bluuebunny/crossref_metadata_2025 huggingface dataset:
Early hospital trainings in patients with left ventricular mechanical support: influence on exercise tolerance and muscle strength
Authors: Smolis-Bak E , Chwyczko T , Zalucka L , Noszczak E , Bogucki M , Segiet-Swiecicka A , Piotrowicz R , Dabrowski R
Published: October 2021

Background

In extreme cases of heart failure, the only method of treatment is heart transplantation. Due to the insufficient number of organs for transplantation, left ventricular assist devices (LVAD) are increasingly being used. Rehabilitation of patients with LVAD is a very important element of complex therapy due to the long-term immobilization of these patients awaiting transplant or regeneration of the heart. The aim of the study was to assess the impact of early hospital rehabilitation on exercise tolerance, muscle strength and complex coordination in patients after LVAD implantation.

Material and methods

The study included 37 patients (35 men), aged 19–66 years, mean 58.7 years, after LVAD implantation. All of them underwent standard rehabilitation in the postoperative and rehabilitation department. The patients have started and continued trainings in a rehabilitation department for 4–5 weeks: endurance trainings, general fitness exercises with elements of balance and coordination exercises, elements of resistance exercises. Before the start of rehabilitation and after its completion, all patients underwent: cardiopulmonary exercise testing (CPET), a six-minute walk tests (6-MWT), the tests of strength of the right and left hand grip, strenght of muscles of the lower limbs and complex coordination (up and go test). There were no adverse events that would justify changing the mode or discontinuing rehabilitation.

Results

A significant increase in the value of most of the parameters studied was observed after the completion of hospital rehabilitation: VO2peak [ml/kg/min], baseline: 10.60 (9.60, 12.90) vs. 12.85 (11.60, 15.73), p<0.001; 6-MWT [m]: 322.81 (113.62) vs. 416.12 (106.37), p<0.001; 30 second chair stand: no of stands: 9.12 (3.60) vs. 11.18 (4.50), p<0.001; up & go [sec] 9.18 (8.07, 10.50) vs. 7.58 (6.69, 9.04), p<0.001; left hand grip strengh [kg]: 30.04 (8.38) vs. 31.91 (8.10), p<0.011; right hand grip strengh [kg]: 31.52 (9.88) vs 33.20 (8.72), ns.

Conclusions

Early hospital rehabilitation in patients after implantation of left ventricular assist devices has significant benefits in terms of exercise tolerance, muscular strength and complex coordination. Complex rehabilitation is safe and effective in this group of patients.

Funding Acknowledgement

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): STRATEGMED II - RH-ROT - NATIONAL RESEARCH AND DEVELOPMENT CENTER
VAD related infections and the risk of pump thrombosis and thromboembolic events: a EUROMACS study
Authors: Zijderhand C.F , Antonides C.F.J , Veen K.M , Schoenrath F , Gummert J , Nemec P , Merkely B , Musumeci F , Meyns B , De By T , Bogers A.J.J.C , Caliskan K
Published: October 2021

Background

In patients supported by a ventricular assist device (VAD) major infections are a frequently reported adverse event with increased morbidity and mortality.

Purpose

The purpose of this study was to investigate the possible association between infections and cerebrovascular accidents (CVAs) in VAD patients.

Methods

An analysis of the European Registry for Patients Assisted with Mechanical Circulatory Support (EUROMACS) was performed identifying all patients aged ≥18 years with a LVAD or BiVAD implantation. Infections were categorized as VAD-specific infections, VAD-related infections and, non-VAD infections. An extended Kaplan-Meier analysis for the risk of CVA and mortality with infection as a time-dependent covariate was performed. Furthermore, a multivariable Cox proportional hazard model was performed including 24 variables.

Results

For this analysis 3784 patients were included, with 45 patients being supported by a BiVAD and 3739 by an LVAD. The majority of patients were male (83.2%) and 60.5% had an INTERMACS patient profile 2 or 3. During follow-up, 3108 major infections were identified in 1385 (36.6%) of the patients, while 673 CVAs were identified in 545 (14.4%) of the patients. Extended Kaplan-Meier analysis with first infection as time-dependent covariate revealed a hazard ratio (HR) for CVA of 1.95 (95% CI: 1.57–2.36; p<0.005) (Figure) and 1.50 (95% CI: 1.33–1.68, p<0.005) for mortality. Multivariable analysis confirmed a significant association for infection and CVAs with a HR of 1.46 (95% CI: 1.29–1.64). With infections subcategorized, VAD-specific (HR: 1.57 (95% CI: 1.18–2.09)) and VAD-related infections (HR: 2.04 (95% CI: 1.44–2.89)) remained significantly associated with CVA but non-VAD infections (HR: 1.22 (95% CI: 0.92–1.64)) were not.

Conclusion

Both VAD-related and VAD-specific infections are associated with a significantly increased risk of CVA with increased risk of mortality.

Funding Acknowledgement

Type of funding sources: None. KM freedom of CVA and infection
Prediction of outcomes after heart transplantation by machine learning models
Authors: Briasoulis A , Moustakidis S , Tzani A , Doulamis I , Kampaktsis P
Published: October 2021

Background

Models based on traditional statistics for the prediction of outcomes after heart transplantation (HT) have moderate accuracy. We sought to develop and validate state-of-the-art machine learning (ML) models to predict mortality and acute rejection after contemporary HT.

Methods

We included adult HT recipients from the UNOS database between 2010–2018 using solely pre-transplant clinical and laboratory variables. The study cohort was randomly split in a derivation and a validation cohort with a 3:1 ratio. An effective feature selection algorithm was used to identify strong predictors of 1-year mortality and rejection in the training cohort. Results were used to train the ML models, which were then internally tested using the validation cohort. LIME explainability analysis was used for the best performing ML model. A similar subgroup analysis was performed for 3- and 5-year survival.

