bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the incidence of cerebral embolic events underestimated in Takotsubo cardiomyopathy?
Authors: Lepage S , Ilinca M , Vignola A , Trudel-Deschenes C , Daneault-Peloquin I , Malick M
Published: October 2024

Introduction

Although initially considered a benign cause of transient left ventricular dysfunction, Takotsubo cardiomyopathy (TCM or stress cardiomyopathy) has become an increasingly recognized cause of cerebral embolic events. Prior case series have suggested a 0.9% to 3% risk of ischemic stroke following the diagnosis of TCM. With the growing number of cases of stress cardiomyopathy reported since the COVID pandemic, we want to evaluate if the risk of stroke in the literature has been underestimated.

Purpose

In our study, we want to evaluate the risk of ischemic stroke one year following the diagnosis of Takotsubo cardiomyopathy in our university health centre. We also want to evaluate the time interval between the incidence of stroke and the initial diagnosis of TCM.

Methods

In this retrospective single-centre observational study, we collected data from 267 consecutive patients hospitalized for a diagnosis of Takotsubo cardiomyopathy (confirmed by echocardiography and cardiac catheterization) between May 2008 and December 2017 at our medical centre in Sherbrooke. All patients were followed for a minimum of one year. We excluded 14 patients with a prior history of stroke or a diagnosis of atrial fibrillation in the year following the diagnosis of TCM. We used a descriptive statistical analysis to evaluate the rate and time to event up to 1 year after the diagnosis.

Results

253 patients were included in the study. The cohort was composed of 220 females (88% of the population), and the mean age was 69 years (SD: 11.8 years). Among this population, we identified 15 patients presenting with a stroke within a year after the diagnosis of stress cardiomyopathy, with a crude incidence of 5.9%. The median time interval between the incidence of stroke and the initial diagnosis of TCM was 17 days (2 to 298 days; an inter-quartile range of 3 to 105 days). The proportion of patients that reached the primary endpoint in the first 30 days was 67%.

Conclusion

According to our study, the risk of stroke in the year following the diagnosis of TCM is significantly higher than what is currently described in the literature. The fact that 10 of the 15 events occurred in the first 30 days may suggest a therappy design to lower the risk during that critical period could be explored. However, further studies are needed to address this issue.
Independent risk factors of ejection fraction deterioration post discharge in hospitalized heart failure patients with mildly reduced ejection fraction
Authors: Wu M X , Peng X , Zhu Y L , Liu Z C , Huang H B , Zhang L L , Liao M , Zhao W J , He W F , Tan D , Zeng J P
Published: October 2024

Background

The identification of independent risk factors for left ventricular ejection fraction (LVEF) deterioration is of clinical importance in patients diagnosed heart failure with mildly reduced ejection fraction (HFmrEF). This study aimed to determine the independent risk factors of LVEF deterioration post discharge among hospitalized HFmrEF patients.

Methods

This retrospective study analyzed data from 807 HFmrEF patients admitted to our hospital between January 2015 and August 2020. LVEF values were assessed by echocardiography between 6 months and 1 year after discharge. Patients were followed up to a mean of 33 months. The primary endpoint was disease progression expressed as heart failure with reduced ejection fraction (HFrEF) between 6 months and 1 year post discharge. The secondary endpoint was all-cause death. Multivariate logistic regression analysis was conducted to identify independent risk factors associated with LVEF deterioration.

Results

There were 225 patients progressed to HFrEF between 6 months and 1 year post discharge. All-cause death was significantly higher in HFrEF patients (43%) compared to patients with stable LVEF (unchanged or improved, 24%, P<0.001). Multivariate logistic regression analysis showed that the independent risk factors associated with worsening LVEF in patients with HFmrEF were: female (OR=1.71, 95% CI 1.14 to 2.57, P=0.009), higher NT-proBNP (≥2312 pg/ml, OR=1.71, 95% CI 1.14 to 2.57, P=0.010), higher uric acid (≥318 µmol/L, OR=11.63, 95% CI 7.89 to 17.15, P<0.001), and larger end-diastolic left ventricular dimension (OR=1.05, 95% CI 1.02 to 1.08, P<0.001).

Conclusion

Results of this study might help risk stratification to identify hospitalized HFmrEF patients with increased risk of progression to HFrEF post discharge. Patients with above clinical features should undergo more intensively monitoring and enhance care adherence to HF guideline medications. Future studies are needed to validate if tailored guideline adherence management strategies for post-discharged HFmrEF patients based on personalized risk stratification could mitigate LVEF progression and improve survival of these patients.
The impact of ethnicity on clinical outcomes in patients with heart failure and atrial fibrillation
Authors: Fox S , Champsi A , Hardy E , Bunting K , Kotecha D
Published: October 2024

Introduction

Heart failure (HF) and atrial fibrillation (AF) are increasingly prevalent and associated with substantial morbidity (1,2). When HF and AF co-exist, the outcome profile is significantly worse than for either condition in isolation (3). Ethnic background is known to influence disease outcomes and treatment efficacy (4), but there is limited knowledge about how HF, AF and ethnicity interact on mortality and hospital admission.

Purpose

This study aims to address the null hypothesis of no difference in death and cardiovascular events comparing non-white and white patients with HF and concomitant AF, and assess the differential impact of ethnicity in patients with these conditions.

Methods

Individual patient data were obtained from 12 randomized controlled trials (RCTs) in patients with HF. RCT data were harmonised and meta-analysed to investigate the interaction of baseline heart rhythm (sinus rhythm versus atrial fibrillation) and ethnicity (non-white versus white). The primary outcome of all-cause mortality and secondary outcome of cardiovascular (CV)-related mortality were analysed using adjusted Cox regression models and propensity-score matching.

