bluuebunny/crossref_metadata_2025 huggingface dataset:
The dynamic increment of epicardial adipose tissue is associated with reverse remodeling after guideline-directed medical treatment in dilated cardiomyopathy patients
Authors: Xu Y , Guo J J , Li Y J , Chen Y C
Published: October 2024

Background/Introduction

Epicardial adipose tissue (EAT) accumulation is associated with adverse prognosis in patients with HFpEF and a better prognosis in HFrEF patients. Whether EAT is playing a protective role in dilated cardiomyopathy (DCM) patients have been described sparingly.

Purpose

Aim to explore whether the epicardial fat would change along with the dynamic changes in cardiac function and volumes after receiving guideline-directed medical therapy (GDMT) in patients with DCM.

Methods

We prospectively enrolled 232 DCM patients who underwent complete baseline and follow-up Cardiac magnetic resonance (CMR) examinations. The measurement of the epicardial fat composition includes epicardial fat thickness, paracardial fat thickness, and paracardial fat volume, while the measurement of body fat composition includes subcutaneous and visceral abdominal fat, while We used univariable and multivariable logistic regression to evaluate the association between different body and cardiac fat depots with the changes in bi-ventricular structure (delta indexed EDV) and function (delta EF).

Results

The study included 232 patients (mean age 46.1±14.1 years, 157 (67.7%) males). After GDMT, we found that the visceral fat thickness and EAT (thickness and volume) tend to significantly increase. The increase in the (left ventricular reverse remodeling) LVRR group was significantly higher compared with the non-LVRR group. Independently with the changes of BMI and body fat depots, the increment of EAT was associated with the improvement in bi-ventricular function and volumes (significantly positively correlated with the improvement of LVEF (r = 0.499, p < 0.001), and RVEF (r = 0.482, p < 0.001), negatively correlated with delta LVEDVi (r = -0.407, p < 0.001), delta RVEDVi (r = -0.305, p < 0.001)).

Conclusions

After GDMT, the increment of EAT was positively correlated with the improvement of bi-ventricular structure and function, independent of the changes in BMI and body fat depots.Graphic Abstract
Ischemic and bleeding risk after ST-segment elevated myocardial infarction in patients with active cancer
Authors: Dafaalla M , Costa F , Jia H , Wijeysundera H , Rashid M , Graham M , Wojakowski W , Chieffo A , Mintz G , Mamas M
Published: October 2024

Background

Treatment of patients with cancer presenting with ST-elevation myocardial infarction (STEMI) is complex given the increased risk of both thrombotic and major bleeding complications. We evaluated the risk of major bleeding and re-infarction in patients with or without cancer following admission with STEMI

Methods

A nationally-linked cohort of STEMI patients between January 2005 and March 2019 were obtained from the UK Myocardial Infarction National Audit Project (MINAP) registry and the UK national Hospital Episode Statistics Admitted Patient Care (HES APC) registry. Cox proportional hazard models were used, and Kaplan-Meier survival and cumulative survival curves were constructed.

Results

A total of 322,776 STEMI indexed admissions were identified between Jan 2005 and March 2019. Of those, 7050 (2.2%) patients were diagnosed with active cancer. Cancer patients were older with more cardiovascular comorbidities. Cancer patients received invasive coronary angiography (62.2% vs 72.7%, p<0.001) and PCI (58.4% vs 69.5%) less often compared to patients without cancer and were less likely to be prescribed DAPT (85% vs 95.4%). Major bleeding rate at one year was higher in cancer patients (6.5% vs 3.5%) while re-infarction rates were similar (cancer 5.7%, no cancer 5.1%). Adjustment for differences in baseline covariates, a similar risk of re-infarction (SHR 1.10, 95% CI 0.94-1.27) and a 50% increased risk of major bleeding (SHR 1.49, 95% CI 1.30-1.71) was observed in cancer patients.

Conclusion

Compared to non-cancer patients, cancer patients have a higher risk of major bleeding but not of re-infarction. Mitigating bleeding risk in STEMI patients with cancer is of paramount importance to improve outcomes.bleeding risk at 1 yearRe-infarction risk at 1 year
Influence of chronic dietary nitrate on downstream atherogenic metabolites and the enteral microbiome
Authors: Messiha D , Rinke M , Schultz Moreira Amos A , Tratnik A , Hendgen-Cotta U B , Lortz J , Hogrebe K , Kehrmann J , Buer J , Rassaf T , Rammos C
Published: October 2024

Background

Inorganic nitrate, which is abundant in leefy green vegetables and mediates cardioprotective effects through nitric oxide related pathways. The enteral microbiome is an emerging key player in cardiovascular diseases and depends on dietary habits. Whether dietary inorganic nitrate influences atherosclerosis-associated microbiome dependent metabolites like short chain fatty acids (SCFA) and trimethylamine N-oxide (TMAO) has not been elucidated so far.

Purpose

Aim of this study was to investigate the influence of dietary anorganic nitrate intake on atherosclerosis-associated metabolites and the enteral microbiome composition in a healthy trial cohort.

Methods

In this double-blind randomized controlled trial, we included 30 healthy volunteers, who either received dietary nitrate (0,12 mmol/kg bodyweight) or placebo (equimolar amounts of sodium nitrate) for 30 days. The microbiome metabolites TMAO and SCFA were analysed. Furthermore, upstream enteral microbiome composition was analysed by 16S-rRNA sequencing at baseline and follow-up.

Results

Systolic blood pressure significantly decreased after nitrate supplementation (baseline 124,73 mmHg vs follow up 120 mmHg, p < 0.05) with no change in controls. Dietary nitrate supplementation significantly increased TMAO levels (control follow-up 343,88 µg/L vs nitrate follow-up 481,15 µg/L, p < 0.05), while SCFA levels remained unchanged. Mechanistically a change in enteral microbiome composition after dietary nitrate supplementation with decreased abundance of the gram-negative bacteria Akkermansia muciniphila was detected, while overall Shannon diversity, richness and evenness did not differ.

