bluuebunny/crossref_metadata_2025 huggingface dataset:
P974Efficacy of plaque debulking for bifurcated or ostial lesion by directional coronary atherectomy before 2nd generation drug eluting stent (PERFECT2)
Authors: Habara M , Tsuchikane E , Nasu K , Kinoshita Y , Terashima M , Matsubara T , Murata A , Suzuki Y , Kawase Y , Okubo M , Matsuo H , Suzuki T
Published: October 2019

Objectives

We sought to evaluate the efficacy of plaque debulking by directional coronary atherectomy (DCA) before 2nd generation drug-eluting stent (DES) implantation for bifurcated coronary lesions.

Background

Percutaneous coronary intervention (PCI) for bifurcated lesions still remains complex and challenging in terms of restenosis or stent thrombosis regardless of whether simple or complex stenting used.

Methods

Patients with bifurcated lesions were enrolled in this prospective multicenter registry. Pre-2nd generation DES plaque debulking with a novel DCA was conducted. All patients were scheduled to perform a follow up (9–12 months) angiography (coronary angiography or coronary computed tomography). The primary end point was the target vessel failure (TVF) at follow-up. Secondary end points were procedure-related events and major adverse cardiac events at 1 year.

Results

A total of 77 patients with bifurcated lesions were enrolled. PCI with DCA was performed successfully in all without any major procedure-related event and only 1 case needed complex stenting. TVF rate at 9–12 months follow up was 3.9% (3 of 77) and those were all associated with revascularization of the target vessel. Restenosis was only observed at ostial of main-branch in 3cases. No death, no coronary artery bypass grafting, and no myocardial infarction were reported in the patients within the first year.

Figure1

Conclusion

DCA before 2nd generation DES implantation can possibly avoid complex stenting and provide a good mid-term outcome in patients with bifurcated lesions.

Acknowledgement/Funding

None
P975Safety and clinical outcomes of rotational atherectomy: an eleven-year centre experience
Authors: Pereira A R , Cale R , Santos P , Almeida A R , Marques A , Alegria S , Briosa A , Sebaiti D , Vitorino S , Pereira E , Martins C , Pereira H
Published: October 2019

Introduction

Rotational atherectomy (RA) is an adjunctive tool for the management of heavily calcified coronary lesions during percutaneous coronary intervention (PCI), but the clinical outcomes remain unclear. Access site choice is also poorly defined and there is growing evidence that transradial approach (TRA) is associated with lower complications and lower mortality.

Objectives

To assess the safety and long-term outcomes of RA for calcified coronary lesions and to investigate the influence of vascular access site in the efficacy and safety of the procedure.

Methods

Retrospective single-centre study that included consecutive PCI with RA performed from January 2006 to December 2017. Endpoint was a composite of major adverse cardiac events (MACE), defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and target vessel revascularization, at 1- and 5-year.

Results

246 procedures were included in a total of 236 patients (pts): mean age 70.1±9.7 years, 73.6% male; 36.2% had previous PCI, 12.2% vascular peripheral disease (VPD), 24% reduced left ventricle ejection fraction (LVEF) and 6.9% were under hemodialysis. PCI with RA was mostly performed due to stable angina (48.9%) and via TRA (55.3%), with a total of 371 treated segments and a median number of 1 vessel treated per intervention. The left anterior descending artery was the most frequently treated artery (67.5%). Single burr was used in 76% of cases (mean number of burrs 1.23; mean burr size 1.5 mm). Procedural success rate was 94.7%. Complications were recorded in 9.3%, with no procedure related death. Clinical follow-up was complete in 98.8% of pts at 1-year and 81.3% at 5-year (mean time 62.3±41.8 months). Survival free of MACE at 1- and 5-year were 83.7% and 73.2%, respectively. Multivariate Cox regression identified 6 independent predictors (only 1 protector) for 1-year MACE (Fig. A) and 6 independent predictors (all of increased risk) for 5-year MACE (Fig. B). TRA was protector of 1-year MACE and Kaplan-Meier curves showed benefit for both 1- and 5-year MACE occurrence (Fig. C and D), without significant difference in procedural success (p=0.92) and complications (p=0.45) rate comparing to transfemoral approach.

Conclusions

RA followed by stenting was a safe procedure with a high immediate success rate but an increased number of long-term cardiovascular events. Some clinical conditions, such as previous PCI, VPD and reduced LVEF, seems to adversely influence the long-term outcome while TRA appears to be protective.
P1004Diagnosis and management of fetal cardiac arrhythmias: about 100 cases
Authors: Messaoudi Y , Msaad H , Hakim K , Ouarda F
Published: October 2019

Background

Fetal cardiac arrhythmia complicates 1–2% of pregnancies and presents a major risk of morbidity and mortality in 10% of the cases. Different questions raised by this pathology must be asked: Is it necessary to treat the rhythm disorder? What are the risks of an anti-arrhythmic treatment for the fetus and its mother? In case of failure, should the fetus be extracted at the cost of prematurity, or must the therapeutic escalation be attempted?

Purpose

To emphasize the primordial role of fetal echocardiography in the diagnosis and management of fetal cardiac arrhythmias through our own experience and a review of the literature.

Methods

We present a series of 100 cases of fetal rhythm disorders diagnosed and treated in our department of pediatric cardiology during the last 12 years.

