Outcomes of Hospitalizations With Septic Shock Complicated by Types 1 and 2 Myocardial Infarction.

Septic shock is a life-threatening host response to infection and a significant contributor to cost burden in the United States. Furthermore, sepsis-related inflammation has been linked to myocardial infarction (MI). We sought to examine the association of type 1 and type 2 MI with outcomes in hospitalizations admitted with septic shock. The National Readmission Database 2018 was queried to identify hospitalizations with hospital discharge diagnoses of septic shock without MI, septic shock with type 1 MI, or septic shock with type 2 MI. Complex-sample multivariable logistic and linear regression models were used to determine the association of these conditions with clinical outcomes. Of 354,528 hospitalizations with septic shock, 11,519 had type 1 MI (3.2%) and 13,970 had type 2 MI (3.9%). Compared with septic shock without MI, type 1 MI was associated with higher mortality (adjusted odds ratio [OR] 1.67, 95% confidence interval [CI] 1.57 to 1.77), costs (adjusted parameter estimate $4,571, 95% CI 3,020 to 6,122), and discharge to facility (adjusted OR 1.09, 95% CI 1.01 to 1.17). In contrast, septic shock with type 2 MI was associated with similar mortality and discharge to nursing facility and higher costs (adjusted parameter estimate 1,798, 95% CI 549 to 3,047). Septic shock hospitalizations with type 1 MI had higher in-hospital mortality (adjusted OR 1.74, 95% CI 1.60 to 1.90, p <0.001) compared with type 2 MI. In conclusion, type 1 MI is associated with higher mortality and resource utilization among septic shock hospitalizations. Furthermore, type 2 MI was associated with higher resource utilization.

Cardiovascular magnetic resonance characterisation of anthracycline cardiotoxicity in adults with normal left ventricular ejection fraction.

BACKGROUND: Anthracycline therapy may lead to changes in cardiac structure and function not detectable by solely evaluating left ventricular ejection fraction (LVEF). OBJECTIVES: We hypothesized that cardiovascular magnetic resonance (CMR) would identify structural and functional myocardial abnormalities in anthracycline-treated cancer survivors with normal LVEF, compared to a matched control population. METHODS: Forty-five cancer survivors (56 ± 16 yrs., 60% female) with normal LVEF (59.5 ± 4.1%) were studied a median of 11 months (range 3-36) following administration of 237 ± 83 mg/m2 anthracycline, and compared with forty-five healthy control subjects of similar age and sex (53 ± 16 yrs., 60% female) with normal LVEF (60.8 ± 2.4%) using 1.5 T CMR. RESULTS: Significantly smaller indexed left ventricular mass (45.6 ± 8.7 vs 50.3 ± 10.1 g/m2, p = 0.02) and indexed myocardial cell volume (30.5 ± 5.7 vs 34.8 ± 7.2 ml/m2, p = 0.002) were evident in cancer survivors and the latter was inversely associated with cumulative anthracycline dose (r = -0.31, p = 0.02). Surrogate CMR markers of myocardial fibrosis were significantly increased in cancer survivors (native myocardial T1: 1021 ± 40 vs 996 ± 35 ms, p = 0.002; extracellular volume: 29.5 ± 4.5 vs 27.4 ± 2.3%, p = 0.006). CMR-derived feature-tracking global longitudinal strain (GLS) was significantly impaired in cancer survivors (2D GLS -18.3 ± 2.6 vs -20.0 ± 2.0%, p < 0.001; 3D GLS -14.5 ± 2.3 vs -16.4 ± 2.6%, p < 0.001). Parameters exhibited good to excellent (ICC = 0.86-0.98) inter- and intra-observer reproducibility. CONCLUSIONS: Anthracycline-treated cancer survivors with normal LVEF have significant perturbations of LV mass, myocardial cell volume, native myocardial T1, ECV, CMR-derived 2D and 3D GLS, compared to controls, with good to excellent levels of inter- and intra-observer reproducibility.

Impact of Hormonal Therapies for Treatment of Hormone-Dependent Cancers (Breast and Prostate) on the Cardiovascular System: Effects and Modifications: A Scientific Statement From the American Heart Association.

Cardiovascular disease and cancer are the leading causes of death in the United States, and hormone-dependent cancers (breast and prostate cancer) are the most common noncutaneous malignancies in women and men, respectively. The hormonal (endocrine-related) therapies that serve as a backbone for treatment of both cancers improve survival but also increase cardiovascular morbidity and mortality among survivors. This consensus statement describes the risks associated with specific hormonal therapies used to treat breast and prostate cancer and provides an evidence-based approach to prevent and detect adverse cardiovascular outcomes. Areas of uncertainty are highlighted, including the cardiovascular effects of different durations of hormonal therapy, the cardiovascular risks associated with combinations of newer generations of more intensive hormonal treatments, and the specific cardiovascular risks that affect individuals of various races/ethnicities. Finally, there is an emphasis on the use of a multidisciplinary approach to the implementation of lifestyle and pharmacological strategies for management and risk reduction both during and after active treatment.

