bluuebunny/crossref_metadata_2025 huggingface dataset:
The correlation between cardiac magnetic resonance imaging and echocardiography in patients with severe ischaemic cardiomyopathy
Authors: Betemariam T , Morgan H , Mancio J , Alskaf E , Ryan M , Draper J , Papachristidis A , Senior R , Kapetanakis S , Chiribiri A , Perera D
Published: October 2024

Background

Left ventricular ejection fraction is the single metric that guides therapeutic decision-making, risk stratification and prognosis in patients with severely impaired systolic function. Although cardiac magnetic resonance imaging (CMR) is the current reference standard for quantification of ventricular volume and function, echocardiography is used more often as it is more widely available and less expensive.(1)

Aims

To evaluate the correlation between CMR and echocardiography in quantifying left ventricular (LV) volume and function and to determine whether these measurements are associated with clinical outcomes in patients with severe ischemic cardiomyopathy (ICM).

Methods

Participants recruited to the REVIVED-BCIS2 trial who had undergone baseline CMR or echocardiography were included in this analysis. All scans were analyzed in blinded core laboratories as previously reported.(2,3) All volumes were indexed to body surface area. Spearman correlation, Bland Altman analysis and coverage probability methods were performed to assess the correlation between the two modalities.

A Cox proportional hazards model was used to assess the association between imaging metrics and the primary outcome, a composite of all-cause death and aborted sudden death. A sensitivity analysis was conducted a priori, restricted to patients undergoing both scans within 60 days of each other.

Results

A total of 373 participants with paired imaging data were included: mean age 69±9 years, 87% male, BMI 28±5. A moderate correlation was detected for volume measurements between the modalities (end diastolic volume index (EDVI) r=0.66 end systolic volume index (ESVI) r=0.68), with a weaker correlation for LV ejection fraction (EF) (r=0.41). Bland-Altman plots showed moderate agreement in LVEF measurements (Table 1). The sensitivity analysis included 199 patients, and showed similar results (EDVI r=0.72, ESVI r=0.73 LVEF r=0.43, all p<0.000).

Only 7.5% of the paired LVEF measurements were within 5% of each other. 30% of participants were misclassified by echocardiography as having an LVEF>35%. (Figure 1) CMR ESVI was associated with the occurrence of the primary outcome (HR 1.05 per 10ml increment, 95% CI 1.00-1.10) however echo ESVI (HR 1.05 per 10ml increment 95% CI 0.99 – 1.10) and all other imaging metrics were not.

Conclusion

Left ventricular volumes and ejection fraction on CMR and echocardiography were only modestly correlated in this population with severe ICM. When using the binary EF threshold of 35% that is commonly used to select patients of implantable defibrillator therapy, almost a third of patients at risk would have been missed by echocardiography alone. The additional insights provided by CMR, including scar burden, further support preferential use of this modality in the assessment such patients.
Breast arterial calcification: a potential novel imaging marker for HFpEF
Authors: Tu H , Davis E F , Yeong C , Vasanthankumar S , Aldous E , Goel V , Salib A , Xu E , Nerlekar N
Published: October 2024

Background

Breast arterial calcification (BAC) on mammography has been shown to associate with cardiovascular disease, however the association with heart failure (HF) remains largely uncharacterised. BAC is a medial arterial calcification process, which is a marker of vascular stiffness, a key contributor to diastolic dysfunction (DD) and HFpEF. We sought to evaluate the association between BAC and HFpEF.

Purpose

This study aims to assess the relationship between BAC status and HFpEF.

Methods

This retrospective cross-sectional study included 100 consecutive patients with clinically indicated mammography and echocardiography within 6 months of each other. BAC was visually assessed to determine presence or absence. HFpEF was diagnosed based on combined clinical and echocardiographic assessment. DD was defined by Mitter et. al’s(1) criteria after review of echocardiograms. Logistic regression analysis with Odds Ratio (OR) and (95% confidence intervals) are reported for association with any HF, HFpEF, or DD adjusting for modifiable (body mass index, hypertension, hyperlipidaemia, current smoking, diabetes mellitus) and non-modifiable (age, past smoking breast cancer, past ischaemic heart disease (IHD), atrial fibrillation (AF), chronic kidney disease (CKD)) risk factors.

Results

The prevalence of BAC was 27% and 13% had HFpEF and 55.8% had DD. Patients with BAC were older (mean age 73±13 vs 57±13, p<0.01) with greater proportion of hypertension (66.67% vs 39.73%, p=0.02), hypercholesterolaemia (70.37% vs 43.84%, p=0.02), AF (p<0.01), previous IHD (p=0.01), and CKD (p<0.01). After adjustment for these variables, BAC was independently associated with HFpEF diagnosis for modifiable risk factors: (OR 2.47 [0.50-12.10], p<0.27) and non-modifiable factors (OR 6.96 [1.72-33.31], p<0.01). BAC was also independently associated with echo defined DD: adjusted for modifiable risk factors (OR 8.67 [2.49-42.16], p<0.01), and non-modifiable risk factors (OR 8.25 [2.44-38.27], p<0.01).

Conclusions

BAC is associated with HF presence, particularly HFpEF and DD. Further research is required to elucidate the role of shared pathophysiological mechanisms, such as vascular stiffness and general arterial calcification, common to BAC, DD, and HFpEF. In the future, BAC may act as a useful surrogate and opportunistic marker to instigate further review if implemented in established widespread breast-screening programs for detection of subclinical disease.Figure 1:Case example of imaging assess
Sex differences in proteomics of cardiovascular disease: results from the Yale-CMD registry
Authors: Liu Y , Wang Z , Collins S P , Testani J M , Kleinstein S H , Safdar B
Published: October 2024

Background

Cardiovascular disease is the leading cause of death globally, with notable sex differences in its presentation, mechanisms, and outcomes.

