bluuebunny/crossref_metadata_2025 huggingface dataset:
P5355Evaluation of maternal heart rate during the first week postpartum with wearable device
Authors: Gherbesi E , Squillace M , Gobbi C , Schiavone M , Malanchini G , Castelli B , Famiani R , Zippo D , Ossola M W , Bonanomi C , Lombardi F
Published: October 2019

Background

Throughout pregnancy and puerperium significant cardiovascular changes occur. Maternal heart rate (HR) increases from the first to the third trimester of pregnancy, with a further increase during labor. Changes in the postpartum period are less well defined, in particular, the phenomenon of postpartum maternal bradycardia (PMB).

Purpose

To describe the distribution of HR in the first week postpartum, the incidence of PMB and to investigate the relationship between PMB and other maternal factors such as age, BMI and type of delivery.

Methods

Women who gave their informed consent during a clinical evaluation in the third trimester of pregnancy, and delivered at our tertiary centre between 01/01/2018 and 30/09/2018, were included. Within 12 hours from delivery, a wrist-worn tracker with a light-emitting diode (FitBit Alta HR) was applied and then removed one week postpartum. Data were extracted as 5 minutes recordings, each showing a mean HR. Only day-time recordings were considered. PMB was defined as ratio between bradycardia recordings (mean HR<60 bpm) and all recordings >0.6. SPSS was used for statistical analysis.

Results

252 women were included (mean age 35.3±5 years, BMI 23.3±5 kg/m2). 63% of women underwent caesarean section. Mean HR of the total population on day 1 after delivery was 80.7±11 bpm and then progressively decreased, with a mean HR on day 7 of 76.5±12 bpm (figure 1). 24 women developed PMB, with an incidence of 9.5%. The trend of HR in bradycardic women was opposite to that of non-bradycardic women, with an increase from day 1 (55±7 bpm) to day 7 (60.5±9 bpm) (figure 2). Device recordings during the first two days were in agreement with periodic bedside HR measurements. No bradycardic woman experienced syncope or pre-syncope or required treatment. PMB showed a positive correlation with caesarean section vs. vaginal delivery (p<0.01) and maternal age (p<0.05). No correlation was found with BMI and postpartum haemoglobin.

Trend of HR in the first week postpartum

Conclusion

In our population the incidence of PMB identified with wearable device was 9.5% and was associated with caesarean section and maternal age. Considering that HR returned within normal limits 7 days after delivery and no woman was symptomatic, our study suggests that PMB might be considered a benign entity.
P5361Pregnancy in patients with cardiac arrhythmias
Authors: Kirgizova M , Dedkova A , Kisteneva I , Borisova E
Published: October 2019

Introduction

Negative trends in the state of somatic and reproductive health of the female population are observed in the last decades all over the world. On the background of declining birth rates, the problems of managing pregnancy in women with extragenital pathology become relevant.

Aim

To study the effects of cardiac arrhythmias and antiarrhythmic treatment on the course and outcomes of pregnancy.

Material and methods

A total of 55 case histories of pregnant women hospitalized in the Department of Interventional Arrhythmology. All patients signed informed consent to be enrolled in the study. The age of patients ranged from 17 to 41 years (mean age of 30.2±4.0 years). Patients were hospitalized on average at 28.0±6.4 weeks of gestation (from 12 to 37 weeks) and had some form of cardiac arrhythmia.

Results

Cardiac arrhythmias were idiopathic in 65% of cases; the rest of patients had verified cardiovascular diseases. Cardiac arrhythmias were registered in 41 (74%) of women prior to pregnancy and their arrhythmological history lasted for 7.9±1.1 years. Extrasystolic arrhythmia was the most common type of cardiac arrhythmias: ventricular premature beats occurred in 23 pregnant women (42%) including supraventricular premature beats in 8 patients (14%), supraventricular tachycardia in 12 patients (22%), and ventricular tachycardia (VT) in 5 women (9%). In three cases, VTs were hemodynamically significant. Radiofrequency ablation (RFA) of VT was performed in pregnant women at 26, 27, and 32 weeks of gestation. Five patients with gestational ages of 27–34 weeks received RFA for atrial tachycardia and atrioventricular (AV) reciprocal tachycardia to treat symptomatic intracardiac tachycardia (n=4) and continuous recurrent AV nodal tachycardia (n=1), paroxysms of which were accompanied by destabilization of hemodynamics.

AV block was registered in 4 pregnant women (9%); sick sinus syndrome was diagnosed in 1 patient (2%). Implantation of pacemaker was required in 1 case for a second-degree AV block type II (Mobitz type II) at 24 weeks of pregnancy. RFA and pacemaker implantation were carried out with minimal or zero fluoroscopy and only after the 22nd week of pregnancy, that is, without or with reduced radiation risk to the fetus.

16 patients (29%) had cesarean section; the rest of patients had spontaneous vaginal delivery. The average Apgar scores were 8.64 immediately after birth and 9.35 five minutes after birth. Preterm births (n=2) were due to obstetric pathology and were not associated with cardiac arrhythmias. Cardiac arrhythmias were not observed in any patient in childbirth.

Conclusions

Cardiac arrhythmias, observed in patients, did not require termination of pregnancy. Catheter ablation for symptomatic, hemodynamically significant, and life-threatening cardiac arrhythmias made it possible to effectively guide pregnant women to delivery with a close follow-up.
P5363Adherence to statin therapy drives survival of patients with symptomatic peripheral artery disease
Authors: Dopheide J F , Ramadani H , Veit J , Adam L , Papac L , Schindewolf M , Vonbank A , Baumgartner I , Drexel H
Published: October 2019

Background

Statins reduce cardiovascular morbidity and mortality, but adherence is suboptimal. We hypothesized that adherence to statin therapy determines survival in a population at very high cardiovascular risk.

