bluuebunny/crossref_metadata_2025 huggingface dataset:
High sensitivity cardiac troponin I in response to handgrip in women with signs and symptoms of ischemia with no obstructive coronary arteries
Authors: Wei J , Iribarren A , Nelson M D , Cook-Wiens G , Mastali M , Samuels B , Azarbal B , Anderson R D , Handberg E M , Pepine C J , Van Eyk J E , Bairey Merz C N
Published: November 2023

Background

Women with signs and symptoms of ischemia and no obstructive coronary arteries (INOCA) are suspected to have myocardial ischemia, ∼10% have prior myocardial scar often in the absence of acute myocardial infarction (AMI) diagnosis and the development of heart failure with preserved ejection fraction (HFpEF) is relatively frequent. The mechanisms contributing to AMI and HFpEF progression are poorly understood in INOCA.

Purpose

To compare clinical, invasive, and high sensitivity cardiac troponin I (hsTnI) parameters in women with INOCA at rest and in response to isometric handgrip exercise.

Methods

Women with suspected INOCA underwent cannulation of the coronary sinus (CS), handgrip exercise testing and serial CS plasma sampling before, after 3 minutes of isometric handgrip stress at 30% of maximal voluntary contraction, and after 5 minutes of recovery. hsTnI was measured using a commercial immunoassay (R-PLEX, Meso Scale Discovery, Rockville, MD) and compared using t-tests.

Results

A total of 54 women with complete invasive data were included with a mean age of 53 ± 10 years, mean body mass index 28 ± 7 kg/m2. 20 women (37% of the cohort) had detectable CS hsTnI from baseline. Among these women, median values were elevated in response to handgrip (Figure) (baseline median 33.75 (IQR 18.12-67.75) pg/mL vs peak handgrip median 56.23 (IQR 32.84-97.83) pg/mL, signed rank p=0.0007, baseline vs recovery median 52.35 (IQR 32.59-106.27) pg/mL, signed rank p=0.0002).

Conclusion

Among women with INOCA, handgrip stress leads to an increase in hsTnI in more than a third, demonstrating objective evidence of myocardial injury. More work is needed to better understand contribution of coronary microvascular dysfunction to HFpEF progression.
T regulatory cells lose their protective phenotype in patients with coronary artery disease (CAD)
Authors: Burkard A , Marchini T , Hansen S , Olawale Abogunloko T , Wolf D , Westermann D
Published: November 2023

Background

Atherosclerosis is accompanied by an auto-immune response that involves autoreactive T cells recognizing peptides from ApoB-100, the core protein of LDL-cholesterol. It has been suggested by preclinical animal models that regulatory T-cells (Treg) counteract this pathogenic response by secreting anti-inflammatory cytokines and direct contact inhibition at younger ages, but convert into pathogenic T cells, expressing pro-inflammatory cytokines such as IFN-g during aging. It has been proposed that Tregs numbers decrease in patients with coronary artery disease (CAD), but clinical evidence remains sparse. Here, we aimed to systematically characterize Tregs in human CAD.

Methods

Patients with a high cardiovascular risk undergoing coronary angiography were included in the Adaptive Immunity in Atherosclerosis (ANIMATE) exploratory biomarker trial at the University Heart-Centre Freiburg-Bad Krozingen, Germany. Peripheral blood mononuclear cells (PBMCs) were isolated from 359 patients. In a case-control design, we selected 80 patients that were matched according to their clinical parameters and divided into 4 groups: younger ≤ 55-year-old patients without (n=19) or with CAD (n=21), and older ≥ 70-year-old patients without (n=18) or with CAD (n=22). We studied Tregs using flow cytometry by targeting extracellular markers, transcription factors, and cytokine expression.

Results

Younger patients without or with CAD did not show significant changes in the frequency of circulating Tregs defined as CD127-/CD25+/FoxP3+ CD4+ T cells. Surprisingly, the number of Tregs in the older patients with CAD was significantly higher (increased by 2-fold) than in patients without CAD (p=0.0036), raising the question of an age-dependent changes in Tregs function that might affect CAD progression. Accordingly, Treg from older patients with CAD showed a lower baseline expression of atheroprotective IL-10, as well as higher IL-17, TNF-a, and INF-g protein expression as assessed by intracellular flow cytometry. Interestingly, Tregs frequency was significantly increased in patients with arterial hypertension, severe CAD and in patients with previous myocardial infarction. Treg frequencies positively correlated with plasma levels of anti-ApoB IgG autoantibodies. Conversely, Treg fractions negatively correlated with total cholesterol and LDL-C levels.

Conclusion

Here we show that in older patients with CAD, Treg are more frequent and have a more inflammatory phenotype than in controls without CAD. These data support the novel concept of Treg plasticity in CAD and show that protective autoimmunity is lost in the course of disease.
Association between smoking status and subclinical coronary atherosclerosis in asymptomatic men
Authors: Han S , Park G M
Published: November 2023

Background

We sought to evaluate the association between smoking status and subclinical coronary atherosclerosis on coronary computed tomographic angiography (CCTA) in asymptomatic men.

Methods

We analyzed 6,017 asymptomatic men (mean age 53.2±8.0 years) with no history of coronary artery disease who voluntarily underwent CCTA. Among the study participants, 1,200 (19.9%), 2,828 (47.0%), and 1,989 (33.1%) were categorized as never, former, and current smokers, respectively. The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and a degree of stenosis ≥50% was defined as significant. Logistic regression analysis was used to determine the association between smoking status and subclinical coronary atherosclerosis.