Conclusions

In conclusion, our results indicate that dietary nitrate supplementation alters the enteral microbiome with impact on proatherogenic metabolites. Further work is warranted to investigate the causal relationship between dietary nitrate, the microbiome, downstream metabolites, and the clinical relevance of those findings in a cardiovascular diseased cohort.
The clinical impact of cardiac magnetic resonance imaging upon suspected myocardial infarction with non-obstructive coronary artery disease
Authors: Giudicatti L , Telyuk P , Pasupathy S , Gilbert G , Maredia N , Spiro J , Beltrame J , Hillis G , Austin D , Dwivedi G , Rajwani A
Published: October 2024

Background

Cardiac magnetic resonance (CMR) may identify the underlying pathology in myocardial infarction with non-obstructed coronary arteries (MINOCA), however there are scant prospective data evaluating the more important measure of actual change in diagnosis and management consequent to CMR.

Purpose

To evaluate impact of CMR in MINOCA upon diagnosis, diagnostic certainty and management, adjudicated by treating physicians to minimise investigator bias.

Methods

Prospective, multi-center international pre- and post-CMR study of suspected MINOCA. Physician diagnosis, diagnostic certainty and intended management were established by questionnaire before and after CMR. The primary outcome was change in diagnosis or management. Secondary outcomes were change in diagnosis, change in management, change in diagnostic certainty, and number-needed-to-test for de-prescription of dual antiplatelet therapy (DAPT). Potential predictors of impactful CMR were evaluated by multivariable logistic regression analysis.

Results

320 patients referred by 74 clinicians underwent CMR; mean age 55.6 (12.3) years, 48.1% female. CMR was conducted at median 11 days (IQR 6-19) post presentation. CMR led to change in diagnosis or management in 62.8% (95% CI 57.4% - 68.2%, p<0.0001) and significantly increased diagnostic certainty [8/10 post-CMR (5-9) vs 6/10 pre-CMR (4-7), p<0.0001]. Predictors of impactful CMR on multivariable analysis were early CMR (≤14 days), absence of atheroma on coronary angiography, significant pre-CMR diagnostic uncertainty (≤5/10), and a history of vascular disease. DAPT was deprescribed or modified to single antiplatelet in 61.7% patients. The number-needed-to-test to deprescribe DAPT was 2.6 (and 1.6 if a myocardial infarction mimic was co-suspected pre-CMR), which has important cost-benefit implications for CMR in MINOCA.

Conclusions

In this first prospective multi-centre study of CMR in MINOCA where diagnostic utility was adjudicated by the treating physicians, CMR was associated with frequent and significant changes in diagnosis, clinician certainty and clinical care, including frequent de-prescription of DAPT. Early CMR is to be encouraged, particularly in patients where there is significant diagnostic uncertainty and no atheroma on coronary angiography.
Impact of addressing modifiable risk factors on the 10-year risk of cardiovascular disease in individuals with familial hypercholesterolemia: a causal analysis utilising UK biobank
Authors: Stevens C , Vallejo-Vaz A J , Sharabiani M T A , Brandts J , Barkas F , Elshorbagy A , Mahani A , Ray K K
Published: October 2024

Background

Familial hypercholesterolemia (FH) is a prevalent autosomal dominant disorder characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels from birth. These elevated LDL-C levels significantly amplify the lifetime risk of cardiovascular disease (CVD). While the impact of early and effective initiation of lipid-lowering medication (LLM) on CVD risk is well documented in genetically confirmed FH, the additional impact of addressing modifiable lifestyle risk factors (MLRF) in that patient population remains largely unquantified.

Methods

This study quantified the potential effects of successfully managing 4 MLRF (smoking, obesity, alcohol consumption, and low physical activity) on the 10-year incidence of a first CVD diagnosis in adults with genetically confirmed FH treated with LLM within the UK Biobank. The synthesised causal estimates of these 4 MLF were obtained using two recent causal analysis frameworks, namely the doWhy causal calculus framework and the Causal Forest Double Machine Learning Method.

Results

In 660 FH individuals (mean age 56±8 years; 60.15% women), smoking cessation and reducing body mass index below 30 kg/m2 delivered the most substantial risk reductions (pooled estimates, adjusted for the 3 other MLRF: -6.5% and -3.2%, respectively; both p<0.001), followed by initiating moderate or high physical activity (-1.7%; p<0.001; Figure). Notably, cessation of alcohol consumption significantly increased CVD risk (+2.5%; p<0.001), aligning with existing literature.

Conclusion

In over 10 years, reductions in CVD risk ranging from 1.7% to 6.5% were achievable through smoking cessation, BMI reduction, and enhanced physical activity in FH individuals. Leveraging causal inference methodologies facilitates the discernment of which risk factors offer the most pronounced additional benefits beyond lipid-lowering interventions in this high-risk population.Forest Plot of Causal Effect Estimates
Comparison of Lp(a) assessment in patients with atherosclerotic cardiovascular disease between office-based cardiologists and general practitioners
Authors: Weingaertner O , Glueck S , Werdan K , Schorr J , Beier L , De La Llave A , Barth S D , Von Vultee C , Haerer W
Published: October 2024

Background

Elevated lipoprotein(a) (Lp(a)) levels are a major risk factor that contribute to the development of ASCVD. Different guidelines for the treatment of patients with hypercholesterolemia are available in Germany. The German Cardiac Society recognized the 2019 ESC/EAS guideline for the management of dyslipidemia and endorses the measurement of Lp(a) at least once in a lifetime to identify those with very high inherited Lp(a) levels >180 mg/dL (>430 nmol/L) . The Nationale Versorgungsleitlinie, however, does not recommend testing of Lp(a).