Cardiovascular Family History Increases Risk for Late-Onset Adverse Cardiovascular Outcomes in Childhood Cancer Survivors: A St. Jude Lifetime Cohort Report.

BACKGROUND: Survivors of childhood cancer have an increased risk of therapy-related cardiovascular disease. It is not known whether family history of cardiovascular disease further increases risk of adverse cardiovascular outcomes among survivors. METHODS: Family history of cardiovascular disease was collected from 1,260 survivors [median age at diagnosis, 8 years (range, 0-23); age at last follow-up, 35 years (range, 18-66)] of childhood cancer in the St. Jude Lifetime Cohort Study. Multivariable risk models evaluated associations with cardiovascular disease (Common Terminology Criteria for Adverse Events grade 2-4 events) and cardiovascular risk factors. RESULTS: Among survivors exposed to chest-directed radiation and/or anthracycline chemotherapy (n = 824), 7% reported a first-degree family history of heart failure, 19% myocardial infarction, 11% stroke, 26% atherosclerotic disease (myocardial infarction and/or stroke), 62% hypertension, and 31% diabetes mellitus. Eighteen percent of exposed survivors developed heart failure, 9% myocardial infarction, 3% stroke, 11% atherosclerotic disease, 30% hypertension, and 9% diabetes mellitus. Having a first-degree family history of atherosclerotic disease was independently associated with development of treatment-related heart failure [RR, 1.38; 95% confidence interval (CI), 1.01-1.88; P = 0.04] among exposed survivors. Risk for hypertension was increased among exposed survivors with a first-degree family history of hypertension (RR, 1.55; 95% CI, 1.26-1.92; P < 0.0001) or of any cardiovascular disease [myocardial infarction, stroke, or heart failure (RR, 1.30; 95% CI, 1.06-1.59; P = 0.01)]. CONCLUSIONS: Family history of cardiovascular disease and cardiovascular risk factors independently increased risk of heart failure and hypertension among survivors of childhood cancer exposed to cardiotoxic therapies. IMPACT: These data show the importance of cardiovascular family history as a risk factor for cardiovascular disease in survivors of childhood cancer.

Management of Patients with Acute Coronary Syndrome and Cancer.

Cancer patients with acute coronary syndrome (ACS) have significantly greater mortality compared with non-cancer patients. This risk is partly directly attributable to the malignancy; however these patients are frequently undertreated with respect to guideline recommended treatments for ACS due to higher bleeding risks from anemia and thrombocytopenia. Due to exclusion from large clinical trials, there is a paucity of data regarding how to best treat these complex and high-risk patients. PURPOSE OF REVIEW: To review the literature and identify risk factors among cancer patients associated with poor outcomes, pathophysiology of chemotherapy and radiation therapy contributing to accelerated coronary artery disease and ACS, and data regarding outcomes with medical therapy and invasive management. RECENT FINDINGS: Despite an elevated bleeding risk, many cancer patients may benefit from ACC/AHA guideline-directed management for ACS including aspirin, P2Y12 inhibitor, statin, and beta-blocker therapies. Cancer patients with ACS are a uniquely vulnerable population who are often undertreated, and with improved cancer treatments, this population is expected to increase. These patients should be included in future randomized trials to better understand how to balance the complexities of increased bleeding and thrombosis risks during ACS.

Magnetic Resonance Imaging to Detect Cardiovascular Effects of Cancer Therapy: JACC CardioOncology State-of-the-Art Review.

This paper aims to empower and inform cardio-oncologists by providing a practical guide to the clinical application of cardiac magnetic resonance (CMR) in the rapidly evolving field of cardio-oncology. Specifically, we describe how CMR can be used to assess the cardiovascular effects of cancer therapy. The CMR literature, relevant societal guidelines, indication-specific imaging protocols, and methods to overcome some of the challenges encountered in performing and accessing CMR are reviewed.

Changes in Citric Acid Cycle and Nucleoside Metabolism Are Associated with Anthracycline Cardiotoxicity in Patients with Breast Cancer.

