Pre-existing Ischaemic Heart Disease Research Articles

The predictive value of coronary artery calcium deposit for cardiovascular events in patients treated with immune checkpoint inhibitor therapy

Abstract Background Immune checkpoint inhibitors (ICIs) are now a standard of care for the treatment of wide variety of cancers, due to their dramatically improved patient's outcomes. Nevertheless, their use may lead to significant cardiovascular immune-related adverse events (CV irAEs). Objectives We aimed to assess whether pre-treatment coronary artery calcium (CAC) deposit may play as a risk factor for CV irAEs development in patients treated with ICIs therapy. Methods A retrospective single center cohort of patients treated with ICIs therapy, who performed pre-treatment chest computed tomography. Visual CAC assessment was performed, categorized to positive or negative calcium deposit in the coronary arteries. Patients with pre-existing ischemic heart disease were excluded. The primary endpoint was to evaluate the association between positive CAC deposit and the composite CV irAEs, including myocarditis, acute coronary syndrome, heart failure, and arrhythmias. The secondary endpoint was to evaluate its association to all-cause mortality. Results The cohort included 238 patients, with mean age 65±13 years and 53% male representative. The most prevalent type of cancer was lung (36%) and the prominent ICIs regimen was pembrolizumab (54%). High incidence of cardiac risk factors was observed, including hypertension (39%), hyperlipidemia (35%) and diabetes (23%). Overall, 145 (61%) patients were included in the positive CAC deposit group. No significant differences were observed between the positive and negative groups regarding cancer type, ICIs therapy and baseline cardiac risk factors or medical therapy. Over a 12-months follow-up period, positive CAC deposit was not associated with the development of CV irAEs (p=0.139), or increased all-cause mortality (p=0.884). Conclusion The presence of pre-treatment positive CAC deposit did not demonstrate a predictive role in assessing the risk of CV irAEs or all-cause mortality in patients treated with ICIs.

Outcomes of Covid-19 among patients with ischemic heart disease: A propensity matched analysis

BackgroundPrior research has linked cardiovascular diseases with higher COVID-19 mortality and worse hospital outcomes, particularly in severe heart failure. Large population-based data regarding the impact of pre-existing ischemic heart disease (IHD) on COVID-19 outcomes is not well established. ObjectiveTo study the impact of COVID-19 infection on IHD hospital mortality and other outcomes. MethodsThe study included a patient cohort from the 2020 and 2021 National Inpatient Sample (NIS) database. Propensity score matching was used to match the study cohort (COVID-19 with IHD) to controls (COVID-19 without IHD) using a 1:1 matching ratio. The outcomes analyzed were in-hospital mortality, rates of acute kidney injury (AKI), acute myocardial injury (AMI), cardiogenic shock, cardiac arrest, mechanical ventilation, tracheal intubation, pulmonary embolism (PE), ventricular tachycardia (VT), ventricular fibrillation (VF), length of stay (LOS), and total hospitalization charges. ResultsA total of 2,532,652 patients met the inclusion criteria (1,199,008 females [47.3 %), predominantly Caucasian 1,456,203 (57.5 %); mean [SD] age 63, (5.4), including 29,315 (1.1 %) patients with a history of IHD. Following propensity matching, 4,772 COVID-19 patients with and without IHD were matched. IHD patients had higher rates of AMI (adjusted odds ratio (aOR) 3.75, 95 % CI 3.27–4.31, p < 0.001), cardiogenic shock (aOR 2.89, 95 % CI 1.60–5.19, p < 0.001), VT (aOR 3.26, 95 % CI 2.48–4.29, p < 0.001), and VF (aOR 2.23, 95 % CI 1.25–3.99, p < 0.001). The odds ratios of in-hospital mortality, AKI, PE, mechanical ventilation, tracheal intubation, and resource use were not significantly different. ConclusionA history of IHD does not impact COVID-19 mortality but increases the risk of in-hospital cardiac complications.

Associations of fish oil with cardiovascular disease events: results from the Taiwan longitudinal study in aging