Methods and Objectives

LipidSnapshot is a joint research project consisting of two parts. Part 1 is a prospective, non-interventional multicenter research project at office-based cardiologists (OBCs). Data from 1500 adults with known coronary artery disease, peripheral artery disease, prior myocardial infarction and/or ischemic stroke are collected from selected 49 OBCs. The second part is a retrospective, aggregated analysis of anonymous electronic medical records of 82.375 adult outpatient ASCVD patients documented by general practices (GPs) obtained from the IQVIA Disease Analyzer (note: 54% do not provide information on Lp(a) data to IQVIA). Availability of Lp(a) tests and lipid-lowering therapies (LLTs) in ASCVD patients with available LDL-C values within a 12-month period (July 2022-June 2023) were assessed. One of the objectives of LipidSnapshot is to compare the proportion of Lp(a) assessments in ASCVD patients documented by OBCs and GPs and to evaluate gender-, age- and LLTs-related differences in Lp(a) availability in patients documented by OBCs compared to GPs.

Results

Patients treated by OBCs were on average 72.4 (standard deviation (SD) 10.0) years old and 75.8 % were male while patients in the IQVIA dataset were on average 73.0 (SD 13.2) years old and 60.5% were male. The age distribution was comparable between both specialties. OBCs documented Lp(a) in 20.3% of their ASCVD patients, while only 3.0% of ASCVD patients documented by GPs had Lp(a) values documented. The testing rates in male and female patients were comparable between both specialties (OBC: 19.5 vs. 22.9%; GPs: 3.4 vs. 2.5%). For both specialties, Lp(a) testing rate was higher in younger patients compared to older patients (Table 1) and in patients treated with PCSK9-inhibitors (monoclonal antibodies, inclisiran), either as monotherapy or in combination with statins and/or other LLTs (ezetimibe, bempedoic acid, bile acid sequestrants) (Table 2).

Conclusion

The first snapshot revealed differences in healthcare provision of GPs compared to selected OBCs with lower rates of identification of higher risk patients treated by GPs in Germany.Age-related differences in Lp(a)LLT-related differences in Lp(a)
Cardiac MRI traits linked to cardiomyopathy mutations in phenotype naive carriers
Authors: Croon P M , Vugt M , Allaart C P , Asselbergs F W , Ruijsink B , Winter M M , Schmidt A F
Published: October 2024

Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are prevalent forms of cardiomyopathies, characterised by changes in cardiac structure and function, associated with an increased risk of atrial fibrillation (AF), heart failure (HF), and sudden cardiac death (SCD). Due to these potential life-threatening consequences close monitoring of genetic mutation carriers of HCM and DCM, is important. However, disease onset in these subjects is highly variable, with a substantial subset of people only developing disease late-in-life, or not at all, making risk stratification challenging.

We set out to identify cardiac MRI (CMR) based imaging biomarkers of HCM and DCM carriership in phenotype naïve individuals, which were benchmarked against associations with AF and HF.

CMR and whole genome sequencing (n: 42,723) data were sourced from a UK biobank sample free of heart failure at the time of CMR measurements. A previously validated deep learning(DL) network was used to derive 22 CMR traits(1). Adjusted cox regression models were used to determine the CMR associations with the onset of heart failure and atrial fibrillation, providing empirical validation of the DL CMR network. Univariable and multivariable generalised linear models were employed to identify associations with genetic carriership conditional on cardiac risk factors.

14 and 19 CMR measurements were associated with the time until HF (274 cases), AF (704 cases), respectively. These variables included left-ventricle (LV) ejection fraction (EF), LV end systolic volume (ESV), Right-ventricular (RV) EF and right atrial (RA) EF. Using WGS data we identified 154 people with an HCM mutation and 220 with a DCM mutation, where HCM carriership associated with five and DCM with four CMR traits. This included RA-EF (OR 1.26 95%CI 1.10; 1.45), and RV-EF (OR 1.41 95%CI 1.23;1,63) for HCM, and LV-EF (OR 0.72 95%CI 0.62; 0.84), and RV stroke volume (OR 0.75 95CI 0.62; 0.91) for DCM.

By combining deep learning of CMR with large sample size WGS we were able to identify cardiac imaging biomarkers of HCM and DCM carriership in apparently healthy subjects. This could prove relevant for early identification and monitoring of phenotype naïve people.
Redefining genotype-phenotype correlation among patients with arrhythmogenic cardiomyopathy: a CMR cohort study
Authors: La Vecchia G , Bisaccia G , Perotto M , Leo I , Procopio M C , Licordari R , Miaris N , Wong J , Pantazis A , Bucciarelli-Ducci C
Published: October 2024

Background and purpose

Arrhythmogenic cardiomyopathy (ACM) is a poorly defined, life-threatening condition. We aimed at identifying the patterns of regional wall motion abnormalities, fibrosis, and fatty infiltration seen on Cardiac Magnetic Resonance (CMR) and correlate them with the different genetic backgrounds.

Methods

We retrospectively identified ACM patients who underwent CMR and genetic test analysis. We collected data on CMR-derived cardiac volumes, function and tissue characterization.

Results

Seventy-eight patients with a clinical diagnosis of ACM were enrolled. Genetic tests were performed in 65 (83%) and identified a pathogenetic/likely pathogenetic variant in 51 (78%) patients (38% plakophilin-2, 23% desmoplakin, 5% desmoglein, 5% desmocollin and 8% filamin-C). Imaging features varied according to the genetic background, with subepicardial or mid-wall fibrosis distribution affecting predominantly the lateral and inferior segments of the left ventricle (LV) among the different groups and the septal segments in patients with the filamin-C variant. A characteristic LV subepicardial circumferential LGE pattern ("ring-like") was distinctively and almost exclusively associated with the desmoplakin variant.

