Cardiac toxicity of trastuzumab in elderly patients with breast cancer

Breast cancer (BC) is diagnosed in ≥ 65 year old women in about half of cases. Experts currently recommend that systemic therapy is offered to elderly patients with BC, if, based on their overall conditions and life expectancy, it can be reasonably anticipated that the benefits will outweigh the risks of treatment. Like for young subjects, the monoclonal antibody against human epidermal growth factor receptor-2 (HER-2), trastuzumab, represents a valid therapeutic option when BC over-expresses this receptor. Unfortunately, administration of trastuzumab is associated with the occurrence of left ventricular dysfunction and chronic heart failure (CHF), possibly because of interference with the homeostatic functions of HER-2 in the heart. Registry-based, retrospective analyses have reported an incidence of CHF around 25% in elderly women receiving trastuzumab compared with 10%–15% in those not given any therapy for BC, and the risk of CHF has been estimated to be two-fold higher in > 60–65 year old trastuzumab users vs. non-users. Extremely advanced age and preexisting cardiac disease have been shown to predispose to trastuzumab cardiotoxicity. Therefore, selection of older patients for treatment with trastuzumab should be primarily based on their general status and the presence of comorbidities; previous chemotherapy, especially with anthracyclines, should be also taken into account. Once therapy has started, efforts should be made to ensure regular cardiac surveillance. The role of selected biomarkers, such as cardiac troponin, or new imaging techniques (three-dimension, tissue Doppler echocardiography, magnetic resonance imaging) is promising, but must be further investigated especially in the elderly. Moreover, additional studies are needed in order to better understand the mechanisms by which trastuzumab affects the old heart.     

Anthracycline cardiotoxicity in breast cancer patients: synergism with trastuzumab and taxanes

Doxorubicin is known to cause cardiomyopathy and congestive heart failure (CHF) upon chronic administration. A major obstacle to doxorubicin-containing multiagent therapies pertains to the possible development of cardiomyopathy and CHF at lower than expected cumulative doses of doxorubicin. For example, the cardiac toxicity of doxorubicin is aggravated by the anti-HER2 antibody Trastuzumab or by the tubulin-active taxane paclitaxel; however, the mechanisms by which Trastuzumab and paclitaxel aggravate doxorubicin-induced cardiotoxicity are mechanistically distinct: Trastuzumab interferes with cardiac-specific survival factors that help the heart to withstand stressor agents like anthracyclines, while paclitaxel acts by stimulating the formation of anthracycline metabolites that play a key role in the mechanism of cardiac failure. Here, we briefly review the molecular mechanisms of the cardiotoxic synergism of Trastuzumab or paclitaxel with doxorubicin, and we attempt to briefly outline how the mechanistic know-how translates into the clinical strategies for improving the safety of anthracycline-based multiagent therapies.     

Isolated right ventricular infarction due to occlusion of the right ventricular branch in the absence of percutaneous coronary intervention

Isolated right ventricular myocardial infarction accounts for only 3% of all infarctions. It has previously been reported as a complication of percutaneous coronary intervention involving the right coronary artery secondary to occlusion of the right ventricular branch. In the present report, a patient is described in whom isolated right ventricular myocardial infarction developed due to occlusion of the right ventricular branch of the right coronary artery in the absence of percutaneous intervention.     

Assessment of right ventricular systolic function by two dimensional speckle tracking echocardiography in rheumatic mitral valve disease

We assessed the Right Ventricular (RV) systolic function using two dimensional (2D) speckle tracking echocardiography (STE) in Mitral valve disease before and after intervention. 90 patients divided into 3 groups of Mitral stenosis [MS], Mitral regurgitation [MR] and MS with MR were the study subjects. All the patients were subjected to conventional echocardiography and measurement of Right ventricular global longitudinal strain (RVGLS). Prior to intervention, subjects who demonstrated normal RV function by conventional methods, it was found that RVGLS was impaired significantly in the MS and MS with MR groups but normal in the MR group. After intervention, the RVGLS improved significantly in the MS group but not in the other groups. Right ventricular systolic pressure (RVSP) had a significant negative correlation to RVGLS in all 3 groups.     

