bluuebunny/crossref_metadata_2025 huggingface dataset:
Beating the clock: the impact of heart failure duration on CRT efficacy
Authors: Grama E , Codina P , Ruiz-Cueto M , Camblor A , Borrellas A , Santiago-Vacas E , Domingo M , Bazan V , Aranyo J , Villuendas R , Zamora E , Lupon J , Bayes-Genis A
Published: October 2024

Background

Cardiac Resynchronization Therapy (CRT) stands as an established intervention for selected patients with heart failure (HF) presenting with a wide QRS complex. The optimal timing for CRT implantation remains uncertain. Current evidence suggests superior outcomes post-CRT in patients who have not been previously hospitalised for HF and those receiving the implant during their initial hospitalisation for HF.1

Purpose

The primary objective of this study is to investigate the long-term clinical outcomes following CRT implantation relative to the duration of HF previous to the implant. It was analysed in a cohort of consecutive patients from a HF Unit who met the criteria for CRT as recommended by the ESC guidelines (QRS duration ≥150ms, left bundle branch block morphology, and left ventricular ejection fraction (LVEF) ≤35% despite optimal medical therapy).

Methods

We evaluated all patients who received CRT from January 2011 through September 2022. Follow-up ended in September 2023. Patients with CRT indicated for ventricular pacing due to high-degree atrioventricular block were excluded. Patients were categorized into two groups based on the duration of HF progression prior to CRT implantation: more than 3 years and 3 years or less. The primary outcome was all-cause mortality (ACM). Secondary outcomes included a composite of ACM and HF hospitalisation and the proportion of patients who demonstrated a significant improvement in LVEF (defined as an increase of ≥10% from baseline and a subsequent measurement of LVEF ≥40%).

Results

The cohort consisted of 127 patients, mean age 65.8±10.7 years, 23.6% were women, mean LVEF was 28.4±8.6% and 36.2% had ischaemic aetiology (Table 1). 62 patients either died or were hospitalized for HF. Mean follow-up was 4.9±2.7 years. After adjusting for age, sex and baseline LVEF, patients with HF for more than three years before CRT implantation had a worse prognosis: HRs of 2.31 for ACM (p=0.016) and 2.13 for the combined endpoint of ACM+HFH (p=0.010) (Figure 1).

The proportion of patients with improved LVEF after CRT was significantly higher in the group with shorter HF duration (68.25%) compared to the group with longer HF duration (25%), p <0.001.

Conclusions

Our findings reveal that patients with a shorter history of HF (less than three years) prior to CRT implantation exhibit significantly better clinical outcomes. These results highlight the role of early intervention with CRT in patients with HF, suggesting that shorter HF duration prior to CRT may lead to more favourable long-term outcomes.
Prediction of CRT response using a novel CRT responder score in an Asian patient population
Authors: Kondo Y , Sasaki S , Ando K , Soejima K
Published: October 2024

Introduction

Cardiac Resynchronization Therapy (CRT) guidelines, derived from trials among U.S. and European patients, assign weaker recommendations to those with midrange QRS duration (<150ms). Patient height and body size may modulate CRT efficacy. Moreover, these factors may affect CRT utilization and efficacy in Asia.

Aim

The purpose of this analysis was to determine the prediction scoring system model for CRT responders in a Japanese patient population.

Methods

We analyzed the database of the Multicenter Prospective Pilot Study to Test LV Intracardiac Conduction Time as a Predictor of CRT Response (BIO|SELECT) which was a single-arm study conducted at 28 hospitals in Japan. This study enrolled patients eligible for a de-novo CRT-defibrillator (CRT-D) based on current guideline indications, who had no recent or planned cardiac surgery and were planned to receive a Sentus ProMRI OTW quadripolar LV lead and a BIOTRONIK CRT-D with multipole pacing feature. Patients were followed for 7 months after implantation. Four accepted parameters to define CRT response [LVESV (cut-off -15%), LVEF (+5%), BNP (-25%), and NYHA class (one class improvement)] were combined into a composite benefit index (CBI) by forming the normalized sum, with CBI = 4.0 meaning response. The CBI was found to be more robust than the individual 4 parameters due to the reduced influence of noise and measurement errors in single parameters. Several factors were studied to create the scoring tool. The CRT responder score was the sum of these individual scores (range 0-100). To construct a predictive scoring system, logistic regression analysis was performed with a backward selection procedure. In addition, the Akaike information criterion (AIC) was applied to determine the best model among those tested. The score was then assigned employing the β coefficient of each variable divided by the reference value. The model's calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test.

Results

A total of 196 patients were enrolled in this study (mean age 69 years, mean LVEF 30%, left bundle-branch block [LBBB] 58%). The Ooccurrence of CRT response during the 7-month follow-up was 54%. Future CRT responders were significantly predicted by low age (< 70 years)(18 points), female (19 points), prior heart failure hospitalization (16 points), body mass index (<20) (17 points), QRS/height (<0.858)(30 points). This score predicted CRT response well (area under curve 0.72; 95% CI 0.643-0.798). When the cut-off of 63 points or more was applied the sensitivity was 0.56, the specificity was 0.72, and the negative predictive value was 0.58.

