bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of transthyretin amyloid cardiomyopathy in patients hospitalised for heart failure with preserved ejection fraction in an LATAM center
Authors: Decotto S , Fernandez Villar G , Perez De Arenaza D , Villanueva E , Lucas L , Del Castillo S , Rossi E , Belziti C , Pizarro R
Published: October 2024

Introduction

Transthyretin Amyloid cardiomyopathy (ATTR-CM) usually presents as heart failure with preserved ejection fraction (HFpEF). Its diagnosis has a significant clinical impact, as specific treatment is currently available.

Purpose

To assess the prevalence of ATTR-CM in patients hospitalised for HFpEF and increased septal thickness in our institution of general community hospital in Latin America (LATAM).

Methods

Cross-sectional study. Patients hospitalised for HFpEF (>50%) and septal thickness ≥ 12 mm during the period from 8/2019 to 1/2023 were prospectively included. Patients with pacemaker, significant left valve disease and end-stage renal failure (creatinine clearance < 30 ml/min/BSA) were excluded. A pyrophosphate bone scintigraphy (PYP) was planned to be performed in order to assess ATTR-CM. The prevalence of ATTR-CM and its 95% confidence interval were calculated.

Results

A PYP was performed in 59/82 patients hospitalised for HFpEF. Median age was 85 [IQR 78-88] years, and 54% were women. At admission, 61% (n=36) had atrial fibrillation and the median NT Pro-Bnp was 3536 [1700-7748] pg/mL. The mean left ventricle ejection fraction was 57% (+/- 5%). The prevalence of ATTR-CM diagnosed by PYP was 19% (95% CI 9.7-30.1, n=11). There were no significant clinical differences between patients who performed a PYP and did not. Patients with ATTR-CM had lower blood pressure and higher septal thickness, NT Pro-Bnp and troponin levels compared to patients without ATTR-CM (TABLE).

Conclusion

In patients admitted for HFpEF and increased septal thickness, the diagnosis of ATTR-CM was relatively common (one of five had ATTR-CM) in our region (LATAM). We believe that systemic assessment with PYP should be performed in patients hospitalised with HFpEF and increased wall thickness.
Echocardiographic profiles of patients with CPCPH and IPCPH in HFpEF: insights from the PHHF study
Authors: Berthelot E , Fauvel C , Bauer F , Eicher J C , Picard F , Degroote P , Bouvaist H , Damy T , Lamblin N
Published: October 2024

Background

The 2022 ESC/ERS guidelines changed the definition of post-capillary pulmonary hypertension (pcPH) in heart failure (HF) by lowering the level of mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR). Yet, the echocardiographic profile of HF with preserved ejection fraction (PEF) patients according to their mPAP and RVP is not known.

Objectives

To investigate the echocardiographic profile of HFPEF patients according to their mPAP and RVP.

Methods

Stable HF patients with the need for right heart catheterization were enrolled from 2010 to 2018 and prospectively followed-up in this multicenter study. All patients had a right heart catheterization and an echocardiography within the 24 hours. PcPH was characterized by a pulmonary wedge pressure exceeding 20 mm Hg and mean mPAP greater than 20 mm Hg, from an isolated state when PVR was less than 2 Wood units (WU, IpcPH) to a combined form when PVR exceeded 2 WU (CpcPH).

Results

Out of 662 HF patients included in PHHF study, 268 (40%) were classified as having HFpEF (35% male, median age 71 yo). Compared to IpcPH patients, CpcPH patients had higher tricuspid regurgitation peak velocity (sPAP, 3.53 vs 3.00 m/s, p<0.01), lower S tricuspid tissue Doppler velocity (10 vs. 11 cm/s, p 0.01) and TAPSE (18 vs. 21 mm, p< 0.01) and lower TAPSE/sPAP ratio (0.3 vs. 0.4, p<0.01). There were no differences between groups regarding both right ventricle and right atrial diameter and area.

Conclusion

In HFpEF patients with PH, CpcPH patients had worse right ventricular function despite similar remodeling when compared to IpcPH patients
Adipose tissue/ heart lipid transport determines cardiac diastolic function
Authors: Trimarchi G , Grieger M , Sigrist S , Foryst-Ludwig A , Kintscher U
Published: October 2024

Introduction

Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction and often occurring in obese individuals. Previous research has demonstrated that the modification of lipid metabolism can prevent the onset of diastolic dysfunction. In our project we have investigated how lipid transport influences the onset of diastolic dysfunction utilizing heart- and adipose tissue-specific knockdowns of the fatty acid (FA) transport protein 1 (FatP1) in Drosophila melanogaster.

Methods

We generated Drosophila with heart-specific (+/+; Hand4.2-GAL4/UAS-FatP1; tdtK/+) (cFatP1-KD) and adipose tissue-specific (+/+; ppl-GAL4/UAS-FatP1; tdtK/+) (atFat-P1-KD) FatP1 knockdowns using the UAS/GAL4 system. The flies' cardiomyocytes endogenously express tdTomato, facilitating fluorescence-based live imaging of the heart by high-resolution video fluorescence microscopy, as previously described. Cardiac morphology and cardiac lipid accumulation was monitored by confocal microscopy. Additionally, mitochondrial function was evaluated using the glycolytic Seahorse assay of whole hearts.