Results

Compared with never smokers, there were no statistically significant differences in the adjusted odds ratios (ORs) of former smokers for significant coronary artery stenosis, any coronary, calcified, and mixed plaque (p>0.05 for all). However, the adjusted ORs for non-calcified plaque (1.383; 95% confidence interval [CI] 1.024–1.866; p=0.034) were significantly higher in the former smokers. For current smokers, the adjusted ORs for signiﬁcant coronary artery stenosis (1.481; 95% CI 1.099–1.996; p=0.010), any coronary plaque (1.354; 95% CI 1.149–1.595; p<0.001), calciﬁed plaque (1.261; 95% CI 1.069–1.488; p=0.006), non-calciﬁed plaque (1.759; 95% CI 1.283–2.412; p<0.001), and mixed plaque (2.100; 95% CI 1.444–3.054; p<0.001) were signiﬁcantly higher than those of never smokers.

Conclusions

Among asymptomatic men, current smokers had a significant association with subclinical coronary atherosclerosis on CCTA. Former smokers were also associated with non-calciﬁed plaque, suggesting an increased cardiovascular risk.
Prognostic impact of percutaneous coronary intervention in chronic dialysis patients with acute myocardial infarction
Authors: Cosentino N , Trombara F , Bonomi A , Della Rocca M , Lucci C , Resta M , Moltrasio M , Agostoni P G , Genovesi S , Marenzi G
Published: November 2023

Background

Patients on chronic dialysis are less likely to receive percutaneous coronary intervention (PCI) for treatment of acute myocardial infarction (AMI). This is due to the lack of evidence from randomized trials, concerns about possible PCI-related side effects, and multimorbidity. Thus, routine use of PCI for treatment of dialysis patients with AMI remains an unresolved issue.

Purpose

We analyzed data of patients on chronic dialysis hospitalized with AMI (both ST-elevation myocardial infarction [STEMI] and non-ST-elevation myocardial infarction [NSTEMI]) from 2003 to 2018, by using the administrative Lombardy Health Database (Italy). Patients were grouped according to whether they were treated or not with PCI during hospitalization. The primary outcome was in-hospital mortality while 1-year mortality was the secondary endpoint.

Results

During the study period, 265,048 patients were hospitalized with AMI in Lombardy. Of them, 3,206 (1.2%) were on chronic dialysis (age 71±11; 72% males). Among dialysis patients, 44% were treated with PCI, while 54% underwent PCI among non-dialysis patients (P<0.0001). Dialysis was an independent predictor of conservative treatment with medical therapy only (OR 0.75 [95% CI 0.70-0.81]). In-hospital mortality in the dialysis cohort was 15%. It was significantly lower in patients treated with PCI than in those not treated with PCI (11% vs. 19%; P<0.0001). One-year mortality was 47% and it was lower in PCI-treated patients (33% vs. 52%; P<0.0001). The adjusted risk of the study endpoints was significantly lower in dialysis patients treated with PCI: OR 0.62 (95% CI 0.50-0.76) for in-hospital mortality; HR 0.63 (95% CI 0.56-0.71) for 1-year mortality. Similar results were found in STEMI and NSTEMI patients considered separately.

Conclusions

Our real-world data showed that in patients with AMI on chronic dialysis, PCI use is associated with a significant in-hospital and 1-year survival benefit.
Impact of volume and intensive cardiac care unit availability on mortality of patients with acute myocardial infarction- related cardiogenic shock treated at revascularization capable centers
Authors: Barrionuevo Sanchez M I , Viana Tejedor A , Ariza Sole A , Del Prado N , Garcia M , Sanchez Salado J C , Lorente V , Alegre Canals O , Llao Ferrando I , Bernal J L , Fernandez Perez C , De La Cuerda F J , Triguero Llonch L , Comin Colet J , Elola F J
Published: November 2023

Background

Cardiogenic shock (CS) is associated with a high mortality. The purpose of this study was to assess the impact of hospital structure-related variables as volume of CS cases and availability of intensive cardiac care unit (ICCU) on hospital mortality in patients with ACS-related CS treated at high complexity revascularization capable centers (RCC) from a large nationwide registry.

Methods

This was a retrospective observational study including consecutive patients with main or secondary diagnosis of CS (ICD-10 code: R57.0) and ST elevation myocardial infarction (STEMI). Patients discharged from Spanish National Healthcare System (SNHS) RCC were included (2016-2020). Transfers between hospitals were assigned to reference hospital. Exclusion criteria were <35 years, voluntary discharges or stays ≤ 1 day. Low- and high-volumen hospitals were classified by k-means clustering with 79 cases as the cut-off point selected.

The association between the volume of CS cases attended by each center, availability of ICCU and heart transplantation (HT) programs and in-hospital mortality was assessed by multilevel logistic regression models.

Results

The study population consisted of 3,065 CS-STEMI episodes, of whom 1,759 (57.4%) occurred in 26 centers with ICCU. Figure 1 shows the profile, management and complications of patients according to ICCU availability. A significantly greater number of circulatory support procedures a higher stroke incidence and a longer hospital stay were observed at hospitals with ICCU. A total of 17/44 hospitals (38.6%) were high-volume centers and 19/44 (43%) centers had HT programs available. Treatment at HT centers was not significantly associated with a lower mortality (p=0.264). Both high volume of cases and ICCU showed a non-significant trend to an association with lower mortality in the adjustment model (OR: 0.86 and 0.88, respectively). The interaction between both variables was significantly protective (OR 0.71; p=0.025). After propensity score matching mortality was lower in high volume hospitals with ICCU [OR = 0.79; p=0.0075] (figure 2).

Conclusions

Most CS STEMI patients from this series were attended at RCC with high volume of cases and ICCU available. The combination of high-volume and ICCU availability showed the lowest adjusted in-hospital mortality. These data should be taken into account when designing regional networks for CS management.Figure 1Figure 2
GDF-15 adds to GRACE 2.0 for long-term risk prediction in ACS but echocardiographic parameters do not: A SWEDEHEART prognostication study
Authors: Lenell J , Lindahl B , Erlinge D , Jernberg T , Spaak J , Baron T
Published: November 2023

Background

The risk stratification score GRACE 2.0 has lately been validated to predict all-cause death up to three years after acute coronary syndrome (ACS). GRACE 2.0 does not take important prognostic biomarkers and imaging measurements that may improve long-term risk prediction in to account. This study set out to evaluate the clinical value of such parameters analyzed on top of GRACE 2.0.

