bluuebunny/crossref_metadata_2025 huggingface dataset:
TRANSLUMINAL ANGIOPLASTY OF THE RENAL ARTERIES IN PATIENTS WITH FIBROMUSCULAR DYSPLASIA
Authors: Azancot Sarah , Amar Laurence , Lorthioir Aurelien , Azizi Michel
Published: June 2023

Objective:

FMD is the second most frequent cause of renal artery stenosis (RAS) after atherosclerosis and can lead to hypertension. To cure or improve this renovascular hypertension, patient with fibromuscular dysplasia and renal artery stenosis undergo renal artery revascularization by percutaneous renal transluminal angioplasty (PTRA). Although this method has been performed for many years, there have been only few small size trials published. This retrospective single center study aimed to evaluate the rate of cured hypertension after PTRA.

Design and method:

We included all adult patients diagnosed with FMD who were seen in our referral center for hypertension management (Hôpital Européen Georges Pompidou, Paris) from January 2010 to March 2020. Blood pressure response was assessed at 3 month and one year. Primary outcome was one year cured hypertension rate in ambulatory measurement, secondary outcomes were improvement and complication rate.

Results:

Overall, 76 adult patients (87% female, mean age at enrollment 35.5 years) were included. FDM was multifocal in 74% and unisite in 68% of patients. AT baseline, mean day ambulatory blood pressure (dABP) was 141 ± 17/89 ± 14 mmHg under a mean of 2.3 ± 1.37 antihypertensive treatments. All patient underwent PTRA. Stent were inserted in 8 patients (10.5%) with residual stenosis after PTRA and in 8 patients (10.5%) with renal artery dissection, total complication rate was 18.4%. At one-year follow-up, mean dABP was 128 ± 12/78 ± 9 mmHg (p < 0.0001) with 1.1 ± 1.3 treatments (p < 0.0001). In total, 75% beneficiated from renal angioplasty: 31% were cured and 44% were improved. Cured hypertension was associated with low body mass index (BMI) (p = 0.017) and unisite FDM (p = 0.017) on a multivariable analysis.

Conclusions:

In patients with FMD, PTRA is associated with cured hypertension 31% of patients with renal artery FMD undergoing PRTA. Hypertension is more likely to be cured in patient with low BMI and multisite FMD. These results are to be put in perspective with a complication rate of 18.4%.
THE PROGNOSTIC ROLE OF CLINICAL FEATURES AND BIOMARKERS IN PATIENTS HOSPITALIZED WITH CARDIORENAL SYNDROMES
Authors: Theofilis Panagiotis , Vordoni Aikaterini , Volis Nikolaos , Doumani-Korka Georgia , Kampourelli Aikaterini , Xanthopoulou Eleni , Kalaitzidis Rigas
Published: June 2023

Objective:

Cardiorenal syndromes (CRS), involving the heart-kidney cross-talk and the activation of neurohumoral and inflammatory pathways, is an entity characterized by high morbidity and mortality.

The aim of this study was to evaluate the prognostic role of risk factors and biomarkers in patients hospitalized for CRS.

Design and method:

In this prospective, observational cohort study, 113 consecutive patients hospitalized for CRS were enrolled. Socio-demographic characteristics, personal medical history, and prior medication use were recorded upon admission, and echocardiography was performed. Moreover, an array of blood markers were measured. The endpoint of interest was a composite of death or dialysis dependence at discharge.

Results:

Patients were classified into two groups; Group 1 (N = 59): discharged being dialysis-independent, Group 2 (N = 54): death/dialysis dependence at discharge. No major differences were detected in baseline characteristics between the two groups. Group 2 patients used renin-angiotensin-aldosterone system blockers (RAASb) less often (Group 1: 69.5% vs. Group 2: 46.3%, p = 0.01) and more frequently presented with oliguria/anuria (Group 1: 28.8% vs. Group 2: 70.4%, p < 0.001) and any infection (Group 1: 33.9% vs. Group 2: 55.6%, p = 0.02). No dissimilarities were noted in echocardiographic markers. Group 2 patients had significantly lower hemoglobin, serum albumin, bicarbonate, and 25-hydroxy-vitamin D (25OHD). At the same time, N-terminal prohormone brain natriuretic peptide, serum potassium, and parathyroid hormone (PTH) were significantly higher in Group 2 patients (Figure 1). In a multivariate regression analysis, lack of RAASb was independently associated with a 17.7-fold increased risk of death or dialysis dependence at discharge, while the decreasing 25OHD/PTH ratio (beta coefficient -0.01, p = 0.007) and increasing admission serum potassium levels (beta coefficient 0.82, p = 0.03) increased the possibility of facing the composite endpoint. Following a receiver operating characteristic curve analysis, 25OHD/PTH ratio emerged as the most accurate predictor of facing the composite endpoint, with an ideal cutoff of 103.7 (sensitivity 81%, specificity 74%) (Figure 2).

Conclusions:

Lack of prior RAASb use, high admission serum potassium, and a low 25OHD/PTH ratio are associated with poor prognosis in patients hospitalized for CRS.
CHANGES ON LEFT VENTRICULAR FUNCTION AND CHARACTERISTICS ACCORDING TO THE DEGREE OF INTERDIALYTIC WEIGHT GAIN IN MAINTENANCE HEMODIALYSIS PATIENTS
Authors: Anastasiou Vasileios , Alexandrou Maria Eleni , Kamperidis Vasileios , Daios Stylianos , Tsilonis Konstantinos , Theodorakopoulou Marieta , Moysidis Dimitrios , Iatridi Fotini , Giannakoulas George , Ziakas Antonios , Sarafidis Pantelis
Published: June 2023

Objective:

Pronounced pulmonary circulation overloading has been observed in hemodialysis patients with higher fluid intake over the long interdialytic interval. This study aimed to evaluate the impact of the degree of fluid accumulation on left ventricular (LV) systolic and diastolic function and sizing characteristics.

