bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of SGLT-1/2 inhibition on mitochondrial dysfunction in left atrial remodeling during HFpEF
Authors: Bode D , Semmler L , Hegemann N , Primessnig U , Wakula P , Pieske B.M , Messroghli D , Heinzel F.R , Hohendanner F
Published: November 2020

Background

In the DAPA-HF trial, SGLT inhibition reduces cardiovascular mortality in heart failure. However, the mechanism and a potential positive effect in HfpEF remain elusive.

Introduction

LA remodeling is a hallmark feature of HFpEF and commonly associated with LA enlargement and dysfunction. Previous studies of SGLT-2 inhibitor Empagliflozin suggest a utilization of alternative metabolites for energy consumption (i.e. ketone bodies). Additionally, alterations of sodium and calcium ion hemostasis have been reported. We investigated the effect of SGLT inhibition on mitochondrial (dys)function during atrial remodeling in HFpEF.

Methods

Rats (WT: Wistar Kyoto, HFpEF: ZFS-1 Obese (metabolic syndrome)) were obtained at ∼10w and fed Purina 5008 diet. At 17w, animals were randomized to treatment with either vehicle or Sota (30mg/kg/d) for 5w until primary adult cardiomyocytes were isolated for final experiments. Structural information of mitochondria was obtained with Mitotracker Red in either a glucose starved (1h incubation with mannitol) or saturated state. ROS production was assessed with H2-DCF in a starved and saturated condition. Mitochondrial calcium buffer capacity was imaged with Rhod-2 following perforation of the cellular membrane with saponin. Glycolytic dependency of calcium cycling was assessed upon glycolytic inhibition with 2-deoxyglucose during imaging of cytosolic calcium transients with Fura-2.

Results

In a glucose saturated state, LA cardiomyocytes in HFpEF showed increased mitochondrial density, which was ameliorated with Sota. Sota increased mitochondrial calcium buffer capacity in HFpEF, indicating a decrease in mitochondrial resting calcium. Differences in mitochondrial fission could not be detected. However, during glucose starvation cardiomyocytes showed a decrease in mitochondrial fission and ROS production with Sota. A difference in ROS production was not visible when cells were abruptly challenged with high glucose concentrations, but Sota decreased mitochondrial fission, indicating long term protective properties towards ROS. Glycolytic inhibition led to an increase of cytosolic diastolic calcium and calcium transient peak height in HFpEF vs. WT, indicating an increased glucose dependency of cytosolic calcium cycling, which was mitigated with Sota. Additionally, Sota negated an increase in diastolic calcium, when cardiomyocytes where challenged with high concentrations of glucose after starvation.

Conclusion

SGLT1/2 inhibition alters mitochondrial calcium uptake in HFpEF and positively affects mitochondrial structure with subsequent decreases of ROS production and enhanced calcium homeostasis.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Else-Kröner-Fresenius-Stiftung, Deutsches Zentrum für Herz-Kreislaufforschung
Reduced cognitive function is associated with poor outcomes in HFpEF: a post hoc analysis from PARAGON-HF
Authors: Dewan P , Jhund P.S , Anand I.S , Desai A.S , Pieske B , Rizkala A.R , Shah S.J , Shi V.C , Van Veldhuisen D.J , Zannad F , Zile M.R , Solomon S.D , McMurray J.J.V
Published: November 2020

Background

Little is known about the prevalence and consequences of cognitive impairment in patients with heart failure and preserved ejection fraction (HFpEF).

Purpose

To describe the prevalence of cognitive impairment in HFpEF and the association between cognitive function and outcomes in patients with HFpEF.

Methods

In the Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction trial (PARAGON-HF), cognitive function was tested in a subgroup of patients at baseline and during follow-up, using the Mini-Mental State Examination [MMSE] which has a maximum score of 30, with a higher score reflecting better cognitive function. Patients were divided into 3 groups according to baseline score: ≤24 representing cognitive impairment, 25–27 reflecting borderline cognitive impairment and ≥28 normal cognition. The primary endpoint used in this analysis was a composite of first heart failure hospitalization (HFH) or cardiovascular death (CVD). We examined the relationship between baseline MMSE score and this outcome, its components and all-cause mortality. We adjusted for other standard prognostic variables, including NT-proBNP (see Table footnote).

Results

Among the 2895 patients (60% of total) in PARAGON-HF with a baseline MMSE measurement, 415 (14.3%) had a score ≤24, 671 (23.2%) a score 25–27 and 1809 (62.5%) a score ≥28. Over a median follow-up of 35 (IQR 30–41) months, the unadjusted and adjusted risks of the primary composite (Table), its components and all-cause death (Figure) were higher in patients with lower baseline MMSE scores.

Conclusions

Even mild cognitive impairment, as measured by the MMSE, is predictive of adverse outcomes in HFpEF

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): PARAGON-HF was funded by Novartis Pharma
The association of digoxin with mortality in ischemic heart failure: a secondary analysis of the STICH trial
Authors: Pandya L , Brown D.L
Published: November 2020

Background

Digoxin, one of the first treatments for symptoms of congestive heart failure (CHF), is currently used in the management of persistent CHF symptoms as well as for ventricular rate control in atrial fibrillation. Current guidelines suggest digoxin as an adjunct to optimal medical therapy for symptomatic improvement in CHF. However, the data regarding the effect of digoxin use on mortality continue to be conflicting.

