bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of sacubitril/valsartan on cognitive function in patients with HFpEF: a prespecified analysis of PARAGON-HF
Authors: Dewan P , Jhund P.S , Anand I.S , Desai A.S , Gong J , Lefkowitz M.P , Pieske B , Rizkala A.R , Shah S.J , Van Veldhuisen D.J , Zannad F , Zile M.R , Solomon S.D , McMurray J.J.V 
Published: November 2020

Abstract

Background
A theoretical concern has been raised about detrimental effects of sacubitril/valsartan (sac/val) on cognitive function as neprilysin is one of many pathways involved in clearance of amyloid beta peptides from brain tissue.

Purpose
To examine effect of sac/val, compared with valsartan, on cognitive function in patients with heart failure (HF) and preserved ejection fraction (HFpEF).

Methods
In the PARAGON-HF trial, cognitive function was tested in a subgroup of patients at baseline and follow-up, using Mini-Mental State Examination [MMSE] having a maximum score of 30 (higher scores reflect better cognitive function). Change in MMSE score from baseline to 96 wks was a prespecified exploratory endpoint. Other post hoc analyses included “cognitive decline” (fall in MMSE ≥3 pts) and assessment of cognition-related adverse events (AEs).

Results
Among 2895 patients (60% of total) in PARAGON-HF with baseline MMSE measurement, mean (SD) score was 27.4 (3.0) in patients receiving sac/val (1453) and 27.4 (2.9) in patients receiving valsartan (1442). There was no difference between sac/val and valsartan in MMSE score change from baseline to wk 96: sac/val −0.02 (SE 0.07) and valsartan 0.00 (0.07); between-treatment difference −0.02 (95% CI: −0.22 to 0.18); p-value = 0.83. Cognitive decline at 96 weeks occurred in 115 of 1071 evaluable patients (10.7%) in sac/val group and 121 of 1053 patients (11.5%) in valsartan group; risk ratio 0.97 (0.75–1.26), p-value = 0.82. Cognition-related AEs were more frequent, than in PARADIGM-HF (likely as patients in PARAGON-HF were older) but, as in PARADIGM-HF, did not differ between sac/val and comparator treatment (Table).

Conclusions
Cognitive change, measured by MMSE, did not differ between treatment with sac/val & valsartan in patients with HFpEF.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): PARAGON-HF study was funded by Novartis Pharma.
Mortality in a well-defined group of predominantly Caucasian pulmonary sarcoidosis patients
Authors: Huitema M.P , Mathijssen H , Bakker A.L.M , Mager J.J , Grutters J.C , Post M.C 
Published: November 2020

Abstract

Background
Sarcoidosis is an inflammatory systemic disease. Mortality has often been described in patients with more advanced disease, especially in those awaiting lung transplant. The PULSAR study is a cross sectional study prospectively investigating at least two year follow up on mortality in a large prospective, well-defined cohort of Dutch sarcoidosis patients, newly referred to a tertiary centre for sarcoidosis, including data on echocardiography.

Methods
All patients underwent prospective screening. Patients with intermediate or high probability for PH where referred for right heart catheterisation (RHC). In accordance to the guideline PH was defined as a mean PAP ≥25mmHg by RHC. Elevated pulmonary artery pressure was defined as &gt;20 and &lt;25mmHg. The absence of PH was defined as a mean PAP &lt;25mmHg or a low PH probability on echocardiography. Survival was defined as absence of mortality or transplantation at the time of evaluation.

Results
399 patients were included in the analysis. All patients had follow up of at least 2 years. Five patients had died during fallow up, and none were transplanted. The PH prevalence was 3%. PH and elevated pulmonary artery pressure was associated with worse survival. On echocardiography, high PH probability was associated with worse survival compared to low PH probability (HR 1.78, p=0.01). If measurable, RVSP differed significantly between groups.

Conclusion
Only high PH probability and RVSP measurement on echocardiography were associated with mortality

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): ZonMW
The impact of epicardial adipose tissue and right ventricular hypertrophy on diastolic and global function of right ventricle in patients with metabolic syndrome
Authors: Sedaia E , Revenco V , Gutan I , Ochisor V , Vascenco A 
Published: November 2020

Abstract

Background
Metabolic syndrome (MetS) and visceral obesity represent important cardiometabolic risk factors. Right ventricular (RV) function is affected in MetS. Epicardial adipose tissue is a metabolically active organ which might influence cardiac morphology and function, especially in patients with MetS. Epicardial fat thickness (EFT) is proposed as a new marker of visceral obesity.

