Late Cardiac Events Research Articles

Cardiac events after allo-HCT in patients with acute myeloid leukemia

AbstractThis multicenter study sponsored by the GETH-TC investigates the incidence and predictors of early (first 100 days) and late cardiac events (CEs; ECEs and LCEs, respectively) after allo-HCT in patients with acute myeloid leukemia (AML) treated with anthracyclines, focusing on exploring the impact of PTCY on cardiac complications and the impact of CEs on OS and NRM. A total of 1020 patients with AML were included. PTCY was given to 450 (44.1%) adults. Overall, 94 (9.2) patients experienced CEs, with arrythmias, pericardial complications, and heart failure the most prevalent. ECEs occurred in 49 (4.8%) patients within a median of 13 days after allo-HCT, whereas LCEs were diagnosed in 45 (4.4%) patients within a median of 3.6 years after transplant. Using PTCY increased the risk for ECEs in multivariate analysis (hazard ratio [HR], 2.86; P = .007) but did not significantly affect the risk for LCEs (HR, 1.06; P = .892). The impact of variables on outcomes revealed was investigated using multivariate regression analyses and revealed that the diagnosis of CEs decreased the likelihood of OS (HR, 1.66; P = .005) and increased the likelihood of NRM (HR, 2.88; P < .001). Furthermore, despite using PTCY increased ECEs risk, its administration was beneficial for OS (HR, 0.71; P = .026). In conclusion, although the incidence of CEs was relatively low, it significantly affected mortality. Standard doses of PTCY increased ECE risk but were associated with improved OS. Therefore, protocols for preventing cardiac complications among these patients are needed.

The role of the female gender on mid-term outcome after coronary artery bypass grafting: a retrospective study.

Data on female gender differences on clinical prognosis after coronary artery bypass grafting (CABG) are still controversial. We evaluated retrospectively the impact of women patients in comparison with men undergoing CABG on mid-term outcome. Between December 2014 and March 2022, 1,044 consecutive patients (162 females, 15.5%, 882 males, 84.5%) underwent isolated CABG. The mean follow-up was 40±27 (median 38) months. Logistic and Cox model analysis regressions were used to assess the risk of female gender and other variables, Kaplan-Meier estimates to assess survival rates. Women did not have a significant higher operative mortality than men (3.09% vs. 1.93%; P=0.37). There was no difference in the use of left internal mammary artery (97.5% vs. 94.9%; P=0.85). Independent predictors of early mortality were emergency CABG (P<0.0001), percutaneous coronary intervention (PCI) within 30 days (P=0.0026), and higher EuroSCORE II (P=0.0155). At 7.5 years, actuarial survival was 87%±3.6% for female gender vs. 88%±1.9% in male gender (P=0.41), freedom from cardiac death 97%±1.8% vs. 96.6%±1.0% (P=0.6), freedom from major adverse cardiac events (MACE) 87%±6.2% vs. 89.7%±2.5% (P=0.96). Independent predictor of all-causes death and cardiac death was the advanced age (74 years in dead patients vs. 67 years in survivors) (P<0.0001). Female gender was not a predictor of either operative mortality (P=0.34) or worse mid-term outcome (P=0.41). Women undergoing CABG with the same surgical techniques currently adopted for men, do not appear to be associated with worse early prognosis. Freedom from late all-causes mortality, cardiac death and adverse cardiac events are comparable and equally satisfactory, highlighting the positive protective effect of CABG over time also in women.

Long-term results of percutaneous coronary intervention in no-touch vein grafts are significantly better than in conventional vein grafts.

Conventional vein grafts have a high risk of thrombosis and early atherosclerosis. Percutaneous coronary intervention (PCI) in conventional vein grafts is associated with a higher incidence of late adverse cardiac events. The aim of this study was to evaluate the long-term results after PCI in saphenous vein grafts (SVG) harvested with the no-touch technique compared to the conventional technique. This was a single-center, retrospective, cohort study, based on data from the Swedeheart register. The inclusion criterion was individuals who underwent CABG using different vein graft techniques between January 1992 and July 2020, and who required a PCI in SVGs between January 2006 and July 2020. The primary end point was long-term in-stent restenosis. The secondary endpoints were long-term major adverse cardiac events (MACE) and 1-year re-hospitalization rates. The associations between the graft types and the endpoints were evaluated using the Fine and Gray competing-risk regression analysis. The study included 346 individuals (67 no-touch, 279 conventional). The mean clinical follow-up time was 6.4years with a standard deviation of 3.7years. The long-term in-stent restenosis rate for the no-touch grafts was 3.2% compared to 18.7% for the conventional grafts (p < .01), with a subdistribution hazard ratio (SHR) of 0.16 (p = .010). The long-term MACE rate was 27.0% in the no-touch group and 48.3% in the conventional group (p < .01) with a SHR of 0.53 (p = .017). The short-term results were similar in both groups. Percutaneous coronary intervention in a no-touch vein graft was associated with statistically significantly fewer in-stent restenoses and MACE at long-term follow-up compared to a conventional SVG.