Results

The study cohort comprised of 18,625 patients (53±13 years, 73% males). At 1-year after cardiac transplant, there were 2,334 (12.5%) deaths. Out of a total of 134 pre-transplant variables, 39 and 27 were selected as highly predictive of 1-year mortality and acute rejection respectively, and were used in the ML models. Areas under the curve for the prediction of 1-year survival were 0.689, 0.642, 0.649, 0.637, 0.526 for the Adaboost, Logistic Regression, Decision Tree, Support Vector Machine and K-nearest neighbor models respectively, whereas the IMPACT score had an AUC of 0.569. For the prediction of 1-year acute rejection, Adaboost achieved the highest predictive performance (AUC 0.629). LIME explainability analysis identified the relative impact of the 10 strongest predictors of 1-year mortality and acute rejection. Subgroup analysis using a similar methodology for 3- and 5-year survival yielded AUC of 0.609 and 0.610 using 31 and 91 selected variables respectively.

Conclusion

ML models created and validated using a contemporary cohort of the UNOS database showed improved accuracy in predicting survival and acute rejection after HT.

Funding Acknowledgement

Type of funding sources: None.
Short and long term outcomes of cardiac amyloidosis patients listed for heart transplantation in the united states: a propensity-matched analysis
Authors: Akintoye E , Alvarez P , Briasoulis A
Published: October 2021

Background

Heart transplantation (HT) in cardiac amyloidosis (CA) patients has been historically controversial due to the risk of amyloid recurrence. However, recent single-center experiences suggest good outcomes in carefully selected patients. We sought to evaluate contemporary outcomes of CA patients listed for HT in the U.S. and evaluate predictors of survival

Methods

Using data from the United Network for Organ Sharing database on adult patients listed for a donor heart in the U.S. between 2010 and 2019, we identified 3 cohorts of patients, namely CA, dilated cardiomyopathy (DCM), and non-CA restrictive cardiomyopathy (RCM). Propensity-match analysis was used to compare primary outcomes of waitlist mortality and post-transplant graft survival between CA and DCM.

Results

Over the study period, 411 CA patients (mean age 62.7 years, 16.1% female) were added to the waitlist. In the propensity-matched cohorts, the rates of waitlist mortality were 33.7, 15.8, and 15.6 per 100 person-years for CA, DCM, and non-CA RCM, respectively. Compared to DCM, there was significantly higher waitlist mortality for CA (HR=1.75, 95% CI=1.16–2.65). Over the study period, 330 CA patients were transplanted with donor hearts. The 1-year graft survival rates for CA, DCM, and non-CA RCM were 89%, 92%, and 86%, respectively; and 5-year graft survival rates were 78%, 82%, and 76%, respectively. Graft survival for CA was significantly worse than DCM (HR=1.46, 1.03–2.08), and the two most significant risk factors for poor graft survival among CA patients were renal failure requiring dialysis while on the waitlist (HR=5.4, 1.6–17) and prior history of malignancy (HR=1.7, 1.0–29). CA patients with neither of the risk factor had 1- and 5-year graft survival that is comparable to those of DCM (HR=1.18, 0.81–1.74). On the other hand, CA patients with either of the risk factor had 1- and 5-year graft survival of 81% and 65%, respectively, (HR=2.33, 1.40–3.87, compared to DCM).

Conclusion

CA patients experience higher waitlist mortality and worse post-transplant graft survival compared to DCM. However, we identified two risk factors that can be used for further risk-stratification in these patients to achieve comparable graft survival as DCM.

Funding Acknowledgement

Type of funding sources: None.
Quantifying long-term improvements in exercise capacity after cardiac transplantation
Authors: Jones T.N , Chatrath N , Cole D , Dar O
Published: October 2021

Introduction

Cardiac transplantation (CT) is known to improve exercise capacity in patients with advanced heart failure (HF). However, it is unclear whether continued improvements occur after the initial post-operative recovery and whether baseline demographic and disease-related factors influence this improvement.

Purpose

We aimed to quantify the degree of improvement in exercise capacity over time in CT recipients and establish whether baseline characteristics influenced this improvement.

Methods

Retrospective review of the medical records of patients who underwent CT at a single centre was performed. Cardiopulmonary exercise (CPEX) testing is routinely offered pre-CT and at 3, 6, 9, 12, 24, 36 and 48 months post-CT, unless there are contraindications. Baseline demographic and clinical characteristics pre-CT were also collected.

Results

A total of 199 patients underwent CT, of which 138 (69%) were male. The mean age was 44 (SD 14.0) years and mean pre-CT body mass index (BMI) was 25.3 (SD 4.2). In 125 (63%) patients, the underlying aetiology of HF was dilated cardiomyopathy (DCM). 32 (16%) patients had a durable left ventricular assist device (LVAD) as a bridge to CT.

Pre-transplant CPEX was undertaken in 131 (66%) patients, with a mean peak VO2 of 15.5 (SD 6.2) ml/kg/min. Peak VO2 was higher in males (16.6; SD 6.7 vs 13.1; SD 4.0, p=0.002) and those under 50 years old (16.8; 7.2 vs 13.8; 3.9, p=0.005) but was not affected by the underlying aetiology (DCM vs others: 16.3, 6.6 vs 14.1, 5.1, p=0.051), the presence of an LVAD (17.3, 5.0 vs 15.1, 6.3, p=0.119) or pre-transplant obesity (14.5, 3.2 vs 15.7, 6.5, p=0.437).

