bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential hematopoietic effects of SGLT2 inhibitors in patients with cardiac amyloidosis
Authors: Ermolaev N , Willixhofer R , Kronberger C , Rettl R , Binder C , Duca F , Nitsche C , Kammerlander A , Poledniczek M , Gregshammer B , Ahmadi-Fazel D , Kastner J , Bergler-Klein J , Badr-Eslam R
Published: October 2024

Introduction

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have been revealed to have potential hematopoietic effects in patients with heart failure (HF), leading to an improvement in clinical outcome. However, these benefits have not been studied in patients with cardiac amyloidosis (CA), despite CA often causing symptoms of heart failure (HF) and contributing to an iron-deficient state, which further complicates by limiting erythropoiesis and lowering haemoglobin and haemotocrit levels. We aimed to determine the potential of SGLT2i in improving haematological parameters and functional capacity (FC) in amyloidosis patients.

Methods

A prospective analysis was conducted to compare the effects of SGLT2i in a cohort of patients who received the best medical therapy (BMT) alongside SGLT2i (n=20), as opposed to patients receiving only BMT without SGLT2i (n=20). All of patients underwent blood testing and cardiopulmonary exercise testing (CPET) at baseline and after 6 months (IQR:5.0 – 6.0).

Results

The SGLT2i-based therapy resulted in a significant improvement and difference in hematological parameters upon follow-up assessment compared to the control group. In the SGLT2i group, the mean haemoglobin level increased from 13.3 g/dL to 14.5 g/dL, whereas in the control group, it decreased from 12.7 g/dL to 10.9 g/dL (P < 0.001). Furthermore, the haematocrit difference showed a significant increase in the SGLT2i group (+3.8%) compared to a decrease in the control group (-4.4%) (P < 0.001). Additionally, the iron status improved in the SGLT2i-treated group (+6.7 µg/dL) compared to a decrease in the control group (-14.9 µg/dL), although the difference was significant only with a p-value of 0.034. However, neither group demonstrated significant improvement nor regression in CPET parameters. The peak oxygen consumption (peak VO2, (ml/min)/kg) showed no significant change in either group (P = 0.286), as well as VE/VCO2 slope (P = 0.295).

Conclusions

Treatment with SGLT2i could be utilized in the treatment of patients with amyloidosis. This potential benefit in improving hematological parameters warrants further investigation and consideration in clinical practice.
Risk of death, thromboembolic events, and bleeding in elderly patients with Atrial Fibrillation and Clinical Complexity who are not taking oral anticoagulation
Authors: Bucci T , Romiti G F , Hironori I , Gerra L , Huang B , Proietti M , Lip G Y H
Published: October 2024

Background

Patients with Atrial Fibrillation (AF) often exhibit Clinical Complexity (CC), defined as ≥2 features, i.e. patients aged ≥75 years plus a body mass index (BMI) < 23/kg/m2 and/or bleeding history and/or chronic kidney disease. No data are available about the clinical course of patients with Atrial Fibrillation (AF) and CC who are not taking oral anticoagulation (OAC).

Purpose

To assess the risk of thrombotic and hemorrhagic events in patients with Atrial Fibrillation (AF) and CC who are not taking OAC.

Methods

Retrospective study with a health care research network (TriNetX). Based on the ICD-10-CM codes entered between 2011-2022 from 85 health care organizations mainly located in the United States, AF patients ≥75 years with CC were categorized into two groups based on the use of OAC during the last year before the study period. The primary outcomes were the one-year risk of death, major cardiovascular events ([MACE]: heart failure, stroke, and myocardial infarction), and major bleeding (central nervous system, gastrointestinal, internal bleeding, and hypovolemic shock). Secondary outcomes were each component of the primary outcome and catheter ablation. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% CIs following propensity score matching 1:1.

Results

Overall, we identified 271,402 AF CC patients not on OAC (80.1±6.8 years, 46.5% females) and 87,101 AF CC patients on OAC (79.8±6.5 years, 47.6% females). Before PSM, AF CC patients not on OAC showed no significant differences in cardiovascular and bleeding risk factors but were less treated with pharmacological treatment than AF CC patients on OAC. After PSM, no significant differences were found between the two groups, but AF CC not on OAC were at higher risk of all-cause death (HR 1.54, 95%CI 1.50-1.57), MACE (HR 1.13, 95%CI 1.11-1.16), and major bleeding (HR 1.34, 95%CI 1.31-1.38), when compared to AF CC on OAC. AF CC patients not on OAC were associated with a higher risk of each component of the primary outcome and with a lower use of catheter ablation procedures (HR 0.48, 95%CI 0.43-0.54) (Table 1). The risk of the composite outcomes was the highest in those with all the three CC components. A progressive increase in OAC prescription was observed during the follow-up period, with increasing of NOACs and lower use of warfarin being observed. There was a clear temporal relationship between increasing OAC prescription and incidence of bleeding in CC patients (Figure 1)

Conclusions

AF CC patients not on OAC have a high risk of all-cause death, thrombotic and hemorrhagic events. Over time, increasing NOAC use was associated with more bleeding in CC patients. New antithrombotic approaches aimed at reducing thrombotic risk without increasing bleeding risk are needed in these patients.Figure 1 OAC new prescriptions
Edoxaban dose, frailty, and outcomes in patients with atrial fibrillation: the ETNA-AF-Europe 4-year follow-up
Authors: Fumagalli S , Diemberger I , Komen J J , Fronk E M , Kirchhof P , De Caterina R
Published: October 2024

Background

Frailty is a common reason to choose non-recommended (non-rec) doses of non-vitamin-K-antagonist oral anticoagulants in patients with atrial fibrillation (AF); however, it is not known how this practice affects stroke and bleeding outcomes.