Results

Blocking FA-uptake into adipose tissue in atFatP1-KD flies resulted in a highly significant reduction in relaxation velocity (p=0.0009, WT vs. atFatP1-KD), indicative of diastolic dysfunction in flies, while contraction velocity and fractional shortening (systolic function) remained unchanged. Diastolic dysfunction was associated with a significant increase of cardiac lipid droplet (LD) quantity and size in flies lacking FatP1 in adipose tissue (p=0.0275 and p<0.0001, respectively, WT vs. atFatP1-KD). Cardiac mitochondrial function was significantly impaired in atFatP1-KD flies compared to WT flies.

Reducing cardiac FA uptake in heart-specific FatP1 KD flies led to a decrease in end-diastolic diameter and a significant reduction in relaxation and contraction velocity (p<0.0001 and p=0.0001, respectively, WT vs. cFatP1-KD), suggesting impairment in both diastolic and systolic function. Interestingly, the number of cardiac LDs increased in cFATP1-KD, however their size decreased significantly resulting in an overall unchanged lipid content compared to WT flies (p=0.0475 and p=0.0367, respectively, WT vs. atFatP1-KD). Mitochondrial function showed no significant alterations.

Conclusion

This study demonstrates that reducing FA-uptake in adipose or cardiac tissue results in cardiac dysfunction in Drosophila melanogaster. Reduction of adipose tissue FA-uptake results exclusively in diastolic dysfunction likely mediated by cardiac lipid overload and subsequent mitochondrial dysfunction. In contrast, blockade of Fatp1-mediated cardiac FA-uptake induces diastolic/ systolic dysfunction which was unrelated to alterations in cardiac lipid content and mitochondrial dysfunction suggesting alternative mechanisms.

These study identifies FatP1-mediated FA-uptake in adipose tissue as a potential therapeutic target for the treatment of diastolic dysfunction.
Analysis of the left atrial appendage function by intracardiac echocardiography in patients with atrial fibrillation
Authors: Pop S , Moldovan M P , Sarb A , Lazar R D , Avram T , Eotvos C A , Coseriu G , Zehan I , Burde A , Mocan L , Tentea P , Mansour M , Blendea D
Published: October 2024

Introduction

Intracardiac echocardiography (ICE) is frequently performed during catheter ablation procedures in order to guide the transseptal puncture and has been recently used to evaluate the morphology of the LAA.

Purpose

The objective of this study was to evaluate the feasibility of using an ICE catheter placed in the coronary sinus (CS) to delineate the LAA function during catheter ablation for atrial fibrillation.

Methods

We included 21 consecutive patients (age 62±9 years, 5 women, 6 paroxysmal AF) who underwent catheter ablation for AF. An 8-Fr phased-array ICE catheter was used to obtain images of the LAA, while in sinus rhythm. The LAA was visualized with the ICE probe placed sequentially in the left atrium (LA, Figure A), with the ultrasound section plane parallel to the long axis of the left ventricle (LV), and in the CS, with the ultrasound section plane perpendicular to the LV long axis (Figure B). LAA emptying flow velocity, and LAA fractional area change (FAC) were used to evaluate LAA function. There were no procedural complications.

Results

ICE imaging was possible in all cases. The LAA peak flow velocity was similar when the ICE catheter was placed in the LA and in the CS (64±7 cm/s and 62±5cm/s respectively, P=NS). The LAA FAC was significantly lower when the ICE catheter was placed in the CS when compared to an LA location (14±6% vs 36±14%; P<0.001). The LAA FAC measured from the LA correlated with the mitral annular plane systolic excursion while the LAA FAC measured from the CS did not. Thus, LAA contraction in a plane perpendicular to the LV long axis is independent of the LV longitudinal contraction. These results suggest that in our patient group most of the LAA contraction was due to the longitudinal movement of the LV base during systole and diastole.

Conclusions

Imaging of LAA using an ICE probe positioned in the LA and CS was feasible in all cases. The LV longitudinal contraction appears to impact the LAA function.
Transthyretin stabiliser therapy in patients with transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis
Authors: Saugo Faria H , Pozzebon B , Sobral M V , Expedito V , Borges E P , Guimaraes A G
Published: October 2024

Introduction

The safety and efficacy of transthyretin (TTR) stabilisers in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) remains unclear.

Objectives

We aimed to assess whether TTR stabilisers are effective and safe to promote medical optimisation in patients with ATTR-CM.

Methods

We systematically searched PubMed, Embase and Cochrane for studies comparing the use of TTR stabilisers with placebo or no TTR stabilisers in patients with ATTR-CM. Statistical analyses were performed using RevMan 5.1.7. Heterogeneity was examined with the Cochran Q test and I2 statistics. Risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) were computed with a random-effects model for binary endpoints.

Results

We included 2 randomised controlled trials (RCT) and 12 observational studies, comprising 3324 patients, of whom 1563 (47,02%) received TTR stabilisers. Follow-up ranged from 7 to 36 months. TTR stabilisers were significantly associated with lower all-cause mortality (RR 0.32; 95% CI 0.18-0.57; p<0.01) and cardiovascular hospitalisation (RR 0.67; 95% CI 0.52-0.86; p=0.02) as compared with control group. In a sub analysis of RCTs and multivariate-adjusted data, the composite endpoint of all-cause mortality, heart transplant, and cardiac assist device implantation yielded significant lower rates in the TTR stabiliser group (HR 0.46; 95% CI 0.28-0.73; p=0.01).

