bluuebunny/crossref_metadata_2025 huggingface dataset:
Right ventricular myocardial work: a step forward for the assessment of right ventricular to pulmonary artery coupling
Authors: Sforna S , Fortuni F , Biagioli P , Maltempi M , Di Pietro I , Mascelloni M , Fedeli F , Ambrosio G , Carluccio E
Published: October 2024

Background

Right ventricular myocardial work (RVMW) is a novel method for non-invasive assessment of right ventricular (RV) function. By integrating RV global longitudinal strain as systolic function parameter, pulmonary systolic and diastolic pressures as afterload indices, and pulmonary and tricuspid valves timings, RVMW could provide a more comprehensive evaluation of RV function.

Purpose

The aim of this study was to assess patterns of RVMW indices in patients with preserved and impaired RV to pulmonary artery (PA) coupling (RVAC), as assessed by RV free wall longitudinal strain/pulmonary artery systolic pressure (RVFWLS/PASP) ratio.

Methods

We studied by echocardiography 158 consecutive patients with stable HF and left ventricular (LV) systolic dysfunction (LV ejection fraction < 50%). RVAC was assessed by RVFWLS/PASP and patients were grouped according to the median value. Four parameters of RVMW were obtained: RV global work index (RVGWI), RV global constructive work (RVGCW), RV global wasted work (RVGWW) and RV global work efficiency (RVGWE).

Results

According to RVFWLS/PASP ratio, patients were divided into two groups: A) preserved RVAC (RVFWLS/PASP ratio ≥ 0.51; N=84) and B) impaired RVAC (RVFWLS/PASP ratio < 0.51; N= 74). Both RVGWI (371±156 vs 384±207 mmHg%, P=NS) and RVGCW (449±171 vs 516±249 mmHg%, P=NS) did not significantly differ between the two groups (figure 1). However, group B (impaired RVAC) showed significantly greater RV wasted work (94±69 vs 44±30 mmHg%, P=0.0001) and significantly lower RV work efficiency (80±13 vs 88±8 %, P=0.0001) compared to group A (preserved RVAC, figure 2).

Conclusions

RVMW provided new insight in the RV function assessment, highlighting lower efficiency due to higher wasted work in RV to PA uncoupled patients.Figure 1Figure 2
Predictive ability and prognostic correlation of global longitudinal strain in patients with negative dipyridamole stress echocardiography by wall motion criteria
Authors: Mei D A , Moderato L , Lazzeroni D , Binno S , Pastorini G , Magnani G , Gurgoglione F L , Nicolini F , Ardissino D , Niccoli G , Gaibazzi N , Boriani G , Aschieri D
Published: October 2024

Background

Dipyridamole stress echocardiography (DSE) is an established technique to detect coronary artery disease (CAD) and for risk stratification. Speckle Tracking Echocardiography (STE), as an objective and quantitative evaluation of ventricular function, may add incremental value to conventional stress echo analysis.

Purpose

To assess the prognostic value of rest (Rest-GLS) and peak (Peak-GLS) stress global longitudinal strain (GLS) in patients with suspected CAD and negative DSE according to wall motion index (WMI) criteria.

Methods

We retrospectively enrolled patients who underwent DSE at our centre for suspected CAD, with normal WMI. Strain Reserve was calculated as Rest GLS – Peak-GLS (Delta-GLS). We also collected data regarding other conventional parameters such as coronary flow reserve (CFR) of left anterior descending (LAD), left ventricle contractile reserve (LVCR), delta left ventricular ejection fraction (Delta-LVEF), heart rate response (HRR). Our primary endpoint was a composite of all-cause death and coronary revascularization. Receiver operating characteristic (ROC) curves were used to compare the predictive ability of the parameters. Adjusted logistic regression analyses were used to assess associations, also modelled as a restricted cubic spline.

Results

A total of 355 patients were included in the analysis (median age 68.2, IQR 58.2-75.2, 38.0% female). At follow-up, 58 patients met the primary endpoint. Figure 1 shows the ROC curves of different DSE parameters. Delta-GLS and Peak-GLS showed high predictive ability of composite endpoint events (area under the curve [AUC] 0.87, 95% Confidence Interval [CI] 0.82-0.92, AUC, 0.85, 95% CI 0.79-0.91, respectively), which was significantly higher compared with other DSE parameters, included Basal-GLS (P for difference for all < 0.001).

After adjustments for age, previous CAD, sex, and diabetes, reducing values of Rest-GLS, Peak-GLS and Delta-GLS were significantly associated with higher odds of experiencing composite endpoint events (Basal-GLS, odds ratio [OR] 1.13, 95% CI 1.04-1.24; Peak-GLS, OR 1.45, 95% CI 1.32-1.63; Delta-GLS, OR 1.73, 95% CI 1.50-2.04). Plotting the results of the logistic regression analysis on a restricted cubic spline, reducing values of Peak-GLS and Delta-GLS showed a linear increase for the risk of adverse events, while Rest-GLS showed a plateau for lower values.

Conclusion

The use of GLS parameters in DSE can help to better stratify the risk for the patients since they are associated with adverse cardiovascular events.Figure 1Figure 2
Negative long-term prognostic value of stress echocardiography in patients with incomplete revascularization after successful primary PCI
Authors: Boskovic N , Viduljevic M , Dedic S , Rakocevic I , Jovanovic I , Tesic M , Aleksandric S , Banovic M , Nedeljkovic I , Antonijevic N , Petrovic O , Beleslin B , Djordjevic-Dikic A , Giga V
Published: October 2024

Background

The role of stress echocardiography (SECHO) in a risk stratification of patients with incomplete revascularization after primary percutaneous coronary intervention (pPCI) has not been extensively documented.

The Aim

The aim of our study was to assess the negative long-term prognostic value of SECHO after successful pPCI and incomplete revascularization of non-culprit lesions.

