bluuebunny/crossref_metadata_2025 huggingface dataset:
1385Combined tricuspid and mitral vs. isolated mitral valve repair for severe mitral and tricuspid regurgitation: An analysis from TriValve and TRAMI registries
Authors: Mehr M , Taramasso M , Ourrak T , Lurz P , Von Bardeleben R S , Fam N , Lubos E , Boekstegers P , Schillinger W , Plicht B , Eggebrecht H , Baldus S , Senges J , Maisano F , Hausleiter J
Published: October 2019

Background

Edge-to-edge repair has been shown to be a successful therapeutic option for patients with severe mitral regurgitation (MR). Lately, it has also been emerging as a treatment perspective for severe tricuspid regurgitation (TR) in patients at high-risk for cardiac surgery. In patients, with both severe MR and TR the best treatment strategy for patients at high risk for surgery is unknown.

Purpose and methods

We retrospectively analyzed data from the international multicentre TriValve (Transcatheter Tricuspid Valve Therapies) registry and from the German multicentre TRAMI (Transcatheter Mitral Valve Interventions) registry. All patients included into the analysis had both severe MR and TR. Patients from the TRAMI registry (n=106) were treated with edge-to-edge repair in mitral position only. In patients from the TriValve registry (n=122), both valves were treated concomitantly in compassionate and/or off-label use. We sought to compare baseline characteristics, procedural data and 1-year mortality in both treatment groups.

Results

228 patients (77±8 years; 44.3% female) were included into the analysis. All patients showed significant dyspnea on exposure (NYHA III or IV 93.9%). Kidney function (eGFR 42 ml/min/1,72m2) and the proportion of patients with significant pulmonary hypertension (59.0%) and COPD (23.7%) did not differ between the groups, but the proportion of patients with LV-EF <30% (34.9% vs. 18.0%, p<0.001) were higher in the TRAMI cohort.

At discharge, MR was comparably reduced in both groups (MR ≤ I° 75.9% vs. 77.3%, p=0.67). While all patients in both registries had significant TR at baseline, the percentage of patients with TR≥3+ at discharge was reduced to 18.6% in TriValve by the placement of 2±1 tricuspid clips/patient. The rate of in-hospital adverse events and the time of hospitalization did not differ in both cohorts. At 1-year, overall all-cause mortality was 34.0% in the TRAMI cohort and 16.4% in the TriValve cohort (p=0.0002, see figure; after adjustment for LVEF <30%: p=0.049). The rate of patients with NYHA ≤ II at 1 year did not differ between both cohorts (69.4% vs. 67.0%, p=0.54).

1-year mortality TriValve vs. TRAMI

Conclusion

Transcatheter mitral and tricuspid valve repair can result in a significant clinical improvement at 1 year. The concomitant treatment of both valve regurgitations may result in an improved survival, which needs to be confirmed in dedicated prospective trials.
1406Inhaled iloprost, exercise hemodynamics, and ventricular performance in heart failure with preserved ejection fraction
Authors: Cheng J.-F , Wu C.-K , Huang C.-Y , Chen Z.-W , Chen S.-Y , Lin L.-Y
Published: October 2019

Background

A dramatic increase in pulmonary capillary wedge pressure (PCWP) during exercise is observed in patients with heart failure with preserved ejection fraction (HFpEF). The prostacyclin pathway is involved in pulmonary hypertension and iloprost is a prostacyclin analogue. The acute onset vasodilator effect of inhaled iloprost makes it a good candidate to decrease exercise-induced PCWP. This study determined whether iloprost inhalation could improve exercise hemodynamics and cardiac reserve in HFpEF.

Methods

Thirty-four HFpEF subjects were enrolled in this double-blind, randomized, placebo-controlled, parallel-group trial. Subjects received invasive cardiac catheterization and underwent expired gas analysis at rest and during exercise, before and 15 minutes after treatment with either inhaled iloprost or placebo.

Results

At baseline, enrolled subjects showed an increase in PCWP during exercise (PCWP = 16 (14–23) mmHg to 27 (21–36) mmHg; p<0.0001). After drug inhalation treatment, the primary endpoint was achieved whereby exercise PCWP was significantly reduced by iloprost compared to placebo (adjusted mean: 20 (16–29) mmHg vs. 23 (17–32) mmHg; p=0.002). Iloprost showed a trend for better cardiac output reserve with exercise (0.2 (−1.3 to 1.2) L/min vs. −0.7 (−1.9 to 0.1) L/min; p=0.099) and normalized the increase in cardiac output relative to oxygen consumption. Iloprost improved the pulmonary artery pressure flow relationships in HFpEF and showed a trend for increased left ventricular stroke work with exercise compared to placebo, indicating an improvement in ventricular performance with stress.

Table shows exercise baseline-corrected values (exercise values after receiving study drug minus exercise values prior to study drug) Placebo (n=17) Iloprost (n=17) p Value PA systolic, mmHg 0 (−4 to 6) −11 (−23 to −5) <0.0001 PCWP, mmHg −2 (−3 to 2) −7 (−12 to −5) <0.0001 PVR, mmHg/l/min 0 (−0.5 to 0.3) −0.1 (−0.5 to 0.4) 0.9 SVR, DSC 102 (16 to 188) 5 (−162 to 108) 0.057 LVSW, g/beat −3 (−30 to 6) 7 (−13 to 20) 0.079 CO, l/min −0.7 (−1.9 to 0.1) 0.2 (−1.3 to 1.2) 0.099 Stroke volume, ml −8 (−24 to 1) 0 (−19 to 10) 0.3 Values are median (interquartile range).