Prospective Phase II Trial of Primary Lung Tumor Stereotactic Body Radiation Therapy (SBRT) Followed By Concurrent Mediastinal Chemoradiation and Adjuvant Immunotherapy for Locally-Advanced Non-Small Cell Lung Cancer (LA NSCLC)

To report the efficacy and toxicity outcomes of a prospective phase II trial of primary tumor SBRT followed by conventional chemoradiation to the lymph nodes and adjuvant immunotherapy in patients (pts) with unresectable LA NSCLC. Eligible pts included stage II-III LA NSCLC with peripheral primary tumors ≤ 7cm or centrally based tumors that had at least 2 cm separation from involved nodal disease. Pts received SBRT to the primary tumor (50-54 Gy in 3-5 fractions) followed by standard radiation to 60 Gy in 30 fractions to the involved lymph nodes with concurrent platinum doublet chemotherapy. The trial was amended to allow pts without disease progression after chemoradiation to receive adjuvant durvalumab per the PACIFIC trial. The primary endpoint was 1 year progression free survival (PFS), evaluated as a binary variable. Frequencies and proportions were used for reporting this primary endpoint, in addition to adverse events and patterns of failure. Median PFS and OS were estimated using Kaplan Meier methods. Safety and efficacy is reported on the first 50 pts enrolled in the trial with a median follow-up of 24 months (mos) (range, 1-54 mos). Pts were primarily stage IIIA (60%) or stage IIIB (34%), with 6% of pts stage IIB. Overall grade 3 or higher toxicity related to SBRT and/or mediastinal radiation was 8% with two pts (4%) developing grade 3 pneumonitis and one pt having a grade 5 lung infection possibly related to radiation. Overall grade 2 pneumonitis related to SBRT or mediastinal radiation was 20%. Only one pt (2%) developed grade 3 esophagitis. No late cardiac events have been observed. The one-year PFS for all pts was 62% with a median PFS of 26.3 mos and median overall survival of 40.8 mos. Of the 50 pts enrolled, 37 received at least one dose of adjuvant durvalumab. The one-year PFS for pts who received at least one dose of durvalumab was 70.3% with a median PFS not yet reached in this group (median follow-up 24 mos). Patterns of failure were mostly distant with 26% of pts experiencing distant failure, 6% regional, and 2% distant and regional. There was only one local failure (2%) after SBRT in all 50 pts. SBRT to the primary tumor followed by conventional chemoradiation to the involved lymph nodes and adjuvant immunotherapy was well tolerated and showed improved 1-year PFS compared to prior conventional chemoradiation trials for locally advanced NSCLC. The results of this trial will be further evaluated in a randomized phase III study, NRG LU-008. Pts will receive either conventional chemoradiation vs. SBRT to the primary tumor followed by chemoradiation to the involved lymph nodes followed by consolidative immunotherapy to evaluate the possibility of utilization of SBRT as a new standard of care for LA NSCLC.

One-week external beam partial breast irradiation: survival and toxicity outcomes.

According to ASTRO and ESTRO guidelines, external beam Partial Breast Irradiation (PBI) is a valid option for early-stage breast cancer patients. Nevertheless, there is lack of consensus about the best treatment schedule. We retrospectively analysed data of female patients treated at our institution from 2013 to 2022 with adjuvant "one-week" partial breast irradiation. Clinical Target Volume (CTV) was an isotropic expansion of 15mm from the tumour bed (identified as the breast tissue between surgical clips). The treatment schedule was 30Gy delivered with Volumetric Modulated Arc Therapy in 5 daily fractions. The primary endpoint was Local Control (LC). Disease-Free Survival (DFS), Overall Survival (OS) and safety were secondary endpoints. Three hundred and forty-four patients with a median age of 69 (33-87) years were included in the study.After a median follow-up of 34 (7-105) months, 7 patients (2.0%) developed a local recurrence. Three-year LC, DFS and OS actuarial rates were 97.5% (95% CI 96.2%-98.8%), 95.7% (95% CI 94.2%-97.2%), and 96.9% (95% CI 95.7%-98.1%), respectively. Ten (2.9%) patients experienced grade 2 late toxicities. Five (1.5%) patients reported late cardiac major events. Three (0.9%) late pulmonary toxicities were detected. One hundred and five (30.5%) patients reported fat necrosis. Good or excellent cosmetic evaluation following the Harvard Scale was reported in 252 (96.9%) cases by the physicians, while in 241 (89.2%) cases by the patients. "One-week" PBI is effective and safe, and this schedule is a valid option for highly selected early breast cancer patients.

