bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term survival and ourtomes a large cohort of patients underwent with Transcatheter Aortic Valve Replacement: an 10-year single center TAVR experience
Authors: Munoz-Garcia M , Munoz-Garcia E , Munoz Garcia A J , Dominguez-Franco A J , Jimenez-Navarro M F , Alonso-Briales J H , Hernandez-Garcia J M , Gomez-Doblas J J
Published: October 2022

The use of transcatheter aortic valve replacement (TAVR) has expanded as an alternative to surgical aortic valve replacement and has become a widely accepted treatment option for patients with severe aortic stenosis who are considered intermediate- and high-risk surgical candidates. The information concerning the long-term durability of TAV devices is currently limited. The interplay between estimated life expectancy and prosthetic heart valve durability is a key consideration in these discussions. The aim of this study was to determine the clinical outcomes, survival and the factors predicting mortality after TAVR

Methods

From April 2008 to December 2020, the auto-expandible and baloom-expandable prostheses were implanted in 991 patients with symptomatic severe aortic stenosis with intermediate, high and deemed risk.

Results

The mean age was 79.43±6.7 years. The logistic EuroSCORE II and STS score were 5.92±5% and 5.22±3.7%, respectively. The implantation success rate was 98.7%. In-hospital mortality was 3.3%, and the combined endpoint of death, vascular complications, myocardial infarction or stroke had a rate of 17.2%.

The late mortality (beyond 30 days) was 43.2%. Survival at 1, 3, 5, 7, 9 and ten years were 88.2%, 68.2%, 50,1%, 38.1%, 26.3% and 16.4% respectively, after a mean follow-up of 44.8±31 months.

The NYHA functional class improved from 3.3±0.7 to 1.76±0.5 in the follow-up.

At 7 years, 9 patients had severe prosthetic valve dysfunction (severe stenosis and moderate transvalvular regurgitationI. In 7 patients were treated again with TAVR.

The predictors of cumulative mortality were: Charlson index [HR 1.167 (95% CI 1.078–1.264), p=0.001], Readmision Heart Failure [HR 2.793 (95% CI 1.948–4.005), p=0.001], stroke post-TAVR [HR 2.919 (95% CI 1.965–4.336), p=0.001], Left ventricular ejection fraction [HR −1.012 (95% CI 1.002–1.022) p=0.021] and Karnosfky index [HR −0.984 (95% CI 0.975–0.993), p=0,001] but the requirement of pacemaker or residual aortic regurgitation after TAVR were not predictors [HR 0,979 (CI 95% 0.678–1.415), p 0.911] and [HR 1.087 (CI 95% 0.913–1.294), p=0.349].

Conclusions

TAVR is associated with excellent clinical results at follow-up. Long-term survival depends particularly on comorbidities and the left ventricular ejection fraction

Funding Acknowledgement

Type of funding sources: None.
Pattern of cardiovascular risk factors and outcomes of patients older than 80 years and presenting with acute coronary syndromes
Authors: El Amrawy A , Almaghraby A , Abd Elnabi M , Wagdy S
Published: October 2022

Background

Elderly patients presenting with acute coronary syndrome (ACS) are at a higher risk for morbidity, complications and early mortality than younger patients. Elderly are frequently underrepresented in clinical trials.

Methods

A descriptive multi-center study including 760 patients admitted with ACS in order to determine the most frequently encountered cardiovascular risk factors, as well as the in-hospital complications among this age group.

Results

Of the 760 patients, 42.1% were males with a mean age of 85 years. Non-ST-elevation ACS was encountered in 496 patients (65.3%; NSTEMI 50% and unstable angina 15.3%) while STEMI was encountered in 264 patients (34.7%).

Regarding risk factors, 61.1% of patients were hypertensive, 60% were diabetics, 44.7% were smokers, 28.9% had dyslipidemia, 16.8% had a family history of coronary artery disease, and 20% had chronic renal impairment at presentation.

252 patients (33.2%) underwent primary PCI, 440 patients (57.9%) underwent elective PCI, 36 patients (4.7%) underwent coronary artery bypass graft (CABG) surgery while 32 patients (4.2%) were maintained on conservative medical therapy and no patients received fibrinolytic therapy.

In-hospital mortality was only 3.7% (28 patients), cerebrovascular stroke occurred in 16 patients (2.1%) and recurrent infarction occurred only in 8 patients (1.1%).

Conclusions

In patients over 80 years presenting with ACS, female sex, hypertension and diabetes were the most frequently encountered cardiovascular risk factors, with more frequent presentation of NSTEMI than STEMI and in-hospital mortality of 3.7%.

Funding Acknowledgement

Type of funding sources: None.
Complex high-risk indicated percutaneous coronary interventions (CHIP-PCI) in elderly patients
Authors: Marschall A , Marti Sanchez D , Ferreiro J L , Lopez Palop R , Ojeda S , Avanzas P , Jimenez Mazuecos J M , Carrillo Saez P , Gutierez-Barrios A , Pinar E , Linares J A , Diego A , Amat I J , Telleria M J , De La Torre Hernandez J M
Published: October 2022

Introduction

Complex high-risk indicated percutaneous coronary intervention (CHIP-PCI) is a poorly defined concept. A recent large-scale study identified various patient- and procedure-related factors that were associated with in-hospital major adverse cardiac or cerebrovascular events (MACCE), which were used to construct a CHIP-score [1].

Purpose

To investigate the predictive value of patient- and procedure related risk factors, based on the CHIP-score, in a large cohort of elderly patients.

