bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic role of cardiac magnetic resonance in left ventricular non compaction
Authors: Azpiroz Franch M J , Casas Masnou G , Romero A , Gonzalez Del Hoyo M I , Larranaga Moreira J M , Escalona Silva R , Guala A , Limeres Freire J , Bayes De Luna A , Zorio Grima E , Villacorta Arguelles E , Garcia Pavia P , Barriales Villa R , Ferreira Gonzalez I , Rodriguez Palomares J F
Published: October 2022

Introduction

Left ventricular non compaction (LVNC) is a heterogeneous entity with uncertain prognosis. Cardiac magnetic resonance (CMR) is widely used in the diagnosis of LVNC. However, its role in risk stratification has not been well established.

Purpose

Therefore, the aim of our study was to identify prognostic CMR variables in LVNC.

Methods

We conducted a retrospective longitudinal multicentre cohort study of consecutive patients fulfilling CMR LVNC criteria. The endpoints were heart failure (HF), ventricular arrhythmias (VA), systemic embolisms (SE) and all-cause mortality. Biventricular volumes, ejection fraction (LVEF and RVEF) as well as late gadolinium enhancement (LGE) were analysed.

Results

A total of 310 patients were included: age was 44.4±19 and 43% female. LVEF was 47% ± 15%, RVEF was 48±12 and 28 patients (9%) presented LGE. After a median follow-up of 3.8 2.5 years, 40 patients (13%) presented HF, 31 (10%) had VA, SE occurred in 6 (2%) and 3 patients (1%) died. Baseline characteristics of patients with and without HF and VA are described in Table 1.

In univariate analysis, LVEF, LV volumes, LGE, and RVEF were associated with both HF and VA risk. In multivariate analysis, LVEF was the only variable independently associated with HF (HR 0.932, CI 95% 0.88–0.97, p 0.003). Patients with an LVEF >35% were at very low risk of HF (Figure 1A). With regards to VA, LGE was the only independent predictor (HR 2.64, IC 95% 1.059–6.61, p 0.003) (Figure 1B). In LGE negative patients, the arrhythmic risk was higher among those with an LVEF <35% (HR 2.81, 95% CI 1.02–8.12, p 0.047).

Conclusions

In a large multicentre retrospective LVNC study, left ventricular ejection fraction and late gadolinium enhancement were the main predictors of cardiovascular events. Patients with an LVEF <35% and with LGE were at markedly increased risk. Therefore, we suggest that these variables should be combined to enhance risk stratification in LVNC.

Funding Acknowledgement

Type of funding sources: None.
Prevalence and outcomes of atrial fibrillation in older people living in care homes in Wales: a routine data linkage study 2003–2018
Authors: Ritchie L A , Harrison S L , Penson P E , Akbari A , Torabi F , Hollinghurst J , Harris D , Oke O B , Akpan A , Halcox J P , Rodgers S E , Lip G Y H , Lane D A
Published: October 2022

Background

Older care home residents are a high-risk group of people with atrial fibrillation (AF) who are under-represented in clinical trials. Improved understanding of AF epidemiology and management in this population is paramount for health and social care organisations to strategically plan services.

Purpose

To determine the trends in AF prevalence and compare adverse health outcomes in older care home residents aged ≥65 years with AF compared to those without AF.

Methods

Retrospective cohort study of people entering a care home between 2003–2018 using nationwide, population-scale anonymised health and administrative data, provisioned from the Secure Anonymised Information Linkage (1 January 2000–31st December 2018). Direct standardisation was used to calculate AF prevalence by year of care entry (2010–2018). Cox regression analyses were used to estimate the risk of adverse health outcomes.

Results

Between 2003 and 2018, 86,602 people aged ≥65 years became new residents in care homes in Wales. Residents with AF (n=14,493) had a significantly higher risk (adjusted hazard ratio [aHR], 95% confidence interval [CI]) of cardiovascular (aHR 1.27 [1.17 to 1.37], p<0.001) and all-cause mortality (aHR 1.14 [1.11 to 1.17], p<0.001), Figure 1. The risk (sub-distribution hazard ratio [sHR], 95% CI) of ischaemic stroke (adjusted sHR 1.55 [1.36 to 1.76], p<0.001) and cardiovascular hospitalisation (adjusted sHR 1.28 [1.22 to 1.34], p<0.001) was also higher in residents with AF, even when mortality was considered a competing event, Figure 1. There was no significant change in age- and sex-standardised prevalence of AF between 2010 and 2018, 16.79% (95% CI 15.85 to 17.94) and 17.02% (95% CI 16.05 to 17.98), respectively (absolute change 2010–2018: 0.06% [95% CI: −1.38 to 1.50], p=0.93), Figure 2.

Conclusions

This study demonstrates unique data on the epidemiology of AF and associated outcomes in older care home residents. Whilst the prevalence of AF remained stable between 2010–2018, residents with AF had significantly higher risk of adverse health events. Treatment of AF in accordance with guidelines is critical in this population to optimise management and reduce adverse health outcomes.

Funding Acknowledgement

Type of funding sources: None.
COVID-19 vaccine-induced myocarditis vs. immune checkpoint inhibitor-induced myocarditis – same but different?
Authors: Zornitzki L , Havakuk O , Rozenbaum Z , Viskin D , Arbel A , Banai S , Topilsky Y , Laufer-Perl M
Published: October 2022

Background

While immune checkpoint inhibitors (ICI) -induced myocarditis and coronavirus disease 2019 (COVID-19) vaccine-induced myocarditis are considered to be rare; they are both significant side effects, suggested being caused by activation of the immune system against the myocardium. We aimed to assess whether both phenomena share similar presenting characteristics.

