Cardiovascular Management of Patients Undergoing Hematopoietic Stem Cell Transplantation: From Pretransplantation to Survivorship: A Scientific Statement From the American Heart Association.

Hematopoietic stem cell transplantation can cure various disorders but poses cardiovascular risks, especially for elderly patients and those with cardiovascular diseases. Cardiovascular evaluations are crucial in pretransplantation assessments, but guidelines are lacking. This American Heart Association scientific statement summarizes the data on transplantation-related complications and provides guidance for the cardiovascular management throughout transplantation. Hematopoietic stem cell transplantation consists of 4 phases: pretransplantation workup, conditioning therapy and infusion, immediate posttransplantation period, and long-term survivorship. Complications can occur during each phase, with long-term survivors facing increased risks for late effects such as cardiovascular disease, secondary malignancies, and endocrinopathies. In adults, arrhythmias such as atrial fibrillation and flutter are the most frequent acute cardiovascular complication. Acute heart failure has an incidence ranging from 0.4% to 2.2%. In pediatric patients, left ventricular systolic dysfunction and pericardial effusion are the most common cardiovascular complications. Factors influencing the incidence and risk of complications include pretransplantation therapies, transplantation type (autologous versus allogeneic), conditioning regimen, comorbid conditions, and patient age. The pretransplantation cardiovascular evaluation consists of 4 steps: (1) initial risk stratification, (2) exclusion of high-risk cardiovascular disease, (3) assessment of cardiac reserve, and (4) optimization of cardiovascular reserve. Clinical risk scores could be useful tools for the risk stratification of adult patients. Long-term cardiovascular management of hematopoietic stem cell transplantation survivors includes optimizing risk factors, monitoring, and maintaining a low threshold for evaluating cardiovascular causes of symptoms. Future research should prioritize refining risk stratification and creating evidence-based guidelines and strategies to optimize outcomes in this growing patient population.

Androgen Deprivation Therapy/Androgen Receptor Signaling Inhibitor Treatments for Prostate Cancer: Pathophysiology and Review of Effects on Cardiovascular Disease.

Androgen deprivation therapy is the cornerstone of systemic management for prostate cancer but is associated with multiple adverse effects that must be considered during treatment. These effects occur because of the profound hypogonadism that is induced from lack of testosterone or due to the medications used in the treatment or in combination with androgen receptor signaling inhibitors. This article critically reviews the associations between androgen deprivation therapy, androgen receptor signaling inhibitors, and cardiovascular complications such as prolonged QT interval, atrial fibrillation, heart failure, atherosclerosis, coronary heart disease, venous thromboembolism, and peripheral arterial occlusive disease. These unfavorable outcomes reinforce the need for regular cardiovascular screening of patients undergoing androgen deprivation for the management of prostate cancer.

Cardiometabolic risk factors and survival after cancer in the Women's Health Initiative.

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.

Cardiovascular Disease and Breast Cancer: Where These Entities Intersect: A Scientific Statement From the American Heart Association.

Cardiovascular disease (CVD) remains the leading cause of mortality in women, yet many people perceive breast cancer to be the number one threat to women's health. CVD and breast cancer have several overlapping risk factors, such as obesity and smoking. Additionally, current breast cancer treatments can have a negative impact on cardiovascular health (eg, left ventricular dysfunction, accelerated CVD), and for women with pre-existing CVD, this might influence cancer treatment decisions by both the patient and the provider. Improvements in early detection and treatment of breast cancer have led to an increasing number of breast cancer survivors who are at risk of long-term cardiac complications from cancer treatments. For older women, CVD poses a greater mortality threat than breast cancer itself. This is the first scientific statement from the American Heart Association on CVD and breast cancer. This document will provide a comprehensive overview of the prevalence of these diseases, shared risk factors, the cardiotoxic effects of therapy, and the prevention and treatment of CVD in breast cancer patients.

Fabricating a Shell-Core Delayed Release Tablet Using Dual FDM 3D Printing for Patient-Centred Therapy.