Peak VO2 increased within the first year post-CT (Figure 1 and 2). Ongoing improvements were also observed beyond the 1-year time-point, although only the 3-year vs 1-year comparison remained significantly when corrected for multiple comparisons. When analysed with mixed models, time post-CT was a significant predictor of peak VO2 (p=0.001). Additionally, there was a significant interaction between peak VO2 over time with gender (p=0.038), but not with age under 50 years (p=0.244), underlying aetiology being DCM (p=0.05), a previous LVAD (p=0.664) and pre-transplant obesity (p=0.301). Post-hoc analysis showed that males had a greater mean improvement than females in peak VO2 at 1-year compared to pre-CT (7.7, SD 5.5 vs 4.8, SD 4.0 ml/kg/min).

Conclusions

These results demonstrate that exercise capacity improves up to and beyond the first year post-CT. The degree of improvement may be greater in males, although it is not influenced by age, BMI, underlying disease aetiology or the presence of an LVAD pre-CT.

Funding Acknowledgement

Type of funding sources: None.
Self-care behaviours mediate the effect of educational intervention on health-related quality of life of patients with heart failure: causal mediation analysis
Authors: Hwang B , Yu H , Jeong Y , Cho H.-J , Lee H.-Y
Published: October 2021

Background/Introduction

Educational interventions have been developed and tested in an attempt to improve health-related quality of life (HRQOL) for patients with heart failure (HF). While some have shown satisfactory results, the mechanism of the intervention effect on HRQOL remains unclear.

Purpose

To explore whether HF knowledge, self-care behaviours, self-care maintenance, self-care confidence, or social support mediates the effect of intervention on HRQOL of patients with HF

Methods

We analysed data from a randomized controlled trial testing the effect of an educational intervention for patients with HF. The intervention group (n=60) received 1-hour single session education followed by 8-week telephone follow-ups, and the control group (n=62) received care as usual. Study variables were measured at baseline and at 3 and 6 months. Using causal mediation analysis described by Valeri & VanderWeele (2013), we explored the causal pathway between intervention allocation and HRQOL at 6 months with HF knowledge, self-care behaviours, self-care maintenance, self-care confidence, and social support measured at 3 months as potential mediators (Figure 1).

Results

Intervention allocation was significantly associated with HF knowledge, self-care behaviours, self-care maintenance, and self-care confidence at 3 months (all p<0.05), but not with social support at 3 months (p=0.57). In unadjusted models, none of the potential mediators had a significant indirect effect between intervention and HRQOL. When adjusting for age and gender, the indirect effect of self-care behaviours on 6-month HRQOL became significant (indirect effect −6.24, 95% CI: −12.88 to −1.18). When baseline values of the mediator and HRQOL were adjusted in addition to age and gender, the indirect effect of self-care behaviours remained significant (indirect effect −7.18, 95% CI: −13.48 to −2.35) and the indirect effect of self-care maintenance became significant (indirect effect −3.02, 95% CI: −7.94 to −0.07).

Conclusion

Our findings support the mediating role of self-care behaviours on the relationship between the educational intervention and HRQOL of patients with HF. In order to successfully improve HRQOL of patients with HF, educational interventions should aim to promote self-care behaviours, especially by encouraging treatment adherence and self-monitoring.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Seoul National University, College of Medicine Figure 1. Mediation model
The cardiac amyloidosis clinical pathway implementation: a real world experience
Authors: Brons M , Rutten F.H , Minnema M.C , Baas A.F , Asselbergs F.W , Oerlemans M.I.F.J
Published: October 2021

Background/Introduction

Prognosis for patients with cardiac amyloidosis (CA) is determined by disease stage at diagnosis, underlining the importance of timely referral. In 2018, a CA clinical pathway was implemented in an Amyloidosis Expert Center in The Netherlands to increase regional awareness.

Purpose

To evaluate the impact of CA clinical pathway implementation.

Methods

Patients diagnosed before implementation (2007–2018; T1) were retrospectively compared to the period after clinical pathway implementation (2019–2020; T2). Demographics and disease characteristics were collected from electronic health records.

Results

In total, 113 patients were diagnosed, mean age 67.8±8.5 years, 26% female. AL-CA was diagnosed in 62%, ATTR-CA in 38%. The number of CA diagnoses/year increased over time (Figure 1). NYHA class III (45% vs. 24%,p=0.04), CA stage (MAYO/Gillmore stage III or IV; 59% vs. 33%, p=0.03) and delay between symptoms and diagnosis (14.5 vs. 8.4 months, p<0.01) improved considerably between T1 and T2. Reasons for referral changed over time, with increasing awareness for right ventricular hypertrophy (9% vs. 36%) and unexplained HFpEF (22% vs 38%).

Conclusion

CA patients were diagnosed earlier with less severe symptoms. Clinical pathway implementation facilitated regional increased awareness and improved timely referral.

Funding Acknowledgement

Type of funding sources: None.
Bone-vessels relationships: association between calcifications of the iliac arteries with vertebral fractures in hemodialysis patients – results from the VIKI study
Authors: Fusaro M , Tripepi G , Politi C , Aghi A , Taddei F , Schileo E , De Caterina R
Published: October 2021

Background

Vascular calcification and fragility fractures are common age-related disorders, associated with high morbidity and mortality especially in end-stage renal disease. Skeletal disorders occur in dialysis patients. Few studies have provided data on the prevalence of vertebral fractures (VF) and their association with large artery calcifications.

Purpose

We evaluated the relationship of iliac arteries calcifications (IACs) and abdominal aorta calcifications (AACs) with the risk for VFs in hemodialysis (HD) patients.

