bluuebunny/crossref_metadata_2025 huggingface dataset:
Left atrial strain and its correlates to cardiorespiratory endurance in HFpEF patients with paroxysmal atrial fibrillation
Authors: Katbeh A , Moya A , Kodeboina M , Penicka M , Verstreken S , Vanderheyden M
Published: November 2023

Introduction

Patients (pts) with paroxysmal atrial fibrillation are at risk for developing heart failure with preserved ejection fraction (HFpEF) and often have an impaired exercise capacity. Since left atrial (LA) pressure plays a major role in the exercise intolerance, we aimed to characterize the contribution of resting LA mechanical properties, assessed by two dimensional speckle tracking echocardiography upon exercise capacity.

Purpose

To evaluate relationship between LA mechanics, measured by LA strain (LAS) and parameters of exercise capacity in pts with paroxysmal atrial fibrillation.

Methods

The study included 54 pts (64 ± 10 years, 76 % males) with dyspnea (NYHA≥II), paroxysmal atrial fibrillation and preserved LV ejection fraction (≥50%). The likelihood of HFpEF was estimated using H2FPEF score. During sinus rhythm, all patients underwent speckle tracking echocardiography and cardiopulmonary exercise testing (CPET). Peak oxygen uptake (VO2 peak) served as measure of functional capacity and ventilation/carbon dioxide output slope (VE/VCO2) as surrogate of ventilation/perfusion mismatch.

Results

LA contractile strain (S) and strain rate (SR) showed significant correlation with VO2 peak (both p < 0.05). LA reservoir, conduit and contractile LAS, all had significant relationship with VE/VCO2 slope

(all p<0.050). Pts with LASR above the median had significantly higher VE/VCO2 (p=0.025) and lower VO2 peak (p=0.010). In contrast, no correlations were observed between exercise parameters and LA volumes or any other echocardiographic indices.

Conclusions

In HFpEF, VO2 peak and VE/VCO2 are closely related to LA contractile strain, suggesting that abnormalities in LA mechanics may contribute to the blunted exercise capacity. Therefore, we speculate that these markers can be used as an echocardiographic surrogate of functional capacity in HFpEF pts.

Figure 1: Relationship between left atrial reservoir (LASr) and contractile (LASct) strain and peak oxygen consumption (VO2 peak) and ventilatory efficiency (VE/VCO2 slope).

Figure 2: Peak oxygen consumption (VO2 peak) and ventilatory efficiency (VE/VCO2slope) in pts with and without left atrial strain rate above the median.
Triglyceride glucose index, a novel marker of insulin resistance, predicts outcomes in patients with heart failure with preserved ejection fraction
Authors: Iwakura K , Okada M , Tanaka N , Koyama Y , Okamura A , Watanabe H , Tamaki S , Yano M , Hayashi T , Yamada T , Yasumura Y , Sotomi Y , Hikoso S , Sakata Y
Published: November 2023

Background

Insulin resistance (IR) is a characteristic feature of heart failure (HF), and it is present both in diabetic- and non-diabetic patients with HF. It is observed in patients with HF with preserved ejection fraction (HFpEF) as well as in those with HF with reduced ejection fraction (HFrEF). It is still not fully understood how IR can affect the clinical outcome in patients with HFpEF. Triglyceride glucose index (TyG index) is a novel, simple marker of IR which is well correlated with HOMA-IR.

Purpose

To investigate the correlation between TyG index and clinical outcome in patients with hospitalized HFpEF.

Methods

We enrolled 1231 patients registered in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study, which is a multicenter registration of patients hospitalized for acute decompensated HFpEF, for the present study. TyG index was calculated as Ln(serum triglyceride [mg/dL] x fasting blood glucose [mg/dL]/2) using blood sample before discharge. We followed the study patients for median of 387 days (IQR 239-727 days) to observe all-cause death and the major adverse cardiovascular events (MACE; composite of death, heart failure hospitalization and stroke).

Results

We could calculate TyG index in 917 patients (81±9 year old, 55.3% female) with the mean value of 8.5±1.5. Diabetes was observed in 360 (39.3%) patients, and they had higher TyG index than non-diabetic patients (8.8±0.6 vs. 8.4±.05, p<0.0001). Cox proportional hazard model selected TyG index score as an independent predictor for all-cause death regardless of history of diabetes, hypertension and dyslipidemia (p=0.004). We divided patients into 4 groups based on TyG index. Kaplan-Meier curves indicated the difference in all-cause mortality among 4 groups (Figure Left, p=0.0003 by log-rank test). Incidence of MACE was also significantly different among 4 groups (Figure Right, p=0.007 by log-rank test).

Conclusion

TyG index predicted all-cause mortality and MACE in patients with HFpEF regardless of diabetic state.Kaplan-Meier curves for death and MACE
Left atrioventricular coupling index as a prognostic marker of cardiovascular events in heart failure with preserved ejection fraction
Authors: Okada M , Tanaka N , Iwakura K , Seo M , Hayashi T , Yano M , Nakagawa A , Nakagawa Y , Tamaki S , Yamada T , Yasumura Y , Sotomi Y , Hikoso S , Sakata Y
Published: November 2023

Background

Left atrial (LA) structural remodeling is common and considered a marker of increased mortality in patients with heart failure with preserved ejection fraction (HFpEF). However, the left atrium is directly connected to the left ventricle during diastole and their functions are tightly coupled. A single left atrioventricular coupling index (LACI), defined by the ratio between the LA end-diastolic volume (LAV) and the LV end-diastolic volume (LVEDV) assessed by echocardiography, could be useful in the clinical routine to improve the risk stratification of HFpEF.