Methods

This is a retrospective multicenter study of 20 centers, including patients of ≥75 years of age, that underwent PCI in the period of 2012–2019. The primary endpoint of MACCE was defined as cardiovascular death, myocardial infarction, revascularization or stroke. The follow-up time was 1 year. We created univariate and multivariate Cox regression models in order to investigate the predictive value of the CHIP-score variables (other than age, Table 2).

Results

A total of 2724 patients with a mean age of 81 (± 4.3) years were included in the study. Baseline characteristics are depicted in Table 1. The mean CHIP score was 1.74 (± 1.2) and 2262 (83%) had at least one CHIP criteria. At 1-year follow-up, 267 (9.8%) met the primary endpoint. Out of 11 investigated CHIP-score variables, only 5 were independent predictors of 1-year MACCE in adjusted regression models: Prior myocardial infarction (HR 1.56 (95% CI: 1.10–1.90), p=0.009), left ventricular ejection fraction <30% (HR: 2.02 (95% CI: 1.34–3.0, p<0.001), chronic kidney disease (HR 1.55 (95% CI: 1.21–2.02, p<0.001), left main coronary PCI (HR: 2.35 (95% CI: 1.29–4.89, p<0.001) and non-radial access (HR: 1.57 (95% CI: 1.19–1.85, p=0.002). See Table 2 for details. Overall MACCE was 4.5% when CHIP was 0, as compared to 10.7% with any CHIP factor present (p<0.001) (Figure 1). A CHIP of 4+ or higher was present in 246 (9%) patients and was associated with a three-fold increase in 1-year MACCE (HR: 2.9 (95% CI: 2.1–3.9), p<0.001).

Conclusions

The CHIP-score retains significant prognostic value in the elderly population. The implication of a CHIP-score might be a future tool for risk stratification in clinical practice, not only for in-hospital MACCE but also on long-term follow-up. In the special population of elderly patients, 3 patient related and 2 procedure related factors showed to be especially helpful for risk assessment.

Funding Acknowledgement

Type of funding sources: None.
Phenotyping patient-reported health profiles in octogenarians with coronary artery disease – a latent profile analysis
Authors: Instenes I , Breivik K , Allore H , Borregaard B , Deaton C , Larsen A I , Wentzel-Larsen T , Norekval T M
Published: October 2022

Background

Percutaneous coronary intervention (PCI) has demonstrated to be an effective treatment strategy also in octogenarian patients (≥80 years). However, limited studies describe patient-reported outcomes in older adults two months after the PCI procedure.

Purpose

To identify latent health profiles concerning fatigue, generic and disease-specific physical and mental health, anxiety and depression, insecurity, dependency and angina frequency. Further, to investigate if these profiles were associated with sex or cohabitation status.

Method

A prospective cohort multicenter study including 3417 patients was conducted. The following patient-reported outcome measures were used: Level of fatigue was assessed using de novo created questions. Generic physical and mental health was assessed using RAND-12. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Disease-specific physical and mental health status, insecurity and dependency were assessed with Myocardial Infarction Dimensional Assessment Scale, and disease-specific physical limitation, quality of life and angina frequency was assessed with Seattle Angina Questionnaire (SAQ-7). All scales were converted to a 0–100 scale (worst to best). Latent profile analysis was used for phenotyping health profiles and multinomial logistic regression analysis for investigating the association of sex and cohabitation status across health profiles.

Result

A total of 318 octogenarians were included. The mean age was 83.6 years, and 69% were males. Three health profiles differing in the level of fatigue, health status, insecurity and dependency and angina frequency were identified (Figure 1). Health profile 1 (26.1%) represents “Low-level of life satisfaction, high level of insecurity and dependency and monthly frequency of angina”. Health profile 2 (38.1%) represents “Medium-level of life satisfaction, medium-level of insecurity and dependency and monthly frequency of angina”. Health profile 3 (35.8%) represents “High-level of life satisfaction, low level of insecurity and dependency and angina free”. Importantly, female sex was strongly associated with being classified into Health profile 1 compared to Health profile 3 [OR 3.6, 95% CI 1.3–7.9]. Living alone however, did not predict a likelihood of being classified into any particular health profile.

Conclusion

We identified three unique health profiles of octogenarians with coronary artery disease. A quarter of the participants were classified into the “Low-level of life satisfaction” profile. In addition, female sex was strongly associated with being identified into the “Low-level of life satisfaction” profile. These result suggest a need for a more tailored and patient-centered aftercare in octogenarians undergoing PCI.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): MTG Holding AS
Prevalence of RV dysfunction in patients under cardiotoxic chemoterapy: a preliminary analysis
Authors: Maltes S , Rocha B M L , Cunha G J L , Paiva M S , Vasques A C , Freitas P , Guerreiro S , Marta L , Abecasis J , Regina R , Andrade M J , Aguiar C T , Martins A , Mendes M
Published: October 2022

Background

Chemotherapy-induced cardiotoxicity is a serious complication often leading to heart failure. While the left ventricle (LV) has been thoroughly implicated in this process, data is scarce on right ventricular (RV) function following cardiotoxic chemotherapies. Our goal was to determine the prevalence and clinical significance of RV dysfunction in a cohort of patients who had received these drugs.

Methodology

Single-center retrospective study of cancer patients performing 2D transthoracic echocardiogram between January 2020 and December 2021. Those previously exposed to anthracyclines and/or anti-HER2 agents (≥6 months prior to echocardiogram) were included. Patients with known coronary artery disease or cardiomyopathy were excluded. LV function was assessed through LV ejection fraction (LVEF) and global longitudinal strain (GLS). LV cardiotoxicity was defined as per 2020 ESMO guidelines. RV function was considered abnormal if the following criteria were met: tricuspid annular plane systolic excursion (TAPSE) <17 mm, peak systolic velocity of the tricuspid annulus by pulsed wave TDI (S'VD) <12 cm/s, fraction area change (FAC) <35% and mean free wall longitudinal strain (FWLS) >−20%.