PURPOSE: Individualizing gastric-resistant tablets is associated with major challenges for clinical staff in hospitals and healthcare centres. This work aims to fabricate gastric-resistant 3D printed tablets using dual FDM 3D printing. METHODS: The gastric-resistant tablets were engineered by employing a range of shell-core designs using polyvinylpyrrolidone (PVP) and methacrylic acid co-polymer for core and shell structures respectively. Filaments for both core and shell were compounded using a twin-screw hot-melt extruder (HME). CAD software was utilized to design a capsule-shaped core with a complementary shell of increasing thicknesses (0.17, 0.35, 0.52, 0.70 or 0.87 mm). The physical form of the drug and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. RESULTS: A shell thickness ≥0.52 mm was deemed necessary in order to achieve sufficient core protection in the acid medium. The technology proved viable for incorporating different drug candidates; theophylline, budesonide and diclofenac sodium. XRPD indicated the presence of theophylline crystals whilst budesonide and diclofenac sodium remained amorphous in the PVP matrix of the filaments and 3D printed tablets. Fabricated tablets demonstrated gastric resistant properties and a pH responsive drug release pattern in both phosphate and bicarbonate buffers. CONCLUSIONS: Despite its relatively limited resolution, FDM 3D printing proved to be a suitable platform for a single-process fabrication of delayed release tablets. This work reveals the potential of dual FDM 3D printing as a unique platform for personalising delayed release tablets to suit an individual patient's needs.

Bendamustine and Rituximab: Complete Response in a 62-Year-Old Female with an Aggressive Lymphoma and an Ejection Fraction of 20.

The treatment of diffuse large B-cell lymphoma in the presence of cardiac comorbidities can be challenging considering that the standard treatment regimen used for this aggressive subtype of non-Hodgkin lymphoma (NHL) consists of a combination of rituximab, cyclophosphamide, doxorubicin hydrochloride, Oncovin (vincristine), and prednisone (R-CHOP). The use of the anthracycline doxorubicin has been associated with arrhythmias and cardiomyopathy, making patients with cardiac dysfunction poor candidates for R-CHOP. As such, it is imperative to find alternative regimens that omit cardiac toxicity without compromising efficacy for this patient population. We report a case of composite NHL in a patient who received frontline bendamustine with rituximab with encouraging results. Our patient had a left ventricular ejection fraction of 20%, making her a poor candidate for anthracycline-based therapy. We opted to administer bendamustine with rituximab for a total of 6 cycles. She remains disease free 18 months after the completion of therapy.

A Lower Temperature FDM 3D Printing for the Manufacture of Patient-Specific Immediate Release Tablets.

PURPOSE: The fabrication of ready-to-use immediate release tablets via 3D printing provides a powerful tool to on-demand individualization of dosage form. This work aims to adapt a widely used pharmaceutical grade polymer, polyvinylpyrrolidone (PVP), for instant on-demand production of immediate release tablets via FDM 3D printing. METHODS: Dipyridamole or theophylline loaded filaments were produced via processing a physical mixture of API (10%) and PVP in the presence of plasticizer through hot-melt extrusion (HME). Computer software was utilized to design a caplet-shaped tablet. The surface morphology of the printed tablet was assessed using scanning electron microscopy (SEM). The physical form of the drugs and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. In vitro drug release studies for all 3D printed tablets were conducted in a USP II dissolution apparatus. RESULTS: Bridging 3D printing process with HME in the presence of a thermostable filler, talc, enabled the fabrication of immediate release tablets at temperatures as low as 110°C. The integrity of two model drugs was maintained following HME and FDM 3D printing. XRPD indicated that a portion of the loaded theophylline remained crystalline in the tablet. The fabricated tablets demonstrated excellent mechanical properties, acceptable in-batch variability and an immediate in vitro release pattern. CONCLUSIONS: Combining the advantages of PVP as an impeding polymer with FDM 3D printing at low temperatures, this approach holds a potential in expanding the spectrum of drugs that could be used in FDM 3D printing for on demand manufacturing of individualised dosage forms.

Emergence of 3D Printed Dosage Forms: Opportunities and Challenges.

The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry.

