bluuebunny/crossref_metadata_2025_split huggingface dataset:
1200Changes in nocturnal blood pressure post-renal denervation: comparison of treatment versus control groups in SYMPLICITY HTN-3
Authors: Kario K , Bakris G , Pocock S , Fahy M , Bhatt D L 
Published: October 2019

Abstract

Background
Renal denervation (RDN) impacts blood pressure (BP) differently than anti-hypertensive medications by providing a non-reversible 24-hour change in sympathetic tone that is independent of patient adherence. This might lead to differences in the pattern of BP reduction over the 24-hour period related to diurnal variations in sympathetic tone compared with the timing of drug dosing on BP. This “always on” impact of RDN on BP was observed in the 24-hour Ambulatory BP (ABPM) measurements in the SPYRAL HTN-ON MED and OFF MED trials and raises the question of whether this might also be seen in prior studies of RDN.

Purpose
It is hypothesized that SYMPLICITY HTN-3 did not meet its primary efficacy endpoint, in part, due to improved medication adherence and subsequent BP reductions in the control group. We hypothesized that examination of 24-hour ABPM in HTN-3 would illustrate the effects of improved medication adherence in the control group and reveal differences in the pattern of BP reduction between RDN and control groups, thereby demonstrating an impact on sympathetically mediated BP.

Methods
24-hour ABPM measurements were obtained at baseline and 6 months post-randomization per protocol. ABPM was measured and recorded every 30 minutes and a minimum of 21 daytime and 12 night-time acceptable measurements were required for inclusion in the analysis. Mean and standard error of BP were calculated at each timepoint. Night-time was defined as 1:00–6:00AM.

Results
The figure shows hourly mean ABPM at baseline and 6 months for RDN (A) and sham-control groups (B). Changes in ABPM from baseline to 6 months for RDN and sham control groups are shown in (C). Both the RDN and control groups experienced lower mean hourly BP during the day. In contrast, BP reductions from baseline were greater at night and during the pre-awakening morning hours (1:00–6:00AM) in the RDN group compared with the sham control group. ANCOVA baseline BP-adjusted treatment difference for night-time SBP between RDN and control groups was −3.4 mmHg [95% confidence intervals: −6.7, −0.2; p=0.039]. One possible explanation may be that plasma levels of some antihypertensive medications (such as hydralazine and furosemide) may be lower during night-time hours, lessening the effect of BP reduction in the control group.

Conclusions
Analysis of 24-hour ABPM measurements in the RDN group of HTN-3 demonstrate a consistent separation of curves at 6 months compared with baseline. This separation is also seen in the control group in HTN-3 but is minimal at night-time and in the early morning periods, a time when some medications' impact on BP is lessened. Analyses of ABPM data in additional studies (SYMPLICITY HTN-Japan and SPYRAL First-In-Man trials) are planned to further investigate the role of medication adherence in BP reduction after RDN.

Acknowledgement/Funding
The SYMPLICITY HTN-3 trial is funded by Medtronic.
1273Efficacy and safety of prehabilitation before coronary artery bypass grafting
Authors: Argunova Y , Korotkevich A , Belik E , Pomeshkina S , Barbarash O 
Published: October 2019

Abstract

Purpose
To evaluate the effectiveness and safety of high intensity prehabilitation included in the routine preoperative management of patients with coronary artery disease (CAD) for elective on-pump coronary artery bypass grafting (CABG).

Methods
38 male patients with stable CAD referred to on-pump CABG who either underwent prehabilitation or not were assigned into two study groups. Group 1 patients (n=20, the mean age 61.5 years [55; 64] underwent high intensity treadmill exercises. Group 2 patients (n=18, the mean age 62.0 years [56; 65]) underwent routine preoperative management without prehabilitation. Treadmill exercises in Group 1 patients were performed under hemodynamic control and ECG monitoring. The training power of a workout was calculated based on cardiopulmonary exercise test (CPET) performed before preoperative exercises, and was estimated as 80% of the maximal power obtained during the exercise test. Adenosine loading single-photon emission computed tomography (SPECT) was used to measure the parameters of myocardial perfusion before preoperative exercises and on days 5–7 after CABG in both study groups. Biochemical markers of myocardial damage (troponin I, NT-proBNP) were measured before the training session, after it and then in the postoperative period to assess the safety of the prehabilitation program. In-hospital postoperative complications were recorded and analyzed.

