Changes in vascular function and correlation with cardiotoxicity in women with newly diagnosed breast cancer undergoing HER2-directed therapy with and without anthracycline/cyclophosphamide.

Aims: The objective of this study was to assess the effect of HER2-directed therapy (HER2-Tx) on peripheral vasoreactivity and its correlation with cardiac function changes and the additive effects of anthracycline/cyclophosphamide (AC) therapy and baseline cardiovascular risk. Methods and results: Single-centre, prospective cohort study of women with newly diagnosed stage 1-3 HER2-positive breast cancer undergoing HER2-Tx +/- AC. All participants underwent baseline and 3-monthly evaluations with Endo-Peripheral Arterial Tonometry (Endo-PAT), vascular biomarkers [C-type natriuretic peptide (CNP) and neuregulin-1 beta (NRG-1ß)], and echocardiography. Cardiotoxicity was defined as a decrease in the left ventricular ejection fraction (LVEF) of >10% to a value <53%. Of the 47 patients enrolled, 20 (43%) received AC in addition to HER2-Tx. Deterioration of reactive hyperaemia index (RHI) on Endo-PAT by ≥20% was more common in patients receiving HER-Tx plus AC than HER2-Tx alone (65% vs. 22%; P = 0.003). A decrease in CNP and log NRG-1ß levels by 1 standard deviation did not differ significantly between the AC and non-AC groups (CNP: 20.0% vs. 7.4%; P = 0.20 and NRG-1ß: 15% vs. 11%; P = 0.69) nor did GLS (35% vs. 37%; P = 0.89). Patients treated with AC had a significantly lower 3D LVEF than non-AC recipients as early as 3 months after exposure (mean 59.3% (SD 3) vs. 63.8% (SD 4); P = 0.02). Reactive hyperaemia index and GLS were the only parameters correlating with LVEF change. Conclusion: Combination therapy with AC, but not HER2-Tx alone, leads to a decline in peripheral vascular and cardiac function. Larger studies will need to define more precisely the causal correlation between vascular and cardiac function changes in cancer patients.

Detection of Early Myocardial Dysfunction by Imaging Biomarkers in Cancer Patients Undergoing Photon Beam vs. Proton Beam Radiotherapy: A Prospective Study.

1. Background: We sought to determine acute and subacute changes in cardiac function after proton beam (PBT) and photon beam (PhT) radiotherapy (RT) using conventional and two-dimensional speckle tracking echocardiography (2D-STE) in patients with malignant breast and thoracic tumors. 2. Methods: Between March 2016 and March 2017, 70 patients with breast or thoracic cancer were prospectively enrolled and underwent transthoracic echocardiography with comprehensive strain analysis at pretreatment, mid-treatment, end of treatment, and 3 months after RT. 3. Results: PBT was used to treat 44 patients; PhT 26 patients. Mean ± SD age was 55 ± 12 years; most patients (93%) were women. The median (interquartile range) of the mean heart dose was lower in the PBT than the PhT group (47 [27-79] vs. 217 [120-596] cGy, respectively; p < 0.001). Ejection fraction did not change in either group. Only the PhT group had reduced systolic tissue Doppler velocities at 3 months. 2D-STE showed changes in endocardial and epicardial longitudinal, radial, and circumferential early diastolic strain rate (SRe) in patients undergoing PhT (global longitudinal SRe, pretreatment vs. end of treatment (p = 0.04); global circumferential SRe, pretreatment vs. at 3-month follow-up (p = 0.003); global radial SRe, pretreatment vs. at 3-month follow-up (p = 0.02) for endocardial values). Epicardial strain values decreased significantly only in patients treated with PhT. Patients in the PhT group had a significant decrease in epicardial global longitudinal systolic strain rate (GLSRs) (epicardial GLSRs, at baseline vs. at end of treatment [p = 0.009]) and in GCSRe and GRSRe (epicardial GCSRe, at baseline vs. at 3-month follow-up (p = 0.02); epicardial GRSRe, at baseline vs. at 3-month follow-up (p = 0.03)) during treatment and follow-up. No changes on 2D-STE were detected in the PBT group. 4. Conclusions: Patients who underwent PhT but not PBT had reduced tissue Doppler velocities and SRe values during follow-up, suggesting early myocardial relaxation abnormalities. PBT shows promise as a cardiac-sparing RT technology.