A Model-Informed Drug Development Approach to Design a Phase 3 Trial of Teverelix Drug Product in Advanced Prostate Cancer Patients with Increased Cardiovascular Risk.

Teverelix drug product (DP) is a parenteral gonadotropin-releasing hormone (GnRH) antagonist that has been successfully tested in phase 2 trials for hormone-sensitive advanced prostate cancer (APC) and benign prostatic hyperplasia (BPH). In previous APC trials, teverelix DP was administered as intramuscular (IM) and subcutaneous (SC) injections, using a loading dose and (in a single trial) a maintenance dose. Our objective was to derive an optimal dosing regimen for phase 3 clinical development, using a pharmacometrics modeling approach. Data from 9 phase 2 studies (229 patients) was utilized to develop a population pharmacokinetic (PK) model that described the concentration profile accommodating both IM and SC routes of administration. A 2-compartment model with sequential first-order absorption (slow and fast) and lag times best described the PK profiles of teverelix following SC and IM administration. An indirect response model with inhibition of production rate was fit to describe testosterone (T) concentrations based on physiological relevance. The final population PK-pharmacodynamic model was used to conduct simulations of various candidate dosing regimens to select the optimal dosing regimen to achieve clinical castration (T < 0.5 ng/mL by day 28) and to sustain clinical castration for 26 weeks. Model simulation showed that a loading dose of 360 mg SC and 180 mg IM with a maintenance dose of 360 mg SC 6-weekly (Q6W) starting at day 28 can achieve a ≥95% castration rate up to 52 weeks. This dose regimen was selected for phase 3 clinical development, which includes cardiovascular safety assessment in comparison to a GnRH agonist.

Immune Checkpoint Inhibitors and Cardiotoxicity: A Comparative Meta-Analysis of Observational Studies and Randomized Controlled Trials.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have uncommon associations with cardiotoxicity, yet these cardiotoxic effects are associated with high mortality. An accurate assessment of risk for cardiotoxicity is essential for clinical decision-making, but data from randomized controlled trials often differ from real-world observational studies. METHODS AND RESULTS: A systematic search of PubMed, Embase, Cochrane Library, and Scopus was performed, including phase II and III randomized controlled trials (RCTs) and observational studies (OSs) reporting myocarditis or pericardial disease, myocardial infarction, or stroke with an immunotherapy. Odds ratios (ORs) were used to pool results between ICIs and other cancer therapy in RCTs and OSs. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was followed. In total, 54 RCTs (N=38 264) and 24 OSs (N=12 561 455) were included. In RCTs, ICI use resulted in higher risk of myocarditis (OR, 3.55 [95% CI, 2.10-5.98]), pericardial disease (OR, 2.73 [95% CI, 1.57-4.77]), and myocardial infarction (OR, 1.83 [95% CI, 1.03-3.25]), compared with non-ICI (placebo or chemotherapy). In OSs, ICI use was not associated with myocarditis, pericardial disease, or myocardial infarction compared with controls; however, combination ICIs demonstrated higher risk of myocarditis compared with single ICI use (OR, 3.07 [95% CI, 1.28-7.39]). Stroke risk was not increased with use of ICIs in RCTs. CONCLUSIONS: We demonstrated increased risk of ICI myocarditis, pericardial disease, and myocardial infarction in RCTs but not OSs. Results of this study suggest there are differences between ICI cardiotoxicity risk, possibly suggesting differences in diagnoses and management, in clinical trials versus the OSs.

Soluble urokinase plasminogen activator receptor and cardiotoxicity in doxorubicin-treated breast cancer patients: a prospective exploratory study.