Results

16,713 HF patients were included of which 1,899 (11%) were non-white, median age 66 (interquartile range [IQR] 57-73) and 4,703 (28%) women. During median follow-up of 1.4 years (IQR 0.8-2.3), death occurred in 394 (21%) non-white patients and 2,142 (15%) white patients; adjusted hazard ratio (HR) 1.36, 95% CI 1.20-1.54; p<0.001. The impact of ethnicity was greater in patients with coexisting HF and AF (non-white versus white HR 2.05; 95% CI 1.55-2.70; p<0.001), than in those with HF in sinus rhythm (non-white versus white HR 1.24; 95% CI 1.08-1.41; p=0.002). A significant interaction was evident between ethnicity and rhythm status for all-cause mortality (p=0.003), with similar findings using propensity-score matching (Figure 1). An exploratory analysis of beta-blockers versus placebo demonstrated divergent efficacy with respect to mortality for non-white (HR 1.00, 95% CI 0.79-1.27; p=0.99) and white patients (HR 0.70, 95% CI 0.63-0.78; p<0.001); p-interaction=0.008 (Figure 2). For cardiovascular hospitalisation, the non-white cohort also had higher rates, with greatest disparity in patients with combined HF and AF (non-white versus white HR 1.80, 95% CI 1.63-2.37; p<0.001) compared to HF in sinus rhythm (non-white versus white HR 1.23, 95% CI 1.11-1.36; p<0.001); p-interaction=0.012 in propensity-matching.

Conclusion

Non-white patients with HF suffer from substantially higher rates of death and hospitalisation than corresponding white patients, with the presence of comorbid AF significantly worsening this ethnicity-related disparity. In those with HF in sinus rhythm, beta blockers were found to be significantly less effective at reducing mortality in non-white patients.Figure 1 Figure 2
Sex-specific association of NT-proBNP with clinically inapparent structural heart disease in the general population: results from the STAAB study
Authors: Morbach C , Gelbrich G , Schmidbauer L , Sahiti F , Chen M , Cejka V , Frantz S , Heuschmann P U , Stoerk S
Published: October 2024

Background

Guidelines recommend echocardiography in subjects beyond defined levels of natriuretic peptides. The ACC/AHA guidelines on heart failure (HF) state echocardiographic signs of structural heart disease (SHD) that define the precursor stage B of heart failure.

Purpose

To study the age- and sex-specific association between echocardiographically assessed structural heart disease (echoSHD) and NT-proBNP levels in the general population.

Methods

The STAAB study investigates precursor stages of HF in the general population of a medium-sized city in Germany (source population 124,297 inhabitants as of 2011 census). Study participants were recruited between 12/2013 and 10/2017 from the source population without preceding HF diagnosis, stratified for sex and age (30-79 years). For this analysis, we excluded participants with previously diagnosed coronary artery disease. EchoSHD was accepted if one of the following criteria, diagnosed according to current echo guidelines, was detectable at echocardiography: left ventricular (LV) hypertrophy, LV dilation, reduced LV ejection fraction, moderate-to-severe LV valve disease, and LV diastolic dysfunction.

Results

Of 4,649 subjects analysed (93.6% of STAAB participants, age 30-79 years, 53.5% women), 863 (18.6%) had echoSHD. NT-proBNP depended strongly on age and sex (figure). Frequencies of echoSHD varied between women (23.0%) and men (13.5%; P<0.001). EchoSHD was associated with increased NT-proBNP levels in both women (geometric mean ratio 1.18, 95%CI 1.09–1.27, P<0.001; figure) and men (ratio 1.62, 1.46–1.79, P<0.001); P<0.001 for different ratios in both sexes. Of note, age did not influence these ratios as well as their difference (P=0.34 and P=0.95, resp.).

Conclusion

Clinically inapparent echoSHD was associated with higher levels of NT-proBNP, of a magnitude that was relevant in men. The sex difference in the strength of this relationship might be due to different pathophysiological processes leading to SHD and ultimately HF in women and men. It might also indicate the need for adopted definitions of echoSHD in women. Our results further point towards the need of age- and sex-specific NT-proBNP thresholds.NTproBNP according to sex, age, and SHD
Patient characteristics and mortality trends among octogenarians with heart failure over two decades - a Danish nationwide study
Authors: Garred C A H , Elmegaard M , Christensen D M , Zahir D , Malmborg M , Fosboel E , Pardeep J , Mcmurray J , Petrie M , Andersson C , Koeber L , Schou M
Published: October 2024

Background

Mortality rates among octogenarians with heart failure (HF) have changed little despite significant advancements in care over recent decades. Investigating the factors contributing to this trend may offer valuable insights for devising targeted management strategies for the oldest HF patients.

Purpose

We aimed to examine different patient characteristics associated with mortality among octogenarians with HF over the past 20 years.

Methods

From nationwide Danish healthcare registries, we included all patients with new-onset HF between 2001-2020 who were ≥ 80 years old at the time of diagnosis. The patients were categorized into 5-year calendar periods depending on the time of their diagnosis, the first period being between 2001-2005 and the last 2016-2020. The Kaplan-Meier estimator was used to assess the mortality risk. Mortality rates were examined with multivariable Cox regression models, comparing the first (reference) and the last calendar period and adjusting for predefined covariables.