Cancer and Acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Cardiovascular disease and Cancer are the leading causes of mortality in the world. This is due to the aging of the population and the fact that most of the classic cardiovascular risk factors also predispose to cancer. Cardiovascular disease is the most common cause of late morbidity and mortality among cancer survivors. The incidence of cancer and acute coronary syndrome in the same patient requiring PCI is increasing significantly. The reported prevalence of cancer among patients with acute coronary syndrome ranges between 3% and 17%. In our institution in the past ten months, the prevalence of cancer among patients with ACS who underwent PCI was about 10% (3% in active cancer treatment). Patients with cancer and ACS 41% of patients presented as STEMI, 44% as NSTEMI and 15% as unstable angina. Multivessel coronary disease was confirmed in 36%, Takatsubo was diagnosed in 4%, %=% of patient were treated with percutaneous coronary intervention and stents implantation. They were treated with DAPT; in 39% ticagrelor, 10% prasugrel, others clopidogrel. It was found that lung, prostate, stomach, pancreas and breast cancer are the most common types associated with ACS, which corresponds to our observations. A proinflammatory and hypercoagulable state with increased platelet activation and aggregation commonly occurs in cancer, increasing the prevalence of ACS. New cancer treatments have significantly improved cancer survival, on the other hand, this has at the same time led to an increase in the incidence of CVD. In the general population, NSTEMI is the most common clinical presentation of ACS in cancer patients. MINOCA and Takotsubo syndrome can also occur in cancer patients, more often in women. Percutaneous coronary intervention improves the survival rate of ACS patients, lowering early and late cardiac events. One of the most relevant issues strongly limiting the invasive strategy in cancer patients is the prospect of dual antiplatelet therapy required after PCI. The presence of cancer should not limit the effective and safe treatment of ACS but requires a strict assessment of the risk of bleeding and thrombosis, in both cases with pharmacological and interventional treatment.

MO-0641 Late cardiac events from lymphoma treatment -a meta-regression analysis of dose/response

MO-0641 Late cardiac events from lymphoma treatment -a meta-regression analysis of dose/response

Conflicting results on the role of ECG in risk-stratification for sudden cardiac death in childhood hypertrophic cardiomyopathy.

The research group at University College London introduced the concept of standardizing the quantification of risk by assessing risk of sudden death or equivalent malignant arrhythmia event occurring during the subsequent 5 years of follow-up after diagnosis. While the aims in the recent article by Norrish et al.1 published in this journal are laudable, it is imperative to highlight the methodological shortcomings underlying their analysis. The authors aim to assess the ability of the electrocardiogram (ECG) risk-score and other aspects of the 12-lead ECG to predict ‘major arrhythmic cardiac event’. They selected a subset (356/1029) of the multi-centre cohort of paediatric patients with hypertrophic cardiomyopathy (HCM) used to construct the HCM Risk-Kids algorithm, where ECGs had been archived. This subset however consisted mainly of recently recruited patients, and so median follow-up was only 3.9 years (interquartile range Q1–Q3 2.0–7.7).1 A major concern is that Norrish et al. did not restrict their analysis to include only those survivors who had reached 5 years of follow-up (n = 77 + 68 = 145), and the patients who had a ‘major arrhythmic cardiac event’ within 5 years of follow-up (n = 17). Instead they compared all patients without events, even if 25% of them had <2 years follow-up, with all patients who had major arrhythmic cardiac event, even if 8 of them had an event later than 5 years of follow-up. Thus, in fact, only 17 (patients with major arrhythmic cardiac event within 5 years) + 145 (patients with ≥5 years follow-up without event) = 162 of the patients are actually statistically informative about the end-point of major arrhythmic cardiac event within 5 years.1 This constitutes only 46% of the total ECG group analysed. The other 194 actually confuse the results as patients with high-risk ECG features and short follow-up might have had a major arrhythmic cardiac event later on within the 5-year span. Similarly, the ECGs of patients with major arrhythmic cardiac event after >5 years of follow-up might have evolved more ECG changes closer to the event as shown in other studies.2 Thus including these late major arrhythmic cardiac events will underestimate the sensitivity of the method.

Late cardiac events after allogeneic stem cell transplant: incidence, risk factors, and impact on overall survival