Methods

We included patients diagnosed with either ICI or COVID-19 vaccine-induced myocarditis at our medical center. We performed a retrospective assessment of clinical presentation, blood tests, and advanced echocardiography, including speckle strain.

Results

We included 18 patients diagnosed with ICI (ICI group) or COVID-19 vaccine (COVID-19 group)-induced myocarditis, and 20 patients with viral myocarditis (Viral group) as a control group. The median age was significantly older in the ICI group (74 years) compared to the COVID-19 and Viral groups (20 and 24 years), p<0.001. The clinical presentation in the COVID-19 group was more similar to the Viral group, presenting mainly with chest pain and fever, while the ICI group presented mainly with dyspnea. ST-elevation was frequent in the COVID-19 and Viral groups and absent in the ICI group, p=0.004. Median peak high sensitivity troponin I values were markedly lower in the ICI group compared to the COVID-19 and Viral groups (619 ng/L vs. 15527 ng/L vs. 7388 ng/L, p=0.004). While the median left ventricular ejection fraction was 60% among all groups, patients in the ICI group presented with mean lower LV global longitudinal strain (−13%) and left atrial conduit strain (17%), compared to the COVID-19 (−17% and 30%) and Viral groups (−18% and 37%), p=0.016 and p=0.001.

Conclusions

While the suspected mechanism is an activation of the immune system in both ICI and the COVID-19 vaccine-induced myocarditis, we found that the clinical presentation, cardiac biomarkers, and advanced echocardiography of the COVID-19 vaccine, are more similar to viral myocarditis than to ICI-induced myocarditis.

Funding Acknowledgement

Type of funding sources: None.
Emergency department cardiovascular disease encounters and associated mortality in patients with cancer: a study of 20.6 million records from the USA
Authors: Kobo O , Moledina S M , Raisi-Estabragh Z , Chieffo A , Alraies M C , Biondi-Zoccai G , Mohamed M , Roguin A , Mamas M A
Published: October 2022

Background

There is limited data on Emergency department (ED) cardiovascular disease (CVD) presentations and outcomes amongst cancer patients.

Objectives

The present study aimed to describe the clinical characteristics, prevalence, and clinical outcomes of the most common cardiovascular ED admissions in patients with cancer.

Methods

All ED encounters with a primary CVD diagnosis from the US Nationwide-Emergency Department Sample between January 2016 to December 2018 were stratified by cancer type as well as metastatic status. Multivariable logistic regression was performed to determine the adjusted odds ratios of in-hospital mortality in different groups.

Results

From a total of 20,737,247 ED encounters with a primary CVD diagnosis, cancer was present in 3.4%. In patients with cancer the most common CVDs were DVT/PE (20%), hypertensive heart or kidney disease (14.7%), and AF/flutter (11.2%). The distribution of CVDs varied by cancer type, with AF/flutter most common in patients with lung cancer, AMI most common in patients with prostate cancer, heart failure most common in those with haematological malignancies, and patients with colorectal cancer having the greatest frequency of DVT/PE. Cancer status was independently associated with significantly higher risk of mortality in almost all CVD categories, consistent across all the cancer types, amongst which lung cancer patients had the highest risk of mortality across all CVD categories, except intracranial haemorrhage and hypertensive crisis.

Conclusions

Cardiovascular presentations to the ED varied by cancer subtype. Across all cancer subtypes, patients presenting with cardiovascular presentations carried a significantly increased risk of mortality compared to patients with no cancer.

Funding Acknowledgement

Type of funding sources: None.
Cardiorespiratory fitness and left ventricular function in breast cancer survivors a decade after Epirubicin treatment
Authors: Saeter M , Nilsen T S , Johansen S H , Thorsen L , Reinertsen K V , Haugaa K H , Edvardsen T , Sarvari S I
Published: October 2022

Background

Anthracyclines are effective chemotherapeutic agents commonly used in breast cancer (BC) treatment. Cardiotoxicity is a serious adverse effect of anthracyclines, but knowledge of long-term cardiac effects is limited. To our knowledge, no prior study has investigated both cardiorespiratory fitness assessed by peak oxygen consumption (V̇O2 peak) and left ventricular (LV) function in long-term follow up of BC survivors (BCS) treated with anthracyclines.

Purpose

To assess long-term adverse effects of Epirubicin on cardiorespiratory fitness and LV function in BCS.

Methods

The CAUSE-trial is an ongoing study comparing exercise effects in BCS of stage I-III BC recruited from the Cancer Registry of Norway and controls with no cancer diagnosis. We present preliminary results from the baseline assessments in this trial. BCS (n=93) treated with Epirubicin between 2008 and 2013 were compared to age-matched controls (n=11). V̇O2 peak was assessed by incremental treadmill cardiopulmonary exercise test and LV function by echocardiography.

Results

At baseline, BCS were 58±7 years old and had received a cumulative dose of 339±85 mg/m2 Epirubicin 11±1 years before examination. There was no difference in V̇O2 peak between BSC and controls. LV ejection fraction was lower in BCS compared to controls assessed by 2D (57±3% vs. 59±2%, p=0.01) and 3D echocardiography (57±3% vs. 61±4%, p=0.006). LV global longitudinal strain was also lower (in absolute value) in BCS compared to controls (−20.6±1.3% vs. −22.0±1.3%, p=0.002). There was no difference in global work index and efficiency between BCS and controls.