Results

We included 47,754 octogenarian patients with new-onset HF, of whom 13,293 (51%) were diagnosed between 2001-2005 and 12,813 (49%) between 2016-2020. The distribution of males and females changed between the two calendar periods, with 5696 (43%) males in the first period and 6631 (52%) in the last period. The 3-year absolute mortality risk decreased by 8% [95% CI, 7.9-8.0] from 2001-2005 (64% [95% CI, 63.9-64.7]) to 2016-2020 (56% [95% CI, 55.3-56.7]) (p-value <0.001) (Figure 1). After adjustment for covariables, patients diagnosed in the last period exhibited a mortality hazard ratio (HR) of 0.94 [CI 95% 0.90-0.99] (p-value 0.02) compared to those diagnosed in the first period. An interaction was observed between the first and the last calendar periods among patients with a history of myocardial infarction and those aged <85 years. The survival rates improved over time for patients with a history of myocardial infarction (HR 0.80 [95% CI, 0.72-0.90], p-value for interaction<0.001), as well as for those aged between 80 and 85 years (HR 0.86 [95% CI, 0.80-0.91], p-value for interaction<0.001) (Figure 2).

Conclusion

Over two decades the mortality risk among octogenarians with HF has improved slightly, however it remains high. Patients with a history of myocardial infarction and those aged 80 to 85 years emerge as subgroups experiencing the most improved survival rates over time.3-year mortality riskMortality rates in selected subgroups
Disparities in clinical characteristics, treatment, and prognosis among immigrants and native patients in Denmark with new-onset heart failure and reduced ejection fraction
Authors: Sam Aiyad S A A , Vinding N E V , Butt J H B , Kroll J K , Larsson J E L , Schou M S , Fosbol E L F , Logstrup B B L , Schjodt I S , Jhund P S J , Kober L K , Gustafsson F G , Sattar N S , Mcmurray J M , Kristensen S L K
Published: October 2024

Background

Major variations exist in the causes, age at diagnosis, and outcomes of heart failure (HF) in patients from different parts of the world.

Purpose

To elucidate this issue further, we compared the characteristics and outcomes of immigrants living in Denmark and native Danish patients presenting with new-onset HF with reduced ejection fraction (HFrEF).

Methods

By linkage of the Danish Heart Failure Registry, and nationwide administrative registries, we identified patients with new onset HFrEF, from 2005-2021, grouped according to immigration status and, if not native Danish, region of origin, according to the World Bank classification. Outcomes were a 1) composite of HF hospitalization or all-cause death at 3 years follow-up, and 2) initiation and up-titration of guidelines-directed medical therapy (GDMT) at 12 months follow-up. Cox regression analyses adjusted for age, sex, calendar year, HF severity, socioeconomic status, and major comorbidities were used to compare the primary composite outcome.

Results

Of 33,297 patients included, 31,602 (97.9%) were native Danish patients (DK), 1031 (3.1%) were originally from Europe/Central Asia (EUR/CA), 439 (1.3%) from Middle East/North Africa (ME/NAF), 225 (0.7%) from South Asia (SA). The median time since immigration ranged from 20 to 30 years. Compared to DK, patients originating from ME/NAF, and SA were around 10 years younger (median age 62-64 vs. 71 years), had similar median left ventricular ejection fraction (30% vs. 30%), had lower New York Heart Association (NYHA) ≥ class III (14-16% vs. 23%), had more diabetes (39-51% vs. 20%) and ischemic heart disease (IHD) (69-75 vs. 48%), and had less atrial fibrillation (AF) (9-14% vs. 32%) (all p < 0.0001), patients from EUR/CA were generally similar to DK. The crude 3-year cumulative risk of the primary composite outcome was 34% (DK), 31% (EUR/CA), 27% (SA), and 23% (ME/NAF) (Figure 1) In adjusted analyses with DK as the reference, only ME/NAF was associated with a lower risk; hazard ratio (HR) 0.77 (95% confidence interval (CI) 0.62-0.94) (Figure 2). No major differences in the initiation and up-titration of GDMT were observed across groups.

Conclusions

Non-Western immigrants living in Denmark who presented with new-onset HFrEF had a distinct clinical profile, being generally younger, had lower NYHA class but similar LVEF, a greater prevalence of diabetes and IHD and less AF compared to native Danish patients. In addition, they had lower adjusted rates of the primary outcome of HF hospitalization or all-cause death and a similar likelihood of GDMT initiation and up-titration. The reasons for these differences deserve more research.Figure 1 Crude cumulative riskFigure 2 Adjusted rates
Influence of prior heart valve intervention on treatment and disease trajectory after diagnosis of heart failure with reduced ejection fraction
Authors: Sam Aiyad S A A , Ostergaard L M O , Ersboll M K E , Butt J G B , Petersen J K P , Begun X B , Schou M S , Gustafsson F G , Fosbol E L F , Kober L K , Kristensen L K
Published: October 2024

Background and aim

Among patients with heart failure with reduced ejection fraction (HFrEF), knowledge is scarce on whether patients with prior valvular heart disease (VHD) intervention are distinct regarding clinical characteristics, treatment, and prognosis.

Methods

Using the Danish Heart Failure Registry and nationwide administrative registries, we identified patients with new-onset HFrEF from 2008 to 2021. Within this cohort, patients with a prior VHD intervention were identified and matched 1:5 on age-, sex-, in/outpatient presentation, and year of HFrEF diagnosis with remaining patients (controls). Outcomes were 1) baseline use and up-titration of guidelines-directed medical therapy (GDMT) and implementation of implantable cardioverter-defibrillator or cardiac resynchronization therapy with pacemaker/defibrillator (ICD/CRT-P/D) at 6 months follow-up, and 2) a composite of HF hospitalization or all-cause death at 3 years follow-up. The Kaplan-Meier estimator and Cox regression models, adjusted for HF severity, socioeconomic status, and major comorbidities, were used to compare the composite outcome, with patients without prior heart valve intervention as reference.