Results

Forty patients were included (58±13 years; 95% female; 93% with breast cancer; 30%, 20% and 50% previously treated with anthracyclines, anti-HER2 or both, respectively). Mean LVEF and GLS were 56±7% and −17±3%. Overall, 13 patients had current LV cardiotoxicity. RV dysfunction was documented in 15 (38%) patients (7 [18%] with isolated RV dysfunction), most often detected through FWLS (14 [35%], 7 [18%], 6 [15%] and 5 [13%] patients with abnormal FWLS, TAPSE, FAC and S'VD, respectively) – Figure 1. Seven patients (18%) and one patient (3%) had ≥2 and ≥3 abnormal RV parameters. Those with RV dysfunction were more often symptomatic (NYHA class ≥2: 53% vs. 16%; p=0.013), had higher NT-proBNP levels (516 [204–2400] vs. 66 [46–191] pg/mL; p=0.003) and most often had LV cardiotoxicity (62% vs. 26%, p=0.029); pulmonary artery systolic pressures were similar between both groups.

Conclusion

In our cohort of patients treated with cardiotoxic anti-neoplastic drugs, RV dysfunction was observed in two out of every five patients, most often detected by RV 2D strain and associated with worse symptoms and higher NT-proBNP levels. This data suggests that RV cardiotoxicity may be common and clinically impactful in those under cardiotoxic chemotherapies.

Funding Acknowledgement

Type of funding sources: None.
The effect of ACE-I/ARBs and beta blockers on the development of cardiotoxicity in patients with breast cancer
Authors: Umadat G , Gharacholou S M
Published: October 2022

Introduction

Cardiovascular disease has become the leading cause of mortality among breast cancer survivors. Patients with breast cancer who receive treatment with anthracycline and trastuzumab therapies are at risk for the development of non-ischemic cardiomyopathy. The development of heart failure during chemotherapy administration often results in interruption of these life saving therapies.

Purpose

We aim to investigate whether ACE Inhibitors/angiotensin receptor blockers (ACE-I/ARBs) and beta-blockers can be used as primary prophylaxis to prevent the development of chemotherapy induced cardiomyopathy.

Methods

This was a retrospective cohort study investigating women who were diagnosed with breast cancer at our medical center from January 2000 to December 2021. The primary endpoint was the development of cardiotoxicity after treatment with chemotherapy. Cardiotoxicity was defined as a decrease of LVEF by 5% or more to less than 55% in the presence of symptoms of heart failure or an asymptomatic decrease in LVEF by 10% or more to less than 55%. Cox-proportional hazard ratios were conducted to determine the impact of prophylactic ACE/ARBs and beta-blockers on the development of cardiotoxicity. Other baseline characteristics were also investigated for their potential impact on the primary endpoint.

Results

There were 459 patients included in the study of which 70 met criteria for chemotherapy induced cardiomyopathy. Median follow up time of included patients was 12 months and average age was 55 years. Among the included patients, 52% were treated with only trastuzumab, 34% were treated with only anthracycline, and 14% were treated with both therapies. Before chemotherapy was initiated, 15% of patients were taking only ACE-I/ARBs, 7% were taking only beta-blockers, and 5% of patients were taking a combination of ACE-I/ARBS and beta-blockers. There were no significant protective benefits noted for patients who were taking ACE-I/ARBs [HR: 0.49, 95% CI (0.17–1.4)], beta-blockers [HR: 0.50, 95% CI (0.16–1.6)], or both [HR: 1.30, 95% CI (0.44–3.9)]. Notably, there was an increased risk of cardiotoxicity noted for patients who were older [HR: 1.04, 95% CI (1.01–1.1)], smokers within the past 10 years [HR: 2.54, 95% CI (1.41–4.6)], or received a combination of both trastuzumab and anthracycline therapy [HR: 2.52, 95% CI (1.01–6.3)].

Conclusion

Prophylactic use of ACE-I/ARBs and beta-blockers separately or in combination was not associated with beneficial reduction in the development of non-ischemic cardiomyopathy in patients receiving anthracycline or trastuzumab therapies. Older age, smoking within the past 10 years, and combination therapy with both anthracycline and trastuzumab were found to be associated with an increased risk. Further studies are needed to investigate the etiology of how smoking may augment the potential cardiotoxic effects in this population.

Funding Acknowledgement

Type of funding sources: None.
Manganese enhanced magnetic resonance imaging in type 1 and type 2 diabetes mellitus
Authors: Joshi S , Singh T , Kershaw L E , Spath N , Dattani A , Gulsin G S , Semple S I , Williams M W , Gibb F , Forbes S , Reynolds R P , McCann G P , Dweck M R , Newby D E
Published: October 2022

Background

The pathophysiology of diabetic cardiomyopathy has yet to be established although pre-clinical studies suggest a role for altered myocardial calcium handling. Manganese-enhanced magnetic resonance imaging (MEMRI) is a novel non-invasive method of assessing in vivo myocardial calcium handling.

Purpose

To investigate whether myocardial calcium handling is impaired in patients with either type 1 or type 2 diabetes mellitus in the absence of underlying heart disease.

Methods

In a prospective case-control study, patients with type 1 (n=19) or type 2 (n=10) diabetes mellitus and healthy volunteers (n=15) underwent MEMRI. Participants with prior coronary artery disease, cardiomyopathy or an abnormal electrocardiogram were excluded. Manganese dipyridoxyl diphosphate (0.1 mL/kg) was administered over 10 min and myocardial T1 mapping was performed prior to and every 2.5 min for 30 min after contrast infusion (Figure 1). Quantitative manganese uptake analysis was performed by measuring T1 relaxation times in a region of interest within the interventricular septum and compared to the left ventricular blood pool. The rate of myocardial manganese uptake was determined by Patlak modelling [1].

