167 Right ventricular involvement in breast cancer patients undergoing chemotherapy

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Luisa Ferri ◽  
Corinna Bergamini ◽  
Paolo Springhetti ◽  
Lorenzo Niro ◽  
Luca Felice Cerrito ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Right Ventricular ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Free Wall ◽  
Pulsed Doppler ◽  
S Wave ◽  
Absolute Reduction

Abstract Aims Trastuzumab (TZ) and Anthracyclines (AC) are widely used for their key role in breast cancer. However, they may have different side effects on the cardiovascular system. One of the most concerning complications is myocardial dysfunction. Many studies have highlighted the importance of the screening for cardiotoxicity using left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). Nevertheless, there is little data about the right ventricular (RV) involvement. Aim of this study is to analyse the modification of RV systolic function in this setting. Methods One hundred and five women affected by HER-2 positive breast cancer treated with TZ referring to our echo-lab were enrolled in our single centre prospective study. Three patients were excluded due to an early TZ suspension not related to cardiovascular complications, thus 102 patients (97.1%) were eligible for analyses. Eighty-six of these (84.3%) were treated also with AC. All patients underwent consecutive transthoracic echocardiography (TTE) before starting TZ and then every 3 months up to 12 months. 2D-Speckle tracking analysis was performed at baseline and at each examination using Tomtec software. A complete clinical evaluation was also performed at each Follow-up. LV systolic dysfunction was defined as an absolute reduction of LVEF >10% from baseline to LVEF < 53% or a relative reduction of GLS >15% from baseline and an absolute reduction of LVEF >10% from baseline. RV systolic dysfunction was defined as TAPSE <17 mm, pulsed doppler S wave <9.5 cm/s and/or RV free wall strain <20%. Results LV systolic dysfunction occurred in 11 patients (10.8%). TAPSE and pulsed doppler S wave remained within the normal limits in all patients at Follow-up. On the contrary, RV free wall strain was reduced in 11 patients (10.8%), none of whom reported symptoms or signs of right-sided heart failure; 5 of these (45.5%) also presented LV dysfunction. LV and RV systolic dysfunction occurred mainly at the same time. Conclusions Cancer treatment also appears to impact on right chamber myocardium. RV free wall strain analysis seems more reliable in detecting RV systolic dysfunction rather than clinical examination or common echocardiographic parameters, such as TAPSE or pulsed doppler S wave, in the setting of patients with breast cancer treated with chemotherapy. However, further studies are needed to investigate its prognostic role.

scholarly journals Impact of right ventricular dysfunction after MitraClip treatment as a bridge to heart transplantation: insights from the MitraBridge registry

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Munafo ◽  
A Scotti ◽  
R Estevez-Loureiro ◽  
D Arzamendi ◽  
N.P Fam ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Right Ventricular ◽  
Primary Outcome ◽  
Ventricular Dysfunction ◽  
Right Ventricular Dysfunction ◽  
Left Ventricular ◽  
Volume Index ◽  
Left Ventricular Ejection ◽  
End Point