Conclusions

Genetic variants of ACM present some common but also distinctive CMR phenotypes that can help in further characterizing the specific disease signatures associated with different genes. Further studies should investigate the prognostic value of these CMR findings.
AI-enabled cardiac chambers volumetry in coronary calcium scans (AI-CAC) predicts heart failure and outperforms NT-proBNP: The Multi-Ethnic Study of Atherosclerosis
Authors: Naghavi M , Reeves A P , Budoff M J , Li D , Atlas K , Zhang C , Atlas T , Roy S K , Henschke C , Wong N D , Defilippi C , Levy D , Yankelevitz D
Published: October 2024

Introduction

Coronary artery calcium (CAC) scans contain useful information beyond the Agatston CAC score that is not currently reported. We recently reported that artificial intelligence (AI)-enabled cardiac chambers volumetry in CAC scans (AI-CAC) predicted incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis (MESA). In this study, we investigated the performance of AI-CAC for prediction of incident heart failure (HF) and compared it with 10 known clinical risk factors, NT-proBNP, and the Agatston CAC score.

Methods

We applied AI-CAC to 5750 CAC scans of asymptomatic individuals (52% women, White 40%, Black 26%, Hispanic 22% Chinese 12%) free of known cardiovascular disease at the MESA baseline examination (2000-2002). We used the 15-year outcomes data and compared the time-dependent area under the curve (AUC) of AI-CAC versus NT-proBNP, Agatston score, and 10 known clinical risk factors (age, gender, diabetes, current smoking, hypertension medication, systolic and diastolic blood pressure, LDL, HDL, total cholesterol, and hs-CRP) for predicting incident HF over 15 years.

Results

Over 15 years of follow-up, 256 HF events accrued. The AUC for predicting HF with AI-CAC (0.826) was significantly higher than NT-proBNP (0.742) and Agatston score (0.712) (p<.0001), and comparable to clinical risk factors (0.818, p=0.4141). AI-CAC category-free Net Reclassification Index (NRI) significantly improved on clinical risk factors (0.32), NT-proBNP (0.46), and Agatston score (0.71) for HF prediction at 15 years (p<0.0001).

Conclusion

AI-CAC significantly outperformed NT-proBNP and the Agatston CAC score, and significantly improved the AUC and category-free NRI of clinical risk factors for incident HF prediction.
Assessment of experimental circulating biomarkers in volume and pressure overload: insights from a cohort study
Authors: Csengeri D , Engler D , Ohlrogge A , Schofer N , Kalbacher D , Zeller T , Blankenberg S , Kirchhof P , Schnabel R
Published: October 2024

Introduction

Experimental biomarkers including Angiopoietin-2 (ANG2), bone morphogenetic protein 10 (BMP10), fibroblast growth factor 23 (FGF23), and insulin-like growth factor-binding protein 7 (IGFBP7) are hypothesized to reflect cardiac pathophysiological processes that are potentially present in adverse cardiac remodeling in volume or pressure overload. This study aims to elucidate the relationship between these circulating biomarkers and the presence of hemodynamically significant pressure or volume overload and adverse outcomes and compare it to N-terminal pro B-type natriuretic peptide (NT-proBNP).

Methods

We studied the association between the four experimental circulating biomarkers in patients with pressure or volume overload with reference to none/mild valvular disease in N=1302 of an observational outpatient cardiology cohort. The median age was 63.0 (25th/75th quartile 51.5, 71.4) years, 445 (34.2%) were women. Circulating biomarkers were quantified using a novel antibody-based method. Logistic regression models with cox regression plots were employed to assess the association of each biomarker with the severity of valve disease concerning volume or pressure overload, adjusted for age and sex.

Results

In the overall population, elevated levels of ANG2, BMP10, FGF23 and IGFB7 were positively associated with the presence of significant volume overload (ANG2: Odds ratio (OR) 1.26 (95% confidence interval (CI) 1.17-1.35), p<0.001; BMP10: OR 2.57 (CI 1.89-3.48), p<0.001; FGF23: OR 1.51 (CI 1.14-1.20), p=0.004; IGFBP7: OR 1.39 (CI 1.14-1.69), p=0.001, NT-proBNP: OR 1.69 (CI 1.47-1.95), p<0.001). No statistically significant association between circulating biomarkers and pressure overload was observed.

Over a median follow-up of 4 years, 31 (20.1%) participants died in the group of volume overload and 9 (40.9%) individuals in the group of pressure overload. After multivariable-adjustment, elevated levels of BMP 10 showed a borderline association with an increased risk of all-cause mortality in individuals with volume overload compared to none/mild valvular disease: hazard ratio (HR) 1.51 (CI 0.96- 2.38), p=0.075. Higher concentrations of all biomarkers were predictive of all-cause mortality for both individuals with volume overload and those with none/mild valvular disease (ANG2: HR 3.72 (CI 1.67-8.33), p=0.001; BMP10: HR 1.65 (CI 1.20-2.26), p=0.002; FGF23: HR 2.08 (CI 1.65-2.62), p<0.001; IGFBP7: HR 1.55 (CI 1.25-1.91), p<0.001; NT-proBNP: HR 1.72 (CI 1.47-2.00), p<0.001).

