bluuebunny/crossref_metadata_2025 huggingface dataset:
Laughter therapy cardiac rehabilitation in patients with stable coronary artery disease: a randomized clinical trial
Authors: Saffi M , Franzoni L , Nery R , Donelli Da Silveira A , Andrade C , Carvalho G , Stein R
Published: November 2023

Background

Different non-pharmacological strategies have been studied in patients with stable coronary artery disease (CAD). However, the potential benefits of laughter therapy cardiac rehabilitation (LTRehab) for patients with stable CAD have not been fully investigated, especially through randomized clinical trials (RCT).

Purpose

This study aimed to evaluate the impact of LTRehab on functional capacity, endothelial function, and inflammatory biomarkers in CAD patients.

Methods

This is a randomized, parallel-design, examiner-blinded, controlled clinical trial conducted from August 2016 to December 2020. Peak oxygen uptake (VO2peak) and flow-mediated dilation (FMD) were measured using maximal cardiopulmonary exercise testing (CPET) and ultrasound, respectively. Inflammatory biomarkers, including interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, vascular cell adhesion molecule (VCAM), and intercellular adhesion molecule (ICAM), were measured. Thirteen patients were assigned to the LTRehab group, who watched two self-selected comedy sessions per week, and thirteen patients to the control group (CG), who watched two neutral documentaries (24 movies per group). Generalized Estimated Equations were used to identify the main factors of Group, Time, and the interaction between Group*Time. The Bonferroni correction was applied to identify differences. P < 0.05 was considered statistically significant. This study was approved by the Institutional Review Board (protocol No. 13-0124). Furthermore, it was conducted in accordance with Resolution no.466/12 of the National Health Council.

Results

A total of 26 CAD patients (69% male; mean age of 63.58 ± 9.97 years) were included in the study. There was a significant interaction between Group*Time (P<0.01) for VO2peak (LTRehab group: 19.09±0.85 to 21.06±1.00 vs. CG: 23.21±1.74 to 22.24±1.96 mL.kg-1.min-1). There was a mean difference of 1.98±0.45 between times for the LTRehab group with significant Bonferroni correction (P<0.01), but not for the control group (-0.96±0.75, P=0.20). Nitroglycerin-mediated vasodilation (endothelium-independent function) and VCAM showed significant differences in the Time factor (P = 0.02 and P = 0.05, respectively). All CPET tests reached maximal criteria (R>1.10).

Conclusion

This is the first RCT to evaluate the impact of LTRehab on CAD patients, showing an increase in VO2peak and improvements in endothelium-independent function and inflammatory biomarkers. LTRehab may constitute an effective form of cardiac rehabilitation in this patient population.
Treatment effect of respiratory therapy with intermittent hypoxic-hyperoxic training (IHHT) on functional capacity in patients with post COVID19 conditions: a controlled treatment trial
Authors: Shafieesabet A , Alimi B , Muhar J , Schueller P O , Doehner W
Published: November 2023

Introduction

COVID-19 can cause long-term lung and systemic damage that will lead to increasing numbers of patients disabled by reduced functional capacity. Intermittent hypoxia-hyperoxia training (IHHT) is a respiratory therapeutic concept which has been suggested to improve exercise performance via controlled hypoxic conditioning. The purpose of the present study is to investigate the therapeutic effect of IHHT on the recovery process during inpatient rehabilitation in post-COVID conditions.

Methods

A prospective, single-center, randomized controlled trial was conducted in 145 (37 men) patients with post COVID19 conditions aged 27-84 years, who were admitted to a hospitalized rehabilitation program (duration 27±5 days). Patients were 1:1 allocated to the standard rehabilitation program or IHHT on top of standard rehabilitation. The patients in IHHT group attended regular (alternate days) treatments of hypoxia-hyperoxia breathing sessions (10–12% O2 hypoxia breathing followed by 30-35% O2 hyperoxia breathing in 6-8 cycles for a total of 45 min). The primary endpoint of the trial was improvement in walking distance in a six-minute walk test (6MWT) between groups. Further endpoints of functional testing included stair climbing test (SCT), patient global assessment, fatigue assessment scale (FAS) and Quality of life (QoL) assessed by EQ5-D analog scale. Subjective perceived health was assessed by Median Corona Recovery Score (MCRS).

Results

The IHHT group demonstrated in comparison to controls a significant improved primary endpoint (6MWT difference, IHHT group vs controls: 91.7 vs. 32.5m, P<0.001), improved stair climbing (SCT -1.9 vs. -0.5 sek, P<0.001), improved QoL (EQ5-D analog scale change 31.3 vs. 2.9, P<0.001), improved fatigue (FAS -8.9 vs. 3.6, P<0.001) and improved perceived health (MCRS -10.3 vs. -2, P<0.001, all IHHT group vs. controls). The IHHT group exhibited a significant increase in hemoglobin content and a significant decrease in CRP compared to baseline (P<0.001), whereas these changes were not observed in the control group.

Conclusion

Respiratory treatment by IHHT in patients with post COVID conditions resulted in improved functional capacity in multiple of functional tests and in improved QoL and perceived health.
Regular supervised exercise training improves endothelial function, early atherosclerosis, arterial stiffness and endothelial progenitor cells in PCI patients
Authors: Park J , Lim D S , Nam H J , Hong S J , Yu C W , Cha J J , Kim J H , Joo H J , Lim S B
Published: November 2023

Backgrounds

A disrupted balance between endothelial injury and repair induces endothelial dysfunction and endothelial progenitor cells (EPC) augment vascular repair. So, exercise improves endothelial function through increased numbers of EPC. We investigated the effect of training on vascular health by measuring the number of circulating EPC, and assessing flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (IMT) in patients with percutaneous coronary intervention (PCI).