Purpose

We investigated the serum proteomic profiles of coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) patients to uncover sex-specific biological pathways and their roles in disease development.

Methods

Using the Yale-CMD registry's biobank, we performed a secondary analysis on adults with ischemic symptoms who underwent cardiac PET/CT and were not experiencing myocardial infarction, hemodynamic instability, acute heart failure, febrile illness, dialysis, or consent incapacity. Using PET/CT, we classified participants as controls (normal coronary flow reserve [CFR], no perfusion defect or coronary calcification), CAD (if new perfusion defect or known revascularization), or CMD (CFR <2 without defect or calcification). Using proximity extension assays (Olink® Explore 3072) in high-throughput proteomic analysis, we examined 2944 plasma proteins. Differential protein abundance analysis was performed using linear regression models adjusting for age, race, body mass index, history of diabetes, dyslipidemia, hypertension, and smoking to detect significant changes in protein abundance, with false discovery rate (FDR) control. Functional pathway analyses were conducted to identify the biological functions of the sex-differentially expressed proteins.

Results

Between 2014-2020, 91 patients of 190 in the registry provided blood samples for this analysis. Participants had median age 56.0 (50.0 - 62.0) years with 66% females. Among these, 48% were controls, 24% had CAD and 27% had CMD. Using linear regression adjusting for confounders, we identified significant sex differences in protein levels related to reproductive functions across all 3 cohorts (Fig. 1). In the CAD cohort, FSHB was upregulated in females, while INSL3 and EDDM3B were upregulated in males (FDR < 0.05). In the CMD cohorts, 6 proteins were differentially expressed (FDR < 0.05), with SCGB3A1 and HGFAC higher in females, and INSL3, SPINT3, EDDM3B, and KLK3 higher in males. Pathway analysis revealed that among patients with CAD, females had upregulation in immune system processes (Fig. 2A), while males showed upregulation of proteins related to endothelial regulation of blood flow (Fig. 2B). Among patients with CMD, females showed upregulation of lipid and glucose metabolism (Fig. 2C), while males showed upregulation of angiogenesis-related proteins (Fig. 2D).

Conclusion

We demonstrated significant sex differences in proteomic profiles among patients with CAD and CMD, underscoring the potential importance of sex-specific pathways in the pathophysiology of CVD. Our finding supports a need for large-scale validation studies to develop sex-tailored therapeutic strategies and advance precision medicine in cardiovascular health.Differential protein expression by sexPathway overrepresentation
Sex differences in severe aortic stenosis undergoing surgical replacement
Authors: Panichella G , Garofalo M , Bonanni F , Grasso Granchietti A , Berteotti M , Tozzetti V , Cenni N , Bandini M , Servoli C , Grandi G , Del Pace S , Caciolli S
Published: October 2024

Background

Aortic stenosis (AS) is the most common valvular heart disease in developed countries. Sex differences have been described in AS pathophysiology and left ventricular (LV) remodelling, as well as clinical presentation and response to therapies (1). However, sex differences in LV function parameters, namely global longitudinal strain (GLS), have been scarcely explored so far.

Purpose

To investigate sex differences, taking into account GLS, in patients with severe AS referred to surgical aortic valve replacement (SAVR).

Methods

The study population was from a single centre, prospective registry of patients with severe native valve AS who were referred for SAVR between June 2020 to October 2022. Severe AS was defined by standard guideline criteria (2). All patients underwent an echocardiogram immediately before and at least 3 months after surgery.

Results

Table 1 recapitulates sex differences in our population (n=119, 43% women). No differences in age or cardiovascular (CV) risk factors were noted. Clinical presentation and AS etiology were also similar. At baseline, women had lower EuroSCORE (p=0.039), creatinine (p <0.001), and haemoglobin levels (p=0.001). The echocardiogram showed a higher mean aortic valve gradient in women (Gmean, 62 vs. 50 mmHg, p=0.002). Women also had higher relative wall thickness (RWT, 0.49 vs. 0.42, p=0.037), despite lower LV mass index (124.9 vs. 136.6 g/m², p=0.037). Regarding LV function, women showed higher EF (64% vs. 60%, p=0.002) and GLS (16.5% vs. 14.6%, p=0.006) values. This is partially explained by the higher prevalence of concomitant coronary artery disease (CAD) in men, more frequently subjected to a concomitant coronary artery bypass graft than women (CABG, 38% vs. 8%, p <0.001). Post-operative complications had similar rates in men and women. After a median follow-up of 16 (6-18) months, death from any cause (6.0% vs. 1.5%, p=0.186) and rehospitalization for CV causes (14.0% vs. 4.0%, p=0.055) tended to be more frequent among women. When considering patients with severe AS alone (n=89), women had higher Gmean (64 vs. 53 mmHg, p=0.035) and EF (65% vs. 62%, p=0.045) but similar GLS (16.9% vs. 16.6%, p=0.230) as compared to men (Figure 2). At follow-up, EF and GLS failed to improve in both sexes and no differences were noted between women and men (EF 60% vs. 60%, p=0.476; GLS 15.9% vs. 16.0%, p=0.976).

