bluuebunny/crossref_metadata_2025 huggingface dataset:
Trajectories of Cardiac Allograft Vasculopathy After Heart Transplantation and association with mortality: a population-based study
Authors: Bonnet G , Coutance G , Van Keer J , Raynaud M , Aubert O , Bories M.C , Bruneval P , Varnous S , Leprince P , Empana J.P , Naesens M , Patel J.K , Loupy A , Kobashigawa J , Jouven X
Published: November 2020

Background

Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient's mortality. However, the associations between CAV trajectories and mortality remains poorly described.

Purpose

We aimed to identify the different evolutive profiles of CAV and to determine the respective association with all-cause mortality.

Methods

Heart transplant recipients receiving care at 4 academic centers were included. Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessment of clinical, functional, histological and immunological parameters. The mainoutcome was a prediction for CAV trajectories using unsupervised latent class mixed models. We then identified their association with all-cause mortality (NCT04117152).

Results

Overall, 1,301 patients were included (815 and 486 in the development and validation cohorts, respectively). The median follow-up post-transplant was 6.6 years (IQR=4.7) with 4,710 coronary angiographies analyzed (3.6±1.6 CAV assessments per patient). We identified 4 distinct profiles of CAV trajectories over 10 years that were characterized by i)Patients without CAV at baseline and non-progression (n=823, 63.3%), ii) patients without CAV at baseline and late onset CAV progression (n=79, 6.1%), iii) patients with mild baseline CAV and mild progression (n=261, 20.1), iv) patients with mild baseline CAV and accelerated CAV progression (n=138, 10.6%, discrimination 0.95). The 4 CAV trajectories showed gradient for all-cause mortality (p<0.001). Trajectories #3 and #4 were associated with higher mortality rates (10-year patient survival of 73.43% [95% CI 65.18–80.02] and 51.89% [95% CI 38.76–63.51], respectively) as compared with trajectories #1, and #2 that were characterized by 10-year patient survival of 80.01 [95% CI 76.38–84.82] and 83.49% [95% CI 71.34–90.80], respectively (p<0.001).

Conclusion

In a large multicentric and highly phenotyped prospective cohort of heart transplant recipients, we identified 4 robust CAV trajectories. These different profiles were associated with distinct prognosis. Our results provide the basis for a trajectory-based assessment of heart transplant patients for early patient risk stratification and patient monitoring.

Figure 1. Overall 10-year survival probability according to the CAV trajectory in the overall cohort (n=1,301). The left part represents the main profiles CAV grades identified with latent class mixed models. Thick lines represent latent class trajectory; thin lines represent CAV individual patient trajectory. The right part represent the Kaplan Meier curves of the different trajectories.

Funding Acknowledgement

Type of funding source: None
Role of PD-L1 in heart transplant rejection
Authors: Choudhary A , Meijers W , Besharati S , Zhu Q , Lindenfeld J , Brinkley M , Anders R , Moslehi J
Published: November 2020

Background

Acute cellular rejection remains a major cause of morbidity after heart transplantation with up to 30% of patients experiencing at least one rejection episode during the first year. Unfortunately, the mechanism underling rejection remains poorly understood and the gold standard for diagnosing rejection remains frequent cardiac biopsy for rejection surveillance – a process that is both invasive and costly.

Purpose

PD-L1 is a co-inhibitory transmembrane protein that interacts with PD-1 on T cells to inhibit T cell activation. Endothelial PD-L1 expression in the heart has been shown in mouse models to play a key role in attenuating immune-mediated cardiac disease like myocarditis. Recent data that anti-PD-1 and anti-PD-L1 therapy can lead to myocarditis further supports a role for PD-1/PD-L1 signaling in cardiovascular homeostasis. We hypothesize that PD-L1 expression correlates with rejection severity.

Methods

Endomyocardial biopsy from a cohort of 19 heart transplant patients were analyzed for PD-L1 expression using immunohistochemistry and image analysis with HALO software. Each patient had biopsies corresponding to 0R, 1R, and 2R grades of rejection (n=57) and thus each patient served as their own internal control. Detailed clinical data was also collected on these patients from the electronic medical record.

Results

Average PD-L1 levels associated with 0R (n=19), 1R (n=21), and 2R (n=17) rejection were 1.54, 9.15, and 18.90 respectively (P<0.001). In patients who were treated for 2R rejection with increased immunosuppression (n=9), PD-L1 levels decreased from an average of 21.72 before treatment to an average of 5.64 after treatment (P<0.05). A multiple regression was run to see if PD-L1 level was associated with right heart pressures, EKG intervals, echo data, or common lab values. Accounting for age, race, and sex, it was found that PD-L1 was significantly associated with PA pressure (P<0.01, beta = 0.45), PCW pressure (P<0.01, beta = 0.42), and BNP (P<0.01, beta = 0.55).

Conclusions

Upregulation of PD-L1 in the heart is strongly associated with severity of cellular rejection after heart transplantation. Successful treatment of rejection with immunosuppression decreases PD-L1 levels. These data suggest that PD-L1 is a potential biomarker for heart transplant rejection. Further correlation of PD-L1 levels with signs of right heart strain (increased PA and PCW pressure) and systolic dysfunction (BNP) supports a clinical picture of PD-L1 as a useful biomarker for detecting both cellular rejection and reversal of rejection after treatment.

