Early Diastolic Dysfunction after Cancer Chemotherapy: Primary Endpoint Results of a Multicenter Cardio-Oncology Study

Chemotherapy ◽  
2018 ◽  
Vol 63 (2) ◽  
pp. 55-63 ◽  
Author(s):  
Vito Calabrese ◽  
Pierantonio Menna ◽  
Ombretta Annibali ◽  
Grazia Armento ◽  
Armando Carpino ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Cancer Patients ◽  
Troponin I ◽  
Standard Dose ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Events ◽  
Ventricular Ejection Fraction ◽  
Asymptomatic Patients ◽  
Chemotherapy Patients

Asymptomatic diastolic dysfunction (DD) with preserved left ventricular ejection fraction (LVEF) is suspected to precede late cardiac events in cancer survivors treated by chemotherapy. We conducted the first multicenter study of early DD induced by chemotherapy. Patients who were candidates for standard dose chemotherapy were screened for the absence of cardiovascular risk factors, LVEF ≥50%, normal-for-age diastolic function at echocardiography (E/A ratio, E wave deceleration time; DT), normal levels of potential DD biomarkers like Nt-proBNP (≤125 pg/mL), and cardiac troponin I (cTnI, ≤0.05 ng/mL). Mitral Doppler (E/E’) was left at the investigator’s discretion. Chemotherapy-induced DD with preserved LVEF was diagnosed for patients showing LVEF ≥50% and any of the following: Nt-proBNP > 125 pg/mL, cTnI > 0.05 ng/mL, and out-of-range E/A and DT. Eighty patients (68 males, 12 females, median age 49 years) were evaluated at 1 week after chemotherapy (T1). Thirty-three protocol-defined diastolic events were observed (15 Nt-proBNP > 125 pg/mL, 14 grade I DD by E/A and DT, 4 cTnI > 0.05 ng/mL). The events occurred in 29 asymptomatic patients with LVEF ≥50% (36% incidence of DD with preserved LVEF). Interactions occurred between biomarkers and grade I DD. E/E’ abnormalities were not observed. Both anthracycline-based and nonanthracycline regimens induced DD. These findings show that biomarkers and echocardiography intercept early DD in otherwise asymptomatic low-risk cancer patients treated by standard dose chemotherapy. These findings therefore call for the adequate cardiac management of cancer patients.

Hypertension and diabetes

ESC CardioMed ◽  
2018 ◽  
pp. 445-447
Author(s):  
Laura Ernande
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Prognostic Value ◽  
Hypertensive Heart Disease ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Diabetic Patients ◽  
Cardiac Events ◽  
Ventricular Ejection Fraction

Both hypertension and diabetes mellitus (DM) are risk factors for coronary artery disease, resulting in a high risk of heart failure. They also directly impact the heart, leading to hypertensive heart disease and diabetic cardiomyopathy and also potentially causing heart failure. The hypertensive heart is characterized by left ventricular hypertrophy and frequently left atrial dilation. DM is also associated with an increased left ventricular mass. Left ventricular hypertrophy has an important prognostic value both in hypertensive and diabetic patients and may regress with antihypertensive medications. The differential diagnosis between hypertensive heart disease and hypertrophic cardiomyopathy can be sometimes challenging and requires a careful evaluation of the echocardiogram but also of the family history, electrocardiographic abnormalities, or the location of late gadolinium enhancement on cardiovascular magnetic resonance imaging. Hypertension and DM also influence ageing-related left ventricular remodelling. Diastolic dysfunction is frequent both in hypertensive and diabetic patients and is predictive of cardiac events and heart failure. However, diastolic dysfunction in diabetic patients seems to be more associated with age and co-morbidities such as obesity and hypertension than with DM itself. The presence of diastolic dysfunction predicts cardiac events and heart failure in those patients. Both hypertension and DM are risk factors for heart failure with preserved but also with reduced and mid-range ejection fraction. Therefore, left ventricular ejection fraction is a major parameter to evaluate in those patients. Myocardial strain is decreased both in hypertensive and in diabetic patients with normal left ventricular ejection fraction allowing the detection of subclinical systolic alteration and providing incremental prognostic value.

