scholarly journals Incidence of Cardiotoxicity and Validation of the Heart Failure Association- International Cardio-Oncology Society risk stratification Tool in Patients Treated with Trastuzumab for HER2-Positive Early Breast Cancer.

2021 ◽  
Author(s):  
Nicolò Matteo Luca Battisti ◽  
Maria Sol Andres ◽  
Karla A Lee ◽  
Tharshini Ramalingam ◽  
Tamsin Nash ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Early Breast Cancer ◽  
Nyha Class ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Class Iii ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Very High

Abstract PurposeTrastuzumab improves survival in patients with HER2+ early breast cancer. However, cardiotoxicity remains a concern, particularly in the curative setting, and there are limited data on its incidence outside of clinical trials. We retrospectively evaluated the cardiotoxicity rates (left ventricular ejection fraction [LVEF] decline, congestive heart failure [CHF], cardiac death or trastuzumab discontinuation) and assessed the performance of a proposed model to predict cardiotoxicity in routine clinical practice.MethodsPatients receiving curative trastuzumab between 2011-2018 were identified. Demographics, treatments, assessments and toxicities were recorded. Fisher’s exact test, chi-squared and logistic regression were used.Results931 patients were included in the analysis. Median age was 54 years (range 24-83) and Charlson comorbidity index 0 (0-6), with 195 patients (20.9%) aged 65 or older. 228 (24.5%) were smokers. Anthracyclines were given in 608 (65.3%). Median number of trastuzumab doses was 18 (1-18). The HFA-ICOS cardiovascular risk was low in 401 patients (43.1%), medium in 454 (48.8%), high in 70 (7.5%) and very high in 6 (0.6%).Overall, 155 (16.6%) patients experienced cardiotoxicity: LVEF decline≥10% in 141 (15.1%), falling below 50% in 55 (5.9%), CHF NYHA class II in 42 (4.5%) and class III-IV in 5 (0.5%) and discontinuation due to cardiac reasons in 35 (3.8%). No deaths were observed.Cardiotoxicity rates increased with HFA-ICOS score (14.0% low, 16.7% medium, 30.3% high/very high; p=0.002). ConclusionsCardiotoxicity was relatively common (16.6%), but symptomatic heart failure on trastuzumab was rare in our cohort. The HFA-ICOS score identifies patients at high risk of cardiotoxicity

scholarly journals A Randomized Trial Comparing 3- versus 4-Monthly Cardiac Monitoring in Patients Receiving Trastuzumab-Based Chemotherapy for Early Breast Cancer

2021 ◽  
Vol 28 (6) ◽  
pp. 5073-5083
Author(s):  
Susan Dent ◽  
Dean Fergusson ◽  
Olexiy Aseyev ◽  
Carol Stober ◽  
Gregory Pond ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Cardiac Dysfunction ◽  
Controlled Trial ◽  
Left Ventricular ◽  
Cardiac Monitoring ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Trastuzumab Therapy

Purpose: The optimal frequency for cardiac monitoring of left ventricular ejection fraction (LVEF) in patients receiving trastuzumab-based therapy for early breast cancer (EBC) is unknown. We conducted a randomized controlled trial comparing 3- versus 4-monthly cardiac monitoring. Patients and Method: Patients scheduled to receive trastuzumab-containing cancer therapy for EBC with normal (>53%) baseline LVEF were randomized to undergo LVEF assessments every 3 or 4 months. The primary outcome was the change in LVEF from baseline. Secondary outcomes included the rate of cardiac dysfunction (defined as a decrease in the LVEF of ≥10 percentage points, to a value <53%), delays in or discontinuation of trastuzumab therapy, and cardiology referral. Results: Of the 200 eligible and enrolled patients, 100 (50%) were randomized to 3-monthly and 100 (50%) to 4-monthly cardiac monitoring. Of these patients, 98 and 97 respectively underwent at least one cardiac scan. The estimated mean difference in LVEF from baseline was −0.94% (one-sided 95% lower bound: −2.14), which exceeded the pre-defined non-inferiority margin of −4%. There were also no significant differences between the two study arms for any of the secondary endpoints. The rate of detection of cardiac dysfunction was 16.3% (16/98) and 12.4% (12/97) in the 3- and 4-monthly arms, respectively (95% CI: 4.0 [−5.9, 13.8]). Conclusions: Cardiac monitoring every 4 months was deemed non-inferior to that every 3 months in patients with HER2-positive EBC being treated with trastuzumab-based therapy. Given its costs and inconvenience, cardiac monitoring every 4 months should be considered standard practice. Registration: NCT02696707, 18 February 2016.

scholarly journals The central arterial stiffness parameters in decompensated versus compensated states of heart failure: a paired comparative cohort study