Results

The diagnosis was made at an average gestational age of 30 weeks of amenorrhoea. Extra-systoles were by far the most frequent (50 cases), followed by hetero-topic tachycardia (28 cases) and complete atrio-ventricular blocks (22 cases). We have excluded bradycardia and sinus tachycardia from our study. Our attitude regarding extra-systoles was mostly a simple surveillance and the total post natal disappearance was the rule. The tachycardias were distributed as follows: 9 flutters, 16 junctional tachycardias and 3 chaotic atrial tachycardias. 10 patients were in feto-placental anasarca. The medical treatment resulted in a reduction of the in utero tachycardia in 14 cases, 9 were only post natally reduced and 6 died. Mono-therapy was the rule and dual therapy was indicated in case of resistance to medical treatment or in front of a table of foeto-placental anasarch. With a mean follow-up of 2 years, there was no recurrence. A complete atrio-ventricular block was diagnosed in 22 fetuses at an average gestational age of 26 amenorrhea weeks. 4 patients had associated heart disease. The ventricular rate varied from 35 to 70 beats per minute. 7 fetuses were in heart failure. An immunoassay was positive in 10 mothers. At birth, the presence of antibodies against SSA and/or SSB was detected in 8 newborns.15 patients were stimulated epicardially, including the neonatal period. Six patients died.

Conclusion

We conclude that if the prognosis of fetal tachycardia is generally satisfactory, the atrio-ventricular blocks are more reserved because the conduction disorder is irreversible, and even in the absence of associated congenital cardiopathy, complications related to Stimulation in the newborn doesn't remain risk-free.
P1008Increased incidence of supraventricular tachycardia during high influenza activity
Authors: Safavi Naeini P , Rasekh A , Razavi M , Madjid M
Published: October 2019

Background/Introduction

Influenza remains a major risk to human health, estimated to result in 290,000 to 650,000 annual deaths worldwide. The association of influenza with coronary events is well established but influenza's impact on cardiac arrhythmias has received less attention.

Purpose

We investigated the effect of influenza on triggering supraventricular tachycardia (SVT).

Methods

This retrospective observational study included de-identified data from patients who had a Zio patch continuous cardiac monitoring from October 2012 to September 2017. The “influenza activity” was defined as the percentage of positive respiratory specimens that tested for influenza virus during each influenza season per reports from the Centers for Disease Control and Prevention. We included all SVT events from the weeks with the highest and lowest influenza activity up to two consecutive weeks after them. A paired t-test was used to compare the incidence of SVT episodes in weeks with the highest and lowest influenza activity.

Results

We reviewed records of 825869 patients (mean age, 61.06±15.31 years; 48.75% male); of these patients, 49984 had Zio patch during highest and lowest influenza activity time frame. The overall average episodes of SVT per person was 25% higher in the highest influenzas activity period comparing to the lowest activity (59.05 vs 47.26) and the higher incidence of SVT episodes in the highest influenza activity was significant (P value <0.01). A similar significant trend was observed during each individual influenza season.

Figure 1. average number of SVT episodes

Conclusion

High seasonal influenza activity is associated with increased odds of supraventricular tachycardia. Prospective studies are needed to determine the clinical implications of this finding.
P1013Biannular atrial flutter: clinical and electrophysiological characterization by activation and entrainment
Authors: Martinez Cossiani M , Castrejon S , Escobar C , Ortega M , Batlle M , Gonzalez Davia R , Gutierrez Larraya F , Lopez-Sendon J L , Merino J L
Published: October 2019

Introduction

re-entry mechanisms around mitral and tricuspid annuli are frequent causes of left and right atrial flutter (AFt) respectively in patients with ipsilateral atrial pathology. However, clinical and electrophysiological characteristics of other types of atrial re-entries that could involve both AV annuli are less known.

Purpose

characterize biannular atrial flutters.

Methods

4 patients with AFt were submitted for ablation (aged 30, 31, 58 and 61 yo; 2 females). All had a cardiac congenital disease with a prior surgical procedure: 3 atrial septal defects (ASD) with surgical repair and 1 with transposition of the great arteries (TGA) with Senning repair. The AFt had a cycle length (CL) of 290, 315, 330 y 340 ms respectively and 1:1 AV conduction in 3 of them. For the electrophysiological study, a multipolar catheter (20 or 24 poles) was placed in the right atrium (RA) in every patient, showing counterclockwise and clockwise activation in 1 and 3 patients, respectively. Coronary sinus (CS) activation was proximal to distal in one patient and distal to proximal in the other 2. No CS activation could be obtained in the patient with Senning repair.

Results

each AFt was mapped by entrainment from different sites of the RA, showing post-pacing intervals (PPI) similar to the CL of the AFt around the tricuspid annulus in all of them and also from proximal and distal CS in the 3 patients with ASD. Access to the native left atrium (LA) was achieved in the patient with Senning repair, showing PPIs around the mitral annulus that were similar to the LC of the tachycardia. In 2 patients the attempt to get to the LA through the interatrial septum (IAS) could not be achieved and was unattempted in the other one. Recordings and PPIs of the LA roof were obtained from the right branch of the pulmonary artery in 2 patients. Counterclockwise AFt and clockwise AFt by single biannular perimitrotricuspid rotation in 1 and 3 patients respectively. The AFt was ended and no reinduction was possible after radiofrequency application that achieved cavotricuspid isthmus block in all of the patients.