Methods

An analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 1231 patients hospitalized for acute heart failure (diagnosed by using the Framingham criteria) met the inclusion criteria: left ventricular ejection fraction (LVEF) ≥50% and brain natriuretic peptide ≥100 pg/ml. After excluding patients without persistent atrial fibrillation, we enrolled 863 patients (age, 81 ± 9 years; females, 56.1%; atrial fibrillation, 37.2%) whose LAV and LVEDV using the Simpson’s method were available at discharge. Heart failure hospitalizations and cardiovascular deaths were the primary endpoint.

Results

There was little correlation between the LAVI (median 50.2, interquartile range [IQR] 37.1–65.4 ml) and LVEDV (median 80.0, IQR 58.3–102.8 ml) (r = 0.16, p <0.001). As a result, the overall LACI was 0.94 (IQR 0.65–1.34). During a median follow-up of 729 (IQR 407–1180) days after discharge, 304 patients experienced the primary endpoint. The incidence incrementally increased with the LACI quartile groups (Q1: 26.9%, Q2: 37.5%, Q3: 34.0%, Q4: 42.6%, log-rank p = 0.005). After adjusting for age, gender, body mass index, left ventricular filling pressure, and serum brain natriuretic peptide levels, the LACI (hazard ratio, 1.19 per quartile increase; 95% confidence interval, 1.03-1.38; p = 0.021) was a significant predictor of the primary endpoint.

Conclusions

In the PURSUIT-HFpEF Registry, the degree of LA and LV structural remodeling differed between individuals. The LACI was a novel index for predicting cardiovascular outcomes in patients with HFpEF.
Pathophysiological insights into machine-learning-based subphenotypes of acute heart failure with preserved ejection fraction: a biomarker analysis of PURSUIT-HFpEF registry
Authors: Sotomi Y , Tamaki S , Hikoso S , Nakatani D , Okada K , Dohi T , Seo M , Masamichi Y , Hayashi T , Nakagawa A , Nakagawa Y , Ohtani T , Yasumura Y , Yamada T , Sakata Y
Published: November 2023

Background

Our understanding of heart failure with preserved ejection fraction (HFpEF) has evolved from mere left ventricular diastolic dysfunction to a multiorgan disease.

Purpose

This study aimed to investigate the heterogeneous pathophysiology of the several phenotypes of HFpEF with multiple biomarker data.

Methods

This study is a post-hoc analysis of the PURSUIT-HFpEF study (N=1,231), an ongoing, prospective, multi-referral center, observational study of acute decompensated HFpEF [UMIN000021831]. In this registry, there is a pre-defined sub-cohort in which we perform multi-biomarker tests (N=212). We applied the machine-learning-based clustering model that we have previously established to the sub-cohort and classified them into 4 phenotypes: phenotype 1 labeled as "rhythm trouble" (n=69), phenotype 2 "ventricular-arterial uncoupling" (n=49), phenotype 3 "low output and systemic congestion" (n=41), and phenotype 4 "systemic failure" (n=53). Characteristics of biomarker tests in each phenotype were evaluated.

Results

The phenotype 2 characterized by hypertension and cardiac hypertrophy showed the highest value of N-terminal pro-brain natriuretic peptide (NT-proBNP), IL-16, high-sensitive C-reactive protein (CRP), tumor necrosis factor (TNF)-α, growth differentiation factor (GDF)-15, troponin T, and cystatin C, whereas the phenotype 1 presented the lowest value of these markers. The phenotype 3 showed the second highest value of GDF-15 and cystatin C. The phenotype 4 presented a low NT-proBNP value and a relatively high GDF-15.

Conclusions

The specific characteristics of biomarkers in each phenotype confirmed the validity of the machine learning model-based classification. The contribution of inflammation to the pathogenesis considerably differed in different HFpEF phenotypes. Systemic inflammation substantially contributes to the pathophysiology of the classical HFpEF phenotype with cardiac hypertrophy.
Treatment of cardiomyocytes isolated from left ventricular myocardium of dogs with chronic heart failure with ALDA-1, an activator of aldehyde dehydrogenase-2, improves mitochondrial function
Authors: Sabbah H , Singh-Gupta V , Gupta R C , Castle K , Zhang K , Xu J
Published: November 2023

Background

Reactive oxygen species (ROS) generated by dysfunctional mitochondria (MITO) of the failing heart plays an important role in lipid peroxidation of polyunsaturated fatty acids in cell and MITO membranes resulting in the production of aldehydes, such as 4-hydroxy-2-nonenal (4-HNE). MITO aldehyde dehydrogenase-2 (mALDH2) is a key enzyme for the detoxification of endogenous aldehyde substrates through NAD dependent oxidation. ALDH2 catalyzes toxic 4HNE to nontoxic 4HNA in cardiac cells. We previously showed that mALDH2 expression and activity are markedly reduced in MITO of failing LV cardiomyocytes (CM), a maladaptation that can lead to considerable accumulation of 4-HNE in MITO and ultimately to progressive LV systolic and diastolic dysfunction. In this study, we tested the hypothesis that exposure of failing cardiomyocytes to ALDA-1, an activator of mALDH2, improves MITO function.

Methods

Freshly isolated CM from LV myocardium of dogs (n = 7) with heart failure (HF, LV ejection fraction ≤35%) and of normal (NL) dogs (n = 4) were incubated for 1 hour in absence (baseline) and presence of Alda-1 at concentration of 10 µM. After incubation, ADP-stimulated respiration (ADPresp) and maximal rate of ATP synthesis (ATPmax) were measured using Strathklein respirometer and bioluminescence ATP assay kit.

Results

Treatment of isolated CM from HF dogs with 10 µM Alda-1 significantly increased ADPresp (277 ± 18 vs. 189 ± 12 nAtom O/min/mg, p<0.05) and ATPmax (30 ± 3 vs. 16 ± 3 nmoles/min/mg, p<0.05) compared to untreated CM of HF dogs. Treatment of CM from NL dogs with 10 µM Alda-1 had no effect on ADPresp (488 ± 18 vs. 484 ± 19 nAtom O/min/mg) or ATPmax (54 ± 3 vs. 52 ± 2 nmoles/min/mg) compared to untreated NL CM.

