The Cardiovascular Risks Associated with Aromatase Inhibitors, Tamoxifen, and GnRH Agonists in Women with Breast Cancer.

PURPOSE OF REVIEW: Cardiovascular disease accounts for up to 10% of all-cause mortality in women with a diagnosis of breast cancer, and the causes for this are multifaceted. Many women at risk of or with a diagnosis of breast cancer are on endocrine-modulating therapies. It is therefore important to understand the effect of hormone therapies on cardiovascular outcomes in breast cancer patients to mitigate against any adverse effects and to identify those most at risk so that they can be proactively managed. Here we discuss the pathophysiology of these agents, their effect on the cardiovascular system, and the latest evidence on their cardiovascular risks association. RECENT FINDINGS: Tamoxifen appears to be cardioprotective during treatment but not over the longer term, while the effect of AIs on cardiovascular outcomes remains controversial. Heart failure outcomes remain understudied, and the cardiovascular effects of gonadotrophin-releasing hormone agonists (GNRHa) in women need further research, especially since data from men with prostate cancer have indicated an increased risk of cardiac events in GNRHa users. There remains a need for a greater understanding of the effects of hormone therapies on cardiovascular outcomes in breast cancer patients. Further areas of research in this area include developing evidence to better define the optimal preventive and screening methods for cardiovascular effects and the risk factors for patients on hormonal therapies.

Atorvastatin for Anthracycline-Associated Cardiac Dysfunction: The STOP-CA Randomized Clinical Trial.

Importance: Anthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use. Objective: To test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction. Design, Setting, and Participants: Double-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022. Interventions: Participants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months. Main Outcomes and Measures: The primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of <55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months. Results: Of the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P = .001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P = .26). The number of serious related adverse events was low and similar between groups. Conclusions and Relevance: Among patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use. Trial Registration: ClinicalTrials.gov Identifier: NCT02943590.

Multimodality imaging to distinguish between benign and malignant cardiac masses.

BACKGROUND: To compare the diagnostic accuracy of CMR and FDG-PET/CT and their complementary role to distinguish benign vs malignant cardiac masses. METHODS: Retrospectively assessed patients with cardiac mass who underwent CMR and FDG-PET/CT within a month between 2003 and 2018. RESULTS: 72 patients who had CMR and FDG-PET/CT were included. 25 patients (35%) were diagnosed with benign and 47 (65%) were diagnosed with malignant masses. 56 patients had histological correlation: 9 benign and 47 malignant masses. CMR and FDG-PET/CT had a high accuracy in differentiating benign vs malignant masses, with the presence of CMR features demonstrating a higher sensitivity (98%), while FDG uptake with SUVmax/blood pool ≥ 3.0 demonstrating a high specificity (88%). Combining multiple (> 4) CMR features and FDG uptake (SUVmax/blood pool ratio ≥ 3.0) yielded a sensitivity of 85% and specificity of 88% to diagnose malignant masses. Over a mean follow-up of 2.6 years (IQR 0.3-3.8 years), risk-adjusted mortality were highest among patients with an infiltrative border on CMR (adjusted HR 3.1; 95% CI 1.5-6.5; P = .002) or focal extracardiac FDG uptake (adjusted HR 3.8; 95% CI 1.9-7.7; P < .001). CONCLUSION: Although CMR and FDG-PET/CT can independently diagnose benign and malignant masses, the combination of these modalities provides complementary value in select cases.

Cardiovascular Risk in Men with Prostate Cancer: Insights from the RADICAL PC Study.

PURPOSE: We describe the cardiovascular risk profile in a representative cohort of patients with prostate cancer treated with or without androgen deprivation therapy. MATERIALS AND METHODS: We prospectively characterized in detail 2,492 consecutive men (mean age 68 years) with prostate cancer (newly diagnosed or with a plan to prescribe androgen deprivation therapy for the first time) from 16 Canadian sites. Cardiovascular risk was estimated by calculating Framingham risk scores. RESULTS: Most men (92%) had new prostate cancer (intermediate risk 41%, high risk 50%). The highest level of education achieved was primary school in 12%. Most (58%) were current or former smokers, 22% had known cardiovascular disease, 16% diabetes, 45% hypertension, 31% body mass index 30 kg/m2 or greater, 24% low levels of physical activity, mean handgrip strength was 37.3 kg and 69% had a Framingham risk score consistent with high cardiovascular risk. Participants in whom androgen deprivation therapy was planned had higher Framingham risk scores than those not intending to receive androgen deprivation therapy, and this risk was abolished after adjustment for confounders. CONCLUSIONS: Two-thirds of men with prostate cancer are at high cardiovascular risk. There is a positive association between a plan to use androgen deprivation therapy and baseline cardiovascular risk factors. However, this association is explained by confounding factors.