Conclusion

In patients with ATTR-CM, TTR stabilisers were associated with significant lower rates of all-cause mortality and cardiovascular hospitalisations as compared with control group.
Ivabradine prevents doxorubicin-induced cardiotoxicity via attenuating mitochondrial dysfunction and mitochondrial dynamic imbalance in H9C2 cells and rats
Authors: Sripusanapan A , Piriyakunthorn C , Apaijai N , Chattipakorn S , Chattipakorn N
Published: October 2024

Background

Doxorubicin (DOX) is a widely used chemotherapeutic agent, and cardiotoxicity is one of its well-known side effects, which is mediated by cardiac mitochondrial dysfunction. Ivabradine (IVA), a heart rate reduction drug, exerts benefits in various cardiac diseases as shown in both preclinical and clinical studies. However, its roles on DOX-induced cardiotoxicity have never been investigated.

Purpose

We determined whether IVA reduces DOX-induced cardiotoxicity by directly promoting mitochondrial function and maintaining mitochondrial dynamic balance.

Methods

H9C2 cells were divided into 4 groups: 1) Control, 2) DOX (10 μM, 25 h), 3) IVA (3 μM, 25 h), 4) Pretreatment with IVA (3 μM, 1 h), followed by DOX treatment (10 μM, 24 h). Then, cell viability and mitochondrial function were determined. In animal study, male Wistar rats were divided into 4 groups: 1) Control, 2) IVA (10 mg/kg/d, PO), 3) DOX (3 mg/kg/d, 6 doses, IP), 4) Co-treatment with IVA (10 mg/kg/d, PO) and DOX (3 mg/kg/d, 6 doses, IP) for 30 days. Then, heart rate, cardiac function, and cardiac mitochondrial dynamic proteins were determined.

Result

DOX reduced %cell viability of H9C2 cells via increasing cellular and mitochondrial oxidative stress, and reducing mitochondrial respiration (Figure 1A, B). Under DOX-induced cellular injury condition, pretreatment with IVA resulted in increasing %cell viability by 11%, decreasing cellular and mitochondrial oxidative stress; however, IVA did not affect mitochondrial respiration. Consistent with in vitro study, DOX induced cardiac dysfunction as indicated by reduced heart rate and ejection fraction, impaired mitochondrial function and mitochondrial dynamics balance (Figure 1C, D). Co-treatment with DOX and IVA had no further impact on heart rate. DOX-IVA attenuated cardiac mitochondrial dysfunction and mitochondrial dynamics imbalance, thus prevented cardiac dysfunction.

Conclusion

IVA effectively protected against DOX-induced cardiotoxicity through improvement of mitochondrial function, mitochondrial dynamics, and reduction of oxidative stress. These findings suggest the therapeutic potential of IVA in preventing Dox-induced cardiotoxicity.
Clinical validated risk prediction model for development of heart failure after contemporary breast cancer treatment
Authors: Barac A , Chou J , Shara N , Chen L , Shi J , Chlebowski R , Haque R , Potosky A
Published: October 2024

Background

Patients receiving breast cancer (BC) treatment are at risk for heart failure and cardiomyopathy (HF/CM). European Society of Cardiology (ESC) cardio-oncology guidelines recommend baseline cardiovascular (CV) assessment, however, there is limited data about cardiotoxicity risk specific to patients with BC. Our aim was to develop and validate model for prediction of HF/CM in women receiving contemporary treatment for invasive early-stage BC.

Methods

We assembled a cohort women diagnosed with Stage I-III BC from 2008-2020 and followed through 2021 in a large health care plan. Women age >80, with history of HF/CM, and women who received both anthracyclines and trastuzumab were excluded, leaving N=26,044 for analysis. Study cohort was randomly split into derivation (60%) and validation (40%) datasets. Elastic-net penalized Cox proportional hazard model was created using the derivation dataset to select risk factors and to calculate the panelized coefficient which defined the HF/CM risk score. Risk score system was assessed by Hosmer-Lemeshow goodness-of-fit test and area under the ROC curve (AUC). Event rates of <5% constituted low risk; 5-14% moderate; and >15% high risk category. Incident HF/CM events were examined using Kaplan-Meier approach in derivation and validation datasets.

Results

HF/CM risk score had high discrimination ability and sufficiently good model of fit regarding HF/CM events (P value=0.163 and 0.667 from Hosmer–Lemeshow test;AUC 0.751 and 0.764, in derivation and validation sets, respectively). There were 10% of women in the high risk; 30% in moderate; and 60% in low-risk group. Variables associated with the higher HF/CM risk score included age, receipt of anthracycline-based chemotherapy or anti-HER2 therapy, presence of hypertension, diabetes, or history of other CV conditions at baseline. The score pattern showed major effect of age, with anthracycline and anti-HER2 therapy increasing the risk across all age groups (Figure 1). Kaplan-Meier analysis of incident HF/CM over 14 years after BC diagnosis showed significantly lower number of HF/CM events in low risk compared to moderate and high-risk score groups (p<0.0001, Figure 2).

Conclusion

Our robust risk prediction model for HF/CM among women with early-stage BC provides a new tool to identify women at higher CV risk and inform cardiac function monitoring during and after BC treatment. Our findings may guide further validation studies and build evidence for the cardiotoxicity risk stratification in patients with BC.Risk Score for HF/CM by Age/ChemoTxK-M curves of freedom from HF/CM
Latent cytomegalovirus infection associates with impairments in myocardial reperfusion, left-ventricular function, and quality of life after ST-elevation myocardial infarction
Authors: Spray L , Mcintosh A , Mccartney P J , Berry C , Spyridopoulos I
Published: October 2024

Introduction

Cytomegalovirus (CMV) is a ubiquitous herpesvirus affecting the majority of adults in European countries. CMV influences T-lymphocyte biology throughout life. We have previously associated CMV status with adverse left ventricular (LV) remodeling after ST-elevation myocardial infarction (STEMI) in a single-centre study. In this study, we aimed to assess the external validity of these findings.