Abstract Background MitraClip treatment has been recently proposed as a “bridge strategy” solution for advanced heart failure (HF) patients with significant functional mitral regurgitation (MR), who are potential candidates or are waiting for cardiac replacement therapy (LVAD or heart transplantation, HTx). In this clinical scenario, left-ventricular-related right ventricular dysfunction (RVD) represents an important prognostic factor. Purpose Our study aimed to investigate the possible prognostic implication of RVD in advanced HF patients treated with MitraClip as a bridge to HTx strategy. Methods RVD was assessed using the relationship between tricuspid annular peak systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP). All patients from the MitraBridge registry for whom these two echocardiographic parameters were available, were included in the study. A cut-off value of TAPSE/PASP ratio <0.36 was used to defined RVD, as previously reported. The primary outcome was a composite end-point of all-cause death or rehospitalization for HF at 2-year. For patients who underwent LVAD implantation or HTx, follow-up data were censored at the time of those events. Results A total of 80 patients were included in the study. The median TAPSE/PASP ratio was 0.35 (25th-75th: 0.27–0.46), with 43 (54%) patients having a TAPSE/PASP ratio <0.36 (RVD group). The latter had a prevalent MR ischemic etiology (49% vs 38%), with a more frequent history of percutaneous coronary intervention (46.5% vs 22%, p=0.02). Except for TAPSE (15.7±3.6 mm vs 19.2±3.7 mm, p=0.001) and PASP (61±14 mmHg vs 39.5±9.5 mmHg, p<0.001), the other echocardiographic characteristics were similar between the two study groups (overall mean left ventricular ejection fraction 26.9±8%, median left ventricular end-diastolic volume index 120.7, 25th-75th: 102.2–146.5 mL/m2). After a median follow-up time of 508 (25th-75th: 160–899) days, elective HTx occurred in 12 patients (7 from the RVD group), while LVAD implantation was performed in 13 patients (7 from the RVD group). The primary outcome occurred in 30 patients (38%) with a 2-year Kaplan-Meier estimate of freedom from the composite end-point of 41%. At univariate (HR 1.3 95% CI 0.6–2.8, p=0.451) and multivariate (HR 1.6 CI 0.7–3.8, p=0.249) Cox-regression analysis, TAPSE/PASP ratio <0.36 was not identified as an independent predictor of primary outcome. Indeed, at follow-up echocardiographic control (median time 252, 25th-75th: 122–365 days), a significant improvement in TAPSE/PASP ratio was observed in the RVD group (baseline median TAPSE/PASP ratio 0.27, 25th-75th: 0.22–0.32 vs follow-up median TAPSE/PASP ratio 0.37, 25th-75th: 0.28–0.47, p<0.001). Conclusion In advanced HF patients with functional MR, MitraClip treatment could prevent or ameliorate left-ventricular-related RVD, allowing safe access to HTx or LVAD. FUNDunding Acknowledgement Type of funding sources: None.

Prospective evaluation of clinical safety and efficacy of left bundle branch area pacing in comparison with right ventricular sepal pacing

2021 ◽  
Author(s):  
Xing Liu ◽  
Wenbin Li ◽  
Jianping Zeng ◽  
He Huang ◽  
Lei Wang ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Clinical Trial Registry ◽  
Clinical Safety ◽  
Ventricular Ejection Fraction ◽  
Safety And Efficacy ◽  
His Bundle ◽  
Mechanical Synchrony

Abstract BackgroundLeft bundle branch area pacing (LBBaP) has recently emerged as alternative a new physiologic strategy of pacing to His-bundle pacing (HBP) associated with difficulty of lead implantation, His bundle damage, high and unstable thresholds.ObjectiveThe purpose of this study is to compare clinical safety and efficacy of LBBaP with right ventricular sepal pacing (RVSP).MethodsFrom February 2019 to May 2020, consecutive pacing-indicated patients were prospectively enrolled and divided into two groups. Ventricular synchrony index such as QRS duration (QRSd), interventricular mechanical delay (IVMD) and septal-posterior wall motion delay (SPWMD), left ventricular function such as left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF), pacing parameters, and complications were evaluated in perioperative period and during follow-up.ResultsLBBaP was successful in 45 patients (88.2%), and finally 46 patients underwent RVSP. With LBBaP, the ventricular electrical- mechanical synchrony were similar with the native-conduction system (P = .784). However, the ventricular electrical synchrony (QRSd, 108.47 ± 7.64 vs 130.63 ± 13.63 ms, P < .0001) and mechanical synchrony (IVMD, 27.68 ± 4.33 vs 39.88 ± 5.83, P < .0001; SPWMD, 40.39 ± 23.21 vs 96.36 ± 11.55, P < .0001) in the LBBaP group were significantly superior to the RVSP group. No significant differences in LVEDD (46 [44-48.5] vs 47 [44–52] mm, P = .488) and LVEF% (66 [62.5–70] vs 64 [61–68], P = .759) were noted in both two groups at last follow-up. But, in the subgroup analysis, LVEDD was shorter (46 [44–49] vs 50 [47–58] mm, P = .032) and the LVEF% was higher (65 [62–68] vs 63 [58–65], P = .022) in the LBBaP-H (high ventricular pacing ratio > 40%) group compared with RVSP-H group at last follow-up. There was lower capture thresholds (0.59 ± 0.18V vs. 0.71 ± 0.26V, P = 0.011) at implantation in the LBBaP group than RVSP group, and R-wave amplitudes and pacing impedances did not differ between the two groups. No serious complications were found in both two groups at implantation and follow-ups.ConclusionThis study confirms the clinical safety and efficacy of LBBaP, and that produces better ventricular electrical-mechanical synchrony than RVSP. The event of pacing-induced left ventricular dysfunction is lower in the LBBaP-H group than RVSP-H group.Trial registrationTrial registration Chinese Clinical Trial Registry, ChiCTR2100046901, Registered 30 May 2021—Retrospectively registered, http://www.chictr.org.cn/searchproj.aspx?regstatus=1008001.