Results

Participants with type 1 and type 2 diabetes mellitus were older (50±13 and 55±15.3 years) than the healthy volunteers (32±10 years). All participants had preserved left ventricular ejection fraction (type 1 diabetes mellitus, 67.7±6.1%; type 2 diabetes mellitus, 66.8±3.2%; healthy volunteers, 65±3.5%). Mean myocardial manganese uptake was reduced in participants with both type 1 (6.4±0.6 mL/100 g of tissue/min) and type 2 (6.4±0.5 mL/100 g of tissue/min) diabetes mellitus compared with healthy volunteers (8.3±0.5 mL/100 g of tissue/min; p<0.0001 for both, Figure 2). There were no differences in myocardial manganese uptake between those with type 1 or type 2 diabetes mellitus (p=0.22). There was no statistically significant correlation between myocardial manganese uptake and age in the study population (r=−0.28, p=0.07).

Conclusion

Using MEMRI, we have demonstrated that myocardial calcium handling is impaired in patients with either type 1 or type 2 diabetes mellitus even in the absence of left ventricular systolic dysfunction. This suggests altered myocardial calcium handling may underlie, or contribute to, diabetic cardiomyopathy which has implications developing novel therapeutic targets for the prevention and treatment of diabetic cardiomyopathy.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): British Heart Foundation - Clinical Research Training Fellowship (FS/CRTF/20/24087)AstraZeneca - Investigator initiated award (ESR-19-20118)
Valvular changes following anthracycline therapy: is it time to look beyond ejection fraction?
Authors: Zahler D , Arnold J , Rozenbaum Z , Banai S , Arbel Y , Topilsky Y , Laufer-Perl M
Published: October 2022

Background

Advancements in early detection and treatment of breast cancer have improved survival, but with the costs of side effects, with cardiotoxicity being the most significant one. Anthracycline (ANT) is the most recognized therapy leading to cardiotoxicity, mainly manifested as left ventricle (LV) dysfunction. While the changes in LV ejection fraction (LVEF) are well studied, little is known about the effect of ANT on valvular function. We aimed to evaluate the change in valvular function following ANT therapy in patients diagnosed with breast cancer.

Methods

The study population is part of the Israel Cardio-Oncology Registry (ICOR). All patients performed serial echocardiography; before (T1), during (T2), at the end (T3), and following (T4) ANT therapy, assessing valvular changes. Exclusion criteria included age below 18 and baseline LVEF <55%.

Results

The study included 141 female patients diagnosed with breast cancer and treated with ANT with a mean age of 51±12 years (Table 1). During a median follow-up of 255 [IQR 214–313] days, from T1 to T4, we observed a significant increase in the portion of patients developing new mitral regurgitation (MR) (3.5% to 18.7%, p<0.0001), with a trend for developing moderate and above MR (0.7% to 3.3%, p=0.13). While a statistically significant reduction in mean LVEF (60.2%±1.5 to 59.2%±2.7, p=0.0004) and median LV global longitudinal strain (LV GLS) (−21.6% [−20.0 to −23.0] to −20.0% [−19.1 to −21.1], p<0.0001) was observed (Figure 1), the values remain within the normal range with no significant clinical change. In a multivariate binary logistic regression model, age (OR 1.06, 95% CI: 1.01–1.11) and trastuzumab therapy (OR 5.59, 95% CI: 1.95–16.6) were strong independent predictors for MR development, while medical history was not.

Conclusions

MR development following ANT exposure is frequent, increasingly after the completion of ANT therapy. The parallel reduction in LV function might imply a functional mechanism. Larger trials are needed to evaluate the MR prognostic clinical role in cancer patients.

Funding Acknowledgement

Type of funding sources: None.
Coronary artery disease and revascularization associated with immune checkpoint blocker myocarditis – report from an international registry
Authors: Nowatzke J , Guedeney P , Palaskas N , Lehmann L , Ederhy S , Cautela J , Francis S , Courand P Y , Aras M , Arangalage D , Fenioux C , Finke D , Huang S , Moslehi J , Salem J E
Published: October 2022

Purpose

Immune-checkpoint-blocker (ICB) associated myocarditis (ICB-myocarditis) may present similarly and/or overlap with other cardiac pathology including acute coronary syndrome presenting a challenge for prompt clinical diagnosis.

Methods

An international registry was used to retrospectively identify cases of ICB-myocarditis. Presence of coronary artery disease (CAD) was defined as coronary artery stenosis >70% in patients undergoing coronary angiogram.

Results

Among 261 patients with clinically suspected ICB-myocarditis who underwent a coronary angiography, CAD was present in 59/261 (22.6%) (Table 1). Coronary revascularization was performed during the index hospitalization in 19/59 (32.2%) patients. Patients undergoing coronary revascularization less frequently received steroids administration within 24h of admission compared to the other groups (p=0.029). Myocarditis related 90-day mortality was 9/17 (52.7%) in the revascularized cohort, compared to 5/31 (16.1%) in those not revascularized and 25/156 (16.0%) in those without CAD (p=0.001). irAE-related 90-day mortality was 9/17 (52.7%) in the revascularized cohort, compared to 6/31 (19.4%) in those not revascularized and 31/156 (19.9%) in no CAD groups (p=0.007) (Figure 1). All-cause 90-day mortality was 11/17 (64.7%) in the revascularized cohort, compared to 13/31 (41.9%) in no revascularization and 60/158 (38.0%) in no CAD groups (p=0.10). After adjustment on age and sex, coronary revascularization remained associated with ICB-myocarditis-related death at 90 days (Hazard ratio [HR]=4.03, 95%confidence interval [CI] 1.84–8.84, p<0.001) and was marginally associated with all-cause death (HR=1.88, 95% CI 0.98–3.61, p=0.057).