Results

The study cohort comprised 32,713 patients, of whom 1196 (3.6%) underwent a prior VHD intervention (median time since intervention 10 months). After matching, the study population were 1151 cases (median age 74 years, 82% men), and 3769 matched controls. Among cases and controls, median left ventricular ejection fraction was similar (30% vs. 30%) and the proportion in New York Heart Association (NYHA) class II was alike (82% vs 83%). At the time of HFrEF diagnosis, numerically more cases were on a beta-blocker (62% vs. 53%), ACEi/ARB/ARNI (48% vs. 44%), MRA (19% vs. 14%), and more had an implementation of (ICD/CRT-P/D) (17 % vs. 7%) (Figure 1). At 6 months, ≥ 50% of the daily target dose was achieved in (46% vs. 46%) for beta-blockers, (47% vs. 47%) for ACEi/ARBs/ARNI, (31% vs. 33%) for MRA, and implementation of ICD/CRT-P/D was attained in (28% vs. 18%), among cases and controls, respectively (Figure 1). The 3-year risk of HF hospitalization or all-cause death was 25% in cases and 24% in controls (Figure 2) with no significant differences (hazard ratio (HR) 0.95 , 95% confidence interval (CI) 0.84-1.08) compared to controls.

Conclusions

Patients with new-onset HFrEF and prior VHD interventions received more GDMT and had a higher implementation of ICD/CRT-P/D at the time of HFrEF diagnosis. However, following diagnosis, no major differences in GDMT initiation and up-titration, implementation of ICD/CRT-P/D, and the adjusted rates of HF hospitalization or all-cause death were observed among patients with and without prior heart valve intervention.Figure 1 Guideline-directed medicationFigure 2 Crude cumulative risk
Assessing one-year risk of heart failure following first time myocardial infarction and subsequent five-year mortality risk: a nationwide study of 34,401 patients
Authors: Zahir D , Christensen D M , Elmegaard M E , Nouhravesh N N , Garred C G , Fosboel E F , Butler J B , Hernandez A H , Petrie M A R K , Kober L K , Schou M S
Published: October 2024

Introduction

A comprehensive understanding of the post-myocardial infarction (MI) trajectory leading to heart failure (HF) and its profound impact on long-term mortality is imperative for effective secondary prevention and risk assessment.

Methods

We conducted a registry-based nationwide cohort study of all Danish patients with a first MI during 2014 to 2020. Excluding patients with prior HF, individuals were followed for one year post-MI, assessing HF incidence through hospital admissions and visits to elective HF ambulatory clinics. Among those who survived one year, long-term mortality 1-6 years post-index MI was assessed using landmark analysis and Cox proportional hazards models adjusting for age, gender and comorbidities and hazard. Patients were categorized into three groups: not HF, referred for elective HF outpatient follow-up, and acute admission for HF.

Results

Among 34,301 individuals with a first MI and surviving the first year (median age 67.5, and 66.9 % male), 3.3 % were admitted acute for HF while 11.2 % had an elective HF outpatient follow-up within one year of the MI event (see Figure 1a). We observed a significant association between acute HF admissions post-MI and increased five-year mortality risk (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.40-1.90, p-value <0.001, see Figure 1b) (absolute 5-year risk: 18.4 %). In contrast, the five-year mortality risk for patients with elective outpatient HF follow-up was comparable to that of individuals without HF (HR 1.06 [0.94-1.19], p-value 0.34) (absolute 5-year risk: 9.6 vs 8.5 %).

Conclusion

Our findings suggest that acute admission for HF after a first time MI occur in 3.3 % of the patients with a subsequent significantly increased mortality risk compared to patients that do not develop clinical HF. Admission for HF in patients with a first time MI should be considered as a relatively rare but fatal complication.
Anxiety or depression in heart failure across the ejection fraction spectrum
Authors: Settergren C , Benson L , Dahlstrom U , Thorvaldsen T , Savarese G , Lund L H , Shahim B
Published: October 2024

Background

Anxiety or depression are commonly described in patients with heart failure (HF) but few data exist on characteristics and clinical outcomes associated with anxiety or depression across the different HF phenotypes.

Purpose

To assess the prevalence of patient characteristics and clinical outcomes associated with anxiety or depression in patients with HF with preserved, mildly reduced and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF).

Methods

Patients enrolled in the Swedish Heart Failure Registry between 2000-2021 were included. Self-reported anxiety or depression was collected using EuroQoL 5-dimensional questionnaire (EQ-5D) at baseline and follow-up visits. Anxiety or depression was categorized as "not anxious or depressed", "moderately anxious or depressed" or "severe anxious or depressed". The independent associations between baseline characteristics and presence of anxiety or depression were assessed by a multivariable multinominal regression analysis. Cox proportional hazards regressions were performed to model the time to first event according to levels of anxiety or depression. Outcomes included all-cause death and all-cause hospitalizations.