Methods

This study is a retrospective analysis of 354 patients presenting with STEMI, who were recruited to A Trial of Low-Dose Adjunctive Alteplase During Primary PCI (T-TIME) and had blood samples archived. The participants underwent immediate coronary angiography and percutaneous coronary intervention (PCI), serial cardiovascular magnetic resonance (CMR) imaging at 2-7 days and 3 months post-STEMI, and serial assessment of health-related quality of life with the standardised EQ-5D visual analogue scale (VAS). CMV IgG titre was measured in cryopreserved samples from each patient, and patients were categorised as CMV negative, low-positive or high-positive. All analyses were adjusted for infarct location.

Results

Of 354 patients, 175 (49.4%) were CMV IgG titre negative, 89 (25.1%) were low-positive and 90 (25.4%) were high-positive. CMV+ patients were older (62.5 vs 58.7 years) and more likely to be non-White (6.7% vs 2.3%). CMV+ patients displayed several adverse outcomes. First, myocardial reperfusion was impaired. Thrombolysis in myocardial infarction (TIMI) flow grade 3 after PCI, indicating complete reperfusion, was less common in CMV+ patients (76.0% vs 84.6%; p=0.042). CMV+ patients also had a higher TIMI frame count after PCI (p=0.021), and non-significantly less ST-segment resolution at 60 minutes (38.8% vs 48.4%; p=0.066). Impaired myocardial reperfusion appeared to lead to impaired LV function, with LV ejection fraction (LVEF) measured on early CMR lower in CMV+ patients (42.6% vs 45.3%, p=0.004). At 3 months, LV function remained impaired in CMV+ patients (LVEF: 47.8% vs 49.7%; p=0.035). This was mirrored by CMV+ patients displaying higher NT-pro BNP levels at 2-7 days (1381 vs 1172pg/mL, p=0.097) and 3 months (575 vs 338pg/mL, p=0.021). Finally, impaired LV function appeared to affect quality of life. Over 3 months, in contrast to CMV-negative patients, those with the highest CMV IgG experienced almost no improvement in quality of life, measured by change in the EQ-5D VAS (negative: +9.93; high-positive: +0.70; p=0.0002).

Conclusion

CMV+ patients with STEMI experience worse outcomes, with impaired reperfusion, persistently reduced LV function and less improvement in health-related quality of life over 3 months. We hypothesise that the effect of CMV is mediated through immune activation. Future research should explore the mechanisms by which CMV-specific lymphocytes interact with myocardial reperfusion and repair post-STEMI.
Relationships between 18-month kinetics and functional capacity and left ventricular remodeling and cardiac fibrosis in dilated cardiomyopathy
Authors: Wisniowska-Smialek S , Wypasek E , Szymanska M , Dziewiecka E , Banys P , Urbanczyk- Zawadzka M , Krupinski M , Rubis P
Published: October 2024

Introduction

Myocardial fibrosis is a primary pathogenetic process in dilated cardiomyopathy (DCM) that is responsible for progressive cardiac remodeling and functional capacity impairment. We sought to verify whether there were differences between 18-month kinetics of functional capacity and left ventricular remodeling in DCM patients with different types and advancement of fibrosis who were up-titrated with guideline directed pharmacotherapy (GDMT).

Methods

Between May 2019 and September 2020, 99 DCM patients (88 male, mean age 45.2 ± 11.8 years, mean EF 29.7 ± 10%) underwent cardiac magnetic resonance with assessment of replacement fibrosis via late gadolinium enhancement (LGE) and interstitial fibrosis via extracellular volume (ECV). Each patient had serial (baseline, 6-, 12-, 18 month) functional assessment: NYHA class and 6- minute walking test (6-MWT) and follow-up echocardiography, including measurement of left ventricular end-diastolic volume (LVEDvol) and ejection fraction (EF). Patients were divided into LGE-negative and LGE-positive groups, whereas based on median ECV – they were divided into those with ECV below and above median values.

Results

Overall, LGE was identified in 44 (44%) of patients, whereas median ECV was 27.7%. NYHA class was significantly worse in patients with LGE (1.5±0.5 vs. 1.9±0.6) and with higher ECV (1.93±0.6 vs. 1.6±0.5) in comparison to those without LGE and lower ECV. However, NYHA class improved during observational period in all groups. There were no differences in 6-MWT distance in LGE positive and negative groups at all time points. Baseline 6-MWT distance in LGE positive group was 494.2±88.2 vs. 453.9±98.8 meters in LGE negative group. Baseline 6-MWT distance in upper median ECV group was (408.8±103.5 vs. 492.4±92.9 meter) was significantly lower ECV group (p=0.03). During 18 months 6-MWT distance increased only in LGE negative group but in both ECV groups (Figure 1 A-D). There were no differences in EF between patients with and without LGE and also with higher and lower ECV. Baseline EF in LGE positive group was 27.4±11.2% and 31.7±10.6% in LGE negative. Baseline indexed LVEDvol in LGE positive group was 107.7±40.7 vs. 91.8±37.8 ml/m2 (p=0.09) in LGE negative group. EF increased significantly in both groups, whereas indexed LVEDvol decreased only in LGE negative group (Figure 2 A-D).