Conclusions

This study demonstrates that circulating biomarkers involved in distinct pathophysiological pathways of inflammation, fibrosis and calcification are elevated in patients with hemodynamically significant volume overload. Since they are also related to mortality, their clinical role needs to be explored further, also in context with the routine biomarker NT-proBNP.
Novel cardiovascular magnetic resonance imaging heterogeneity biomarkers to diagnose and predict cardiovascular disease: a UK Biobank CMR strain study
Authors: Hesse K , Khanji M , Aung N , Chahal A , Petersen S
Published: October 2024

Background

Myocardial strain evaluation on cardiovascular magnetic resonance imaging (CMR) shows significant promise to investigate cardiac function in vivo. There is concern that derived global longitudinal strain (GLS) and global circumferential strain (GCS) are less sensitive to early pathological cardiac remodelling, especially when regional. By quantifying contractile variability across the myocardium, the absolute longitudinal and circumferential strain coefficients of variation, |CoVLS| and |CoVCS| may facilitate earlier diagnosis and improved prognostication.

Purpose

We compared experimental heterogeneity biomarkers, |CoVLS| and |CoVCS|, to established global strain markers, GLS and GCS, to discriminate prevalent cardiovascular disease (CVD) and predict major adverse cardiovascular events (MACE).

Methods

Prevalent and incident CVD were defined among 44,955 participants from the UK Biobank (UKBB), who had feature-tracking (FT-CMR) derived strain markers. Prevalent CVD was the sum of established cardiovascular diagnoses at the time of baseline CMR, including hypertension, diabetes, atrial fibrillation, coronary artery disease, stroke and heart failure (HF). Incident CVD was newly identified MACE, including death from any cause, myocardial infarction, HF and stroke. Biomarkers were separately regressed against said endpoints, using ordinal logistic and Cox proportional hazards regression respectively. Statistical adjustment was performed for important baseline co-variables, including age, sex, ethnicity, smoking status, body mass index (BMI), low-density lipoprotein (LDL), left atrial volume, left ventricular mass and ejection fraction.

Results

Overall, 30,289 (67.4%) participants had no prevalent CVD, 10,362 (23.0%) had 1 CVD and 29 (0.06%) had ≥5 CVD. |CoVLS|, GLS, |CoVCS| and GCS were associated with a higher odds of prevalent CVD diagnoses (Figure 1). GLS had the greatest strength of association (OR 1.25, 95% CI 1.20-1.29), followed by |CoVCS| (OR 1.14, 95% CI 1.10-1.17). Over median 2.7 years (Q1-Q3 1.9-4.1 years), 966 (2.1%) participants experienced MACE, including 379 (0.8%) deaths, 263 (0.6%) MI, 246 (0.5%) HF, 237 (0.5%) stroke. |CoVLS|, |CoVCS| and GLS were comparable risk markers for MACE (Figure 2). The largest and smallest effect sizes were in predicting HF and death from any cause respectively.

Conclusion

Subclinical cardiac disease is often patchy, diffuse and regional; measures of heterogeneity may be more sensitive to these early pathological signals. We demonstrated that |CoVLS| and |CoVCS| are comparable to GLS and better than GCS in discriminating prevalent cardiac disease and predicting future cardiovascular events. These findings need to be replicated in other population studies and diseased cohorts.
The associations of triglyceride glucose and its derived indexes with 10-year cardiovascular disease risk in a Chinese community-based population
Authors: Luo X Y , Fan F F , Jia J , Zheng B , Zhang Y
Published: October 2024

Background

The triglyceride-glucose (TyG) index has been regarded as a reliable surrogate marker of insulin resistance and an independent predictor of cardiovascular outcomes. However, the associations of the derived TyG indexes with incident CVD risk are controversial, and that the relevant data are sparse for the Chinese population studies.

Objectives

We aimed to investigate the association of TyG index and its derived indexes with incident CVD risk and to compare their predictive capacity in the Chinese community-based population.

Methods

We conducted a prospective cohort study on subjects from a Beijing community in China who were free of prevalent stroke or myocardial infarction at baseline. The primary endpoint was a new-onset major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, first non-fatal stroke, and first non-fatal acute myocardial infarction. Cox proportional-hazards regression analyses and time-dependent receiver operator characteristic curve analyses were performed.

Results

A total of 8,806 participants were included. The mean age was 56.51 ± 8.93 years, and 5,679 (64.5%) were female. The median value of TyG index, TyG-BMI, TyG-WC, and TyG-WHtR were 8.71 (8.34-9.12), 226.37 (201.02-252.87), 720.80 (653.52-791.03), and 4.47 (4.07-4.90), respectively. During a mean 9.7-year follow-up, a total of 877 (10%) cases of MACE were recorded. The Kaplan–Meier curves showed significant differences in cumulative hazards of new-onset MACE among tertiles of abovementioned indexes (Log rank P < 0.0001) (Figure 1). Multivariable Cox regression analyses revealed that TyG index, TyG-BMI, TyG-WC, and TyG-WHtR were positively associated with the hazards of MACE. Compared with tertile 1, the multivariable adjusted HRs (95% CIs) of incident CVD for tertile 3 were 1.26 (1.01-1.56), 1.57 (1.15-2.14), 1.54 (1.19-2.00), and 1.81 (1.40-2.33) for TyG, TyG-BMI, TyG-WC, and TyG-WHtR, respectively (Figure 2). There are no significant differences in the Harrell's C indexes among the various indexes compared to the TyG index (TyG index: 0.758 [0.743-0.774], TyG-BMI: 0.758 [0.743-0.773], TyG-WC: 0.758 [0.743-0.774], and TyG-WHtR: 0.760 [0.745-0.775]).