Methods

Fifty-nine patients who were done PCI recently were randomized to full medical treatments or additional 3 months regular supervised exercise program (4 times a week, 1 hr a day). FMD, baPWV, carotid IMT, HOMA, hs-CRP and lipid profiles were measured and circulating CD34/KDR, CD34/CD117 and CD34/CD133 EPC were quantified by flow cytometry at baselines and after 3 months.

Results

Finally 23 patients joined exercise program(control, N=28). There was no significant difference of baseline characteristics and medication between 2 groups. After 3 months, FMD improved significantly in exercise group (6.62% to 11.48%) compared with control group (7.61% to 8.45%) (P<0.001) (fig 1). Carotid IMT reduced significantly in exercise group (0.759mm to 0.707mm) compared with control group (P=0.015) (fig 2). ba-PWV reduced significantly in exercise group (1529cmm/s to 1455 cmm/s) compared with control group (P=0.016) (fig 3). Numbers of CD34/KDR, CD34/CD117 and CD34/CD133 EPCs increased significantly after exercise compared with control group (P= 0.041, 0.011, 0.022, respectively) (fig 4). We also could see to reduce waist to hip ratio in exercise group compared with control group (P<0.001).

Conclusions

Three months regular supervised exercise improved FMD, ba-PWV, carotid IMT and waist to hip ratio in PCI patients. and it augmented numbers of circulating EPCs. Our results showed that exercise contributes to additional improvement of vascular health in PCI patients with optimal medical treatments.
exercise-induced cardiac remodelling in elite athletes is characterized by a stronger ventricular mass-volume association in females as compared with males: MRI results from the ELITE cohort
Authors: Van Diepen M , Van Hattum J C , Daems J J N , Verwijs S M , Boekholdt S M , Van Randen A , Planken R N , Groenink M , Nederveen A J , Moen M H , Wilde A A M , Pinto Y M , Jorstad H T
Published: November 2023

Background

Differentiation between exercise-induced cardiac remodelling (EICR) and cardiac pathology constitutes a central challenge in sports cardiology. To assist clinicians, theoretical frameworks have been developed: i.e. dynamic sports are associated with ventricular dilatation, static sports with hypertrophy, and sports containing both components with both dilatation and hypertrophy. However, EICR frameworks have been almost exclusively based on findings in male athletes, and whether these associations are found in female athletes is to date unclear.

Purpose

We aimed to investigate intersex differences in left ventricular (LV) remodelling in the extreme phenotypes of elite athletes.

Methods

We included 227 healthy, elite athletes from the ELITE cohort who underwent cardiac magnetic resonance imaging (CMR). Our outcomes of interest were absolute and body surface area (BSA) indexed LV end-diastolic volume, LV end-diastolic wall mass, LV end-diastolic mass-volume ratio to express cardiac remodelling (LV end-diastolic wall mass / LV end-diastolic volume) and correlations of BSA-indexed LV mass with LV end-diastolic volume to compare LV remodelling between sexes.

Results

A total of 122 male and 105 female elite athletes (age 26±6 years) were included. The age and division in sports categories according to the ESC classification were similar between the sexes. Male athletes showed larger indexed LV end-diastolic volumes (127±19 versus 108±14 ml, p <0.001) and indexed LV wall mass (66±12 versus 50±11 grams, p <0.001) compared to female athletes. Male athletes had a proportionally larger LV mass-volume ratio than women (0.53±0.12 versus 0.46±0.09 g/ml, p <0.001). Female elite athletes showed a moderate association between indexed LV mass increase with indexed LV end-diastolic volume increase (Spearman’s rho 0.45, p <0.001), whereas male athletes showed a weak association (Spearman’s rho 0.25, p =0.006).

Conclusions

Elite male athletes have larger left ventricular volumes and wall mass, with a greater mass-volume ratio, than their female counterparts. However, female athletes demonstrate a stronger mass-volume association than males. Our findings suggest the presence of distinct sex-dependent features of EICR.
Burden and causes of sudden cardiac arrest in children: implications for preparticipation screening
Authors: Graziano F R A , Schiavon M , Cipriani A , Savalla F , De Gaspari M , Bauce B , Rizzo S , Calore C , Thiene G , Paiaro P , Corrado D , Basso C , Zorzi A
Published: November 2023

Introduction

Competitive sports activity may increase the risk of life-threatening ventricular arrhythmias and sudden cardiac death (SCD) in athletes with underlying cardiovascular diseases (CVD). Preparticipation screening (PPS) offers the potential to early identify CVD and reduce this risk, but the optimal age of sport PPS start is not known.

Purpose

The aim of this study is to assess the burden of sudden cardiac arrest (SCA) and the diagnostic yield of PPS for CVD at risk of SCA in two different age groups: 8-11 year-old and 12-15 year-old.

Methods

Data on the incidence and causes of SCA from 2011 to 2020 were retrieved from the sudden death registry of our region, hospital records and local press. During the same period, we assessed 25,251 young competitive athletes aged 8-15 years who underwent 58,185 annual PPS (mean 2.3/athlete) including history, physical examination, ECG and exercise testing. Further tests were required in case of abnormalities at first-line screening.