Purpose

The aim of this retrospective study was to evaluate the association of digoxin therapy with mortality in patients with ischemic heart failure defined by severe left ventricular (LV) dysfunction and coronary artery disease (CAD) in the Surgical Treatment for Ischemic Heart Failure (STICH) trial.

Methods

STICH randomized 1012 patients with CAD and LV ejection fraction<35% to coronary artery bypass graft (CABG) surgery and medical therapy vs. medical therapy alone. Factors predictive of digoxin use were identified with a binomial logistic regression model. Multivariable Cox proportional hazards modelling was performed with digoxin use modelled as a segmented time-dependent covariate. The model was adjusted for baseline clinical characteristics (including age, race, hypertension, hyperlipidemia, diabetes mellitus, peripheral vascular disease, NYHA heart failure class, previous myocardial infarction, atrial fibrillation, creatinine level, smoking status, and STICH treatment group) and stratified based on sex. All covariates were verified to meet the proportional hazards assumption. The primary outcome was all-cause mortality. Secondary outcomes included death and hospitalization due to cardiovascular causes. Relative risks were expressed as adjusted hazard ratios (aHR) with 95% confidence intervals (CI).

Results

Of the 1012 patients, 351 (35% [36% of male patients and 27% of female patients]) reported digoxin use for some duration during the study period. Significant predictors of digoxin use included minority status, NYHA class, previous myocardial infarction, and baseline diagnosis of hypertension, diabetes, or atrial fibrillation. At a mean follow-up of 9.8 years, 566 patients (55.7%) experienced all-cause mortality and 387 patients (38.1%) died due to cardiovascular causes. The adjusted Cox proportional hazards model demonstrated that digoxin use was independently associated with an increased risk of all-cause mortality (aHR 1.22, 95% CI: 1.00–1.49, P=0.049). Digoxin use was also associated with increased risk of cardiovascular death (aHR 1.29, 95% CI: 1.02–1.64, P=0.032). There was no impact of digoxin on hospitalization for cardiovascular causes.

Conclusion

Use of digoxin in patients with ischemic heart failure was associated with an increased risk of both all-cause and cardiovascular death.

Funding Acknowledgement

Type of funding source: None
Usefullness of peak mitral regurgitation velocity to left ventricular outflow tract time velocity integral ratio as a new prognostic marker for one year and long term mortality in failing heart
Authors: Ozcan Cetin E.H , Balci K , Cetin M.S , Unal F , Tekin Tak B , Ekizler F.A , Erdol M.A , Ozcan F , Ozeke O , Cay S , Temizhan A , Topaloglu S , Aras D
Published: November 2020

Background and aim

Systemic vascular resistance (SVR) is useful for risk estimation and therapy guidance in HF. It has been showed that the ratio of peak mitral regurgitation velocity (MRV) to left ventricular outflow tract velocity-time integral (LVOT VTI) correlated positively with SVR. We aimed to assess the association of MRV/LVOT VTI ratio with established prognostic markers and its prognostic role for predicting one year and long term composite end-points in patients with HF and reduced ejection fraction (HFrEF).

Material and methods

We prospectively enrolled a total of 72 patients with HFrEF and 10 control subjects. Patients were followed up patients for median 40.5 months. Primary composite endpoint (CEP) was defined as any of these outcomes including requiring mechanical circulatory support, cardiac transplantation and all-cause mortality.

Results

CEP(+) patients had higher MRV/LVOT VTI ratio than others (0.48±0.15 vs. 0.39±0.18 p=0.012). MRV/LVOT VTI ratio was positively correlated with functional status (β=0.539, p=0<001), serum BNP level (β=0.479, p<0.001),troponin I (β=0.415, p<0.001), and Uric acid level (β=0.235 p=0.018) and negatively correlated with SEATTLE score derived life expectancy (β=−0.248, p=0.032). Adjusted with other parameters, every 0.1 increase in MRV/LVOT VTI ratio increased the one-year CEP risk by 27% and long-term CEP risk by 24.6%. In Kaplan Meier analysis, patients with MRV/LVOTVTI ratio ≥0.39 had more long-term CEP compared to others.

Conclusion

MRV/LVOT VTI ratio seemed to be useful predictor of poor prognosis associated with other established HF prognostic markers.

Figure 1

Funding Acknowledgement

Type of funding source: None
Prognostic implications of late gadolinium enhancement for re-worsening left ventricular ejection fraction in patients with dilated cardiomyopathy: a longitudinal study of left ventricular function
Authors: Nabeta T , Ishii S , Ikeda Y , Maemura K , Oki T , Yazaki M , Fujita T , Naruke T , Inomata T , Ako J
Published: November 2020

Background

Re-worsening left ventricular ejection fraction (LVEF) after initial recovery occurs in some patients with dilated cardiomyopathy (DCM). However, prevalence and predictors of re-worsening LVEF in longitudinal follow-up are unclear. Late gadolinium enhancement of cardiovascular magnetic resonance (LGE-CMR) can evaluate the damage of myocardial tissue.

Purpose

This study sought to evaluate the clinical parameters including LGE-CMR to predict re-worsening LVEF in patients with recent-onset DCM.

