bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic impact of SGLT2-inhibitor therapy on survival in patients with transthyretin amyloid cardiomyopathy
Authors: Toferer C , Schwegel N , Santner V , Zach D K , Hoeller V , Wallner M , Gollmer J , Aziz F , Von Lewinski D , Kolesnik E , Ablasser K , Zirlik A , Sourij H , Verheyen N
Published: October 2024

Background

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) significantly improve cardiovascular outcomes in patients with heart failure across the whole spectrum of ejection fraction. Recently published data indicates the safety and tolerability of SGLT2i therapy in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). However, there is a lack of evidence regarding the impact of SGLT2i therapy on clinical outcomes in those patients.

Purpose

This study aims to investigate the association between SGLT2i therapy and clinical outcomes in patients with ATTR-CM.

Methods

This is an analysis of a prospective registry conducted at an expert center for hypertrophic cardiomyopathies. We included all participants with a confirmed diagnosis of ATTR-CM, who were enrolled until December 2022. Prior and concomitant SGLT2i treatment was systemically assessed according to the patient interview and medical records. Patients’ outcomes were retrieved from local medical and health insurance records.

Results

We enrolled 116 patients, of whom 7 patients (6%) were treated with SGLT2i at inclusion and 44 patients (38%) were started on SGLT2i therapy during the observational period while 65 patients (56%) were SGLT2i-naïve. There were no significant differences in baseline characteristics between groups, as shown in the table. Median (interquartile range) age was 80 (76-82) years with 15% females. Median N-terminal pro-brain natriuretic peptide (NT-proBNP) was 2844 (1519-5033) pg/ml, median estimated glomerular filtration rate (eGFR) 58 (46-69) ml/min/1,73m2, and median troponin T 56 (34-83) pg/ml.

During a median follow-up of 2.6 (1.8-3.7) years, 28 patients (24%) died, of whom 6 patients (5%) were in the treatment group and 22 patients (19%) in the control group. In univariate Cox-regression analysis, SGLT2i treatment was significantly associated with a lower mortality (HR 0.325, 95%CI 0.132-0.802, p=0.015). This association persisted after adjusting for age and sex (HR 0.347, 95%CI 0.139-0.867, p=0.023). However, when treatment initiation time was considered, the benefit did not remain statistically significant. No significant associations between SGLT2i treatment and worsening heart failure hospitalizations or cardiovascular death were observed.

Conclusion

In a prospective registry-based cohort of patients with ATTR-CM, SGLT2i therapy was associated with significantly better survival, with a potential treatment initiation time bias. These results suggest that SGLT2i may exert beneficial effects in patients with ATTR-CM and warrant a randomized controlled trial.
Feasibility of ultra-low volume contrast pulmonary arterial injection protocol for CTA in TAVI candidates with severe renal failure
Authors: Babbaro M , Perillo N , Bedogni F , Spagnolo P
Published: October 2024

Introduction

Computer tomography angiography (CTA) has an important role in patient screening before TAVI. The high volumes of iodinated contrast media (CM) injected during the examination represents the main limitation of CTA with a dose-dependent association with contrast-induced nephropathy.

Purpose

Show the feasibility of an ultra-low-dose CM pulmonary arterial injection protocol for CTA in TAVI candidates in high risk patients with severe renal failure.

Methods

In our retrospective study seventy-seven (77) patients with CKD on stage 3b or worse (eGFR ≤ 45/min/1.73 m2) underwent pre-procedural CTA for TAVI-planning with a pulmonary arterial administration of CM.

All CTA examinations were performed using a Dual Source 256-slice CT system. All enhanced CT acquisitions were performed using our dedicated biphasic injection protocol composed of two connected phases of contrast medium injection using different amount of CM (8, 10, 15 and 20 ml) according to BMI (<22 kg/m2; 22-24 kg/m2; 24-28 kg/m2; >28 kg/m2). The CM was administered directly into the pulmonary artery in all patients. For each examination was measured Intraluminal attenuation at thoraco-abdominal aorta and along the ilio-femoral vessels using the ROI (mean SD in HU) as objective image parameters (Picture 1). Serum creatinine and the eGFR were recorded pre-TAVI CT scan and after the procedures as reference of CM to renal function.

Results

CTA was successfully performed in all patients. Mean creatinine was 2.25 ± 0,76 mg/dL and mean GFR was 26.5± 8.1 mL/min/m2. Mean vessel attenuation was 352±164 HU at the aortic annulus, 238.1 ± 141,3 HU in the aortic arch and 266±168 in the iliac arteries (Picture 2).

The mean image noise was 28.2 ± 7 HU in the aortic annulus, 24.4 ± 10,9 in the right external iliac artery, and 25. ± 12,8 HU in the left external iliac artery. After CTA examination, a total of 74 patients (96%) underwent TAVI. Mean CM dose administered during TAVI procedure was 150,6 ± 85,8. Three patients (3.9%) were abolished for TAVI.

Postprocedural settings complications were recorded. A total of 31 patients (41%) had grade 1 paravalvular regurgitation, 10 patients (14%) grade 2. No cases of valve embolization or anulus rupture occured. No major vascular complications occured. No significant differences between creatine and eGFR pre and post procedures (p<0,001).

Conclusions

The use of an ultra-low-dose CM pulmonary arterial injection protocol for CTA in TAVI candidates does not affect the renal function and procedural success rate is high and the clinical outcomes after TAVI is satisfactory according to the litterature.
Genotype predicts heart failure independent of left ventricular ejection fraction and NT-proBNP levels in hypertrophic cardiomyopathy
Authors: Bakalakos A , Protonotarios A , Coats C J , Monda E , Cannie D E , O' Mahony C , Syrris P , Lorenzini M , Elliott P M
Published: October 2024

Background/Introduction

Hypertrophic cardiomyopathy (HCM) is a myocardial disease associated with progression to heart failure. In around 40% of cases, the disease is caused by variants in genes encoding sarcomere proteins.