Conclusions

The CRT responder score is a novel approach for the prediction of CRT response, but should be validated and further improved to increase its predictive value. This approach highlights the role of preventing the development of severe heart failure and could help to identify individuals who might benefit from CRT.
Improving time-efficiency and accuracy in echocardiography: real-time automated measurements of left ventricular global longitudinal strain using deep learning
Authors: Holmstrom V , Smistad E , Dalen H , Stolen S , Lovstakken L , Holte E , Ostvik A , Grenne B
Published: October 2024

Background

Accurate quantification of left ventricular (LV) systolic function is fundamental in echocardiography. LV Global Longitudinal Strain (GLS) offers advantages over LV ejection fraction, being more sensitive, reproducible and offering better prognostic value. However, existing semi-automatic methods are time-consuming and heavily operator-dependent. Additionally, poor image quality and foreshortening decrease accuracy and reproducibility of GLS. As a result, these challenges lead to suboptimal efficiency and underutilization of GLS quantification in clinical practice.

Purpose

Our objective was to develop a deep learning (DL) application for real-time automated measurements of GLS, capable of providing tracking quality and foreshortening feedback during scanning. Subsequently, we aimed to validate the novel method in a prospective cohort study.

Methods

Deep learning networks were trained to identify apical views, identify timing of end-systole and end-diastole, conduct cardiac segmentation, estimate myocardial motion, assess LV length in each view for foreshortening detection, and present real-time visualization of tracking quality and GLS values for three cardiac cycles to the operator for review (Figure 1). The DL method was validated in a prospective cohort of 40 patients included regardless of image quality. Agreement with manual measurements obtained using semi-automatic software (EchoPAC version 204, GE HealthCare, Horten, Norway) was evaluated. Bland-Altman statistics and Pearson's correlation coefficient were used to evaluate agreement and correlation.

Results

Feasibility for real-time DL measurements of GLS was 98%, with one patient excluded due to poor image quality. There was good agreement (Bias 0.7%, LoA: -1.6 to 3.1%, figure 2) and excellent correlation (Pearson’s correlation coefficient of 0.93, p<0.001) between the real-time DL application and manual reference measurements for GLS. Using the DL application during scanning resulted in a 58% (95% CI 56%-61%) reduction in time required for scanning and post-processing to obtain GLS values, compared to using the semi-automatic method. Average time consumption was 2 minutes and 16 seconds for the DL method and 5 minutes and 27 seconds for the reference method.

Conclusion

Using deep learning, real-time fully automated measurement of GLS during scanning is feasible, time-saving, and provides good agreement with reference methods. Real-time measurements also offer the potential to reduce operator-related variability by integrating tools to provide image and tracking quality feedback to the user, ultimately benefiting patients.Application user interfaceAgreement between DL and reference
Optimal anticoagulation strategy for left ventricular assist device patients undergoing thoracentesis: a retrospective study
Authors: Hegde S , Barnett C F , Shah N , Mohammed S
Published: October 2024

Background

Left ventricular assist devices (LVADs) are associated with thromboembolic risks necessitating anticoagulation, yet balancing these risks with bleeding concerns remains challenging. Current practice involves warfarin with a target INR of 2-3 alongside anti-platelet therapy. However, consensus on anticoagulation management is lacking, particularly during sub-therapeutic INR or procedural settings. Common strategies include bridging anticoagulation with heparin or enoxaparin, temporary cessation of anticoagulation during the procedure or uninterrupted anticoagulation.

Purpose

To evaluate and compare the incidence of bleeding and thromboembolic events in LVAD patients undergoing thoracentesis, with a focus on determining the optimal anticoagulation strategy during procedures.

Methods

Retrospective data was collected over one year from LVAD patients undergoing thoracentesis at a large academic center. Patients were categorized into ‘bridge’ (received intravenous heparin for bridging during thoracentesis) and ‘no-bridge’ (did not receive bridging anticoagulation) groups. Warfarin was paused before procedure and resumed after procedure in both groups. Baseline characteristics, including age, sex, race, BMI, LVAD type, and INTERMACS profile, were recorded. Primary outcomes were major bleeding and thromboembolic events within 30 days of warfarin cessation. Statistical analysis used t-test/Wilcoxon for continuous variables and Chi-square/Fisher exact test for categorical variables. A p-value <0.05 was considered significant.

Results

During the study, twenty LVAD patients underwent thirty-two thoracenteses (nineteen bridge, thirteen no-bridge). The demographics were similar among the two groups. Warfarin was held for an average of 5.5 ± 4.6 days before and resumed 4.1 ± 4.6 days after the procedure in the bridge group and 3.8± 3.2 days before and 1.7 ± 2.5 days after in the no-bridge group. Major bleeding occurred in 73.7% of bridge group cases versus 30.8% of no-bridge group cases (p=0.059). 63.2% of bridge group patients had a bloody pleural effusion on thoracentesis compared to 46.2% of no-bridge group patients (p value= 0.34). Average transfusion requirements were 2.8 units and 2 units in the bridge and the no-bridge groups respectively (p=0.658). Thromboembolic events included a 10.5% ischemic CVA rate in the bridge group, with none in the no-bridge group. No other arterial thromboembolic events, pump thrombosis or DVT/PE were observed in either group.

Conclusion

In LVAD patients undergoing thoracentesis, a non-bridging strategy does not appear to elevate the risk of thrombosis compared to a bridging approach. Moreover, the incidence of bleeding, while not statistically significant, trended higher in the bridging group.
Association of gut microbiota imbalance with risk of postoperative infections in patients with left ventricular assist device
Authors: Takenaka S , Nagai T , Sato T , Kamiya K , Mizuguchi Y , Takahashi Y , Naito S , Saiin K , Kazui S , Hamaya T , Mori Y , Ishizaka S , Wakasa S , Anzai T
Published: October 2024

Background

Infections are the most common complications following left ventricular assist device (LVAD) implantation and associated with adverse events. Gut microbial imbalance may predispose to mucosal colonization with pathogens, resulting in a risk of subsequent serious infections. However, it remains unclear whether gut microbiota imbalance is associated with postoperative infections in patients with LVAD.