Results
Both study groups were comparable in the main clinical and demographic parameters, intraoperative clinical parameters as well as in preoperative CPET and SPECT results. There were no cases of complications during prehabilitation. The analysis of myocardial perfusion parameters demonstrated that patients who had undergone prehabilitation had significantly higher accumulation of radiopharmaceuticals than those in the control group in basal segments (74.9±3.98% vs. 70.3±7.40% p=0.04), middle (86.7±5.24% vs. 79.6±10.43%, p=0.03) and apical (85.8±5.03% vs. 79.0±8,67%, p=0.02) myocardium. The stress-induced ischemia (SDS) was less pronounced in Group 1 compared to Group 2 (0 scores and 0.9±0.53 scores, respectively, p=0.04). Myocardial perfusion defect significantly decreased during the infusion of adenosine (SSS) (p=0.013), as well as the SDS index (p=0.018) in the prehabilitation group after CABG compared with the baseline. Both groups had similar serum troponin I levels within the normal range before and after CABG. NT-pro BNP levels significantly increased in the postoperative period in patients who did not undergo prehabilitation (p=0.003). Patients who underwent prehabilitation had a significantly lower incidence of the in-hospital postoperative complications compared to patients without exercise trainings (p=0.002).

Conclusion
The inclusion of high intensity preoperative exercises in the routine preoperative management of patients referred to elective CABG is safe and effective method of cardioprotection improving surgical outcomes.
1335Tricuspid anular dilatation is associated with higher mortality in patients undergoing TAVR
Authors: Deseive S D C , Steffen J , Beckmann M , Jochheim D , Curta A , Mehilli J , Hagl C , Massberg S , Hausleiter J 
Published: October 2019

Abstract

Background
Tricuspid annular dilatation is an increasingly recognized entity associated with poor outcomes in patients with valvular heart disease, which led to upvaluation of tricuspid annuloplasty in current European and U.S. guidelines on valvular heart disease.

Purpose
To investigate the prognostic role of tricuspid annular dilatation measured in multi-slice CT (MDCT) datasets in patients undergoing transfemoral aortic valve replacement (TAVR).

Methods
All consecutive patients with available MDCT data undergoing TAVR at our institution between 2013 und 2016 were included. Maximal septal-lateral diameter was obtained from 3-dimensional MDCT datasets. Receiver-operating curves (ROC) analysis was performed to obtain an ideal cut-off for septal-lateral dilatation in systolic and diastolic heart phase. All-cause mortality served as endpoint.

Results
The study included 1137 patients, of whom 299 died within a mean follow-up period of 1.8±1 years. Mean patient's age was 80.6 years and 51.5% were women. TAVR was performed via transfemoral approach in all patients and balloon-expandable prosthesis were used in 69.4% of patients. ROC analysis revealed a cut-off of 45.7 mm for diastolic MDCT scans (n=859) and 36.1 mm for systolic MDCT scans (n=278). Patients above this threshold experienced a significantly higher mortality within the follow-up period (s. attached Figure, hazard ratio 1.63 with 95% CI 1.39 and 1.92, p<0.001). Tricuspid annular dilatation had no impact on procedural outcomes including device failure (2.4 vs. 2.9%, p=0.7), need for permanent pacemaker implantation (17.6 vs. 21.3%, 0.16, acute myocardial infarction (0.3 vs. 1.2%, p=0.18) and acute stroke (1.8 vs. 1.1%, p=0.28) defined according to Valve Academic Research Consortium-2 (VARC-2) criteria.