Methods

Single center observational study with 691 symptomatic PAD patients admitted to a tertiary university center between 2010 and 2017. Outcome was evaluated over a mean follow-up of 50±26 months. We related statin adherence and LDL-C target attainment to total mortality.

Results

At the first contact, 73% of our PAD patients were on statins with a significant increase in statin use to 81% (p<0.0001) at follow-up: Statin dosage, normalized to simvastatin 40 mg, increased from 50 to 58 mg/ day (p<0.0001), and was paralleled by a mean decrease of LDL-C from 97 to 82 mg/ dL (p<0.0001). The proportion of patients receiving a high intensity statin increased over time from 38 to 62% (p<0.0001). Percent LDL-C decrease over time was highest in patients with high intensity statin treatment, followed by moderate, low intensity or non-statin treatment, respectively (p=0.01).

Patients never receiving statins had a higher mortality rate (34%) as compared to patients being on statins (20%) or having newly received a statin (15%; p<0.01). Moreover, patients on intensified statin medication had the lowest mortality (10%), whereas patients who terminated statin medication or reduced the statin dosage had a higher mortality rate (33% and 43%, respectively; p<0.05).

Figure 1

Conclusion

Our data prove that statin treatment, particularly high-intensity therapy, reduces mortality in symptomatic PAD. In terms of mortality, patients benefit even from de novo statin therapy (“it is never too late”), whereas dose reduction or statin discontinuation have deleterious effects. A strategy of intensive and sustained statin therapy is worthwhile.

Acknowledgement/Funding

None
P5367Indirect comparison of the safety and efficacy of alirocumab and evolocumab: from a comprehensive meta-analysis of 30 randomized controlled trials
Authors: Guedeney P , Sorrentino S , Giustino G , Chapelle C , Claessen B , Ollier E , Laporte S , Camaj A , Kalkman D N , Vogel B , De Rosa S , Indolfi C , Collet J P , Mehran R , Montalescot G
Published: October 2019

Background

Alirocumab and evolocumab, two proprotein convertase subtilisin–kexin type 9 inhibitors, have both been associated with improved outcomes in patients with atherosclerotic cardiovascular disease in addition to standard lipid-lowering therapies. However, their comparative safety and efficacy profiles are unknown.

Purpose

To compare the safety and efficacy of alirocumab versus evolocumab.

Methods

We conducted a systematic review and network meta-analysis of placebo-controlled randomized trials available up to November 2018 evaluating the safety and efficacy of alirocumab and evolocumab. We estimated risk ratio and 95% confidence intervals using fixed effect model in a frequentist pairwise and network metanalytic approach. The primary safety endpoints were any adverse events leading to treatment-discontinuation, injection site reaction, systemic allergic reaction, neurocognitive events, ophthalmologic events and new-onset of diabetes mellitus (DM) or worsening of pre-existing DM. The primary efficacy endpoints were all-cause and cardiovascular (CV) death, myocardial infarction (MI) and stroke. This study was registered in PROSPERO (CRD42018090768).

Results

A total of 30 trials, enrolling 59,026 patients were included in this analysis, of whom 13,607 received alirocumab and 17,931 received evolocumab. Mean weighted follow-up time was 2.5 years, with an exposure time of 144,907 patients-years. Eligibility criteria varied significantly across trials evaluating alirocumab and evolocumab. There were no significant differences between alirocumab and evolocumab in terms of safety endpoints, except for injection site reaction with a 27% increased risk of injection site reaction with alirocumab compared to evolocumab (Figure). Compared with evolocumab, alirocumab was associated with a reduction of all-cause death but not CV death. There were no significant differences in MI or stroke between alirocumab and evolocumab.

Conclusion

Alirocumab and evolocumab share a similar safety profile. No significant differences were observed across the efficacy endpoints, except for all-cause death, which may be related to heterogeneity of the studied populations between the two drugs.
P5391Systemic administration of high-mobility group box 1 can suppress adverse post-infarction ventricular remodeling in a rat infarction model by enhancing self-regeneration
Authors: Goto T , Miyagawa S , Tamai K , Matsuura R , Harada A , Ueno T , Toda K , Kuratani T , Sawa Y
Published: October 2019

Background

High-mobility group box 1 protein (HMGB1) reportedly enhances CXCR4-positive bone marrow-derived mesenchymal stem cell (BM-MSC) recruitment to damaged tissue to promote tissue regeneration.

Purpose

Our aim of this study is to evaluate whether systemic administration of HMGB1 might promote tissue repair in a rat myocardial infarction (MI) model.

Methods

We prepared 26 MI model rats with high ligation of the left coronary artery. Two weeks later, HMGB1 (3 mg/kg/day) or phosphate-buffered saline (control: 3 mL/kg/day) was administered for 4 days via femoral vein. Cardiac performance was evaluated by ultrasonography, left ventricular (LV) remodeling via immunostaining. We then used immunostaining to examine MSC recruitment to damaged tissue in green fluorescent protein bone marrow transplantation (GFP-BMT) model rats, and also performed intravital imaging using two-photon microscopy to visualize BM-cells recruitment in real time.

Results

Compared with control rats, there was a significant improvement in the left ventricular ejection fraction of the HMGB1 group (HMGB1 vs. control: 48.6% ± 5.5% vs. 33.6% ± 5.4%; p<0.01) at 4 weeks after each administration. LV remodeling, characterized by interstitial fibrosis, cardiomyocyte hypertrophy, and a decrease of capillary density, was significantly attenuated in the HMGB1 group compared with control rats. On QT-PCR analysis, VEGF mRNA expression was significantly higher in the HMGB1 group than in the control (border zone; 1.6±0.6 vs. 1.1±0.2; p=0.02, septal zone; 1.1±0.1 vs. 0.9±0.1; p<0.01). In GFP-BMT rats, GFP+/PDGFR+ cells were significantly mobilized to the border zone in the HMGB1 group compared with the control (1331±197 vs. 615±45 /mm2; p<0.01), leading to formation of newly developed vasculature (Figure 1). In intravital imaging, more GFP+ cells were mobilized to the infarction area in the HMGB1 group than in the control, which was further enhanced at 12h later. Additionally, SDF-1 expression in the peri-infarction area increased significantly in MI rats compared with normal rats (MI vs. normal; 2.1±0.4 vs. 0.9±0.1; p<0.01), in where some cell-adhesions of vascular endothelial cells were destroyed.

