Endobronchial ultrasound: A novel screening test for pulmonary hypertension prior to major pulmonary surgery.

Objectives: Pulmonary hypertension (PH) is an important physiologic variable in the assessment of patients undergoing major thoracic operations but all too often neglected because of the need for right heart catheterization (RHC) due to the inaccuracy of transthoracic echocardiography. Patients with lung cancer often require endobronchial ultrasound (EBUS) as part of the staging of the cancer. We sought to investigate whether EBUS can be used to screen these patients for PH. Methods: Patients undergoing a major thoracic operation requiring EBUS for staging were included prospectively in the study. All patients had also a RHC (gold standard). We aimed to compare the pulmonary artery pressure measurements by EBUS with the RHC values. Results: A total of 20 patients were enrolled in the study. The prevalence of abnormal pulmonary artery pressure was 65% based on RHC. All patients underwent measurement of the pulmonary vascular acceleration time (PVAT) by EBUS with no adverse events. Linear regression analysis comparing PVAT and RHC showed a correlation (r = -0.059, -0.010 to -0.018, P = .007). A receiver operator characteristic curve (area under the curve = 0.736) was used to find the optimal PVAT threshold (140 milliseconds) to predict PH; this was used to calculate a positive and negative likelihood ratio following a positive diagnosis of 2.154 and 0.538, respectively. Conclusions: EBUS interrogation of pulmonary artery hemodynamic is safe and feasible. EBUS may be used as a screening test for PH in high-risk individuals.

COVID-19 severity and cardiovascular outcomes in SARS-CoV-2-infected patients with cancer and cardiovascular disease.

Background: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. Objectives: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. Methods: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated. Results: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p<0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31-1.74] vs. OR 1.04 [95% CI 0.90-1.20], pinteraction <0.001). Conclusions: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701).

Long-term outcomes in patients with chronic lymphocytic leukemia treated with ibrutinib: Focus on hypertension and cardiovascular toxicity.

BACKGROUND: Continuous ibrutinib administration is needed to maintain efficacy in patients with chronic lymphocytic leukemia (CLL) and, as such, long-term toxicity is a concern. The authors report the 5-year follow-up of patients with CLL who received treatment with ibrutinib with a focus on hypertension and cardiovascular toxicities. METHODS: Patient characteristics were assessed, including blood pressure, cardiovascular disease, disease progression, and death. Univariate logistic regression analysis assessed the relation of patient characteristics and the development of new or worsened hypertension. The incidence of hypertensive outcomes was evaluated using competing risk. Survival was estimated using the Kaplan-Meier method. RESULTS: Three hundred patients with CLL who were treated with ibrutinib on clinical trials were included. The median patient age at study enrollment was 65 years (range, 29-83 years). Seventy percent of patients were men, and 88% were Caucasian. Sixty-nine percent of patients had hypertension at baseline, and 47% were on antihypertensive medication. Eighty-eight percent had relapsed or refractory CLL. New-onset and worsening hypertension were common, occurring in 68.5% and 38% of patients, respectively. Systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg was observed in 16.9% of patients. Hypertension was reversible after ibrutinib discontinuation. Older age, male sex, tobacco use, and chronic kidney disease were associated with ibrutinib-related hypertension. Baseline hypertension was not associated with major adverse cardiovascular events in ibrutinib-treated patients nor with event-free or overall survival. CONCLUSIONS: Hypertension is a common toxicity in patients with CLL who receive ibrutinib but is manageable in most patients. Other than chronic kidney disease, baseline cardiovascular disease did not affect ibrutinib-related hypertension nor was hypertension associated with major adverse cardiovascular events or survival. PLAIN LANGUAGE SUMMARY: Ibrutinib is an effective treatment for patients with chronic lymphocytic leukemia. Ibrutinib is a well tolerated therapy, however hypertension can develop or worsen in patients receiving ibrutinib and other cardiovascular events are significant challenges to the use of this drug. This may be particularly true in patients with heart disease. Short-term side effects may worsen heart disease, but the long-term impact is unknown. The long-term results of ibrutinib on heart disease and hypertension are described.