Cohort identification and results

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health grants R56 HL141466 and R01 HL141466
A nationwide analysis of 16 year trends in cardiac transplantation for cardiac sarcoidosis
Authors: Isath A , Perembeti S , Correa A , Chahal A , Padmanabhan D , Rao S , Garg V , Contreras J
Published: November 2020

Background

Orthotopic heart transplant (OHT) is indicated for end-stage heart failure due to cardiac sarcoidosis (CS). However, utilization of OHT for CS has been controversial due to concern for involvement of other organs by sarcoidosis affecting long term outcomes.

Purpose

Our objective was to study the trends in OHT in patients with CS in the United States using Healthcare Cost and Utilization Project (HCUP) National (nationwide) Inpatient Sample (NIS) from 1999 to 2014.

Methods

Using NIS data, we identified patients older than 18 years with cardiac sarcoidosis using codes ICD 9-CM codes of 135 and 425.8. Among these patients, we identified those who underwent cardiac transplantation using ICD 9-CM procedure codes 37.5 and 33.6. We presented categorical data as percentages and continuous data as mean or median as appropriate.

Results

A weighted total of 24231 hospitalizations for CS was extracted from 1999 to 2014 of which 248 (1.02%) CS patients underwent OHT. The trends in cardiac transplant for CS is as shown in Figure 1.

The mean age of CS patients undergoing OHT was 51.7±1.1 years and 60.4% (n=150) were males. 114 (45.9%) were Caucasians and 27.8% (n=25) were African-American. 100% of the transplants were performed at medium (n=5) or large sized (n=243) teaching hospitals and 97.9% of cardiac transplants were also done at teaching hospitals. Heart transplants were mostly done in the South (36.3%) followed by Midwest (26.2%), West (25%) and Northeast (12.5%). Private insurance was the major payor source which covered 149 (60.1%) patients followed by Medicare covering 65 (26.2%) patients.

A total of 10 (3.9%) cardiac sarcoidosis patients died during the same hospitalization for cardiac transplantation. Following OHT, 84.2% (n=209) were discharged home and 11.6% (n=29) to short term hospitalization. The mean cost of hospitalization for OHT in CS when adjusted for inflation was 535144±56060 dollars while the average length of stay for heart transplant for CS was 46.2±6.6 days.

Conclusions

Cardiac transplant trends in CS have not changed from 1999 to 2014 despite recent studies showing improved outcomes and are associated with substantial cost of hospitalization and length of stay. Majority of cardiac transplant was done in Caucasians despite cardiac sarcoidosis being more common in African-Americans.

Funding Acknowledgement

Type of funding source: None
Reduced NT-proBNP threshold for risk prediction in high-risk elderly with subclinical heart failure: support from cardiopulmonary exercise testing
Authors: Potter E , Woessner M , Marwick T.H
Published: November 2020

Background

Subclinical heart failure (HF) is divided into Stage A and B (SAHF and SBHF) depending on structural or functional cardiac abnormalities. However, risk of HF progression is not solely dependent on echocardiographic abnormalities. Data on oxygen consumption (VO2) and other prognostic cardiopulmonary exercise test (CPET) markers in subclinical HF, particularly in the elderly, is lacking. VO2 may refine risk prediction and provide pathological insight in subclinical HF.

Methods

Asymptomatic individuals were recruited through primary care if they were ≥65 years with ≥1 non-ischaemic risk factor for HF. Clinical evaluation determined risk profile, biometrics and NT-proBNP. Treadmill CPET was undertaken with a modified Bruce protocol. Low V02 was defined as ≤20th percentile of age and gender specific VO2 in healthy individuals. SBHF defined as systolic (global longitudinal strain, GLS ≤16%), diastolic (E/e' ≥15, E/e' >10 with left atrial enlargement or impaired relaxation with other changes or left ventricular (LV) hypertrophy (LV mass index >95 g/m2 in women or >115 g/m2 in men).

Results

Of the 91 included individuals (age 71±4 years, 53% female), 46 (51%) had SBHF, average NT-proBNP was 60pg/ml (26–99mg/ml) and did not differ by HF stage (59 [26–85] pg/ml vs. 60 [30–99] pg/ml for Stage A vs. B respectively, p=0.94). Average peak VO2 was 19.8 (16–22.6) ml/kg/min and was low in 71 (78%). VO2 did not differ by HF stage (19.9 [17.7–22.4] ml/kg/min vs. 19.7 [16–22.8] ml/kg/min for SAHF vs. SBHF respectively, p=0.62). NT-proBNP was significantly higher in those with abnormal VO2 (66 [34–110] pg/ml vs 31 [20–70] pg/ml, p=0.016). Within each HF stage, low VO2 was associated with higher NT-proBNP (Figure). Of those with NT-proBNP >100pg/ml, 95% (22/23) had low VO2 compared with 72% of those ≤100pg/ml, p=0.02 (non-signifcant for 125pg/ml cut-off). No associations were found between SBHF or individual echo abnormalities and VO2. In logistic regression analysis NT-proBNP was a significant univariable predictor of low VO2 and remained significant after adjustment for other significant univariables (BMI) (OR 1.02 [95% CI 1.0001–1.03], p=0.048).

Conclusion

Low VO2 identifies a high-risk cardiac phenotype within subclinical HF stages, but is not necessarily associated with LV dysfunction. Levels of NT-proBNP beneath the cut-off used for HF exclusion may assist risk stratification in this population.