Conclusions

In a population of all-comers patients with severe AS undergoing SAVR, women showed higher Gmean, EF, and GLS values. This is partially due to the higher prevalence of a concomitant CAD in men. When considering patients with AS alone, women still had higher EF and Gmean than men, despite a similar GLS. Future larger prospective studies with longer follow-up are needed in order to further characterize such differences and correlate them with specific outcomes.
Sex differences in outcomes of percutaneous left atrial appendage closure
Authors: Ryuzaki S , Kondo Y , Nakano M , Nakano M , Kajiyama T , Ito R , Chiba T , Yoshino Y , Komai Y , Takanashi Y , Kobayashi Y
Published: October 2024

Background

Atrial fibrillation (AF) is the most common arrhythmia in adults and is associated with an increased risk of embolic stroke. In a previous survey, 91% of nonrheumatic AF-related left atrial thrombi was originated in the left atrial appendage (LAA). Percutaneous left atrial appendage closure (LAAC) with the Watchman device has been shown to be noninferior to anticoagulation therapy in clinical trials for stroke prevention in nonrheumatic AF. It has been used in Japan since September 2019 only for patients who are at the high risk of bleeding events. The WATCHMAN family is the only left atrial appendage closure (LAAC) device in Japan.

Since long time ago, sex differences have been attracting attention in the cardiology. Due to the cardiovascular protective effects of endogenous estrogens, premenopausal women are thought to be less likely to develop cardiovascular disease. Whereas, in area of AF, Female with AF have higher stroke risk and female with AF have severe after effect. However, there are few studies on sex differences in LAAC implantation outcomes.

Purpose

We aimed to identify the sex differences of outcomes of LAAC in Japanese patients.

Methods

A total of 118 consecutive patients who underwent LAAC at our hospital from January 2020 to August 2023 were prospectively analyzed. Various patient characteristics, comorbidities, and outcomes were identified and compared between male and female.

Results

Results are shown in Table. Female were older (79 vs. 73 years, p = 0.0009), thinner (Body mass index 22 vs. 24 kg/m2, p = 0.0326), and less likely to have had diabetes (19 vs. 40%, p = 0.0340). Pulmonary embolism was significantly more common in female after LAAC. If anticoagulants are discontinued after LAAC, women’s susceptibility to coagulation may become apparent.

Conclusions

LAAC was feasible and safe for Japanese patients of both genders. However, these results could have a relevant impact on the antithrombotic management of patients who are at the high risk of embolic considering sex difference. Especially, we should pay great attention when discontinuing anticoagulants after LAAC in female.
Preliminary data on short-term outcomes within the cardio-obstetrics registry
Authors: Siry D S , Hoerbrand I H , Haney A C H , Frey N F , Ehlermann P E , Beckendorf J B
Published: October 2024

Background

Pregnancy leads to physiological changes within the cardiovascular system such as increased plasma volume and cardiac output or hypercoagulability. These changes can be challenging for women with pre-existing cardiovascular disease with higher risks of complications. The guidelines of the European Society of Cardiology recommend treating high-risk patients in specialized centres by an interdisciplinary pregnancy heart team. In a team-based approach, the Pregnancy Heart Team was founded at our university hospital, in order to establish specific structures of communication and responsibility.

Methods

A prospective registry of all patients treated by the Pregnancy Heart Team between November 2022 and March 2024 was established. Patients consisted of women with pre-existing cardiovascular disease undergoing pregnancy as well as women who developed pregnancy-associated cardiovascular disease. Patients were evaluated throughout pregnancy by lab work and echocardiography during each trimester as well as in the postpartum period.

Results

In total 39 women (mean age 34±5 years) were prospectively included in the registry. 17 patients (43.5%) were classified as mWHO ≥ III. 17 patients (43.5 %) with pre-existing (pregnancy-associated) cardiovascular disease were managed throughout pregnancy and delivery. 9 patients (18.4 %) developed pregnancy-associated cardiovascular diseases such as peripartum cardiomyopathy or spontaneous coronary artery dissection. Preliminary data shows that mean left-ventricular ejection fraction remained stable during pregnancy with a non-significant trend towards lower values postpartum. Cardiac biomarkers such as high-sensitivity troponin T and NT-pro-BNP showed a non-significant trend towards increased values in the third trimester and postpartum. Adverse maternal outcomes occurred in 14 patients (35.9 %), including preterm premature rupture of membranes (12.2%), gestational hypertension (7.6%), gestational diabetes (5.1%), preeclampsia/eclampsia (7.6%) and delivery-associated complications (10.2%). Fetal complications included macrosomia (10.2%) or intrauterine growth retardation (5.1%).

Discussion

These preliminary data of a real-world patient collectivedemonstrate that a significant number of patients experienced adverse pregnancy outcomes which was associated with a trend towards increased cardiac biomarkers throughout pregnancy and postpartum. As recent studies have shown, interpretation of standard parameters such as cardiac biomarkers is not fully understood during pregnancy, especially in women with pre-existing cardiovascular disease. Our data may aid to understand prognostic implications of cardiac biomarkers during pregnancy.
Proteome profiling in patients with peripartum cardiomyopathy according to ethnicity a biomarker study on the EORP cohort
Authors: Kodogo V , Viljoen C , Chakafana G , Hoevelmann J , Jackson A , Al-Farhan H , Goland S , Tromp J , Van Der Meer P , Karaye K , Kryczka K , Mebazaa A , Bauersachs J , Sliwa K
Published: October 2024

Background

Peripartum cardiomyopathy (PPCM) is a pregnancy-associated form of heart failure, which occurs in previously healthy women towards the end of pregnancy and in the first months postpartum. Previous reports showed a varying prevalence of PPCM across different regions and potentially a higher incidence in patients with black African ethnicity. The correct and timely diagnosis remains challenging and there is a need for novel disease-specific biomarkers. Accuracy in diagnosing PPCM can be improved by using serum-protein biomarkers such as QSOX1, adiponectin and ITIH3 in addition to NT-proBNP. However, it still needs to be ascertained whether there are ethnic differences in proteomic profiles amongst patients with PPCM with different ethnicities.

