scholarly journals Differences in the characteristics and contemporary cardiac outcomes of patients with light-chain versus transthyretin cardiac amyloidosis

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255487
Author(s):  
Osnat Itzhaki Ben Zadok ◽  
Mordehay Vaturi ◽  
Iuliana Vaxman ◽  
Zaza Iakobishvili ◽  
Noa Rhurman-Shahar ◽  
...  

Aims To compare the baseline cardiovascular characteristics of immunoglobulin light-chain (AL) and amyloid transthyretin (ATTR) cardiac amyloidosis (CA) and to investigate patients’ contemporary cardiac outcomes. Methods Single-center analysis of clinical, laboratory, echocardiographic and cardiac magnetic resonance imaging (CMRi) characteristics of AL and ATTR-CA patients’ cohort (years 2013–2020). Results Included were 67 CA patients of whom 31 (46%) had AL-CA and 36 (54%) had ATTR-CA. Patients with ATTR-CA versus AL-CA were older (80 (IQR 70, 85) years versus 65 (IQR 60, 71) years, respectively, p<0.001) with male predominance (p = 0.038). Co-morbidities in ATTR-CA patients more frequently included diabetes mellitus (19% versus 3.0%, respectively, p = 0.060) and coronary artery disease (39% versus 10%, respectively, p = 0.010). By echocardiography, patients with ATTR-CA versus AL-CA had a trend to worse left ventricular (LV) ejection function (50 (IQR 40, 55)% versus 60 (IQR 45, 60)%, respectively, p = 0.051), yet comparable LV diastolic function. By CMRi, left atrial area (31 (IQR 27, 36)cm2 vs. 27 (IQR 23, 30)cm2, respectively, p = 0.015) and LV mass index (109 (IQR 96, 130)grams/m2 vs. 82 (IQR 72, 98)grams/m2, respectively, p = 0.011) were increased in patients with ATTR-CA versus AL-CA. Nevertheless, during follow-up (median 20 (IQR 10, 38) months), patients with AL-CA were more frequently admitted with heart failure exacerbations (HR 2.87 (95% CI 1.42, 5.81), p = 0.003) and demonstrated increased mortality (HR 2.51 (95%CI 1.19, 5.28), p = 0.015). Conclusion Despite the various similarities of AL-CA and ATTR-CA, these diseases have distinct baseline cardiovascular profiles and different heart failure course, thus merit tailored-cardiac management.

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Evan Appelbaum ◽  
Caitlin Harrigan ◽  
Warren J Manning ◽  
Frederick L Ruberg ◽  
Michael Gibson ◽  
...  

Background : Cardiac amyloidosis is generally described as a disease with left ventricular (LV) wall thickening, but data supporting LV morphologic differences between types of amyloidosis are lacking. We sought to examine LV morphologic differences between patients with light chain (AL) and transthyretin (TTR)-type amyloidosis with cardiac involvement using volumetric cardiovascular magnetic resonance (CMR). Methods : Patients with proven AL (n =21) and TTR amyloidosis (n =14) underwent cine CMR using standard methods. Volumetric LV mass, LV volumes, and LV mass/volume ratio were measured by an independent core lab blinded to all patient data, using a contiguous short-axis stack of images covering the left ventricle. Results : Both groups demonstrated a male predominance (TTR 86%, AL 67%) with patients in the TTR group older than AL group (74±8yr vs 61 ± 12yr p=0.002). There were no differences in the degree of heart failure symptoms in the TTR and AL groups: NHYA Class I: 4 vs 5; Class II/III: 9 vs 15; Class IV: 0 vs 1, respectively (p=0.68). The maximum anteroseptal thickness was greater in the TTR group (17.9 ± 3.6mm vs. 14.1 ± 3.3mm; p<0.001). Left ventricular end-diastolic mass was also greater in TTR compared to AL amyloid (236 ± 63g vs. 186 ± 61 g; p=0.02) with no significant difference in LV end-diastolic volume (TTR: 154 ± 32 ml vs. 155 ± 45 ml; p=0.89). The LV mass to volume ratio for TTR amyloidosis was significantly greater than the AL group (1.58 ± 0.5 vs. 1.24 ± 0.4; p=0.02). Conclusions : These data demonstrate that LV morphology differs between TTR and AL cardiac amyloidosis, with increased wall thickness and mass in TTR despite similar baseline symptoms and clinical characteristics. Given the reported more aggressive course of AL vs. TTR cardiac amyloidosis, the clinical significance of these findings needs to be further evaluated.