NT-proBNP by VO2 in subclinical HF

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Dr E Potter is supported by a PhD Scholarship from Monash University, Melbourne, Australia
Negative impact of skeletal muscle impairment in older patients with heart failure with reduced versus preserved ejection fraction
Authors: Konishi M , Kagiyama N , Saito H , Saito K , Ogasahara Y , Maekawa E , Kitai T , Momomura S , Tamura K , Kimura K , Kamiya K , Matsue Y
Published: November 2020

Background/Introduction

Reduced functional capacity is an important phenotype of heart failure (HF), even though it may be considered multifactorial, especially in HF with preserved ejection fraction (HFpEF). Impairment in skeletal muscle may be one of extra-cardiac factors for reduced functional capacity and subsequent poor outcome.

Purpose

We sought to investigate the impact of the impairment in skeletal muscle, defined by the cut-offs proposed by the international consensus, on functional capacity and clinical outcome, in HF patients with preserved and reduced EF (HFrEF).

Methods

This is a multicenter prospective study including 1317 consecutive older (≥65 years) hospitalized patients with HF [HFpEF (ejection fraction ≥45%, n=675, 82±7 years, 46.4% male) and HFrEF (ejection fraction <45%, n=642, 78±8 years, 68.4% male)].

Results

HFrEF patients were more likely to have low skeletal muscle mass measured by bioelectrical impedance analysis (30.9% vs 22.1%, p=0.003) whereas less likely to have low muscle strength (handgrip strength; 62.9% vs 73.8%, p<0.001) than HFpEF, resulting in similar prevalence of sarcopenia between the two groups (21.6% vs 18.1%, p=0.19). In HFrEF, presence of sarcopenia was an independent predictor of reduced functional capacity assessed by a 6-minute walk distance (standardized beta=−0.093, p=0.039 in multivariate linear regression analysis) and 1-year mortality (adjusted hazard ratio (aHR) and 95% CI; 2.14 (1.22–3.70), p=0.009 in multivariate Cox-regression analysis). In patients with HFpEF, sarcopenia could predict mortality (aHR and 95% CI; 2.23 (1.23–3.91), p=0.009), though its association with reduced functional capacity was not significant after multivariate adjustment (standardized beta=−0.059, p=0.20). Kaplan-Meier survival curves in HFpEF and HFrEF are shown (Figure).

Conclusion(s)

In older patients with HF, sarcopenia was similarly contributed to mortality in HFpEF and HFrEF whereas its influence on functional capacity was pronounced in HFrEF.

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Japan Heart Foundation Research Grant
Gray matter atrophy but not vascular brain injury is related to cognitive impairment in patients with heart failure
Authors: Leeuwis A , Amier R.P , Marcks N , Nijveldt R , Hooghiemstra A.M , Brunner-La Rocca H.P , De Roos A , De Bresser J , Bron E.E , Niessen W.J , Buijs M , Barkhof F , Van Rossum A.C , Van Der Flier W.M
Published: November 2020

Background

Cognitive impairment in heart failure (HF) interferes with the capacity to self-care and is associated with adverse health outcomes. This underlines the importance of detecting the extent and nature of cognitive impairment in HF. We report on the presence and mutual association of neuroimaging markers and cognitive impairment in patients with HF.

Method

We included 147 patients with HF (69±10yrs; 32%F; MMSE 29±1) and 121 reference participants (66±8yrs; 46%F; MMSE 29±1) from the Dutch multicenter Heart-Brain study. Brain MRI scans were rated for (lacunar) infarcts and microbleeds. Total grey and white matter volume, hippocampal volume and white matter hyperintensity (WMH) volume were calculated. We used a standardized neuropsychological test battery to measure cognition and calculated compound z-scores for each cognitive domain. Associations between neuroimaging markers and cognitive functioning were investigated using linear regression analyses, with separate models for each cognitive domain. We adjusted for participant group, age, sex and education. To investigate whether associations differed according to participant group, interaction terms were included in our analyses.

Result

Patients with HF had lower total grey matter volume and more vascular brain injury compared to the reference group, including WMH (median (interquartile range) 1.7 (40) versus 0.6 (1.8), p<0.001), (sub-)cortical infarcts (13% versus 3%, p<0.01) and lacunar infarcts (28% versus 10%, p<0.001). Cognitive impairment was found in 18% of HF, most often in the domains of memory and attention/psychomotor speed. Overall, we found associations between smaller total grey matter volume and worse global cognition, more cortical and lacunar infarcts (standardized beta [stβ] = −0.14–0.56, p<0.05). Stratification for participant group showed associations between worse global cognition and smaller total (stβ=0.43, p<0.01) and hippocampal (stβ=0.22, p<0.05) grey matter volumes in HF. We found no association between cognition and vascular brain injury.

Conclusion

Patients with HF exhibit cognitive deficits more pronounced in the domains of memory and attention/psychomotor speed. Grey matter atrophy, but not vascular brain injury seems to be related to cognitive impairment in HF.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Cardiovasculair Onderzoek Nederland (CVON)
18F-FDG PET/CT brain glucose metabolism as a marker of different types of depression comorbidity in chronic systolic heart failure patients
Authors: Lyra V , Parissis J , Kallergi M , Rizos E , Filippatos G , Kremastinos D , Chatziioannou S
Published: November 2020

Background/Introduction

Depression comorbidity is an important issue in heart failure (HF) disease. Results from the recent prospective randomized trial MOOD-HF did not provide a rationale for the indiscriminate use of antidepressants in depressed HF patients.

Purpose

The study investigated whole-brain and regional-brain glucose metabolism in HF patients with 18F-FDG PET/CT and its association with depression comorbidity.