Conclusions

Iloprost inhalation improved hemodynamic deficit during exercise in patients with HFpEF. Prospective trials testing long-term iloprost therapy in this population are warranted.
1415Dose antihypertensive medication improve accelerated age-dependent decline of GFR in hypertension?
Authors: Ohno K , Takase H , Machii M , Nonaka D , Sugiura T , Ohte N , Dohi Y
Published: October 2019

Background/Introduction

An impairment of kidney function is a risk not only for end stage renal disease but also for cardiovascular events. Hypertension is known to accelerate an age-dependent decline in glomerular filtration rate (GFR).

Purpose

Effects of antihypertensive medications on yearly changes of estimate GFR (eGFR) in hypertensive patients were investigated.

Methods

Consecutive 5110 subjects (male=3196, 52.3±11.3 year-old) who participated in our physical check-up program during 2010 and 2012 were enrolled and followed up for 5 years. The average and the yearly change of eGFR during the 5 years were calculated in each individual and the both values were compared in hypertensive and normotensive subjects. Effect of antihypertensive medication on eGFR was also investigated. The modified Modification of Diet in Renal Disease study formula for the Japanese population was used for calculating eGFR.

Results

In hypertensive subjects (n=1408), the baseline and the average of eGFR were smaller (74.8±14.6 vs. 80.4±13.6, p<0.001 and 72.1±13.2 vs. 77.9±11.9 mL/min per 1.73 m2, p<0.001, respectively) and the yearly decline of eGFR was greater (0.96±1.41 vs. 0.84±1.19 mL/min per 1.73 m2 per year, p<0.01) than in normotensive subjects (n=3702). The baseline and the average of eGFR were smaller in hypertensive patients with (n=1234) than without (n=174) antihypertensive medication (74.3±14.6 vs. 78.3±13.8, p<0.001 and 71.7±13.2 vs. 74.9±12.7 mL/min per 1.73 m2, p<0.01, respectively). Although the yearly decline of eGFR in hypertensive patients with medication tended to be smaller than the decline in those without medication (0.94±1.41 vs. 1.09±1.42 mL/min per 1.73 m2 per year), this did not reach a statistical significance (p=0.213). Neither the number, classes of antihypertensive medications nor systolic blood pressure during the follow-up period did affect the average or yearly decline of eGFR in hypertensive patients.

Conclusions

As compared to normotensive subjects, eGFR was reduced and a yearly decrease in eGFR during the 5 years was accelerated in hypertensive patients. Although antihypertensive medication may reduce an accelerated age-dependent decline of kidney function in hypertension, observational period in this study was too short to clarify such beneficial effects of antihypertensive medications.
1436Overexpression of Cytotoxic T-Lymphocyte Associated Antigen-4 suppresses aortic immunoinflammatory responses and prevents angiotensin II-induced abdominal aortic aneurysm formation in mice
Authors: Amin H , Sasaki N , Yamashita T , Mizoguchi T , Hayashi T , Emoto T , Matsumoto T , Yoshida N , Tabata T , Horibe S , Kawauchi S , Rikitake Y , Hirata K
Published: October 2019

Aims

Vascular inflammation via T-cell-mediated immune responses has been shown to be critically involved in the pathogenesis of abdominal aortic aneurysm (AAA). T-cell coinhibitory molecule cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4) is known to act as a potent negative regulator of immune responses. However, the role of this molecule in the development of AAA remains completely unknown. In the present study, we determined the effects of CTLA-4 overexpression on experimental AAA.

Methods and results

We continuously infused 12-week-old CTLA-4 transgenic (CTLA-4-Tg)/apolipoprotein E–deficient (Apoe−/−) mice (n=35) or control Apoe−/− mice (n=40) fed a high-cholesterol diet with angiotensin II by implanting osmotic mini-pumps and evaluated the development of AAA. Ninety percent of angiotensin II-infused mice developed AAA, with 50% mortality because of aneurysm rupture. Overexpression of CTLA-4 significantly reduced the incidence (66%), mortality (26%), and diameter (18%) of AAA (incidence: P=0.0104; mortality: P=0.031; diameter: P=0.011). These protective effects were associated with a decreased number of effector CD4+ T cells and the downregulated expression of costimulatory molecules CD80 and CD86, ligands for CTLA-4, on CD11c+ dendritic cells in lymphoid tissues. In addition, by performing in situ zymography of the abdominal aortic aneurysm lesions, we observed a trend toward a decrease in MMP activity in the aneurysmal lesion following overexpression of CTLA-4. Finally, CTLA-4-Tg/Apoe−/− mice had reduced macrophage and CD4+ T cell accumulation and MMP activity in the aneurysmal lesion, leading to attenuated aortic inflammation, preserved vessel integrity, and decreased susceptibility to AAA and aortic rupture.

Conclusion

Our findings suggest that CTLA-4 protects against AAA by suppressing immunoinflammatory responses and could be an attractive therapeutic target for AAA.
1446A greater healthy behaviors score is associated with a lower risk of all-cause and cause specific mortality: insight from two prospective multi-ethnic surveys
Authors: Mazidi M , Katsiki N , Mikhailidis D P , Rysz J , Banach M
Published: October 2019

Background

Mortality from non-communicable diseases (NCDs) is influenced bymodifiable risk factors. Simple tools which do not require laboratory tests, (blood pressure (BP) [B], exercise [E], weight [W], alimentation [A] (fruit and vegetable consumption), and tobacco [T] (BEWAT) may estimate the risk of all-cause and cause specific mortality.

Purpose

Therefore, we evaluated the link between BEWAT and mortality in a randomly selected sample of the US population.

