Transthyretin amyloid cardiomyopathy (ATTR-CM) is an infiltrative disorder characterized by extracellular myocardial deposits of amyloid fibrils, with poor outcome, leading to heart failure and death, with significant treatment expenditure. In the era of a novel therapeutic arsenal of disease-modifying agents that target a myriad of pathophysiological mechanisms, timely and accurate diagnosis of ATTR-CM is crucial. Recent advances in therapeutic strategies shown to be most beneficial in the early stages of the disease have determined a paradigm shift in the screening, diagnostic algorithm, and risk classification of patients with ATTR-CM. The aim of this review is to explore the utility of novel specific non-invasive imaging parameters and biomarkers from screening to diagnosis, prognosis, risk stratification, and monitoring of the response to therapy. We will summarize the knowledge of the most recent advances in diagnostic, prognostic, and treatment tailoring parameters for early recognition, prediction of outcome, and better selection of therapeutic candidates in ATTR-CM. Moreover, we will provide input from different potential pathways involved in the pathophysiology of ATTR-CM, on top of the amyloid deposition, such as inflammation, endothelial dysfunction, reduced nitric oxide bioavailability, oxidative stress, and myocardial fibrosis, and their diagnostic, prognostic, and therapeutic implications
Background: In this study, we aimed to describe the impact of MBs on atherosclerosis and survival, in patients with coronary artery disease (CAD). Methods: We retrospectively studied 1920 consecutive patients who underwent conventional coronary angiography for suspected CAD. Atherosclerotic load (AL), defined as the sum of degrees of stenosis, and general atherosclerotic load (GAL), representing the sum of AL, were compared between patients with MB and a control group without MB; patients in these groups were similar in age and sex. We assessed survival at 10 years after the last enrolled patient. Results: Prevalence of MB was 3.96%, predominantly in the mid-segment of left anterior descendent artery (LAD). In the presence of MB, GAL was lower (158.1 ± 93.7 vs. 205.3 ± 117.9, p = 0.004) with a lesser AL in the proximal (30.3 ± 39.9 vs. 42.9 ± 41.1, p = 0.038) and mid-segments (8.1 ± 20.0 vs. 25.3 ± 35.9, p < 0.001) of LAD. Based on a Multinominal Logistic Regression, we found that the presence of MB on LAD (regardless of its location on this artery) is a protective factor against atherosclerotic lesions, decreasing the probability of significant stenosis, especially of those ≥70%, on the entire artery (B −1.539, OR 4660; 95% CI = 1.873–11.595, p = 0.001) and on each of its segments as well: proximal LAD (B −1.275, OR 0.280; 95% CI = 0.015–5.073; p = 0.038), mid-LAD (B −1.879, OR 6.545; 95% CI = 1.492–28.712; p = 0.013) and distal LAD (B −0.900, OR 2.459, 95% CI = 2.459–2.459, p = 0.032). However, 10-year survival was similar between groups (76.70% vs. 74.30%, p = 0.740). Conclusion: The presence of MB on LAD proved to be a protective factor against atherosclerosis for the entire artery and for each of its segments, but it does not influence long-term survival in patients with CAD.