Methods

Twenty-nine hospitalized patients with symptomatic systolic HF disease (LVEF<40%), NYHA class II-IV and mean age of 55.5±12.0 years participated in the study. All patients had echocardiography, blood sampling, HF-adapted and psychometric questionnaires before discharge and a brain 18F-FDG PET/CT scan after discharge. Semi-automated PET/CT image analysis was performed on all patients and 30 matched controls. The metabolic index SUVmean was calculated for the whole-brain and three brain regions (prefrontal cortex, amygdala and hippocampus), implicated in depression pathogenesis. A standardized SUVmean was also estimated by dividing depression-related regional-brain SUVmean with the whole-brain SUVmean.

Results

HF patients had lower average whole-brain SUVmean (3.90±1.49 vs 5.10±1.35, p=0.001), average regional-brain SUVmean (4.57±2.31 vs 9.96±3.58, p<0.001) and average standardized SUVmean (1.28±0.60 vs 2.07±1.32, p<0.001) compared to controls.

Whole-brain SUVmean had a statistically significant correlation to patient age (r=−0.39, p=0.031), NYHA class (p=0.027), LVEF in the major group of 21 NYHA III-IV patients (p=0.018), diabetes comorbidity (p=0.001), creatinine levels (r=−0.49, p=0.005) and depression (r=−0.36, p=0.049). Regional-brain SUVmean was correlated to whole-brain SUVmean (r=0.53, p=0.002) and depression (r=0.46, p=0.011). The standardized SUVmean, in particular, was found to be a robust index that could differentiate HF patients with “epiphenomenal” (>0.93) or “real” (≤0.93) depression.

Conclusion

HF patients with more severe disease showed whole-brain and regional-brain hypometabolism in 18F-FDG PET/CT scan, which is consistent with impaired cerebral perfusion.

Depressed HF patients (Beck Depression Inventory score >13) exhibited different metabolic patterns that could be used to differentiate between “epiphenomenal” and “real” depression. Namely, presence of whole-brain hypometabolism suggested “epiphenomenal” depression. Absence of whole-brain hypometabolism suggested “real” depression. When the pattern of whole-brain hypometabolism included significant relative, depression-related regional hypometabolism (standardized SUVmean ≤0.93), “real” depression was the most likely diagnosis. The distinction is important, as different types of comorbid depression suggest different treatment approach.

Summarizing figure

Funding Acknowledgement

Type of funding source: None
Prevalence and prognosis in cancer therapy-related cardiovascular diseases from big data of electronic health record in Japan
Authors: Nohara S , Ishii K , Shibata T , Obara H , Miyamoto T , Kakuma T , Ueno T , Fukumoto Y
Published: November 2020

Background

Recent advance in cancer therapy has improved the cancer prognosis, which also increased the number of elder cancer survivors. Yet the anticancer agents have some serious side effects on cardiovascular system. Although there have been previous studies regarding cancer-specific and/or therapeutic agents-specific cardiovascular side effects in the selected patients, real-world data of the epidemiology for the impact of cardiovascular diseases (CVD) in cancer survivors is still limited due to the lack of comprehensive dataset. In this regard, the electronic health record (EHR), a big data, from the National Health Insurance in Japan provides a unique opportunity to obtain the suitable dataset.

Purpose

The purpose of this study was to clarify the prevalence of various CVD after the use of anticancer agents and the prognosis in cancer survivors using EHR in Japan.

Methods

This study was a retrospective cohort study using the database of Medical Data Vision (MDV) Co., Ltd. (Tokyo, Japan). The database covered 129 hospitals of all of the Designated Cancer Hospitals in Japan. The total number of patients was 17.85 million, which covered 14% of the total Japanese population. We extracted 140,327 cancer patients who received anticancer agents between April 2008 to January 2017. We identified CVD as pulmonary thromboembolism (PTE), atrial fibrillation (AF), ischemic heart disease (IHD), ventricular arrhythmia, pericarditis patients after the use of anticancer agents, according to International Classification of Diseases, 10th revision (ICD-10) codes. Hypertension (HT) patients were also identified according to ICD-10 codes, with the use of one or more anti-HT drugs after the HT diagnosis.

Results

The mean follow-up period was 1.53 years and mean age (standard deviation) was 69.2 (11.6) years old. The population over 75 years old were 36.2%, while males were 59.0%. There were prostate cancer (28.3%), lung cancer (13.8%), and colon cancer (13.2%) in males, and breast cancer (43.1%), colon cancer (12.6%), and lung cancer (8.6%) in females. Among them, 3,371 patients (2.4%) were diagnosed as PTE, 2,193 patients (1.6%) as AF, 4,085 patients (2.9%) as stable coronary artery disease, 681 patients (0.5%) as acute myocardial infarction (AMI), 749 patients (0.5%) as ventricular arrhythmia, 238 patients (0.2%) as pericarditis, 7,693 patients (5.5%) as HT. The cumulative survival rate was 65.6% in all cancer patients, 50.7% in PTE, 53.4% in AF, 61.7% in stable coronary disease, 52.7% in AMI and 45.9% in HT after the use of anticancer agents.

Conclusion

This study indicated that the prevalence of each CVD was less than 10% after the use of anticancer agents, but that patients with cancer therapy-related CVD had worse prognosis.

Funding Acknowledgement

Type of funding source: None
Depression and one-year survival of patients with heart failure in China: analysis from the China-PEACE Prospective Heart Failure study
Authors: Gao M , Xing F , Hu D , Huang X , Hu S , Li J
Published: November 2020

Background

Depression is prevalent among patients with heart failure (HF), but data exploring association of depression with risk of death in patients with HF is scarce in China. We investigated the relationship between depression and all-cause mortality of heart failure in China.