Results

A total of 45,247 patients were included among whom 58% reported none, 38% moderate and 5% severe anxious or depressed with similar distribution across the HF phenotypes (Figure). Several characteristics were associated with anxiety or depression with the strongest ones for severe versus none being higher NYHA class (OR 3.10 (2.77-3.47)), liver disease (OR 1.99 (1.56-2.55)), in-patient setting (OR 1.62 (1.43-1.84)), smoking (OR 1.75 (1.52-2.00)) while others were inversely related including male sex (OR 0.51 (0.46-0.56)), higher age (OR 0.60 (0.53-0.67)), referral to HF nurse clinic (OR 0.82 (0.72-0.94)) and higher income level (OR 0.68 (0.62-0.76)). The risk of all-cause death and all-cause hospitalizations increased with increasing levels of anxiety or depression across all HF phenotypes during 12 months of follow up. Severe anxiety or depression had a stronger association with all-cause death in hospitalized patients and all-cause hospitalizations in out-patients.

Conclusion

In this large contemporary cohort of patients with HF in a real-world setting, anxiety or depression was frequently and similarly distributed across all HF phenotypes. Higher NYHA class, liver disease and in-patient setting were strongly associated with the anxiety or depression while male sex, higher age, and higher income were inversely related with anxiety or depression. Anxiety or depression was significantly associated with worse outcomes at 12 months follow up.Proportion anxiety or depression
Exome sequencing in over 63,000 patients in TIMI trials uncovers pathogenic cardiomyopathy variant carriers with high risk for heart failure and cardiovascular death
Authors: Kany S , Melloni G E M , Jurgens S J , Berg D , Bonaca M , Giugliano R P , Wiviott S D , Bhatt D L , Steg P G , Raz I , Pirruccello J P , Sabatine M S , Ruff C T , Ellinor P T , Marston N A
Published: October 2024

Background

Rare genetic variants predisposing to cardiomyopathy (CMP) confer increased risk for adverse events. The prevalence of CMP variants in contemporary cardiovascular (CV) trials and their association with prevalent heart failure (HF) and incident HF hospitalizations (HHF) is not established.

Purpose

We aimed to identify carriers of rare pathogenic/likely pathogenic (PLP) variants for dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) in well-phenotyped clinical trial cohorts and to evaluate their prognostic significance.

Methods

Rare variants were identified from high-quality exome sequencing data from 5 large clinical trials (ENGAGE AF-TIMI 48, SAVOR-TIMI 53, PEGASUS-TIMI 54, DECLARE-TIMI 58, FOURIER (TIMI 59)). Putatively pathogenic variants for cardiomyopathy were identified using phenotype- and gene-specific curation of protein-truncating variants and high-confidence variant classifications from ClinVar. We conducted logistic regression for prevalent disease and Cox proportional hazard models for incident HHF, both adjusted by age, sex, trial, and first 10 principal components and using those without CMP variants as the reference. Sensitivity analysis by history of HF at baseline was performed for prospective outcomes.

Results

In 63,700 participants, we identified 866 CMP variant carriers of which 518 identified as DCM carriers (age 65±9 yrs, male 66%), 194 HCM carriers (65.5±9 yrs, male 69%), and 125 ARVC carriers (66±9 yrs, male 77%). Out of the 518 DCM variant carriers, 402 had a PLP variant in TTN.

DCM variant carriers had higher odds of history of HF (Odds ratio [OR] 1.94, 1.57-2.39, p<0.0001) whereas this was not observed for HCM variant carriers (OR 1.18, 0.85-1.65, p=0.33) or ARVC variant carriers (OR 1.23, 0.80-1.90, p=0.35).

Over a mean follow-up of 2.5 years, the rate of HHF was significantly higher for DCM variant carriers (Hazard ratio [HR] 1.58, 1.14-2.20, p=0.006), HCM variant carriers (HR 2.78, 1.87-4.13, p<0.001), and ARVC variant carriers (HR 1.89, 1.02-3.53, p=0.04). These associations were, if anything, stronger in patients without HF at baseline (HR 2.06, 1.30-3.25) than in patients with HF at baseline (HR 1.48, 1.12-1.95). DCM variant carriers also had a higher rate of CV death (HR 1.50, 1.05-2.12, p=0.02), which was not observed for HCM (HR 1.10, 0.57-2.11, p=0.78) or ARVC (HR 0.35, 0.09-1.41, p=0.14) variant carriers.

Conclusion

In 5 contemporary CV trials, CMP variant carriers have an increased rate of HHF, while DCM variant carriers also have a higher rate of CV death. These findings motivate better identification of these high-risk individuals and the incorporation of genetic testing in CV trials.
Multimorbidity patterns in adults admitted to hospital with heart failure: an analysis of 175 million hospitalisation episodes
Authors: Carson O , Batty J A , Del Toro T , Hall M
Published: October 2024

Background

The prevalence of heart failure (HF) is increasing as a result of population ageing, improved survival following myocardial infarction and the widespread uptake of evidence-based HF treatments. Greater understanding of multimorbidity patterns in patients with HF may enable the development of treatment strategies that target multiple, related long-term conditions (LTCs), producing synergistic benefits.

Purpose

To characterise multimorbidity patterns in patients with HF and compare these to a matched population without HF.

Methods

A retrospective matched cohort study was conducted using the United States National Readmission Database (NRD), 2010–2020. International Classification of Disease (ICD) codes were used to identify HF and 92 other common LTCs. The most frequent combinations of LTCs were identified for individuals with HF and a control cohort of individuals of the same age and sex, with a non-HF-related hospital admission in the same year (matched in a 1:5 ratio). Multivariable regression analysis (adjusted for age, sex, socioeconomic status, tobacco use, year of hospitalisation, and hospital characteristics) was used to evaluate the association between multimorbidity burden, length of stay (LOS; negative binomial regression) and 30-day readmission (logistic regression).