Conclusions

Systemic administration of HMGB1 mobilized BM-MSCs to the damaged myocardium via the SDF-1/CXCR4 signaling complex. Those BM-MSCs might migrate to extracellular matrix in the border zone via the gap of each endothelial cell, leading to induction of angiogenesis and reduced fibrosis.

Acknowledgement/Funding

None
P5398CircRNAs deregulation in heart failure patients
Authors: Greco S , Made' A , Longo M , Tikhomirov R , Castelvecchio S , Menicanti L , Martelli F
Published: October 2019

Background

Circular RNAs (circRNAs) are an emerging class of noncoding RNAs stemming from the splicing and circularization of pre-mRNAs exons. CircRNAs can regulate transcription and splicing, sequester microRNAs acting as “sponge” and inducing the respective targets, and bind to RNA binding proteins. Recently, they have been found deregulated in dilated cardiomyopathies (DCM), one of the cardiovascular diseases with the worst rate of morbidity and mortality, and whose molecular mechanisms are only partially known.

Purpose

Therein, we will evaluate in ischemic DCM patients the modulation of 17 circRNAs, 14 out of them obtained from literature data on DCM ischemic or not, while the other 3 were circRNAs not characterized in the heart previously. The study aims to identify circRNAs candidates for further functional characterization in DCM. In addition, as differential expression (DE) analysis is not easily performed for circRNAs in RNA-seq datasets, the validated circRNAs will be used to set up the most specific and sensitive bioinformatics pipeline for circRNA-DE analysis.

Methods

We designed divergent and convergent specific primers for 17 circRNAs and their host gene, respectively, and their amplification efficiency was measured by RT-qPCR. Transcripts expression was measured in left ventricle biopsies of 12 patients affected by non end-stage ischemic HF and of 12 matched controls.

Results

We identified cPVT1, cANKRD17, cBPTF as DE, and validated the modulation of 5 out of the 14 DCM-related circRNAs (cHIPK3, cALPK2, cPCMTD1, cNEBL, cSLC8A1), while cPDRM5, cTTN1 showed opposite modulation, which may be due to the specific disease condition. All of them were modulated differently from the respective host gene. CircRNA/miRNA interactions were predicted using Starbase 3.0. Next, mRNAs-targets of the identified miRNAs were predicted by mirDIP 4.1 and intersected with gene expression datasets of the same patients, previously obtained by microarray analysis.

We found that cBPTF and cANKRD17 might sponge 12 and 2 miRNAs, respectively. Enrichment analysis of the relevant targets identified several important pathways implicated in DCM, such as MAPK, FoxO, EGFR, VEGF and Insulin/IGF pathways. In addition, deep RNA-Seq analysis that is currently ongoing and the validated circRNAs will be used to optimize the bioinformatics pipeline for circRNA DE analysis.

Conclusions

We identified a subset of circRNAs deregulated in ischemic HF potentially implicated in HF pathogenesis.
P5408Initiating angiotensin receptor blockade and neprilysin inhibitor (ARNI) in acute heart failure with mechanical support
Authors: Hsin H T , Chiu K M
Published: October 2019

Introduction

Heart failure still poses great threat to the afflicted patients and enormous burden to our health-care community. Thanks to the ushering of “Angiotensin Receptor Blockade and Neprilysin Inhibitor (ARNI), Entresto®”, we have made further progress by saving one out of 5 of our patients with chronic heart failure in this decade. Current treatment guidelines have suggested the commencement of ARNI in patients with chronic stable heart failure. There is no mention of starting ARNI in the very beginning of the acute phase of heart failure, especially in the patients needing mechanical support. We try to illustrate the clinical picture and implication of ARNI in acute heart failure.

Method

The study was conducted in a 20-bed based cardiovascular intensive care unit of a tertiary-referring center of Taiwan. We enrolled patients of cardiogenic shock, who were put on left ventricular assist device (LVAD) (CentriMag). Those who were dependent on any vasopressors (eg. nor-adrenaline or vasopressin) were excluded. Concurrent usage of inotropes, such as adrenalin, dopamine or dobutamine, would not preclude our application of ARNI and enrollment. The endpoint of this study were: successful weaning of LVAD, cardiovascular death, and the percentage of achieving guideline-suggested target dose of ARNI.

Results

From Jan. 2017 to Jan. 2019., there were 30 patients put on LVAD with CentriMag. Thirteen patients were excluded as their hemodynamics depended on nor-adrenaline. Seventeen patients of 53.1±9.6-year-old were enrolled and 13 of them were successfully rid of LVAD. Four patients succumbed during the support of LVAD, and 3 of them were due to cardiovascular death. Upon enrollment the LVEF was 18±10.1% and NT pro-BNP was 10327±12629 pg/ml. Fifty-three percent of the enrollee could be prescribed with the target dose of 200mg bid Entresto® within 5.1±3.6 days of initiating ARNI, but only 23.5% could tolerate 200mg bid as maintenance. On initiating ARNI, on-going acute kidney injury were taking place in 76.5% of our enrollee, but only 23.5% suffered persistent renal failure, depending on long-term renal replacement therapy. After 27.8±23.0 days of LVAD, the LVEF improved (43.3±23.0%) sufficing the weaning off.

