Anthracycline-related cardiotoxicity: epidemiology, surveillance, prophylaxis, management, and prognosis

2018 ◽  
Author(s):  
Daniela Cardinale ◽  
Carlo Maria Cipolla
Keyword(s):  
Heart Failure ◽  
Cardiac Dysfunction ◽  
Cell Injury ◽  
Clinical Effectiveness ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Current Standard ◽  
Converting Enzyme Inhibitors ◽  
Ventricular Ejection Fraction

Anthracycline-induced cardiotoxicity is of considerable concern, as it may compromise the clinical effectiveness of treatment, affecting both quality of life and overall survival in cancer patients, independently of the oncological prognosis. It is probable that anthracycline-induced cardiotoxicity is a unique and continuous phenomenon starting with myocardial cell injury, followed by progressive left ventricular ejection fraction (LVEF) decline that, if disregarded and not treated progressively leads to overt heart failure. The main strategy for minimizing anthracycline-induced cardiotoxicity is early detection of high-risk patients and prompt prophylactic treatment. 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 its prevention. At present, anthracycline-induced cardiotoxicity can be detected at a preclinical phase, very much before the occurrence of heart failure symptoms, and before the LVEF drops by measurement of cardiospecific biochemical markers or by Doppler myocardial and deformation imaging. The role of troponins in identifying subclinical cardiotoxicity and treatment with angiotensin-converting enzyme inhibitors, in order to prevent LVEF reduction is an effective strategy that has emerged in the last 15 years. If cardiac dysfunction has already occurred, partial or complete LVEF recovery may still be achieved if cardiac dysfunction is detected early after the end of chemotherapy and heart failure treatment is promptly initiated.

Anthracycline-related cardiotoxicity: epidemiology, surveillance, prophylaxis, management, and prognosis

ESC CardioMed ◽  
2018 ◽  
pp. 1160-1167
Author(s):  
Daniela Cardinale ◽  
Carlo Maria Cipolla
Keyword(s):  
Heart Failure ◽  
Cardiac Dysfunction ◽  
Cell Injury ◽  
Clinical Effectiveness ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Myocardial Cell ◽  
Current Standard ◽  
Converting Enzyme Inhibitors ◽  
Preclinical Phase ◽  
Myocardial Cell Injury

Anthracycline-induced cardiotoxicity is of considerable concern, as it may compromise the clinical effectiveness of treatment, affecting both quality of life and overall survival in cancer patients, independently of the oncological prognosis. It is probable that anthracycline-induced cardiotoxicity is a unique and continuous phenomenon starting with myocardial cell injury, followed by progressive left ventricular ejection fraction (LVEF) decline that, if disregarded and not treated progressively leads to overt heart failure. The main strategy for minimizing anthracycline-induced cardiotoxicity is early detection of high-risk patients and prompt prophylactic treatment. 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 its prevention. At present, anthracycline-induced cardiotoxicity can be detected at a preclinical phase, very much before the occurrence of heart failure symptoms, and before the LVEF drops by measurement of cardiospecific biochemical markers or by Doppler myocardial and deformation imaging. The role of troponins in identifying subclinical cardiotoxicity and treatment with angiotensin-converting enzyme inhibitors, in order to prevent LVEF reduction is an effective strategy that has emerged in the last 15 years. If cardiac dysfunction has already occurred, partial or complete LVEF recovery may still be achieved if cardiac dysfunction is detected early after the end of chemotherapy and heart failure treatment is promptly initiated.

scholarly journals Expert Comment: Is Medication Titration in Heart Failure too Complex?

2017 ◽  
Vol 03 (01) ◽  
pp. 25 ◽  
Author(s):  
John J Atherton ◽  
Annabel Hickey ◽  
◽  
◽  
Keyword(s):  
Heart Failure ◽  
Large Scale ◽  
Beta Blockers ◽  
Point Of Care ◽  
Angiotensin Receptor Blockers ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Converting Enzyme Inhibitors ◽  
Ventricular Ejection Fraction

Large-scale randomised controlled trials (RCTs) have demonstrated that angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and beta-blockers decrease mortality and hospitalisation in patients with heart failure (HF) associated with a reduced left ventricular ejection fraction. This has led to high prescription rates; however, these drugs are generally prescribed at much lower doses than the doses achieved in the RCTs. A number of strategies have been evaluated to improve medication titration in HF, including forced medication up-titration protocols, point-of-care decision support and extended scope of clinical practice for nurses and pharmacists. Most successful strategies have been multifaceted and have adapted existing multidisciplinary models of care. Furthermore, given the central role of general practitioners in long-term monitoring and care coordination in HF patients, these strategies should engage with primary care to facilitate the transition between the acute and primary healthcare sectors.