Aims

To delineate possible differences in serum protein biomarker profiles across different ethnic groups within the EURObservation Research Programme (EORP) multi-national cohort of women with PPCM.

Methods

Demographic and clinical data, as well as serum samples were collected from 84 patients with PPCM from seven EORP participating countries. Serum proteomic profiling was conducted using DIA-based label-free quantitative (LFQ) LC-MS at the time of diagnosis from depleted serum samples. Mass spectrometry data were analyzed by Spectronaut v15 using a study-specific spectral library. From the 84 patients in the EORP PPCM registry on whom we performed proteomic analyses, 82 patients self-declared their ethnicity. These 82 patients were assessed for any ethnical differences in their proteomic expression profile using unsupervised principal component analysis (PCA).

Results

In this cohort of 82 women with PPCM, the mean age was 30.5±6.7 years (Table 1). Three quarters of this cohort had no hypertension during pregnancy and only 13.8% had a prior diagnosis of PPCM. The mean left ventricular ejection fraction (LVEF) was 35% at time of first diagnosis, with no difference between the ethnic groups. However, women of Middle Eastern decent had more severe LV dilatation (LVEDD: 64.0 (62.0-65.0) mm). Three hundred and twenty-nine (329) proteins were identified in the serum samples. As depicted in Figure 1, PCA did not yield a distinct separation between the different ethnic groups. Principal component 1 (PC1) accounted for 15.2% of the total variability in protein expression among ethnic groups, PC2 explained a comparatively lower percentage at 12%.

Conclusion

The protein biomarkers identified in PPCM patients showed no discernible racial differences, demonstrating consistent performance across all ethnic groups.
A diagnosis of vascular ehlers-danlos syndrome in childhood: clinical and molecular features of 63 individuals
Authors: Wilkinson N , Cervi E , Wagner B , Von Klemperer K , Andrew T , Ghali N , Van Dijk F
Published: October 2024

Background

Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder characterised by generalised severe tissue friability and predominantly caused by pathogenic COL3A1 variants. Diagnosis of vEDS in childhood primarily occurs due to a positive family history and/or the occurrence of an early arterial or intestinal event. However, little has been reported on additional clinical characteristics and management in this population.

Purpose

This study aims to identify critical drivers of a childhood vEDS diagnosis in individuals diagnosed through a national EDS service.

Methods

63 individuals (24 index, 31 females) with a clinical and genetic diagnosis of vEDS in childhood (< 18 years) were identified through a national EDS service, and childhood cardiovascular surveillance was conducted through joint inherited cardiovascular disease clinics.

Results

Diagnosis of vEDS in childhood occurred at a median age of 7 years (IQR 3-12) and was predominantly driven by positive family history of vEDS (55.5%). Clinical investigations were directly initiated by occurrence of a major clinical event in n=13 (20.6%), and a total of 17 major clinical events in childhood were recorded in 13 individuals. First events occurred at a median age of 11 years (IQR 0-13) and vascular events, though infrequent, occurred as early as the first year of life. In individuals who did not have a positive family history or major event, easy and/or excessive bruising was the most frequent cause for referral (60%).

Conclusions

This cohort provides further details of the clinical and genetic characteristics of children with vEDS and contributes new insight into drivers of vEDS diagnosis in childhood and the importance of long-term management, including paediatric cardiovascular surveillance.
Association between cardiac consultation and outcomes in patients with perioperative myocardial infarction/injury
Authors: Glarner N C , Puelacher C , Gualandro D , Pargger M , Mueller C
Published: October 2024

Introduction

Perioperative cardiac complications are a frequent occurrence and can lead to high short- and long-term mortality rates after major noncardiac surgery. No single intervention has yet demonstrated its effectiveness in treating perioperative myocardial infarction/injury (PMI). In this large prospective multicentre study, we aimed to evaluate the association between postoperative cardiac consultation and major adverse cardiac event (MACE) and all-cause death within 365 days in patients with PMI after undergoing major noncardiac surgery.

Methods

We prospectively included consecutive patients undergoing major inpatient noncardiac surgery at two hospitals who were eligible for the institutional active PMI surveillance and response programme. For this analysis, only patients with PMI who were directly transferred to the regular ward following surgery were included. In the case of a PMI, the standardised structured institutional response included assessing the patient for possible symptoms, recording a 12-lead ECG and a cardiac consultation. The specific scope of the PMI workup and management was determined by the attending clinical cardiologist following an institutional flowchart. Our primary endpoint was the occurrence of MACE (defined as a composite of cardiovascular death, MI, AHF, and life-threatening arrhythmia) within 365 days, excluding the initial PMI. All-cause death after 365 days was the secondary endpoint. Multivariable Cox proportional hazard models were used to evaluate the association of cardiac consultation with MACE and all-cause death after 365 days.

Results

During the period between October 2014 and September 2019, the BASEL-PMI study programme enrolled 14294 patients. After the exclusion of patients without PMI, with a postoperative ICU stay, multiple inclusion, or palliative setting 1048 patients remained. Among those, 434 patients received postoperative cardiac consultation (41.4%). Patients had a median age of 77 years and 44.8% were female.

After adjustment, patients who received a postoperative cardiac consultation had a lower risk of having MACE after 365 days (adjusted hazard ratio [aHR] = 0.54, 95% confidence interval [CI] 0.37 - 0.79, p-value = 0.001) and a lower risk of death of any cause after 365 days (aHR = 0.66, 95%CI 0.44 - 1.00, p-value = 0.048).