Purpose

To assess clinical outcomes in frail patients with AF receiving non-rec vs recommended (rec) doses of edoxaban using 4-yr follow-up data from ETNA-AF-Europe.

Methods

The prospective, observational ETNA-AF-Europe study followed patients with AF receiving edoxaban for up to 4 yrs. In ETNA-AF-Europe, perceived frailty was based on investigators’ own clinical binary judgement in each patient. Objective frailty was determined using a simplified adaptation of the Rockwood’s Frailty Index. For objective frailty, patients with missing index were categorised as non-frail. Patients with perceived or objective frailty were combined for this analysis. Baseline characteristics and hazard ratios (HRs) with 95% confidence intervals (CIs) assessing risk of outcomes in frail patients prescribed non-rec vs rec edoxaban doses (i.e., non-rec 60mg vs rec 30mg and non-rec 30mg vs rec 60mg) are presented. Data were adjusted for age, sex, and derived versions of the CHA2DS2-VASc and HAS-BLED scores. Net clinical benefit was defined as any stroke/systemic embolic event (SEE), transient ischaemic attack, venous thromboembolic event, major bleeding, or cardiovascular death, whichever came first.

Results

Of 13164 patients, 1786 were frail (13.6%; perceived frailty [n=1410], age [IQR]: 82.0 [78.0-86.0] yrs, women: 57.9%; objective frailty [n=540], age [IQR]: 77.0 [71.0-82.0] yrs, women: 31.9%; both, n=164). Baseline characteristics are reported in Table 1.

Risk of all-cause death was higher in frail patients treated with non-rec 30mg vs rec 60mg (HR [95% CI]: 1.44 [1.06,1.96]). The annualised rate [CI] of any stroke/SEE was non-significantly higher (HR [95% CI]:1.60 [0.80,3.20]) with non-rec 30mg (n=169; 2.25 [1.25,4.06]) vs rec 60mg (n=622; 1.54 [1.08,2.20]). There was, however, no association between treatment received and risk (HR [95% CI]) of major bleeding (1.19 [0.58,2.43]) or net clinical benefit (1.26 [0.84,1.87]) (Figure 1).

In frail patients who received non-rec 60mg (n=183) vs rec 30mg (n=695), risk of any stroke/SEE (HR [95% CI]) was higher (2.15 [1.03,4.49]), but there were no significant differences in the risk (HR [95% CI]) of major bleeding (1.03 [0.52,2.01]), net clinical benefit (1.15 [0.78,1.71]), or all-cause death (0.79 [0.59,1.05]) (Figure 1).

Conclusions

In this large European AF registry, the presence of frailty should not drive dosing recommendations for edoxaban. In particular, when compared with the rec 60mg dose, the non-rec 30mg (reduced) dose, was associated with more all-cause death and no benefits on major bleeding.Baseline Characteristics
Long-term mortality outcomes of southeast asian patients with aortic stenosis
Authors: Ong J , Leow A , Ching K , Goh F Q , Chew N W S , Kong W K F , Yeo T C , Sia C H , Poh K K
Published: October 2024

Background

Limited data exists on mortality outcomes of aortic stenosis (AS) in Southeast Asians. Insights into this may confer prognostic benefits and affect therapeutic targets.

Purpose

Our study aims to provide insights into 10-year mortality outcomes and prognostic indicators of AS in this cohort.

Methods

Consecutive patients (n = 703) with echocardiographic diagnoses of AS at a tertiary academic hospital in Southeast Asia were studied. Demographics, co-morbidities and outcomes were collected. Multivariate Cox regression model was constructed.

Results

55.2% (n = 388) of patients had mild AS, 29.3% (n = 206) had moderate AS, and 15.5% (n = 109) had severe AS. Out of 431 deaths, 35.8% (n = 86) of known cases were cardiovascular. The leading cause of cardiovascular mortality was coronary-linked in 20.8% (n = 50); 7.9% (n = 19) was valvular aortic stenosis; 2.5% (n = 6) was cardiac failure, 1.3% (n = 3) was sudden cardiac death, and 2.9% (n = 7) was ischaemic stroke. Of 154 (64.2%) non-cardiovascular mortality, sepsis caused 40% (n = 97) of deaths, malignancy in 11.7% (n = 28), renal failure in 5% (n = 12) and respiratory failure in 1.7% (n = 4). 44.3% (n = 191) of cases were unknown. Higher proportions of AS patients with cardiovascular death had hyperlipidaemia (p = 0.027) and coronary artery disease (p = 0.028). Multivariable Cox regression showed age (HR 1.041, 95% CI: 1.020-1.062, p < 0.001), anaemia (HR 2.121, 95% CI: 1.535-2.930, p < 0.001) and prior cardiovascular hospitalisation (HR 1.420, 95% CI: 1.040-1.938, p = 0.027) to be significant predictors of all-cause mortality. Aortic valve replacement was a significant protective factor of all-cause mortality after adjustments for age, gender, comorbidities, and echocardiographic findings (HR 0.313, 95% CI 0.131-0.747, p = 0.009).

Conclusions

Non-cardiovascular death was the leading cause of mortality in Southeast Asians with AS. Ischaemic heart disease was the commonest cause of cardiovascular mortality. Predictors of all-cause mortality included age, anaemia and prior cardiovascular hospitalisation. Valvular replacement was protective of all-cause mortality in AS.
Sex differences in clinical data and long-term outcomes of elderly patients with acute myocardial infarction presenting with cardiogenic shock undergoing 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

Data on contemporary clinical practice and long-term outcomes for sex differences in elderly patients with acute myocardial infarction (MI) who have undergone percutaneous coronary intervention (PCI) presenting with cardiogenic shock (CS) is limited.