Conclusions

reentry around both AV annuli is possible as a single loop, counterclockwise or clockwise, of simultaneous rotation as a clinical mechanism of Aft. This type of AFt seems to be associated to absence or severe damage in the IAS.
P1016Novel surgical ablation technique using ultrasonic scalpel for atrial fibrillation in mitral valve surgery
Authors: Tsukui H , Fujita K , Iwasa S , Yamazaki K
Published: October 2019

Objective

Radiofrequency, cryoablation and cut-and-sew technique have been used for surgical ablation to treat atrial fibrillation. Ultrasonicscalpel is a surgical instrument used to simultaneously cut and cauterize tissue by ultrasound vibration. This device causes minimal lateral thermal tissue damage and increases the tissue penetration depth linearly with time. These features are suitable for surgical ablation for atrial fibrillation. This study evaluated surgical ablation with ultrasonic scalpel for atrial fibrillation.

Methods

From October 2017 to February 2019, 46 patients (mean age: 71.8 years [46–86], 28 male) with mitral valve procedure underwent surgical ablation using ultrasonic scalpel for atrial fibrillation. The ablation lines were carried out with Cox maze procedure or pulmonary vein isolation (PVI) on cardiopulmonary bypass. Endocardial atrial wall was ablated by direct touch with blade in a few seconds at energy level 5. Pathological study of left atrial wall received ablation with ultrasonic scalpel was carried out.

Results

Type of preoperative atrial fibrillation was persistent in 33 and paroxysmal in 13 patients. Mean left atrial diameter was 49.0 mm (35–81). Surgical ablation using ultrasonic scalpel was carried out to left atrium only or PVI in 33 patients and both atria in 13 patients. Mean surgical ablation time was 4 minutes and 21 seconds. Mitral valve repair and replacement were performed in 33 and replacement in 13 patients, respectively. Simultaneous surgery included 43 tricuspid valve repairs, 11 aortic valve replacements, and 7 coronary artery bypass grafting. Cardiopulmonary bypass and aortic cross-clamp times were 142.6 (70–261) and 98.6 (47–202) minutes, respectively. No operative death or perioperative stroke were observed. Thirty-eight patients (82.6%) returned to sinus rhythm immediately after surgery. Sinus rhythm was maintained in 30 patients (65.2%) in the mid-term period with average 142.2 days after surgery (7–426 days). Pathological study showed the atrial walls were not ablated transmurally. No complications including bleeding and tissue injury were observed.

Conclusion

Surgical ablation with ultrasonic scalpel for atrial fibrillation was feasible and provided satisfactory outcomes immediately after surgery and at mid-term. This technique can be performed in a short time without complications. Interestingly, pathological study showed no transmural tissue ablation despite of successful outcomes. This may imply transmural ablation is not necessarily mandatory for surgical ablation. Long-term follow-up are required to evaluate this technique.
P1021Comparative efficacy of microfidelity technology vs standard ablation for atrioventricular nodal ablation
Authors: Levine J L , Xiang K , Su J , Hsu S , Kim R J , Elayi S , Catanzaro J N
Published: October 2019

Background

Microfidelity Cateter Technology has proven efficacy in ablating atrial arrhythmias in multiple pilot studies. Closely spaced radial microelectrodes render a focused near-field electrogram. Case series suggest that this catheter design facilitates accurate ablations with fewer radiofrequency (RF) lesions. Atrioventricular junction (AVJ) ablation is regarded as a straightforward procedure, but case records show wide variance in procedure times and number of RF lesions required.

Methods

Twenty-four patients scheduled for AVJ ablation were randomized to treatment with either the Microfidelity technology or standard 8mm/8 French ablation catheter. Both groups located the AVJ by fluoroscopic landmarks and His electrograms, and the MiFi group used electroanatomical mapping to create the location of his electrograms. The primary endpoints were development of Junctional Rhythm (JR) or Complete Heart Block (CHB), and time from first RF lesion until rhythm change. Secondary endpoints included number of RF applications.

Results

Patients were randomized one-to-one to the MiFi arm or standard ablation arm. JR or CHB was achieved in all patients. Time from first RF lesion until JR/CHB was: (Median/IQR) 325 sec/250–1270 sec. vs 287 sec/101–406 sec. Number of RF applications was 5/3–15 applications vs 4.5/1–5 applications. Total procedure time in the lab was 134 min/73.5–172.5 min vs 58 min/52–146 min.

Microfidelity Technology vs Standard

Conclusion

Analysis suggests that the MiFi catheter is efficacious in ablating the AVJ, but requires greater RF duration and number of lesions, with wider case-by-case variability to achieve JR or CHB. Microfidelity technology and electroanatomical mapping did not result in faster time to completion than using fluoroscopic landmarks and His electrograms alone. Preoperative choice of sheath for catheter stability and contact may also play a role in a more efficient timely successful ablation of the AV node.

Acknowledgement/Funding

Boston Scientific
P1025Clinical predictors for the improvement of left ventricular ejection fraction and prognosis after catheter ablation of atrial fibrillation in patients with systolic dysfunction
Authors: Nagaoka K , Mukai Y , Kawai S , Takase S , Sakamoto K , Inoue S , Ikeda S , Chishaki A , Tsutsui H
Published: October 2019

Background

Catheter ablation (CA) of atrial fibrillation (AF) improves left ventricular ejection fraction (LVEF) and clinical outcomes in patients with left ventricular systolic dysfunction (LVSD). However, predictors of the improvement of LV function and clinical outcomes by CA were poorly understood.

Purpose

We examined the efficacy of CA in AF patients with LVSD and predictive factors associated with clinical outcomes.

