bluuebunny/crossref_metadata_2025_split huggingface dataset:
P6285Protective effects of exercise on vascular function are mediated by NADPH oxidase 4
Authors: Morawietz H , Langbein H , Shahid A , Hofmann A , Mittag J , Bornstein S R , Brunssen C 
Published: October 2019

Abstract

Background/Introduction
Physical activity is one of the most potent strategies to prevent endothelial dysfunction. Recent evidence indicates vaso-protective properties of H2O2 produced by main endothelial NADPH oxidase isoform 4 (Nox4) in the vasculature.

Purpose
Therefore, we hypothesized that Nox4 connects physical activity with vaso-protective effects.

Methods and results
Analysis of endothelial function by Mulvany myograph showed endothelial dysfunction in wild-type as well as in Nox4−/− mice after 20 weeks on high-fat diet. Access to voluntary running wheels during high-fat diet prevented endothelial dysfunction in wild-type but not in Nox4−/− mice. Mechanistically, exercise led to increased H2O2 release in the aorta of wild-type mice with increased phosphorylation of eNOS pathway member AKT serine/threonine kinase 1 (Akt1), subsequently. Both effects were diminished in aortas of Nox4−/− mice. Deletion of Nox4 also led to decreased capacity for intracellular calcium release and reduced phenylephrine-mediated contraction, whereas potassium-induced contraction was unaffected. H2O2 scavenger catalase reduced phenylephrine-contraction in wild-type mice. Supplementation of H2O2 increased phenylephrine-induced contraction in Nox4−/− mice. Exercise induced key regulator of mitochondria biogenesis peroxisome proliferative activated receptor gamma, coactivator 1 alpha (Ppargc1a) in wild-type but not Nox4−/− mice. Furthermore, exercise induced citrate synthase activity and reduced mitochondria mass in the absence of Nox4. Thus, Nox4−/− mice became less active and ran less compared with wild-type mice.

Conclusions
Nox4 derived H2O2 plays a key role in exercise-induced adaptations of eNOS and Ppargc1a pathway and intracellular calcium release. Hence, loss of Nox4 diminished physical activity performance and vascular protective effects of exercise.

Acknowledgement/Funding
This work was supported by a research grant of the German Cardiac Society (DGK) (to H.L.) and DFG (Grant MO 1695/4-1 to H.M.).
P6310Risk predictors of cardiac allograft vasculopathy after heart transplantation: results from the United States Organ Procurement and Transplantation Network
Authors: Fluschnik N , Geelhoed B , Becher P M , Brunner F J , Schrage B , Knappe D , Bernhardt A , Blankenberg S , Kobashigawa J , Reichenspurner H , Schnabel R B , Magnussen C 
Published: October 2019

Abstract

Background
Cardiac allograft vasculopathy (CAV) is a major long-term complication after heart transplantation leading to chronic graft failure and increased mortality.

Purpose
The aim of this study was to determine recipient- and donor-related risk factors for the development of CAV in patients after heart transplantation.

Methods
Overall, data from 34,994 heart transplant recipients prospectively enrolled from July 2004 to March 2015 in the Organ Procurement and Transplantation Network (OPTN) were analyzed. Patients aged <18 years and those without information about CAV and re-transplantation were excluded. Multivariable-adjusted analyses were performed to identify recipient- and donor-related risk factors for new-onset CAV. The mean follow-up time was 66.8 months. Analyses are based on OPTN data as of March 6, 2017.

Results
Of 34,994 patients after heart transplantation, 12,668 (36.2%) patients developed CAV. Mean age was 52±12 years for the recipients (76.1% men) and 31±12 years for the donors (71.0% men), respectively.
In recipients, male sex (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.09–1.19, p<0.001), African American ethnicity (HR 1.11, 95% CI 1.06–1.17, p<0.001), body mass index (BMI) (HR per 5 kg/m2 increase 1.08, 95% CI 1.06–1.11, p<0.001) and smoking (HR 1.07, 95% CI 1.01–1.13, p=0.03) were associated with incident CAV. Moreover, recipients with ischemic (HR 1.30, 95% CI 1.09–1.55, p=0.003) and hypertrophic cardiomyopathy (HR 1.26, 95% CI 1.02–1.57, p=0.03) had a higher risk for new-onset CAV than patients with other cardiomyopathies.
In donors, age (HR 1.11, 95% CI 1.10–1.11, p<0.001), male sex (HR 1.28 95% CI 1.22–1.34, p<0.001), BMI (HR per 5 kg/m2 increase 1.04, 95% CI 1.02–1.05, p<0.001), smoking (HR 1.09, 95% CI 1.04–1.13, p<0.001), diabetes (HR 1.21 95% CI 1.09–1.36, p<0.001) and arterial hypertension (HR 1.13, 95% CI 1.07–1.20, p<0.001) were associated with new-onset CAV. Contrarily, African American (HR 0.93, 95% CI 0.88–0.98, p=0.007) and Hispanic ethnicity (HR 0.94, 95% CI 0.89–0.99, p=0.03) seemed to be protective.

