bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of GPCR autoantibodies with clinical, histological, metabolic and hemodynamic features in non-ischemic heart failure patients
Authors: Karschnia M , Zweck E , Scheiber D , Heidecke H , Barthuber C , Kelm M , Roden M , Westenfeld R , Szendroedi J , Boege F
Published: October 2022

Background

Roughly one third of cases of chronic heart failure (HF) are caused by genetic predisposition, metabolic stress and cardiac inflammation. Animal studies suggest that heart-reactive autoantibodies, most notably those directed against G-protein-coupled receptors (GPCR), could also play a pathogenetic role in the disease. However, so far, a causal link between humoral GPCR-autoimmunity and human non-ischemic heart failure other than Chagas' cardiomyopathy remains unclear.

Purpose

Here, we investigated possible associations of GPCR autoantibodies with inflammatory, hemodynamic, metabolic and functional parameters in patients with chronic non-ischemic HF unrelated to Chagas' disease.

Methods

We prospectively included 95 patients with newly diagnosed non-ischemic heart failure of unknown origin. Basic cardiac characterization comprised transthoracic echocardiography, cardiac magnetic resonance imaging, coronary angiography and right heart catheterization with endomyocardial biopsy. Mitochondrial oxidative phosphorylation capacity and coupling was measured using high-resolution respirometry in permeabilized myocardial fibers. A panel of candidate GPCR-autoantibodies was determined by validated and certified immune-assays in peripheral venous blood of the HF-patients and 60 matched healthy individuals. Results were normalized to total IgG.

Results

Among 10 candidate GPCR-autoantibodies determined, only autoantibodies for α1-adrenergic receptor (α1AR), β1-adrenergic receptor (β1AR), muscarinic receptor M5 (M5AR), angiotensin II receptor type 1 (AT1R) and type 2 (AT2R) exhibited HF-associated alterations:

Autoantibodies against β1AR, M5R and AT2R were increased. Autoantibodies against α1AR and AT1R were decreased (Figure). These alterations were significant (p<0.01), but not, or only weakly, correlated with markers of cardiac inflammation, cardiac damage, hemodynamics, endomyocardial histology or left ventricular inflammation judged by T2-mapping.

However, in HF-patients, increased AT2R autoantibodies were associated with improved myocardial mitochondrial coupling (r=−0.27, p=0.021), and decreased AT2R autoantibodies were associated with insulin resistance (r=−0.24 p=0.027).

Conclusion(s)

Some previously postulated alterations of GPCR autoantibodies were confirmed in thoroughly characterized HF-patients. However, association of these alterations with cardiac function was not traceable, which argues against a specific pathogenic role. Our data are compatible with multifaceted interactions of GPCR-autoantibodies with the myocardium and potentially with glucose metabolism, possibly indicating a disease-modifying or compensatory role.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Research comission of the Heinrich-Heine University Duesseldorf
Titin truncating variant cardiomyopathy and related sarcomere insufficiency causes high energy demand resulting in mitochondrial dysfunction, autophagosome formation, and apoptosis
Authors: Stroeks S L V M , Verdonschot J A J , Lunde I G , Henkens M T H M , Willemars M , Schianchi F , Luiken J F P , Wang P , Derks K , Krapels I P C , Vanhoutte E K , Jones E A V , Brunner H G , Nabben M , Heymans S R B
Published: October 2022

Background/Objectives

Titin truncating variants (TTNtv) are the most prevalent genetic cause of dilated cardiomyopathy (DCM), resulting in upregulation of cardiac transcripts of oxidative phosphorylation (1,2). However, the underlying molecular mechanism(s) and cellular consequences of these findings remain unknown.

Methods and results

To gain insight into the metabolic changes and cellular consequences of a TTNtv, metabolic, mitochondrial, and survival pathways were studied in human TTNtv DCM hearts and isolated cardiomyocytes of TTNtv mice. TTNtv resulted in a significant increase of cardiac transcripts of glycolysis, citric acid cycle, mitochondrial fission, autophagy, and apoptosis when comparing RNAseq in 24 TTNtv and 27 mutation-negative DCM cardiac biopsies. Furthermore, a decrease in the area of myofibrils in human TTNtv hearts (TTNtv vs. mutation-negative DCM: 46%, and 62%, P=0.001), and an increase of mitochondrial (49% and 31%, P=0,001) and autophagosome areas (4% and 2%, P=0.002) was observed using transmission electron microscopy (TEM). Similar patterns of cardiomyocyte disorganization and stress could be seen in TTNtv hearts of mice even without a phenotype. Additionally, observed swollen mitochondria by TEM and decreased quantity of OXPHOS proteins by immunoblotting in murine TTNtv hearts indicate mitochondrial stress. Mitochondrial oxygen consumption at baseline and the maximum respiration in TTNtv cardiomyocytes of mice increased by a factor of 1.8 and 1.5 respectively (both P≤0.05), compared to WT. Furthermore, palmitate oxidation in TTNtv cardiomyocytes increased by 1.3 fold (P=0.005) compared to WT mice, suggestive of increased energy demand in TTNtv.