Methods

The study was performed in a subset of 773 patients from the TOTAL-AMI cohort with ACS subjects recruited from three Swedish hospitals between 2008 and 2014. Biomarkers were analyzed with a Proximity Extension Assay panel and the echocardiographic parameters, Left Ventricular Ejection Fraction (LVEF) and Global Longitudinal Strain (GLS), were assessed at a core lab. LVEF, GLS and two high yield biomarkers (NTproBNP and GDF-15) were analyzed with Cox proportional hazards regression by stepwise addition of each variable to a baseline model with GRACE 2.0. The C-index was assessed for each model. All models were adjusted for treatment with betablockers and/or RAAS-inhibitors. Outcome was all-cause death at three years.

Results

Forty-one patients had died at three years follow-up. The mean population age was 64 years and 77% were men. Median LVEF was 55 % (inter quartile range: 47-60). LVEF, GLS and GDF-15 all emerged as independent predictors of three-year death in the multivariable models with GRACE 2.0 and medical treatment. Only GDF-15 rendered substantial improvement in the C-index on top of GRACE 2.0 (0.755 to 0.810). The echocardiographic measurements did not improve prognostication on top of GRACE 2.0 and GDF-15.

Conclusions

GRACE 2.0 emerged as a strong long-term risk-predictor irrespective of the biomarkers and imaging measurements. Although LVEF, GLS and GDF-15 also emerged as independent predictors of three-year death only GDF-15 improved the C-index to an extent that may be considered clinically meaningful.
Normal values for left atrial strain, volume and function derived from three-dimensional echocardiography in the general population
Authors: Yafasov M , Javier Olsen F , Grundtvig Skaarup K , Hoejbjerg Lassen M , Dyrby Johansen N , Boje Jensen G , Schnohr P , Moegelvang R , Biering Soerensen T
Published: November 2023

Background

Three-dimensional echocardiographic (3DE) assessment of the left atrium (LA) is a new modality of potential clinical value. Age- and sex-based normative values are needed to benchmark these parameters for clinical use.

Methods

The study included 4,466 participants from a prospective longitudinal cohort study in the general population, among these 2,082 participants underwent 3DE of the LA. Exclusion criteria were hypertension, diabetes, ischemic heart disease, history of stroke, atrial fibrillation, heart failure, use of heart medication, chronic kidney disease, use of pacemaker, significant valve regurgitation or valve stenosis. Healthy participants were included to establish normative values for LA strain, volume, and function by 3DE. The effects of age and sex on 3DE parameters were also evaluated. Mean volumes per second for included participants was 62.4±5.7.

Results

After excluding participants with comorbidities, the final study population constituted of 979 healthy participants, median age was 44 years (interquartile range 32-56 years), 40% men. The median and limits of normality (2.5th and 97.5th percentiles) for functional and volumetric measures were: LA reservoir strain (LASr) 30.8% (18.4-44.2%), LA conduit strain (LAScd) 19.1% (6.8-32.0%), LA contractile strain (LASct) 11.7% (4.3-22.2%) (Figure 1) total LA emptying fraction (LAEF) 61.4% (47.8-71.0%), passive LAEF 37.7% (17.4-53.9%), active LAEF 37.4% (22.2-52.5%), LA minimum volume index (LAVimin) 10.2 (5.9-18.5) ml/m2, and LA maximum volume index (LAVimax) 26.8 (16.5-40.1) ml/m2 (Figure 2). All parameters changed significantly with increasing age (p value for all <0.001). Significant sex-specific differences were observed for all parameters except for active LAEF. Sex significantly modified the association between age and LASr (p for interaction<0.001), LAScd (p for interaction<0.001), LAVimin (p for interaction=0.037), and total LAEF (p for interaction=0.034).

Conclusion

We present age- and sex specific reference material including limits of normality for LA strain, volume, and function by 3DE.
Health outcomes after myocardial infarction: a population study of 56 million people in England
Authors: Hall M , Smith L , Wu J , Hayward C , Batty J A , Lambert P C , Hemingway H , Gale C P
Published: November 2023

Background

Information about the health outcomes of people with myocardial infarction (MI) is required to determine individual health needs, enable earlier detection and treatment of new onset disease, and inform health service planning. Although estimating 10 year cardiovascular disease risk is an established part of primary prevention, this is not the case for MI where comprehensive evidence for the long term impact of MI on subsequent major health outcomes is lacking. Such information is critical not only for the development of guideline recommendations, but also to underpin shared decision making.

Methods

This nationwide cohort study includes 34,116,257 adults in England, contributing 145,912,852 hospitalisations between 1st January 2008 and 31st January 2017 (final follow-up 27th March 2017). The absolute risk of 11 non-fatal health outcomes following MI (subsequent MI and new hospitalisations of heart failure, atrial fibrillation, cerebrovascular disease, peripheral arterial disease, severe bleeding, renal failure, diabetes, dementia, depression, cancer) and all-cause mortality was calculated via standardised cumulative incidence functions (CIFs) over nine years of follow-up. CIFs were estimated from flexible parametric survival models adjusted for age, sex, year, deprivation and competing risk of death. Risk-set matching by age, sex, and year of hospitalisation determined the relative risk of incident health outcomes compared with non-MI cases.