Purpose

This study aimed to investigate contemporary clinical data and long-term clinical outcomes according to sex differences in elderly patients undergoing PCI for acute MI complicated by CS.

Methods

We analyzed data from a nationwide, prospective, and real-world registry comprising elderly patients (≥65 years) with acute MI who have undergone PCI and presented with CS. Of the 540 patients included, 228 were women, and 312 were men. We compared major adverse cardiac events (MACE; all-cause death, recurrent MI, any revascularization, stroke, heart failure [HF] readmission, or definite/probable stent thrombosis [ST]) and the components of MACE between the groups using multivariable Cox regression, propensity score (PS) matching, and PS-adjusted analyses.

Results

Compared to men, women were younger and had higher incidences of hypertension and elevated pro-BNP levels. No significant differences were observed in other cardiovascular risk factors, left ventricular systolic function levels, or adherence to guideline-directed medical therapy between the groups. Over a median follow-up of 1035 days, MACE, all-cause death, and cardiac death occurred in 257 (47.6%), 212 (39.3%), and 170 (31.5%) patients, respectively. Women exhibited significantly increased risks of MACE (overall: 53.5% vs. 43.3%, hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.97, p=0.023; PS-matched: n=368, 52.3% vs. 41.8%, HR 0.73, 95% CI 0.53-0.94, p=0.033), all-cause death (overall: 44.7% vs. 35.3%, HR 0.77, 95% CI 0.58-0.97, p=0.032; PS-matched: 42.8% vs. 33.4%, HR 0.71, 95% CI 0.54-0.95, p=0.041), cardiac death (overall: 35.1% vs. 28.8%, HR 0.81, 95% CI 0.60-0.97, p=0.048; PS-matched: 34.4% vs. 26.9%, HR 0.78, 95% CI 0.54-0.95, p=0.043) compared to men. There were no significant differences in the risks of recurrent MI, any revascularization, stroke, HF readmission, and definite/probable ST between the groups.

Conclusions

In this nationwide registry, women compared to men exhibited increased risks of long-term clinical outcomes in elderly patients with acute MI who have undergone PCI presenting with CS.
Lipid lowering therapy in patients aged 90 years or older with acute myocardial infarction:a multicenter cohort study
Authors: Huo L K , Hu S T , Gu T S , Zhang Y K , Jiang C , Zhang J K , Wu X , Liu X , Liu T , Chen K Y
Published: October 2024

Background

Lipid-lowing therapy significantly reduce adverse cardiovascular events in patients with acute myocardial infarction (AMI). However, evidence regarding the efficacy of lipid-lowing therapy in extremely elderly patients with AMI is limited.

Purpose

This study aims to evaluate major adverse cardiovascular events (MACCE) at 1 year in relation to taking lipid-lowing therapy (statins) among patients aged 90 years or older.

Methods

The data for this study were derived from a retrospective cohort comprising patients admitted to secondary or tertiary hospitals from 2010 to 2023. Patients were grouped by lipid-lowing therapy: statins group (n=549) and not taking statins group (n=811). The primary endpoint was MACCE, a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, at 1 year. Secondary endpoints included cardiac death (CD), stroke, and recurrence of myocardial infarction at 1 year. Inverse probability treatment weighting (IPTW) based on propensity scores was performed to balance baseline characteristics. A multivariate adjusted Cox proportional hazard model evaluated the association between lipid-lowing therapy and clinical endpoints.

Results

Of the 1,360 patients, 77.2% were men, and the median age was 92 years. During 1 year follow up, 35.3% of patients experienced MACCE, and 28.7% died due to CD. After IPTW, the incidence of MACCE was lower in the statins group compared to the non-statins group (33.3% vs. 42.6%, p=0.036), as was 1- year mortality due to CD (26.2% vs.35.9%, p=0.021). However, there were no differences in the incidence of stroke (2.8% vs. 4.5%, p＞0.274) or recurrence of myocardial infarction (4.7% vs. 5.1%, p=0,855) at 1 year. Kaplan-Meier analysis showed a lower probability of 1-year MACCE and CD in the statins group (log-rank test, p<0.001). Multivariate Cox regression analysis demonstrated that statin therapy reduced the incidence of MACCE (aHR 0.67; 95%CI, 0.40–0.91; p=0.009) and 1-year CD (aHR 0.63; 95%CI, 0.45–0.87; p=0.005).

Conclusions

Lipid-lowering therapy with statins was associated with a significantly lower risk of 1-year MACEE and cardiac death in elderly patients aged over 90 years with AMI. These findings support the use of lipid-lowing therapy in elderly individuals.
Delirium and risk of incident cardiovascular events in elderly: data from a global health research network
Authors: Proietti M , Bucci T , Romiti G F , Pipitone E , Corica B , Bellelli G , Lip G Y H
Published: October 2024

Introduction

Delirium is a common complication of acute medical disorders. A strong association between cardiovascular events and the occurrence of delirium has been recorded. Thus far, no data are available regarding the risk of incident cardiovascular events after delirium onset in older adults.

Methods

Using data from TriNetX, a global health federated research network, we performed a propensity score matched (PSM) analysis of older adults (age ≥65 years) admitted to the emergency department (ED) reporting delirium within two weeks, who were compared with those without delirium. We evaluated the occurrence of a composite outcome of cardiovascular events (myocardial infarction, ischemic stroke, heart failure, intracranial haemorrhage, ventricular arrhythmias, takotsubo syndrome, and atrial fibrillation) at 30 days and 1 and 3 years of follow-up.

Results

4,480,229 patients were retrieved for the analysis, and 82,693 (1.8%) reported delirium. Before PSM, patients reporting delirium were older, with more prevalent comorbidities. After PSM, a total of 165,386 patients were included in the analysis (mean (SD) age 76.6 (9.0) years, 51.1% females). Throughout the entire follow-up period, the cumulative composite cardiovascular events outcome was significantly higher in patients which reported delirium [Red Line, Figure 1].