Reclassification of Treatment Strategy with Fractional Flow Reserve in Cancer Patients with Coronary Artery Disease.

Background and Objectives: Cancer and coronary artery disease (CAD) often coexist. Compared to quantitative coronary angiography (QCA), fractional flow reserve (FFR) has emerged as a more reliable method of identifying significant coronary stenoses. We aimed to assess the specific management, safety and outcomes of FFR-guided percutaneous coronary intervention (PCI) in cancer patients with stable CAD. Materials and Methods: FFR was used to assess cancer patients that underwent coronary angiography for stable CAD between September 2008 and May 2016, and were found to have ≥50% stenosis by QCA. Patients with lesions with an FFR > 0.75 received medical therapy alone, while those with FFR ≤ 0.75 were revascularized. Procedure-related complications, all-cause mortality, nonfatal myocardial infarction, or urgent revascularizations were analyzed. Results: Fifty-seven patients with stable CAD underwent FFR on 57 lesions. Out of 31 patients with ≥70% stenosis as measured by QCA, 14 (45.1%) had an FFR ≥ 0.75 and lesions were reclassified as moderate and did not receive PCI nor DAPT. Out of 26 patients with <70% stenosis as measured by QCA, 6 (23%) had an FFR < 0.75 and were reclassified as severe and were treated with PCI and associated DAPT. No periprocedural complications, urgent revascularization, acute coronary syndromes, or cardiovascular deaths were noted. There was a 22.8% mortality at 1 year, all cancer related. Patients who received a stent by FFR assessment showed a significant association with decreased risk of all-cause death (HR: 0.37, 95% CI 0.15−0.90, p = 0.03). Conclusions: Further studies are needed to define the optimal therapeutic approach for cancer patients with CAD. Using an FFR cut-off point of 0.75 to guide PCI translates into fewer interventions and can facilitate cancer care. There was an overall reduction in mortality in patients that received a stent, suggesting increased resilience to cancer therapy and progression.

Evaluation of contemporary echocardiographic and histomorphology parameters in predicting mortality in patients with endomyocardial biopsy-proven cardiac AL amyloidosis.

Introduction: This study examined the role of echocardiographic and cardiac histomorphology parameters in predicting mortality in patients with cardiac AL amyloidosis. Methods: Patients with endomyocardial biopsy-proven cardiac AL amyloidosis treated at MD Anderson Cancer Center between 6/2011 and 6/2020 were identified. Stored echocardiographic images and endomyocardial biopsy samples were processed for myocardial strain analysis and a detailed histomorphology characterization. Results: Of 43 patients; 44% were women and 63% white. Median age was 65 years; 51% underwent stem cell transplantation (SCT). Thirty patients (70%) died during follow up (median follow up: 4.1 years). Lower LA strain (<13.5%) and absence of SCT as a time-varying covariate were significantly associated with increased risk of death in the multivariate cox regression analysis. Higher LV mass and lower RV tricuspid annular plane systolic excursion were associated with increased odds of having ≥5% interstitial amyloid deposition on biopsy in the multivariate logistic regression analysis. Conclusion: Lower LA strain independently predicted mortality in our cohort, and its performance in the routine assessment of AL amyloidosis may be beneficial. Furthermore, SCT for cardiac AL amyloidosis was associated with improved OS. These findings need to be confirmed by larger studies in the era of contemporary systemic therapies.

Clinical Impact of Cardiovascular Magnetic Resonance in Cancer Patients With Suspected Cardiomyopathy.