Method

Adults aged ≥20 years, enrolled in the Third National Health and Nutrition Examination Survey (NHANES-III, 1988–1994) and continuous NHANES (2005–2010), and followed up to December 31st 2011, were included in the present analysis. Multiple Cox regressionswere applied to evaluate the associations between the total BEWAT score and each of its components with all-cause and cause specific mortality.

Results

Overall, 22,968 participants (47.1% men) were included in the present analysis (mean age: 47.4 years). Individuals in the highest BEWAT tertile (T3) had a 25% lower risk of mortality compared with T1 [hazard ratio (HR): 0.75, 95% confidence interval (CI): 0.71–0.79], further corrections slightly diluted the magnitude of link to 22% (HR: 0.78, 95% CI: 0.75–0.81) (Figure). In a fully adjusted model, individuals in T3 also had a 26% lower risk of cardiovascular disease (CVD) mortality compared with those in T1 (HR: 0.74, 95% CI: 0.64–0.83), similar trends were observed across the BEWAT tertiles for cancer mortality risk (participants in T3 had a 31 and 26% lower risk for cancer death in Models 1 and 2, respectively). For sensitivity analyses after excluding smoking from the total BEWAT score, in the fully adjusted model the association between the BEWAT score and cancer death was attenuated but remained significant (HR: 0.80, 95% CI: 0.72–0.89 for T3 vs T1). Furthermore, total BEWAT score (without the BP component) could still predict CVD mortality (T3= HR: 0.71, 95% CI: 0.61–0.82).

All-cause death and BEWAT tertiles.

Conclusion

A higher BEWAT status is beneficial regarding all-cause and cause specific mortality. Our results highlight the value of modifiable risk factors as a simple and affordable variable for evaluating the risk of mortality.
2166A multicenter echocardiographic comparison on pacemaker-induced tricuspid valve regurgitation: leadless versus transvenous single-chamber and dual-chamber pacing therapy
Authors: Beurskens N E G , Van Drooge J , Tjong F , Bon R , Dasselaar K , Gorter T , Maass A , Knops R
Published: October 2019

Background

Pacemaker (PM) lead interference with tricuspid valve (TV) function is an important determinant of hemodynamic compromise and is associated with substantial morbidity and mortality. Lead-related TV regurgitation (TR) can potentially be mitigated by leadless pacemaker (LP) therapy by eliminating the presence of a transvalvular lead.

Purpose

This large multicenter study aimed to evaluate the impact of LP therapy on TV function in comparison with an age –, sex, and follow-up duration -matched cohort of transvenous single-chamber (VVI) and dual-chamber (DDD) PM recipients.

Methods

Leadless, and transvenous VVI and DDD-PM recipients who underwent an echocardiographic study prior to the procedure and 15±6 months thereafter between January 2013 and September 2018 at two tertiary centers in the Netherlands were included. We used the data of a prospectively acquired population that comprised consecutive patients who underwent LP implantation who were 1:1 matched to transvenous VVI-PM and DDD-PM patients.

Results

A total of 198 patients (129 males, age 79±8.2 years) were included, of whom 66 were implanted with a LP (two models: Nanostim, Micra LP), and 66 with a transvenous VVI and 66 with DDD-PM. In the total cohort, the Wilcoxon signed-rank test revealed that TR severity was graded more severe in 87 (44%), equally in 104 (53%), and less severe in 7 (4%) patients (p<0.001) compared with baseline echocardiographic findings. Worsening TR was observed in 28 (42%) of the LP (p<0.001) and 34 (52%) of transvenous VVI-PM (p<0.001), and 25 (38%) of the DDD-PM recipients (p<0.01). Binary logistic regression analysis showed that LP recipients were equally prone to increasing TV dysfunction compared with transvenous PMs (p=0.42). Septal position of the leadless intracardiac device (odds ratio 3.6, p=0.03) was associated with worsening TR. In the total cohort, 30 (15%) patients had heart failure hospitalization during the follow-up period.

Conclusions

TR is a malignant disease which can result in high rates of heart failure hospitalization. This study revealed an unexpected high proportion of patients with worsening TR following LP therapy, yet it was comparable to conventional PM systems. The mechanical impact of the LP near the TV apparatus is the most likely cause of this phenomenon since the septal positioning of the device was associated with increasing TV incompetence. The general consensus was that LP therapy mitigates the risk for TV dyfunction due to the circumvention of transvalvular leads. Therefore, the current results are highly clinically relevant as the contradict expected performance of the LP approach.
2201Coronary angioplasty patients' preferences for information about treatment risks: a survey study
Authors: Astin F , Stephenson J , Probyn J , Holt J , Marshall K , Conway D
Published: October 2019

Background

Percutaneous Coronary Intervention (PCI) is the commonest invasive procedure in cardiology. Before treatment consent must be given. As part of this communication process patients receive information about the risks and benefits of PCI and alternative treatments. Published studies tell us that the amount and quality of the information received by patients undergoing PCI is variable; benefits are often overestimated, risks forgotten and alternative treatments not always considered. Very little is known about patients' preferences for PCI risk information. Aim: To describe patients' preferences for formation about PCI treatment risk as part of the informed consent process Methods: A cross-sectional survey was distributed to 350 participants treated with PCI across 10 PCI centres in England.

Results

Three hundred and twenty six participants completed the survey. Thirty percent of the sample reported needing help to understand written medical information. Fifty-one percent were treated with elective PCI, 75% were male, average age of 66.5 years. Recall and comprehension of PCI information given during the consent process was generally limited; 47% and 61% agreed that patients do not usually understand, or remember, the information given to them respectively. Eighty-eight percent of urgent PCI patients wanted to know about all possible risks compared to 90% of elective cases. Most participants (88% urgent and 94% elective) believed that PCI would reduce their risk of a future heart attack.