P1868Risk of arrhythmias after myocardial infarction in patients with left ventricular systolic dysfunction according to mode of revascularization: a CARISMA substudy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Thomsen ◽  
S Pedersen ◽  
P K Jacobsen ◽  
H V Huikuri ◽  
P E Bloch Thomsen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Loop Recorder ◽  
Ventricular Ejection Fraction ◽  
New Onset

Abstract Introduction The CARISMA trial was the first study to use continuous monitoring for documentation of long-term arrhythmias in post-infarction patients with left ventricular dysfunction. During the study duration (2000–2005), primary PCI (pPCI) as treatment of acute myocardial infarction was introduced approximately midway (2002) on the enrolling centres. Purpose The aim of this study was to describe the influence of mode of revascularization after myocardial infarction (AMI) on long-term risk of risk of new onset atrial fibrillation, ventricular tachyarrhythmias and brady arrhythmias. Methods The study is a sub-study on the CARISMA study population that consisted of patients with AMI and left ventricular ejection fraction ≤40%, which received an implantable loop recorder and was followed for 2 years. After exclusion of 15 patients who refused device implantation and 26 with pre-existing arrhythmias, 268 of the 312 patients were included. Choice of revascularization was made by the treating team independently of the trial and was retrospectively divided into primary percutaneous intervention (pPCI), subacute PCI (24 hours to 2 weeks after AMI), primary thrombolysis or no revascularization. Endpoints were new-onset of arrhythmias and major cardiovascular events (MACE). The Kaplan-Meier (figure 1) and Mantel-Byar methods were used for time to first event risk analysis. Results A total of 77 patients received no revascularization, whereas 49 received thrombolysis only and 142 received PCI. At two-years follow up patients treated with any PCI had a significant lower risk (0.40, n=63) of any arrhythmia compared to patients treated with trombolysis (0.60, n=30) or no revascularization (0.68, n=16) (p<0.001, unadjusted) (figure 1). Risk of MACE was significant higher in patients with any arrhythmia (0.25, n=76) compared to no arrhythmia (0.11, n=93) at two years follow-up (p=0.004, unadjusted). Figure 1 Conclusion(s) The long-term risk of new onset arrhythmias after AMI was significantly lower in patients treated with any PCI compared to patients not revascularized or treated with thrombolysis. Risk of MACE was significantly higher in patients with new onset arrhythmias compared to patients with no arrhythmias.