Methods

We included patients with recent-onset DCM who had an LVEF <45% and underwent LGE-CMR at diagnosis. We performed yearly echocardiographc follow-up [median 6 [4–8.3] years]. Initial LVEF recovery defined as patients increased in >5% LVEF from baseline and had an LVEF≥45% after medical therapy. Patients were divided into three groups: (1) Improved: defined as those with sustained LVEF ≥45% after initial LVEF recovery; (2) Re-worse: those with decreased >5% and had an LVEF <45% after initial LVEF recovery. and (3) Not-improved: those with no initial LVEF recovery during follow-up. To evaluate the prognostic factors for Re-worsening LVEF after initial LVEF recovery, multivariate logistic regression analysis performed between the Improved group and the Re-worse group. Cardiac events defined as hospitalization due to heart failure and sudden death.

Results

Of 138 patents, 82 patients (59%) were the Improved group, 42 patients (30%) were the Re-worse group, and 14 (10%) were the Not-improved group. Loess curves of long-term LVEF trajectories showed that LVEF in the Re-worse group increased first 2 years and declined slowly thereafter (Fig. 1A). Re-worsening LVEF occurred 4.5±2.2 years after initial LVEF recovery. Multivariate logistic regression analysis demonstrated that LGE area at baseline (Odds ratio: 1.09, 95% confidence interval (CI) 1.02–1.18, p=0.014) and Log brain natriuretic peptide (BNP) at initial LVEF recovery (Odds ratio: 1.53, 95% confidence interval (CI) 1.01–2.31, p=0.042) were independent predictors for Re-worsening LVEF. Kaplan Meier analysis demonstrated that the risk of cardiac events in the Re-worse group was significantly higher (hazard ratio: 3.93, 95% CI 1.49–10.36, p=0.006) than in the Improved group and lower risk than in the Not-improved group (hazard ratio: 0.28, 95% CI 0.12–0.62, p=0.002) (Fig. 1B).

Conclusion

Re-worsening LVEF occurred in 30% of patients in patients with recent-onset DCM. LGE area and BNP at initial LVEF recovery were independently associated with re-worsening LVEF after initial LVEF recovery.

Figure 1

Funding Acknowledgement

Type of funding source: None
Sex differences in ventricular remodeling and long-term heart failure outcomes following acute coronary syndrome
Authors: Adamson P , Verryt T , Frampton C.M , Troughton R , Doughty R.N , Richards A.M
Published: November 2020

Background

Compared with men, women are at increased risk of heart failure hospitalization following acute coronary syndrome (ACS).

Purpose

We sought to determine whether this increased hazard was associated with differing patterns in left ventricular (LV) remodeling over the first 12 months after ACS.

Methods

In a prospective multi-centre observational cohort study, 2,140 patients with ACS underwent echocardiography at 1, 4, and 12 months following the index event. Heart failure hospitalisation events were captured over a median 4.8 (IQR 3.4–6.5) years and relative risk compared between women and men using a multivariable Cox model adjusted for baseline demographics (age and systolic blood pressure) and echocardiographic variables (LV end diastolic and end systolic volumes, LV ejection fraction, interventricular septal wall thickness, and E/e') captured at baseline and 12 months.

Results

The 609 (28.5%) women were older (mean [SD] age 70 [12] versus 65 [12] years), had higher systolic blood pressure, demonstrated smaller increases in peak myocardial biomarkers, and were less likely to undergo coronary revascularization during the index admission (41.9% versus 62.0%; p<0.001 for all). After indexing for body surface area, women had smaller LV end diastolic and end systolic volumes, greater LV ejection fractions, and greater septal wall thickness and diastolic filling pressure estimates (E/e' 14 versus 11; p<0.001 for all). Diastolic volumes further diverged at 12 months (p=0.05) and septal wall thickness increased compared with men (p=0.016). In unadjusted and adjusted analyses women were at increased risk of future heart failure hospitalization (unadjusted HR 1.5, 95% CI 1.2–1.9, adjusted HR 1.6, 95% CI 1.1–2.4).

Conclusions

Women experience a more concentric remodeling pattern over the 12 months following ACS. Women remain at increased risk of long-term heart failure hospitalization after accounting for clinical and echocardiographic characteristics.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): National Heart Foundation of New Zealand, New Zealand Health Research Council
The combined effect of Sacubitril-valsartan treatment on right ventricular function and cardiorespiratory response in patients with chronic heart failure
Authors: Chrysohoou C , Terzis I , Xanthopoulou M , Tzorovili E , Konstantinou C , Solomou E , Magkas N , Antoniou C.K , Xydis P , Dilaveris P , Tousoulis D
Published: November 2020

Cardiorespiratory response, right ventricular and global diastolic function is known to deteriorate the clinical course of patients with chronic heart failure with reduced ejection fraction (HFrEF), even under optimal treatment. In this work we sought to evaluate the impact of sacubitril/valsartan initiation in patients with chronic HFrEF in NYHA clinical status II-III, under optimal medical and invasive treatment. Methods 180 patients (85% male, mean age 62±9 years old, 60% ischemic heart failure, 73% with ICD, 45%with CRT and 45% with diabetes mellitus) in NYHA classification II-III-, who were prescribed Sacubitril-Valsartan were evaluated.

Clinical status, biochemical parameters, cardiorespiratory exercise response and bi-ventricular Doppler indices were evaluated at first visit and 6 months after. The pulsed tissue Doppler imaging of the systolic and diastolic function of mitral and tricuspid annulus was characterized by the systolic waves Smv and Stv, and the diastolic waves: Emv and Amv; E was the early filling wave in transmitral velocity. Left atrial maximal volume and global longitudinal strain of the left ventricle (GLPS) were measured. In cardiorespiratory exercise Vo2max, VE/VCO2 and Mets achieved were evaluated. All of them received b-blockers, 90% eplerenone or spironolactone, 25% ivabradine and 90% diuretic treatment. Seventy percent of them started with the dose of 50mg of sacubitril/valsartan; while 80% finally received the full dose of 200 mg bid. One third of them were on clinical status NYHA III.