Anthracyclines and HER2-targeted antibodies are very effective for the treatment of breast cancer, but their use is limited by cardiotoxicity. In this nested case-control study, we assessed the role of intermediary metabolism in 38 women with breast cancer treated with anthracyclines and trastuzumab. Using targeted mass spectrometry to measure 71 metabolites in the plasma, we identified changes in citric acid and aconitic acid that differentiated patients who developed cardiotoxicity from those who did not. In patients with cardiotoxicity, the magnitude of change in citric acid at three months correlated with the change in left ventricular ejection fraction (LVEF) and absolute LVEF at nine months. Patients with cardiotoxicity also demonstrated more pronounced changes in purine and pyrimidine metabolism. Early metabolic changes may therefore provide insight into the mechanisms associated with the development of chemotherapy-associated cardiotoxicity.

Long term cardiovascular magnetic resonance phenotyping of anthracycline cardiomyopathy.

BACKGROUND: Anthracycline cardiomyopathy contributes to the morbidity and mortality of cancer survivors but long-term data are lacking. This study sought to describe the phenotype of long-term anthracycline cardiomyopathy, the prevalence of myocardial fibrosis and its association with cardiac remodeling, systolic function and clinical outcomes. METHODS AND RESULTS: We undertook contrast-enhanced CMR in 81 cancer survivors at median 5 years after anthracycline (mean dose 279 SD 89 mg/m2). Participants were aged 55 SD 14 years; 68% were female. Mean LVEF was impaired (49 SD 12%), driven by a pathological increase in iLVESV (47 SD 23 ml/m2). 19% of participants exhibited LGE, which was associated with significant adverse left ventricular remodeling and reduced systolic function (iLVEDV: 102 SD 34 vs 83 SD 21 ml/m2, p = 0.03; iLVESV 61 SD 32 vs 43 SD 20 ml/m2, p = 0.03; LVEF: 43 SD 11 vs 50 SD 12%, p = 0.03). In subgroup analysis of 36 patients, 36% had elevated native T1 measurements, which was associated with significant adverse left ventricular remodeling (iLVEDV: 97 SD 22 vs 74 SD 19 ml/m2, p = 0.002; iLVESV: 56 SD 22 vs 35 SD 15 ml/m2, p = 0.005), reduced systolic function (LVEF 44 SD 13 vs 55 SD 9%, p = 0.01), and hospitalizations for heart failure (38% vs 9%, p = 0.03). Absolute native T1 measurements correlated significantly with iLVEDV (p ≤ 0.001, R2 0.33), iLVESV (p < 0.001, R2 0.36), LVEF (p < 0.001, R2 0.35), LAVi (p = 0.04, R2 0.12) and MAPSE (p = 0.02, R2 0.14). CONCLUSIONS: Long-term anthracycline cardiomyopathy is characterized by pathologically increased iLVESV. Both LGE and elevated native T1 measurements were associated with significant adverse cardiac remodeling and reduced systolic function, and the latter with heart failure hospitalizations.

Contemporary Role of Echocardiography for Clinical Decision Making in Patients During and After Cancer Therapy.

Early recognition of cancer therapy-related cardiac dysfunction (CTRCD) provides an opportunity to mitigate cardiac injury and risk of developing late cardiac events. Echocardiography serves as the cornerstone in the detection and surveillance of CTRCD in patients during and after cancer therapy. Guidelines from professional societies and regulatory agencies have been published on approaches to surveillance, diagnosis, and treatment of CTRCD, although adoption as standard of care remains limited given the lack of evidence on the prognostic value of asymptomatic left ventricular (LV) dysfunction in the oncology population. The frequency of cardiac monitoring and the appropriateness of the Food and Drug Administration (FDA)-recommended cardiac monitoring schedule in all patients receiving trastuzumab for breast cancer has been challenged. Interruption versus continuation of oncological therapy in the setting of asymptomatic LV dysfunction remains a clinical conundrum given the uncertain balance of the risk of cardiac dysfunction and benefit of oncology efficacy. Despite their limitations, echocardiographic measures of LV function continue to play a pivotal role in clinical decision making, with global longitudinal strain emerging as a promising tool in informing and facilitating the selection of cancer treatment and optimizing cardiovascular outcomes. This review highlights the key recommendations of the existing guidelines and discusses recent developments in cardio-oncology imaging practices with the aim of providing practical guidance on the role and use of echocardiography in challenging clinical cases in cardio-oncology.

Multi-Modality Imaging in the Assessment of Cardiovascular Toxicity in the Cancer Patient.