Conclusions

Higher TyG and its derived indexes are significantly associated with an increased risk of 10-year MACE. Our results suggest that TyG and its derived indexes may serve as a useful marker for stratifying CVD risk in the general population.
Impaired strain in diabetic patients with stable coronary artery disease assessed by cardiac magnetic resonance
Authors: Boros G A B , Hueb W , Rezende P C , Toledo L O , Andrade V C , Cicupira A , Garcia R M R , Scudeler T L , Lima E G , Rochitte C E , Nomura C H , Ramires J A F , Kalil Filho R
Published: October 2024

Background

Type 2 diabetes mellitus (T2DM) can contribute or lead to myocardial structural derangement by multiple mechanisms, including ischemic cardiomyopathy and, more rarely and of difficult evaluation, diabetic cardiomyopathy. Early stages of myocardial dysfunction can be assessed by strain analysis with cardiac magnetic resonance feature tracking (CMR-FT), however, there is no studies that examined deformation parameters in diabetic patients with stablished coronary artery disease (CAD).

Purpose

We sought to compare the strain parameters of patients with and without T2DM with stable CAD.

Methods

Patients with stable multivessel CAD and preserved left ventricular ejection fraction (LVEF), included in the MASS V trial, underwent contrast-enhanced cardiac magnetic resonance before revascularization procedures. Patients were stratified according to T2DM diagnosis at baseline. Feature tracking was performed using short-axis cine images and 2- and 4-chamber long-axis images. The left ventricular endocardial and epicardial contours of the end diastole phase were manually delineated in all images. Automatically tracking contours were performed to calculate left ventricular global longitudinal (LVGLS), circumferential (LVGCS) and radial (LVGRS) strain (FIGURE 1).

Results

Of 202 patients studied, 88 (44%) were diabetic and 114 (56%) non-diabetic. Baseline characteristics were similar between groups (age 70 ± 10 vs 69 ± 11; 69% vs 68% males; LVEF 65 ± 13 vs 67 ± 9). Mean Syntax score was 21.2 ± 8.5 vs 20.4 ± 8.5 (P=0.52) in diabetic and non-diabetic, respectively. There were no differences in left ventricle volumes, mass and LVEF. Mean LGE mass was 2.3 ± 0.9 vs 1.9 ± 0.9 grams (P=0.32) respectively in T2DM and control groups. Strain values were all reduced in T2DM patients, as shown in FIGURE 2 (LVGLS: -15.5% ± 2.3% vs -17.5% ± 2.7%, P=0.02; LVGCS: -15.4% ± 2.6% vs -17.4% ± 3.0%, P=0.03; LVGCS: 25.9% ± 5.9% vs 29.5% ± 7.2%, P=0.01). Multivariable analyses adjusted for age, sex, BMI, hypertension, Syntax score and LGE mass showed no differences in the results.

Conclusion

In this study, T2DM was associated with impaired deformation parameters (decreased left ventricular global longitudinal, circumferential, and radial strain). These findings suggest myocardial dysfunction in diabetic patients when compared to control subjects in the setting of stable multivessel CAD.FIGURE 1FIGURE 2
Is left atrial reservoir strain a superior modality to predict acute left ventricular failure in hypertensive patients
Authors: Rameshwar R , Meenakshi K , Saishree K V , Arshad Ali C , Narayanasamy A G , Mohammed Adil A M
Published: October 2024

Background

The left atrium (LA) plays an important role in the pathophysiology of heart failure. Left Atrial function has 3 components and their relative contributions, under normal circumstance, include reservoir(40%), conduit (35%), and active pump(25%) function(1). All these functions can be assessed by their respective strain, measured in trans thoracic echocardiography usually by speckle tracking, from apical 4 and 2 chamber views. Of the 3 types of LA strain, LA reservoir strain (LAS-r), is the best reflection of atrial function(2). LA strain can detect LA dysfunction even before obvious LA enlargement, aiding preclinical diagnosis of cardiac dysfunction.

Purpose

To assess if Left atrial reservoir strain was a superior modality to predict acute Left Ventricular Failure in hypertensive patients.

Methodology

Our study cohort consisted of 200 hypertensive patients, 84 females and 116 males, 40 to 71 years old with hypertension duration of 6 months to 21 years .Patients with other co morbidities were excluded. All were on treatment and had BP ranging from normal to high. Sixty two (31%) had experienced one or more episodes of acute left ventricular failure(LVF). Patients underwent in addition to routine investigations, detailed ECHO including measurement of left ventricular global longitudinal strain(LVGLS- normal > -18) and LAS-r (Normal >35).

Results and Discussions

All patients had normal ejection fraction. 128 (64%) had LVDD. 102(79.8%) had grade 1 LVDD, 24 (18.6%) had grade II LVDD and 2 (1.6%) had Grade III. Forty eight (37.5%) of the 128 with LVDD experienced acute LVF and 23(47.9%) of them had grade 11 LVDD or more. Forty two (21%) had reduced LVGLS, of these, 18(42.9%) experienced acute LVF and of these, 14(77.8%) had in addition reduced LAS-r. One hundred and two (51%) had reduced LAS-r (LAS-r <25), of which 61(59.8%) had experienced acute LVF. 63(31.5%) had increased LA volume of which 37( 58.7%) had experienced acute LVF. 5.7% of patients with BP <150/90 had reduced LAS-r, 69.5% with BP between 150/90- 169/100 had reduced LAS-r and 85.4% with BP > 170 had reduced LAS-r. Of the 62 patients with acute LVF, 18(29%) showed reduced LVGLS, 48(77.4%) had LVDD, 37(59.7%) had increased LA volume and 61(98.4%) had reduced LAS-r indicating that the latter was an earlier, better predictor of acute LVF than the former three. Although there were no age or gender differences in the findings, the prevalence of reduced LAS-r was higher with less well controlled BP.