Methods

In China PEACE 5p-HF Study, we prospectively enrolled patients primarily hospitalized with HF from 52 diverse hospitals throughout China during 2016–2018. All the patients were followed up for 1 year. About 10% patients in the cohort from 41 hospitals was included for the measurement of depression state at convenience. Depression was measured by the Patient Health Questionnaire-8 depression scale (PHQ-8) at baseline. Depression state was categorized into major depressive disorder (10–24 points), minor depression (5–10 points) and no depression (0–5 points). Cox proportional hazards regression analyses, controlling for established risk factors as age, gender, LVEF, NYHA, medication use and medical history, were used to evaluate how depression were related to end point of death from any cause.

Results

Total 584 patients were included in our analysis, with median age 69 (IQR 60–77) years, and 40.8% female. Among these patients, 36.0% had major depressive disorder (n=210), 33.9% had minor depression (n=198). There were 70 (12%) patients died within 1 year after discharge. Major depressive disorder was associated with higher all-cause mortality compared with no depression (hazard ratio=2.18, 95% confidence interval 1.36–3.50, p=0.001). While minor depression was not significantly associated with all-cause mortality.

Conclusions

Major depression is an independent risk factor for all-cause mortality in hospitalized patients with HF in China. It is necessary to screen for psychological health in hospitalized patients to targeting intervention.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): National Key Research and Development Program from the Ministry of Science and Technology of China
The relationship between diastolic blood pressure and the risk of cardiovascular events in patients with atrial fibrillation: the Fushimi AF registry
Authors: Ikeda S , Iguchi M , Ogawa H , Aono Y , Doi K , Hamatani Y , Fujino A , An Y , Ishii M , Masunaga N , Esato M , Wada H , Hasegawa K , Abe M , Akao M
Published: November 2020

Background

Hypertension is one of the major risk factors of cardiovascular events in patients with atrial fibrillation (AF). However, relationship between diastolic blood pressure (DBP) and cardiovascular events in AF patients remains unclear.

Methods

The Fushimi AF Registry is a community-based prospective survey of AF patients in Japan. Follow-up data were available in 4,466 patients, and 4,429 patients with available data of DBP were examined. We divided the patients into three groups; G1 (DBP<70 mmHg, n=1,946), G2 (70≤DBP<80, n=1,321) and G3 (80≤DBP, n=1,162), and compared the clinical background and outcomes between groups.

Results

The proportion of female was grater in G1 group, and the patients in G1 group were older and had higher prevalence of heart failure (HF), diabetes mellitus (DM), chronic kidney disease (CKD). Prescription of beta blockers was higher in G1 group, but that of renin-angiotensin system-inhibitors and calcium channel blocker was comparable. During the median follow-up of 1,589 days, in Kaplan-Meier analysis, the incidence rates of cardiovascular events (composite of cardiac death, ischemic stroke and systemic embolism, major bleeding and HF hospitalization during follow up) were higher in G1 group and G3 group than G2 group (Figure 1). When we divided the patients based on the systolic blood pressure (SBP) at baseline (≥130 mmHg or <130 mmHg), the incidence of rates of cardiovascular events were comparable among groups. Multivariate Cox proportional hazards regression analysis including female gender, age (≥75 years), higher SBP (≥130 mmHg), DM, pre-existing HF, CKD, low left ventricular ejection fraction (<40%) and DBP (G1, G2, G3) revealed that DBP was an independent determinant of cardiovascular events (G1 group vs. G2 group; hazard ratio (HR): 1.40, 95% confidence intervals (CI): 1.19–1.64, G3 group vs. G2 group; HR: 1.23, 95% CI: 1.01–1.49). When we examined the impact of DBP according to 10 mmHg increment, patients with very low DBP (<60 mmHg) (HR: 1.50,95% CI:1.24–1.80) and very high DBP (≥90 mmHg) (HR: 1.51,95% CI:1.15–1.98) had higher incidence of cardiovascular events than patients with DBP of 70–79 mmHg (Figure 2). However, when we examined the impact of SBP according to 20 mmHg increment, SBP at baseline was not associated with the incidence of cardiovascular events (Figure 3).

Conclusion

In Japanese patients with AF, DBP exhibited J curve association with higher incidence of cardiovascular events.

Funding Acknowledgement

Type of funding source: None
Adverse cardiovascular outcome predicted by left atrial strain in acute decompensated heart failure
Authors: Barki M , Losito M , Carrozzo M , Caracciolo M.M , Rovida M , Bandera F , Alfonzetti E , Guazzi M
Published: November 2020

Background

A significant proportion of patients hospitalized for acute decompensated heart failure (ADHF) are readmitted to the hospital within 30 days, resulting in a major social and economic burden. Thus, risk stratification and identification of targets of therapy is of basic importance. Non-invasive imaging modality such as transthoracic echocardiography (TTE) represents a cornerstone tool to approach this clinical scenario for early recognition of high-risk patients.

Purpose

To define whether left atrial (LA) dynamics, evaluated by means of speckle tracking echocardiography (STE), may represent a predictor of cardiac events and early re-hospitalization in patients admitted to the emergency department (ED) for ADHF, in comparison with other non-invasive established prognostic index in heart failure (HF) such as NT-proBNP, B-lines at lung ultrasonography (LUS) and right ventricular (RV) to Pulmonary Circulation (PC) uncoupling evaluated through Tricuspid Annular Plane Systolic Excursion (TAPSE)/Pulmonary Arterial Systolic Pressure (PASP) ratio.