Conventional versus hypofractionated postmastectomy proton radiotherapy in the USA (MC1631): a randomised phase 2 trial.

BACKGROUND: Proton therapy is under investigation in breast cancer as a strategy to reduce radiation exposure to the heart and lungs. So far, studies investigating proton postmastectomy radiotherapy (PMRT) have used conventional fractionation over 25-28 days, but whether hypofractionated proton PMRT is feasible is unclear. We aimed to compare conventional fractionation and hypofractionation in patients with indications for PMRT, including those with immediate breast reconstruction. METHODS: We did a randomised phase 2 trial (MC1631) at Mayo Clinic in Rochester (MN, USA) and Mayo Clinic in Arizona (Phoenix, AZ, USA) comparing conventional fractionated (50 Gy in 25 fractions of 2 Gy [relative biological effectiveness of 1·1]) and hypofractionated (40·05 Gy in 15 fractions of 2·67 Gy [relative biological effectiveness of 1·1]) proton PMRT. All patients were treated with pencil-beam scanning. Eligibility criteria included age 18 years or older, an Eastern Cooperative Oncology Group performance status of 0-2, and breast cancer resected by mastectomy with or without immediate reconstruction with indications for PMRT. Patients were randomly assigned (1:1) to either conventional fractionation or hypofractionation, with presence of immediate reconstruction (yes vs no) as a stratification factor, using a biased-coin minimisation algorithm. Any patient who received at least one fraction of protocol treatment was evaluable for the primary endpoint and safety analyses. The primary endpoint was 24-month complication rate from the date of first radiotherapy, defined as grade 3 or worse adverse events occurring from 90 days after last radiotherapy or unplanned surgical interventions in patients with immediate reconstruction. The inferiority of hypofractionation would not be ruled out if the upper bound of the one-sided 95% CI for the difference in 24-month complication rate between the two groups was greater than 10%. This trial is registered with ClinicalTrials.gov, NCT02783690, and is closed to accrual. FINDINGS: Between June 2, 2016, and Aug 23, 2018, 88 patients were randomly assigned (44 to each group), of whom 82 received protocol treatment (41 in the conventional fractionation group and 41 in the hypofractionation group; median age of 52 years [IQR 44-64], 79 [96%] patients were White, two [2%] were Black or African American, one [1%] was Asian, and 79 [96%] were not of Hispanic ethnicity). As of data cutoff (Jan 30, 2023), the median follow-up was 39·3 months (IQR 37·5-61·2). The median mean heart dose was 0·54 Gy (IQR 0·30-0·72) for the conventional fractionation group and 0·49 Gy (0·25-0·64) for the hypofractionation group. Within 24 months of first radiotherapy, 14 protocol-defined complications occurred in six (15%) patients in the conventional fractionation group and in eight (20%) patients in the hypofractionation group (absolute difference 4·9% [one-sided 95% CI 18·5], p=0·27). The complications in the conventionally fractionated group were contracture (five [12%] of 41 patients]) and fat necrosis (one [2%] patient) requiring surgical intervention. All eight protocol-defined complications in the hypofractionation group were due to infections, three of which were acute infections that required surgical intervention, and five were late infections, four of which required surgical intervention. All 14 complications were in patients with immediate expander or implant-based reconstruction. INTERPRETATION: After a median follow-up of 39·3 months, non-inferiority of the hypofractionation group could not be established. However, given similar tolerability, hypofractionated proton PMRT appears to be worthy of further study in patients with and without immediate reconstruction. FUNDING: The Department of Radiation Oncology, Mayo Clinic, Rochester, MN, the Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, USA, and the US National Cancer Institute.

Fate of concomitant tricuspid regurgitation in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Owing to a lack of supportive data, tricuspid regurgitation (TR) is usually not addressed in patients undergoing coronary artery bypass grafting (CABG). Here we evaluated changes in TR degrees over time and its impact on survival in patients undergoing CABG. METHODS: We reviewed the data of 9726 patients who underwent isolated CABG between January 2000 and January 2021. According to preoperative TR severity, patients were stratified into nonsignificant (none to trivial, mild) and significant (moderate to severe) TR groups. We excluded patients who had undergone previous tricuspid valve surgery, pacemaker placement, and concomitant valve or ablative surgery. Propensity score matching and Cox proportional hazards models were used to identify associations between TR grade and the primary outcome of all-cause mortality. The secondary outcome was change in TR severity on the last echocardiogram. RESULTS: After propensity score matching, 380 patients in each group were identified. At baseline, 359 patients had moderate TR (94.5%) and 21 (5.5%) had severe TR. On the last follow-up echocardiogram, TR had improved in 40.5% of the patients in the significant TR group. Kaplan-Meier survival curves showed significantly lower survival in patients with significant preoperative TR compared to those with nonsignificant TR (P < .001). After adjusting for other confounders, survival was no worse in the patients with significant TR group (hazard ratio, 1.05; 95% confidence interval, 0.80-1.38; P = .70). CONCLUSIONS: Significant preoperative TR improved in 40.5% of patients after isolated CABG. After adjusting for other factors, significant TR did not affect long-term survival.