Results

Over 10 years, 21 sudden deaths and 5 resuscitated SCA occurred: 6 in athletes (incidence 0.7/100.000/year) versus 20 in non-athletes (0.7/100.000/year). 67% athletes versus 5% non-athletes who suffered SCA were successfully resuscitated (aborted sudden cardiac death=aSCD), (results according to the age-group in Figure 1). Idiopathic ventricular fibrillation was the most common diagnosis accounting for 14/26 (54%) cases. The incidence of SCA was 0.2/100.000/year in the age group 8-11 year-old versus 1.3/100.000/year in the age group 12-15 year-old. By PPS, 26 (0.1%) athletes received a diagnosis of at-risk CVD, significantly more often in children ≥12 year-old (0.06%/evaluation) than <12 year-old (0.02%/evaluation, p=0.02), (Figure 2). During follow-up, 2 screened athletes suffered SCA due to idiopathic ventricular fibrillation, both ≥12 year-old at the time of PPS.

Conclusions

The incidence of SCA was 6 times higher in the age group 12-15 years compared with the 8-11 years group. Similarly, the diagnostic yield of PPS for at-risk CVD was significantly higher after 12 years of age. This suggests that systematic PPS may not be justified before 12 year-old.Figure 1Figure 2
Cardiac magnetic resonance imaging in athletes with suspected structural myocardial disease: results of a high volume single-center study
Authors: Vago H , Balla D , Szabo L , Juhasz V , Bodor C S , Fekete B , Csonka K , Sydo N , Csulak E , Kiss O , Czimbalmos C S , Suhai F , Dohy Z S , Becker D , Merkely B
Published: November 2023

Introduction

Structural heart disease is one of the leading causes of sudden cardiac death in athletes. Cardiac magnetic resonance imaging (CMR) has a key role in the diagnosis, providing accurate functional and morphological information.

Aim

To investigate the prevalence of structural heart disease and the etiology of sudden cardiac death (SCD) in athletes.

Methods

We enrolled athletes (training ≥6 hours/week) who underwent CMR due to suspected structural myocardial disease at our Heart and Vascular Center between 2009 and 2022. We also performed cardiogenetic testing with new-generation sequencing (174 genes) in athletes with confirmed structural heart disease and/or malignant arrhythmia who gave consent.

Results

CMR was performed on a total of 556 athletes (445 male, 24±10 age). The indications for CMR were as follows: aborted sudden cardiac death/sustained ventricular tachycardia (3%), ECG (46%) or echocardiographic abnormality (36%), positive family history of SCD or cardiomyopathy (CMP) (3%), or athletes' complaints (31%). Structural myocardial abnormalities were confirmed in 99 athletes: hypertrophic (HCM) in 27, arrhythmogenic (AC) in 11, dilated (DCM) CMP in 7, and left ventricular non-compaction (LVNC) in 9 cases. MR images consistent with Fabry disease were found in 5 patients. We have discovered post-myocardial infarction scars in 10 cases, and atypical non-ischemic scarring (excluding hinge point fibrosis) was observed in 32 athletes. Besides pathological abnormalities, minor alterations were identified in 76 patients. Among the athletes examined after aborted sudden cardiac death/sustained ventricular tachycardia (n=18), we found structural heart disease in 14 patients, AC was confirmed in 7, HCM in two, non-ischemic fibrosis in three cases and LVNC in one athlete. Cardiogenetic test was performed in 26 athletes, we found pathogenic or likely pathogenic mutations in 5 cases, typical of HCM, AC, DCM (MYBPC3, PKP2, LMNA, TTN). The genetic test showed VUS (variant of unknown significance) in 15 additional athletes.

Conclusions

HCM was identified as the most frequent CMP, whereas AC and nonischaemic scar was the leading cause of SCD or SVT in our athletes.Figure A)Short axis late gadolinium ehancement CMR image of a 26-year-old female tennis player with hypertrophic cardiomyopathy and nonischemic fibrosis (arrow) and MYBPC3 pathogenic variant.Figure B)Short axis late gadolinium enhancement CMR image of a 40-year-old male elite discus thrower with sustained ventricular tacchycardia and nonischaemic scar formation (arrows). LMNA and titin pathogenic variants could be detected.
Prediction of genetic cardiomyopathy by whole exome sequencing and myocardial strain in patients with concentric left ventricle hypertrophy
Authors: Soh M , Park J , Shin J
Published: November 2023

Introduction

Genetic cardiomyopathies (CMP) are a group of inherited diseases that can lead to heart failure and sudden cardiac death. Left ventricular hypertrophy (LVH) is common findings in these diseases, but the diagnosis can be challenging due to their heterogeneous clinical presentations. Myocardial strain and whole exome sequencing (WES) are a powerful tool for early detection of genetic CMP.

Purpose

We aim to investigate the utility of the combination of myocardial strain and WES in the diagnosis of genetic CMP in patients with LVH.

Methods

We performed WES with buccal swab test on a total of 65 patients who had concentric LVH and decreased global average strain (GAS) by echocardiography between July 2021 and December 2022. The genetic data was analyzed to identify disease-causing genetic variants, and the clinical data and echocardiographic findings were collected and analyzed. Logistic regression analysis was performed to identify the predictive factors of genetic cardiomyopathy, and receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic accuracy of these factors.

Results

Of the 65 patients, we identified 10 patients with genetic cardiomyopathy by WES, including hypertrophic CMP, cardiac amyloidosis, and Fabry disease. The diagnostic yield of WES was 15.4% for genetic CMP. Logistic regression analysis showed that sex, diastolic blood pressure, interventricular septal thickness at end diastole (IVSd) and end systole (IVSs), posterior wall thickness at end diastole (PWd), and GAS were significant predictors of genetic CMP (p<0.05 for all). ROC curve analysis showed that IVSs had the highest area under the curve (AUC) value of 0.711 (p=0.037), with a sensitivity of 60.0% and a specificity of 67.3%.

