Atherosclerotic Cardiovascular Events in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Retrospective Cohort Study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are effective therapies for numerous cancers, but have been associated with atherosclerotic cardiovascular disease (ASCVD). This study aimed to identify predictors for ASCVD events among cancer patients treated with ICIs and the cardiovascular risk factor (CVRF) control of those who developed ASCVD. METHOD: A single-centre retrospective study of 366 cancer patients who received ICIs from 2018 to 2020 was performed. Demographic, baseline CVRF, cancer history, and ICI regimen data were obtained from medical records. The primary end point of ASCVD events was defined as myocardial infarction, coronary revascularisation, ischaemic stroke, or acute limb ischaemia. Cox proportional multivariable modelling and competing risks analysis were performed to assess ASCVD predictors. Descriptive analysis was performed to describe CVRF management among those who developed ASCVD events. RESULTS: Over a median follow-up of 3.4 years (2.8-4.3), 26 patients (7.1%) experienced 27 ASCVD events (seven myocardial infarction, one coronary revascularisation, 13 ischaemic stroke, and six acute limb ischaemia events). There were 226 (61.8%) cancer-related deaths and no cardiac deaths. History of ASCVD before ICI initiation was independently associated with ASCVD events on traditional Cox modelling (hazard ratio [HR] 4.00; 95% confidence interval [CI] 1.79-8.91; p<0.01) and competing risks analysis (HR 4.23; 95% CI 1.87-9.60; p<0.01). A total of 17 patients developed ASCVD events after ICI cessation (median 1.4 years). Among those with ASCVD events, 12 had prior ASCVD, 16 had hypertension, nine had hypercholesterolaemia, and four had diabetes, and nine were actively smoking. Variable prescription of cardiovascular preventative therapies was noted. CONCLUSIONS: History of ASCVD was associated with subsequent ASCVD events among patients treated with ICIs, which could occur even after active treatment was stopped. Identification and aggressive management of modifiable CVRFs should be considered throughout cancer survivorship in patients who received ICI treatment.

Cardiologists' knowledge and perceptions of the seasonal influenza immunisation.

BACKGROUND: Seasonal influenza immunisation reduces cardiovascular events in high-risk patients, but 50% do not receive routine immunisation. The perceptions and current role of cardiologists in recommending and prescribing influenza immunisation has not been well described. METHODS: We used an exploratory sequential mixed methods design. Semi-structured interviews of 10 cardiologists were performed to identify themes for quantitative evaluation. 63 cardiologists undertook quantitative evaluation in an online survey. The interviews and surveys addressed (a) attitudes and behaviours regarding influenza immunisation and (b) preventative care in cardiology. RESULTS: One quarter (25.4%, n = 16) of cardiologists recommended influenza immunisation to all patients. Less than half (49.2%, n = 31) recommended influenza immunisation to secondary prevention patients. Almost 1/3 of respondents (31.7%, n = 20) were uncertain or unaware of the guidelines regarding influenza immunisation and patients with cardiac disease. Most cardiologists believed that general practitioners were responsible for ensuring patients received influenza immunisation (76.2%, n = 48). CONCLUSIONS: Despite reducing cardiovascular events in high-risk patients, influenza immunisation is not widely recommended by cardiologists. Further clinician education is needed to address the knowledge gaps which prevent recommendation and uptake of this guideline directed treatment.

Blood pressure surveillance in cancer patients treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICI) are cancer therapies that have been associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). Blood pressure (BP) measurements are routinely performed during day oncology center visits for administration of ICI therapy but are often not assessed temporally to screen and monitor hypertension, which could independently increase the risk of ASCVD in cancer survivorship. This study reports the feasibility of using serial BP measurements from routine visits to day oncology center to diagnose and monitor hypertension control in cancer patients receiving ICIs.

Identifying Patients at High Risk of Left Atrial Appendage Thrombus Before Cardioversion: The CLOTS-AF Score.