Delirium was associated with cardiovascular events at 30 days (HR 1.96, 95% CI 1.92-2.00) ,1 year (HR 1.75, 95% CI 1.72-1.78) and 3 years (HR 1.67, 95% CI 1.64-1.69) of follow-up, as well as for each of its components (Table 1). The presence of delirium was also associated with a higher risk of all-cause death and hospital access (Table 1), evaluated as secondary outcomes.

In patients with delirium associated with the occurrence of incident cardiovascular events, there was a higher risk of recurrent cardiovascular events at 1 year (HR 3.11, 95% CI 2.92-3.31) and 3 years (HR 2.84, 95% CI 2.67-3.01) of follow-up.

Conclusions

In a large, unselected cohort of older adults admitted to ED, occurrence of delirium was associated with a higher risk of cardiovascular events, both in the short and long-term follow-up.Figure 1:Delirium and CV EventsTable 1:Cox Regression Analysis
Sodium-glucose co-transporter-2 inhibitors : a potential cardioprotective agent?
Authors: Stratinaki M , Maragkoudakis S , Stavrakis S , Papoutsaki E , Korela D , Aletras G , Honda E , Garidas G , Georgopoulou T , Eleftheriadou E , Pitarokoilis M , Liapi D , Kafkala K , Foukarakis E
Published: October 2024

Background

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are one of the cornerstones in the treatment of patients with heart failure (HF) , regardless the ejection fraction (EF) or the presence of diabetes mellitus (DM). Other types of medications used in the treatment of heart failure , like angiotensin converting enzyme inhibitors (ACEi) or beta-blockers (BB) have shown some degree of cardioprotection in high risk patients receiving cardiotoxic chemotherapy, but data on SGLT2i are very limited.

Purpose

To examine the possible differences in the development of anthracycline cardiotoxicity in diabetic patients receiving SGLT2i compared to those who don’t.

Methods

We retrospectively analysed the data from the oncological as well as hematological patients of our hospital. Group 1 (SGLT2) included patients with cancer who received anthracycline treatment and diabetes on treatment with SGLT2i. Group 2 (control) included patients with cancer who received anthracycline treatment and diabetes but with treatment other than SGLT2i. We recorded the basic demographic parameters, the development of cardiotoxicity (heart failure incidence, heart failure admissions, new cardiomyopathy [>10% decline in ejection fraction to <50%], and clinically significant arrhythmias) as well as the abnormal levels of troponin I (tnI) and natriuretic peptides (NTproBNP).

Results

Age, sex, ethnicity, cancer type, cancer stage, and other cardiac risk factors were similar between groups. The mean duration of the follow up was 2 years. In the SLT2 group were included 86 patients and in the control group 97. The rates of the cardiotoxicity events were recorded as follow : (SGLT2 vs control)

Heart failure (7.4% vs 31.9%, p<0.01), heart failure admissions (3.4% vs 12.3%, p<0.05), new cardiomyopathy (6.1% vs 27.2%, p<0.05), arrhythmias (2.7% vs 24.3%, p<0.01), abnormal tnI levels (4.2% vs 14.7% , p< 0.01), abnormal NTproBNP levels (6.4% vs 30.9%, p<0.01)

Conclusions

SGLT2 inhibitors were associated with lower rate of cardiac events among patients with cancer and DM who were treated with anthracyclines. Further studies are needed in order to test the possible cardioprotective effects of SGLT2 inhibitors in patients at high cardiac risk treated with anthracyclines.
Arrhythmogenic effects of DEHP exposure: insights into cardiac electrophysiology and myocardial cells
Authors: Lin T , Sung Y L S , Chung C L C , Lin C Y L
Published: October 2024

Introduction

Hemodialysis patients, who are exposed to plasticizers through the hemodialysis circuit, face a high risk of cardiovascular disease (CVD). Plasticizers, such as the endocrine-disrupting compound Di(2-ethylhexyl) phthalate (DEHP), have emerged as potential contributors to CVD. This study explores the impact of DEHP on cardiac electrophysiology and myocardial cells, providing insights into its cardiotoxic effects.

Methods

We employed optical mapping techniques to assess cardiac electrophysiology in Langendorff-perfused rat hearts exposed to DEHP, comparing them to a control group. Additionally, we evaluated the effect of DEHP on cardiac muscle cells using H9C2 rat cardiomyoblasts.

Results

Prolonged DEHP exposure resulted in elevated heart rate, increased electrocardiographic variability, and higher low-frequency values, indicative of sympathetic nervous system overactivity. Action potential duration at APD80 increased, leading to greater action potential triangulation. Electrical alternans observed in the DEHP-treated group heightened the risk of arrhythmias. Single-cell analysis revealed severe mitochondrial damage, myocardial cell apoptosis, and disrupted calcium ion balance.

Conclusion

This study highlights DEHP's cardiotoxicity, suggesting its potential role in arrhythmogenesis and cardiac dysfunction. Environmental pollutants like DEHP warrant consideration as contributors to cardiovascular diseases, emphasizing the need for further research on preventive strategies.
Increased prevalence of coronary atherosclerosis in cancer survivors: a matched cross-sectional study with coronary CT angiography
Authors: Polomski E A S , Heemelaar J C , De Ronde M E S , Al Jaff A A M , Mertens B J A , Van Dijkman P R M , Jukema J W , Antoni M L
Published: October 2024

Background

Cancer and atherosclerosis share many risk factors. Although cardiovascular disease is highly prevalent among cancer survivors, it is unknown whether coronary atherosclerosis is present at a younger age in patients with a history of cancer.