BACKGROUND: Soluble urokinase plasminogen activator receptor is an inflammatory biomarker that may prognosticate cardiovascular outcomes. We sought to determine the associations between soluble urokinase plasminogen activator receptor and established markers of cardiotoxicity in breast cancer patients receiving doxorubicin. METHODS: We conducted a prospective cohort study of women with newly diagnosed breast cancer receiving standard-dose doxorubicin (240 mg/m2) at Rush University Medical Center and Rush Oak Park Hospital (Chicago, IL) between January 2017 and May 2019. Left ventricular ejection fraction, global longitudinal strain, and cardiac biomarkers (N-terminal prohormone B-type natriuretic peptide, troponin-I, and high-sensitivity C-reactive protein) were measured at baseline and at intervals up to 12-month follow-up after end of treatment. The associations between soluble urokinase plasminogen activator receptor and these endpoints were evaluated using multivariable mixed effects linear regression. RESULTS: Our study included 37 women (mean age 47.0 ± 9.3 years, 60% white) with a median baseline soluble urokinase plasminogen activator receptor level of 2.83 ng/dL. No participant developed cardiomyopathy based on serial echocardiography by one-year follow-up. The median percent change in left ventricular strain was -4.3% at 6-month follow-up and absolute changes in cardiac biomarkers were clinically insignificant. There were no significant associations between soluble urokinase plasminogen activator receptor and these markers of cardiotoxicity (all p > 0.05). CONCLUSIONS: In this breast cancer cohort, doxorubicin treatment was associated with a very low risk for cardiotoxicity. Across this narrow range of clinical endpoints, soluble urokinase plasminogen activator receptor was not associated with markers of subclinical cardiotoxicity. Further studies are needed to clarify the prognostic utility of soluble urokinase plasminogen activator receptor in doxorubicin-associated cardiomyopathy and should include a larger cohort of leukemia and lymphoma patients who receive higher doses of doxorubicin.

Cardiovascular Diseases Increase Cancer Mortality in Adults: NHANES-Continuous Study.

BACKGROUND: Both cancer and cardiovascular disease (CVD) are the leading causes of death worldwide. Although our previous study detected a relationship between CVD and cancer incidence, limited evidence is available regarding the relationship between CVD, cardiovascular risk factors, and cancer mortality. METHODS AND RESULTS: A prospective cohort study using data from the continuous NHANES (National Health and Nutrition Examination Survey, 1999-2016) merged with Medicare and National Death Index mortality data, through December 31, 2018. We included individuals with no history of cancer at baseline. The primary exposure was CVD at baseline. We also conducted a comprehensive risk factor analysis as secondary exposure. The main outcome was cancer mortality data collected from Medicare and National Death Index. We included 44 591 adult individuals representing 1 738 423 317 individuals (52% female, 67% non-Hispanic White, and 9% Hispanic). Competing risk modeling showed a significantly higher risk of cancer mortality in individuals with CVD (adjusted hazard ratio [aHR], 1.37 [95% CI 1.07-1.76], P=0.01) after adjusting for age, sex, and race and ethnicity. Notably, cancer mortality increased with aging (aHR, 1.08 [95% CI 1.05-1.11], P<0.0001), current smoking status (aHR, 6.78 [95% CI, 3.43-13.42], P<0.0001), and obesity (aHR, 2.32 [95% CI, 1.13-4.79], P=0.02). Finally, a significant interaction (P=0.034) was found where those with CVD and obesity showed higher cancer mortality than those with normal body mass index (aHR, 1.73 [95% CI, 1.03-2.91], P=0.04). CONCLUSIONS: Our study highlights the close relationship between cardiovascular health and cancer mortality. Our findings suggest that obesity may play a significant role in cancer mortality among individuals with CVD. These findings emphasize the need for a more proactive approach in managing the shared risk factors for CVD and cancer.

Cardiovascular Risk Stratification of Patients Undergoing Hematopoietic Stem Cell Transplantation: The CARE-BMT Risk Score.