Conclusion

Our study highlights the utility of WES and myocardial strain with echocardiographic data in diagnosing genetic CMP, especially in patients with concentric LVH. These findings support the integration of genetic testing and advanced imaging techniques in the diagnostic approach for patients with suspected genetic cardiomyopathies.
Association of adverse pregnancy outcomes with cardiovascular risk profile in later life - lessons learned from a large prospective population-based cohort-study
Authors: Unger E , Makarova N , Borof K , Aarabi G , Blankenberg S , Augustin M , Waldeyer C , Zengin-Sahm E , Magnussen C , Behrendt C A , Schnabel R B , Zyriax B C
Published: November 2023

Background

An increased cardiovascular risk profile in parous women in later life has been related to maternal outcomes of pregnancy such as hypertension, diabetes, excessive weight gain as well as fetal outcomes such as preterm birth or excessive birth weight.

Methods

Using data from a large, monocenter, prospective, long-term, population-based cohort, we analysed self-reported data on pregnancy, risk factors and health status of 1,970 women. We examined the correlations between gestational hypertension (gHTN), gestational diabetes (gDM) and excessive weight gain during pregnancy with hypertension (HTN), diabetes (DM), hyperlipoproteinemia (HLP) and body-mass-index (BMI) in later life. Regarding adverse fetal outcomes, we investigated correlations between preterm birth and later hysterectomy/ovariectomy of parous women and birth weight of >4,000 g with parous women’s BMI in later life. The Wilcoxon rank sum test and the Pearson's Chi-squared test were carried out to prove associations. Further logistic regression analyses are planned to assess cardiovascular outcomes such as myocardial infarction, stroke, heart failure and atrial fibrillation in these parous women. The p-value of 0.05 was defined as a standard for significance.

Results

The median age of 1,970 women upon examination was 63 years. The proportion of gestational hypertension was 8.7%. 18% of women gained more than 20 kg and 2.4% had diabetes during pregnancy. 10% delivered newborns with a birth weight of <2,500 g. 14% delivered newborns with a birth weight of >4,000 g. 19% were smokers and had hyperlipoproteinaemia, 59% were hypertensive and 33% had metabolic syndrome. We found positive correlations between gestational hypertension and hypertension in later life as well as between gestational diabetes and diabetes mellitus. Excessive weight gain during pregnancy was found to relate to elevated BMI in later life as well as current smoking status. Excessive weight gain during pregnancy did, however, not relate to HLP. High birth weight of >4,000 g correlated with elevated BMI in later life.

Conclusions

In a population-based sample, we were able to demonstrate that pregnancy-related manifestations of cardiovascular risk factors are indeed related to an increased risk profile in later life. There is a profound need for better individual risk stratification in women based on pregnancy-related data in order to deliver optimised early preventative strategies and potentially reduce cardiovascular events in later life.
Cardiovascular risk in rare autoimmune diseases, lessons from a primary antiphospholipid syndrome patients
Authors: Djokovic A , Stojanovich L , Stanisavljevic N , Zdravkovic M , Djulejic V , Matic P
Published: November 2023

Background

Antiphospholipid syndrome is a thrombo-inflammatory disease driven by circulating autoantibodies (aPL) that recognize cell surface phospholipids and phospholipid-binding proteins. In the absence of an underlying connective tissue disorder, the persistent presence of these antibodies associated with recurrent fetal losses and arterial or venous thrombosis is defined as a primary antiphospholipid syndrome (PAPS) with a prevalence of 1/2000 people, predominantly female.

Purpose

Estimation of cardiovascular risk presence based on markers of subclinical cardiovascular impairment.

Methods

100 PAPS patients, with an average age of 47.70±13.14y, 93.7% females, were included in the study. Anticardiolipin antibodies (aCL IgG/IgM), anti-ß2 glycoprotein-I (anti-ß2GPI IgG/IgM), and lupus anticoagulant (LAC) were determined. Abnormal cut-off values used for left ventricular diastolic dysfunction (LVDD) were septal E ́<7 cm/sec, lateral E ́ <10 cm/sec, average E/E ́ ratio >14, LA volume index (LAVI) >34 mL/m2, and peak tricuspid regurgitation velocity >2.8 m/sec. LVDD was present if more than half parameters were with abnormal values. Endothelial dysfunction was assessed through ultrasound measurement of brachial artery flow-mediated dilation (FMD) and atherosclerosis progression by ultrasound assessment of intima-media thickness (cIMT) on carotid arteries (common carotid artery, CCA, internal carotid artery, ICA). The results were compared to 90 healthy, age and sex-matched controls.

