Subclinical cardiac damage monitoring in breast cancer patients treated with an anthracycline-based chemotherapy receiving left-sided breast radiation therapy: subgroup analysis from a phase 3 trial.

OBJECTIVE: This study, derived from the phase 3 SAFE trial (ClinicalTrials.gov identifier: NCT2236806), explores subclinical cardiac damage in breast cancer patients receiving anthracycline-based chemotherapy and left-sided breast radiation therapy (RT). MATERIALS AND METHODS: Eligible patients were randomized to a cardioprotective pharmacological therapy (bisoprolol, ramipril, or both) or placebo, with cardiac surveillance at multiple time-point using standard and 3-dimensional echocardiography. Dosimetric parameters were analysed, including mean heart dose (MHD) and various metrics for heart substructures, employing advanced contouring techniques and auto-contouring software. RESULTS: In the analysis of left-sided breast RT patients, the study encompassed 39 out of 46 irradiated individuals, focusing on GLS and 3D-LVEF outcomes with ≥ 10% worsening, defined as subclinical heart damage. Distinct RT schedules were used, with placebo exhibiting the highest ≥ 10% worsening (36.4%). In terms of treatment arms, bisoprolol exhibited 11.1% worsening, while ramipril 16.7% and bisoprolol + ramipril 25%. For patients with no subclinical damage, the mean MHD was 1.5 Gy; for patients with subclinical heart damage, the mean MHD was 1.6 Gy (p = 0.94). Dosimetric parameters related to heart and heart substructures (left anterior descending artery, right and left atrium, right and left ventricle) showed no statistically significant differences between patients with and without subclinical damage. CONCLUSION: Our results emphasize the crucial role of cardioprotective measures in mitigating adverse effects, highlighting RT as having negligible influence on cardiac performance. An extended follow-up assessment of the whole series is warranted to determine whether a subclinical effect could significantly influence clinical outcomes and cardiac events.

Cardioprotective Strategy for Patients With Nonmetastatic Breast Cancer Who Are Receiving an Anthracycline-Based Chemotherapy: A Randomized Clinical Trial.

IMPORTANCE: Several studies have evaluated cardioprotective strategies to prevent myocardial dysfunction in patients who are receiving cardiotoxic therapies. However, the optimal approach still represents a controversial issue. OBJECTIVE: To determine whether pharmacological cardioprevention could reduce subclinical heart damage in patients with breast cancer who are being treated with anthracycline-based chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: The SAFE trial was a 4-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study conducted at 8 oncology departments in Italy. It was a prespecified interim analysis on the first 174 patients who had completed cardiac assessment at 12 months. The study recruitment was conducted between July 2015 and June 2020. The interim analysis was performed in 2020. Patients were eligible for trial inclusion if they had indication to receive primary or postoperative systemic therapy using an anthracycline-based regimen. Patients with a prior diagnosis of cardiovascular disease were excluded. INTERVENTIONS: Cardioprotective therapy (bisoprolol, ramipril, or both drugs compared with placebo) was administered for 1 year from the initiation of chemotherapy or until the end of trastuzumab therapy in case of ERBB2-positive patients. Doses for all groups were systematically up-titrated up to the daily target dose of bisoprolol (5 mg, once daily), ramipril (5 mg, once daily), and placebo, if tolerated. MAIN OUTCOMES AND MEASURES: The primary end point was defined as detection of any subclinical impairment (worsening ≥10%) in myocardial function and deformation measured with standard and 3-dimensional (3D) echocardiography, left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS). RESULTS: The analysis was performed on 174 women (median age, 48 years; range, 24-75 years) who had completed a cardiological assessment at 12 months and reached the end of treatment. At 12 months, 3D-LVEF worsened by 4.4% in placebo arm and 3.0%, 1.9%, 1.3% in the ramipril, bisoprolol, ramipril plus bisoprolol arms, respectively (P = .01). Global longitudinal strain worsened by 6.0% in placebo arm and 1.5% and 0.6% in the ramipril and bisoprolol arms, respectively, whereas it was unchanged (0.1% improvement) in the ramipril plus bisoprolol arm (P < .001). The number of patients showing a reduction of 10% or greater in 3D-LVEF was 8 (19%) in the placebo arm, 5 (11.5%) in the ramipril arm, 5 (11.4%) in the bisoprolol, arm and 3 (6.8%) in the ramipril plus bisoprolol arm; 15 patients (35.7%) who received placebo showed a 10% or greater worsening of GLS compared with 7 (15.9; ramipril), 6 (13.6%; bisoprolol), and 6 (13.6%; ramipril plus bisoprolol) (P = .03). CONCLUSIONS AND RELEVANCE: The interim analysis of this randomized clinical trials suggested that cardioprotective pharmacological strategies in patients who were affected by breast cancer and were receiving an anthracycline-based chemotherapy are well tolerated and seem to protect against cancer therapy-related LVEF decline and heart remodeling. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT2236806.