Methods

Our study consisted of 194 patients (mean age 59±10years, male 136; 70.1%) successfully treated with pPCI, who performed SECHO according to Bruce protocol in order to assess residual ischemia in coronary artery with non-culprit lesion other than treated vessel. Lesion severity of non-culprit coronary arteries was assessed by quantitative coronary angiography. Duke treadmill score, functional capacity (Metabolic Equivalents - METs), achieved target heart rate (THR), chronotropic incompetence, heart rate recovery (HRR), wall motion score index (WMSI) and ejection fraction were calculated in all patients. Slow HRR was defined as ≤18 beats/min. Median follow up of the patients was 96 ± 32.5 months for the occurrence of all-cause mortality and non-fatal myocardial infarction (MI).

Results

Out of 194 patients, 38 (19.6%) had positive SECHO test, and 7 patients (3.6%) were lost to follow up so they were excluded from further analysis. During the follow-up period 29 out of 149 patients (18.8%) had an adverse event (20 deaths and 9 non-fatal MI). Negative predictive value of SECHO test was 81.2%. Median time from MI to SECHO test was 8 months. Using the Cox regression analysis, univariate predictors of adverse events were slow HRR (HR 3.750 [95% CI 1.620-8.679], p=0.002), Duke score (HR 0.866 [95% CI 0.755-0.994], p=0.040) and chronotropic incompetence (HR 0.310 [95% CI 0.107-0.895], p=0.030). In the multivariate analysis only the slow HRR remained an independent predictor of adverse events (HR 3.329 [95% CI 1.417-7.825], p=0.006). Using the Kaplan-Meier survival curve we see that the patients with slow HRR had much shorter event-free time (slow HRR 117.2 ± 13.4 months vs normal HRR test 139.4 ± 4.2 months, Log Rank 4.988, p=0.026). (Figure 1.)

Conclusion

SECHO test has excellent negative long-term prognostic value in patients with incomplete revascularization of non-culprit lesions after successful pPCI while patients with slow HRR have more pronounced risk for the occurrence of adverse events.Figure 1.Kaplan-Meier survival curve
A practical risk model based on Lasso-Cox regression for angina with nonobstructive coronary arteries (ANOCA) patients
Authors: Li M M , Liu Q D , Zhang Y , Xu M J , Zhang M
Published: October 2024

Background

Coronary flow reserve (CFR) reduction is currently one of the main criteria for risk-stratifying patients with angina and nonobstructive coronary artery disease (ANOCA). However, CFR depends on resting and vasodilated coronary hemodynamics, and a theoretical concern remains that physiological changes may inadvertently affect the result.

Purpose

We aim to fit different risk models for patients with ANOCA, which further provides applicable guidance to clinical doctors for their patients.

Methods

Between May 2018 and October 2023, 251 consecutive patients who were diagnosed as ANOCA were enrolled from Qilu Hospital of Shandong University, and the median follow-up was 800 (493, 1221) days. Demographic characteristics, cardiovascular risk factors, cardiac structure and function index, echocardiography-derived coronary flow velocity, coronary flow velocity-time integral, and CFR were collected. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression analyses were used to screen for significant parameters that were included to develop a novel predictive nomogram model. Receiver operating characteristic curve and calibration curve were used to evaluate the performance and clinical utility of the nomogram.

Results

In LASSO regression selection, five variables, diabetes, global work efficiency (GWE), global wasted work (GWW), decreased hyperemic coronary flow velocity (<0.63m/s), and peak flow velocity-derived CFR<2.5 (Figure 1) showed their correlation to the occurrence of major adverse cardiovascular events (MACE). Univariate Cox regression analysis shows that diabetes (hazard ratio [HR] = 4.108; 95% confidence interval [CI], 2.296–7.350; p = 0.001), GWE (HR = 0.890; 95% CI, 0.856–0.926; p = 0.001), GWW (HR = 1.005; 95% CI, 1.004–1.007; p = 0.012), decreased hyperemic coronary flow velocity (HR =3.405; 95% CI, 1.730–6.702; p = 0.001) and peak flow velocity-derived CFR<2.5 (HR =3.456; 95% CI, 1.898–6.292; p = 0.001) were predictors of recurrent chest pain. Multivariate analysis showed that the association of diabetes (HR = 2.735; 95% CI, 1.452–5.152; p = 0.002), GWW (HR = 1.004; 95% CI, 1.001–1.007; p = 0.010), and peak flow velocity-derived CFR<2.5 (HR = 2.650; 95% CI, 1.306–5.380; p = 0.007) with MACE remained statistically significant after adjusting for other variables. A nomogram incorporated the predictors mentioned above; it is presented in Fig.2. Internal validation showed that the model has good predictive performance. The areas under the curve (AUCs) for prediction of the risk of MACE was 0.849 (Fig.3). The calibration curve for predicting chest pain recurrence shows a good agreement between prediction and observation (Fig.4).

Conclusions

Diabetes, GWE, GWW, decreased hyperemic coronary flow velocity (<0.63m/s), and peak flow velocity-derived CFR<2.5 are significant in identifying the occurrence risk of MACE for ANOCA patients.
3D echocardiography and biomarkers for early diagnosis and prediction of chemotherapy induced right ventricular dysfunction in non-Hodgkin lymphoma patients
Authors: Mihalcea D , Memis H , Vladareanu A M , Vinereanu D
Published: October 2024

Background

RCHOP (rituximab, cyclophosphamide, doxorubicin, oncovin, prednisone) use in non-Hodgkin's lymphoma (NHL) is limited by the risk of cardiotoxicity. Although the prognostic value of right ventricular (RV) function in mortality and morbidity has been well established, its involvement in chemotherapy-induced cardiotoxicity remains unclear.

Aim

To define new parameters able to detect early RV cardiotoxicity.