Conclusions

In our study, LAS-r, irrespective of the age or sex, was an earlier better predictor of acute LVF than reduction of LVGLS, LVDD or increased LA volumes, in hypertensive patients. The prevalence of reduced LAS-r was higher in patients with poorly controlled BP. Prognostic significance of LAS-r can help influence early clinical decision making and for defining early management.TABLE 1TABLE 2
Prognostic significance of pre-procedure wall shear stress in the ascending aorta in patients with aortic stenosis undergoing transcatheter aortic valve replacement
Authors: Hamaya T , Nagai T , Kamiya K , Takahashi Y , Mizuguchi Y , Tsuneta S , Kazui S , Yasui Y , Mori Y , Saiin K , Naito S , Takenaka S , Ishizaka S , Sato T , Anzai T
Published: October 2024

Background

Accurate prognostication before the procedure is challenging in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Recently, blood flow dynamics assessed by four-dimensional flow cardiovascular magnetic resonance imaging (4D-flow CMR) showed a significant reduction in average wall shear stress (WSS) in the ascending aorta (AAo) after TAVR. However, the prognostic value of pre-procedure average WSS in the AAo is controversial.

Purpose

We aimed to investigate whether pre-procedure average WSS was associated with clinical outcomes in patients with AS undergoing TAVR.

Methods

We prospectively examined 159 consecutive AS patients who underwent TAVR (57 males, mean age 83.6 ± 4.7 years, median left ventricular ejection fraction 63.4%) between May 2018 and May 2022. We assessed average WSS in the AAo before TAVR using 4D-flow CMR. We divided the patients into high WSS (≥6.60 Pa, n = 79) and low WSS (<6.60 Pa, n = 80) groups according to the median value of pre-TAVR WSS. The primary outcome of interest was a composite of all-cause death and hospitalization for worsening heart failure.

Results

Patients with high WSS had lower age compared to those with low WSS. There were no significant differences on sex, body mass index, systolic blood pressure, hemoglobin, serum albumin, N-terminal pro b-type natriuretic peptide, left ventricular ejection fraction, mean transaortic valvular gradient, annulus area in aortic valve and AAo diameter between the groups. During a median follow-up period of 19.8 months (interquartile range 6.0-37.1), the primary outcome more frequently occurred in patients with low WSS than in those with high WSS (28% vs 5%, P <0.001) (Figure 1). A multivariable Cox regression showed that lower WSS independently associated with increased risk of the primary outcome (hazard ratio 0.69, 95% confidence interval [CI] 0.53-0.91, P <0.001), even after adjustment for significant prognostic covariates including age, sex, serum albumin, history of chronic obstructive pulmonary disease, peripheral artery disease and malignancy, and estimated glomerular filtration rate. Predictive performance for the primary outcome was improved when adding the value of WSS in the AAo to representative prognostic factors (c-index 0.81 95%CI 0.72-0.90 vs. 0.77 95%CI 0.67-0.88) (Figure 2).

Conclusions

In patients with AS who underwent TAVR, lower average WSS in the AAo before procedure was associated with higher risk of worse clinical outcomes, suggesting that pre-TAVR average WSS in the AAo would be a surrogate marker and useful for the risk stratification.Survival analysis for primary outcomePredictive performance
The role of semi-quantitative parameters of thallium-201 myocardial perfusion imaging in predicting mortality rate among CKD population
Authors: Liu Y H , Huang T C , Chang C C , Tsai W C , Su W Y , Huang T H , Wang S L , Lin M Y , Lin Y T , Chen S C , Kuo M C , Chiu Y W , Wu P H
Published: October 2024

Background

Chronic kidney disease (CKD) is a major public health concern worldwide, with high morbidity and mortality rates. Myocardial perfusion imaging (MPI) is a non-invasive diagnostic tool that can detect early-stage cardiovascular disease in CKD patients.

Purpose

This study aimed to investigate the role of semi-quantitative parameters of Thallium-201 MPI in predicting mortality rates among CKD patients.

Methods

This retrospective study included 579 CKD patients who underwent Thallium-201 MPI between October 2005 and December 2019. Semi-quantitative parameters were analyzed using automation software, including transient ischemic dilation (TID), lung-to-heart ratio (LHR), total perfusion deficit (TPD), summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), summed thickening percent (ST%), summed motion percent (SM%), stress end-diastolic volume (EDV), stress end-systolic volume (ESV), and stress left ventricular ejection fraction (LVEF). The primary endpoint was overall mortality.

Results

During a median follow-up of 52 months, 148 patients died. The older age group, lower hemoglobin levels, and lower estimated glomerular filtration rate (eGFR) were associated with higher mortality rates. The semi-quantitative parameters that predicted overall mortality included LHR above 0.4, elevated ST% , increased stress EDV and ESV, and reduced stress LVEF in a multivariable Cox regression model.

Conclusion

Thallium-201 MPI with semi-quantitative parameters can predict mortality rates in CKD patients without a definite diagnosis of coronary artery disease. The identified parameters, including LHR above 0.4, elevated ST levels, increased stress EDV and ESV, and reduced stress LVEF can assist in early detection the mortality risk in CKD patients.Characteristics of CKD PatientsMultivariable Analysis
Cardiometabolic multimorbidity and associated risk factors in a cohort identified through community-based screening in Eastern Nepal
Authors: Sharma S K , Gautam U , Bhattarai U , Katuwal P , Perone S A , Zimmermann K , Heller O
Published: October 2024

Background

Cardiometabolic multimorbidity constitutes a major cause of premature mortality and morbidity in low- and middle-income countries like Nepal. Early detection of associated risk factors and timely management at primary care centres can significantly reduce the impact at individual level. Lack of quality research data in resource poor setting often pose a challenge to plan for efficient delivery of health services.

Purpose

This analysis of secondary data from a cohort identified through a community based NCD intervention program intends to explore the distribution of cardiometabolic multimorbidity and associated risk factors in adult population of Eastern Nepal.