Conclusion

Myofibrillar insufficiency in human TTNtv DCM augments the cardiac oxygen and energy consumption, leading to pronounced morphological and functional mitochondrial decompensation. Swelling, damage and fission of mitochondria is further characterized by autophagosome formation and increased apoptosis pathways in TTNtv hearts.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Double-Dose consortium by Dutch Cardiovascular Alliance (DCVA)
Clinical impact of chronic kidney disease on appendicular skeletal muscle mass and mortality in hospitalized patients with acute heart failure
Authors: Akiyama E , Konishi M , Sato R , Matsuzawa Y , Iwahashi N , Kosuge M , Ebina T , Sato N , Takeda S , Hibi K , Tamura K , Kimura K
Published: October 2022

Introduction

Heart failure (HF) is a clinical syndrome associated with diverse metabolic disturbances. Recent studies including ours suggest that skeletal muscle plays an important role in the pathogenesis of chronic HF and chronic kidney disease (CKD). However, the effect of renal function on skeletal muscle mass in HF remains unclear.

Purpose

The purpose of this study was to investigate the impact of chronic kidney disease on appendicular skeletal muscle mass in hospitalized patients with acute HF (AHF).

Methods

We assessed lean body mass by dual energy X-ray absorptiometry in 418 hospitalized patients with AHF (age 71±13, left ventricular ejection fraction (LVEF) 39±17%, estimated glomerular filtration rate (eGFR) at discharge 46±19 mL/min/1.73 m2). Low appendicular skeletal muscle mass index (ASMI, appendicular skeletal muscle mass/height2) was defined according to the Asia Working Group for Sarcopenia criteria (<7.0 kg/m2 in male, <5.4 kg/m2 in female). CKD was defined as eGFR <60 mL/min/1.73 m2 at discharge.

Results

CKD was observed in 77% of hospitalized patients with AHF (eGFR ≥60 mL/min/1.73 m2, n=96, 23%, eGFR 30–59 mL/min/1.73 m2, n=233, 56%, eGFR <30 mL/min/1.73 m2, n=89, 21%). ASMI positively correlated with eGFR (r=0.16, P=0.002). ASMI decreased according to CKD categories (eGFR ≥60 mL/min/1.73 m2; ASMI 6.75±0.14 kg/m2, eGFR 30–59 mL/min/1.73 m2; ASMI 6.24±0.08 kg/m2, eGFR <30 mL/min/1.73 m2; ASMI 6.24±0.13 kg/m2, p=0.003, Figure 1). During a median follow-up of 37 months, 92 (22%) of 418 patients died. The combination of ASMI and CKD identified subgroups with a significantly different probability of all-cause death (log-rank test p<0.001, Figure 2).

Conclusions

CKD was associated with decreased skeletal muscle mass in hospitalized patients with AHF. CKD and skeletal muscle mass independently correlated with mortality after AHF episode. The cross link between kidney and skeletal muscle might play an important role in the pathogenesis of AHF.

Funding Acknowledgement

Type of funding sources: None.
A clinical and echocardiographic score to differentiate pulmonary hypertension due to heart failure with preserved ejection fraction from idiopathic pulmonary hypertension: the PH-HFPEF score
Authors: Dardi F , Ballerini A , Guarino D , Donato F , Bertozzi R , Martini G , Magnani I , Manes A , Palazzini M , Galie' N
Published: October 2022

Background

One of the most challenging differential diagnoses in pulmonary hypertension clinical practice, is the discrimination between idiopathic pulmonary arterial hypertension (IPAH) and pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF).

Aim

We elaborate a score (considering patient clinical history, demographics, and echocardiographic characteristics) that can predict, noninvasively, PH-HFpEF vs IPAH diagnosis.

Methods

Data were prospectively collected on 466 consecutive patients with a final diagnosis of IPAH or PH-HFpEF referred to a single tertiary pulmonary vascular disease centre. Data included clinical history, demographics, and parameters of an electrocardiogram and a transthoracic echocardiogram. A multivariate regression model was developed to predict a PH-HFpEF diagnosis, and an integer risk score was generated using adjusted regression coefficients of the multivariate logistic regression analysis.

Results

At the multivariate logistic regression a high ratio between left and right ventricular dimensions, a history of atrial fibrillation (AF), a high body mass index (BMI), a reduced mitral deceleration time and a high E-wave at trans-mitral doppler, an advanced age and a high right ventricular fractional area change (FAC) were predictors of PH-HFpEF. The derived PH-HFPEF score is shown in Table 1 and, with a cut-point ≥11, it yielded a specificity/sensitivity, respectively, for the diagnosis of PH-HFpEF, of 100%/49% with an AUC of 0.987.

Conclusions

The PH-HFPEF score can predict PH-HFpEF vs IPAH. The PH-HFPEF score may be used to potentially avoid an invasive diagnostic testing in almost half of PH-HFpEF patients.

Funding Acknowledgement

Type of funding sources: None.
Insight into the relationship between heart rate and mortality in patients in sinus rhythm with heart failure with preserved ejection fraction
Authors: Nakagawa Y , Sairyo M , Miyazawa K , Tamaki S , Yano M , Hayashi T , Yamada T , Yasumura Y , Hikoso S , Sotomi Y , Sakata Y
Published: October 2022

Background

There are several reports showing that elevated heart rate (HR) is associated with poor outcomes in patients in sinus rhythm (SR) with heart failure with preserved ejection fraction (HFpEF), although the association is weak or none in HFpEF patients with atrial fibrillation (Af). However, in previous studies, cardiac and non-cardiac factors which may be associated with elevated HR, have not been fully adjusted for.

Purpose

The purpose of this study is to explore covariates of elevated HR and to investigate the relationship between heart rate and mortality in HFpEF patients in SR.

Methods and results

Of the 1161 patients, who registered prospective multicenter, observational study of patients with HFpEF (PURSUIT-HFpEF), 726 patients in SR were examined. We performed laboratory testing and echocardiography in the compensated stage (in stable condition after treatment of acute decompensated HF). Geriatric nutritional risk index (GNRI) was calculated as nutrition index. Resting heart rate (HR) was analyzed as categorical (tertiles, T1–3). We followed the patients for median of 598 days (interquartile range 329–1028 days) to observe the outcome all-cause mortality.