Methods

51 patients (22 men, 61±14 years) with NHL scheduled for RCHOP, with three dimensional (3D) left ventricular (LV) ejection fraction (EF) >50%, were assessed at baseline, after 3rd and 6th cycle for right ventricular (RV) parameters: 3D EF, two dimensional (2D) global longitudinal strain (GLS) and free wall LS (FWLS), peak systolic annular velocity (S’), tricuspid annulus systolic excursion (TAPSE) and fractional area change (FAC). Biomarkers (troponin I, NT-pro-BNP) were measured. Cardiotoxicity was defined as LVEF reduction below 50% or preserved LVEF with LV LS decrease more than 15% from baseline.

Results

15 (29%) of patients developed LV cardiotoxicity (group 1) while 36 did not fulfill this criteria (group 2). There was a significant reduction of RVEF, GLS, and FWLS, but not of RV S’, FAC, and TAPSE, starting with the 3rd cycle, with greater changes in group 1 vs. group 2 (see Table). RVEF reduction correlated with changes of FWLS, GLS, RV S’, and troponin (r=0.612, r=0.513, r=0.362, r=-0.358, respectively; all p<0.05). Reduction of FWLS after the 3rd cycle was the best independent predictor for RVEF decrease after the 6th cycle (R²=0.433, p<0.0001). FWLS decrease with more than 26% predicted cardiotoxicity after the 6th cycle (sensitivity of 81%; specificity of 78%).

Conclusion

3D EF, 2D systolic deformation, and troponin I are able to detect early chemotherapy-induced right ventricular cardiotoxicity, and to predict further decline of RVEF in NHL patients. Thus, routine follow-up of RV function, along with the LV function, should be assessed during and after chemotherapy.RV parameters and troponin during RCHOP
Changes in mitral and tricuspid valve morphology after surgical repair of pectus excavatum
Authors: Goda A , Fujimoto T , Murakami T , Wada T , Kiyama R , Nakaoka T , Akasaka T , Uemura S , Masuyama T
Published: October 2024

Background

The effect of pectus excavatum (PE) on cardiac morphology and function has been reported previously. The right heart chamber size and cardiac output improved after the surgical correction of PE. However, the effect on the mitral and tricuspid valve has not been investigated.

Purpose

Our purpose was to investigate the morphological changes in the tricuspid and mitral valve after PE surgery.

Methods

We enrolled 25 patients who underwent Nuss surgery for PE repair. The inclusion criteria were 1) aged 15 years or older, 2) Haller Index of more than 5.0, and 3) transesophageal echocardiography (TEE) during PE surgery. We measured RV size and the sphericity index of tricuspid and mitral valve using 3D echocardiography before and after the elevation of the sternum. The sphericity index was calculated as the ratio of anterior-posterior (AP)/medial-lateral (ML) dimeter for the mitral valve (MV) and septal-lateral (SL) / AP dimeter for the tricuspid valve (TV).

Results

Mean age was 26±11 years, and 28% was female. The Haller index was 6.9 ± 2.8. All patients had normal left ventricular and right ventricular function evaluated with transthoracic echocardiography. The chamber diameter of the base and mid in RV increased after the elevation of the chest. The AP and SL dimeter were enlarged after the elevation of the chest in the TV, and the sphericity index of TV did not change. On the other hand, AP diameter increased but ML diameter was constant in the MV, and the sphericity index of MV increased after the elevation of the chest. Therefore, the annulus size was increased but the morphology was not changed in the TV. Unlike the TV, the morphology of MV annulus became close to circular from flat shape. In several patients, trivial mitral regurgitation was observed after elevation of chest, and possibly affected by the morphological change of the MV annulus.

Conclusions

The surgical repair for pectus excavatum effected not only right ventricular morphology but also on the tricuspid and mitral valve. The annulus change was different between the tricuspid and mitral valve.
The association between left ventricular mass index and all-cause mortality
Authors: Chang H C , Sung S H
Published: October 2024

Background

Left ventricular hypertrophy (LVH) has been associated with a higher risk of all-cause mortality. However, there is a lack of optimal cut-off values for grading the severity of LVH in the general population.

Purpose

We aim to investigate the association between the left ventricular mass index (LVMi) estimated by echocardiography and all-cause mortality and determine the optimal cut-off values of LVMi for the general population to predict outcomes.

Methods

Consecutive participants undergoing echocardiography in a tertiary medical center in Taiwan during 2005-2021 were enrolled. LVMi was calculated using the cube formula from the linear method. The primary outcome was all-cause mortality by linking to the National Death Registry. The association between LVMi and all-cause mortality was assessed using the joinpoint linear regression analysis to derive the optimal cut-off values for LVMi. Using the Kaplan-Meier methods, we validated our results with a community-based cohort with a long-term follow-up period.

Results

85,503 participants (age 64.3 ± 16.9 years, 53.7% men) were enrolled. During a mean follow-up of 67.6 ± 48.5 months, there were 14,565 deaths (17%). A U-shaped relationship between LVMi and the risk of all-cause mortality could be observed. The joinpoint linear regression analysis revealed that LVMi could be categorized into the following groups (less than 66 gm/m2, 66-87 gm/m2, 88-132 gm/m2, 133-170 gm/m2, and more than 171 gm/m2), with each group representing a different risk for all-cause mortality. (Figure 1) In the validated cohort categorized by the cut-off values of LVMi, the Kaplan-Meier analysis showed divergent risks for all-cause mortality between different groups in the community-indwelled populations (Figure 2, log-rank P-value< 0.001).