The Burden of Uncontrolled Cardiovascular Risk Factors in Men With Prostate Cancer: A RADICAL-PC Analysis.

Background: Cardiovascular disease (CVD) incidence is higher in men with prostate cancer (PC) than without. Objectives: We describe the rate and correlates of poor cardiovascular risk factor control among men with PC. Methods: We prospectively characterized 2,811 consecutive men (mean age 68 ± 8 years) with PC from 24 sites in Canada, Israel, Brazil, and Australia. We defined poor overall risk factor control as ≥3 of the following: suboptimal low-density lipoprotein cholesterol (>2 mmol/L if Framingham Risk Score [FRS] ≥15 and ≥3.5 mmol/L if FRS <15), current smoker, physical inactivity (<600 MET min/wk), suboptimal blood pressure (BP) (≥140/90 mm Hg if no other risk factors, systolic BP ≥120 mm Hg if known CVD or FRS ≥15, and ≥130/80 mm Hg if diabetic), and waist:hip ratio >0.9. Results: Among participants (9% with metastatic PC and 23% with pre-existing CVD), 99% had ≥1 uncontrolled cardiovascular risk factor, and 51% had poor overall risk factor control. Not taking a statin (odds ratio [OR]: 2.55; 95% CI: 2.00-3.26), physical frailty (OR: 2.37; 95% CI: 1.51-3.71), need for BP drugs (OR: 2.36; 95% CI: 1.84-3.03), and age (OR per 10-year increase: 1.34; 95% CI: 1.14-1.59) were associated with poor overall risk factor control after adjustment for education, PC characteristics, androgen deprivation therapy, depression, and Eastern Cooperative Oncology Group functional status. Conclusions: Poor control of modifiable cardiovascular risk factors is common in men with PC, highlighting the large gap in care and the need for improved interventions to optimize cardiovascular risk management in this population.

Recurrent acute coronary syndrome caused by a primary aortic valve sarcoma: grand rounds and literature review.

Background: Malignant tumours of the aortic valve apparatus are extremely rare and difficult to diagnose. Their proximity to the coronary ostium may cause an acute coronary syndrome (ACS) either by infiltration or by embolization. Case summary: We report a case of primary aortic valve undifferentiated sarcoma causing recurrent episodes of ACS, and we provide a literature review for primary cardiac valve tumours. This case also highlights the need for further evaluation of other causes of ACS in patients with minimal coronary artery disease risk factors and recurrent ACS. Conclusions: The majority of valve tumours are fibroelastomas. Sarcomas are rare and lead to poor outcomes.

The utility of tissue Doppler imaging for the noninvasive determination of left ventricular filling pressures in patients with septic shock.

BACKGROUND: Pulmonary artery wedge pressure (PAWP) is an important indicator of volume status in septic patients. Although it requires invasive pulmonary artery catheterization (PAC), a noninvasive method to assess PAWP would be clinically useful in this select patient population. Diastolic indices using transthoracic echocardiography (TTE) may provide an accurate estimate of PAWP. OBJECTIVE: To determine whether echocardiographic Doppler assessment is accurate in estimating PAWP in patients with septic shock. METHODS: A retrospective chart review was performed of 320 patients admitted with a diagnosis of septic shock from 2007-2008. Of the total patient population, 40 patients fulfilled the inclusion criteria, having undergone both TTE and PAC within 4 hours. Spectral Doppler indices including peak early (E) and late (A) transmitral velocities, E/A ratio, and E-wave deceleration time were measured. Tissue Doppler indices including S', E' and A' velocities were determined. Pulmonary artery wedge pressure values measured invasively were compared to the dimensionless index of E/E' in each patient. RESULTS: The mean age was 68 +/- 12 years with 28 males (70%). On echo assessment, 28% of patients had evidence of mild left ventricular diastolic dysfunction while 17% of patients had moderate diastolic dysfunction. Pulmonary artery wedge pressures ranged from 7 to 31 mm Hg with a mean of 18 +/- 5 mm Hg. The mean E/E' was 11 +/- 8. Linear regression analysis between PAWP and E/E7apos; demonstrated a strong correlation (r = .84, P < .05). CONCLUSION: Tissue Doppler indices using TTE is a feasible and strong predictor of PAWP in patients with septic shock.