Purpose

The purpose of this study is to evaluate the prevalence of coronary atherosclerosis in different age groups of patients with a history of cancer compared to matched controls.

Methods

Consecutive patients with a history of cancer aged >30 years who underwent evaluation for coronary artery disease with coronary computed tomography angiography (CCTA) between 2010 and 2023 were included in this cross-sectional study. Patients with a history of cancer were matched 1:2 to a control population without oncological history using propensity score matching. Patients were matched on age, gender, body mass index, hypercholesterolemia, hypertension, diabetes, use of statins and smoking status. The presence of atherosclerosis in the main coronary arteries was compared between the groups.

Results

The study population consisted of 313 patients with an oncological history and 626 matched control patients. The median age during CCTA scan was 59.4 [50.4-67.5] years and 66.1% of the patients were female. Coronary atherosclerosis was observed in 258 (82.4%) patients with a history of cancer compared to 461 (73.6%) control patients with a risk ratio of 1.12 [95% CI: 1.04-1.20], p<0.01. Mainly younger patients with a history of cancer aged between 30-59 years had a significant increased prevalence of coronary atherosclerosis with a risk ratio of 1.18 [1.04-1.33] compared to healthy controls (p=0.02). In our study population, thoracic radiotherapy was not associated with an increased prevalence of coronary atherosclerosis. Calcified plaques were observed more frequently in patients with a history of cancer (14.4% vs. 9.3% respectively, p=0.018).

Conclusion

Patients with a history cancer have a higher prevalence of coronary atherosclerosis as observed on CCTA compared to matched patients without cancer. This effect was most pronounced in younger patients aged 30-59 years. There is an unmet need to define strategies for cardiovascular disease monitoring and prevention in this growing patient population of patients with a history of cancer.Presence of coronary atherosclerosisRadiotherapy and atherosclerosis
The impact of peptide receptor radionucleotide therapy with Lutetium-177 DOTATATE on cardiac metastases in neuroendocrine tumors
Authors: Scalia I , Sonbol B , Farina J M , Pereyra M , Wang Y , Bekaii-Saab T S , Yang M , Connolly H M , Pellikka P A , Herrmann J , Halfdanarson T R , Starr J S , Luis A S , Arsanjani R , Ayoub C
Published: October 2024

Background

Cardiac metastasis from neuroendocrine tumors (NET) is rare and has been thought to potentially result in life threatening sequalae. Peptide receptor radionucleotide therapy (PRRT), such as Lutetium-177 (Lu-177) DOTATATE, has been validated as effective treatment for patients with NET who have progressed on somatostatin analogue (SSA) therapy and more recently suggested for use in SAA-naïve higher risk grade 2 and grade 3 NETs. However, Lu-177 DOTATATE therapy has been found to have potentially serious adverse effects both locally and systemically. Overall, the clinical significance of cardiac metastasis of NET, as well as the safety and efficacy of Lu-177 DOTATATE in this cohort, has not been thoroughly evaluated.

Purpose

This study assessed the outcomes and clinical consequences of cardiac metastatic involvement in patients with NET. Furthermore, this study investigated the safety of Lu-177 DOTATATE therapy in patients with cardiac metastases from NET.

Methods

All patients who underwent 68Ga-DOTATATE positron emission tomography for evaluation of NET across three tertiary centers between 2016 and 2022 were retrospectively evaluated. Patients with evidence of cardiac metastasis were further evaluated. Baseline characteristics, treatment modality, and clinical outcomes including mortality, arrhythmia or conduction disease, carcinoid heart disease, and heart failure admissions were recorded. Patients with cardiac metastases were grouped and compared based on therapeutic modality (conservative therapy with surveillance or SSA, Lu-177 DOTATATE therapy, or surgical resection of metastases).

Results

From 3253 patients with NET, 51 patients were identified to have cardiac metastases (mean age 66.7 ± 12.2 years, 54% male). Three patients underwent surgical resection of cardiac metastases, and in two of whom this was concomitant while undergoing valve surgery for carcinoid heart disease. Patients with cardiac metastasis had significantly higher mortality than patients without cardiac metastasis (HR 2.12, 95%CI 1.00 – 4.52, p = 0.049, Figure 1A). Median follow-up from diagnosis of cardiac metastasis was 3.64 years [IQR 1.59 – 5.64]. There was no significant difference in clinical outcomes between patients that received Lu-177 DOTATATE therapy (n = 27) and conservative therapy (n = 21). Specifically, there was no significant difference in mortality risk at five years post the diagnosis of cardiac metastasis between these groups (p = 0.47, Figure 1B).

Conclusion

Patients with cardiac metastasis from NETs have worse clinical outcomes than NET patients without cardiac metastatic involvement. Lu-177 DOTATATE therapy appears to be safe in patients with cardiac metastasis from NET.Figure 1AFigure 1B
A study to assess the ability of the HFA-ICOS risk stratification tool to predict cancer therapy-related cardiac dysfunction for patients receiving anthracycline chemotherapy
Authors: Bannister C , Tam To B , Byrne A , Simela C , Cannata A , Bromage D , Ghosh A K , Mcdonagh T
Published: October 2024

Introduction

The use of anthracycline chemotherapy is complicated by the risk of developing cancer therapy-related cardiac dysfunction (CTRCD). The Heart Failure Association (HFA) and International Cardio-Oncology Society (ICOS) have jointly published a novel cardiovascular risk stratification tool for patients receiving anthracycline chemotherapy which categorises patients according to their risk of CTRCD (1). The risk tool has not yet been validated for use in the United Kingdom.

Purpose

In this study, we test the ability of the HFA-ICOS risk stratification tool to predict CTRCD for patients receiving anthracycline chemotherapy.