Findings: There were 433,361 individuals with MI (mean age 67·4 years (SD 14·4); n=286,728 (65·3%) male). Following MI, all-cause mortality was the most frequent event (CIF 37·8%, 95% CI 37·6─37·9%), followed by heart failure (29·6%; 29·4─29·7%), renal failure (27·2%; 27·0─27·4%), atrial fibrillation (22·3%; 22·2─22·5%), severe bleeding (19·0%; 18·8-19·1%), diabetes (17·0%; 16·9─17·1%), cancer (13·5%; 13·3─13·6%), cerebrovascular disease (12·5%; 12·4─12·7%), depression (8·9%; 8·7─9·0%), dementia (7·8%; 7·7─7·9%), subsequent MI (7·1%; 7·0─7·2%), and peripheral arterial disease (6·5%; 6·4─6·6%). Compared with 2,001,301 matched controls, first hospitalisation of all non-fatal health outcomes were increased after MI, except for dementia (HR 1·01; 0·99─1·02) and cancer (HR 0·56; 0·56─0·57).

Interpretation: Up to a third of patients with MI develop heart failure or renal failure, 7% have another MI and four in ten die within ten years. The incidence of heart failure, atrial fibrillation, cerebrovascular disease, peripheral arterial disease, severe bleeding, renal failure, diabetes, and depression, but not dementia or cancer, was higher than expected during the normal life course without MI. Improved post-MI preventative strategies, encompassing enhanced surveillance and detection, are required to tackle the high incidences of heart failure, atrial fibrillation, cerebrovascular disease, and renal failure observed in this population.
Long-term outcomes of patients with ischemia and no obstructive coronary artery disease (INOCA) - a systematic review and meta-analysis
Authors: Odanovic N , Schwann A , Zhang Z , Kapadia S , Kunnirickal S , Parise H , Tirziu D , Ilic I , Lansky A , Pietras C , Shah S
Published: November 2023

Background

Myocardial ischemia with no obstructive coronary artery disease (INOCA) is an increasingly recognized syndrome that encompasses coronary vasomotor disorders such as coronary microvascular dysfunction (CMD) and coronary vasospasm. However, the prognosis of patients with INOCA is not well defined.

Purpose

To perform a systematic review and meta-analysis of previous studies evaluating the long-term prognosis of patients with INOCA stratified by the underlying vasomotor disorder.

Methods

We searched Medline, Embase, Web of Science, and Cochrane databases combining terms for INOCA and outcomes to identify observational studies evaluating the prognosis of patients with INOCA published between 1984 and 2021. The primary outcomes were composite of all-cause death and MI, and major adverse cardiovascular events (MACE) at annual intervals for up to 5-year follow-up. Meta-analytic averages with 95% confidence intervals (CI) of the incidence of primary outcomes for INOCA, each INOCA endotype, and by method used to determine the diagnosis were calculated using the random effect models.

Results

We identified a total of 52 studies (19765 patients) meeting eligibility criteria. Of those, 22 included patients with vasospastic angina and 34 with microvascular angina. The rate of all-cause death and MI in the vasospastic angina group was 0.7 (95% CI 0.4-1.0)/100 patient-years [Figure 1] and the rate of MACE was 1.1 (95% CI 0.6-1.9)/100 patient-years [Figure 2]. For patients with microvascular angina the rate of all cause death and MI was 1.2 (95% CI 0.7-1.7)/100 patient-years [Figure 1] and the rate of MACE was 2.8 (95% CI 1.8-4.0)/100 patient-years [Figure 2]. Patients with evidence of microvascular dysfunction by non-invasive (CFR) or invasive (CFR, IMR, TIMI frame count) criteria had 2.7 times higher all-cause death and MI rates than patients whose diagnosis was established solely based on an abnormal exercise or imaging stress test (2.6 (95% CI, 0.8-5.1) vs. 0.7(95% CI, 0.4-1.2)/100 patient-years, p=0.034).

Conclusions

Overall, patients with INOCA have a low rate of MACE events or death, although there is heterogeneity based on the underlying phenotype. Patients with vasospastic angina have a relatively benign long-term prognosis, whereas patients with microvascular angina have a significantly higher rate of MACE at long-term follow-up. Among patients with microvascular angina, those with objective evidence of abnormal microvascular function (such as reduced CFR) had 2.7 times higher rates of all-cause death and MI.Incidence of all cause death and MIIncidence of MACE
Declining trends of mortality from ischemic heart disease in European Union 28 countries from 2011 to 2017
Authors: Venturoli E , Cimaglia P , Matese C , Pangallo G , Campo G , Marco Z
Published: November 2023

Aims

We sought to analyze the mortality trend due to ischemic heart disease (IHD) in Europe between 2011 and 2017.

Methods

We used the free publicly available EUROSTAT death certificate database to examine age-adjusted IHD mortality rates (per 100.000 people) and relative average annual percentage change (AAPC) across all European Union 28 countries (EU28) from 2011 to 2017 using the International Classification of diseases, Tenth Revision (ICD-10) codes I20-I25. Deaths occurring before the age of 65 were defined as premature deaths. To calculate annual trends in IHD-related mortality, we assessed the average annual percent change (AAPC) and relative 95% confidence intervals (CIs) using Joinpoint regression analysis (Joinpoint Regression Program version 4.9.1.0 (National Cancer Institute, Bethesda, USA).

Results

Over the study period, 4,478,563 deaths (2,386,442 males) due to IHD occurred in EU28. Age-adjusted IHD death rates steadily decline over the study period from 139.9 to 118.2 per 100,000 people [AAPC: -3.0 (95% CI: -3.8 to -2.2), p<0.0001]. Such reduction was more pronounced in women (from 186.6 to 161.1 per 100,000 people) [AAPC: -3.6 (95% CI: -4.6 to -2.5), p<0.001] than in men (from 105.4 to 86.4 per 100,000 people) [AAPC: -2.6 (95% CI: -3.2 to -2.0), p<0.001] (Figure 1). Moreover, age-adjusted IHD death rates resulted higher in subjects age ≥65 years old; however, a more pronounced decrease was observed in those <65 years (from 21.3 to 17.8) [AAPC: 3.0-, 95% CI: -3.5 to -2.6), p<0.0001] compared to those age ≥65 years old (from 626.3 to 532.4) [AAPC: -2.7, 955 CI: -3.3 to -2.0), p<0.0001).