Purpose
The objective of our study was to evaluate the role of EFT and RV hypertrophy in global (determined by Tei index) and diastolic function of RV in patients with MetS.

Methods
The study included 85 subjects with MetS (mean age 52±9.1 years) and 85 controls without MetS (mean age 50±8.9 years, P=0.06). MetS was defined by ≥3 criteria of International Diabetes Federation and American Heart Association/National Heart, Lung, and Blood Institute. All the subjects underwent complete 2D echocardiography with the assessment of the ratio of early and late diastolic tricuspid flow velocities (Et/At), the ratio of early diastolic tricuspid flow velocity and early diastolic tricuspid annular velocity (Et/e't), Et deceleration time (DT), RV end-diastolic free wall thickness (EDWT) and EFT. We determined Tei index of RV by pulsed and pulsed tissue Doppler.

Results
All the parameters of RV diastolic function, as well as Tei index, were significantly changed in MetS group: Et/At 0.85±0.39 vs. 1.17±0.43, P&lt;0.001; Et/e't 5.1±1.3 vs. 4.5±0.8, P&lt;0.001; DT 235±8 ms vs. 208±14 ms, P&lt;0.001; Tei index by pulsed Doppler (0.48±0.05 vs. 0.34±0.06, P&lt;0.001) and by pulsed tissue Doppler (0.58±0.05 vs. 0.46±0.04, P&lt;0.001). Also, RV EDWT was significantly higher in MetS patients (6.3±0.8 mm vs. 4.6±1.2 mm, P&lt;0.001) and positively correlated with Tei index (r=0.658, P&lt;0.001; fig.1.A), Et/e't (r=0.269, P&lt;0.001) and EFT (r=0.547, P&lt;0.001). EFT was higher in MetS subjects (7.9±0.07 mm vs. 5.4±1.2 mm, P&lt;0.001) and correlated with RV Tei index (r=0.614, P&lt;0.001; fig.1.B), Et/e't (r=0.432, P&lt;0.001). Multivariate regression analysis showed that systolic blood pressure, plasma glucose level, EFT and RV EDWT were independently associated with RV global and diastolic dysfunction in patients with MetS (P&lt;0.05 for all parameters).

Conclusions
Our findings support that MetS is associated with diastolic and global dysfunction of RV. In subjects with MetS increased EFT and RV hypertrophy are independently associated with RV diastolic and global function.

Funding Acknowledgement
Type of funding source: None
Non-fatal cardiovascular events preceding sudden cardiac death in patients with an acute myocardial infarction complicated by heart failure: insights from the High-Risk-Myocardial-Infarction database
Authors: Hui S , Sharma A , Docherty K , McMurray J.J.V , Pitt B , Dickstein K , Pfeffer M.A , Girerd N , Rossignol P , Ferreira J.P , Zannad F 
Published: November 2020

Abstract

Background
Sudden cardiac death (SCD) is responsible for 20–40% of mortality following acute myocardial infarction (AMI). The risk of SCD is even higher among patients with AMI complicated by heart failure (HF) (either clinically apparent HF or left ventricular dysfunction). The temporal relationship between an AMI complicated by HF and subsequent SCD and the association of non-fatal cardiovascular (CV) events following AMI with SCD has yet to be described.

Purpose
Among patients with AMI complicated by HF, we evaluated the probability and temporal association of subsequent non-fatal cardiovascular (CV) events (HF hospitalization, recurrent MI, or stroke) and SCD.

Methods
The High-Risk Myocardial Infarction (HRMI) database contains 28,771 patients with signs of HF or reduced LV ejection fraction (&lt;40%) after AMI. Among patients with an AMI complicated by HF, we used adjudicated cause of death from the HRMI Database to identify: 1) the temporal distribution of SCD among patients following an index AMI; 2) the probability of having SCD following a non-fatal CV event following the index AMI.