The Kaplan analysis revealed that there was a significant difference between heart rate and mortality (log-rank, p=0.001). Characteristics were compared between patients in T1 (HR ≤63) and T3 (HR ≥75). There were no differences in cardiac factors between patients in T1 and T3. C-reactive protein (CRP) was significantly higher in patients in T3 than those in T1 (p=0.0004,). GNRI was significantly lower in patients in T3 than those in T1 (p=0.001). After adjustment for covariates including N-terminal pro-B type natriuretic peptide and estimated glomerular filtration rate, CRP and GNRI significantly correlated with HR (continuous variable) by multiple regression analysis (beta-coefficient = 1.52, p=0.003 and beta-coefficient = −0.14, p=0.04, respectively). Taking T1 as the reference, multivariable Cox regression analysis revealed that T3 was independently associated with mortality (hazard ratio: 2.10, 95% confidence interval: 1.33–3.32, p=0.001).

Conclusion

Although elevated HR was associated with enhanced inflammation and malnutrition, it itself was an independent predictor of death in HFpEF patients in SR.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Roche Diagnosis K.K.Fuji Film Toyama Chemical Co. Ltd.
Right atrial function in HFpEF in sinus rhythm vs. atrial fibrillation
Authors: Schoenbauer R , Hana F , Duca F , Koschutnik M , Dona C , Nitsche C , Sponder M , Lenz M , Loewe C , Beitzke D , Hengstenberg C , Mascherbauer J , Kammerlander A A
Published: October 2022

Aims

We sought to study the prognostic impact of right atrial (RA) size and function in patients with heart failure with preserved ejection fraction (HFpEF) in sinus rhythm (SR) vs. atrial fibrillation (AF).

Methods and results

Consecutive HFpEF patients were enrolled and indexed RA volumes and emptying fractions (RA-EF) were assessed by cardiac magnetic resonance imaging (CMR). For patients in SR during CMR feature tracking of the RA wall was performed (Figure 1). In addition, all patients underwent right and left heart catheterization, 6 min walk test, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) evaluation. We prospectively followed patients and used Cox regression models to determine the association of RA size and function with a composite endpoint of heart failure hospitalization and cardiovascular death. A total of 188 patients (71% female patients, 70±8 years old) were included of whom 96 (51%) were in SR. Eighty-five patients reached the combined endpoint during a follow-up of 72 (33–101) months. After multivariate cox regression analysis adjusted for age, NT-proBNP level, right ventricular ejection fraction and HF functional class, impaired RA strain (Figure 1A) (HR 0.959; 95% CI [0.924–0.996], P=0.024), RA conduit strain (Figure 1A) (HR 0.944; 95% CI [0.898–0.993], P=0.027) and RA conduit strain rate (Figure 1B) (HR 0.990; 95% CI [0.883–0.998], P=0.013) were significantly associated with adverse outcome for patients in SR (Table 1). In persistent AF, no RA imaging parameter was related to outcome after multivariate regression analysis.

Conclusions

In HFpEF patients in SR, CMR parameters of impaired RA conduit function show the best association with adverse cardiovascular outcome. In persistent AF, RA parameters lose their prognostic ability.

Funding Acknowledgement

Type of funding sources: None.
Long-term cardiac adverse effects after modern Hodgkins lymphoma treatment
Authors: Bjerring A W , Smeland K H B , Baerug I , Haugaa K H , Kiserud C E , Edvardsen T , Sarvari S I
Published: October 2022

Background

Hodgkin's lymphoma (HL) frequently affects both children and young adults. Traditional treatment of HL is effective but associated with a life-time prevalence of cardiac disease exceeding 50%. Treatment protocols were modified in 1997 to reduce cardiotoxicity, primarily by reducing both radiation fields and doses.

Purpose

To assess the long-term impact of the modified treatment protocols on left ventricular cardiac function.

Methods

HL survivors (n=244) treated with anthracycline-based chemotherapy using modified treatment protocols in 3 centres in Norway between 1997 and 2007 were included in this cross-sectional study. Of these, 130 (53%) also received mediastinal radiotherapy. They were compared to controls recruited from the general population (n=58) matched for age, sex, and risk-factors. Echocardiography was performed in all subjects.

Results

The participants were on average 46±9 years old and had received treatment on average 17±3 years before examination. Echocardiographic parameters are shown in the table. Reduced left ventricular (LV) ejection fraction (EF) (<52%) was found in 19 HL-survivors and three controls (13% vs. 6%, p=0.24). Reduced LV global longitudinal strain (GLS) (> −18.0%) was found in 41 HL survivors and three controls (25% vs. 6%, p<0.05). There was no difference in prevalence of reduced GLS between HL survivors who received mediastinal radiotherapy and those who did not (26% vs. 24%, p=0.70).

Conclusion

While a minority of HL survivors did have a slight reduction in longitudinal deformation, the effect was small and importantly, we found no difference in EF between HL survivors treated with modified protocols and controls. Mediastinal radiotherapy did not seem to increase the prevalence of reduced cardiac function in HL survivors.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): South-Eastern Norway Regional Health Authority
Pulmonary artery pressure-guided therapy in patients with heart failure using the CardioMEMS device and HF readmissions: analysis of the National Readmissions Database
Authors: Briasoulis A , Kishino Y , Kuno T , Malik A
Published: October 2022

Background

Pulmonary artery pressure (PAP)-guided therapy in patients with heart failure (HF) using the CardioMEMS device (CMM), an implantable PAP sensor, has shown to reduce HF hospitalizations in previous studies. We sought to evaluate the clinical benefit of the CMM device in regard to 30-day, 90-day and 180-day readmission rates in real-world usage.