Conclusion

Our findings indicate no difference in cardiorespiratory fitness between BCS and controls a decade after Epirubicin treatment. Systolic LV function was slightly lower in BCS compared to controls. Importantly, systolic LV function in BCS was within normal range, and the difference is probably not of clinical importance. There was no difference in myocardial work between BCS and controls.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): The Cancer Registry of Norway
Cardiac MRI findings in COVID-19 vaccine-related myocarditis: pooled analysis of 435 patients
Authors: Samimisedeh P , Jafari Afshar E , Shafiabadi N , Rastad H
Published: October 2022

Background

Myocarditis following COVID-19 vaccination is a rare adverse event that was recently reported.

Understanding the pattern and severity of myocardial injury in myocarditis caused by COVID-19 vaccination is imperative for improving care of the patients.

Purpose

To detect the pattern and severity of myocardial injury in patients with myocarditis following COVID-19 vaccination based on cardiac MRI findings.

Study type

Systematic review.

Method

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically reviewed the literature by screening 2404 databases using boolean operators and the relevant key terms covering COVID-19 vaccine, myocarditis, and Cardiac MRI. We included all observational MRI studies on patients with suspected myocarditis following COVID-19 vaccination. Cardiac MRI findings, including T1, T2, ECV, LGE, and left ventricular ejection fraction, were extracted from included studies.

Statistical tests

As a single case series, individual-level patient data (IPD) studies were pooled with aggregated–level data (AD) studies through two-stage analyses. For this purpose, first, data from all case series and case reports with IPD were aggregated using one-stage IPD analyses.

Results

Based on our two-stage pooled analyses of IPD and AD studies, diagnosis of myocarditis using lake luoise criteria was confirmed in 74% (95% confidence interval (CI): 49% to 94%) of patients. Cardiac MRI abnormalities included elevated T2 in 67% (95% CI: 45% to 87%), myocardial LGE in 91% (95% CI: 81% to 99%) [having a subepicardial/midwall pattern: 99.5%], impaired LVEF (<50%) in 4% (95% CI: 0.0% to 9.0%). Also, elevated T1 and ECV (>30), reported only by some IPD studies, was detected in 72.5% (66/91) and 32% (16/50) of patients, respectively.

Data conclusion

Myocardial injury in COVID-19 vaccine-associated myocarditis may have a similar pattern compared to other forms of acute myocarditis. Despite other myocarditis, Preserved LVEF is a common finding in these patients.

Funding Acknowledgement

Type of funding sources: None.
The effect of the location of arteriovenous fistula on the right ventricle in end stage renal disease patients indicated for hemodialysis
Authors: Ali S , Abdel-Shafee M , Kamal H M , Salah A
Published: October 2022

Background

End-stage renal disease (ESRD) has significantly increased in developing countries such as Egypt [1]. There are many sites for arteriovenous fistula (AVF) creation. The most common sites for AVF are radio-cephalic AVF (RC-AVF) followed by brachio-cephalic AVF (BC-AVF) [2]. To date, there are no significant studies discussing the possible correlation between the AVF location and abnormalities in the right ventricle (RV) in hemodialysis (HD) patients.

Objective

To determine the best location for AVF in order to ensure the least possible hazardous side effects of the AVF on the RV.

Methods

Our study, designed as an interventional study, included 50 ESRD patients referred for primary AVF construction to start HD for the first time. Patients were divided into two groups, 25 patients each. one group underwent a RC-AVF construction and the other had a BC-AVF. We assessed the RV by two dimensional transthoracic echocardiography (2D TTE) twice for each patient, firstly just before the AVF surgery and secondly three months after AVF construction.

Results

There was a statistically significant difference in between study groups regarding change in RV Tei index (p=0.001) with a decrease in the radial group (Mean ± SD = −0.19±0.2) and an increase in the brachial group (Mean ± SD = 0.02±0.12), and regarding the right ventricular outflow tract proximal diameter (p<0.001) with a decrease in the radial group (Mean ± SD = −2.32±5.49) and a larger increase in the brachial group (Mean ± SD = 2.94±3.14). Changes in the other RV dimensions and functional parameters did not show statistically significant difference.

Conclusion

After three months follow up, despite the fact that all the RV parameters remained within the normal range, the RV indices with the RC-AVF were associated with either improvement or less decline than with the BC-AVF.

Funding Acknowledgement

Type of funding sources: None.
Post-dialysis heart rate variability predicted mortality in chronic hemodialysis patients
Authors: Osataphan N , Wongcharoen W , Phrommintikul A , Putchagarn P , Noppakun K
Published: October 2022

Background

Autonomic disturbance is common in end stage renal disease (ESRD) and may be responsible for mortality in these patients. Heart rate variability (HRV) is the useful tool to assess for autonomic function. The predictive value of HRV on overall-mortality and proper timing of HRV measurement in chronic hemodialysis patients remain to be determined.

Propose

To evaluate the predictive value of HRV on all-cause mortality and explore the proper timing of HRV assessment by performing repeated HRV measurements at different time points including before, during and after hemodialysis.

Methods

We enrolled ESRD on hemodialysis patients between April 2018 to December 2018. HRV measurements were recorded 10 minutes before hemodialysis, 4 hours during hemodialysis and 10 minutes after hemodialysis. Baseline characteristics, clinical parameters and all-cause mortality were recorded. Cox-proportional hazard regression was used for the analysis of the association between HRV parameters with all-cause mortality.

Results

There were 163 patients enrolled to the study. After a median follow up of 40.4 months, 37 (22.7%) patients were expired. From multivariable Cox proportional hazard regression, the post-dialysis HRV parameters including lower very low frequency (VLF) (hazard ratio [HR], 0.900; 95% confidence interval [CI], 0.850–0.953; p<0.001), lower normalized low frequency (nLF) (HR, 0.954; 95% CI, 0.922–0.987; p=0.007), lower LF/HF ratio (HR, 0.268; 95% CI, 0.103–0.699; p=0.007) and higher normalized high frequency (nHF) (HR, 1.047; 95% CI, 1.012–1.083; p=0.007) were the independent predictors for all-cause mortality. HRV parameters at pre-dialysis and during dialysis were not associated with all-cause mortality. Patients with post-dialysis LF/HF ratio lower than the median value (<1.1) had a significantly higher all-cause mortality (log rank p=0.006) (Figure 1).

