bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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&lt;0.001, ESLVI: 33.84 vs. 26.83, p&lt;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&lt;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

Abstract

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) &gt;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 &lt;50%.

Methods
By searching our centralized database, we identified 1491 HCM patients with at least &gt;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

Abstract

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 &gt;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

Abstract

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

Abstract

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

Abstract

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&lt;0.001), the total pulmonary ventilation (VE) (p&lt;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&gt;40mmHg during exercise (area under the curve: 0.657, p&lt;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

Abstract

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

Abstract

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&lt;0.01), VP (r=0.60, p&lt;0.01), and CP (rs=0.68, p&lt;0.01), but negative correlation between HGI and VE/VCO2 slope (rs=−0.45, p&lt;0.01). HGI was grouped by terciles: T1 (&lt;0.59), T2 (0.59–1.02), and T3 (&gt;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&lt;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&lt;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

Abstract

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.