Methods

We queried the National Readmission Database (NRD) to identify patients who underwent CMM implantation (ICD 9 & 10 codes) between the years 2014 to 2019 and studied their HF readmissions. We compared CMM patients and their readmissions with a matched cohort of patients with HF without CMM. Multivariable Cox regression analysis was performed to adjust for other predictors of readmissions.

Results

Prior to matching we identified 5,326,530 weighted HF patients without CMM and 1842 patients with CMM. After propensity score matching for several patients and hospital related characteristics, the cohort consisted of 1839 patients with CMM and 1924 with HF without CMM. Before matching, CMM patients were younger (67.0±13.5 years vs 72.3±14.1 years, P<0.001), more frequently males (62.7% vs 51.5%, P<0.001), with higher rates of prior percutaneous coronary intervention (16.9% vs 13.2%, P=0.002), peripheral vascular disease (29.6% vs 17.8%, P<0.001), pulmonary circulatory disorder (38.7% vs 23.2%, P<0.001), atrial fibrillation (51.2% vs 45.3%, P=0.002), prior left ventricular assist device (1.8% vs 0.2%, P<0.001), high income (32.2% vs 16.4%, P<0.001) and acute kidney disease (43.8% vs 29.9%, P<0.001). Readmission rates at 30-days were 17.3% vs. 20.9% for patients with vs. without CMM respectively and remained statistically significant after matching (17.3% vs. 21.5%, p=0.002). The rates of 90-day (29.1% vs 36.5%, p=0.002) and 180-day (39.6% vs. 46.6%, p=0.009) readmissions were lower in the CMM group. In a multivariable regression model, CMM was associated with lower risk of readmissions (HR, 0.75, 95% CI 0.63–0.89, p=0.001).

Conclusion

The CMM device was associated with reduced HF rehospitalization rates in a nationally representative cohort of HF patients.

Funding Acknowledgement

Type of funding sources: None.
Hemodynamics of acute decompensated heart failure in patients with very low NP levels
Authors: Subramanian V , Segar M , Wang T W , Pandey A P
Published: October 2022

Background/Introduction

Natriuretic Peptides are hormones secreted by the heart in response to cardiomyocyte stretch. The principal biological action of NP is natriuresis, diuresis and vasodilation. These are salutary effects in acute decompensated heart failure (ADHF). Some patients admitted with ADHF have very low NP levels. It is unknown if this is due to a defect in biosynthesis or inadequate stimulation.

Purpose

We analyzed data from the National heart Lung and Blood institute sponsored ESCAPE trial which included patients admitted with acute decompensated heart failure who underwent hemodynamic assessment with pulmonary artery catheters at admission and after diuresis. Our aim was to evaluate if there were characteristic hemodynamic findings among patients with very low NP levels at admission which differed from those who had elevated NP levels at admission.

Methods

We performed a secondary analysis of the ESCAPE Trial. We defined very low BNP as patients with BNP level at admission <50 pg/mL. We then compared baseline characteristics between the groups. Continuous groups were compared using X-square test, and Categorical variables were compared using Wilcoxon-signed-Rank-Sum test. We compared groups by Demographic, Anthropometric, Laboratory, and Functional status. We then performed propensity matching on Age, Sex, and BMI and then compared groups.

Results

25/351 patients had very low BNP (<50pg/mL). Patients in the low BNP group had higher BMI than those with elevated BNP (35.8 vs. 28.9 p<0.001). The cohort with low BNP was younger. (50.2 vs. 56.4 p=0.029). In propensity matched cohorts of Age, Sex, BMI. Cardiac output was elevated in the low BNP cohort. (5.2 vs. 3.9 p=0.011). However, Cardiac Index was similar between the groups (2.2 vs. 2.0 p=0.244). Patients in the Low NP group had lower pulmonary capillary wedge pressure (PCWP) compared to those with elevated BNP. (16.5 vs. 25.4 p=0.023). The groups had similar RA pressures (11.5 vs. 13.0 p=0.515). The calculated transmural pressure (PCWP – RA pressure) was lower in the low NP group. There was a reduction in BNP levels at discharge among the group with elevated BNP at admission (1072.6 (baseline) 798.8 (discharge)) In the low BNP group there was an increase in BNP at time of discharge (20.2 (baseline) to 172.7 (discharge)). In follow-up, the low BNP group had reduction in BNP compared to their discharge levels. The group with elevated BNP had elevated BNP at follow-up in 3 and 6 months. Length of stay was shorter in the Low BNP group (6.2 vs. 8.8, p=0.052).

Conclusion(s)

In this secondary analysis of the ESCAPE trial, we find that those patients admitted with ADHF who have unexpectedly low BNP have lower transmural pressures at baseline compared to those who have elevated BNP levels. This suggests that there may not be adequate stimulus for cardiac wall distention and release of BNP.

Funding Acknowledgement

Type of funding sources: None.
Sex related difference in heart failure development in patients after first myocardial infarction; role of galectine-3
Authors: Dekleva M , Djuric T , Djordjevic A , Soldatovic I , Stankovic A , Stevanovic A , Zivkovic M
Published: October 2022

Cardiac remodeling after the first myocardial infarction (MI) appears to be more successful in women than in men, but more frequently associated with heart failure (HF) development. Galectin-3 expression is upregulated in remodeling and failing myocardium and circulatory level is activated in hypertrophy, fibrosis and inflammation.