Conclusion

There was a U-shaped relationship between LVMi and the risk of all-cause mortality. Grading for the severity of LVH using the LVMi is warranted for the risk assessment in the general population.Figure 1Figure 2
Basal inferior-septal segment is highly susceptible to deformation in the clinical spectrum of transthyretin-derived cardiomyopathy
Authors: Tsuruda T , Nakada H , Yamamura Y , Matsuura Y , Suiko Y , Komaki S , Tanaka H , Moribayashi K , Ideguchi T , Terada T , Ota T , Yamamoto K , Nishihira K , Shibata Y , Kaikita K
Published: October 2024

Background

The prevalence of transthyretin-derived cardiomyopathy (ATTR-CM) is increasing; however, understanding the morphological and functional manifestations within the left ventricle (LV) across the spectrum of heart failure (HF) remain limited.

Purpose

This study aims to assess the longitudinal strain (LS) using 2D speckle-tracking echocardiography in ATTR-CM patients and compared them with the features of magnetic resonance imaging (MRI).

Methods

2D speckle-tracking echocardiography evaluated LS in 63 histology-confirmed ATTR-CM patients (median age: 78 years; male: 94%), with and without developing HF. Additionally, native T1 and extracellular volume (ECV) measured using MRI were compared with LS in 18-segments depicted on a Bull’s eye plot.

Results

Patients were grouped based on HF status: Group 1 (no HF symptoms, n=10), Group 2 (HF with preserved LV ejection fraction (LVEF), n=17), and Group 3 (reduced LVEF, n=36). Group 3 exhibited higher levels of brain natriuretic peptide and troponin T, and lower estimated glomerular filtration rate, compared with Group 1 and 2. Echocardiography revealed heightened LV thickness and decreased LVEF in Group 3. LS analysis revealed susceptibility to deformation in the basal inferior-septal segment, persisting even in Group 1. MRI revealed a high average native T1 level with minimal standard deviation (indicative of tissue homogeneity). However, this level increased as distance from the inferior-septal segment grew in the basal and mid-ventricular slices. Contrast images displayed maximal ECV in the basal and mid-ventricular inferior-septum, a phenomenon persisting in Group 1. Segmental LS decline, as assessed by echocardiography, correlated with ECV expansion but not with native T1 values.

Conclusion

2D speckle-tracking echocardiography can identify segmental LS impairment in ATTR-CM patients, potentially reflecting amyloid burden and fibrosis extent. Our data suggest that amyloid deposition might be widespread from the basal inferior-septal segment to other areas.
Cardiac contractility index, a novel biomarker of incident heart failure amongst people with normal left ventricular ejection fraction in the UK Biobank
Authors: Cole C , Straw S , Drozd M , Conning-Rowland M , Kamalathasan S , Lowry J , Paton M F , Slater T A , Levelt E , Kearney M T , Witte K K , Cubbon R M , Gierula J , Brown O I
Published: October 2024

Background

Cardiac contractility index (CCI) is a simple non-invasive measure of myocardial contractility defined by systolic blood pressure divided by indexed left ventricular end-systolic volume. Although left ventricular ejection fraction (LVEF) is essential for phenotyping patients with suspected heart failure (HF), it is load dependent and insensitive to subtle subclinical ventricular dysfunction. Left ventricular (LV) strain, although more sensitive at detecting subtle disturbances in myocardial function, also does not reflect loading conditions and dependency on image quality and inter-vendor variability limit widespread use. The ability of CCI to identify patients with subclinical left ventricular dysfunction at risk of developing HF is unknown.

Purpose

We aimed to: 1) explore the relationship between CCI with conventional imaging biomarkers of LV systolic dysfunction and 2) assess whether CCI could identify those at increased risk of incident HF in people without pre-existing left ventricular dysfunction in the UK Biobank imaging study.

Methods

We explored the relationship between CCI and laboratory and imaging biomarkers of systolic function, including LVEF and LV strain. Scatter plots were constructed for CCI with LVEF and LV strain. Pearson’s coefficients (r) and coefficient of determination (r2) were calculated to assess for correlations. People with sex-specific thresholds of abnormally low LVEF derived from within the same cohort (<48% for men, and <51% for women) were then excluded. CCI was then dichotomised as being high or low based its median value (4.4 mmHg/ml/m2). Age-sex adjusted Cox proportional hazards ratios (HR) with 95% CIs were estimated for the primary outcome of incident HF (derived from linked national digital registries) in addition to modelling with restricted cubic splines.

Results

We included 38,215 people (median age 55 years, 48% men). There was moderate correlation between CCI with LVEF (r=0.53 [0.53-0.54], R2=0.29; p<0.001), LV global circumferential strain (r=-0.50 [-0.50- -0.49], R2=0.25; p<0.001) and radial strain (r=-0.49 [0.48-0.50], R2=0.24; p<0.001), although was only weekly correlated with LV global longitudinal strain (r=-0.19 [-0.20- -0.18], R2=0.03; p<0.001) (Figure 1A). Using sex-specific thresholds 33,739 (88.3%) had a normal LVEF. During 195,584 person-years of follow-up (median 5.5 years), a total of 221 (0.7%) participants developed HF. Age-sex adjusted low CCI at baseline was associated with an increased risk of incident HF (adjusted HR 1.33 [1.01-1.75]; p=0.043). The association between CCI and incident HF was curvilinear (Figure 1B).

Conclusions

CCI identifies people with subclinical left ventricular systolic dysfunction at risk of developing incident heart failure.
Heart failure and renal outcomes in patient treated with GLP1 agonists
Authors: Del-Cuerpo-Salinas N , Cazorla-Morallon D , Perez-Ferrandiz A , Lopez-Ayala J M , Claramunt-Bayarri A M , Bodi-Beneito C , Martinez-Rey-Ranal E , Quintanilla-Tello M A , Frutos-Garcia M A
Published: October 2024

Introduction

Glucagon-like peptide-1 receptor (GLP1) agonists are emerging as a primordial treatment for diabetes and to reduce cardiovascular burden, both of them factors that play an important role in the developing of renal chronic disease and heart failure, and vice versa.