Conclusion

Post-dialysis period could be the most appropriate timing for HRV measurement. The HRV parameters at post-dialysis including lower VLF, lower nLF, higher nHF and lower LF/HF ratio were the independent predictors for all-cause mortality in chronic hemodialysis patients.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Faculty of Medicine endowment fund for medical research, Chiang Mai University, Thailand
Inter-field strength agreement of cardiovascular magnetic resonance cine-derived strain and strain rate measures: a randomised study
Authors: Ayton S L , Alfuhied A , Gulsin G S , Parke K S , Wormleighton J V , Arnold J R , Moss A J , Singh A , Graham-Brown M P M , McCann G P
Published: October 2022

Background

Left ventricular (LV) strain and strain rate measurements can be derived from routinely acquired cardiovascular magnetic resonance (CMR) cine images by feature tracking techniques. However, the inter-field strength agreement of strain measurements derived from these techniques is not known. We hypothesised that there would be excellent inter-field strength agreement (between 1.5 and 3 Tesla [T]) for the measurement of global strain and strain rate derived from cine imaging.

Methods

Prospective, randomised cross-over observational study. Healthy volunteers each underwent CMR scans at 1.5T and 3T within 30 minutes on the same day in a randomised order. Retrospectively ECG gated, short and long-axis balanced steady state free precession cine images were obtained using standardised acquisition parameters at both field strengths. Two software packages were used to derive LV global longitudinal, circumferential and long and short axis radial systolic strain, peak systolic, early diastolic and late diastolic strain rates. All strain values are expressed as positive numbers.

Results

Twenty-two subjects (mean age 36±12 years; 45% male) were studied. No differences in heart rate and blood pressure measurements during scanning were observed between field strengths. The abstract figure shows an example of strain analysis and Bland-Altman plots for global longitudinal and circumferential strain. Minimal bias was seen in all strain and strain rate measurements between field strengths using the first software package. Strain and strain rate values derived from long axis images (longitudinal and long axis radial) showed poor to fair agreement (intraclass correlation co-efficient (ICC) range 0.39–0.71), whereas measures derived from short axis images (circumferential and short axis radial) showed good to excellent agreement between field strengths (ICC range 0.78–0.91). Similar results were observed with the second software package, though the differences in agreement between long and short axis derived measures were less pronounced.

Conclusion

Longitudinal strain and strain rate measures derived from CMR feature tracking have poor inter-field strength agreement between 1.5T and 3T. By contrast, agreement of circumferential and short axis radial strain and strain rate measurements at 1.5T and 3T is good. These results need to be considered when assessing strain at different field strengths.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): United Kingdom National Institute for Health Research
Trend in CV mortality among patients with mental disorder in the US between 1999–2020
Authors: Hamuda N , Abert T , Zahalka M E , Zidan A , Saada M , Levi Y , Abu Fanne R , Meisel S R , Roguin A , Kobo O
Published: October 2022

Background

Patients with mental disorders are at increased risk of cardiovascular mortality. While the overall cardiovascular mortality rate in the western world is in decline, there is no up-to-date data on the cardiovascular mortality rates among patients with mental disorders. We aimed to assess the cardiovascular mortality trends over the last two decades among patients with mental co-morbidities in the US.

Methods

Using Centers for Disease Control and Prevention Wide-Ranging, Online Data for Epidemiologic Research (CDC WONDER) Multiple Cause of Death data set, we determined national trends in age-standardized mortality rates attributed to cardiovascular diseases in patients with and without mental disorders, from 1999 to 2020, stratified by mental disorders subtype, age, gender, race, and place of residence.

Results

Among more than 18.7 million cardiovascular deaths in the United States, 13.5% were patients with a concomitant mental disorder. During the study period, among patients with mental disorders, the age-adjusted mortality rate increased by 113.9% (vs 44.8% decline in patients with no mental disorder). In patients with mental disorders, the age-adjusted mortality rate increased more significantly among patients whose mental disorder in secondary to substance abuse (+532.6%) than among with organic mental disorders, such as dementia or delirium (+6.2%), while among patients with mood disorders the age-adjusted CV mortality rate dropped by 23.5%. Men patients, minorities, and residents of more rural areas experienced a more prominent increase in the age-adjusted cardiovascular mortality compared to women, white, and residents of metro areas.

Conclusions

While there was an overall reduction in cardiovascular mortality in the US in the past two decades, we demonstrated an overall increase in cardiovascular mortality among patients with mental disorders. The increase was more significant among patients with substance abuse-related mental disorders, in men, minorities, and residents of rural areas.

Funding Acknowledgement

Type of funding sources: None.
Left atrial strain at CMR is a strong independent prognostic predictor in DCM, superior to LV-GLS, LVEF and LAVI, and incremental to LGE
Authors: Raafs A G , Vos J L , Henkens M T H M , Verdonschot J A J , Gerretsen S , Knackstedt C , Hazebroek M R , Nijveldt R , Heymans S R B
Published: October 2022

Background

The left atrium (LA) is an early sensor of left ventricular (LV) dysfunction. LA size and new-onset atrial fibrillation (AF) are associated with an increased risk of mortality and heart failure (HF) progression in patients with dilated cardiomyopathy (DCM). Whether abnormal LA strain measured at cardiac magnetic resonance (CMR) – a new technology to study atrial function – may predict overall outcome in DCM – either or not leading to new onset AF – remains completely unknown.