This study aimed to investigate the potential role of sex differences in the following: risk factors, structural and functional left ventricle (LV) changes, coronary angiography, expression of Galectin-3 and it's circulating level for HF occurrence during 6 months in patients after first MI.

Material and methods

The prospective study included patients with the first MI treated with the primary percutaneous coronary intervention (p PCI) who underwent Doppler echocardiography within 2±1 days of MI and after 6 months. Relative LGALS-3 mRNA expression in peripheral blood were detected by TaqMan® technology. Expression and concentration of Galectin-3 was obtained by ELISA method. Presence of HF was confirmed by clinical examination and Doppler echocardiography. Assessment of p PCI and description of coronary angiography was performed at the patient's admission time.

Results

The study included 137 men and 44 women, who were significantly older (57.8 vs. 54.4, p=0.034), with higher LDL cholesterol (3.54±0.93 vs. 4.03±1.27, p=0.027) without differences among angiographic characteristics and medications. In the acute phase of MI, the significantly lower indexed LV volumes were found in women compared to men (EDLVI: 58.3 vs. 49.6, p<0.001, ESLVI: 33.84 vs. 26.83, p<0.001), but the grade of LV remodeling (delta LVDVI, delta LVESVI) during 6 months and changes in LV ejection fraction (deltaLVEF) were similar (p=ns). Incidence of LV hypertrophy and HF development was significantly higher in women 70% vs. 44.6%, p=0.034, 37.5% vs.19.3%, p=0.02). Females have had a higher degree of LV diastolic dysfunction (DD) in the early and late phase after MI (p=0.038, p=0.027). There were significant correlations between grade of DD and level of Gal-3 expression (p=0.001). The relative expression of LGALS-3 mRNA in peripheral blood was higher in females (p=0.007) with upregulation of circulating Gal-3 in females (44.66 vs. 16.30, p<0.001) and in HF patients (31.1 vs. 21.2, p=0.025).

Conclusion

Sex specific actions such as LV hypertrophy, diastolic dysfunction, upregulation of Galectin-3 expression and higher circulating level may explain more incidence of HF in female. Difference in model and determinants of HF between men and women can be important for further therapy including Gelectin-3 inhibition.

Funding Acknowledgement

Type of funding sources: None.
Clinical scenarios of HCM-related mortality: relevance of age and stage of disease at presentation
Authors: Zampieri M , Salvi S S , Fumagalli C F , Argiro' A A , Zocchi C Z , Del Franco D A , Iannaccone G I , Palinkas E P , Giovani S G , Ferrantini C F , Cappelli F C , Olivotto I O
Published: October 2022

In the early days, Hypertrophic cardiomyopathy (HCM) has long been considered a malignant disease.

However, contemporary descriptions of HCM report low mortality rates, largely due to heart failure-related complications (HF), while sudden cardiac death (SCD) rates are consistently low. Ageing with HCM is not uncommon and competing risk of acquired cardiovascular (CV) and non-CV diseases becomes relevant over time.

Purpose

To describe the disease stage at presentation and the modes of death in a cohort of consecutive HCM patients followed at a national referral centre over the last two decades. Stages of disease were defined according to Circ. Heart Fail. 2012, as follows:

1) “Classic HCM phenotype” characterized by LV ejection fraction (EF) >65%.

2) “Adverse remodeling” characterized by LVEF in the range of 50% to 65%.

3) “Overt dysfunction” is the end-stage clinical evolution characterized by a LVEF <50%.

Methods

By searching our centralized database, we identified 1491 HCM patients with at least >1 year of follow-up between January 2000 and December 2020, 191 of whom died in the same period. In 30 the cause of death could not be ascertained. The remaining 161 constituted our study cohort.

Results

Of the 161 patients who died, 103 (64%) died due to HCM-related causes, whereas 58 (36%) died from non-HCM-related causes such as coronary artery disease (other CV) or other non CV causes.

Modes of death varied based on the stage of disease at diagnosis:

– Fifty-six (35%) patients had a “classic” HCM phenotype at diagnosis. Of these, about half died of HCM-related causes (n=30; 54%), versus 45% with non-HCM-related death. Differently from the other 2 stages, the single most common cause of death was “other non-CV related” mortality, in 44%. Among HCM-related causes, SCD prevailed (n=15; 27%) while HF-related events were only 8 (14%).

– Of the 86 (53%) patients with “adverse remodeling” at diagnosis, more than half died of HCM-related causes (n=57, 66%), largely due to HF (n=33, 38%); SCD occurred in 18 (21%) individuals. This stage included the highest percentage of patients who died of stroke (n=6; 7%).

– Of the 19 (12%) patients in “overt dysfunction” at diagnosis, HF represented the cause of demise in almost three quarters (n=14, 74%); SCD and non-HCM causes accounted for only 10% and 16% respectively.

Conclusions

Most HCM patients die due to complications of their own disease, mainly in the context of HF. Modes of death vary with the stage of disease, with SCD becoming less prevalent in more advanced phases of progression, when competitive risks of HF-related events become overwhelming. These data highlight an unmet medical need in the prevention of disease progression associated with HCM.

Funding Acknowledgement

Type of funding sources: None.
The relation between change in left ventricular systolic function and subsequent mortality in patients with chronic heart failure
Authors: Brown O I , Sklirou M , Cuthbert J J , Abel A A , Samuel N A , Kazmi S , Clark A L
Published: October 2022

Background

Increasing severity of impairment of left ventricular systolic dysfunction (LVSD) in patients with chronic heart failure (CHF) is associated with higher mortality. However, the relation between temporal changes in LVSD severity and long-term clinical outcome is unknown.