Assessment of right ventricular mechanics in patients with mitral stenosis by two-dimensional deformation imaging

Background: It is well known that right ventricular (RV) dysfunction occurs early before clinical systemic congestion in patients with mitral stenosis (MS). Therefore, we aimed to evaluate the role of two-dimensional (2D) strain imaging in the assessment of subclinical RV dysfunction. Methods: Fifty-nine patients with isolated MS (mild and moderate) and 31 healthy control subjects constituted the study population. RV peak longitudinal strain (RV-LS) and strain rate (RV-LSr) measurements were obtained from apical four-chamber view. Results: There were no significant differences in left ventricular ejection fraction (LV-EF) and RV fractional area change between control and MS groups. RV strain (23.5 ± 7.2 vs. 18.63 ± 6.3, P = 0.001) and RV strain rate (1.72 ± 0.54 vs. 1.37 ± 0.66, P = 0.01) measurements were significantly lower in patients with MS than the control group. However, RV strain and strain rate measurements were comparable between MS subgroups. Correlation analysis revealed that there was poor correlation between RV-LS/LSr and mean-maximum gradients and echoscore but moderate correlation between RV-LS and RV-Sr in systolic pulmonary artery pressure and planimetric mitral valve area. Conclusion: We demonstrated that patients with MS had lower RV functions using 2D strain imaging and this is independent from severity of MS. In the detection of subclinical RV dysfunction in patients with MS, 2D strain imaging appears to be useful. (Echocardiography, 2012;00:1-6).     

Echocardiography in the assessment of right heart function.

Assessment of right heart function remains difficult despite rapid technological echocardiographic developments. This review addresses the anatomical and physiological basis for assessment of right ventricular function. It also addresses advantages and limitations of individual echocardiographic techniques currently used in clinical and academic practice. The review concludes that volume calculation and estimation of ejection fraction is not ideal for clinical assessment of right ventricular function. Regional myocardial wall motion detection by M-mode and tissue Doppler velocities are probably the best useful methods in clinical practice. 1D and 2D strain, velocity vector imaging and 4D echocardiography need further evaluation before considering them as routine investigations. A global interest needs to be given to a very important neglected entity, 'right ventricle', which has been shown to predict exercise tolerance and outcome in a number of syndromes.     

The mechanics of left ventricular dysfunction in patients with Churg-Strauss syndrome

Background: Heart is frequently involved in Churg‐Strauss syndrome (CSS). However, the mechanics of left ventricular (LV) dysfunction in CSS has not been studied. Objective: To assess the mechanics of LV function and to characterize the contribution of longitudinal, circumferential and rotational deformation to LV dysfunction in CSS. Methods: We enrolled 22 CSS patients (eight males, mean age 43.2 ± 9.5 years) in remission of their disease and 22 sex‐ and age‐matched healthy subjects. All patients underwent conventional and two‐dimensional speckle‐tracking echocardiography. Global longitudinal, circumferential and rotational deformation parameters were calculated. Results: CSS subjects demonstrated lower LV ejection fraction (EF) than controls (56.6 ± 15.0% vs 63.8 ± 3.4%; P < 0.05). When compared to those with LVEF ≥ 50% (n = 14), CSS patients with LVEF < 50% (n = 7) had decreased global peak‐systolic longitudinal and circumferential strain/strain rate (all P < 0.001) and tended to have lower global peak‐systolic radial strain (P = 0.05). There were no differences between these two subgroups in global peak‐systolic radial strain rate and LV twist/torsion. When comparing individual systolic and diastolic parameters early diastolic longitudinal and circumferential strain rate demonstrated the highest correlation with corresponding global longitudinal and circumferential peak‐systolic strain/strain rate (r < ?0.80, P < 0.001 for all correlations). Conclusions: In CSS LV systolic dysfunction strongly correlates with longitudinal and circumferential, but not radial or rotational systolic components, indicating that impaired LV systolic function may result predominantly from impaired contraction of inner and middle, but not outer myocardial fiber layers. The spatial correspondence between systolic and diastolic deformation parameters suggests the similar impact of pathologic process on systolic and diastolic function in CSS. (Echocardiography 2012;29:568‐578)     