Results

Eight of the patients discontinued the medication due to hypotension or renal function worsening. All patients expressed improvement in clinical status; while diuretic therapy was down titrated in all of them and discontinued in 30%. As compared with the initial examination, tricuspid annulus systolic wave velocity increased by 5% (p=0.04); maximum volume of left atrium was decreased by 6% (p=0.004); GLPS average was improved by 41% (p=0.001) and E/Emv ratio was decreased by 22% (p=0.04). Moreover, improvement in Stv was more prominent in DCM as compared to IHF patients; In cardio respiratory exercise VE/VCO2 decreased by 5% (p=0.05); while VO2 max showed a trend in improvement (p=0.06), with no difference detected between DCM and ICM patients; although there was a significant increase (47%) in METS achieved (p=0.02).

Conclusion

Sacubitril/valsartan initiation was associated with improved left diastolic function and right ventricular function, along with functional status improvement in patients with HFrEF. These finding underline the beneficial role of sacubitril/valsartan initiation on the hemodynamic course of patients with systolic heart failure and clinical status deterioration.

Funding Acknowledgement

Type of funding source: None
Right ventricular dysfunction by 3D echocardiography is the best predictor for death and re-hospitalization in patients with heart failure with reduced ejection fraction
Authors: Mihaila S , Velcea A , Andronic A , Rimbas R.C , Chitroceanu A , Calin S.I , Vinereanu D
Published: November 2020

Background

In patients with heart failure with reduced ejection fraction (HFrEF), right ventricular (RV) size and dysfunction by 2-dimensional echocardiography (2DE) were identified as risk factors for mortality and morbidity, but 3-dimensional echocardiography (3DE) enabled itself as a more reproducible and accurate method.

Aim

To assess the comparative prognostic value of parameters of RV size and dysfunction, measured by 2DE and 3DE, in patients with ischemic and non-ischemic HFrEF, on optimal clinical care, at long-term follow-up.

Methods

142 consecutive patients (62±12 yrs, 104 males) with HFrEF, in sinus rhythm, were assessed by 2DE and 3DE, including RV full-volume acquisitions. RV diameter (RVd), RV end-systolic (RV_EDA) and end-diastolic areas (RV_ESA), RV fractional area change (RVFAC), and 2D_TAPSE were measured by 2DE. RV end-diastolic (RV_EDV) and end-systolic volumes (RV_ESV), RV ejection fraction (RV_EF), and 3D_TAPSE were measured by a dedicated 3DE software. Patients were followed for 37±16 months after the index event. Primary outcome was cardiac death (CD). Secondary outcomes were: 1) HF hospitalizations (HFH); 2) a composite cardiac events (CE) end-point of CD or HFH, myocardial infarction, coronary revascularization, arrhythmias, or CRT.

Results

38 CD, 47 HFH, and 62 CE occurred during follow-up. Mean RVd was 34±7 mm, RV_EDA 20±11 cm2, RV_ESA 12±5 cm2, RV_FAC 37±13%, RV_EDV 84±25 ml/m2, RV_ESV 52±22 ml/m2, and RV_EF 39±10%. Mean 2D_TAPSE was 18±4 mm, while mean 3D_TAPSE was 16±4 mm. By 2DE, only RV_ESA and RV_FAC, but not RV_EDA or RVd, correlated with CD, HFH, and CE. 2D_TAPSE correlated with HFH, but not with CD or CE, while 3D_TAPSE correlated with all primary and secondary outcomes. By 3DE, RV_ESV, but not RV_EDV, correlated with CD, HFH, and CE. Moreover, 3D RV_EF had better correlations with primary and secondary outcomes than 2D RV_FAC (z=3.8, z=2.5, and z=2.5, all p<0.01). By multivariate linear regression analysis including RV_ESA, RV_FAC, RV_ESV, RV_EF, and 3D_TAPSE, only RV_EF was an independent predictor for CD and HFH (r2=0.68 and r2=0.30, both p<0.001).

Conclusion

In patients with ischemic and non-ischemic HFrEF, 3DE parameters of RV size and dysfunction are better predictors for death and re-hospitalization than 2DE parameters. The RV_EF measured by 3DE was the best predictor for death in patients with HFrEF.

Funding Acknowledgement

Type of funding source: None
Clinical characteristics and long-term mortality of patients with midrange ejection fraction undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction
Authors: Vratonjic J , Milasinovic D , Asanin M , Vukcevic V , Zaharijev S , Pavlovic A , Jelic D , Radomirovic M , Zobenica V , Mehmedbegovic Z , Stankovic G
Published: November 2020

Background

Previous studies associated midrange ejection fraction (mrEF) with impaired prognosis in patients with ST-elevation myocardial infarction (STEMI).

Purpose

Our aim was to assess clinical profile and short- and long-term mortality of patients with mrEF after STEMI treated with primary percutaneous coronary intervention (PCI).

Methods

This analysis included 8148 patients admitted for primary PCI during 2009–2019, from a high-volume tertiary center, for whom echocardiographic parameters obtained during index hospitalization were available. Midrange EF was defined as 40–49%. Adjusted Cox regression models were used to assess 30-day and 5-year mortality hazard of mrEF, with the reference category being preserved EF (>50%).