Purpose

To determine the prognostic value of CMR derived LA strain in DCM patients.

Methods

A total of 488 DCM patients (age 54 [46–62] years, 61% male) undergoing CMR were prospectively enrolled in the Maastricht Cardiomyopathy Registry between 2004 and 2018. Outcome consisted of the combination of sudden or cardiac death, HF hospitalization or life-threatening arrhythmias. LA reservoir (passive LA filling), conduit (passive LV filling), and booster strain (active LV filling) were measured using feature tracking strain analysis of the 2- and 4-chamber long-axis cines (Figure 1). Given the non-linearity of continuous variables, cubic spline analysis was performed to dichotomize.

Results

Seventy out of 488 DCM patients (14%) reached the endpoint (follow-up 6 [4–9] years). Age, NYHA class ≥3, late gadolinium enhancement (LGE) presence, LV ejection fraction (EF), LA volume index (LAVI), LV global longitudinal strain (GLS), and LA reservoir and conduit strain were univariably associated with worse outcome (all p-values <0.02). LA conduit strain was superior to reservoir strain to predict outcome. LA conduit strain, NYHA class ≥3 and LGE remained associated in the multivariable model (Figure 2A), while age, NTproBNP, LVEF, LA ejection fraction, LAVI and LV-GLS did not. Adding LA conduit strain to NYHA class and LGE significantly improved the calibration, accuracy, and reclassification of the prediction model (p<0.05). In patients without known AF and sinus rhythm (n=425) during CMR, 10% developed new-onset AF (paroxysmal or persistent) at long-term. Higher age, male sex, NYHA class ≥3, higher LAVI and impaired booster strain were all univariably associated with new-onset AF. Age and impaired booster strain remained as independent predictors of new-onset AF in the multivariable analysis (Figure 2B).

Conclusions

LA conduit strain on CMR is a strong independent prognostic predictor in DCM, superior to LV-GLS, LVEF and LAVI, and incremental to LGE. In addition, LA booster strain is an independent predictor of new-onset AF.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation
Incidence and impact of venous thromboembolism in hospitalized patients with Crohn-disease
Authors: Keller K , Sivanathan V , Schmitt V H , Ostad M A , Munzel T , Espinola-Klein C , Hobohm L
Published: October 2022

Background

Prevalence of Crohn's disease (CD) is high in North America and in Europe ranging between 100 and 350 patient-cases per 100,000 citizens. CD is characterized by chronic inflammation with a progressive course and is often associated with different intestinal as well as extra-intestinal complications. CD is associated with both, other inflammatory diseases such as ankylosing spondylitis and psoriasis as well as venous thromboembolism (VTE). CD causes an activation of coagulation system, which might be the main reason for an increased risk of thromboembolic complications. Beside previous study results regarding higher VTE risk of patients with CD in comparison to the general population, particularly, data on impact of VTE on survival and risk factors for the occurrence of VTE in CD are sparse.

Purpose

The objectives of our study were to provide evidence about the current and past prevalence of VTE events in hospitalized patients with CD and to investigate the impact of VTE on outcomes of CD patients.

Methods

The German nationwide inpatient sample was screened for patients admitted due to CD (ICD-code K50) (source: RDC of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005–2018, own calculations). CD hospitalizations were stratified for VTE and risk factors for VTE and impact of VTE on in-hospital case-fatality rate were investigated.

Results

Overall, 333,975 patients-cases with hospital admissions due to CD were counted in Germany (median age 38.0 [IQR 24.0–52.0] years, 56.0% females) during the observational period between 2005 and 2018. VTE rate increased slightly from 0.6% to 0.7% (β 0.000097 [95% CI 0.000027 to 0.000167], P=0.007) from 2005 to 2018 and with age-decade of life (β 0.0017 [95% CI 0.0016 to 0.0019], P<0.001). In total, 0.7% (n=2,295) of the CD inpatients had an event of VTE. Patients with VTE were in median 12 years older (49.0 [34.0–62.0] vs. 37.0 [24.0–52.0] years, P<0.001) and CD colon-manifestations were more prevalent in those patients (32.0% vs. 27.7%, P<0.001). Age ≥70 years, obesity, colon-involvement, cancer, surgery, thrombophilia, and heart failure were strongly associated with higher risk of VTE in CD patients.

In-hospital death occurred 15-times more often in CD with VTE than without (4.5% vs. 0.3%, P<0.001). VTE was independently associated with substantially increased in-hospital case-fatality rate (OR 9.31 [95% CI 7.54–11.50], P<0.001).

Conclusions

VTE is a life-threatening event in hospitalized CD patients associated with 9.3-fold increased case-fatality rate. Older age, obesity, colon involvement, cancer, surgery, thrombophilia and heart failure were strong risk factors for VTE in patients with CD.

Funding Acknowledgement

Type of funding sources: None.
CMR derived left ventricular intraventricular pressure gradients identify different patterns associated with prognosis in patients with dilated cardiomyopathy
Authors: Vos J L , Raafs A G , Henkens M T H M , Van Deursen C J , Pedrizzetti G , Rodwell L , Heymans S R B , Nijveldt R
Published: October 2022

Introduction

The direction of blood flow in the left ventricle (LV) is determined by intraventricular pressure gradients (IVPGs) between apex and base, which are altered when cardiac function declines. New cardiac magnetic resonance (CMR) post-processing software enables estimating LV-IVPGs. To date, the prognostic value of CMR derived IVPGs in patients with dilated cardiomyopathy (DCM) remains unknown.