scholarly journals Discontinuation/Dose Reduction of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers during Acute Decompensated Heart Failure in African-American Patients with Reduced Left-Ventricular Ejection Fraction

Cardiology ◽  
2017 ◽  
Vol 137 (2) ◽  
pp. 121-125 ◽  
Author(s):  
Jesse A. Kane ◽  
Joseph K. Kim ◽  
Syed Abbas Haidry ◽  
Louis Salciccioli ◽  
Jason Lazar
Keyword(s):  
Heart Failure ◽  
Renal Function ◽  
Enzyme Inhibitors ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Converting Enzyme Inhibitors ◽  
Ventricular Ejection Fraction

Objectives: Patients with heart failure (HF) and reduced left-ventricular ejection fraction (LVEF) benefit from angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blocker (ARB) therapy. While dose reduction/discontinuation (r/d) of β-blockers (BB) and furosemide in acute decompensated HF (ADHF) worsen outcomes, data on ACEI/ARB are lacking. Methods: To determine the frequency and reasons for ACEI/ARB therapy r/d in ADHF patients, we studied 174 patients with LVEF <40% on ACEI/ARB and BB therapy upon admission over 1 year. Results: ACEI/ARB doses were r/d in 17.2% because of acute kidney injury (56.7%), hypotension (23.3%), and hyperkalemia (10%). Clinical characteristics were similar between patients with r/d and continued therapy. Admission and discharge creatinine (Cr) levels were higher in the r/d group. On multivariate analysis, admission Cr and admission systolic blood pressures were independent predictors of r/d. Among patients with renal dysfunction cited as the r/d reason, Cr did not significantly rise in 23.5%. The r/d group had a longer length of stay (LOS). Conclusions: ACEI/ARB dose is reduced and/or discontinued in nearly one-fifth of all ADHF admissions, and LOS is longer in the ACEI/ARB r/d group. While impaired renal function is the most frequently cited reason, nearly one-fourth of the patients had stable renal function. ACEI/ARB r/d therapy in the setting of ADHF merits further study.

Abstract 1213: Cardiac Overexpression of Epac1 in Transgenic Mice Protects Heart from Lipopolysaccharide-induced Cardiac Dysfunction and Inhibits JAK-STAT Pathway

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Satoshi Okumura ◽  
Yunzhe Bai ◽  
Meihua Jin ◽  
Sayaka Suzuki ◽  
Akiko Kuwae ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cyclic Amp ◽  
Transgenic Mice ◽  
Cardiac Function ◽  
Proinflammatory Cytokines ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Stat Pathway

The sympathetic nervous system and proinflammatory cytokines are believed to play independent roles in the pathophysiology of heart failure. However, the recent identification of Epac (exchange protein activated by cyclic AMP), a new cyclic AMP-binding protein that directly activates Rap1, have implicated that there may be a potential cross talk between the sympathetic and cytokine signals. In order to examine the role of Epac in cytokine signal to regulate cardiac function, we have generated transgenic mice expressing the human Epac1 gene under the control of alpha-cardiac myosin heavy chain promoter (Epac1-TG), and examined their response in lipopolysaccharide (LPS)-induced cardiac dysfunction, a well established model for sepsis-induced cardiac dysfunction. Sepsis-induced cardiac dysfunction results from the production of proinflammatory cytokines. At baseline, left ventricular ejection fraction (LVEF) was similar (TG vs. NTG, 67±1.7 vs. 69±2.1%, n =7–9). The degree of cardiac hypertrophy (LV(mg)/tibia(mm)) was also similar at 3 months old (TG vs. NTG 4.0±0.1 vs. 4.2±0.1, n =5–6), but it became slightly but significantly greater in Epac1-TG at 5 month old (TG vs. NTG 4.9±0.1 vs. 4.4±0.1, p< 0.05, n =5–7). LPS (5mg/kg) elicited a significant and robust reduction of LVEF in both Epac1-TG and NTG, but the magnitude of this decrease was much less in Epac1-TG at 6 hr after injection (TG vs. NTG 48±2.4 vs. 57±1.8%, p< 0.01, n =6–9). At 24 hr after injection, cardiac function was restored to the baseline in both Epac1-TG and NTG. We also examined the activation of JAK-STAT pathway at 24 hr after injection. The tyrosine phosphorylation of STAT1 (Tyr701) and STAT3 (Tyr705) in LV, which is an indicator of STAT activation, was reduced to a greater degree in Epac1-TG by 31±8.8% ( p< 0.05, n =4) and 29±5.9% ( p< 0.05, n =7), respectively, relative to that in NTG. Taken together, Epac1 protects the heart from the cytokine-induced cardiac dysfunction, at least in part, through the inhibition of the JAK-STAT pathway, suggesting the beneficial role played by sympathetic signal to antagonize proinflammatory cytokine signal in heart failure.