Conclusion

The very beginning of acute heart failure may have the highest surge of neurohormonal bombardment by renin-agiotensin-aldosterone system. Initiating ARNI in this stage, particularly in patients needing mechanical support, may offer some clinical benefit, regardless of initial renal function.

Acknowledgement/Funding

None
P5419Cardiac reverse remodeling and recovery in dilated cardiomyopathy medication-naive patients requiring durable left ventricular assist device support
Authors: Taleb I , Yin M Y , Koliopoulou A G , Taleb M , Dranow E , Kemeyou L , McKellar S H , Caine W , Wever-Pinzon O , Alharethi R , Kfoury A G , Fang J C , Stehlik J , Selzman C H , Drakos S G
Published: October 2019

Background

Occasionally new onset cardiomyopathy patients (pts) present late and with such advanced disease stage that they cannot tolerate heart failure (HF) drug therapy. We sought to investigate the cardiac recovery (CR) potential following a combination of left ventricular assist device (LVAD) and guideline-directed HF drug therapy in this medication-naive population.

Methods

Chronic advanced HF requiring durable continuous-flow LVAD were prospectively evaluated. Patients with acute HF (myocarditis etc.) or post LVAD follow up <3 months were excluded. The “meds-treated” group (n=203) comprised patients treated adequately with at least one neurohormonal blocking agent during their HF history (b-blocker, ACEI/ARB, Aldosterone antagonist) and “meds-naive” group (n=8) comprised patients who were never before treated adequately with any HF medication. Baseline and follow up clinical, hemodynamic, imaging and laboratory data were analyzed. LVAD patients were phenotyped as CR responders or non responders, based on published predefined criteria.

Results

Univariate analysis showed that “med-naive” patients were younger, more likely to be on intravenous vasoactive agents, temporary mechanical support and with lower INTERMACS profile before LVAD implantation. Interestingly, no differences were seen in HF symptoms duration or other comorbidities. Baseline and follow up hemodynamics were similar in both groups, besides higher right atrial pressure pre-LVAD in the “meds-naive” group (16 vs 11 mmHg; p=0.04). Baseline echocardiographic (including LV dilation) and biochemical parameters revealed no differences between the groups, besides lower LVEF and higher BNP in the “meds-naive” group (14 vs 19%; p=0.03 and 2352 vs 1270; p=0.03, respectively). CR rates were significantly higher on “meds-naive” versus “meds-failed” group (50.0 vs 13.8%; p=0.005). Despite higher cardiac recovery rates in the “meds-naive” group the time course and magnitude of the favorable functional and structural response was similar among the CR responders of each of the 2 groups.

Conclusion

Young patients with new onset dilated cardiomyopathy sometimes present late, with advanced disease stage, unable to tolerate HF medications and requiring durable LVAD support. This patient population appears to have a potential for CR up to 50% and this could be factored in decisions surrounding their long-term therapeutic options.
P5426His-bundle pacing in CHF-patients with narrow QRS and chronic AF using dual-chamber ICD - an upgrade from single-chamber to dual-chamber ICD
Authors: Ciesielski A , Slawuta A , Boczar K , Zabek A , Malecka B , Gajek J
Published: October 2019

A single-chamber ICD is a standard method for primary SCD prophylaxis. In patients with chronic atrial fibrillation it dose not contribute to the regularization of heart rate, which is crucial for proper treatment.

The aim of our study was to assess the efficacy of direct His-bundle pacing in patients with congestive heart failure and chronic atrial fibrillation using upgrade from single chamber to dual-chamber ICD.

Methods

The study population included 21 patients with CHF and chronic AF implanted primarily with single chamber ICD with etablished pharmacotherapy and stable clinical status.

Results

The echocardiography measurements at baseline and during ollow-up were presented in the table:

Table 1 Baseline Follow-up p-value LVEDD (ms) 67.7±10.7 64.5±8.6 <0.05 EF (%) 27.0±4.8 33.2±6.9 <0.05 NYHA class 2.8±0.6 1.9±0,5 <0.05

During short 4-months of follow-up the mean values of EF and LV dimensions significantly improved. This was also accompanied by functional status improvement.

Conclusions

His-bundle-based pacing in CHF-chronic AF patients contributes to significant echocardiographic and clinical improvement. Standard single-chamber ICD implantation in CHF-chronic AF patients yields only SCD prevention without influence on remodeling process.
P5427Mid-term comparison of clinical outcomes between continuous-flow left ventricular assist devices
Authors: Itzhaki Ben Zadok O , Ben-Avraham B , Shaul A , Hammer Y , Rubachevski V , Baruch I , Aravot D , Kornowski R , Ben Gal T
Published: October 2019

Background

Continuous-flow left ventricular assist devices (cf-LVADs) are increasingly applied in patients with advanced heart failure (HF). Comparative data regarding cf-LVADs are lacking. We aim to determine the outcomes of patients supported with HeartMate 2 (HM2), HeartWare (HW) and HeartMate 3 (HM3).

Methods

A retrospective analysis of patients who underwent cf-LVAD implantation at our institution between 2008–2017. Follow-up duration was 18 months post implantation.

Results

Included were 105 cf-LVAD-supported patients of whom 51% (n=54), 24% (25) and 25% (26) underwent implantation of HM2, HW and HM3, respectively. Patients supported with HM3 versus HM2 had lower risk of thrombosis (0% vs. 37%, p=0<0.001), while patients supported with HM3 versus HW had lower risk of non-GI bleeding (15% vs. 46%, HR 0.28, CI 0.095, 0.85, p=0.024) and reduced unplanned hospitalizations (median 1 (interquartile range 0, 3) vs. 3 (interquartile range 2, 11), p=0.001). Patients supported with HM3 had a reduced risk of stroke compared with either HM2 or HW (0% vs. 26%, p=0.033 and 0% vs. 42%, p=0.005, respectively). Importantly, survival free from stroke or device exchange was higher in patients with HM3 compared to patients supported with either HM2 or HW (100% vs. 72%, p=0.029 and 100% vs. 56%, p=0.003, respectively) (Figure).

