Ischaemic heart disease is a leading cause of morbidity and mortality in both women and men. Compared with men, symptomatic women who are suspected of having myocardial ischaemia are more likely to have no obstructive coronary artery disease (CAD) on coronary angiography. Coronary vasomotor disorders and coronary microvascular dysfunction (CMD) have been increasingly recognized as important contributors to angina and adverse outcomes in patients with no obstructive CAD. CMD from functional and structural abnormalities in the microvasculature is associated with adverse cardiac events and mortality in both sexes. Women may be particularly susceptible to vasomotor disorders and CMD due to unique factors such as inflammation, mental stress, autonomic, and neuroendocrine dysfunction, which predispose to endothelial dysfunction and CMD. CMD can be detected with coronary reactivity testing and non-invasive imaging modalities; however, it remains underdiagnosed. This review focuses on sex differences in presentation, pathophysiologic risk factors, diagnostic testing, and prognosis of CMD.

Background Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of newly diagnosed cardiovascular disease in patients treated with ICIs at a large, tertiary care center. Methods All patients with a cancer diagnosis who received any ICI treatment in the University of Florida’s Integrated Data Repository from 2011 to 2017 were included. Cardiovascular disease was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment. Results Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one new cardiovascular disease after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Incident cardiovascular disease was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in ICI treated patients with a concomitant diagnosis of incident cardiovascular disease was higher compared to those who did not (66.1% vs. 41.4%, odds ratio = 2.77, 1.55–4.95, p = 0.0006). Conclusions This study suggests a high incidence of newly diagnosed cardiovascular disease after the initiation of ICI therapy in a real-world clinical setting.

Background Cardiometabolic abnormalities are a leading cause of death among women, including women with cancer. Methods This study examined the association between prediagnosis cardiovascular health and total and cause‐specific mortality among 12,076 postmenopausal women who developed local‐ or regional‐stage invasive cancer in the Women's Health Initiative (WHI). Cardiovascular risk factors included waist circumference, hypertension, high cholesterol, and type 2 diabetes. Obesity‐related cancers included breast cancer, colorectal cancer, endometrial cancer, kidney cancer, pancreatic cancer, ovarian cancer, stomach cancer, liver cancer, and non‐Hodgkin lymphoma. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for important predictors of survival. Results After a median follow‐up of 10.0 years from the date of the cancer diagnosis, there were 3607 total deaths, with 1546 (43%) due to cancer. Most participants (62.9%) had 1 or 2 cardiometabolic risk factors, and 8.1% had 3 or 4. In adjusted models, women with 3 to 4 risk factors (vs none) had a higher risk of all‐cause mortality (HR, 1.99; 95% CI, 1.73‐2.30), death due to cardiovascular disease (CVD) (HR, 4.01; 95% CI, 2.88‐5.57), cancer‐specific mortality (HR, 1.37; 95% CI, 1.1‐1.72), and other‐cause mortality (HR, 2.14; 95% CI, 1.70‐2.69). A higher waist circumference was associated with greater all‐cause mortality (HR, 1.17; 95% CI, 1.06‐1.30) and cancer‐specific mortality (HR, 1.22; 95% CI, 1.04‐1.42). Conclusions Among postmenopausal women diagnosed with cancer in the WHI, cardiometabolic risk factors before the cancer diagnosis were associated with greater all‐cause, CVD, cancer‐specific, and other‐cause mortality. These results raise hypotheses regarding potential clinical intervention strategies targeting cardiometabolic abnormalities that require future prospective studies for confirmation. Lay Summary This study uses information from the Women's Health Initiative (WHI) to find out whether cardiac risk factors are related to a greater risk of dying among older women with cancer. The WHI is the largest study of medical problems faced by older women in this country. The results show that women who have 3 or 4 risk factors are more likely to die of any cause, heart disease, or cancer in comparison with women with no risk factors. It is concluded that interventions to help to lower the burden of cardiac risk factors can have an important impact on survivorship among women with cancer.

Aims The American College of Cardiology appropriate use criteria (AUC) provide clinicians with evidence-informed recommendations for cardiac care. Adopting AUC into clinical workflows may present challenges, and there may be specific implementation strategies that are effective in promoting effective use of AUC. We sought to assess the effect of implementing AUC in clinical practice. Methods and results We conducted a meta-analysis of studies found through a systematic search of the MEDLINE, Web of Science, Cochrane, or CINAHL databases. Peer-reviewed manuscripts published after 2005 that reported on the implementation of AUC for a cardiovascular test or procedure were included. The main outcome was to determine if AUC implementation was associated with a reduction in inappropriate/rarely appropriate care. Of the 18 included studies, the majority used pre/post-cohort designs; few (n = 3) were randomized trials. Most studies used multiple strategies (n = 12, 66.7%). Education was the most common individual intervention strategy (n = 13, 72.2%), followed by audit and feedback (n = 8, 44.4%) and computerized physician order entry (n = 6, 33.3%). No studies reported on formal use of stakeholder engagement or ‘nudges’. In meta-analysis, AUC implementation was associated with a reduction in inappropriate/rarely appropriate care (odds ratio 0.62, 95% confidence interval 0.49–0.78). Funnel plot suggests the possibility of publication bias. Conclusion We found most published efforts to implement AUC observed reductions in inappropriate/rarely appropriate care. Studies rarely explored how or why the implementation strategy was effective. Because interventions were infrequently tested in isolation, it is difficult to make observations about their effectiveness as stand-alone strategies. Study registration PROSPERO 2018 CRD42018091602. Available from https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018091602.