Methods

The VIKI Study is a cross-sectional study involving 387 HD patients from 18 Italian dialysis centers, assessing demographic, clinical and biochemical data in such patients. Biochemical data included bone health markers such as vitamin K levels, vitamin K-dependent proteins, vitamin 25(OH)D, alkaline phosphatase, parathormone, calcium, phosphate, Bone Gla Protein and Matrix Gla Protein. The presence of VF, IACs and AACs were determined through standardized radiograms of the spine. A >20% reduction of vertebral body height was considered a VF. We quantified vascular calcifications by measuring the length of calcium deposits along the abdominal arteries, classifying the degree of severity for the IACs and AACs with a specific score (mild: 0.1–3 cm; moderate: 3.1–5 cm; and severe >5 cm) previously validated for AACs.

Results

The prevalence of IACs was 56.1%, and of AACs 80.6%. After adjusting for confounding variables, the presence of IACs was associated with 73% higher odds of VF (p=0.028), whereas we found no association (p=0.294) for AACs. The presence of IACs associated with VF irrespective of calcification severity. Patients with IACs had lower levels of the vitamin K2, menaquinone 7 (0.99 vs 1.15 ng/ml; p=0.003), and deficiency of this marker became greater when adjusting for triglyceride levels (0.57 vs 0.87 ng/ml; p<0.001).

Conclusions

The presence of IACs, regardless of their extent, appears to be a clinically relevant risk factor for VFs. The association is further enhanced by including vitamin K, a main player in bone and vascular health, in the model. Prospective studies are needed to confirm these findings both in chronic kidney disease patients and in the general population.

Funding Acknowledgement

Type of funding sources: None.
Protection of bone mineral density in heart failure patients:audit on current clinical practice in a busy tertiary care hospital cardiology department in Ireland
Authors: Tariq S , Stroiescu A , Mannion J , Caples N , O'Callaghan P , O'Reilly M , Ryan A , Owens P
Published: October 2021

Background

The strong association between heart failure (HF) and osteoporosis is well recognised. Heart failure, due to its multiple risk factors and common pathogenesis with osteoporosis can lead to low bone mineral density (BMD) and increase the risk of fragility fractures. The mortality of HF patients following these fractures is high. Current National Osteoporosis Foundation Guidelines recommend that pharmacological therapy should be reserved for postmenopausal women and men aged 50 years or older who present with a hip or vertebral fracture, where the vertebral fractures may be clinical or identified on a radiograph alone.

Methods

Most HF patients have frequent chest radiographs over their course years. We aimed to audit the prevalence of osteoporosis and current practice of prescribing BMD-protection in patients attending the HF clinic in a busy tertiary care hospital in Ireland. 100 patients attending the clinic in the last one year were randomly selected and clinical, medication and chest radiograph information on this cohort was collected via the hospital electronic information system. All those patients with Radiologist confirmed vertebral compression fractures (VCF) on their plain chest radiographs were audited regarding osteoporosis screening and bone protection prescription.

Results

Due to limited penetration,18 out of 100 chest radiographs were inconclusive,reducing the sample size to 82. 9 out of the remaining 82 patients had radiologist confirmed VCF on their plain chest radiographs whereas 2 patients had VCF incidentally picked up on their lumbar spine x-rays. All patients were aged more than 50. 4 were female and 7 male. Median ejection fraction calculated was 35%. 3 out of 11 were smokers,8 had atrial fibrillation and were on anticoagulation,4 had DM-II and 2 had CKD. 10 were on loop diuretics. Of note,4 patients were on calcium and vitamin D supplements but only 1 patient was on antiresorptive therapy for osteoporosis.

Conclusion

Despite its strong association with heart failure,Osteoporosis remains undertreated in this patient cohort.Due to the significant mortality and morbidity associated with major osteoporotic fractures, doctors should carefully assess and screen heart failure patients for osteoporosis and initiate specific therapy where indicated.

Funding Acknowledgement

Type of funding sources: None.
Cancer incidence and mortality according to pre-existing heart failure in a community-based cohort
Authors: Bertero E , Robusto F , Rulli E , D'Ettorre A , Staszewsky L , Maack C , Lepore V , Latini R , Ameri P
Published: October 2021

Background

Studies assessing whether heart failure (HF) is associated with an excess risk of cancer and cancer-related mortality yielded conflicting results. Here, we assessed the incidence and mortality of cancer according to the presence of HF in a community-based cohort.

Methods

By reviewing the health care records of the Puglia region in Italy, we first selected individuals ≥50-year-old, with no history of cancer within 3 years before the baseline evaluation and ≥5 years of follow-up, during the period from January 1st, 2005 to December 31st, 2013. Next, we matched 1:1 104,020 subjects with HF at baseline and 104,020 controls based on age, sex, Charlson Comorbidity Index, Drug-Derived Complexity Index, and follow-up duration. Cancer incidence and mortality were analyzed by Kaplan-Meier method and Cox regression models. Fine and Grey's regression model was also used to compare cancer-specific mortality while taking into account the competing risk of non-cancer death.

Results

Overall, the mean age of the study population was 76±10 years and the mean follow-up was 5.7 years. The incidence rate of cancer in HF patients and controls was 21.36 (95% CI, 20.98–21.74) and 12.42 (95% CI, 12.14–12.72) per 1000 person/years, respectively, corresponding to a 76% higher risk of incident cancer in HF patients (HR, 1.76; 95% CI, 1.71–1.81). HF patients also died from cancer more frequently than controls (HR 4.11; 95% CI, 3.86–4.38; Figure 1). This excess mortality was highest when age was <70 years (HR 7.54, 95% CI 6.33–8.98), and declined in subjects aged 70–79 years (HR 3.80, 95% CI 3.44–4.19) and ≥80 years (HR 3.10, 95% CI 2.81–3.43). The association of HF with cancer mortality was confirmed in the competing risk analysis (HR 3.48, 95% CI 3.27–3.72), as well as the interaction with age: <70 years of age: HR 6.65, 95% CI 5.60–7.94; 70–80 years: HR 3.14, 95% CI 2.84–3.48; and ≥80 years: HR 2.81, 95% CI 2.55–3.10.