Method

Among consecutive 795 patients undergone initial RFCA at our hospital, we studied 51 patients with LVSD (LVEF ≤50%). Improved LVEF more then 5% at 1-year after CA was classified as “responder” to CA. We analyzed clinical variables and echocardiographic parameters before and after the CAs.

Results

In the responder group, LVEF was significantly improved 1-year after catheter ablation compared with the non-responder group. (ΔLVEF 22±12% vs. −1±4%, p<0.001). The responder group was significantly younger, had more non-paroxysmal AF, smaller LV systolic diameter and lower plasma BNP level before CA (Table). Late gadolinium enhancement (LGE)-positive rate in cardiovascular magnetic resonance imaging (CMR) before CA was higher in the non-responder group than in the responder group (100% [6/6] vs. 38% [5/13], p<0.005). After CAs of AF, event-free survival from hospitalization for heart failure was significantly higher in the responder group (Figure) with less AF recurrence (27% vs. 47%, p=0.04) than in the non-responder group.

Baseline characteristics Responder (N=35) Non-Responder (N=16) P value Age, y 62±11 69±8 p<0.01 Male, n (%) 26 (74) 13 (76) NS Non-pAF 26 (74) 4 (24) p<0.01 LAD, mm 48±7 48±8 NS LAVI, ml/m2 54±17 58±20 NS LVDd, mm 54±7 58±10 NS LVDs, mm 43±7 48±10 p=0.05 EF, % 37±8 38±8 NS BNP (pg/ml) 278±225 684±848 p<0.05

Conclusion

Younger age, absence of LV dilatation, lower plasma BNP, or absence of LGE may well predict favorable clinical outcomes after CA in patients with LVSD.
1136Prognostic impact of mineralocorticoid receptor antagonists in patients hospitalized for acute heart failure
Authors: Yaku H , Kato T , Morimoto T , Inuzuka Y , Tamaki Y , Yamamoto E , Yoshikawa Y , Ozasa N , Kuwahara K , Kimura T
Published: October 2019

Background

The favourable effect of mineralocorticoid receptor antagonists (MRAs) on mortality was established in patients with stable heart failure (HF) with reduced ejection fraction (EF). However, its prognostic effect of MRAs in acute decompensated heart failure (ADHF) including HF with preserved EF (HFpEF) was unclear.

Purpose

This study sought to investigate the long-term impact of MRA on the post-discharge outcomes in patients with ADHF.

Methods

From the consecutive 3717 patients hospitalized for ADHF and discharged alive in the KCHF registry, we developed the propensity score (PS) for MRA use and constructed the PS-matched cohort. We compared the effect of MRA use on the primary outcome measure of all-cause death or HF hospitalization.

Results

A total of 1678 patients (45%) received MRA at discharge from the index hospitalization. Median follow-up was 470 days with 96% 1-year follow-up rate. In the PS-matched cohort (N=1034 in each group), the cumulative 1-year incidence of the primary outcome measure was significantly lower in the MRA group than in the no MRA group (28.4% vs. 33.9%, P=0.003) (Figure 1). The cumulative 1-year incidence of HF hospitalization was significantly lower in the MRA group than in the no MRA group (18.7% vs. 24.8%, P<0.001), while there was no difference in mortality between the 2 groups (15.6% vs. 15.8%, P=0.85). There was no interaction between the effect of MRA and the 3 subgroups stratified by EF (EF <40%, EF 40–49%, EF ≥50%) (interaction P=0.12).

Figure 1

Conclusion

The use of MRA was associated with lower risk for the primary composite outcome of all-cause death or HF hospitalization in patients hospitalized for ADHF including HFpEF, which was mainly driven by the lower risk for HF hospitalization.
1137A life support based comprehensive treatment regimen dramatically lowers the in-hospital mortality of patients with fulminant myocarditis —- a multiple center study
Authors: Chen C , Li S , Cui G L , Zhou N , Jiang J G , Wang D W
Published: October 2019

Background

Fulminant myocarditis (FM) is characterized by rapid onset and progression to cardiac and circulatory failure. It has high mortality; however, patients may benefit from short-term circulatory support. This study evaluated the therapeutic efficacy of a life support–based comprehensive treatment regimen (LSBCTR) for FM and demonstrated that it saved the lives of FM patients.

Methods

One hundred and fourteen FM patients were recruited from January 2007 to October 2017 were divided into two groups: those who received LSBCTR (65 cases), including management of fluids and nutrients, use of antiviral drugs and large doses of glucocorticoids (methylprednisolone over 200 mg) and immunoglobulins, continuous renal replacement therapy (CRRT), and life support (artificial positive pressure respiration, intra-aortic balloon pump [IABP] with or without extracorporeal membrane oxygenation [ECMO]), and those who received traditional methods (74 cases). The primary endpoints were in-hospital death and length of hospital stay for survivors.

Results

Of the population, 41 patients (36.0%) died in the hospital. In-hospital mortality rates were 3.0% (2/65) for the LSBCTR group and 52.7% (39/74) for the traditional treatment group (P<0.001). Early life support (IABP with or without ECMO and a respirator) and early applications of CRRT, antiviral therapy, and sufficient doses of glucocorticoids and immunoglobulins individually contribute to the efficiency of reducing in-hospital mortality. Vasoactive agents did not improve prognosis, especially noradrenaline, which dramatically increased the incidence of death.

Conclusion

Our data described comprehensive treatment for patients with FM that can dramatically reduce in-hospital mortality. Its generalization and application in clinical practice will efficiently save lives.