P6237Clinical utility of echocardiographic left-ventricular ejection fraction monitoring for cardiotoxicity risk assessment in patients with HER2+ early breast cancer undergoing trastuzumab-based therapy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F Posch ◽  
T Glantschnig ◽  
S Firla ◽  
M Smolle ◽  
M Balic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
One Year ◽  
Over Time

Abstract Background Monitoring left-ventricular ejection fraction (LVEF) is a routinely-practiced strategy to survey patients with breast cancer (BC) towards cardiotoxic treatment effects. However, whether the LVEF as a single measurement or as a trajectory over time is truly sufficient to identify patients at high risk for cardiotoxicity is currently debated. Purpose To quantify the prognostic impact of LVEF and its change over time for predicting cardiotoxicity in women with HER2+ early BC. Methods We analyzed 1,136 echocardiography reports from 185 HER2+ early BC patients treated with trastuzumab ± chemoimmunoendocrine therapy in the neoadjuvant/adjuvant setting (Table 1). Cardiotoxicity was defined as a 10% decline in LVEF below 50%. Results Median baseline LVEF was 64% (25th-75th percentile: 60–69). Nineteen patients (10%) experienced cardiotoxicity (asymptomatic n=12, symptomatic n=7, during treatment n=19, treatment modification/termination n=14), Median time to cardiotoxicity was 6.7 months, and median LVEF decline in patients with cardiotoxicity was 18%. One-year cardiotoxicity risk was 7.6% in the 35 patients with a baseline LVEF≥60% and 24.5% in the 150 patients with a baseline LVEF<60% (Hazard Ratio (HR)=3.45, 95% CI: 1.35–8.75, Figure 1). During treatment, LVEF declined significantly faster in patients who developed cardiotoxicity than in patients without cardiotoxicity (1.3%/month vs. 0.1%/month, p<0.0001). A higher rate of LVEF decrease predicted for higher cardiotoxicity risk (HR per 0.1%/month higher LVEF decrease/month=2.50, 95% CI: 1.31–4.76, p=0.005), and cardiotoxicity risk increased by a factor of 1.7 per 5% absolute LVEF decline from baseline to first follow-up (HR=1.70, 95% CI: 1.30–2.38, p<0.0001). Thirty-six patients (19%) developed an LVEF decline of at least 5% from baseline to first follow-up (“early LVEF decline”). One-year cardiotoxicity risk was 6.8% in those without early LVEF decline and a baseline LVEF≥60% (n=117), 15.7% in those without an early LVEF decline and a baseline LVEF<60% (n=65), and 66.7% in those with an early LVEF decline and a baseline LVEF<60% (n=3), respectively (log-rank p<0.0001). Table 1. Baseline characteristics Age (years, median [IQR]) 55 [49–65] Estrogen receptor positive (n, %) 124 (67%) Neoadjuvant setting (n, %) 103 (56%) Figure 1. Risk of Cardiotoxicity. Conclusion Both a single LVEF measurement and the rate of LVEF decrease strongly predict cardiotoxicity in early BC patients undergoing HER2-targeted therapy. Routine LVEF monitoring identifies individuals at high risk of cardiotoxicity that may benefit from more sensitive screening techniques such as strain imaging.

P3118CMR Fast-SENC intramyocardial LV & RV segmental strain detects cardiotoxicity during oncology treatment and impact of cardioprotection therapy before echocardiography

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Steen ◽  
M Montenbruck ◽  
P Wuelfing ◽  
S Esch ◽  
A K Schwarz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Lower Sensitivity ◽  
Pharmacological Agents ◽  
Ventricular Ejection Fraction ◽  
The Impact

