bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dapagliflozin in a real-world population with chronic heart failure: how many would be eligible?
Authors: Maltes S.F.C , Rocha B.L , Cunha G.L , Presume J.P , Campos L , Henriques C , Rodrigues C.A.P.F , Araujo I , Fonseca M.C 
Published: November 2020

Abstract

Background
In patients with heart failure (HF) and reduced left ventricle ejection fraction (LVEF), the sodium-glucose cotransporter inhibitor (iSGLT2) dapagliflozin has recently been shown to reduce the risk of worsening heart failure or death from cardiovascular causes in the DAPA-HF trial. Results of iSGLT2 in HF with preserved LVEF are awaited. Our goal was to investigate how many patients in a real-world setting would be eligible for dapagliflozin according to the DAPA-HF criteria.

Methods
This is a single-center retrospective study enrolling consecutive patients followed in an HF Clinic from 2013 to 2019. The key DAPA-HF inclusion criteria [i.e., Left Ventricular Ejection Fraction (LVEF) &lt;40% and NT-proBNP &gt;600pg/mL (or &gt;900pg/ml if AF)] and exclusion criteria [estimated glomerular filtration rate (eGFR) &lt;30ml/kg/1.73m2, systolic blood pressure (SBP) &lt;95mmHg] were considered.

Results
Overall, 479 patients (mean age 75.7±12.8 years; 50.4% male; 78.8% with hypertension; 45.0% with an eGFR &lt;60ml/min/1.73m2; 36.5% with type 2 diabetes mellitus; 33.5% ischaemic HF) were assessed. Of these, 155 (33.2%) patients had LVEF &lt;40%. Patients had a mean SBP of 131±28 mmHg, a median eGFR of 48 (IQR 33–65) ml/min/m2 and a NT-proBNP of 2183 (IQR 1010–5310) pg/mL Overall, according to the DAPA-HF trial key criteria, 88 patients (18.3%) would be eligible for dapagliflozin. The remainder would be excluded due to a LVEF&gt;40% (67.5%), eGFR &lt;30 ml/min/1.73m2 (19.4%), NT-proBNP &lt;600 pg/mL (or &lt;900 pg/mL if AF) (16.7%) and/or SBP &lt;90mmHg (2.1%) (figure 1). If we limit the analysis to those with a LVEF &lt;40%, 56.7% would be eligible for dapagliflozin. The remainder would be excluded due to a eGFR &lt;30ml/kg/1.73m2 (20%), NT-proBNP &lt;600 pg/mL (or &lt;900 pg/mL if AF) (16.1%) and/or SBP &lt;90mmHg (8.4%) (figure 1).

Conclusion
Roughly one in every five patients in our real-world HF cohort would be eligible to start dapagliflozin according to the key criteria of the DAPA-HF trial. The main reason for non-eligibility was a LVEF &gt;40%. These findings highlight the urgent need for disease-modifying drugs in mid-range and preserved LVEF. The results of ongoing iSGLT2 trials in these LVEF subgroups are eagerly awaited.

Funding Acknowledgement
Type of funding source: None
Increased oxygen uptake and utilization in the peripheral muscles, rather than cardiac function reserve, may be determinants of increased peak VO2 by cardiac rehabilitation in heart failure
Authors: Hasegawa H , Kono T , Sakane K , Matsuoka T , Soyama A , Murakami S , Hoshiga M 
Published: November 2020

Abstract

Background
Peak oxygen consumption (peak VO2) is a major prognostic parameter in heart failure (HF). Previous studies have shown a relationship between peak VO2 and impaired oxygen uptake and utilization in the peripheral muscles. The purpose of this study was to clarify the determinant of increased peak VO2 by cardiac rehabilitation (CR) in patients with HF.

Methods
We performed echocardiography during upright ramp bicycle cardiopulmonary exercise test in 30 HF patients (61±1 years of age, 80% male) before and 6 months after CR. HR reserve was determined as the change in HR from rest to peak exercise, expressed as a percentage of the predicted maximal HR reserve. Elastance index (EAI) and LV end-systolic elastance index (ELVI) were derived as the ratio of end-systolic pressure to stroke volume index and end-systolic volume index, respectively. End-systolic pressure was estimated from the equation 0.9 × brachial systolic blood pressure. Ventriculo-arterial coupling (VAC) was calculated as the quotient of EAI and ELVI. The ratio of LDEDVI to E/e' mean was used to evaluate LV diastolic compliance. Systemic vascular resistance index was calculated as mean arterial pressure divided by echocardiography calculated cardiac index and multiplied by 80. The arterial venous oxygen content difference (C (A-V) O2 gradient) was calculated by using the Fick equation as: VO2/echocardiography calculated cardiac output.