Conclusions

Treatment of CM from HF dogs with Alda-1 improved overall MITO function. Activation of mALDH2 represents a potential viable therapeutic target for treating HF.
Effect of vitamin D receptor genetic polymorphism on the clinical response to angiotensin converting enzyme inhibitors therapy among breast cancer patients with chemotherapy induced cardiomyopathy
Authors: Al-Ansary I , Mokhtar R , Khorshid H , Schaalan M , Sarhan N
Published: November 2023

Background

Blockade of the renin-angiotensin-aldosterone system (RAAS) is the cornerstone treatment of chemotherapy induced cardiomyopathy (CIC) yet, variability in response to angiotensin converting enzyme inhibitors (ACEIs) acting on the RAAS is well-documented. Vitamin D was found to play a role in regulating RAAS. Previous studies revealed an inverse relationship between levels of vitamin D in serum and RAAS activation.

Purpose

The current study is primarily to evaluate the association between genetic variants in the vitamin D receptor (VDR) and clinical response to ACEIs among breast cancer patients receiving chemotherapy with CIC.

Methods

A total of 60 breast cancer patients with CIC (mean ejection fraction 30%) on β-blocker therapy were started on a ACEIs and followed for 6 months. Post-ACEIs-treatment changes in ejection fraction (EF) and serum potassium (K) were evaluated. We genotyped VDR gene polymorphisms including; ApaI (rs7975232), TaqI (rs731236), BsmI (rs1544410) and FokI (rs2228570) variants using TaqMan technique. Stepwise linear regression was performed to identify genetic and clinical factors associated with variability in ACEIs response, with adjustment for all potential confounding covariates.

Results

BsmI (rs1544410) (CT) heterozygous and TaqI (rs731236) (GA) genotypes had a significant increase in EF (12.8% and 10.8 %, respectively) and serum K (1.1 mEq/L and 0.91 mEq/L respectively); adjusted-p = 0.0001 and 0.004 for ∆EF and adjusted-p = 0.005 and 0.002 for ∆K. In contrast, (AA) homozygous carriers of the ApaI SNP (rs7975232) had a smaller increase in EF (∆EF = 1.2%) and K (∆K = 0.1 mEq/L) compared to (CA) (∆EF = 6.5%, ∆K = 0.73mEq/L) and (CC) (∆EF = 9%, ∆K = 0.9mEq/L) carriers; adjusted-p = 0.003 for ∆EF, adjusted-p = 0.004 for ∆K. Finally, for the FokI SNP (rs2228570), there was no significant change in EF and serum K level.

Conclusion

The results from this study highlight that BsmI (rs1544410) and TaqI (rs731236) are strong predictors of response to ACEIs therapy in chemotherapy-induced cardiomyopathy (CIC).
Prognostic value of 6-minute walking test for early prediction of doxorubicin induced cardiotoxicity
Authors: Muckiene G , Vaitiekus D , Zaliaduonyte D , Zabiela V , Verseckaite-Costa R , Juozaityte E , Jurkevicius J
Published: November 2023

BACKGROUND/OBJECTIVES

The 6-minute walking test (6MWT) is an easily performed, widely available and well-tolerated test for assessing the functional capacity of patients with HF in everyday clinical practice. The measurement properties of the 6MWT, such as reliability and validity, have been studied in patients with chronic heart failure, coronary artery disease, and cancer. However, little is currently known about the 6MWT and cardiotoxicity. The study was aimed at assessing the incidence of cancer therapy-related cardiovascular toxicity, identified the role of 6MWT as early predictor of early onset cardiotoxicity.

Methods

We performed a prospective study of 85 patients with breast cancer, treated with doxorubicin-based chemotherapy in the Department of Oncology and Hematology. 2D echocardiography and speckle tracking echocardiography were performed before anticancer treatment was started and after the treatment. We defined anthracycline-induced subclinical cardiotoxicity if a decline in global longitudinal strain (GLS) by >15% from baseline was observed and based on that patients were divided into two groups– patients with subclinical cardiotoxicity and patients without subclinical cardiotoxicity. The 6MWT was developed by the American Thoracic Society comprehensive guidelines. The 6MWT was performed in a long straight hospital corridor, over a 30-m distance. Statistical analysis was performed with „IBM SPSS statistics 27.0" program. Statistical significance level p<0.05.

Results

In the study population statistically significant GLS reduction was detected before and after the anticancer treatment (-21±0.53 vs. -18.1± 1.18, p<0.01). Of 85 women (mean age, 54.5 (9.3) years) subclinical left ventricle dysfunction was identified in 51 (60%). We found a significant negative correlation between baseline 6MWT and cardiotoxicity (r = 0.3 and p = 0.02). The baseline 6MWT results were significantly lower among patients with subclinical cardiotoxicity (494.3 ± 40.5 m vs 629.8 ± 60.1 m, p<0.001). The diagnostic validity of 6 MWT as a cardiotoxicity biomarker was evaluated using the non-parametric ROC curve (Pic. 1). We obtained an optimal cut-off point of 6MWT of ≤540m. (AUC = 0.98; p < 0.001).

Conclusions

Baseline 6MWT may be used as independed prognostic predictor of subclinical anthracycline-induced cardiotoxicity.ROC curve for 6MWT and cardiotoxicity
Behavior of coronary sinus oxygen saturation and cardiac output in systolic heart failure
Authors: Mettke F , Kirsch K , Surber R , Schulze P C , Grosse A
Published: November 2023

Background

CRT implantation is indicated in advanced systolic heart failure (LV-EF < 35%) on optimal medical therapy and left bundle branch block with wide QRS complex (QRS > 150 ms). This study investigates the influence of different variables on venous saturation in the coronary sinus during HFrEF.