Purpose

To evaluate the role of genotype in predicting heart failure (HF) outcomes.

Methods

In this observational single-centre cohort study, consecutive patients with HCM were assessed for heart failure clinically stratified by genetic status into genotype-elusive which included those with no significant variants (G-) or variants of unknown significance (VUS) and genotype-positive (G+) with pathogenic/likely pathogenic (LP/P) variants. Heart failure endpoint was defined as left ventricular assist device implantation, heart transplantation or heart-failure-related death. The incidence of HF endpoint was compared between genotypes during follow-up using a time-to-event analysis.

Results

474 patients (50.9 ±14.5 years, 67.3 males) with HCM (25% with left ventricular (LV) outflow obstruction) were followed for 10.9 years (IQR 5.1-13.5). G+ LP/P patients (201/474 (42.4%)) were younger (45.8. ±14.0 years) compared to G- (225/474 (47.5%), 55.2 ±13.4 years) and VUS (48/474 (10.1%), 52.0 ± 15 years); 29/474 (6.1%) reached the heart failure endpoint. The incidence of heart failure endpoints was 12.4% (25/201) in the G+ LP/P group compared to 1.5% (4/273) in the gene elusive group. A multivariate Cox proportional hazards model including NT-proBNP and LV ejection fraction (LVEF) and genetic status showed that G+ LP/P was associated with increased risk of heart failure outcomes (HR: 5.11, 95% CI: 1.43–18.25, p=0.012). Every 100-unit rise in NT-proBNP was associated with a 41% increase in risk (HR: 1.41, 95% CI: 1.20–1.66, p<0.0001). A one-unit (1%) reduction in LVEF correlated with a 10% increase in heart failure risk (HR: -0.90, 95% CI: 0.87–0.93, p<0.0001).

Conclusion(s)

Genetic status is a predictor of heart failure outcomes independent of LVEF and NT-proBNP levels in HCM. This underscores the importance of genetic testing in the clinical management of HCM.
Trans-femoral transcatheter intramyocardial septal radiofrequency ablation: a novel therapeutic approach for obstructive hypertrophic cardiomyopathy
Authors: Huang Y , Fang Z , Zhou S
Published: October 2024

Background

Septal reduction techniques play a pivotal role in mitigating morbidity and mortality among patients with obstructive hypertrophic cardiomyopathy (oHCM). While trans-apical intramyocardial septal radiofrequency ablation (PIMSRA or LIWEN procedure) has shown promise in reducing left ventricular outflow tract (LVOT) gradients and improving symptoms in oHCM patients, it is associated with complications such as cardiac tamponade and atrioventricular block.

Objective

This study introduces a novel approach for transcatheter radiofrequency ablation of hypertrophic septum via femoral access, utilizing the DragonFire Transcatheter Myocardial Puncture and Radiofrequency Ablation System. We aim to evaluate its safety and medium-term outcomes in patients with oHCM.

Methods

A prospective, single-center, single-arm study of tf-PIMSRA was conducted in patients with drug-refractory oHCM. Ten patients were enrolled and underwent the procedure under the guidance of transesophageal echocardiography. The primary outcome was 30-day major adverse clinical events, with secondary outcomes including 90-day improvements in outflow obstruction and quality of life.

Results

All patients, with an average age of 57±10 years, including 4 males, underwent the procedure successfully without any complications, including major adverse clinical events or conduction abnormalities. The average duration of the procedure was 125.2±34.6 minutes, with an average ablation time of 38.69±18.29 minutes and ablation energy of 3.60±1.49KJ. At 90-day follow-up, significant reductions were observed in peak LVOT gradients (resting gradient: from 82.00 [56.00] mmHg to 14.00 [6.25] mmHg; p < 0.001; provoked gradient: from 102.00 [76.25] mmHg to 33.00 [16.50] mmHg; p = 0.002), and interventricular septum thickness (from 22.00 [19.00] mm to 17.00 [15.00] mm; p = 0.002). These improvements were associated with enhancements in NYHA functional classification (from 3.00 [2.75] to 1.00 [1.00]; p < 0.0001), Kansas City Cardiomyopathy Questionnaire scores (from 59.00 [44.50] to 80.00 [77.25]; p < 0.02), 6-minute walk distance (from 441 [400] m to 480 [465] m; p < 0.01), and pro B-type natriuretic peptide levels (from 1738.00 [1113.25] pg/ml to 252.00 [200.00] pg/ml; p = 0.002). All patients achieved New York Heart Association functional class I or II at follow-up.

Conclusions

Transfemoral PIMSRA appears to be a safe and effective procedure for relieving LVOT obstruction and symptoms in patients with drug-refractory oHCM. These findings support further investigation through randomized clinical trials comparing it with established septal reduction therapies.Patient-Level Outcomes for the trans-fem
The added value of advanced echocardiography in dilated cardiomyopathy: looking at the right heart
Authors: Hadareanu D R , Hadareanu C D , Stoiculescu F M , Florescu C , Donoiu I
Published: October 2024

Introduction and aims

Right ventricular (RV) dilation and dysfunction significantly impact the prognosis of dilated cardiomyopathy (DCM) patients, and early detection of subclinical changes is mandatory. Furthermore, right atrial (RA) size and function are still often neglected in DCM patients. Accordingly, our aims were to evaluate (i) right heart chambers and tricuspid annulus (TA) subclinical remodeling, and (ii) the prognostic value of RA compared to left atrial (LA) size and function in patients with DCM without clinical RV involvement, RV pressure/volume overload or sustained atrial tachyarrhythmias by advanced echocardiography techniques.

Materials and methods

Sixty-eight patients out of a cohort of 106 patients with DCM (mean age 60 years, 35 men) were evaluated by comprehensive transthoracic two- (2DE) and three-dimensional (3DE) and speckle-tracking (2DSTE) echocardiography, were compared to 62 age- and sex-matched healthy controls (mean age 61 years, 32 men), and were followed-up for 37 ± 16.6 months.

