bluuebunny/crossref_metadata_2025 huggingface dataset:
P1621m6A RNA-methylation in the progression of heart failure
Authors: Buchholz E , Berulava T , Ellerdashvilli V , Pena T , Lbik D , Mohamed B , Sloan K , Bohnsack M , Hasenfuss G , Fischer A , Toischer K
Published: October 2019

Introduction

N6-Methyladenosine (m6A) is the most abundant modification of RNA and was found to be a dynamic and reversible process. It is found in many classes of RNA, such as mRNA, noncodingRNA (ncRNA) and microRNA (miR). mRNA methylation can affect splicing, transport and storage or decay, ncRNA methylation might influence signal transduction directly as well as it might affect miR interference. Deregulation of such epigenetic processes and aberrant gene expressions are important mechanisms in heart failure. Here we studied the potential relevance of m6A RNA-methylation in cardiac hypertrophy and heart failure development.

Methods and results

m6A RNA-methylation was analysed via methylated RNA immunoprecipitation (meRIP) and subsequent next generation sequencing (NGS). Our data shows that approximately one quarter of the transcripts in the healthy mouse (24.09%) and human heart (14.6%) exhibit m6A RNA-methylation. A mild positive correlation of m6A RNA-methylation at the 5'UTR and coding region with transcript level was observed while m6A RNA-methylation at the 3'UTR showed a mild negative correlation.

We analysed heart failure in mice and humans and observed that changes in m6A RNA-methylation exceed changes in gene-expression (in human data 1219 differentially methylated and 198 diff. expressed, with 30 showing changes in both methylation and expression; in mouse data 1135 diff. methylated and 127 diff. expressed, with 47 showing changes in both methylation and expression). In mouse and human heart failure, transcripts with altered m6A RNA-methylation were mainly linked to metabolic and regulatory pathways while changes in transcript level mainly represented changes in structural plasticity. In the diseased state m6A RNA-methylation showed no correlation to transcript level. To gain further insight into m6A mediated effects on the translational level, polysome-sequencing was applied. These data provide evidence that in the diseased heart changes in m6A RNA-methylation affect RNA translation, represented by a positive correlation (r=0.37, p=2.2e-16) of log2fc changes in translation and m6A methylation.

Conclusions

Our study describes m6A RNA-methylation at the genome-wide level in the human heart. The mouse model provides evidence that changes in m6A RNA-methylation plays an important role in heart failure development by affecting regulatory pathways distinct from those genes with altered expression levels. Our data suggest that modulation of epitranscriptomic processes such as m6A-methylation might be an interesting target for therapeutic interventions.

Acknowledgement/Funding

CRC 1002
P1622Cancer drugs induce functional and structural impairment in adult cardiomyocytes
Authors: Altomare C , Biemmi V , Torre E , Rocchetti M , Ferrandi M , Pernigoni N , Barile L , Milano G , Vassalli G
Published: October 2019

Introduction

The addition of anti-human epidermal growth factor receptor 2 (HER2; ErbB2) monoclonal antibody Trastuzumab (TRZ) to Doxorubicin (DOXO) chemotherapy is associated with a synergistic increase in cardiac toxicity. While previous studies have addressed the toxicity of both agents on isolated cardiomyocytes (CMs), little is known regarding this process in vivo, especially with respect to electrophysiological changes.

Purpose

To investigate electrical and structural changes in LV and RV CMs using an in vivo rat model of DOXO/TRZ cardiotoxicity.

Methods

Rats received 6 IP injections of either DOXO or TRZ over a 2-week period, or 6 doses of DOXO followed by 6 doses of TRZ (COMBO), or saline as a control. In-vivo echocardiography was performed. Electrical activity and Ca2+ handling were assessed in LV and RV CMs from rat hearts. Single cell patch-clamp and field stimulation experiments were performed. Spontaneous sarcoplasmic reticulum Ca2+ release events (Ca2+ sparks) were recorded at x100 magnification in line-scan mode (sampling rate 0.7 kHz) from 2 μM Fluo4-AM loaded CMs. To assess T-tubular disarray, CMs were incubated with di-3-ANEPPDHQ and periodic component was quantified by Fast Fourier Transform (FFT) analysis of confocal microscopy images.

Results

DOXO, and to a greater extent COMBO treatment was associated with significant increases in both LV end-systolic and end-diastolic volumes, and decreases in LVEF and fractional shortening. By contrast, TRZ alone merely increased LV end-systolic volume. Electrophysiological studies showed increases in action potential duration (APD), beat-to-beat variability of repolarization (BVR), delayed after depolarizations (DADs), and Ca2+-sparks in both DOXO and COMBO groups. Stimulated intracellular Ca2+ transients (1,2 and 4 Hz) showed significant changes with respect to time to peak, tau decay, amplitude, and fractional release in the DOXO group. These changes were associated with a significant downregulation of sarco/endoplasmic reticulum Ca2+ ATPase pump (SERCA) expression. From a structural viewpoint, these changes were associated with T-tubular disarray in the DOXO and COMBO groups.

Conclusions

DOXO, and to a greater extent COMBO treatment (but not TRZ alone) cause LV dysfunction in vivo. Moreover, both DOXO and COMBO treatments, but not TRZ alone, induce electrophysiological abnormalities and both structural and functional changes in the sarcoplasmic reticulum. These findings provide novel insights into the cellular mechanisms of CM dysfunction and arrhythmias associated with combined DOXO/TRZ therapy.