Design and method:

For the present analysis, 41 patients receiving maintenance hemodialysis thrice-weekly were divided by the recommended threshold of interdialytic-weight- gain corrected for dry weight (IDWG%) into a higher (>4.5%) and a lower ( < 4.5%) IDWG% group. All participants underwent 4 echocardiographic assessments at the start and the end of the 3-day and the 2-day interdialytic interval in a crossover design.

Results:

Over the 3-day interval, significant increments in stroke volume (SV) were observed for both groups, but were more prominent in the higher IDWG% group (>4.5% 18.63 ± 22.84vs. <4.5%12.6 ± 14.48mmHg, p = 0.04). Similarly, a greater increase in cardiac output was evidenced in patients with higher IDWG% over the 2- day interval (>4.5%1.31 ± 1.38 vs.<4.5%0.36 ± 2.08L/m 2, p = 0.012). With regards to diastolic function, a significant increase in E/A and E/E’m ratios was observed over the 3-day interval, but significant between-group differences in interdialytic changes were detected only for the E/A ratio (IDWG>4.5% 0.35 ± 0.29 vs. <4.5% 0.06 ± 0.44, p = 0.035). Left atrial dimensions and LV mass were enlarged to a similar extent in both study-groups during both intervals.

Conclusions:

Patients exceeding the recommended threshold of interdialytic fluid accumulation experience higher increases in SV and deterioration of preload- dependent indexes of diastolic function, particularly during the 3-day interval.
SALT SENSITIVITY AND HYPERTENSIVE NEPHROPATHY: A LINK TO BE DISCOVERED
Authors: Lanzani Chiara , Simonini Marco , Lorena Citterio , Laura Zagato , Garcia Luz Maria Gonzalez , Francesca Tunesi , Marianna Contursi , Paola Maiucchi , Paolo Manunta
Published: June 2023

Objective:

Sodium sensitivity is defined as a change in blood pressure depending on sodium intake, which is present in about 30% of the adult population. According to blood pressure variation in salt load test we can classify the population in 3 categories: sodium sensitive (SS), sodium resistant (SR), inverse sodium sensitivity (ISS), based on, respectively, an increase, a non-significant variation or a decrease in the blood pressure values following the administration of sodium. It is reported that SS subjects have, independently from other risk factors, an increased risk of cardiovascular diseases. Moreover, SNPs located in genes related with Na+ metabolism, aldosterone synthesis and tubular sodium reabsorption in the kidney are related to salt sensitivity phenotype. The aim of this study is to analyze the relationship between sodium sensitivity and the development of hypertensive kidney damage in patients with primary hypertension.

Design and method:

A cohort of 712 naïve hypertensive patients were classified for salt-sensitivity using acute saline test (NaCl 308 mEq / 2h / iv).127 patients (follow-up > 5 years- median 11) were selected for the present analysis (SS, n = 40; 0 SR, n = 46; RSS, n = 41).

We analyzed annual decline of the eGFR (CDK-EPI) (Delta-eGFR) and development of microalbuminuria (MicrAlb) as renal outcome. Moreover, genetic polymorphism involved in salt sensitive hypertension has been investigated.

Results:

No differences in Delta-eGFR was observed among the groups. However, SR subjects develop earlier microalbuminuria (p = 0.002) even with an adequate pressure control. Genotypes analysis revealed: polymorphism in CYP11B2 and NEDD4L to be protective against decline in eGFR. For microalbuminuria HSD3B1 and ADD3 seem to be a risk factors, whereas KL, PKD and TRPC6 polymorphism result protective factors.

Conclusions:

Unexpectedly these finding suggests that SR patients are more at risk of developing hypertensive nephropathy than other groups of patients. Moreover genotypes associated with salt sensitivity play different and complex role in kidney damage in hypertension. Improvement in salt sensitivity testing and standardization will be needed to allow all this pathophysiological knowledge to be translated in a clinical setting
DISCREPANCIES BETWEEN DIETARY AND URINE NA/K RATIO CAN BE EXPLAINED BY ALDOSTERONE, CORTISOL AND URINE VOLUME
Authors: Vliet Myrthe van , Zwager Charlotte , Rauh Manfred , Titze Jens , Engberink Rik Olde
Published: June 2023

Objective:

Increased urine sodium-to-potassium (Na/K) ratio is associated with hypertension and cardiovascular disease. However, we demonstrated that urine Na/K ratio does not accurately reflect dietary Na/K ratio. As rhythmic patterns of sodium storage and release are associated with aldosterone and cortisol levels and previous studies linked tissue sodium accumulation to water conservation, we investigated whether the discrepancy between urine and dietary Na/K ratio could be explained by these factors.

Design and method:

We performed a post-hoc analysis of the long-term sodium balance studies Mars105 and Mars520. Ten healthy participants consumed a diet with known sodium and potassium content. For 105 or 205 days 24-hour urine samples were collected. We calculated the difference between urine and dietary Na/K ratio. A linear mixed-effect model was used to determine whether this difference varied across salt intake levels. Furthermore, we fitted two linear mixed-effect models to explain discrepancies between urine and dietary Na/K ratio. In the first, sodium intake, potassium intake, urine aldosterone and urine cortisol were fixed effects and for each factor random slopes per participant were allowed. In the second, sodium intake, potassium intake and urine volume were fixed effects and for each factor random slopes per participant were allowed. We analysed the salt intake levels 6, 9 and 12 grams separately.

Results:

Urine Na/K ratio underestimated dietary Na/K ratio (median difference -0.21, IQR -0.47 to 0.09). The discrepancy was significantly larger at higher salt intake levels (mean difference -0.11, -0.22 and -0.36 for 6, 9 and 12 grams salt intake, respectively, P < 0.001). At all salt intake levels, higher aldosterone levels were associated with underestimation of the dietary Na/K ratio (Figure 1A). In contrast, higher urine cortisol and higher urine volume were associated with overestimation of the dietary Na/K ratio (Figure 1B and C respectively).