scholarly journals Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction

2017 ◽  
Vol 214 (7) ◽  
pp. 1877-1888 ◽  
Author(s):  
Takuma Tsuda ◽  
Mikito Takefuji ◽  
Nina Wettschureck ◽  
Kazuhiko Kotani ◽  
Ryota Morimoto ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Cardiac Dysfunction ◽  
Hormone Receptor ◽  
Adenosine Monophosphate ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Corticotropin Releasing Hormone ◽  
Ventricular Ejection Fraction ◽  
Releasing Hormone

Heart failure occurs when the heart is unable to effectively pump blood and maintain tissue perfusion. Despite numerous therapeutic advancements over previous decades, the prognosis of patients with chronic heart failure remains poor, emphasizing the need to identify additional pathophysiological factors. Here, we show that corticotropin releasing hormone receptor 2 (Crhr2) is a G protein–coupled receptor highly expressed in cardiomyocytes and continuous infusion of the Crhr2 agonist, urocortin 2 (Ucn2), reduced left ventricular ejection fraction in mice. Moreover, plasma Ucn2 levels were 7.5-fold higher in patients with heart failure compared to those in healthy controls. Additionally, cardiomyocyte-specific deletion of Crhr2 protected mice from pressure overload-induced cardiac dysfunction. Mice treated with a Crhr2 antagonist lost maladaptive 3′-5′-cyclic adenosine monophosphate (cAMP)–dependent signaling and did not develop heart failure in response to overload. Collectively, our results indicate that constitutive Crhr2 activation causes cardiac dysfunction and suggests that Crhr2 blockade is a promising therapeutic strategy for patients with chronic heart failure.

scholarly journals NONCOMPACT LEFT VENTRICULAR MYOCARDIUM (CLINICAL CASE)

2018 ◽  
Vol 35 (3) ◽  
pp. 87-92
Author(s):  
A V Tuev ◽  
L M Vasilets ◽  
O V Khlynova ◽  
L A Nekrutenko ◽  
Yu I Nazipova ◽  
...  
Keyword(s):  
Primary Prevention ◽  
Clinical Case ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Pressure Control ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Left Ventricular Myocardium ◽  
Converting Enzyme Inhibitors ◽  
Ventricular Ejection Fraction

The paper presents the clinical case of a 28-year-old patient, diagnosed noncompact myocardium of the left ventricle. The disease debuted from heart rate disturbance; Lown’s grade 4B ventricular premature beats were revealed according to the results of durable electrocardiogram monitoring. In echocardiography, significant decrease in the left ventricular ejection fraction was stated. After magnetic resonance imaging of the heart, the presence of two layers of myocardium, compact and noncompact with the latter exceeding the compact layer more than twofold was diagnosed. The patient underwent slow titration of the dose of angiotensin-converting enzyme inhibitors up to the maximum under the arterial pressure control. The following recommendations were given: anticoagulants for primary prevention of thromboembolic complications, planned implantation of a two-chamber artificial cardioaverter-defibrillator for primary prevention of sudden heart death.

Trastuzumab-mediated cardiac dysfunction (CDx) outside of clinical trials: Single Asian center experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20732-e20732
Author(s):  
J. Park ◽  
S. Han ◽  
D. Oh ◽  
J. Kim ◽  
H. Lee ◽  
...  
Keyword(s):  
Enzyme Inhibitors ◽  
Angiotensin Receptor Blockers ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Left Ventricular ◽  
University Hospital ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Converting Enzyme Inhibitors ◽  
Ventricular Ejection Fraction ◽  
Lower Baseline