BackgroundThere is limited data on the impact of cardiac disease on long term outcomes of allogeneic stem cell transplant (alloSCT). Our study aims to describe the incidence of late cardiac events after alloSCT, identify risk factors for developing a late cardiac event, and illustrate the impact of late cardiac events on overall survival.MethodsPatients who underwent alloSCT from 2007 to 2017 and survived more than 1 year after transplant (N = 804) were included. Gray’s sub-distribution methods, while accounting for death as a competing risk, were used to calculate the cumulative incidence of late cardiac events. Univariate regression models based on Gray’s sub-distribution were fitted to assess the potential predictive effects of baseline characteristics on the risk of developing any late cardiac events. Univariate Cox proportional hazard regression models were used to evaluate the association between late cardiac events and overall survival.ResultsThe cumulative incidence of a late cardiac event at 5 years after transplant was 22% (95% CI 19–25%). The most frequent cardiac event was a decline in LVEF to < 45% with a cumulative incidence of 9% (95% CI 7–11%). Patients were at significantly increased hazard of developing a late cardiac event if they had a history of congestive heart failure prior to alloSCT (HR 4.53, 95% CI 2.57–7.97, p-value < 0.001), a decline in LVEF to < 45% (HR 3.95, 95% CI 2.09–7.47, p-value < 0.001) or cerebral vascular accident (HR 3.13, 95% CI 1.38–7.06, p-value 0.004). Transplant characteristics such as primary disease, donor type, use of TBI, myeloablative conditioning regimen or tyrosine kinase inhibitor had no significant association with late cardiac events. Almost all cardiac events demonstrated a significantly increased risk of death. This hazard was the highest in patients who experienced an atrial arrhythmia (HR 10.6, 95% CI 7.7–14.6).ConclusionAdverse cardiac events are relatively common late after alloSCT with identifiable risk factors such as medical comorbidities prior to transplant and are associated with a negative impact on overall survival.

Real-World Examination of Revascularization Strategies for Left Main Coronary Disease in Ontario, Canada

BackgroundRandomized trials have compared percutaneous coronary intervention and coronary artery bypass grafting (CABG) in patients with left main coronary artery disease undergoing nonemergent revascularization. However, there is a paucity of real-world contemporary observational studies comparing percutaneous coronary intervention (PCI) and CABG. ObjectivesThe purpose of this study was to compare the long-term clinical outcomes of CABG versus PCI in patients with left main coronary disease. MethodsClinical and administrative databases for Ontario, Canada, were linked to obtain records of all patients with angiographic evidence of left main coronary artery disease (≥50% stenosis) treated with either isolated CABG or PCI from 2008 to 2020. Emergent, cardiogenic shock, and ST-segment elevation myocardial infarction patients were excluded. Baseline characteristics of patients were compared and 1:1 propensity score matching was performed. Late mortality and major adverse cardiac and cerebrovascular events were compared between the matched groups using a Cox proportional hazard model. ResultsAfter exclusions, 1,299 and 21,287 patients underwent PCI and CABG, respectively. Prior to matching, PCI patients were older (age 75.2 vs 68.0 years) and more likely to be women (34.6% vs 20.1%), although they had less CAD burden. Propensity score matching on 25 baseline covariates yielded 1,128 well-matched pairs. There was no difference in early mortality between PCI and CABG (5.5% vs 3.9%; P = 0.075). Over 7-year follow-up, all-cause mortality (53.6% vs 35.2%; HR: 1.63; 95% CI: 1.42-1.87; P < 0.001) and major adverse cardiac and cerebrovascular events (66.8% vs 48.6%; HR: 1.77; 95% CI: 1.57-2.00) were significantly higher with PCI than CABG. ConclusionsCABG was the most common revascularization strategy in this real-world registry. Patients undergoing PCI were much older and of higher risk at baseline. After matching, there was no difference in early mortality but improved late survival and freedom from major adverse cardiac and cerebrovascular events with CABG.

Changes in CT Attenuation Values of Pericardium Months after Radiotherapy as Surrogates for Later Major Cardiotoxicity

<h3>Purpose/Objective(s)</h3> Radiation-induced pericardial disease (RIPD) can manifest as pericardial swelling, thickening, effusion, fluid or calcification. While mostly asymptomatic or underdetected due to self-limiting nature, RIPD could be a surrogate marker for radiation-induced cardiotoxicity. Pericardial screening is not part of standard of care (SOC) for thoracic cancer patients' radiotherapy (RT). Here, we analyze SOC images in patients treated with thoracic RT for radiographically identifiable pericardial changes. We hypothesize that these changes have potential signatures for predicting late major cardiac events. <h3>Materials/Methods</h3> In this retrospective study, pericardium was manually contoured following standard contouring atlases in 30 locally advanced non-small cell lung cancer patients (15 females, 15 males) treated with chemoradiation. A 4mm inner wall was generated as the region of interest. Using pre-RT and (average 10-month) post-RT CT scans, we investigated whether changes in pericardium Hounsfield unit (HU) could predict major late cardiac events reported in patients' clinical records. Taking the effect of contrast-enhancement in some scans into account, HU value ranges representing effusion/fluid, normal tissue and calcification were considered as [-10,30], [31,132] and [133,500], respectively. Support vector machine analysis was performed using data from 24 patients with ≤12 months follow-up for training, and data from the remaining 6 patients for testing. Other parameters of interest for late cardiotoxicity were pericardial doses (mean and max), patient age at the time of RT, sex, history of cardiovascular diagnoses, smoking status, diabetes and hypertension. The CT scans were also revisited by a radiologist for verification of the existence of effusion, fluid, calcification or implants. <h3>Results</h3> In the training group, 11 patients, and in the testing group, 1 patient had a reported major cardiotoxicity several years post-RT. In the cohort of 30 patients, median changes, from pre-RT to post-RT, in the volumes of low, mid, and high HU regions were 17, 24 and 27cc, respectively. In the training set, the volumes of [31,132] HU region showed significant reduction (Mann-Whitney non-parametric test) from pre-RT to post-RT in CT scans of the patients with late cardiotoxicity (p=0.049) compared to those without. Also, patient age at the time of RT was a significant predictor of late cardiotoxicity (p=0.008), while mean dose to pericardium showed borderline significance (p = 0.09). Due to the confounding effect of both contrast-enhancement and implants on the higher HU value analysis, the accuracy of the classification model was limited in training group to 92% and in the test group to 67% (total 4 errors in patients with pre-existing calcifications). <h3>Conclusion</h3> Our preliminary study suggests that radiation-induced cardiotoxicity may be modelled based on patient demographic, dosimetric parameters, and detectable changes in pericardium sac HU volumes.