Role of biomarkers in cardioncology

2011 ◽  
Vol 49 (12) ◽  
Author(s):  
Daniela Cardinale ◽  
Michela Salvatici ◽  
Maria T. Sandri
Keyword(s):  
Troponin I ◽  
Cardiac Injury ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Left Ventricular Ejection ◽  
Cardiac Events ◽  
Current Standard ◽  
Converting Enzyme Inhibitors ◽  
Ventricular Ejection Fraction

AbstractCardiotoxicity is a serious adverse effect of anticancer drugs, impacting on quality of life and overall survival of cancer patients. According to the current standard for monitoring cardiac function, cardiotoxicity is usually detected only when a functional impairment has already occurred, precluding any chance of preventing its development. Over the last decade, however, a new approach, based on the use of cardiac biomarkers, has emerged, and has proven to be an effective alternative strategy for early detection of subclinical cardiac injury. In particular, the role of troponin I in identifying patients at risk of cardiotoxicity and of angiotensin-converting enzyme inhibitors in preventing left ventricular ejection fraction reduction and late cardiac events represent an effective tool for the prevention of this complication.

scholarly journals The association of high-sensitivity cardiac troponin I and T with echocardiographic stages of heart failure with preserved ejection fraction

2019 ◽  
Vol 56 (4) ◽  
pp. 431-441
Author(s):  
Julia Hoffmann ◽  
Michael Behnes ◽  
Uzair Ansari ◽  
Kathrin Weidner ◽  
Philip Kuche ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Troponin I ◽  
High Sensitivity ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction ◽  
Grade Iii

Background This study evaluates the associations between high-sensitivity troponin I and T (hs-TnI/hs-TnT) and the stages of heart failure with preserved ejection fraction (HFpEF)/diastolic dysfunction. Methods Blood samples for biomarker measurements (hs-TnI/hs-TnT/NT-proBNP) were collected within 24 h of routine echocardiographic examination. Patients with left ventricular ejection fraction <50%, right ventricular dysfunction and moderate-to-severe valvular heart disease were excluded. Graduation of diastolic dysfunction was determined according to current guidelines. Results A total of 70 patients were included. Hs-TnT concentrations increased significantly according to the progression of diastolic dysfunction ( P = 0.024). Hs-TnT was able to discriminate patients with diastolic dysfunction grade III (AUC = 0.737; P = 0.013), while NT-proBNP revealed a greater AUC (AUC 0.798; P = 0.002). Concentrations of hs-TnI increased only numerically according to the increasing stages of diastolic dysfunction ( P = 0.353). In multivariable logistic regression models, hs-TnT concentrations > 28 ng/L were associated with diastolic dysfunction grade III (OR = 4.7, P = 0.024), even after adjusting for NT-proBNP. Conclusion Increasing concentrations of hs-TnT may reflect the stages of diastolic dysfunction being assessed by echocardiography, whereas hs-TnI does not show any association with diastolic dysfunction.

scholarly journals CBR3 V244M is associated with LVEF reduction in breast cancer patients treated with doxorubicin

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jennifer K. Lang ◽  
Badri Karthikeyan ◽  
Adolfo Quiñones-Lombraña ◽  
Rachael Hageman Blair ◽  
Amy P. Early ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Care Center ◽  
Left Ventricular ◽  
The Body ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Echocardiographic Parameters ◽  
The Impact

Abstract Background The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts. Objectives This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment. Methods We recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson’s biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA). Results Breast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups. Conclusions CBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.

scholarly journals An Exploration of Heart Failure Risk in Breast Cancer Patients Receiving Anthracyclines with or without Trastuzumab in Thailand: A Retrospective Study

2021 ◽  
Vol 11 (3) ◽  
pp. 484-493
Author(s):  
Jukapun Yoodee ◽  
Aumkhae Sookprasert ◽  
Phitjira Sanguanboonyaphong ◽  
Suthan Chanthawong ◽  
Manit Seateaw ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Factors Associated ◽  
Palliative Intent ◽  
Increased Risk