BACKGROUND: Evidence guiding the pre-hematopoietic stem cell transplantation (HSCT) cardiovascular evaluation is limited. We sought to derive and validate a pre-HSCT score for the cardiovascular risk stratification of HSCT candidates. METHODS AND RESULTS: We leveraged the CARE-BMT (Cardiovascular Registry in Bone Marrow Transplantation) study, a contemporary multicenter observational study of adult patients who underwent autologous or allogeneic HSCT between 2008 and 2019 (N=2435; mean age at transplant of 55 years; 4.9% Black). We identified the subset of variables most predictive of post-HSCT cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, heart failure, stroke, atrial fibrillation or flutter, and sustained ventricular tachycardia. We then developed a point-based risk score using the hazard ratios obtained from Cox proportional hazards modeling. The score was externally validated in a separate cohort of 919 HSCT recipients (mean age at transplant 54 years; 20.4% Black). The risk score included age, transplant type, race, coronary artery disease, heart failure, peripheral artery disease, creatinine, triglycerides, and prior anthracycline dose. Risk scores were grouped as low-, intermediate-, and high-risk, with the 5-year cumulative incidence of cardiovascular events being 4.0%, 10.3%, and 22.4%, respectively. The area under the receiver operating curves for predicting cardiovascular events at 100 days, 5 and 10 years post-HSCT were 0.65 (95% CI, 0.59-0.70), 0.73 (95% CI, 0.69-0.76), and 0.76 (95% CI, 0.69-0.81), respectively. The model performed equally well in autologous and allogeneic recipients, as well as in the validation cohort. CONCLUSIONS: The CARE-BMT risk score is easy to calculate and could help guide referrals of high-risk HSCT recipients to cardiovascular specialists before transplant and guide long-term monitoring.

NEW-ONSET CARDIAC AMYLOIDOSIS WHILE IN REMISSION FROM SYSTEMIC AL AMYLOIDOSIS.

In light chain amyloidosis, a reduction in dFLC to below 40 mg/l is a prerequisite for organ recovery as nearly half of the patients who achieve very good partial haematological responses have improvement in the function of the involved organ. We describe a patient who developed new-onset cardiac amyloidosis despite a post-treatment reduction in dFLC to <10 mg/l. LEARNING POINTS: Patients with light chain (AL) amyloidosis may develop new cardiac involvement despite achieving haematological remission.In patients with AL amyloidosis, a very good partial haematological response (dFLC <10 mg/l) does not obviate the need for regular cardiac monitoring.

Unusual vasovagal-type autonomic dysfunction secondary to immune checkpoint inhibitor therapy.

We present the case of a patient with oral squamous cell carcinoma treated with the programmed death ligand inhibitor, pembrolizumab, an immune checkpoint inhibitor. She subsequently developed vasovagal-type autonomic dysfunction thought to be secondary to the pembrolizumab. The patient's vasovagal symptoms resolved with the initiation of oral glucocorticoids.

Artificial intelligence modelling to assess the risk of cardiovascular disease in oncology patients.

Aims: There are no comprehensive machine learning (ML) tools used by oncologists to assist with risk identification and referrals to cardio-oncology. This study applies ML algorithms to identify oncology patients at risk for cardiovascular disease for referrals to cardio-oncology and to generate risk scores to support quality of care. Methods and results: De-identified patient data were obtained from Vanderbilt University Medical Center. Patients with breast, kidney, and B-cell lymphoma cancers were targeted. Additionally, the study included patients who received immunotherapy drugs for treatment of melanoma, lung cancer, or kidney cancer. Random forest (RF) and artificial neural network (ANN) ML models were applied to analyse each cohort: A total of 20 023 records were analysed (breast cancer, 6299; B-cell lymphoma, 9227; kidney cancer, 2047; and immunotherapy for three covered cancers, 2450). Data were divided randomly into training (80%) and test (20%) data sets. Random forest and ANN performed over 90% for accuracy and area under the curve (AUC). All ANN models performed better than RF models and produced accurate referrals. Conclusion: Predictive models are ready for translation into oncology practice to identify and care for patients who are at risk of cardiovascular disease. The models are being integrated with electronic health record application as a report of patients who should be referred to cardio-oncology for monitoring and/or tailored treatments. Models operationally support cardio-oncology practice. Limited validation identified 86% of the lymphoma and 58% of the kidney cancer patients with major risk for cardiotoxicity who were not referred to cardio-oncology.

Cancer Treatment-Related Cardiovascular Toxicity in Gynecologic Malignancies: JACC: CardioOncology State-of-the-Art Review.