Conclusions:

Sodium intake, aldosterone, cortisol and urine volume can explain the discrepancy between dietary and urine Na/K ratio. These data suggest that tissue sodium accumulation contributes to the inability to estimate dietary intake using the Na/K ratio in a single 24-hour urine collection.
TNF ALPHA INHIBITOR USE AFFECTS BIRTHWEIGHT INDEPENDENTLY OF THE SOLUBLE FMS-LIKE TYROSINE KINASE 1 / PLACENTAL GROWTH FACTOR RATIO IN PREGNANT WOMEN WITH RHEUMATOID
Authors: Kluivers Anna , Witte-Quaak Cornelia H. , Smeele Hieronymus T.W. , Neuman Rugina I. , Saleh Langeza , Visser Willy , Dolhain Radboud J.E.M. , Danser A.H. Jan
Published: June 2023

Objective:

The use of tumor necrosis factor ↑ (TNF↑) inhibitors in pregnant women with rheumatoid arthritis (RA) improves birthweight, while in women with preeclampsia high levels of soluble fms-like tyrosine kinase 1 (sFlt-1) result in a reduction in birthweight, possibly because binding of placental growth factor (PlGF) to sFlt-1 reduces its activity. Here we studied whether the beneficial effect of TNF↑ inhibitors on birthweight involves a reduction in sFlt-1 and an improved sFlt-1/PlGF ratio.

Design and method:

Levels of sFlt-1 and PlGF were retrospectively determined in each trimester for 158 women enrolled in a prospective study on pregnancy and RA (Preconception Counseling in Active RA study) and treated according to a treatment protocol aimed at minimal disease activity.

Results:

Half (52.5%) of the women used TNF↑ inhibitors during (part of) their pregnancy. There was no significant difference in the levels of sFlt-1 and PlGF or their ratio between TNF↑ inhibitor users and non-users when comparing the biomarker values per trimester. Correction for parity, other drug use (sulfasalazine, prednisone, hydroxychloroquine), trimester, and disease activity score (DAS28CRP) did not alter this outcome. The well-known negative correlation between sFlt-1 and birthweight was observed in women not using TNF↑ inhibitors and became stronger in each subsequent trimester. Remarkably, this association was entirely absent in all trimesters in women using TNF↑ inhibitors.

Conclusions:

TNF↑ inhibitor use by pregnant women with RA does not alter the levels of sFlt-1 and PlGF or their ratio, although it did annihilate the negative correlation between sFlt-1 and birthweight. This indicates that TNF↑ inhibitor use improves birthweight independently of the sFlt-1/PlGF ratio.
EFFECTS OF THE DUAL ENDOTHELIN ANTAGONIST APROCITENTAN ON AMBULATORY BLOOD PRESSURE INDICES IN PATIENTS WITH RESISTANT HYPERTENSION. RESULTS FROM THE PRECISION STUDY
Authors: Schlaich Markus , Weber Michael A. , Bakris George L. , Flack John M. , Lu Wentao , Haskell Lloyd P. , Wang Ji -Guang , Narkiewicz Krzysztof
Published: June 2023

Objective:

The phase-3 PRECISION trial demonstrated both the safety and the efficacy of aprocitentan to lower office blood pressure (BP) in patients with resistant hypertension. Here, we report on the effects on relevant indices of ambulatory BP measurements (ABPM).

Design and method:

A total of 730 patients with resistant hypertension were randomized to aprocitentan 12.5 mg (n = 243), 25 mg (n = 243), or placebo (n = 244). Paired ABPM results at baseline and week 4 of double-blind treatment were available for n = 174, n = 182, and n = 178 patients, respectively. Changes in 24h ABPM from baseline to week 4 were pre-defined as a secondary endpoint. Here, we analyzed effects on 24h average BP, daytime BP, night-time BP, nocturnal dipping, and BP load. Statistical significance was assessed using the Wilcoxon rank-sum test.

Results:

At week 4, after placebo correction, aprocitentan decreased 24-hour ambulatory SBP (-4.2 mmHg; 95% CI: –6.2, –2.1 for the 12.5-mg dose and –5.9 mmHg; 95% CI: –7.9, –3.8 for the 25-mg dose). The placebo-corrected SBP-lowering was more pronounced during night-time (–5·1 and –7·4 mmHg) compared with daytime (–3·8 and –5·3mmHg) for the 12.5 and 25mg doses, respectively. At baseline, non-dipper rates were 66%, 62%, and 60% for the 12.5mg, 25mg of aprocitentan, and placebo groups, respectively. Non-dippers had a particularly pronounced reduction in night-time systolic BP compared with dippers for both 12.5mg (-11.25 vs -2.79mmHg; p < 0.01) and 25mg of aprocitentan (-13.12 vs -6.29mmHg; p < 0.01). After 4 weeks of treatment, the proportion of non-dippers who had normalization of their dipping pattern was 44%, 40% and 31% for 12.5mg, 25mg of aprocitentan, and placebo, respectively. The change in BP load for both daytime and night-time was more pronounced with both doses of aprocitentan (-18.7/-24.5% for 12.5mg; -20.7/-21.1% for 25mg) compared to placebo (-9.2/-6.6 %; p < 0.001 for all comparisons).

Conclusions:

In patients with resistant hypertension, aprocitentan resulted in substantial ambulatory BP lowering, particularly during night-time. This was associated with reduction in non-dipping rates and BP load. These findings further support the likely clinical benefit of aprocitentan in resistant hypertension.
EFFECT OF BAROREFLEX ACTIVATION THERAPY ON BLOOD PRESSURE: THE BAT-STUDY – A RANDOMIZED SHAM CLINICAL PILOT TRIAL
Authors: Simonsen Rasmus , Vikatmaa Pirkka , Vikatmaa Leena , Groop Per -Henrik , Tikkanen Ilkka , Gordin Daniel
Published: June 2023

Objective:

To explore the effects of baroreflex activation therapy (BAT) on blood pressure in individuals with refractory hypertension.