Results

DCM patients have RV and RA global longitudinal dysfunction by 2DSTE, and higher RA minimum volumes (Vmin) and TA areas despite having normal RV volumes and ejection fraction (EF) and RA maximum volumes (Vmax) by 3DE compared to controls (Table). RA and RV strain correlate with each other (r=0.360, p=0.013 for RA reservoir and r=0.347, p=0.017 for conduit strain). TA area correlates with RA contractile strain (r=-.293, p=0.046) and RV free-wall strain (r=0.373, p=0.008), RA Vmax (r=0.513, p<0.001), RV (r=0.404, p=0.004 for end-diastolic and r=0.444, p=0.001 for end-systolic) and left ventricular (LV) volumes (r=0.394, p=0.016) and LV EF (r=-.361, p=0.028). RA reservoir strain (AUC=0.769) has higher value for outcome prediction compared to LA strain (p=0.02 between them).

Conclusion

Patients with DCM have RV longitudinal dysfunction and decreased RA function, in the absence of clinical RV involvement or atrial arrhythmias, and decreased RA strain is associated with an increased risk of hospitalization and cardiac death.Comparison of right heart parametersPrognostic value of atrial function
Myocardial DNA damage is responsible for the relationship between genotype and treatment response in patients with dilated cardiomyopathy
Authors: Dai Z , Ko T , Nomura S , Inoue S , Fujita K , Onoue K , Kuramoto Y , Asano Y , Amiya E , Hatano M , Takeda N F , Morita H , Saito Y , Takeda N H , Komuro I
Published: October 2024

Background

Dilated cardiomyopathy (DCM) is one of the leading causes of heart transplantation. Our group and others have previously reported that DNA damage accumulation in myocardial tissue and certain genetic variants such as those in LMNA are associated with treatment response and prognosis (ref 1-5). However, the potential association between myocardial DNA damage and genotype, and their contribution when combined to predicting treatment response, remains unclear.

Methods

We identified the deleterious variants in cardiomyopathy-related genes by analyzing the whole exome sequencing data from 89 patients with DCM who were recruited from two participating facilities. Immunostaining of γ-H2A.X, a DNA damage marker, was performed on endomyocardial biopsy specimens from the same patients, from which the percentage of nuclei positive for γ-H2A.X signals (%γ-H2A.X) was calculated. Left ventricular reverse remodeling (LVRR) was assessed by transthoracic echocardiography at 1 year after biopsy. We examined the associations among genotype, myocardial DNA damage, and the achievement of LVRR.

Results

Among the 89 patients with DCM, 11 (12.4%) carried pathogenic or likely pathogenic (P/LP) variants in sarcomere genes such as TTN, and 21 (23.6%) carried P/LP variants in non-sarcomere genes such as LMNA, while the rest had no P/LP variants in cardiomyopathy-related genes (Figure A). Patients with P/LP variants in sarcomere genes had a lower %γ-H2A.X [21.2 (10.7–29.0)% vs. 7.0 (4.3–12.4)%, P = 0.002] (Figure B), and a higher probability to achieve LVRR at 1-year (81.8% vs. 23.8%, P = 0.003) (Figure C) when compared to those with P/LP variants in non-sarcomere genes. The odds ratio for carriers of P/LP variants in sarcomere genes to achieve LVRR was 14.40 (95%CI 2.31–89.94) compared to that for carriers of P/LP variants in non-sarcomere genes. However, this effect was markedly attenuated after adjusting for the proportion of γ-H2A.X-positive nuclei [adjusted odds ratio 6.05 (95%CI 0.86–42.53)] (Table).

Conclusions

Among patients with DCM, carriers of P/LP variants in sarcomere genes showed less DNA damage and a favorable treatment response, when compared with carriers of P/LP variants in non-sarcomere genes. Our results suggest that myocardial DNA damage was partially responsible for the relationship between genotype and treatment response in patients with DCM.Figure, panels A-C
Cardiac sympathetic innervation, assessed with 123I-MIBG SPECT, predicts left ventricular function improvement in patients with newly diagnosed dilated cardiomyopathy
Authors: Dziewiecka E , Holcman K , Kostkiewicz M , Wisniowska-Smialek S , Szot W , Winiarczyk M , Stepien A , Graczyk K , Przytula N , Kyslyi V , Gasiorek J , Plazak M , Kapczynski N , Rubis P
Published: October 2024

Introduction

Beta-blockers (BB) are commonly prescribed medications for heart failure (HF) due to their ability to counteract the increased sympathetic nervous system (SNS) activity seen in HF, resulting in downregulation and desensitization of β-receptors. In patients with dilated cardiomyopathy (DCM), the introduction of BB therapy can lead to left ventricular ejection fraction (LVEF) improvement in 30-50% of cases. Single-photon emission computed tomography (SPECT) with 123I-meta-iodobenzylguanidine (MIBG) is a useful tool for assessing cardiac SNS activity. Healthy individuals typically exhibit high SPECT-MIBG uptake and low washout rate (WR) due to normal β-receptor levels and low norepinephrine (NE) levels, respectively (Fig 1A). While better SPECT-MIBG results have been associated with LVEF improvement in the general HF population, less data is available for DCM patients.

Purpose

This study aimed to evaluate the predictive value of MIBG-SPECT for LVEF improvement in newly diagnosed DCM patients.

Methods

Twenty-one DCM patients (mean age 47 ± 10 years, 90% male, baseline LVEF 29.5 ± 8.7%, left ventricular end-diastolic volume (LVEDV) 114 ± 36 ml/m2) with stable HF symptoms (NYHA class 1.8 ± 0.6) and newly diagnosed DCM underwent baseline MIBG-SPECT and echocardiography. HF therapy was initiated and up-titrated, and echocardiography was repeated at 6 months. Semi-quantitative parameters from MIBG-SPECT, including the MIBG uptake ratio from the heart and mediastinum (H/M) at 15 minutes (-15) and 4 hours (-4), as well as the WR [WR = (H/M-15 - H/M-4) / H/M-15], were evaluated. Patients were stratified based on median WR - 8.79 (IQR 5.17-12.90).