CAR-T Therapy in Lymphoma Patients With Coexisting Cardiomyopathy or Cardiac Lymphomatous Involvement.

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the management of aggressive hematologic malignancies. However, its role in patients with lymphoma and cardiac metastasis or cardiomyopathy remains undefined due to potentially life-threatening complications such as ventricular rupture, cardiac tamponade, and circulatory failure. We present a case series of patients with lymphoma and cardiomyopathy or cardiac metastasis managed with chimeric antigen receptor T-cell therapy. (Level of Difficulty: Advanced.).

Association of Anthracycline With Heart Failure in Patients Treated for Breast Cancer or Lymphoma, 1985-2010.

Importance: Anthracyclines increase the risk for congestive heart failure (CHF); however, long-term cumulative incidence and risk factors for CHF after anthracycline therapy are not well defined in population-based studies. Objective: To compare the long-term cumulative incidence of CHF in patients with breast cancer or lymphoma treated with anthracycline therapy compared with healthy controls from the same community. Design, Setting, and Participants: This retrospective population-based case-control study included data from the Rochester Epidemiology Project. Participants included residents of Olmsted County, Minnesota, diagnosed with breast cancer or lymphoma from January 1985 through December 2010 matched for age, sex, and comorbidities with healthy controls, with a final ratio of 1 case to 1.5 controls. Statistical analysis was performed between July 2017 and February 2022. Exposures: Cancer treatment and CHF risk factors. Main Outcomes and Measures: The main outcome was new-onset CHF, as defined by the modified Framingham criteria. Cox proportional hazards regression was used to estimate hazard ratios (HRs) to compare the risk of CHF in participants with cancer vs controls, adjusted for age, sex, diabetes, hypertension, hyperlipidemia, coronary artery disease, obesity, and smoking history. Results: A total of 2196 individuals were included, with 812 patients with cancer and 1384 participants without cancer. The mean (SD) age was 52.62 (14.56) years and 1704 participants (78%) were female. Median (IQR) follow-up was 8.6 (5.2-13.4) years in the case group vs 12.5 (8.7-17.5) years in the control group. Overall, patients with cancer had higher risk of CHF compared with the control cohort even after adjusting for age, sex, diabetes, hypertension, coronary artery disease, hyperlipidemia, obesity, and smoking status (HR, 2.86 [95% CI, 1.90-4.32]; P < .001). After adjusting for the same variables, CHF risk was greater for patients with cancer receiving anthracycline (HR, 3.25 [95% CI, 2.11-5.00]; P < .001) and was attenuated and lost statistical significance for patients with cancer not receiving anthracyclines (HR, 1.78 [95% CI, 0.83-3.81]; P = .14). Higher cumulative incidence for patients treated with anthracyclines vs comparator cohort was observed at 1 year (1.81% vs 0.09%), 5 years (2.91% vs 0.79%), 10 years (5.36% vs 1.74%), 15 years (7.42% vs 3.18%), and 20 years (10.75% vs 4.98%) (P < .001). There were no significant differences in risk of CHF for patients receiving anthracycline at a dose of less than 180 mg/m2 compared with those at a dose of 180 to 250 mg/m2 (HR, 0.54 [95% CI, 0.19-1.51]) or at a dose of more than 250 mg/m2 (HR, 1.23 [95% CI, 0.52-2.91]). At diagnosis, age was an independent risk factor associated with CHF (HR per 10 years, 2.77 [95% CI, 1.99-3.86]; P < .001). Conclusions and Relevance: In this retrospective population-based case-control study, anthracyclines were associated with an increased risk of CHF early during follow-up, and the increased risk persisted over time. The cumulative incidence of CHF in patients with breast cancer or lymphoma treated with anthracyclines at 15 years was more than 2-fold that of the control group.

