Right Heart Changes Impact on Clinical Phenotype of Amyloid Cardiac Involvement: A Single Centre Study

Abstract

Amyloidosis is due to deposition of an excessive amount of protein in many parenchymal tissues, including myocardium. The onset of cardiac Amyloidosis (CA) is an inauspicious prognostic factor, that can lead to sudden death. We retrospectively analyzed 135 patients with systemic amyloidosis, admitted to our ward between 1981 and 2019. Among them, 54 patients (46.30% F / 53.70% M, age 63.95±12.82 years) presented CA at baseline. In 53 patients, there was associated with multiorgan involvement, while in one there was primary myocardial deposition. As control group, we enrolled 81 patients (49.30% F / 50.70% M, aged 58.33±15.65) who did not meet the criteria for CA. In 44/54 of patients CA was associated with AL, 5/54 with AA, 3/54 of patients with ATTR, in 1/54 AL was related to hemodialysis and 1/54 to Gel-Amyloidosis. The most common AL type was IgG (28/44); less frequent forms were either IgA (7/40) or IgD (2/40), while seven patients had a λ free light chain form. The 32 AL with complete Ig were 31 λ-chain and just one k-chain. CA patients presented normal BP (SBP 118.0±8.4 mmHg; DBP 73.8±4.9 mmHg), while those with nCA had increased proteinuria (p=0.02). TnI and NT-proBNP were significantly increased compared to nCA (p= 0.031 and p=0.047, respectively). In CA patients we found an increased LDH compared to nCA (p=0.0011). CA patients were also found to have an increased interventricular septum thickness compared to nCA (p=0.002), a decreased Ejection Fraction % (p=0.0018) and Doppler velocity E/e’ ratio (p=0.0095). Moreover, CA patients were seen to have an enhanced right atrium area (p=0.0179), right ventricle basal diameter (p= 0.0112) and wall thickness (p=0.0471) as compared to nCA, as well as an increased inferior cava vein diameter (p=0.0495). TAPSE was the method chosen to evaluate systolic function of the right heart. In CA subjects very poor TAPSE levels were found compared to nCA patients (p=0.0495). Additionally, we found a significant positive correlation between TAPSE and lymphocyte count (r=0.47; p=0.031) as well as Gamma globulins (r=0.43, p=0.033), Monoclonal component (r=0.72; p=0.047) and IgG values (r=0.62, p=0.018). On the contrary, a significant negative correlation with LDH (r=-0.57, p=0.005), IVS (r=-0.51, p=0.008) and diastolic function evaluated as E/e’ (r=-0.60, p=0.003) were verified. CA patients had very poor survival compared to controls (30 vs. 66 months in CA vs nCA, respectively, P=0.15). Mean survival of CA individuals was worse also when stratified according to NT-proBNP levels, using 2500 pg/mL as class boundary (174 vs. 5.5 months, for patients with lower vs higher values than the median, respectively p=0.013). In much the same way, decreased right heart systolic function was correlated with a worse prognosis (18.0 months median survival, not reached in subjects with lower values than 18mm, p=0.0186). Finally, our data highlight the potential prognostic and predictive value of right heart alterations characterizing amyloidosis, as a novel clinical parameter correlated to increased LDH and immunoglobulins levels. Overall, we confirm the clinical relevance of cardiac involvement and propose that right heart evaluation may be considered as a new marker for clinical risk stratification in patients with amyloidosis.

Cardiac Amyloidosis: A Review of Current Imaging Techniques

“…Both mitral and tricuspid annular plane systolic excursion (MAPSE, TAPSE) have been proven to be prognostic indicators in CA (29,30). The relatively early impairment of longitudinal function with preserved radial function, affecting predominantly basal segments over apical segments, is uncommon in other cardiomyopathies and is highly characteristic of CA.…”

Imaging-Guided Treatment for Cardiac Amyloidosis

“…Although CA has been classically regarded as a cause of HFpEF, this terminology underestimates the effect of amyloid infiltration on systolic function. Longitudinal function is typically affected before radial contraction and was classically reflected in a reduced mitral and tricuspid annular plane systolic excursion (MAPSE and TAPSE) [ 29 , 30 ]. Advances in longitudinal strain (LS) measurements through speckle tracking provide more accurate estimations of longitudinal function, and regional strain measurements that predominantly affect the basal segments with apical sparing.…”

Cancer-Associated Angiogenesis: The Endothelial Cell as a Checkpoint for Immunological Patrolling

“…Multiple myeloma (MM) is a clonal proliferation of malignant plasma cells (PCs) accumulating and disseminating in the bone marrow (BM) with ensuing induction of focal skeletal lesions and osteoporosis driving myeloma bone disease, anemia, renal insufficiency, hypercalcemia [ 72 ], higher infection rates [ 73 , 74 , 75 ], and secondary life-threatening complications [ 76 , 77 , 78 ]. MM represents an ideal model of colonization and interaction of tumor cells in the bone microenvironment [ 79 , 80 , 81 ], where the immune-milieu [ 82 , 83 ] and aberrant angiogenesis shape a permissive ecosystem, supporting disease progression via a plethora of autocrine [ 84 , 85 ] and paracrine loops [ 86 , 87 ].…”