Radiation-Induced Acute Cardiotoxicity in Women with Left Sided Breast Cancer: Results from a Phase II Prospective Clinical Trial

<h3>Purpose/Objective(s)</h3> Women with left sided breast cancer (BC) who receive adjuvant radiotherapy (RT) have increased risk of subsequent cardiac events, which may be mitigated by maintaining mean heart dose (MHD) below a threshold of 3 Gy. We hypothesized that early MRI evaluation of cardiac functional changes can identify acute cardiac insult and predict for the risk of long-term cardiac complications. Here we report the findings of a phase II prospective clinical trial evaluating RT-related LV structure and function using cardiac MRI in women with left sided BC treated with adjuvant RT. <h3>Materials/Methods</h3> Patients with left sided BC were enrolled into a single institutional phase II study. After informed consent, patients were allocated for breast RT with free breathing (FB) or with deep inspiratory breath hold (DIBH) delivery, if the predicted MHD was ≤3 Gy (≤ 5 Gy, if also regional nodal RT) or > 3 Gy (> 5 Gy, if regional nodal RT), respectively, on initial FB planning. Cardiac MRI was performed at baseline (pre-RT), and at 16 and 52 weeks. Cardiac toxicity was defined as change in the indexed LV end diastolic volume (LVEDVi), LV ejection fraction (LVEF), indexed LV end systolic volume (LVESVi) and indexed LV mass (LV MASSi). Estimation of multiple serum cardiac biomarkers were also done at the three time points. Continuous variables were expressed as mean ± standard deviation, and ANOVA analysis was used to identify correlation between changes in cardiac parameters from baseline to 16 and 52 weeks, when compared to cardiac radiation dosimetric data. <h3>Results</h3> Of the 69 participants, 25 received RT with FB technique. 44 received RT with DIBH, of which 23 also had received adjuvant chemotherapy (CT) prior to RT. For the FB, DIBH (no CT), and DIBH (with CT) cohorts, MHD was 1.70 ± 0.93 Gy, 1.93 ± 1.30 Gy, and 2.26 ± 1.15 Gy and mean LV dose was 2.47 ± 1.48 Gy, 3.18 ± 1.93 Gy, and 3.23 ± 1.82 Gy, respectively. Evaluation of LVEDVi, LVEF, LVESVi, and LV MASSi showed no statistical difference between the 3 treatment arms. No statistical correlation was noted between LVEF changes (≥ 5% and ≥ 10% from baseline) and the cardiac dosimetric data; all p values > 0.1. Prior CT did not measurably impact cardiac function. <h3>Conclusion</h3> In this prospective study, no significant post-RT cardiac events were demonstrable by functional imaging. This supports the significance of maintaining MHD ≤ 3 Gy to minimize or prevent RT related cardiac toxicity in women with left sided BC. Our observation warrants further investigation in a large prospective setting to evaluate late cardiac events. Analysis of serum cardiac biomarkers is currently ongoing.

Surgical Management of Aortic Regurgitation in Takayasu's Arteritis: A Systematic Review of Techniques and Outcomes.