Age, Hypertension, and Exercise Capacity are Independently Associated with Likelihood of Multi-Vessel Disease in Patients Referred for Treadmill Exercise Testing: The Intermediate-High-Workload Treadmill Score (IHWTS).

Background: To identify factors that increase the specificity of the treadmill exercise test (TMET), and develop a novel scoring system which accounts for functional capacity to aid in determining the need for further testing. Methods: We retrospectively evaluated the electronic health records of 600 patients who had positive TMET results and follow-up stress echocardiography from 1-January-2004, through 31-December-2016. Correlations between clinical and aerobic variables and multivessel disease (MVD) were determined. Duke Treadmill Score (DTS) was calculated and compared with a novel scoring system titled the Intermediate-High-Workload Treadmill Score (IHWTS) that used variables associated with MVD. Results: In total, 124 of 600 patients (21%) had coronary catheterization, and 51 of these patients (41%) had MVD. Mean (SD) DTS was -2.10 (6.3) among patients with MVD vs -0.16 (5) among patients without MVD (p = 0.06). Mean (SD) functional aerobic capacity (FAC) was 76% (20%) among patients with MVD vs 90% (21%) among patients without MVD (p < 0.001). Mean (SD) metabolic equivalent (MET) was 7 (2) among patients with MVD vs 8 (2) among patients without MVD (p = 0.002). Only 6 (12%) of patients with MVD achieved 9 MET or greater on TMET. DTS less than 4 did not distinguish between patients with and without MVD (p = 0.67). Age, hypertension and FAC were independently associated with MVD (all p < 0.05). Conclusions: Our novel scoring system IHWTS utilized age, hypertension, and FAC appeared comparable to DTS to risk-stratify patients regardless of baseline symptoms. Clinical parameters such as hypertension along with exercise functional capacity should be considered when evaluating a positive TMET result in patients that achieve an intermediate-high workload > 5 Metabolic Equivalents (METs).

Characterization of myocardial mechanics and its prognostic significance in patients with severe aortic stenosis undergoing aortic valve replacement.

Aims: Aortic stenosis (AS) induces characteristic changes in left ventricular (LV) mechanics that can be reversed after aortic valve replacement (AVR). We aimed to comprehensively characterize LV mechanics before and after AVR in patients with severe AS and identify predictors of short-term functional recovery and long-term survival. Methods and results: We prospectively performed comprehensive strain analysis by 2D speckle-tracking echocardiography in 88 patients with severe AS and LV ejection fraction ≥50% (mean age 71 ± 12 years, 42% female) prior to and within 7 days after AVR. Patients were followed for up to 5.2 years until death from any cause or last encounter. Within days after AVR, we observed an absolute increase in global longitudinal strain (GLS) (-16.0 ± 2.0% vs. -18.5 ± 2.1%, P<0.0001) and a decrease in apical rotation (10.5 ± 4.0° vs. 8.3 ± 2.8°, P = 0.0002) and peak systolic twist (18.2 ± 5.0° vs. 15.5 ± 3.8°, P = 0.0008). A baseline GLS is less negative than -16.2% was 90% sensitive and 67% specific in predicting a ≥ 20% relative increase in GLS. During a median follow-up of 3.8 years, a global circumferential systolic strain rate (GCSRs) less negative than -1.9% independently predicted lower survival. Conclusion: In patients with severe AS, a reversal in GLS, apical rotation, and peak systolic twist abnormalities towards normal occurs within days of AVR. Baseline GLS is the strongest predictor of GLS recovery but neither was associated with long-term survival. In contrast, abnormal baseline GCSRs are associated with worse outcomes.

Concrete proof of Murphy's law: a case report of intracardiac cement embolization.

Background: The literature describing the complications following kyphoplasty is limited. This case report is a reminder that novel therapeutic strategies can be associated with unexpected complications. Case summary: A 61-year-old woman with rheumatoid arthritis and degenerative lumbar disc disease underwent open posterior instrumented fusion with bilateral open L2 vertebroplasty elsewhere. A month after discharge, she presented to our institution with acute chest pain and dyspnoea. A subsequent gated cardiac computed tomography (CT) angiogram showed three distinct cardiopulmonary emboli. One of the cement fragments had perforated the inferior wall of the right ventricle close to the base of the posterior tricuspid valve leaflet with a moderate circumferential pericardial effusion. Operative extraction of multiple cement emboli as well as repair of the tricuspid valve was pursued. Postoperative echocardiogram showed trivial tricuspid regurgitation after repair. The patient had an uneventful postoperative course and was discharged from the hospital on postoperative Day 5. Discussion: Cement embolization following kyphoplasty can be associated with serious complications such as vascular injury, hypoxaemia, pulmonary artery obstruction, and cardiac perforation. Clinicians must maintain a high index of suspicion as cement embolism may not always present acutely.