2017 ◽  
Vol 68 (7) ◽  
pp. 1506-1511
Author(s):  
Cerasela Mihaela Goidescu ◽  
Anca Daniela Farcas ◽  
Florin Petru Anton ◽  
Luminita Animarie Vida Simiti

Oxidative stress (OS) is increased in chronic diseases, including cardiovascular (CV), but there are few data on its effects on the heart and vessels. The isoprostanes (IsoP) are bioactive compounds, with 8-iso-PGF25a being the most representative in vivo marker of OS. They correlate with the severity of heart failure (HF), but because data regarding OS levels in different types of HF are scarce, our study was aimed to evaluate it by assessing the urinary levels of 8-iso-PGF2aand its correlations with various biomarkers and parameters. Our prospective study included 53 consecutive patients with HF secondary to ischemic heart disease or dilative cardiomyopathy, divided according to the type of HF (acute, chronic decompensated or chronic compensated HF). The control group included 13 hypertensive patients, effectively treated. They underwent clinical, laboratory - serum NT-proBNP, creatinine, uric acid, lipids, C reactive protein (CRP) and urinary 8-iso-PGF2a and echocardiographic assessment. HF patients, regardless the type of HF, had higher 8-iso-PGF2a than controls (267.32pg/�mol vs. 19.82pg/�mol, p[0.001). The IsoP level was directly correlated with ejection fraction (EF) (r=-0.31, p=0.01) and NT-proBNP level (r=0.29, p=0.019). The relative wall thickness (RWT) was negatively correlated with IsoP (r=-0.55, p[0.001). Also 8-iso-PGF25a was higher by 213.59pg/�mol in the eccentric left ventricular (LV) hypertrophy subgroup comparing with the concentric subgroup (p=0.014), and the subgroups with severe mitral regurgitation (MR) and moderate/severe pulmonary hypertension (PAH) had the highest 8-iso-PGF2a levels. Male sex, severe MR, moderate/severe PAH, high LV mass and low RWT values were predictive for high OS level in HF patients.Eccentric cardiac remodeling, MR severity and PAH severity are independent predictors of OS in HF patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pankaj Garg ◽  
Hosamadin Assadi ◽  
Rachel Jones ◽  
Wei Bin Chan ◽  
Peter Metherall ◽  
...  

