ANMCO position paper on vericiguat use in heart failure: from evidence to place in therapy.

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.

Primary mediastinal large B-cell lymphoma and pregnancy: a challenging clinical scenario.

A 26-weeks pregnant woman presented with progressively worsening dyspnoea and poor general conditions. Using low-dose radiation multi-imaging techniques and thoracic biopsy a primary mediastinal large B cell was diagnosed. A multidisciplinary approach identified the correct hemodynamic management, the best therapeutic strategy and the timing for delivery.

Cardiovascular Structural and Functional Parameters in Idiopathic Pulmonary Fibrosis at Disease Diagnosis.

INTRODUCTION: Prevalence of cardiac and vascular fibrosis in patients with Idiopathic Pulmonary Fibrosis (IPF) has not been extensively evaluated. AIM: In this study, we aimed to evaluate the heart and vessels functional and structural properties in patients with IPF compared to healthy controls. An exploratory analysis regarding disease severity in IPF patients has been done. METHODS: We enrolled 50 patients with IPF (at disease diagnosis before antifibrotic therapy initiation) and 50 controls matched for age and gender. Heart was evaluated through echocardiography and plasmatic NT-pro-brain natriuretic peptide that, together with patients' symptoms, allow to define the presence of Heart Failure (HF) and diastolic dysfunction. Vessels were evaluated through Flow Mediated Dilation (FMD - endothelial function) and Pulse Wave Velocity (PWV-arterial stiffness) RESULTS: Patients with IPF had a prevalence of diastolic disfunction of 83.8%, HF of 37.8% and vascular fibrosis of 76.6%. No statistically significant difference was observed in comparison to the control group who showed prevalence of diastolic disfunction, HF and vascular fibrosis of 67.3%, 24.5% and 84.8%, respectively. Disease severity seems not to affect PWV, FMD, diastolic dysfunction and HF. CONCLUSIONS: Patients with IPF early in the disease course do not present a significant CV fibrotic involvement when compared with age- and sex-matched controls. Bigger and adequately powered studies are needed to confirm our preliminary data and longitudinal studies are required in order to understand the time of appearance and progression rate of heart and vascular involvement in IPF subjects.

Chemotherapy-related cardiac dysfunction: the usefulness of myocardial work indices.

AIMS: The role of left ventricular global longitudinal strain (GLS) in the diagnosis of subclinical cardiac damage induced by anticancer drugs is now consolidated. Considering some strain disadvantages such as the dependence on the haemodynamic loading conditions, the aim of our study was to investigate the usefulness of non-invasive myocardial work indices (MWI) derived from pressure-strain analysis, in the early diagnosis of cardiotoxicity. METHODS AND RESULTS: We enrolled 61 consecutive patients with breast cancer undergoing adjuvant treatment with anthracycline-containing chemotherapy followed by taxane + trastuzumab. Patients underwent a cardiological evaluation with 2D echocardiography including measurement of the left ventricular ejection fraction (LVEF) and other conventional parameters of systolic and diastolic function, GLS and MWI at baseline (T0), 3 months (T1) and 6 months (T2) after starting chemotherapy. At T1 and T2, we did not find a significant reduction in LVEF but we found a significant reduction in GLS and MWI (p value < 0.05). In addition, at T2, 31% of patients developed subclinical cardiac dysfunction defined as a relative decrease ≥ 12% of GLS from baseline. Global work index (GWI), global constructive work (GCW) and global work efficiency (GWE) decreased significantly in both patients with subclinical dysfunction and in those without subclinical dysfunction (p value < 0.05). Patients with subclinical dysfunction at T2 showed lower values of GCW at T0. CONCLUSION: MWI changed significantly during chemotherapy and appeared to alter precociously compared to GLS. Therefore, a multiparametric approach including left ventricular GLS and MWI measurements should be used in the evaluation of patients undergoing cardiotoxic antineoplastic treatment.

[ANMCO Position paper: Vericiguat use in heart failure: from evidence to place in therapy]. / Position paper ANMCO: Impiego di vericiguat nello scompenso cardiaco: dalle evidenze al posizionamento terapeutico.

In the growing therapeutic armamentarium for heart failure management, vericiguat represents an innovative therapeutic option. The biological target of this drug is different from that of other drugs for heart failure. Indeed, vericiguat does not inhibit neurohormonal systems overactivated in heart failure or sodium-glucose cotransporter 2 but stimulates the biological pathway of nitric oxide and cyclic guanosine monophosphate, which is impaired in patients with heart failure. Vericiguat has recently been approved by international and national regulatory authorities for the treatment of patients with heart failure and reduced ejection fraction who are symptomatic despite optimal medical therapy and have worsening heart failure. This ANMCO position paper summarizes 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.

Secondary Prevention and Extreme Cardiovascular Risk Evaluation (SEVERE-1), Focus on Prevalence and Associated Risk Factors: The Study Protocol.

INTRODUCTION: Despite significant improvement in secondary CardioVascular (CV) preventive strategies, some acute and chronic coronary syndrome (ACS and CCS) patients will suffer recurrent events (also called "extreme CV risk"). Recently new biochemical markers, such as uric acid (UA), lipoprotein A [Lp(a)] and several markers of inflammation, have been described to be associated with CV events recurrence. The SEcondary preVention and Extreme cardiovascular Risk Evaluation (SEVERE-1) study will accurately characterize extreme CV risk patients enrolled in cardiac rehabilitation (CR) programs. AIM:  Our aims will be to describe the prevalence of extreme CV risk and its association with newly described biochemical CV risk factors. AIM: Our aims will be to describe the prevalence of extreme CV risk and its association with newly described biochemical CV risk factors. METHODS: We will prospectively enrol 730 ACS/CCS patients at the beginning of a CR program. Extreme CV risk will be retrospectively defined as the presence of a previous (within 2 years) CV events in the patients' clinical history. UA, Lp(a) and inflammatory markers (interleukin-6 and -18, tumor necrosis factor alpha, C-reactive protein, calprotectin and osteoprotegerin) will be assessed in ACS/CCS patients with extreme CV risk and compared with those without extreme CV risk but also with two control groups: 1180 hypertensives and 765 healthy subjects. The association between these biomarkers and extreme CV risk will be assessed with a multivariable model and two scoring systems will be created for an accurate identification of extreme CV risk patients. The first one will use only clinical variables while the second one will introduce the biochemical markers. Finally, by exome sequencing we will both evaluate polygenic risk score ability to predict recurrent events and perform mendellian randomization analysis on CV biomarkers. CONCLUSIONS: Our study proposal was granted by the European Union PNRR M6/C2 call. With this study we will give definitive data on extreme CV risk prevalence rising attention on this condition and leading cardiologist to do a better diagnosis and to carry out a more intensive treatment optimization that will finally leads to a reduction of future ACS recurrence. This will be even more important for cardiologists working in CR that is a very important place for CV risk definition and therapies refinement.