Abstract Background The incidence of cardiotoxicity during cancer therapy is underestimated due to limitations of current diagnostic tests. Current biomarkers (BNP, NT-pro-BNP, hs-Troponin, etc.) and imaging calculations (e.g. echocardiography) such as left ventricular ejection fraction (LVEF) are currently included in the guidelines to designate cardiotoxicity during cancer therapy. Unfortunately, these diagnostics identify systemic damage in symptomatic patients after the heart is unable to compensate for regional dysfunction. Fast-SENC segmental intramyocardial strain (fSENC) is a unique cardiac magnetic resonance imaging (CMR) test that regionally detects subclinical intramyocardial dysfunction in 1 heartbeat. Methods This single center, prospective Prefect Study was used to evaluate cardiotoxicity and the impact of cardioprotective therapy in Breast Cancer and Lymphoma patients (NCT03543228). fSENC was acquired with a 1.5T MRI and processed with the software to quantify intramyocardial strain. Segmental strain was measured in three short axis scans (basal, midventricular, apical) with 16 LV/6 RV longitudinal segments & three long axis scans (2-, 3-, 4-chamber) with 21 LV/5 RV circumferential segments. fSENC CMR was performed before chemotherapy, during and after anthracycline/taxane therapy, at 1 year follow-up, and as needed in between designated follow-up periods. Cardioprotective therapy was offered to patients meeting the definition of cardiotoxicity by the ESC Guidelines on Cardiotoxicity and/or ESMO Clinical Practice Guidelines or those observing a substantial decline in cardiac function. Results Two hundred eight (208) CMRs were performed in fifty-two (52) patients (44 female). Patients had an average (± stdev) age of 53 (15) yrs, BMI of 26 (5) kg/m2; 77% had breast cancer, 23% had Lymphoma. fSENC CMRs required 11 (2) min total exam time. The % of normal fSENC (segmental stain <−17%) with a threshold of 65% showed a sensitivity of 87% and specificity of 89% in detecting cardiotoxicity while echocardiography GLS with a threshold of −17% observed a sensitivity of 20% and specificity of 88%. Figure 1 shows receiver operating characteristic curves for fSENC based on the percent of normal myocardium, and echocardiography global longitudinal strain (GLS) respectively. Global fSENC had substantially lower sensitivity than segmental fSENC despite having higher accuracy than the other global metrics. Figure 1 Conclusion Segmental fSENC intramyocardial strain detects subclinical dysfunction due to cardiotoxic response of chemotherapy before other biomarkers and imaging modalities. The ability to detect the subclinical cardiotoxicity of chemotherapy agents, or other pharmacological agents that cause or worsen heart failure, enables proactive prescription of cardioprotective medications to avoid tissue remodeling that precedes systemic cardiac dysfunction and worsening of global measures such as LVEF and current biomarkers.

P4553Clinical and prognostic value of right ventricular dysfunction in patients with chagas heart disease during acute decompensated heart failure

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S R R Siqueira ◽  
S M Ayub-Ferreira ◽  
P R Chizzola ◽  
V M C Salemi ◽  
S H G Lage ◽  
...  
Keyword(s):  
Heart Failure ◽  
Right Ventricular ◽  
Prognostic Value ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Jugular Venous Distension