Advances in Multimodality Imaging in Cardio-Oncology: JACC State-of-the-Art Review.

The population of patients with cancer is rapidly expanding, and the diagnosis and monitoring of cardiovascular complications greatly rely on imaging. Numerous advances in the field of cardio-oncology and imaging have occurred in recent years. This review presents updated and practical approaches for multimodality cardiovascular imaging in the cardio-oncology patient and provides recommendations for imaging to detect the myriad of adverse cardiovascular effects associated with antineoplastic therapy, such as cardiomyopathy, atherosclerosis, vascular toxicity, myocarditis, valve disease, and cardiac masses. Uniquely, we address the role of cardiovascular imaging in patients with pre-existing cardiomyopathy, pregnant patients, long-term survivors, and populations with limited resources. We also address future avenues of investigation and opportunities for artificial intelligence applications in cardio-oncology imaging. This review provides a uniform practical approach to cardiovascular imaging for patients with cancer.

Pulmonary artery capacitance and pulmonary vascular resistance as prognostic indicators in acute pulmonary embolism.

Aims: The non-invasive calculation of right ventricular (RV) haemodynamics as pulmonary artery (PA) capacitance (PAC) and pulmonary vascular resistance (PVR) have proved to be feasible, easy to perform, and of high prognostic value. We, therefore, evaluated whether baseline PAC and PVR could predict clinical outcomes for patients with acute pulmonary embolism (PE). Methods and results: We prospectively followed 373 patients [mean (standard deviation) age, 64.1 (14.9) years; 58.4% were men, and 27.9% had cancer] who had acute PE and transthoracic echocardiography within 1 day of diagnosis from 1 March 2013 through 30 June 2020. Pulmonary artery capacitance was calculated as left ventricular stroke volume/(PA systolic pressure - PA diastolic pressure). Pulmonary vascular resistance was calculated as (tricuspid regurgitant velocity/RV outflow tract velocity time integral) × 10 + 0.16. These two variables were calculated retrospectively from the values obtained with transthoracic echocardiography. Pulmonary artery capacitance was acquired in 99 (27%) patients and PVR in 65 (17%) patients. Univariable and bivariable logistic regression analyses, and receiver operating characteristic curves were used to evaluate the ability of these haemodynamic measurements to predict mortality up to 6 months. After using bivariable models to adjust individually for age, cancer, and pulmonary hypertension. Pulmonary vascular resistance was associated with all-cause mortality at 3 months [area under the curve (AUC) 0.75, 95% confidence interval (CI) 0.61-0.86; P = 0.01], and 6 months (AUC 0.81; 95% CI 0.69-0.91; P ≤ 0.03). Pulmonary artery capacitance was associated with all-cause mortality at 30 days (AUC 0.95; 95% CI 0.82-0.99; P < 0.001) and 3 months (AUC 0.84; 95% CI 0.65-0.99; P = 0.003). Conclusion: Non-invasive measurement of RV haemodynamics could provide prognostic information of patients with acute PE. Pulmonary artery capacitance and PVR are potentially important predictors of all-cause mortality in these patients and should be explored in future studies.

Serial Left and Right Ventricular Strain Analysis in Patients Recovered from COVID-19.