Acknowledgement/Funding

Swiss League against Cancer
P1664Pharmacological treatment patterns in heart failure: a real world cohort study
Authors: Bosco-Levy P , Favary C , Jove J , Lassalle R , Moore N , Droz-Perroteau C
Published: October 2019

Background

Although the efficacy and safety of existing therapies of heart failure (HF) have been demonstrated in clinical trials in the last 35 years, little is known about the treatment patterns of HF in clinical practice, especially in France.

Objectives

To describe the treatment initiation patterns and the subsequent treatment changes among HF patients, in the first year following an incident hospitalisation for HF, in a French real-world setting.

Methods

A cohort of patients aged 40 years old and older, with an incident hospitalisation for HF between January 1, 2008 and December 31, 2013, was identified in the EGB, a 1/97 permanent random sample of the French nationwide claims database. All patients who died during the index hospitalization or with a period of at least 3 consecutive months with no healthcare dispensing recorded were excluded. All included patients were followed one year. HF drugs of interest were: beta blockers (BB), angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), aldosterone antagonists (AA), diuretics, digoxin or ivabradine. Drug exposure was assessed quarterly using a Proportion of Days Covered >66% (>60 days out of the 90 days of the quarter covered by the treatment of interest), by considering HF drugs individually or in combination. Drug changes were assessed between each quarter over the first year of follow-up.

Results

Between 2008 and 2013, 7,387 from the EGB were included in the cohort study. The mean age at baseline was 77.7 years (±12.0 years) and 51.6% were women. During the follow-up, 24.4% of patients died and 20% did not receive any HF treatment. During the first quarter following initial hospitalisation, 42.7% of patients had diuretics, 26.0% had BB, 25.7% had ACEI, 7.4% had ARB, 7.6% had AA, 4.7% had digoxin and 1.3% had ivabradine. the most frequent combination was BB/ACE/ARB (23.4%). These proportions remained globally constant in each quarter of the follow-up. The main change occurred between thee first and the second quarter and concerned 53.1% of the initially untreated patients; by the second quarter, 22.2% of them initiated a BB/ACI/ARB combination, 13% a diuretic alone, 7.4% a BB and 4.9% a BB/ACI/ARB/AA combination.

Conclusion

This study provides precious information on treatment patterns after an initial hospital admission for HF at a time when new treatments for HF are emerging.

Acknowledgement/Funding

None
P1670Incidence and prognosis of late-onset right ventricular failure following continuous-flow left ventricular assist device implantation as bridge to transplantation
Authors: Ruiz Cano M J , Schoenbrodt M , Paluszkiewicz L , Laurenroth V , Al-Khalil R , Kizner L , Gummert J , Morshuis M
Published: October 2019

Early right ventricular failure (RVF) remains a frequent complication and is one of the main factors associated to early mortality following left ventricular assist device (LVAD) implantation. However, late-onset RVF (LoRVF) has emerged as an increasing concern, but little is known about its incidenceand underlying mechanisms.

Methods and results

We retrospectively analysed the 1-year hemodynamic and clinical data from all patients that, between 2016 and 2018, underwent a right heart catheterization (RHC) after continuous-flow LVAD implantation as bridge to transplantation. Sixty-six patients (84% males, 53±11 years, 60% implanted in Intermacs 1–2, 52% HeartWare LVAD, 48% HM3 LVAD), out of 187 LVAD implants, were studied. LoRVF was defined as central venous pressure>18 mmHg with cardiac index<2.3 L/min/m2 during RHC.

LoRVF was present in 17 patients (25.7%) and 12 (71%) of them manifested concomitant clinical signs of RVF. Eleven of the patients who presented LoRVF (65% of the LoRVF) had a pulmonary capillary wedge pressure (PCWP)>15 mmHg. Isolated LoRVF (LoRVF criteria + PCWP≤15 mmhg) was found in 6 patients (35% of the LoRVF) and accounted for 9% of the studied population. Fifty percent of patients who presented isolated LoRVF could be successfully transplanted in high urgent status due to severe chronic RVF and 1 patient died to refractory RVF. We did not find an association between isolated LoRVF and age, renal function, type of LVAD, persistent increased pulmonary vascular resistances or the previous need of temporary right ventricular support due to early acute RVF following LVAD. There was however a significant association between the presence of atrial fibrillation and isolated LoRVF (p<0.05).

Incidence and prognosis of LoRVF

Conclusion

Late-onset RVF is a frequent complication during LVAD support as bridge to transplantation. Most of the cases are associated to a lesser degree of left ventricular unloading. The presence of isolated late-onset RVF with normal PCWP has an impact on the long-term prognosis and the need of urgent heart transplantation and is not related to early RVF following LVAD implantation or persistent increased pulmonary vascular resistance.
P1683Optimal serum uric acid levels for hypertension: 5-year cohort study
Authors: Kuwabara M , Niwa K , Hisatome I
Published: October 2019

Background

Although hyperuricemia is known as a risk factor for hypertension, the optimal range of serum uric acid (SUA) for preventing hypertension has not been established, especially in a healthy population.

Methods

This is a 5-year cohort study to clarify the optimal SUA for hypertension. Subjects consisted of Japanese adults between 30 and 85 years of age were enrolled in the study at our Center for Preventive Medicine, and available at enrollment (2004) and at 5-year follow-up (2009). We excluded the study subjects who were hypertensive, diabetic, dyslipidemic, had a history of gout or hyperuricemia on medications, or if they had chronic kidney disease as estimated glomerular filtration rate <60 ml/min/1.73m2. Linear and logistic regression analyses were used to examine the relationship between each 1 mg/dL of serum uric acid range and development of hypertension with multiple adjustments for age, smoking, drinking habits, body mass index and baseline systolic blood pressure.