Conclusion
Both recipient and donor male sex as well as the classical cardiovascular risk factors BMI and smoking were associated with incident CAV. On the donor side, additionally, diabetes and arterial hypertension were related to new-onset CAV. Diverse ethnicities were differentially related to new-onset CAV. Further studies are needed to clarify whether modification of cardiovascular risk factors as well as improved donor selection will reduce CAV burden.
P6316Hemodynamic response to rapid saline loading in heart transplant recipients
Authors: Kodeboina M , Di Gioia G , Colaiori I , Verstreken S , Goethals M , Dierckx R , Heggermont W , Bartunek J , Vanderheyden M 
Published: October 2019

Abstract

Introduction
A pulmonary capillary wedge pressure (PCWP) ≥25 mm Hg following volume load or exercise has been proposed as a partition value for detection of HfpEF. However, the hemodynamic response to volume challenge in heart transplant (Tx) recipients has never been studied.

Methods
24 heart Tx recipients (age: 65 years) with normal LV function (55±7%) and without rejection and graft vasculopathy underwent right heart catheterization to measure hemodynamic response to volume loading before and after a rapid saline infusion of 7mL/kg over 10 min. PCWP, right atrial pressure (RAP), mean pulmonary artery pressure (AP) were obtained and the PCWP and indexed (i) stroke volume (SV) data were used to construct Starling (SVindex/PCWP) curves. Pts were categorized in those with elevated filling pressures (Group A, n=13 pts) defined by a PCWP ≥15 mm Hg at rest or ≥25 mm Hg following volume loading vs those without (Group B, n=11 pts).

Results
No difference in age of donor and transplant heart, baseline hemodynamics and EF was noted between both groups. Saline infusion significantly increased PCWP and mean AP in both Groups (table 1) without any significant change in BP and heart rate. Interestingly saline infusion was associated with a significant rise in SV and SVi in Group B not in Group A pts. Moreover, in Group B pts the Starling curves revealed a larger SVi at any give PCWP compared to Group A pts (Fig.1).
Table 1 All (n=24) Group A (n=13) Group B (n=11) Baseline Volume Loading Baseline Volume Loading Baseline Volume Loading RAP (mm Hg) 5.3±4.1 9.2±4.8* 7.6±4.8 11.4±5.2* 3.8±2.5 7.3±1.9* Mean AP 18.4±5.4 24.1±5.9* 21.7±5.1 26.8±6.5** 14.9±2.4 20.8±2.6* PCWP 12.1±4.9 16.8±6.7* 15.0±4.9 19.8±6.5** 8.4±1.9 14.6±3.7* SV 71.4±19.6 72.5±23.6 73.2±6.2 72.4±6.2 69.2±14.6 79.2±3.9 SViml/m2) 37.4±9.2 37.9±11.2 36.7±7.1 38.7±9.9 35.3±6.0 40.5±5.2* *p<0.01 compared to baseline; **p<0.05 compared to baseline.
Figure 1

Conclusions
In the transplanted heart volume loading increases filling pressures and is able to unmask left ventricular diastolic dysfunction. Interestingly, those with HFpEF are characterized by a blunted Frank Starling response as evidenced by higher PCWP and failure to increase SV for any given PCWP. Further prospective studies are warranted to unravel the underlying mechanisms.
P6323Exercise capacity as predictor for anaemia or iron deficiency in patients with chronic heart failure
Authors: Ebner N , Dinopoulos G , Evertz R , Garfias Macedo T , Godoy B , Springer J , Von Haehling S 
Published: October 2019

Abstract

Background
Anaemia and iron deficiency (ID) are important factors for muscle function and exercise capacity in patients with chronic heart failure (HF). Their interaction in HF remains to be defined.