The HF-related risk applied to the majority of cancer types, with the exception of neoplasm of the male reproductive system. Interestingly, among HF patients a high consumption of loop diuretic (>37.5 mg/d of furosemide) was associated with a higher mortality for cancer (HR 1.34, 95% CI 1.26–1.42 vs. ≤37.5 mg/d).

Conclusions

The analysis of this large community-based sample suggests that HF does portend an increased risk of cancer and cancer-related mortality, which is blunted, yet remains substantial, with increasing age and competing risk of dying from other causes. The risk of cancer may be heightened when HF is poorly compensated.

Funding Acknowledgement

Type of funding sources: None. Figure 1. Cancer mortality in HF patient
Role of inflammation and comorbidities in the association of heart failure with incident cancer in the HUNT3 cohort
Authors: Bertero E , Carmisciano L , Jonasson C , Maack C , Ameri P
Published: October 2021

Background

Conflicting data exist regarding the risk of cancer in patients with heart failure (HF). It was first reported that incident cancer is more common among patients with than without HF, whereas more recent studies indicate that this association is primarily driven by comorbidities. HF, cancer, and comorbidities, such as chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), share numerous risk factors, including a state of chronic low-grade inflammation reflected by elevated circulating levels of pro-inflammatory cytokines. The objective of this analysis was to assess whether chronic low-grade inflammation, as measured by levels of high-sensitivity C-reactive protein (hsCRP), and comorbidities mediate the association of HF with incident cancer.

Methods

We used data from the 3rd wave of the Nord-Trøndelag Health Study (HUNT3), a population-based study that enrolled 50,803 individuals ≥18-year-old between October 2006 and June 2008 in the Nord-Trøndelag County (Norway), from the Cancer Registry of Norway and from the administrative health care records of the same region. Associations between baseline characteristics and the development of cancer were assessed using Cox proportional hazards regression models, using time from HUNT3 enrollment as the time scale. Analyses were performed using R statistical software, version 4.0.2.

Results

In HUNT3, hsCRP was measured in 47,571 individuals at the time of enrollment. Of these, we excluded 2,308 patients because of missing information, leaving a cohort of 45,263 subjects. Figure 1 shows the characteristics of the study population at baseline stratified by hsCRP tertiles. The prevalence of cardiovascular disease, comorbidities, and obesity was progressively higher with increasing concentrations of hsCRP.

During a median follow-up of 12 years, there were 66/408 cases of incident cancer in patients with HF at baseline and 5,024/47,163 in subjects without HF, with a more than 2-fold (HR 2.30; 95% CI 1.80–2.93; p<0.001) increase in risk of developing cancer. After adjusting for age and sex, the excess risk decreased to 43% (HR 1.43; 95% CI 1.12–1.82). When including hsCRP in the model, the HF-related risk of cancer was 33% (HR 1.33; CI 1.04–1.70; p=0.022). Furthermore, when body mass index, CKD, COPD, and smoking and drinking habits were included in the model, the risk of cancer in HF patients compared to individuals without HF was no longer significant (HR 1.23; 95% CI 0.94–1.60; p=0.127). Age, male sex, hsCRP, COPD, obesity, and smoking habits were all associated with an increased risk of cancer (Figure 2).

Conclusions

The increased risk of cancer in HF patients compared with the general population is at least in part explained by concomitant inflammation and comorbidities.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2
Cardiac rest and stress metabolism in type 2 diabetes (T2D): can the diabetic heart flex under stress?
Authors: Athithan L , Parke K.S , Ladwiniec A.H , Adlam D , Gulsin G.S , Marsh A.M , Sian M , McCann G.P , Levelt E
Published: October 2021

Background

Efficient matching of energy supply to demand is essential for maintaining normal cardiac function. Altered cardiac metabolism may contribute to the development of cardiac dysfunction by impairing metabolic flexibility in type 2 diabetes (T2D).

Purpose

We aimed to evaluate the effect of T2D on myocardial substrate preferences in response to acute increases in cardiac workload and the effects on contractile function utilising simultaneous coronary sinus (CS) and aorta blood sampling and cardiac magnetic resonance (CMR) imaging

Methods

Eligible participants without obstructive coronary artery disease (>50% luminal coronary artery stenosis on coronary angiography) underwent transmyocardial arteriovenous blood sampling. Metabolites in paired coronary sinus and arterial samples were quantified to determine myocardial fuel selection at rest and during a stress protocol with intravenous dobutamine. Free fatty acid (FFA), glucose, 3-hydroxybutyric acid (3HBA) and lactate utilisation at rest and haemodynamic stress was calculated as an extraction fraction % (EF). Participants underwent dobutamine stress multiparametric CMR imaging at 3.0 Tesla (Skyra, Siemens, Germany) on a separate visit within 21 days to quantify cardiac volumes, function and perfusion.

Results

Two thousand and sixty-one participants were screened and due to stringent inclusion and exclusion criteria for this mechanistic study, three T2D patients and five matching controls were enrolled. Baseline demographics and metabolic and CMR results are documented in Table 1. At peak stress levels there was a significant increase in FFA use from rest to stress in controls only (p=0.002). There were no significant differences in FA or glucose uptake between T2D patients and controls at rest or stress. 3HBA EF was significantly increased in T2D during stress (25.04% vs 5.31%, p=0.007). Mean FFA and 3-HBA changes calculated as extraction fraction at stress and rest are illustrated in Figure 1.