Purpose

We therefore investigated the effects of change of LVSD as measured by serial echocardiography on all-cause mortality in patients with CHF.

Methods

Patients with CHF defined as the presence of compatible symptoms and either at least moderate LVSD or NTproBNP >125 ng/L were enrolled. LVSD was qualitatively assessed as: none, mild, moderate, and severe. Echocardiography was performed at baseline and 12 months. The primary endpoint was all-cause mortality. Cox proportional hazard models were used to assess the relation between changes in LVSD and outcome. Hazard ratios (HR) are reported with 95% confidence intervals (CI).

Results

At baseline, 170 (11%) had no, 231 (16%) mild, 633 (43%) moderate and 453 (30%) severe LVSD. Amongst patients with either moderate or severe LVSD at baseline, 40% had improvement in function at 12 months (figure 1). Amongst patients with no LVSD at baseline, only 14% had deterioration of function. During subsequent median follow up of 2773 days, 868 patients died. Worsening of LVSD was associated with increasing all-cause mortality in patients with moderate LVSD and severe LVSD at baseline, but this was not significant after adjustment for covariables (table 1). Improvement of LVSD was independently associated with better survival in patients with moderate LVSD at baseline (HR 0.72 (95% CI: 0.53–0.98, p=0.04).

Conclusion

Greater severity of LVSD at baseline is associated with increasing likelihood of improvement. Amongst patients with moderate LVSD, improvement in LVSD is independently associated with survival.

Funding Acknowledgement

Type of funding sources: Public Institution(s).
Geographic variation in heart failure with reduced ejection fraction: insights from the VICTORIA trial
Authors: Tsutsui H , Lam C S P , Zhang J , Godoy-Palomino A , Tziakas D , Cohen-Solal A , Freitas C , Patel M J , Ezekowitz J A , Hernandez A F , Pieske B , O'Connor C M , Westerhout C M , Alemayehu W , Armstrong P W
Published: October 2022

Background

Geographic differences and background therapy have not been explored in the global VICTORIA trial, which enrolled high-risk patients with recent worsening heart failure with reduced ejection fraction (HFrEF).

Methods and results

Among 5050 patients enrolled in 5 pre-specified geographic regions, 34% were from Eastern Europe, 18% Western Europe, 23% Asia Pacific, 14% Latin and South America, and 11% North America (Table 1). Patients from Western Europe were older, had more atrial fibrillation, and lower glomerular filtration rates. Patients from Eastern Europe had more coronary artery disease and exhibited more advanced symptoms (∼50% New York Heart Association [NYHA] class III), whereas those from Latin and South America were less symptomatic (∼70% NYHA class II). North American patients had the largest body mass index as well as more diabetes and hypertension. Levels of NT-proBNP at randomization and MAGGIC risk scores were highest in Western European patients. Evidence-based triple medication therapy was used most frequently in Latin and South America and less frequently in North America; conversely, cardiac resynchronization therapy and implantable cardioverter defibrillators were most frequently used in North America and least frequently in Latin and South America. The overall primary composite event rate (cardiovascular death or HF hospitalization) in the placebo arm was 36.6/100 person-years over a median of 10.8 months and after adjusting for the MAGGIC score. When examined by region, these event rates were nominally highest in North America and lowest in Western Europe.

Conclusion

Substantial regional differences exist in characteristics and treatments among patients in this global trial of patients with HFrEF and a recent worsening event. These findings demonstrate the continuing unmet needs and opportunities for enhancing care in HFrEF.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): VICTORIA was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and Bayer AG, Wuppertal, Germany.
Systolic blood pressure time in range and long-term clinical outcomes in patients with ischaemic cardiomyopathy
Authors: Zhou Z , Fu G , Jian B , Liang M , Chen G , Wu Z
Published: October 2022

Background

The relationship between systolic blood pressure (SBP) control and long-term clinical outcomes in patients with ischaemic cardiomyopathy remains unclear. It has been previously reported that either too high or too low SBP may lead to a poorer prognosis. But current SBP control metrics may not take into account the possible effects of fluctuating SBP overtime on patients.

Purpose

This study aimed to estimate the association between time in range (TIR) of SBP and long-term clinical outcomes in patients with ischaemic cardiomyopathy.

Methods

This study was a post-hoc analysis of The Surgical Treatment of Ischaemic Heart Failure (STICH) trial, a randomized controlled trial with two hypotheses that enrolled participants with coronary artery disease and left ventricular ejection fraction ≤35%. The SBP target range of the TIR was defined as 110 to 130 mmHg and the SBP TIR was calculated by linear interpolation method. Patients were equally divided into four groups by quartiles of TIR. Multivariable-adjusted Cox proportional hazards regression models were constructed to compare the effects of different levels of TIR on a 10-year prognosis. The primary outcome was all-cause mortality. Subgroup analyses were performed according to whether patients were assigned to coronary artery bypass grafting (CABG) or medical therapy (MED), and in populations with different baseline SBP.

Results

A total of 1194 eligible patients were included according to the purpose of our study. Compared with patients in the quartile 4 group (TIR 77.87–100%), the fully adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of all-cause mortality were 1.32 (0.98–1.78) for quartile 3 group (TIR 54.81–77.63%), 1.40 (1.03–1.90) for quartile 2 group (TIR 32.59–54.67%), and 1.53 (1.14–2.04) for quartile 1 group (TIR 0–32.56%) (P for trend = 0.005). When evaluated TIR as a continuous variable, per 1-SD decrement (29.28%) in TIR significantly increased the incidence of all-cause mortality [1.15 (1.04–1.26)]. Similarly, the decrement in TIR significantly elevated the risk of cardiovascular (CV) mortality and the risk of all-cause mortality plus CV rehospitalization. Consistent results were also observed in subgroup analyses of either CABG or MED, or different baseline SBP, indicating the robustness of our findings.