Results

After 6-months of HF therapy up-titration, 18 patients improved LVEF, and the mean LVEF increase was 7.7 ± 10.4%. Although, patients with WR > median did not differ in terms of baseline LVEF (30.2 ± 7.0 vs. 27.7 ± 9.6, p=0.52), they had worse LVEF at 6 months (32.0 ± 11.0 vs. 40.6 ± 9.2%, p=0.04). Moreover, WR at baseline strongly correlated with 6-month LVEF (R=-0.51, p=0.01) and was a significant predictor of 6-month LVEF (β=-0.55 ± 0.19, p=0.009). Moreover, WR could successfully predict LVEF improvement ≥ 10% (OR 1.27 [95%CI 1.01-1.61], p=0.03; AUC 0.82 [95%CI 0.63-0.99], p<0.001) with a cut-off point of 8.0 (sensitivity 88%, specificity 77%) (Fig 1B).

Conclusion

Most DCM patients demonstrated LVEF improvement during 6 months of HF therapy up-titration. Baseline WR from MIBG-SPECT was found to be a reliable predictor of significant LVEF improvement in this patient population.Fig1.A-SPECT-MIBG results. B-ROC curve.
A systematic review and meta-analysis to determine the biological sex ratio in monogenic genetic and non-genetic dilated cardiomyopathy
Authors: Bergan N , Prachee I , Prasad S , Gregson J , Ware J , Tayal U
Published: October 2024

Background

Dilated cardiomyopathy (DCM) is characterised by left ventricular or biventricular systolic dysfunction and dilatation, in the absence of abnormal loading conditions or coronary artery disease (1). Up to 30% of cases have an identified monogenic cause, usually with autosomal dominant (AD) inheritance (2). The disease appears to be twice as common in males, suggesting either a sex specific penetrance or a potential difference in expressivity. This sex ratio has not been systematically evaluated for genetic forms of DCM.

Purpose

To assess the sex ratio in patients with all-cause DCM compared to genetic (monogenic) and gene-elusive subtypes, defined by the presence or absence of a pathogenic variant in DCM-associated genes.

Methods

A literature search was conducted to identify cohorts of DCM patients with identifiable sex ratios. Exclusion criteria were patients with syndromic, X-linked, mitochondrial, or autosomal recessive (AR) DCM. Studies with a small cohort size (n<100), a paediatric population, unidentifiable sex ratio, or ischaemic and peripartum DCM were excluded. 98 studies with a total of 36,662 participants were included in this study. A random-effects meta-analysis generated a pooled proportion of female participants with a 95% confidence interval (95% CI) for an overall DCM cohort as well as for the subtypes – all genetic DCM, individual gene level for 10 key DCM genes (including titin, TTN, and lamin, LMNA), and gene elusive DCM.

Results

The overall DCM cohort had a 0.30 female proportion (95% CI: 0.28-0.32; Figure 1). This corresponds to a male:female (M:F) ratio of 2.38:1. This ratio did not significantly change in patients with an identified causative DCM variant (0.31 [95% CI 0.26-0.36]; M:F ratio of 2.22:1; p=0.563). There was also no significant difference when compared to patients who had been genetically tested with no identified variant (0.30 [95% CI 0.24-0.37]; M:F ratio of 2.29:1; p=0.814). Furthermore, the ratio within participants with AD gene variants was not significantly different for the specific genes of TTN (0.28 [95% CI 0.22-0.36]; M:F ratio of 2.51:1) and LMNA (0.35 [95% CI 0.27-0.44]; M:F ratio of 1.84:1). Overall, the sex ratio amongst patients with these AD gene variants was similar to the all-cause group (0.34 [95% CI 0.28-0.40]; M:F ratio of 1.98:1; p=0.18); Figure 2.

Conclusions

This meta-analysis suggests that DCM is twice as prevalent in males than females, even in pooled monogenic genetic subtypes with an equally prevalent genetic risk factor, indicating a difference in penetrance between the sexes. Further studies are required to determine the drivers of this sex specific penetrance.Forest plots: overall DCM cohortForest plots: gene-specific DCM cohort
Clinical and laboratorial profile of patients with ATTR cardiomyopathy: comparison between wild type and p.Val142Ile forms in the Brazilian population
Authors: Simoes M , Jadan G , Correia E B , Carvalho A A S , Macedo A V S , Schwartzmann P V , Scheinberg P , Antunes M O , Coelho-Filho O R , Mangini S , Coneglian F S , Valicelli F H , Garibaldi P M M , Marques-Junior W , Fernandes F
Published: October 2024

Background

In Brazil, besides the wild type (wt) form, transthyretin amyloid cardiomyopathy (ATTR-CM) is predominantly caused by hereditary form with Val142Ile mutation. Considering that both forms occur in elderly people, the clinical presentation may be similar. We sought to compare the clinical presentation of patients with wt and Val142Ile mutation in a Brazilian cohort of ATTR-CM patients.

Methods

Among the 642 patients enrolled in REACT/SP, 283 presented ATTR-CM, being 85 wt and 90 Val142Ile patients. We compared the main clinical characteristics between groups.