Conclusions

We demonstrate for the first time in vivo that the diabetic heart switches to ketone bodies during increased workloads as a significant fuel source. At present, it is unknown whether enhanced ketone body metabolism in T2D is beneficial, maladaptive, or a bystander. As the energetic properties of ketones are favourable, increased myocardial ketone oxidation could be an adaptive change designed to compensate for defects in myocardial energy metabolism in diabetes. Further, larger studies are warranted.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): British Heart Foundation - Clinical Research Training FellowshipWellcome Trust Seed Grant Table 1Figure 1
The efficacy of using a holistic 4-domain approach in evaluating frailty in ambulatory patient with heart failure
Authors: Sze S , Pellicori P , Zhang J , Weston J , Squire I B , Clark A L
Published: October 2021

Background

Recently, the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) proposed a four-domain approach to assess frailty in patients with heart failure (HF), to tailor treatment and potentially improve outcomes. The efficacy of such approach in detecting frailty and predicting outcome in patients with HF is unknown.

Aim

To study the prevalence and prognostic value of four different types of frailty deficits: clinical, physical, cognitive and social frailty in ambulatory patients with HF.

Methods

We assessed prospectively consecutive patients attending a routine follow-up visit. Patients with ≥5 non-HF comorbidities were classified as having a clinical deficit. Those who scored ≥3 using the Fried criteria were classified as having a physical deficit. Those who failed to complete a clock test accurately were classified as having a cognitive deficit. Those who lived alone or in a residential home were classified as having a social deficit. All patients were followed for a minimum of 1 year. The primary end point is all-cause mortality.

Results

We enrolled 467 patients (67% male, median (25th–75th centile) age 76 (69–82) years, median (25th–75th centile) NT-proBNP 1156 (469–2463) ng/L). 65% of patients had clinical deficits, 52% had a physical deficit, 39% had a social deficit and 18% had a cognitive deficit. 28% had 2, 19% had 3, 8% of patients had all 4 deficits; 16% had none. An increasing number of frailty deficits was associated with worse symptoms, higher NT-proBNP and less likelihood of being prescribed guideline-indicated HF treatment.

During a median follow-up of 554 days, 82 patients died. The presence of any frailty deficit was associated with increased risk of mortality. (Figure 1) The more frailty deficit a patient had, the higher the risk of mortality (Figure 2). A base model (including age, body mass index, NYHA class and log [NT-proBNP]) for predicting mortality at 1 year achieved a C-statistic of 0.78. Addition of all four deficits improved the performance of the base model (C-statistic = 0.82).

Conclusion

Clinical, physical, cognitive and social deficits are common in patients with HF and are associated with a poor outcome. Future studies should evaluate how a domain-based approach can be used to optimise care for frail patients with HF.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2
Influence of diabetes, heart failure, and NT-proBNP on cardiovascular outcomes in patients with atrial fibrillation – insights from a cohort study of 7,412 patients with extended follow-up
Authors: Hofer F , Pailer U , Sulzgruber P , Gerges C , Winter M P , Giugliano R P , Gottsauner-Wolf M , Huelsmann M , Kazem N , Koller L , Schoenbauer R , Niessner A , Hengstenberg C , Zelniker T A
Published: October 2021

Background

Diabetes and heart failure (HF) promote atrial fibrillation (AF) and are associated with an increased risk of adverse cardiovascular (CV) events in patients with AF. Because of effective anticoagulation options, AF patients are now more likely to develop HF than a stroke or a systemic embolic event. Appropriate risk stratification of patients with AF should therefore not only consider the risk for stroke but also for HF events.

Methods

Patients with AF admitted to a tertiary academic center between 01/2005 and 07/2019 were identified through a search of electronic health records. The primary outcome of interest was CV death or hospitalization for HF (HHF). We used Cox regression models adjusted for age, sex, estimated glomerular filtration rate, diabetes, HF, body mass index, prior myocardial infarction, hypertension, smoking, C-reactive protein, and LDL-C. To select the most informative variables and overcome the limitations of stepwise regression procedures, we performed a least absolute shrinkage and selection operator logistic regression in a model that incorporated diabetes, HF, NT-proBNP, and the covariates for adjustment in combination with 10-fold cross-validation.

Results

In total, 7,412 patients (median age 70 years, 39.7% female) were included in the present analysis and followed over a median of 4.6 years. Both diabetes (Adjusted (Adj.) hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.55 to 2.25) and HF (Adj. HR 2.57, 95% CI 2.22 to 2.98) were significantly associated with CV death/HHF after multivariable adjustment. Compared to patients with diabetes, HF patients had a higher risk of HHF but a similar risk of CV and all-cause death. There was a robust relationship between CV death/HHF and NT-proBNP (Adj. HR for 1-unit increase in standardized log-transformed biomarker 1.86, 95% CI 1.67 to 2.07). NT-proBNP showed good discriminatory performance (AUC 0.78, 95% CI 0.77–0.80), and the addition of NT-proBNP to the covariates used for adjustment resulted in a significant AUC improvement (Δ=0.04, P<0.001). With least absolute shrinkage and selection operator logistic regression, the strongest associations for CV death/HHF were obtained for NT-proBNP (OR 2.69 per 1-SD in log-transformed biomarker), HF (OR 1.73), and diabetes (OR 1.65).

Conclusion

These findings suggest that the influence of diabetes and HF expand beyond the risk of stroke and systemic embolic events to CV death/HHF in an unselected AF patient population. NT-proBNP may provide improved risk assessment in AF patients.