Multiple myeloma (MM) is the second most frequent hematologic cancer in the United States. Carfilzomib (CFZ), an irreversible proteasome inhibitor being used to treat relapsed and refractory MM, has been associated with cardiotoxicity, including heart failure. We hypothesized that a multi-omics approach integrating data from different omics would provide insights into the mechanisms of CFZ-related cardiovascular adverse events (CVAEs). Plasma samples were collected from 13 MM patients treated with CFZ (including 7 with CVAEs and 6 with no CVAEs) at the University of Florida Health Cancer Center. These samples were evaluated in global metabolomic profiling, global proteomic profiling, and microRNA (miRNA) profiling. Integrative pathway analysis was performed to identify genes and pathways differentially expressed between patients with and without CVAEs. The proteomics analysis identified the up-regulation of lactate dehydrogenase B (LDHB) [fold change (FC) = 8.2, p = 0.01] in patients who experienced CVAEs. The metabolomics analysis identified lower plasma abundance of pyruvate (FC = 0.16, p = 0.0004) and higher abundance of lactate (FC = 2.4, p = 0.0001) in patients with CVAEs. Differential expression analysis of miRNAs profiling identified mir-146b to be up-regulatein (FC = 14, p = 0.046) in patients with CVAE. Pathway analysis suggested that the pyruvate fermentation to lactate pathway is associated with CFZ-CVAEs. In this pilot multi-omics integrative analysis, we observed the down-regulation of pyruvate and up-regulation of LDHB among patients who experienced CVAEs, suggesting the importance of the pyruvate oxidation pathway associated with mitochondrial dysfunction. Validation and further investigation in a larger independent cohort are warranted to better understand the mechanisms of CFZ-CVAEs.

Objective Limited data is available about the effect of implanted valve size on prosthesis–patient mismatch (PPM) incidence and aortic gradient (AG) after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). We compared PPM incidence and postprocedural AG between TAVR and SAVR patients considering the impact of implanted valve size. Methods From March 20, 2012, to September 30, 2015, 563 consecutive patients underwent TAVR ( n = 419) or isolated SAVR ( n = 144). Postprocedural transthoracic echocardiography was obtained within 30 days; AG, effective orifice area (EOA), and EOA index were calculated. Results A total of 381 patients in TAVR group and 82 patients in SAVR group were included. Mean preoperative AG and mean aortic valve area were not significantly different between the 2 groups. Postprocedural AG was significantly lower in TAVR than SAVR group, 7.74 ± 5.39 versus 14.27 ± 8.16 ( P < 0.001). Between patients who had TAVR and SAVR with a valve size ≤23 mm, SAVR patients were 3 times more likely to have greater than mild AG after the procedure, OR: 3.1 (95% CI, 1.1 to 8.9) ( P < 0.001). PPM incidence was significantly higher in SAVR group than TAVR group, 44 (53.7%) versus 112 (29.4%), OR = 2.8 (95% CI, 1.7 to 4.5) ( P < 0.001). The PPM incidence was also higher in SAVR group than TAVR group among those who had the procedures with a valve size ≤23 mm, 35 (64.8%) versus 56 (47.9%), OR = 2 (95% CI, 1.1 to 3.9) ( P = 0.048). Postprocedural outcomes were comparable between the 2 groups. Conclusions In comparison to SAVR, TAVR is associated with less PPM and lower AG, especially in patients receiving a valve size ≤23 mm.

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Introduction: Multiple Myeloma (MM) is the second most frequent hematologic cancer in the United States. Carfilzomib (CFZ), a proteasome inhibitor used to treat relapsed and refractory MM, has been associated with cardiotoxicity including heart failure (HF). Hypothesis: We hypothesized that a multi-omics approach integrating data from different omics will provide insights into the mechanisms of CFZ-induced HF. Methods: Plasma samples were collected from 13 MM patients treated with CFZ (including 7 with symptomatic HF and 6 with no HF) at the University of Florida Health Cancer Center. Global metabolomics profiling was performed using a LC/MS metabolomic platform. Global proteomic profiling was performed on LC/MS/MS platform with ~ 370 proteins quantified by iTRAQ analysis. TaqMan ® OpenArray ® Human MicroRNA Panel, containing 754 human microRNAs (miRNAs), was used for miRNA profiling. Pathway integrative analysis was performed to identify genes and pathways that are differentially expressed between those who developed HF versus those who did not. Features with p-value < 0.05 were considered statistically significant. Results: The cohort mean age was 61 years and 38.5% were men. Proteomics data identified up-regulation of lactate dehydrogenase B (LDHB) (fold change [FC]=8.2, p=0.01) in those who developed HF compared to those who did not. Metabolomics data identified lower plasma abundance of pyruvate (FC=0.16, p=0.0004) and higher abundance of lactate (FC=2.4, p=0.0001) in HF patients. Using miRNA target gene prediction tools, we observed that LDHB regulated by miR-139 which downregulated in HF patients (FC=0.03). Multi-omics integrative analysis suggested that the pyruvate fermentation to lactate (pyruvate oxidation) pathway is associated with CFZ-related HF. Conclusion: In this pilot multi-omics integrative analysis, we observed down-regulation of pyruvate and up-regulation of LDHB among patients with CFZ-related HF, which suggests the importance of pyruvate oxidation pathway and mitochondrial dysfunction in CFZ-related HF and that this pathway might be regulated by miR-139. Further investigation in a larger independent cohort is warranted to better understand the mechanisms of CFZ-related HF.