Use of Sacubitril/valsartan in patients with cardio toxicity and heart failure due to chemotherapy.

BACKGROUND: Cancer therapy-related cardiac dysfunction (CTRCD) is a critical problem with an impact on both oncological and cardiovascular prognosis, especially when it prevents patients from receiving cancer treatment. Standard therapy for heart failure (HF) is recommended for CTRCD, but there is no well-established evidence on how sacubitril/valsartan may help cancer patients with cardiotoxicity. OBJECTIVES: The aim of this trial was to study the effectiveness of sacubitril-valsartan in patients with CTRCD treated in cardio-oncology units. METHODS: We enrolled 635 patients with breast cancer and followed them with echocardiography and NT- proBNP. Patients who developed left ventricular dysfunction and heart failure were treated with angiotensin-converting enzyme inhibitors (ACEI) (enalapril) or angiotensin receptor blockers (ARB) (valsartan), aldosterone antagonists (eplerenone), digitalis and diuretics (furosemide), as needed. When patients remained symptomatic and met the PARADIGM-HF inclusion criteria, sacubitril/valsartan was started instead of enalapril or valsartan. We analyzed clinical, laboratory and echocardiographic variables to determine the beneficial effects of sacubitril/valsartan on left ventricular remodeling (improvement of left ventricular ejection fraction (LVEF), left ventricle internal diameter in diastole), diastolic dysfunction (E/e' ratio), reduction in NT-proBNP levels, New York Heart Association (NHYA) class and improvement in the 6-min walk test. Also, we analyzed serum creatinine and potassium levels to determine treatmentsafety in this population. Median follow-up was 20 months. RESULTS: Twenty-eight patients developed cardiotoxicity and were treated with sacubitril/valsartan. The sacubitril/valsartan dose was 100 mg (sacubitril 49 mg/valsartan 51 mg) in 12 patients (42.85%) and 200 mg (sacubitril 97 mg/valsartan 103 mg) in 16 patients (57.15%). No deaths were reported, and one patient underwent heart transplantation. Baseline median NT-proBNP was 997.5 pg/ml (IQR 663.8 - 2380.8), which decreased to a median of 416.5 pg/ml (IQR 192.0-798.2) on follow-up with p < 0.001. Baseline NYHA functional class was III (78.6%) or IV (21.4%), and it improved to I (57.1%) or II (42.9%) on follow-up. LVEF increased with treatment from 26.7 ± 5.4% to 32.3 ± 5.5% (p < 0.001). There were also significant improvements in left ventricle internal diameter in diastole (LVIDD), diastolic function, 6-min walk test, and mitral valve regurgitation. There were no differences between basal and follow-up levels of serum creatinine or potassium. CONCLUSION: Sacubitril/valsartan might be a promising treatment option in patients with refractory CTRCD.

Role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies: a position statement from the Cardio-Oncology Study Group of the Heart Failure Association and the Cardio-Oncology Council of the European Society of Cardiology.

Serum biomarkers are an important tool in the baseline risk assessment and diagnosis of cardiovascular disease in cancer patients receiving cardiotoxic cancer treatments. Increases in cardiac biomarkers including cardiac troponin and natriuretic peptides can be used to guide initiation of cardioprotective treatments for cancer patients during treatment and to monitor the response to cardioprotective treatments, and they also offer prognostic value. This position statement examines the role of cardiac biomarkers in the management of cancer patients. The Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the Cardio-Oncology Council of the ESC have evaluated the current evidence for the role of cardiovascular biomarkers in cancer patients before, during and after cardiotoxic cancer therapies. The characteristics of the main two biomarkers troponin and natriuretic peptides are discussed, the link to the mechanisms of cardiovascular toxicity, and the evidence for their clinical use in surveillance during and after anthracycline chemotherapy, trastuzumab and HER2-targeted therapies, vascular endothelial growth factor inhibitors, proteasome inhibitors, immune checkpoint inhibitors, cyclophosphamide and radiotherapy. Novel surveillance clinical pathways integrating cardiac biomarkers for cancer patients receiving anthracycline chemotherapy or trastuzumab biomarkers are presented and future direction in cardio-oncology biomarker research is discussed.

Doppler Tissue Imaging positive preejection velocity wave is a sign of non-transmural necrosis: comparison with delayed-enhancement cardiac magnetic resonance.

AIMS: Our purpose was to test the hypothesis that Tissue Doppler Imaging (TDI)-derived positive preejection velocity (PPV) is associated with transmural extent of necrosis in delayed-enhancement cardio-magnetic resonance (DE-CMR) in patients with reperfused myocardial infarction (MI). METHODS AND RESULTS: Longitudinal myocardial velocities were recorded by TDI in 24 patients with MI reperfused with primary angioplasty, using an Acuson-Sequoia equipment. The same day a CMR study was performed, including cine images in short axis and long axis views and DE images in the same views using a 3D-T1-Turbo-field-echo sequence, 15 min after administration of gadodiamide. Transmural extent of hyperenhancement in each segment was compared to presence or absence of PPV wave. A total of 384 segments were evaluated. Normo-hypokinetic segments (100%) showed a PPV wave, whereas it was only present in 53% of akinetic-dyskinetic segments (p=0.0005). One hundred percent of the segments with absent-mild DE showed a PPV wave; this percentage was lower in segments with intermediate and transmural DE (63 and 10%, p=0.001). The presence of PPV wave in an akinetic segment ruled out transmural necrosis with 97% sensitivity and 90% specificity. CONCLUSIONS: The absence of PPV is strongly associated to transmural necrosis in MI and therefore to absence of viability.