Conclusions

Regardless of the presence of replacement and to some extent of interstitial fibrosis, functional and cardiac morphological improvement was observed during 18 months observation in DCM patients on GDMT. The greatest improvement occurred during the first 3 (occasionally 6) months which was associated with the greatest escalation of GDMT. Further dose escalation was not associated with a significant improvement in both functional and morphological parameters.
Determinants of changes in peak oxygen consumption in patients with new onset heart failure
Authors: Jensen M , Thunestvedt M T , Lamberts M L , Schou M S , Nielsen S N , Elmegaard M E , Nouhravesh N N , Holt A H , Shurenberg C S , Wolsk E W
Published: October 2024

Background

Patients with heart failure (HF) with reduced ejection fraction (HFrEF) have a high risk of mortality. Cardio-Pulmonary Exercise Test (CPET) assesses peak oxygen consumption (pVO2) which is considered a key predictor of mortality and morbidity in patients with HFrEF. Factors responsible for the changes in pVO2 could consequently be of interest, as optimizing these factors may improve prognosis and overall quality of life in patients with HFrEF.

Purpose

To investigate factors contributing to changes in pVO2 within a contemporary cohort of new-onset patients with HFrEF.

Methods

From December 2022 to September 2023, patients with new-onset HFrEF (European Society of Cardiology (ESC) criteria) were included from a HF outpatient clinic, who after referral to the clinic underwent 12 weeks of HF management according to ESC guidelines. This included physical training and optimization of pharmacological management of HFrEF. Baseline characteristics, CPET, medication and echocardiography were collected at referral and after 12 weeks. Changes in pVO2 were investigated according to baseline characteristics, changes in medication, and changes in echocardiographic parameters in both uni- and multivariable linear regression models. Significant independent variables were identified using stepwise selection (p<0.1), adjusted for age and sex. A p-value of 0.05 was considered significant.

Results

We included 48 patients with new-onset HFrEF with a median age of 73 (interquartile range (IQR): 60-77) years, 10 (20.8%) women, a baseline median left ventricular ejection fraction (LVEF) of 30% (IQR: 25-35), and a baseline median pVO2 of 17.3 ml/min/kg (IQR: 14.1-21.9). After 12 weeks, pVO2 improved with a mean of +2.18 ml/min/kg (95% confidence interval (CI) 1.25 to 3.10, p<0.01) and LVEF improved with a mean of +11.7% (95% CI 7.9 to 15.6, p<0.01). In univariable analyses increasing age were negatively associated with pVO2 changes (p=0.04) and increasing minute ventilation (MV) and initiation of sodium-glucose cotransporter (SGLT2) inhibitors were all positively associated with pVO2 changes (p<0.01 and p=0.03, respectively). Other clinical variables included in the analysis were not significantly associated with a change in pVO2. In the multivariable analysis, body mass index emerged as an independent variable negatively associated with pVO2 changes, and MV and initiation of SGLT2 inhibitors remained significantly positively associated with pVO2 changes.

Conclusion

Optimal pharmacological management and physical training in patients with new-onset HFrEF, induce a significant recovery of cardiorespiratory performance and ejection fraction. Furthermore, our results suggest that the initiation of SGLT2 inhibitors in patients with new-onset HFrEF appears to improve their pVO2 already after 12 weeks of optimal HF management.Table 1:BaselineTable 2:Associations
Use and associations with mortality/morbidity of guideline-directed medical therapy use in heart failure with improved ejection fraction: a PS-matched analysis from the swedish heart failure registry
Authors: Basile C , Benson L , Lindberg F , Guidetti F , Dahlstrom U , Lund L , Savarese G
Published: October 2024

Background

Guideline-directed medical therapy reduces mortality/morbidity in heart failure (HF) with reduced ejection fraction (EF). However, evidence about its use and prognostic role once EF has improved is limited.

Purpose

To assess use and associations with mortality/morbidity of renin-angiotensin system inhibitors (RASi), angiotensin-receptor neprilysin inhibitors (ARNi), beta-blockers (BBL), and mineralocorticoid receptor antagonists (MRA) in patients with HF and improved EF (HFimpEF).

Methods

We analyzed patients with HFimpEF, defined as a first recorded EF <40% and a subsequent EF ≥40%, registered in the Swedish HF registry between 2004 and 2021. Index date was the SwedeHF registration reporting the second (i.e. improved) EF assessment. To reduce the bias related to the initial recommendation for MRA limited to more severe HF (NYHA III-IV), the assessment of MRA was restricted to patients with index date 2016 or later, when Swedish guidelines on HF included a recommendation for MRA in patients with NYHA class II–IV. The association between treatment use and the composite outcome cardiovascular mortality (CVM)/HF hospitalization (HHF) (with censoring >3 years) was assessed by Cox proportional hazard models in a 2:1 propensity score-matched cohort. Propensity scores for treatment use were calculated by a logistic regression model including 38 variables, achieving a standardized mean difference <0.1 for all evaluated variables. Since matching reduces the sample size and may limit generalizability, a Cox proportional hazard model was fitted in the overall cohort adjusting, rather than matching, for the propensity score (Overall HR).

Results

Of 4700 patients with HFimpEF (mean age 68±12 yrs, 70% male), 94%, 95%, and 50% received RASi/ARNi, BBL, and MRA, respectively. Regardless of the specific treatment, non-users had lower BMI, education level and use of other HF medications, but older age, higher EF at improvement, higher NT-proBNP, and more likely peripheral artery disease, anemia, and valvular disease. In the matched cohorts, RASi/ARNi use was associated with a statistically significant lower risk of CVM/HHF [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.53–0.95] (Figure). There was no statistically significant association between CVM/HHF and beta-blockers (HR 0.75, (95% CI 0.53-1.08), and MRA (HR 1.16, 95% CI 0.90-1.49). These results were consistent after adjustment for the propensity score in the overall cohort (Figure).