Conclusions

In EU28, IHD-related mortality declined from 2011 to 2017, especially in women and in subjects aged <65 years old.
Introducing the original web score calculator GARDENIA risk score for severe coronary artery (re)stenosis
Authors: Sarenac D , Tatomir U T
Published: November 2023

Background/Introduction

There are a large number of scores that are used for cardiovascular risk assessment and different online calculators are used to perform it. Risk prediction models provide risk estimates that can assist our decision making and improve guiding for individual clinical outcomes and personalized preventive care.

Purpose

GARDENIA score is designed to predict highly suspicious probability of significant coronary stenosis in patients without proven CAD or those who have already been revascularized.

Methods

GAR²DE²NIA is an acronym that incorporates following parameters :

Gender, Age, Renal impairment, Respiratory disease, Diabetes Melittus, Echo abnormalities, ECG abnormalities, New symptoms, Ischaemia, Atrial fibrillation.

The pointing scale was formed (-1 to 2) on the personal interpretation of evidence based data and is applied and designed as web calculator. The established cut-off values for the risk of significant coronary stenosis is 4. For values below 4, the probability of significant CAD is low, below 0 is very low, equal or greater than 4 significant CAD is high and above 8 is very high.

Results

Standard statistical formulas for sensitivity, specificity, PPN and NPV were used ( sensitivity 91,43%, specificity 73,33%, PPV 88,89, NPV 78,57). Estimated pilot sample size of 100 patients, was tested on patients cohort treated at the Institute for Cardiovascular Disease Dedinje in the year of 2022.

Conclusion

This original score is to be checked throughout everyday clinical practice. It is easy to use. It can help in decision making in risk stratification and further treatment of the patients who has never been to cardiologist before, those who has already been revascularized and are symptomatic again or need any kind of non cardiac surgery and the patients we have doubts about what to do next.GARDENIA score calculator
Coronary vasomotor disorders in ANOCA patients: insights from the CADOSA registry
Authors: La S , Tavella R , Wu J , Zeitz C , Arstall M , Sinhal A , Worthley M , Beltrame J
Published: November 2023

Background

Patients with Angina and Non-Obstructive Coronary Arteries (ANOCA), require further investigation to elucidate the underlying cause of their symptoms (i.e. functional coronary angiography to assess the presence of coronary vasomotor disorders) but are frequently discharged with the non-diagnostic label of ‘unspecified chest pain’.

Purpose

To compare the 3-year clinical outcomes (mortality and readmission) in ANOCA patients with a ‘coronary vasomotor disorder’ diagnosis with those discharged with an ‘unspecified chest pain’ diagnosis.

Methodology

Using the CADOSA (Coronary Angiogram Database of South Australia) registry, consecutive patients undergoing coronary angiography between 2012-2018 were included. Among 8,932 symptomatic patients undergoing elective angiography, 2,245 were ANOCA (stenosis <50%) patients. Of this cohort, 170 (8%) had documented coronary vasomotor diagnosis (vasospastic angina 3% and microvascular angina 5%), and the remaining 2,075 (92%) were discharged with ‘unspecified chest pain’.

Results

In the overall ANOCA cohort (n=2,245, 61±11 years, 59% female) only 6% underwent functional coronary angiography. Compared to the unspecified chest pain cohort, those with a coronary vasomotor disorder diagnosis were (a) younger (61±11 vs 58±11, p<0.05), (b) more often to present to the emergency department with chest pain in the year prior to their coronary angiogram (19% vs 35%, p<0.05), (c) more likely prescribed anti-ischaemic medications at discharge (74% vs 88%, p<0.05), but (d) less likely to be discharged with cardioprotective medications (81% vs 73%, p<0.05). At 3-year follow-up, all-cause mortality was similar between those with coronary vasomotor diagnosis and those with unspecified chest pain (1% vs 2%, p>0.05), but those with a coronary vasomotor disorder were more likely to (i) present to the emergency department for chest pain (38% vs 16%) and (ii) be readmitted for chest pain (29% vs 10%), compared to those with unspecified chest pain, all p<0.05.

Conclusion

In this analysis of real-world practice, few ANOCA patients undergo functional angiography. Consequently, many ANOCA patients are discharged without thorough investigation to aid in appropriate diagnosis. Even when a diagnosis is made, ongoing symptom burden is severe. This study highlights the need to both appropriately investigate and identify patients at high risk for ongoing high symptom burden so treatment can be personalised to optimise management.
Does ischaemia testing predict worse adverse outcomes in ANOCA patients?
Authors: La S , Tavella R , Wu J , Zeitz C , Arstall M , Sinhal A , Worthley M , Beltrame J
Published: November 2023

Background

Following the recent ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) it was revealed that the extent of ischaemia was not associated with an increased risk for adverse outcomes after adjustment for coronary artery disease (CAD) severity. How the extent of ischemia applies to outcomes for patients with stable angina without obstructive CAD is unknown.

Purpose

To determine if the presence of ischaemia impacted on 3-year clinical outcomes (mortality and readmission) in patients with Angina and Non-Obstructive Coronary Arteries (ANOCA).

Methods

ANOCA was defined as those presenting with chest pain symptoms consistent with angina and undergoing an elective angiogram. All consecutive ANOCA (stenosis <50%) enrolled in the CADOSA (Coronary Angiogram Database of South Australia) Registry between 2012-2018 were included. CADOSA captures all public hospital patients undergoing coronary angiography.