Conclusion

A significant proportion of PCI patients find it difficult to recall or understand information about treatment risks. It is recommended that patients are given health-related information designed to accommodate different health literacy levels in advance of their treatment.

Acknowledgement/Funding

National Institute for Health Research Research for Patient Benefit Programme Grant Reference Number PB-PG-0712-28089
2202Instant analysis of the ECG with a new digital technique during palpitations reduce symptoms, anxiety, depression, and increase HRQOL in women
Authors: Carnlof C , Insulander P , Jensen-Urstad M , Schenck-Gustafsson K
Published: October 2019

Background

Palpitation is common, particularly in women, and usually benign caused by premature atrial/ventricular beats or stress-induced sinus tachycardia. Palpitations may cause disturbing symptoms, anxiety, depression, and decreased health related quality of life (HRQOL). Uncommonly, arrhythmias of clinical importance such as atrial fibrillation or paroxysmal supraventricular or ventricular tachycardia may be the cause.

Purposes

To evaluate if instant analysis of underlying heart rhythm during palpitations reduce symptoms, anxiety, depression, and increase HRQOL.

Methods

In all, 913 women (age 56±11 years) with palpitations causing anxiety were recruited from social web sites. Coala Heart Monitor® was used by participants and ECG recorded twice a day and at symptoms for 60 days. The system uses a well-validated algorithm to analyze heart rhythm, is connected to the user's smartphone and provides immediate response to the user. In cases of non-benign arrhythmias, the result was also analyzed manually. Questionnaires addressing symptom (Symptom severity and frequency checklist (SCL), anxiety, depression Hospital anxiety and depression scale (HADS), Generalized Anxiety Disorder (GAD-7) and HRQOL (RAND-36)) were analyzed before and after two months. Exclusion criterium was known atrial fibrillation.

Results

Between June 2018 and November 2018, 280 474 recordings (both chest and thumbs) ECG recordings were automatically analyzed. Frequency and severity of symptoms decreased (frequency from 23.7±8.4 to 19.7±8.5 (p<0.001), severity from 22.7±4.9 to 21±4.4 (p<0.001)). Total anxiety measured by HADS decreased from 6.4±4.2 to 5.7±4.2 (p<0.001) and depression from 5.1±3.9 to 4.6±4.1 (p<0.001). Generalized anxiety disorder decreased from 5.6±4.8 to 4.7±4.6 (p<0.001) and HRQOL increased in all domains (p<0.001). In 83% of recordings during symptomatic palpitation, benign premature atrial or ventricular beats, sinus tachycardia, or normal sinus rhythm were found.

Conclusions

Instant analysis of the ECG with direct response to the user during palpitations reduce symptoms, anxiety, depression, and increase HRQOL in women.
2207Cardiovascular outcome in THEMIS -like type 2 diabetes patients in Sweden: a nationwide observational study
Authors: Hasvold L P , Erlinge D , Svennblad B , Janzon M , Lindholm D , Sundell K A , Jernberg T , James S
Published: October 2019

Background

The THEMIS study (NCT01991795; in analysis phase; n=19,349) compares the effect of dual antiplatelet therapy (DAPT) vs ASA alone for the prevention of major cardiovascular (CV) events in type 2 diabetes (T2D) patients with coronary artery disease (CAD) at high CV risk, but without prior myocardial infarction (MI) or stroke. However, there is a lack of real-life data on CV risk in a THEMIS-like population compared to MI patients, where treatment with DAPT is guideline standard. The aim of this study was to investigate the CV risk in a THEMIS-like population vs an MI population

Methods

Patients invasively managed in Sweden (2006–2014) were identified using the SWEDEHEART registry and the National Patient Registry. Two populations were studied: a THEMIS-like population including patients with CAD and T2D, ≥1 vessel disease or elective percutaneous coronary intervention [PCI], and no prior stroke or MI), and a MI patient population alive at discharge. The cumulative incidence of the primary composite outcome (CV death (CVD)/MI/stroke) was estimated 3 years after index using the Kaplan-Meier method, and with probability plots adjusted for age, sex, atrial fibrillation, and heart failure. A 30 days blanking period for outcome was added to ensure capture of new events (index THEMIS-pop.: after angiography; index MI-pop.: after discharge).

Results

Overall, 6,534 THEMIS-like patients and 96,638 MI patients were included. At index, the THEMIS-like patients (CAD and T2D without previous MI/stroke) were aged 67.1 years (mean), 26.6% women, 9.2% AF, and 4.7% HF, while the MI patients were aged 67.3 years (mean), 30.7% women, 15.5% T2D, 17.9% previous MI, 5.2% stroke, 6.4% AF, and 4.8% HF. Three-year cumulative incidence for the composite outcome CVD/MI/stroke was 0.149 (95% CI 0.140, 0.158) for THEMIS-like patients, and 0.148 (95% CI 0.145, 0,15) for MI patients (p=0.88 log rank test) (Figure). Corresponding adjusted probably plots: 0.135 (95% CI 0.127, 0.143) and 0.131 (95% CI 0.128, 0.133). MI was the main risk driver with greatest cumulative incidence in both populations (0.091 vs 0.087) (Figure).

Figure 1

Conclusions

In this Swedish real-life setting, THEMIS-like patients, followed from 30 days after invasive intervention, had a similar long-term risk for CV events compared with MI patients surviving 30 days after discharge, with MI as the main risk driver, despite having no previous ischemic events. The present data indicate that long-term ischemic risk prevention should be a key strategy in coronary artery disease patients with diabetes requiring elective invasive intervention.