Clinical Trial: NCT03268642.
1177Insights on mitochondrial energetics in obstructive hypertrophic cardiomyopathy
Authors: Lombardi M , Lazzeroni D , Rimoldi O , Girolami F , Pisano A , Benedetti G , Alfieri O , D'Amati G , Foglieni C , Camici P
Published: October 2019

Background

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy, heterogeneous in phenotype and clinical course. The genotype-phenotype relationship and associated molecular mechanisms are still incompletely understood. In the HCM milieu, increased energy cost of force production, impairing performance and mitochondrial function, may be associated to patients' genotype and/or phenotype.

Purpose

To determine abnormalities in mitochondrial energetics in HCM and their possible relationship with genotype and clinical phenotype of patients.

Methods

Septal myectomies from characterized patients with obstructive HCM (HOCM, n=18) and donor hearts discarded from transplantation (CTRL, n=8) have been compared. HOCM patients were screened and demographic, clinical and instrumental data (routine ECG, echocardiography and cardiac magnetic resonance-CMR) were collected.

Genetic analysis was performed on total DNA extracted from myectomies by NGS on MiSeq platform using the TruSight Cardio Sequencing kit and testing a panel of 26 genes.

Activity and amount of mitochondrial enzymes generating/scavenging reactive oxygen species were investigated.

Results

Within the HOCM cohort 30% of patients was bearing mutations in sarcomeric genes associated with HCM.

The amount and/or activity of mitochondrial Complex I NADH dehydrogenase, of SOD2 and (m)-aconitase were upregulated in HOCM vs. CTRL. NADH dehydrogenase level was inversely correlated with the degree of mitral valve regurgitation and mitral valve backward volume by CMR (Spearman R=−0.5 and −0.8, respectively).

The Complex V enzyme ATP synthase activity decreased, whilst its amount was comparable in HOCM vs. CTRL. Analogously the SOD1 activity was similar in HOCM and CTRL.

No difference in mitochondrial DNA (mtDNA) copy number was found.

Results were unrelated to HCM-associated mutations.

Conclusions

HOCM hearts are characterized by mitochondrial hyperactivity aimed at quenching reactive oxygen species, but decreased ATP synthase activity. Overall, these data suggest an abnormal mitochondrial activity in the myocardium of HOCM patients independent of the presence of HCM-associated mutations. Moreover, our results underpin the markedly abnormal cellular energetics of HOCM, identifying potential therapeutic targets.

Acknowledgement/Funding

NET-2011-02347173, Italian Minister of Health
1198Women and non-diabetic patients react more strongly to radiofrequency renal sympathetic denervation
Authors: Zweiker D , Lambert T , Steinwender T , Weber T , Niederl E , Koppelstaetter C , Hohenstein-Scheibenecker K , Rohla M , Reindl-Schwaighofer R , Kindslehner C , Gruener P , Auer J , Dechant C , Zirlik A , Zweiker R
Published: October 2019

Background/Introduction

Three recently published sham-controlled studies proved the efficacy of renal denervation (RDN) in hypertensive patients. However, there it is still unclear which patients should be selected for RDN.

Purpose

This study seeks to clarify which patient subgroups benefit most from radiofrequency RDN by analysing a nationwide multicentre registry database.

Methods

This is a post-hoc analysis from the multicentre Austrian Transcatheter Renal Denervation Registry hosted by the Austrian Society of Hypertension. We correlated change of systolic blood pressure (BP) after RDN to gender and presence/absence of comorbidities. Bivariate correlation and multiple linear regression analyses were performed.

Results

291 patients (43% female, median age 64 years) undergoing RDN between April 2011 and September 2014 were included in this analysis. Mean baseline ambulatory 24-hour BP (systolic/diastolic) was 150±18/89±14 mmHg and mean baseline office BP was 170±16/94±14 mmHg.

After RDN, mean ambulatory 24-hour BP reduction was 9±19/6±16 mmHg. The following features were associated with a good response to RDN: high baseline systolic ambulatory BP (ρ=0.53, p<0.001), high baseline diastolic office BP (ρ=0.40, p<0.001), female gender (ρ=0.10, p=0.049), absence of diabetes mellitus (DM, ρ=0.11, p=0.033), and absence of peripheral arterial disease (ρ=0.17, p=0.002). Multivariate analysis identified high baseline systolic ambulatory BP, female gender and absence of DM as independent predictors for systolic ambulatory BP reduction (systolic ambulatory BP: HR 5.83 [95% CI 4.83–6.83], p<0.001; absence of DM: HR 5.82 [2.04–9.60], p=0.003; female gender: HR 5.07 [1.46–8.68], p=0.006), although women and patients without DM had lowest baseline ambulatory BP. Furthermore, both women and patients without DM used significantly less antihypertensives after RDN (female vs male: 4.0±1.3 vs 4.4±1.3, p=0.002; no DM vs DM: 4.0±1.3 vs 4.6±1.3, p<0.001).

Figure 1

Discussion

Ambulatory BP reductions after RDN were substantially more pronounced in female and in non-diabetic patients despite lower baseline BP. It is concluded that in terms of efficacy female patients and non-diabetics might be more suitable for RDN.