Results

Among 8,932 symptomatic patients undergoing elective angiography, 1,169 patients (60±11 years, 59% female) with ANOCA underwent ischaemic stress testing prior to angiography. Of these patients, 185 (16%) had no evidence of ischaemia (ANOCA ischaemia negative), and 984 (84%) had documented evidence of ischaemia (ANOCA ischaemia positive). The ANOCA ischaemic negative patients (relative to the ANOCA ischaemic positive patients) were (a) younger (58±11 vs 61±11, p<0.05), (b) in the year preceding diagnostic angiography, more often presented to the emergency department with chest pain (36% vs 21%, p<0.05) and required hospital admission (28% vs 14%, p<0.05), and (c) had more disabling angina, as assessed by the Canadian Cardiovascular Society Score (CCSS; CCSC-IV 19% vs 13%, p>0.05). At 3-year post-angiography follow-up, (i) cardiac mortality was similar (ANOCA negative 0% vs ANOCA positive 0.1%, p>0.05), but the ANOCA negative patients were more likely to present to the emergency department (26% vs 14%, p< 0.05) and require hospital readmission (18% vs 8%), compared to the ANOCA positive patients.

Conclusion

Patients with ANOCA and negative ischaemic testing have more disabling symptoms, with frequent emergency department presentations and readmissions, compared to those with a positive ischaemic test. Hence the presence of ischaemia on stress testing is not predictive of clinical outcomes and further investigation is required to identify predictors of outcomes in ANOCA.
Comparing the effect of obesity on major adverse cardiovascular events in patients hospitalized with coronavirus disease-2019 (COVID-19): insights from the national inpatient sample (NIS) database
Authors: Gwira-Tamattey E , Gajjar R , Deangelo S , Shoura S , Nissan N , Asemota I
Published: November 2023

Introduction

Recent studies have shown an ‘obesity paradox,’ which refers to improved hospital outcomes and prognosis in obese individuals when compared to their non-obese counterparts. This paradox is evident when myocardial infarction (MI), venous thromboembolism (VTE), and cardiovascular mortality are considered. There is limited information extrapolated from large inpatient databases describing inpatient hospital outcomes of patients with obesity and concomitant COVID-19.

Purpose

To determine the association of obesity with inpatient mortality of acute (MI), cerebrovascular accidents (CVA) and cardiovascular death in patients with COVID-19 using the NIS database.

Methods

The NIS database for calendar year 2020 was queried to identify adult hospitalizations with a primary diagnosis of COVID-19 and a secondary diagnosis of obesity. Cases were identified using International Classification of Diseases – 10 Clinical Modification (ICD-10-CM) codes. The primary outcome was inpatient mortality; secondary outcomes were length of stay (LOS), total hospital charge (THC), and inpatient complications. Linear, univariate, and multivariate logistic regression were used to analyze the outcomes and adjust for confounders.

Results

A total of 1,050,045 hospitalizations for COVID-19 were identified, 292,800 (27.9%) of which had the co-diagnosis of obesity. Out of the identified hospitalizations with COVID-19 and obesity, 29,290 (10%) died. After multivariate adjustment for confounding variables, obesity was associated with increased inpatient mortality (adjusted odds [aOR] 1.37; 95% confidence interval [CI] 1.32-1.42, p < 0.001), while CVA and acute MI were negatively associated with obesity (aOR 0.81; CI 0.68-0.97, p = 0.023 and aOR 0.92; CI 0.86-0.99, p = 0.026, respectively). Additionally, obesity was associated with multiple inpatient complications, including but not limited to: sepsis (aOR 1.44; CI 1.38-1.51, p < 0.001); acute respiratory failure (aOR 1.46; CI 1.43-1.50, p < 0.001), need for intubation (aOR 1.66; CI 1.60-1.73, p < 0.001), need for mechanical ventilation (aOR 1.69; CI 1.62-1.75, p < 0.001); cardiac arrest (aOR 1.32; CI 1.23-1.42, p < 0.001); and need for cardiopulmonary resuscitation (aOR 1.37; CI 1.26-1.50, p < 0.001).

Conclusion

The findings of this study are inconsistent with the obesity paradox. Obese patients hospitalized with COVID-19 had an increased association of mortality and inpatient complications; however, there was a negative association between obesity and CVA and acute MI.
Left atrial appendage geometry and function using transesophageal three-dimensional echocardiography in atrial fibrillation: a new approach to characterize left atrial thrombogenic milieu
Authors: Soulat-Dufour L , Simon T , Lang S , Ederhy S , Adavane-Scheuble S , Chauvet-Droit M , Capderou E , Arnaud C , Addetia K , Lang R , Scheuble A , Hammoudi N , Beraud A , Boccara F , Cohen A
Published: November 2023

Background

Little data is available on the evaluation of left atrial appendage (LAA) geometry and function using three-Dimensional (3D) transoesophageal echocardiography (TEE).

Purpose

We hypothesized that 3D LAA geometry evaluated using dedicated TEE software could be integrated in the evaluation of the thromboembolic milieu in patients hospitalized for atrial fibrillation (AF).

Methods

We prospectively studied 206 hospitalized patients with AF with two-dimensional transthoracic echocardiography (TTE) and 3D TEE of the LAA within 24 hours of admission. 3D parameters were analysed off-line using Tomtec software (4D Cardio-View, Generic Volume, Philips) (Figure 1). Patients were divided into two groups according to the presence (n = 35) or absence (n = 171) of LAA sludge/thrombus on admission.