Anthracycline-based regimens with or without anti-human epidermal growth factor receptor (HER) 2 agents such as trastuzumab are effective in breast cancer treatment. Nevertheless, heart failure (HF) has become a significant side effect of these regimens. This study aimed to investigate the incidence and factors associated with HF in breast cancer patients treated with anthracyclines with or without trastuzumab. A retrospective cohort study was performed in patients with breast cancer who were treated with anthracyclines with or without trastuzumab between 1 January 2014 and 31 December 2018. The primary outcome was the incidence of HF. The secondary outcome was the risk factors associated with HF by using the univariable and multivariable cox-proportional hazard model. A total of 475 breast cancer patients were enrolled with a median follow-up time of 2.88 years (interquartile range (IQR), 1.59–3.93). The incidence of HF was 3.2%, corresponding to an incidence rate of 11.1 per 1000 person-years. The increased risk of HF was seen in patients receiving a combination of anthracycline and trastuzumab therapy, patients treated with radiotherapy or palliative-intent chemotherapy, and baseline left ventricular ejection fraction <65%, respectively. There were no statistically significant differences in other risk factors for HF, such as age, cardiovascular comorbidities, and cumulative doxorubicin dose. In conclusion, the incidence of HF was consistently high in patients receiving combination anthracyclines trastuzumab regimens. A reduced baseline left ventricular ejection fraction, radiotherapy, and palliative-intent chemotherapy were associated with an increased risk of HF. Intensive cardiac monitoring in breast cancer patients with an increased risk of HF should be advised to prevent undesired cardiac outcomes.

scholarly journals The role of neurohormonal blockers in the primary prevention of acute-, early-, and late-onset anthracycline-induced cardiotoxicity

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Ahmed Ayuna ◽  
Nik Abidin
Keyword(s):  
Primary Prevention ◽  
Myocardial Injury ◽  
Troponin I ◽  
Late Onset ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Main Body ◽  
Converting Enzyme Inhibitors ◽  
Ventricular Ejection Fraction

Abstract Background Anthracycline-induced cardiotoxicity has been classified based on its onset into acute, early, and late. It may have a significant burden on the quality and quantity of life of those exposed to this class of medication. Currently, there are several ongoing debates on the role of different measures in the primary prevention of cardiotoxicity in cancer survivors. Our article aims to focus on the role of neurohormonal blockers in the primary prevention of anthracycline-induced cardiotoxicity, whether it is acute, early, or late onset. Main body of the abstract PubMed and Google Scholar database were searched for the relevant articles; we reviewed and appraised 15 RCTs, and we found that angiotensin-converting enzyme inhibitors (ACEI) and B-blockers were the most commonly used agents. Angiotensin II receptor blockers (ARBs) and mineralocorticoid receptor antagonists (MRAs) were used in a few other trials. The follow-up period was on the range of 1–156 weeks (mode 26 weeks). Left ventricular ejection fraction (LVEF), left ventricular diameters, and diastolic function were assessed by either echocardiogram or occasionally by cardiac magnetic resonance imaging (MRI). The occurrence of myocardial injury was assessed by troponin I. It was obvious that neurohormonal blockers reduced the occurrence of LVEF and myocardial injury in 14/15 RCTs. Short conclusion Beta-blockers, especially carvedilol and ACEI, especially enalapril, should be considered for the primary prevention of acute- and early-onset cardiotoxicity. ARB and MRA are suitable alternatives when patients are intolerant to ACE-I and B-blockers. We recommend further studies to explore and establish the role of neurohormonal blockers in the primary prevention of the acute-, early-, and late-onset cardiotoxicity.

scholarly journals Statins to mitigate cardiotoxicity in cancer patients treated with anthracyclines and/or trastuzumab: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Mary Obasi ◽  
Arielle Abovich ◽  
Jacqueline B. Vo ◽  
Yawen Gao ◽  
Stefania I. Papatheodorou ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cohort Studies ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Weighted Mean ◽  
Ventricular Ejection Fraction