BackgroundThe effectiveness of fish oil in preventing cardiovascular events is still debating. Some studies indicate a correlation between the use of fish oil supplements and reduced mortality or decreased incidence of stroke. However, other studies show no significant association between fish oil intake and stroke prevention, indicating an ongoing debate. This study aimed at exploring which subjects may benefit more from fish oil supplementation.MethodsThis study utilized the data obtained through face-to-face interview from the Taiwan Longitudinal Study in Aging (TLSA). A total of 3,652 participants were included from the 2003 baseline data, after excluding patients with pre-existing ischemic heart disease or stroke. Participants were divided into two groups based on whether taking fish oil supplement or not. Participants were followed until 2015, estimating and comparing the all-cause mortality and cumulative incidence rate of stroke between both groups.ResultsThe results of the 12-year longitudinal study showed that the cumulative incidence rate of stroke in the fish oil supplementation group was 5.7%, compared to 7.7% in the non-supplemented group (P < 0.05). Additionally, the crude hazard ratio for stroke was significantly lower in the fish oil supplementation group (HR = 0.686;95% CI 0.476–0.987). However, after adjusting potential confounders, the adjusted risk of stroke was lower only for the diabetic patients supplemented with fish oil (aHR = 0.123; 95% CI 0.016–0.930) compared to non-diabetic patients (aHR = 0.917; 95% CI 0.616–1.364).ConclusionThis study suggests that there is an association between fish oil supplementation and a lower cumulative incidence rate of subsequent stroke among diabetic patients.

Cardio-cerebrovascular adverse outcomes in patients with influenza with and without preexisting cardiovascular disease: Oral antiviral agents impact.

This study aimed to compare the 2-year cardio-cerebrovascular adverse outcomes of patients with influenza with and without preexisting cardiovascular disease (preCVD) treated with oral antiviral agents in the outpatient clinic. Oral antiviral agents are routinely prescribed to treat influenza infection with a positive rapid-antigen test in the outpatient clinic; however, influenza-associated cardio-cerebrovascular outcomes have not yet been characterized in patients with preCVD treated with oral antiviral agents. Data between 2006 and 2016 were extracted from the National Health Database of South Korea. A total of 865,522 patients with influenza treated with oral antiviral agents were selected in South Korea and classified as preexisting ischemic heart disease (IHD), heart failure (HF), or atrial fibrillation (AF), and 2-year cardio-cerebrovascular outcomes were analyzed using a Cox proportional hazard regression model. Among the participants, 96,433 had preCVD (11.1%; mean age, 46 years) including IHD (86.4%), HF (23.1%), and AF (12.5%). The incidence of new-onset IHD, AF, HF, and death was similar between patients with influenza with and without preCVD. The incidences of IHD and stroke were 0.489 and 0.047 per 100-person year in the preCVD group, respectively. The incidence of cardiovascular mortality was 0.489 per 100-person year in the preCVD group, and the hazard ratio for cardiovascular mortality in the preCVD group was not significantly different from that in patients without preCVD. Based on the national health data, 2-year cardio-cerebrovascular adverse outcomes were not significantly different between patients with and without preCVD treated with oral antiviral agents.

Preventing 5-fluorouracil-induced ischemic events in very high-risk cardiac patients: A retrospective cohort analysis (SQCCCRC protocol).

e24112 Background: 5-Fluorouracil (5-FU), a potent chemotherapy agent for various cancers, is linked to cardiotoxicity, particularly in patients with pre-existing ischemic heart disease. The incidence varies, necessitating effective preventive strategies. Among the several mechanisms responsible for 5-FU-induced myocardial ischemia are coronary vasospasm and endothelial injury. Therefore, prevention of ischemic events in very high-risk patients by controlling modifiable cardiac risk factors and good medical treatment including vasodilators are a potential strategy in preventing 5-FU ischemic events. Methods: To assess the effectiveness and safety of a protocol involving Amlodipine and Isosorbide dinitrate in preventing 5-FU-induced ischemic events in very high-risk cardiac patients with documented ischemic heart disease. Nineteen patients underwent 252 cycles of 5-FU chemotherapy, with 12 patients (181 cycles) following the pre-defined protocol (5-FU Protocol Group) and 7 patients (71 cycles) not adhering (Missed 5-FU Protocol Group). The primary outcome measure was the prevention of 5-FU-induced ischemic events, evidenced by the absence of chest pain, elevated Troponin levels, or ECG changes during 5-FU infusion. Results: The 5-FU Protocol Group demonstrated significant reductions in ischemic events, chest pain with p-values of 0.009 for both outcomes. Additionally, the occurrence of ECG changes post-5FU and an increase in Troponin levels was significantly lower in the 5-FU Protocol Group, with p-values of 0.036 for both parameters. Although not statistically significant, there was a lower 5FU-related mortality rate in the 5-FU Protocol Group compared to the missed 5-FU Protocol Group (0% vs. 14.3%, p = 0.37). The incidence of cancer-related mortality did not exhibit a statistically significant difference between the two groups. To evaluate this, we specifically examined and compared the occurrence of ischemic events in both the 5-FU Protocol Group and the Missed 5-FU Protocol Group. The comparison was conducted using the Fisher exact test. Conclusions: The use of vasodilators may be effective in preventing 5-Fluorouracil-Induced ischemic events in very high-risk cardiac patients with documented coronary artery disease. This approach may help reduce the risk of cardiac events and improve the safety of chemotherapy in this vulnerable patient population. Monitoring cardiotoxicity with maximum tolerated medical treatment and dedicated hospital protocols may be a good prophylaxis approach. Further studies are needed to confirm the safety and efficacy of this approach in a larger patient population, and to assess its impact on long-term cardiac outcomes.