Results
Median follow-up was 1.9 years. Mean age was 65.0±11.5 years and 70% were male. The incidence of CV death was 7.9 per 100 patient-year [py] and for SCD was 3.1 per 100py (40% of CV deaths). SCD rates were highest in the early period (&lt;90 days) after AMI and decreased over time. Recurrent MI preceded 9.6% of SCD after a median time of 145 days; HF hospitalization preceded 17.0% of SCD after a median 144 days; and stroke preceded 2.7% of SCD after a median of 138 days (vs. non-sudden CV death: MI 46.6% at 1 days, HF hospitalization: 30.9% at 67 days, stroke 12.9% at 9 days). The incidence of SCD preceded by HF hospitalization was significantly higher than SCD without preceding HF hospitalization.

Conclusion
Among patients with AMI complicated by HF, SCD predominantly occurred in the early “high-risk” period after AMI; SCD rates decreased afterwards. Patients with non-fatal HF hospitalizations during follow-up may have a higher subsequent SCD risk. Preventing HF onset after MI may help decreasing SCD.
Proportion of sudden cardiac death

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Lucien Award, McGill University
Prognostic value of the cardiorespiratory optimal point during submaximal exercise testing
Authors: Dias Ferreira Reis J.P , Goncalves A , Bras P , Ferreira V , Viegas J , Rio P , Moreira R , Pereira Silva T , Timoteo A , Soares R , Cruz Ferreira R 
Published: November 2020

Abstract

Background
Peak oxygen consumption (pVO2) is a key parameter in assessing the prognosis of heart failure with reduced ejection fraction (HFrEF) patients (pts). However, it is a less reliable parameter when the cardiopulmonary exercise test (CPET) is not maximal. It is crucial to identify the submaximal exercise variables with the best prognostic power (PP), in order to improve the management of pts that cannot attain a maximal CPET.

Purpose
The aim of this study was to evaluate and compare the PP of several exercise parameters in submaximal CPET for risk stratification in pts with HFrEF.

Methods
Prospective evaluation of adult pts with HFrEF submitted to CPET in a tertiary center. A submaximal CPET was defined by a respiratory exchange ratio (RER) ≤1.10. Pts were followed up for at least 1 year for the primary endpoint of cardiac death and urgent heart transplantation/ ventricular assist device implantation. Several CPET parameters were analyzed as potential predictors of the combined endpoint and their PP (area under the curve - AUC) was compared to that of pVO2, using the Hanley and McNeil test.

Results
CPET was performed in 487 HF pts, of which 317 (66%) performed a submaximal CPET. Pts averaged 57±12 years of age, 77% were male, 45.7% had ischemic cardiomyopathy, with a mean LVEF of 30.4±7.6%, a mean heart failure survival score of 8.6±1.1. The mean pVO2 was 17.1±5.5 ml/kg/min and the mean RER 1.01±0.08. During a mean follow-up (FU) time of 11±1 months, 18 pts (6%) met the primary endpoint. Cardiorespiratory optimal point (OP - VE/VO2) had the highest AUC value (0.915, p=0.001), followed by the partial pressure of end-tidal CO2 at the anaerobic threshold - PETCO2L (0.814, p&lt;0.001). pVO2 presented an AUC of 0.730 (p=0.001). OP≥31 and PETCO2L ≤37mmHg had a sensitivity of 100 and 76.9% and a specificity of 71.1 and 67%, respectively, for the primary outcome. OP presented a significantly higher PP than pVO2 (p=0.048), whether PETCO2L didn't achieve any statistical significance (p=0.164). Pts with anOP≥31 presented a significantly lower survival free of HT during FU (log rank p=0.002).

Conclusion
OP had the highest PP for HF events of all parameters analyzed for a submaximal CPET. This parameter can help stratify the HF pts physiologically unable to reach a peak level of exercise.

Funding Acknowledgement
Type of funding source: None
HLM, a TNM-like classification for heart failure, compared with other nosologies at 12 months follow-up
Authors: Severino P , Pucci M , Mariani M.V , D'Amato A , Infusino F , Birtolo L.I , Morano G , D'Ascenzo F , Maestrini V , Mancone M , Fedele F 
Published: November 2020

Abstract

Background
Heart failure (HF) is the pandemic of the third millennium with the highest mortality among general population, while lung cancer is the second most common cause of death. As cancer, HF can affect close organs, as lungs, or can reach peripheral organs (kidney, liver, brain), leading to multi-organ dysfunction, like cancer metastasis.