BACKGROUND: Strain analysis of transthoracic echocardiography (TTE) is a sensitive tool to detect myocardial dysfunction in those affected by COVID-19. Consideration of preexisting cardiovascular disease is important in detecting changes related to COVID-19. We sought to assess serial TTE changes in patients recovered from COVID-19 compared with baseline, pre-COVID-19 exams, with a focus on left and right ventricular longitudinal strain. METHODS: This retrospective review of serial TTEs in confirmed COVID-19 patients at Mayo Clinic sites included patients who had a TTE within 2 years prior to confirmed COVID-19 diagnosis, and the first available outpatient TTE after diagnosis was used as a comparison. Patients with interval cardiac surgery, procedure, or device placement (n = 9) were excluded. Biventricular strain was retrospectively performed on both echocardiograms. RESULTS: Of 259 individuals, ages 60 ± 16 years, 47% female, and 88% Caucasian, post-COVID-19 TTEs were performed a median of 55 days (interquartile range, 37-92) following diagnosis. No clinically significant TTE changes were noted, although left ventricular ejection fraction was higher (58% vs 57%, P = .049) and tricuspid annulus plane systolic excursion was lower (20 vs 21 mm, P = .046) following COVID-19. Baseline left ventricular global longitudinal strain (LV GLS) and right ventricular free wall strain (RV FWS) were normal (-19.6% and -25.8%, respectively) and similar following COVID-19 (-19.6% and -25.7%, P = .07 and .77, respectively). In the 74 inpatients, no significant change from baseline was seen for LV GLS (-19.4% vs -19.1%, P = .62), RV FWS (-25.5% vs -25.0%, P = .69), or left ventricular ejection fraction (57% vs 57%, P = .71). A significant worsening in strain occurred in 27 patients, 16 (6.8%) of the 237 with LV GLS and 14 (6.0%) of the 235 with RV FWS. Ten (20%) patients reporting new symptoms following COVID-19 had worsened strain, compared with 5 (7%) with persistent/progressive symptoms and 11 (9%) with no new symptoms (P = .04). CONCLUSIONS: While patients with new symptoms following COVID-19 were more likely to have a worsening in absolute strain values, no clinically significant change in TTE parameters was evident in most patients following COVID-19 regardless of symptom status.

Automated Global Longitudinal Strain Exhibits a Robust Association with Death in Asymptomatic Chronic Aortic Regurgitation.

BACKGROUND: Whether automated left ventricular global longitudinal strain (LVGLS) is associated with outcomes in patients with asymptomatic aortic regurgitation (AR) is unknown. The aim of this study was to explore the impact of automated LVGLS on survival and compare it with conventional left ventricular (LV) parameters in patients with chronic asymptomatic AR. METHODS: LVGLS (presented as an absolute value) was measured using fully automated two-dimensional strain software in consecutive patients with isolated chronic moderate to severe or greater AR between 2004 and 2020; the incremental value of LVGLS was assessed. Limited correction of endocardial border tracking was performed if needed. RESULTS: Of 550 asymptomatic patients (mean age, 60 ± 17 years; 86% men), average LVGLS was 17 ± 3% (first and second tertiles, 15.8% and 18.5%). In 16% of cases, tracking border was partially corrected; average time for analysis was 25 ± 5 sec. At a median of 4.8 years (interquartile range, 1.5-9.9 years), 87 patients had died (19 died after aortic valve surgery). Separate multivariable models adjusted for age, sex, Charlson index, AR severity, and time-dependent aortic valve surgery demonstrated that LV ejection fraction (hazard ratio [HR] per 10%, 0.9), LV end-systolic volume index (LVESVi; HR per 5 mL/m2, 1.08) and LVGLS (HR per unit, 0.87) were independently associated with death (P ≤ .018 for all); however, LVGLS remained statistically significant (HR: 0.86-0.9; P ≤ .007) when compared head-to-head with LV ejection fraction, LVESVi, and LV end-systolic dimension index. The association of LVGLS and mortality was consistent across all subgroups (P for interaction ≥ .08 for all). Spline curves showed that continuous risk for death rose at LVGLS < 15%. Those with LVGLS < 15% had a 2.6-fold risk for death (95% CI, 1.54-4.23) while those with LVGLS < 15% plus LVESVi ≥ 45 mL/m2 had 3.96-fold risk (95% CI, 1.94-8.03). CONCLUSIONS: In this large cohort of asymptomatic patients with moderate to severe or greater AR, automated LVGLS was feasible, efficient, and independently associated with death in head-to-head comparisons with conventional LV ejection fraction, LV end-systolic dimension index, and LVESVi. An automated LVGLS threshold of <15% alone or combined with LVESVi ≥ 45 mL/m2 was significantly associated with increased mortality risk and may be considered in early surgery decision-making.

Stress Echo 2030: The Novel ABCDE-(FGLPR) Protocol to Define the Future of Imaging.