Results

LVDD was significantly more prevalent in PAPS patients compared to healthy controls (24.8% vs. 2.2%, p=0.001). FMD was significantly lower in PAPS patients (10.76±5.15% vs. 14.20±6.76%, p=0.0001) and cIMT values were significantly higher (left ICA 0.80±0.29mm vs 0.56±0.20mm, p=0.001). All markers of subclinical atherosclerosis were significantly related to age and standard atherosclerotic risk factors present. Regarding aPL profile, anti-ß2GPI IgG positive PAPS patients had higher levels of cIMT ICA left (p=0.049) and LAC positive higher prevalence of LVDD (p=0.047) CONCLUSIONS: PAPS patients impose significantly higher prevalence of subclinical cardiovascular involvement compare to healthy population. Timely recognition, along with vigorous control of standard atherosclerotic risk factors and a proper therapeutic (antithrombotic and/or anticoagulant) regime, is of great importance.
Worse outcomes in young women compared to men presenting with ST-elevation myocardial infarction: a 15-year statewide population-linkage cohort study
Authors: Lazarovska S , Brieger D , Hyun K , Ng A , Chow V , Kritharides L , Philip R
Published: November 2023

Background

Gender disparity in outcomes among patients presenting with acute ST-elevation myocardial infarction (STEMI) is well recognised. It is unclear whether the gap has improved with contemporary management and therapies over time. This study compared the 30-day mortality between women and men admitted with STEMI from 2003-2017.

Purpose

To examine whether the gender disparity in 30-day mortality following STEMI is consistent across patient age groups and whether it has changed over time with contemporary management.

Methods

We used the NSW Admission-Patient-Data-Collection (APDC) database which maintains the admission records of more than 97% of the state’s healthcare facilities to identify consecutive STEMI patients admitted from 1-Jan-2003 to 31-Dec-2017. Cause-specific mortality (classified as cardiac, non-cardiac) was identified from death certificates. Multivariable logistic regression analysis was performed to examine the impact of gender on mortality adjusted for comorbidities, admission year-groups, PCI during STEMI, and stratified by age groups of ≤60, 61-70 and >70yo.

Results

The study cohort comprised 65033 STEMI patients: 32% women (n=20825; median age 76.1yrs); 68% men (n=44208; median age 63.8yrs). The overall 30-day all-cause and cardiac mortality was 11.5% and 8.3% respectively, with women having worse outcomes compared to men (all-cause: 17.0% vs 8.9%; cardiac: 12.2% vs 6.5% respectively, both p<0.0001). Following adjustment, higher mortality among women persisted: adjusted odds ratio [aOR]=1.65 (95% confidence interval [CI]=1.40-1.94) and 1.55 (95%CI=1.28-1.87) for total and cardiac mortality respectively. The gender disparity in mortality did not change during the study period. There was an interaction between age and gender so that differences in gender specific mortality were greater in younger than in older patients: total mortality women vs men ≤60yrs aOR=1.65 (95%CI=1.40-1.94), >70yrs aOR=1.19 (95%CI=1.12-1.27), p(interaction)=0.0011; cardiac mortality women vs men ≤60yrs aOR=1.55 (95%CI=1.28-1.87), >70yrs aOR=1.17 (95%CI=1.09-1.25), p(interaction)=0.026. Unexpectedly, a similar age-gender interaction was observed for non-cardiac mortality: women vs men ≤60yrs aOR=1.88 (95%CI=1.41-2.51), >70yrs aOR=1.15 (95%CI=1.03-1.28), p(interaction)=0.0063.

Conclusion

Women admitted with STEMI have significantly higher 30-day mortality than their male counterparts, with no improvement in gender disparity during the study period. The gender-bias is most pronounced in the younger age-group across and is observed for both cardiac and non-cardiac mortality. Further efforts are needed to identify the drivers of worse outcomes following STEMI in younger women.
Tobacco smoking upregulates CRLF1 expression in the atherosclerotic lesions in sex- and plaque-type specific manner
Authors: Lan T , De Kleijn D P V , Den Ruijter H M R , Pasterkamp G P , Mokry M M
Published: November 2023

Background

Tobacco smoking is known to impact the development of atherosclerotic disease. Interestingly, females who smoke have a higher risk of cardiovascular disease( CVD) than males. It is established that smoking can lead to changes in DNA methylation and gene expression. We, therefore, hypothesised that smoking influences gene expression in a sex- and plaque-type-specific manner.

Method

We executed bulk RNA sequencing of 654 carotid plaques and single sequencing in 46 plaques. We analysed the transcriptomes of 625 carotid plaques from smokers (n= 226) and non-smokers (n = 399) and performed the differential gene expression in plaques between smokers and non-smokers. The analysis was repeated separately in males and females. The observed gene expression differences were also associated with pathological and molecular plaque characteristics.

Results

After correction for multiple testing, CRLF1 was found to be significantly higher expressed in smokers than non-smokers (Log2FC=0.48, FDR =0.012) (Figure 1a). Single-cell RNA-seq analyses revealed specific expression of CRLF1 in the synthetic smooth muscle cell population. The smoking-associated CRLF1 overexpression was larger in females (log2FC=0.93) compared to males (log2FC=0.35) (Figure1b). Furthermore, the effect was restricted to plaque types with a higher content of smooth muscle cells.

Conclusion

Our results show the sex and plaque type-specific effect of smoking on gene expression in carotid plaques. The higher upregulation of the CRLF1 gene in female smokers suggests mechanistic clues to a higher risk of smoking-related CVD in women.Figure 1
Risk factors for coronary artery complications after prosthetic pulmonary valve implantation in congenital heart diseases
Authors: Kwon H , Song M K , Lee S Y , Kim G B , Kwak J G , Cho S K , Kim W H
Published: November 2023

Background

The incidence and risk factors for coronary artery complications in patients who underwent pulmonary valve replacement or valved conduit interposition for congenital heart diseases were unknown.

Purpose

This study was an extension of the previous study† to investigate the incidence and risk factors of coronary artery complications among patients who underwent prosthetic pulmonary valve implantation.