Improvements in early detection and treatment of gynecologic malignancies have led to an increasing number of survivors who are at risk of long-term cardiac complications from cancer treatment. Multimodality therapies for gynecologic malignancies, including conventional chemotherapy, targeted therapeutics, and hormonal agents, place patients at risk of cancer therapy-related cardiovascular toxicity during and following treatment. Although the cardiotoxicity associated with some female predominant cancers (eg, breast cancer) have been well recognized, there has been less recognition of the potential adverse cardiovascular effects of anticancer therapies used to treat gynecologic malignancies. In this review, the authors provide a comprehensive overview of the cancer therapeutic agents used in gynecologic malignancies, associated cardiovascular toxicities, risk factors for cardiotoxicity, cardiac imaging, and prevention strategies.

Cardiovascular Events After Hematopoietic Stem Cell Transplant: Incidence and Risk Factors.

Background: Hematopoietic stem cell transplantation (HSCT) is associated with various cardiovascular (CV) complications. Objectives: We sought to characterize the incidence and risk factors for short-term and long-term CV events in a contemporary cohort of adult HSCT recipients. Methods: We conducted a multicenter observational study of adult patients who underwent autologous or allogeneic HSCT between 2008 and 2019. Data on demographics, clinical characteristics, conditioning regimen, and CV outcomes were collected through chart review. CV outcomes were a composite of CV death, myocardial infarction, heart failure, atrial fibrillation/flutter, stroke, and sustained ventricular tachycardia and were classified as short-term (≤100 days post-HSCT) or long-term (>100 days post-HSCT). Results: In 3,354 patients (mean age 55 years; 40.9% female; 30.1% Black) followed for a median time of 2.3 years (Q1-Q3: 1.0-5.4 years), the 100-day and 5-year cumulative incidences of CV events were 4.1% and 13.9%, respectively. Atrial fibrillation/flutter was the most common short- and long-term CV event, with a 100-day incidence of 2.6% and a 5-year incidence of 6.8% followed by heart failure (1.1% at 100 days and 5.4% at 5 years). Allogeneic recipients had a higher incidence of long-term CV events compared to autologous recipients (5-year incidence 16.4% vs 12.1%; P = 0.002). Baseline CV comorbidities were associated with a higher risk of long-term CV events. Conclusions: The incidence of short-term CV events in HSCT recipients is relatively low. Long-term events were more common among allogeneic recipients and those with pre-existing CV comorbidities.

Global Cardio Oncology Registry (G-COR): Registry Design, Primary Objectives, and Future Perspectives of a Multicenter Global Initiative.

BACKGROUND: Global collaboration in cardio-oncology is needed to understand the prevalence of cancer therapy-related cardiovascular toxicity in different risk groups, practice settings, and geographic locations. There are limited data on the socioeconomic and racial/ethnic disparities that may impact access to care and outcomes. To address these gaps, we established the Global Cardio-Oncology Registry, a multinational, multicenter prospective registry. METHODS: We assembled cardiologists and oncologists from academic and community settings to collaborate in the first Global Cardio-Oncology Registry. Subsequently, a survey for site resources, demographics, and intention to participate was conducted. We designed an online data platform to facilitate this global initiative. RESULTS: A total of 119 sites responded to an online questionnaire on their practices and main goals of the registry: 49 US sites from 23 states and 70 international sites from 5 continents indicated a willingness to participate in the Global Cardio-Oncology Registry. Sites were more commonly led by cardiologists (85/119; 72%) and were more often university/teaching (81/119; 68%) than community based (38/119; 32%). The average number of cardio-oncology patients treated per month was 80 per site. The top 3 Global Cardio-Oncology Registry priorities in cardio-oncology care were breast cancer, hematologic malignancies, and patients treated with immune checkpoint inhibitors. Executive and scientific committees and specific committees were established. A pilot phase for breast cancer using Research Electronic Data Capture Cloud platform recently started patient enrollment. CONCLUSIONS: We present the structure for a global collaboration. Information derived from the Global Cardio-Oncology Registry will help understand the risk factors impacting cancer therapy-related cardiovascular toxicity in different geographic locations and therefore contribute to reduce access gaps in cardio-oncology care. Risk calculators will be prospectively derived and validated.