[ANMCO Position paper: Amyloidosis for the clinical cardiologist. A "clinical primer" from the ANMCO Rare Disease Working Group]. / Position paper ANMCO: L'amiloidosi per il cardiologo clinico. Un "clinical primer" dell'Area Malattie Rare ANMCO.

Cardiac amyloidosis, in the three forms of immunoglobulin light chain (AL), transthyretin (ATTR) wild type (ATTRwt) and mutated (ATTRv) amyloidosis, is an increasingly known and recognized disease in the cardiovascular setting. The first stage of the patient's journey is the clinical suspicion of the disease, which is placed, in presence of a hypertrophic phenotype, by the identification of red flags, both extracardiac and cardiac clues whose presence increase the probability of being faced with a patient with this disease. The second stage is represented by diagnosis, which occurs with certainty through the identification of amyloid substance in cardiac tissue. This stage is spotted in wo parts, i.e. disease confirmation and disease etiology definition (AL vs ATTRwt vs ATTRv). However, it is possible in some selected cases to make a diagnosis of ATTR without the need for tissue assessment, in presence of a positive grade 2-3 bisphosphonate scintigraphy and absence of monoclonal component. Once the diagnosis has been made, the third stage is the assessment of prognosis, the fourth is the patient therapy pathway and fifth is the follow-up plan. Prognosis evaluation is based on different staging systems at the onset of the disease, whose applicability in the era of new effective therapies is still to be defined. To date, the transthyretin tetramer stabilizer tafamidis is the only approved treatment for both wild-type and mutant ATTR cardiomyopathy without polyneuropathy, while ATTRv with associated neuropathy can benefit from treatment with patisiran, an inhibitor of hepatic protein synthesis. Therapies for complications and comorbidities, must be addressed individually, due to the lack of specific clinical trials on this category of patients. In fact, it is important to take into consideration the risks linked to the use of some drugs due to the infiltration of the conduction tissue by the amyloid substance, which increases the risk of bradycardia and heart blocks, the tendency towards hypotension and the increased thromboembolic risk. It is also essential to follow the course of the disease and the efficacy of the treatment in affected patients with a standardized follow-up, and to identify early the signs/symptoms of the disease in asymptomatic TTR mutation carriers.This ANMCO position paper on amyloidosis aims to provide the clinical cardiologist with a practical summary of the disease, to accompany the patient with amyloidosis in the various stages of his journey.

Cardiovascular maladaptation to exercise in young hypertensive patients.

BACKGROUND: Impairment of the adaptive mechanisms that increase cardiac output during exercise can translate to a reduced functional capacity. We investigated cardiovascular adaptation to exertion in asymptomatic hypertensive patients, aiming to identify the early signs of cardiac and vascular dysfunction. METHODS AND RESULTS: We enrolled 54 subjects: 30 patients (45.1±11.9years, 19 males) and 24 age-matched healthy controls (44.4±9.6years, 14 males). Speckle-tracking echocardiography (STE) and echo-tracking were performed at rest and during exertion to assess myocardial deformation and arterial stiffness. RESULTS: E/E' increased from rest to peak exercise more in patients than in controls (peak stage: p=0.024). Global longitudinal strain increased significantly from rest to peak stage in controls (p=0.011) whereas it remained unchanged in patients (p=0.777). Left atrial (LA) reservoir was significantly increased throughout the exercise only in controls (p=0.001) whereas it was almost unchanged in patients (p=0.293). LA stiffness was significantly higher in patients than in controls both at rest (p=0.023) and during exercise (p<0.001). Beta index and pulse wave velocity (PWV) increased during exercise in both groups, showing higher values in patients in each step. CONCLUSIONS: Our study showed a more pronounced maladaptation during exercise, with respect to rest, of the cardiovascular system with impaired cardiac-vessel coupling in hypertensive patients compared to healthy subjects. Exercise echocardiography implemented by STE and echo-tracking is invaluable in the early detection of these cardiovascular abnormalities.