Results

The wt in comparison to Val142Ile patients, respectively, presented: older age (78.4+/-8.5 vs 74.2+/-8.1 y.o., p = 0.0009); similar proportion of males (82% vs 81%, p=0.85); lower proportion of blacks (11% vs 39%, p=0.0001); similar prevalence of heart failure (HF) symptoms (85% vs 79%, p=0.33); higher prevalence of syncope (13% vs 2%, p=0.008) and Pacemakers (PM) implantation (8% vs 1%, p=0.027); similar prevalence of neuropathy manifestations (38% vs 51%, p=0.17); lower creatinine (1.5+/-0.8 vs 2.1+/-2.1 mg/dL, p=0.02) and NT-ProBNP levels (2860.0+/-2843.3 vs. 5488.3+/-5455.6 pg/ml, p=0.0001); reduced interventricular septal thickness (15.6+/-3.3 vs 17.0+/-3.3 mm, p= 0.006), posterior left ventricular (LV) posterior wall thickness (14.2+/-2.4 vs 16.2+/-4.4 mm, p=0.0003), higher LV ejection fraction (52.0+/-10.1 vs 48.2+/-13.6%, p=0.038), higher global LV longitudinal strain (8.6+/-8.7 vs 3.4+/-9.8, p=0.0003), smaller LV diastolic diameter (45.9+/-6.1 vs 43.0+/-7.3 mm, p=0.005) at 2D-Echocardiogram.

Conclusions

In the Brazilian population wt and Val142Ile patients had similar clinical presentation regarding HF and neuropathy symptoms, but higher prevalence of syncope and PM in wt patients. Conversely, Val142Ile patients presented more severe amyloid cardiac infiltration.
DPD quantification correlates with ECV and disease severity in patients with ATTR-CM
Authors: Rettl R , Calabretta R , Duca F , Kronberger C , Binder C , Willixhofer R , Dona C , Beitzke D , Loewe C , Nitsche C , Hengstenberg C , Badr Eslam R , Bergler-Klein J , Hacker M , Kammerlander A
Published: October 2024

Background

The pathophysiological hallmark of transthyretin amyloid cardiomyopathy (ATTR-CM) is the deposition of amyloid within the myocardium. However, the association between myocardial amyloid load and quantitative cardiac 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) uptake is barely investigated.

Purpose

We aimed to investigate the relationship between quantitative cardiac 99mTc-DPD uptake and myocardial amyloid load, assessed by extracellular volume (ECV) on cardiac magnetic resonance (CMR) imaging, along with cardiac function in patients with ATTR-CM.

Methods

Forty ATTR-CM patients underwent 99mTc-DPD single-photon emission computed tomography/computed tomography (SPECT/CT) and CMR imaging.

Results

We observed significant correlations (r, Spearman's correlation coefficient) between the standardized uptake value (SUV) retention index and myocardial amyloid load (ECV: r=0.677, p<0.001; native T1 time: r=0.430, p=0.006), longitudinal cardiac function [right ventricular longitudinal strain (RV-LS): r=0.472, p=0.002], cardiac biomarkers (NT-proBNP: r=0.543, p<0.001; troponin T: r=0.401, p=0.011), exercise capacity [6-min walking distance (6MWD): r=-0.410, p=0.010] and disease stage [National Amyloidosis Centre (NAC) ATTR stage: r=0.479, p=0.002]. ATTR-CM patients were divided into two cohorts based on the median of the SUV retention index (low cardiac uptake: <5.19 mg/dL, n=20; high cardiac uptake: ≥5.19 mg/dL, n=20). We observed significant between-cohort differences in terms of ECV (p<0.001), native T1 time (p=0.011), RV-LS (p=0.007), NT-proBNP (p<0.001), troponin T (p=0.030), 6MWD (p=0.002) and NAC ATTR stage (I: p<0.001, II: p=0.030, III: p=0.021).

Conclusions

In ATTR-CM, quantitative cardiac 99mTc-DPD uptake correlates with myocardial amyloid load, longitudinal cardiac function, cardiac biomarkers, exercise capacity, and disease stage. DPD quantification may provide a valuable tool for quantifying and monitoring cardiac disease burden in affected individuals.Table.Baseline Characteristics.Figure.Correlations.
RV-PA uncoupling is a strong predictor of 3-year all-cause mortality in transthyretin amyloid cardiomyopathy
Authors: Schwarting S , Poledniczek M , Metodiev Y , Stolz L , Hofmann E , Hegenbart U , Schoenland S , Kaeaeb S , Massberg S , Frey N , Aus Dem Siepen F
Published: October 2024

Background

Right ventricle to pulmonary artery coupling (RV-PAc) describes the right ventricle's ability to adjust to an increased afterload which, in case of transthyretin amyloid cardiomyopathy (ATTR-CM), can result from increased left ventricular diastolic stiffness due to fibril deposition. While RV-PAc is a validated prognostic parameter in pulmonary arterial hypertension (PAH), its prognostic relevance in ATTR-CM remains unclear. This study sought to evaluate the prognostic implications of impaired RV-PAc on survival in ATTR-CM.

Methods

In this two-centre study, RV-PAc was investigated by the echocardiographic surrogate of ratio of tricuspid annular plane systolic excursion to estimated pulmonary arterial systolic pressure (TAPSE/PASP) in 418 ATTR-CM patients, all treated with TTR stabilizer. The primary outcome was all-cause mortality. Receiver operation curves and Youden’s J analysis were applied to identify an optimal cut-off value of RV-PAc ratio.

Results

Within a median time of 631 (IQR 361-983) days after diagnosis, 14.4% of patients died. RV-PAc ratio at first presentation emerged as a robust marker for risk stratification with a determined optimal cut-off of 0.382mm/mmHg (area under the curve (AUC) 0.746, 95% CI 0.68-0.82). Patients with RV-PAc ratio ≤0.382mm/mmHg (impaired RV-PAc, n=158) exhibited significantly lower survival (HR 4.07, 95% CI 2.26-7.33, p<0.001) within 3 years of follow up than those with RV-PAc ratio > 0.382mm/mmHg. In multivariate Cox regression analysis, incorporating a range of known prognostic variables, reduced RV-PAc was a strong echocardiographic predictor of mortality (Hazard Ratio (HR) 2.99, 95% Confidence Interval (CI) 1.63-5.51, p <0.001).