IntroductionTakayasu's arteritis (TA) is an inflammatory condition that affects large vessels and frequently involves the aortic valve causing valve regurgitation. Surgical management is recommended for symptomatic severe aortic regurgitation (AR); however, the optimal surgical approach is yet unclear. This study aims to review surgical treatment options for AR in TA and determine which procedure has a lower chance of late postoperative events and/or mortality. MethodsAn electronic database search was performed within PubMed, EMBASE, Web of Science, and SCOPUS to identify articles from 1975 to 2016 focusing on surgical management of the AR in TA. ResultsTwenty seven studies encompassing a total of 194 cases (77% females) were included. Isolated aortic valve replacement (AVR) was performed in 105/194 cases (54%) (Group A), while combined aortic valve and root replacement (CAVRR) was performed in 87/194 (45%) (Group B). Prosthetic valve detachment was reported in 10/105 cases (9.5%) in group A and 1/87 cases (1.2%) in group B (p = 0.02). Dilation of the residual aorta was reported in 10/105 cases (9.5%) in group A and 1/87 cases (1.2%) in group B (p = 0.02). Any late (≥ 30 d) postoperative cardiac event was reported in 26/105 cases (24.8%) in group A, and in 7/87 cases (8.1%) in group B (p = 0.003). ConclusionsAlthough CAVRR is a more complex procedure, it might offer a better outcome in terms of late postoperative cardiac events compared to isolated AVR procedure. Future prospective studies are required to help determine the best surgical approach in such a population.

Hypofractionated Whole-Breast Irradiation Focus on Coronary Arteries and Cardiac Toxicity-A Narrative Review.

Breast cancer is the most common cancer among women worldwide, which is often treated with radiotherapy. Whole breast irradiation (WBI) is one of the most common types of irradiation. Hypo-fractionated WBI (HF-WBI) reduces the treatment time from 5 to 3 weeks. Recent radiobiological and clinical evidence recommended the use of HF-WBI regardless of the age or stage of disease, and it is proven that hypo-fractionation is non-inferior to conventional fractionation regimen irradiation. However, some studies report an increased incidence of heart-related deaths in the case of breast irradiation by hypo-fractionation, especially in patients with pre-existing cardiac risk factors at the time of treatment. Due to the new technical possibilities of radiotherapy techniques, HF-WBI can reduce the risk of cardiac toxicity by controlling the doses received both by the heart and by the anatomical structures of the heart. The radiobiological “double trouble”, in particular “treble trouble”, for hypo-fractionated regimen scan be avoided by improving the methods of heart sparing based on image-guided irradiation (IGRT) and by using respiration control techniques so that late cardiac toxicity is expected to be limited. However, long-term follow-up of patients treated with HF-WBI with modern radiotherapy techniques is necessary considering the progress of systemic therapy, which is associated with long-term survival, and also the cardiac toxicity of new oncological treatments. The still unknown effects of small doses spread in large volumes on lung tissue may increase the risk of second malignancy, but they can also be indirectly involved in the later development of a heart disease. It is also necessary to develop multivariable radiobiological models that include histological, molecular, clinical, and therapeutic parameters to identify risk groups and dosimetric tolerance in order to limit the incidence of late cardiac events. MR-LINAC will be able to offer a new standard for reducing cardiac toxicity in the future, especially in neoadjuvant settings for small tumors.

Definitive results of a phase III adjuvant trial comparing six cycles of FEC-100 to four cycles of AC in women with operable node-negative breast cancer: the NSABP B-36 trial (NRG Oncology).

Results from adjuvant trials evaluating 6 cycles of epirubicin-based chemotherapy regimens suggested these programs may be more effective than 4 cycles of doxorubicin-based chemotherapy. NSABP B-36 was a phase III clinical trial originally designed as a 2 × 2 factorial study comparing 6 cycles of 5-FU, epirubicin, and cyclophosphamide (FEC-100) to 4 cycles of conventional doxorubicin and cyclophosphamide (AC) with celecoxib or placebo. Shortly after activation, concerns regarding increased cardiovascular risks among selective COX-2 inhibitors resulted in a decision to remove the celecoxib/placebo from the trial. Women with histologically node-negative invasive breast cancer who had undergone primary surgery with a lumpectomy or total mastectomy were eligible. Primary endpoint was disease-free survival (DFS). Between May 2004 and July 2008, 2722 patients were enrolled. Administration of FEC-100 did not result in improvement in DFS compared to AC (HR 1.09; 95% CI 0.92-1.29, p value = 0.31). The effect of FEC-100 compared to AC on DFS was significantly different for receptor-positive (HR 1.32, 95% CI 1.05-1.66) compared to receptor-negative patients (HR 0.86, 95% CI 0.66-1.11) (treatment-by-receptor status interaction p value = 0.02). There was no statistically significant difference in the effect of treatment on overall survival (OS) with FEC-100 compared to AC (HR 1.06; 95% CI 0.84-1.35, p value = 0.61). Overall, Grade 3 and 4 adverse events were more frequent in the FEC-100 group. The results of B-36 do not support use of six-cycle anthracycline-based regimens in node-negative breast cancer. Prolongation of anthracycline-based therapy with FEC-100 does not improve DFS or OS, relative to AC for 4 cycles, and was associated with expected increases in toxicity. A statistically significant interaction between treatment and hormone receptor status favoring AC in hormone-receptor-positive breast cancers is consistent with the hypothesis that optimal duration of chemotherapy may be four cycles in these patients. Late cardiac events and deaths prior to recurrence or second cancer were infrequent on both arms, but slightly higher with FEC-100. ClinicalTrials.gov: NCT00087178.