Purpose
We proposed a new staging system named HLM, analogous to TNM classification used in oncology, which refers to heart damage (H), lung involvement (L), and malfunction (M) of peripheral organs. The aim of this study is a comparison between HLM and NYHA, ACC/AHA and MAGGIC scores to assess the most accurate prognosis of HF patients in terms of rehospitalization for acute HF (AHF) or major adverse cardiac and cerebrovascular events (MACCE), and cardiac death.

Methods
We performed a single-center observational study of HF patients. All parameters for heart, lungs and peripheral organs function were examined. Each patient was classified according to HLM, NYHA, ACC/AHA and MAGGIC score at the entrance and at the discharge. Rehospitalization for MACCE or AHF and cardiac death were checked at 12 months follow up.

Results
We enrolled 2054 patients: 68.5% males, 31.3% females, mean age 70.18±7.48 years. Among them, overall survival curves regarding rehospitalization for MACCE, AHF and cardiac death at 12 months, show that HLM classification is as valid as the others (p&lt;0.001). In particular, the area under the ROC curve (AUC) is greater for HLM than NYHA, ACC/AHA and MAGGIC score in terms rehospitalisation for MACCE (HLM=0.687; NYHA=0.642; ACC/AHA=0.604; MAGGIC=0.657) or AHF (HLM=0.662; NYHA=0.652; ACC/AHA=0.604; MAGGIC=0.662) and cardiac death (HLM=0.783; NYHA=0.712; ACC/AHA=0.623; MAGGIC=0.737).

Conclusion(s)
According to our results, HLM classification has greater prognostic power compared to other nosologies in terms of rehospitalization for MACCE, AHF and cardiac death for HF patients, thanks to a more accurate evaluation of the systemic impact of heart failure. Such a multivariable, holistic approach should be used in HF patients, rather than a “cardiocentric” approach, in order to address the pathophysiological mechanisms underlining heart abnormalities, improving clinical management and costs.

Funding Acknowledgement
Type of funding source: None
Evidence of occult right ventricular dysfunction in morbidly obese patients
Authors: Samuel Kulifay S.L.K , Dominic Lattanzio D.S.L , Brandon Mikolich B.M.M , Ronald Mikolich J.R.M 
Published: November 2020

Abstract

Background
Abnormalities of right ventricular (RV) strain have been shown to occur prior to impairment of global right ventricular function, measured by global RV ejection fraction (RVEF) in patients with increased RV afterload, such as pulmonary hypertension. Obesity is a form of increased afterload involving both the right and left cardiac circulations, raising suspicion that impaired RV strain may be an early indicator of myocardial dysfunction.

Purpose
This study was designed to assess impairment of RV strain in obese patients with normal right ventricular ejection fraction (RVEF) using cardiac MRI Fast SENC (strain encoded) pulse sequences.

Methods
An institutional cardiac imaging database was queried for all patients with body mass index (BMI) greater than 35 kg/m2 who underwent measurement of RV global longitudinal strain (GLS), RV global circumferential strain (GCS) and 37 segmental strain measurements using cardiac MRI Fast-SENC pulse sequences. Global RVEF was computed for all patients using a standard cardiac MRI method using non-automated hand drawn RV endocardial borders. Global and regional strain measurements were compared to a cohort of healthy volunteers who also underwent CMR Fast-SENC imaging. Abnormal myocardial strain was defined as a value greater than −17%.

Results
Of the 356 patients in the database, 48 had a BMI greater than 35 kg/m2. Mean RV GLS and GCS for the study cohort were −16.6 and −15.8 respectively. For healthy volunteers RV GLS and GCS were −20.8 and −19.0 respectively. Comparison of mean RV GLS and GCS of both groups were statistically significant ANOVA p&lt;0.001. The number of normal RV segmental strain values was significantly decreased in obese patients when compared to the normal cohort, ANOVA p&lt;0.001 (Figure 1). Furthermore, the prevalence of abnormal RV GCS in morbidly obese patients with normal RVEF greater than or equal to 40% was 84% (21 of 25 patients).