Results

Of 13,070 subjects enrolled at this step, we included 6,476 subjects (46.9±10.1 years old, 34.6% men) without comorbidities. The cumulative incidences of hypertension over 5 years were 5.9% in women and 12.1% in men. The lowest cumulative incidences of hypertension were 2.6% in 2.0–3.0 mg/dL of serum uric acid in women and 6.9% in 4.0–5.0 mg/dL in men. In contrast, the highest uric acid range showed highest cumulative incidence of hypertension both in women (28.6% in 8.0–9.0 mg/dL) and men (21.0% in ≥9.0 mg/dL). Hypouricemic (<2.0 mg/dL) subjects had higher cumulative incidences of hypertension than subjects with 2.0–3.0 mg/dL of serum uric acid levels, we excluded these subjects in multivariable logistic analysis. The odds ratio of 1 mg/dL increase of serum uric acid for developing hypertension was 1.395 (95% CI, 1.182–1.648) in women and 1.139 (95% CI, 1003–1.294) in men after multiple adjustments.

Conclusion

The optimal serum uric acid range for preventing hypertension was 2.0–3.0 mg/dL in women and 4.0–5.0 mg/dL in men. Higher uric acid levels increase cumulative incidence of hypertension.

Acknowledgement/Funding

None
P1719Sex-specific PCI strategies in patients with AMI and cardiogenic shock: a substudy of the culprit-shock trial
Authors: Rubini Gimenez M , Zeymer U , Desch S , De Waha-Thiele S , Ourrak T , Meyer-Saraei R , Schneider S , Fuernau G , Akin I , Savonitto S , Jeger R , Thiele H
Published: October 2019

Background and purpose

Women are more likely to suffer from a cardiogenic shock (CS) as the most severe complication of an acute myocardial infarction (AMI) and tend to have a higher mortality. Data concerning optimal management among women with CS are lacking. Aim of this study was therefore to better define characteristics of women suffering a CS and to investigate the influence of sex on different coronary revascularisation strategies

Methods and results

In the CULPRIT-SHOCK trial, patients with CS complicating AMI and multivessel coronary artery disease were randomly assigned to one of the following coronary revascularisation strategies: either percutaneous coronary intervention (PCI) of the culprit lesion only or immediate multivessel PCI. Primary end-point was a composite of death from any cause or severe renal failure leading to renal-replacement within 30 days after randomisation. We investigated sex-specific differences in general and according to the revascularisation strategies.

Among all 706 randomised patients 26% were women. After 30 days, the primary end-point occurred in 55% women and 49% men (p=0.20), showing a relative risk of 1.14; 95% CI 0.94–1.38; p=0.17, women vs. men. Those women were older, more frequent diabetic and had more peripheral artery disease and less frequent smokers and less often family history of coronary artery disease.

Regarding revascularisation strategy the composite end-point occurred in 55.8% women treated with the culprit-only strategy (vs. 42.4% men, p=0.04) and in 54.7% women in the multivessel group (vs. 55.6% men, p=0.99). This resulted in a no-significant difference among both groups (interaction p-value of 0.11).

Conclusions

In this large randomised trial among patients with multivessel coronary disease and CS complicating AMI, women had similar outcome for mortality and severe renal failure. Sex did not show to influence mortality and renal failure according to the different coronary revascularisation strategies. These data suggest that women and men presenting with CS should be treated equally.
P1732The additive value of pre- and post-reperfusion cardiac troponin T levels in risk stratification of patients with ST-segment elevation myocardial infarction
Authors: Coelho-Lima J , Ahmed J , Georgiopoulos G , Adil S E R , Gaskin D , Bakogiannis C , Sopova K , Ahmed F , Ahmed H , Bagnall A , Stellos K , Stamatelopoulos K , Spyridopoulos K
Published: October 2019

Background

Despite therapeutic advances, mortality rates following ST-segment elevation myocardial infarction (STEMI) are still alarmingly high. There is conflicting evidence regarding the prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) measurements before and after primary percutaneous coronary intervention (PPCI) over traditional predictors of mortality in STEMI patients.

Purpose

To determine the additive prognostic value of pre- and 12h post-PPCI hs-cTnT levels in STEMI patients

Methods

Retrospective longitudinal study including 3,113 consecutive STEMI patients treated with PPCI at a university hospital covering a population of 1.6 million in the North East of England. Clinical, procedural, and laboratory data were prospectively collected during patient hospitalization while hs-cTnT measurements were performed at admission to the catheterization laboratory and at 12h post-PPCI. Median follow-up was 53 months. The study endpoints were in-hospital and overall mortality. Mortality data were obtained from the UK Office of National Statistics.

Results

Admission hs-cTnT >515ng/L (4th quartile) was independently associated with in-hospital mortality [HR=2.39 per highest to lower quartiles; 95% CI: 1.44 to 3.97; p=0.001] after multivariate adjustment for a core clinical model of in-hospital mortality prediction. Likewise, admission hs-cTnT >515ng/L independently predicted overall mortality (HR=1.25 per highest to lower quartiles; 95% CI: 1.00 to 1.57; p=0.044) after adjustment for covariates significantly associated with this endpoint. Admission hs-cTnT correctly reclassified risk for in-hospital death [net reclassification index (NRI)=44.1%, p<0.001) and overall mortality (NRI=60.4%, p<0.001). Conversely, 12h hs-cTnT was not independently associated with mortality.