Acknowledgement/Funding

AstraZeneca
2208The interaction effect between myocardial infarction and comorbidity: nationwide cohort study
Authors: Schmidt M , Horvath-Puho E , Ording A G , Lash T L , Botker H E , Sorensen H T
Published: October 2019

Background

Comorbid diseases may influence the prognosis of acute myocardial infarction (MI) directly by increasing the mortality hazard and indirectly by modifying treatment intensity.

Purpose

To examine whether comorbid diseases and MI interact to increase mortality beyond the sum of their independent effects.

Methods

Using Danish medical databases, we conducted a nationwide cohort study of patients diagnosed with MI between 1995 and 2016 (n=179,515) and a comparison cohort of persons without MI (n=880,347)matched on age, sex, and comorbidities in the Charlson Comorbidity Index. The study outcome was time-to-death and the cohorts were followed from the MI/index date until death, emigration, five years of follow-up, or 31 December 2016, whichever came first. Standardized mortality rates with 95% confidence intervals (CIs) were computed using age and sex weights based on the inception MI cohort. The interaction was examined on the additive scale by calculating the interaction contrasts (the difference in rate differences), which measure the combined mortality effect of MI and comorbidity that cannot be explained by summing their individual effects. The follow-up period was stratified by the first 30 days, 31-days to one year, and >1–5 year after the index date. Analyses were repeated within strata of comorbidity levels (1, 2–3, 4+).

Results

62% of patients were male. The median age was 70 (interquartile range: 60, 80) years. Among individuals without comorbidity, the mortality rate per 1000 person-years during 30-day follow-up was 1,851 (95% confidence interval: 1,818 to 1,884) for myocardial infarction patients and 22 (21 to 24) for comparison cohort members, yielding a rate difference of 1,829. For individuals with low comorbidity, corresponding baseline mortality rates per 1,000 person-years were 2,498 (2,436 to 2,560) in the myocardial infarction and 54 (50 to 57) in the comparison cohort (rate difference=2,444). The interaction contrast was 616, indicating that the interaction accounted for 25% (616/2,498) of the total mortality rate in MI patients with low comorbidity. The percentage of the 30-day mortality rate explained by interaction increased further for moderate (35%) and severe (45%) comorbidity levels. Absolute and relative interaction effects were largest within the first 30 days, but similar dose-response patterns were observed during 31–365 days and 1–5 years of follow-up (all p-values for trends<0.002).

Conclusions

Comorbidities interact with myocardial infarction to increase short- and long-term mortality beyond that explained by the additive effect of myocardial infarction and comorbid diseases acting alone

Acknowledgement/Funding

Department of Clinical Epidemiology's Research Foundation; Program for Clinical Research Infrastructure (PROCRIN)
2210Symptomatic severe aortic stenosis: predictor factors and outcomes
Authors: Almeida I , Gomes R , Joao I , Cruz I , Pereira R , Quadrado M , Pereira H
Published: October 2019

Introduction

The natural history in aortic stenosis (AS) is a slowly progressive process which begins as aortic sclerosis and subsequently progresses to severe opening restriction, conditioning symptoms development. At this time, surgical aortic valve replacement is strongly recommended due to its poor prognosis.

Purpose

Evaluation of predictor factors of symptomatic severe AS and its prognostic impact.

Methods

Single center retrospective analysis of patients' data accompanied in cardiology consultation due to severe AS diagnosed between 2015–2016. Data was collected regarding clinical and echocardiographic parameters to determine predictor factors of stablished endpoints.

Results

150 patients were reviewed, mean age 76.6±9.0 years, 72% males. 68.7% had hypertension, 42% dyslipidaemia and 32.7% diabetes. 64.7% of the patients had symptoms attributable to severe AS: 48% dyspnoea, 12% angina and 4.7% syncope. 7.3% of the patients were hospitalized due to acute heart failure in this context. Comparing echocardiographic parameters between symptomatic versus non-symptomatic patients with severe AS, symptomatic patients had higher values of aortic maximum velocity (4.5±0.5 vs 4.3±0.4 m/sec, p<0.001) and mean gradient (50.1±12.7 vs 43.2±7.7 mmHg, p<0.001). There were no significant differences regarding mean aortic valvular area neither left ventricle ejection fraction. At univariate analysis, predictor factors of symptoms attributable to severe AS development were: hypertension (odds ratio (OR) 2.044, confidence interval (CI) 1.004–4.161, p 0.049), anaemia (OR 0.420, CI 0.207–0.851, p 0.016), aortic maximum velocity (OR 5.497, CI 2.014–15.000, p 0.001) and mean gradient (OR 1.073, CI 1.029–1.118, p 0.001). At multivariate analysis, only aortic maximum velocity showed to be independent predictor factor of symptomatic severe AS (p 0.012). Hospitalization and all-cause mortality rates (respectively: 9.3 vs 9.4%, p 0.975; and 25.8 vs 34%, p 0.305) did not differ between groups.

Conclusion

In patients with severe AS, aortic maximum velocity showed to be the only independent predictor factor of symptoms development, however it was not associated with an increased hospitalization or mortality rates.
2227Limited impact of concomitant coronary artery by-pass grafting on long-term outcomes after surgical aortic valve replacement: a nationwide propensity matched study
Authors: Kyto V , Sipila J , Pikkarainen E , Rautava P , Gunn J
Published: October 2019

Objective

Coronary artery disease is a common comorbidity of aortic stenosis. Addition of coronary artery by-pass grafting (CABG) to surgical aortic valve replacement (SAVR) is viable solution for treating both. Modern era impact of concomitant CABG to long-term outcomes is however inadequately known. We set out to study long-term outcomes of patients with or without CABG added to SAVR.