Results

mrEF was present in 29.8% (n=2 427), whereas low ejection fraction (EF<40%) was documented in 24.7% of patients (n=2 016). mrEF was associated with a higher baseline risk as compared with preserved EF patients, but lower when compared with EF<40%, in terms of prior MI (14.5% in mrEF vs. 9.9% in preserved EF vs. 24.2% in low EF, p<0.001), history of diabetes (26.5% vs. 21.2% vs. 30.0%, p<0.001), presence of Killip 2–4 on admission (15.7% vs. 6.9% vs. 26.5%, p<0.001) and median age (61 vs. 59 vs. 64 years, p<0.001). At 30 days, mortality was comparable in mrEF vs. preserved EF group, while it was significantly higher in the low EF group (2.7% vs. 1.6% vs. 9.4%, respectively, p<0.001). At 5 years, mrEF patients had higher crude mortality rate as compared with preserved EF, but lower in comparison with low EF (25.1% vs. 17.0% vs. 48.7%, p<0.001) (Figure). After adjusting for the observed baseline differences mrEF was independently associated with increased mortality at 5 years (HR 1.283, 95% CI: 1.093–1.505, p=0.002), but not at 30 days (HR 1.444, 95% CI: 0.961–2.171, p<0.001).

Conclusion

Patients with mrEF after primary PCI for STEMI have a distinct baseline clinical risk profile, as compared with patients with reduced (<40%) and preserved (≥50%) EF. Importantly, mrEF did not have a significant impact on short-term mortality following STEMI, but it did independently predict the risk of 5-year mortality.

Funding Acknowledgement

Type of funding source: None
Liver stiffness as measured by transient elastography is an independent predictor of outcomes in patients with chronic heart failure
Authors: Avila D.X , Villacorta H.V , Cabrita C.M.L , Santos R.B.G , Ribeiro M.L , Gismondi R.A , Mocarzel L.O , Guarana T
Published: November 2020

Background

Patients with chronic heart failure (HF) may have liver abnormalities due to systemic congestion. Transient elastography (TE) has been used to assess liver stiffness (LS) in patients with primary liver disease. Some studies have suggested that congestion can influence liver stiffness.

Purposes

We sought to assess the role of LS in the prediction of outcomes in patients with chronic HF.

Methods

Nine-three consecutive patients with chronic HF were screened and fulfilled the inclusion criteria which consisted of signs or symptoms of HF and left ventricle ejection fraction (LVEF) less than 50%. Patients with concomitant liver disease were excluded or techical problems during TE. Patients underwent routine laboratory tests, liver function tests and TE. The primary endpoint was time to first event, which was defined as a composite of cardiovascular death or HF hospitalization.

Results

Mean follow up was 219±86 days. Nine patients were excluded due to exclusion criteria or technical problems during the TE. Eighty-four patients were included in the final analysis. Mean age was 63.2±12.2 and 57 (67.8%) were male. Mean ejection fraction and median NT-proBNP were, respectively, 38.7±14.3% and 1,140 pg/mL (interquartile range 224.3–2,810.3). Median LS for the entire population was 5.35 (3.7–10.65) kPa. LS correlated with NT-proBNP (r=0.54; p<0.0001), total bilirubin (r=0.47; p<0.001), direct bilirubin (r=0.66; p<0.0001), alkaline phosphatase (r=0.57; p<0.0001); γ-glutamyl-transpeptidase (r=0.59; p<0.0001), and age (r=−0.22; p=0.03). A Receiver Operating Characteristic (ROC) curve was performed and a cut point of 5.9 kPa showed sensitivity of 80% and specificity of 64.1% with area under the curve of 0.73. Mean event-free survival time for patients above and below this cutoff was 215.2±20 vs 302.8±7.2 days (p=0.0001; log rank test). Using Cox proportional hazard model (independent variables: LS as a continuous variable, age, gender, NT-proBNP, LVEF, and creatinine), only LS was independently associated with the primary endpoint (hazard ratio 1.05, 95% confidence interval 1.01–1.09; for each increment of one unit of LS).

Conclusion

LS correlates with biomarkers of myocardial stretch and several liver function tests and is an independent predictor of outcomes in patients with chronic HF.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): Own funding and examinations carried out with a welfare fund.
Trends in cause-specific readmissions in heart failure with preserved versus reduced and mid-range ejection fraction
Authors: Cui X.T , Thunstrom E , Dahlstrom U , Zhou J.M , Ge J.B , Fu M
Published: November 2020

Background

It remains unclear whether the readmission of heart failure (HF) patients has decreased over time and how it differs among HF with preserved ejection fraction (EF) (HFpEF) versus reduced EF (HFrEF) and mid-range EF (HFmrEF).

Methods

We evaluated HF patients index hospitalized from January 2004 to December 2011 in the Swedish Heart Failure Registry with 1-year follow-up. Outcome measures were the first occurring all-cause, cardiovascular (CV) and HF readmissions.

Results

Totally 20,877 HF patients (11,064 HFrEF, 4,215 HFmrEF, 5,562 HFpEF) were included in the study. All-cause readmission was highest in patients with HFpEF, whereas CV and HF readmissions were highest in HFrEF. From 2004 to 2011, HF readmission rates within 6 months (from 22.3% to 17.3%, P=0.003) and 1 year (from 27.7% to 23.4%, P=0.019) in HFpEF declined, and the risk for 1-year HF readmission in HFpEF was reduced by 7% after adjusting for age and sex (P=0.022). Likewise, risk factors for HF readmission in HFpEF changed. However, no significant changes in cause-specific readmissions were observed in HFrEF. Time to the first readmission did not change significantly from 2004 to 2011, regardless of EF subgroup (all P-values>0.05).