Results

From a total of 175,388,410 hospitalisation episodes, 3,913,924 individuals with an HF-related hospitalisation were identified and matched to 19,552,954 controls (Figure 1a). The median (interquartile range, IQR) age of a patient admitted with HF was 74 (63–85) years; 1,856,268 (47.5%) were female. The most common comorbidities in those with HF were hypertension (87.2 vs. 72.8% in matched controls), chronic kidney disease (CKD; 55.3 vs. 34.6%), coronary artery disease (CAD; 53.7 vs. 31.0%), dyslipidaemia (46.9 vs. 39.7%), diabetes (46.6 vs. 33.9%), atrial fibrillation (AF; 43.0 vs. 23.0%) and anaemia (33.2 vs. 30.1%; p all < 0.001). Patients with HF had a greater number of LTCs compared with matched controls (median [IQR] 7 [5–9] vs. 6 [4–8]; p < 0.001). From 2010–2020, the number of LTCs in those with an HF admission increased (from 6 [4–8] in 2020, to 8 [6–10] in 2020; Figure 1b). The most common multimorbidity patterns in those with HF are presented in Figure 2. In the HF cohort, a greater multimorbidity burden was associated with a longer LOS (+6% for each additional LTC; 95% confidence interval [CI] 5–7%; p<0.001) and greater risk of 30-day readmission (adjusted odds ratio [aOR] for 6 vs. 0 LTCs: 1.15, 95% CI 1.08–1.22; aOR for ≥12 vs. 0 LTCs: 1.54, 95% CI 1.45–1.64).

Conclusions

Patients admitted to hospital with HF have a significant burden of multimorbidity, which has increased over time and is associated with increased length of stay and unplanned hospital re-admission. The high prevalence of multiple LTCs warrants the development of novel treatment strategies that target common multimorbidity patterns observed in HF.
Sex-specific clinical outcomes and healthcare resource utilization in the 5 years following hospitalization for heart failure
Authors: Averbuch T , Lee S F , Zagorski B , Pandey A , Petrie M C , Biering-Sorensen T , Xie F , Van Spall H G C
Published: October 2024

Background

Heart failure (HF) a leading cause of hospitalization, and sex differences in care have been described.

Purpose

We assessed sex-specific clinical outcomes and healthcare resource utilization following hospitalization for HF.

Methods

This was an exploratory analysis of patients hospitalized for HF across 10 Canadian hospitals enrolled in the Patient-Centred Care Transitions in HF pragmatic cluster-randomized trial. Primary outcome was all-cause mortality. Secondary outcomes included all-cause readmissions, HF readmissions, emergency department (ED) visits, and healthcare resource utilization. Outcomes were obtained via linkages with administrative datasets.

Results

The 4441 patients (50.7% female) had high event rates. At 5 years of follow-up, 63.6% male and 65.5% of male and female patients, respectively, had died (p=0.19); 85.4% and 84.4% of male and female patients, respectively, were readmitted with no sex differences in mean [SD] all-cause readmissions (males, 2.8 [7.8] and females, 3.0 [8.4], p=0.54) or HF readmissions (males, 0.9 [3.6] and females, 0.9 [4.5], p=0.80) per person. The mean (SD) annual total healthcare costs per patient was $80334 (116762) for males and $81010 (112625) for females, with no sex difference (p=0.90); however, there were sex differences in cost breakdown: males incurred greater costs from specialist, hemodialysis, and day surgical care, and females incurred greater costs from home visits and long-term care.

Conclusions

Males and females were at similarly high risk of mortality and readmissions, and had similar total healthcare costs following hospitalized for HF. Notwithstanding similar risks, males received relatively more specialist and invasive care, and females received relatively more supportive care.
Excess mortality and hospitalizations associated with seasonal influenza in patients with heart failure
Authors: Modin D , Claggett B , Johansen N D , Solomon S D , Trebbien R , Krause T G , Jensen J U S , Martel C J M , Andersen M P , Gislason G , Biering-Soerensen T
Published: October 2024

Background

Influenza virus may cause severe infection in patients with heart failure. It is accepted that influenza infection is associated with increased morbidity and mortality in patients with heart failure. However, less is known about the excess burden of morbidity and mortality caused by influenza infection in patients with heart failure at a population level.

Purpose

To estimate the excess burden of morbidity and mortality as determined by annual excess number of deaths and hospitalizations associated with influenza infection in patients with heart failure.

Methods

We collected nationwide data on weekly number of deaths and hospitalizations among patents with heart failure in Denmark and weekly estimates of influenza circulation as determined by the proportion of positive influenza samples analyzed at all Danish Hospitals. These data were correlated in a time series linear regression model and this model was used to estimate the annual excess number of deaths and hospitalizations attributable to influenza circulation among patients with heart failure in Denmark.

Results

Data were available from 2010 to 2018 encompassing 8 influenza seasons with an annual mean of 25180 samples tested for influenza. Among an annual mean of 70570 patients with heart failure, our model estimated that influenza activity was associated with an annual excess of 250 all cause deaths (95%CI 144-489) corresponding to 2.6% of all all-cause deaths (95%CI 1.5% - 5.1%). Similarly, influenza activity was associated with an annual excess of 115 cardiovascular deaths (95%CI 62-244) corresponding to 2.9% of all cardiovascular deaths (95%CI 1.5% - 6.1%) among patients with heart failure. Influenza activity was also associated with an annual excess of 251 hospitalizations for pneumonia or influenza (95%CI 107-533) corresponding to 5.0% of all hospitalizations for pneumonia or influenza.