Conclusion
Tricuspid annular dilatation assessed with MDCT in patients undergoing TAVR is associated with 63% higher all-cause mortality. Future studies will have to determine whether interventional tricuspid annuloplasty techniques can reduce mortality in this group of patients.
1336Outcome analysis of systolic or diastolic CT acquisition prior to transcatheter aortic valve replacement to estimate prothesis size
Authors: Steffen J , Deseive S , Beckmann M , Jochheim D , Rizas K , Curta A , Hagl C , Mehilli J , Massberg S , Hausleiter J 
Published: October 2019

Abstract

Background
Computed tomography (CT) imaging is considered as standard of care for transcatheter aortic valve replacement (TAVR) prothesis sizing. ECG-triggered high-pitch helical CT data acquisition on dual-source CT systems is associated with less contrast volumes, but CT image reconstruction of the aortic valve is limited to a single time point within the cardiac cycle. Although systolic CT imaging of the aortic valve is recommended due to the changes in aortic annulus area during the cardiac cycle, this recommendation is not supported by clinical outcome data.

Purpose
The study aimed to assess the impact of systolic vs. diastolic CT imaging of the aortic annulus for TAVR sizing on patient outcomes in a large series of patients.

Methods
In the study CT images of 1346 patients undergoing TAVR at our centre from 2013–2016 were re-evaluated. Patients were stratified into two groups with 0–35% and 36–99% of the RR-interval as systolic and diastolic CT imaging. Outcomes according to VARC2-criteria at 30 days and long-term survival were analysed.

Results
CTs of 1135 out of 1346 patients were analysed retrospectively, 278 (24.5%) of which were acquired during systole and 859 (75.5%) during diastole. Mean age was 80.6±7.6 years and 52.2% were female. Mean follow-up, available for 83.4% of patients, was 2.1±0.8 years. No significant difference in baseline characteristics was observed across both groups.
Aortic annular area measurements were significantly larger in systole (mean aortic anulus area: systole: 4.8±1.0 cm2; diastole: 4.5±1.0 cm2, p<0.01), resulting in larger implanted valves. Balloon-expandable valves were used in 69.4% of patients; the need for post-dilation did not differ between both groups (systole 4.7%, and diastole 7.5%; p=0.13).
There was no difference between groups concerning the combined endpoints for device success or early safety according to VARC2-criteria. Overall 30-day mortality was 3.4% (systole: 4.2% and diastole: 3.1%, p=0.35). Device failure occurred in 2.7% (systole: 2.9% and diastole: 2.7%, p=0.83). Permanent pacemaker implantation was required in 20.1% (systole: 18.7%, and diastole: 20.5%; p=0.55). Stroke rate at 30 days was 2.9%, n=33 and was similar in the two groups. The landmark analysis demonstrates the 30-day and 1-year mortality rates for both groups (Figure).
Figure 1. Landmark analysis mortality

Conclusion
The current analysis does not suggest that systolic CT imaging for TAVR sizing is associated with improved early or late outcomes. Accordingly, full-cycle CT imaging which usually is associated with higher contrast volumes, should be avoided in this elderly population, which often presents with reduced kidney function.
1347The flu vaccine and mortality in hypertension. A Danish nationwide cohort study
Authors: Modin D , Claggett B , Joergensen M E , Koeber L , Benfield T , Schou M , Jensen J U , Solomon S , Trebbien R , Fralick M , Vardeny O , Pfeffer M A , Torp-Pedersen C , Gislason G , Biering-Soerensen T 
Published: October 2019

Abstract

Background
Influenza infection is associated with an increased risk of acute myocardial infarction (AMI) and stroke. It is currently unknown whether influenza vaccination may reduce mortality in patients with hypertension.

Purpose
To determine whether influenza vaccination is associated with lower risks of death in hypertensive patients without significant cardiovascular or other chronic disease.

Methods
Using nationwide registers, we identified all patients with hypertension in Denmark during 9 consecutive influenza seasons in the period 2007–2016 who were treated with at least 2 different classes of antihypertensive medication (beta-blockers, diuretics, calcium antagonists or renin-angiotensin system inhibitors). Patients who were not 18–100 years old or had ischemic heart disease, heart failure, chronic obstructive lung disease, cancer or cerebrovascular disease were excluded. Prior to each influenza season we assessed the exposure to influenza vaccination. End-points were death from all causes, from AMI or stroke, or cardiovascular death. For each season, patients were followed from December 1 until April 1 the next year, spanning the period of high influenza activity in Denmark.