Objectives: To assess the clinical impact of Cardiovascular Magnetic Resonance (CMR) in clinical decision making of cancer patients with a suspected cardiomyopathy in a tertiary cancer center. Background: Cardiomyopathies of diverse etiologies are frequently encountered in a Cardio-Oncology practice. The clinical impact of CMR after a presumptive diagnosis of cardiomyopathy has not been studied in cancer patients. Methods: We reviewed data on cancer patients with presumptive diagnosis of cardiomyopathy who underwent CMR in a tertiary cancer center. The clinical impact of CMR was defined as either change in clinical diagnosis or management post CMR results. Univariate and multivariate logistic regression models were used to assess whether any of the baseline characteristics were predictive of the clinical impact of CMR. Results: A total of 110 consecutive patients were identified. Clinical impact of CMR was seen in 68 (62%) patients. Change in the clinical diagnosis and management was seen in 56 (51%) and 41 (37%) of patients, respectively. The most common change was prevention of endomyocardial biopsy in 26 patients (24%). Overall, patients with higher left ventricular ejection fraction (LVEF) by echocardiography (echo), clinical impact was influenced more by CMR (LVEF of 37.2 ± 12.3% vs. 51.5 ± 11.6%, p < 0.001). Cancer diagnosis of multiple myeloma was associated with change in the management post CMR (adjusted OR of 25.6, 95% CI 4.0-162.4, p = 0.001). Suspicion of infiltrative cardiomyopathy was associated with a higher likelihood of change in diagnosis. Having an LVEF≥40 by echo was associated with change in diagnosis and management by CMR. Conclusions: Utilization of CMR has a significant clinical impact in cancer patients with suspected cardiomyopathy. Patients with cancer diagnosis of multiple myeloma, suspicion of infiltrative cardiomyopathy and those with higher LVEF by echo seem to benefit more from CMR.

Ibrutinib-Associated Cardiovascular Events in a Patient Wearing an Implanted Loop Recorder.

Ibrutinib is a well-tolerated and effective therapy used for the treatment of chronic lymphocytic leukemia (CLL). However, its use has been associated with cardiovascular events such as atrial fibrillation (Afib), hypertension, and ventricular arrhythmias. Cardiac arrhythmias represent a significant cause of morbidity and mortality. Implanted loop recorders have been integrated into our clinical practice and have been considered a useful tool in guiding the management of patients with cardiac arrhythmias. We report a case that describes our experience on a patient diagnosed with CLL treated with ibrutinib.

A Rare Case of Testicular Teratoma Metastasizing to the Right Ventricle.

We describe a case of testicular teratoma with metastasis to the right ventricle. The mass nearly completely resolved with chemotherapy, obviating the need for upfront surgery. We review the workup of intracardiac metastatic tumors. (Level of Difficulty: Intermediate.).

QT Prolongation in Cancer Patients.

Background: QT prolongation and torsades de pointes pose a major concern for cardiologists and oncologists. Although cancer patients are suspected to have prolonged QT intervals, this has not been investigated in a large population. The purpose of this study was to analyze the QT interval distribution in a cancer population and compare it to a non-cancer population in the same institution. Methods: The study was a retrospective review of 82,410 ECGs performed in cancer patients (51.8% women and 48.2% men) and 775 ECGs performed in normal stem cell donors (47.9% women and 52.1% men) from January 2009 to December 2013 at the University of Texas MD Anderson Cancer Center. Pharmacy prescription data was also collected and analyzed during the same time period. Correction of the QT interval for the heart rate was performed using the Bazett and Fridericia formulas. Results: After QT correction for heart rate by the Fridericia formula (QTcF), the mean and 99% percentile QTc for cancer patients were 414 and 473 ms, respectively. These were significantly longer than the normal stem cell donors, 407 and 458 ms, p < 0.001, respectively. Among the cancer patients, the QTc was longer in the inpatient setting when compared to both outpatient and emergency center areas. The most commonly prescribed QT prolonging medications identified were ondansetron and methadone. Conclusion: Our study demonstrates significantly longer QTc intervals in cancer patients, especially in the inpatient setting. Frequently prescribed QT prolonging medications such as antiemetics and analgesics may have a causative role in QT prolongation seen in our cancer hospital.

Case Discussion and Literature Review: Cancer Immunotherapy, Severe Immune-Related Adverse Events, Multi-Inflammatory Syndrome, and Severe Acute Respiratory Syndrome Coronavirus 2.