Methods

A retrospective study of patients ≥18 years who received anthracycline chemotherapy between January 2019 to January 2023 at two cardio-oncology centres in the United Kingdom. Patients were eligible if they had ≥1 follow up echocardiogram after the end of anthracycline treatment. Patients receiving HER-2 targeted therapies were excluded. Patients were classified into low/medium/high/very-high risk categories using the HFA/ICOS tool. The prevalence of CTRCD was assessed during the follow up period; a minimum of 6 months after the end of chemotherapy.

Results

288 patients met eligibility criteria for the study. 59 patients (20%) were treated for leukaemia, 104 (36%) lymphoma, 63 (22%) sarcoma and 49 (17%) breast cancer. The mean age was 49±18yrs, with 56% females. The mean cumulative dose of doxorubicin (or equivalent) was 235±104mg/m2. Using the HFA/ICOS tool, 50% of patients were deemed low risk, 31% medium risk, 16% high risk and 3% very high risk at baseline.

Using guideline recommended CTRCD definitions, there was an overall incidence of 9% of symptomatic CTRCD and 22% of asymptomatic CTRCD (Table 1). The incidence of symptomatic CTRCD significantly increased as the baseline risk of CTRCD increased. 20% of patients deemed high or very-high risk at baseline subsequently developed symptomatic CTRCD (Fig 1). Furthermore, patients at high or very-high risk were 4.4 times more likely to develop symptomatic CTRCD than patients who were low risk (OR 4.4, 95% CI 1.7-11.6, p=0.003).

There was no association with baseline risk and the development of asymptomatic CTRCD. The incidence of mild asymptomatic CTRCD may be underestimated due to the lack of routine surveillance with cardiac biomarkers and left ventricular global longitudinal strain (LV GLS) imaging for asymptomatic disease during the study period.

Conclusion

The novel HFA/ICOS risk stratification tool is useful in predicting patients who will develop symptomatic CTRCD in a contemporary UK setting.
A matter of inflammation: CAR T-cell therapy and atrial fibrillation
Authors: Chen S , Gonzalez H , Ghorbanzadeh A , Korleski J , Donisan T , Lewis B , Lin Y , Herrmann J
Published: October 2024

Background

Chimeric antigen receptor (CAR) T-cell therapy has been revolutionary in the treatment of blood cancers, but has been associated with arrhythmias such as atrial fibrillation (AF). Whether the incidence of AF has changed over time and if contributing risk factors are present remains to be defined.

Methods

Leveraging the Mayo Electronic Medical Record, we extracted a cohort of patients who underwent CAR T-cell therapy between 2016 and 2022. From this cohort, we identified those who had a diagnosis of AF at any point. We then defined the endpoint of interest as the first episode of new or recurrent AF during or after CAR T-cell infusion. Fine and Gray subdistribution hazard modeling was used to calculate the association of patient characteristics to the endpoint of interest. Variables with P<0.20 in univariate modeling were chosen for the multivariate model. Significance was defined as P<0.05.

Results

There were 328 patients who underwent CAR T-cell therapy between 2016 and 2022. Of this cohort, 27 (8.2%) patients had a pre-existing diagnosis of AF, of which 6 had recurrence of AF after CAR T (22.2%), while 21 (77.8%) did not. Of the 301 patients without a prior history of AF, 8 (2.7%) patients developed new-onset AF after CAR T. The majority of the 14 new or recurrent AF events (4.3% overall incidence) occurred within 30 days of receiving CAR T (N=10, 71.4%), the remainder after 180 days (Figure 1). No trend in declining incidence over time was noted. Prior AF, neurotoxicity, and inflammation (cytokine release syndrome and macrophage activating syndrome-like (MAS-L)) were strongly associated with the risk of developing new or recurrent AF (Table 1). Only presence of MAS-L remained an independent predictor in the multivariate model (HR 15.4, 95% CI 3.9-61.2, P<0.001).

Conclusion

AF is mainly seen early following CAR T-cell therapy, and mainly in association with severe inflammatory responses. Early and aggressive treatment of CRS and MAS-L may be recommendable for patients undergoing CAR-T therapy, especially for those with a prior history of AF.
Angiotensin II as a linking factor in cardiovascular disease enhanced cancer growth
Authors: Van Berlo B , Civati C , Esposito P , De Keulenaer G W , Guns P J D F , Segers V F M
Published: October 2024

Introduction

Several publications have demonstrated that cardiovascular diseases (CVD) promote tumor growth in mouse models of breast, lung, and colon cancer, suggesting a causal relationship between both diseases. Cancer and CVD share several risk factors and pathophysiological mechanisms, including inflammation, oxidative stress, neurohormonal activation, and immune system dysfunction that combined could explain why patients with CVD are prone to develop cancer.

Recent reports also suggest a link between hypertension and lung cancer, and between cardiac hypertrophy and breast cancer. Angiotensin II (ANGII) is a hormone involved in blood pressure regulation, vascular hemostasis and hypertrophy development. Moreover, ANGII is cancerogenic by increasing proliferation of several cancer cell types. Hence, ANGII could be a link in CVD-induced enhancement of cancer growth. Here, we investigated whether ANGII treatment, and subsequent hypertension and cardiac hypertrophy, could promote cancer growth and metastasis.

Methods

ANGII (2000ng.kg-1.min-1, 4w) was administered to 10w old C57B6/J mice using subcutaneous osmotic minipumps. After 3w, 5*10^5 Lewis lung carcinoma (LLC) cells or 2*10^5 MC38 colon cancer cells were injected onto the right flank of the mice. Tumor growth was monitored over 21d using a digital caliper. Tumor volume was calculated using the following formula:

Length × width² × 0.5

On day 22, mice were sacrificed for further post-mortem analysis. Cardiac echography was performed after 3w of ANGII treatment and before sacrifice to assess cardiac function (data not shown). To assess the formation of cardiac fibrosis trichrome staining’s were performed. In addition, the effect of ANGII on LLC metastasis was investigated. Mice were treated with ANGII as described above. LLC cells, 2*10^6, were injected intravenously (i.v.). Mice were sacrificed 21d after cell injection. Metastatic growth was visualized and quantified by organ weighing and H&E staining.