Purpose

The aim of this study was to investigate whether gut microbiota imbalance was associated with postoperative infections in patients with LVAD.

Methods

We prospectively examined 22 consecutive LVAD patients who were admitted to a university hospital for routine check-ups and had stool cultures taken between March 2022 and December 2023. All patients had no signs of infection. The patients were divided into two groups according to positive (normal bacterial flora and other bacteria including Streptococcus viridans, Klebsiella, or Extended-spectrum β-lactamase Escherichia coli; n = 7) and negative (normal bacterial flora only; n = 15) for stool culture. The primary outcome was serious infection requiring hospitalisation treated with intravenous antimicrobial agents.

Results

Patients were predominantly male (68%) and the median age was 49 (interquartile range [IQR] 29-58) years. There were no significant differences in age, sex, primary aetiology of heart failure, type of LVAD devices, time on LVAD support, the history of infection, or antibiotics use within six months between the groups. During a median follow-up period of 316 days (IQR 242-559), the primary outcome occurred in seven patients (32%), including four hospitalisation for driveline infections, two pneumoniae and bacterial bloodstream infections, and one lung abscess and bacterial bloodstream infection. Kaplan–Meier analysis showed that the adverse events more frequently occurred in LVAD patients with positive for stool culture (P = 0.010) (Figure). A multivariable Cox regression analysis showed that positive for stool culture was independently associated with an increased subsequent risk of the primary outcome (hazard ratio 6.99, 95% confidence interval 1.17-41.7, P = 0.033), even after adjustments for age, male, body mass index, diabetes, INTERMACS profile, mechanical circulatory support, serum creatinine, serum albumin, and white blood cell count, which are known to be strong determinants of worse clinical outcomes in patients with LVAD.

Conclusions

In patients with LVAD, gut microbial imbalance was associated with subsequent serious infections. These findings suggest that the screening of stool culture might be useful for early identification of high-risk patients for infectious complication after LVAD implantation.
Establishing normal global longitudinal strain values in heart transplant patients: a novel approach to enhancing detection of rejection and cardiac allograft vasculopathy
Authors: Albulushi A , Al-Abri U
Published: October 2024

In the realm of heart transplantation, accurate cardiac monitoring is pivotal for patient outcomes. This study pioneers in filling a critical void by delineating the normative values of Global Longitudinal Strain (GLS), specifically tailored for heart transplant recipients, distinguishing them from the general population. We conducted a retrospective analysis on a cohort of 110 patients who underwent heart transplantation, meticulously compiling echocardiographic data over the first 18 months post-operation. Our research focused on two primary indicators of cardiac function: Ejection Fraction (EF) and Global Longitudinal Strain (GLS).

The data indicated that EF values remained within the normal range and relatively stable throughout the monitoring period. In contrast, GLS values exhibited a gradual increase over time, suggesting a post-transplant myocardial adaptation process. However, these GLS values did not reach the established reference ranges for non-transplanted, healthy hearts, highlighting the distinctive physiological landscape of transplant recipients. Our study elucidates the superior sensitivity of GLS in detecting subtle myocardial changes that might precede clinically apparent dysfunction, advocating its utility as a crucial surveillance tool for this demographic.

By pinpointing the modified GLS benchmarks applicable to post-heart transplant patients, our findings advocate for a recalibrated echocardiographic assessment protocol. Such a protocol can significantly enhance the surveillance for post-transplant complications, most notably graft rejection and the onset of cardiac allograft vasculopathy (CAV). The study posits that incorporating these refined GLS thresholds into routine post-transplant evaluations could facilitate early intervention, potentially mitigating adverse outcomes and improving the long-term prognosis for heart transplant recipients. Thus, our research underscores the need for updated clinical guidelines that integrate these novel echocardiographic insights, paving the way for improved patient-centric cardiac care in the transplant setting.
Treatment with mTOR Inhibitors as primary immunosuppression after combined heart and kidney transplantation
Authors: Alnsasra H , Asleh R , Khalil F , Akiki E , Briasoulis A , Dean P , Bentall A , Kushwaha S
Published: October 2024

Background

It has been hypothesized that combined heart and kidney transplantation (HKT) may lead to immune modulation and attenuation of cardiac allograft vasculopathy (CAV) progression. Sirolimus (SRL) has been shown to mitigate the progression of CAV and confer renal protection. With the increasing use of SRL as primary immunosuppression in heart transplant (HT) recipients, the effect of HKT on CAV progression compared to HT-only remains undetermined.

Purpose

We sought to investigate the patterns of conversion from calcineurin inhibitors (CNI) to SRL, and its impact on CAV progression and outcomes in HKT compared to HT-only in a cohort with frequent use of SRL as primary immunosuppression.

Methods

A cohort of 302 patients who underwent either HT only (n=262) or combined HKT (n=40) was analyzed. CAV progression was assessed by measuring the delta (Δ) annual change in plaque volume (PV) normalized to vessel length (PV/VL in mm3/mm) and plaque index (PI) (%) (calculated as the PV to VV ratio) between baseline and last follow-up coronary intravenous ultrasound (IVUS). Clinical adverse outcomes included all-cause death and CAV-associated events. Secondary outcomes included differences in renal function and incidence of SRL-associated proteinuria (defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL) between HT-only and HKT recipients.