Pediatric, adolescent and young adult (AYA) patients receiving novel cancer immunotherapies may develop associated toxicities with overlapping signs and symptoms that are not always easily distinguished from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/clinical sequelae. We describe 2 diagnostically challenging cases of SARS-CoV-2 and Multi-Inflammatory Syndrome-Adult (MIS-A), in patients with a history of acute lymphoblastic leukemia following cellular therapy administration and review evolving characterization of both the natural course of SARS-CoV-2 infection and toxicities experienced in younger cancer immunotherapy patients. Vigilant monitoring for unique presentations and epidemiologic surveillance to promptly detect changes in incidence of either condition may be warranted.

Immune Checkpoint Inhibitor (ICI)-Related Cardiotoxicity.

The growing success of immune checkpoint inhibitors (ICIs) has led to improved outcomes in several types of cancers with studies looking for expanding their indications and use. However immune-related adverse events have been recognized of which myocarditis is associated with a high mortality. Other cardiac events such as arrhythmias, pericardial disease, and coronary atherosclerosis have been observed in patients on ICI therapy. These cardiac toxicities are thought to be the result of increased inflammatory responses after inhibition of specific checkpoint proteins on T cells. Although cardiotoxicities related to immunotherapy are reportedly rare, they can be severe and associated with life-threatening conditions such as fulminant myocarditis, hemodynamic instability, and cardiac arrest. We will review the most commonly reported cardiovascular toxicities associated with ICIs and their management.

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.

Prevention of Cardiac Implantable Electronic Device-Related Infection in Patients With Cancer: The Role of a Comprehensive Prophylactic Bundle Approach That Includes the Antimicrobial Mesh.

BACKGROUND: Oncological patients have several additional risk factors for developing a cardiac implantable electronic device (CIED)-related infection. Therefore, we evaluated the clinical impact of our comprehensive bundle approach that includes the novel minocycline and rifampin antimicrobial mesh (TYRX) for the prevention of CIED infections in patients living with cancer. METHODS: We retrospectively reviewed all consecutive patients who had a CIED placement at our institution during 2012-2017 who received preoperative vancomycin, intraoperative pocket irrigation with bacitracin and polymyxin B, plus TYRX antimicrobial mesh, followed by postoperative oral minocycline. RESULTS: A total of 154 patients had a CIED, with 97 permanent pacemakers (PPMs), 23 implantable cardioverter defibrillators (ICDs), and 34 cardiac resynchronization therapy (CRT) devices. An underlying solid cancer was present in 62% of patients, while 38% had a hematologic malignancy. Apart from a higher proportion of surgical interventions in the PPM group than in the ICD and CRT groups (P = .007), no other oncologic variables were statistically significantly different between groups. Despite an extensive median follow-up period (interquartile range) of 21.9 (6.7-33.8) months, 16 patients (10%) had a mechanical complication, while only 2 patients (1.3%) developed a CIED infection, requiring the device to be explanted. CONCLUSIONS: Our comprehensive prophylactic bundle approach using TYRX antimicrobial mesh in an oncologic population at high risk for infections was revealed upon extensive follow-up to be both safe and effective in maintaining the rate of CIED infection at 1.3%, well within published averages in the broader population of CIED recipients.

Acute myocardial infarction in a high-risk cancer population: Outcomes following conservative versus invasive management.

BACKGROUND: The benefits of invasive versus noninvasive management in oncology patients with acute myocardial infarction (AMI) are unclear. We aimed to retrospectively determine outcome differences between conservative and invasive management of AMI in cancer patients. METHODS: Patients from our institution between March 2016 and December 2018 with type 1 and type 2 AMI (excluding STEMI) were classified into 2 groups: medical therapy only and invasive strategies. Analyzed outcomes were overall survival (OS), procedural complications, subsequent events, and hospice referral. Kaplan-Meier method and log-rank test were used to compare OS between subgroups. Cox proportional hazards regression analyses were conducted to find factors associated with OS. RESULTS: We included 201 patients. Type 1 MI was seen in 152 patients (76%) and type 2 MI in 49 (24%). Median OS was 13 months. Most presented with symptoms other than dyspnea or chest pain (49%) and with ECG revealing changes other than ST-segment depression and T-wave inversion (62%). Patients with type 2 MI had worse OS than patients with type 1 MI (HR = 2.3, p = 0.0002). Early coronary angiography (≤72 h; HR = 0.327, p < 0.0001), late coronary angiography (>72 h; HR = 0.496, p = 0.0426), and percutaneous coronary intervention (HR = 0.481, p = 0.0116) were associated with better OS than noninvasive approaches. Single and dual agent antiplatelet therapy, beta blockers, and statins were each associated with better OS. CONCLUSIONS: Cancer patients without STEMI who underwent invasive treatment for AMI had better OS compared with those treated only medically, with the highest benefit when coronary angiography was performed within 72 h of admission for AMI.