Methods

Seventy patients (mean age 75.6±11 years, 57% males) presenting with ADHF were prospectively enrolled within 24–48 hours from admission. In the acute phase and at pre-discharge the following variables have been collected: NT-proBNP, B-lines, TAPSE/PASP ratio, Left Atrial Volume indexed (LAVi) and global-peak atrial longitudinal strain (G-PALS).

Results

During a median follow-up of nine months we observed 18 events consisting of 7 deaths, 8 re-hospitalizations for ADHF, 1 re-hospitalization for acute coronary syndrome, 1 stroke and 1 mitral valve replacement. Multivariate Cox-regression analysis identified LAVi and GPALS at discharge, along with NT-proBNP, B-lines and TAPSE/PASP ratio, as independent predictors of major adverse CV events (LAVi: p=0.04; GPALS: p=0.05; NT-proBNP: p<0.001; B-lines: p=0.03; TAPSE/PASP: p<0.001) (Table 1).

Conclusions

Short-term re-hospitalization in ADHF is crucial and the identification of a higher risk through sensitive and potentially new hemodynamic phenotypes is of relevance. Our findings, although preliminary, may suggest a primary role of LA dynamics in this context.

Funding Acknowledgement

Type of funding source: None
Impact of simple nutrition index on the long-term mortality of acute decompensated heart failure patients with preserved left ventricular ejection fraction: insight from PURSUIT-HFpEF registry
Authors: Kikuchi A , Yamada T , Watanabe T , Morita T , Furukawa Y , Tamaki S , Kawasaki M , Kawai T , Seo M , Yasumura Y , Hayashi T , Yano M , Hikoso S , Sakata Y
Published: November 2020

Background

The novel nutrition index; triglyceride (TG) × total cholesterol (TG) × body weight (BW) index (TCBI) has been reported to be an easy and useful predictor for patients with coronary artery disease. However, there is no information available on the prognostic value of TCBI in patients with heart failure with preserved LVEF (HFpEF) who admitted with acute decompensated heart failure (ADHF).

Methods and results

Data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study. PURSUIT-HFpEF study is a prospective multicenter observational study in which collaborating hospitals recorded clinical, echocardiographic, and outcome data of ADHF pts with HFpEF. We enrolled consecutive 757 HFpEF patients who admitted with ADHF from June 2016 to June 2019. TCBI was calculated by the formula; TG × TC × BW / 1000 at the discharge. After we excluded patients with in-hospital death or without sufficient data, we analyzed 419 patients. The primary endpoint was all-cause mortality. During a median follow up period of 1.1 (0.9–1.9) years, 59 patients died. ROC analysis revealed that TCBI at discharge was a fair discriminator for predicting all-cause mortality (AUC 0.676, sensitivity 53%, specificity 78%). Multivariate Cox proportional analysis showed that TCBI (p=0.002) was an independent predictor for all cause death after adjustment with major confounders such as age, gender, NT-proBNP, hemoglobin and serum creatinine level. We divided patients into 4 groups according to quartiles of TCBI. Kaplan-Meier analysis showed a significantly higher risk of all-cause death in relation to the decrease in TCBI.

Conclusion

TCBI, a simple and novel nutrition index, is a useful and strong long-term prognostic indicator in ADHF patients with HFpEF.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Roche Diagnositics K.K.; Fuji Film Toyoma Chemical Co. Ltd.
Prognostic impact of free-fat mass index on elderly patients with acute decompensated heart failure: from CURE-HF registry
Authors: Kanai M , Motoki H , Okano T , Kimura K , Minamisawa M , Yoshie K , Kato T , Saigusa T , Ebisawa S , Okada A , Kuwahara K
Published: November 2020

Background

Free-Fat Mass Index (FFMI) is an indicator of malnutrition and sarcopenia. We hypothesized that low FFMI would be associated with worse prognosis in elderly patients with heart failure.

Methods

In 800 patients who discharged after treatment for HF were prospectively enrolled from 13 medical centers. Free-Fat Mass Index was calculated dividing the square of the patients heights in meters into lean body mass. All-cause mortality (cardiovascular, non-cardiovascular) was followed-up by telephone interview and chart review.

Results

In our study cohort (median age, 78 [range 72–87]), FFMI was 16.7 [15.2, 18.0]. All-cause mortality was observed in 211 patients during 631 [266, 983] days follow-up. In Kaplan-Meier analysis, lower FFMI was associated with all-cause mortality. Furthermore, FFMI was an independent predictor of mortality after adjustment for age, gender, albumin, hemoglobin, creatinine, brain natriuretic peptide, and left ventricular ejection fraction (HR 95% CI: 0.841 (0.745–0.944), p=0.004). In subgroup analysis, low FFMI was associated with both cardiac and non-cardiac mortality in patients with HF with reduced ejection fraction (EF) (Log-rank p=0.002, p=0.013, respectively) (Figure). Furthermore, low FFMI was significantly associated non-cardiac death in patients with preserved EF (Log-rank p=0.033) (Figure).

Conclusions

Free-Fat Mass Index was significantly associated with mortality in elderly patients with HF.