Results

Patients with LAA sludge/thrombus had more frequently a history of heart failure together with higher values of BNP, CRP and hemoglobin. These patients received less frequently angiotensin II receptor antagonist treatment on admission. Concerning the echocardiographic characteristics, patients with LAA sludge/thrombus exhibited higher left atrial (LA) volume, lower left ventricular ejection fraction (LVEF) and cardiac output. In the 2D TEE study they had lower LAA emptying and filling flow velocities compared to those without sludge/thrombus. 3D TEE showed overall higher 3D end-systolic (ES) and end-diastolic (ED) LAA measurements (ostium area, length, volume), and more frequently the absence of a chicken wing morphology. There were no intergroup differences regarding the number of LAA lobes (Table 1).

Conclusion

3D characterization of LAA geometry and function depicts a degree of appendage remodeling in AF that appears to be associated with the degree of thrombogenicity. Further investigation is needed to determine the impact of this remodeling on outcomes in these patients.
Prevalence of traditional cardiovascular risk factors in subjects with unrecognized myocardial infarction: a systematic review and meta-analysis
Authors: Van Oortmerssen J A E , Ntlapo N , Tilly M J , Boersma E , Roeters Van Lennep J E , Kavousi M
Published: November 2023

Background

Unrecognized myocardial infarction (UMI) is defined as myocardial ischemia (MI) that was not recognized as such during the acute phase, but later identified by pathological Q waves on an electrocardiogram (ECG), myocardial imaging evidence, or pathological findings on autopsy. Previous studies found that UMI accounts for up to 50% of all MIs, especially in women and the elderly. UMI is associated with increased risk of adverse cardiovascular outcomes and mortality, similar to subjects with recognized myocardial infarction (RMI). However, associated risk factors of UMI remain understudied.

Purpose

We aimed to summarize and combine the evidence on the associations between traditional cardiovascular risk factors and UMI in the general population. We also sought to assess sex differences in these risk factors.

Methods

A systematic search of general population-based cohort studies investigating UMI and reporting traditional cardiovascular risk factors of subjects with UMI and subjects without MI was performed through Embase, Medline, and Google Scholar up to 7 February 2023. Study selection, data extraction and risk of bias were assessed independently by 2 authors. Pooled standardized mean differences (SMD) or odds ratios (ORs) with 95% confidence intervals (CI) of traditional cardiovascular risk factors were determined, comparing UMI to subjects without MI. Random-effects meta-analyses were performed. If data allowed, analyses were repeated stratified by sex.

Results

A total of 17 studies were included involving 216,858 individuals, among which 4,717 experienced UMI (mean age 66.1±8.3 year, 49% women). UMI was diagnosed through ECG in 14 studies and MRI in 3 studies. All studies established diagnosis of UMI and risk factors in a cross-sectional manner. Compared to subjects without MI, individuals with UMI demonstrated significantly larger values of BMI (SMD 0.05, 95% CI 0.03-0.08) and SBP (SMD 0.25, 95% CI 0.12-0.39), and higher prevalence of hypertension (OR 1.71, 95% CI 1.07-2.72) and diabetes mellitus (DM) (OR 1.81, 95% CI 1.40-2.34). Risk factors were reported stratified by sex in 3 studies. The relation between hypertension and UMI was stronger in women than in men. In contrast, the association of DM with UMI was weaker in women. However, these differences were statistically non-significant.

Conclusion

BMI, SBP, hypertension and diabetes mellitus are associated with an increased risk of UMI, similar to RMI. Limited evidence from studies stratified for sex indicate a differential impact of traditional risk factors on UMI in women and men.
Independent causal effect of remnant cholesterol on atherosclerotic cardiovascular outcomes: a Mendelian randomization study
Authors: Grzelakowska K , Vine D , Proctor S , Raggi P , Kubica J , Navarese E P
Published: November 2023

Background

Observational studies suggested that residual risk of cardiovascular events following LDL-cholesterol (LDL-C) lowering may be linked to remnant cholesterol (RC).

Purpose

We conducted a large-scale Mendelian Randomization (MR) study to investigate the causal role of RC to predict coronary artery disease (CAD), myocardial infarction (MI) and stroke risk.

Methods

Outcome sources included 19,273 subjects of European ancestry from 14 cohorts, as well as data in 115,078 individuals from the OpenGWAS public data infrastructure. Over 12,000,000 SNPs were screened. We estimated the genetic association with outcomes from the Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium, the Metastroke consortium as well as the Global Lipids Genetics Consortium. Our approach was to use genetic variants as instruments, thereby minimizing residual confounding, and reverse causation biases of observational studies.

Results

By leveraging data from a combined sample of ∼917,000 participants, we found evidence for a significant causal effect of RC on the risk of CAD (OR 1.51 per each mg/dL unit increase in RC, 95% CI 1.42–1.60), MI (OR 1.57, 1.21–2.05) and stroke (OR 1.23,1.12–1.35). There was no evidence of pleiotropy. Mediation analysis showed that the total effect of RC on CAD and MI was mainly direct: ORDirect 1.49 (1.37-1.61) for CAD and ORDirect 1.80 (1.70-19.1) for MI without a meaningful indirect effect exerted on these outcomes via the LDL-C mediator. Lifelong genetic inhibition of RC led to a 40% MI risk reduction which is superior to any intensity of pharmacological reduction from clinical trials with an average 3.5 years follow-up.

Conclusions

This large-scale MR study showed a robust genetic causal association between RC and cardiovascular outcomes. The effect on CAD and MI is independent of LDL-C. Early screening for RC along with long-term inhibition of RC should be the focus of future therapeutic interventions.
Refining the prognosis of patients with AF using 3D transesophageal echocardiography of the left atrial appendage
Authors: Soulat-Dufour L , Simon T , Lang S , Ederhy S , Adavane-Scheuble S , Chauvet-Droit M , Capderou E , Arnaud C , Addetia K , Lang R , Scheuble A , Hammoudi N , Beraud A , Boccara F , Cohen A
Published: November 2023

Background

Left atrial (LA) volume is considered an echocardiographic marker of thrombosis risk and prognosis in atrial fibrillation (AF). Limited data is available on the prognostic value of left atrial appendage (LAA) volume in AF as evaluated with three-dimensional (3D) transoesophageal echocardiography (TEE).