Funding Acknowledgement

Type of funding sources: None. Figure 1. Forest Plot
Similar incidence of over and underdiagnosis of heart failure in hospitalized patients with type 2 diabetes mellitus
Authors: Medovchshikov V , Yeshniyazov N , Khasanova E , Kobalava Z
Published: October 2021

Purpose

To assess the incidence of over and underdiagnosis of heart failure (HF) in hospital patients with type 2 diabetes mellitus (T2DM)

Methods

In the single-center prospective study (registry) from 01.08.2018 to 31.01.2019 we included 1008 patients admitted to the city hospital. Key inclusion criteria: a history of T2DM, age ≥40 years. Key exclusion criteria: any other disorders of carbohydrate metabolism, age <40 years, acute coronary syndrome, functionally dependent patients. We assessed the presence of HF in the diagnosis at admission by the following criteria: the presence of HF stage C or D (ACCF/AHA) and at least II NYHA functional class. All patients underwent standard echocardiography and NT-proBNP assessment at 1–3 days after admission. The diagnosis of HF was established by the 2016 ESC HF Guidelines. After the examination, the patients were divided into subgroups: “Confirmed HF” (HF was in the diagnosis, its presence was confirmed), “Unconfirmed HF” (HF was in the diagnosis, its presence was excluded), “First diagnosed HF” (HF was not in the diagnosis, its presence was confirmed) and “Absent of HF” (HF was not in the diagnosis and its presence was excluded). We also analyzed the reasons for admissions in all patients.

Results

The presence of HF in the diagnosis at admission was in 68.8% (n=693) of patients and, accordingly, it was absent in 31.2% (n=315). By the ESC HF Guidelines HF was diagnosed in 68.1% (n=686) and, accordingly, in 31.9% (n=322) it was excluded. The analysis results by the diagnosis at admission are presented in Fig. 1. The analysis of the reasons for admission depending on the HF status is presented in Fig. 2. In 35 patients admitted with HF decompensation the presence of HF was not confirmed and the diagnosis was revised: atrial fibrillation in 11 (31,4%) patients, exacerbation of COPD – 7 (20,0%), pulmonary embolism – 6 (17,1%), pneumonia – 4 (11,4%), kidney diseases – 4 (11,4%), and asthma – 3 (8,7%).

Conclusion

Among hospitalized patients with T2DM, there is a similar incidence of over and underdiagnosis of HF. Patients with first diagnosed HF were more likely to be admitted for reasons unrelated to cardiovascular diseases (CVD), most often with hyperglycemia (Fig. 2). Patients with unconfirmed HF – for reasons related to CVD, while the reason for admission in a quarter of patients was HF decompensation (Fig. 2). Despite the availability of examination for HF, the problem of its diagnosis is still relevant.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2
Prognostic value of simple risk index and plasma volume status in patients with acute decompensated heart failure
Authors: Yamada T , Watanabe T , Morita T , Kawasaki M , Kikuchi A , Kawai T , Seo M , Nakmura J , Kayama K , Fukunami M
Published: October 2021

Background

Increased heart rate (HR) and low systolic blood pressure (SBP) are associated with adverse clinical outcomes in patients admitted for acute decompensated heart failure (ADHF), and simple risk index (SRI) based on easily assessed clinical characteristics (age, HR, and SBP) provides prognostic information. On the other hand, plasma volume (PV) expansion plays an essential role in heart failure, and PV status is has been reported to be associated with adverse outcomes in ADHF patients. However, there is no information available on the value of the combination of SRI and PV status in patients admitted for ADHF.

Methods and results

We studied 301 patients admitted for ADHF. At the admission, SRI was calculated as (HR x [age/10]2)/SBP. PV status was calculated as the following: Actual PV = (1 − hematocrit) x [a + (b x body weight)] (a=1530 in males and a=864 in females, b=41 in males and b=47.9 in females), Ideal PV = c x body weight (c=39 in males and c=40 in females), and PV status = [(actual PV − ideal PV)/ideal PV] x 100(%). During a follow-up period of 4.3±3.2 yrs, 95 patients had all-cause death (ACD) and 68 patients had cardiovascular death (CVD). At multivariate Cox analysis, SRI and PV status were significantly associated with ACD and CVD, independently of the prior history of heart failure hospitalization and serum creatinine and sodium levels, after the adjustment with serum albumin level and anemia. Patients with both greater SRI (≥35.1 by ROC analysis; AUC 0.599 [0.524–0.674]) and greater PV status (≥8.1% by ROC analysis; AUC 0.625 [0.550–0.700]) had a significantly higher risk of ACD and CVD than those with either or none of them (ACD: 49% vs 27% vs 24%, p<0.0001, CVD: 39% vs 18% vs 15%, p<0.0001,respectively).

Conclusion

The combination of SRI and PV status might be useful for stratifying patients at risk for the total mortality and cardiovascular death in patients with ADHF.

Funding Acknowledgement

Type of funding sources: None.
Long-term prognostic value of the combination of malnutrition and fib-4 index in patients admitted with acute decompensated heart failure
Authors: Yamada T , Watanabe T , Morita T , Kawasaki M , Kikuchi A , Kawai T , Seo M , Nakamura J , Kayama K , Fukunami M
Published: October 2021

Background

Malnutrition is associated with increased mortality risk in patients with acute decompensated heart failure (ADHF). Cardiohepatic interactions have been a focus of attention among heart failure. It was reported that liver stiffness assessed by non-invasive fibrosis marker such as Fibrosis-4 (FIB4) index provide prognostic information in ADHF patients. However, there is no information available on the long-term prognostic value of the combination of malnutrition and FIB4 index in patients admitted for ADHF.