Mid-term event-free survival by VAD type

Conclusions

HM3 device presents the best currently available prognostic and adverse events profile when compared to HM2 and HW. We believe that HM3 should be offered as the device of choice for mechanically-supported advanced HF patients
P5438Cardiac abnormalities after induction of endoplasmic reticulum stress are associated with mitochondrial dysfunction and connexin43 expression
Authors: Liu T , He J , Gong M , Luo C , Zhao Y , Li G , Tse G
Published: October 2019

Background

The endoplasmic reticulum (ER) is responsible for protein synthesis and calcium storage. ER stress, reflected by protein unfolding and calcium handling abnormalities, has been studied as a pathogenetic factor in cardiovascular diseases.

Purpose

The aim of this study is to examine the effects of ER stress on mechanical and electrophysiological functions in the heart and explore the underlying molecular mechanisms.

Methods

A total of 30 rats were randomly divided into control, ER stress induction (tunicamycin) and ER stress inhibition (4-phenylbutyric acid, 4-PBA) groups.

Results

ER stress induction led to significantly systolic and diastolic dysfunction as reflected by maximal increasing/decreasing rate of left intraventricular pressure (±dp/dt), LV peak systolic pressure, LV development pressure and LV end-diastolic pressure. Epicardial electrical mapping performed in vivo revealed reduced conduction velocity, increased conduction heterogeneity and spontaneous ventricular tachycardia. Masson's trichrome staining revealed marked fibrosis in the myocardial interstitium and sub-pericardium and thickened epicardium. Western blot analysis revealed increased pro-fibrotic factor TGF-β1, decreased mitochondrial biogenesis protein PGC-1a, decreased mitochondrial fusion protein MFN2. These changes were associated with decreased mitochondrial membrane potential (MMP) and connexin 43 translocation to mitochondria. These abnormalities can be partially prevented by the ER stress inhibitor 4-PBA.

Conclusions

Our study shows that ER stress induction can produce cardiac electrical and mechanism dysfunction as well as structural remodeling. Mitochondrial function alterations are contributed by CX43 transposition to mitochondria. These abnormalities can be partially prevented by the ER stress inhibitor 4-PBA.

Acknowledgement/Funding

National Natural Science Foundation of China (No. 81570298 to T.L.)
P5439Protective effect of angiotensin-neprilysin inhibition compared to angiotensin inhibition on ventricular arrhythmias in spontaneous hypertensive rats
Authors: Lin T T L , Sung Y L S , Syu J Y S , Hsu H J H , Lin K Y L , Lin S F L
Published: October 2019

Background

Angiotensin-neprilysin inhibition compared to angiotensin inhibition decreased sudden cardiac death in patients with reduced ejection fraction heart failure. The protective effect from ventricular arrhythmia in diastolic heart failure (DHF) remains unknown.

Methods

The spontaneous hypertensive rat (SHR) has been well established as a suitable model for studies of DHF. A total of 18 10-week-old male SHR were divided into three groups: sacubitril/valsartan, valsartan and saline (0.9%) (n=6 in each group). Eighteen 10-week-old male Wistar-Kyoto rats (WKY) were served as the control group. After two weeks feeding with sacubitril/valsartan, valsartan and saline in SHR and WKY. Optical mapping was performed to measure the electrical dynamic of cardiac ventricle and the maximal slope of action potential duration restitution was calculated. An S1–S2 pacing protocol was applied at the right ventricle to determine inducibility of ventricular tachycardia and fibrillation (VT/VF).

Results

SHR revealed increased LV mass than those treated with sacubitril/valsartan, and valsartan. Compared with WKY, SHR had significantly higher max slope (1.32±0.12 vs. 0.28±0.08, p<0.001). SHR was less prone to arrhythmogenicity after treated with valsartan than saline (0.29±0.04 vs. 1.32±0.12, p<0.001). Furthermore, the max slope was even lower in SHR treated with sacubitril/valsartan than those with valsartan (0.10±0.03 vs. 0.29±0.04, p=0.005). The incidence of induced sustained VT/VF (duration >2 second) was significant higher in SHR compared with WKY (18±11.1% vs. 0%, p<0.001) and also higher in SHR treated with valsartan compared with those with sacubitril/valsartan (7±6.5% vs. 5±2.9%, p=0.036).

Conclusions

Angiotensin-neprilysin inhibition could provide better protection from ventricular arrhythmia than valsartan in SHR, warranting the further investigation of angiotensin-neprilysin inhibition in DHF patients.
P5440Systolic/diastolic effects of chronic treatment with omecamtiv mecarbil in minipigs with post-myocardial infarction Heart Failure with reduced Ejection Fraction (HFrEF)
Authors: Caillaud D , Baudot X , Gouraud L , Lucats L , Pruniaux M P , Janiak P
Published: October 2019

Background

Omecamtiv mecarbil (OM), a novel myosin ATPase activator, is currently developed for the treatment of Heart Failure with reduced Ejection Fraction (HFrEF). Phase I in healthy volunteers and patients showed that the positive inotropic effect of OM was associated with an impairment of diastolic function as assessed by change in E peak, e' wave and E/e' ratio.

Purpose

The diastolic impact of chronic treatment with OM has not been described yet. This study investigates the balance between positive inotropic effect and the diastolic impairment after chronic treatment with OM in a post-myocardial infarction (Post-MI) swine model of HFrEF.