Conclusion

CAD may exist concomitantly with ICB-myocarditis and portend a poorer outcome when revascularization is performed. This is potentially mediated thru delayed diagnosis and treatment or more severe presentation of ICB-myocarditis.

Funding Acknowledgement

Type of funding sources: None.
Incidence of cardiovascular events in patients treated with immune checkpoint inhibitors
Authors: Laenens D , Yu Y , Santens B , Jacobs J , Beuselinck B , Bechter O , Wauters E , Staessen J , Janssens S , Van Aelst L
Published: October 2022

Background

In rare cases, immune checkpoint inhibitors (ICIs) cause immune-mediated myocarditis. However, the true incidence of other major adverse cardiovascular events (MACE) following ICI treatment remains unknown, mainly because late occurring side effects are rarely reported in prospective clinical trials.

Purpose

To identify the incidence and risk factors of MACE in a real-life ICI-treated cancer cohort and to compare the incidence with non-ICI-treated cancer patients and population controls.

Methods

In total, 672 ICI-treated patients were included. The primary endpoint was MACE, a composite of acute coronary syndrome, heart failure, stroke and transient ischemic attack. Secondary outcomes were acute coronary syndrome and heart failure separately. Incidence rates were compared between groups after matching according to age, sex, cardiovascular history and cancer type.

Results

Incidence of MACE was 10.3% during a median time of follow-up of 13 months (IQR 6 to 22). In multivariable analysis, a history of heart failure (hazard ratio (HR): 2.27; 95% confidence interval (CI): 1.03 to 5.04; p=0.043) and valvular heart disease (HR 3.01; 95% CI: 1.05 to 8.66; p=0.041) remained significantly associated with MACE.

Cumulative incidence rates were significantly higher in the matched ICI group (rate at full range of follow-up (rate): 8.51; 95% CI: 6.18 to 11.4) compared with the cancer cohort not exposed to ICI (rate: 5.20; 95% CI: 3.56 to 7.35; p=0.032) and the population controls (rate: 2.55; 95% CI: 2.16 to 2.99; p<0.001) mainly driven by a higher risk of heart failure events (Figure 1).

Conclusions

Cardiovascular events during and after ICI treatment are more common than currently appreciated. Patients at risk are those with a history of cardiovascular disease. Compared with matched cancer and population controls, MACE incidence rates are significantly higher, suggesting a potential harmful effect of ICI treatment besides the underlying risk.

Funding Acknowledgement

Type of funding sources: None.
Baseline left atrial reservoir strain provides independent and incremental prognostic value in predicting chemotherapy related cardiotoxicity
Authors: Yu C , Negishi T , Thavendiranathan P , Pathan F , Penicka M , Cote M A , Massey R J , Miyazaki S , Shirazi M , Santoro C , Vinereanu D , Kosmala W , Thomas L , Marwick T H , Negishi K
Published: October 2022

Background

Currently, few baseline imaging biomarkers can predict chemotherapy induced cardiotoxicity (CTx). The early identification of CTx is critically important as it determines the prospect of LV function recovery (1).

Purpose

We aimed to determine if baseline left atrial (LA) reservoir strain (LAS) is predictive of CTx.

Methods

We performed retrospective analysis of the SUCCOUR study, an international multicentre randomized controlled trial. CTx was defined as an asymptomatic drop of >10% in left ventricular ejection fraction (LVEF) compared to baseline to <55%. LAS analysis was performed using semi-automated speckling tracking of the LA in the four and two chamber views using EchoPAC. Analysis was performed at one year follow up. Cox proportional hazard analysis, c-statistics and Akaike information criterion (AIC) statistical analysis was performed.

Results

After excluding 78 with inadequate images, 229 were included in the analysis. Most participants were female (n=215, 94%), with a mean age of 54±12 years. Median follow up was 1.02 years (IQR 0.98–1.07). A smoking history was the commonest cardiac risk factor (n=68, 30%). Breast cancer was the main cancer type (n=205, 90%). The mean baseline 3D LVEF, LV global longitudinal strain (GLS), LAS, and LA volume index (LAVI) were 61±4%, 20.6±2.5%, 28.6±7.9%, and 28±9ml/m2, respectively. Participants that developed CTx had a lower LAS at baseline compared to those that did not (25.5±7.4% vs 29.0±7.9% respectively; p=0.027). At 1-year follow-up, 29 patients (13%) developed CTx. On univariable Cox proportional hazard analysis, higher baseline LAS was associated with a lower risk of CTx (HR 0.95, 95% CI 0.90–0.99; p=0.026) but other parameters including baseline GLS was not (p=0.17). In nested Cox models (Figure 1), adding LAS significantly improved the model's predictive accuracy for CTx compared to other clinical and imaging parameters. When LAS was added to the same models it showed improvements in the c-statistics and AIC score (Figure 1).

Conclusion

Baseline LAS is an independent and incremental predictor of CTx. LAS could be used for baseline risk stratification in oncology patients who receive potentially cardiotoxic chemotherapy.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): GE Healthcare
Cardiac magnetic resonance relaxometry compared to left ventricular ejection fraction in the identification of anthracycline related cardiac changes: a systematic review and meta-analysis
Authors: Yu C , Pathan S , Jeyaprakash P , Pathan F , Kritharides L , Negishi K
Published: October 2022

Background

Anthracyclines are associated with cancer therapeutics related cardiac dysfunction (CTRCD). The identification of CTRCD currently uses a change in left ventricular ejection fraction (LVEF). Myocardial damage associated with anthracyclines include myocardial inflammation and oedema. This can be assessed using cardiac magnetic resonance (CMR) relaxometry techniques; T1 and T2 mapping and extracellular volume (ECV) fraction.