Conclusion

Impaired adaption of the RV to increased afterload is associated with worse outcome in ATTR-CM patients. RV-PAc ratio can serve as an echocardiographic predictor for all-cause mortality within three years after diagnosis. Therefore, determination of RV-PAc could improve risk stratification for ATTR-CM patients.Figure_1_Kaplan-Meier curves
Health-related quality of life disparity in cardiac sarcoidosis versus other myocardial diseases
Authors: Raak-Tarkiainen J , Lehtonen J
Published: October 2024

Background

Sarcoidosis, a systemic inflammatory disorder, can manifest as progressive inflammatory heart disease, termed cardiac sarcoidosis (CS). Despite advances in treatment, the impact of CS on health-related quality of life (HRQoL) remains incompletely understood. This study aimed to compare HRQoL between patients with CS and those with non-inflammatory cardiomyopathies, namely dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM).

Purpose

To assess and compare HRQoL across patients with cardiac sarcoidosis and non-inflammatory cardiomyopathies.

Methods

A total of 240 CS patients (86% response rate), 96 DCM patients (55% response rate), and 81 HCM patients (65% response rate) completed the RAND-36 general health-related questionnaire, comprising eight dimensions. Patients listed for transplantation were excluded. Clinical data were obtained from the Finnish myocardial inflammatory diseases registry for CS patients and from medical records in hospitals for HCM and DCM patients.

Results

Median age ranged from 56 to 59 years across the groups. Unlike DCM, which typically presents with heart failure symptoms, a substantial proportion (82%) of CS patients presented with advanced atrioventricular block or ventricular arrhythmias, while HCM cases were often incidentally detected or identified through family screening. Most CS patients (94%) had implanted pacemakers or ICDs, compared to a lower proportion in HCM (26%) and DCM (63%). DCM patients exhibited a higher prevalence of impaired LVEF (<50%) compared to CS and HCM patients. Functional impairment, as measured by NYHA class, was most pronounced in DCM patients. CS patients experienced more adverse events between diagnosis and the study entry, particularly sustained ventricular tachycardia/ventricular fibrillation. However, heart failure hospitalizations did not significantly differ between groups.

Table 1 presents a comparative analysis of patient-reported outcomes across four functional and mental dimensions to assess the relative burden of disease among patients with CS, HCM, and DCM. While the functional dimensions in CS exhibited disparities from both HCM and DCM, no significant differences were observed in the mental dimensions between CS and HCM. CS patients reported lower scores in the domains of role physical, and general health compared to either HCM or DCM counterparts.

Conclusion

Patients with CS demonstrated significantly poorer HRQoL compared to those with non-inflammatory cardiomyopathies. This underscores the substantial burden of disease associated with CS and highlights the importance of comprehensive management strategies to address both clinical and quality of life aspects in affected individuals.
Improving early mortality risk detection in light-chain cardiac amyloidosis patients with routine echocardiographic indicators and mayo staging
Authors: Li J , Qiu L , Guo F , Sun K , Xu X , Tian Z , Zhang S
Published: October 2024

Background

Light-chain cardiac amyloidosis (AL-CA) is a fatal cardiomyopathy caused by the deposition of monoclonal immunoglobulin light-chain in the cardiac fibers, conduction system, valves, and other parts of the heart. The Mayo 2004 staging system is widely used to assess the prognosis of AL-CA. Those in the highest-risk categories, Mayo 2004 stage IIIb, exhibit extremely poor responses to conventional treatment regimens, resulting in high early mortality rates. However, within the same stage, prognostic outcomes among patients can still vary significantly. Hence, a more detailed stratification of high-risk patients is crucial for pinpointing those at extreme risk.

Objective

To investigate whether conventional echocardiographic measurements can enhance the identification of high-risk patients with early mortality in AL-CA on the basis of existing risk stratification.

Methods

Continuous enrollment of patients diagnosed with AL-CA at our center from May 2020 to December 2022. Clinical data, echocardiography, and follow-up results of the patients were collected. Logistic regression analyses were used to identify risk factors for early mortality, with risk factor thresholds calculated using Receiver Operating Characteristic (ROC) curves. Kaplan-Meier survival analysis was employed to assess endpoint events. The diagnostic efficacy of the model was evaluated using the area under the ROC curve and the Integrated Discrimination Improvement (IDI).

Results

A total of 76 patients were included with an average age of 59±10 years. Among them, 51 were male (67.1%). The median follow-up duration was 10 months (ranging from 5 to 20 months). Early mortality, defined as death within 6 months, occurred in 20 patients (26.3%). Twenty-three patients were categorized under the Mayo 2004 stage IIIb (30.3%). The 6-month mortality rate for patients in the Mayo 2004 stage IIIb was 56.5%. The sensitivity of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity ratio divided left ventricular ejection fraction [(E/e’) /LVEF] in predicting early mortality in patients with AL-CA is 63%, and the specificity is 92%.When compared to the Mayo 2004 stage IIIb alone, (E/e')/LVEF≥0.5 combined with the Mayo 2004 stage IIIb had an area under the curve of 0.731 and 0.824, respectively, in the ROC curve. The IDI was 0.113 (95% CI: 0.013-0.213, P=0.026), representing an 11.3% enhancement in the predictive value of early mortality in AL-CA patients.

Conclusion

Routine echocardiography derived E/e' to LVEF ratio offered added prognostic value for early mortality beyond Mayo staging.Kaplan-Meier survival curve
Prognostic significance of right ventricular dysfunction in patients with TTR amyloidosis
Authors: Istratoaie S , Al Wazzan A , Antonelli J , Oger E , Donal E
Published: October 2024

Background

Transthyretin amyloidosis (ATTR) is increasingly recognized as a cause of heart failure (HF) that now benefits from effective treatment. While the role of right ventricular (RV) systolic dysfunction has been widely accepted as an independent predictor of poor prognosis in HF patients, its implications in ATTR remain poorly understood. Right ventricular free wall strain (FWS) over pulmonary arterial systolic pressure (PAsP) has been recently proposed as an accurate and sensitive tool to evaluate RV function and its coupling to the afterload.