Abstract Introduction The occurrence of right ventricular disfunction (RVD) is common in heart failure (HF) patients due to Chagas' disease (ChD). However, its clinical and prognostic value has not been studied during episodes of acute decompensated heart failure (ADHF). Purpose Evaluate the prognostic value of RVD in ADHF patients with ChD during hospitalization and after 180 days of discharge compared to other etiologies. Methods We analysed a prospective cohort of consecutive 768 patients admitted for ADHF between March 2013 and October 2018; 490 (63.7%) patients were male and the median age was 58 (48.3–66.8) years and left ventricular ejection fraction was 26% (median) (IQR 22–35%). We compared the clinical characteristics and the prognosis of ChD patients according to the presence of RVD in the echocardiogram to other etiologies. Results RVD was presented in 289 (37.6%) patients. Among patients with non-chagasic etiologies, those with RVD were younger [53 (41–62) vs 61 (52–70) years, p<0.0001], had high levels of BNP in the moment of hospitalization [1195 (606–2209) vs 886 (366– 555) pg/mL], p<0,0001], received more inotropes (79.2% vs 57.9%, p<0,0001), had longer hospitalization [35 (17–51) vs 21 (10–37) days, p<0.001] and more clinical signs of congestion as hepatomegaly (49% vs 28.6%, p<0.0001); jugular venous distension (68.3% vs 41.2%, p<0.0001) and leg edema (65.4% vs 49.2%, p=0.001). Among patients with ChD, those with RVD were older [61 (48- 66) vs 58 (48 - 67) years, p=0.017], and had more frequently signs of hypoperfusion (56.8% vs 36.5%, p=0.029), jugular venous distension (72.8% vs 52.8%, p=0.01) and hepatomegaly (56.8% vs 31.1%, p=0.011), higher BNP levels [1288 (567–2180) vs 1066 (472–2007) pg/mL, p=0.006] and more frequent use of intravenous inotropes (88.9% vs 67.1%, p=0.003); additionally ChD patients with RVD had a higher rate of death and transplant during hospitalization (51.2% vs 38.3%, p=0.001). When all groups were compared together, ChD patients with RVD had the highest rate of death, transplant and readmissions at 180-days of follow-up (Figure). Figure 1 Conclusion Patients with RVD demonstrated a distinct clinical presentation, biomarkers and worse prognosis in all etiologies. ChD patients with RVD in ADHF had the worst prognosis with the highest rate of death, heart transplant e rehospitalization in follow-up.

Cardiac safety of pegylated liposomal doxorubicin (PLD) in combination with trastuzumab (T) in patients with metastatic breast cancer (MBC): Results from a multicenter phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1106-1106 ◽  
Author(s):  
E. Stickeler ◽  
D. O. Watermann ◽  
J. Woll ◽  
M. Foeldi ◽  
G. Gitsch
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Safety ◽  
Ventricular Ejection Fraction ◽  
Cardiac Side Effects

1106 Background: Combination therapy of doxorubicin and trastuzumab is highly effective for Her2 positive MBC but characterized by frequent cardiac toxicity (CT). PLD can significantly reduce CT compared to conventional doxorubicin. Patients and Methods: 15 patients were enrolled in a phase II trial to evaluate cardiac safety of T (4 mg/Kg loading dose day 2, followed by weekly 2 mg/Kg) in combination with PLD (40 mg/m2 IV bolus day 1, q 28 d). 75% of pts. presented with more than 1 metastatic site and 40% for second line treatment. PLD was administered for 6 or 9 cycles, respectively, T until disease progression. To assess CT, all pts were evaluated with electrocardiogram (ECG) and echocardiograms (E) for Left Ventricular Ejection Fraction (LVEF) at baseline, every cycle during PLD and T, and every three months during T therapy alone. CT was defined as appearance of signs/ symptoms of congestive heart failure and/or an absolute decrease in LVEF > 10 units (below 50%) or decrease in LVEF > 15 units (above 50%). Results: Four pts. received 6 cycles, 4 pts. received 9 cycles of PLD, 4 pts discontinued treatment due to PD, 3 pts. due to toxicity. After a median follow up time of 15.4 months, 6 pts. (42.9%) demonstrated a clinical benefit and median OS was 16.2 months. Non cardiac side effects were mild with only 3 CTC Grade 3 events of 247 treatment cycles (1.2%). Three pts. developed minor ECG changes without pathological significance and 5 pts. had minor changes in their E with slight diastolic (n=3) or systolic (n=2) dysfunction. During follow-up, 3 pts. were diagnosed with pathological E findings, including 1 slight decrease of LVEF, one diffuse hypokinesia and one strong decrease in LVEF.The median LVEF in the study cohort was 66.1% at baseline, 62.7% after 6 cycles of therapy, 64.4% at the first follow up and did not change significantly until the 5 th examination. Conclusions: This study supports the combination of PLD and H in pts. with HER2 overexpressing metastatic breast cancer as a safe and feasible therapy. Due to the promising clinical response rates in this prognostically unfavorable group, this combination should be evaluated in larger studies as a potential regimen for adjuvant treatment of breast cancer. No significant financial relationships to disclose.