Methods

Patients (excluding infective endocarditis) aged ≥50 years with isolated first-time SAVR with or without CABG in Finland between 2004–2014 (n=7060) were retrospectively studied using nationwide registries. Propensity score matching (1:1) was used to identify patients with comparable baseline features (n=2188 with and n=2188 without concomitant CABG). Outcomes were 10-year all-cause mortality, stroke, major bleeding and myocardial infarction. Median follow-up was 6.1 years.

Results

In matched population mortality after SAVR was comparable with or without CABG (31.0% vs. 32.7%; HR 1.05; CI 0.93–1.20; p=0.428). However, if CABG was performed solely with venous grafts mortality was higher (35.9%; HR 1.21; CI 1.02–1.43; p=0.030 vs. no-CABG). Myocardial infarction was more common in patients with CABG (13.4% vs. 6.9%; HR 1.62; CI 1.22–2.17; p=0.0008). Occurrence of stroke was comparable with or without CABG (15.1% vs. 13.5%; p=0.933). Rate on any major bleeding was also comparable (20.0% with vs. 21.9% without CABG; p=0.496). Gastrointestinal (8.1% vs. 10.3%; p=0.978) and intracranial bleeds (6.0% vs. 5.5%; p=0.383) were also comparable between study groups.

Conclusions

Matched patients with or without concomitant CABG had comparable long-term mortality, stroke and major bleeding rates after SAVR. Our results suggest that successful concomitant CABG has limited impact on long-term outcomes after SAVR.

Acknowledgement/Funding

Finnish Cardiac Society, Finnish Cultural Foundation, Governmental VTR-funding
2395LGE CMR predicts sudden death and VT in adults with repaired tetralogy of Fallot - a prospective study with 3500 patient follow up years
Authors: Ghonim S , Gatzoulis M A , Smith G C , Heng E , Ernst S , Li W , Keegan J , Diller G P , Dimpoulos K , Moon J C , Pennell D J , Babu-Narayan S V
Published: October 2019

Background

Adults with repaired tetralogy of Fallot (rtoF) are at risk of ventricular arrhythmia and sudden cardiac death (SCD). Cross-sectional data suggest association of late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) with adverse clinical risk factors

Purpose

We sought to determine prognosis related to LGE CMR.

Methods

In this prospective cohort study the primary composite outcome comprised the first of cardiovascular death (SCD or heart failure-related), aborted SCD (successfully resuscitated cardiac arrest or appropriate AICD shock for ventricular fibrillation), and clinical sustained ventricular tachycardia (VT>30 seconds duration).

Results

In 531 rtoF patients (median age 32; 23–42, 296 (56%) male, NYHA≥II 17%) followed up after LGE CMR for median 5 (1.7–8.9) years, there were 39 primary composite outcomes: 10 SCD, 11 heart failure related deaths (2 perioperative RV failure), 2 aborted SCD and 16 clinical sustained VT events. At study end, there were 28 ventricular arrhythmic events in 28 rtoF patients (10 SCD, 16 clinical sustained VT, 2 aborted VF) that were significantly predicted by RV LGE extent (HR 1.45 CI: 1.3–1.6; P<0.001).

Univariable predictors of the primary outcome were RV LGE score; HR: 1.44 (1.31–1.57; p<0.001), (Figure) together with older age; HR: 1.05 (1.02–1.07; P<0.001), late repair; HR: 1.04 (1.02–1.07; p<0.001), lower RV ejection fraction; HR: 0.92 (0.89–0.95; p<0.001), larger RVOT akinetic length; HR: 1.04 (1.02–1.06; p<0.001) larger right atrial area; HR: 1.2 (1.12–1.29; p<0.001); higher BNP levels; HR: 1.01 (1–1.02; p<0.001), lower peak VO2; HR: 0.89 (0.83–0.96; p=0.001), prior atrial arrhythmia; HR: 5.3 (2.8–10.07; p<0.001), and non-sustained VT; HR: 4.1 (2.1–7.7; p<0.001). Inducible VT did not predict the primary outcome; HR: 2.1 (0.57–8; p=0.25)

In multivariable analysis both RV LGE score and indexed right atrial area (RAAi) only, remained predictive of the primary outcome (HR 1.29 CI: 1.12–1.49; p<0.001 and HR 1.1 CI: 1.02–1.12; p=0.01, respectively). Patients could accordingly be stratified such that supramedian RV LGE score (≥5) and RAAi ≥16cm2/m2 had 5-year event free survival 84% vs 94% for supramedian RV LGE score (≥5) and RAAi <16cm2/m2 or 98% for inframedian RV LGE score with RAAI<16cm2/m2. Figure.

Conclusions

For every unit increase in CMR defined RV fibrosis score there is a 44% increased risk of sudden cardiac death and VT. LGE CMR and maximal right atrial area should therefore be incorporated into risk stratification for sudden death in adults with rTOF.

Acknowledgement/Funding

British heart foundation
2422Outcome of histologically-proven fulminant versus acute non-fulminant myocarditis with left ventricular systolic dysfunction. Evidence from the International Registry on Acute Myocarditis
Authors: Ammirati E , Veronese G , Brambatti M , Merlo M , Potena L , Okumura T , Pinney S , Braun O , Van De Heyning C M , Montero S , Shimokawa H , Sinagra G , Adler E , Frigerio M , Camici P G
Published: October 2019

Background

Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular (LV) dysfunction requiring inotropes and/or mechanical circulatory support. Based on a retrospective single-center study published in 2000, patients with FM were considered to have better outcomes than those affected by acute non-fulminant myocarditis (NFM) presenting with LV systolic dysfunction (LVSD). Recently, this tenet was challenged, though substantial disagreement still exists.