Conclusion

In a large multicentre prospective cohort study, postoperative cardiac consultation in patients with PMI was associated with a reduced risk of MACE and all-cause death after 365 days.Kaplan-Meier curve for MACE
Clinical prediction model of main adverse cardiovascular and cerebrovascular events for elderly patients with acute coronary syndrome
Authors: Xu J , Li Q , Yuan D , Wang P , Hao Y , Zhu P , Song Y , Yao Y , Jiang L , Wang J , Zhao X , Song L , Yuan J , Zhang Y
Published: October 2024

Background

Age is an independent factor for adverse outcomes in acute coronary syndrome (ACS). With the accelerated aging process, there is an increasing incidence of ACS in the elderly; however, research on this population is underrepresented. Due to the unique presence of multiple diseases and organ changes in the elderly, specialized risk assessment tools are required.

Purpose

To explore the risk factors for poor prognosis of elderly patients with ACS and establishing a risk stratification tool.

Methods

The derivation cohort consisted of 1674 elderly ACS patients consecutively enrolled in a single center from January 2013 to December 2013. The validation cohort included 2333 elderly ACS patients consecutively enrolled in nine medical centers from January 2015 to May 2019. All patients were followed up for 2 years, and the study endpoint was defined as major adverse cardiovascular and cerebrovascular events (MACCE). Model selection was performed using Cox regression and the Akaike Information Criterion (AIC) to construct the final risk assessment model. The performance of the predictive model was evaluated in the derivation and validation cohorts using the c-index, receiver operating characteristic (ROC) curves, and calibration curves.

Results

A total of 1,674 elderly ACS patients (70.97±4.68 years, 23.24% female) were included in the derivation cohort, and 210 cases (12.54%) of MACCE were recorded during the 2-year follow-up period. In the validation cohort, there were 2,333 elderly ACS patients (72.13±5.82 years, 35.83% female), with 364 cases (15.60%) of MACCE documented during the 2-year follow-up. Initially, 25 variables were preliminarily selected based on the results of univariate Cox regression and the clinical importance of these variables. Subsequently, these variables were included in a multivariable Cox model, and model selection was performed based on the AIC, resulting in the final selection of 10 variables (including age, cardiac insufficiency, current smoker, DAPT use, history of PCI or CABG, IABP use, number of lesions, residual SYNTAX score, preoperative HGB, and preoperative PLT). Then we developed and validated a nomogram to predict the 2-year MACCE in elderly ACS patients based on the assessment of 10 clinically easily obtainable variables during hospitalization. In both the derivation and validation cohorts, the nomogram demonstrated good discriminative ability (AUC of 0.723 and 0.699, c-index of 0.727 and 0.661, respectively) and calibration (calibration curves closely approximating the 45-degree diagonal line). The Kaplan-Meier analysis reveals significant differences in MACCE incidence rates between groups stratified by the median predicted probability (p<0.001).

Conclusion

Our study developed and validated a practical nomogram for predicting the 2-year risk of MACCE in elderly patients with ACS.
The real-world safety of ticagrelor among older adults (above 75 years): a pharmacovigilance study from the FDA data
Authors: Lerman T , Yacoby I , Fishman B , Goldman A , Talmor-Barkan Y , Itelman E , Orvin K , Eisen A , Kornowski R , Levi A
Published: October 2024

Introduction

Potent P2Y12 inhibitors are recommended in conjunction with Aspirin for the treatment of acute coronary syndrome. Since Prasugrel is relatively contraindicated in patients older than 75 years, Ticagrelor remains the primary potent P2Y12 inhibitor option for this age group. However, its safety profile among older adults has not been adequately examined.

Purpose

To examine Ticagrelor safety profile among older adults (≥75 years) patients

Methods

We conducted a retrospective pharmacovigilance study utilizing the FDA Adverse Event Reporting System (FAERS) database. We employed disproportionality analysis comparing Ticagrelor to Clopidogrel. We evaluated the reporting of predefined adverse events (dyspnea, bradyarrhythmia, complete AV block [CAVB], intracranial hemorrhage, gastrointestinal hemorrhage, acute kidney injury [AKI], and gout) in adults (<75 years) and older adults (≥75 years). For each group, we calculated reporting odds ratio (ROR) and its 95% confidence interval and compared them by calculating P for interaction.

Results

The FAERS database encompassed 6,476 adverse event reports for Ticagrelor; 4,795 (74%) adults and 1,681 (26%) older adults. Among older adults and compared to Clopidogrel, Ticagrelor was not associated with an increased reporting for dyspnea (ROR 3.3 [2.7-3.9] vs. 3.9 [3.5-4.5]), bradyarrhythmia (ROR 4.1 [2.5 – 6.7] vs 5.4 [3.9 – 7.6]) intracranial hemorrhage (ROR 1.1 [0.7-1.7] vs. 1.1[0.8-1.5]), CAVB (ROR 11.5 [3.1–42.4] vs. ROR 27.8 [6.7-116.3]), and gout (ROR 3.8 [0.5-27] vs. 3.9 [2-7.5]). AKI was reported more frequently among older adults (ROR 2.3 [1.5-3.6] vs. 0.6 [0.4-0.9]). Ticagrelor was not associated with an increased reporting of GI hemorrhage.

Conclusion

According to the FAERS, Ticagrelor is generally safe for use in older adults (≥75 years) with no significant increase in the reporting of major adverse events compared to adults (<75 years), except for a higher reporting of AKI.
The long-term clinical benefit of early versus delayed invasive strategies in elderly patients with non-ST-segment elevation myocardial infarction who have undergone percutaneous coronary intervention
Authors: Choe J C , Kim M S , Lee S H , Ahn J H , Lee H W , Oh J H , Choi J H , Lee H C , Cha K S , Jeong M H
Published: October 2024

Background

The data regarding long-term outcomes of early versus delayed invasive strategies in elderly patients who have undergone percutaneous coronary intervention (PCI) for non-ST-segment elevation myocardial infarction (NSTEMI) is limited.