Results
A total of 608,452 Patients were followed for a median of 5 seasons (interquartile-range: 2–8 seasons), with total follow-up time of 975,902 person-years. The vaccine coverage during study seasons ranged from 26% to 36%. During follow-up, 21,571 patients died of all-causes (3.5%), 12,270 patients died of cardiovascular causes (2.0%) and 3,846 patients died of AMI/stroke (0.6%). Vaccination was associated with older age, Diabetes Mellitus, atrial fibrillation, lower educational level, lower income and higher medication use. In unadjusted analysis considering all seasons, vaccination was significantly associated with increased risk of all-cause death, cardiovascular death and death from AMI/stroke. However, following adjustment for season, age, sex, comorbidities, medications, income, education, and more, vaccination was significantly associated with reduced risks of all-cause death, cardiovascular death and death from AMI/stroke (Figure).
PY, person-years.

Conclusion
In a nationwide study spanning 9 consecutive influenza seasons including more than 600,000 hypertensive patients without significant cardiovascular disease identified through medication use, influenza vaccination was significantly associated with a reduced risk of death from all-causes, cardiovascular causes and AMI/stroke. Influenza vaccination may improve patient outcome in hypertension.

Acknowledgement/Funding
Daniel Modin was supported by the Herlev & Gentofte University Hospital Internal Research Fund and by the Novo Nordisk Foundation.
1405Sequential nephron blockade with diuretics improves diastolic dysfunction in patients with resistant hypertension, a substudy a the PHARES trial
Authors: Fouassier D , Blanchard A , Bobrie G , Boutouyrie P , Azizi M , Hulot J S 
Published: October 2019

Abstract

Introduction
Hypertension is one of the major contributors to cardiac diastolic dysfunction as observed in patients with heart failure and preserved ejection fraction. Different therapeutics strategies have been proposed to control blood pressure (BP) but their independent impact on cardiac function remain undetermined. In patients referred to our center for uncontrolled hypertension, we compared changes in cardiac parameters between two strategies consisting of sequential nephron blockade with intensive diuretics (NBD) or sequential renin angiotensin blockade (RAB).

Purpose
To determine evolution of BNP levels and echocardiographic (TTE) parameters of diastolic dysfunction according to strategies to control BP.

Methods
After 4-weeks treatment with 300mg irbesartan + 12.5mg hydrochlorothiazide + 5mg amlodipine, 140 patients with uncontrolled hypertension were randomized to either complete nephron blockade with sequential introduction of 25mg spironolactone, 20 to 40mg furosemide and 5mg amiloride (NBD group, n=74) or complete RAAS blockade with 5 to 10mg ramipril and 5 to 10mg bisoprolol (RAB group, n=67). BNP levels and TTE parameters according to ESC guidelines were assessed at baseline and week 12.

Results
BNP levels were not significantly different in the two groups at baseline (mean±SD 30.1±37.0pg/mL in NBD versus 22.6±22.3pg/mL in RAB, p=0.147) but significantly decreased in NBD at week 12 (20.1±22.7pg/mL in NBD versus 55.2±60.4pg/mL in RAB, p<0.0001). At week 12, only 9 (12%) patients in NBD presented BNP levels >35pg/mL versus 37 (55%) in RAB (p<0.001).
Concordantly, TTE parameters such as left ventricular end-diastolic diameter (mean±SD, 49±4mm in NBD and 52±5mm in RAB, p=0,004) and left atrial area (16.9±3.6cm2 in NBD and 19.1±3.7cm2 in RAB, p=0,003) improved significantly in NBD group. The proportions of patients presenting ≥2 criteria of diastolic dysfunction according to ESC guidelines in NBD and RAB group respectively were 31.2% and 19.3% at baseline vs. 3.1% and 32.2% after 12 weeks (p=0.001). In a multivariate analysis, NBD treatment was significantly associated with a decline in BNP levels (p<0.01) even after adjustment on daytime systolic BP lowering, heart rate, renal function, age and gender.

Conclusion
In patients with uncontrolled hypertension, intensive nephron blockade with sequential addition of diuretics improves markers of diastolic dysfunction independently of BP lowering.
1418Adverse effects of spironolactone in long-term treatment of resistant arterial hypertension
Authors: Vaclavik J , Jelinek L , Jarkovsky J , Benesova K , Tavacova D , Kamasova M , Kocianova E , Vykoupil K 
Published: October 2019

Abstract

Background
Spironolactone is recommended as a fourth line antihypertensive drug by current hypertension guidelines. This drug had relatively few adverse effects in short term clinical trials, but data about their occurrence during long-term treatment of resistant hypertension are scarce.