Funding Acknowledgement

Type of funding source: None
Diagnosing heart failure from chest X-ray images using deep learning
Authors: Matsumoto T , Kodera S , Shinohara H , Kiyosue A , Higashikuni Y , Akazawa H , Komuro I
Published: November 2020

The development of deep learning technology has enabled machines to achieve high-level accuracy in interpreting medical images. While many previous studies have examined the detection of pulmonary nodules and cardiomegaly in chest X-rays using deep learning, the application of this technology to heart failure remains rare. In this study, we investigated the performance of a deep learning algorithm in terms of diagnosing heart failure using images obtained from chest X-rays. We used 952 chest X-ray images from a labeled database published by the National Institutes of Health. Two cardiologists respectively verified and relabeled these images, for a total of 260 “normal” and 378 “heart failure” images, and the remainder were discarded because they had been incorrectly labeled. In this study “heart failure” was defined as “cardiomegaly or congestion”, in a chest X-ray with cardiothoracic ratio (CTR) over 50% or radiographic presence of pulmonary edema. To enable the machine to extract a sufficient number of features from the images, we used the general machine learning approach called data augmentation and transfer learning. Owing mostly to this technique and the adequate relabeling process, we established a model to detect heart failure in chest X-ray by applying deep learning, and obtained an accuracy of 82%. Sensitivity and specificity to heart failure were 75% and 94.4%, respectively. Furthermore, heatmap imaging allowed us to visualize decisions made by the machine. The figure shows randomly selected examples of the prediction probabilities and heatmaps of the chest X-rays from the dataset. The original image is on the left and its heatmap is on the right, with its prediction probability written below. The red areas on the heatmaps show important regions, according to which the machine determined the classification. While some images with ambiguous radiolucency such as (e) and (f) were prone to be misdiagnosed by this model, most of the images like (a)–(d) were diagnosed correctly. Deep learning can thus help support the diagnosis of heart failure using chest X-ray images.

Heatmaps and probabilities of prediction

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI
Quantifying inflammation using interleukin-6 for improved phenotyping and risk stratification in acute heart failure
Authors: Michou E , Wussler D , Belkin M , Strebel I , Kozhuharov N , Sabti Z , Nowak A , Lopez Ayala P , Flores D , Gualandro D , Breidthardt T , Mueller C
Published: November 2020

Background

Acute heart failure (AHF) is the most common cause of hospital admission and continues to have unacceptable high rates of mortality and morbidity. In contrast to acute myocardial infarction, the pathophysiology of AHF is incompletely understood and risk-prediction is poorly defined.

Aim

We aimed to quantify systemic inflammation to assess its possible role in the pathophysiology and risk stratification of patients with AHF.

Methods

Using a novel Interleukin-6 immunoassay with unprecedented sensitivity (limit of detection 0.01ng/l) we quantified systemic inflammation in unselected patients presenting with acute dyspnea to the emergency department in a multicenter study. Plasma concentrations of NT-proBNP (open label) and Interleukin-6 (blinded) were measured at presentation and at discharge. The final diagnosis of AHF and the AHF phenotype were adjudicated by two independent cardiologists. 1-year mortality was the prognostic endpoint.

Results

Among 2042 patients, 1026 (50.2%) had an adjudicated diagnosis of AHF. Interleukin-6 concentrations were significantly higher in AHF patients compared to patients with other causes of dyspnoea (11.2 [6.1–26.5] ng/l vs 9.0 [3.2–32.3] ng/l, p<0.0005). Among patients with AHF Interleukin-6 concentrations were elevated (>4.45ng/l) in 83.7% of them. Among the different AHF phenotypes, Interleukin-6 concentrations were highest in patients with cardiogenic shock (25.7 [14.0–164.2] ng/l) and lowest in patients with hypertensive HF (9.3 [4.8–21.6] ng/l, p=0.001). Inflammation as quantified by Interleukin-6 was a strong predictor of 1-year mortality both in AHF as well as in other causes of acute dyspnea (Figure). During in-hospital treatment Interleukin-6 concentrations significantly decreased in AHF patients. However, changes in the extend of systemic inflammation (delta Interleukin-6) were poorly correlated with changes in hemodynamic stress as quantified by NT-proBNP (delta NT-proBNP, Φc=0.11, p=0.004).

Conclusions

An unexpectedly high percentage of patients with AHF have subclinical systemic inflammation that can be quantified by Interleukin-6, which seems to contribute to the AHF phenotype and to the risk of death.

Kaplan Meier curves for mortality

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Swiss National Science Foundation, Swiss Heart Foundation, European Union, Stiftung für kardiovaskuläre Forschung Basel, University of Basel, University Hospital Basel
Bedside ultrasound assessments of jugular venous compliance to track central venous pressure change during the treatment of decompensated heart failure
Authors: Fatima S , Lambert W , Nouraie S , Simon M , Pacella J
Published: November 2020

Background

Accurate volume status assessment is crucial for the treatment of acute decompensated heart failure (ADHF). Volume status assessment by physical exam is inaccurate, necessitating invasive measurement with right heart catheterization (RHC), which carries safety, pragmatic (scheduling, holding anticoagulants, etc) and financial burdens. Therefore, a reliable, non-invasive, cost-effective alternative is desired. Previously, we developed an ultrasound (US) based technique to measure internal jugular vein (IJV) compliance during RHC which was used for single time point central venous pressure (CVP) predictions. We now aim to apply this technique to track acute changes in CVP during diuresis for ADHF in patients with an in-dwelling pulmonary artery catheter.

Purpose

The objective of our study was to devise a rapid, portable and reliable alternative to RHC to track acute volume changes during treatment of ADHF.