Conclusion

Our results indicate that influenza activity likely causes substantial morbidity and mortality among patients with heart failure. Notably, our study suggests that approximately 2.6% of all deaths and 5.0% of all hospitalizations with influenza or pneumonia may be attributed to influenza in patients with heart failure.
Explainable machine learning and multi-modal data for predicting readmission in patients with heart failure
Authors: Chae R , Zhou J , Car J , Zhu T , Lu L
Published: October 2024

Background

Cardiovascular diseases (CVDs) are among the leading causes of mortality and morbidity globally, with an estimated 1 million hospital admissions for CVD in England in 2019/20, leading to 5.5 million bed days. In addition, patients with CVDs have a notably high rate of hospital readmission, with approximately one in four patients experiencing heart failure (HF) being readmitted within one month of discharge. We explored whether machine learning models trained on electrocardiogram (ECG) and patient electronic health records (EHRs) can support decision-making and risk management and ultimately improve health outcomes for HF patients.

Purpose

The project aims to develop a machine learning model to predict health outcomes for HF patients. To test the hypothesis, we trained and tested an explainable machine learning model to predict the risk of mortality and hospital readmission rate for HF patients.

Methods

We used EHR data and tabulated ECG records to train an XGBoost model to predict the risk of 30-day mortality and 30-day hospital readmission for HF patients. EHR data from a cohort of 2,868 patients with their ECG records were used for model development. We extracted a total of 78 features from the ECG data, such as heart rate variability (HRV), P-wave durations, and QT intervals. These ECG features were combined with coded and free-text EHR data (e.g., demographic information, diagnosis, medication history, and lab results) and used as tabular inputs to the XGBoost model. Of the 2,868 patients, an internal set of 574 patients stratified by age, sex, and health outcomes (30-day mortality and 30-day hospital readmission) were held out for testing.

Results

Among 2,868 HF patients with 10-year follow-up, 1065 patients were reported for mortality or hospital readmission within 30 days of discharge. When the machine learning model was trained on ECG data in addition to EHR data, the model was able to predict patient mortality and hospital readmission rate in the test set with an area under the curve (AUC) of 0.91 and 0.70, respectively. For mortality prediction, the model achieved a sensitivity and specificity of 0.81 and 0.82, respectively, when employing an operating point with minimum difference between the sensitivity and specificity. When the threshold was adjusted to favor sensitivity at 0.91, the model specificity decreased to 0.74. The machine learning model also identified high sensitive troponin levels, QT dispersion, and lactate dehydrogenase levels as features of high importance for predicting the outcomes for HF patients.

Conclusions

Our developed machine learning model was able to predict mortality and readmission risks in HF patients using multi-modal data. Upon further validation, the machine learning model has the potential to be tested for supporting clinical decision-making and risk management for HF patients.ROC CurveFeature Importance
Assessment of quality of life using EuroQol 5-Dimension questionnaire level sum score in patients with HFrEF, HFmrEF, and HFpEF: a patient-level meta-analysis of DAPA-HF and DELIVER
Authors: Yang M , Kondo T , Talebi A , Jhund P S , Vaduganathan M , Hernandez A F , Lam C S P , Martinez F A , De Boer R A , Kosiborod M N , Kober L , Ponikowski P , Sabatine M S , Solomon S D , Mcmurray J J V
Published: October 2024

Background

The impact of SGLT2 inhibitors on generic quality of life in heart failure (HF) has not been evaluated.

Purpose

To quantify individual dimension scores and the Level Sum Score of the EQ-5D-5L (EQ-5D-LSS) in patients with HFrEF and HFmrEF/HFpEF, the association between these scores and outcomes, and the impact of treatment with dapagliflozin on these scores.

Methods

The 5 dimensions of the descriptive section of the EQ-5D-5L include mobility ("walking around"), self-care ("washing or dressing self"), usual activities ("e.g., work, study, housework, family or leisure activities"), pain/discomfort ("pain or discomfort"), and anxiety/depression ("anxious or depressed"). Each dimension is divided into 5 levels (1-5) i.e., no problem, slight problem, moderate problem, severe problem, and extreme problem (cannot do activity/extreme symptom). All dimensions and severity levels contribute equally when calculating the LSS. The individual dimension scores and the LSS were analyzed in patients with HFrEF and HFmrEF/HFpEF in the DAPA-HF and DELIVER trials, which compared dapagliflozin to placebo.

Results

Scores varied markedly by question with 37/30/33% of patients reporting no, a slight, or a moderate or greater problem for mobility; 67/20/13% for self-care; 40/33/27% for usual activities; 45/32/23% for pain/discomfort; and 57/27/16% for anxiety/depression. Compared to lower (better) LSS, patients with higher (worse) LSS were more often female, had more comorbidities, and had worse HF status. Compared to patients free from any problem across all dimensions (i.e. LSS of 5), the hazard ratios (95% CI) for time to first cardiovascular death or worsening HF were 1.27 (1.10-1.47), 1.70 (1.46-1.98), and 2.31 (1.88-2.85) in those with LSSs of 6-10, 11-15, 16-25 points, respectively. Patients randomized to dapagliflozin experienced greater improvement and less worsening across all EQ-5D-5L dimensions except pain/discomfort (Figure).