Conclusion

In patients with HFimpEF use of GDMT was high. Treatment with RASi/ARNi was associated with lower morbidity and mortality, whereas no statistically significant association was observed with beta-blockers which might be explained by limited statistical power.Composite outcome.
MELD score as predictor of mortality in patients with advanced heart failure: a longitudinal evaluation
Authors: Cacciatore F , Curcio F , Chiappetti R , Amarelli C , Maiello C , Mattucci I , Flocco V , Gerundo G , Mazzella F , Abete P , Cacciatore F
Published: October 2024

Aims

Advanced heart failure (AHF) is characterized by recurrent episodes of hemodynamic instability, frequent hospitalizations leading to a progressive decline in quality of life, and high mortality rates. The objective of this study was to assess the clinical associations of the MELD score and its efficacy in predicting mortality among patients with AHF.

Methods

102 patients with AHF were enrolled, all patients included in the study were on top of tolerated medical therapy according to guidelines. The MELD score was measured at baseline, and every 6 months during follow-up. All patients underwent echocardiographic assessment, six-minute walking test, and cardiopulmonary testing with evaluation of VO2 max and VE/VCO2.

Results

The mean age of the study group was 57.8±11.9 years. There were 26 deaths during a follow-up period of 31.9±15.4 months. The mean NYHA class was 2.8±0.6, ejection fraction was 26.5±6.3%, TAPSE was 17.5±4.1 mm, and NT-pro-BNP was 2746.0±2475.9 pg/mL. The mean VO2 max was 11.7±3.5 ml/kg/min, and the distance covered in the six-minute walk test was 270.1±151.5 meters. Data stratified by mortality showed that deceased patients had higher NYHA class (2.7±0.6 vs. 3.2±0.3; p<0.001), NT-pro-BNP levels (4767.2±2888.1 vs. 1884.0±1669.5 pg/mL; p<0.001), and MELD score (19.3±3.8 vs. 11.9±5.1; p<0.001) compared to those who were alive at follow-up. Multiple regression analysis revealed a positive correlation between MELD score and NT-pro-BNP (Beta = 0.300; p=0.010), and a negative correlation between MELD score and TAPSE (Beta = -0.236; p=0.026). Cox regression analysis identified MELD score as a predictor of mortality (HR = 1.113; 95%CI = 1.011-1.225; p=0.029), independently by the effect of age, NYHA class, NT-pro-BNP, ejection fraction, TAPSE, and VO2 max. Changes in MELD score percentage, considered as a dichotomous variable (≤100% and >100%), were found to be predictors of mortality. Receiver operating characteristic (ROC) curves showed an area under the curve (AUC) of 0.897 for MELD score and mortality.

Conclusions

The MELD score and its longitudinal changes are effective predictors of mortality in patients with AHF, regardless of age, NYHA class, and NT-pro-BNP.
SGLT2 inhibitors are associated with development of heart failure with improved ejection fraction
Authors: Yang C D , Wang X Q
Published: October 2024

Background

Heart failure (HF) with improved ejection fraction (EF), termed HFimpEF, has been proposed as a new HF classification associated with better clinical outcomes. Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce cardiovascular death and hospitalization for HF irrespective of diabetes.

Purpose

Analyze the effect of SGLT2 inhibitors on the development of HFimpEF.

Methods

Consecutive HF with reduced EF (HFrEF) patients with follow-up echocardiogram at around 12 months were enrolled from 2017 to 2022. Patients were classified into HFimpEF (follow-up EF > 40% and ≥ 10% absolute increase) or otherwise persistent HFrEF based on repeat echocardiograms after 12 months. A 1:2 propensity score matched analysis was performed.

Results

Of all the HFrEF patients in the cohort, 46.6% of patients developed HFimpEF. We matched 93 and 186 patients treated with or without SGLT2 inhibitors according to propensity score. In the matched cohort, treatment with SGLT2 inhibitors was associated with nearly a doubled likelihood of the development of HFimpEF (OR: 1.978 [95% CI 1.184~3.346]). Subgroup analysis revealed this association was only present in HF patients with an ischemic etiology (OR: 3.427 [95% CI 1.614~7.573], P for interaction=0.022). There was no significant interaction term between SGLT2 inhibitors and the presence of diabetes for the development of HFimpEF.

Conclusions

This study reveals that treatment with SGLT2 inhibitors is associated with increased likelihood of HFimpEF, especially in those with an ischemic etiology.
Ferric derisomaltose versus usual care in patients with heart failure, reduced ejection fraction, and iron deficiency: a short-term UK cost-utility analysis based on the IRONMAN RCT
Authors: Pollock R , Kalra P R , Mcmurray J J V , Graham F J , Pellicori P , Cleland J G F , Ford I
Published: October 2024

Background

In the IRONMAN trial, patients with heart failure (HF), a reduced ejection fraction and iron deficiency who were randomly assigned to ferric derisomaltose (FDI), rather than usual care, had a lower rate of the composite of hospitalization for heart failure (HHF) and cardiovascular (CV) death (rate ratio, RR, 0.82; 95% CI 0.66 to 1.02; p=0.07). A COVID-19 sensitivity analysis, censoring data at 1 year of follow-up showed a greater magnitude of treatment effect (RR 0.66; 95% CI 0.48 to 0.91; p=0.011).

Purpose

Patient-level data from IRONMAN were used to evaluate the effectiveness and cost-utility of FDI compared to usual care for patients with a current or recent HHF, or raised plasma natriuretic peptide concentrations, from a UK National Health Service (NHS) perspective.