e20732 Background: Trastuzumab is an effective drug for the treatment of HER2 positive breast cancer (BC) and CDx has been reported as a major toxicity. The purpose of our study was to investigate the trastuzumab mediated CDx in practice setting and the treatment outcome at single Asian center. Methods: We retrospectively analyzed 181 HER2-overexpressing BC patients (pts) who were treated with trastuzumab containing regimen between January 2005 and December 2007 at Seoul National University Hospital. We investigated the incidence of CDx and the degree of reversibility using echocardiography (EchoCG) and identify the risk factors to predict CDx. Results: Among 181 patients (pts), 112 were treated for palliative purpose and 139 had previously received anthracycline-based chemotherapy. Baseline EchoCG results were available in 129 pts (median age 47; range 25–79) and median left ventricular ejection fraction (LVEF) was 59% (range 45–70). Median follow-up duration was 21 months. LVEF decreased more than 5% points in 37 out of 129 (28.6%). According to the national cancer institute common terminology criteria for adverse events, grade (G) 2 and G 3/4 CDx developed in 4 (3.1%) and 8 (6.2%) pts respectively. Seven pts experienced symptomatic heart failure (HF). 3 among 5 pts who experienced discontinuation of trastuzumab could resume trastuzumab after median 146 (range 94–163) days of discontinuation. Median LVEF was 54% (range 45–63) at baseline in pts who experienced G2–4 CDx and deceased to 45% (range 30–49) after median 175 (range 65–415) days of trastuzumab treatment. HF treatment was initiated in 9 pts. 4 pts received angiotensin converting enzyme inhibitors (ACEI), 3 pts angiotensin receptor blockers (ARB) and 2 pts ACEI or ARB with diuretics. Occurrence of CDx (G2–4) was associated with higher anthracycline cumulative doses (p=0.039) and lower baseline LVEF (p=0.003). The incidence of symptomatic HF was related with past medical history such as hypertension (p=0.019) and lower baseline LVEF (p=0.005). Among the pts who had G2–4 CDx, LVEF was restored to 54% (range 40–59) which was similar to baseline at median 187 (range 56–477) days after the diagnosis of CDx. Conclusions: The majority pts with trastuzumab-mediated CDx were asymptomatic and LVEF could be reversible. No significant financial relationships to disclose.

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 Lingguizhugan decoction attenuates doxorubicin-induced heart failure in rats by improving TT-SR microstructural remodeling

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xueping Li ◽  
Guangmin Xu ◽  
Shujun Wei ◽  
Baocheng Zhang ◽  
Huan Yao ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
The Body ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Heart Weight ◽  
Ventricular Ejection Fraction

Abstract Background Lingguizhugan decoction (LGZG), an ancient Chinese herbal formula, has been used to treat cardiovascular diseases in eastern Asia. We investigated whether LGZG has protective activity and the mechanism underlying its effect in an animal model of heart failure (HF). Methods A rat model of HF was established by administering eight intraperitoneal injections of doxorubicin (DOX) (cumulative dose of 16 mg/kg) over a 4-week period. Subsequently, LGZG at 5, 10, and 15 mL/kg/d was administered to the rats intragastrically once daily for 4 weeks. The body weight, heart weight index (HWI), heart weight/tibia length ratio (HW/TL), and serum BNP level were investigated to assess the effect of LGZG on HF. Echocardiography was performed to investigate cardiac function, and H&E staining to visualize myocardial morphology. Myocardial ultrastructure and T-tubule-sarcoplasmic reticulum (TT-SR) junctions were observed by transmission electron microscopy. The JP-2 protein level was determined by Western blotting. The mRNA level of CACNA1S and RyR2 and the microRNA-24 (miR-24) level were assayed by quantitative RT-PCR. Results Four weeks after DOX treatment, rats developed cardiac damage and exhibited a significantly increased BNP level compared with the control rats (169.6 ± 29.6 pg/mL versus 80.1 ± 9.8 pg/mL, P < 0.001). Conversely, LGZG, especially at the highest dose, markedly reduced the BNP level (93.8 ± 17.9 pg/mL, P < 0.001). Rats treated with DOX developed cardiac dysfunction, characterized by a strong decrease in left ventricular ejection fraction compared with the control (58.5 ± 8.7% versus 88.7 ± 4.0%; P < 0.001). Digoxin and LGZG improved cardiac dysfunction (79.6 ± 6.1%, 69.2 ± 2.5%, respectively) and preserved the left ventricular ejection fraction (77.9 ± 5.1, and 80.5 ± 4.9, respectively, P < 0.01). LGZG also improved the LVEDD, LVESD, and FS and eliminated ventricular hypertrophy, as indicated by decreased HWI and HW/TL ratio. LGZG attenuated morphological abnormalities and mitochondrial damage in the myocardium. In addition, a high dose of LGZG significantly downregulated the expression of miR-24 compared with that in DOX-treated rats (fold change 1.4 versus 3.4, P < 0.001), but upregulated the expression of JP-2 and antagonized DOX-induced T-tubule TT-SR microstructural remodeling. These activities improved periodic Ca2+ transients and cell contraction, which may underly the beneficial effect of LGZG on HF. Conclusions LGZG exerted beneficial effects on DOX-induced HF in rats, which were mediated in part by improved TT-SR microstructural remodeling.

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