The debut of renal chronic disease and the manifestation of acute renal injury/failure can lead to the discontinuation of treatment, which in patients suffering from heart failure who tend to be polymedicated could end up in lessening their survival.

Methods

A metanalysis of randomized clinical trials (RCT) comparing GLP1 agonists with placebo was performed. The endpoint of the study was to analyze all-cause mortality, hospitalization or urgent medical visit for heart failure, a kidney outcome composite, which is slightly heterogenic depending on the RCT, and the manifestation of acute renal injury/failure as an adverse effect or that lead to the discontinuation of treatment. The meta-analysis was performed using the inverse variance method, using the fixed effects model when there was no heterogeneity and the random effects model when heterogeneity is significant.

Results

A sum of 9 randomized controlled trial were included where a GLP1 agonists such as albiglutide, dulaglutide, exenatide, liraglutide, lixinatide or semaglutide compared with placebo. 77684 patients were incorporated, while 39497 were treated with a GLP1 agonists. The mean age was of 63.7 years (SD ± 1.97 years), 60080 (77.3%) suffered from diabetes, 60552 (77.9%) from cardiovascular disease and 14367 from chronic heart failure (18.4%). The mean eGFR was 77.3 mL/min (SD ± 3.3 mL/min).

As showed in the forest plots, treatment with GLP1 agonists reduced all-cause mortality by 12% (RR: 0.88, 95% CI 0.83-0.92; p<0.001), hospitalization or urgent medical visit for heart failure by 10% (RR: 0.90, 95% CI 0.83-0.98; p<0.001), the kidney composite outcome by 22% (RR: 0.78, 95% CI 0.70-0.87; p<0.001), while it showed no statistical reduction in acute renal injury/failure (RR: 0.89, 95% CI 0.79-1.01; p=0.069).

Conclusion

Treatment with a GLP1 agonists reduced the incidence of all-cause mortality by 12%. In addition, hospitalization or urgent medical visit for heart failure was decreased by 10%. In terms of renal asessment, the composite of kidney function was reduced by 22%, while the manifestation of acute renal injury/failure, though no statistical signification was accomplished, showed some evidence of beneficial effect but more RCTs are needed to prove it. Hence, GLP1 analogues appear as a possible new pillar of treatment for heart failure and renal disease in determined patients.
Dual pathway inhibition in patients with atherosclerosis with and without heart failure: insights from the XATOA Registry
Authors: Gouda P , Ezekowitz J , Gay A , Vogtlander K , Aboyans V , Debus S , Fox K A A , Zeymer U , Welsh R
Published: October 2024

Introduction

Patients with atherosclerotic cardiovascular disease (ASCVD) are at a high-risk of experiencing a major adverse cardiovascular event, with 1 in 10 individuals experiencing an event within four years (1). To address this risk of secondary cardiovascular events, there have been renewed efforts to enhance secondary prevention therapies through the application of guideline-directed medical therapy. One secondary prevention strategy is the use of dual pathway inhibition (DPI) therapy with aspirin and vascular-dose rivaroxaban (2.5mg twice daily), which simultaneously targets both the platelet activation and thrombin generation pathways. Patients with concomitant ASCVD and heart failure (HF) are a subgroup with a higher risk for ischemic events, but have not been adequately represented in recent clinical trials.

Purpose

To explore the risks and benefits of DPI therapy in a generalizable population of patients with concomitant ASCVD and HF.

Methods

The Xarelto plus Acetylsalicylic acid Treatment patterns and Outcomes in patients with Atherosclerosis (XATOA) registry is a prospective, multicentre registry of patients with either coronary artery or peripheral artery disease that were initiated on DPI (2). The primary endpoint was a composite of cardiovascular death, myocardial infarction or stroke and the safety outcome was major bleeding. Multivariable logistic regression was performed to assess the association of HF status and ejection fraction (EF) on the outcomes of interest.

Results

Of 5532 participants, 4022 (72.7%) had documentation of HF status. Of those 873 (21.5%) had a history of heart failure (EF >40% - 461; EF ≤40% - 181, EF unknown – 231). Over a median follow-up of 465 days (IQR – 372-576), the primary outcome occurred in 4.9% of participants with HF compared to 2.4% in those without HF (aHR 1.57 95% CI 1.02-2.41). The safety outcome was similar in patients with and without HF (0.9% versus 1.11%; aHR 0.7 95% CI 0.31-1.67). Among patients with HF, those with an EF of ≤40% demonstrated a non-significant trend towards higher rates of adverse events including MACE (8.8% versus 3.5%; aHR 1.38; 95% CI 0.59-3.22) compared to those with an EF of > 40%.

Conclusion

In a generalizable cohort of patients with atherosclerotic disease and HF, the use of DPI is associated with similar outcomes to those observed in recent randomised controlled clinical trials.Table 1 - Demographics by HF statusFigure 1 - MACE by HF status
Treatment strategy for heart failure patients with guideline-directed medical therapy intolerance: a real-world prospective study
Authors: Chen J L , Gao L , Zhang D Y
Published: October 2024

Background

Guideline-directed medical therapy (GDMT) reduces the incidence of worsening events in patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, in actual clinical practice, a proportion of patients are unable to tolerate complete GDMT.

Purpose

This study aimed to assess the medication strategy for patients with HFrEF who are intolerant to GDMT.

Methods

A total of 110 patients admitted with acute HF were included in the study. The patients were non-randomly assigned to receive complete or incomplete GDMT after assessment by doctors before discharge from the hospital. All patients were followed up for 180 days. The primary composite endpoint was worsening HF-associated events, including death or rehospitalization due to HF, and the need for intravenous diuretic therapy. The secondary endpoints were the New York Heart Association functional class, blood pressure, and cardiac structure and function assessed by echocardiography.