Methods

In this study, blood gas analyses (BGA) of patients undergoing CRT implantation were performed at our center. Patients with an electrophysiological study but without structural heart disease served as a control group.

In all patients a BGA from the coronary sinus was performed. Arterial and central venous saturation were used to determine cardiac output (CO) according to Fick's principle. Oxygen uptake was calculated from body surface area and age.

Results

In total, the study population included 19 patients in the CRT and 18 patients in the control group. The median age of the CRT group was 75 years (54-87 years) and in the control group 58 years (36-81 years). In the CRT group 53% had ischaemic cardiomyopathy.

The saturation in the coronary sinus was 30.3% in CRT patients and was therefore significantly lower than in the control group (40.0%, p = 0.02). However, CO at rest did not differ in both groups (CRT 6.8 L/min vs. control 7.4 L/min.). It was observed that the coronary sinus saturation was independent of CO and the genesis of heart failure. In contrast, QRS width before CRT implantation was negatively correlated with saturation in the coronary sinus (r = - 0.58, p = 0.01).

Conclusion

In patients with systolic heart failure and despite a normal CO, a decreased oxygen saturation in the coronary sinus at rest was found compared to cardiac healthy subjects. CS saturation correlates negatively with the width of the QRS complex. It is not dependent on age, LV function and the genesis of heart failure.
Associations between baseline heart rate and blood pressure and time to events in HFrEF patients: data from the QUALIFY international registry
Authors: Abdin A , Schoepe J , Anker S , Cowie M , Filippatos F , Wagenpfeil S , Ponikowski P , Tavazzi L , Komajda M , Boehm M
Published: November 2023

Aims

Low systolic blood pressure (SBP) and high resting heart rate (RHR) are both risk indicators for heart failure (HF) outcomes. The purpose of this analysis is to evaluate the associations between RHR and SBP at baseline and time to events in HF patients with reduced ejection fraction (HFrEF) in the QUALIFY international registry.

Methods and results

The QUALIFY registry enrolled 7317 patients with left ventricular ejection fraction (LVEF) ≤40% and previous HF hospitalization within 1–15 months. Complete Follow-up data were available from 5138 patients. The relationship between RHR and SPB on outcomes were analyzed according to baseline values as high RHR (H-RHR) ≥ 75 vs. low RHR (L-RHR) < 75 bpm) and high SBP (H-SBP): ≥ 110 vs. low SBP (L-SBP): <110 mmHg and analyzed according to each of the following 4 phenotypes: (H-RHR/L-SBP, L-RHR/L-SBP, H-RHR/H-SBP and L-RHR/H-SBP (reference group)). Compared to patients with reference group, patients with L-RHR/L-SBP had the highest all-cause mortality (hazard ratio (HR) 2,57, 95% CI 1.85–3.56 vs. HR 0.80, 95% CI 0.72–0.89, P<0.001). After adjustment for age, Sex, NYHA, AF and eGFR rate, all-cause mortality remains the highest between the all groups (HR 2.62, 95% CI 1.88–3.66 P = <0.001), followed by L-RHR/L-SBP (HR 1.74, 95% CI 1.24–2.45 P = 0.001 and H-RHR/H-SBP (HR 1.44, 95% CI 1.08–1.92 P = 0.01).

H-RHR/L-SBP and after adjustment was associated with the worst outcomes for other endpoints: CV death and HF hospitalization HR 1.83, CI 1.66-2.42, p = <0.001), CV mortality (HR 2.7, CI 1.69-4.33, p = <0.001) and HF hospitalization (HR 1.71, CI 1.30-2.25, p = <0.001)

Conclusion

HFrEF patients, who have previously been hospitalized for HF presented with L-SBP and H-RHR, were at greater risk for all case mortality and CV death and HF hospitalization
Sex difference in incidence, risk factors of heart failure and subsequent mortality in general population: Results from the China PEACE million persons project
Authors: Qiu W , Cai A , Feng Y
Published: November 2023

Background

Epidemiological study of sex differences in incidence and risk factors of heart failure (HF), and subsequent mortality attributed to HF in the Chinese general population is lacking.

Purpose

To assess the sex differences in the incidence and risk factors of HF, and evaluate the population attributable fractions (PAFs) for the subsequent mortality among the Chinese general population.

Methods

Data were from a sub-cohort of the Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project in Southern China. Between 2016 and 2020, 102,358 community residents aged 35 to 75 from 8 sites in Guangdong Province were screened, and 80 individuals with a history of HF were excluded. Participants were divided into two groups by sex and the study outcome was HF incidence. Fine and Gray models were conducted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) accounting for the competing risk of all-cause mortality. Propensity score matching analysis and subgroup analyses were used to verify the robustness of the results. Adjusted PAFs of HF for all-cause and cardiovascular mortality were evaluated by sex.

Results

Of the 102,278 participants, 60.5% were women, and the mean age was 54.3 years. Compared with men, women were younger and less likely to smoke and drink, and had lower socioeconomic status and lower comorbid burdens. After a median follow-up of 3.52 years (343758 person-years), 1588 cases of incident HF (4.62 (95% CI: 4.40-4.85) per 1000 person-year) were identified. Compared with men (6.37 (95% CI: 5.95-6.80) per 1000 person-year), women had a lower incidence rate of HF (3.49 (95% CI: 3.24-3.75) per 1000 person-year, P<0.001). After adjusting for the covariates, women had 31% (95% CI: 0.61-0.79) lower risk for HF than men. The results were consistent in the propensity score matching cohort and across all subgroup analyses (all P sex-subgroups interaction >0.05). Although female was associated with a lower risk of HF, women had a higher PAF (24.2, 95% CI: 16.0-31.6) for subsequent cardiovascular mortality than men (16.5, 9%% CI: 11.3-21.5). Several significant differences in modifiable risk factors for HF were also noted between sexes.