Acknowledgement/Funding

The Austrian Renal Denervation Registry was funded by the Austrian Society of Hypertension.
1337Myocardial extracellular volume in patients with aortic stenosis undergoing valve intervention - A multicentre T1 mapping study
Authors: Everett R , Treibel T , Fukui M , Lee H , Rigolli M , Singh A , Tastet L , Musa T A , Chin C , Om S Y , Captur G , Funk S , Clavel M A , Clavel M A , Cavalcante J , Cavalcante J , Dweck M R , Dweck M R
Published: October 2019

Background

The development of myocardial fibrosis is a key mechanism in the transition from compensated hypertrophy to heart failure in aortic stenosis (AS). Focal and diffuse fibrosis can be quantified using cardiac magnetic resonance (CMR) imaging late gadolinium-enhanced (LGE) and T1 mapping techniques.

Purpose

To assess T1 mapping measures of fibrosis in patients with severe AS referred for aortic valve intervention, and determine their associations with clinical characteristics, disease severity and long-term clinical outcome.

Methods

In this international prospective cohort study, patients with severe AS underwent contrast enhanced CMR with T1 mapping and LGE prior to aortic valve intervention. Image analysis was performed by a single core laboratory and the extracellular volume fraction [ECV%] calculated from T1 mapping images. The presence of LGE was determined visually and quantified using the full-width-at-half-maximum technique.

Results

Four-hundred and forty patients (70±10 years, 59% male) from ten international centres were enrolled. Aortic valve intervention was performed 15 [4 to 58] days following CMR. Within a follow-up of 3.8 [2.8 to 4.6] years, 52 patients died.

ECV% (mean 27.7±3.6%) correlated with increasing age, Society of Thoracic Surgeons Predicted Risk of Mortality score, known coronary artery disease, lower peak aortic-jet velocity, larger left ventricular (LV) mass, lower LV ejection fraction, and presence of LGE (P<0.05 for all). Following adjustment for all demographic and clinical variables, ECV% remained associated with age (P=0.028), LV ejection fraction (P<0.001) and presence of LGE (P=0.035).

Univariable predictors of all-cause mortality included age, male sex, impaired LV ejection fraction and presence of LGE (all P<0.05). A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6 and 52.7 deaths per 1000 patient-years; log-rank test, P=0.009). ECV% was independently associated with all-cause mortality following adjustment for age, sex, impaired LV ejection fraction and presence of LGE (HR per unit increase in ECV: 1.10, 95%, (1.02–1.19), P=0.013).

ECV440 abstract iamge

Conclusion

In patients with severe aortic stenosis scheduled for aortic valve intervention, extracellular volume-based T1 mapping correlates with LV decompensation. ECV% is a strong independent predictor of late all-cause mortality and is a potential therapeutic target.
2153The relation between systemic inflammation and incident cancer in patients with stable cardiovascular disease; a cohort study
Authors: Van 'T Klooster C C , Ridker P M , Hjortnaes J , Van Der Graaf Y , Asselbergs F W , Westerink J , Aerts J G J V , Visseren F L J
Published: October 2019

Background

Chronic systemic low-grade inflammation, measured by elevated plasma concentrations of high sensitive C-reactive Protein (CRP), is a risk factor for cardiovascular disease (CVD). There is evidence that systemic low-grade inflammation is also related to a higher risk of cancer.

Purpose

In the present prospective cohort study the relation between systemic low-grade inflammation and risk of cancer was evaluated in patients with clinically manifest vascular disease.

Methods

In total 7178 patients from the SMART cohort with manifest cardiovascular disease and plasma CRP levels ≤10 mg/L were included. Data of the cohort were linked to the Dutch national cancer registry. Cox regression models were fitted to study the relation between CRP and incident cardiovascular disease as well as incident cancer. Cancer types were classified according to anatomical location of origin, as well as histopathological subtype, irrespective of their anatomical location of origin. To adjust for potential confounding, age, sex, smoking status, packyears of smoking, and body mass index were added to the models, and additional cardiovascular risk factors, including diabetes mellitus, and systolic blood pressure.

Results

After a median follow-up time of 8.3 years (interquartile range 4.6–12.3) 1289 recurrent cardiovascular events (myocardial infarction, stroke, or vascular mortality) and 1072 incident cancer diagnoses were observed. CRP level was related to recurrent cardiovascular disease risk (HR 1.57; 95% CI 1.35–1.82) (Figure 1A), as well as risk of CVD and/or cancer (HR 1.45; 95% CI 1.29–1.62) (Figure 1B) comparing the third tertile of CRP to the first tertile. CRP concentration was related to total cancer risk (HR 1.33; 95% CI 1.13–1.55 for the third tertile of CRP compared to the first tertile) (Figure 1C). Especially incident lung cancer, independent of histopathological subtype, was related to CRP level (HR 2.64; 95% CI 1.77–3.93 for the third tertile of CRP compared to the first) (Figure 1D). No effect modification by smoking status or years of smoking cessation was observed of the relation between CRP and lung cancer (p-values for interaction >0.05). Incidence of epithelial neoplasms and especially squamous cell neoplasms were related to CRP concentration, irrespective of their anatomical location of origin (HR 1.17; 95% CI 1.08–1.27, and HR 1.11; 95% CI 1.02–1.20 for 1 mg/L higher CRP level respectively). Sensitivity analyses accounting for reverse causality by excluding patients with a cancer diagnosis within 1 and within 2 years of follow up showed similar results.