Conclusions

Although the burden of all-cause readmission remained highest in HFpEF versus HFrEF and HFmrEF, a declining temporal trend in 6-month and 1-year HF readmission rates was found in patients with HFpEF, suggesting that non-HF-related readmission represents a big challenge for clinical practice.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): The SwedeHF was funded by the Swedish National Board of Health and Welfare, the Swedish Association of Local Authorities and Regions.
Geographic variation in the outcome of patients hospitalized for heart failure: analysis of a nationwide inpatient database
Authors: Yotsumoto H , Kaneko H , Itoh H , Kiriyama H , Kamon T , Fujiu K , Morita K , Michihata N , Jo T , Morita H , Yasunaga H , Komuro I
Published: November 2020

Background

The prevalence of heart failure (HF) is increasing in developed countries. Considering the significant socioeconomic burden of HF, nationwide actions against HF are indispensable. To that end, relevant information on regional variations among HF patients are required.

Purpose

We aimed to explore the geographic variations in the characteristics and outcomes of hospitalized HF patients using a nationwide inpatient database.

Methods and results

Using the Diagnosis Procedure Combination database which is a nationwide inpatient database in Japan, we carried out a comprehensive analysis of 447,818 hospitalized patients with HF (median age 81 years, 238,192 men) who were admitted between January 2010 and March 2018 in Japan. We divided the study population into seven geographical regions based on the location of the admitted hospital. Background characteristics were almost similar among all seven regions. The implementation rates of intubation, hemodialysis, inotropic agent, and advanced circulatory supports including intra-aortic balloon pumping and extracorporeal membrane oxygenation varied among the seven regions. There was a significant difference in the length of hospital stay and the in-hospital mortality among the seven regions. The multivariable logistic regression analysis including baseline clinical charasteristics and medication administered within two days after hospital admission fitted with a generalized estimation equation for in-hospital mortality showed that there was still a significant difference in the in-hospital mortality among the seven regions (Table).

Conclusion

The analysis of a nationwide inpatient database showed that geographical variations existed regarding the outcomes of patients hospitalized for HF. This suggests the necessity of further efforts to establish a standardized medical care system in this era of HF pandemic.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grants from the Ministry of Health, Labour and Welfare, Japan (19AA2007 and H30-Policy-Designated-004) and the Ministry of Education, Culture, Sports, Science and Technology, Japan (17H04141)
Inverse association of mortality and BMI in patients with cardiomyopathy of any etiology
Authors: Brazile T , Mulukutla S , Thoma F , Saba S
Published: November 2020

Background

Obesity is a worldwide epidemic that has been associated with poor outcomes. Previous studies have demonstrated an inverse relationship between body mass index (BMI) and patients' outcomes, the “obesity paradox”, in several diseases.

Purpose

We sought to evaluate whether the obesity paradox applies to cardiomyopathy patients of all etiologies, using all-cause mortality as the primary endpoint.

Methods

We conducted a retrospective study of cardiomyopathy patients (n=18,003) seen within the UPMC network between January 2011 and December 2017. Patients were divided into 4 BMI categories (underweight, normal weight, overweight, and obese) and stratified by left ventricular ejection fraction (LVEF): <20%, 20–35%, and 36–50%. A Cox proportional hazards model was created to assess the independent predictive value of BMI on mortality.

Results

Over a median follow-up of 2.28 years, higher BMI was associated with better survival for the overall cohort (Figure) and within LVEF strata (p<0.0001). The most common cause of hospitalization was subendocardial infarction among underweight and normal weight patients and heart failure among overweight and obese patients. Cox proportional hazards model showed that BMI, age, and comorbid conditions of COPD, CKD, and CAD are independent predictors of death.

Conclusion

Our results support the existence of an obesity paradox impacting all-cause mortality in cardiomyopathy patients of all etiologies even after adjusting for LVEF. Additional research is needed to understand the effect of weight loss on survival once a diagnosis of cardiomyopathy is established.

Figure 1. Kaplan-Meier Survival Estimates

Funding Acknowledgement

Type of funding source: None
A real-world assessment of the burden associated with hospitalizations in US patients with heart failure and left ventricular ejection fraction (LVEF) greater than 40%
Authors: Lahoz R , Studer R , Farries G , Proudfoot C , Suminska S , Watkin A , Fagan A , Corda S , Houchen E , Mather P.J
Published: November 2020

Background and purpose

Heart failure (HF) is one of the leading causes of hospitalization among older adults and is associated with a large burden of disease for the individual, the patient's family, healthcare systems, and society. This study assessed the burden of hospitalizations in patients with HF with LVEF >40% in the United States (US).

Methods

This retrospective, non-interventional study identified adult patients with incident or prevalent HF in Optum® de-identified Electronic Health Record (EHR) dataset (2007–2018) between 01/01/2013 and 31/12/2017. Optum's longitudinal EHR repository is derived from dozens of healthcare provider organizations in the US, that include more than 700 Hospitals and 7000 Clinics; treating >95 million patients receiving care in the US. Patients were followed for up to 1 year or until last active date whichever occurred first. Comorbidities, all-cause hospitalizations (AcH) and primary cause HF hospitalizations (HFH) were analysed.