Recursive multiresolution convolutional neural networks for 3D aortic valve annulus planimetry.

PURPOSE: Transcatheter aortic valve replacement (TAVR) is the standard of care in a large population of patients with severe symptomatic aortic valve stenosis. The sizing of TAVR devices is done from ECG-gated CT angiographic image volumes. The most crucial step of the analysis is the determination of the aortic valve annular plane. In this paper, we present a fully tridimensional recursive multiresolution convolutional neural network (CNN) to infer the location and orientation of the aortic valve annular plane. METHODS: We manually labeled 1007 ECG-gated CT volumes from 94 patients with severe degenerative aortic valve stenosis. The algorithm was implemented and trained using the TensorFlow framework (Google LLC, USA). We performed K-fold cross-validation with K = 9 groups such that CT volumes from a given patient are assigned to only one group. RESULTS: We achieved an average out-of-plane localization error of (0.7 ± 0.6) mm for the training dataset and of (0.9 ± 0.8) mm for the evaluation dataset, which is on par with other published methods and clinically insignificant. The angular orientation error was (3.9 ± 2.3)° for the training dataset and (6.4 ± 4.0)° for the evaluation dataset. For the evaluation dataset, 84.6% of evaluation image volumes had a better than 10° angular error, which is similar to expert-level accuracy. When measured in the inferred annular plane, the relative measurement error was (4.73 ± 5.32)% for the annular area and (2.46 ± 2.94)% for the annular perimeter. CONCLUSIONS: The proposed algorithm is the first application of CNN to aortic valve planimetry and achieves an accuracy on par with proposed automated methods for localization and approaches an expert-level accuracy for orientation. The method relies on no heuristic specific to the aortic valve and may be generalizable to other anatomical features.

A Case of TAVR Complicated by Severe Functional Mitral Regurgitation.

Mitral regurgitation (MR) is a known complication of transcatheter aortic valve replacement (TAVR). We report a case of a 90-year-old man with severe symptomatic aortic stenosis who underwent elective TAVR. The procedure was complicated by severe functional MR from left ventricular stunning and dilatation caused by hypotension throughout the procedure. An Impella CP (Abiomed, Inc, Danvers, MA) was inserted to unload the left ventricle and decrease its size with subsequent improvement in MR severity, which was sustained after Impella CP removal. In conclusion, we present the first case of successful management of post-TAVR severe functional MR with an Impella CP.

Optimal Fluoroscopic Projections of Coronary Ostia and Bifurcations Defined by Computed Tomographic Coronary Angiography.

OBJECTIVES: The aim of this study was to define the optimal fluoroscopic viewing angles of both coronary ostia and important coronary bifurcations by using 3-dimensional multislice computed tomographic data. BACKGROUND: Optimal fluoroscopic projections are crucial for coronary imaging and interventions. Historically, coronary fluoroscopic viewing angles were derived empirically from experienced operators. METHODS: In this analysis, 100 consecutive patients who underwent computed tomographic coronary angiography (CTCA) for suspected coronary artery disease were studied. A CTCA-based method is described to define optimal viewing angles of both coronary ostia and important coronary bifurcations to guide percutaneous coronary interventions. RESULTS: The average optimal viewing angle for ostial left main stenting was left anterior oblique (LAO) 37°, cranial (CRA) 22° (95% confidence interval [CI]: LAO 33° to 40°, CRA 19° to 25°) and for ostial right coronary stenting was LAO 79°, CRA 41° (95% CI: LAO 74° to 84°, CRA 37° to 45°). Estimated mean optimal viewing angles for bifurcation stenting were as follows: left main: LAO 0°, caudal (CAU) 49° (95% CI: right anterior oblique [RAO] 8° to LAO 8°, CAU 43° to 54°); left anterior descending with first diagonal branch: LAO 11°, CRA 71° (95% CI: RAO 6° to LAO 27°, CRA 66° to 77°); left circumflex bifurcation with first marginal branch: LAO 24°, CAU 33° (95% CI: LAO 15° to 33°, CAU 25° to 41°); and posterior descending artery and posterolateral branch: LAO 44°, CRA 34° (95% CI: LAO 35° to 52°, CRA 27° to 41°). CONCLUSIONS: CTCA can suggest optimal fluoroscopic viewing angles of coronary artery ostia and bifurcations. As the frequency of use of diagnostic CTCA increases in the future, it has the potential to provide additional information for planning and guiding percutaneous coronary intervention procedures.

The Prognostic Value of Late Gadolinium Enhancement in Nonischemic Heart Disease.