Conclusions
These findings suggest that morbidly many obese patients have occult RV dysfunction despite a normal RVEF. This occult RV dysfunction not only affects RV global GLS and GCS, but also the percentage of normal segmental strain values. Detection of occult RV dysfunction is of clinical significance in that it may provide an opportunity for treatment before development of symptomatic right heart failure.
Figure 1

Funding Acknowledgement
Type of funding source: None
Effects of tafamidis on exercise capacity, cardiac function and myocardial amyloid deposition in patients with transthyretin amyloid cardiomyopathy
Authors: Rettl R , Mann C , Dachs T , Duca F , Binder C , Dusik F , Seirer B , Badr Eslam R , Hengstenberg C , Bonderman D 
Published: November 2020

Abstract

Background
Transthyretin amyloid cardiomyopathy (ATTR-CA) is caused by deposition of amyloid fibrils in the myocardium. Tafamidis is a kinetic stabilizer of TTR that prevents tetramer dissociation and amyloidogenesis.

Methods
Thirty-eight patients with diagnosis of ATTR-CA were treated with tafamidis (20mg or 61mg) for a period of six months. In our explorative analysis we aimed to evaluate the effects of tafamdis by changes from baseline of the serum NT-proBNP concentration, 6MWD, as well as cardiac structure and function, compared to untreated amyloidosis patients.

Results
The analysis showed a significant reduction in the serum NT-proBNP concentration in tafamidis-treated patients compared to untreated patients (median difference, −1042.5 pg/mL, p=0.015). Tafamidis also improved the walking distance at month six, while reduction in untreated patients was observed (mean difference, +29.27 m, p=0.175). Echocardiographic findings revealed a decrease in LV size (mean, −1.56 mm) as well as improvements regarding the LA size (mean difference, −2.51 mm) and the GLS (mean difference, 0.80%) in tafamidis-treated patients. T1 mapping in cardiac MRI showed a decrease in ECV (mean, −1.79%) in patients receiving tafamidis, while an increase in ECV in untreated patients was observed (mean, +0.41%).

Conclusion
Treatment with tafamidis for a period of six months in patients with ATTR-CA results in a significant improvement in NT-proBNP levels and may have positive effects on exercise capacity, cardiac function and myocardial amyloid deposition compared to untreated amyloidosis patients.
Picture 1. Change from baseline.

Funding Acknowledgement
Type of funding source: None
The combination of angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter-2 inhibitors in heart failure with reduced ejection fraction patients comorbid with diabetes mellitus
Authors: Hsiao F.C , Lin C.P , Chang P.C , Wang C.L , Chu P.H 
Published: November 2020

Abstract

Background
Angiotensin receptor-neprilysin inhibitor (ARNI) and dapagliflozin were two new drugs that were proved to reduce clinical events in patients with HFrEF. However, evidence about the combination use of these two drugs in patients with both HFrEF and DM is lacking. The purpose of present study is to elucidate the clinical benefit of combining ARNI and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in this population.

Methods
Patients who have HFrEF and received ARNI, or ACEi, or ARB plus any antidiabetic agents (ADA) were identified from original medical records of 8 major branches of Chang Gung Memorial Hospital. Patients were divided into four groups: 1. ARNI + SGLT2i; 2. ACEi/ARB + SGLT2i; 3. ARNI + other ADA; 4. ACEi/ARB + other ADA. Primary clinical event is the composite of CV death or readmission for heart failure at 1-year (time to event outcome). Primary renal event is the composite of decrease of eGFR more than 50% or progression to ESRD at 1-year follow up (binary outcome).

Results
2628 patients were identified. Among them, 170, 288, 391, and 1772 patients were divided into group 1 to 4, respectively. After multivariable adjustment, patients in group 1 had significantly lower incidence of primary clinical event (adjusted hazard ratio [aHR] 0.63, 95% CI 0.45–0.89) and primary renal event (adjusted odds ratio 0.32, 95% CI 0.14–0.74) than patients in group 4. Patients in group 1 had borderline lower incidence of primary clinical event (aHR 0.71, 95% CI 0.49–1.02) than patients in group 3. Patients in group 1 and group 2 had no difference in the incidence of primary clinical events (aHR 0.98, 95% CI 0.66–1.46) Surprisingly, patients in group 2 had significantly lower incidence of primary clinical event (aHR 0.72, 95% CI 0.54–0.97) than patients in group 3.

Conclusion
In patients with both HFrEF and DM, a combination of ARNI + SGLT2i significantly improved clinical and renal outcomes, comparing to a combination of ACEi/ARB + other ADA. In patients who already received ARNI, SGLT2i marginally improved clinical outcome. In addition, a combination of ACEi/ARB + SGLT2i significantly improved clinical outcome, comparing to a combination of ARNI + other ADA.

Funding Acknowledgement
Type of funding source: None