Design and method:

This investigator-initiated randomized, double-blinded sham-controlled pilot trial included five Finnish patients with refractory hypertension. Participants were found eligible if they were 18 - 70 years old with a daytime systolic ambulatory blood pressure (ABP) of 145 mmHg or higher, and/or a daytime diastolic ABP of 95 mm Hg or higher. Patients were on 3 or more antihypertensive drugs including a diuretic. A witnessed drug intake prior to ABPM was implemented. The Barostim Neo System was implanted for modulation of the autonomic nervous system by direct electrical stimulation of the carotid baroreceptors. After 1 month following implantation, all participants were randomized to either 8 months of baroreflex activation therapy (BAT-system on) or continuous pharmacotherapy (BAT-system off) followed by continuous BAT-therapy for all participants for 8 months. The complete design is outlined in the Figure. 24-hour ABP-measurements were performed per protocol. The primary outcome was defined as a change in ambulatory systolic blood pressure after 8 months of BAT, compared to pharmacotherapy.

Results and conclusions: After 8 months of follow-up BAT decreased mean systolic daytime blood pressure by 11.8 mmHg in three participants randomized to BAT, while in the two remaining participants randomized to continuous pharmacotherapy mean systolic daytime blood pressure increased by 8.7 mmHg. When pooling all daytime systolic 24-hour ABP-measurements across the entire follow-up, BAT-therapy was associated with a 9.2 mmHg lower mean blood pressure as compared to continuous pharmacotherapy (143.5 mmHg [95% CI:142.2 - 144.9] vs 152.7 mmHg [151.1 - 154.2], P < 0.0001). In linear mixed models with the BAT-system's status as a fixed effect, day-time systolic blood pressure recordings from 24-hour ABP-measurements at baseline and after 8 months of follow-up were compared between individuals on BAT and continuous pharmacotherapy. Here, BAT-therapy was associated with a reduction in mean systolic day-time blood pressure of -11.7 mmHg (P < 0.0001). In conclusion, BAT-therapy may be a promising tool in lowering systolic blood pressure in individuals with refractory hypertension.

Figure. Study design. ABPM = ambulatory blood pressure measurement. Device = Control of Device.
WORKLOAD-INDEXED HYPERTENSIVE RESPONSE TO EXERCISE ACROSS THE HEART FAILURE SPECTRUM
Authors: Pugliese Nicola Riccardo , Biase Nicolò De , Punta Lavinia Del , Balletti Alessio , Armenia Silvia , Buralli Simona , Mengozzi Alessandro , Taddei Stefano , Metra Marco , Pagnesi Matteo , Borlaug Barry A. , Williams Bryan , Masi Stefano
Published: June 2023

Objective:

Limited evidence is available regarding the impact of workload-indexed hypertensive response to exercise (HRE) in patients at different stages of the heart failure (HF) spectrum.

We evaluated the prevalence, pathophysiologic and prognostic correlates of HRE, evaluated by the systolic blood pressure (SBP)/Workload slope, across the HF spectrum as defined by the American College of Cardiology/American Heart Association.

Design and method:

We prospectively enrolled 58 healthy controls, 201 subjects at risk of developing HF (HF Stages A-B), and 369 patients with a definite diagnosis of HF (Stage C) and either preserved (HFpEF) or reduced (HFrEF) left ventricular ejection fraction. All patients underwent a combined cardiopulmonary-exercise stress echocardiography test. We recorded two SBP measurements for each patient: the first within the first minute of exercise and the last at peak effort. The SBP/Workload slope was calculated as the difference in SBP over the corresponding increment in watts (W): (SBPpeak – SBPfirst)/(Wpeak – Wfirst). In each subgroup, we divided patients according to SBP/Workload slope tertiles, using sex-specific cut-off values; HRE was defined as the highest SBP/Workload slope tertile in each HF stage. A composite of all-cause mortality and hospitalization for cardiovascular reasons was chosen as the primary outcome.

Results:

The median SBP/Workload slope was 0.53 (interquartile range 0.36 - 0.72) mmHg/W and was steeper in women than men in all subgroups. After adjusting for age and sex, SBP/Workload slope in controls was similar to HFrEF but significantly lower than Stages A-B and HFpEF. In all HF stages, patients with HRE showed significantly lower peak oxygen consumption and peripheral oxygen extraction. After a median follow-up of 16 months, HRE was independently associated with adverse outcomes (Hazard Ratio 2.05, 95% confidence interval 1.81 - 5.18). Kaplan-Meier analysis confirmed a worse survival probability in Stages A-B and HFpEF, but not HFrEF. After adjusting for clinical and echocardiographic variables, patients in the highest SBP/Workload tertile had a 47% higher risk of the primary outcome than subjects in the lowest tertile.

Conclusions:

HRE is associated with peculiar pathophysiological features and possibly worse prognosis in patients in the earliest stages of cardiovascular disease and in those with HFpEF.
EMPAGLIFLOZIN IMPROVES IMPAIRED SENSITIVITY OF AFFERENT NEURONS WITH RENAL AXONS
Authors: Rodionova Kristina , Ditting Tilmann , Hilgers Karl F. , Linz Peter , Schmieder Roland E. , Ott Christian , Schiffer Mario , Amann Kerstin , Veelken Roland
Published: June 2023

Objective:

Afferent renal nerve pathways likely play a role in salt sensitive hypertension. We recently reported that high salt diet (HS) impairs these afferent renal pathways in rats. Now we tested the hypothesis that during HS a decrease in sensitivity of renal afferent neurons is prevented by the SGLT2 inhibitor empagiflozin.

Design and method:

Respective groups of rats were put on HS containing 8% NaCl or a normal diet. Two groups (HS, controls) received empagiflozin 20 mg/kg BW/day orally. Renal neurons were retrogradely labeled with DiI. In culture, labeled dorsal root ganglion neurons (DRG Th11-L2) with renal afferents were investigated electrophysiologically using current clamp mode to assess action potential generation during current injection. Neurons were characterized as tonic highly active ( less than 5 action potentials, AP) and phasic less active neurons (more than 5 AP upon stimulation).

Results:

In neurons from rats on HS, the relation of tonic highly active neurons to less active phasic neurons shifted consistently towards phasic units (63,8% tonic neurons in controls vs. 42%* on HS, *p < 0.05, z-test). However, continuous treatment with empagiflozin preserved the proportion of tonic neurons as in controls (67,9% on HS with concomitant administration of empagiflozin). In controls, empagiflozin did not affect the proportion of tonic to phasic neurons (63,8% tonic neurons in controls vs. 67,9% on HS & empagliflozin, p = 0.7, z-test). Blood pressure and heart rate were not altered by HS and/or treatment with any chosen dose of empagiflozin.