Conclusion

Admission, but not 12h post-reperfusion, hs-cTnT predicts mortality and improves risk stratification in the PPCI era. These results support the role of hs-cTnT in risk stratification of post-STEMI patients and challenge the cost-effectiveness of routine 12h hs-cTnT measurements.
P1733Dynamic changes of high-sensitivity troponin I after non-invasive stress-testing
Authors: Neumann J T , Gossling A , Soerensen N , Zeller T , Blankenberg S , Sinning C , Westermann D
Published: October 2019

Objective

In patients with suspected coronary artery disease (CAD) and intermediate pretest probability non-invasive stress-testing is recommended in current guidelines. However, sensitivity and specificity of these tests are limited. We aimed to investigate the additional diagnostic value of high-sensitivity troponin I concentrations measured before and after stress-testing.

Methods

We included patients undergoing non-invasive stress-testing in a prospective cohort study. All patients provided written informed consent, were at least 18 years old and underwent either stress-echocardiography, stress-MRI or myocardial perfusion scintigraphy. Baseline parameters were collected by questionnaire and chart review. Blood samples were collected before, and one hour after the stress-test. Troponin was measured using the Abbott Architect high-sensitivity troponin I (hs-TnI) assay. The diagnostic performance to predict a pathological stress-test was evaluated by calculation of the area under the ROC curve (AUC) using baseline hs-TnI concentrations and the absolute change after one hour. An optimal cutoff was determined by maximization of the Youden Index. Univariate odds ratios (OR) were calculated to identify predictors for a pathological stress-test. Additionally ORs for the optimal hs-TnI cutoff were calculated in a multivarite regression with adjustment for baseline variables.

Results

In total 391 patients with a median age of 70 years were included. 66.8% were males, 83.4% had prevalent hypertension, 55.9% had dyslipidemia and 55.4% had a prior history of CAD. A pathological stress-test was reported in 21.5% and these patients had a higher cardiovascular risk profile, compared to patients with a non-pathological stress-test. The baseline hs-TnI concentrations were 4.7 ng/L in the overall population, 4.2 ng/L in patients with a non-pathological stress-test and 8.4 ng/L (p<0.001) in patients with a pathological stress-test. There was no significant hs-TnI changes one hour after stress-testing. The AUC for the baseline hs-TnI was 0.65 and the optimal cutoff was determined at 7.7 ng/L. Most cardiovascular risk factors were predictors for a pathological stress-test. The OR for an elevated hs-TnI above the optimized cutoff was 3.34 (95% CI 2.03, 5.52). In a multivariate model a baseline hs-TnI above 7.7 ng/L showed an OR of 2.07 (95% CI 1.04, 4.12; p-value 0.039)

Conclusion

In patients undergoing non-invasive stress-testing, hs-TnI concentrations did not significantly change one hour after exercise. However, an elevated troponin concentration is an independent predictor for a pathological stress-test.
P1737Influence of peripheral arterial disease on prognosis in patients with left main coronary artery disease treated with percutaneous coronary intervention
Authors: Martinez Leon A , Adeba Garcia A , Garcia Iglesias D , Florez Llano P , Flores Fuentes A , Gutierrez De La Varga L , Almendarez Lacayo M , Diaz-Chiron Sanchez L , Capin Sampedro E , Suarez Cuervo A , Avanzas Fernandez P , Garcia Perez L , Moris De La Tassa C
Published: October 2019

Introduction

Percutaneous coronary intervention (PCI) in patients with left main (LM) coronary artery disease is acquiring an important role in the last years as an alternative to coronary artery bypass grafting (CABG) in selected patients. The objective of the study was to evaluate predictors of mortality in patients with LM coronary artery disease treated with PCI.

Methods

Prospective and observational study of consecutive patients referred to our centre for coronary angiography, with LM coronary artery disease, whom PCI was decided in a “Heart team” as a strategy for revascularization between July 2015 and December 2017. Baseline clinical, analytical and coronary angiography data were collected. Follow-up was conducted in person or by telephone for a minimum of one year. We analysed the predictive variables of mortality by means of an uni and multivariate logistic regression model. In addition, a survival analysis was performed.

Results

A total of 191 patients were recruited. The average age was 72 years (±11.4), 79% males. 42% had previous documented coronary artery disease. PCI was performed in the context of acute coronary syndrome in 81% of them. The mean follow-up period was 17.9 months (± 8.3). After multivariate analysis, the following variables remained as independent predictors of mortality: the hemodynamic situation of the patient, assessed by the Killip-Kimball scale (OR 1.58, 95% CI 1.03–2.43; p=0.04) and the presence of peripheral arterial disease (PAD) (OR 2.61, 95% CI 1.03–6.67; p=0.04) (table 1). The ROC curve of the multivariate model showed an AUC of 0.796 (figure 1A). In the survival analysis, patients with PAD had a significantly lower survival, with a median survival of 6 months, compared to 13.9 months in those without PAD, with p=0.008 (figure 1B).