Immune Checkpoint Inhibitors (ICIs)-Related Cardiotoxicity.

The growing success of immune checkpoint inhibitors (ICIs) has led to effectively treating several types of cancers. Even though their use has been associated with the development of cardiac adverse effects, which may decrease the overall survival in cancer patients. These cardiac toxicities are thought to be the result of targeting specific checkpoint proteins on normal myocardial cells leading to over stimulation of the immune system as well as secondary downstream off-target effects on normal tissue.Although cardiotoxicities related to immunotherapy are reportedly rare, they can be severe and associated with life-threatening conditions such as fulminant myocarditis, hemodynamic instability, and cardiac arrest.We will review the most commonly reported cardiovascular toxicities associated with ICIs and their management.

Immunomodulatory treatment of immune checkpoint inhibitor-induced myocarditis: Pathway toward precision-based therapy.

Immune checkpoint inhibitor (ICI)-induced myocarditis carries a poor prognosis and is not fully understood. Similar to lymphocytic myocarditis and acute cellular rejection in heart transplant, ICI-induced myocarditis requires immune suppressive strategies. We aimed to describe ICI-induced myocarditis by presenting findings of comprehensive cardiovascular evaluations and outcomes of patients following a therapeutic approach similar to autoimmune disorders or allograft transplant rejection, and to discuss the molecular basis of the benefits of immune modulation and statins in ICI-myocarditis. Three patients with ICI-induced myocarditis (2 with positive biopsies and 1 based on cardiac magnetic resonance imaging with negative biopsy) underwent a complete cardiovascular workup, including cardiac catheterization with endomyocardial biopsy. Treatment was with intravenous immunoglobulins (IVIG) and statins in all cases, with additional colchicine (2 cases) or hydroxychloroquine (1 case). Immunohistochemical analysis demonstrated varied subsets of T cells involved in the inflammatory response. Therapy with IVIG and statins led to symptom resolution and cardiac function normalization at 1-month follow-up in all patients. Cancer therapy was resumed in all patients. One patient expired 10 months after the myocarditis episode due to advanced malignancy; two patients were alive, free of heart failure symptoms and cancer progression, at 1-year follow-up, and 1 patient was rechallenged with ICI. We suggest that treatment with IVIG and statins may allow for a prompt resumption of anti-cancer therapy (including ICI) and improve outcomes.

Identifying Hemostatic Thresholds in Cancer Patients Undergoing Coronary Angiography Based on Platelet Count and Thromboelastography.

Objectives: To evaluate the role of platelet count and thromboelastogram (TEG) in the treatment of thrombocytopenic cancer patients with suspected coronary artery disease (CAD). Background: Cancer patients with CAD and thrombocytopenia are often treated non-invasively (i.e., without coronary angiography when clinically indicated) due to perceived high risk of bleeding. We sought to evaluate coagulability based on TEG and determine if platelet count and TEG could predict bleeding risk/mortality among cancer patients undergoing coronary angiography (CA). Methods: Baseline demographics, platelet count, and TEG parameters were recorded among cancer patients that underwent CA and had a concomitant TEG. Logistic regression and univariate proportional hazards regression analysis were performed to determine the impact of platelet count and coagulability on 24-month overall survival (OS). Results: All patients with platelet count <20,000/mm3 and nearly all patients with platelet count 20,000-49,000/mm3 were hypocoagulable based on TEG results. In contrast, nearly all patients with platelet counts of 50,000-99,999/mm3 had normal TEG results and OS similar to those with platelet counts of ≥100,000/mm3. Coagulability based on TEG was not associated with OS. However, a platelet count of <50,000/mm3 was associated with worse 24-month OS (hazard ratio = 2.76; p = 0.0072) when compared with a platelet count of ≥100,000/mm3. No major bleeding complications were observed in all groups. Conclusion: The majority of cancer patients with platelet counts of <50,000/mm3 were hypocoagulable based on TEG and had worse OS at 24 months. The relatively normal TEGs in the >50,000/mm3 groups, as well as the improved survival, suggest that with appropriate clinical indication and risk/benefit assessment, a cut-off of 50,000/mm3 platelets can be considered for CA in cancer patients.