Methods
A total of 280 out-patients with stable chronic HF were enrolled with mean age of 67.0±10.7 years, 21%female, mean left ventricular ejection fraction (LVEF) was 38.9±13.4%, mean Body Mass Index (BMI) 29.3±5.5 kg/m2]. Anaemia was defined according to World Health Organization criteria [Haemoglobin (Hb) <13 g/dL in men and <12 g/dL in women]. ID was defined as ferritin <100 μg/L or ferritin <100 <300 μg/L than with transferrin saturation (TSAT) <20%. Exercise capacity was assessed by spiroergometry (peakVO2), 6 minute walk test (6MWT), short physical performance battery test (SPPB), hang grip strength (HGS) and leg force (LF). All patients were followed up for a mean of 8 month.

Results
A total of 89 (32%) chronic HF patients had anaemia and 142 (51%) had iron deficiency at baseline. Patients with anaemia showed significant lower exercise capacity compared to patients without anaemia (peak VO2: 15.3±4.6 vs. 18.5±4.8 kg/min p<0.0001, 6MWT: 365.2±135.5 vs. 461.6±127.4 m p<0.0001, SPPB: 9.4±2.3 vs. 11.0±1.6 total points p<0.0001, HGS: 32.5±10.0 vs. 38.8±12.4 kg p<0.0001, LF: 31.4±11.0 vs. 41.3±21.6 kg p<0.0001). The same we found in patients with ID compared to patients without ID (peak VO2: 16.3±5.1 vs. 18.6±4.5 kg/min p=0.001, 6MWT: 400.0±140.8 vs. 458.8±128.4 m p=0.0008, SPPB: 10.0±2.1 vs. 10.9±1.7 total points p=0.0003, HGS: 34.5±11.9 vs. 39.3±11.7 kg p=0.001, LF: 35.7±23.4 vs. 40.5±13.6 kg p=0.04). After a Follow up of mean 8 month 53 patients develop a new onset of either anaemia (n=24) or ID (n=29). Logistic regression analysis showed that gender, 6 minute walk distance, SPPB, HGS and presence of diabetes mellitus at baseline are significantly associated with the development of anaemia or ID (all p<0.05). The strongest predictor was lower SPPB (p=0.0008). Interestingly known determinates lower peak VO2, higher age, higher NYHA class, Creatinine, and hsCRP were not predictive in our cohort to develop anaemia or ID after 8 month (all p>0.05).

Conclusion
Both anaemia and ID are strongly associated with reduced exercise capacity in patients with HF. The effect of anaemia and iron deficiency together is stronger than that of anemia and ID alone. Reduced SPPB, 6MWT, and HGS are important risk factors for the development of anaemia or ID.
P6344Volume overload-triggered pathological myocardial remodeling occurs in the absence of calcium/calmodulin-dependent protein kinase type II delta
Authors: Elkenani M , Mohamed B A , Buchholz E , Lbik D , Schnelle M , Hasenfuss G , Toischer K 
Published: October 2019

Abstract

Background
Calcium/calmodulin-dependent protein kinase type II delta (CamKIIδ), the predominant cardiac CaMKII isoform, has been implicated in the progression of myocardial infarction- and pressure overload-induced pathological remodeling and heart failure, but its role in volume overload (VO) has not been defined. We have previously reported an activation of CamKII during transition to HF in VO.

Purpose
Here, we analyzed the impact of CamKIIδ deletion in VO-triggered myocardial remodeling and heart failure development.

Methods
CaMKIIδ knockout (CaMKIIδ-KO) and wild-type (WT) littermates were exposed to aorto-caval shunt-induced VO, and the progression of myocardial remodeling was assessed by serial echocardiography, histological and molecular analyses.

Results
CaMKIIδ-KO and WT littermates exhibited similar mortality pattern in response to VO. Serial echocardiographic measurements showed a comparable eccentric myocardial remodeling, altered left ventricle geometry and perturbed ventricular function after shunt. At 12 weeks post-shunt both CaMKIIδ-KO and WT mice experienced comparable increases in relative heart weight, cardiomyocyte diameter, cardiac apoptosis, and hypertrophic genes expression.

Conclusion
We therefore conclude that CaMKIIδ signaling is dispensable for the progression of pathological cardiac remodeling induced by VO. This should be considered before CaMKII inhibition is approved therapeutically for HF treatment.
P6355The behavior of atrial fibrillation in patients with heart failure hospitalization
Authors: Fukunaga M , Hirose K , Isotani A , Morinaga T , Ando K 
Published: October 2019

Abstract

Background
Relationship between atrial fibrillation (AF) and heart failure (HF) is often compared with proverbial question of which came first, the chicken or the egg. Some patients showing AF at the HF admission result in restoration of sinus rhythm (SR) at discharge. It is not well elucidated that the restoration into SR during hospitalization can render the preventive effect for rehospitalization.