Results

120,606 patients with HF and LVEF >40% (54% female) with a mean (SD) age of 71 (13) yrs were included, representing 80,324.74 patient-yrs follow-up (days). Common comorbidities were hypertension (91.8%), ischemic heart disease (IHD, 71.4%), atrial fibrillation (AF, 54.8%), renal disease (54.1%), type 2 diabetes (T2D, 50.7%), obesity (44.6%) and anemia (39%). Comorbidities including IHD (72.9% vs. 68.4%), AF (56.4% vs. 51.6%) and T2D (51.1% vs. 49.9%) were more often recorded in patients with LVEF >40-≤60% than >60% cohort while hypertension (91.6% vs. 92.2%), renal disease (53.8% vs. 54.6%), obesity (43.9% vs. 46.1%) and anemia (38.1% vs. 40.9%) had significantly higher frequency in the LVEF >60% cohort. The annualized AcH rate for patients with LVEF>40% was 1.44 and annualized HFH rate was 0.24 with a median length of stay of 3 and 4 days, respectively. Annualized hospitalization rates were significantly higher for women than men (both AcH and HFH). AcH rates were significantly higher and HFH rates were significantly lower for patients with LVEF>60% compared with LVEF >40-≤60.

Conclusions

This study demonstrates that patients with HF and LVEF >40% experience significant burden from comorbidities and hospitalizations from any-cause and for HF. The hospitalization rates are higher in women (both AcH and HFH) or patients with LVEF >60% (AcH only). Further focus on reduction of hospitalizations and interdisciplinary management of patients with HF should be warranted.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Novartis Pharma AG
Concordance between patient and physician reported symptoms in patients with heart failure and a LVEF equal to or less than 60%: a multinational survey in the EU
Authors: Fonseca A.F , Corda S , Lahoz R , Proudfoot C , Jackson J , Cotton S , Studer R
Published: November 2020

Background and purpose

Heart Failure (HF) is associated with symptoms such as dyspnoea and fatigue, however, physicians and patients' perception of HF symptoms may differ. This study aimed to explore the extent to which symptoms experienced by patients with HF are recognized by their physician and if physicians over- or under-reported HF symptoms.

Methods

A cross-sectional study of patients with HF was conducted in France, Germany, Italy, Spain and the United Kingdom (Disease Specific Programme in HF by Adelphi Real World). Patient record forms (PRFs) were completed by 257 cardiologists and 158 general practitioners (GPs) for consecutively consulting patients. The same patients were invited to complete a patient self-completion questionnaire (PSC). Only responses from PRFs with an associated PSC were analysed. Concordance was calculated as agreement between PSC and PRF when both were aligned with the presence or absence of HF symptom out of the total number of matched pairs. The over- or under-reporting of the occurrence of symptoms by the physicians relative to patient-reported symptoms was also calculated by taking the patient perspective and evaluating how often a patient-reported symptom was not recognized in the PRF (physician under-reporting) and vice versa (physician over-reporting).

Results

792 HF patients with LVEF ≤60% (35% female) with a mean age of 68.6 years were included. 58% of PRFs were completed by cardiologists and 42% by GPs. The most common patient reported HF symptoms were dyspnoea when active (74%), fatigue (59%) and oedema (42%) (Figure 1a).

Overall, a high concordance rate was observed in reporting of HF symptoms between patients and their physicians ranging between 75% for fatigue and 94% for gastric/intestinal discomfort (Figure 1b). In non-concordant cases, most symptoms were under-reported by physicians, except dyspnoea when active and fatigue/weakness which were over-reported in 34/33%, respectively. The frequency of over-reporting of HF symptoms by the physicians was higher for more frequently patient reported symptoms while under-reporting was observed in less frequently reported symptoms such as gastric/intestinal discomfort, swelling of abdomen, inability to sleep, paroxysmal nocturnal dyspnoea and orthopnoea (Figure 1c).

Conclusions

The current study suggests that there is an overall high concordance between physicians and patients in reporting HF symptoms. However, while physicians were aware of the most prevalent HF symptoms experienced by patients, it was more common to under-report the less frequent HF symptoms. Ensuring patient education and good communication between patients and their physicians might help better and earlier identification of HF symptoms.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Novartis Pharma AG
Dementia screening in elderly high-risk patients following heart failure decompensation may predict unfavorable long-term clinical outcomes
Authors: Stepien K , Furczynska P , Zalewska M , Nowak K , Wlodarczyk A , Owsianka I , Skorek P , Zalewski J , Nessler J
Published: November 2020

Background

Recently heart failure (HF) has been found to be a new dementia risk factor, nevertheless their relations in patients following HF decompensation remain unknown.

Purpose

We sought to investigate whether a screening diagnosis for dementia (SDD) in this high-risk population may predict unfavorable long-term clinical outcomes.

Methods

142 patients following HF decompensation requiring hospitalization were enrolled. Within a median time of 55 months all patients were screened for dementia with ALFI-MMSE scale whereas their compliance was assessed with the Morisky Medication Adherence Scale. Any incidents of myocardial infarction, coronary revascularization, stroke or transient ischemic attack (TIA), revascularization, HF hospitalization and bleedings during follow-up were collected.