Conclusions

This study suggested that in patients with ischaemic cardiomyopathy, a higher SBP TIR was significantly associated with a decreased risk of all-cause mortality, CV mortality and the composite of all-cause mortality plus CV rehospitalization, regardless of whether the patient received CABG or MED, and the level of baseline SBP. Our findings support that TIR might be a substitutable metric of SBP control for long-term clinical outcomes in patients with ischaemic cardiomyopathy.

Funding Acknowledgement

Type of funding sources: None.
Peak oxygen consumption is associated with the inotropic reserve in patients with heart failure with reduced ejection fraction undergoing cardiopulmonary testing
Authors: Soulaidopoulos S , Stamoulopoulos I , Fragoulis C , Kalos T , Xydis P , Konstantinou K , Chrysohoou C , Tsioufis K
Published: October 2022

Background

The role of cardiopulmonary exercise testing (CPET) in the prognostic evaluation of heart failure with reduced ejection fraction (HFrEF) is powerful and well-established. Nevertheless, the value of CPET in predicting left ventricular inotropic reserve in HFrEF remains unknown.

Purpose

The investigation of possible associations between CPET variables and left ventricular contractile reserve in patients with HFrEF.

Methods

Consecutive patients aged ≥18 years old with a diagnosis of heart failure and a left ventricular ejection fraction ≤40%, as assessed by echocardiography, were prospectively enrolled. Demographic and clinical data were recorded. All subject underwent CPET with either a Bruce or a modified Bruce protocol. Peak oxygen consumption (VO2), carbondioxide production (VCO2), minute ventilation to carbon dioxide production (VE/VCO2) slope, minute ventilation (VE), and VO2/heart rate (HR) values were calculated, while hemodynamic parameters during the test were also measured.

Results

In total, 191 patients with HFrEF were included in the analysis. The mean age was 58.8±11.8 years and 30 (15.7%) patients were women. Ischemic heart disease was the etiology of HFrEF in 101 (52.9%) patients, whereas 90 (47.1%) patients had a history of dilated cardiomyopathy. The mean exercise time was 7.6±.3 minutes. Mean peak VO2 and VE/VCO2 slope values were calculated at 19.1±6.1 ml kg–1 min–1 and 43.7±10.1, respectively. According to peak VO2 values, 70 patients (37.2%) were in Weber class A, 57 (29.8%) in class B, 48 (25.1%) in class C and 15 (7.9%) in class D. In univariate analysis, the change between rest and peak systolic blood pressure (ΔSBP), which is considered to reflect the left ventricular inotropic reserve, was positively correlated to the peak VO2 (p<0.001), the total pulmonary ventilation (VE) (p<0.001) and the peak heart rate during exercise (p=0.02). In multivariable analysis, peak VO2 was independently, linearly associated with the ΔSBP during CPET (Figure 1) (β=0.661, p=0.022). In Roc analysis, it was found that a cut-off value for peak VO2 of 16 ml kg–1 min–1 exhibits 64% sensitivity and 60% specificity in predicting a ΔSBP>40mmHg during exercise (area under the curve: 0.657, p<0.001 – Figure 2).

Conclusion

The peak oxygen consumption during cardiopulmonary testing represents an acceptable predictor of inotropic reserve in patients with HFrEF.

Funding Acknowledgement

Type of funding sources: None.
Epidemiology of cardiac amyloidosis and burden on health care system in Germany: a retrospective analysis from 2009 to 2018
Authors: Pfister R , Ihle P , Ruhnke T , Guenster C , Michels G , Seuthe K , Hellmich M , Ney S
Published: October 2022

Aims

Improved imaging modalities contributed to increasing disease awareness of cardiac amyloidosis. Contemporary data on frequency trends and impact on health system are lacking.

Methods and results

In a retrospective study using health claims data of the largest German statutory health insurance patients with a diagnostic code of amyloidosis and concomitant heart failure or cardiomyopathy between 2009 and 2018 were identified. Temporal trends in frequency, patient characteristics, all-cause mortality and measures of health care burden were examined.

8,279 patients were identified of whom 5,618 were incident without diagnosis of amyloidosis within the previous year. Prevalence increased from 15.5 to 47.6 per 100,000 person-years, and incidence increased from 4.8 to 11.6 per 100,000 person-years, with a continuous steepening in the slope of incidence trend. Age and male gender significantly increased whereas prevalence of myeloma and nephrotic syndrome significantly decreased over time. Median (IQR) survival time after first diagnosis was 2.5 years (0.5 to 6 years), with a 9% (95% CI 2–15%, p=0.008) reduced risk of death in the second compared to the first five years of observation. In the first year after diagnosis mean total health care costs were 21,955 € (median 9,873 €, IQR 3,922 to 24,714 €) per person.

Conclusion

The rise in patients with cardiac amyloidosis has continuously accelerated in the last decade which, based on patient characteristics, is mainly driven by underlying wildtype transthyretin amyloidosis. Considering the adverse outcome and high health care burden further effort should be put on early detection of the disease to implement treatment.