Uni and multivariate analysis Univariate analysis Multivariate analysis OR (95% CI) p OR (95% CI) p Killip-Kimbal scale 1.94 (1.39–2.72) 0 1.58 (1.03–2.43) 0.04 LVEF 0.96 (0.93–0.99) 0.01 0.99 (0.95–1.03) 0.46 Mitral regurgitation 2.54 (1.12–5.63) 0.02 1.60 (0.55–4.56) 0.38 Number of affected vessels 1.96 (1.24–3.29) 0.01 1.78 (1.03–3.37) 0.05 PAD 2.54 (1.16–5.49) 0.02 2.61 (1.03–6.67) 0.,04

Figure 1

Conclusion

Although PCI revascularization of LM coronary artery disease is an attractive alternative to CABG in selected patients, a word of caution should be raised in patients with PAD, as in the present study this variable was an important predictor of short-medium term mortality.
P1740Clinical impact of symptom onset-to-balloon time and door-to-balloon time on 1-year adverse event in patients with ST-segment elevation myocardial infarction
Authors: Kim G , Choi W , Kim J , Ahn T
Published: October 2019

Background and objectives

The impact of treatment delays to reperfusion on patient mortality after primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI) is controversial. we evaluated the relation between the delay in the time to reperfusion during primary PCI and the 1-year clinical outcome of patients with STEMI treated by primary angioplasty.

Methods

The study enrolled 6,676 patients (age, 62.5±12.6 years; 26.5% female) with STEMI who underwent primary angioplasty onset between November 2005 and March 2012 from the KAMIR and KorMI Registry. The patients were divided into three groups according to the symptom onset-to-balloon (STB) time: group I, II, III (≤180 minutes, >180 ∼ ≤360 minutes, >360 minutes), and divided into three groups according to the door-to-balloon (DTB) time: group A, B, C (≤90 minutes, >90 ∼ ≤120 minutes, >120 minutes). The 1-year cardiac death and major adverse cardiac event (MACE) rates were compared among the three groups of time variables

Results

The cardiac death rate was 7.9% and MACE rate was 16.9% at one year follow-up. The 1-year cardiac death rate among STB time groups were significantly higher in group II (95% CI=1.05–2.60:p=0.030) and group III (95% CI=1.14–2.74:p=0.011), while that among DTB time groups were not significantly different based on a multivariate Cox proportional analysis, which was adjusted by age, sex, diabetes mellitus, hypertension, systolic blood pressure, left ventricular ejection fraction, peak level of CK-MB, anterior myocardial infarction. The 1-year MACE rate were not significantly different among STB time groups and DTB time group A, B, but was significantly higher in group C (95% CI=1.08–1.58:p=0.006).

Conclusions

These results suggest that, in patient with STEMI treated by primary angioplasty, STB time rather than DTB time was related 1-year clinical outcome especially cardiac death after adjustment for baseline characteristics. Therefore, all efforts should be made to shorten the total ischemic time in patients with acute myocardial infarction
P1749Mortality in ST segment elevation myocardial infarction treated with primary percutaneous intervention in Norway A report from the Norwegian registry of invasive cardiology (NORIC)
Authors: Larsen A I , Loland K H , Hovland S , Eek C , Fossum E , Trovik T , Uchto M , Hegbom K , Larsen T , Moer R , Rotevatn S
Published: October 2019

Introduction

Limitations of the current reports on prognosis in ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), are that they are based on selected samples from hospitals voluntary registries, trials and surveys and thereby lack full population coverage. In contrast to most developed countries, Sweden and the UK were for a long term, the only two countries worldwide that had continuous national clinical registries for acute coronary syndrome with mandated participation for all hospitals. This is now also the case in Norway. Of all STEMIs admitted to hospital in Norway, 77% is treated with PCI (2016). Since 2013 invasive coronary procedures is registered in The Norwegian registry for invasive cardiology (NORIC).

Purpose

The purpose of the current report from NORIC was to assess the mortality rates in patients treated with PCI for STEMI in Norway. Moreover we sought to assess the relationship between mortality and age at admission in this population.

Methods

NORIC, which is a part of the Norwegian Cardiovascular Disease Registry (NCDR), is a national person-identifiable health registry that does not require consent from the registered individual. Data were registered from 1st of January 2013 to 13th of June 2018.

Results

During this period 10524 patients were registered with a STEMI. The incidence is calculated for the years of 2015–2017 when the registry had full national coverage. The incidence of STEMI treated with PCI in Norway was (53 in 2015, 50 in 2016 and 52 in 2017 per 100 000). For patients younger than 80 years at admission, the mortality rates were 4.9%, 6.8% and 8.0% at 30 days, 365 days and 730 days respectively. For patients older than 80 years at admission the mortality rates were 8.3%, 15.6% and 19.0% at 30 days, 365 days and 730 days respectively. The mortality rates stratified by age are illustrated in figure 1.

Survival stratified by age

Conclusions

Mortality in STEMI patients offered primary PCI in Norway is equal or even lower than the mortality reported from well-established national registries from UK and Sweden. This indicates a well functioning treatment strategy despite challenging geography. Age is an important determinant of mortality.
P1762Prognostic significance of in-hospital incomplete and terminated revascularization in patients with acute myocardial infarction and without reduced left ventricle ejection fraction
Authors: Francuz P , Podolecki T , Mazurek M , Wloch L , Swiatkowski A , Honisz G , Swierad M , Kurek T , Chodor P , Lenarczyk R , Kalarus Z , Kowalczyk J
Published: October 2019

Introduction

In-hospital incomplete and terminated at discharge myocardial revascularization has significant impact on mortality after acute myocardial infarction (AMI), also in patients (pts) with reduced left ventricle ejection fraction (LVEF) ≤35%. However, subjects with LVEF >35%, who are not candidates for implantable cardioverter defibrillators, are still at risk. Authors hypothesized, that in those pts, the prognosis could be related to completeness of revascularization.