Methods

DCM patients from the Maastricht Cardiomyopathy Registry, who underwent a CMR, were included. The software estimates the LV-IVPGs (between apex and base) by using the myocardial movement and velocity of a reconstructed 3D-LV model (derived from feature-tracking strain analysis of 2-, 3- and 4-chamber cine images). The primary outcome was a combined endpoint of heart failure (HF) hospitalisations, life-threatening arrhythmias and (sudden) cardiac death.

Results

In total, 447 DCM patients were included (age 55 interquartile range [46–63] years; 60% male). During a median follow-up of 6 [4–9] years, 66 patients (15%) reached the primary endpoint. In 168 patients (38%), a temporary pressure reversal from base-apex to apex-base during the systolic-diastolic transition was observed (figure). After correction for covariates that were univariably associated with outcome (p<0.100, age, NYHA-class≥3, and left atrial (LA) conduit strain), flow reversal from base-apex to apex-base in the diastole was independently associated with outcome in the total cohort (HR 2.91, 95%-Confidence interval (95%-CI) [1.16–7.32], p=0.023; Table). In patients without pressure reversal (N=279) in the systolic-diastolic transition, IVPG during the total cardiac cycle (HR 0.88 [0.81–0.96], p=0.003), the systolic ejection force (HR 0.92 [0.87–0.97], p=0.003), and the E-wave decelerative force “C” (passive diastolic filling, HR 0.85 [0.74–0.97], p=0.013) were predictors of outcome, independent of other covariates (age, sex, NYHA class ≥3, LV ejection fraction, late gadolinium enhancement, LV longitudinal strain, LA volume index and LA conduit strain, table).

Conclusion

CMR-derived LV-IVPG analysis showed pressure reversal in the systolic-diastolic transition in one-third of DCM patients, and flow reversal was an independent predictor of worse outcome in these patients. In patients without this pressure reversal, LV-IVPG during the total cardiac cyle, the systolic ejection force, and the E-wave decelerative force were predictors of outcome, independent of all evauluated clinical and imaging parameters.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Netherlands Cardiovascular Research Initiative (initiative with support of the Dutch Heart Foundation) and CVON (She-PREDICTS, grant 2017-21 & CVON-DCVA Double Dosis 2021)
Impact of alirocumab added to high-intensity statin therapy on platelet function in AMI patients: a pre-specified substudy of the randomized, placebo-controlled PACMAN-AMI trial
Authors: Ueki Y , Haner J , Losdat S , Gargiulo G , Bar S , Otsuka T , Kavaliauskaite R , Mitter V , Temperli F , Shibutani H , Siontis G , Valgimigli M , Windecker S , Koskinas K , Raber L
Published: October 2022

Background

Previous small observational studies have suggested a potential association of proprotein convertase subtilisin kexin type 9 (PCSK9) and platelet reactivity. However, the role of the PCSK9 inhibitor alirocumab on platelet aggregation among patients with acute myocardial infarction (AMI) remains unknown.

Purpose

We investigated the effect of alirocumab on P2Y12 reaction unit (PRU) on top of high-intensity statin therapy among AMI patients receiving dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor (ticagrelor or prasugrel).

Methods

This was a pre-specified, powered, pharmacodynamic substudy nested within the PACMAN (effects of the PSCK9 antibody AliroCuMab on coronary Atherosclerosis in patieNts with Acute Myocardial Infarction) trial, a randomized, double-blind trial comparing biweekly alirocumab (150mg) versus placebo in AMI patients undergoing percutaneous coronary intervention (PCI). Patients recruited at Bern University Hospital, receiving DAPT with either ticagrelor or prasugrel at 4 weeks and adherent to the study drug (alirocumab or placebo) were analyzed for the current study. The VerifyNow P2Y12 point-of-care assays were used to measure PRU at baseline (i.e. before first study drug administration), 4 weeks, and 52 weeks after study drug administration (higher PRU levels indicating greater platelet aggregation). The primary endpoint was PRU at 4 weeks.

Results

Among 139 randomized patients (mean age 58.2 years [SD, 9.5], 21 [15.0%] women, mean LDL-C level 150.6mg/dL [SD, 30.9]), baseline characteristics were well balanced between groups including baseline PRU (50.0 [IQR, 120.0] in the alirocumab group vs. 62.0 [IQR, 122.0] in the placebo group, P=0.75). At 4 weeks, mean LDL-C was significantly lower in the alirocumab group (23.5 [SD, 23.7] mg/dL vs. 74.4 [SD, 30.5] mg/dL, P<0.001). The majority of patients received ticagrelor DAPT at 4 weeks (57 [86.4%] vs. 69 [94.5%], P=0.14). There were no significant differences in PRU at 4 weeks (12.5 [IQR, 27.0] vs. 19.0 [IQR, 30.0], P=0.26) and at 52 weeks (25.0 [IQR, 37.0] vs. 34.0 [IQR, 59.0], P=0.07) (Figure). Consistent results were observed in 126 patients treated with ticagrelor (i.e. after excluding 13 patients treated with prasugrel) at 4 weeks (13.0 [IQR, 20.0] vs. 18.0 [IQR, 27.0], P=0.28).

Conclusion

Among AMI patients receiving DAPT with potent P2Y12 inhibitors, alirocumab had no significant effect on platelet function as assessed by PRU.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Bern University Hospital
Perioperative rosuvastatin therapy increases creatine kinase and the risk of acute kidney injury in patients undergoing cardiac surgery
Authors: Wijesurendra R , Sardell R , Hill M , Jayaram R , Samuel N , Staplin N , Emberson J , Collins R , Zheng Z , Haynes R , Casadei B
Published: October 2022

Introduction

In patients undergoing cardiac surgery, perioperative statin therapy does not prevent atrial fibrillation or myocardial injury, but results in increased creatinine levels after surgery. Here we investigated the incidence of acute kidney injury (AKI) in 1922 patients scheduled for elective cardiac surgery who were randomized to perioperative rosuvastatin (20 mg once daily) or placebo in the Statin Therapy In Cardiac Surgery (STICS) trial.