Results

The main reasons for GDMT intolerance were renal insufficiency (41.8%) and hypotension (26.4%). GDMT-intolerant patients had lower eGFR (50.4 ml/min/1.73 m² vs. 70.9 ml/min/1.73 m²; p=0.002) compared with those who tolerated GDMT, and included more patients with chronic kidney disease (56.4% vs. 23.6%, p<0.001) and higher NT-proBNP levels (5340 pg/ml vs 8080 pg/ml, p=0.039) at baseline. While patient mortality was similar between the two groups, the rate of worsening HF events was lower in patients with GDMT (hazard ratio: 0.736; 95% confidence interval: 0.389−1.393) and vericiguat treatment (p<0.001). In terms of the secondary endpoint, patients who received GDMT showed greater improvements in cardiac structure and function although there was no statistical difference between the groups. In the prespecified subgroup analysis of the effects of vericiguat on the primary endpoint, the incidence of worsening HF events was reduced by vericiguat, regardless of whether the patient was comorbid with GDMT or not, or whether they had a previous history of HF (p-interaction= 0.519 and 0.227, respectively).

Conclusions

Patients with early in-hospital initiation of complete GDMT and continuous GDMT after discharge had better outcomes compared with patients who were intolerant to GDMT. Co-administration of vericiguat with or without GDMT may reduce the incidence of worsening HF events in HF patients within 180 days.Results of the primary endpoint
Serial changes of 99mTc- pyrophosphate uptake in patients with hereditary transthyretin amyloid cardiomyopathy treated with tafamidis
Authors: Yu A , Chen Y , Tsai C , Chao C , Su M , Chou C , Shun C , Hsueh H , Juang J , Lee M , Tseng P , Hsieh S , Lin Y , Cheng M
Published: October 2024

Objective

Transthyretin amyloid cardiomyopathy (ATTR-CM) arises from the deposition of amyloid in the heart, resulting in adverse outcomes. Tafamidis has demonstrated potential in slowing disease progression. Our research group, alongside others, has documented cases where decrease in cardiac tracer uptake were observed through bone scintigraphy after tafamidis treatment.[1-8] This study aims to assess the efficacy of Technetium-99m (99mTc)-pyrophosphate (PYP) scintigraphy in longitudinally monitoring tafamidis treatment for hereditary ATTR-CM over an extended follow-up period.

Methods

We retrospectively analyzed a prospective cohort of hereditary ATTR-CM patients treated with tafamidis (61 mg/day) retrospectively. A control group comprised hereditary ATTR-CM patients who hadn't received eplontersen, inotersen, tafamidis, or patisiran. 99mTc-PYP SPECT/CT scans were conducted at baseline and 1-3 years post-treatment, measuring visual score, planar heart to contralateral lung (H/CL) ratio, and volumetric heart to lung (H/L) ratio.

Results

Twenty hATTR-CM patients received tafamidis, with the other ten in the control group. After a 2-year follow-up, the tafamidis group experienced a significant decrease in volumetric heart to lung (H/L) ratio (3.817 to 3.011, p < 0.001), while the control group showed no significant change (3.775 to 3.621, p = 0.121)(Figure 1B). Significant decreases in volumetric H/L ratio were noted in the first year of tafamidis treatment (-21.71%), with minimal changes in the subsequent two years (-0.77% in the second year and -2.41% in the third year)(Figure 2B).

Conclusion

A significant initial reduction in 99mTc-PYP uptake was observed in hereditary ATTR-CM patients during the first year of tafamidis treatment. However, this effect was not sustained in the subsequent two years. Further investigation is warranted to comprehend the long-term efficacy of tafamidis in these patients.Changes in 99mTc-PYP uptake at 2 yearsChanges between 1st, 2nd and 3rd year
A newly developed small-molecule ErbB4 agonist reduces reactive cardiac fibrosis and adverse ventricular remodelling after myocardial infarction in a sex-specific manner
Authors: Goovaerts B , Civati C , Feyen E , De Keulenaer G W , Segers V F M
Published: October 2024

Background

The beneficial effects of the neuregulin/ErbB pathway on the diseased heart have been well-established. The anti-fibrotic and cardioprotective aspects of neuregulin are largely attributable to the activation of the ErbB4 receptor. We recently developed a small-molecule selective ErbB4 agonist, which reduced collagen production in cultured fibroblasts and prevented oxidative-stress induced cardiomyocyte death in vitro.

Purpose

In order to evaluate the in vivo effects of this small-molecule ErbB4 agonist (referred to as compound, Cpd), we assessed its effect on left ventricular remodelling, cardiac fibrosis and cardiac function in a murine model of myocardial infarction (MI). Since there is a potential interaction between ErbB4 and the oestrogen receptor, we also aimed to evaluate whether these effects were sex-dependent. We hypothesised that Cpd would attenuate left ventricular remodelling, reduce cardiac fibrosis and help retain cardiac function in a sex-specific manner.

Methods

Mice were divided by sex and then further divided into three experimental groups: a sham group, an MI group receiving Cpd (MI/Cpd), and a control MI group receiving vehicle only (MI/Veh). MI was induced by ligating the left descending coronary artery. Seven days after MI, mice started treatment with either Cpd (2mg/kg/d) or its vehicle through subcutaneous osmotic minipumps. Cardiac ultrasound was performed weekly until mice were sacrificed after four weeks of treatment. Hearts were excised and stained with Masson’s trichrome to assess reactive cardiac fibrosis in the myocardium of the left ventricle, located remote from the infarction scar. A WGA-isolectinB4-DAPI immunofluorescent stain was performed to assess cardiomyocyte cross-sectional area in order to evaluate cardiomyocyte hypertrophy.