Purpose

To evaluate the risk of death and major adverse cardiovascular events (MACE) among pts with AMI and LVEF>35% in relation to myocardial revascularization status.

Methods

Single center prospective study encompassed 445-pts with AMI and LVEF>35%, who were treated with percutaneous coronary intervention and who survived in-hospital period. Study population was divided into two groups: group 1. – 73-pts with in-hospital incomplete and terminated revascularization at discharge; group 2. – 372-pts with complete or incomplete revascularization, in whom scheduled procedures were planned and performed (either percutaneous or surgical). The incidence of death and MACE was compared between groups during mean follow-up of 47.5 months after AMI. MACE was defined as a composite of death, recurrent AMI, non-scheduled revascularization, acute heart failure, stroke. Independent predictors for death were identified with multivariate Cox-regression models and expressed as hazard ratio (HR) with 95% confidence interval (CI).

Results

Patients in group 1. had higher mortality rate than in group 2. (26.4% vs. 9.1%; p<0.001) – figure 1. The difference in the incidence of MACE was higher in group 1. than in group 2. (59.7% vs. 28.2%; p<0.001). The analysis of particular MACE showed, that in group 1. the incidence of recurrent AMI, non-scheduled revascularization and stroke was higher than in group 2. (17.8% vs. 8.9%; p=0.022, and 33.3% vs. 16.1%; p=0.001, and 6.8% vs. 2.4%; p=0.048, respectively). Independent risk factors for death were: age ≥65 years (HR: 4.2; CI: 2.1–8.0) and incomplete and terminated myocardial revascularization at hospital discharge (HR: 2.5; CI: 1.4–4.4).

Conclusions

After invasive treatment of AMI, the prognosis in patients with LVEF>35% is related to revascularization status. In-hospital incomplete and terminated revascularization at discharge is an independent risk factor for death in this population.
P1775Outcomes in patients with left ventricular non-compaction phenotype and normal left ventricular ejection fraction
Authors: Rebellius L , Berzins Schoenenberger R , Anwer S , Rogler S , Kuzo N , Schmid D , Pazhenkottil A P , Heiniger P S , Gruner C , Tanner F C
Published: October 2019

Introduction

Left ventricular non-compaction (LVNC) is a rare cardiomyopathy with a progressive clinical course, resulting in symptoms such as heart failure, cardiac arrhythmias, or thrombo-embolic events. Little is known about the natural course of disease, in particular in individuals with normal LV ejection fraction (EF) at diagnosis. In this study, we aim to evaluate the outcome of this group of patients.

Methods

48 LVNC patients with normal LV EF at diagnosis (defined as ≥50% by Simpson) were retrospectively analysed followed-up for median duration of 3656 days (2017–4965). All outcome data and conventional echocardiographic parameters were obtained; and in 27 patients, LV and right ventricular (RV) global longitudinal strain (GLS) were also determined using TomTec Image Arena (v.4.6).

Results

Mean age was 25.5 years. Median LVEF was 58.5% [IQR: 52.75 - 65.25]). The localization of non-compacted segments displayed a typical distribution with apical and inferolateral midventricular segments most frequently involved. Although LVEF was normal at baseline, median LV GLS was 16.8% (IQR: 20.0 - 14.2) and RV GLS was 18.7% (23.3–15.6). Furthermore, only 30 patients (73.2%) had a normal diastolic function, while others showed impaired relaxation (19.5%; n=8) or restrictive filling pattern (7.3%; n=3). During follow-up, LVEF decreased slightly from the initial visit (59%, [53.3–65.0]) to last follow-up (56%, [53.0–61.8], p=0.0009), and LV end-systolic and end-diastolic volumes increased (p=0.009 and 0.001, respectively). The other echocardiographic parameters did not show any significant changes. During follow-up, 3 patients (7.7%) died, 5 (12.8%) were hospitalized for heart failure, 3 (7.7%) had a thromboembolic event, 5 (12.8%) a syncope, 3 (8.1%) a non-sustained ventricular tachycardia, 9 (22.5%) a supraventricular tachycardia, and 14 (35.9%) suffered other complications during follow-up. The change in LVEF and LV volumes during follow-up was not significantly associated with outcome.

Conclusion

Patients presenting with a LVNC phenotype and normal LVEF did not display a completely normal LV function as revealed by LV strain and LV diastolic function. LVEF decreased slightly during follow-up, but was surprisingly stable in most patients. Nevertheless, a significant number of individuals experienced a clinically relevant event. Hence, a LVNC phenotype is important even in individuals with normal LVEF and such patients should be followed-up regularly.
P1777Concordance and discordance among the recommended echocardiographic parameters for the assessment of mitral regurgitation severity
Authors: Uretsky S , Aldaia L , Marcoff L , Koulogiannis K , Rosenthal M , Gillam L
Published: October 2019

Background

The EACVI and ACC/AHA guidelines recommend assessing several echocardiographic parameters when evaluating mitral regurgitant severity. In a given patient, these parameters can be discordant making the assessment of mitral regurgitation challenging.

Purpose

To assess the degree to which echocardiographic parameters of MR severity are concordant.

Methods

This analysis included 131 consecutive patients with primary mitral regurgitation enrolled in a prospective multicenter study. Nine parameters were included in this analysis (PISA –derived regurgitant volume, PISA-derived EROA, vena contracta, color Doppler jet/LA area, LA volume index, LVEDVI, peak E wave, pulmonary vein systolic flow reversal, and presence of flail leaflet). Each echocardiographic parameter was determined to represent severe or nonsevere mitral regurgitation according to the guidelines. A concordance score was calculated as: (the number of concordant parameters/9) * 100 so that a higher score reflects greater concordance. Each echocardiogram was graded as having mild, moderate, or severe mitral regurgitation using the guideline recommended integrated approach.