Conclusions:

In rats, chronically elevated sodium intake (8% NaCl) reduced the sensitivity and stimulability of renal afferent DRG neurons. Under these circumstances, concomitant treatment with the SGLT2 inhibitor empagiflozin preserved the function of renal afferent DRG neurons. SGLT 2 inhibitors may help to treat dysfunction of renal innervation in cardiovascular disease.
LINEAR AND NON-LINEAR HEART RATE VARIABILITY INDICES AT REST AND IN RESPONSE TO PHYSICAL AND MENTAL STRESS: A COMPARATIVE STUDY BETWEEN HEMODIALYSIS AND PERITONEAL DIALYSIS PATIENT
Authors: Faitatzidou Danai , Dipla Konstantina , Theodorakopoulou Marieta , Koutlas Aggelos , Sampani Erasmia , Tsitouridis Alexandros , Dimitriadis Chrysostomos , Pateinakis Panagiotis , Zafeiridis Andreas , Papagianni Aikaterini , Sarafidis Pantelis
Published: June 2023

Objective:

Cardiac arrhythmias and sudden death are the leading causes of cardiovascular mortality in end-stage-kidney-disease(ESKD). Autonomic dysfunction contributes to the arrhythmogenic background of ESKD patients. This is the first study to compare linear and non-linear heart-rate-variability(HRV) indices between hemodialysis(HD) and peritoneal(PD) patients, both at rest and in response to mental- and physical-stimulation maneuvers.

Design and method:

Thirty-four HD and 34 PD patients matched for age, sex, and dialysis-vintage, as well as 17 age- and sex-matched controls were studied. Autonomic function was examined by linear and non-linear-HRV indices. Heart-rate was recorded continuously with Finometer-PRO at rest and during orthostatic, mental-arithmetic, sit-to-stand, and handgrip-exercise tests.

Results:

No significant between-group differences were observed in resting HRV indices(RMSSD: HD:57.1 ± 81.1 vs PD:69.6 ± 113.4ms; p = 0.792) except for DFA-a1 index(HD:0.87 ± 0.40 vs PD:0.70 ± 0.20, p = 0.047). All HRV indices during the mental arithmetic test (RMSSD HD:128.2 ± 346.0 vs PD:87.5 ± 150.0ms; p = 0.893) and the physical stress tests were similar between HD and PD patients. Both dialysis groups presented similar patterns of HRV responses to orthostatic and handgrip exercise tests; however, after the sit-to-stand test RMSSD, SD1, SD2 and DFA-a2 indices were higher compared to rest only in HD patients(RMSSD: 57.1 ± 81.1 vs 126.7 ± 185.7ms, p = 0.028), suggesting a greater difficulty of HD patients in recovering normal ANS function following a physical stress-test.

Conclusions:

HRV indices at rest and after mental and physical stimulation did not differ between HD and PD patients, however the ANS response following the sit-to-stand test was more impaired in HD. These findings suggest that ANS dysfunction is not largely affected by dialysis modality but small differences in normal ANS recovery may exist.
PATIENT PREFERENCES IN PHARMACEUTICAL AND DEVICE-BASED TREATMENTS FOR UNCONTROLLED HYPERTENSION
Authors: Kandzari David , Weber Michael A. , Poulos Christine , Cohen Sidney , Debruin Vanessa , Pathak Atul
Published: June 2023

Objective:

Radiofrequency renal denervation (RDN) safely reduces high blood pressure (BP) in hypertensive (HTN) patients. Patient preference regarding such a treatment over antihypertensive (AH) drugs for uncontrolled HTN is poorly understood.

Design and method:

A recent discrete choice experiment (DCE) study in patients with uncontrolled HTN identified the reduction in systolic BP as the most important driver of patient preference between interventional treatments (e.g. RDN) or drugs. Using a predictive model consisting of the preference weights for safety and efficacy attributes from the DCE study, we calculated patients’ treatment preferences in 3 typical clinical scenarios in HTN management. Each scenario presented a choice to either initiate/increase AH drugs, or to have interventional treatment such as RDN: (1) AH drug naïve: initiate AH drugs vs. interventional treatment (2) mild-moderate HTN, 1-3 AH drugs: increasing AH drugs vs. intervention with no drug changes, (3) severe HTN (systolic BP >150mmHg, >3 AH drugs): increasing AH drugs vs. intervention with no drug changes.

In each scenario, the average predicted probability of choosing one treatment over the other was calculated based on a benefit-risk profile from the sum of preference-weighted treatment attributes (type of treatment, changes in AH drugs, office systolic BP reducing efficacy, effect duration, risk of drug side effects, interventional treatment adverse events). Values of the treatment attributes were derived from the literature, expert opinion, and published RDN studies (SPYRAL HTN OFF-MED, ON-MED, Global SYMPLICITY Registry).

Results:

In (1), 17% preferred interventional treatment without drugs vs 83% preferred initiation of drugs. In (2), 24% preferred interventional treatment without increasing drugs vs 76% preferred increasing drugs. In (3), 45% preferred interventional treatment without increasing drugs vs 55% preferred increasing drugs. Preference differences were driven by the magnitude of office systolic BP reductions with each treatment. Risks of treatment-related adverse events were less important to treatment choices.

Conclusions:

Preference for RDN ranged from one-fifth to one-half of patients depending on clinical scenario. The increase mirrored the extent of prior treatment with AH drugs and HTN severity on drugs. Patient preference was driven predominantly by efficacy and minimally by safety of treatment.
USE OF ANTIHYPERTENSIVE COMBINATION THERAPY DURING THE COVID-19 PANDEMIC - A CROSS-SECTIONAL, NATION-WIDE STUDY 2019-2021
Authors: Dobrowolski Piotr , Prejbisz Aleksander , Bozek Gabriel , Kon Beata , Machnio Aneta , Urbanski Filip , Madry Roman Topor , Kreutz Reinhold , Januszewicz Andrzej , Milkowski Maciej
Published: June 2023

Objective:

To assess changes in the use of antihypertensive drug combinations during the COVID-19 pandemic and the degree of adherence to the recommendations of more frequent use of combination therapy by ESC/ESH 2018 guidelines, data of all patients who filled a prescription for an antihypertensive drug in Poland were analyzed.