Purpose

Our study sought to analyze whether indexing FWS to PASP should integrate the set of fundamental data we have to assess the prognosis of ATTR patients.

Methods

191 consecutive patients diagnosed with ATTR were enrolled. A comprehensive echocardiographic examination was part of the systematic evaluation. The primary outcome was a composite of cardiovascular mortality and hospitalization caused by heart failure worsening.

Results

After a median follow-up of 24 months, among patients with ATTR [median age 82 (77, 85), 89.5% male], the primary composite outcome occured in 26%. Cardiovascular mortality rate was 7.3% and the hospital event rate was 18.8%. Tricuspid annular plane systolic excursion (TAPSE), FWS, TAPSE/PAsP and PAsP were univariately significant risk factors for adverse outcome.

In multivariate Cox regression analysis, after adjustment of confounding factors, FWS/PASP emerged as an independent predictor of the composite endpoint of cardiac death and rehospitalization (HR 1.61, 95% CI 1.07-2.42, p=0.021). Based on receiver-operating characteristic analysis, the optimal FWS/PASP cut-off value for event prediction was 42.5% (area under the curve = 0.749, p = 0.001).

Conclusion

Right ventricular function assessed with speckle-tracking echocardiography is an independent prognostic marker for cardiac mortality and heart failure hospitalization in patients with ATTR. FWS/PAsP should be integrated into regular clinical practice for a better evaluation and follow-up of ATTR patients.
Cardiac transthyretin amyloidosis in patients with conduction system disease
Authors: Pudich J , Seleng J , Syler J , Palickova N , Kapsova E , Drienikova D , Musiolova K , Pudichova H , Plasek J , Vaclavik J
Published: October 2024

Background/Introduction

Cardiac amyloidosis (CA) is characterized by extracellular deposition of misfolded proteins in the heart. The data suggest that cardiac amyloidosis is underappreciated as a cause of common cardiac diseases or syndromes. More than 98% of currently diagnosed cardiac amyloidosis result from fibrils consisting of monoclonal immunoglobulin light chains (AL) or transthyretin (ATTR). The natural history of ATTR cardiomyopathy commonly includes both the conduction system disease and arrhythmias, which may occur years before the onset of heart failure. Conduction abnormalities are commonly encountered among patients with CA and constitute an important cause of morbidity and mortality. Most reports agree that pacemakers are most common in wild type ATTR-CA, followed by hereditary ATTR-CA and, finally, AL-CA.

Purpose

As unexplained LV wall thickness ≥ 12 mm is a screening sign of possible cardiac ATTR, systematicscreening for CA in patients requiring permanent pacemakers with unexplained LV wall thickness of ≥ 12 mm seems to be rational and could possibly lead to early diagnosis of cardiac ATTR. To the best of our knowledge, the usefulness of such screening has not been investigated before. This project, therefore, aims to determine the prevalence of cardiac ATTR and its subtypes in this preselected group, and to propose the most suitable battery of diagnostic procedures for this purpose.

Methods

Population to be tested: Consecutive patients ≥50 years referred for permanent pacemaker implantation with unexplained LV wall thickness ≥12 mm determined by echocardiography. The research protocol was that of an open-label prospective study. Biochemistry samples including serum troponin I and NT-proBNP were collected before pacemaker implantation. All patients were screened for ATTR-CA according to the recommendations of the Position statement of the ESC Working group on myocardial and pericardial diseases. Tc-DPD scintigraphy scan served as a gold standard for determining the diagnosis of cardiac ATTR.

Results

Out of 100 consecutive patients meeting inclusion criteria, 15 % suffered from amyloidosis (12 patients were diagnosed with ATTR and 3 with AL cardiac amyloidosis). Table 1 shows a variety of parameters, many of which differed between patient groups with and without amyloidosis, confirming the wide range of parameters significantly associated with cardiac amyloidosis; our ongoing research in this field could lead to the development of a scoring system for detection of cardiac amyloidosis.

Conclusions

The prevalence of cardiac amyloidosis in the investigated group was 15 %. Systematic screening for ATTR in patients with unexplained LV wall thickness ≥ 12 mm requiring permanent pacemaker implantation seems to be rational and could possibly lead to an earlier diagnosis of cardiac amyloidosis, especially ATTR.
Characterizing the progression of subclinical cardiac amyloidosis through artificial intelligence applied to electrocardiographic images and echocardiograms
Authors: Oikonomou E K , Sangha V , Coppi A , Krumholz H M , Miller E J , Khera R
Published: October 2024

Background

Transthyretin amyloid cardiomyopathy (ATTR-CM) follows an indolent course and may remain undiagnosed for many years before resulting in clinical disease.

Purpose

To assess the utility of scalable artificial intelligence (AI) methods applied to electrocardiographic (ECG) images and echocardiograms in detecting longitudinal changes that precede the clinical diagnosis of ATTR-CM.

Methods

Across 5 hospitals of a large U.S.-based hospital system, we identified a total of 234 patients (age 79 [IQR:70-85] years, n=56 (23.9%) women) with ATTR-CM, defined by the presence of a positive bone scintigraphy scan (or pharmacotherapy with an approved transthyretin stabilizer) between 2015 and 2023. Using 10:1 age- and sex-matched controls, we independently trained convolutional neural network algorithms to discriminate ATTR-CM from controls using i) ECG images (AUROC 0.915) or ii) echocardiographic studies by incorporating all available views (AUROC 0.93). In a leave-out testing set of n=82 individuals with serial ECGs and n=49 individuals with serial echocardiograms we characterized longitudinal patterns in the evolution of the AI ECG and echo-based scores, and estimated the percentage of individuals that would have screened positive across distinct time intervals.