Results

Overall, 217 (72%) patients were converted from CNI to SRL as primary immunosuppression. HT recipients were more likely to be converted to SRL than combined HKT recipients (74% vs. 55%, P=0.01). HKT was associated with significantly higher ΔPV/VL (P=0.01) and a trend toward a higher ΔPI (P=0.06) than HT-only, but this association was markedly attenuated after adjustment to SRL conversion. HKT was associated with similar risk of death (adjusted hazard ratio [HR] 0.69, 95%CI: 0.28-1.71, P=0.43) and CAV-related events (adjusted HR 0.83, 95% CI: 0.30-2.31, P=0.72). Conversion to SRL was significantly associated with decreased risk of death and CAV-related events in the overall cohort. This association was not modified by the type of organ transplantation (Pinteraction=NS), and without a significant effect on estimated glomerular filtration rate (eGFR) or proteinuria.

Conclusions

HKT recipients compared to HT-only were less likely to be converted from CNI to SRL-based immunosuppression and had a greater CAV progression but without significant differences in all-cause mortality or CAV-related events. The clinical benefit and safety of conversion to SRL appeared similar in the HKT and isolated HT cohorts.
Early postoperative Fibrinogen-to-Albumin Ratio prognosticate 6-month procedural success in patients undergoing orthotopic heart transplantation
Authors: Sokolski M , Byszuk P , Ptak J , Przybylski R , Bochenek M , Krupka D , Szwajkowski M , Zakliczynski M
Published: October 2024

Background

The Fibrinogen-to-Albumin ratio (FAR) has emerged as a novel biomarker, integrating liver function and inflammatory reaction with proven prognostic value in heart failure (HF) patients. This study aims to evaluate its significance in advanced HF patients treated with orthotopic heart transplantation (HTx).

Methods

Mean fibrinogen, albumin and FAR values were analyzed one week post-HTx. The primary endpoint of the study was 6-month all-cause mortality. Regression models incorporating parameters significantly different between survivor and deceased groups (troponin, potassium, asparagine aminotransferase [AST]) were developed to assess predictive value of FAR. Additionally, the Spearman's rank correlation between FAR and inflammatory biomarkers (C-reactive protein [CRP], procalcitonin, white blood cells (WBC)] and liver enzymes [AST, alanine aminotransferase [ALT], gamma-glutamyl transpeptidase [GGTP]) were calculated.

Results

The analysis included 104 patients undergoing HTx with a median age of 53 years (44.5-62.5), 82% were male, 44% had ischaemic aetiology of HF. Within 6 months post-HTx 17 patients (16%) died. Mean fibrinogen in all patients was (3.18 ± 0.83), albumin (3.17 ± 0.35) and FAR (1.01 ± 0.28). Deceased patients exhibited lower 1 week post HTx mean fibrinogen (2.46 ± 1.13) compared to survivors (3.30 ± 0.70), lower albumin (2.93 ± 0.43) vs. (3.21 ± 0.32), and lower FAR median (0.73, 0.53-1.16) vs. (0.99, 0.88-1.18), all p<0.05. The post-HTx fibrinogen independently predicted death: (RR 0.37, p=0.003, 95% CI [0.19,0.71]), as did post-HTx albumin: (RR 0.21, p=0.05, 95% CI [0.04,1.0]). FAR was also an independent risk factor: (RR 0.08, p=0.009, 95% CI [0.01,0.54]). There were significant correlations between FAR and CRP (R=0.30, p=0.003), and GGTP (R=0.25, p=0.045). FAR was not significantly correlated with procalcitonin, WBC, AST and ALT.

Conclusions

Early post-HTx fibrinogen, albumin and FAR are independent predictors of an unfavorable prognosis in HF patients undergoing HTx. In contrast to chronic HF, early post-HTx FAR was inversely correlated with mortality. The calculated correlation between FAR, inflammatory markers and liver enzymes suggests limited association with inflammatory processes and liver function in this population.
Baroreflex activation therapy in heart failure patients with reduced ejection fraction: a long-term follow up
Authors: Wang D , Mueller-Leisse J , Hillmann H A K , Eiringhaus J , Berliner D , Karfoul N , Schmitto J D , Ruhparwar A , Bauersachs J , Duncker D
Published: October 2024

Introduction

Heart failure with reduced ejection fraction (HFrEF) is a major public health concern with substantial morbidity and mortality. Overactivation of the sympathetic nervous system is a key pathophysiological process driving heart failure progression. Baroreceptor activation therapy (BAT) targets this autonomic imbalance and is a promising treatment strategy for patients with HFrEF. Current short-term studies indicate that BAT provides symptomatic relief, improvement in left ventricular function and cardiac biomarkers. However, data regarding the long-term effect of BAT on HFrEF are scarce.

Purpose

This study aims to assess long-term outcome in HFrEF patients who underwent BAT.

Methods

Patients with HFrEF who received BAT between 2014-2023 were followed until latest available follow-up. Symptom burden, echocardiography and laboratory testing were assessed before BAT implantation and in subsequent follow ups.