Design and method:

Patients who filled at least one prescription from ATC groups C02, C03, C07-10, C10BX in each of the years 2019, 2020 and 2021 were extracted from the obligatory prescription database of the National Health Service in Poland. This database covers all filled prescriptions in Poland. We have excluded from the analysis patients with diagnosis of heart failure. Combination therapy was assumed if prescriptions of two drugs overlapped for at least 40 days. In the case of the use of single pill combinations (SPC), the combined use of the individual substances included in the SPC was automatically recognized by the database. The frequencies were analyzed for the years 2019, 2020 and 2021 respectively.

Results:

In years 2019, 2020 and 2021 – 10,328,341, 9,478,949 and 9,637,595 patients fulfilled the inclusion criteria. One antihypertensive drug was used by 28.5, 28.0 and 28.3% of patients. The remaining patients used two antihypertensive drugs 27.4, 28.1 and 28.0%, three antihypertensive drugs 21.6, 22.2 and 22.1%, four antihypertensive drugs 12.7, 12.8 and 12.7% and 5 or more antihypertensive drugs 9.8, 9.0 and 9.0%. There was a modest increase in two drug SPC, which were used by 28.0, 28.7 and 29.8% of patients. There was an increase in the use of three drug SPC – 2.6%, 2.9% and 3.4% of patients.

Conclusions:

Although a modest, significant increase in the frequency of SPC use, both based on two and three antihypertensive drugs, was found, the COVID-19 pandemic and the ESC/ESH 2018 recommendations supporting the use of combination treatments, have had little impact on the prevalence of combination treatment in Poland.
GUIDELINES-BASED THERAPEUTIC STRATEGIES FOR CONTROLLING HYPERTENSION IN NON-CONTROLLED HYPERTENSIVE PATIENTS FOLLOWED BY FAMILY PHYSICIANS IN PRIMARY HEALTH CARE. THE GPHT-PT STUDY
Authors: Polonia Jorge , Pereira Raul
Published: June 2023

Objective:

In a prospective open study conducted in Primary Care by GPs, we evaluated the efficacy of a single pill of candesartan + amlodipine as the only anti-HT medication in patients (18 - 80 years) with uncontrolled hypertension (HT) (BP > 140/or > 90 mm Hg, either treated with anti-HT monotherapies (Group I), or combinations with hydrochlorothiazide (HCTZ) (Group II), or not receiving medication at all (Group III).

Design and method:

Each of 100 GPs recruited the first 25 patients without CV events and with uncontrolled HT. Three groups were defined in the first (v0) clinical evaluation and evaluated in 2 more moments (v6 and v12 weeks) in which office blood pressure (BP, mean of 2 of 3 records) was evaluated as in guidelines. Control of HT = BP< 140/90 mmHg. ANOVA repeated measurements controlling as covariant the age (X = 61.95; ± 9.69).

Results:

Of 1234 patients recruited, 762 (age 61 + 10 years, 52% women) completed the 12 weeks of study: (Group I, n = 332, 58% women; Group II, n = 77, 42% women; Group III, n = 343, 51% women). According to severity, patients were medicated with one of 3 (morning) fixed combination candesartan/amlodipine dosage: 8/5 or 16/5 or 16/10 mg/day. SBP/DBP values (mm Hg). In Group I BP = 156/91 + 12/11 (v0); v12 : SBP/DBP -25/-14 mm Hg <0.01 and 85% pts controlled with 8/5 (67%), 16/5 (17%), 16/10 (16%). In Group II BP = 161/93 + 16/13 (v0); v12 SBP/DBP -29/-14 mm Hg <0.01 and 91% pts controlled with 8/5 (44%), 16/5 (17%), 16/10 (39%). In Group III BP = 167/95 + 15/10 (v0); v2 : SBP/DBP -34/-17 mm Hg <0.01 and 76% controlled patients with 8/5 (54%), 16/5 (29%), 16/10 (17%). There was no weight variation during the study. From v6 and v12 BP falled but without statistical significance.

Conclusions:

In patients with uncontrolled HT (under monotherapy, combinations with HCTZ or non-medicated) followed by GPs, therapeutic measures in accordance with guidelines with a fixed combination ARB/amlodipine allowed to achieve HT control at 12 weeks in 76 - 91% of previously uncontrolled patients, reinforcing the advantages of implementing these strategies in primary clinical practice.
REAL-WORLD ANALYSIS ON DRUG UTILIZATION, CARDIOVASCULAR HOSPITALIZATION AND HEALTHCARE COSTS OF PATIENTS ON SINGLE PILL VS FREE COMBINATION OF PERINDOPRIL/BISOPROLOL IN ITALY
Authors: Masi Stefano , Kobalava Zhanna , Veronesi Chiara , Giacomini Elisa , Esposti Luca Degli , Tsioufis Konstantinos
Published: June 2023

Objective:

The present real-world analysis aims to compare the drug utilization, CV hospitalizations and healthcare direct costs related to the use of single-pill combination (SPC) or free-combination of perindopril/bisoprolol (PER/BIS) in a large Italian population.

Design and method:

This observational retrospective analysis was based on administrative databases covering approximately 7 million subjects across Italy. All adult subjects receiving PER/BIS as SPC or free combination between January 2017-June 2020 were included. Subjects were followed for 1 year after the first prescription of PER/BIS as free-combination ( ± 1 month) or SPC. Before comparing the SPC and free-combination cohorts, propensity score matching (PSM) was applied to balance the baseline characteristics. Adherence was defined by proportion of days covered (PDC) and time to treatment discontinuation (evaluated by Kaplan-Meier curves). Given that the SPC PER/BIS can be taken as half a tablet a day, the PDC was calculated assuming the prescription of one tablet/day or half tablet/day. Mean annual healthcare direct costs were analyzed as overall drugs, hospitalizations and outpatient services costs during follow-up.