2022 ◽  
Vol 74 (1) ◽  
Author(s):  
Ahmed El Fol ◽  
Waleed Ammar ◽  
Yasser Sharaf ◽  
Ghada Youssef
Keyword(s):  
Heart Failure ◽  
Arterial Stiffness ◽  
Ejection Fraction ◽  
Pulse Wave ◽  
Nyha Class ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Class Iii ◽  
Ventricular Ejection Fraction ◽  
Reduced Ejection Fraction

Abstract Background Arterial stiffness is strongly linked to the pathogenesis of heart failure and the development of acute decompensation in patients with stable chronic heart failure. This study aimed to compare arterial stiffness indices in patients with heart failure with reduced ejection fraction (HFrEF) during the acute decompensated state, and three months later after hospital discharge during the compensated state. Results One hundred patients with acute decompensated HFrEF (NYHA class III and IV) and left ventricular ejection fraction ≤ 35% were included in the study. During the initial and follow-up visits, all patients underwent full medical history taking, clinical examination, transthoracic echocardiography, and non-invasive pulse wave analysis by the Mobil-O-Graph 24-h device for measurement of arterial stiffness. The mean age was 51.6 ± 6.1 years and 80% of the participants were males. There was a significant reduction of the central arterial stiffness indices in patients with HFrEF during the compensated state compared to the decompensated state. During the decompensated state, patients presented with NYHA FC IV (n = 64) showed higher AI (24.5 ± 10.0 vs. 16.8 ± 8.6, p < 0.001) and pulse wave velocity (9.2 ± 1.3 vs. 8.5 ± 1.2, p = 0.021) than patients with NYHA FC III, and despite the relatively smaller number of females, they showed higher stiffness indices than males. Conclusions Central arterial stiffness indices in patients with HFrEF were significantly lower in the compensated state than in the decompensated state. Patients with NYHA FC IV and female patients showed higher stiffness indices in their decompensated state of heart failure.

Plasma Somatostatin in Advanced Heart Failure: Association with Cardiac Filling Pressures and Outcome

Cardiology ◽  
2020 ◽  
Vol 145 (12) ◽  
pp. 769-778
Author(s):  
Tania Deis ◽  
Louise Balling ◽  
Kasper Rossing ◽  
Søren Boesgaard ◽  
Caroline Michaela Kistorp ◽  
...  
Keyword(s):  
Heart Failure ◽  
Nyha Class ◽  
Venous Pressure ◽  
Left Ventricular ◽  
Advanced Heart Failure ◽  
Left Ventricular Ejection ◽  
Heart Catheterization ◽  
Pathophysiological Mechanism ◽  
Class Iii ◽  
Ventricular Ejection Fraction

<b><i>Background:</i></b> Somatostatin inhibits intestinal motility and hormonal secretion and is a potent arterial vasoconstrictor of the splanchnic blood flow. It is unknown if somatostatin concentrations are associated with central hemodynamic measurements in patients with advanced heart failure (HF). <b><i>Methods:</i></b> A prospective study of HF patients with a left ventricular ejection fraction (LVEF) &#x3c;45% referred to right heart catheterization (RHC) for evaluation for heart transplantation (HTX) or left ventricular assist device (LVAD). <b><i>Results:</i></b> Fifty-three patients were included with mean LVEF 18 ± 8% and majority in NYHA-class III–IV (79%). Median plasma somatostatin concentration was 18 pmol/L. In univariable regression analysis, log(somatostatin) was associated with increased central venous pressure (CVP; <i>r</i><sup>2</sup> = 0.14, <i>p</i> = 0.003) and a reduced cardiac index (CI; <i>r</i><sup>2</sup> = 0.15, <i>p</i> = 0.004). When adjusted for selected clinical variables (age, gender, LVEF, eGFR and BMI), log(somatostatin) remained a significant predictor of CVP (<i>p</i> = 0.044). Increased somatostatin concentrations predicted mortality in multivariable models (hazard ratio: 5.2 [1.2–22.2], <i>p</i> = 0.026) but not the combined endpoint of death, LVAD implantation or HTX. <b><i>Conclusions:</i></b> Somatostatin concentrations were associated with CVP and CI in patients with HF. The pathophysiological mechanism may be related to congestion and/or hypoperfusion of the intestine. Somatostatin was an independent predictor of mortality in advanced HF.