Results
Peak VO2 and C (A-V) O2 gradient were increased by CR. However, heart rate reserve, systolic reserve, VAC, diastolic reserve and vasodilation reserve were unchanged by CR (Table 1).

Conclusions
Increased oxygen uptake and utilization in the peripheral muscles, rather than cardiac function reserve, may be determinants of increased peak VO2 by CR in HF.
Table 1

Funding Acknowledgement
Type of funding source: None
Left ventricular volumes at baseline and outcome in heart failure patients undergoing cardiac resynchronization therapy
Authors: Kostyukevich M , Van Der Bijl P , Mertens B , Vo M , Marsan N.A , Delgado V , Bax J.J 
Published: November 2020

Abstract

Background
Studies evaluating the relationship between baseline left ventricular (LV) volumes and long-term prognosis in heart failure (HF) patients undergoing cardiac resynchronization therapy (CRT) are lacking.

Purpose
To evaluate the association of LV end-systolic and end-diastolic volumes (ESV and EDV) with long-term prognosis in patients with HF treated with CRT.

Methods
Patients from an ongoing institutional HF registry who received CRT according to contemporary guidelines were included. All patients underwent standard transthoracic echocardiography. LV volumes were measured using the biplane method during off-line analysis. Primary end-point included all-cause mortality, implantation of left ventricular assist device or heart transplantation, which were assessed according to the national death registry and case records.

Results
In total, 1165 patients with feasible LV volume assessment were included (mean age 67±10 years; 74.8% males; 55.3% with non-ischemic aetiology of HF). After a median follow-up of 75 (40; 123) months, the primary end-point occurred in 708 (60.8%) patients. Median baseline LV ESV was 151 (108; 198) ml and EDV was 202 (156; 258) ml. All patients were divided into quartiles according to the baseline EDV and ESV: those with larger volumes were significantly younger, more frequently male and had longer QRS durations (p&lt;0.001). Heart failure aetiology, glomerular filtration rate, quality of life and 6-minute walking test distance did not differ significantly between the groups (p&gt;0.05). To investigate the association between long-term prognosis and baseline LV volumes (EDV and ESV), a Cox proportional hazards model was constructed with variables known to influence the mortality of HF patients (age, gender, aetiology, QRS duration, and estimated glomerular filtration rate). When separately included in a multivariate analysis, baseline LV ESV and LV EDV were both independently associated with the primary end-point (p&lt;0.001). To demonstrate hazard change across the range of LV ESV and EDV as continuous variables, an adjusted (for covariates influencing HF mortality) spline curve was drawn, showing an increased mortality risk when the baseline LV ESV and EDV are larger than 100 ml and 200 ml, respectively (Figure).

Conclusion
LV volumes before CRT implantation are independently associated with prognosis during long-term follow-up. Our findings indicate the importance of taking baseline LV remodelling into consideration to identify patients at high mortality risk after CRT implantation.

Funding Acknowledgement
Type of funding source: Public grant(s) – EU funding. Main funding source(s): The author acknowledges funding received from the European Society of Cardiology in form of an ESC Training Grant
Partial normalisation of cardiac mechanics with active CRT in patients with chronic failure: a novel application of 3.0T CMR
Authors: Koshy A , Gierula J , Paton M , Swoboda P , Toms A.G , Saunderson C , Shelley D , Broadbent D , Plein S , Kearney M.T , Witte K.K 
Published: November 2020

Abstract

Introduction
Cardiac resynchronisation therapy (CRT) is a routine treatment for chronic heart failure (CHF) with reduced ejection fraction and conduction delay to improve prognosis. Cardiac mechanics in patients with CHF are believed to be altered from controls based on invasive and echocardiographic based data. Technological advancements in cardiac magnetic resonance (CMR) and devices enable investigation of the cardiac response to CRT over a range of heart rates.

Methods
Patients with a CRT-D device were enrolled from heart failure clinics at Leeds General Infirmary, UK. After a MRI safety assessment, a baseline device check was conducted by a cardiac physiologist. Left ventricular (LV) volumes and systolic BP were measured at baseline and heart rates of 75, 90, 100, 115, 125, and 140 (randomised order) with CRT active and intrinsic conduction. All scans were conducted using a 3.0 T Siemens Prisma MRI scanner. Analysis of the scans used commercially available software. LV contractility was derived as a ratio of the LV end systolic volume and systolic BP. A post scan device interrogation was conducted to assess for scanning safety. Control participants with a 3.0T MR-conditional dual chamber pacemakers completed a similar protocol.