Results

23 patients (mean age 66±10 years, 83% men) with HFrEF were included in the study. Etiology of heart failure was ischemic in 70%. The majority of patients (96%) suffered from NYHA III with a mean left ventricular ejection fraction (LVEF) of 23±8% and NTproBNP of 2463±2922pg/ml. Complication occurred in one patient during BAT implantation (4%). Mean follow-up was 3±2 (max. 7.5) years. BAT reduced NYHA classification in 12 patients (52%) after 1 year, of which 1 patient remained in ameliorated NYHA for 7.5 years. Evolution of NYHA functional class over time is shown in Figure 1. Echocardiographic evaluation revealed significant improvement in LVEF of 9±9% after 1 year (p<0.001) and by 11±9% after 2 years (p=0.005). In long-term a trend towards improved LVEF could be observed (Figure 2). In addition, BAT mildly reduced NTproBNP in the first 2 years (after 1 year non-significantly by -396±1006pg/ml and significantly after 2 years by -566±651pg/ml (p=0.039)). Seven patients reaching recommended replacement time underwent device exchange. Four patients deceased during observation time.

Conclusion

BAT resulted in a substantial reduction in NYHA classification, improvement in LVEF, and a delayed reduction in NTproBNP levels. These findings highlight the long-term efficacy and potential benefits of BAT as a therapeutic intervention for patients with HFrEF.Sankey plot of NYHA class over timeAlteration of LVEF over time
mortality trends and effects of acute pulmonary embolism on acute right heart failure patients: a nationwide perspective
Authors: Devarakonda P , Reddy P , Deekonda S , Ramireddy K , Manoharan S , Moreno P
Published: October 2024

Background

Acute right ventricular failure is a significant cause of death, frequently overshadowed by left heart failure. Despite their frequent coexistence, no studies have correlated the relationship between acute pulmonary embolism (APE) and acute right heart failure (ARHF). Our analysis aims to establish a connection between them and evaluate the mortality trend.

Methods

We investigated NIS 2016–2020 to identify hospitalizations with ARHF. Using a multivariate model adjusted for age and gender, sex and national trends were calculated for mortality and cardiogenic shock among these patients.

Results

A total of 1.8 million hospitalizations with RVHF were identified, with a mean age of 70 years. The trends in mortality and cardiogenic shock among these patients showed a steady increase. Of them, 42,569 patients had concomitant APE. The mortality is significantly higher among ARHF with APE (odds ratio (OR): 2.46, CI (confidence interval): 2.26-2.68, p<0.01). Cardiogenic shock, cardiac arrest, total charges, and LOS are also significantly higher among the concomitant acute PE group, as shown in Table 1 below.

Conclusions

In this study, we observed an increasing trend in ARHF mortalities and cardio›genic shock. We also discovered a high death rate among patients with concurrent APE. More research and diligent monitoring of patients with ARHF in the setting of APE is required to know more about these results.
Phenotype groups in atrial cardiomyopathy and their prognosis
Authors: Ilieva R , Kinova E , Slavchev B , Georgieva N , Kalaidzhiev P , Goudev A
Published: October 2024

Background

Atrial cardiomyopathy (ACM) includes patients with heterogenous demographic characteristics and comorbidities. Defining phenotype groups with similar clinical characteristics is important for the effective treatment of these patients, and for their prognosis and prevention of ACM.

Purpose

To conduct a cluster analysis that could help us in phenotyping ACM and exploring the clinical complexity of this entity.

Methods

We performed a hierarchical cluster analysis based on Ward’s Method using 10 clinical binary variables (hypertension, diabetes mellitus, heart failure, obesity, chronic obstructive pulmonary disease, cancer, coronary artery disease, sinus node dysfunction or atrio-ventricular block, implanted pacemaker, and ischemic stroke), identifying the optimal number of clusters. We investigated differences in demographic, laboratory and echocardiographic parameters, and treatment between defined clusters, and assessed the impact of these factors on prognosis.

Results

Of 724 evaluated consecutive patients with dilated left atrium only 200 met the criteria for advanced atrial cardiomyopathy, defined as severely dilated left atrium with volume index (LAVI) ≥ 48 ml/m2, preserved left ventricular systolic function - ejection fraction ≥ 50%, without an overt valvular or ventricular disease, and were included in the analysis. Mean age of the studied population was 73.91 ± 9.74 years, 58 % of them were women. We identified 4 clusters: cluster 1 (n = 73, 36%) were younger overweight patients with paroxysmal atrial fibrillation (AF); cluster 2 (n = 56, 28%) - old patients with congestive heart failure (CHF) and low body mass index (BMI); cluster 3 (n = 34, 17%)- diabetic patients with obesity and CHF; and cluster 4 (n = 37, 19%) old patients with tachycardia-bradycardia syndrome, implanted pacemakers, and long -standing AF. Over a mean follow up of 20.6 months cluster 2 had the highest mortality rate (28.6%), followed by cluster 3 (20.6%), compared to the lower mortality rate of cluster 1 and 4 (11% and 10.8%, respectively, p=0.047). The presence of heart failure (HR 4.4, CI 1.5 ÷12.7, p=0.006), cancer (HR 3.3, CI 1.6 ÷ 6.9, p=0.002) and greater than moderate tricuspid regurgitation (HR 5.4, CI 2.6 ÷ 11.3, p<0.001) were predictors of poor outcome.

Conclusion

In patients with advanced atrial cardiomyopathy, four main clusters were identified, differentiated by distinct comorbidities. Both clinical and echocardiographic parameters were found to be associated with an increased risk of mortality.Phenotype clusters of ACMKaplan-Meier curves of clusters
Post-prandial acyl ghrelin infusion in heart failure patients increases gastric emptying rate
Authors: Webb D , Hage C , Ljung-Faxen U , Pironti G , Thorvaldsen T , Andersson D C , Stahlberg M , Lund L H , Hellstrom P M
Published: October 2024

Background

Acyl ghrelin (ghrelin) increases cardiac output (CO) and contractility in patients with heart failure with reduced ejection fraction (HFrEF). In healthy humans, ghrelin increases gastric emptying rate (GER) and hunger, a potential add-on benefit for HFrEF patients suffering from cachexia with symptoms of delayed gastric emptying and loss of appetite.