Funding Acknowledgement

Type of funding sources: None.
Rediscovering CPET: the prognostic value of hemodynamic gain index in heart failure
Authors: Borges-Rosa J , Martinho S , Almeida J P L , Milner J , Oliveira-Santos M , Goncalves L
Published: October 2022

Introduction

Cardiopulmonary exercise testing (CPET) is recommended in patients with heart failure (HF) to optimize exercise prescription and as part of the evaluation for heart transplantation. Hemodynamic gain index (HGI) derived from CPET has been proposed as a new marker of risk stratification in general population cohorts.

Purpose

We aimed to evaluate the prognostic value of HGI in patients with HF.

Methods

We conducted a single-centre study assessing consecutive patients with HF who underwent CPET from 2013 to 2017. HGI was calculated based on heart rate (HR) and systolic blood pressure (SBP): HGI = [(HRpeak × SBPpeak) − (HRrest × SBPrest)] / (HRrest × SBPrest). Classic and recently proposed variables were collected, including peak O2 uptake (pVO2), minute ventilation–CO2 production (VE/VCO2 slope), circulatory power (CP = pVO2 × peak SBP), and ventilatory power (VP = peak SBP/(VE/VCO2) slope). The primary outcome was a composite of HF hospitalization, heart transplant, and all-cause mortality.

Results

A total of 212 patients (mean age 55.4±10.9, 76.9% male) were included. Most patients had dilated cardiomyopathy (43.9%) followed by ischaemic aetiology (38.7%), with a mean left ventricle ejection fraction of 29±13%. The most used exercise protocol was the modified Naughton (76.6%), followed by the original Naughton (18.7%), and Bruce (4.8%). Mean pVO2 was 16.7±5.9mL O2 kg–1 min–1 and median VE/VCO2 slope was 37.5 [32.7–44.3]. Mean VP was 3.46±1.31mmHg while median CP was 1927 [1427–2697]mmHg min/mL/kg. Mean HGI was 0.90±0.5 bpm/mmHg. Despite weak, there were significant positive correlations between HGI and mean pVO2 (rs=0.55, p<0.01), VP (r=0.60, p<0.01), and CP (rs=0.68, p<0.01), but negative correlation between HGI and VE/VCO2 slope (rs=−0.45, p<0.01). HGI was grouped by terciles: T1 (<0.59), T2 (0.59–1.02), and T3 (>1.02). After a median follow-up of 71 [49–81] months, the primary outcome occurred in 66.0% of patients (rehospitalization, heart transplant, and all-cause death occurred in 56.1%, 25.9%, and 32.5%, respectively). In the T1 group, the multivariable-adjusted odds ratio (OR) for the primary outcome was 3.73 (95% CI 1.97–7.06, p<0.01) compared to the T3. In the T2 group, the multivariable-adjusted OR for the primary outcome was 0.47 (95% CI 0.27–0.81, p<0.01) compared to T1. There were no significant differences between T2 and T3 groups. Kaplan-Meier estimates of primary outcome during follow-up according to HGI tercile are shown in Figure 1.

Conclusion

HGI is inversely associated with the composite of HF hospitalization, heart transplant, and all-cause mortality in patients with heart failure, enhancing the role of CPET in risk stratification.

Funding Acknowledgement

Type of funding sources: None.
History of stroke in patients with heart failure: prevalence, baseline characteristics and clinical outcomes
Authors: Yang M , Kondo T , Butt J H , Abraham W T , Desai A S , Kober L , Martinez F A , Packer M , Pfeffer M A , Rouleau J L , Solomon S D , Zile M R , Jhund P S , McMurray J J V
Published: October 2022

Background

Stroke is an important but neglected comorbidity in patients with heart failure (HF). Little is known about the characteristics and outcomes of HF patients with a history of stroke.

Purpose

To examine the prevalence of prior stroke in patients with HF and reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), the clinical characteristics of patients with a history of stroke, and the clinical outcomes in patients with prior stroke compared to those without.

Methods

Individual patient data analysis using three recent HFrEF trials (ATMOSPHERE, PARADIGM-HF, and DAPA-HF) and HFpEF trials (CHARM-Preserved, I-Preserve, TOPCAT-Americas, and PARAGON-HF). Cox regression was used to analyze clinical outcomes.

Results

Among 20159 HFrEF patients enrolled, 1683 (8.3%) had a history of stroke and among the 13252 patients with HFpEF 1287 (9.7%) had a prior stroke. Compared to patients without stroke, those with stroke were slightly older and more likely to have a history of hypertension, myocardial infarction, atrial fibrillation, diabetes, carotid artery disease, and peripheral artery disease (for both HFrEF and HFpEF). Patients with a history of stroke had worse NYHA class and KCCQ scores, and a higher rate of fatigue; they also had a higher median NT-proBNP level and lower eGFR than those without prior stroke (whether HFrEF or HFpEF). Systolic BP, pulse pressure and LVEF did not differ susbtantialy between patients with and without a history of stroke. The table shows outcomes according to history of stroke or not, stratified by LVEF phenotype. During follow-up, all fatal and non-fatal outcomes were significantly more common in patients with a history of stroke. The augmentation of risk tended to be greater in patients with HFpEF than HFrEF, but was not statistically different.

Conclusion

Approximately 1 in 11 patients in recent HF trials had a history of stroke and these patients were at higher risk of fatal and non-fatal events than those without prior stroke. HF hospitalization as well as atherothrombotic events (myocardial infarction and stroke) were more common among patients with prior stroke – patients with prior stroke had at least 30% higher risk of all events examined, regardless of LVEF, and more than double incidence of repeat stroke.

Funding Acknowledgement

Type of funding sources: Other.