Kaplan Meier curves per CRP tertile

Conclusion

Chronic systemic low-grade inflammation, measured by plasma CRP levels ≤10mg/L, is a risk factor for incident cancer, markedly lung cancer, independent of smoking status, in patients with stable cardiovascular disease.
2161Redox-mediated PKA-RIalpha localisation to the lysosome inhibits myocardial calcium release and robustly reduces myocardial injury
Authors: Simon J N , Vrellaku B , Monterisi S , Chu S , Rawlings N , Lomas O , Marchal G A , Waithe D , Gajendragadkar P , Jayaram R , Channon K , Swietach P , Zaccolo M , Eaton P , Casadei B
Published: October 2019

Background

Kinase oxidation is a critical signalling mechanism through which changes in the intracellular redox state alter cardiac function. In the myocardium, type-1 protein kinase A (PKARIα) can be reversibly oxidised, forming interprotein disulphide bonds within the holoenzyme complex. However, the effect of PKARIα oxidation on downstream signalling in the heart, particularly under states of oxidative stress, remains unexplored.

Purpose

To determine the direct functional consequences of PKARIα oxidation in the heart and investigate their impact on ischaemia/reperfusion (I/R) injury.

Methods and results

Experiments using the AKAR3ev FRET biosensor in murine left ventricular (LV) myocytes and Fluorescence Recovery After Photobleaching (FRAP) of GFP-tagged wild-type (WT) and mutant RIα proteins expressed in RIα-null fibroblasts showed that PKARIα oxidation does not increase the kinases' catalytic activity, but enhances its binding to A-kinase anchoring proteins (AKAP; n=30–39/N=3, p<0.01). Super-resolution microscopy revealed localisation of oxidised PKARIα to lysosomes in WT myocytes, which was completely absent in “redox dead” Cys17Ser PKARIα knock-in mice (KI; panel A; n=38–41/N=3, p<0.01) and reduced when AKAP binding was prevented using the RIAD disruptor peptide (30.6±5.1% reduction; n=35–37/N=3, p<0.01).

Displacement of PKARIα from lysosomes resulted in spontaneous sarcoplasmic reticulum calcium release and dramatic calcium oscillations in KI LV myocytes (panel B), which were preventable by ryanodine receptor blockade (1 mM tetracaine; n=14, p<0.01), acute depletion of endolysosomal calcium stores (100 nM bafilomycin; n=7; p<0.01), or lysosomal two-pore channel inhibition (5 μM Ned-19; n=9; p<0.05).

I/R (secondary to cardiopulmonary bypass) was found to induce PKARIα oxidation in the myocardium of patients undergoing cardiac surgery (panel C; n=18, p<0.05). Absence of this response in KI mouse hearts resulted in 2-fold larger infarcts (p<0.01) and a concomitant reduction in LV contractile recovery (final LVDP of 55.9±8.6 vs 82.5±7.1 mmHg in WT; n=7–8, p<0.05), both which were prevented by addition of Ned-19 at the time of reperfusion (panel D; n=4, p<0.01).

Conclusions

Oxidised PKARIα acts as a potent inhibitor of intracellular calcium release in the heart through its redox-dependent interaction with the lysosome. In the setting of I/R, where PKARIα oxidation is induced, this regulatory mechanism is critical for protecting the heart from injury and offers a novel target for the design of cardioprotective therapeutics.

Acknowledgement/Funding

British Heart Foundation CH/12/3/29609, RG/16/12/32451; Garfield-Weston Foundation MPS/IVIMS-11/12-4032; Wellcome Trust Fellowship 0998981Z/12/Z
2179Clinical significance of device-derived activity in ICD and CRT-D patients - Data from MADIT-RIT
Authors: Kutyifa V , Jones P , Goldenberg I , Brown M , Zareba W , Stein K , McNitt S , Polonsky S , Rosero S
Published: October 2019

Background

The Multicenter Automatic Defibrillator Implantation Trial – Reduce Inappropriate Therapy (MADIT-RIT) enrolled 1500 patients and showed that novel ICD programming reduced inappropriate therapy and improved survival. However, the role of device-derived patient activity to predict mortality is not known.

Methods

In 1500 patients enrolled in MADIT-RIT, device-derived patient activity was captured daily. Device-derived activity was averaged for the first 30 days following randomization, and utilized in this study to predict mortality post-30 days. Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression models were used to evaluate all-cause mortality by 30-day device derived patient activity quintiles, and as a 3-level function of 30-day device derived patient activity (Q1, Q2–3, Q4–5).

Results

There were a total of 1463 patients with data available (98%), 66 of them died during the follow-up post-30 days. Patients in the lowest quintile (Q1: 4%∼1 hour daily activity) of device-derived activity were older, they were more often female, and they more often had diabetes and NYHA class III HF symptoms. Patients in the lowest quintile of 30-day device derived median activity (1 hour daily activity) had the highest risk of mortality, 15% in 2 years as compared to Q2–3 (1–2 hours daily activity, 8–7% 2-year mortality), and Q4–5 (>2 hours daily activity, 2–3% 2-year mortality) (Figure, p<0.001 for the overall duration). Each quintile decrease in device-derived 30-day median patient activity was associated with a significant, 41% increase in mortality (HR=1.41, 95% CI: 1.15–1.71, p=0.001). Patients with the lowest level of 30-day median patient activity (Q1) had 4.13-times higher risk of mortality as compared to the highest level of activity patients, Q4–5 (HR=4.13, 95% CI: 1.89–9.03, p<0.001). Patients with intermediate levels of activity (Q2–3) still had a 2.8-fold increase in death as compared to the highest activity level cohort of patients (HR=2.79, 95% CI: 1.31–5.91, p=0.008).