Prior cardiac ischemic injury exacerbates immune checkpoint inhibitor-induced cardiotoxicity

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Momentum grant of the Hungarian Academy of Sciences Introduction Immune checkpoint inhibitors (ICI), such as monoclonal antibodies targeting programmed death ligand-1 (PD-1), revolutionized cancer treatment. However, they can lead to several cardiovascular adverse effects, ranging from mild cardiac dysfunction to fulminant, lethal myocarditis. Nevertheless, the mechanisms and risk factors behind the diverse forms of ICI-induced cardiotoxicity are not entirely understood currently. Purpose In this study, we hypothesized that a prior cardiac ischemic injury, leading to acute immune cell infiltration and activation, but without subsequent heart failure, can exacerbate the cardiotoxicity and cardiac inflammation caused by anti-PD-1 monoclonal antibodies. Furthermore, we aimed to investigate in our mouse model whether abatacept, an inhibitor of T-cell co-stimulation, can ameliorate ICI-induced cardiac effects. Methods First, we treated 8 weeks-old C57BL/6J mice with isoprenaline (ISOP group, 160 mg/kg, n = 43) or with its solvent (CON group, n = 38), to induce reversible cardiac ischemia. Validation of the ischemic injury was performed in 6 randomly selected animals from each group two days after the treatment with histology and echocardiography. After this, the animals underwent 16 weeks of recovery period, followed by echocardiography to confirm cardiac functional recovery. Here, mice from both groups were randomized to three further treatment groups: isotype control, anti-PD-1 alone, or anti-PD-1 combined with abatacept and were treated for two weeks, with three weekly intraperitoneal injections (immune checkpoint inhibition phase). Echocardiography, qRT-PCR and histology was performed to evaluate cardiac function and inflammation. Results Two days after the initial ISOP treatment, mice displayed significant reduction in ejection fraction and infiltration of inflammatory cells were seen on histology. During the recovery period, 8 mice from the ISOP group and one mouse from the CON died. After the immune checkpoint inhibition phase, mice with prior ischemic injury and anti-PD-1 treatment (ISOP + anti-PD-1 alone) showed significant cardiac dysfunction on echocardiography, while animals with abatacept treatment (ISOP+anti-PD-1+abatacept) showed normal cardiac function. With qRT-PCR and histology, increased infiltration of T-cells and macrophages was seen in the myocardium of the ISOP+anti-PD-1 treated group compared to CON animals, with increased expression of pro-inflammatory cytokines, including Il17a, Il23 and Ifng. However, no cardiac infiltration was seen in mice without prior ischemic injury and the pro-inflammatory cytokine response was less pronounced as well. Conclusions Prior cardiac ischemic injury without overt cardiac dysfunction exacerbates cardiac inflammation and cardiotoxicity induced by anti-PD-1 immune checkpoint inhibition therapy. Patients with pre-existing ischemic heart disease may be at greater risk for developing ICI-induced severe cardiac adverse events.Hypothesis

Preeclampsia Risk in Pregnant Patients With Preexisting Ischemic Heart Disease [ID 2683588

INTRODUCTION: Preeclampsia (PreE) affects 1 in 25 U.S. pregnancies. Recognized risk factors include obesity, chronic hypertension, and diabetes, and PreE may elevate risk of cardiovascular disease (CVD) later in life. Despite shared vascular integrity concerns with known risk factors, there is no clear link between preexisting CVD, particularly ischemic heart disease (IHD), and increased risk of PreE during pregnancy. This study investigates whether preexisting IHD heightens risk of PreE in pregnant patients, and if this relationship can be explained by elevated rates of hypertension, diabetes, and obesity. METHODS: Data were obtained from the Healthcare Cost and Utilization Project (HCUP) national database, containing comprehensive de-identified patient data on U.S. hospital encounters. ICD-10 codes for IHD, chronic hypertension, gestational and preexisting diabetes, obesity, and PreE were used to identify relevant cases among delivery admissions. Data were analyzed using logistic regression, controlling for confounders. RESULTS: The sample included 1,670,527 patients who delivered between 2016 and 2019. Although no differences by race were observed, patients with IHD were significantly older and more likely to qualify for Medicaid. After controlling for age and insurance status, pregnant patients with IHD were nearly three times more likely to develop PreE than those without IHD (OR 2.75 [1.93–3.39]). With adjustment for possible mediators including chronic hypertension, preexisting and gestational diabetes, and obesity, IHD was still associated with a twofold increased risk of PreE (OR 2.07 [1.44–2.99]). CONCLUSION: Pregnant women with preexisting IHD face significantly higher risk of developing PreE, even when considering comorbidities including obesity, diabetes, and hypertension. Preeclampsia is a leading cause of maternal morbidity and mortality worldwide. As the incidence of IHD rises, understanding the potential interactions between these conditions becomes crucial. Further research is needed to clarify connections between IHD and PreE, especially in identifying IHD and its risk factors to improve PreE prophylaxis and management.