Methods

AKI post-surgery was defined according to international guidelines using plasma creatinine. Biomarkers related to kidney function, muscle injury and inflammation were investigated, including cystatin C, total creatine kinase (CK), troponin I, growth differentiation factor 15 (GDF-15), interleukin-6 (IL-6), procalcitonin, and placental growth factor (PGF).

Results

At 48 hours post-surgery, AKI was significantly more common in patients allocated to rosuvastatin compared to placebo when defined by creatinine (24.7% vs 19.3%; OR 1.37 [95% CI 1.10–1.70]; p=0.005; Figure 1A) or by cystatin C (9.2% vs 5.1%; OR 1.86 [95% CI 1.29–2.67]; p<0.001; Figure 1B). Elevations in CK to >10x and >40x baseline level were also more frequent in rosuvastatin-allocated patients compared to placebo (30.9% vs 26.5%, p=0.02, and 2.1% vs 0.7%, p=0.02, respectively; Figure 1C). Post-operative concentrations of troponin I, GDF-15, IL-6, procalcitonin, and PGF were similar between the groups (Table 1).

Conclusions

Perioperative rosuvastatin initiation increased the absolute risk of AKI after cardiac surgery by 4–5%. Rosuvastatin also led to greater elevations in post-operative creatine kinase, but did not affect other biomarkers of tissue injury, inflammation, and myocardial injury. Further research is needed to delineate the underlying mechanism of AKI with perioperative rosuvastatin.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): British Heart Foundation
Statin therapy in children with familial hypercholesterolemia: a meta-analysis
Authors: Lewek J , Surma S , Bytyci I , Banach M
Published: October 2022

Background

Familial hypercholesterolemia (FH) is a genetic disorder that may develop serious vascular damage leading to a high risk of the development of premature of cardiovascular disease (CVD).

Purpose

The aim of this meta-analysis was to evaluate the efficacy of statins on lipid profile in children patients with diagnosed FH.

Methods

We systematically searched selected electronic databases from inception until 15th March 2022. Main endpoints were lipid profile: total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and apolipoprotein B (Apo-B), lipoprotein(a) (Lp(a)). Random effects mean reduction were used to evaluate the efficacy of statins.

Results

Eight randomized controlled trial (RCTs) with a total of 1025 children patients with FH (statins n=529) were included in the meta-analysis. At mean follow-up was 10.4 months. We showed that in the group of children treated with statins, compared to control, higher mean TC reduction −1.95 mmol/L (−75 mg/dL) [95% CI, −1.36 to −2.54; p<0.001], TG reduction −0.13 mmol/L (−11.5 mg/dL) [−0.04 to −0.23; p<0.001], and LDL-C reduction −1.94 mmol/L (−75 mg/dL) [−1.43 to −2.45; p<0.001] were observed with significantly higher increase of the mean HDL-C, 0.37 mmol/L (14.3 mg/dL) [0.04 to 0.69; p=0.03] (Figure 1). In addition, the statins significantly reduced Apo-B [−0.50 g/L; p<0.001] and did not significantly affect Lp(a) [0.13 mg/dL; p=0.87] in statins group (Figure 2).

Conclusions

The results of our meta-analysis clearly showed that children treated with statin therapy had significantly improved lipid profile with lack of effect on Lp(a). This data might help to improve statin therapy in FH children, which is highly underused worldwide.

Funding Acknowledgement

Type of funding sources: None.
Lower risk of gout in sodium glucose cotransporter 2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors in type-2 diabetes patients: a propensity score-matched study
Authors: Chou O H I , Liu X , Zhou J , Jing F , Li L , Lee S , Wong W T , Zhang Q , Chang C , Liu T , Tse G , Cheung B M Y
Published: October 2022

Background

The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) versus dipeptidyl peptidase-4 inhibitors (DPP4I) on the risk of new gout diagnosis have not been explored. This study aims to compare the effects of SGLT2I against DPP4I on gout risks in a Chinese population.

Methods

This was a retrospective population-based cohort study of patients with type-2 diabetes mellitus treated with SGLT2I or DPP4I between January 1st, 2015 and December 31st, 2020 in Hong Kong. The study outcomes are new-onset gout and all-cause mortality. Propensity score matching (1:1 ratio) between SGLT2I and DPP4I was performed. Univariable and multivariable Cox regression analysis models were conducted. Competing risks models and multiple approaches based on the propensity score were applied.

Patients

This study included 60996 patients (median age: 62.3 years old, 54.96% males; SGLTI group: n=21690; DPP4I group: n=39306).

Results

In the matched cohort, 1096 developed gout (IR: 2.52%) and 2195 died (IR: 5.05%). Univariable Cox regression showed that SGLT2I use was associated with lower risks of new diagnosis of gout (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.30–0.39; P-value<0.0001) and all-cause mortality (HR: 0.35; 95% CI: 0.32–0.39; P-value<0.0001) compared to DPP4I. The associated remained for both new diagnosis of gout (HR: 0.46; 95% CI: 0.37–0.57; P-value<0.0001) and all-cause mortality (HR: 0.38; 95% CI: 0.33–0.44; P-value<0.0001) after adjusting for significant demographics, past comorbidities, and non-SGLT2I/DPP4I medications. The risks of gout were lowered in each types of SGLT2I. The results were consistent on competing risk and other propensity score approaches analyses.