Surgical aortic valve replacement and left ventricular remodeling: Survival and sex-related differences.

OBJECTIVES: To analyze how left ventricular (LV) remodeling and hypertrophy geometry evolve after surgical aortic valve replacement (SAVR) in octogenarian patients, and identify potential sex-related differences and implications for long-term outcomes. METHODS: In 170 patients with aortic stenosis ([AS], age 80 ± 4 years, 59% women), hypertrophy geometry and remodeling (LV index) were reanalyzed one year post-SAVR. The six-year outcomes were evaluated. RESULTS: Pre-SAVR, 65% of the women and 38.6% of the men (P < .001) showed adaptive remodeling. Concentric hypertrophy was prevalent in adaptive remodeling, and mixed and dilated hypertrophy were more prevalent in maladaptive remodeling. At one year, the remodeling patterns and sex distribution were similar to those observed pre-SAVR, but the LV index decreased in women and increased in men (P < .0001). Women with adaptive remodeling had a higher incidence of persistent concentric hypertrophy with higher LV filling pressures. Long-term survival was better in women and worse in men with adaptive remodeling (P = .039). Men with adaptive remodeling and men with concentric hypertrophy had the highest risk of cardiac death. This risk was similar between sexes for patients with maladaptive remodeling and dilated hypertrophy. Women with LV ejection fraction >55% had a lower risk of cardiac death than men. CONCLUSIONS: The long-term outcomes of SAVR differ between sexes in older patients with AS and adaptive LV remodeling. The LV index facilitates studying the pathways of adaptation to AS. The follow-up shifts help explain the sex differences in long-term outcomes post-SAVR. Concentric hypertrophy is associated with the highest risk of cardiac death in men.

Cardiac Metastasis of Sacral Chordoma.

Chordoma is a rare tumor, usually diagnosed when the disease is advanced. Despite its slow growth, it is locally aggressive and has a poor long-term prognosis. Surgery is the mainstay treatment. Although cardiac metastases are very rare, the heart is frequently involved in systemic neoplastic diseases. This report describes a typical case of metastatic chordoma: the age at first diagnosis, the site of the primary tumor, and the slow growth of the cardiac metastasis were all typical features. Surgical excision of the mass from the right ventricular outflow tract is described together with echocardiographic, radiologic, and histopathologic characteristics of the metastatic chordoma.

Papillary fibroelastoma of the right atrial appendage: Is it that rare?

Papillary fibroelastoma (PF) of the right atrium accounts for 2% of nonvalvular cases, and right appendage (RAA) PF was described only once in literature. We present three cases of RAA PF in patients with unrelated symptoms undergoing 3-dimensional transesophageal echocardiographic examination (3D-TEE) scheduled for conventional indications. Key to diagnosis in routine practice resides in systematic examination of the right atrium and RAA in live 3D-TEE imaging with backward and forward navigation of the real-time pyramidal data. A review of literature is provided. Our experience demonstrates that systematic imaging of all cardiac structures with 3D-TEE allows refining PF nosology.

Left ventricular mass regression after aortic valve replacement: Sex differences or effect of different methods of indexation?