Abstract Purpose Cardiotoxicity affects 5–16% of cancer patients who receive anthracyclines and/or trastuzumab. Limited research has examined interventions to mitigate cardiotoxicity. We examined the role of statins in mitigating cardiotoxicity by performing a systematic review and meta-analysis of published studies. Methods A literature search was conducted using PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Central. A random-effect model was used to assess summary relative risks (RR), weighted mean differences (WMD), and corresponding 95% confidence intervals. Testing for heterogeneity between the studies was performed using Cochran’s Q test and the I2 test. Results Two randomized controlled trials (RCTs) with a total of 117 patients and four observational cohort studies with a total of 813 patients contributed to the analysis. Pooled results indicate significant mitigation of cardiotoxicity after anthracycline and/or trastuzumab exposure among statin users in cohort studies [RR = 0.46, 95% CI (0.27–0.78), p = 0.004, $${ }I^{2}$$ I 2  = 0.0%] and a non-significant decrease in cardiotoxicity risk among statin users in RCTs [RR = 0.49, 95% CI (0.17–1.45), p = 0.20, $$I^{2}$$ I 2  = 5.6%]. Those who used statins were also significantly more likely to maintain left ventricular ejection fraction compared to baseline after anthracycline and/or trastuzumab therapy in both cohort studies [weighted mean difference (WMD) = 6.14%, 95% CI (2.75–9.52), p < 0.001, $$I^{2}$$ I 2  = 74.7%] and RCTs [WMD = 6.25%, 95% CI (0.82–11.68, p = 0.024, $$I^{2}$$ I 2  = 80.9%]. We were unable to explore publication bias due to the small number of studies. Conclusion This meta-analysis suggests that there is an association between statin use and decreased risk of cardiotoxicity after anthracycline and/or trastuzumab exposure. Larger well-conducted RCTs are needed to determine whether statins decrease risk of cardiotoxicity from anthracyclines and/or trastuzumab. Trial Registration Number and Date of Registration PROSPERO: CRD42020140352 on 7/6/2020.

Trastuzumab-Associated Cardiac Adverse Effects in the Herceptin Adjuvant Trial

2007 ◽  
Vol 25 (25) ◽  
pp. 3859-3865 ◽  
Author(s):  
Thomas M. Suter ◽  
Marion Procter ◽  
Dirk J. van Veldhuisen ◽  
Michael Muscholl ◽  
Jonas Bergh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Adverse Effects ◽  
Cancer Patients ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Neo Adjuvant Chemotherapy

Purpose The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2–positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF ≥ 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. Results Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m2 v 257 mg/m2) or epirubicin (480 mg/m2 v 422 mg/m2) and had a lower screening LVEF and a higher body mass index. Conclusion Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.

Abstract 13785: Left Ventricular Contractile Entropy in 99mTc-Sestamibi SPECT is a Novel Prognostic Predictor in Patients with Non-ischemic Dilated Cardiomyopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Naoaki Kano ◽  
Takahiro Okumura ◽  
Akinori Sawamura ◽  
Naoki Watanabe ◽  
Hiroaki Mori ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Sampling Point ◽  
Cardiac Events ◽  
Ventricular Ejection Fraction ◽  
Qrs Duration ◽  
Non Ischemic Dilated Cardiomyopathy ◽  
The Mean ◽  
99Mtc Sestamibi

Background: It has been reported that mechanical dispersion of myocardial contraction is increased in failing myocardium. However little is known about the association between contractile entropy evaluated by myocardial scintigraphy and prognosis in patients with non-ischemic dilated cardiomyopathy (NIDCM). Purpose: We aimed to investigate the prognostic value of contractile entropy in patients with NIDCM. Methods: Forty-seven patients (38 male, 55.1 years) with NIDCM were performed gated 99mTc-sestamibi myocardial perfusion SPECT (GMPS) and endomyocardial biopsy. Entropy was automatically calculated as a result of contractile phase analysis for each myocardial sampling point from GMPS, and it reflects a dispersion of global mechanical contraction. All patients were allocated into two groups based on the median of entropy; HE-group: entropy≥0.61 and LE-group: entropy<0.61. All patients were followed up at the mean of 2.8 years. Results: The mean QRS duration, left ventricular ejection fraction (LVEF) and plasma brain natriuretic peptide (BNP) levels were 114 msec, 35% and 225 pg/mL, respectively. Although there were no significant differences in QRS duration and plasma BNP levels between the two groups, LVEF was lower in the HE-group than in the LE-group (31.1% vs 39.8%, p=0.002). In Kaplan-Meier survival analysis, cardiac event rate was significantly higher in the HE-group (Figure). Cox proportional hazard analysis revealed that the HE-group was a significant determinant of cardiac events (Hazard Ratio: 7.66; 95%CI: 0.070-2.532; p=0.033). The mRNA expression level of sarcoplasmic endoplasmic reticulum Ca2+ ATPase (SERCA2a) in biopsy specimens was significantly lower in the LE-group (p=0.015). Conclusion: Contractile entropy, reflecting an impairment of global left ventricular contraction, might be useful to predict a poor prognosis in patients with NIDCM.

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