AbstractCardiac magnetic resonance (CMR) is emerging as an important tool in the assessment of heart failure with preserved ejection fraction (HFpEF). This study sought to investigate the prognostic value of multiparametric CMR, including left and right heart volumetric assessment, native T1-mapping and LGE in HFpEF. In this retrospective study, we identified patients with HFpEF who have undergone CMR. CMR protocol included: cines, native T1-mapping and late gadolinium enhancement (LGE). The mean follow-up period was 3.2 ± 2.4 years. We identified 86 patients with HFpEF who had CMR. Of the 86 patients (85% hypertensive; 61% males; 14% cardiac amyloidosis), 27 (31%) patients died during the follow up period. From all the CMR metrics, LV mass (area under curve [AUC] 0.66, SE 0.07, 95% CI 0.54–0.76, p = 0.02), LGE fibrosis (AUC 0.59, SE 0.15, 95% CI 0.41–0.75, p = 0.03) and native T1-values (AUC 0.76, SE 0.09, 95% CI 0.58–0.88, p < 0.01) were the strongest predictors of all-cause mortality. The optimum thresholds for these were: LV mass > 133.24 g (hazard ratio [HR] 1.58, 95% CI 1.1–2.2, p < 0.01); LGE-fibrosis > 34.86% (HR 1.77, 95% CI 1.1–2.8, p = 0.01) and native T1 > 1056.42 ms (HR 2.36, 95% CI 0.9–6.4, p = 0.07). In multivariate cox regression, CMR score model comprising these three variables independently predicted mortality in HFpEF when compared to NTproBNP (HR 4 vs HR 1.65). In non-amyloid HFpEF cases, only native T1 > 1056.42 ms demonstrated higher mortality (AUC 0.833, p < 0.01). In patients with HFpEF, multiparametric CMR aids prognostication. Our results show that left ventricular fibrosis and hypertrophy quantified by CMR are associated with all-cause mortality in patients with HFpEF.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Daniel H Katz ◽  
Usman A Tahir ◽  
Debby Ngo ◽  
Mark Benson ◽  
Yan Gao ◽  
...  

Background: Increased left ventricular (LV) mass is associated with future adverse cardiovascular events including heart failure (HF). Both increased LV mass and HF disproportionately affect black individuals. To understand the mechanisms that drive disease, particularly in black individuals, we undertook a proteomic screen in a black cohort and compared it to a white cohort. Methods: We measured 1305 plasma proteins using an aptamer-based proteomic platform (SOMAscan™) in 1772 black participants in the Jackson Heart Study (JHS) with available baseline LV mass as assessed by 2D echocardiography, as well as 1600 free of HF with follow-up assessment of incident cases. Mean follow-up time was 11 years; 152 cases of incident HF hospitalization were identified. Models were adjusted for age, sex, body mass index, estimated glomerular filtration rate (as calculated by CKD-EPI equation), systolic blood pressure, hypertension treatment, presence of diabetes, total/HDL cholesterol, prevalent coronary disease, and current smoking status. Incident HF models were also adjusted for incident coronary heart disease. We then compared protein associations in JHS to those observed in whites from the Framingham Heart Study (FHS) to examine significant differences. Results: In JHS, there were 112 proteins associated with LV mass and 10 proteins associated with incident HF hospitalization with FDR <5%. Several proteins showed expected associations with both LV mass and HF, including N-terminal pro-BNP (β = 0.04 [0.02, 0.05], p = 1.0 x 10 -8 , HR = 1.46 [1.20, 1.79], p = 0.0002). The strongest association with LV mass was more novel: leukotriene A4 hydrolase (LKHA4) (β = 0.05 [0.04, 0.06], p = 2.6 x 10 -15 ). Conversely, Fractalkine/CX3CL1 showed a novel association with incident HF (HR = 1.32 [1.14, 1.54], p = 0.0003). While proteins like Cystatin C and N-terminal pro-BNP showed consistent effects in FHS, LKHA4 and Fractalkine were significantly different. Conclusions: We identify several novel biological pathways specific to black individuals hypothesized to contribute to the pathophysiologic cascade of LV hypertrophy and incident HF including LKHA4 and Fractalkine. Further studies are needed to validate these results and elucidate the detailed underlying mechanisms.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Bethany A Austin ◽  
Brendan Duffy ◽  
Rene Rodriguez ◽  
Carmela Tan ◽  
Randall C Starling ◽  
...  