Purpose

In this meta-analysis, we compared the magnitude of the changes in LVEF and CMR relaxometry techniques wihtin a month of anthracycline therapy completion.

Methods

We performed a structured literature review as per the PRISMA guidelines across three databases (EMBASE, MEDLINE, and SCOPUS) for studies evaluating CMR relaxometry parameter at baseline and soon after completion of anthracycline therapy (3–5 months post baseline). CMR parameters pre and post anthracycline-based chemotherapy were abstracted. A random effects model was used to pool mean difference (MD) in LVEF and ECV given standardisation in imaging acquisition techniques. A random effects model was used to pool standardized mean difference (SMD) in LVEF, T1, T2 and ECV after anthracycline to adjust for variations in imaging techniques and comparison between techniques.

Results

A total of 174 patients were included from seven studies. 91% were female with a mean age of 55.6 years. The pooled MD in LVEF and ECV was −3.15% [95% CI −4.99, −1.31] and 1.61% [0.90, 2.32], respectively. The pooled SMD in LVEF, T1, T2 and ECV was −0.61 [−0.96, −0.25] 0.34 [0.04, 0.63], 0.67 [0.12,1.21], 0.6 [0.31, 0.89], respectively (Table 1).

Conclusions

T2 mapping, ECV and LVEF can identify early myocardial changes better than T1 mapping. These changes suggest there is marked oedema in the myocardial injury from anthracycline therapy. Whilst these findings support the role of CMR relaxometry in identifying CTRCD, further studies are required.

Funding Acknowledgement

Type of funding sources: None.
Increased epicardial adipose tissue volume after anthracycline chemotherapy is associated with a low risk of cardiotoxicity in breast cancer
Authors: Kwon S , Nam B D , Kwon S H , Bang D W
Published: October 2022

Introduction

Chemotherapy-induced cardiotoxicity is a critical issue for patients with breast cancer. Epicardial adipose tissue (EAT) is located between the myocardial surface and the visceral layer of the pericardium. Change of EAT is associated with cardiac dysfunction.

Purpose

Considering that early detection of patients at risk of developing cardiotoxicity during and after anthracycline-based chemotherapy is the most important factor in reducing and reversing cardiac function, there is a need to identify a simple and novel imaging marker that can predict cardiotoxicity at an early stage. Therefore, the objective of the present study was to investigate the relationship between EAT and chemotherapy-induced cardiotoxicity.

Methods

This retrospective study analyzed EAT on chest computed tomography (CT) of patients with early breast cancer using automatic, quantitative measurement software between November 2015 and January 2020. Changes in EAT before and after initiation of chemotherapy were compared according to the type of anticancer drug. Subclinical cardiotoxicity was defined as worsening ≥10% in left ventricular ejection fraction to an absolute value >50% with a lower limit of normal measured with standard echocardiography.

Results

Among 234 patients with breast cancer, 85 were treated with adjuvant anthracycline-based (AC) and 149 were treated with non-anthracycline based (non-AC) chemotherapy. There was a significant increase in EAT volume index (mL/kg/m2) at the end of chemotherapy compared to that at the baseline in the AC group (3.33±1.53 vs. 2.90±1.52, p<0.001), but not in the non-AC group. During the follow-up period, subclinical cardiotoxicity developed in 20 (8.6%) patients in the total population (15.3% in the AC group and 4.8% in the non-AC group). In the multivariable analysis, EAT volume index increment after chemotherapy was associated with a lower risk of subclinical cardiotoxicity in the AC group (Odds ratio: 0.364, 95% CI: 0.136–0.971, p=0.044).

Conclusions

Measurement of EAT during anthracycline-based chemotherapy might help identify subgroups who are vulnerable to chemotherapy-induced cardiotoxicity. Early detection of EAT volume change could enable tailored chemotherapy with cardiotoxicity prevention strategies.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Medical Technology Development Program of the National Research Foundation of Korea (NRF) funded by the Korean government (MSIT).
Cardiac autonomic modulation with donepezil attenuates pyroptosis and mitochondrial dysfunction, leading to improved left ventricular function in trastuzumab-induced cardiotoxicity in rats
Authors: Khuanjing T , Maneechote C , Ongnok B , Prathumsap N , Arinno A , Chunchai T , Arunsak B , Chattipakorn S C , Chattipakorn N
Published: October 2022

Background

Trastuzumab (Trz)-induced cardiotoxicity (TIC) is one of the most common cardiovascular complications of targeted anticancer agents. Cardiac inflammation, cardiac mitochondrial dysfunction, oxidative stress, and cardiac autonomic dysfunction have been identified as potential mechanisms underlying the adverse effects of TIC. Although cardiac inflammation is one of the key mechanisms triggering “pyroptosis”, i.e. a new inflammatory form of programmed cell death, the association between TIC and pyroptosis is still largely unknown. Moreover, the modulation of cardiac autonomic activity using an acetylcholinesterase inhibitor (AChE) has been shown to exert cardioprotection in various heart diseases. However, the role of donepezil (DPZ), an AChE, in treating TIC has never been investigated.

Purpose

We evaluated the cardioprotective effects of DPZ on left ventricular (LV) function, cardiac mitochondrial function, and pyroptosis in rats with TIC. We hypothesised that DPZ reduces mitochondrial dysfunction and pyroptosis, leading to a reduction of LV dysfunction in TIC rats.