Outcomes of patients with coronavirus disease versus other lung infections requiring venovenous extracorporeal membrane oxygenation

BackgroundPatients with Coronavirus Disease (COVID-19) often develop severe acute respiratory distress syndrome (ARDS) requiring prolonged mechanical ventilation (MV), and venovenous extracorporeal membrane oxygenation (V–V ECMO).Mortality in COVID-19 patients on V–V ECMO was exceptionally high; therefore, whether survival can be ameliorated should be investigated. MethodsWe collected data from 85 patients with severe ARDS who required ECMO support at the University Hospital Magdeburg from 2014 to 2021. The patients were divided into the COVID-19 group (52 patients) and the non-COVID-19 group (33 patients). Demographic and pre-, intra-, and post-ECMO data were retrospectively recorded. The parameters of mechanical ventilation, laboratory data before using ECMO, and during ECMO were compared. ResultsThere was a significant difference between the two groups regarding survival: 38.5% of COVID-19 patients and 63.6% of non-COVID-19 patients survived 60 days (p = 0.024). COVID-19 patients required V–V ECMO after 6.5 days of MV, while non-COVID-19 patients required V–V ECMO after 2.0 days of MV (p = 0.048). The COVID-19 group had a greater proportion of patients with ischemic heart disease (21.2% vs 3%, p = 0.019). The rates of most complications were comparable in both groups, whereas the COVID-19 group showed a significantly higher rate of cerebral bleeding (23.1 vs 6.1%, p = 0.039) and lung bacterial superinfection (53.8% vs 9.1%, p = <0.001). ConclusionThe higher 60-days mortality among patients with COVID-19 with severe ARDS was attributable to superinfection, a higher risk of intracerebral bleeding, and the pre-existing ischemic heart disease.

The Impact of Gender on the Postoperative Consumption of Intensive and Intermediate Care Resources

Gender disparities when delivering healthcare are attributed to gender bias and gender-related pathophysiology. We examined the interaction of gender with the provision of postoperative intensive and intermediate care. Specifically whether for major surgeries, co-morbidities and lengths-of-surgery, women receive intensive and intermediate care as often as men. A two-phase prospective study performed in an Israeli university medical center explored utilization of postoperative intensive/intermediate care. Phase 1 examined gender differences in a broad range of postoperative intensive and intermediate patients. Phase 2 examined consecutive patients undergoing major abdominal and vascular surgeries to ascertain whether for similar surgeries and co-morbidities, women were as likely as men to receive intensive/intermediate care. Phase 1 ( n = 1883)—Proportionately more males were admitted to intensive/intermediate areas because they more often were trauma victims or had pre-existing ischemic heart disease. Female admissions were notable for obstetrical emergencies and post-meningioma excisions. Phase 2 ( n = 796)—The proportion of males and females receiving intensive/intermediate care did not differ after specific surgeries, for example, hepatectomy, carotid endarterectomy. However, among patients with underlying ischemic heart disease men, more often than women (15% vs. 21%, p &lt; 0.05), received intensive care after elective surgery. Although pathophysiologic differences resulted in more men than women, receiving postoperative intensive/intermediate care, gender bias might also be operative. These observations highlight the importance of considering the influence of gender when choosing a postoperative care location to insure that gender differences in the levels of care are due to pathophysiology and not gender bias.

Impact of Pre-Existing Ischemic Heart Disease on Severe Maternal Morbidity and Mortality During Delivery Hospitalizations

