In the growing therapeutic armamentarium for heart failure (HF) management, vericiguat represents an innovative therapeutic option. The biological target of this drug is different from that of other drugs for HF. Indeed, vericiguat does not inhibit neuro-hormonal systems overactivated in HF or sodium–glucose co-transporter 2 but stimulates the biological pathway of nitric oxide and cyclic guanosine monophosphate, which is impaired in patients with HF. Vericiguat has recently been approved by international and national regulatory authorities for the treatment of patients with HF and reduced ejection fraction who are symptomatic despite optimal medical therapy and have worsening HF. This ANMCO position paper summarises key aspects of vericiguat mechanism of action and provides a review of available clinical evidence. Furthermore, this document reports use indications based on international guideline recommendations and local regulatory authority approval at the time of writing.
Background Chemotherapeutic drugs may cause many complications affecting the cardiovascular system. There is a strong evidence suggesting the impact of this drugs on the left ventricle (LV), whereas less data regarding cardiotoxicity on the right ventricle (RV) exist. Purpose The aim of this study was to intercept early subclinical RV changes in patients treated with anthracyclines, using advanced echocardiography, with the hope that these could potentially be used to predict ventricular dysfunction. Methods In our single-center study, 20 female patients with breast cancer treated with anthracyclines were enrolled from 2019 to 2021. Cardiological evaluation and echocardiogram were performed at baseline (T0), 3 months (T1) and 6 months (T2) after initiation of chemotherapy. RV systolic function was calculated by estimation of conventional 2D echocardiographic and Doppler parameters (TAPSE, S’RV, FAC). Advanced echocardiography evaluation of right ventricular function was performed to quantify the following parameters: 3D right ventricular end-diastolic volume (RVEDV), 3D end-systolic volume (RVESV), 3D stroke volume (RVSV), 3D ejection fraction (RVEF), global longitudinal strain of the RV (RVGLS) and longitudinal free wall strain of the RV (RVLFS). Results Only 2 patients developed cardiotoxicity according to the criteria of the 2022 ESC Guidelines. Regarding the impact of chemotherapy on RV function, no statistically significant changes were found in conventional echocardiographic parameters (TAPSE, S’RV, FAC). In contrast, speckle tracking analysis of the RV showed a statistically significant reduction in both global strain [global RVGLS -23.3 ± 2.2% at T0 vs -19.5 ± 10.9% at T1 (p<0.0001); global RVGLS -23.3 ± 2.2% at T0 vs -19.8 ± 3.2% at T2 (p<0.0001)] and free wall strain [RVLFS -30.02 ± 3.3% at T0 vs -18.2 ± 21.2% at T1 (p=0.0001); RVLFS -30.02 ± 3.3% at T0 vs -23.7 ± 4.6% at T2 (p=0.0006)]. We observed a statistically significant increase in RVEDV at T1 compared to baseline [3D RVEDV 81.3 ± 16,9 ml al T0 vs 82.6 ± 19.2 ml at T1 (p=0,04)], whereas there were no significant changes at T2. Estimation of RVESV revealed the same trend, with a statistically significant increase in this parameter at T1 compared to baseline [3D RVESV 34.4 ± 10.4 ml at T0 vs 37.8 ± 10.8 ml at T1 (p=0.01)]. In relation to the RVEF, a minimal statistically significant reduction was observed at both T1 and T2 compared to T0 [3D RVEF 63.7 ± 4.3% at T0 vs 62.7 ± 4% at T1 (p= 0.01); 3D RVEF 63.7 ± 4.3% at T0 vs 58.7 ± 6% at T2 (p= 0.02)]. Conclusions RV speckle tracking and 3D echocardiography seemed to intercept subclinical damage due to anthracyclines earlier than conventional parameters. Further studies are needed to confirm our results and to evaluate their prognostic impact.