Cardiac amyloidosis (CA) is generally associated with a poor prognosis and significantly increased mortality. We sought to identify predictors of longer-term survival in patients with EMB documented CA. Forty-five consecutive EMB documented CA patients were studied from 1/98 –12/03. Age, gender, NYHA class, medications, presence of light chain amyloid and ECG voltage were recorded. Baseline left ventricular ejection fraction (LVEF), deceleration time (DT), diastology, LV mass, interventricular septal (IVS) thickness and myocardial performance index (MPI) [(isovolumic contraction time + isovolumic relaxation time)/ejection time] were recorded. Length of follow-up and all-cause mortality were recorded. Mean age was 66 ±10 years with 34 (76 %) men. NYHA class > 2 and low voltage on ECG [S (V1) + R (V5) ≤12] were noted in 26 (58 %) and 12 (27 %) patients, respectively. Mean LVEF, IVS thickness and LV mass were 46 % ±13, 1.7 cm ±0.42 and 303 grams ±114, respectively. DT <150 msec and MPI > 0.6 were found in 19 (42 %) and 15 (33 %) patients, respectively. At median follow-up of 1.7 years, there were 25 (56%) deaths. On univariate Kaplan-Meier survival analysis, NYHA class > 2, DT <150 msec and lack of beta-blocker use were associated with increased mortality (log-rank statistic p-values <0.001, <0.05 and 0.01, respectively). Cox Proportional Hazard Survival Analysis is shown in the table . In patients with EMB-documented CA, s urvival is more strongly associated with NYHA functional class compared to ECG and echocardiographic variables, including DT and MPI. Evaluation of advanced imaging techniques such as cardiac magnetic resonance in predicting prognosis in these patients is warranted. Table: Cox Proportional Hazard Analysis of Various Clinical, Electrocardiographic and Echocardiographic Predictors of Mortality in Patients with Biopsy Proven Cardiac Amyloidosis


2020 ◽  
Vol 22 (1) ◽  
pp. 82-91 ◽  
Author(s):  
Issa Farah Issa ◽  
Jordi Sanchez Dahl ◽  
Steen Hvitfeldt Poulsen ◽  
Farhad Waziri ◽  
Christian Torp Pedersen ◽  
...  

Abstract Aims Native valve aortic stenosis is associated with adverse remodelling of the left ventricle and remodelling is stopped or even reversed with aortic valve replacement (AVR). However, the degeneration of bioprostheses and development of structural valve deterioration (SVD) may affect this. Methods and results To assess the association with SVD, remodelling and outcome 451 patients from a single surgical centre who had undergone AVR with a Mitroflow pericardial bioprosthesis were studied. All patients were assessed in 2014 and a subgroup of patients (N = 327) were re-exanimated again after at least 18 months [median time of 27 (interquartile range, IQR 26–33) months] including echocardiography, measurements of N-terminal pro-brain natriuretic peptide, and assessment of functional status. SVD was based on echocardiography. Moderate SVD was present in 63 patients (14%) and severe SVD in 19 (4%), in the subgroup with follow-up echocardiography 48 patients (15%) patients had moderate to severe SVD at first examination. Patients with SVD had significantly greater increase in left ventricular (LV) mass index [21.6 g/m2 (IQR 5.7–48.3 g/m2) vs. 9.1 g/m2 (−8.6 to 27.3 g/m2), P = 0.01]. Further, patients with SVD had lower LV ejection fraction [55% (IQR 51–62%) vs. 60% (IQR 54–63%), P = 0.01] at follow-up. During follow-up, 94 patients (21%) met the composite endpoint of death or reoperation due to SVD and 41 patient readmitted for heart failure. In multivariable Cox regression analysis, severe SVD [hazard ratio (HR) 2.64 (1.37–5.07), P = 0.004] was associated with composite endpoint, and readmission for heart failure [HR 3.82 (1.53–9.51), P = 0.004]. Conclusion SVD in aortic bioprostheses is associated with adverse LV remodelling and adverse outcome.


2018 ◽  
Vol 46 (9) ◽  
pp. 3959-3969 ◽  
Author(s):  
Zichuan Zhang ◽  
Peize Wang ◽  
Fei Guo ◽  
Xinmin Liu ◽  
Taiyang Luo ◽  
...  