Results

SDD was established in 37 patients (26%) based on the result of an ALFI-MMSE score of <17 points. By multivariate analysis the lower results of the ALFI-MMSE score were associated with a history of stroke/TIA (β=−0.29, P<0.001), peripheral arterial disease (PAD) (β=−0.20, P=0.011) and lower glomerular filtration rate (β=0.24, P=0.009). During the follow-up, patients with SDD were more often rehospitalized following HF decompensation (48.7% vs 28.6%, P=0.014) than patients without SDD, despite a similar level of compliance (P=0.25). Irrespective of stroke/TIA history, SDD independently increased the risk of rehospitalization due to HF decompensation (HR 2.22, 95% CI 1.23–4.01, P=0.007).

Conclusions

As shown for the first time in literature patients following decompensated HF, a history of stroke/TIA, PAD and impaired renal function independently influenced SDD. In this high-risk population, SDD was not associated with patients' compliance but irrespective of the stroke/TIA history it increased the risk of recurrent HF hospitalization.

The survival free of rehospitalization

Funding Acknowledgement

Type of funding source: None
Clinical impact of the determination of natriuretic peptides on long-term follow-up of patients treated in the Heart Failure Unit
Authors: Perea Armijo J , Lopez Aguilera J , Duran Torralba C , Castillo Dominguez J.C , Anguita Sanchez M
Published: November 2020

Introduction

The use of natriuretic peptides has spread in recent years as a diagnostic tool in patients with heart failure (HF). However, its influence on the prognosis of these patients has not been clearly established. Thus, our main aim was to know the characteristics of patients with increased levels of NT-proBNP and to analyze its impact on long-term prognosis in terms of mortality and readmissions due to heart failure.

Material and methods

We selected cases from the heart failure unit at HURS which had a NT-proBNP determination at first consultation. Patients were divided into two groups: GROUP 1 (NT-ProBNP <10000) and GROUP 2 (NT-ProBNP >10000). Clinical, echocardiographic and treatment variables were collected and patients were followed up for readmissions due to heart failure and all-cause mortality.

Results

A total of 280 patients were selected. The mean age of the cohort was 66.74±13.88 years and was male-dominated (64%). In group 1, there was a higher initial left ventricular ejection fraction (LVEF) (43.19% vs 40.36%; p=0.057), lower basal creatinine (1.13 mg/dL vs 1.53 mg/dL; p=0.001), lower creatinine at the end of follow-up (1.27 mg/dL vs 1.79 mg/dL; p=0.001) and a lower NT-proBNP at the end of follow-up (4039 pg/mL vs 17140 pg/mL; p=0.000) than in group 2. In addition, group 2 showed a higher percentage of chronic kidney disease (55% vs 29%; p=0.000) than group 1, with no differences in their main variables. With 110 months of follow-up, patients with NT-proBNP levels>10000 had a similar hospital readmission rate compared to the group with lower NT-proBNP levels (81.2% vs 84.8% log rank p=0.133).With a mean of 130.01±9.11 months of follow-up, patients with NT-proBNP levels>10000 had a tendency to higher mortality from any cause than those with lower NT-proBNP levels (84.4% vs 48.4%, log rank p=0.000).

Conclusion

Patients with NT-proBNP levels>10000 are associated with a lower LVEF at baseline and a higher proportion of chronic kidney disease. In the long term, patients with NT-proBNP levels>10000 had the same rate of readmissions for heart failure but a higher rate of death from any cause.

Kaplan-Meier analysis

Funding Acknowledgement

Type of funding source: None
Exploring sex-specific patterns of mortality predictors among patients undergoing cardiac resynchronization therapy: a machine learning approach
Authors: Tokodi M , Behon A , Merkel E.D , Kovacs A , Toser Z , Sarkany A , Csakvari M , Lakatos B.K , Schwertner W.R , Merkely B , Kosztin A
Published: November 2020

Background

The relative importance of variables explaining sex differences in outcomes is scarcely explored in patients undergoing cardiac resynchronization therapy (CRT).

Purpose

We sought to implement and evaluate machine learning (ML) algorithms for the prediction of 1- and 3-year all-cause mortality in patients undergoing CRT implantation. We also aimed to assess the sex-specific differences and similarities in the predictors of mortality using ML approaches.

Methods

A retrospective registry of 2191 CRT patients (75% males) was used in the current analysis. ML models were implemented in 6 partially overlapping patient subsets (all patients, females or males with 1- or 3-year follow-up data available). Each cohort was randomly split into a training (80%) and a test set (20%). After hyperparameter tuning with 10-fold cross-validation in the training set, the best performing algorithm was also evaluated in the test set. Model discrimination was quantified using the area under the receiver-operating characteristic curves (AUC) and the associated 95% confidence intervals. The most important predictors were identified using the permutation feature importances method.

Results

Conditional inference random forest exhibited the best performance with AUCs of 0.728 [0.645–0.802] and 0.732 [0.681–0.784] for the prediction of 1- and 3-year mortality, respectively. Etiology of heart failure, NYHA class, left ventricular ejection fraction and QRS morphology had higher predictive power in females, whereas hemoglobin was less important than in males. The importance of atrial fibrillation and age increased, whereas the relevance of serum creatinine decreased from 1- to 3-year follow-up in both sexes.

Conclusions

Using advanced ML techniques in combination with easily obtainable clinical features, our models effectively predicted 1- and 3-year all-cause mortality in patients undergoing CRT implantation. The in-depth analysis of features has revealed marked sex differences in mortality predictors. These results support the use of ML-based approaches for the risk stratification of patients undergoing CRT implantation.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Research, Development and Innovation Office of Hungary