Purpose

Aim of the present study is to provide additional evidence on the outcome of FM and to ascertain if patient stratification based on the main histologic subtypes can provide additional prognostic information.

Methods

Two hundred and twenty patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms <30 days) presenting with LVSD were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The primary endpoint was the occurrence of cardiac death or heart transplant (HTx) within 60 days from admission and at long-term follow-up.

Results

Patients with FM (N=165) had significantly higher rates of cardiac death and HTx compared with those with NFM (N=55), both at 60 days (28.0% vs. 1.8%, p=0.0001) and at 7-year follow up (47.7% vs. 10.4%, p<0.0001; Figure). At Cox-multivariate analysis, the histologic subtype emerged as a further variable affecting outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis both at 60 days (62.5% vs. 26.3% vs. 21.0%) and at 3 years (81.3% vs. 39.9% vs. 37.3%, overall p<0.0001). In a sub-analysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with NFM both at 60 days (19.5% vs. 0%, p=0.005) and up to 7 years (41.4% vs. 3.1%, p=0.0004).

Outcome of FM vs NFM

Conclusions

The results of this international registry confirm that patients with FM have higher rates of cardiac death and HTx both in the short and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.

Acknowledgement/Funding

None
2425Evaluation of myocardial gene expression profiling for superior diagnosis of idiopathic giant cell myocarditis in a large cohort of patients with acute cardiac decompensation
Authors: Escher F , Pietsch H P , Gross U G , Lassner D L , Schultheiss H P
Published: October 2019

Background

Idiopathic giant cell myocarditis (IGCM) diagnostics is based on differential patterns of inflammatory cell infiltration, and multinucleated giant cells (GCs) in histological sections of endomyocardial biopsies (EMBs). However, the sampling error is high for the detection of focally GCs by histopathology. We report on a clinical evaluation of a recently published method for improved differential diagnosis of this frequently fatal disease by myocardial gene expression profiling.

Objective

This is to improve the diagnostics of IGCM by gene expression profiling, and to demonstrate the feasibility of this method in clinical practice in a large cohort of patients.

Methods

In this multicenter study, EMBs of n=427 patients with clinically acute cardiac decompensation and suspected acute myocarditis were screened (mean age 47.03±15.69 years). In each patient, EMBs were analyzed by histology, immunohistology, molecular virology, and gene expression profiling.

Results

Out of the total of n=427 patient samples examined, GCs could be detected in 26 cases (6.0%) by histology. An established myocardial gene profile – consisting of 27 genes – was revealed resulting in a specified profile of 5 genes (chemokine receptor 5 (CCR5), chemokine receptor 6 (CCR6); carnitine palmitoyltransferase I (CPT1), toll-like receptor 8 (TLR8), and chemokine (C-C motif) ligand 20 (CCL20)) which identified histologically proven IGCM with high specificity in 25 of the 26 patients (96.2%). Applying this newly established profiling on the remaining patient samples, additional n=31 (7.3%) patients were identified for IGCM without any histological proof of myocardial GCs.

Conclusions

Myocardial gene expression profiling is a reliable method in clinical practice to predict IGCM even without direct histological proof of GCs in EMB section. The gene profiling is of high clinical relevance to overcome the sampling error of purely histological examination, and to control the effectiveness of the therapy. The data clearly show the importance to take EMB in unexplained acute decompensation to get a diagnosis and improve the prognosis.
P1216Evaluation of alphavbeta3 integrin-targeted positron emission tomography and photoacoustic tracer for imaging of carotid plaque in apoE–/– mice
Authors: Yao Y , Li L B , Ji Y , Ma G , Wu Y , Hu X , Yang M , Fan Q
Published: October 2019

Background

Cardiovascular disease is the leading cause of death in the world. The majority of cardiovascular events result from the rupture of vulnerable atherosclerotic plaques, which are characterized by high and active macrophage content. The integrin αVβ3 is expressed by activated macrophages and endothelial cells in atherosclerotic lesions and thus is a marker of high-risk plaques. Therefore, 89Zr-RGD-melanin nanoparticle (MNP) positron emission tomography (PET)/photoacoustic imaging (PAI) imaging of αVβ3 expression in plaques might provide a novel noninvasive biomarker of plaque vulnerability.

Purpose

In this study, the intrinsic photoacoustic signals and the native strong chelating properties with metal ions of MNP, positron-emitting metal ions 89Zr and αVβ3 integrins targeting ability of cyclic c (RGDfC) peptide was employed to construct an efficient nanoplatform. And we evaluated the feasibility of 89Zr-RGD-MNP PET/PAI of αVβ3 expression in vivo and in vitro.

Methods

We conjugated αVβ3 integrins, cyclic c (RGDfC) peptide, to MNP and chelated the long-lived positron-emitting nuclide 89Zr. The bio-stability and targeting action was detected in macrophages. And the PET/PAI imaging was performed in apoE−/− mice with partial carotid ligation leading to atherosclerosis. In PET imaging, tracer uptake was measured in the stenotic areas of the carotid arteries, as well as on the contralateral side at different time points in vivo. In PAI, photoacoustic signal was measured in the atherosclerosis of the carotid arteries in vivo. Melanin staining and immunohistochemistry of αVβ3 expression were detected in atherosclerosis of the carotid arteries.