Cardiotoxicity after doxorubicin and AZD2171, an oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor, in patients (pts) with breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 554-554 ◽  
Author(s):  
N. Denduluri ◽  
A. W. Berman ◽  
U. Vatas ◽  
C. K. Chow ◽  
D. R. Rosing ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ejection Fraction ◽  
Kinase Inhibitor ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Acute Ischemia ◽  
Ventricular Ejection Fraction ◽  
Cardiac Stress ◽  
Tac Chemotherapy

554 Background: AZD2171 selectively inhibits VEGFR 1,2,3. This trial examined the safety and efficacy of AZD2171 with anthracycline-containing therapy. Methods: Pts with previously untreated Stage IIB and III breast cancer received neoadjuvant AZD2171 (30mg) alone for one cycle (1 week) followed by daily AZD2171 and TAC chemotherapy with docetaxel (T), doxorubicin 50 mg/m2 (A) cyclophosphamide (C) for 6 cycles (Cy) every 3 weeks. Pts underwent breast surgery after completing neoadjuvant therapy. Eligible pts had left ventricular ejection fraction (EF) = 50%, and no uncontrolled HTN or cardiac history. Pts underwent electrocardiogram (EKG), and troponin first day (D) of every Cy and 24 hours after TAC as well as serial echocardiograms (echo). Cardiac stress MRI with dipyridamole was performed when pts had decreases in EF by echo. Results: Two pts received 2 Cy of AZD2171 alone, 9 Cy with TAC and AZD2171, and 1 Cy with TAC alone. Pt 1 and Pt 2 developed hypertension requiring medical therapy Cy4, D1 (148/97 mm Hg) and Cy2, D2 (169/93 mm Hg) respectively. Pt 1 had asymptomatic decrease in EF from 65% to 40% (grade 2) with global hypokinesis pre-Cy5 by echo. Troponin and EKG were negative for acute ischemia. Cardiac stress MRI was normal and EF returned to 60% within 48 hours. The pt continued therapy and pre-Cy7 EF was 51% by echo. Cumulative A dose received was 250mg/m2 pre-Cy7. AZD2171 was held while Cy7 TAC was continued. EF was 57% by echo 1 month after Cy7 TAC. Pt 2 had asymptomatic decrease in EF from 65% to 50% pre-Cy4 by echo with mild global hypokinesis. Troponin and EKG were negative for acute ischemia. Cardiac stress MRI showed EF of 56% with no ischemia. She continued AZD2171 and TAC. Pre-Cy5 EF was 35–40% (grade 3) with global hypokinesis. Troponin and EKG were negative. Cumulative dose of A received was 150mg/m2. AZD2171 and A were stopped; T and C were continued. EF normalized to 55% by cardiac stress MRI and echo within 21 days. Conclusion: Due to the systolic dysfunction that occurred with concurrent AZD2171 and doxorubicin administration, the study is closed. Future trials should administer AZD2171 and anthracyclines sequentially with stringent monitoring of blood pressure and ejection fraction. No significant financial relationships to disclose.

Safety of adjuvant trastuzumab (T) in elderly patients with breast cancer.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 282-282 ◽  
Author(s):  
L. Militello ◽  
P. Carli ◽  
S. Spazzapan ◽  
C. Lestuzzi ◽  
G. Miolo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Elderly Patients ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Her2 Breast Cancer ◽  
Minor Adverse Event