Background Transesophageal echocardiography-guided direct cardioversion is recommended in patients who are inadequately anticoagulated due to perceived risk of left atrial appendage thrombus (LAAT); however, LAAT risk factors remain poorly defined. Methods and Results We evaluated clinical and transthoracic echocardiographic parameters to predict LAAT risk in consecutive patients with atrial fibrillation (AF)/atrial flutter undergoing transesophageal echocardiography before cardioversion between 2002 and 2022. Regression analysis identified predictors of LAAT, combined to create the novel CLOTS-AF risk score (comprising clinical and echocardiographic LAAT predictors), which was developed in the derivation cohort (70%) and validated in the remaining 30%. A total of 1001 patients (mean age, 62±13 years; 25% women; left ventricular ejection fraction, 49.8±14%) underwent transesophageal echocardiography, with LAAT identified in 140 of 1001 patients (14%) and dense spontaneous echo contrast precluding cardioversion in a further 75 patients (7.5%). AF duration, AF rhythm, creatinine, stroke, diabetes, and echocardiographic parameters were univariate LAAT predictors; age, female sex, body mass index, anticoagulant type, and duration were not (all P>0.05). CHADS2VASc, though significant on univariate analysis (P<0.001), was not significant after adjustment (P=0.12). The novel CLOTS-AF risk model comprised significant multivariable predictors categorized and weighted according to clinically relevant thresholds (Creatinine >1.5 mg/dL, Left ventricular ejection fraction <50%, Overload (left atrial volume index >34 mL/m2), Tricuspid Annular Plane Systolic Excursion (TAPSE) <17 mm, Stroke, and AF rhythm). The unweighted risk model had excellent predictive performance with an area under the curve of 0.820 (95% CI, 0.752-0.887). The weighted CLOTS-AF risk score maintained good predictive performance (AUC, 0.780) with an accuracy of 72%. Conclusions The incidence of LAAT or dense spontaneous echo contrast precluding cardioversion in patients with AF who are inadequately anticoagulated is 21%. Clinical and noninvasive echocardiographic parameters may identify patients at increased risk of LAAT better managed with a suitable period of anticoagulation before undertaking cardioversion.

Breast arterial calcification and epicardial adipose tissue volume, but not density are independently associated with cardiovascular risk.

BACKGROUND: Mammographically detected breast arterial calcification (BAC) has been proposed as surrogate marker for coronary artery disease (CAD) in women. Epicardial adipose tissue (EAT) and peri-coronary adipose tissue (PCAT) are inflammatory fat depots linked to atherogenesis. BAC has demonstrated association with inflammation, therefore we aimed to determine the association between BAC, EAT and PCAT. METHODS: Single-centre, retrospective, cross-sectional study of women with digital mammography and coronary computed tomography angiography (CCTA). EAT and PCAT were quantitively assessed using semi-automated software. Patient demographics and cardiovascular risk factors were obtained from medical records and mammograms reviewed for BAC. Pre-test cardiovascular risk was determined with CAD Consortium Score. Chi-square, t-test and Mann-Whitney U tests were used to assess between group differences. Multivariable linear and logistic regression modelling was conducted to adjust for confounders. RESULTS: Among 153 patients (age 61, SD 11) included in this study, BAC was present in 37 (24%) patients. BAC-positive patients had higher EAT volume (EATv) (110.2 mL, SD 41 mL vs 94.4 mL, SD 41 mL, p = 0.02) but this association was not significant after adjusting for cardiovascular risk factors (p = 0.26). BAC did not associate with EAT density or PCAT. BAC and EATv were strongly associated with cardiovascular risk and CAD independent of each other: CV risk (BAC OR 7.55 (3.26-18.49), p < 0.001, EATv OR 1.02 (1.01-1.03), p < 0.001), CAD presence (BAC OR 4.26 (1.39-13), p = 0.01; EATv OR 1.01 (1.0-1.03), p = 0.04). CONCLUSION: BAC and EATv are independent predictors of CV risk and CAD, but don't independently associate with each other, the relationship confounded by shared cardiovascular risk factors. BAC doesn't appear to associate with adipose tissue density and its presence may be cumulative result of long-term exposure to CV risk factors.