Purpose
To evaluate the occurrence and type of adverse effects of spironolactone during long-term treatment and their possible clinical and laboratory predictors.

Methods
We prospectively followed 274 patients with resistant arterial hypertension who started treatment with spironolactone between September 2007 and December 2016. The duration of spironolactone use, its dose, the incidence of adverse events, blood pressure, and laboratory findings were recorded at baseline and during the last clinical examination.

Results
Patients were followed for an average of 35 (± 29) months, the mean dose of spironolactone was 27.5 mg/day. Adverse effects occurred in 72 patients (26.3%) and in 61 (84.7%) lead to discontinuation of spironolactone. The most common adverse reactions were gynaecomastia (30.6%), hyperkalaemia (30.6%) and symptomatic hypotension (26.4%). The mean duration of spironolactone treatment before their occurrence was 25 (± 27) months. According to the Kaplan-Meier curve, the median for the incidence of adverse events would be 97 months (91.5–102.5 months), i.e. 50% of patients could be treated with no adverse events for more than 8 years. Adverse events were more common in the elderly (hazard ratio – HR 1.38, P=0.007), patients with higher baseline serum creatinine (HR 1.12, P=0.035) and patients taking angiotensin receptor blockers (HR 1.65, P=0.040).
Kaplan-Meier estimate – adverse events

Conclusion
During long-term treatment of resistant hypertension with spironolactone, more than a quarter of patients experience adverse reactions that usually require discontinuation of spironolactone.

Acknowledgement/Funding
Supported by the grants of Palacký University in Olomouc Nr. IGA_LF_2016_038 and IGA_LF_2017_029.
1443Safety of red yeast rice supplementation: a systematic review and meta-analysis of randomized controlled trials
Authors: Fogacci F , Banach M , Mikhailidis D P , Bruckert E , Toth P P , Watts G F , Reiner Z , Mancini G B J , Rizzo M , Mitchenko O , Pella D P , Fras Z , Sahebkar A F G , Vrablik M , Cicero A F G 
Published: October 2019

Abstract

Background
Recently, concerns regarding the safety of red yeast rice (RYR) have been raised after the publication of some case reports claiming toxicity.

Purpose
Since the previous meta-analyses on the effects of RYR were mainly focused on its efficacy to improve the lipid profile and other cardiovascular parameters, we carried out a meta-analysis on safety data derived from the available randomized controlled clinical trials (RCTs).

Methods
Primary outcomes were musculoskeletal disorders (MuD). Secondary outcomes were non-musculoskeletal adverse events (Non-MuD) and serious adverse events (SAE). Subgroups analyses were carried out considering the intervention (RYR alone or in association with other nutraceutical compounds), monacolin K administered daily dose (≤3, <3–5 and >5 mg/day), follow-up (>12 or ≤12 weeks), with statin therapy or statin-intolerance and type of control treatment (placebo or statin treatment).

Results
Data were pooled from 52 RCTs comprising 110 treatment arms, which included 8503 subjects, with 4421 in the RYR arm and 4287 in the control one. Monacolin K administration was not associated with increased risk of MuD (odds ratio [OR]=0.94, 95% confidence interval [CI] 0.53,1.65). (Figure below presents the forest plot comparing the RYR associated risk of MuD in the entire population). Moreover, we found a reduced risk of Non-MuD (OR=0.59, 95% CI 0.50, 0.69) and SAE (OR=0.54, 95% CI 0.46, 0.64) vs. control. Subgroups analyses confirmed the high tolerability profile of RYR. Furthermore, increasing daily doses of monacolin K were negatively associated with increasing risk of Non-MuD (slope: −0.10; 95% CI: −0.17, −0.03; two-tailed p<0.01).
Forest plot on RYR link with MuD risk.

Conclusions
Based on our data, RYR use as lipid-lowering dietary supplement seems to be overall tolerable and safe in a large population of moderately hypercholesterolaemic subjects.

Acknowledgement/Funding
None