Methods

HFrEF was induced in minipigs after myocardial infarction caused by a 150-min left anterior descending (LAD) artery occlusion performed under angiography. HFrEF minipigs were treated with OM at 3 mg/kg PO BID for 15 days (n=4), a dose known to increase systolic ejection time (SET) by ∼50 ms as achieved in healthy volunteers and patients at plasma levels between 200–300 ng/ml. Echocardiogram was performed before and after 15 days of treatment with OM. An additional echocardiogram was conducted 7 days after the last administration.

Results

One year after MI, minipigs displayed increased left ventricular end-diastolic volume index (LVEDVi 151±3.7ml/m2 vs 100±8.9ml/m2 before infarction) and decreased LVEF (42±2.5% vs 68±4.4% before infarction) associated with a pseudo-normal mitral pattern. A two-week treatment with OM increased SET by 64ms (p<0.0001 vs before treatment) and EF to 49±3.8% (p=0.07 vs before treatment) as well as it improved SVi by 13%. This inotropic effect was associated with a decrease of mitral E peak (p=0.01 vs before treatment) and e' waves, and with the prolongation of deceleration time (p<0.05 vs before treatment). OM treatment was associated with marked reduction of LVEDVi to 117±13.2ml/m2 (p<0.05 vs before treatment) concomitant with a ∼20% increase in diastolic septum and posterior wall thicknesses. None of these systolic or diastolic effects remained 7 days post OM treatment completion.

Conclusion

Similarly to clinical description, OM treatment increased LVEF and SVi principally through extension of SET. It provides positive inotropic effects associated with diastolic impairment resulting in impaired ventricular filling as assessed by LVEDVi decrease and the thickening of ventricular wall in diastole. Whether this profile will allow a beneficial reverse remodeling, needs to be investigated in a longer chronic study.

Acknowledgement/Funding

Sanofi sponsored study
P5441Ventricular dysfunction and fibrosis precedes atrial conduction defects in JDP2 overexpression mice
Authors: Parahuleva M , Bornbaum J , Heger J , Kockskaemper J , Schieffer B , Schulz R , Euler G
Published: October 2019

Introduction

JDP2 (Jun Dimerization Protein 2) was recently characterized as potential prognostic marker for progression of heart failure after myocardial infarction. Furthermore, persistent cardiac-specific JDP2 overexpression provokes ventricular dysfunction, atrial dilatation and atrial fibrillation.

Purpose

In this study we investigated, if ventricular dysfunction is predisposed to atrial fibrillation. Therefore, we analyzed ventricular function in mice with 1 and 5 weeks of JDP2 overexpression and compared gene expression in ventricular and atrial tissues at these time points.

Methods

JDP2 expression was under control of a Tet-off system. Therefore, JDP2 overexpression was started by withdrawal of doxycycline diet in 4-week-old mice. After 1 or 5 weeks, cardiac function was determined by echocardiography and ECG. mRNA expression was analyzed by real-time RT-PCR and protein expression in western blots.

Results

After 1 or 5 weeks, JDP2 mRNA levels were increased in ventricular and atrial tissues of JDP2 mice. Already after 1 week ventricular dysfunction emerged in JDP2 mice: Ejection fraction decreased from 64.6±10.4% in WT to 58.8±9.3% in JDP2 mice, fractional shortening from 38.3±7.9% in WT to 27.4±4.8% in JDP -mice, and cardiac output from 23.0±4.7 ml/min in WT to 19.4±3.3 ml/min in JDP2 mice (n=11–16, p<0.05). In ventricular tissues, elastin mRNA expression increased, and the calcium handling protein SERCA decreased within one week of JDP2 overexpression (n=6, p<0.05 vs. WT). After 5 weeks of JDP2 overexpression ventricular dysfunction became even stronger with a cardiac output of 13.6±2.5 ml/min (n=11, p<0.05 vs. WT). Still reduction in SERCA protein was observed, and increased mRNA levels of fibrotic marker genes were detected, as well as contractile function of isolated cardiomyocytes of JDP2 mice continued to decline. In atrial tissue, besides the 3.6 times increase of JDP2 mRNA, no changes could be detected within one week. In addition, ECG recordings over 30 minutes on awake mice did not show any abnormalities after one week of JDP2-overexpression. Atrial dilatation became evident only after 5 weeks of JDP2 overexpression. ECG-recordings revealed prolonged PR-intervals (34.6±3.9 ms in JDP2-mice vs. 30.2±7.0 ms in WT) and broadened QRS-complexes (15.8±2.8 ms in JDP2 mice vs. 13.9±1.7 ms in WT, n=10–12, p<0.05). At the same time point, mRNA of the calcium-handling proteins PLB, NCX and SERCA, and of the fibrotic marker genes collagen I, fibronectin and elastin were dramatically reduced in atrial tissue of JDP2 compared to WT mice (n=6, p<0.05), and may be functionally involved in atrial conduction defects.

Conclusion

Enhanced expression of JDP2 provokes ventricular dysfunction and fibrosis within one week, whereas changes in the atrial tissue and conduction defects occur later and seem to be a secondary effect that is provoked by the pre-existing ventricular dysfunction.
P5453Cardiorenal biomarker N-acteyl-beta-D-glucosaminidase (NAG) potentially predicts mortality in chronic heart failure - A 10 year follow up
Authors: Schober A D , Strack C , Bauer S , Hubauer U , Schober A L , Uecer E , Maier L S , Luchner A , Jungbauer C G
Published: October 2019

Background

The strong relation between chronic heart failure (CHF) and chronic kidney disease (CKD) is well known as cardiorenal syndrome (CRS). The current study focused on the impact of novel markers of kidney injury next to the established cardiac marker NT-proBNP as predictors for mortality in patients with CHF in a long term follow up.

Methods

We conducted a prospective longitudinal study. The novel renal biomarkers kidney injury molecule-1 (KIM-1), N-acteyl-β-D-glucosaminidase (NAG) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) were assessed from urine samples. Additionally, blood levels of NT-proBNP were determined. The primary endpoint all-cause mortality was evaluated after a median follow-up of 104 months (interquartile range 42–117 months).