Results

In the leave-out testing set 52.4% and 34.7% of all individuals who went on to receive a diagnosis of ATTR-CM would have screened positive by AI deployed to ECGs and echocardiograms, respectively, 1 to 3 years before their confirmatory testing, with the percentage increasing to 75.6% and 69.4% in the 12 months before their eventual diagnosis (A). Across both modalities, there was a longitudinal increase in AI predictions when comparing the median of all studies performed more than a year before diagnosis versus the median of any studies performed within 12 months of diagnosis (AI-Echo: 0.20 [IQR: 0.04-0.35] to 0.49 [0.24-0.59] & AI-ECG: 0.07 [0.02-0.20] to 0.32 [0.11-0.49], p<0.001 for both) (B), consistent with evolution in the ECG and echocardiographic signature of ATTR-CM before its clinical diagnosis.

Conclusions

We demonstrate that AI applied directly to ECG images and echocardiography may enable scalable monitoring of subclinical ATTR-CM progression.
Coronary plaque volume burden and composition in patients with non-hemodynamically significant coronary artery plaques and systemic inflammation
Authors: Martinez Vives P , Ramos-Cano P , Monteagudo-Ruiz J M , Piris A , Garcia-Sebastian C , Carrion-Sanchez I , Antonana S , Hinojar R , Garcia-Martin A , Gonzalez A , Jimenez-Nacher J J , Arribas Marcos A , Fernandez Mendez M A , Zamorano J L , Fernandez-Golfin C
Published: October 2024

Introduction

Atherosclerotic coronary disease is a leading cause of morbidity and mortality worldwide. Systemic inflammation can affect plaque composition and thus increase cardiovascular risk. Identifying plaque characteristics in these patients could be useful to learn how inflammation (identified by easy to access parameters, like high ferritin and CRP) affects plaque composition in these challenging patients.

Purpose

We aimed to evaluate the association of systemic inflammation identified by high ferritin and/or high C-reactive protein (CRP) with coronary plaque volume and composition in patients with non-hemodynamically significant coronary artery plaques (stenosis <50%).

Methods

We prospectively recruited 109 patients referred for noninvasive CT angiography (from November 2023 to January 2024) with suspected coronary artery disease. 20 had totally/partially non-calcified, non-significant coronary plaques (stenosis <50%). Plaque volume was measured. Plaque components were stablished as calcified (>200 UH), lipidic (<60 UH) and fibrous (60-200 UH). Systemic inflammation was identified when ferritin was >300 ng/mL and/or C-reactive protein CRP was >5 mg/L, according to our laboratory high normal limits. CT scan images were acquired with a 128 detectors dual-layer CT scan with prospective-retrospective/synchronization. Intravascular iodine-based contrast agent was administered.

Results

Mean age was 60 ± 11 years old and 75% of patients were men. 55% had high blood pressure, 65% were current or previous smokers and 40% had dyslipidemia (35% received statins). 10% were diabetic. There were no difference between groups for these characteristics.

We analyzed 33 plaques. Fibrous plaque volume was found to be significantly higher in patients with high ferritin (66.9 vs 32.5 mm3; p = 0.04) and in patients with high CRP (78.7 vs 36.4 mm3; p = 0.05). The percentage of fibrous plaque tended to be higher in patients with higher ferritin and CRP (54.9 vs 38.9; p = 0.06 and 60.6 vs 40.7%; p = 0.07, respectively).

Conclusions

Systemic inflammation affecting coronary plaque composition in non-hemodynamically significant coronary atherosclerotic disease can by identified by high ferritin and high CRP levels. It is associated with higher fibrous plaque volumes. This finding suggest that systemic inflammation can associate more vulnerable plaques and might benefit from more aggressive management of non-hemodynamically significant atherosclerosis.TableFigure
Evaluation of bleeding events in a cohort of patients with transthyretin cardiac amyloidosis
Authors: Moreno De Redrojo Cortes L , Gallego Delgado M , Eiros Bachiller R , Canadas Salazar J , Garcia Berrocal B , Perez Sanchez P , Sanchez Puente A , Rincon Diaz L M , Garcia Monsalvo M , Laffond Elvira A , Hernandez Martos A , Bracho Bracchitta D , Alvarez Martinez C , Sanchez Fernandez P L , Villacorta Arguelles E
Published: October 2024

Introduction and purpose

transthyretin amyloidosis is an infiltrative disease with several comorbidities, including bleeding. The aim of this study was to evaluate the incidence of bleeding in patients with transthyretin amyloidosis and the underlying risk factors that promote bleeding.

Methods

a retrospective observational study was conducted on a cohort of patients with transthyretin amyloidosis diagnosed between 2016 and 2023 according to the diagnostic criteria of the Working Group on Myocardial and Pericardial Diseases of the European Society of Cardiology. Bleeding risk was calculated according to HAS-BLED score and bleeding events at follow-up were analysed.

Results

184 patients were diagnosed with a median age of 84 years [IQR 79-8], 154 (8%) males. 123 patients (67%) were on anticoagulant therapy. 91 patients (50%) had a bleeding event, with a total of 189 events recorded and a median time from transthyretin amyloidosis diagnosis to bleeding of 10 months [IQR 6-14]. The most frequent bleeding sites were gastrointestinal (32%) and cutaneous (22%). 35 patients (39%) had a haemorrhage which fulfilled severe bleeding criteria and 4 patients died of haemorrhagic causes. As a consequence of bleeding, 6 atrial appendage closure were indicated and anticoagulation therapy was modified in 15 individuals. The incidence rate of haemorrhage was 50 bleeds per 100 patient-years and 58 per 100 patient-years in patients on anticoagulant treatment. Anticoagulant therapy resulted in a 3,5-fold raise in bleeding (95% CI 2-7) and a punctuation ≥2 in HAS-BLED score increased haemorrhages 4,6 times (95% CI 2-9), with higher rates of bleeding the higher the score on the scale.

Conclusions

bleeding is a frequent complication in transthyretin amyloidosis, with a higher risk in those individuals with anticoagulant therapy or with a HAS-BLED score ≥2. Subsequently, it should be considered in the follow-up both haemorrhagic risk and anticoagulant treatment, with the aim of implementing strategies to reduce the bleeding risk.