Objective This study was performed to assess the prevalence of nonalcoholic fatty liver (NAFL) in patients with symptomatic congestive heart failure (CHF) and compare the clinical features with those of patients without NAFL. Methods In total, 102 patients with CHF were divided into NAFL and non-NAFL groups according to their hepatic ultrasonography findings. All patients underwent transthoracic echocardiography and cardiac magnetic resonance examination. Follow-up was performed for major cardiovascular events (MACE) and readmission due to heart failure at 1, 3, 6, and 12 months after the index hospitalization. Results NAFL was detected in 37 of 102 patients (36.27%). Compared with the non-NAFL group, patients with NAFL were younger, had a higher body mass index and left ventricular (LV) mass index, and had more severe fibrosis. MACE and readmission occurred in 15 patients in the NAFL group and 29 patients in the non-NAFL group, without a significant difference. Linear regression analysis revealed that after adjusting for confounders, NAFL was independently associated with the LV fibrosis size and the ratio of the LV fibrosis size to the LV mass index. Conclusions NAFL is present in more than one-third of patients with CHF and is associated with the severity of LV fibrosis.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Fabio Fazzari ◽  
Francesco Cannata ◽  
Daniele Banfi ◽  
Marta Pellegrino ◽  
Beniamino Pagliaro ◽  
...  

Abstract Aims Repetitive Levosimendan treatment in advanced heart failure patients has not been investigated yet via myocardial work indices (MWI), which could more accurately detect the effects of this both inotropic and vasodilatory drug. The aims of this study were (1) to describe variations of myocardial work indices, as a consequence of repetitive Levosimendan infusions and (2) to assess the prognostic value of myocardial work parameters in these patients. Methods and results Fourteen patients with advanced heart failure treated with intermittent in-hospital levosimendan infusions were prospectively included. Clinical, laboratory, and echocardiographic assessment were performed before and after every Levosimendan infusion. The primary endpoint was a composite of any episode of decompensated HF, urgent HF rehospitalization, cardiogenic shock, cardiac arrest and cardiovascular death at 4–6 weeks follow-up after each planned infusion. During follow-up (mean: 150 ± 99 days) a total of 37 infusions were performed and a total of 11 cardiovascular events occurred. Global constructive work (GCW), global work efficiency (GWE), and global work index (GWI) increased after Levosimendan infusion in 62.2%, 73.0%, and 70.3% of cases, with significant differences between patients with and without outcomes [delta GCW: −7.36 mmHg% (134.12) vs. 113.81 mmHg% (204.41), P = 0.007; delta GWE: −3.27% (8.38) vs. 4.30% (5.58), P = 0.002]. Delta value of GWE showed the largest area under curve (AUC: 0.82, 95% CI: 0.64–1.00, P = 0.002) for outcome prediction with a cut-off point of 0.5%. Independent prognostic value of GWE variation was confirmed in multivariable regression models (OR: 0.825, 95% CI: 0.702–0.970, P = 0.02). Conclusions GWE and GCW provided incremental and independent prognostic value at short-term follow-up over traditional echocardiographic parameters. The differentiation of patients into ‘workers’, whose GWE improved after Levosimendan infusion, and ‘non-workers’, who failed to improve their GWE, permitted to identify patients at higher risk of forthcoming cardiovascular events. Monitoring these patients with MWI may have relevant clinical implications.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Zikry Deitch ◽  
D Haberman ◽  
S Lifshitz ◽  
S Tshori ◽  
Y Fabricant ◽  
...  