Purpose
To investigate the impact of restoration into SR during hospitalization for readmission rate of the HF patients showing AF.

Methods
We enrolled consecutive 640 HF patients hospitalized from January 2015 to December 2015. Patients data were retrospectively investigated from medical record. Patients showing atrial fibrillation on admission but unrecognized ever were defined as “incident AF”; patients with AF diagnosed before admission were defined as “prevalent AF”. Primary endpoint was a composite of death from cardiovascular disease or hospitalization for worsening heart failure. Secondary endpoints were death from cardiovascular disease, unplanned hospitalization related to heart failure, and any hospitalization.

Results
During mean follow up of 19 months, 139 patients (22%) were categorized as incident AF and 145 patients (23%) were categorized as prevalent AF. Among 239 patients showing AF on admission, 44 patients were discharged in SR (39 patients in incident AF and 5 patients in prevalent AF). Among incident AF patients, the primary composite end point occurred in significantly fewer in those who discharged in SR (19% vs. 42% at 1-year; 23% vs. 53% at 2-year follow-up, p=0.005). To compare the risk factors related to readmission due to HF with the cox proportional-hazards model, AF only during hospitalization [Hazard Ratio (HR)=0.37, p<0.01] and prevalent AF (HR=1.67, p=0.04) was significantly associated. There was no significant difference depending on LVEF.

Conclusion
Newly diagnosed AF with restoration to SR during hospitalization was a good marker to forecast future prognosis.
P6362Impact of the 2017 AHA/ACC hypertension guideline on hypertension prevalence and cardiovascular risk factors in a healthy older cohort
Authors: Chowdhury E K , Nelson M R , Ernst M E , Margolis K L , Beilin L J , Johnston C I , Murray A M , Woods R L , Wolfe R , Tonkin A M , Williamson J D , Stocks N P , McNeil J , Reid C 
Published: October 2019

Abstract

Background
The 2017 American Heart Association (AHA)/American College of Cardiology (ACC) hypertension guideline recommends a target blood pressure (BP) of <130/80 mmHg regardless of age, which is lower than previously recommended BP goals.

Purpose
We aimed to determine how much the updated classification for high BP would increase the overall prevalence of “hypertension” in an otherwise healthy elderly population. Additionally, we explored the cardiovascular disease (CVD) risk factor distribution in those newly classified “hypertensives” to determine whether the increased prevalence of hypertension was accompanied by an increase in other modifiable CVD risk factors.

Methods
We used baseline data from 19,114 participants (16,703 in Australia and 2,411 in the USA) aged ≥65 years who were enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) study between 2010 and 2014. Participants were classified as having hypertension using either: (a) pre-2017 thresholds (SBP ≥140 mmHg or mean DBP ≥90 mmHg and/or on anti-hypertensive) or (b) 2017 AHA/ACC guidelines (SBP ≥130 mmHg or DBP ≥80 mmHg and/or on anti-hypertensive). We assessed the presence of cardiovascular disease risk factors such as diabetes, hypercholesterolemia, smoking, obesity, reduced renal function among these hypertensive participants and also estimated their predicted risk over 10 years.

Results
Based on pre-2017 thresholds, 74% of the participants met the criteria for hypertension. Hypertension prevalence increased to 87% when the more stringent 2017 guideline was applied. 29% of this subset of newly classified hypertensive participants did not have any other identifiable traditional CVD risk factors. Further, a significantly lower 10-year predicted cardiovascular risk (22% versus 26%, p<0.001) among those newly classified hypertensive participants was observed in relation to those having hypertension based on pre-2017 guideline (Figure 1).
Figure 1. 10-year predicted CVD risk among hyoertensive and newly classified hypertensive ASPREE participants by presence of CVD risk factor

Conclusion
As expected, the prevalence of hypertension increased among the healthy elderly when applying the new AHA-2017 guideline; however, the increased prevalence occurs despite lack of an accompanying increase in additional CVD risk factors or predicted 10-year risk. Our findings suggest an individualized approach is needed in evaluating high BP among the healthy elderly.

Acknowledgement/Funding
National Institute on Aging and the National Cancer Institute at NIH; NHMRC Australia, Monash University, Victorian Cancer Agency (Australia)
P6368Blood pressure control in a registry of clinical practice, PINNACLE-BRAZIL REGISTRY
Authors: Avezum A , Cordeiro Mattos A , Oliveira G B F , Pinto I M , Rombaldi A R , Fonseca H A R , Bocchese J I , Saback G , Taborga P R C , Silva T O , Campoa R N , Ferreira M H B , Savioli Neto F , Magalhaes C C , Saraiva J F K 
Published: October 2019

Abstract

Introduction
The prevalence of hypertension is estimated to be nearly 50% among Brazilian adults. Achieving an adequate control of this CVD risk factor is challenging but truly relevant on a public health perspective, as this is the top-ranking cause of all deaths globally.