超声三维斑点追踪技术评价肝硬化患者右心室心肌功能

目的探讨三维斑点追踪技术在评价肝硬化患者右室心肌功能中的应用价值。方法将47例肝硬化患者按照Child-Pugh分级分为A、B、C三组,对照组为30例健康志愿者。应用三维斑点追踪技术(3D-STI)分析各组患者及对照组右心室整体面积应变(GAS)、各节段心肌峰值面积应变(AS)、心肌不同步指数(ASDI)及右室射血分数(RVEF)。结果A组各指标较对照组无明显差异,B组部分心肌节段AS、GAS、ASDI较对照组及A组增加(P0.05),RVEF较对照组差异无统计学意义,C组部分心肌节段AS、GAS较对照组及A组减低(P0.05),ASDI较对照组及A组增加(P0.05),RVEF较对照组及A组明显减低(P0.05)。结论肝硬化会引起右心室心肌损伤,超声斑点追踪技术可有效评价肝硬化不同阶段右心室心肌功能。     

The impact of right ventricular function assessed by 2‐dimensional speckle tracking echocardiography on early mortality in patients with inferior myocardial infarction

Background

Right ventricular (RV) involvement in inferior myocardial infarction (MI) increases in‐hospital morbidity and mortality.

Hypothesis

RV systolic dysfunction assessed by 2‐dimensional speckle tracking echocardiography (STE) might be a predictor of early mortality in patients with acute inferior MI.

Methods

Eighty‐one consecutive patients with acute inferior MI (mean age, 60.8 ± 12.7 years; 18 females) were included. RV myocardial involvement was defined as an elevation >1 mm in V₁ or V₄R within 12 hours of symptom onset. RV function was assessed by STE. Patients were followed for 30 days for all‐cause mortality.

Results

Thirty‐eight patients had RV myocardial involvement, and they had significantly lower tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (RVS), and left ventricular (LV) and RV global longitudinal strain (GLS). Nine patients (11%) died within 30 days. The mean age of mortality group was higher with more female frequency. They had significantly higher pro‐BNP, hs‐troponin T, and creatinine levels, but lower hemoglobin levels. TIMI 3 flow was significantly less achieved in mortality group. RV myocardial involvement was more frequent in the mortality group, and they had significantly lower TAPSE, RVS, and LV and RV GLS. Multivariate analysis revealed that age and RV GLS were independent predictors of early mortality. RV GLS ≤ –14% predicted early mortality in patients with acute inferior MI with a sensitivity of 88.9% and a specificity of 62.5% (AUC: 0.817, P = 0.002).

Conclusions

RV GLS may be useful in predicting early mortality in patients with acute inferior MI.     

Preoperative therapy with epidoxorubicin and docetaxel plus trastuzumab in patients with primary breast cancer: a pilot study

Purpose Combining anthracyclines and taxanes are to date the most active cytotoxic treatment option in the neoadjuvant and palliative therapy of breast cancer patients. Adding trastuzumab to these cytotoxic agents can improve outcome for women with human epidermal growth factor receptor 2 (HER2)-overexpressing advanced breast cancer. We conducted a pilot study of preoperative epidoxorubicin and docetaxel plus trastuzumab in outpatient patients suffering from breast cancer.Patients and methods Fourteen consecutive patients were enrolled in this prospective clinical pilot trial. Preoperative treatment consisted of weekly trastuzumab (4 mg/kg body-weight loading dose, 2 mg/kg/week maintenance dose), in combination with weekly epidoxorubicin (30 mg/m² body surface area [BSA]) and docetaxel (35 mg/m² BSA) once a week for 6 weeks followed by 1 week off therapy.Results Patients received a total of 30 cycles (median: 2 cycles, range: 2–3 cycles) of this therapeutic regimen. Outpatient epidoxorubicin and docetaxel plus trastuzumab were well tolerated. A major response to this preoperative therapy regimen could be demonstrated in 12 of 14 patients (86%) leading to breast-conserving surgery in 11 of 14 patients (79%).Conclusions We conclude that outpatient epidoxorubicin and docetaxel plus trastuzumab are safe in the neoadjuvant treatment of patients suffering from breast cancer, based on a favorable side-effect and activity profile. Thus, this regimen can be considered for further clinical trials.Work under the Auspices of CLEXO (Center of Excellence for Clinical and Experimental Oncology)     

Tissue Doppler assessment of right ventricular function in female patients with limited form of systemic sclerosis

