Cardio-oncology最新文献

Introduction: Anthracycline-induced cardiotoxicity is a significant concern for breast cancer patients undergoing treatment, often leading to chronic cardiovascular complications and reduced long-term survival. The study aimed to systematically evaluate the efficacy of nine classes of pharmacological agents in protecting against cardiotoxicity in breast cancer patients treated with anthracyclines.

Methods: A comprehensive search of databases was performed from January 2000 to October 2024 to identify randomized controlled trials (RCTs) investigating cardioprotective agents. The risk of bias in the studies was evaluated using the Cochrane risk-of-bias tool. Bayesian network meta-analysis was conducted in Stata 15.1.

Results: Of 3718 studies identified, 29 RCTs involving 2599 patients were included in the network systematic review. The study found that trimetazidine significantly improved left ventricular ejection fraction (LVEF), with a Surface Under the Cumulative Ranking (SUCRA) of 94.0%. The combination of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker with beta-blocker (AA-BB) significantly improved global longitudinal strain (GLS), with a SUCRA of 72.8%. Dexrazoxane was highly effective, significantly reducing B-type natriuretic peptide (BNP) levels, cardiac troponin (cTn) levels, and the E/e' ratio (ratio of the mitral early filling velocity to the mean early relaxation tissue velocity), with SUCRA values of 98.9%, 98.2%, and 99.9%, respectively. Additionally, mineralocorticoid receptor antagonist (MRA) showed the highest SUCRA of 88.4% for improving the E/A ratio (ratio of the mitral early diastolic velocity to the late diastolic velocity).

Discussion: Trimetazidine, ACEI/ARB, beta-blocker, dexrazoxane, and MRA demonstrate potential as cardioprotective agents in breast cancer patients undergoing anthracycline chemotherapy. Further research is needed to elucidate the specific cardioprotective mechanisms against anthracycline-induced cardiotoxicity.

Background: The risk of drug-induced corrected QT interval (QTc) prolongation is an important consideration in clinical decision-making for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC). This retrospective analysis described concomitant QTc-prolonging medication use in patients with HR+/HER2- mBC who received first-line (1L) treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) plus an aromatase inhibitor (AI).

Methods: This retrospective claims analysis utilized the Optum Clinformatics Data Mart database to identify patients with HR+/HER2- mBC who initiated 1L CDK4/6i plus AI treatment between January 2017 and March 2022. Exposure to QTc-prolonging medications (overall and by Torsades de Pointes [TdP] risk, per www.crediblemeds.org ) was assessed at index (i.e., CDK4/6i treatment initiation) and during follow-up (i.e., duration of CDK4/6i treatment) in the overall cohort and cohorts stratified by patient age.

Results: A total of 1517 patients met the study criteria; 33.8%, 35.5%, and 30.8% were aged < 65, 65-74, and ≥ 75 years, respectively. Exposure to ≥ 1 QTc-prolonging medication or ≥ 1 medication with known TdP risk was observed in 53.3% and 15.4% of patients at index, respectively, and 78.6% and 57.1% of patients during follow-up, respectively. Patients were exposed to QTc-prolonging medications for 54.6% of total person-time during follow-up. Patients aged ≥ 65 years had higher exposure to medications with conditional TdP risk than those aged < 65 years, primarily driven by increased diuretic use.

Conclusions: QTc-prolonging medication use was common in patients with HR+/HER2- mBC receiving 1L CDK4/6i plus AI treatment, highlighting the importance of reviewing concomitant medications to inform CDK4/6i selection and patient monitoring while on treatment.

Background: Stem Cell Transplantation (SCT) is a cornerstone therapy in managing several malignant and benign hematological conditions. Atrial fibrillation/atrial flutter (AF) are commonly encountered in patients receiving SCT. There is a paucity of large-scale data on the prevalence of AF and their effect on outcomes following SCT.

Methods: The United States National Readmission Database (NRD) was used to identify hospitalized patients who underwent SCT. Baseline demographics, comorbidities, the presence or absence of AF, the indication, and type of SCT were identified using diagnostic and procedural International Classification of Diseases 10th Edition (ICD-10) codes. Patients with AF were compared to those without AF for differences in baseline characteristics, in-hospital mortality, cardiovascular (CV) complications, length and cost of hospitalization, and post-discharge 90-day readmissions and mortality.