Conclusions

SGLT2I use was associated with lower risks of new gout diagnosis compared to DPP4I use.

Funding Acknowledgement

Type of funding sources: None.
The DPP4 inhibitor linagliptin exacerbated heart failure due to energy deficiency via downregulation of glucose absorption and utilization in mice
Authors: Shiraki A , Oyama J , Shimizu T , Node N
Published: October 2022

Background

It was reported that glucagon-like peptide-1 has cardio-protective effects, however, the occurrence of heart failure was increased with DPP4 inhibitor in some large clinical trials.

Purpose

The purpose of the present work was to clarify whether DPP4 inhibitor had any effects on chronic, dilated heart failure and to identify the mechanisms.

Methods

Heart / Muscle-specific Manganese superoxide dismutase (Mn-SOD)-deficient mice, (H/M-Sod−/−) which exert dilated cardiomyopathy were randomized to receive low dose (1 mg/kg) linagliptin, HF-L group; high dose (10 mg/kg) linagliptin, HF-H group; mixed with food, or normal food, HF group; for eight weeks. Then, evaluation was performed in cardiac function and pathophysiological changes.

Result

Interestingly, the mice treated with linagliptin treatment exhibited shorter life span and greater heart/body weight ratio. Echocardiographic studies showed decreased contractility in the HF-H group with compared to the HF control group. In Sirius Red staining, severer fibrosis was also observed in the linagliptin groups. HbA1c levels did not change among three groups, however, glycogen content in the liver was significantly decreased in the linagliptin groups. Similarly, indirect calorimetry showed decreased carbohydrate consumption in the HF-H group compared to the HF control group, suggesting worsening of heart failure was due to unavailability of carbohydrates as an energy source. Therefore, we fed a diet containing 33 wt% glucose to the HF-H group as complementary experiments. As a result, adequate glucose supplementation reduced cardiac fibrosis and cardiac function, while worsened life span, HbA1c levels and CHO consumption were not changed. Therefore, we hypothesized that there might be a change in the absorption of glucose in intestine or utilization ability of glucose in body another experiments were performed. 13C, which was released from mice after the oral administration of 13C glucose and measured by respiratory gas analysis, was significantly reduced in HF-H mice. The measurements the amount of 13C in feces revealed increased levels of unabsorbed glucose by linagliptin treatment in HF. In addition, GLUT2, a glucose transporter, in small intestine, was downregulated in the HF-H and the HF-HG groups. On the other hand, the cardiac uptake of Deoxy-D-glucose, 2-[1,2-3H(N)] (3H-2DG), which was injected from mice tail vein, was not different between in the HF-H group and in the HF control group. Taken together, linagliptin treatment may inhibit glucose transport in intestine in HF.

Conclusions

Linagliptin treatment exacerbated heart failure, resulting in shortened life span, worsened cardiac function, and fibrosis of the myocardium. DPP4 inhibitor may promote the cardiac cachexia and exacerbate heart failure at least, in part, through modification of glucose absorption and utilization.

Funding Acknowledgement

Type of funding sources: None.
Anti-inflammatory potential of SGLT2 inhibitors: a systematic review and meta-analysis of preclinical studies in rodents
Authors: Theofilis P , Sagris M , Oikonomou E , Antonopoulos A S , Siasos G , Tsioufis K , Tousoulis D
Published: October 2022

Background

Sodium-glucose cotransporter-2 (SGLT2) inhibition is at the forefront of scientific research due to their astonishing effect in ameliorating the prognosis of cardiorenal diseases. Several mechanisms have been proposed for these pleiotropic effects, including anti-inflammatory ones.

Purpose

Our systematic review and meta-analysis aimed to assess the effect of SGLT2 inhibitors on inflammatory markers in experimental rodent models.

Methods

We conducted a literature search to detect studies examining the effect of SGLT2 inhibitors on inflammatory markers [interleukin-6 (IL-6), C reactive protein (CRP), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP1)] in rodent animal models. Consequently, a meta-analysis of the included studies was performed, assessing the differences in the levels of the inflammatory markers between the treatment and the control group as its primary outcome. Studies not reporting in vivo experiments on mice/rats or not measuring inflammatory markers in the plasma or serum were excluded. Moreover, studies not administering SGLT2 inhibitors as treatment or simultaneously utilizing SGLT2 inhibitors with other treatment were further excluded. Effect sizes were pooled via random-effect model and results are expressed as standardized mean difference (SMD) with 95% confidence intervals (CIs). Correction for small-sample bias was also applied with the use of Hedge's g. I2 was chosen as the measure of between-studies heterogeneity.

Results

The systematic literature review yielded 30 studies whose meta-analysis suggested that treatment with an SGLT2 inhibitor resulted in decreases of IL-6 [standardized mean difference (SMD): −1.49, 95% CI −2.00 to −0.99, I2: 71%), CRP (SMD: −2.17, 95% CI −2.80 to −1.53, I2: 64%), TNF-α (SMD: −1.68, 95% CI −2.05 to −1.31, I2: 38%), and MCP1 (SMD: −2.04, 95% CI −2.91 to −1.17, I2: 66%) (Figure 1). The effect was of lesser magnitude in cases of empagliflozin use (p for interaction=0.03 to 0.05). Possible publication bias was noted in the case of IL-6 and CRP. The findings remained largely unaffected after the sensitivity analyses and the exclusion of outlying studies.

Conclusion

The present meta-analysis suggests that SGLT2 inhibition results in reduction of inflammatory markers in rodents, suggesting an anti-inflammatory mechanism of action

Funding Acknowledgement

Type of funding sources: None.