Results

149 adolescents (mean age 62±12 years) with CHF (mean ejection fraction 32±9%) were enrolled. 79 (53%) patients died. The secondary endpoint was reached by 104 patients (70%).

The renal marker NAG (HR 1.02, p=0.002) was a significant and independent predictor for all-cause mortality next to the established cardiac biomarker NTproBNP (HR 1.0, p<0,001) using Cox regression analysis, opposite to KIM-1 as well as NGAL (each p=n.s.). Similar results were obtained for the combined endpoint of all-cause mortality and hospitalization for heart failure.

In a multivariate analysis model with biomarkers and clinical parameters NAG (HR 1.02, p=0.036) remained a significant predictor for all-cause mortality next to NT-proBNP (HR 1.0, p=0.027, older age (HR 1.04, p=0.004), the lack of diabetes mellitus (HR 0.39, p<0.001), reduced EF (HR 0.97, p=0.034) and creatinine (HR 1.45, p=0.026). Again similar results were obtained for the secondary endpoint.

Patients were stratified into groups with markers above and below Youden Index to calculate Kaplan-Meier analysis. A combined analysis of NT-proBNP (< and ≥1906 pg/mL) and NAG (< and ≥10 U/gUCr) revealed an increase of the predictive value of each marker: patients with all three markers above Youden index had the highest mortality rate (79%) compared to patients with one (43%) or none (26%) marker above Youden Index.

All-cause Mortality

Conclusion

The current 10-years long-term follow-up suggests that the tubular biomarker NAG as cardiorenal biomarker in combination with NT-proBNP may allow to discriminate a high-risk collective of chronic heart failure patients. These findings emphasize the close relationship of kidney injury and renal function in patients with CHF.
P5460Prevalence of left atrial enlargement in patients undergoing an echocardiogram for cardiovascular risk stratification at an esh excellence centre in italy
Authors: Muiesan M L , Salvetti M , Paini A , Aggiusti C , Bertacchini F , Stassaldi D , Capellini S , Casella E , Arnoldi C , Agabiti Rosei E
Published: October 2019

Background

Left atrial (LA) enlargement (LAE) is associated to an increased risk of cardiovascular complications, and in particular of atrial fibrillation. The 2018 ESH/ESC Hypertension guidelines suggested the use of LA volume instead of linear dimensions, and for the first time proposed the indexation to height2 (h2)

The aim of our study was to assess the prevalence of left atrial dilatation in a large sample of patients undergoing an echocardiogram for cardiovascular risk stratification at an ESH excellence centre in Italy.

Design and methods 3872 subjects undergoing a diagnostic work-up for arterial hypertension (known or suspect) were analysed. The mean age was 56±15 years, BMI 26±5 kg/m, 44% normal weight, 39% overweight, 17% obese, 53% males. Left atrial volume was measured by the area-length method using the apical 4-chamber and 2-chamber views.

Results

The prevalence of left ventricular hypertrophy (LVH) was 11% when indexing for BSA and 12% when indexing for height2.7. LAE was observed in 30% of subjects when indexing for h2 and in 9% when indexing for BSA. In obese or overweight subjects the prevalence of LAE was 38% of subjects when indexing for h2 and in 11% when indexing for BSA. The different prevalence of LAE was particularly evident in extremely obese patients.

LAE was very common in patients with LVH: 62% and 26% when indexing for h2 and for BSA, respectively. Interestingly, it was frequent also in patients without LVH, in particular when the indexation for h2 was used (25% as compared to 7% when indexing for BSA).

Conclusions

In a large sample of subjects undergoing a diagnostic work-up for arterial hypertension LAE was frequently observed, particularly when the new indexation proposed by the 2018 ESH/ESC hypertension guidelines was used. Even in the absence of clear-cut LVH, LAE was observed in one quarter of subjects. The indexation to BSA leads to an under-recognition of LAE, in particular in patients with overweight and/or obesity
P5466Exaggerated exercise blood pressure response is accompanied by increased sympathetic activity and arterial stiffness in subjects with high normal blood pressure
Authors: Kalos T , Tsioufis C , Dimitriadis K , Vogiatzakis N , Kasiakogias A , Iliakis P , Konstantinidis D , Xanthopoulou M , Kakouri N , Laina A , Andrikou E , Tousoulis D
Published: October 2019

Background/Introduction

The clinical importance of a hypertensive response to exercise (HRE) in subjects with high normal blood pressure (BP) is not fully elucidated, while sympathetic overactivity and arterial stiffening are linked with adverse cardiovascular prognosis.

Purpose

The aim of this study was to assess the relation of HRE with sympathetic drive as assessed by muscle sympathetic nerve activity (MSNA) and arterial stiffness in subjects with high normal BP.

Methods

42 subjects with high normal office BP [defined as office systolic BP=130–139 mmHg and office diastolic BP=85–89 mmHg (age: 53±9 years, 29 males, office BP: 134/84 mmHg, 24-hour BP: 114/72 mmHg)] with a negative treadmill exercise test (Bruce protocol) were divided into those with HRE (n=12) (peak exercise systolic BP ≥210mmHg in men and ≥190 mmHg in women) and those without HRE (n=30). Arterial stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV) values. In all participants sympathetic drive was assessed by MSNA estimations based on established methodology (microneurography).

Results

Subjects with a HRE compared to those without exhibited higher waist circumference (108.2±5.3 vs 94.7±9.2 cm, p=0.001) and were characterized by greater levels of carotid to femoral PWV (8.5±0.8 vs 7.0±0.9 m/sec, p<0.001) and sympathetic nerve traffic as reflected by MSNA levels (41.1±1.5 vs 32.1±1.9 bursts per 100 heart beats, p<0.001), while did not differ regarding metabolic profile and left ventricular mass index (p=NS). In the total population, peak exercise systolic BP was related to 24-h systolic BP (r=0.229, p<0.05), PWV (r=0.218, p=0.002), and MSNA (r=0.214, p<0.05). Moreover, MSNA was related to waist circumference (r=0.33, p=0.004) and office systolic BP levels (r=0.31, p<0.05) but there was no association with PWV values (p=NS).