Methods

Fifteen male Wistar rats were randomly divided into the control group (n=5, 0.9% normal saline solution, ip) and the Trz group (n=10, 4 mg/kg/day for 7 days, ip). Trz-treated rats were subdivided into the vehicle group (n=5, drinking water, po) and the DPZ group (n=5, 5 mg/kg/day for 7 days, po). At the end of the experiment, echocardiography was performed, and the heart was removed to determine the cardiac mitochondrial function and pyroptosis.

Results

Compared with the control group, %LV ejection fraction (%LVEF) was significantly decreased in the Trz group (Fig. 1A). Trz treatment also markedly increased cardiac mitochondrial reactive oxygen species (ROS) production and mitochondrial depolarisation, as indicated by a lower red/green fluorescence intensity ratio (Fig. 1B and C, respectively). Furthermore, Trz induced pyroptosis by increasing NLR family pyrin domain containing 3 (NLRP3) expression and cleaved Gasdermin D/Gasdermin D ratio, compared to the control group (Fig, 1D–F). Notably, DPZ co-treatment potentially reduced mitochondrial ROS production, mitochondrial depolarisation, and pyroptosis (NLRP3 and cleaved Gasdermin D/Gasdermin D ratio), leading to improved %LVEF (Figure 1).

Conclusion

DPZ alleviated cardiac dysfunction in TIC rats by improving mitochondrial function and reducing pyroptosis. These findings suggested that DZP could be a novel effective pharmacological intervention against TIC.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): 1. The National Science and Technology Development Agency Thailand2. The Thailand Research Fund (RGJ)
Effect of serum lipid profile on the risk of breast cancer: systematic review and meta-analysis of 1,717,054 women
Authors: Nouri M , Mohsenpour M A , Katsiki N , Ghobadi S , Jafari A , Faghih S , Banach M , Mazidi M
Published: October 2022

Background

Dyslipidemia has been linked to breast cancer incidence. However, conflicting results exist regarding the associations between lipid components and breast cancer development.

Purpose

The aim of the present meta-analysis was to further investigate the relationships between serum lipid profile and the risk of breast cancer.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed to conduct the present systematic review and meta-analysis. Databases such as the PubMed, EMBASE, and Web of Sciences, were searched up to the end of January 2021, using certain MeSH and non-MeSH keywords and their combination to extract related published articles.

Results

Twenty-six prospective studies met the inclusion criteria involving 1,717,054 women, of whom 36,590 were diagnosed with breast cancer during the follow-up. A negative and significant association was found between HDL-C levels and the risk of breast cancer [relative risk (RR): 0.85, 95% CI: 0.72–0.99, I2: 67.6%, p=0.04) (Figure). In contrast, TG (RR: 1.02, 95% CI: 0.91–1.13, I2: 54.2%, p=0.79), total cholesterol (TC) (RR: 0.98, 95% CI: 0.90–1.06, I2: 67.2%, p=0.57), apolipoprotein A (ApoA) (RR: 0.96, 95% CI: 0.70–1.30, I2: 83.5%, p=0.78) and LDL-C (RR: 0.93, 95% CI: 0.79–1.09, I2: 0%, p=0.386) were not associated with breast cancer development. In studies adjusting for hormone use and physical activity, TC was positively correlated to breast cancer risk (RR: 1.05, 95% CI: 1.01–1.10 and 1.05, 95% CI: 1.01–1.10, respectively), as was TG in studies adjusting for baseline lipids (RR: 0.92, 95% CI: 0.85–0.99) and race (RR: 1.80, 95% CI: 1.22–2.65).

Conclusions

In the present meta-analysis, HDL-C was inversely related to breast cancer risk. In contrast, no significant associations were found for TC (except after adjusting for hormone use and physical activity), TG (except after adjusting for baseline lipids and race), LDL-C and ApoA. Overall, data on the links between lipids and breast cancer are conflicting. However, there is increasing evidence supporting that low HDL-C is related to an increased risk for this malignancy. Further research is needed to establish the associations between different lipid components and breast cancer risk in certain populations.

Funding Acknowledgement

Type of funding sources: None.
Low-dose anticoagulation for peripheral deep vein thrombosis of the lower extremities in cancer patients
Authors: Nonaka A , Fukuda Y
Published: October 2022

Background

Venous thromboembolism (VTE) is a frequent complication in cancer patients and is often detected as asymptomatic peripheral deep vein thrombosis (DVT). However, guidelines for peripheral DVT have not been established in either general cardiology or onco-cardiology. Furthermore, in cancer patients, it is generally considered difficult to administer standard doses of anticoagulants due to the high risk of bleeding caused by thrombocytopenic tendency during chemotherapy, as well as bleeding lesions such as gastrointestinal and gynecological cancers.

Treatment of peripheral DVT with direct oral anticoagulants (DOACs) may minimize the worsening of bleeding and prevent the transition to proximal DVT.

Objective

The purpose of this study was to investigate the optimal treatment for peripheral DVT in cancer patients.

Methods

242 consecutive patients with peripheral DVT of the lower extremities (excluding complications of pulmonary thromboembolism or proximal DVT) were examined by venous ultrasound from April 2019 to March 2020. 190 patients could be followed up by ultrasound examination, for up to 2 years. The course of the DVT was retrospectively examined. In cases of anticoagulant therapy, standard and low dosage of DOACs were evaluated.

Results

142 patients were treated with anticoagulant (AC) therapy (group AC(+)), 48 patients were without AC therapy (group AC(−)). (4 of the 142 patients were treated with warfarin and the rest with DOACs).