Aims None of the conventional echocardiographic parameters alone predict increased NTproBNP level and symptoms, making diagnosis of heart failure with preserved ejection fraction (HFpEF) very difficult in some cases, in resting condition. We evaluated LA functions by 2D speckle tracking echocardiography (STE) on top of conventional parameters in HFpEF and preHF patients with diastolic dysfunction (DD), in order to establish the added value of the LA deformation parameters in the diagnosis of HFpEF. Methods We prospectively enrolled 125 patients, 88 with HFpEF (68±9 yrs), and 37 asymptomatic with similar risk factors with DD (preHF) (61±8 yrs). We evaluated them by NTproBNP, conventional DD parameters, and STE. Global longitudinal strain (GS) was added. LA reservoir (R), conduit (C), and pump function (CT) were assessed both by volumetric and STE. 2 reservoir strain (S) derived indices were also measured, stiffness (SI) and distensibility index (DI). Results LA R and CT functions were significantly reduced in HFpEF compared to preHF group (all p<0.001), whereas conduit was similarly in both groups. SI was increased, whereas DI was reduced in HFpEF group (p<0.001). By adding LA strain analysis, from all echocardiographic parameters, SR_CT<-1.66/s and DI<0.57 (AUC = 0.76, p<0.001) demonstrated the highest accuracy to identify HFpEF diagnosis. However, by multivariate logistic regression, the model that best identifies HFpEF included only SR_CT, GS and sPAP (R2 = 0.506, p<0.001). Moreover, SR_CT, DI, and sPAP registered significant correlation with NTproBNP level. Conclusions By adding LA functional analysis, we might improve the HFpEF diagnosis accuracy, compared to present guidelines. LA pump function is the only one able to differentiates preHF from HFpEF patients at rest. A value of SR_CT < -1.66/s outperformed conventional parameters from the scoring system, reservoir strain, and LA overload indices in HFpEF diagnosis. We suggest that LA function by STE could be incorporated in the current protocol for HFpEF diagnosis at rest as a major functional criterion, in order to improve diagnostic algorithm, and also in the follow-up of patients with risk factors and DD, as a prognostic marker. Future studies are needed to validate our findings.
Left ventricular non-compaction (LVNC) with preserved ejection fraction (EF) is still a controverted entity. We aimed to characterize structural and functional changes in LVNC with heart failure with preserved EF (HFpEF). Methods: We enrolled 21 patients with LVNC and HFpEF and 21 HFpEF controls. For all patients, we performed CMR, speckle tracking echocardiography (STE), and biomarker assessment for HFpEF (NT-proBNP), for myocardial fibrosis (Galectin-3), and for endothelial dysfunction [ADAMTS13, von Willebrand factor, and their ratio]. By CMR, we assessed native T1 and extracellular volume (ECV) for each LV level (basal, mid, and apical). By STE, we assessed longitudinal strain (LS), globally and at each LV level, base-to-apex gradient, LS layer by layer, from epicardium to endocardium, and transmural deformation gradient. Results: In the LVNC group, mean NC/C ratio was 2.9 ± 0.4 and the percentage of NC myocardium mass was 24.4 ± 8.7%. LVNC patients, by comparison with controls, had higher apical native T1 (1061 ± 72 vs. 1008 ± 40 ms), diffusely increased ECV (27.2 ± 2.9 vs. 24.4 ± 2.5%), with higher values at the apical level (29.6 ± 3.8 vs. 25.2 ± 2.8%) (all p < 0.01); they had a lower LS only at the apical level (−21.4 ± 4.4 vs. −24.3 ± 3.2%), with decreased base-to-apex gradient (3.8 ± 4.7 vs. 6.9 ± 3.4%) and transmural deformation gradient (3.9 ± 0.8 vs. 4.8 ± 1.0%). LVNC patients had higher NT-proBNP [237 (156–489) vs. 156 (139–257) pg/mL] and Galectin-3 [7.3 (6.0–11.5) vs. 5.6 (4.8–8.3) ng/mL], and lower ADAMTS13 (767.3 ± 335.5 vs. 962.3 ± 253.7 ng/mL) and ADAMTS13/vWF ratio (all p < 0.05). Conclusion: LVNC patients with HFpEF have diffuse fibrosis, which is more extensive at the apical level, explaining the decrease in apical deformation and overexpression of Galectin-3. Lower transmural and base-to-apex deformation gradients underpin the sequence of myocardial maturation failure. Endothelial dysfunction, expressed by the lower ADAMTS13 and ADAMTS13/vWF ratio, may play an important role in the mechanism of HFpEF in patients with LVNC.