Aim

Determine if post-prandial ghrelin infusion increases GER and hunger in HFrEF patients; compare to CO.

Methods

This study was a component of a double-blind placebo-controlled trial of acyl ghrelin vs. placebo in HFrEF. Patients (n=29) arrived fasted and received a 500 kcal breakfast and 1.5 g paracetamol. They next received placebo (vehicle, n=15) or ghrelin infusion (0.1 µg/kg/min, n=14) for 120 min. Blood was tapped for plasma at 0, 30, 60, 120 and 150 min into the meal. Plasma concentration of paracetamol was measured to assess GER of a liquid bolus. Hunger scores and CO were recorded. Mann-Whitney rank sum test was used for statistics.

Results

Paracetamol peaked at 30 min in 8 of 14 (57%) in the ghrelin treatment group versus 1 of 15 (7%) in the placebo group (P=0.004, Fig 1). Remaining patients peaked at later time points. There were no anomalous peaks at 0 min baseline or 2880 min (2 days). The ghrelin treatment group data was segregated into rapid (peak at 30 min, n=8) and slow (peak >30 min, n=6) GER subgroups. The rapid subgroup had a ghrelin treatment effect on CO (one-way repeat measures) (P<0.001, Fig 2). Baseline (t=0) CO for the rapid GER subgroup was 4.06 ±1.41 L/min (median ±SD) and 3.95 ±0.62 L/min for the slow GER subgroup (P=0.31). Data points shown are median ± SEM, each patient normalized to own baseline (100%); * P<0.05, ** P<0.01, *** P<0.001, pairwise comparison to baseline. Hunger gradually increased. The greatest increase in hunger was at 150 min, at which time median fold increase in hunger relative baseline was 1.6 (placebo), 1.7 (ghrelin, slow GER) and 2.3 (ghrelin, rapid GER). These hunger differences between groups did not reach significance. However, this trend was consistent with ghrelin induction of hunger, especially in those with potent GER and CO responses.

Conclusions

Ghrelin increases GER, and potentially hunger, in HFrEF patients in addition to increasing CO. Some HFrEF patients may benefit from this add-on effect.Fig 1.Time of paracetamol peak.Fig 2.Cardiac output.
An Elevated FIB-4 Score is associated with the severity of heart failure
Authors: Bielecka-Dabrowa A , Sakowicz A , Banach M , Slot M
Published: October 2024

Background

Liver disease and heart failure (HF) are known to be closely associated. Non-invasive tests (NIT), such as the FIB-4 score, have been recommended by different guidelines to rule out advanced liver fibrosis and to stratify the risk of liver-related outcomes in patients with chronic liver diseases.

Purpose

Thus, our goal was to evaluate the connection between the FIB-4 index, heart failure, associated comorbidities, and cardiological biomarkers that predict the risk of liver fibrosis in patients with heart failure.

Methods

HF patients hospitalized in the cardiology department were divided into a group with an FIB-4 index <1.3 (indicating a low risk of liver fibrosis) (n=53) and a group with an FIB-4 index ≥1.3 (indicating intermediate and high risk of fibrosis) (n=59). Clinical examinations, laboratory results, echocardiography with Vivid E95-GE Healthcare, non-invasive body mass analysis with Body Composition Analyzer (Tanita Pro), and measurements of NT-proBNP, growth differentiation factor 15 (GDF-15), galectin-3, fatty acid-binding protein (FABP), copeptin, and vascular endothelial growth factor (VEGF) concentrations were performed.

Results

The patients with an FIB-4 index ≥1.3 had significantly higher: left ventricular volume index (LAVI) (p=0.004), E/E’ ratio (p=0.004) and lower left ventricular ejection fraction (p=0.003) compared to group with low risk of liver fibrosis. There were no differences in body mass compartments between groups except for ECW/TBW (%) - an index of body water distribution, which was lower in low-risk liver fibrosis group (p=0.0002). Patients with an FIB-4 index ≥1.3 had also lower: GFR MDRD (median 59.95 vs 85.1 mL/min/1.73 m²; p<0.001), total cholesterol (116.5 vs 15 mg/dL; p=0.002), LDL cholesterol (median 56 vs 93 mg/dL; p<0.0001) and HDL cholesterol (median 39 vs 47 mg/dL; p=0.03). Regarding heart failure biochemical biomarkers, patients with low risk of liver fibrosis had significantly lower level of NT-proBNP (median 37 vs 161 pg/ml; p<0.0001), GDF-15 (median 399.6 vs 898.9 pg/ml; p<0.0001) and FABP (median 101 vs 264,7 pg/ml; p=0.04). In a multiple logistic regression model the factors that were independently associated with the risk of liver fibrosis in HF patients based on an FIB-4 index were GDF-15 >724 pg/ml (OR 33.7, 95%CI: 6.5-174.2; p=0.0001), and NT-proBNP >129 pg/ml (OR 19.9, 95% CI: 3.8-103; p=0.0001) (Figure 1)