With stress echo (SE) 2020 study, a new standard of practice in stress imaging was developed and disseminated: the ABCDE protocol for functional testing within and beyond CAD. ABCDE protocol was the fruit of SE 2020, and is the seed of SE 2030, which is articulated in 12 projects: 1-SE in coronary artery disease (SECAD); 2-SE in diastolic heart failure (SEDIA); 3-SE in hypertrophic cardiomyopathy (SEHCA); 4-SE post-chest radiotherapy and chemotherapy (SERA); 5-Artificial intelligence SE evaluation (AI-SEE); 6-Environmental stress echocardiography and air pollution (ESTER); 7-SE in repaired Tetralogy of Fallot (SETOF); 8-SE in post-COVID-19 (SECOV); 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE); 10-SE for mitral ischemic regurgitation (SEMIR); 11-SE in valvular heart disease (SEVA); 12-SE for coronary vasospasm (SESPASM). The study aims to recruit in the next 5 years (2021-2025) ≥10,000 patients followed for ≥5 years (up to 2030) from ≥20 quality-controlled laboratories from ≥10 countries. In this COVID-19 era of sustainable health care delivery, SE2030 will provide the evidence to finally recommend SE as the optimal and versatile imaging modality for functional testing anywhere, any time, and in any patient.

Anthracycline treatment, cardiovascular risk factors and the cumulative incidence of cardiovascular disease in a cohort of newly diagnosed lymphoma patients from the modern treatment era.

The development of cardiovascular disease (CVD) in long-term survivors of lymphoma is of increasing importance. Here, we characterize the cumulative incidence and risk factors for CVD in lymphoma patients diagnosed in the current treatment era. From 2002-2015, newly diagnosed lymphoma patients (>18 years) were enrollment into a prospective cohort study that captured incident CVD, consisting of congestive heart failure (CHF), acute coronary syndrome (ACS), valvular heart disease (VHD), and arrhythmia. The cumulative incidence of CVD was calculated with death modeled as a competing risk. We estimated the association of treatment with anthracyclines or radiotherapy and traditional CVD risk factors with incidence of CVD using hazard ratios (HR) and 95% confidence intervals (CI) estimated from Cox regression. After excluding prevalent CVD at lymphoma diagnosis, the study consisted of 3063 patients with a median age of 59 years (range 18-95). The cumulative incidence of CVD at 10-years was 10.7% (95% CI, 9.5%-12.1%). In multivariable analysis, increasing age (HR = 1.05 per year, p < 0.001), male sex (HR = 1.36, p = 0.02), current smoker (HR = 2.10, p < 0.001), BMI > 30 kg/m2 (HR = 1.45, p = 0.01), and any anthracycline treatment (HR = 1.57, p < 0.001) were all significantly associated with risk of CVD. Anthracyclines were associated with increased risk of CHF (HR = 2.71, p < 0.001) and arrhythmia (HR = 1.61, p < 0.01), but not VHD (HR = 0.84, p = 0.58) or ACS (HR = 1.32, p = 0.24) after adjustment for CVD risk factors. Even in the modern treatment era, CVD remains common in lymphoma survivors and preventive efforts are required that address both treatment and CVD risk factors.

Outcomes of cardiac resynchronization therapy in patients with chemotherapy-induced cardiomyopathy.

BACKGROUND: Several chemotherapy agents are associated with the development of non-ischemic cardiomyopathy (NIC). When chemotherapy-induced cardiomyopathy (CHIC) is associated with left bundle branch block (LBBB) and a left ventricular ejection fraction (LVEF) 35% or lower, cardiac resynchronization therapy (CRT) is often utilized to improve cardiac function and relieve symptoms. OBJECTIVE: To determine the echocardiographic and clinical outcomes of CRT in patients with CHIC. METHODS: The study included 29 patients with CHIC (CHIC group) and 58 patients with other types of NIC (control group) who underwent CRT implantation between 2004 and 2017. The primary endpoints were changes in LVEF, left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD) at 6-18 months after CRT. The secondary outcomes included changes in left ventricular global longitudinal strain (GLS), systolic strain rate (SRS), early diastolic strain rate (SRE), and overall survival. RESULTS: Out of 29 patients with CHIC, 62.1% received chemotherapy for lymphoma, 13.7% for breast cancer, and 24.1% for sarcoma. The agent implicated in 93.1% of the patients was an anthracycline. Half of the patients had LBBB. The mean baseline LVEF was 28% ± 8%. The mean baseline QRS duration was 146 ± 26 ms. Twenty-eight patients had post-CRT follow-up data. CRT was associated with improvement in echocardiographic outcomes in the CHIC group and the control group. There was no difference in overall survival between the two groups (log-rank p = .148). CONCLUSION: CRT improves left ventricular function and reverses remodeling in patients with CHIC.