Conclusion

In the Chinese general population, women were associated with a lower risk of HF but they have a higher cardiovascular mortality fraction attributed to HF than men. Sex-specific prevention strategies and therapies for HF should be warranted in the future.Graphic AbstractHF incidence across subgroups by sexes
Temporal shift in heart failure diagnoses among hospitalized patients within a large US integrated health system
Authors: Gluckman T , Chiu S T , Rider D , Tseng P , Mudd J , Remick J , Canonico M , Bonaca M
Published: November 2023

Background

Heart failure (HF) is a major cause of morbidity and mortality. Its rising prevalence and attributable cost have also made it a key focus in value-based care.

Historically, most HF admissions among Medicare beneficiaries in the US have been disproportionately accounted for by a limited number of International Classification of Disease (ICD) diagnosis codes (I50.2, systolic heart failure; I50.3, diastolic heart failure; and I50.4, combined systolic and diastolic heart failure). In 2017, however, a significant shift in assigned codes was observed nationally, with hypertensive heart disease with heart failure (I11.0) and hypertensive heart disease with heart failure and chronic kidney disease (I13.0 and I13.2) accounting for a large majority of assigned ICD-10 codes (1).

Purpose

To better understand the pattern of assigned ICD-10 codes among patients hospitalized for HF since 2017.

Methods

We performed a retrospective cross-sectional analysis of patients admitted to a large integrated health system within the western US between 1/1/2018 and 10/1/2022 with a principal diagnosis of HF (defined by one of the above ICD-10 codes). More specifically, we sought to further understand the demographics, clinical characteristics, and treatment patterns of HF patients across all payers as part of a quality improvement initiative. Patient-level analyses were not performed; rather, all hospitalizations were considered independent events.

Results

Over the nearly 5-year period, 61,238 HF hospitalizations occurred, involving 43,234 patients, with 76% having more than 1 hospitalization. Hypertensive heart disease with HF and chronic kidney disease was the most common HF diagnosis, accounting for just over half of all admissions (Figure). Hypertensive heart disease with HF was the next most common HF diagnosis, accounting for just over one-third of admissions. Consistent with the previous observed shift in HF diagnoses among US Medicare beneficiaries in 2017, systolic HF, diastolic HF, and combined systolic and diastolic HF accounted for <10% of HF admissions in 2022.

Conclusions

Hypertensive heart disease with HF and chronic kidney disease and hypertensive heart disease with HF now constitute the predominant HF diagnoses for hospitalized patients across payers. This has important implications for quality improvement initiatives and health services research that utilize real-world data, as precise characterization of distinct phenotypes of HF may now be less reliant on coding than before.HF diagnoses (2018-2022)
Clinical red flags associated with transthyretin amyloid cardiomyopathy in patients with left ventricular hypertrophy: results of the TTRACK study
Authors: Damy T , Garcia-Pavia P , Piriou N , Cappelli F , Barriales-Villa R , Munteanu C , Bahus C , Keohane D , Mallaina P , Elliott P
Published: November 2023

Background

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a life-threatening, systemic disorder that results in progressive physical disability, substantially reduced quality of life, and high morbidity and mortality rates. ATTR-CM is an underrecognized cause of increased left ventricular (LV) wall thickness in older adults, and delayed diagnosis can lead to worse clinical outcomes. To facilitate early identification of patients with LV hypertrophy (LVH) at risk for ATTR-CM, greater recognition of diagnostic ‘red flags’ is required.

Purpose

To determine the association between diagnostic red flags and ATTR-CM in patients with LVH.

Methods

TTRACK is a multicentre, non-interventional epidemiological study (ClinicalTrials.gov: NCT03842163). Eligible patients were ≥50 years of age and had unexplained LVH (LV maximum wall thickness ≥15 mm [echocardiogram]). After undergoing technetium-99m-DPD/-PYP/-HMDP-labelled bone scintigraphy, scans were categorized by the degree of tracer uptake in the heart; Perugini grades 0, 1, 2 and 3 represented absent, low, moderate and high uptake, respectively. Immunofixation electrophoresis was used to detect monoclonal protein abnormalities; grade 2 and 3 scans without evidence of monoclonal gammopathy were considered diagnostic for ATTR-CM. The frequency of predetermined clinical disease markers was compared in patients without monoclonal protein abnormalities and grade 0 or grade 2/3 scans.

Results

Of 766 eligible patients with scintigraphy data, 521 (68.0%) had grade 0 cardiac uptake; 37 (4.8%) had grade 1; and 208 (27.2%) had grade 2/3. Among patients with moderate/high uptake, 137 (65.9% of those with grade 2/3 uptake; 17.9% of the overall cohort) had no monoclonal protein abnormalities (ATTR-CM); 56 (26.9%) had monoclonal gammopathy of undetermined significance or light chain amyloidosis; and 15 (7.2%) patients had unknown monoclonal test findings. On univariable analysis, carpal tunnel syndrome (odds ratio [95% CI], 27.7 [16.7, 46.1]), permanent atrial fibrillation (3.4 [2.2, 5.2]), male sex (2.9 [1.8, 4.8]) and advanced heart failure (1.8 [1.2, 2.9]) were the strongest predictors for grade 2/3 scans; on multivariable analysis, carpal tunnel syndrome (50.3 [23.4, 108.0]), male sex (9.1 [3.9, 21.3] and age (1.7 [1.4, 2.1]) were the strongest predictors (Figure).