BackgroundThe impact of pre-existing ischemic heart disease (IHD) on pregnancy is incompletely described. ObjectivesThe purpose of this study was to compare adverse pregnancy outcomes between those with IHD and those with a cardiac diagnosis categorized by the modified World Health Organization classification and those without a cardiac diagnosis. MethodsThis retrospective study used the 2015 to 2018 Nationwide Readmissions Database. Delivery hospitalizations, comorbidities, and outcomes were identified using diagnosis and procedure codes. The exposure was isolated IHD. The primary outcome was severe maternal morbidity (SMM) or death during the delivery hospitalization, analyzed using adjusted relative risk (aRR) regression and weighted to account for the Nationwide Readmissions Database's complex survey methods. ResultsOf 11,556,136 delivery hospitalizations, 65,331 had another cardiac diagnosis, and 3,009 had IHD alone. Patients with IHD were older and had higher rates of diabetes and hypertension. In unadjusted analyses, adverse outcomes were more common among patients with IHD alone than among patients with no cardiac disease and modified World Health Organization class I-II disease. After adjustment, patients with IHD alone were associated with a higher risk of SMM or death (aRR: 1.51; 95% CI: 1.19-1.92) than those without a cardiac disease. In comparison, the aRR was 1.90 (95% CI: 1.76-2.06) for WHO class I-II diseases and 5.87 (95% CI: 5.49-6.27) for WHO II/III-IV diseases. Nontransfusion SMM or death (aRR: 1.60; 95% CI: 1.11-2.30) and cardiac SMM or death (aRR: 2.98; 95% CI: 1.75-5.08) were also higher for those with IHD. ConclusionsIsolated IHD in pregnancy is associated with worse outcomes than no cardiac disease during delivery hospitalization and approximates the risk associated with WHO I-II diagnoses.

Abstract 11089: Comparison of Long-Term Cardiovascular Events of Influenza Patients With versus Without Pre-Existing Cardiovascular Disease in the Infection Treated With Antiviral Agents

Introduction: The antiviral agents are highly recommended to prevent cardiovascular mortality in patients with pre-existing cardiovascular disease in the pandemic era, but the long-term cardiovascular mortality have not yet been comprehensively characterized in the influenza infection treated with antiviral agents. Hypothesis: This study aimed to compare long-term cardiovascular mortality of influenza patients with versus without pre-existing cardiovascular disease in patients with anti-viral agents. Methods: The data were extracted from the National HealthDatabase from 2001 to 2010, which covers nearly the entire population of South Korea. 865,522 influenza patients treated with anti-viral agents were selected and cardiovascular disease was classified as atrial fibrillation (AF), heart failure (HF), ischemic heart disease (IHD) and 5-year mortality were analyzed using Cox proportional hazard regression model. Results: Of these, 96,433 patients (11.1%, mean age 46) had IHD (86.4%), HF (23.1%) and AF (12.5%) in the influenza infection treated with anti-viral agents. The incidence of IHD was 0.25 per 100-person year in the pre-existing IHD, 0.25 per 100-person year in the pre-existing HF and 0.20 per 100-person year in the pre-existing AF. The incidence of myocarditis was 0.008 per 100-person year in the pre-existing IHD, 0.006 per 100-person year in the pre-existing HF and 0.01 per 100-person year in the pre-existing AF. The incidence of cardiovascular death was 0.49 per 100-person year in the pre-existing IHD, 0.47 per 100-person year in the pre-existing HF and 0.47 per 100-person year in the pre-existing AF. Conclusions: Long-term cardiovascular mortality in influenza patients with pre-existing cardiovascular disease treated with antiviral agents were not significantly different from those without pre-existing cardiovascular disease.

Healthcare Resource Utilization and Costs for Empagliflozin Versus Glucagon-Like Peptide-1 Receptor Agonists in Routine Clinical Care in Denmark.

The sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin has shown reductions in major adverse cardiac events similar to glucagon-like peptide-1 receptor agonists (GLP-1RAs). However, evidence is limited about how these therapies compare regarding overall healthcare resource utilization and costs in routine clinical care. We conducted a comparative cohort study based on linked prospective healthcare databases for the entire population of Denmark during 2015-2018. We included 13,747 new users of empagliflozin and 13,249 new users of GLP-1RAs. Propensity scores were applied to balance potential confounders across the two treatment groups through inverse probability treatment weighting (IPTW). We assessed directly referable costs per person-year associated with healthcare resource utilization (inpatient, emergency room, and outpatient clinic hospital care, primary care health services, and prescription medication costs at pharmacies) among drug initiators while on-treatment. The two IPTW cohorts were well balanced at baseline (median age 61years, 60% men, diabetes duration 6.7years, 19% with pre-existing ischemic heart disease, 8% with pre-existing cerebrovascular disease), with similar healthcare costs in the previous year. During follow-up, average on-treatment costs per person-year were very similar among empagliflozin and GLP-1 RA initiators for the following services: inpatient hospitalizations (13,565 DKK versus 13,275 DKK), hospital outpatient clinic visits (12,007 DKK versus 12,152 DKK), emergency room visits (370 DKK versus 399 DKK), and primary care services (4108 DKK versus 4302 DKK). Total costs for any prescription drugs were clearly lower for empagliflozin initiators than for GLP-1 RA initiators (8946 DKK versus 14,029 DKK). In sum, overall healthcare costs on-treatment were lower for empagliflozin initiators (38,995 DKK per person-year) than for GLP-1RA initiators (44,157 DKK per person-year). In this nationwide population-based cohort study, average healthcare costs after drug initiation and while on treatment were lower for empagliflozin initiators than for GLP-1RAs initiators, driven by lower drug costs. The study protocol and analysis plan have been registered on the website of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCEPP) ( http://www.encepp.eu/encepp/viewResource.htm?id=37726 , first protocol registration 4 June 2019), and on clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT03993132 , first posted 20 June 2019).