Radiation-Induced Heart Disease.

Cancer incidence and survivorship have had a rising tendency over the last two decades due to better treatment modalities. One of these is radiation therapy (RT), which is used in 20-55% of cancer patients, and its basic principle consists of inhibiting proliferation or inducing apoptosis of cancer cells. Classically, photon beam RT has been the mainstay therapy for these patients, but, in the last decade, proton beam has been introduced as a new option. This newer method focuses more on the tumor and affects less of the surrounding normal tissue, i.e., the heart. Radiation to the heart is a common complication of RT, especially in patients with lymphoma, breast, lung, and esophageal cancer. The pathophysiology is due to changes in the microvascular and macrovascular milieu that can promote accelerated atherosclerosis and/or induce fibrosis of the myocardium, pericardium, and valves. These complications occur days, weeks, or years after RT and the risk factors associated are high radiation doses (>30 Gy), concomitant chemotherapy (primarily anthracyclines), age, history of heart disease, and the presence of cardiovascular risk factors. The understanding of these mechanisms and risk factors by physicians can lead to a tailored assessment and monitorization of these patients with the objective of early detection or prevention of radiation-induced heart disease. Echocardiography is a noninvasive method which provides a comprehensive evaluation of the pericardium, valves, myocardium, and coronaries, making it the first imaging tool in most cases; however, other modalities, such as computed tomography, nuclear medicine, or cardiac magnetic resonance, can provide additional value.

Cardiovascular Care of the Oncology Patient During COVID-19: An Expert Consensus Document From the ACC Cardio-Oncology and Imaging Councils.

In response to the coronavirus disease 2019 (COVID-19) pandemic, the Cardio-Oncology and Imaging Councils of the American College of Cardiology offers recommendations to clinicians regarding the cardiovascular care of cardio-oncology patients in this expert consensus statement. Cardio-oncology patients-individuals with an active or prior cancer history and with or at risk of cardiovascular disease-are a rapidly growing population who are at increased risk of infection, and experiencing severe and/or lethal complications by COVID-19. Recommendations for optimizing screening and monitoring visits to detect cardiac dysfunction are discussed. In addition, judicious use of multimodality imaging and biomarkers are proposed to identify myocardial, valvular, vascular, and pericardial involvement in cancer patients. The difficulties of diagnosing the etiology of cardiovascular complications in patients with cancer and COVID-19 are outlined, along with weighing the advantages against risks of exposure, with the modification of existing cardiovascular treatments and cardiotoxicity surveillance in patients with cancer during the COVID-19 pandemic.

The Many Faces of Itraconazole Cardiac Toxicity.

Itraconazole is well known for carrying a black-box warning for new or worsening congestive heart failure. Single cases of other cardiac- and fluid-related disturbances have been reported periodically since its issuance. We describe a large cohort of patients on itraconazole experiencing a breadth of cardiac- and fluid-related toxicities, ranging from new-onset hypertension to cardiac arrest. A retrospective, single-center, large case series at a large tertiary medical center was conducted. Patients with itraconazole and cardiac toxicity-including hypertension, cardiomyopathy, reduced ejection fraction, and edema-in medical record between January 1, 1999, and May 21, 2019, were identified and assigned a Naranjo score; 31 patients were included with a Naranjo score of 5 or higher. There were slightly more male subjects than female subjects, average age was 66, and all subjects were Caucasian. Median time until presentation of adverse effects was 4 weeks (range: 0.3 to 104 weeks). Most common symptom was edema (74% of patients), followed by heart failure without and with preserved ejection fraction (19.4% and 22.6% of patients, respectively). Worsening or new hypertension was also common (25.8% of patients). Rarer were pulmonary edema, pericardial effusion, and cardiac arrest that occurred in 1 patient. In most cases, clinicians stopped itraconazole (74%) or decreased itraconazole dose (19%), resulting in improvement or resolution of symptoms. In 4 cases, the adverse effect did not resolve. Itraconazole can cause a range of possible serious cardiac and fluid-associated adverse events. Dose decrease or cessation usually resulted in symptomatic improvement or reversal.