Immune-Checkpoint Inhibitor-Related Myocarditis: Where We Are and Where We Will Go.

Immune checkpoint inhibitors (ICIs) are specific monoclonal antibodies directed against inhibitory targets of the immune system, mainly represented by programmed death-1 (PD1) ligand-1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4), thus enabling an amplified T-cell-mediated immune response against cancer cells. These drugs have significantly improved prognosis in patients with advanced metastatic cancer (e.g., melanoma, non-small cell lung cancer, renal cell carcinoma). However, uncontrolled activation of anti-tumor T-cells could trigger an excessive immune response, possibly responsible for multi-organ damage, including, among others, lymphocytic myocarditis. The incidence of ICIs-induced myocarditis is underestimated and the patients affected are poorly characterized. The diagnosis and management of this condition are mainly based on expert opinion and case reports. EKG and ultrasound are tests that can help identify patients at risk of myocarditis during treatment by red flags, such as QRS complex enlargement and narrowing of global longitudinal strain (GLS). Therapy of ICI-related myocarditis is based on immunosuppressors, monoclonal antibodies and fusion proteins. A future strategy could involve the use of microRNAs. This review considers the current state of the art of immune-related adverse cardiovascular events, focusing on histological and clinical features, diagnosis and management, including current treatments and future pharmacological targets.

Echocardiographic probability of pulmonary hypertension: a validation study.

BACKGROUND: According to current guidelines, the diagnosis of pulmonary hypertension (PH) relies on echocardiographic probability followed by right heart catheterisation (RHC). How echocardiography predicts PH recently redefined by mean pulmonary arterial pressure (mPAP) >20 mmHg instead of ≥25 mmHg and pulmonary vascular disease defined by pulmonary vascular resistance (PVR) ≥3 or >2 WU has not been established. METHODS: A total of 278 patients referred for PH underwent comprehensive echocardiography followed by RHC. 15 patients (5.4%) were excluded because of insufficient quality echocardiography. RESULTS: With PH defined by mPAP >20 mmHg, 23 patients had no PH, 146 had pre-capillary PH and 94 had post-capillary PH. At univariate analysis, maximum tricuspid regurgitation velocity (TRV) 2.9-3.4 m·s-1, left ventricle (LV) eccentricity index >1.1, right ventricle outflow tract acceleration time (RVOT-AT) <105 ms or notching, RV/LV basal diameter >1 and pulmonary artery diameter predicted PH, whereas inferior vena cava diameter and right atrial area did not. At multivariable analysis, only TRV ≥2.9 m·s-1 independently predicted PH. Additional independent prediction of PVR ≥3 WU was offered by LV eccentricity index >1.1, and RVOT-AT <105 ms and/or notching, but with no improvement of optimal combination of specificity and sensitivity or positive prediction. CONCLUSIONS: Echocardiography as recommended in current guidelines can be used to assess the probability of redefined PH in a referral centre. However, the added value of indirect signs is modest and sufficient quality echocardiographic signals may not be recovered in some patients.

[Pulmonary arterial hypertension or heart failure with preserved ejection fraction? Beyond heart catheterization: a roadmap for challenging cases]. / Ipertensione arteriosa polmonare o scompenso cardiaco a funzione sistolica conservata? Al di là del cateterismo cardiaco: una "roadmap" per i casi difficili.

The cause of dyspnea may remain uncertain even after a complete non-invasive clinical workup, and a right heart catheterization is performed to achieve a definitive diagnosis. Although pulmonary artery wedge pressure (PAWP) is key for the differential diagnosis between pulmonary arterial hypertension (PAH) and heart failure with preserved ejection fraction (HFpEF), the diagnosis may be challenging because PAWP may be normal after diuretic administration in HFpEF patients on optimal medical therapy. In order to avoid misdiagnosis, building a pre-test probability of pre- or post-capillary pulmonary hypertension is crucial. Current guidelines on pulmonary hypertension suggest to interpret hemodynamics in the context of clinical picture and imaging, mainly echocardiography. Indecisive measurements of PAWP in patients with an intermediate to high clinical probability of HFpEF can be repeated after a fluid challenge test with rapid infusion of 7 ml/kg or 500 ml of saline. The procedure is simple and does not take much catheterization laboratory time. A post-fluid challenge PAWP >18 mmHg strongly supports the diagnosis of occult HFpEF. A possible alternative to fluid challenge test is exercise or dobutamine stress test. However, exercise hemodynamics is not feasible in all catheterization laboratories and may be difficult to interpret due to wide swings in intrathoracic pressures. Otherwise, dobutamine infusion during right heart catheterization may be potentially more practical than exercise stress, but requires further validation studies to determine its utility. The aim of this case report is to provide a practical roadmap for challenging cases, when the differential diagnosis between PAH and HFpEF is uncertain.