Methods

Retrospective cohort study was performed for the patients who underwent cardiac CT or invasive coronary angiography after the prosthetic pulmonary valve implantation at the tertiary referral hospital from June 1986 to May 2021. The rotation angle of the aorta and angles of both coronary artery orifices were measured on a Picture Archiving and Communication System (Figure 1). The Cox regression analysis was used to identify variables predicting the occurrence of coronary artery complications. Survival rates were assessed by Kaplan-Meier analysis.

Results

Coronary artery complications were identified in 25 patients among the 341 patients (7.3%), and two of them died. The median age at diagnosis of coronary artery complications was 20 years (interquartile range: 12.5-25 years). The coronary artery complication-free survival rate was predicted to be 97.3% at 5 years, 92.5% at 10 years, 85.5% at 20 years, and 61.1% at 30 years. The risk of cardiac death was 1.865 times higher [95% CI: 0.403, 8.628] in patients with coronary artery complications than in those without it; nevertheless, the difference was not statistically significant (p-value = 0.425). Among the patients with coronary artery complications, congenital coronary anomalies were identified in 11 (44 %), interarterial course of coronary artery in 18 (72 %), and intramural course in 4 patients (16%). Interarterial course and intramural course of the coronary artery were associated with a 4.4 and 10.6-fold increased risk of coronary artery complications, respectively. When subgroup analysis was performed in patients with tetralogy of Fallot and pulmonary atresia, the aortic root rotated more clockwise in patients with coronary artery compression than in patients without it (128.0°± 19.9° versus 113.5°± 23.7°, p-value = 0.024). The cut-off value of the rotation angle to predict the occurrence of coronary artery compression was 133˚ (Figure 2).

Conclusion

Preoperative and postoperative long-term coronary assessment should be performed in patients with conotruncal anomalies undergoing prosthetic pulmonary valve implantation, especially in those with abnormal courses of coronary arteries or severe rotation of aortic root. The rotation angle of aorta could be measured on cardiac CT angiography prior to surgery, and the location of the prosthetic valve or conduit should be carefully determined.Measurement of anglesKaplan-Meier curves
Machine learning to predict myocardial injury and death after non-cardiac surgery
Authors: Nolde J , Schlaich M P , Sessler D I , Mian A , Corcoran T B , Chow C K , Chan M T V , Borges F K , Mcgillion M H , Myles P S , Mills N L , Devereaux P J , Hillis G S
Published: November 2023

Background/Introduction

Myocardial injury after non-cardiac surgery (MINS) is defined as prognostically relevant myocardial injury due to ischaemia that occurs within 30-days of non-cardiac surgery.

Purpose

The aim of this study was to test whether machine learning, using neural networks, can accurately predict this frequent and important complication.

Methods

Using data from 24,589 participants in the Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) study, who had non-cardiac surgery and post-operative high-sensitivity troponin T (hs-TnT) levels measured, a deep neural network was trained to predict the primary outcome of MINS and the secondary outcome of death within 30-days. Validation was performed on a separate, randomly selected, subset of the study population with model discrimination and accuracy (number of correct predictions) determined.

Results

Using only data available pre-operatively, the deep neural network predicted MINS with an area under the receiver operating characteristic curve (AUROC) of 0.75 (95% confidence interval [95% CI] 0.74-0.76) and death at 30-days with an AUROC of 0.83 (95% CI 0.79-0.86). Addition of basic intra-operative and early post-operative data increased the AUROC for MINS to 0.77 (95% CI 0.76-0.78) and death to 0.87 (95% CI 0.85-0.90). The deep neural network trained on the full dataset (pre-operative, intra-operative and early post-operative) predicted MINS with an accuracy of 70% and death within 30-days with an accuracy of 89%.

Conclusions

Neural networks can be trained to predict MINS and death within 30-days of non-cardiac surgery and the inclusion of intra-operative and early post-operative data improves predictive accuracy. These techniques may be useful clinically to predict adverse outcomes after non-cardiac surgery.MINS outcomesDeath Outcomes
The incidence of coronary artery disease in all Swedish liver transplant patients between 1987 and 2020: A national prospective study
Authors: Lewinter C , Widman L , Hagstrom H
Published: November 2023

Background

Liver transplant (LT) is potentially curing end stage liver disease (ESLD). During and afterwards LT surgery, coronary artery disease (CAD) events are among the most frequent and serious complications. Risk factors before and after LT are largely unidentified in large national registers.

Purpose

To identify risk factors of CAD before and after LT in all Swedish patients between 1987 and 2020.

Methods

Data of all Swedish LT patients between 1987 and 2020 were retrieved from the Swedish Patient register. LT patients, aetiologies of ESLD, and comorbidities were identified through ICD- 9 and -10 codes. We included a reference group for comparison without LT, having similar age, gender, and municipality. All data were cross-linked to Statistics Sweden and the national Cancer registry to include survival and cancer history. The only exclusion criteria were expatriated LT patients. The primary outcome was the composite of CAD events being acute myocardial infarction, coronary artery revascularisation and angina. Time to CAD event was assessed through cox regressions with competing risks of mortality unrelated to CAD. Cumulative incidence plots were created for comparison between LT and non-LT patients.

Results

A total of 2925 LT patients and 27589 matching cohorts were retrieved (Figure 1). The mean age of the total population was 54.0 years and 62.6% were men. The most predominant aetiology of ESLD was autoimmune disease (28.2%) followed by hepatocellular carcinoma (22.9%). CAD events was diagnosed in 4.5% of the patients before LT. The most prevalent risk factors of CAD at baseline were diabetes (21.8%) and hypertension (21.4%). During a median follow-up of 9.5 years, the incidence of CAD was significantly higher in LT patients as compared with non-LT patients but was not associated to gender(Figure 2).