Allogeneic Mesenchymal Cell Therapy in Anthracycline-Induced Cardiomyopathy Heart Failure Patients: The CCTRN SENECA Trial.

BACKGROUND: Anthracycline-induced cardiomyopathy (AIC) may be irreversible with a poor prognosis, disproportionately affecting women and young adults. Administration of allogeneic bone marrow-derived mesenchymal stromal cells (allo-MSCs) is a promising approach to heart failure (HF) treatment. OBJECTIVES: SENECA (Stem Cell Injection in Cancer Survivors) was a phase 1 study of allo-MSCs in AIC. METHODS: Cancer survivors with chronic AIC (mean age 56.6 years; 68% women; NT-proBNP 1,426 pg/ml; 6 enrolled in an open-label, lead-in phase and 31 subjects randomized 1:1) received 1 × 108 allo-MSCs or vehicle transendocardially. Primary objectives were safety and feasibility. Secondary efficacy measures included cardiac function and structure measured by cardiac magnetic resonance imaging (CMR), functional capacity, quality of life (Minnesota Living with Heart Failure Questionnaire), and biomarkers. RESULTS: A total of 97% of subjects underwent successful study product injections; all allo-MSC-assigned subjects received the target dose of cells. Follow-up visits were well-attended (92%) with successful collection of endpoints in 94% at the 1-year visit. Although 58% of subjects had non-CMR compatible devices, CMR endpoints were successfully collected in 84% of subjects imaged at 1 year. No new tumors were reported. There were no significant differences between allo-MSC and vehicle groups with regard to clinical outcomes. Secondary measures included 6-min walk test (p = 0.056) and Minnesota Living with Heart Failure Questionnaire score (p = 0.048), which tended to favor the allo-MSC group. CONCLUSIONS: In this first-in-human study of cell therapy in patients with AIC, transendocardial administration of allo-MSCs appears safe and feasible, and CMR was successfully performed in the majority of the HF patients with devices. This study lays the groundwork for phase 2 trials aimed at assessing efficacy of cell therapy in patients with AIC.

Cardiac toxicities of anticancer treatments: chemotherapy, targeted therapy and immunotherapy.

PURPOSE OF REVIEW: Current oncologic treatments have shown improvement in overall survival in cancer patients. However, the cardiac toxicities of cancer therapeutics, particularly chemotherapy, targeted therapy and immunotherapy can have life-threatening side effects. RECENT FINDINGS: A MEDLINE search for cardiovascular toxicities associated with Federal Drug Administration (FDA)-approved cancer treatments including chemotherapy, targeted therapy and immunotherapy was performed. We included comprehensive articles and research articles establishing the incidence, diagnosis, monitoring and management of cardiovascular toxicities related to cancer treatments until January 2019.This review highlights the mechanisms and epidemiology of cardiotoxicity associated with some cancer treatments. The most common cardiovascular side-effects are discussed at an introductory level with emphasis on those related with the development of heart failure. SUMMARY: Cardiovascular side effects of cancer treatments are common and might affect the survival in cancer patients. Recognition and management of these side effects require understanding of their mechanisms and their clinical manifestations. A multidisciplinary approach with understanding of both the cardiovascular and oncologic risks is necessary in order to provide well tolerated and effective cardio-oncology care.