Conclusions

In the TTRACK study, 18% of patients ≥50 years of age with unexplained LVH ≥15 mm had ATTR-CM. Carpal tunnel syndrome, male sex and advanced age were associated with a greater likelihood of ATTR-CM.
The association between left ventricular ejection fraction and long-term survival: a large hospital-based cohort study in taiwan
Authors: Chang H C , Sung S H
Published: November 2023

Background

Left ventricular ejection fraction (LVEF) is the most commonly used metric for quantifying left ventricular function. A U-shaped relationship between LVEF and long-term survival with a nadir between 60-70% has been reported in the western, regardless of age, sex, or prevalent heart failure. However, the distribution of mortality risk across the spectrum of LVEF among Asian population remains unclear.

Purpose

We aim to investigate the distribution of mortality risk across the spectrum of LVEF among Asian population, as well as among different subgroups.

Methods

In this large hospital-based cohort study, consecutive participants who underwent echocardiography (2002-2021) in a tertiary medical center in Taiwan were included. LVEF was measured by echocardiography using biplane Simpson’s method. All LVEFs were categorized into intervals of 5% from <20% to ≥70%. The National Death Registry was linked to identify mortality and causes of death. Cox proportional hazards regression was used for analyses with adjustment for age, sex, body mass index, and comorbidities.

Results

A total of 142,834 participants (age 60.6 ± 18.4, men 50.5%) were included. During a mean follow-up of 58.1 ± 47.1 months, 17,317 subjects (12.1%) died. Overall, adjusted hazard ratios (HR) for all-cause mortality showed a U-shaped relationship between LVEF and long-term survival with a nadir of risk at LVEF of 60-70%. Compared with the reference group (LVEF: 60-65%), subjects with LVEF> 70% had a HR of 1.21 (95% confidence interval [CI]: 1.12-1.30) and those with LVEF of 50-55% had a HR of 1.28 (95% CI: 1.22-1.35). (Figure) Similar results with a nadir at 60-70% could also be observed when stratified by the age of 65, sex, comorbidities of hypertension, or diabetes.

Conclusions

A U-shaped relationship between LVEF and long-term survival with a nadir at LVEF of 60-70% can also be observed in the Asian population. This result may support the use of LVEF> 70% to define supranormal LVEF in Asian subjects.Figure
Contemporary insights into the epidemiology, impact and treatment of secondary tricuspid regurgitation across the heart failure spectrum
Authors: Heitzinger G , Pavo N , Winter M P , Spinka G , Dannenberg V , Prausmueller S , Dona C , Halavina K , Mascherbauer K , Nitsche C , Strunk G , Hengstenberg C , Huelsmann M , Bartko P E , Goliasch G
Published: November 2023

Background

Tricuspid regurgitation secondary to heart failure (sTR) is common with considerable impact on survival and hospitalization rates. Currently, insights into epidemiology, impact, and treatment of sTR across the entire heart failure (HF) spectrum are lacking yet are necessary for informed health care decision-making.

Purpose

To investigate (i) the demographic aspects of sTR overall and according to HF subtype, (ii) the association of sTR with mortality compared to expected survival in the age and sex matched community (iii) differences in subgroups, to identify patients at increased risk of mortality and (iv) to assess treatment demand and utilization for sTR in a unique setting with a population-wide health-care plan and state-of-the-art medical facilities.

Methods

This population-based study included individual data from 13469 patients with HF and sTR over a 10-year period. Primary outcome measure was long-term mortality.

Results

Overall, heart failure with preserved ejection fraction (HFpEF) was the most frequent (57%, n = 7733) HF subtype and the burden of comorbidities was high. Severe sTR was present in 1514 patients (11%), most common among patients with reduced EF (HFrEF) (20%, n = 496). Mortality of patients with sTR was higher than expected survival of sex- and age-matched community and independent of HF subtype (moderate sTR: Hazard ratio [HR] 6.32; 95% Confidence Interval [CI] 5.88-6.80, P<0.00, severe sTR: HR 9.04; 95% CI 8.27-9.87, P<0.001). In comparison to HF and no/mild sTR patients, mortality increased for moderate sTR (HR 1.58, 95%CI 1.48-1.69, P<0.001) and for severe sTR (HR 2.19, 95%CI 2.01-2.38, P<0.001). Survival is presented in Figure 1. This effect prevailed after multivariate adjustment and was similar across all HF subtypes (Figure 2). In subgroup analysis severe sTR mortality-risk was more pronounced in younger patients (<70a). Moderate and severe sTR were rarely treated surgically or percutaneously (3%, n = 147), despite availability of state-of-the-art facilities and universal health care.

Conclusion

sTR is frequent, increasing with age and associated with excess mortality independent of left ventricular ejection fraction. Nevertheless, sTR is rarely treated surgically or percutaneously. With the projected increase in HF prevalence and population ageing the data suggest a major burden for health-care systems, that needs to be adequately addressed. Low-risk transcatheter treatment options may provide a suitable alternative.Figure 1Figure 2
Comparative effectiveness of GDMT in the prevention of HF morbidity and death among patients with HFrEF in a U.S. database
Authors: Coyle C R , Ru B , Gaggin H K , Mcmullen C J , Stevenson A S , Ai L , Bash L D , Ambrosy A P
Published: November 2023

Background

The incremental benefit of comprehensive over conventional guideline-directed medical therapy (GDMT) in real-world setting has not been well demonstrated in patients with heart failure with reduced ejection fraction (HFrEF). This study aims to compare patients on GDMT, including first-line therapy from the most recent US guidelines on the prevention of worsening heart failure events (WHFE) and all-cause death.

Methods

This study used Optum’s de-identified Clinformatics® Data Mart Database to identify patients who have diagnosed HFrEF and prescription fills for components of GDMT ("Conventional GDMT" i.e., ACEi or ARB, and beta-blocker) and first-line therapy from the most recent US guidelines ("2022 GDMT:" i.e., ARNi, MRA, beta-blocker, SGLT2i) between Jan2020 and Mar2022. This study characterized patients on both types of GDMT and compared the residual risk of WHF events (HF hospitalizations or receipt of IV diuresis) and death.