Conclusion

LT patients have a significant higher risk of CAD events as compared with a reference group not having ESLD. Whether pre- or post LT risk factors of CAD can explain this higher risk needs to be investigated.Figure 1:Flow chartFigure 2:Cumulative incidence of CAD
Guideline adherence to statin therapy and association with major adverse cardiac events in high-risk patients following major noncardiac surgery
Authors: Glarner N C , Puelacher C , Menosi Gualandro D , Lurati Buse G , Gerhard H , Grossenbacher M , Mueller D , Bolliger D , Mueller C
Published: November 2023

Introduction

Statins are widely used for the prevention of coronary artery disease (CAD) and associated secondary cardiovascular complications. Despite established evidence in acute and chronic cardiovascular disease, the optimal perioperative use of statins remains uncertain. We aimed to evaluate adherence to current guideline recommendations regarding statin therapy in high-risk patients undergoing major noncardiac surgery and its association with major adverse cardiac event (MACE).

Methods

Class I indications for statin therapy according to current ESC clinical practice guidelines were assessed among consecutive high-risk patients undergoing major noncardiac surgery enrolled in a prospective multicentre cohort study. The primary endpoint MACE, a composite of cardiovascular death and spontaneous acute myocardial infarction, was recorded during 120-day follow up and centrally adjudicated by cardiologists blinded to statin therapy. As a co-primary endpoint, perioperative myocardial infarction/injury (PMI) due to a type 1 MI (T1MI) or likely type 2 MI (lT2MI) within the first three postoperative days was used. After multivariable adjustment with inverse probability of treatment weighting (IPTW) to account for differences between statin and non-statin users, we performed a Cox proportional hazard model with MACE and a logistic regression model with PMI due to T1MI or lT2MI as endpoints.

Results

Between October 2014 and February 2018, we included 8116 high-risk patients undergoing major noncardiac surgery. 4227 of 8116 patients (52.1%) had at least one class I indication for statin therapy. The most common indication for statin use was CAD in 2235 patients (52.9%) followed by diabetes with comorbidities in 1676 patients (39.6%) and peripheral artery disease in 1514 patients (35.8%). From all patients with a class I indication for statin use, only 2440 (57.7%) were on statins preoperatively. Usage was highest in patients with prior myocardial infarction (828/1110 [74.6%]) and lowest in patients with chronic kidney disease stage 3-5 (494/996 [49.6%]).

During the follow up of 120 days, 192 MACE occurred (4.6%) including 116 cardiovascular deaths. After multivariable adjustment, preoperative use of statins was associated with a reduced risk of MACE (weighted hazard ratio 0.59, 95% confidence interval [CI] 0.41-0.86; p = 0.006). PMI due to T1MI or lT2MI occurred in 508 of 4170 (12.2%) patients. After IPTW, the weighted odds ratio for PMI in patients receiving preoperative statin therapy was 1.15 (95%CI 1.01-1.31; p = 0.036).

Conclusion

Current adherence to guideline-recommended statin therapy in the noncardiac surgery population is suboptimal. The use of statins was associated with reduced rates of adverse cardiac events within 120 days, but not with cardiac PMI.Percentage of patients receiving statinsMACE within 120 days
Potential cardioprotective effects of acetylcholinesterase inhibitors in patients with Alzheimer's disease
Authors: Rampa L , Gaspardone C , Fiore G , Romagnolo D , Cerutti A , Santangelo R , Magnani M , Piscazzi G , Sgherzi G , Filippi M , Margonato A , Fragasso G
Published: November 2023

Background

In patients with mild to moderate Alzheimer's disease (AD), acetylcholinesterase inhibitors (AChE-I) are commonly employed to improve cognitive function. They increase the amount of acetylcholine (ACh) in the neuronal synapses, but bradycardia, cardiac electrical conduction blocks and hypotension due to muscarinic M2 receptor stimulation are potential side effects. However, whether these "side effects" could play a potential protective effect on cardiovascular (CV) events is not yet well defined.

Purpuses

To evaluate potential beneficial cardiac effects of AChE-Is in patients with AD, in terms of reduction of major adverse cardiovascular events (MACEs).

Methods

We conducted a retrospective, monocentric, observational cohort study in patients referred to our hospital. Two groups were considered: the interventional group included AD patients treated with AChE-I. The control group enrolled a cohort of subjects matched for age and comorbidities, recruited between caregivers of intervention group subjects that were cognitively unimpaired and not taking AchE-I. The primary endpoint was a composite of hospitalization for heart failure (HF), non-fatal acute myocardial infarction (AMI), myocardial revascularization, hospitalization for cardiovascular (CV) causes, cardiovascular mortality and occurrence of stroke and/or TIA during total 5 year follow-up period (MACEs). Secondary endpoints were each individual component of the primary end point, total deaths, non-cardiovascular death and incidence of pacemaker implant.

Results

221 AD patients treated with AChE-I (91 with Donepezil, 130 with Rivastigmine) were included in intervention group and 221 non-AD patients in control group. Groups were homogeneous in terms of age, gender and main cardiovascular risk factors, except for family history of cardiovascular diseases (CVD), which was more frequent in control group. During a median follow-up of 3.1 years the primary endpoint occurred in 24 patients in intervention group (2.1 per 100 patient-years) compared to 56 patients in the control group (5.0 per 100 patient-years). Therefore, AChE-I therapy resulted a protective factor from primary endpoint (HR 0.48, 95% CI 0.24-0.95; p= 0.036). Even not significant, the difference was mainly driven by myocardial revascularization (3.2% in intervention group vs 6.8% in controls) and hospitalization for heart failure (4.5% in intervention group vs 14.5% in controls). Non-CVD mortality was significantly higher in treatment group (13,6% in intervention group vs 2,7% in controls). No significant difference was observed between groups in terms of other secondary outcomes.