P05-13 Associations between occupational physical activity and progression of carotid atherosclerosis among middle-aged women, are those with pre-existing cardiovascular disease more vulnerable?

BackgroundWorkers with high occupational physical activity (OPA) experience higher risk of cardiovascular diseases (CVD) than sedentary workers. In an ageing workforce, greater proportions will be expected to have CVD, and pre-existing CVD are shown to increase vulnerability to exposure of high OPA. However, most of the epidemiological evidence is derived from male cohorts, excluding those with pre-existing CVD, and using clinically manifest disease outcomes that are prone to healthy worker selection bias. To address these limitations and to highlight whether pre-existing CVD indicate vulnerability, this study investigated the effects of OPA on pre-clinical asymptomatic progression of carotid artery intima-media thickness (IMT) among women.MethodsWomen participants (N = 905) of the population-based Kuopio Ischemic Heart Disease Study (KIHD) with data on OPA and IMT were included. Linear mixed models, stratified by pre-existing CVD, estimated the association between OPA and the IMT progression from baseline (1998-2001) through 8-years of follow-up.ResultsNon-stratified analysis showed the greatest 8-year IMT progressions by exposure to light standing or moderately heavy active work (both 0.13 mm). Stratified analysis on within group changes and total level of IMT showed exposure to light standing and moderately heavy active work to give the greatest 8-year IMT progressions, especially pronounced among normotensives and those with pre-existing stenosis or ischemic heart disease (IHD). Women with pre-existing CVD ended up with the greatest total IMT levels (sum of baseline and estimated 8-year IMT change), in spite of less 8-year IMT change than among women with out pre-existing CVD. This may be explained by their initial high IMT level, combined with a celling effect of the change.ConclusionExposure to light standing work and moderately heavy active work was associated with accellerated progression of IMT, especially pronounced among normotensives or workers with pre-existing stenosis or IHD. The majority of the reported 8-year IMT progressions are at a clinically relevant magnitude of 0.1 mm, which associates with an 11% increased risk of acute myocardial infarction.

Predictors of weaning failure in case of VA ECMO implantation

The use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) for the treatment of refractory cardiogenic shock has increased significantly. Nevertheless, early weaning may be advisable to reduce the potential for severe complications. Only a few studies focusing on ECMO weaning predictors are currently available. Our objective was to evaluate factors that may help predict failure during VA ECMO weaning. We included 57 patients on VA ECMO support previously considered suitable for weaning based on specific criteria. Clinical, haemato-chemical and echocardiographic assessment was considered before and after a “weaning test” (ECMO flow < 2 L/min for at least 60 min). ECMO removal was left to the discretion of the medical team blinded to the results. Weaning failure was defined as a patient who died or required a new VA ECMO, heart transplant or LVAD 30 days after ECMO removal. Thirty-six patients (63.2%) were successfully weaned off VA ECMO, of whom 31 (54.4%) after the first weaning test. In case of first test failure, 3 out of 7 patients could be weaned after a 2nd test and 3 out of 4 patients after a 3rd test. Pre-existing ischemic heart disease (OR 9.6 [1.1–83]), pre-test left ventricular ejection fraction (LVEF) ≤ 25% and/or post-test LVEF ≤ 40% (OR 11 [0.98–115]), post-test systolic blood pressure ≤ 120 mmHg (OR 33 [3–385]), or length of ECMO support > 7 days (OR 24 [2–269]) were predictors of weaning failure. The VA ECMO weaning test failed in less than 40% of patients considered suitable for weaning. Clinical and echocardiographic criteria, which are easily accessible by a non-expert intensivist, may help increase the probability of successful weaning.