Late gadolinium enhancement (LGE) has become a standard clinical tool to evaluate myocardial fibrosis to define myocardial viability in the context of ischemic myocardial disease. More recently, LGE has also been used to characterize the presence and pattern of fibrosis in nonischemic cardiomyopathies. It yields unique and valuable diagnostic and prognostic insights for myriad nonischemic clinical indications and has become a key part of routine cardiac MR imaging, and a tool to guide treatment. This article reviews the technical aspects of LGE performance and its diagnostic and prognostic implications in nonischemic cardiomyopathy.

Assessment of Cardiac Masses by Cardiac Magnetic Resonance Imaging: Histological Correlation and Clinical Outcomes.

Background Cardiac magnetic resonance imaging ( CMR ) provides useful information for characterizing cardiac masses, but there are limited data on whether CMR can accurately distinguish benign from malignant lesions. We aimed to describe the distribution and imaging characteristics of cardiac masses identified by CMR and to determine the diagnostic accuracy of CMR for distinguishing benign from malignant tumors. Methods and Results We examined consecutive patients referred for CMR between May 2008 and August 2013 to identify those with a cardiac mass. In patients for whom there was histological correlation, 2 investigators blinded to all data analyzed the CMR images to categorize the mass as benign or malignant. For benign masses, readers were also asked to specify the most likely diagnosis. Benign masses were defined as benign neoplastic or non-neoplastic. Malignant masses were defined as primary cardiac or metastatic. Of 8069 patients (mean age: 58±16 years; 55% female) undergoing CMR , 145 (1.8%) had a cardiac mass. In most cases (142, 98%), there was a known cardiac mass before the CMR study. Among 145 patients with a cardiac mass, 93 (64%) had a known history of malignancy. Among 53 cases that had histological correlation, 25 (47%) were benign, 26 (49%) were metastatic, and 2 (4%) were malignant primary cardiac masses. Blinded readers correctly diagnosed 89% to 94% of the cases as benign versus malignant, with a 95% agreement rate (κ=0.83). Conclusions Although C MR can be highly effective in distinguishing benign from malignant lesions, pathology remains the gold standard in accurately determining the type of mass.

Statin Use and Risk of Vascular Events Among Cancer Patients After Radiotherapy to the Thorax, Head, and Neck.

Background This study aimed to explore whether statins reduce radiation-induced vascular complications in cancer patients postradiotherapy to the thorax, head, and neck. Methods and Results We conducted a retrospective cohort study within a provincial linked database of 5718 cardiac patients with thorax and head or neck cancer having undergone radiotherapy between 2000 and 2011. One thousand five hundred fifty-two patients were identified as nonstatin users and 4166 as statin users. The primary outcome of interest was the composite of cerebrovascular (transient ischemic attack, and fatal or nonfatal stroke) or cardiovascular events (fatal or nonfatal myocardial infarction). Time-dependent Cox proportional hazard analyses were performed. The crude event rate was 10.31% for nonusers and 9.03% for statin users (hazard ratio of 0.92 [95% CI 0.76-1.10, P=0.3451]), over a mean time to event/censoring of 534±687 days for nonusers and 594±706 days for the statin users. After adjusting for age, sex, prior history of stroke/transient ischemic attack or myocardial infarction, diabetes mellitus, dyslipidemia, atrial fibrillation, chronic kidney disease, heart failure, and hypertension, statin use postradiotherapy was associated with a nonsignificant 15% relative risk reduction, but a strong trend toward reducing the primary outcome (hazard ratio=0.85 95% CI 0.69-1.04, P=0.0811). The use of statins was associated with a significant reduction of 32% for the outcome of stroke alone (hazard ratio=0.68, 95% CI 0.48-0.98, P=0.0368). Conclusions Statin use post radiation therapy was associated with a significant reduction in stroke, with a trend toward significantly reducing cardiovascular and cerebrovascular events.

Optimal fluoroscopic viewing angles of right-sided heart structures in patients with tricuspid regurgitation based on multislice computed tomography.