Conclusions

Among patients with AD, use of AChE-I may be protective for CV outcomes, especially reducing HF hospitalisation and myocardial revascularization.Kaplan-Meier of cumulative MACEsNumber of Event/Years
Long-term prognosis of elderly patients undergoing atrial septum defect closure: are we acting too late?
Authors: Lima M R L , Maltes S M , Madeira S M , Carmo Mendes I C M , Anjos R A , Mendes M M
Published: November 2023

Introduction

Atrial septum defects (ASD) are the third most common congenital heart defect affecting adults and often goes unrecognized due to the absence of significant symptoms and unspecific signs at physical examination. Yet, long-term exposure to chronic right heart volume overload can have deleterious effects, with almost all patients becoming symptomatic by the fifth or sixth decade. However, whether ASD closure in an elderly patient affects their average life expectancy (ALE) is still unknown.

Aim

To assess the relationship between ASD closure (surgical or percutaneous) and ALE in a Portuguese cohort of patients older than 65 years old.

Methods

Single-centre retrospective study including all consecutive patients older than 65 years old that underwent isolated ASD closure (surgical or percutaneous) between January 1998 and December 2020. Baseline characteristics were assessed as well as the predicted ALE (as determined per pre-defined national ALE tables) for every given patient at the time of the ASD closure.

Results

A total of 37 patients with a mean age at closure of 69±5 years, 76% female, were included. Most patients presented with heart failure (62%), 14% with ischemic stroke, and 51% had an atrial arrythmia. 22% patients had severe tricuspid regurgitation, the mean systolic pulmonary artery pressure (SPAP) was 50±11mmHg and a median Qp/Qs of 2.1 [1.2-2.5]. Five patients were treated surgically. The mean size of the ASD was 21±7mm and those treated surgically had a higher mean size (24±7mm vs 21±9mm). During the mean FUP of 9.3±5.2 years, 16 patients died (37%). The mean age of death was 79.4±5.8 years and did not differ significantly from the expected mean ALE of 84.3±1.3 years (p=0.304). Patients who did not reach the predicted ALE at the time of the procedure (N=12, 33%) had higher SPAP (58±10 vs 46±8mmHg; p=0.001) and presented more frequently with severe tricuspid regurgitation (42 vs 12%, p=0.040) (figure 1A). There was no difference in terms of mortality regarding method of closure (p=0.096).

Conclusion

Overall survival of elderly patients that underwent late ASD closure did not differ significantly from the expected ALE, nevertheless one-third of the patients died prematurely. A premature death was associated with higher SPAP and a more severe tricuspid regurgitation. These results suggest that late-ASD closure does not overcome the effects of long-term right chamber overload and pulmonary hypertension, thus arguing in favour of earlier intervention.
Prognostic significance of thyroid disease in atrial fibrillation
Authors: Vasilopoulou A , Bekiaridou A , Papazoglou A , Patsiou V , Zergioti M , Lambropoulou C , Kostakakis D , Kyriakideli M , Spacho M , Samaras A , Moysidis D , Kartas A , Ziakas A , Zanos S , Giannakoulas G
Published: November 2023

Background

Thyroid disease (THD) has often been associated with atrial fibrillation (AF) triggering, through endocrine mechanisms. Still, data on the impact of hypothyroidism on AF are contradictory. Our aim was to correlate the THD profile with the incidence of hard clinical endpoints in AF patients.

Methods

This post- hoc analysis of the MISOAC-AF RCT included hospitalized patients with AF and available history of THD. Patients were classified by categories of thyroid disease history (hyperthyroidism, hypothyroidism, euthyroidism). Unadjusted and adjusted hazard ratios (aHRs) were calculated using Cox regression models. Comparison groups included euthyroid compared to hypothyroid and hyperthyroid AF patients, respectively. All-cause mortality, cardiovascular death (CVD) and hospitalizations were the outcomes of interest. Survival analysis with the Kaplan-Meier curves was performed to analyze time-to-event data.

Results

A total of 496 AF patients followed-up for a mean of 2.7 years period, had available THD history and were included in the study. Of them, 16 patients (3.2%) were hyperthyroid, 141 (28.4%) hypothyroid, and 339 (68.4%) euthyroid. Patients with hypothyroidism had higher hospitalization rates during follow-up (aHR: 1.57, 95% CI: 1.12 to 2.20, p=0.008, p=0.025) compared to the euthyroid group. Higher TSH levels were correlated with an increased risk of CVD (aHR: 1.03, 95%CI: 1.01 to 1.05, p=0.007) and hospitalizations (aHR: 1.06, 95%CI: 1.01 to 1.12, p=0.03), while lower T3 levels were correlated with higher all-cause mortality rates (aHR: 0.51, 95%CI: 0.31 to 0.82, p=0.006) and CVD risk (aHR: 0.42, 95%CI: 0.23 to 0.77, p=0.005).

Conclusions

In AF patients, hypothyroidism was associated with increased hospitalizations, while elevated TSH levels and decreased T3 levels were associated with increased CVD and all-cause mortality respectively.Hypothyroidism and clinical outcomes