Results

The mean concordance score was 74±13% for the entire cohort. There were 4 (4%) patients with complete agreement of all parameters and 32 (25%) with agreement of 5 of the 9 parameters. There was greater discordance in patients with severe MR and eccentric jets but no difference between patients with prolapse or flail leaflets (Figure 1). Clinical predictors of discordance were vena contracta and the peak E wave.

Figure 1

Conclusion

In this series, there was imperfect concordance between the recommended echocardiographic parameters of MR severity in patients undergoing evaluation for mitral regurgitation. The discordance was worse with more severe mitral regurgitation and there was no ideal predictor of discordance. These findings highlight the challenges facing echocardiographers when assessing the severity of mitral regurgitation and underscore the importance of using the integrated approach recommended by professional societal guidelines.

Acknowledgement/Funding

None
P1778Changes in size of ascending aorta in patients with bicuspid aortic valves
Authors: Garcia-Ruiz M V , Becerra Munoz V M , Robledo-Carmona J , Rodriguez-Bailon I , De Teresa Galvan E
Published: October 2019

Introduction

It is well known that bicuspid aortic valve (BAV) is associated with premature valve dysfunction and ascending aorta dilation. However, limited data still exists regarding the rate of growth of the ascending aorta and the risk factors associated with it in these patients.

Methods

We analyzed prospectively baseline characteristics and echocardiographic data from 192 adult patients with BAV followed in an Adult Congenital Heart Disease Unit from 2007 until 2018.

The exclusion criteria were: patient's without at least 2 echocardiographic examinations >6 months apart, and patients with aortic valve and/or ascending aorta surgery at baseline o at follow up (except aortic coarctation).

Following the ASE guidelines two cardiologists experts in echocardiography made all the studies at baseline and follow-up where they measured the aortic root and ascending aortic diameters, as well as typified the aortic valve and analyzed the degree of stenosis (AS) and regurgitation (AR).

Statistical analysis was performed using Stata 13.1, and a p value of ≤0.05 was considered significant.

Results

97 patients were finally included (70 male, mean age 37.56±18.9 years). 66 patients had type A BAV (68.04%), 21 type B (21.7%), 2 type C (2.06%) and 7 unicuspid (7.22%). 19 patients had hypertension (19.59%) and 9 had a corrected aortic coarctation. In baseline echocardiogram, 20 had aortic stenosis ≥ moderate (20.6%) and 38 regurgitation ≥ grade II (39.18%). Mean diameter of ascending aorta was 35.78mm ± 6.73.

With a mean follow-up time of 50.53±27.05 months, mean rate of diameter progression was 0.76 mm/year at the proximal ascending aorta (95% CI 0.6 to 1.2). Progression was significantly higher in patients with moderate or severe aortic stenosis (0.65 vs. 1.17 mm/year, p=0.021). Age, sex, hypertension, AR and high baseline diameters (≥40mm or ≥45mm) were not associated with progression. In a direct comparison between the two more frequent forms of BAV, Type A and Type B, rate of diameter progression was significantly higher in Type B (0.61 vs. 1.05 mm/year, p=0.044).

In a multivariate analysis, none of the variables statistically associated to major progression were found to be predictors of growth of the ascending aorta.

Conclussions

In our population of BAV patients, mean rate of diameter progression at the proximal ascending aorta was 0.76 mm/year. Moderate-severe AS, and having type B BAV were associated, but not predictors, of higher growth rates.
P1782Synchrotron-based 4D-X-ray Phase Tomography of fresh chordae tendineae of mitral valve
Authors: Tsukube T , Yokawa K , Okita Y , Ataka K , Hoshino M , Yagi N
Published: October 2019

Background

Mechanical properties of chordae tendineae of mitral valve (MV) are still not fully investigated. Synchrotron-based X-ray phase tomography (XPCT) is a powerful tool to measure biological soft tissues. Recently, we have developed dynamic X-ray phase tomography (4D-XPCT) to discuss the dynamic phenomena of biological samples quantitatively and applied to chordae tendineae of MV (MVCT).

Purpose

This study evaluated 4-dimensional changes of MVCT and clarified structural changes of MVCT during cardiac cycles.

Methods

The X-ray energy for 4D XPCT was set to 20keV. The effective pixel size was 7.8μm. Fresh MVCT extracted from a pig heart were measured in the specially designed container filled with normal cold saline. MVCT installed on the sample stage was stretched and released with a continuous oscillation of 0.5Hz during a phase tomographic measurement. The amount of stretch was 400μm where a mechanical load caused by stretching was approximately 1N. In this measurement, projection images were acquired with a frame rate of 20Hz during a single sawtooth wave. Therefore, apparent frame rate of 20Hz is expected in 4D phase tomography. Cross section was determined by simple thresholding based on the density. In this case, the threshold was set to 1.018g/cm3.

Results

X-ray phase tomographic images of MVCT at the released (A) and stretched (B) conditions are shown in Fig. 1a. The load applied to the sample and change of the cross section obtained from tomography during stretching and releasing are shown in Fig. 1b and 1c, respectively. The diameter of chordae tendinea were changed approximately 2.5% during stretching and returned to initial diameter during releasing.