Results: Between January 2016 and September 2020 there were 59,284 weighted admissions for SCT, of which 5797 (9.8%) patients had AF. Patients in the AF group were more likely to be older males with an increased burden of baseline comorbidities compared to the no-AF group ((64 [9] vs. 56 [14] years, p < 0.001) and (3893 [67%] vs. 30,886 [58%] males, p < 0.001) respectively). Adjusted for differences in baseline demographics, comorbidities, indication and type of SCT, patients with AF had higher in-hospital mortality (adjusted odds ratio (AOR) 3.65 [3.02-4.41]) and adverse events including cardiac complications [composite of acute heart failure, acute myocardial infarction, cardiogenic shock, and cardiac arrest] (AOR 4.92 [4.22-5.75]), bleeding (AOR 1.32 [1.15-1.53]), and respiratory failure (AOR 3.40 [2.97-3.90]) compared to patients without AF. Additionally, the AF group had longer hospitalizations (21 [16-27] vs. 19 [15-25] days, p < 0.001) with higher cost ($268,031 [$170,957-$455739] vs. $250,178 [$153,680-$415239], p < 0.001) compared to the no-AF group. Among survivors to hospital discharge, patients with AF also had higher adjusted 90-day all-cause inpatient mortality (adjusted hazard ratio (AHR) 1.54 [1.19-1.99], p = 0.001), all-cause readmissions (AHR 1.15 [1.07-1.24], p < 0.001), and CV readmissions (AHR 2.29 [1.85-2.82], p < 0.001).

Conclusions: In a large national cohort of SCT recipients, AF were common and independently associated with increased in-hospital mortality and CV adverse events, along with increased 90-day mortality and readmissions among survivors to hospital discharge.

Cardiovascular adverse events (CVAE) are clinically relevant side effects during treatment with the proteasome inhibitor carfilzomib. We investigated the predictive value of cardiac biomarkers for onset of CVAE in patients with newly diagnosed high-risk multiple myeloma treated with isatuximab, carfilzomib, lenalidomide, and dexamethasone in the GMMG-CONCEPT study (NCT03104842). Patients included in this prospective, multicenter correlative study were eligible if a serum sample before treatment initiation and at ≥ 1 later study time point were available. N-terminal pro-b-type natriuretic peptide (NT-proBNP) and high-sensitive Troponin I (hsTropI) were measured using immunoassays. Time-to-event analyses were performed using Kaplan-Meier estimators and log-rank test was used for statistical analysis. Among 126 patients included in this study, 40 reported incident CVAE. No significant differences were observed for age, sex, cardiovascular risk factors and cardiovascular comorbidities between patients who experienced CVAE compared to patients without CVAE. NT-proBNP levels were elevated at baseline in 96 (76%) patients. Neither baseline levels nor change in NT-proBNP level during early induction cycles were predictive for the occurrence of CVAE. In contrast, elevation of hsTropI above the 99th percentile was rare. Patients with hsTropI level ≥ 2.9 ng/L, corresponding to the lower limit of quantification, showed a higher risk for CVAE compared to patients with hsTropI < 2.9 ng/L at baseline (p = 0.0023). In conclusion, in patients with newly diagnosed high-risk multiple myeloma undergoing carfilzomib-based quadruplet treatment, low hsTropI pretreatment levels are of high negative predictive value for the occurrence of CVAE whereas elevated NT-proBNP levels are very common before treatment initiation.

Background: Chimeric Antigen Receptor (CAR) T-cell therapy (CAR-T) has emerged as a promising treatment for specific hematological malignancies. While some studies suggest an association between CAR-T and atrial fibrillation (AF), more data are needed on the association of AF with CAR-T outcomes.

Methods: This retrospective cohort study utilized the National Inpatient Sample (NIS) 2017-2020 to explore in-hospital outcomes in cancer patients with AF while undergoing CAR-T. Comparisons were drawn between patients with and without AF during the hospitalization, assessing various parameters including mortality rates, length of hospital stay, and occurrences of acute heart failure, pulmonary edema, and gastrointestinal (GI) bleeding.

Results: Of the 236,270 cancer-related hospitalizations, 1,030 cases (0.44%) received CAR-T. The average age of CAR-T recipients was 55.6 years ± 18.1 years, and females constituted 40.5% of the total CAR-T recipients. Of the 1030 patients receiving CAR-T, 97 (9.4%) had an associated diagnosis of AF during their hospitalization. A multivariable logistic regression analysis, adjusted for age, sex, race, comorbidity, and income, revealed that hospitalized cancer patients who underwent CAR-T therapy with AF had increased odds of in-hospital mortality (adjusted odds ratio, aOR: 3.87), acute pulmonary edema (aOR: 3.29), GI bleeding (aOR: 5.46), acute heart failure (aOR: 10.2), and extended hospital stays (Beta coefficient: 0.18) compared to hospitalizations with CAR-T but without AF. Similar results were observed in two sensitivity analyses: one limited to patients with diffuse B-cell lymphoma, and another excluding patients who had sepsis or respiratory failure while receiving CAR-T therapy.