Results

In females (n=25), Cpd significantly decreased left ventricular end-diastolic volume compared to vehicle (LVEDV, Fig.1A, 80±23 µl vs.108±29 µl, p=0.045) and induced a slightly increased left ventricular ejection fraction (LVEF, Fig.1B, 32±12% vs. 22±9%, p=0.086). In addition, Cpd significantly reduced reactive interstitial fibrosis myocardium (Fig.1C, fibrotic area, 1.4±1.0% vs. vehicle: 3.8±3.1%, p=0.0363). In males (n=30), Cpd had no significant effects on either of the parameters mentioned above, (Fig.1E-G). There was no significant treatment effect in either group on cardiomyocyte cross sectional area (Fig.1D, Fig.1H).

Conclusion

Treatment with the novel small-molecule ErbB4 agonist attenuates left ventricular dilation and reactive interstitial fibrosis after MI in female mice, but not in males. These data support the premise that small molecule-induced ErbB4 activation is a potential new therapy for heart failure, especially in female patients. The mechanisms underlying the sex-dependent effects warrant further exploration.Figure 1
Beta-blocker use and outcomes in patients with heart failure and mildly reduced and preserved ejection fraction
Authors: Matsumoto S , Henderson A D , Boer R A D , Lam C S P , Martinez F A , Packer M , Redfield M M , Rouleau J L , Veldhuisen D J V , Vaduganathan M , Zannad F , Zile M R , Jhund P S , Solomon S D , Mcmurray J J V
Published: October 2024

Background

Concerns have been raised about the appropriateness of use and safety of beta-blockers (BBs) in patients with heart failure and mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF). However, randomized trial evidence is still lacking.

Purpose

To perform an observational analysis of the association between BB use and clinical outcomes in a large dataset of patients with HFmrEF and HFpEF.

Methods

We pooled individual patient data from four large HFmrEF/HFpEF trials (I-Preserve, TOPCAT, PARAGON-HF, and DELIVER). The associations between baseline BB use and outcomes were analyzed. The primary outcome was the composite of cardiovascular death or HF hospitalization.

Results

Among the 16,951 patients included, the mean left ventricular ejection fraction (LVEF) was 56.8%, and 13,400 (79.1%) had HFpEF (LVEF ≥50%). Overall, 12,812 patients (75.6%) received a BB. The median bisoprolol-equivalent dose of BB was 5.0 (Q1-Q3: 2.5-5.0) mg with BB continuation rates of 95.1% at 1 year and 93.1% at 2 years (in patients who survived more than 1 and 2 years, respectively). Overall, the hazard ratio (HR) for the primary outcome did not differ between BB users and non-users (HR: 0.98 [95% CI: 0.91-1.05]) but among patients with HFmrEF, BB users had a lower HR (0.84 [95% CI 0.71-0.98]), whereas in HFpEF the HR was similar BB users and non-users (0.99 [95% CI 0.92-1.08]). However, after comprehensive adjustment for known prognostic variables, including NT-proBNP, BB use was associated with a better outcome in the overall cohort (HR 0.81 [0.74-0.88]), and this association was maintained across the range of LVEF (Figure 1). In subgroup analyses, the risk of the primary outcome was similar in BB users and non-users with or without a history of myocardial infarction, with or without a history of hypertension, or with or without a baseline heart rate <70 bpm. By contrast, a better outcome with BB use was seen in patients with atrial fibrillation compared to those without atrial fibrillation (Figure 2).

Conclusions

Although this is an observational analysis of non-randomized treatment, there was no suggestion that BB use was associated with worse HF outcomes even after extensive adjustment for other prognostic variables.

Figure Legends

Figure 1. Association between beta-blocker use and outcomes across the range of LVEF. Risk in beta-blocker users versus non-users is shown as an adjusted continuous hazard ratio

Figure 2. Association between beta-blocker use and non-use in the overall population and clinically relevant patient subgroups, shown as an adjusted hazard ratio (HR). The outcome analyzed was the composite of CV death or HF hospitalization (primary outcome)Figure 1Figure 2
Long-term follow-up of the TRED-HF trial
Authors: Cheng L , Hammersley D , Ragavan A , Javed S , Mukhopadhyay S , Gregson J , Han J , Ware J , Tayal U , Pennell D J , Cleland J G F , Prasad S K , Halliday B P
Published: October 2024

Background

The TRED-HF trial (1) found that 44% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short term after withdrawal of medical therapy. The longer-term risk of relapse is uncertain.

Purpose

This follow-up aims to investigate the longer-term risk of relapse in patients with recovered DCM and any possible predictive factors.

Methods

TRED-HF trial participants were followed until May 2023. The primary outcome was DCM relapse defined as >10% reduction in left ventricular (LV) ejection fraction to <50%, doubling in N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) to >400ng/L, or clinical recurrence of heart failure (HF). Therapy intensity for HF was calculated using QUAD scores. The incidence of relapse was calculated using Kaplan-Meier estimates. Predictors of relapse were investigated using Cox proportional hazard modelling.

Results

For all fifty-one patients, median follow-up from enrolment was 6 (IQR: 6-7) years. Overall, thirty-three patients (65%) relapsed with an estimated 5-year relapse rate of 61% (95% CI 45-73). Twenty patients relapsed during the randomised trial, nine of whom had a recurrent relapse during follow-up (Figure 1). Thirteen patients relapsed for the first time after completion of the trial; of those, one patient did not have therapy withdrawn during the trial, 8 had restarted low intensity HF therapy and 4 patients stayed on no therapy. Five patients stayed off HF therapy and did not relapse. The overall mean intensity of HF therapy was lower after the trial compared to enrolment (mean difference in QUAD score -6 [-8 to -4]; p<0.001). A mean reduction in medication intensity was also seen at the point of relapse during the trial and during follow-up (Figure 2). Of relapses during follow-up, seven had identifiable triggers (arrhythmia (n=4), pregnancy (n=1), hypertension (n=1), infection (n=1)). Patients taking more HF medications at baseline or with higher baseline NT-pro-BNP were more likely to relapse. Corrected atrial fibrillation was associated with reduced future risk of relapse.