Purpose

We aimed to investigate the long-term clinical benefit of early versus delayed invasive strategies in elderly patients who underwent PCI for NSTEMI.

Methods

From a nationwide, prospective, real-world registry of 13,104 patients with acute myocardial infarction (MI) who underwent PCI, 2818 elderly patients (aged ≥70 years) who underwent PCI for NSTEMI were included. Of these, 2299 patients were treated with an early invasive strategy (early invasive group), and 519 were treated later (delayed invasive group). The incidence of major adverse cardiac events (MACE; all-cause death, recurrent MI, any revascularization, stroke, readmission due to heart failure [HF], or definite/probable stent thrombosis [ST]) and the components of MACE were compared using multivariable Cox regression, propensity score (PS) matched, and PS-adjusted analyses.

Results

During a median follow-up of 1047 days, MACE, all-cause death, and cardiac death occurred in 1018 (36.1%), 660 (23.4%), and 423 patients (15.0%), respectively. The early invasive group showed significantly lower risks of MACE (entire: 35.0% vs. 41.2%, hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.66-0.90, p=0.001; PS-matched: n=984, 33.3% vs. 40.8%, HR 0.75, 95% CI 0.62-0.91, p=0.005), all-cause death (entire: 22.5% vs. 27.4%, HR 0.76, 95% CI 0.63-0.92, p=0.004; PS-matched: 21.8% vs. 27.2%, HR 0.75, 95% CI 0.58-0.90, p=0.005), cardiac death (entire: 13.8% vs. 20.2%, HR 0.64, 95% CI 0.51-0.79, p<0.001; PS-matched: 13.1% vs. 19.4%, HR 0.67, 95% CI 0.55-0.86, p=0.011), and readmission due to HF (entire: 6.5% vs. 9.2%, HR 0.64, 95% CI 0.46-0.89, p=0.007; PS-matched: 6.7% vs. 9.4%, HR 0.68, 95% CI 0.51-0.96, p=0.017) than the delayed invasive group. There were no significant differences in the risks of recurrent MI, any revascularization, stroke, and definite/probable ST between the groups. Furthermore, in patients aged ≥80 years, the early invasive group had significantly reduced rates of MACE (42.9% vs. 49.5%, HR 0.71, 95% CI 0.55-0.91, p=0.039), all-cause death (31.7% vs. 39.0%, HR 0.71, 95% CI 0.55-0.92, p=0.010), and cardiac death (20.9% vs. 31.0%, HR 0.59, 95% CI 0.44-0.80, p=0.001) compared to the delayed invasive group.

Conclusions

In elderly patients with NSTEMI, an early invasive intervention strategy was associated with favorable long-term clinical outcomes compared to a delayed invasive intervention strategy.
Insights into cardiac amyloidosis screening in TAVI from a Greek/Cypriot Cohort: the GRECA-TAVI registry
Authors: Antonopoulos A , Tsampras T , Ioannides M , Eftychiou C , Panagiotopoulos I , Naka K , Zacharoulis A , Ktenopoulos N , Katsimaglis G , Vavouranakis E , Koutelou M , Toutouzas K , Kochiadakis G , Tsioufis K , Vlachopoulos C
Published: October 2024

Background

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a disease with a poor prognosis and an unknown prevalence in the general population. Specific patient subgroups are at higher risk, such as patients with severe aortic stenosis (AS).

Purpose

To investigate the prevalence of ATTR-CM in Greek and Cypriot patients with severe AS that undergo Transcatheter Aortic Valve Implantation (TAVI).

Methods

A total of eight (n=8) tertiary hospital centers from Greece and Cyprus formed part of the GRECA-TAVI registry to evaluate the prevalence of ATTR-CM in patients undergoing TAVI. The inclusion criteria were diagnosis of severe AS in the presence of left ventricular hypertrophy (i.e. ≥12mm). Patients were referred for ATTR-CM screening by Tc99m-DPD or Tc99m-PYP bone scintigraphy. A complete hematologic workup was performed in all patients to rule out plasma cell dyscrasias. Cases with equivocal bone scintigraphy findings were not included in analysis.

Results

A total number of n=303 AS patients were screened from January 2023 until February 2024. Screening for CA with Tc99m-DPD/PYP bone scintigraphy and hematological tests was complete for all the patients included in the study. A positive bone scan (i.e. Perugini scale 2 or 3) was found in n=31 or 10.2% of the patients. The mean age of patients was not significantly different between AS patients with and without ATTR-CM (82,25 ±1,8 vs. 81,21 ±0,44 respectively, p=0.478). A male predominance was found in the ATTR-CM subgroup, although this was not statistically significant compared to non-ATTR-CM patients (%male: 64.5% vs. 49.3%, respectively, p=0.13). ATTR-CM patients had a lower LVEF compared to non-ATTR-CM patients (47.5% ±2.13 vs. 55% ±0.75, p=0.046).

Conclusions

The prevalence of ATTR-CM in this cohort of patients with severe AS undergoing TAVI was ~10%. These findings call for the implementation of national screening strategies for ATTR-CM which still remains significantly underdiagnosed in many geographic parts of the globe.
Multidisciplinary strategies for cardiotoxicity management in ambulatory care: exploring practices, insights, and prospects for advancement
Authors: Payo Anez L , Haase T , Harst L , Ibrahim K , Christoph M , Koesters M , Schmitt J , Quick S
Published: October 2024

Background

The management of cardiotoxicity, a significant concern in chemotherapy patients, necessitates a multidisciplinary approach. This study investigates the variability in cardiotoxicity management in outpatient settings across different medical specialties, which may lead to inconsistencies in patient care.