Role of hypertension on new onset congestive heart failure in patients receiving trastuzumab adjuvant chemotherapy for early breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11556-e11556
Author(s):  
Nicola Maurea ◽  
Giulia Russo ◽  
Stefania Gori ◽  
Giovanna Piscopo ◽  
Clemente Cipresso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Congestive Heart Failure ◽  
Early Breast Cancer ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Trastuzumab Therapy ◽  
New Onset

e11556 Background: Adjuvant trastuzumab therapy improves survival of Human Epidermal growth factor Receptor 2 (HER2)-positive women with early breast cancer (EBC). Trastuzumab-induced cardiotoxicity is not uncommon, occurring prevalently asymptomatic in the first three months of therapy. In the setting of community patients, the incidence, timing and phenotype of new onset congestive heart failure (CHF) is unknown. Methods: 499 consecutive HER2-positive women (mean age 55+11) with EBC treated with Trastuzumab between January 2008 and June 2009 at 10 Italian institutions were followed-up for 1 year. We evaluated incidence, time of occurrence, clinical features associated with CHF. Left ventricular ejection fraction (LVEF) was evaluated by echocardiography at baseline and 3-6-9-12 months during Trastuzumab therapy. Results: CHF occurred in 16 patients (3.2%), who were older and had a higher prevalence and higher degree of hypertension in comparison with patients who had not CHF. All CHF patients had a significant reduction in LVEF with a mean peak of – 12 points % detected at 3-month follow up. CHF occurred in 7 patients (44%) within 3-month follow-up, 4 patients (25%) between 3-6 months, 3 patients (19%) between 6-9 months and 2 patients (12%) between 9-12 months. Trastuzumab was discontinued in 10 of 16 patients and re-started in 5 after LVEF recovery. New onset CHF was predicted by the presence of hypertension (OR 2.9 [CI 1.1 – 7.9]. Conclusions: In clinical practice new onset CHF occurs seldom in HER-positive women with EBC, prevalently in the first six months of therapy. CHF is invariably associated with a significant reduction in LVEF and is predicted by a history of hypertension.

Anthracycline, taxane, and trastuzumab-based neoadjuvant chemotherapy in HER2-positive early breast cancer: phase II trial

2022 ◽  
pp. 030089162110675
Author(s):  
Benedetta Conte ◽  
Filippo Montemurro ◽  
Alessia Levaggi ◽  
Eva Blondeaux ◽  
Chiara Molinelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Early Breast Cancer ◽  
Phase Ii ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Objective: Neoadjuvant chemotherapy has become the preferred treatment in HER2-positive early breast cancer. Several trials investigated the neoadjuvant efficacy of dual HER2 blockade with anthracycline-free chemotherapy, whereas few data are available on single-agent trastuzumab and anthracycline-based regimens, which represent the standard of care in the adjuvant setting. This phase II, single-arm trial assessed anthracycline-based chemotherapy and trastuzumab as neoadjuvant treatment for high-risk HER2-positive breast cancer. Methods: Forty-three patients with stage II–III HER2-positive breast cancer were treated with 4 courses of neoadjuvant 5-fluorouracil 600 mg/m2, epirubicin 90 mg/m2, cyclophosphamide 600 mg/m2 (FEC ×4) every 21 days, followed by 12 courses of weekly paclitaxel 80 mg/m2 and trastuzumab 2 mg/Kg IV (loading dose 4 mg/kg). Results: Pathologic complete response (pCR) was observed in 22 (51%) of 43 patients. After a median follow-up of 6 years, the 5-year disease-free survival and overall survival were 85.8% (95% confidence interval 75.9%–97%) and 89.6% (80.4%–99.8%), respectively. A temporary decrease in left ventricular ejection fraction was observed in two patients. No cardiac death or congestive heart failure occurred. One patient died due to febrile neutropenia. Conclusions: FEC ×4 followed by paclitaxel and trastuzumab was associated with high pCR rates and favorable long-term outcomes. However, this regimen was associated with relevant hematologic toxicity.

Emerging Cardiac Resynchronisation Therapy Indications

2011 ◽  
Vol 7 (1) ◽  
pp. 29
Author(s):  
Charlotte Eitel ◽  
Gerhard Hindricks ◽  
Christopher Piorkowski ◽  
◽  
◽  
...  
Keyword(s):  
Heart Failure ◽  
Systolic Heart Failure ◽  
Cardiac Resynchronisation Therapy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Current Evidence ◽  
Class Iii ◽  
Ventricular Ejection Fraction ◽  
Cardiac Resynchronisation ◽  
Resynchronisation Therapy

Cardiac resynchronisation therapy (CRT) is an efficacious and cost-effective therapy in patients with highly symptomatic systolic heart failure and delayed ventricular conduction. Current guidelines recommend CRT as a class I indication for patients with sinus rhythm, New York Heart Association (NYHA) functional class III or ambulatory class IV, a QRS duration ≥120ms, and left ventricular ejection fraction (LVEF) ≤35%, despite optimal pharmacological therapy. Recent trials resulted in an extension of current recommendations to patients with mild heart failure, patients with atrial fibrillation, and patients with an indication for permanent right ventricular pacing with the aim of morbidity reduction. The effectiveness of CRT in patients with narrow QRS, patients with end-stage heart failure and cardiogenic shock, and patients with an LVEF >35% still needs to be proved. This article reviews current evidence and clinical applications of CRT in heart failure and provides an outlook on future developments.