Funding Acknowledgements Type of funding sources: None. Background The aim of our study was to assess subclinical cardiac effects of anthracyclines (ANTs) in women treated for breast cancer (BC). Methods We enrolled 46 female patients with BC undergoing adjuvant treatment with anthracycline-containing chemotherapy (CT) followed by taxane (paclitaxel/docetaxel). Patients underwent physical examination, electrocardiogram (ECG) and standard transthoracic echocardiography (TTE) including evaluation of diastolic and systolic function, measured as left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (GLS) and myocardial work (MW) expressed as global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE). The parameters were measured at baseline (T0) and at 3 months (T1) and 6 months (T2) follow up. Results All patients completed the chemotherapy cycles. No significant cardiovascular adverse events were observed during treatment. Neither 2D left ventricular ejection fraction (LVEF) nor E/e’ ratio evaluation at TDI were significantly changed after treatment. Conversely, GLS was significantly reduced at T1 and T2 since baseline (GLS - 19,99 % IQR -20,6 -19,3 % at T0 vs -17,88 % IQR -18,8 -16,9 % at T1, p< 0,00 1 and -16,71 % IQR 17,6 -15,7 % at T2, p< 0,001). Consensually, a significant reduction in myocardial work was also measured (GWI 2115 mmHg% IQR 1888 – 2342 mmHg% at T0 vs 1714 mmHg% IQR 1557 – 1870 mmHg% at T1, p< 0,0001 and 1694 mmHg% IQR 1482 – 1907 mmHg% at T2, p< 0,0001). Conclusion Our study demonstrates that evaluation of myocardial work allows very early detection of subclinical cardiac damage induced by chemotherapy, consensually to the reduction of the GLS. A multiparametric assessment of the myocardial function, including myocardial work and GLS, could improve the accuracy of risk stratification of cardiotoxicity in patients undergoing ANTs treatment.
A 33 years old patient came to our attention, pregnant in her 26th week. She had dyspnoea, cough and weight loss (up to 45 kg of weight) in the previous two weeks. During urgent gynecological check-up she was found in poor general conditions, tachypnoic (respiratory rate >30 acts/minutes) with pale skin and bilateral jugular turgor. There was nothing relevant in her past medical history except for a thrombocytopenia appeared 2 months before. She consulted a haematologist who recommended to look for JAK2 mutation that was excluded. Echocardiography revealed a voluminous hypoechoic mass extrinsically imprinting the roof and the anterior wall of the right atrium that also involved inferior vena cava as a sleeve; a flow acceleration with an average gradient of 6 mmHg was documented at the level of right lower pulmonary vein and a possible infiltration of atrial wall was seen. Left ventricle was normal in size and kinesis; right ventricle also showed preserved contractility of the free wall with reduction in the distal outflow portion due to diffuse soft thickening that surrounded this portion and that extended cranially towards the trunk of pulmonary artery and ascending aorta. There also was a layer of circumferential pericardial effusion, apparently organized, with irregular profile of visceral pericardial sheet adjacent to diaphragmatic wall of right ventricle. On chest contrast computed tomography (CT) a voluminous mediastinal solid mass (13 × 16 × 18 cm) was confirmed with inhomogeneous enhancement for central necrotic components determining complete atelectasis of middle and upper right lung lobes and compression of superior vena cava, of some branches of pulmonary artery and ipsilateral pulmonary veins too; supra-aortic trunks and aorta were surrounded by the mass but open; the mass enveloped the right posterolateral area of the heart, displacing it to the left and compressing right atrium with apparent pericardial infiltration. Moreover there were approximately 16 mm of pericardial effusion and multiple mediastinal adenopathies. A chest and abdomen magnetic resonance confirmed the presence of the known voluminous heteroplastic formation occupying almost all right hemithorax, indissociable from the pericardium, with compression of right heart chambers and cavae veins. A thoracic biopsy of mediastinal mass was urgently performed under ultrasound guidance and followed by systemic steroid therapy. Histological examination showed off the diagnosis of primary large B cell lymphoma of the mediastinum (PMBCL, according to WHO classification 2016). A steroid therapy and chemotherapy cycles were started (Cyclophosphamide-Hydroxydaunorubicin-Oncovin-Prednisone—CHOP scheme). On the second day after chemotherapy, we saw a sudden worsening of clinical conditions: the patient had severe respiratory distress and signs of low cardiac output such as hypotension, elevated heart rate, increased blood lactates, low venous oxygen saturation (SVO2 45%), and elevation N-terminal prohormone of brain natriuretic peptide (NT-proBNP); she was therefore admitted to intensive care unit (ICU) where a gradual optimization of haemodynamic parameters. Then she underwent a second cycle of chemotherapy: dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) and was then successfully discharged. In such cases a careful evaluation and balancing of both haematological and gynecological–obstetric aspects is needed and it requires a multidisciplinary team approach in order to identify the best diagnostic and therapeutic pathway and, most of all, the best timing for delivery depending on gestational age.
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