Methods

We used an observational, prospective study design and recruited 15 patients from the CCU between 7/19–12/19 being treated for ADHF (systolic or diastolic) with IV diuretics +/−inotropic agents who underwent PA catheter insertion for continuous CVP monitoring. 13 of 15 patients received milrinone infusions. US images of the IJV were obtained at end expiration and during the strain phase of Valsalva at multiple 2–3 hr intervals. Change in IJV cross sectional area (ImageJ) was used as a measure of IJV compliance. Patients unable to perform the Valsalva maneuver and on mechanical circulatory support were excluded.

Results

Calculated % change in CSA of IJV was plotted against CVP. An inverse relationship was observed between CVP and % change in CSA of IJV. The data was fit with an inverse exponential regression shown in Figure 1 (R2=0.36, root mean square error = 3.19). Fivefold cross validation showed a stable model for predicting CVP based CSA (R2=0.34, root mean square error = 3.26)

Conclusion

Serial portable US assessment of IJV compliance can act a surrogate measure of CVP and,therefore, can provide reliable information on acute hemodynamic changes in ADHF.

Funding Acknowledgement

Type of funding source: None
Effect of comprehensive vasodilation vs usual care on mortality and heart failure rehospitalization in women with acute heart failure
Authors: Wussler D , Walter J , Kozhuharov N , Goudev A , Flores D , Maeder M , Shrestha S , Gualandro D , De Oliveira M.T , Kobza R , Rickli H , Breidthardt T , Muenzel T , Erne P , Mueller C
Published: November 2020

Background

Guidelines recommend evaluating the risk/benefit ratio of novel therapies individually in women and men, as the pathophysiology and the response to treatment may differ between women and men. Among patients with acute heart failure (AHF), a strategy of intensive vasodilation, compared with usual care, overall did provide comparable outcomes.

Purpose

To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation in women with AHF.

Methods

In a randomized, open-label blinded-end-point trial patients hospitalized for AHF were enrolled in 10 hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Inclusion criteria were AHF expressed by acute dyspnea and increased plasma concentrations of natriuretic peptides, systolic blood pressure ≥100mmHg, and a plan for treatment in a general ward. Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization or usual care. The primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days.

Results

Among 788 patients randomized, 781 completed the trial and were eligible for the primary end point analysis. Of these 288 (36.9%) were women. The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 53 female patients (37.9%) in the intervention group (including 28 deaths [20.0%]) and in 34 female patients (23.0%) in the usual care group (including 22 deaths [14.9%]) (absolute difference for the primary end point, 14.9%; adjusted hazard ratio, 1.67 [95% CI: 1.08–2.59]; P=0.02). Clinically significant adverse events with early intensive and sustained vasodilation vs usual care included hypotension (8% vs 2%).

Conclusion

Among women with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, had a detrimental effect on a composite outcome of all-cause mortality and AHF rehospitalization at 180 days.

Cox Proportional Hazard Curve

Funding Acknowledgement

Type of funding source: None
Is primary graft failure still a challenge in time of venoarterial extracorporeal membrane oxygenation?
Authors: Borderias T , Gonzalez Lizarbe S , Sanchez J , De Tapia B , Catoya S , Cabrera I , Molina M , Lozano M , Lujan E , Canteli A , Castrillo C , Ruiz Lera M , Sarralde J.A , Cobo M , Burgos V
Published: November 2020

Introduction

Primary graft failure (PGF) is the leading cause of early mortality after heart transplantation (HT). Its increasing incidence during the last decade may be triggered by the disbalance between receptors and donors that forces the acceptance of suboptimal organs.

Purpose

The aim of our work was to analyse the mechanical circulatory support (MCS) with VA-ECMO in refractory to inotropes PGF and determinate its impact in terms of graft function recovery and survival.

Methods

A retrospective study, analyzing our database of circulatory assist devices between 2009 and 2019. During this period, 252 devices have been implanted (154 ECMOs and 98 ventricular assist devices) and 201 patients have received a HT. We describe the characteristics and evolution of all PGF cases managed with VA-ECMO.

Results

Thirty nine patients (19.4%) developed PGF, defined as significant left, right or biventricular systolic dysfunction in the first 24 hours after HT, associated with hemodynamic instability and requiring high dose of inotropes, intra-aortic balloon pump (IABP) or VA-ECMO. Twenty two cases (56.4%) underwent a VA-ECMO implantation by peripheral cannulation as a bridge to recovery.

The median age was 50.8 (44.3–57.3) years and 77% were male. Biventricular dysfunction was observed in 50% and isolated right ventricular dysfunction in the remaining 50%. At the time of implantation, 59% had IABP and the median of inotropic score was 24 (8–40). Two complications occurred during implantation (one because of a complex vascular access and one due to a malposition of the venous cannula). Anticoagulation was started after a median of 19 hours (10–28; 59% sodic heparin and 36% bivalirudin).

The median support duration was 6.2 days (3–9.2). Graft function was recovered in 90%, making it possible to withdraw the device successfully in 82% of patients. The remaining 18% deceased during the support (2 because of multiorgan failure and 2 due to absence of function recovery).The median hospital length of stay was 63 days (33–93) and hospital and 1-year survival was 68.1%.

Conclusion

The support with VA-ECMO allowed graft function recovery in 90% of severe PGF cases, with a similar survival rate to other centres with MCS. In a scenario with a mortality rate superior to 50%, the MCS programs have managed to increase survival, avoid retransplantation in times of donor shortage and handle the use of suboptimal donors with better chances of success.

Funding Acknowledgement

Type of funding source: None