P697: PONATINIB IN A REAL-LIFE SETTING: A RETROSPECTIVE ANALYSIS FROM THE MONITORING REGISTRIES OF THE ITALIAN MEDICINES AGENCY (AIFA)

Background: The efficacy and safety of ponatinib, a third-generation tyrosine kinase inhibitor (TKI), are mainly reported in sponsored clinical trials. Aims: The aim of this study, based on a retrospective analysis from the monitoring Registries of the Italian Medicines Agency (AIFA wMRs), is to provide real-world data on daily practice management, treatment modifications and outcome of a large cohort of chronic myeloid leukemia (CML) patients treated with ponatinib. Methods: AIFA wMRs is an administrative database whose main scope is monitoring the appropriateness of drug prescription in Italy. Information collected through the wMRS included demographic (place of birth, age, and sex) and clinical data (BCR-ABL levels, mutations and chromosomal abnormalities if evaluated), drug prescription and administration data (date of prescription and administration, dose administered, dose changes, occurrence of adverse events as yes/no dichotomic variable, reasons for treatment interruption and/or discontinuation) and response to treatment (response assessment was requested every 90 days). Subjects who had not been administered ponatinib for ≥ 120 days were adjudicated as “discontinued” even in the absence of the “end of treatment form”. Time to treatment discontinuation (TTD) was defined as the time occurring between the date of first administration and the date of treatment discontinuation for any cause, including death. Results: Overall, 666 CML subjects were eligible for analysis: 515 patients had chronic phase (CP) CML, 50 accelerated phase (AP) and 101 blast phase (BP). Median age at baseline was 58.7 years, male prevalence (57.1%). Median time from diagnosis to start of ponatinib was 2.35 years: 259 (38.9%) subjects had received 2 lines of treatment, 260 (39.0%) 3 lines and 147 (22.1%) 4 or more lines. Mutational status was available for 58.3% of patients (n=388), with a T315I mutation reported in 46 (6.9%) patients and other mutations (the most represented being E255K, F317L, Y253H and V299L) in 99 (14.9%) subjects. At baseline, 181 patients (27.2%) had arterial hypertension, 33 (5.0%) a history of arterial and/or venous thromboses, 32 (4.8%) a pre-existing ischemic heart disease, and 13 (2.0%) a history of congestive heart failure. Overall, 593 patients (89.0%) were evaluable for best response. Ten cases (1.7%, 3 AP/BP and 7 CP) did not achieve molecular response, whereas 58 patients (8.7%, 26 AP/BP patients and 32 CP) reached a BCR/ABL1 ratio between 1% and 10% IS. A MR2 (less than 1%IS) was obtained by 82 subjects (12.3%, 20 AP/BP and 62 CP patients); 128 patients (19.2%, 12 AP/BP and 116 CP patients) achieved a molecular response ranged between MR3 (0.1%) and MR4 (0.01% IS) and 266 (39.9%, 44 AP/BP and 222 CP patients) a deeper molecular response (< 0.01% IS). With a median follow-up of 14.4 months, 136 subjects (20.4%) required at least one dose reduction due to adverse events; 309 patients (46.4%) had their dose decreased in the absence of any evidence of side effects. Treatment discontinuation occurred in 144 patients (21.6%): intolerance (7.4%), primary resistance (3.5%) and acquired resistance (5.6%). Kaplan-Meier estimated TTD was 47.2 months (CI 95% 39.3 – NA) and 7.3 months (CI 95% 4.6 – 11.8) for CP and AP/BP patients, respectively. The probability of treatment discontinuation did not significantly differ for ponatinib in second, third or subsequent line of therapy (p=0.58). Summary/Conclusion: This real-life investigation shows that ponatinib dose reductions were mainly performed in the absence of reported toxicity rather than owing to the occurrence of adverse reactions.

1156-P: Ischaemic Heart Disease in Type 2 Diabetes Before and After Diagnosis: Impact on Expected Lifetime and Trends 1996–2020

Background: Complications can be present at type 2 diabetes (T2D) diagnosis or develop later. We describe trends in burden of ischaemic heart disease (IHD) in T2D. Methods: T2D cases in Denmark 1996-2020 in a national diabetes register were used. Events of IHD 1994-2020 were from the National Patient Register. Prevalence of IHD at time of T2D was described by a binomial model. New IHD and death during follow-up were analysed by rate models and used to estimate the time in the states (no IHD / IHD at T2D / IHD after T2D) . Results: 410,4 persons with T2D 1996-2020 were included; 61,378 with pre-existing IHD. Prevalence of IHD at T2D diagnosis was increasing 1.7%/year. Incidence rates of IHD after diagnosis was decreasing 5.7%/year. Mortality among T2D persons without IHD decreased 5.7%/year; for those with IHD it decreased 3.5%/year. During the first years, expected lifetime was 8.1 and 8.8 years for men diagnosed at age 65 in 1998 and 2018, respectively. Time without IHD was 6.2 and 6.9 years, with new IHD 0.9 and 0.5 years and with preexisting IHD 1.0 and 1.5 years in 1998 and 2018. We saw an increase in expected lifetime, partly as increase in lifetime with preexisting IHD. Similar patterns were seen for women and for persons diagnosed in other ages. Conclusions: We saw an increase in expected lifetime, as well as decreasing mortality rates regardless of IHD status. Prevalence of IHD at the time of diagnosis was increasing, possibly due to more detailed diagnoses of IHD; in our data only IHD complications after 1994 are included which may be a partial explanation of the increase in prevalent IHD at the date of T2D diagnosis. In general the IHD burden in T2D in Denmark is decreasing. Disclosure B.Carstensen: Stock/Shareholder; Novo Nordisk A/S. K.K.Clemmensen: Employee; Novo Nordisk A/S, Research Support; AstraZeneca, Novo Nordisk Foundation, Stock/Shareholder; Lundbeck, Novo Nordisk A/S. H.Amadid: Stock/Shareholder; Novo Nordisk.