Figure 1

Conclusions

This result demonstrated that the 4D-XPCT had a capability to trace the detail of deformation process in the biological soft tissues during continuous oscillation. Even chordae tendinea are mainly consisted of collagen fibers, diameter of the chordae was changed according to stretching and releasing.
P1795Impact of severe aortic stenosis treatment strategy in low-risk patients: a propensity matched analysis of surgical aortic valve replacement versus transcatheter aortic valve implantation
Authors: Brizido C , Madeira M , Brito J , Teles R C , Goncalves M , Oliveira A F , Nolasco T , Carmo J , Neves J P , Almeida M S , Mendes M
Published: October 2019

Introduction

Recent studies suggest that transcatheter aortic valve implantation (TAVI) benefits might extend to lower risk patients. Our goal was to compare the impact of treatment strategy in mortality and peri-procedural complications in a low-risk severe aortic stenosis population.

Methods

Single-center retrospective study which screened patients undergoing intervention from June/2009 to July/2016 (682 isolated aortic valve replacement patients) and from June/2009 to July/2017 (400 TAVI patients). Low-risk was defined as EuroScore II <4% for single non-CABG procedure. After excluding patients with EuroScore II ≥4%, previous cardiac surgery and/or undergoing pre-treatment PCI, 544 AVR and 119 TAVI patients were included.

TAVI patients were propensity score paired in a 1:1 ratio with a group of AVR patients, matched by age, NYHA class, diabetes mellitus, COPD, atrial fibrillation, creatinine clearance and LVEF <50% (mean standardized difference <10% for matching variables). All patients completed at least 1 year of follow-up. Outcomes were adjudicated according to VARC2 criteria.

Results

A total of 158 patients (79 AVR and 79 TAVI) were matched (mean age 79±6 years, 79 men). Median EuroScore II was 2.3% (IQR 1.6–3.0%), 46% were in NYHA class ≥3 and 91% had preserved ejection fraction. Main comorbidities were hypertension (n=105, 67%), diabetes mellitus (n=48, 30%), COPD (n=35, 22%) and coronary artery disease (n=30, 19%). Most patients had at least mild renal function impairment and median creatinine clearance was 58 ml/min (IQR 43–62 ml/min).

The 30-day mortality was 2.5% (n=2 in each group) and there were no differences in in-hospital complications. During a median follow-up of 3.8 years (IQR 2.1–6.1), 67 deaths occurred (39 on the AVR group and 28 on the TAVI group), and treatment strategy did not influence all-cause mortality (HR 0.97, 95% CI 0.60–1.60, log rank p=0.92) - figure 1. By multivariate analysis, need for dialysis during hospitalization remained the only independent predictor of all-cause mortality (adjusted HR 6.40, 95% CI 1.57–28.14, p=0.01).

Figure 1

Conclusion

In this low-risk matched population, treatment strategy did not influence mortality neither complications. Older age, higher NYHA class and renal impairment were the main contributors to the predicted surgical risk. These results suggest that both options are safe for low-risk patients, even though Heart Team remains essential to contemplate other variables that might alter patient management.
P1802Management and outcomes of infective endocarditis in adults with congenital heart disease
Authors: Ly R , Lebeaux D , Pontnau F , Compain F , Gaye B , Iserin L , Ladouceur M
Published: October 2019

Background

Causes, epidemiology and microbiology of infective endocarditis (IE) have evolved in recent decades. Although novel tools for the diagnosis and therapeutic strategies have emerged, mortality and morbidity remain high. These trends may particularly concern the growing population of adults with congenital heart disease (CHD) who are at increased risk for IE.

Purpose

We aimed to characterize IE in CHD patients and describe management and outcome in this setting. We also sought to determine the risk factors associated with in-hospital death in CHD patients.

Methods

From January 2000 to June 2018, 666 consecutive episodes of IE in adults were recorded in our center. Among them, 143 concerned CHD, including 5 implantable cardiac electronic devices-lead infections, all managed by an IE team including CHD specialists. Cases were classified according to modified Duke criteria.

Results

CHD patients were significantly younger (37 years IQR [26–52]), with a more common history of cardiac reoperations (numbers of sternotomies≥2 in 35.7%) and infective endocarditis (19.7%, p<0.01) compared to non-CHD patients. There were more infections of valve-containing prosthetics (44% vs. 30%, p<0.04), and the right heart side (41.5%, p<0.01) in CHD patients. Forty-nine percent of them had a simple CHD, 12.7% a moderate, and 36.4% a complex. A predisposing event could be identified in only 34% of cases. Oral streptococci/Streptococci bovis and Staphylococcus aureus were the most frequently microorganisms isolated (32.4% and 20.4%, respectively). Surgery was performed in 90 episodes (62%), and was selected in emergency (<24h) in 61% (figure 1). In-hospital mortality was 12.7% and was directly related to IE in 10/18 cases. CHD patients had a significant lower risk of death compared to non-CHD patients (OR=0.47, p=0.026, p<0.01), even after adjustment for age, and the infected heart side. On multivariate analysis the complexity of CHD (if simple CHD: OR=0.07 IQR [0.01 to 0.44], p<0.01) and the white blood cell count (OR=1.18 IQR [1.04 to 1.33], p=0.01) were the strongest predictive factors of in-hospital death in the CHD group.

Conclusions

Mortality associated with IE in CHD patients is lower than in acquired heart disease. The multidisciplinary approach by IE team and CHD specialists may have improved management and outcome in this setting. However, risk for death remains high in complex lesions. Larger prospective studies on IE in adults with CHD are needed to develop guidelines in these complex patients.