Conclusion

Our study suggests association between an elevated FIB-4 score and heart functions, and kidney impairment with fluid overload but not with higher total and low density cholesterols fractions or percentage of fat. Higher GDF-15 and NT-proBNP levels are independently associated with the risk of liver fibrosis based on an FIB-4 index. FIB-4 index in HF patients is an easy method to monitor the risk of liver fibrosis and might help to predict the HF progression and CVD complications.
Obesity and renal impairment in patients with heart failure and reduced ejection fraction: another obesity paradox?
Authors: Matsumoto S , Henderson A D , Shen L , Desai A S , Swedberg K , Claggett B L , Lefkowitz M P , Rouleau J L , Vaduganathan M , Packer M , Zile M R , Jhund P S , Solomon S D , Mcmurray J J V
Published: October 2024

Background

Obesity is associated with poor cardiovascular outcomes in patients with HF and reduced ejection fraction (HFrEF). However, whether obesity is associated with worse kidney outcomes in HFrEF has not been evaluated.

Purpose

To estimate the association between obesity and change in estimated glomerular filtration rate (eGFR) over time in patients with HFrEF.

Methods

In this post hoc analysis of the PARADIGM-HF trial, body mass index (BMI) and eGFR was collected in 8,389 patients. Change in eGFR over time was assessed according to baseline BMI (normal weight: BMI <25.0, overweight: BMI 25-29.9, and obesity: BMI ≥30).

Results

The number of patients in each BMI category was: 2,421 (BMI <25.0), 3,249 (BMI 25-29.9), and 2,719 (BMI ≥30), respectively. Patients with obesity were younger but had worse health status (worse NYHA class and KCCQ scores) and had more comorbidities including diabetes mellitus and hypertension. At baseline, eGFR was lower in patients who were overweight (BMI 25-29.9) and obese (BMI ≥30), compared to those with normal weight. Urine albumin-creatinine ratio (UACR) and kidney injury molecule-1 (KIM-1) were also higher in patients with obesity. However, the rate of change in eGFR per year (eGFR "slope") in the overall cohort did not differ according to BMI: change in eGFR per year was -1.8 [-2.1, -1.6] mL/min/1.73m2 for the normal weight category, -1.6 [-1.8, -1.3] mL/min/1.73m2 for those who were overweight, and -1.5 [-1.8, -1.3] mL/min/1.73m2 for those with obesity; P=0.21) (Figure 1). Among those without diabetes at baseline, those who were obese had a significantly less steep eGFR slope compared to patients in the other BMI categories. In those with diabetes at baseline, the eGFR slope was steeper than in patients without diabetes but was similar across all three BMI categories (Figure 2).

Conclusions

Although baseline kidney function was more impaired in HFrEF patients with obesity, high BMI was not associated with a more rapid subsequent rate of decline in eGFR.

Figure 1. eGFR slope over time according to BMI at baseline in patients with HFrEF in PARADIGM-HF

Figure 2. eGFR slope over time according to BMI at baseline in patients with HFrEF in PARADIGM-HF with and without diabetes at baselineFigure 1Figure 2-A and 2-B
Long-term clinical-pathologic results of enzyme replacement therapy in pre-hypertrophic fabry disease cardiomyopathy
Authors: Frustaci A , Verardo R , Galea N , Alfarano M , Marchitelli L , Sansone L , Belli M , Cristina M , Frustaci E , Russo M A , Chimenti C
Published: October 2024

Background

Limited ability of ERT in removing Gb-3 from cardiomyocytes is recognized for advanced FDCM. Pre-hypertrophic FDCM is believed to be cured or stabilized by ERT. However, no pathologic confirmation is available. We report here in the long-term clinical-pathologic impact of ERT on pre-hypertrophic FDCM.

Purpose

Long-term clinical-pathologic impact of ERT on pre-hypertrophic FDCM.

Methods

Fifteen Fabry patients with LVMWT ≤ 10.5 mm at CMR required EMB because of angina and/or ventricular arrhythmias. EMB showed coronary small vessel disease in angina cohort and vacuoles in smooth muscle cells and cardiomyocytes around 20% of cell surface containing myelin bodies at electron microscopy. Patients received α-agalsidase in 8 and β-agalsidase in 7 cases. Both groups referred symptoms improvement except 2 patients treated with α- and β-agalsidase respectively. After ERT administration ranging from 4 and 20 years all patients had control CMR and LVEMB because of persistence of symptoms or patients enquiry on disease resolution.

Results

In 13 asymptomatic FDCM patients, LVMWT and LV-mass, cardiomyocyte diameter, vacuole surface/cell surface ratio and vessels remained unchanged or minimally increased (LV-mass augmented by < 2%) even after 20 years observation and storage material was still present at electron microscopy. In 2 symptomatic patients, FDCM progressed with larger and more engulfed by Gb-3 myocytes being associated to myocardial virus-negative lymphocytic inflammation.

Conclusions

ERT stabilizes storage deposits and myocyte dimensions in 87% of patients with pre-hypertrophic FDCM. Gb-3 is never completely removed even after long-term treatment. Immune-mediated myocardial inflammation can overlap limiting ERT activity.

Figure Legend

Patient 11 (24-year-old man) with genetic and biopsy-proven diagnosis of FDCM before and after 20 years ERT.

CineMR (A,B) and LGE (C,D) images, performed at baseline (A,C) and 20 years after ERT (B,D) show normal LV wall thickness (8mm and 10 mm) and absence of fibrotic areas.

Panel E and F represent semithin section of Epon-embedded EMB samples, stained with basic fuchsin, showing mildly hypertrophied cardiomyocytes containing storage material that result unmodified after long-term ERT administration.