BackgroundCardiac involvement in systemic sclerosis (SSc) is often clinically occult. The aim of this study was the evaluation of early subclinical right ventricular (RV) involvement in patients with limited form of systemic sclerosis by tissue Doppler.MethodsTwenty female patients with limited cutaneous SSc and 20 control female subjects, matched for age were studied with transthoracic echocardiography and tissue Doppler imaging (TDI) to assess RV function. Patients with pulmonary hypertension, chronic renal failure, diabetes mellitus, hypertension, heart failure, left ventricular hypertrophy, ischemic or rheumatic heart disease were excluded.ResultsPatients with limited form SSc had significant lower tricuspid annulus peak systolic velocities (S_T) (9.95 ± 1.78 vs. 11.05 ± 1.53 cm/s, p < 0.044), early (E_T) (9.65 ± 1.30 vs. 12.50 ± 1.23 cm/s, p < 0.0001), late (A_T) diastolic velocity (12.60 ± 2.01 vs. 18.15 ± 1.81 cm/s, p < 0.0001), and tricuspid annular plane systolic excursion (TAPSE) (23.05 ± 3.50 vs. 26.50 ± 1.90, p < 0.001) compared to controls. Myocardial performance index (MPI) of the RV was higher in SSc patients compared to controls (0.41 ± 0.05 vs. 0.30 ± 0.02, p < 0.0001). There were significant correlations between disease duration and S_T and RV MPI (r = ?0.883, p < 0.0001; r = 0.686, p < 0.001, respectively).ConclusionsPatients with limited form of SSc present with pulsed-tissue Doppler imaging indices indicative of right ventricle dysfunction, which had significant correlations with disease duration. Tissue Doppler is a valuable non-invasive tool for detecting RV myocardial involvement in patients with limited SSc.     

Serial assessment of postoperative ventricular mechanics in young children with tetralogy of Fallot: Comparison of transannular patch and valve‐sparing repair

Background: Little is known about the early time course of biventricular function and mechanics after tetralogy of Fallot (TOF) repair. We sought to evaluate and describe the evolution of the right ventricle (RV) after TOF repair in young infants and children using conventional echocardiographic parameters and global longitudinal strain (GLS).
Methods: A retrospective review was performed of all patients with TOF and pulmo‐ nary stenosis who underwent repair from January 2002 to September 2015 and had at least 3 serial postsurgical echocardiograms spanning from infancy to early child‐ hood (<8 years). Student’s t test was performed to compare patients who underwent valve sparing (VS) versus transannular patch (TAP) repair. ANOVA was used to track measures of ventricular systolic function over time.
Results: We analyzed 151 echocardiograms performed on 42 patients. Pulmonary regurgitation (PR, moderate or severe) and the RV to left ventricular (LV) basal dimen‐ sion ratio were higher in TAP patients (P < .04 at all‐time points). Along with a signifi‐ cant increase in RV basal diameter Z‐score in the TAP group (P < .001), there was an improvement in RV and LV GLS over time in both groups (P < .001). The LV GLS at last follow‐up was lower in patients who underwent reoperation than those who did not (P = .050). LV GLS at the last follow‐up echocardiogram was lower in patients with significant PR than those without (P < .001).
Conclusions: Ventricular function appeared improve over time from the initial post‐ operative period in TOF patients. TAP repair was associated with a progressively higher RV/LV ratio in young children. GLS and RV/LV basal diameter ratio may be useful when following young children after TOF repair. Further research is necessary to understand the trajectory of ventricular functional and volumetric changes in young children in order to provide the most effective lifetime management of pa‐ tients with TOF.     

Biatrial and right ventricular deformation imaging: Implications of the recent EACVI consensus document in the clinics and beyond

In this review, right ventricular (RV), right atrial (RA), and left atrial (LA) strain in some selected clinical situations has been discussed in light of the current literature. To exemplify the significance of the use of multichamber strain, we have provided some illustrations of common cardiac problems. The recently published European Association of Cardiovascular Imaging (EACVI) consensus document for standardization of RV, RA, and LA strain, using the currently available software, has fulfilled the aspirations of investigators world over who have been studying atrial strain using a bailed‐out algorithm designed principally to quantify left ventricular deformation. The purpose of this review was to reiterate the value of the application of RV and biatrial strain imaging in research and day‐to‐day clinical practice, using the 2‐dimensional speckle tracking echocardiography (2D‐STE). Also, we present a short report on how RA strain may remain coupled to pulmonary hemodynamics. Besides, we have highlighted the technical challenges of atrial strain quantification. We have not used the nomenclature of chamber deformation proposed by the EACVI document as the publications cited in this review have used different sets of nomenclature.