Results
Scanning was conducted in 17 CRT patients and 13 controls with a pre and post device and lead interrogation. No patient experienced symptoms related to scanning or device failure. The mean LV ejection fraction at baseline in the CRT cohort was 33.7±12.9%. Left ventricular ejection fraction fell across both cohorts as paced heart rate increased with reduced deterioration in control patients and those with CRT active. Peak LV cardiac output was significantly higher during active CRT (p&lt;0.05). LV contractility was relatively static with CRT disabled (r2=0.13, p=0.38) and improved with CRT active (r2=0.91, p=0.01) and in controls (r2=0.74, p=0.01). Peak LV strain occurred at 100bpm during active CRT and in control patients whereas CRT disabled resulted in earlier deterioration.

Conclusion
We have demonstrated improvements in cardiac output and contractility consequent to active CRT using 3.0T CMR and subsequently validated via strain analysis. CRT appears to partially normalise cardiac mechanics across the range of heart rates studied. Further work is required to explore this phenomenon on a cellular or metabolic level.

Funding Acknowledgement
Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): AK is supported by an unconditional grant provided by Medtronic
Prognostic value and usefulness of Pulmonary Artery Pulsatility index (PAPi) in evaluation of heart transplant candidates
Authors: Bellettini M , Pidello S , Gallone G , Frea S , Masetti M , Sabatino M , Boschi S , Giustetto C , Boffini M , Rinaldi M , Potena L , De Ferrari G.M 
Published: November 2020

Abstract

Background
Heart transplantation (HTx) is considered the best available treatment for patients with end stage heart failure. Candidate evaluation with right heart catheterization (RHC) is fundamental in order to exclude pulmonary hypertension with irreversible high pulmonary vascular resistance (PVR), which is associated with elevated post-HTx mortality. PVR, rather than directly measured, is derived by cardiac output and pulmonary artery pressures, which are strictly dependent on right ventricular (RV) function. The pulmonary artery pulsatility index (PAPi) is a hemodynamic parameter integrating the information of RV function and of pulmonary circulation, which could be useful in pre-HTx evaluation.

Purpose
We designed this study to evaluate the potential predictive influence of pre-HTx PAPi on post-HTx survival and to assess whether this index could add useful information in the pre-HTx evaluation of patients with advanced heart failure.

Methods
Consecutive adult HTx recipient at two medium-large tranplant centers between 2000 and 2017 with available data on pre-HTx RHC were retrospectively included. PAPi was calculated as the ratio of pulmonary artery pulse pressure to right atrial pressure. PAPi values in the lowest quartile were defined as reduced (PAPi&lt;1.67). The primary endpoint was all-cause mortality at 1-year post-HTx. The association of reduced PAPi with the primary endpoint was evaluated. Cox regression was used to adjust for clinical and hemodynamic variables. Analyses stratified by PVR status (≥3 WU vs. &lt;3 WU) were also performed.

Results
Among 655 HTx recipients (female 20,8%, age 53±11 years), median pre-HTx PAPi was 3.0 (interquartile range 1.67–5.32). Patients in the lowest versus the remaining PAPi quartiles had significantly reduced 1-year survival (78.0% vs 87.2%, p=0.006), also after adjusting for age, estimated glomerular filtration rate, total bilirubin, high PVR and urgent transplantation (adj-hazard ratio: 0.64; 95% confidence interval 0.51–0.82). When stratifying patients by estimated PVR status, reduced PAPi was associated with worse 1-year survival among patients with normal PVR (78.3% vs. 88.3% p=0.011), but not in those with increased PVR (78.0% vs. 82.6%, p=0.36) (Figure 1).

Conclusions
Pre-HTx PAPi, integrating information of RV function and pulmonary circulation, provides incremental prognostic value over traditional clinical and hemodynamic parameters among HTx recipient. The prognostic value appears important among patients with normal estimated PVR, possibly due to an underestimation of PVR in patients with impaired RV function. The integration of PAPi in the pre-HTx evaluation may lead to better patient selection and post-HTx survival.
Figure 1. 1 year survival stratified by PVR status

Funding Acknowledgement
Type of funding source: None
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

Abstract

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&lt;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&lt;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

Abstract

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&lt;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&lt;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&lt;0.01, beta = 0.45), PCW pressure (P&lt;0.01, beta = 0.42), and BNP (P&lt;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

Abstract

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