Background Left ventricular non-compaction (LVNC) is associated with increased risk of heart failure (HF). If LVNC or hyper-trabeculation in HF with preserved ejection fraction (HFpEF) is an adaptive or stand-alone condition that contribute to generation of HF is not clearly understood yet. Aim To describe LV functional and structural parameters in HFpEF with LVNC by comparison with HFpEF without LVNC. Methods We assessed 42 patients with HFpEF, 21 with LVNC (61±9 yrs) and 21 without LVNC, age and risk factors matched (LVC), by NTproBNP, 2D echocardiography (2DE), speckle-tracking (STE), and cardiac magnetic resonance (CMR) (Figure 1). LVNC diagnosis was based on Petersen and Jacquier criteria, by the NC/C ratio and the percentage of NC myocardium. Two gradients were calculated: a base to apex gradient (LVbase-apex) and an endo-epicardial gradient (LVendo-epi). LV mass, LV end-diastolic volume (LVEDV), and T1 mapping with extracellular volume (ECV) were measured, while mean value of native T1 for apical segments (apicalT1), mean value of ECV for apical (apical ECV), and basal segments (basal ECV), and gradient between them (ECV base-apex) were calculated. Results In the LVNC, mean NC/C ratio was 2.9±0.5mm and the percentage of NC myocardium 24.4±8.8%. NTproBNP was higher in LVNC group (294±282 vs. 163±71 pg/ml, p=0.047). Functional findings were consistent with the structural changes from CMR. LVNC patients have higher native T1 in the apical segments (Table). ECV was globally expanded in LVNC compared to LVC (p=0.002) suggesting diffuse fibrosis, but the difference between groups was more relevant for apical ECV (29.6±3.9% vs 25.1±2.8%, p<0.001), with a higher ECV base-apex gradient in LVNC group. ECV base-apex gradient was negatively correlated with the percentage of NC myocardium (p=0.003, R=0.64). Conclusion Patients with HFpEF with LVNC have more fibrosis, with more severe changes in the apical segments on CMR than HFpEF without NC. They have also significantly decreased apical deformation, lower base to apex deformation gradient and lower transmural deformation gradient, due to non-compaction itself, which involves the endocardial layer. These findings suggests that NC in HFpEF is an independent condition rather than an adaptive one. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of Research and Innovation, CNCS-UEFISCDI.
Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): 2 National Grants of the Romanian Ministry of Research and Innovation - UEFISCDI: "Heart Preserved" and "PRO HEART 3D. Background The so-called left ventricle non-compaction (LVNC), better described as excessive trabeculation, is a highly debated myocardial phenotype. One of the main debates is whether excessive trabeculation is a remodeling feature due to volume load and LV dilation, or is the primary cause of LV dysfunction with LV dilation in the advanced stages. Purpose We aim to evaluate the relationship of LV trabeculations with LV volumes and systolic function in patients with LVNC. Methods 50 patients with suspected LVNC were evaluated by cardiac magnetic resonance (CMR), transthoracic echocardiography (TTE), and N-terminal prohormone of brain natriuretic peptide (NTproBNP). To avoid over-diagnosis of LVNC, we analyzed 27 patients confirmed by CMR, with a positive Jacquier criterion [the percentage of non-compact myocardium mass (NCCM) >20%], excluding those having only a positive Petersen criterion. By CMR, we measured left ventricular end-diastolic volume index (LVEDVi), left ventricular end-systolic volume index (LVESVi), and left ventricular ejection fraction (LVEF). By TTE, we measured global longitudinal strain (GLS), and we performed myocardial work analysis (MWA), as a less afterload-dependent parameter than GLS, measuring global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Results Clinical and biological characteristics, CMR, GLS, and MWA results are detailed in Table 1. Mean percentage of NCMM was 29.45±10.3%. 89% of patients had HF, with LVEF ranging from 17% to 73%. There was no correlation between percentage of NCMM and LVEDVi. Instead, percentage of NCMM correlated positively with LVESVi (R=0.389, p = 0.045) and negatively with LVEF (R=-0.507, p = 0.007) (Figure 1). There was also no correlation between percentage of NCMM and GLS. Percentage of NCMM correlated negatively with GWE (R=-0.539, p = 0.004) (Figure 1), but not with GWI (p = 0.161), GCW (p = 0.249), or GWW (p = 0.060). By linear regression, per 10% increase in NCMM, LVEF decrease by 8.3% and GWE decrease by 4.2%. Percentage of NCCM had a trend to correlate positively with logNTproBNP (R=0.321, p = 0.103). Conclusions Our results suggest that excessive trabeculation in patients with LVNC is not a marker of chronic preload. LVNC seems to be a distinct cardiomyopathy, with a spectrum of systolic impairment proportional to the degree of hypertrabeculation. MWA is a promising tool to evaluate the functional implication of LV trabeculations.
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