Purpose
We aimed to describe crude and simple metrics of blood pressure management (including its control), as based on current guideline-derived recommendations, after one year of the clinical practice registry

Methods
Patients with documented Hypertension were included by using electronic case report form based on the ACC PINNACLE Registry. The registry has been enrolling patients from general practitioners and specialists. The main goal of the PINNACLE program is to improve the quality of care in “real world” clinical practice. Patients data were evaluated after 01 year of follow-up on regular clinical appointments and the differences on clinical practice were evaluated

Results
Currently, PINNACLE-Brazil has enrolled 7598 patients, with 87% of diagnosed hypertension. Percentage of patients with a diagnosis of hypertension who had a blood pressure measurement <140/90 mmHg was 47.9% (baseline) and 57.3% (follow-up). Percentage of patients who had a blood pressure <140/90 mm Hg, or who had a blood pressure ≥140/90 mm Hg and were prescribed ≥2 antihypertensive medications were 67.1% on baseline and 71.2% after 1 year.

Conclusion
The preliminary data of PINNACLE Registry in Brazil shows that a significant proportion of hypertensive patients (nearly half) have not presented with adequate control of blood pressure levels and, moreover, a large proportion have not been treated with recommended combination of 02 or more antihypertensive medications to reach targeted BP levels the quality of care was improving after 01 year of registry.

Acknowledgement/Funding
ACC Foundation
P6372Does modification of activity regimes optimize the effect of high physical activity on hypertensive heart disease?
Authors: Schluter K.-D , Schreckenberg R , Wolf A , Kutsche H , Troidl C , Simsekyilmaz S , Niemann B , Schulz R 
Published: October 2019

Abstract

Aims and background
Spontaneously hypertensive rats (SHR) are a suitable model of essential hypertension and allow analyze the progression of hypertension and hypertension-dependent end-organ damage. In this model, acute improvement of physical activity (free running wheel activity) exerts known beneficial effects (such as lowering oxidative stress). However, these initial beneficial effects are lost during the continuation of high physical activity and translate into mal-adaptive processes, suggesting that not any high physical activity exerts beneficial effects. It has been hypothesized that the skeletal muscle release myokines, that contribute to the beneficial effects of exercise. However, myokines, such as IL-6, are induced by an acute increase in work load not by continuous work load. Therefore, we analyzed whether modification of high physical activity, i.e. intermittent free running wheel activity, modify the long-term impact on long lasting hypertension.

Methods
38 female SHR aged 6 weeks (pre-hypertensive state) were randomly allocated to one of the following groups: Sedentary (S; standard holding condition) imitating the condition of sedentary life style, high activity (HA; life-long free running wheel) imitating the condition of active life style, temporary activity (TA; 6 months free running wheel and 3 months sedentary) imitating the loss of active life style during ageing, and finally intermittent activity (IA; 10 months repetitive access to running wheels every 4 weeks) imitating altered workloads. All rats were sacrificed at the age of 10 months.

Results
IA was the only treatment regime that effectively lowered blood pressure (P syst: 186±11 vs. 165±6 mmHg), improved ejection fraction (EF: 56±5 vs. 63±2%), and displayed clear molecular profile of adaptive myocardial hypertrophy rather than mal-adaptive hypertrophy. Moreover, only IA reduced the number of circulating monocytes (377±102 vs. 220±16 /μl), a cell population that immigrated in the left ventricle. The number of monocytes was directly correlated with the expression of MMP12, BNP, ANP, biglycan, collagen-1, actinin, β-MHC, and somatstatin but inversely related to β-adrenoceptor, Glut-4, and UCP3 expression. Finally, IA increased the skeletal expression of IL-6 and decreased the renal expression of AT1 receptors.

Conclusion
The data confirm the previous findings that not all type of physical activity beneficially affects hypertensive-dependent disease. In contrast, the data support the hypothesis that alterations in work load are required triggering the release of myokines from the skeletal muscle and identify the amount of circulating monocytes as a main trigger of mal-adaptive hypertrophy in these rats. The data are important with respect to optimize life style suggestions for patients with essential hypertension.

Acknowledgement/Funding
DFG (ERAGON and SFB 1213)