group. However, the use of SGLT2i has been shown as a significant factor associated with improved survival and comorbidity rate in our study population.

Funding Acknowledgement

Type of funding sources: None.