DVT worsened in 8 patients (5.6%) in the AC(+) group and 23 patients (47.9%) in the AC(−) group. DVT worsening was significantly less in the AC(+) group (p<0.0001).

There were no cases of worsening to proximal type in the AC(+) group and 4 cases (17.4%) in the AC(−) group.

Of the 138 patients who used DOACs as AC therapy, 62 used half or less than the standard dose for maintenance (low-dose DOAC group), and 76 used the standard dose as maintenance (standard-dose DOAC group).

In the low-dose DOAC group, DVT worsened in 5 cases, remained unchanged in 7 cases, and improved in 50 cases. In the standard-dose DOAC group, there were 4 cases of worsening DVT, 3 cases of no change, and 69 cases of improvement. There was no significant difference in the DVT treatment effect between the two groups.

There were no thrombus-related deaths.

Conclusion

Peripheral DVT worsens in about half of cancer patients without anticoagulation, and 17% of these worsen to proximal VTE. In addition, low-dose DOACs are found to be as effective as standard-dose DOACs in treating peripheral DVT in cancer patients. Peripheral DVT treatment with low-dose DOACs can reduce the risk of bleeding complications and thrombus-related mortality in cancer patients and should be one of the supportive treatments for the completion of cancer management.

Funding Acknowledgement

Type of funding sources: None.
Cancer as a risk factor for physical dysfunction and poor prognosis in patients with cardiovascular disease
Authors: Miki T , Kamiya K , Hamazaki N , Nozaki K , Ichikawa T , Yamashita M , Uchida S , Noda T , Ueno K , Yamaoka-Tojo M , Maekawa E , Sasaki J , Matsunaga A , Ako J
Published: October 2022

Introduction

The emerging interdisciplinary field of cardio-oncology is of interest to clinicians because a history of cancer or cancer treatment is considered a severe risk factor for cardiovascular disease (CVD). Both cancer and CVD can reduce skeletal muscle mass; together, they can lead to a poorer prognosis. However, it is unclear whether a patient's cancer history can lower physical function and lead to a poor prognosis with the coexistence of cancer history and physical dysfunction in patients with CVD. This study aimed to identify the relationship between cancer history and physical function, as well as the prognostic value of their combination, in patients with CVD.

Methods

We reviewed 3,640 patients with CVD (mean age, 67.9±13.5 years) who underwent physical-function tests (gait speed and 6-min walking distance [6MWD]). We performed multivariate linear regression analysis to assess potential associations between cancer history and physical-function tests in patients with CVD. Additionally, we used the Kaplan–Meier curve and Cox regression analyses to assess survival and prognostic significance for patients divided into four groups according to the presence or absence of cancer history and high or low physical function.

Results

In multivariate linear regression analysis, cancer history was independently associated with lower gait speed and 6MWD (gait speed, P=0.048 and 6MWD, P=0.040). A total of 581 deaths occurred over a median follow-up period of 3.08 years (interquartile range: 1.36–5.27). For all-cause mortality, patients with a history of cancer and reduced physical function were found to have a significantly higher mortality risk even after adjusting for several covariates (gait speed, HR: 1.66, P=0.003 and 6MWD, HR: 1.71, P=0.003).

Conclusion

Cancer history was correlated with physical dysfunction in patients with CVD. Moreover, the coexistence of cancer history and physical dysfunction resulted in poorer prognosis in patients with CVD.

Funding Acknowledgement

Type of funding sources: None.
Five-year cardiovascular outcomes in patients with chronic myeloid leukemia treated with imatinib, dasatinib or nilotinib: data from a large multinational collaborative network
Authors: Belo Nunes R , Da Costa L M A , Bachour P , Cantarelli M J , Neves P D M , Oliveira G B F
Published: October 2022

Background

BCR-ABL tyrosine kinase inhibitors (TKI) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, concern has arisen about the cardiac safety profile of these drugs.

Purpose

To compare long-term risks of adverse cardiovascular and cerebrovascular events (ACE), heart failure or left ventricular ejection fraction (LVEF) <50% and venous thromboembolic events (VTE) in patients with CML treated with first-line Bcr-ABL TKIs, using data from a large multinational network.

Methods

Patients aged ≥18 years with chronic myeloid leukemia treated with imatinib or dasatinib or nilotinib and without prior cardiovascular or cerebrovascular disease. We used propensity score matching to balance the cohorts. The 5-year cumulative incidences and hazard ratios were calculated.

Results

We identified 3,722 patients with CML under treatment with Imatinib (n=1,906), Dasatinib (n=1,269) and Nilotinib (n=547). Patients with imatinib compared to dasatinib showed higher risk for ACE (hazard ratio 2,13, 95% IC 1.15–3.94, p=0.016). Patients with imatinib presented lower risk than nilotinib for ACE (hazard ratio 0.50, 95% IC 0.30–0.83, p=0.0074). In relation to heart failure or LVEF <50%, patients with imatinib had higher risk than dasatinib (hazard ratio 9.41, 95% IC 1.22–72.17, p=0.03), but no significant difference was observed between imatinib and nilotinib (hazard ratio 0.48, 95% IC 0,215–1.01, p=0.064). The probability of survival (Kaplan Meier curves) without ACE, heart failure or LVEF <50% and VTE are depicted in the Central Illustration.

Conclusions

In a large cohort of patients with CML, those treated with nilotinib had higher 5-year risk of adverse cardiovascular and cerebrovascular events, while patients with dasatinib showed lower risk than patients with imatinib. The risk of heart failure was higher in patients with imatinib than in patients with dasatinib, but not when compared to nilotinib.

Funding Acknowledgement

Type of funding sources: None.