Prediction of cardiac events following concurrent chemoradiation therapy for non-small-cell lung cancer using FDG PET.

No imaging biomarkers are available for the prediction of cardiac events following concurrent chemoradiation therapy (CCRT) for non-small-cell lung cancer (NSCLC). We evaluated whether F-18 fluorodeoxyglucose positron emission tomography (FDG PET) early after CCRT, in addition to cardiac dosimetry, could predict late cardiac events in NSCLC. We retrospectively enrolled 133 consecutive patients with locally advanced, unresectable stage III NSCLC, who underwent FDG PET early after CCRT and survived at least 6months. The primary endpoint was cardiac event ≥ grade 2 according to the Common Terminology Criteria for Adverse Events (version 5.0). Myocardial FDG uptake was measured and its association with the risk of cardiac events was evaluated. FDG PET was performed after a median interval of 11days of completing CCRT. Overall, 42 (32%) patients experienced cardiac events during a median follow-up of 45months. The mean heart dose, maximum left ventricular (LV) standardized uptake value (SUV), changes in maximum and mean LV SUV, right ventricular uptake, tumor stage, white blood cell count, and diabetes were associated with cardiac events in univariable analysis. In multivariable analysis, maximum LV SUV (cutoff > 12.84; hazard ratio [95% confidence interval] = 2.140 [1.140-4.016]; p = 0.018) was an independent predictor of cardiac events along with the mean heart dose (> 11.1Gy; 3.646 [1.792-7.417]; p < 0.001) and tumor stage (IIIB; 1.986 [1.056-3.734]; p = 0.033). It remained predictive of cardiac events in those with higher mean heart dose but not in those with lower mean heart dose. Early FDG PET after CCRT for NSCLC could aid in predicting late cardiac events, especially in patients with higher mean heart dose.

High-speed rotational atherectomy in coronary artery calcification: The randomized ROTAXUS and PREPARE-CALC trials.

The clinical outcomes of high-speed rotational atherectomy (RA) to optimize target lesion preparation in coronary artery calcification (CAC) have been examined in several trials. This study was conducted to evaluate the safety and efficacy of RA for CAC. Patient data were pooled from ROTAXUS and PREPARE-CALC. The primary endpoint was the in-stent late lumen loss and major adverse cardiac events at 9 months. Secondary endpoints included in-segment late lumen loss, binary restenosis, strategy success, procedural duration, and contrast amount. Four hundred and forty patients were enrolled from Germany in this study, 220 patients were randomized to the RA group and 220 patients were randomized to the Control group. Despite similar baseline characteristics, significantly more patients in the Control group were crossover (14.1% vs. 2.3%, p < 0.0001), resulting in higher strategy success in the RA group (95.0% vs. 82.3%, p < 0.0001). At 9 months, in-stent late lumen loss was higher in the RA group (0.34 ± 0.52 mm vs. 0.24 ± 0.47 mm, p = 0.03) and procedural duration was longer in the RA group (76.3 ± 41.8 min vs. 67.0 ± 38.8 min, p = 0.02). major adverse cardiac events (17.8% vs. 25.2%, p = 0.06), in-segment late lumen loss (0.28 ± 0.66 mm vs. 0.17 ± 0.55 mm, p = 0.05), binary restenosis (7.3% vs. 8.2%, p = 0.71 in-stent; 7.7% vs. 9.0%, p = 0.62 in-segment), and contrast amount (215.5 ± 112.5 ml vs. 203.7 ± 96.5 ml, p = 0.24) were similar in both groups. Lesion preparation with upfront RA before drug-eluting stent implantation is feasible in CAC, is more strategy successful, and is associated with excessive in-stent late lumen loss and excellent clinical outcomes at 9 months although longer procedural duration.

Is Radiation-Induced Cardiac Toxicity Reversible? Prospective Evaluation of Patients With Breast Cancer Enrolled in a Phase 3 Randomized Controlled Trial