Cancer therapy can be associated with both cardiac and vascular toxicity. Advanced multi-modality imaging can be used to stratify patient risk, identify cardiovascular injury during and after therapy, and forecast recovery. Echocardiography continues to be the mainstay in the evaluation of cardiac toxicity. Particularly, echocardiography-based strain imaging is useful for risk stratification of patients at baseline, and detection of subclinical left ventricle (LV) dysfunction during therapy. Cardiac magnetic resonance (CMR) serves a complementary role in the patient with poor echocardiographic or equilibrium radionuclide angiographic image quality or in situations where a more accurate and precise LV ejection fraction measurement is needed to inform decisions regarding discontinuation of chemotherapy. New CMR techniques like T1 and T2 mapping and positron emission tomography (PET) imaging will help us better understand the structural, pathological, and metabolic myocardial changes associated with ventricular dysfunction or release of serum biomarkers. CMR may also be helpful in the evaluation of vascular complications of cancer therapy. Stress echocardiography, stress CMR, computed tomography, and PET are excellent imaging options in the evaluation of ischemia in patients receiving therapies that could potentially cause vasospasm or accelerated atherosclerosis.

Diagnostic Strategies for Early Recognition of Cancer Therapeutics-Related Cardiac Dysfunction.

Cardiovascular toxicity in the form of cardiac dysfunction continues to be an obstacle for patients with cancer. Survival and quality of life of cancer survivors are frequently affected by increased incidence of cardiovascular disease. The involvement of the cardiovascular system by primary or secondary malignancies, as well as its dysfunction secondary to the administration of antineoplastics, has led to the development of a new discipline called Cardio-Oncology, an exciting cardiology subspecialty with more questions than answers and as a result an enormous opportunity for research in the field. Multidisciplinary efforts have been focused on the prevention, diagnosis, and treatment of cancer therapeutics-related cardiovascular dysfunction (CTRCD). This review article will focus on the early diagnosis of left ventricular dysfunction associated with chemotherapy. Currently, the identification of cardiac toxicity associated with cancer treatment is the cornerstone for critical decisions regarding anticancer therapy and cardioprotective strategies. Its early detection, especially in subclinical phases, allows immediate intervention to prevent further impairment of the myocardium and other cardiovascular structures. The most significant published studies were selected for this revision, providing an updated document for the health professionals involved in the care of patients with cancer. We examined the current evidence and recommendations for biochemical and noninvasive diagnostic techniques, including their specific role for identification of CTRCD. Traditional and advanced imaging modalities, used alone or in combination with cardiovascular biomarkers, are essential for the recognition of cardiotoxicity during cancer therapy. Evolving basic and clinical research are focused on the development of more sensitive and specific diagnostic tools and for the recognition of cardiac toxicity.

Cost-effectiveness of strain-targeted cardioprotection for prevention of chemotherapy-induced cardiotoxicity.

BACKGROUND: Cancer chemotherapy increases the risk of heart failure. This cost-effectiveness model compared strain-guided cardioprotection with other protective strategies using a health care payer perspective and five-year time horizon. METHODS: Three cardioprotection strategies were assessed: 1) usual care (EF-guided cardioprotection, EFGCP) with cardioprotection initiated on diagnosis of LVEF-defined cardiotoxicity (EF-CTX), 2) universal cardioprotection (UCP) for all such patients, and 3) strain-guided cardioprotection (SGCP - treatment of patients with subclinical cardiotoxicity [S-CTX]). A Markov model, informed by the published literature on transitional probabilities, costs and quality-adjusted life years (QALYs) was developed to assess the incremental cost-effectiveness ratio (ICER). Costs, effects and ICER of each specified cardioprotective strategy were assessed over a 5-year range, with sensitivity analyses for significant variables. RESULTS: In the reference case of a 49year old woman with stage IIb breast cancer treated with sequential anthracyclines and trastuzumab, strain-guided cardioprotection (3.79 QALYS and $4159 cost over 5years) dominated both UCP (3.64 QALYs and $5967 cost over 5years) and EFGCP (3.53 QALYs and $7033 cost over five years). Model results were dependent on the probabilities of patients developing subclinical LV dysfunction, with UCP dominating alternative strategies at probabilities ≥51%. Variations in the cost of cardioprotective medications and probabilities of cardioprotection side-effects had no effect on model conclusions. CONCLUSIONS: In patients at risk of chemotherapy-related cardiotoxicity, strain-guided cardioprotection provides more QALYs at lower cost than standard care or uniform cardioprotection.

The Utility of Point-of-Care Biomarkers to Detect Cardiotoxicity During Anthracycline Chemotherapy: A Feasibility Study.