Subcutaneous Trastuzumab with Pertuzumab and Docetaxel in HER2-Positive Metastatic Breast Cancer: Final Analysis of MetaPHER, A Phase 3b Single-Arm Safety Study

2020 ◽  
Author(s):  
Sherko Kümmel ◽  
Carlo Alberto Tondini ◽  
Jacinta Abraham ◽  
Zbigniew Nowecki ◽  
Bartosz Itrych ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
The Body ◽  
Left Ventricular Ejection ◽  
Fixed Dose ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction

Abstract BACKGROUND Intravenous trastuzumab, pertuzumab, and docetaxel is first-line standard of care for patients with HER2-positive metastatic breast cancer. Subcutaneous trastuzumab plus intravenous pertuzumab and chemotherapy has shown similar safety and tolerability to intravenous trastuzumab in patients with HER2-positive early and metastatic breast cancer; however, in the metastatic setting, this has yet to be shown globally.METHODS In this open-label, single-arm, multicenter phase 3b study, eligible patients were ≥18 years old with histologically/cytologically confirmed previously untreated HER2-positive metastatic breast cancer. All patients received ≥1 dose of subcutaneous trastuzumab (fixed-dose 600 mg) plus intravenous pertuzumab (loading dose: 840 mg/kg; maintenance dose: 420 mg/kg) and docetaxel (≥6 cycles; initial dose 75 mg/m2) every 3 weeks. The primary objective was safety and tolerability; secondary objectives included efficacy.RESULTS At clinical cutoff, 276 patients had completed the study; median duration of follow-up was 27 months. The most common any-grade adverse events were diarrhea, alopecia, and asthenia. The most common grade ≥3 adverse events were neutropenia, febrile neutropenia, and hypertension. There were no cardiac deaths and mean left ventricular ejection fraction was stable over time. Median investigator-assessed progression-free survival was 18.7 months; objective response rate was 75.6%.CONCLUSIONS Efficacy/safety results of subcutaneous trastuzumab plus intravenous pertuzumab and docetaxel in metastatic breast cancer are consistent with historical evidence of intravenous trastuzumab. These findings further support the body of evidence indicating that subcutaneous administration does not affect the safety and efficacy profile of trastuzumab in HER2-positive breast cancer. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02402712 (date of registration: 30th March 2015)

scholarly journals Plasma Kynurenine Predicts Severity and Complications of Heart Failure and Associates with Established Biochemical and Clinical Markers of Disease

2019 ◽  
Vol 44 (4) ◽  
pp. 765-776 ◽  
Author(s):  
Thomas Bernd Dschietzig ◽  
Karl-Heinz Kellner ◽  
Katrin Sasse ◽  
Felix Boschann ◽  
Robert Klüsener ◽  
...  
Keyword(s):  
Heart Failure ◽  
Nyha Class ◽  
Linear Regression Analysis ◽  
Binary Logistic Regression ◽  
Multiple Linear Regression Analysis ◽  
Left Ventricular ◽  
The Body ◽  
Left Ventricular Ejection ◽  
Clinical Markers ◽  
Ventricular Ejection Fraction

Background: Kynurenine, a metabolite of the L-tryptophan pathway, plays a pivotal role in neuro-inflammation, cancer immunology, and cardiovascular inflammation, and has been shown to predict cardiovascular events. Objectives: It was our objective to increase the body of data regarding the value of kynurenine as a biomarker in chronic heart failure (CHF). Methods: We investigated the predictive value of plasma kynurenine in a CHF cohort (CHF, n = 114); in a second cohort of defibrillator carriers with CHF (AICD, n = 156), we determined clinical and biochemical determinants of the marker which was measured by enzyme immunoassay. Results: In the CHF cohort, both kynurenine and NT-proBNP increased with NYHA class. Univariate binary logistic regression showed kynurenine to predict death within a 6-month follow-up (OR 1.43, 95% CI 1.03–2.00, p = 0.033) whereas NT-proBNP did not contribute significantly. Kynurenine, like NT-proBNP, was able to discriminate at a 30% threshold of left ventricular ejection fraction (LVEF; AUC-ROC, both 0.74). Kynurenine correlated inversely with LVEF (ϱ = –0.394), glomerular filtration fraction (GFR; ϱ = –0.615), and peak VO2 (ϱ = –0.626). Moreover, there was a strong correlation of kynurenine with NT-proBNP (ϱ = 0.615). In the AICD cohort, multiple linear regression analysis demonstrated highly significant associations of kynurenine with GFR, hsCRP, and tryptophan, as well as a significant impact of age. Conclusions: This work speaks in favor of kynurenine being a new and valuable biomarker of CHF, with particular attention placed on its ability to predict mortality and reflect exercise capacity.

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