BACKGROUND: The influence of sex on regression of left ventricular (LV) hypertrophy (LVH) after aortic valve replacement (AVR) for aortic stenosis (AS) remains elusive. The lack of consensus on how to correct LV mass (LVM) for body size, and different normalcy values, contribute to inconclusive results. METHODS: In 164 consecutive patients (mean age 80 ± 4 years, 59% females) with AS, we analyzed LVM (Devereux formula) before and 1 year after AVR (St.Jude Trifecta bio-prosthesis). LVM was indexed to BSA (Du Bois and Gehan formulas), to height1.7 and height2.7 . Limits of normalcy were (women and men, respectively): <95 and <115 g/m², BSA-indexed LVM; <60 and <81 g/m, LVM/height1.7 ; <44 and <48 g/m, LVM/height2.7 . RESULTS: Women had smaller BSA, but not body mass index, than men. AS severity and incidence of hypertension did not differ. LVM indexed to height2.7 was greater in women. LVH incidence was similar in males and females. Independently of the indexation method, LVH reduced significantly (P < 0.0001). LVM reduction was greater in women (P < 0.05 for all methods). At follow-up, nearly half the patients, irrespective of sex, showed residual LVH, and diastolic dysfunction. CONCLUSIONS: We tested different methods of LVM indexation in AS patients. LVM was similar between men and women. Indexation to height2.7 gives higher LVM in women because of their shorter stature. LVH prevalence is independent of sex. Irrespective of the indexation method, LVM reduction is greater in females, whereas LVM normalization occurs in equal proportion. Persistent LVH and diastolic dysfunction suggest earlier AVR in elderly.

Myocardial perfusion echocardiography and coronary microvascular dysfunction.

Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation, but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography (MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction, respectively, and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall, MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice, but the approval of regulatory authorities is lacking.

Characterization of Löeffler eosinophilic myocarditis by means of real time three-dimensional contrast-enhanced echocardiography.

Löeffler endocarditis is a rare myocardial disease often due to eosinophil leukemia or idiopathic hypereosinophilic syndrome. Degranulation of eosinophils within the eosinophil infiltrated myocardium is associated with myocardial necrosis due to the release of toxic cationic proteins, and with mural thrombi formation, which can occur anywhere in the ventricles. Thrombus formed on denuded myocardium is replaced by fibrosis as the final pathological stage of the disease, eventually leading to restrictive cardiomyopathy. We describe a multimodality imaging approach to the diagnosis and follow-up evaluation of Löeffler disease complicated by thrombus formation and neoangiogenesis of LV apex.

The challenge of integrated echocardiographic approach in percutaneous closure of paravalvular leak.

Paravalvular leak after prosthetic mitral valve surgery may lead to symptomatic mitral regurgitation and hemolytic anemia requiring reoperation. Percutaneous closure of paravalvular leaks is a relatively recent technique still considered a challenging procedure burdened by possible complications, to be offered only to poor redo surgical candidate patients. Multimodality imaging is advocated to plan and guide the procedure, to minimize the risk of complications. We report on a case of dehisced prosthetic mitral valve in which transthoracic real time three-dimensional echocardiography was used to locate the dehiscence area and characterize mitral paraprosthesis leak, whereas intracardiac echocardiography was used to guide and monitor the percutaneous closure procedure.

Effects of dipyridamole on cardiac and systemic haemodynamics: real-time three-dimensional stress echo beyond regional wall motion.

AIMS: Coronary vasodilation and coronary steal are the basis for routine use of dipyridamole in stress echocardiography for non-invasive assessment of coronary artery disease (CAD). This study investigates dipyridamole effects on cardiac (regional function, synchronicity and contractility) and systemic (ventricular arterial coupling) haemodynamics during real-time three-dimensional (RT3D) stress echocardiography in very low CAD risk patients. METHODS: From our RT3D stress echocardiography database, we identified 132 subjects (75 men, aged 68 ± 10 years) referred to stress echocardiography because of risk factors and/or atypical chest pain, who had normal baseline echocardiography, negative dipyridamole stress echocardiography and uneventful 2-year follow-up. All participants had good-quality RT3D datasets acquired during dipyridamole stress echocardiography (0.84 mg/kg in 10 min). From full volume datasets, ventricular volumes, regional subvolume curves and dyssynchrony index (SDI) were obtained; ventricular arterial coupling was calculated as stroke volume/end-systolic volume. RESULTS: In all participants, ventricular arterial coupling increased, whereas SDI decreased. End-systolic volume decreased and stroke index increased independently of pressure drop; the relationship between heart rate and arterial pressure changes was non-linear (quadratic regression, r = 0.368, P < 0.0001). The decrease in systemic resistance showed a curvilinear behaviour with respect to the ventricular arterial coupling increase. CONCLUSION: In a large population of normal individuals, dipyridamole administration improved ventricular energetics and better synchronization of regional contraction may be one of the mechanisms. The relationship between blood pressure and heart rate response suggests that heart rate response is of little help in identifying the systemic haemodynamic response to dipyridamole.