Methods and results

We studied 294 patients admitted for ADHF, who were discharged with survival. Nutritional status was evaluated by Geriatric Nutritional Risk Index (GNRI) calculated as follows: 14.89 × serum albumin (g/dl) + 41.7 × BMI/22, and malnutrition was defined as GNRI <92. FIB4 index was calculated by the formula: age (yrs) × AST[U/L] / (platelets [103/μL] × (ALT[U/L])1/2), and abnormal FIB4 index was defined as >2.67. During a mean follow-up period of 4.3±3.3 yrs, 94 patients had all-cause death. At multivariate Cox regression analysis, GNRI and FIB4 index were significantly associated with the total mortality, independently of prior heart failure hospitalization, systolic blood pressure, and serum creatinine level. Patients with malnutrition and abnormal FIB4 index had a significantly higher risk of the total mortality than those with either and none of them (49% vs 32% vs 20%, p<0.0001, respectively).

Conclusions

The combination of malnutrition and FIB4 index might be useful for stratifying ADHF patients at higher risk for the total mortality.

Funding Acknowledgement

Type of funding sources: None.
Safety of endomyocardial biopsy in new-onset acute heart failure requiring veno-arterial extracorporeal membrane oxygenation
Authors: Van Der Boon R M A , Den Dekker W K , Meuwese C L , Lorusso R , Von Der Thusen J H , Constantinescu A C , Manintveld O C , Delnoij T S R , Van Der Heijden J J , Van Mieghem N M D A , Den Uil C A
Published: October 2021

Background

Refractory cardiogenic shock (CS) complicating new onset acute heart failure (new-AHF) is a medical emergency, requiring immediate mechanical circulatory support (MCS) to prevent hemodynamic deterioration. When non-invasive testing is impossible, endomyocardial biopsy (EMB) has an important role in determining the etiology of new-AHF.

Purpose

The aim of this study was to determine the procedural safety of EMB in patients with new-AHF requiring VA-ECMO. Additionally, we describe the detection rate of an underlying etiology of new-AHF on histopathological examination.

Methods

A retrospective, multicenter cohort of patients undergoing EMB while requiring VA-ECMO for new-AHF between 1990 and 2020 was compared with a cohort of non-transplant related biopsies not requiring VA-ECMO. Primary endpoint of the study was the safety of EMB with a secondary endpoint being the detection rate of an underlying etiology causing new-AHF on histopathologic examination.

Results

A total of 23 patients underwent EMB while requiring VA-ECMO (10.0%), 125 (54.3%) during an unplanned admission and 82 (35.7%) in elective setting. Major complications occurred in 8.3% of all procedures with a significantly higher rate in patients requiring VA-ECMO (26.1% vs. 8.0% vs. 3.7%,p=0.003), predominately due to occurrence of sustained ventricular tachycardia or need of resuscitation (13.0% vs. 3.2% vs. 1.2%,p=0.02). EMB led to a histopathological diagnosis in 78.3% of the patients requiring VA-ECMO which consisted primarily of patients with myocarditis (73.9%).

Conclusions

EMB in patients requiring VA-ECMO can be performed albeit with a substantial risk of major complications. This risk of the procedure was offset by a high detection rate of an underlying etiology on histopathological examination. The important therapeutic and prognostic implications of EMB in this population warrant further refinement to improve procedural safety.

Funding Acknowledgement

Type of funding sources: None. Major safety endpoints according to EMB
Efficacy and feasibility of heart failure nurses to deliver a lungs and inferior vena cava ultrasound assessment (LUICA) protocol and prediction of outcomes
Authors: Zisis G , Yang Y , Whitmore K , Lay M , Huynh Q , Neil C , Carrington M , Marwick T H
Published: October 2021

Background/Introduction

Congestion is the main cause for hospital admission and readmission in heart failure (HF), with almost half being discharged with symptoms that suggest residual congestion. Novel non-invasive assessments (eg. lung ultrasound; [LUS], and Inferior Vena Cava [IVC]) may be used to assess congestion. A LUs and IvC Assessment (LUICA) delivered by HF nurses before discharge, could detect residual congestion, optimise diuresis and guide post discharge treatment.

Purpose

To determine the ability of HF nurses to successfully learn a LUICA protocol, obtain interpretable images, provide diagnostic reports and predict outcomes.

Methods

A teaching program focused on quantification of congestion by counting B-lines and reporting estimated right atrial pressure (e-RAP) from IVC congestion. LUICA readings were dichotomised based on lung congestion (≥10 vs <10 B-lines), the presence of lung pathology (consolidation, atelectasis, effusion) and IVC congestion (e-RAP >3mmHg vs 3mmHg). LUICA (8 lung zones + 2 IVC zones) was added to pre-discharge review (4 days post-admission) by HF nurses in 108 hospitalised pts (72±13 years; 58% male) with acute HF, fluid overload, and a variety of lung pathology. Images were assessed for quality (good, usable, measurable or not measurable) and interpreted by a LUICA expert and HF nurses, blinded to admission diagnosis. The predictive value of LUICA readings for patient outcomes (readmission or mortality) was expressed as risk ratio.

Results

The quality at the majority of the images was assessed as good or usable (expert: 82/107, nurses: 66/107, p=0.02). Readmission was predicted by both experts and nurses (picture 1).

Conclusions

HF nurses can be adequately trained in a 10 Zone LUICA and successfully obtain interpretable images. The predictive power of their interpretation is similar to experts.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): The University of MelbourneBaker Heart & Diabetes Institute Readmission risk ratio based on LUICA