Methods

This report is a part of integrated NCD management strategy, a KHDC (Kidney, Hypertension, Diabetes, and Cardiovascular disease) program, implemented through community-based screening and interventions focused on primary level healthcare centres. The KHDC program involved screening of 14,517 individuals aged 18 years and above at baseline during a period of 2019-2023 for selected NCDs, including, cardiovascular diseases, hypertension, diabetes, and kidney disease. Individual level data was collected through anthropometric measurements, participants’ self-report, vitals assessment, laboratory parameters and diagnostic adjuncts including ECG and Echocardiography. Outcome of cardiometabolic multimorbidity1 was defined as presence of two or more of diabetes mellitus, and cardiovascular diseases including myocardial infarction and stroke.

Results

About 12.8% (n=1862) of the participants had at least one cardiometabolic multimorbidity, while less than one per cent (n=47) had two or more multimorbidity. Presence of at least one multimorbidity was associated with older age ≥ 40 years [OR: 3.870 (95% CI: 3.285-4.558)], male gender [OR: 1.326 (95% CI: 1.202-1.463)], BMI ≥ 23 kg/cm2 [OR: 1.348 (95% CI: 1.208-1.503)], current tobacco consumption [OR: 1.164 (95% CI: 1.038-1.305)] and co-occurrence of hypertension [OR: 1.736 (95% CI: 1.550-1.943)]. The presence of both diabetes mellitus and cardiovascular disease was associated with age ≥ 40 years [OR: 7.612 (95% CI: 1.846-31.395)] and co-occurrence of hypertension [OR: 2.544 (95% CI: 1.401-4.620)].

Conclusion

Disproportionate burden of cardiometabolic multimorbidity was apparent among adult population screened in our program. Older age and co-occurrence of hypertension was identified as contributing factors for the presence of such multimorbidity. A baseline information on the distribution and risk factors for the same among general population can provide a valuable insight into understanding the disease progression and prognostic outcomes.Table of Outcomes
Comparing PCSK9 inhibitor prescription rates within high-risk populations: diabetes mellitus, multi-territory vascular disease, multivessel and recurrent coronary artery disease
Authors: He W B , Jape D , Nanayakkara S , Shaw J
Published: October 2024

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are subsidised in Australia for treatment of hypercholesterolemia in particularly high-risk patients with atherosclerotic cardiovascular disease (ASCVD). These high-risk groups are defined as: diabetes mellitus (with age≥60, Aboriginal or Torres Strait Islander origin or microalbuminuria), recurrent ASCVD (≥2 events within 5 years), multivessel coronary disease (≥50% stenosis in ≥2 large vessels) and multi-territory vascular disease (concurrent cerebrovascular or peripheral vascular disease).

Methods

A retrospective observational analysis was conducted on high-risk patients with LDL>2.6 admitted to a quaternary hospital with ASCVD between 2020-2022. Australian Pharmaceutical Benefits Scheme (PBS) criteria was applied to assess and compare PCSK9 inhibitor eligibility and prescription rates within high-risk populations.

Results

In total, 477 ASCVD patients with LDL>2.6 were included. This was further categorised into: multivessel coronary disease (n=239, 50.1%), diabetes mellitus (n=60, 12.6%), recurrent ASCVD (n=55, 11.5%) and multi-territory vascular disease (n=32, 6.7%), p<0.001. When 2020 PBS criteria was applied, the number of eligible patients were 16/239 (6.7%), 5/60 (8.3%), 13/55 (23.6%) and 4/32 (12.5%) respectively, p=0.002. Of PBS eligible patients, the number prescribed PCSK9 inhibitors were: 7/16 (43.8%) for multi-vessel coronary disease, 1/5 (20%) for diabetes mellitus, 4/13 (30.8%) for recurrent ASCVD and 1/4 (25%) for multi-territory vascular disease patients (p=0.73).

Conclusion

Although there was a significantly higher prevalence and proportion of eligible multivessel coronary disease patients, prescribing rates for PCSK9 inhibitor therapy remain low amongst all high-risk eligible groups including diabetes mellitus, multi-territory vascular disease, multivessel and recurrent coronary artery disease.
Relationship of cumulative low-density lipoprotein cholesterol with atherosclerosis
Authors: Yamaji T , Yusoff F , Kajikawa M , Kishimoto S , Maruhashi T , Nakano Y , Higashi Y
Published: October 2024

Background

The relationship between cumulative low-density lipoprotein cholesterol (LDL-C) exposure and progression of atherosclerosis remains uncertain.

Objective

The aim of this study was to determine the relationship between cumulative LDL-C level and flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation (NID) and the presence of plaque in the common carotid artery (CCA).

Methods

This was a cross-sectional study. We measured FMD in 8208 subjects, NID in 1822 subjects, and CCA plaque in 591 subjects who were not taking lipid-lowering drugs. The subjects were divided into four groups based on cumulative LDL-C exposure: <4000 mg･year/dL, 4000-4999 mg･year/dL, 5000-5999 mg･year/dL, and ≥6000 mg･year/dL.

Results

The odds ratio of the lower quartile of FMD in the cholesterol-year-score <4000 mg･year/dL group was significantly higher than the odds ratios in the other groups (Figure 1A). The odds ratio of the lower quartile of NID in the <4000 mg・year/dL group was significantly higher than the odds ratios in the 5000-5999 mg･year/dL and ≥6000 mg･year/dL groups (Figure 1B). The odds ratio of the prevalence of CCA plaque in the <4000 mg・year/dL group was significantly higher than that in the ≥6000 mg･year/dL group (Figure 1C).

Conclusions

Endothelial dysfunction occurred from cumulative LDL-C exposure of 4000 mg・year/dL, vascular smooth muscle dysfunction occurred from cumulative LDL-C exposure of 5000 mg･year/dL, and prevalence of CCA plaque occurred from cumulative LDL-C exposure of 6000 mg･year/dL.Graphical abstractFigure 1