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, which 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, aged 63.95 ± 12.82) presented CA at baseline. In 53 patients, it was associated with a multiorgan involvement, while in one there was a primary myocardial deposition. As a 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 and 3/54 of patients with ATTR, and in 1/54 AL was related to hemodialysis and in 1/54 to Gel-Amyloidosis. The most common AL type was IgG (28/44); less frequent forms were either IgA (7/44) or IgD (2/44), 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 an 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 had an enhanced right atrium area (p = 0.0179), right ventricle basal diameter (p = 0.0112) and wall thickness (p = 0.0471) compared to nCA, and an increased inferior cava vein diameter (p = 0.0495) as well. 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 components (r = 0.72; p = 0.047) and IgG values (r = 0.62, p = 0.018). Conversely, 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 rates 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, a decreased right heart systolic function was correlated with a worse prognosis (18.0 months median survival, not reached in subjects with lower values than 18 mm, 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 suggests that right heart evaluation may be considered as a new marker for clinical risk stratification in patients with amyloidosis.

The Importance of Multimodality Imaging in the Diagnosis and Management of Patients with Infiltrative Cardiomyopathies: An Update

“…Although elevated values of estimated pulmonary arterial pressure have been observed in CA patients (CA 38.27 ± 10.67 vs. nCA 28.38 ± 3.75 mmHg; p = 0.0053), there were no differences regarding the tricuspid regurgitation velocity between the two groups. At the same time, a decreased TAPSE indicated a worse prognosis and displayed a significant positive correlation with lymphocyte count, gamma globulins, monoclonal components, and immunoglobulin G values, while the inferior vena cava diameter, the right atrium area, and the estimated pulmonary arterial pressure correlated only with diastolic function, evaluated as E/e' ratio [39]. In order to compare the right ventricular involvement in transthyretin amyloidosis and hypertrophic cardiomyopathy, Arvidsson et al evaluated the echocardiographic conventional parameters and the RV global and segmental strain of 42 subjects with ATTR amyloidosis and echocardiographic evidence of left ventricular hypertrophy (cardiac ATTR), 19 ATTR subjects with normal LV wall thickness (non-cardiac ATTR), 25 patients with biopsy proven or genetically diagnosed HCM, and 30 healthy volunteers.…”

Cardiovascular Risk in Patients With Takayasu Arteritis Directly Correlates With Diastolic Dysfunction and Inflammatory Cell Infiltration in the Vessel Wall: A Clinical, ex vivo and in vitro Analysis

“…Using a previously standardized flow-chart ( 30 ), two-dimensional echocardiography was performed to measure aortic root diameter (Ao) in parasternal long-axis view during both systolic (AoS) and diastolic phases (AoD) by an ECG-guided point measurement. In the same position, one-dimensional echocardiography (M-mode) was used to obtain end-diastolic measurements of interventricular septum thickness (IVS), posterior wall thickness (PWD), and left ventricular internal diameter (LVD).…”

A Review of Current and Evolving Imaging Techniques in Cardiac Amyloidosis

“…A host of echocardiographic parameters, including dimension and function measures, has elucidated the impact of CA on the right heart. In a prior study comparing patients with CA vs. controls, those with CA showed increased RV size, RV basal diameter, IVC, RV wall thickness resulting in reduced total RV volume, and reduced systolic function as measured by tricuspid annular plane systolic excursion (TAPSE) [ 34 ]. Another study of AL patients investigated echocardiogram and doppler myocardial imaging (DMI) right heart parameters and found evidence of abnormal RV systolic function by TAPSE and DMI modalities, with a systolic strain of the basal segment of the RV free wall and TAPSE being most useful in distinguishing AL patients from controls [ 35 ].…”