Association between cardiovascular risk factors and intracranial hemorrhage in patients with acute leukemia.

Intracranial hemorrhage is seen more frequently in acute leukemia patients compared to the general population. Besides leukemia-related risk factors, also risk factors that are present in the general population might contribute to hemorrhagic complications in leukemia patients. Of those, cardiovascular risk factors leading to chronic vascular damage could modulate the occurrence of intracranial hemorrhage in these patients, as during their disease and treatment acute endothelial damage occurs due to factors like thrombocytopenia and inflammation. Our aim was to explore if cardiovascular risk factors can predict intracranial hemorrhage in acute leukemia patients. In a case-control study nested in a cohort of acute leukemia patients, including 17 cases with intracranial hemorrhage and 55matched control patients without intracranial hemorrhage, data on cardiovascular risk factors were collected for all patients. Analyses were performed via conditional logistic regression. Pre-existing hypertension and ischemic heart disease in the medical history were associated with intracranial hemorrhage, with an incidence rate ratio of 12.9 (95% confidence interval [CI] 1.5 to 109.2) and 12.1 (95% CI 1.3 to110.7), respectively. Both pre-existing hypertension and ischemic heart disease seem to be strong predictors of an increased risk for intracranial hemorrhage in leukemia patients.

New Imaging Signatures of Cardiac Alterations in Ischaemic Heart Disease and Cerebrovascular Disease Using CMR Radiomics.

Background: Ischaemic heart disease (IHD) and cerebrovascular disease are two closely inter-related clinical entities. Cardiovascular magnetic resonance (CMR) radiomics may capture subtle cardiac changes associated with these two diseases providing new insights into the brain-heart interactions.Objective: To define the CMR radiomics signatures for IHD and cerebrovascular disease and study their incremental value for disease discrimination over conventional CMR indices.Methods: We analysed CMR images of UK Biobank's subjects with pre-existing IHD, ischaemic cerebrovascular disease, myocardial infarction (MI), and ischaemic stroke (IS) (n = 779, 267, 525, and 107, respectively). Each disease group was compared with an equal number of healthy controls. We extracted 446 shape, first-order, and texture radiomics features from three regions of interest (right ventricle, left ventricle, and left ventricular myocardium) in end-diastole and end-systole defined from segmentation of short-axis cine images. Systematic feature selection combined with machine learning (ML) algorithms (support vector machine and random forest) and 10-fold cross-validation tests were used to build the radiomics signature for each condition. We compared the discriminatory power achieved by the radiomics signature with conventional indices for each disease group, using the area under the curve (AUC), receiver operating characteristic (ROC) analysis, and paired t-test for statistical significance. A third model combining both radiomics and conventional indices was also evaluated.Results: In all the study groups, radiomics signatures provided a significantly better disease discrimination than conventional indices, as suggested by AUC (IHD:0.82 vs. 0.75; cerebrovascular disease: 0.79 vs. 0.77; MI: 0.87 vs. 0.79, and IS: 0.81 vs. 0.72). Similar results were observed with the combined models. In IHD and MI, LV shape radiomics were dominant. However, in IS and cerebrovascular disease, the combination of shape and intensity-based features improved the disease discrimination. A notable overlap of the radiomics signatures of IHD and cerebrovascular disease was also found.Conclusions: This study demonstrates the potential value of CMR radiomics over conventional indices in detecting subtle cardiac changes associated with chronic ischaemic processes involving the brain and heart, even in the presence of more heterogeneous clinical pictures. Radiomics analysis might also improve our understanding of the complex mechanisms behind the brain-heart interactions during ischaemia.

Cardiac Morbidity in Adolescents and Young Adult Survivors of Hodgkin Lymphoma

Cardiac Morbidity in Adolescents and Young Adult Survivors of Hodgkin Lymphoma

Adverse effects of sympathetic activation should not be neglected during the coronavirus disease 2019 pandemic.

Adverse effects of sympathetic activation should not be neglected during the coronavirus disease 2019 pandemic.