BACKGROUND: Anthracycline chemotherapy is associated with an increased risk of developing heart failure (HF). The current standard for detecting HF or cardiotoxicity during chemotherapy involves episodic cardiac imaging typically at prescribed intervals and there are limited studies examining techniques beyond measuring left ventricular (LV) function. This study explores whether cardiac biomarkers troponin I (TnI) and B-type natriuretic peptide (BNP) could be part of a screening strategy for early detection of the development of cardiotoxicity in patients undergoing anthracycline chemotherapy. METHODS AND RESULTS: Patients were enrolled from a single medical center. Cardiac biomarkers (TnI, BNP) were measured before and within 24 hours after completion of anthracycline administration for each cycle of therapy. Cardiac imaging was obtained at baseline and at completion of chemotherapy (commonly at 6 or 12 months) or based on clinical suspicion of a cardiac event. Of the enrolled 109 patients, 11 (10.1%) experienced cardiac events; all of these patients had at least 1 BNP value >100 pg/mL before the cardiac event. Significant reduction in LV ejection fraction as defined for cardiotoxicity occurred in only 3 of 10 patients (30%) with a cardiac event. CONCLUSIONS: The use of cardiac biomarkers, particularly BNP, may allow early detection of cardiotoxicity related to anthracycline chemotherapy.

Cardiac Outcomes in Adult Survivors of Childhood Cancer Exposed to Cardiotoxic Therapy: A Cross-sectional Study.

BACKGROUND: Studies of cardiac disease among adult survivors of childhood cancer have generally relied on self-reported or registry-based data. OBJECTIVE: To systematically assess cardiac outcomes among survivors of childhood cancer. DESIGN: Cross-sectional study. SETTING: St. Jude Children's Research Hospital. PATIENTS: 1853 adult survivors of childhood cancer, aged 18 years or older, who received cancer-related cardiotoxic therapy at least 10 years earlier. MEASUREMENTS: Baseline history and physical examination, fasting metabolic and lipid panels, echocardiography, electrocardiography, and 6-minute walk test. RESULTS: One half of the survivors (52.3%) were men with a median age of 8 years (range, 0 to 24 years) at cancer diagnosis and 31 years (range, 18 to 60 years) at evaluation. Cardiomyopathy was present in 7.4% survivors (newly identified at the time of evaluation in 4.7%), coronary artery disease in 3.8% (newly identified in 2.2%), valvular regurgitation or stenosis in 28.0% (newly identified in 24.8%), and conduction or rhythm abnormalities in 4.4% (newly identified in 1.4%). Nearly all survivors were asymptomatic. The prevalence of cardiac conditions increased with age at evaluation, ranging from 3% to 24% among survivors aged 30 to 39 years to 10% to 37% among those aged 40 years or older. In multivariable analysis, survivors exposed to anthracycline doses of 250 mg/m2 or more had greater odds of cardiomyopathy (odds ratio, 2.7 [95% CI, 1.1 to 6.9]) than those who were not exposed. Survivors exposed to heart radiation also had increased odds of cardiomyopathy (odds ratio, 1.9 [CI, 1.1 to 3.7]) compared with those who were not exposed. Radiation exposure greater than 1500 cGy with any anthracycline exposure conferred the greatest odds for valve findings. LIMITATIONS: Sixty-one percent of survivors exposed to anthracycline chemotherapy or cardiac-directed radiation participated. A comparison group and longitudinal assessments were not available. CONCLUSION: Cardiovascular screening identified considerable subclinical disease among adult survivors of childhood cancer. PRIMARY FUNDING SOURCE: National Cancer Institute, American Lebanese Syrian Associated Charities.

Anthracycline-Induced Cardiomyopathy in Adults.

Anthracyclines are one of the most commonly used antineoplastic agent classes, and a core part of the treatment in breast cancers, hematological malignancies, and sarcomas. Their benefit is decreased by their well-recognized cardiotoxicity. The purpose of this review is to outline the presentation, mechanisms, diagnosis, and treatment of anthracyclines-induced cardiotoxicity. Symptomatic heart failure occurs in 2% to 5% of patients treated with anthrayclines and may be higher in older patients or patients with cardiovascular risk factors. The mechanisms involved in anthracycline-induced cardiotoxicity involve myocyte loss by apoptosis in the presence of a limited regenerative capacity. Once symptomatic, anthracycline-induced cardiotoxicity is associated with markedly decreased survival. Left ventricular ejection fraction (LVEF), mostly determined using echocardiography, is used to monitor patients treated with anthracyclines. As more than 1/3 of patients treated with anthracyclines do not recover their baseline LVEF once it is decreased, more sensitive echocardiographic indices of LV function such as myocardial deformation or biomarkers have been studied in patients monitoring. Cardioprotective treatments such as angiotensin-converting enzyme inhibitors, beta-blockers, iron chelators, statins, and metformin are also the topic of research efforts.