Purpose

We hypothesized that 3D LAA volume is associated with prognosis in patients hospitalized with AF.

Methods

We prospectively evaluated 206 patients hospitalized for AF with two-dimensional transthoracic echocardiography (TTE) and 3D TEE of the LAA within 24 hours of admission. 3D parameters were analysed off-line using Tomtec software (4D Cardio-View, Generic Volume, Philips). The primary composite outcome was all-cause death during at 2 years follow up.

Results

The median age of the study group was 66.3 ± 11.5 years with 129 (62.6%) men. In the global population, at admission, the median 3D LAAV was 9.02 (6.96-12.15) ml. Patients were divided into two groups according to the median 3D LAAV: Group 1: LAAV < 9ml (103 patients) and Group 2: LAAV ≥ 9ml (103 patients). Patients with LAAV ≥ 9ml had more frequently a history of heart failure and chronic obstructive pulmonary disease. There were no significant intergroup differences in CHA2DS2-VASc score. Patients with LAAV ≥ 9ml had higher values of BNP and CRP and lower LVEF, higher LA volumes, higher E/e’, lower LAA emptying flow velocity, and higher 3D ES LAA ostium area. There were no statistical differences in LAA spontaneous echo contrast and LAA morphology between groups (Table 1). Kaplan–Meier curves demonstrated a significant difference in survival according to the 3D ES LAAV: 3 deaths occurred in the group with 3D ES LAA volume < 9mL and 11 in the group with 3D ES LAA Volume≥9mL (p=0.0315) (Figure 1).

Conclusion

Among LAA parameters, 3D LAA end-systolic volume is significantly associated with a worse outcome in patients with AF. Further investigations are needed to evaluate this unique parameter against usual geometric and functional LA/LAA parameters.
New-onset atrial fibrillation in chronic coronary syndrome outpatients. Insights from the international CLARIFY registry
Authors: Gautier A , Picard F , Ducrocq G , Elbez Y , Fox K M , Ferrari R , Ford I , Tardif J C , Tendera M , Steg P G
Published: November 2023

Background and Aims

Data on new-onset atrial fibrillation (NOAF) in patients with chronic coronary syndromes (CCS) are scarce. This study aims to describe the incidence, predictors and impact on cardiovascular outcomes of NOAF in CCS patients.

Methods

Data from the international (45 countries) CLARIFY registry (prospeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) were used. Among 29,001 CCS outpatients without previously reported AF at baseline, patients with at least one episode of AF/flutter diagnosed during 5-year follow-up were compared with patients in sinus rhythm throughout the study.

Results

The incidence rate of NOAF was 1.12 [95% confidence interval (CI) 1.06-1.18] per 100 patients-year (cumulative incidence at five years: 5.0%). Independent predictors of NOAF were increasing age, increasing body mass index, treated hypertension, history of peripheral artery disease, alcohol intake and low left ventricular ejection fraction, while high triglycerides were associated with lower incidence. NOAF was associated with a substantial increase in the risk of adverse outcomes, with adjusted hazard ratios of 2.52 (95%CI 2.11-3.01) for the composite of cardiovascular death, myocardial infarction or stroke, 3.22 (95%CI 2.63-3.94) for cardiovascular death, 1.55 (95%CI 1.08-2.22) for myocardial infarction, 2.80 (95%CI 2.0-3.91) for stroke, 2.64 (95%CI 2.23-3.11) for all cause death, 9.38 (95%CI 8.02-10.97) for hospitalization for heart failure and 4.33 (95%CI 2.94-6.39) for major bleeding.

Conclusion

Among CCS patients, NOAF is common and is strongly associated with worse outcomes. Whether more intensive preventive measures and more systematic screening for AF would improve prognosis in this population deserves further investigation.FlowchartGraphical Abstract
Effect of LPA gene on CAD risk among diabetic patients
Authors: Sousa F , Mendonca I , Sa D , Temtem M , Henriques E , Freitas S , Rodrigues M , Borges S , Guerra C , Ornelas I , Drumond A , Sousa A C , Dos Reis R P
Published: November 2023

Introduction

Previous research reported that the LPA gene is a strong and independent predictor of CAD in non-diabetic patients but not in patients with type 2 diabetes mellitus (T2DM). These results suggest that the LPA gene might contribute less to CAD risk in patients with T2DM than in the general population.

Objective

Investigate, in our population, the association between the LPA gene variant rs3798220 T>C and CAD risk among the total, diabetic and non-diabetic populations.

Methods

3161 individuals (1724 coronary patients and 1437 controls) were genotyped for LPA rs3798220 T>C. This variant has a MAF <2%; hence the risk homozygous CC is a rare genotype, and we used the heterozygous CT in our analysis. Bivariate and multivariate logistic regression evaluated LPA heterozygous genotype (CT) and CAD risk in the whole population, in the group with T2DM (n=782) and without T2DM (n=2379). The multivariate model was adjusted to the main traditional risk factors for CAD.

Results

After multivariate analysis, LPA CT remained a strong and independent predictor of CAD risk in the whole and non-diabetic populations (OR=2.12; 95%CI: 1.43-3.14; p<0.0001 and OR=2.56; 95%CI: 1.64-4.00; p<0.0001, respectively). However, this association was less pronounced in the diabetic population (OR= 1.12; 95%CI: 0.47-2.65; p=0.799).

Conclusions

Our results show that the effect of the homozygous LPA genotype on CAD risk among the diabetic population might differ from that in non-diabetics, with less impact on diabetic patients. Many aspects of the genetic regulation of Lp(a) in diabetics are not fully understood, and other genetic and environmental factors may be crucial to CAD risk in diabetes, such as those linked to insulin resistance and hyperglycemia.