Results:

The original cohort included 11,440 and 6,521 patients taking the SPC and free PER/BIS combination, respectively. After PSM, two balanced SPC and free-combination cohorts of 4,688 patients were obtained (mean age 70 years, approximately 50% male). Proportion of adherent patients (PDC > = 80%) was higher for those on SPC (45.5% and 76.3% assuming one SPC/day or half SPC/day, respectively) than those on free-combination (38.6%), p < 0.001. The PER/BIS combination was discontinued by 35.8% in SPC cohort and 41.7% of patients in the free-combination cohort (p < 0.001, Figure 1A). The SPC cohort had less cardiovascular (CV) hospitalizations (5.3%) and shorter CV hospital admissions (0.4 ± 2.3 days) than the free-combination cohort (7.4% and 0.6 ± 2.9 days), p < 0.001 for both comparisons (Figure 1B). Mean annual total healthcare costs were lower in the SPC (1,999€) than in the free-combination (2,359€) cohort (details on cost items are presented in Figure 1B).

Conclusions:

Patients treated with PER/BIS SPC have higher adherence, lower risk of drug discontinuation, reduced risk of CV hospitalization, and lower healthcare costs than those on free-combination.
IMPACT OF RAMIPRIL/AMLODIPINE DOSE COMBINATIONS OF SINGLE-PILL VERSUS FREE EQUIVALENT COMBINATIONS ON PERSISTENCE AND MAJOR ADVERSE CARDIOVASCULAR EVENTS: A REAL-WORLD ANALYSIS
Authors: Farsang Csaba , Burnier Michel , Narkiewicz Krzysztof , Rokszin György , Abonyi-Tóth Zsolt , Kovács Gábor , Potukuchi Praveen Kumar , Abdel-Moneim Mohamed , Simonyi Gabor
Published: June 2023

Objective:

Guidelines recommend use of single-pill combination (SPC) for management of hypertensive patients. Very few studies compared SPCs and free equivalent combinations (FEC) focusing on short-term persistence and major adverse cardiovascular events (MACE) outcomes. This study assessed the impact of different dose combinations of ramipril/amlodipine (R/A) SPC versus FEC on treatment persistence and MACE in patients with hypertension over a 5-year period.

Design and method:

This real-world, retrospective, observational cohort study was performed using National Health Insurance Fund of Hungary database. The study included hypertensive patients aged > = 18 years who initiated on R/A SPC or FEC, of different dose combinations: R/A 5/5 mg, 5/10 mg, 10/5 mg and 10/10 mg, between 01 April 2012 and 31 December 2018. Primary endpoint was the long-term persistence rate, applying 90-days grace period, between R/A SPC and FEC. Secondary endpoint was the rate of MACE (composite of non-fatal myocardial infarction, stroke, hospitalization for heart failure and all-cause death). Analyses were performed using Cox-proportional hazard model and propensity score sub-classification method to adjust the imbalances in baseline characteristics.

Results:

Overall, 173,206 patients with hypertension were included (SPC group, N = 104,882 [61%], and FEC group, N = 68,324 [39%]); R/A 5/5 mg representing the largest proportion (N = 107,992 [62%]). In SPC and FEC groups, mean (SD) age was 61.31 (13.75) and 66.08 (13.10) years and proportion of male was 45.4% and 43.1%, respectively. As shown in Table 1, the rate of non-persistence was significantly lower with all R/A SPCs compared to FECs from Month 1 to Month 24 (P < 0.001). Thereafter, the rate of non-persistence remained significantly lower in the SPC groups except in the R/A 5/5 mg dose. MACE was significantly reduced with all R/A SPCs compared to FECs (HR 0.68–0.73; P < = 0.002). There was no impact of age and gender on the association between the treatment and persistence rate or MACE outcomes.

Conclusions:

Our results confirm the beneficial effects of SPCs compared to FECs in achieving long-term improvement on persistence rate and MACE outcomes in patients with hypertension and support current guidelines recommending a widespread use of SPCs.
THE INFLUENCE OF DEPRESSION IN HYPERTENSIVE ELDERLY PATIENTS
Authors: Munteanu Alice Elena , Ispas Irina , Ionita Iulia Teodora , Casian Mihnea
Published: June 2023

Objective:

Depression and cardiovascular diseases are two common pathological entities in the elderly, their incidence increasing with advancing age. Clinicians have empirically observed that depression is an independent risk factor for hypertension, thus showing the need to demonstrate this hypothesis through clinical trials and also the correlation of depression with the occurrence of other cardiovascular diseases.

Design and method:

The study was carried out on 127 patients in the Emergency County Hospital dr. Pompei Samarian Calarasi, with cardiovascular disease, including hypertension, and/or depression. The presented study is observational, analytical, retrospective. The study group was randomized according to inclusion and exclusion criteria established prior to patient selection.

Results:

Hypertension is very common in the elderly. We observe a significant increase in blood pressure values with age.

Patients at low, moderate, and high cardiovascular risk tend to have mild or moderate depression, and those at very high risk tend to have moderate or severe depression.

Depression influences cardiovascular risk factors, favoring the increase of serum cholesterol and triglyceride values and favoring the decrease of serum HDL-cholesterol values, the influence of depression being statistically significant.

The proportion of patients with hypertension who associate depression increases with increasing blood pressure values. To emphasize the importance of depression in hypertension, we excluded patients with metabolic syndrome. It has been observed that in these patients the association between depression and hypertension increases, emphasizing the fact that depression represents a cardiovascular risk factor.

Studying the relationship between the severity of depression and the degree of arterial hypertension, it was observed that in patients with high blood pressure, the degree of depression is high.