Abstract Background Aortic Stenosis (AS) is the most common valvular heart disease in the Western world. Wild-type transthyretin amyloid (wtATTR) affects the heart, causing restrictive cardiomyopathy. Deposits can be found in up to 25% of individuals >85 years of age at autopsy. Recently several reports showed a relatively high prevalence of transthyretin cardiac amyloidosis (TTR-CA) in patients with AS. Objectives The aim of this study was to examine the clinical effects of TTR-CA in patients who have undergone aortic valve replacement therapy and evaluate the outcome of the intervention. Methods We recruited patients who underwent surgical (AVR) or percutaneous (TAVI) aortic valve intervention between 2011 and 2018. The patients underwent a Tc99m-PYP scan using SPECT technology which has been shown to be valid for the diagnosis of TTR-CA. We reviewed patient files before (time point 1) and after intervention (time point 2) and at 2 years (time point 3) follow up, and collected data on hospitalizations, laboratory, and echocardiography. Results The study included 86 patients, mean age 78±6 years, 55% women. Twenty-nine (33%) participants were diagnosed as positive (VAS 2 and 3) for transthyretin cardiac amyloidosis.There were no differences in baseline characteristics between patients with and without TTR-CA in cardiovascular risk factors and co-morbidities, laboratory parameters and nutritional status. There were no differences in baseline echocardiographic parameters including valve gradients and left ventricular hypertrophy. However, the patients with TTR CA had more advanced diastolic dysfunction compared to patients without TTR CA (P=0.03) and higher pulmonary artery pressure (44±14.75mmhg vs 30.5±11.38mmhg, p=0.06). Before the intervention, patients with transthyretin cardiac amyloidosis had 3.26 times more hospitalizations due to heart failure as compared to patients in the negative group (p=0.01). After the intervention, diastolic function remained more severely affected in the positive group at all follow-up points compared to the negative group (p=0.05). Similar observations were seen in the measurements of pulmonary arterial pressure (p=0.019 at time 2 and p=0.015 at time 3). Consistent with the echocardiographic findings, patients with transthyretin cardiac amyloidosis had 2.84 times more hospitalizations after intervention for heart failure than patients in the negative group (p=0.02). Conclusions Co-existence of transthyretin cardiac amyloidosis and aortic stenosis in the older population is associated with a more severe clinical presentation and with more advanced clinical and echocardiographic signs of heart failure. Improvement after valvular intervention might be limited in terms of symptoms and hospitalizations in this subgroup. Acknowledgement/Funding None


Author(s):  
In-Chang Hwang ◽  
Youngil Koh ◽  
Jun-Bean Park ◽  
Yeonyee E Yoon ◽  
Hack-Lyoung Kim ◽  
...  

Abstract Aims  We aimed to analyse the time-serial change of cardiac function in light-chain (AL) cardiac amyloidosis patients undergoing active chemotherapy and its relationship with patient outcome. Methods and results  Seventy-two patients with AL cardiac amyloidosis undergoing active chemotherapy who had two or more echocardiographic examinations were identified from a prospective observational cohort (n = 34) and a retrospective cohort (n = 38). Echocardiographic parameters were obtained immediately prior to 1–3, 3–6, 6–12, and 12–24 months after the first chemotherapy. Study endpoint was a composite of death or heart transplantation (HT). During a median of 32 months (interquartile range 8–51) follow-up, 33 patients (45.8%) died and 4 patients (5.6%) underwent HT. Echocardiograms immediately prior to the first chemotherapy did not show differences between the patients with adverse events vs. those without. Significant increase in mitral E/e′ ratio and decline in left ventricular global longitudinal strain (LV-GLS) was observed, starting at 3–6 months after the first chemotherapy only in those who experienced adverse events on follow-up, which was also evident in those who responded to chemotherapy. Multivariate analysis demonstrated that B-natriuretic peptide &gt;500 pg/mL and troponin I &gt;0.15 ng/dL at initial diagnosis, hospitalization for heart failure, E/e′ &gt;15, and LV-GLS &lt;10% during follow-up were independent predictors of outcome. Conclusions  In AL cardiac amyloidosis patients undergoing active chemotherapy, the deterioration of LV function may occur, starting even at 3–6 months after the first chemotherapy. Serial echocardiography may help identify those who experience a clinical event in the near future despite active chemotherapy.


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