Conclusion

In subjects with high normal BP, a HRE identifies a state of arterial stiffening and sympathetic overdrive, as reflected by increased PWV and MSNA levels respectively. These finding suggest that exercise testing provides additional clinical information regarding the vascular status and modulation of sympathetic tone in this setting.
P5468Systolic versus diastolic blood pressure as predictors of cardiovascular events among treated hypertensive patients: a 6-year prospective study
Authors: Kasiakogias A , Tsioufis C , Konstantinidis D , Iliakis P , Leontsinis I , Konstantinou K , Koumelli A , Kakouri N , Dimitriadis K , Tousoulis D
Published: October 2019

Background/Introduction

There has been a long debate regarding the association of systolic versus diastolic blood pressure with cardiovascular outcome and data regarding hypertensive patients under treatment have been conflicting.

Purpose

To investigate the association of different patterns of uncontrolled blood pressure (BP) among treated hypertensive patients.

Methods

We prospectively studied 1507 treated hypertensive patients (age 59±11 years) that are followed in the setting of a single-center, clinic-based registry. During follow-up, patients underwent regular visits for hypertension and risk factor management. Based on the cut-off limits for uncontrolled hypertension of office systolic BP≥140mmHg and diastolic BP≥90mmHg, study participants were divided into four groups: those with controlled hypertension (796 patients, 53% of the population), uncontrolled systolic BP (257 patients, 17%), uncontrolled diastolic BP (135 patients, 9%) and uncontrolled systolic and diastolic BP (319 patients, 21%). The outcome studied was the composite of cardiovascular morbidity set as coronary artery disease and stroke, and the controlled hypertension group served as reference.

Results

The median follow-up period was 6.4±3.0 years and the composite endpoint (13 strokes and 41 cases of coronary artery disease) occurred in 54 patients (3.6%). Unadjusted Cox regression analysis showed that, compared to the reference group of controlled hypertensives, the risk for cardiovascular morbidity was similar in patients with uncontrolled diastolic BP (HR: 0.88, 95% CI: 0.26–2.97) but significantly higher in patients with uncontrolled systolic BP (HR: 2.17, 95% CI: 1.08–4.36), while patients with both uncontrolled systolic and diastolic BP showed the worse prognosis (HR: 2.35, 95% CI: 1.24–4.43). This pattern of risk was overall sustained after adjusting for different sets of confounders.

Conclusions

Among treated hypertensive patients, uncontrolled systolic BP is associated with a greater risk for cardiovascular events compared to uncontrolled diastolic BP while uncontrolled systolodiastolic hypertension presents with the worse prognosis.
P5469Isolated systolic hypertension and combined systolic-diastolic hypertension for prediction of new-onset diabetes mellitus: Data from a 8-year-follow-up study
Authors: Liatakis I , Tsioufis C , Dimitriadis K , Konstantinidis D , Koutra E , Leontsinis I , Kouremeti M , Iliakis P , Vogiatzakis N , Karaminas N , Thomopoulos K , Tousoulis D
Published: October 2019

Background/Introduction

Isolated systolic hypertension (ISH) and combined systolic-diastolic hypertension (CH) are related with increased cardiovascular risk, while new-onset diabetes mellitus (NOD) is linked with atherosclerosis progression.

Purpose

The aim of the present study was to compare the predictive role of ISH and CH for the incidence of NOD in a cohort of essential hypertensive patients.

Methods

We followed up 1435 non-diabetic essential hypertensives with office systolic blood pressure (BP)≥140 mmHg [mean age 57 years, 730 males, office BP=153/92 mmHg] for a mean period of 8 years. All subjects had at least one annual visit and at baseline underwent echocardiographic study and blood sampling for estimation of metabolic profile. Patients with baseline ISH exhibited office systolic BP ≥140 mmHg and office diastolic BP <90 mmHg, while those with CH had office systolic BP ≥140 mmHg and office diastolic BP ≥90 mmHg. Moreover, NOD was defined if at one or more of the follow-up visits a previously non-diabetic patient reported being on insulin or an oral hypoglycemic drug or if casual plasma glucose concentration ≥200 mg/dl or fasting glucose concentration ≥126 mg/dl or 2-h post load glucose ≥200 mg/dl during an oral glucose tolerance test.

Results

The incidence of NOD over the follow-up period was 4.2% (n=60). Patients with ISH (n=460) compared to those with CH (n=975) were older (65±11 vs 54±10 years, p<0.0001), had at baseline lower waist circumference (94.5±11 vs 99±13 cm, p<0.0001), office systolic BP (149±12 vs 155±13 mmHg, p<0.0001), office diastolic BP (80±8 vs 98±6 mmHg, p<0.0001), while did not differ regarding left ventricular mass index, glucose and lipid levels (p=NS for all). Univariate Cox regression analysis revealed that baseline ISH (hazard ratio=2.143, p=0.016) and CH (hazard ratio=1.272, p=0.029) predicted NOD. However, in multivariate Cox regression model, age (hazard ratio=1.039, p<0.001), baseline glucose levels (hazard ratio 1.011, p=0.016), waist circumference (hazard ratio=1.067, p<0.001) and ISH (hazard ratio=1.651, p=0.029) but not CH turned out to be independent predictors of NOD.

Conclusions

In essential hypertensive patients, ISH but not CH exhibits independent prognostic value for NOD. These findings support that ISH constitutes a hypertensive phenotype of increased metabolic risk needing careful evaluation and treatment.