Results

The Conventional and 2022 GDMT cohorts included 26,517 and 2,775 patients, respectively. The Conventional GDMT cohort was older (74 vs. 68 years), more often female (41% vs. 33%) and white (67% vs. 60%). In general, they had more comorbidities, but a smaller proportion had diabetes mellitus (53% vs. 67%) and PVD (37% vs. 58%). The unadjusted Kaplan Meier curves show time from GDMT initiation to WHFE, or all-cause death was significantly (p<0.01) faster in the Conventional GDMT cohort compared to 2022 GDMT cohort. The unadjusted HR for experiencing a WHFE or all-cause death after starting GDMT was 0.88 (p<0.01) and 0.48 (p<0.001), comparing the 2022 GDMT cohort to Conventional GDMT cohort. These results were attenuated (WHFE: HR: 0.90, p = 0.02; all-cause death: HR: 0.66, p<0.001) after adjusting for demographic characteristics and comorbidities.

Conclusion

In this sample, patients on the most recent GDMT (2022 GDMT cohort) had better outcomes than those on conventional GDMT. However, the improvement was less noticeable in the prevention of WHFE. Results highlight the ongoing risk of HF-related morbidity and all-cause mortality among patients with HFrEF, despite the use of first-line therapy and underscores the need for therapeutics beyond optimized GDMT to lower the risk in this high-risk population.
The global burden of heart failure: a systematic analysis for the Global Burden of Disease Study 2021
Authors: Roth G A , Dorsey H , Decleene N , Razo C , Stark B , Johnson C
Published: November 2023

Background

Heart failure is a common reason for hospitalization and is associated with high health care costs and high symptom burden. Updated estimates of global and regional prevalence and underlying causes of HF may be helpful in guiding health policy and investment priorities.

Purpose

To provide comparable and consistent estimates of heart failure burden as part of the Global Burden of Disease (GBD) 2021.

Methods

We identified all available data on prevalence, incidence, and mortality for heart failure in the general population. Sources included published scientific literature, administrative records from national health systems, and vital registration data. We generated estimates of heart failure prevalence using DisMod-MR 2.1, a geospatial modelling software program. We then estimated the proportion of prevalent heart failure due to each of 27 underlying aetiologies to produce age-, sex-, location-, year-, and aetiology-specific estimates of heart failure burden.

Results

In 2021, there were 56.5 million (95% Uncertainty Interval (UI): 49.7 million to 63.7 million) prevalent cases of heart failure globally. There were 27.3 million (24.0 to 30.8) prevalent cases in females and 29.2 million (25.6 to 33.0) cases among males. Age-standardized prevalence increased from 647.9 (556.3 to 739.9) per 100,000 in 1990 to 682.7 (602.8 to 766.8) per 100,000 in 2021. The North Africa and Middle East super region had the highest age-standardized prevalence in 2021 (780.5 per 100,000 (658.7 to 907.6)) and South Asia had the lowest age-standardized prevalence (600.1 per 100,000 (526.5 to 671.4)). In 2021, Ischaemic heart disease, hypertensive heart disease, and other cardiomyopathy were responsible for the majority of prevalent heart failure cases worldwide, at 33.8% (28.4% to 38.3%), 22.6% (19.0% to 27.1%), and 8.2% (7.0% to 9.6%), respectively. Country specific estimates for both sexes combined in 2021 are shown in the map.

Conclusion

Heart failure is a highly prevalent condition, particularly in older age groups. As populations age and risk profiles change around the world, knowledge of the global epidemiology of heart failure will be critical in preventing or treating its underlying aetiologies in order to decrease its overall burden.Heart failure prevalence, 2021
Impact of patient characteristics on heart failure and cardiomyopathy onset related to pregnancy from 1997 to 2019. Swedish nationwide register-based study
Authors: Basic C , Toska T , Schaufelberger M , Svanevik T , Rosengren A , Thunstrom E
Published: November 2023

Background

The aetiology of heart failure (HF) in young patients is heterogenic. Cardiomyopathies are common causes in young patients, that often unmask in situations of higher physical demands, as pregnancy or delivery, presenting with HF signs and symptoms. Peripartum cardiomyopathy (PPCM) is one form associated with delivery. However, even other, such as dilated or hypertrophic cardiomyopathy may present during pregnancy. Despite major advances in care, there is still a lack of knowledge about factors that trigger heart failure onset during pregnancy and delivery.

Aim

To evaluate the association of baseline characteristics for HF and cardiomyopathy (CM) onset related to delivery, and investigate incidence rate for HF and cardiomyopathies related to delivery over time.

Method

All women 18 to 50 years registered in the National Patient Register (NPR) from 1st January 1997 to 31st December 2019 were included. Time of delivery was obtained from the Swedish Medical Birth Register (MBR), time of death from the Cause of Death Register. Women with HF, CM and peripartum cardiomyopathy (PPCM) were identified from the NPR with international classification codes for disease ICD-10: I50, I42, I43 and 090.3, used for the first time 90 days prior or 180 days after delivery, and other comorbidities. Patients were compared with five controls without HF or CM from the Total Population Register matched by age, year of delivery, and county. Linear regression was used to test trend changes in use of ICD codes. The impact of baseline characteristics for onset av HF, CM and PPCM in patient compared to controls is presented as odds ratio (OR). Body mass index (BMI) was registered at the beginning of pregnancy.