Methods

An extensive questionnaire-based study was conducted to assess the current practices and viewpoints of cardiologists, oncologists, and gynecologists in the management of cardiotoxicity among patients receiving outpatient chemotherapy in Germany. The survey engaged 1,329 medical professionals through an online platform, with a participation rate of 9.9%, amounting to 132 respondents.

Results

Respondents reported managing a combined total of 1,905 chemotherapy patients monthly, with individual patient loads ranging from 1 to 200. Notably, only a fraction of these patients – 37% under oncologist care and 48% under gynecologist care – underwent routine cardiological examinations. As shown in Figure 1, the three most common causes of cardiological presentations in patients undergoing chemotherapy were due to acute patient complaints (65.2%), before the start of chemotherapy (91.3%), and after the end of chemotherapy (78.3%). Furthermore, 37% of healthcare providers reported incorporating chemotherapy-induced cardiovascular toxicity risk assessments in their clinical routines. Medical history, ECG, and echocardiography were the most frequent examinations. Notably, 91.3% did not include cardiac biomarker measurements in their follow-up procedures (Figure 2). More than half of the participants (56%) expressed a need for simplified cardio-oncology guidelines. The majority of participants (84% and 83%, respectively) requested tools to assist in cardiovascular toxicity risk assessment and the implementation of appropriate therapeutic measures for patients undergoing chemotherapy.

Conclusions

The study draws attention to significant interdisciplinary care gaps in managing cardiotoxicity, which may contribute to an increased risk of undiagnosed cardiovascular complications in chemotherapy patients. The evident variability in cardiotoxicity management practices among different medical specialties underscores the critical need for heightened awareness and enhanced collaborative efforts. The implementation of comprehensive interdisciplinary clinical pathways and the establishment of a dedicated cardio-oncology network could potentially address these challenges, particularly in supporting primary care physicians.Figure 1Figure 2
Adverse Myocardial and vascular side effects of Immune Checkpoint Inhibitors: a prospective multimodal cardiovascular assessment (AMICI study)
Authors: Mirabel M , Eslami A , Thibault C , Oudard S , Mousseaux E , Wahbi K , Fabre E , Marijon E , Villefaillot A , Lillo-Lelouet A , Bruno R M , Soulat G , Hulot J S
Published: October 2024

Background

Immune checkpoint inhibitors (ICIs) are transformative treatments in oncology, yet they are also associated with a range of cardiovascular (CV) events.

Purpose

To identify the incidence of CV events (including subclinical) in patients receiving ICIs for solid cancer, either alone or in association with other cancer therapies (e.g., chemotherapies, target therapies).

Objectives and methods

The Adverse Myocardial and vascular side effects of Immune Checkpoint Inhibitors(AMICI) study prospectively assessed the incidence of CV changes by means of a thorough multimodal assessment. This included repeated CV imaging (transthoracic echocardiograms (TTE), cardiac magnetic resonance imaging (CMR)), serum biomarkers (troponin, brain natriuretic peptides in a single laboratory), and ambulatory ECG monitoring, before and during (at 6 weeks and at 6 months) ICI therapy (Figure). Cardiovascular events included myocarditis, pericarditis, acute coronary syndrome, heart failure (HF), high degree conduction abnormalities (defined as new grade 2 or 3 atrioventricular block) or sustained ventricular arrhythmias (defined as 3 or more ventricular beats at a rate ≥ 120/min), CV death as a composite endpoint, validated by an independent expert panel

Results

Out of 130 solid cancer patients considered for ICI therapy, 49 patients (38 (77.6%) male; mean age 64.3 (­SD 11.0) years old) were included (June 2020 -December 2021). 22 (55.1%) suffered from kidney or bladder cancer; 7 (14.3%) had CV disease prior to cancer diagnosis; 4 (8.2%) received PD1 and CTLA4 inhibitors. Early CV events were observed in 9 (18.4%) patients at mean 40.1 (SD 5.9) days, with heart failure (HF) in 5 (10.2%), ventricular arrhythmias or new conduction disorders in 4 (8.2%) patients. History of AF (HR 4.49 (CI 1.11-18.14), P=0.035) predicted early CV events at 6 weeks (Table). At 6 months follow-up, 18 CV events were observed in 15/49 (31%) patients, with 6 (12.2%) HF events, 5 (10.2%) significant ventricular arrhythmias or conduction disorders and 4 (8.2%) AF. There was a significant decline in LVEF (P<0.001) in patients even in the absence of CV event (P=0.003) or HF (P=0.003). Higher creatinine at inclusion (HR 0.99 [0.98-1.00], P=0.006) predicted HF.

Conclusions

Cardiovascular complications arising during cancer treatment with ICIs are primarily due to the exacerbation of pre-existing HF or the onset of non-inflammatory heart rhythm disorders. The majority of these CV changes manifest shortly after starting ICIs and do not need hospital admission. Our results suggest that more close follow-up may be needed in patients with underlying CV conditions when starting ICI therapy, by means of CMR and ambulatory ECG holter monitoring.
Early rhythm control of atrial fibrillation in cancer survivors: a nationwide population-based cohort study
Authors: Han S , Lee S R , Choi E K , Kim B , Han K D , Choi J M , Lee K Y , Ahn H J , Kwon S , Oh S , Lip G Y H
Published: October 2024

Background

Though early rhythm control (ERC) in patients with atrial fibrillation (AF) is effective in reducing stroke, the benefit of ERC has not been well-elucidated in cancer survivors. This study aimed to compare the risk of ischemic stroke between ERC and usual care in cancer survivors with AF and cancer.