Results

LLC tumor growth was significantly increased by ANGII treatment. In addition, post-mortem tumor weight was increased (0.62 ± 0.05 g control vs. 1.17 ± 0.24 g ANGII). Furthermore, we found lung weight increased in the ANGII-treated group injected i.v. with LLC cells, indicating an increase in metastatic growth (0.41 ± 0.08 g control vs. 0.57 ± 0.04 g ANGII). Interestingly, MC38 tumor growth decreased in the ANGII treated group as portrayed by the tumor weight (0.42 ± 0.06 g control vs. 0.19 ± 0.05 g ANGII). Figure 1 shows the tumor growth over time and tumor volume, weight post-mortem.

Conclusion

Our data suggest a role for ANGII in CVD-enhanced cancer growth, but also that this effect is not universal, illustrated by a differential effect of ANGII on distinct cancer types. Although further investigation is required to unravel the role of ANGII, screening cancer patients with CVD comorbidities for ANGII involvement might be warranted.
PVC induced QT prolongation for unmasking the LQTS
Authors: Jalabadze K , Ketevani Khetsuriani K K , Ia Avaliani I A , Mindia Butskhridze M B , Giorgi Papiashvili G P , Kakhaber Etsadashvili K E
Published: October 2024

Background

Long QT Syndrome (LQTS) is a congenital or acquired disorder of cardiac ion channels resulting in disturbances of myocardial repolarization, usually manifested by QT prolongation. Diagnostic criteria include the presence of the corrected QT interval (QTc) of at least 480ms (milliseconds) in repeated 12-lead ECGs or confirmed LQTS gene mutations. Patients with LQTS have an increased likelihood of developing life-threatening ventricular arrhythmias and sudden cardiac death. Hence, establishing an accurate diagnosis is crucial.

Purpose

About 50% of patients with LQTS presents with normal or borderline QTc interval. Such cases warrant additional work-up to confirm the diagnosis and can often get overlooked. Based on two separate patient cases we hypothesized that significant QTc interval prolongation occurring after premature ventricular contractions (PVCs) may be a valuable diagnostic clue for suspected LQTS or potentially life-threatening arrhythmia in cases with unclear diagnosis. Above mentioned patients displayed normal baseline QTc interval values that prolonged only after PVC. Later, one of them was diagnosed with congenital and another with drug-induced LQTS (see ECG 1).

Methods

We observed QT interval behavior after PVC in three prespecified groups:(I) Electrocardiographically affected LQTS subjects (QTc ≥480ms) – 10 patients, (II) Control group of unaffected, asymptomatic, otherwise healthy subjects (QTc<460ms) – 72 patients, (III) Index Group of 2 patients with baseline QTc interval of 360-460ms, prolonged only after PVC. 24-hour-ECG records were analyzed. We calculated means of QTc interval before and after PVC in abovementioned three groups and compared them to each other using ANCOVA analysis.

Results

The QT interval after PVC increased 488+23ms in the first and 390+10ms in the second group. In contrast to the index group, the QT interval was prolonged by 380+160ms after PVC. Post-PVC QTc interval mean difference adjusted to covariate, baseline QTc interval values, were statistically insignificant between I and II groups (P=0.o66), but significant between both I -III(P=0.000055) and II-III groups (P<.0001).

Conclusion

There are several studies indicating that PVCs affect QT interval, but the phenomena need more investigation. From the perspective of our study, we have also observed that QTc interval indeed increased after PVCs in both ECG-phenotype positive LQTS individuals and healthy subjects, but not in the extent of the index patients. Our study is limited by the small number of concealed LQTS cases. However, it gives us some basis to think, that this finding could be particularly useful to suspect and unmask concealed LQTS in the patients with non-diagnostic baseline ECG.ECG1
The prognostic significance of Weber and ventilatory CPET classifications in amyloidosis patients
Authors: Santos Patarroyo S , Ortega-Aviles L , Grogan M , Allison T
Published: October 2024

Background

Cardiopulmonary exercise testing (CPET) has emerged as an important tool for risk stratification and prognosis assessment in patients with cardiac diseases. The Weber and Ventilatory Functional Classification have been correlated with outcomes in patients with Heart Failure (HF). Weber classification is based on VO2: Weber class A, peak VO2 >20 mL/kg per minute; class B, peak VO2 16–20 mL/kg per minute; class C, peak VO2 10–16 mL/kg per minute; and class D, peak VO2 ≤10 mL/kg per minute and Ventilatory classification on VE/VCO2 slope I-IV (Figure A). Although VO2 and VE/VCO2 variables have found altered in the amyloidosis population, the applicability of this classification in a cohort of amyloidosis patients and its correlation with all-cause mortality have not been explored.

Purpose

To evaluate if the Weber and Ventilatory Classification of HF predicts mortality amyloidosis patients.

Methods

194 with diagnosis of amyloidosis who underwent CPET from February 2010 to February 2024 were included in this retrospective cohort study. Patients with at least one CPET complete data were included in the analysis. Data on the type of amyloidosis, comorbidities, and echocardiogram were retrieved from medical records. Cohort was divided into two groups according to the Weber Classification: Weber Class A/B and Weber Class C/D. Individuals with CPET studies after heart transplant were excluded from the analysis. Statistical analyses including Fisher’s exact test, chi-square, Tukey-Kramer (TK), Cox regression model analysis, proportional hazards model for time to event, and Kaplan–Meier curves were performed. A p-value <0.05 was considered significant.