Figure 1

Conclusions

Device-derived 30-day median patient activity predicted subsequent all-cause mortality in ICD and CRT-D patients enrolled in MADIT-RIT. Patients with low and moderate levels of 30-day device-derived median patient activity (less than 2 hours daily activity) were at a significantly higher risk of death, and these cohorts warrant further investigation and management to improve outcomes.

Acknowledgement/Funding

MADIT-RIT was funded by an unrestricted research grant from Boston Scientific to the University of Rochester.
2182Sirtuin 5 regulates arterial thrombosis by modulating endothelial plasminogen activator inhibitor-1
Authors: Liberale L , Akhmedov A , Nageswaran V , Bonetti N , Miranda M X , Montecucco F , Beer J H , Luscher T F , Camici G G
Published: October 2019

Introduction

Arterial thrombosis as a result of plaque rupture or erosion is a crucial event in myocardial infarction and stroke. Oxidative stress and inflammation promote endothelial dysfunction and play a pivotal role in destabilization of the atherosclerotic plaque. Sirtuin 5 (SIRT5) is a member of the sirtuin protein family with function as a NAD+-dependent protein desuccinylase and demalonylase. Being implicated in the regulation of different pathophysiological processes among which production of reactive oxygen species and transcription of inflammatory mediators, SIRT5 plays a role in the development of several cardiovascular diseases such as myocardial infarction and stroke. To date, the possible involvement of SIRT5 as a mediator of arterial thrombosis remains to be investigated.

Purpose

In this study we investigate the putative role of this protein in arterial thrombosis by using an established in vivo mouse model. The translational value of animal findings as well as the molecular mechanism underlying the observed effect will be investigated also in primary human aortic endothelial cells (HAECs).

Methods

SIRT5 knockout (KO) as well as SIRT5 transgenic (TG) animals were used for in vivo experiments. HAECs treated with SIRT5 silencing RNA (si-SIRT5) and stimulated with tumor necrosis factor (TNF)-α were used for in vitro assays.

Results

When compared to WT animals, SIRT5 KO mice display blunted carotid artery thrombus formation as underlined by delayed time to occlusion in a photochemical injury model. Oppositely, in SIRT5 TG mice the formation of an occlusive thrombus is accelerated (Fig 1). Mechanistically, SIRT5 KO and WT animals show no difference in terms of vascular tissue factor (TF) activity, TF concentration in plasma and expression of TF pathway inhibitor (TFPI) in the aorta. In line with the observed reduced thrombogenicity, SIRT5 KO animal express reduced level of the pro-thrombotic plasminogen activator-1 (PAI-1), as assessed by western blot in aorta lysate. Of interest, SIRT5 genetic deletion does not affect platelet aggregation, as assessed by ex-vivo collagen-induced aggregometry. In HAECs, SIRT5-silencing inhibits PAI-1 expression in response to TNF-α. Real-time polymerase chain reaction revealed that inhibition of PAI-1 expression occurs at the mRNA level. This effect is mediated by reduced activation of the MAP kinase Erk 1/2, but not JNK (Fig 1).

Conclusions

SIRT5 mediates arterial thrombosis by increasing endothelial PAI-1 expression. Hence, SIRT5 may be an effective therapeutic target in the context of atherothrombosis.
2199Cardiovascular risk behaviour is an emerging health issue in developing countries
Authors: Negesa L , Magarey J , Rasmussen P , Hendriks J
Published: October 2019

Background

Previously, cardiovascular disease (CVD) was considered the “Disease of the Rich”, however nowadays also populations with low socioeconomic status have been identified at increased risk of developing CVD. The global progress in CVD prevention is scarce particularly in developing countries, which are facing a high burden of CVD whilst there is limited availability of resources and evidence to educate and modify lifestyle behaviours in the population. Moreover, there is a lack of infrastructure and policy making in these countries.

Purpose

The goal of the study was to quantify the prevalence of different cardiovascular risk behaviours among patients with known cardiovascular conditions in a developing countries.

Methods

A hospital based cross-sectional survey was conducted in two referral hospitals in Ethiopia. Outpatient unit patients who had a confirmed diagnosis of CVD were eligible for participation in the study. Data were collected through face-to-face interviews with patients using validated tools; WHO STEPs instrument and international physical activity questionnaire.

Results

A total of 287 CVD patients were recruited, 56% were females and 90% were urban residents. All patients had inadequate consumption of fruit and vegetables, 20% were current khat chewers, 19% were current alcohol drinkers and only 1% were current smokers. The prevalence of low physical activity (defined as less than 600 MET-minutes per week) in the total population was 51.6% for both sexes; more than half of the total population were physically inactive. Moreover, females had a significantly higher prevalence of physical inactivity as compared to males, 58% vs 43.2%, P=0.017. Approximately one-third (30%) of patients had only one of these risk behaviours, more than half (52%) had two, 18% had three or more risk behaviours. The majority (70%) of the patients had multiple risk behaviours (Table 1), the prevalence of these did not significantly vary with sex, residence and educational level (p>0.05).

Conclusion

Patients with CVD maintain unhealthy lifestyles even though attending follow up care with a specific focus on risk management. The findings of this study demonstrate a high prevalence of physical inactivity, alcohol consumption and inadequate fruit and vegetable consumption in developing countries. The emerging increase of CVD and the continuation of unhealthy lifestyle in patients is somewhat comparable with western countries, demonstrating an emerging global problem. Moreover, this study shows the existing follow-up care is ineffective and provides evidence for policy makers that health services reform is required. Implementation of lifestyle support programs should be considered for the disease prevention policy agenda in developing countries.