Results

89Zr-RGD-MNP showed excellent bio-stability and targeting action. PET imaging showed specific tracer accumulation at plaques in the left carotid artery, confirmed by competitive receptor blocking studies and the contrast in the right carotid artery. In the biodistribution studies, the left carotid (5.29%±0.78%) showed higher uptake than the right carotid (2.11%±1.55%). PAI showed the PA signal in the surgery group (452±85 a.u.) were stronger than the control (156±45 a.u.) and blocking group (254±66 a.u). The result was consistent with PET imaging and the presence of nanoparticles, as indicated by pathological examinations. These results presented good in vivo multimodality imaging (PET/PAI) properties.

Conclusions

We have developed 89Zr-labeled atherosclerotic plaques imaging agents based on the natural melanin nanoparticle. 89Zr-RGD-MNP demonstrates specific tracer accumulation in mice atherosclerotic carotid plaques. In this model, its uptake was associated with αVβ3 expression. 89Zr-RGD-MNP is a potential tracer for noninvasive imaging in atherosclerosis.

Acknowledgement/Funding

National Natural Science Foundation of China 81770452, 81470401
P1224Statin treatment in children with familial hypercholesterolemia in Scandinavia
Authors: Svendsen K , Walaas Krogh H , Bogsrud M P , Holven K B , Retterstol K
Published: October 2019

Introduction

New European guidelines recommend that patients with familial hypercholesterolemia (FH) should initiate treatment with statins at age 8–10 years. The number of children using statins has not yet been investigated. The aim of the present study was to describe the number of statin users <19 years of age in the Scandinavian countries: Sweden, Denmark and Norway.

Methods

In the Scandinavian countries, statins are only available by prescription, and there are national registries for the use of perscriptional drugs. In the present study, we assumed that the number of children using statins is equivalent to a positive FH diagnosis in these countries. Using the estimated frequency of FH of 1:250, we calculated the number of expected children with FH per year. Next, the percentage of all FH children who were treated according to the national registries were calculated. We also calculated changes between 2006 and 2016.

Results

As shown in Table 1, 1086 children 5–19 years in Scandinavia used statins in 2016. In the ages 10–19 years, statins were more frequent used in Norwegian FH children than in children from Denmark and Sweden (Figure 1). Nevertheless, the number of children aged 5–19 years using statins increased from about 2% to 4% between 2006 and 2016 in Sweden and Denmark (n=109 and n=136 respectively) and from about 5% to 10% in Norway (n=340).

Discussion

We observed a modest increase in statin users aged 5–19 years in the Scandinavian countries during a 10-year period. Nevertheless, our findings indicate that it will take decades to implement the current Statin-recommendation. Possible reasons for the difference in the degree of treatment between the countries will be discussed during the presentation, in particular with respect to genetic testing and cascade screening.

Table 1. Statin use according to age and gender Age (year) Male, N (%) Female, N (%) Both Sexes, N (%) 5–9 36 (3) 30 (3) 67 (6) 10–14 158 (15) 127 (12) 294 (27) 15–19 327 (30) 395 (36) 725 (67) 0–19 521 (48) 552 (51) 1086 (100)

Figure 1. Percent of FH children using statins

Conclusions

Despite increased statin use during the last years, there is still a severe undertreatment of children with FH in the Scandinavian countries.
P1234Weight fluctuation demonstrates residual atrial arrhythmogenic substrate despite final weight loss in a chronic sheep model: implications for epicardial fat and fibrofatty infiltrates
Authors: Agbaedeng T A , Twomey D J , Thanigaimani S , Linz D , Lau D H , Mahajan R , Sanders P
Published: October 2019

Background

Obesity-mediated epicardial adipose tissue (EAT) expansion drives fat cell infiltration which forms the unique substrate for atrial fibrillation (AF). The LEGACY study showed the benefits of weight loss but an attenuated response with weight fluctuation. How fluxes in weight impacts the atrial substrate in not known.

Objective

To investigate EAT and the atrial substrates due to weight fluctuation, with comparison to stable obesity.

Methods

We studied 24 sheep in 3 equal groups over 80 weeks: 1. Obesity induced by high calorie diet fed ad libitum; 2. Weight fluctuation induced by 20-week cycle of weight gain/loss (20:20:20:20); and 3. Lean controls fed quality hay to maintain baseline weight. All sheep underwent: daily weight measurement; haemodynamic and imaging assessments (cardiac MRI; dual-energy X-ray absorptiometry; and matrix assisted laser desorption infrared lipid imaging); electrophysiological studies and electroanatomic mapping; histological and structural analysis. Evaluations included: atrial voltage, conduction velocity, and refractoriness (7 sites, 2 cycle lengths), electrogram fractionation, EAT volume, fibro-fatty infiltration, myolysis of myocytes, and spatial distribution of intra-atrial lipids.

Results

The Table shows the group differences. Compared to reference controls, obesity demonstrated: Increased atrial volume and pressure, abnormal atrial electrical properties, expanded EAT and ensuing fibro-fatty infiltrations, and myolysis of myocytes. Despite comparable weight and EAT with controls, weight fluctuation resulted in extensive and severe fibro-fatty infiltrations, and twofold greater myolysis that persisted. Moreover, characteristic profiles and abundance of lipid species in the atrial myocardium were noted on further evaluation. More importantly, EAT and fibro-fatty infiltrates strongly correlated with increased atrial volume and pressure; with only fibro-fatty infiltrates correlating with fractionated electrograms (r=0.71, p<0.001) and conduction slowing (r=−0.59, p=0.006). Similarly, atrial myolysis exhibited significant correlations with atrial enlargement and haemodynamics, and electrical substrates (p<0.05 for all).

Conclusions

Obesity induces fibro-fatty replacement of atrial myocytes and deterioration of contractile units, which may drive impaired electrical remodeling. Despite final weight loss, weight fluctuation demonstrates residual electro-structural, fibro-fatty and contractile substrates.