Results

Out of the 194 patients, 94 were classified as Weber A-B and 100 as Weber B-C. The age at stress test was similar between the groups: Weber A/B 62.9 ± 11.7 years and Weber C/D 62.3 ± 10.7 years (p=0.087). Ejection Fraction was similar between groups, 32% and 28.9% in A-B and C-D respectively (p =0.207). Higher levels of NT-proBNP were found in the Weber C/D group. The prevalence of comorbidities was balanced among the groups except chronic kidney disease, which was higher in Weber Class C/D (40%) vs (20.2%) in Weber Class A/B (Table 1). Cox analysis revealed a strong association between higher Weber class and the outcome HR 2.36 (1.18 – 4.71) p=0.014. For Higher Ventilatory Class (Group III-IV) similar results were found HR 2.95 (1.60 – 5.45) p=0.005(Table 2). Mortality was significantly higher during the follow-up in the Weber C/D group (25%) vs (10%) in the Weber A-B group p=0.007(Figure D).

Conclusion

Weber and ventilatory Classification based on CPET, besides predicting outcomes in patients with cardiac disease, are strong predictors of mortality in patients with amyloidosis. These findings suggest that this patient group benefits from earlier stratification to assess prognosis and the potential requirement for transplant independently from other factors.
Low clinical utility of global longitudinal strain in a real-world breast cancer population
Authors: Ruane L , Prasad S , Atherton J
Published: October 2024

Background

The 2022 European Society of Cardiology (ESC) Cardio-Oncology guidelines recommend the use of global longitudinal strain (GLS) to detect mild asymptomatic cancer therapy related cardiac dysfunction (ma-CTRCD). However, it remains unknown how to best manage these patients in order to prevent clinically significant CTRCD.

Purpose

To assess the course and outcomes of breast cancer patients meeting criteria for ma-CTRCD.

Methods

Echocardiograms and medical records were assessed for breast cancer patients receiving trastuzumab or an anthracycline, who underwent serial echocardiographic monitoring, including routine GLS. CTRCD was defined as an absolute decline in LVEF of >10% to <50%. ma-CTRCD was defined as a relative decline in average GLS of >15%, in the absence of significant LVEF decline. Normal was defined as no significant change in LVEF or GLS during cancer therapy. Clinical and echocardiographic course post ma-CTRCD detection was assessed. Baseline risk factors were compared between the three groups.

Results

878 echocardiograms from 258 patients were analysed. GLS analysis was available in 76% of echocardiograms. CTRCD occurred in 23 (9%) and ma-CTRCD in 63 (24%). Only eight ma-CTRCD patients had management altered (cancer therapy withheld/ceased in three and heart failure medication commenced in six). Only two ma-CTRCD patients subsequently developed CTRCD, and GLS improved in 74%. Compared to the normal group (172, 67%), at baseline the ma-CTRCD group had higher average GLS (-21.8 vs -19.4, p<0.0001) and less borderline/abnormal average GLS (4% vs 36%, p<0.004).

Conclusion

Isolated declines in GLS are common and may have low clinical utility in preventing CTRCD. The findings support ESC guideline recommendations that cancer therapy should not be withheld in these patients. Those with higher baseline GLS may be more prone to clinically insignificant declines in GLS during cancer therapy.
Incidence of acute cardiovascular hospitalizations and association with hemodynamic biomarkers in cancer patients treated with Immune Checkpoint Inhibitor therapy
Authors: Mann C , Spannbauer A , Gyoengyoesi M , Riesenhuber M , Huelsmann M , Gottsauner-Wolf M , Gerges C , Laengle S , Raderer M , Hengstenberg C , Zelniker T A , Begler-Klein J
Published: October 2024

Background/Introduction

Immune checkpoint inhibitors (ICI) have significantly improved outcomes for several malignancies. Despite these benefits, patients with cancer face an increased risk for the development of cardiovascular disease due to mutual risk factors, similar biological mechanisms, as well as cardiotoxic side effects of therapy. Therefore, there is a pressing need for effective risk stratification strategies.

Purpose

This study aimed to explore the association between NT-proBNP levels and the risk of acute cardiovascular hospitalizations and death in patients who receive ICI.

Methods

We used electronic health records of patients treated with ICI who had available baseline NT-proBNP levels at our hospital, a tertiary academic center, between January 2017 and July 2022. The primary outcome of interest was the composite of acute cardiovascular hospitalization or death. The associations between NT-proBNP and outcomes were analyzed using cox regression models adjusted for age, sex, serum creatinine, diabetes, HF, CAD, hypertension, AF, LDL-C, and CRP.

Results

In total, 550 patients (35% female, median age 65 yrs) were included in the study. The median NT-proBNP levels were 272 pg/mL (IQR 102-742 pg/mL) and 388 (71%) patients had NT-proBNP levels ≥125 pg/mL. During a median FU of 67 weeks, 190 patients (35%) died, and 103 CV hospitalizations occurred in 76 patients (14%). Compared with patients with NT-proBNP concentrations <125, those with NT-proBNP concentrations ≥125 pg/ml had significantly higher event rates of the combined endpoint (12-Month KM event rates: 38% vs 21%, P<0.001). After multivariable adjustment, NT-proBNP remained independently associated with an increased risk of cardiovascular hospitalization and death (Adjusted HR for 1-SD increase in log-transformed biomarker 1.64, 95% CI 1.24 to 2.14; Figure).

Conclusion

These data highlight NT-proBNP levels as a valuable marker for identifying patients at increased risk of cardiovascular complications during ICI therapy.