Methods

A cost-utility analysis (CUA) was conducted covering the first year after randomization. Numbers-needed-to-treat (NNTs) were calculated for the primary endpoint censored at 1 year. In the CUA model, patient survival and rates of (re)hospitalization due to HF, other CV events, infections, respiratory conditions, and other non-CV events were modeled based directly on data from the IRONMAN RCT. UK-specific costs were obtained from the national schedule of NHS costs. Quality of life was estimated based on EQ-5D-5L data collected from patients included in the IRONMAN RCT. Results were undiscounted and reported as absolute and incremental costs in 2023 pounds sterling, and quality-adjusted life expectancy in quality-adjusted life years (QALYs). A willingness-to-pay threshold of £20,000 per QALY was adopted to allow calculation of a net monetary benefit (NMB), a summary measure of the overall value of FDI in monetary terms, capturing changes in both cost and QALY outcomes.

Results

The NNT analysis showed that 9 patients would need to be treated with FDI to avoid one composite primary endpoint event (CV death and HHF) over 1 year. Relative to usual care, FDI was associated with an improvement of 0.01 QALYs per patient over 1 year (0.58 versus 0.57 QALYs). Total average costs per-patient were £1,672 for FDI, versus £1,975 for usual care, leading to a saving of £302 per patient with FDI. The cost of iron procurement was more than offset by reductions in costs of (re)hospitalizations (Figure). FDI was therefore dominant over usual care, yielding an NMB of £483 over 1 year.

Conclusions

This short-term, within-trial CUA suggests that FDI both improves QALYs and reduces healthcare expenditure versus usual care when administered to patients with HF and iron deficiency in the UK. Iron repletion with FDI may be a prudent allocation of healthcare resources in this patient population.Breakdown of costs
O2 consumption overshoot in patients with heart failure: crossing the line
Authors: Carvalho R , Gomes D , Pohle C , Lima M R , Amador R , Bello A R , Santos R , Paiva M S , Rocha B , Brizido C , Moreno L , Durazzo A , Mendes M , Adragao P , Cunha G
Published: October 2024

Background

Cardiopulmonary exercise testing (CPET) is among the most valuable clinical tools for evaluating disease severity and physical activity limitations in heart failure (HF) patients. Peak oxygen uptake (pVO2) reflects maximal cardiac output during exercise, and it is considered a major parameter in selecting candidates for cardiac transplantation. VO2 overshoot, a transient increase in VO2 during recovery from maximal exercise, has been frequently observed in HF patients and is attributed to the transient increase in cardiac output caused by the mismatch between cardiac contractility and afterload reduction. However, the prognostic significance of this phenomenon remains to be fully established.

Purpose

This study aimed to characterize the prognostic significance of VO2 overshoot following peak exercise in individuals with HF.

Methods

This retrospective single-center study included consecutive adult patients with chronic (>3 months) and stable HF, with left ventricular ejection fraction (LVEF) <50%, who underwent CPET between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sitting passively for 2 minutes). VO2 overshoot kinetics during recovery were measured and described as the time until post-exercise VO2 fell below pVO2 for at least 15 seconds. Please refer to Figure 1A for an example of normal and prolonged VO2 overshoot. The study endpoint was time to cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) over 1-year follow-up.

Results

A total of 254 patients were included (mean age 59 ± 12 years; 83% males; mean LVEF 34 ± 9%; 70% with ischemic HF; 77% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean predicted pVO2% 52 ± 16%; mean VE/VCO2 slope 41 ± 13). The VO2 overshoot had a normal distribution (Figure 1B) and lasted on average for 45 ± 33 seconds. There were no differences between patients that had an overshoot higher and below average. Overall, during follow-up, 25 patients met the composite endpoint (12 CV deaths, 9 urgent heart transplants, and 4 LVAD). Univariate analysis showed a significant relationship between VO2 overshoot and the outcome of interest (HR 1.01, 95% CI 1.00 – 1.02, p=0.027). In multivariate analysis, this association remained significant, even after adjusting for pVO2 and VE/VCO2 slope (HR 1.01, CI 95% 1.00– 1.02, p=0.026).

Conclusion

This study delves into the intriguing phenomenon of VO2 overshoot in patients with heart failure, shedding light on its potential prognostic significance. The independent association between VO2 overshoot and the composite endpoint suggests that this transient increase in oxygen consumption may carry prognostic value. Further studies should confirm these findings.
Exercise stress testing recovery kinetics: the forgotten phase
Authors: Carvalho R , Amador R , Domingues M S , Pereira J C , Bello A R , Gomes D , Santos R , Paiva M S , Rocha B , Brizido C , Moreno L , Durazzo A , Mendes M , Adragao P , Cunha G
Published: October 2024

Background

Impaired exercise capacity is a cardinal feature of heart failure (HF). Peak oxygen uptake (pVO2) and ventilatory efficiency (VE/VCO2 slope) during exercise are well-consolidated prognostic markers in patients with HF. A previous study suggested that abnormally prolonged VO2 recovery, specifically the failure to decrease VO2 from peak exercise by 10.5 mL/kg/min at 180 seconds of the recovery phase, predicts adverse outcomes in HF. However, it is unknown to what extent the recovery of VEqCO2, a marker of ventilation/perfusion mismatch, adds prognostic value to the already existing parameters.

Purpose

The aim of this study was to characterize the functional and prognostic significance of VEqCO2 kinetics following peak exercise in individuals with HF.