Conclusions

In patients with recovered DCM, the risk of relapse after therapy withdrawal increased with longer follow-up. Lower doses of HF medications and recurrent external triggers contributed to relapse. Few patients who stopped medications had sustained remission. Recovery of DCM after correction of AF was associated with a low risk of relapse provided atrial fibrillation did not recur.
Interplay between strain pattern-based classification of dyssynchrony and myocardial scar in CRT patients
Authors: Duchenne J , Calle S , Larsen C K , Devos D , Aalen J , Galli E , Mirea O , Puvrez A , Penicka M , Bogaert J , Donal E , Hopp E , Smiseth O A , Timmermans F , Voigt J U
Published: October 2024

Introduction

Echocardiography-derived septal strain patterns are valuable for predicting volumetric reverse remodelling and survival in patients undergoing cardiac resynchronization therapy (CRT). Nevertheless, presence of myocardial scarring in the left ventricle (LV) is known to attenuate CRT treatment response.

Purpose

This study aims to investigate the interplay between septal strain patterns and myocardial scarring in CRT candidates, and how they link to outcome after CRT.

Methods

In this prospective multicentre study, CRT candidates from five European institutions underwent pre-implantation assessments using speckle-tracking strain analysis on echocardiography and cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE). Dyssynchrony was graded through analysis of septal strain curves, categorizing patients into five distinct patterns, denoted as strain Stage-0 through strain Stage-4 (Fig. A). LGE of the LV wall was quantitatively assessed using CMR (as a percentage). The study endpoints were volumetric reverse remodelling (volume responder = more than 15% decrease LV end-systolic volume) after one year, and all-time all-cause mortality.

Results

A total of 267 patients, with a mean age of 66±11 years (69% males, 90% left bundle branch block [LBBB]) presented with an average LV ejection fraction (EF) of 30±7%. With each stepwise increase in strain stage, global LV scarring decreased (p<0.01; Fig. B) and the proportion of volume responders increased (all p<0.0001; Fig. C). ROC curves demonstrated that the predictive power of strain stages for CRT volumetric response was not significantly improved when scarring percentage was added (AUC 0.78 [95% CI: 0.69-0.83] vs. 0.81 [95% CI: 0.71-0.90]; p>0.05; Fig. D). In a multivariate cox regression model – including clinical characteristics that were significantly related to survival in univariate analysis – a patients’ strain stage was the only significant predictor of survival, also outperforming scar burden as determinant of outcome (HR 0.68; p=0.041; Fig. E).

Conclusions

Septal strain patterns show a strong association with the extent of reverse remodelling and outcome in CRT-treated patients. An inverse relationship is observed between pre-implant strain stages and the extent of myocardial scarring. However, scar burden did not provide incremental predictive value over the strain stages. Strain-pattern-based dyssynchrony assessment is a meaningful predictive marker which integrates information on myocardial dysfunction due to dyssynchrony as well as scar burden.
The role of fibrosis and inflammation for response and outcome prediction in candidates to cardiac resynchronization therapy: is response the right answer?
Authors: Beltrami M , Galluzzo A , Bonacchi G , Garofalo M , Checchi L , Perrotta L , Ricciardi G , Pieragnoli P , Palazzuoli A
Published: October 2024

Background

Cardiac resynchronization therapy (CRT) is an established treatment in selected patients suffering from heart failure with reduced ejection fraction (HFrEF). It has been proposed that myocardial fibrosis and inflammation could influence CRT "response" and outcome.

Purpose

Our study investigated the long-term prognostic significance of cardiac biomarkers in HFrEF patients with an indication for CRT.

Methods

86 consecutive patients referred for CRT implantation were retrospectively evaluated. The soluble suppression of tumorigenicity 2 (sST2), galectin-3 (Gal-3), N-terminal portion of the B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR) were measured at baseline and after 1 year of follow-up. An echocardiographic reduction of LV end-systolic volume ≥15% was used to define a patient as responder to CRT. Multivariate analyses were performed to evaluate their correlation with the primary composite outcome of cardiovascular mortality and heart failure hospitalizations at a mean follow-up of 9 ± 2 years.

Results

44% of patients experienced the primary outcome. the mean baseline values of NT-proBNP, Gal-3, and sST2 were significantly higher compared with the patients without cardiovascular events. At the multivariate analyses, baseline Gal-3 [cut-off: 38.5 ng/ml, AUC: 0.63, p=0.03, (OR 7.13 [1.12;45.41], p=0.03), together with TAPSE>17.5 mm (OR 10.86 [3.15;37.44], p<0.001) significantly correlated with the structural response to CRT in several prediction models. Baseline Gal-3 [cut-off: 16.6 ng/ml, AUC: 0.91, p<0.001, HR 8.33 (1.88–33.33), p = 0.005] and sST2 [cut-off: 35.6 ng/ml AUC: 0.91, p<0.001, HR 333 (250–1,000), p = 0.003] significantly correlated with the composite outcome in the prediction models with high likelihood (Table). At Kaplan-Meyer curve patients with both high baseline sST2 and Gal-3 had the lowest survival probability (Figure). Among the parameters evaluated at 1-year follow-up, sST2, eGFR, and the variation from baseline to 1-year of Gal-3 levels showed a strong association with the primary outcome [HR 1.15 (1.08–1.22), p < 0.001; HR: 0.84 (0.74–0.91), p = 0.04; HR: 1.26 (1.10–1.43), p ≤ 0.001, respectively]. Conversely, the echocardiographic definition of CRT response did not correlate with any outcome.

Conclusion

In HFrEF patients with CRT, sST2, Gal-3, and renal function were associated with the combined endpoint of cardiovascular death and HF hospitalizations at long term follow-up, while the echocardiographic CRT response did not seem to influence the outcome of the patients.