282 Background: T is a mainstay in adjuvant therapy for HER2+ breast cancer (BC) patients (pts). Safety and efficacy of T in elderly patients are largely unknown. In HERA trial, NSABP B-31, NCCTG N9831 only 16% of pts were older than 60 years. Risk factors for T related cardiotoxicity are age (>50 y/o), hypertension, baseline LVEF (left ventricular ejection fraction <55%), previous antracycline therapy and BMI. Methods: Charts of pts >65 y/o with early HER2+ BC treated with T as adjuvant or neoadjuvant therapy at our institution were retrospectively reviewed. Primary endpoint was the evaluation of T cardiac toxicity and safety. Results: 22 elderly out of 172 pts (12%) were identified: 19 pts were treated only with surgery and adjuvant chemotherapy with concomitant or sequential T, 3 more pts also received neoadjuvant chemotherapy concomitant with T. According to Balducci’s criteria, fit, vulnerable and frail pts were 20, 2, 0 respectively. Median age was 69 y/o (range 65-76). Hormonal status was negative in 10/22 (45%). 21/22 were histologic grade 3. Median follow-up was 33 months. Baseline comorbidities were the following: hypertension (G2-3) in 17 pts, diabetes mellitus in 1, supra/infraventricular arrhythmia (G1-2) in 3 and 1 pts. Antracyclines were administered in 16 pts (liposomal-doxorubicin in 5 pts), a sequential taxane-regimen was used in 3 more pts. Neoadjuvant weekly Paclitaxel and concomitant T was used in 3 pts. Median basal LVEF was 65% (range 59-74%). 2 pts developed an asymptomatic 10% LVEF drop from baseline (left ventricular systolic dysfunction G1) during T treatment. Known cardiac risk factors were hypertension in 1 pt and previous antracycline based chemotherapy in both. They recovered within 9 months. One minor adverse event was atrial fibrillation (G2) during T treatment. Conclusions: T was well tolerated in elderly pts. More data are needed in order to understand the correlations between T related toxicity and cardiovascular risk factors. Long term safety of T treatment should verify the reversibility of cardiac T related toxicity on elderly pts.

Trastuzumab-Related Cardiotoxicity: Calling Into Question the Concept of Reversibility

2007 ◽  
Vol 25 (23) ◽  
pp. 3525-3533 ◽  
Author(s):  
Melinda L. Telli ◽  
Sharon A. Hunt ◽  
Robert W. Carlson ◽  
Alice E. Guardino
Keyword(s):  
Breast Cancer ◽  
Left Ventricular ◽  
Stopping Rules ◽  
Left Ventricular Ejection ◽  
Adjuvant Trastuzumab ◽  
Ventricular Ejection Fraction ◽  
International Research Group ◽  
Number Of Patients ◽  
B 31

Purpose To assess the spectrum and reversibility of the cardiotoxicity observed in the adjuvant trastuzumab trials. Design The design and efficacy of the major adjuvant trastuzumab trials was assessed, including the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31, North Central Cancer Treatment Group N9831, Herceptin Adjuvant, Breast Cancer International Research Group 006, and Finland Herceptin trials. The cardiotoxicity data were evaluated with a focus on the follow-up cardiac evaluations of women who were diagnosed with cardiotoxicity. Proposed mechanisms of trastuzumab-related cardiotoxicity were considered. The natural history of congestive heart failure (CHF) was reviewed with the goal of placing the trastuzumab experience in context. Results Up to 4% of patients enrolled onto the adjuvant trastuzumab trials experienced severe CHF during treatment. In these trials, early stopping rules that identified an unacceptable level of cardiotoxicity were never reached. Despite this, a large number of patients on these trials experienced some form of cardiotoxicity that ultimately required discontinuation of trastuzumab. Approximately 14% of patients in the NSABP B-31 trial discontinued trastuzumab because of asymptomatic decreases in left ventricular ejection fraction (LVEF). Results of follow-up cardiac evaluations of patients diagnosed with any degree of cardiotoxicity in the NSABP B-31 trial document that a clinically significant proportion of patients have sustained decrements in their LVEF to less than 50%. Conclusion Adjuvant trastuzumab provides substantial benefits to patients with human epidermal growth factor receptor 2–positive breast cancer, however, competing immediate and long-term cardiovascular risks are a great concern. Continued cardiac follow-up of these women is of critical importance.

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