Conclusions: In cancer patients receiving CAR-T, inpatient AF is independently associated with a higher risk of in-hospital mortality, acute pulmonary edema, gastrointestinal bleeding, acute heart failure, and prolonged hospitalization.

Background: Neoadjuvant chemotherapy-immunotherapy is the new standard of care for high-risk early-stage triple negative breast cancer (TNBC). As anthracyclines, pembrolizumab, and radiotherapy may each contribute to an increased risk of cardiovascular events, real-world assessment of early cardiovascular changes is of clinical interest.

Methods: Retrospective analysis of 85 women with early-stage TNBC treated with chemotherapy-pembrolizumab between 2018 and 2023 and had ≥ 1 transthoracic echocardiogram (TTE) available. Grade ≥ 2 cardiac common terminology criteria for adverse events (CTCAE) cumulative incidence estimates and Fine-Gray regressions (accounting for non-cardiac death as a competing risk) were calculated. Electrocardiogram (ECG) and TTE parameters during/following systemic therapy (vs. baseline) were compared.

Results: The median follow-up from immunotherapy start was 18.7 months [interquartile range (IQR) 13.6-39.1]. The median age was 50 years (IQR 38-61), 19% had hypertension, most (82%) with no detectable coronary artery calcium (CAC = 0), and 0% known cardiovascular disease. 9/85 (11%) experienced a grade ≥2 cardiac event with a median onset of 7.3 months (IQR 4.0-8.0) and a one-year cumulative incidence of 9.6%. Most (7/9) were grade 2 (n = 5 ejection fraction [EF] decline, n = 1 heart failure, n = 1 pericarditis); 2/9 were grade ≥ 3 (myocarditis, urgent percutaneous coronary intervention); all occurred among those receiving carboplatin, paclitaxel, doxorubicin, and cyclophosphamide-based therapy. Adjusting for age and CAC, mean left anterior descending coronary artery radiation dose was associated with an increased risk of cardiac events (sub-distribution hazard ratio 1.16/Gy, 95% confidence interval 1.01-1.35; p = 0.041). QTc prolongation ≥450ms was more common during treatment vs. baseline (39% vs. 15%; p = 0.025). On assessment for recovery, early grade 2 EF decline recovered in 3/5 patients (2/5 with absence of follow-up). In those with baseline and post-treatment TTE, 5/20 (25%) developed new moderate diastolic dysfunction, that persisted in a later TTE in 2/5 patients, downgraded to mild in 1/5, and not reevaluated by TTE in 2/5.

Conclusion: Early cardiovascular toxicity was observed during multi-modality TNBC treatment, even in young patients with low cardiovascular risk profiles, highlighting the importance of diligent surveillance. Longer follow-up and further studies are warranted, given the degree of recovery and later effects of these treatments may not yet be fully observed.

Background: Cardiovascular toxicity concerns have limited the use of anthracyclines and trastuzumab among breast cancer patients with cardiovascular disease (CVD) but evidence on real-world prescribing patterns is scarce. We aimed to describe the use of these drugs in women with and without CVD when diagnosed with non-metastatic breast cancer in Sweden.

Methods: Using Swedish national registers (2010-15), we identified breast cancer treatment and prior CVD from hospital and prescription data. We calculated prevalence of anthracycline and trastuzumab use in women with and without prior CVD, and estimated prevalence ratios (PR) comparing these groups, adjusted for age, stage, and other patient and tumour-related factors.

Results: Among 32,590 women with breast cancer, 10,702 (33%) had prior CVD. Anthracycline use was lower in those with vs without prior CVD (2,169/10,702 [20.3%] vs 8,654/21,888 [39.5%], crude PR 0.51, 0.49-0.53); the PR attenuated after adjustment for age and other factors (adj-PR 0.90, 0.87-0.93). There was substantial variation by type of CVD: patients with heart failure were much less likely to receive anthracyclines (adj-PR 0.46, 0.35-0.57) while prior venous thromboembolism (VTE) had no impact (adj-PR 0.98, 0.88-1.09). Among HER2 + patients, trastuzumab use showed similar patterns, with prevalence of 630/1,100 [57.3%] vs 2,279/2,866 [79.5%] for any vs no prior CVD (crude PR = 0.72, 0.68-0.76, adjusted PR = 0.95, 0.90-0.99); adjusted PRs for specific outcomes ranged from 0.77 (0.61-0.93) for heart failure, to 1.04 (0.92-1.15) for VTE.

Conclusion: While prior CVD was associated with lower use of potentially cardiotoxic breast cancer therapies, substantial numbers of patients with CVD still received these treatments, with marked variation by type of CVD. These real-world data suggest variable cardiovascular toxicity risk stratification before anticancer therapy and highlight the need for evidence-based guidance on negotiating the risk-benefit balance in these patients.