Results

Between 1997 and 2019 we identified 2 347 723 deliveries, and 694 women with HF, CM or PPCM, median age 33 (29; 37) years and 3 465 controls. Out of those 493 (71%) had HF, 201 (29%) had any CM and 195 (28.1%) had PPCM. Over time the incidence rate of all conditions increased significantly, se Figure 1. Median BMI at the start of pregnancy increased significantly over time in patients with HF from 22 (20;28) to 27 (23;32), beta 0.1323 (p = 0.0216). Compared to controls patients with congenital heart disease OR at 18.32 (10.04-33.41), valve disease OR at 22.65 (8.55-60.03), arrythmia OR at 7.45 (4.06-13.67), hypertension OR at 7.89 (4.26-14.63), diabetes mellitus type II OR at 8.07 (2.63-24.74) and gestational diabetes OR at 3.93 (2.54-6.07) (all p<0.001) to for HF, CM or PPCM onset related to delivery, also BMI >22,5 at the beginning of pregnancy, lower education level and income, se Figure 2.

Conclusion

Over 22 years we observed a significant increase in the incidence rate of HF and CM related to delivery. BMI already >22,5 was associated with higher risk for HF or any CM onset in relation to delivery.
Prediction of incident heart failure through deep learning-based analysis of 1-lead ECGs
Authors: Neyazi M , Bremer J , Knorr M , Brederecke J , Ojeda F , Blankenberg S , Schnabel R B
Published: November 2023

Background/Introduction

Identification of individuals at risk for heart failure (HF) can lead to early intervention. However, large scale screening for incident HF in the general population is insufficient, partly due to the limited capacities in health care systems and number of health care specialists. One-lead ECGs, e.g. from wearables capable of deriving this biomarker, are becoming more popular in the population. This holds the potential to identify individuals at risk who could benefit from a referral to a HF specialist.

Purpose

We examined the ability to predict three-year HF incidence from 1-lead ECGs using a deep learning (DL) model that was trained on data from the UK Biobank (UKB).

Methods

The UKB was established in 2006 and contains data from 500,000 participants from the British general population. N = 100,551 1-lead ECGs from 91,898 unique participants were used for this study. This includes 57,897 3-lead resting ECGs written during ergometry exams between 2006 and 2010 (Exam 1; median age 56.7 years, 46.2% men) and at the first follow-up from 2010-2013 (Exam 2; median age 61.3 years, 49% men) and 32,828 12-lead resting ECGs which were acquired between 2014 and 2020 (Exam 3; median age 63.5 years, 48.4% men). Lead I was extracted from the ECGs for all analyses. A 1D-Convolutional Neural Network was used for prediction of the 3-year risk of incident HF. A comparison with the CHARGE-AF score was performed using a nested 6-fold cross-validation scheme. The models were evaluated using the Area Under the Curve (AUC).

Results

In all three exams, the DL model was able to reliably detect 3-year incident HF (AUC; Exam 1: 0.738, Exam 2: 0.822, Exam 3: 0.738) while the CHARGE-AF score provided slightly better predictions at Exam 1 and Exam 3 (AUC 0.766, 0.748), but lower results in Exam 2 (AUC 0.736). Combining both models led to increased discriminatory properties across all exams (AUC; Exam 1: 0.812, Exam 2: 0.832, Exam 3: 0.788).

Conclusion

The derived DL model shows high discriminatory ability in the prediction of incident HF from 1-lead ECGs. The predictive ability can be further increased when combined with simple clinical variables from the CHARGE-AF score. This study represents another step towards the application of DL-based analysis of the ECG to advance health care.
Serum iron dynamics and mortality in patients with heart failure: A population-based cohort study
Authors: Ren Q W , Tsang T W , Chan H C , Yiu K H
Published: November 2023

Background

Iron deficiency (ID) is common among patients with heart failure (HF). Little is known about the impact of serum iron dynamics on mortality in HF.

Methods

Using a previously validated territory-wide clinical information registry, all eligible patients with HF (N = 112, 938) from 1996 to 2020 were enrolled. The index date was defined as the date of which HF was first diagnosed. Iron, ferritin and transferrin saturation (TSAT) values were retrieved both at baseline (1 year before index date) and during follow-up period (1 year after the index date until study end). The association between iron levels and risk of mortality was evaluated both on a continuous scale using restricted cubic spline curves and by categories using Cox proportional hazards regression model with competing risk as appropriate. Cut-points of iron were determined by the optimal equal-HR method. Inverse probability of treatment weighting (IPTW) was used to balance the covariates among iron groups. Changes in iron from baseline to follow-up were expressed by Sankey curve. The outcome was all-cause mortality.

Results

The mean age of the cohort was 73.0±12.2 years and 51,340 (45.5%) were male. The association between iron levels and the risk of all-cause mortality was a U-shaped curve. The risk of all-cause mortality reached a nadir between iron levels of 8.2 umol/L and 25.8 umol/L and was lowest at 13.5 umol/L. Accordingly, iron levels were divided into 3 groups: low iron (≤8.2 umol/L), midrange (8.2-25.8 umol/L), high iron (>25.8 umol/L). Compared to those who remained at midrange iron level during follow-up, risk of mortality was higher in those with persistently low and persistently high iron levels (HR 1.32, 95%CI 1.27 to 1.38; HR 2.24, 95%CI 1.74 to 2.89, respectively). Further, changes in iron levels from low to high (HR 1.41, 95%CI 1.24 to 1.61); mid to low (HR 1.15, 95%CI 1.10 to 1.20), mid to high (HR 1.29, 95%CI 1.13 to 1.49); high to low (HR 1.36, 95%CI 1.15-1.60), or high to mid (HR 1.18, 95%CI 1.00-1.38) also demonstrated higher risks of mortality. (Table 1)

Conclusion

The prevalence of low iron status is high among patients with HF. Both low or high iron levels at baseline, and changes to the lower or higher ends of the iron level spectrum during follow-up were associated with higher risks of all-cause mortality.cubic spline curve