AIMS: This study sought to analyse multislice computed tomography (MSCT) data of patients with tricuspid regurgitation and to report the variability of fluoroscopic viewing angles for several right-sided heart structures, as well as chamber views of the right heart in order to determine the optimal fluoroscopic viewing angles of six right-sided heart structures and right-heart chamber views. METHODS AND RESULTS: The MSCT data of 44 patients with mild to severe tricuspid regurgitation (TR) were retrospectively analysed. For each patient, we determined the optimal fluoroscopic viewing angles of the annulus/orifice en face view of the tricuspid valve, atrial septum, superior vena cava (SVC), inferior vena cava (IVC), coronary sinus (CS) and pulmonary valve. In this TR patient cohort, the average fluoroscopic viewing angle for the en face view of the tricuspid valve annulus was LAO 54-CAUD 15; RAO 10-CAUD 66 for the SVC orifice; LAO 27-CRA 59 for the IVC orifice; RAO 28-CRA 19 for the CS orifice; RAO 33-CAUD 33 for the atrial septum and LAO 13-CAUD 52 for the pulmonary valve annulus. The average viewing angle for right-heart chamber views was LAO 55-CAUD 15 for the one-chamber view; RAO 59-CAUD 54 for the two-chamber view; RAO 27-CRA 19 for the three-chamber view and LAO 5-CRA 60 for the four-chamber view. CONCLUSIONS: MSCT can provide patient-specific fluoroscopic viewing angles of right-sided heart structures. This information may facilitate transcatheter right-heart interventions.

Preparing the Cardiovascular Workforce to Care for Oncology Patients: JACC Review Topic of the Week.

Cardiovascular disease and cancer are the 2 main causes of death in the United States. They intersect on multiple levels, sharing common causal mechanisms and epidemiological risk factors. The growing prevalence and complexity of cardiovascular disease and cancer have resulted in the development of the discipline of cardio-oncology. Preparing the cardiovascular workforce for the care of a growing population of cancer patients is necessary to enhance the delivery of high-quality cardiovascular care for patients with cancer. The goal of this review is to present the dedicated efforts of the cardio-oncology community to meet the growing need for education and training of cardiovascular practitioners providing care to cancer patients and survivors. Integration in general cardiology training programs and the efforts of the stakeholder organizations serve as an example of how a multidimensional, innovative approach can address provider education and training needs in a relatively new discipline.

Chiari network endocarditis: not just an innocent bystander.

A Chiari's network, noted in approximately 2% of the general population, is a congenital remnant of the sinus venosum valve present in the right atrium. We report a case of a 67-year-old male who presented with acute infective endocarditis of the tricuspid valve due to coagulase-negative Staphylococci. Despite appropriate antimicrobial therapy for 2 weeks, the patient remained febrile with septic emboli to the pulmonary vasculature. Repeat transthoracic echocardiography (TTE) revealed persistent vegetations adherent to the tricuspid valve, extending onto the Chiari network, necessitating surgical intervention.

Contemporary Role of Echocardiography for Clinical Decision Making in Patients During and After Cancer Therapy.

Early recognition of cancer therapy-related cardiac dysfunction (CTRCD) provides an opportunity to mitigate cardiac injury and risk of developing late cardiac events. Echocardiography serves as the cornerstone in the detection and surveillance of CTRCD in patients during and after cancer therapy. Guidelines from professional societies and regulatory agencies have been published on approaches to surveillance, diagnosis, and treatment of CTRCD, although adoption as standard of care remains limited given the lack of evidence on the prognostic value of asymptomatic left ventricular (LV) dysfunction in the oncology population. The frequency of cardiac monitoring and the appropriateness of the Food and Drug Administration (FDA)-recommended cardiac monitoring schedule in all patients receiving trastuzumab for breast cancer has been challenged. Interruption versus continuation of oncological therapy in the setting of asymptomatic LV dysfunction remains a clinical conundrum given the uncertain balance of the risk of cardiac dysfunction and benefit of oncology efficacy. Despite their limitations, echocardiographic measures of LV function continue to play a pivotal role in clinical decision making, with global longitudinal strain emerging as a promising tool in informing and facilitating the selection of cancer treatment and optimizing cardiovascular outcomes. This review highlights the key recommendations of the existing guidelines and discusses recent developments in cardio-oncology imaging practices with the aim of providing practical guidance on the role and use of echocardiography in challenging clinical cases in cardio-oncology.

Fluoroscopic Anatomy of Right-Sided Heart Structures for Transcatheter Interventions.

Performing transcatheter tricuspid valve interventions requires a thorough knowledge of right-heart imaging. Integration of chamber views across the spectrum of imaging modalities (i.e., multislice computed tomography, fluoroscopy, and echocardiography) can facilitate transcatheter interventions on the right heart. Optimal fluoroscopic viewing angles for guiding interventional procedures can be obtained using pre-procedural multislice computed tomography scans. The present paper describes fluoroscopic viewing angles necessary to appreciate right-heart chamber anatomy and their relationship to echocardiography using multislice computed tomography.