Myocardial perfusion defects after breast radiation therapy (RT) correlate with volume of irradiated left ventricle (LV). We aimed to determine the relationship between myocardial perfusion, LV dosimetry, and grade ≥2 late cardiac events in patients with breast cancer undergoing adjuvant RT. A randomized study evaluated the benefit of inverse-planned intensity modulated radiation therapy over forward-planned intensity modulated radiation therapy for radiation toxicity in breast cancer. A secondary endpoint was evaluating cardiac perfusion by single-photon emission computed tomography done at baseline, 6 months, 1 year, 2 years, and 5 years post-RT. We used receiver operating curve and regression analysis to identify association between perfusion, radiation dose-volumes, and the risk of late cardiac events. Of 181 patients who received adjuvant RT, 102 were patients with cancer in the left breast (called in this study the left-sided group) and 79 were patients with cancer in the right breast (called in this study the right-sided group). Median follow-up was 127 months (range, 19-160 months). A significant worsening of perfusion defects occurred after RT in the left-sided group, which improved by 1 year. Late cardiac events were found among 16 patients (17.2%) in the left-sided group and 4 patients (5.5%) in the right-sided group. Perfusion changes did not correlate with late cardiac events, but LV dose-volumes correlated with late cardiac events. Maintaining the LV volume receiving 5 Gy and 10 Gy to <42 cc and <38cc, respectively, can reduce the risk of radiation-related late cardiac events at 10 years to <5% over baseline. RT was associated with short-term perfusion defects that improved within 1 year and was not correlated with late cardiac events. The ventricular volumes receiving 5 Gy and 10 Gy were correlated with late cardiac events.

Revascularization strategies in patients with multivessel coronary artery disease: a Bayesian network meta-analysis.

Summary Treatment modalities for multivessel disease have rapidly evolved, yet the preferred strategy remains controversial. This meta-analysis compared outcomes after on-pump (ONCAB), off-pump coronary artery bypass grafting (OPCAB), percutaneous coronary intervention (PCI) or hybrid coronary revascularization. A comprehensive search for observational studies and randomized controlled trials published by August 2020 was performed. A Bayesian network meta-analysis was conducted for early (<30 days) and late (>12 months) outcomes. A total of 119 studies were included (n = 700 458 patients). The main analysis was confined to 31 randomized controlled trials (n = 24 932 patients). PCI was associated with lower early mortality [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.31–0.79] and stroke (OR 0.22, 95% CI 0.06–0.60) rates compared with ONCAB, whereas a reduced risk of early myocardial infarction was observed with OPCAB compared with ONCAB (OR 0.53, 95% CI 0.32–0.83). Late target vessel revascularization and major adverse cardiac and cerebrovascular events were both increased with PCI compared with ONCAB, OPCAB and hybrid coronary revascularization (by 127–203% and 59–64%, respectively), and late major adverse cardiac events were increased in PCI compared with ONCAB and OPCAB (by 64% and 59%). However, PCI was associated with a significantly lower risk of late stroke compared with ONCAB (OR 0.70, 95% CI 0.52–0.89). Sensitivity analyses (i) including observational studies and (ii) limiting to studies with recent cohorts confirmed the findings of the main analysis. Surgical approaches for revascularization remain superior to PCI in patients with multivessel disease. Hybrid coronary revascularization might be viable for some patients, although more evidence from randomized controlled trials is warranted.

Prediction of radiation-related cardiotoxicity using F-18 FDG PET in non-small-cell lung cancer

Abstract Background Radiation-related cardiotoxicity has been refocused nowadays as the follow-up was increased amomg the patients with advanced lung cancer. The early recognition of the occult cardiotoxicity enables the early intervention preventing clinically significant cardiac events or worsening of severity. Purpose We aim to search whether the F-18 fluorodeoxyglucose positron emission tomography (FDG PET) performed immediately after radiotherapy could predict the late cardiac events. Methods We retrospectively enrolled 133 patients with locally advanced, unresectable stage III NSCLC who underwent F-18 fluorodeoxyglucose positron emission tomography (FDG PET) immediately after CCRT for the response evaluation and survived at least for 6 months. Heart was recontoured according to the RTOG 0617 secondary analysis atlas for the dose volume analysis. Standardized uptake values (SUV) of the left ventricular myocardium were measured on FDG PET images. The patients were regularly followed up for the disease progression and complications. The primary end-point was the cardiac events grade ≥2 based on the Common Terminology Criteria for Adverse Events (version 5.0). Results FDG PET was performed at median interval of 11 days after CCRT. Fourty-two patients experienced cardiotoxicity during a median follow-up of 47 months (range, 12 – 123 months). In univariable analysis, mean heart dose, maximum SUV of the left ventricle (LV SUVmax), white blood cell count, and diabetes were associated with the risk of cardiotoxicity. In multivariable analysis, only higher mean heart dose (&amp;gt;11.1 Gy, hazard ratio 3.930 [95% confidence interval 1.933–7.988]; p=0.0002) and higher LV SUVmax (&amp;gt;12.84, 2.189 [1.162–4.124]; p=0.0152) were independently associated with increased risk of cardiotoxicity. In subgroup analyses, LV SUVmax remained predictive of cardiotoxicity among those with higher mean heart dose, but not among those with lower mean heart dose. Conclusion Early FDG PET after CCRT for NSCLC could predict the late cardiac events, especially in patients with high dose cardiac irradiation. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by a grant of the Basic Science Research Program through the National Research Foundation funded by the Ministry of Education, Republic of Korea (Principal Investigator: Sang-Geon Cho)