Panel G and H are ultrastructural evidence of storage material to consist of myelin bodies (panel G) that remain unchanged after ERT (Panel H).
Clinical and financial implications of inpatient and outpatient management strategies for worsening heart failure
Authors: Greene S J , Kaltenbach L A , Fonarow G C , Chiswell K , Kittipibul V , Hernandez A F , Hammill B G , Butler J , Felker G M
Published: October 2024

Introduction

Hospitalizations for worsening heart failure (HF) represent an enormous public health and financial burden. Accordingly, select centers have developed outpatient worsening HF (WHF) management strategies focused on care in emergency departments (ED), observation units, or intravenous (IV) diuretic clinics. However, broad use of these outpatient strategies and the associated outcomes and healthcare costs remain unclear.

Methods

Among US Medicare beneficiaries age ≥65 years hospitalized for HF in the Get With The Guidelines Heart Failure registry 2010-2018, we identified patients with a post-discharge non-fatal WHF event. Patients were divided into 4 mutually exclusive groups defined by type of first post-discharge WHF event (HF hospitalization, ED visit with ED discharge, observation unit stay, and outpatient clinic visit with IV diuretics). Following each type of WHF event, mortality, home-time (days alive and out of any healthcare institution), and healthcare costs were compared over the subsequent 12-months. Costs of the initial WHF management strategy were also assessed.

Results

Among 181,827 patients hospitalized for HF, during the 12-months post-discharge, 83,971 (46.2%) survived with no WHF event, 36,697 (20.2%) died prior to a WHF event, and 61,159 (33.6%) had a WHF event. Of patients with a WHF event, 48,612 were managed with HF hospitalization (79.5%), 8,139 (13.3%) with an ED visit, 1,767 (2.9%) with an observation unit stay, and 2,641 (4.3%) with an outpatient IV diuretic visit.

Compared with HF hospitalization, patients with WHF managed in the ED, observation unit, or IV diuretic clinic experienced lower subsequent mortality (Figure 1). Mean 12-month home-time was lowest following HF hospitalization (207 ± 144 days), intermediate following ED (238 ±136 days) and outpatient IV diuretic visits (252 ±128 days), and highest following observation unit stays (277 ± 125 days). For the initial WHF event, median (25th, 75th) total per-patient costs were highest for HF hospitalization and lowest for outpatient IV diuretic visits (Figure 2). Over the 12-months following the WHF event, median total per-patient costs were highest following outpatient IV diuretic visits, intermediate following HF hospitalization and ED stays, and lowest following observation unit stays.

Conclusions

In a nationwide analysis of older US adults, 1 in 5 episodes of recurrent WHF were exclusively managed as an outpatient within the ED, observation unit, or IV diuretic clinic. High rates of death and substantial reductions in home-time occurred following WHF regardless of inpatient or outpatient management, but were worse following HF hospitalization. Outpatient IV diuretic administration was the least expensive initial management strategy, but was associated with the highest per-patient costs over the subsequent 12 months.
The impact of the 2022 definition of pulmonary hypertension on long-term clinical outcomes in patients with heart failure with preserved ejection fraction
Authors: Sera F , Ohtani T , Seo M , Hayashi T , Yano M , Nakagawa A , Nakagawa Y , Tamaki S , Yamada T , Yasumura Y , Hikoso S , Okada K , Nakatani D , Sotomi Y , Sakata Y
Published: October 2024

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Backgrounds: In recent years, the definitions of pulmonary hypertension (PH) have been revised for early diagnosis and risk stratification of patients with PH. Using the 2015 definitions, the development of a precapillary component of PH in addition to a postcapillary PH was associated with right heart dysfunction and poor prognosis in patients with heart failure (HF) with preserved ejection fraction (HFpEF). However, the prognostic impact of revised definitions of PH in patients with HFpEF has not been fully evaluated.

Purpose

We investigated the impact of the 2018 and 2022 ESC/ERS definitions of PH on long-term clinical outcomes using data from a prospective, multicenter, observational study of patients with HFpEF (PURSUIT-HFpEF).

Methods

A total of 250 patients hospitalised with acute HF who underwent right heart catheterisation after initial HF treatment were divided into PH categories according to the 2018 and 2022 definitions: isolated postcapillary PH (Ipc-PH), precapillary PH, combined postcapillary and precapillary PH (Cpc-PH), and unclassified PH. The incidence of the composite endpoint of all-cause death and HF rehospitalisation after discharge was compared across the PH categories.

Results

The overall prevalence of PH defined as a mPAP > 20 mmHg was 54%. Applying the 2022 definition, 42 patients (17%) were reclassified as either precapillary PH or Cpc-PH, resulting in a significant increase in the propotion of patients classified as having PH with a precapillary component (precapillary PH and Cpc-PH) compared with the 2018 definition (26% vs. 11%, p<0.0001). At a median follow-up of 822 days after discharge, PH with a precapillary component was associated with poor clinical outcomes according to the 2018 definition (Figure 1A), but according to the 2022 definition, clinical outcomes did not differ across the PH categories (Figure 1B). PVR ≥3 Wood units (WU) was a significant prognostic indicator, but there was no significant difference between the PVR 2-3 WU and PVR ≤2 WU categories (Figure 2).

Conclusions

The 2022 definition showed no association between PH classification and clinical outcomes. In patients with HFpEF, PVR ≥3 WU was identified as the key factor increasing the risk of all-cause death and HF hospitalisation.Figure 1Figure 2