Conclusions

The EQ-5D-5L individual dimension questions revealed problems not often associated with (pain) or quantified in (anxiety/depression) HF and demonstrated the marked limitation of ordinary activities experienced by many patients with HF. Most EQ-5D-5L domain questions, including anxiety/depression, improved with dapagliflozin. The LSS, incorporating these domains was associated with clinical outcomes.
Prevalence of stage B heart failure in healthy adults and people with type 2 diabetes
Authors: Cowley A C , Dattani A , Yeo J L , Brady E M , Marsh A , Sian M , Parke K S , Wormleighton J , Arnold J R , Singh A , Mccann G P , Gulsin G S
Published: October 2024

Introduction

People with Type 2 Diabetes (T2D) are at increased risk of heart failure, and as such are classified as having Stage A Heart Failure (SAHF). Those with additional evidence of raised filling pressures, biochemical or structural cardiac changes, without heart failure symptoms, are deemed to have Stage B heart failure (SBHF). Identifying patients with SBHF may help determine those at highest risk of disease progression.

Purpose

The aim of this work was to assess the prevalence of SBHF in a cohort of asymptomatic healthy volunteers and people with T2D characterised according to current American Heart Association/American College Cardiology/Heart Failure Society of America.

Methods

A single-centre, prospectively recruited cohort of middle-aged asymptomatic adults with T2D and healthy volunteers, with no history or signs of cardiovascular disease, underwent comprehensive cardiac phenotyping with transthoracic echocardiography and circulating brain natriuretic peptide. Healthy volunteers with risk factors for heart failure, including hypertension and obesity, were excluded from analysis. Prevalence of SBHF was determined by comparing cardiovascular data to proposed standards, left ventricular ejection fraction and global longitudinal strain parameters were omitted from analysis due to data availability.

Results

We included 383 T2Ds (diabetes duration 9(5,15) years) and 65 healthy volunteers (Table 1); 91% of those with T2D and 65% of healthy volunteers met ≥1 criteria for SBHF (Table 2). Median number of SBHF criteria met in the T2D cohort was 3 (2,4); in particular, a large proportion of the cohort met defined cut offs for relative wall thickness (70.6%), lateral e’ (62.2%), septal e’ (54.1%) and LV wall thickness (47.4%). Of the 65 healthy volunteers, median number of SBHF criteria met was 1 (0,2.5). In healthy volunteers, SBHF was most commonly defined by lateral e’ (40.0%), septal e’ (38.3%), relative wall thickness (32.2%), left atrial volume indexed (22.4%) and serum brain natriuretic peptide (23.3%). Of note, brain natriuretic peptide levels met current SBHF parameters in 18.8% of healthy volunteers and 9.9% people with T2D, which may be attributable to the exclusion of obesity in the healthy volunteer group.

Conclusion

Using currently proposed standards, a high proportion of middle-aged asymptomatic people with T2D, and healthy volunteers without any risk factors for heart failure, would be categorised as having SBHF. These data strongly suggest that the majority of the proposed parameters for the definition of SBHF are not specific for a UK population and if applied will incorrectly classify many asymptomatic people at high risk of developing heart failure.
Clinical correlates and prognostic impact of cognitive decline in patients with heart failure and preserved ejection fraction: insights from PARAGON-HF
Authors: Shen L , Dewan P , Ferreira J P , Jhund P S , Desai A S , Lam C S P , Martinez F , Packer M , Redfield M M , Rouleau J L , Veldhuisen D J , Zannad F , Zile M R , Solomon S D , Mcmurray J J V
Published: October 2024

Background

Cognitive decline is common in patients with heart failure (HF), but its clinical correlates and prognostic impact are not well understood in this population.

Purpose

To examine the baseline variables associated with cognitive decline and the associations between cognitive decline and HF outcomes in patients with heart failure and preserved ejection fraction (HFpEF).

Methods

We analyzed cognitive function, as measured by the Mini-Mental State Examination (MMSE), in 2895 patients with HFpEF enrolled in a pre-specified sub-study of PARAGON-HF. Logistic regression analysis was performed to determine the factors associated with cognitive decline i.e., a decrease in MMSE score of ≥3 points by 48 weeks. Time-updated Cox proportional hazards regressions and semiparametric proportional rates models were used to examine the subsequent risk of clinical outcomes after a decline in MMSE scores of ≥1-, 2- and 3-points during follow-up respectively, adjusted for known prognostic variables including NT-proBNP and baseline MMSE.

Results

A total of 450 (15.5% of the population) patients experienced a decrease in MMSE score of ≥3 points from baseline, at any follow-up visit. The corresponding number for a decrease in MMSE score of ≥2 points and ≥1 point was 755 (26.1%) and 1231 (42.5%), respectively. Independent predictors of cognitive decline at 48 weeks included older age, living in Latin America or the Asia/Pacific region, ischemic etiology, prior HF hospitalization, history of stroke/TIA, and lower serum albumin level (Figure 1). There was a graded relationship between the size of the decrease in MMSE score from baseline and the subsequent risk of mortality. Notably, a decrease of ≥3 points was associated with a 50% increase in the subsequent risk of death from any cause (adjusted HR 1.53, 95% CI 1.10-2.11) and a 90% elevation in risk of death from cardiovascular causes (1.89, 1.25-2.86), respectively, after extensive adjustment for known prognostic variables and baseline MMSE score. By contrast, cognitive decline during follow-up was not associated with a higher risk of HF hospitalization or the composite of HF hospitalization or CV death (Figure 2).

Conclusions

In patients with HFpEF, a decline in MMSE score during follow-up is independently associated with a graded increase in the risk for mortality, but not of HF hospitalization.The predictors for cognitive declineRisk of outcomes after a decline in MMSE