Conclusions:

Considering all these aspects, we emphasize the importance of the correct and early diagnosis of depression in elderly patients, this being an important risk factor for cardiovascular diseases, including hypertension, often ignored in medical practice.
A SIGNIFICANT INCREMENT IN LEFT ATRIAL PRESSURE AFTER CRYOBALLOON ABLATION INDICATE WORSE ATRIAL FUNCTION: EVIDENCE FROM APPEARANCE-AF TRIAL
Authors: Zhongyuan Ren , Wu Jiayu , Xu Yawei , Zhao Dongdong , Zhao Yifan , Maimaitiaili Rusitanmujiang
Published: June 2023

Objective:

Left atrial pressure (LAP) is a direct reflection of left atrial function, while LAP could fluctuate following left atrial procedure. The pattern of LAP change in response to pulmonary vein isolation (PVI) and its significance remain to be explored. This study aimed to investigate the pattern of LAP change before and after PVI, and its correlation with other clinical profiles.

Design and method:

28 patients underwent PVI using cryoballoon ablation were included (from APPEARANCE-AF trial). Pre-ablation and post-ablation LAP were directly measured via catheter. The correlation of LAP change with demographics, biochemical measurements, and speckle traced echocardiographic indexes of left atrium (LA) were investigated.

Results:

The included cohort has a mean age of 73.8±8.4 years old, with 12 male (42.9%). Instant PVI was achieved in all patients without complications. The average mean LAP (mLAP) measured before and after PVI was 8.2±4.5 mmHg (pre mLAP) and 14.0±6.5 mmHg (post mLAP), with a significant increment (↗mLAP: 5.8±4.5 mmHg, P<0.001). The change in LAP significantly correlated with LA strain rate in reservoir (LASr, r = -0.58, P = 0.001) and conduit phase (LAScd, r = 0.63, P<0.001) and LA ejection fraction (r = -0.48, P = 0.014). Correspondingly, patients with larger LAP increment (inc-mLAP, increment of mLAP>5 mmHg, n = 14) presented significant worse atrial function indicated by LASr (17.3%±5.6% ninc-mLAP vs 11.5%±7.3% inc-mLAP, P = 0.030), LAScd (-9.6%±2.2% ninc-mLAP vs -5.7%±3.6% inc-mLAP, P = 0.003).

Conclusions:

PVI could significantly increase LAP, and a higher change of LAP might indicate worse atrial function. The prognostic value of LAP change necessitates further follow-up evaluation.
RISK STRATIFICATION OF STAGE B HEART FAILURE USING HOME BLOOD PRESSURE MONITORING AND EFFECT ON THE INCIDENCE OF HEART FAILURE
Authors: Wachi Sumika , Narita Keisuke , Hoshide Satoshi , Kario Kazuomi
Published: June 2023

Objective:

Recently, the international guideline recommends use of the universal definition of Stage B heart failure (HF) based on cardiac biomarkers for risk stratification of asymptomatic HF. There is a few study reporting the association between home blood pressure (BP) and the stage B of HF. We thus assessed this issue by using the dataset of the nationwide prospective study regarding home BP monitoring, the Japan Morning Surge Home BP (J-HOP) study.

Design and method:

In the J-HOP study, 4,310 outpatients with cardiovascular risk were enrolled and underwent a consecutive 14-days home BP monitoring in morning and evening. In the present study, we assessed 3,218 participants after excluding participants with pre-history of HF and other cardiovascular diseases and lack of data in biomarkers. NT-proBNP 125pg/ml or Hs-cTnT >0.014ng/ml in women, >0.022ng/ml in men were defined as the Stage B of HF based on the guideline (n = 604).

Results:

In the multivariable logistic model, increase of morning home systolic BP was significantly associated with the risk of the stage B of HF (adjusted OR per 10mmHg, 1.25; 95%CI, 1.16–1.33). After followed-up of median 6 years, 19 patients were hospitalized for HF. The stage B of HF was at greater risk of developing heart failure than the stage A patients (adjusted HR, 3.76; 95% CI, 1.40–10.06) in the multivariable Cox model.

Conclusions:

From our findings, morning home BP might be useful for risk stratification of early stage of HF.
A COMMERCIAL-OFF-THE-SHELF FREQUENCY MODULATED CONTINUOUS WAVE RADAR FOR VITAL SIGN MONITORING
Authors: D’Elia Massimo Emiliano , Zarudniev Mykhailo , Bonnet Stephane
Published: June 2023

Objective:

Radar systems are capable of retrieving remotely micro-movements with very high precision. Millimeter-wave radars are already used in several medical applications (e.g. sleep disorders, heart beat rate, patient monitoring) and have shown promising results towards a remote Doppler cardiogram or arterial pulse wave measurements techniques. In this work, we tested a 122 GHz commercial-off-the-shelf (COTS) Frequency Modulated Continuous Wave (FMCW) radar for vital (respiratory and cardiac) signals monitoring. This required the setting up of a very precise experimental bench and the investigation of a robust data processing procedure.

Design and method:

An experimental bench (see Figure 1-a) has been set up with a high precision Newport linear actuator: a small target can be then displaced with less than 3 μm accuracy. Such system can replicate the thorax displacements due to the respiratory and cardiac activity. Two different motions were simulated: a ‘large’ 8 mm displacement at 0.15 Hz (a.k.a. respiratory) and a ‘small’ 0.5 mm at 1 Hz (a.k.a. cardiac). Furthermore, a shaker system can be used to reproduce completely arbitrary movements, even from real acquired Electrocardiogram (ECG) data. In this case, however, a reference measurement system would be necessary to determine the accuracy.

Results:

A first measurement set was dedicated to evaluate the accuracy of the radar system: around 50 acquisitions for each type of displacements were carried out. The accuracy of the radar measurements results in the order of ∼10 μm (see Figure 2). A second measurement set tested the dynamic resolution: in this case, a 0.4 Hz sinusoidal signal and a 0.8 Hz pulsation mix were fed to the shaker system. The radar is capable of retrieving both signal signatures (see Figure 3), with errors due to the combination of sharp pulse rise and low radar sampling frequency

Conclusions:

We show that a COST radar is able to retrieve vital signs chest displacements with a good accuracy in both amplitude and dynamics, thus representing a valid option for a remotely continuous cardiovascular monitoring. Next objectives are In Vivo measurements with an in-house radar system and measurements of blood pulse waves.