Methods

This retrospective single-center study included consecutive adult patients with chronic (>3 months) and stable HF with left ventricular ejection fraction (LVEF) <50% who underwent cardiopulmonary exercise testing (CPET) between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sittng passively for 2 minutes). VO2 and VEqCO2 kinetics during recovery, described as the absolute difference to peak VO2 (difVO2) and VEqCO2 (difVEqCO2), were measured at 30, 60, 120, and 180 seconds. Outcomes were assessed as a composite of cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) implantation at 1 year.

Results

A total of 238 patients were included (mean age 58 ± 12 years; 82% males; mean LVEF 34 ± 10%; 68% with ischemic HF; 75% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean VE/VCO2 slope 41 ± 12). During the 1-year follow-up, 19 patients met the endpoint (8 CV deaths, 8 urgent heart transplants, and 3 LVAD). ROC curve analysis showed that the best correlation between difVEqCO2 and outcomes was apparent at difVEqCO2 of 180 seconds (AUC 0.83) with a cut-off value of 1 (sensitivity 93%, specificity 58%). These patients, who had a decrease in VEqCO2 (difVEqCO2 >1) at 180 seconds, were significantly older (p=0.02), had a lower LVEF (p<0.001), and higher NYHA (p<0.001). They were at an increased risk of cardiovascular events compared to those with an increase in VEqCO2 (difVEqCO2 <1) at 180 seconds (event-free survival at 1 year 86% vs. 98%, log-rank p<0.001). In multivariate analysis, the statistical association between difVEqCO2 and outcomes remained significant, even after adjusting for difVO2 at 180 seconds (HR 4.315, CI95% (1.349-13.804), p=0.014).

Conclusion

Abnormal VEqCO2 kinetics in the recovery period of CPET is an easily recognizable non-invasively derived measurement that predicts outcomes in HF. VEqCO2 may complement the evaluation of VO2 and other parameters during recovery to further improve prognostic risk stratification in HF.
Artificial intelligence assessment of heart failure and mortality after acute stroke
Authors: Oh M Y , Lee M S , Kang S R , Kwon J M
Published: October 2024

Background/Introduction

The adverse cardiovascular outcomes following a stroke have shown significant associations with post-stroke mortality. However, studies focusing on predicting heart failure and its impact on long-term mortality are scarce.

Purpose

To address this gap, we employed an commercially approved artificial intelligence/machine learning enabled software as a medical device (AiTiALVSD version 1.00.00) which uses only 12 lead electrocardiogram data, resulting probability score for predicting left ventricular systolic dysfunction. We derived the AiTiALVSD probability score from initial ECGs at stroke admission, and assess its implications for prediction of heart failure and long-term mortality.

Methods

We collected data from 335 ischemic stroke patients admitted to a cardiovascular center during acute periods between 2013 and 2019. The AiTiALVSD score was employed to predict heart failure with reduced ejection fraction and heart failure with mild reduced ejection fraction, analyzed through logistic regression. Subsequently, we used the Cox Hazard proportional model, incorporating the AiTiALVSD score and clinical factors, to predict long-term mortality.

Results

The model incorporating the AiTiALVSD score with clinical variables demonstrated a higher AUC for predicting heart failure (0.905 [95% CI, 0.827-0.927] vs. 0.828 [95% CI, 0.749-0.907], p<0.004) than clinical variables alone. Moreover, for long-term mortality prediction, this model outperformed the conventional mortality score (AUC, 0.884 [95% CI, 0.836-0.933] vs. 0.755 [95% CI, 0.690-0.820], p<0.001).

Conclusion

Multivariable models which combine the AiTiALVSD score with clinical factors, effectively predicts heart failure and long-term mortality. This model could enhance therapeutic strategy tailoring by providing acute phase prognostic predictions for individual stroke patients.Prediction performance for heart failurePrediction performance for mortality
Healthcare utilization following acute myocardial infarction findings from RECORD MI registry
Authors: Talha K , Hammonds K , Afzal A , Alhamdow A , Bennett M , Bomar J , Ettlinger J , Gottlieb R L , Martinez Traba M , Priest E , Schmedt N , Shaver C , Widmer R , Zeballos C , Butler J
Published: October 2024

Background

As therapeutic options and epidemiology have evolved rapidly, the contemporary healthcare utilization following acute myocardial infarction (MI) is not well known.

Methods

All patients admitted with MI between 01/2015 and 12/2021 in the Baylor Scott & White health system were studied. Patient characteristics and outcomes including hospital readmissions, cardiovascular (CV)-related hospital readmissions, emergency department (ED) encounters, and outpatient visits were studied.

Results

Of 6804 patients, 6556 were discharged alive. Median age was 69 years, 60% were male, and 77% had non-ST elevation MI (NSTEMI); 1172 (22%) had an LVEF <40%, 493 (7.5%) were revascularized within 3 months of discharge, and 1090 (17%) had multivessel disease. The number of unique patients with first hospital readmission within 30-days, 3-months, and 12-months were 844 (13%), 1372 (21%) and 2306 (35%), respectively, with a higher risk in patients with NSTEMI, prior heart failure (HF), new HF, and LVEF <40%. ED visits at 12 months for any cause were 2401 (37%) and for CV cause were 1321 (20%), with a higher risk in patients with prior HF. Patients with at least 1 primary care visit within 12 months of discharge were captured for 4102 (63%), CV specialty visits for 5009 (76%), and non-CV visits for 3860 patients (59%), with similar distribution across subgroups (Table).

Conclusions

Post-MI patients had a high risk of readmissions, and ED and outpatient visits, especially amongst those with a prior or new HF diagnosis.