Methods

This nationwide observational study was conducted using the Korean National Health Insurance Service database. Patients aged 20 years or older with newly diagnosed AF between 2009 and 2018 were included. Patients who received rhythm control therapy within 1-year of AF diagnosis were defined as the ERC group, while the remaining patients were defined as the usual care group. The risk of ischemic stroke in the ERC group compared to the usual care group was evaluated in long-term cancer survivors (cancer diagnosis ≥5 years) and the non-cancer group.

Results

A total of 591,692 patients were included in the study (18,747 patients [3.2 %] with cancer, mean age 65.7±14.6 years, 53.7% men, mean CHA2DS2-VASc score 3.3±2.0). The proportion of patients receiving ERC was slightly higher in cancer survivors compared to the non-cancer group (28.0% vs 25.3%, p<0.001).

During a mean 4-year follow-up, incident stroke occurred in 52,500 patients (1,338 in cancer survivors, 51,182 in non-cancer). The ERC group showed a lower risk of stroke than the usual care group, regardless of the presence of cancer history(Figure); adjusted hazard ratio [95% confidence interval] 0.67 [0.58-0.76] in cancer survivors, 0.76 [0.74-0.78] in the non-cancer group (p-for-interaction=0.125). The effect of ERC on the risk of ischemic stroke in cancer group was consistent across all subgroups, including different cancer types or use of chemotherapy.

Conclusion

ERC was associated with a lower risk of ischemic stroke among long-term cancer survivors. An integrated approach incorporating appropriate rhythm control strategies should be considered for cancer survivors with newly diagnosed AF.
Educational attainment and cardiovascular outcomes in prostate cancer: observations from 3700 men in 6 countries in the RADICAL PC study
Authors: Guha A , Pinthus J , Valle F , Piccoli R , Dusilek C , Duceppe E , Kann A , Fradet V , Shayegan B , Violette P , Koo C , Beato P , Villareal N , Cavalli G , Leong D
Published: October 2024

Background

Educational attainment has been associated with improved cardiovascular outcomes in individuals with or at high risk for cardiovascular disease (CVD). There is little information on the relationship between education and CVD outcomes in individuals with cancer. Also, we have limited understanding of what mediates the relationship between education and these outcomes.

Purpose

To evaluate the relationship between educational attainment in patients with PC and CVD event (CVE) or all-cause mortality.

Methods

We prospectively studied 3,778 men with PC from 55 sites in 7 countries (median age 69 years), 46% on ADT. Inclusion criteria were one of: PC diagnosed in the past 12 months; started ADT within the past 6 months; or plan to start ADT in the next month. Educational attainment was classified as those who attained primary school education vs. those who attained high school education vs. those who attained greater than high school education. Participants were followed for a median of 2.5 years from enrolment to document CVE: myocardial infarction, angina, stroke, cerebrovascular disease, peripheral arterial disease, arterial revascularization, heart failure, venous thromboembolism, and atrial fibrillation. The primary outcome for this analysis was CVE or death. All outcomes were evaluated by Cox proportional hazards models adjusted sequentially for age, race, physical activity levels, tobacco use, and alcohol use.

Results

Among 3,778 participants, 726 (19%) achieved primary school education, 1,001 (27%) high school, and 2,051 (54%) greater than high school education.

On univariate analysis, as compared with participants with greater than high school education, those with high school education and primary school education had respective HR (95% CI) of 1.33 (1.05-1.69) and 2.19 (1.71-2.83).

Adding age, race, tobacco, and alcohol use to the Cox model progressively attenuated the association between education and the primary outcome. Eventually, after adjustment for these characteristics and physical activity levels, the relationship between education and the primary outcome was no longer significant (Table).

Conclusion

This finding suggests that patterns of tobacco and alcohol use and physical activity, which are modifiable behaviors, account for the relationship between education and death or CVE in patients with prostate cancer.Table
Safety and efficacy of immune checkpoint inhibitors in patients with pre-treatment reduced left ventricular function
Authors: Tzuberi M T , Brzezinski R B , Flint N F , Solemsn M S , Waissengrin B W , Barak R B , Golomb I G , Wolf I W , Topilsky Y T , Banai S B , Kapusta L K , Laufer-Perl M
Published: October 2024

Background

Immune checkpoint inhibitors (ICIs) have revolutionized the clinical outcomes of cancer. Nevertheless, the response varies across populations and their use may lead to ICIs-related adverse events (irAEs), including cardiovascular (CV) irAEs, which can be life-threatening. Limited evidence exists regarding the safety and efficacy of ICIs therapy in patients presenting with pre-treatment reduced left ventricular ejection fraction (LVEF).

Objectives

To evaluate the safety and efficacy of ICIs therapy in patients with pre-treatment reduced LVEF.

Methods

Retrospective single center cohort of patients treated with ICIs therapy, who performed pre-treatment LVEF assessment. The primary endpoint was to evaluate the safety of ICIs among this population, assessed by CV irAEs (composite of myocarditis, acute coronary syndrome, heart failure, and arrhythmia). The secondary endpoint was to evaluate the efficacy of ICIs, assessed by all-cause mortality and progression-free survival (PFS).

Results

The cohort included 307 patients with 30 (10%) patients presenting with pre-treatment reduced LVEF, with a mean LVEF of 39±7%. While a significantly higher prevalence of CV irAEs was observed in the reduced LVEF group (37% vs. 14%, p=0.004), following a multivariable cox regression analysis including baseline cardiovascular diseases and risk factors, pre-treatment reduced LVEF did not remain a significant predictor (p=0.635). No significant differences were observed between the groups regarding all-cause mortality and PFS.

Conclusions

Pre-treatment reduced LVEF was found to be safe with no significant impact on efficacy among patients treated with ICIs.