bluuebunny/crossref_metadata_2025 huggingface dataset:
4933Comparison of left ventricular global longitudinal strain measurements using contrast-enhanced and non-contrast echocardiographic images
Authors: Liang S
Published: October 2019

Background

Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) are two important index for the quantification of left ventricular systolic function. With the help of ultrasound contrast agents, we can improve the definition of endocardial borders and allow the quantification of LVEF in patients with poor image quality. However, the feasibility of GLS measurements in contrast-enhanced images is still controversial.

Purpose

Our study aimed to explore the feasibility of GLS measured by velocity vector imaging (VVI) in contrast-enhanced images, compare the difference of measurements in contrast-enhanced and non-contrast images, and analyze the relation between LVEF and GLS in both conditions.

Methods

A total of 133 patients with cancer, who were registered for transthoracic echocardiography as well as contrast-enhanced echocardiography were studied. LVEF was measured using the biplane modified Simpson's rule and GLS was measured with offline VVI analysis of the three standard apical views in non-contrast and contrast-enhanced images respectively. Linear regression was performed to derive correlation coefficients between LVEF and GLS both in non-contrast and contrast-enhanced images.

Results

GLS measurements in non-contrast images were discarded in 2/133 patients (1.5%), while in contrast-enhanced images were obtained in all patients. LVEF (64.12±7.47% vs. 66.25±8.61%, respectively; P<0.01) and GLS (−20.99±4.67% vs. −23.40±4.58%, respectively; P<0.01) were both significantly higher in the presence of contrast agents. A linear regression between LVEF and GLS in non-contrast images (r=0.627, P<0.001) was observed, as well as in contrast-enhanced images (r=0.649, P<0.001).

Conclusions

GLS measured by VVI in contrast-enhanced echocardiography is a feasible and reliable index for the quantification of left ventricular systolic function, even in patients with poor image quality. Compared with the measurements in non-contrast images, both LVEF and GLS measurements are higher in the presence of contrast agents.
4945Inclisiran-mediated reductions in Lp(a) in the ORION-1 trial
Authors: Stoekenbroek R M , Ray K K , Landmesser U , Leiter L A , Wright R S , Wijngaard P L , Kallend D , Kastelein J J
Published: October 2019

Background

PCSK9 inhibitors and statins both lower LDL-C by increasing LDL-receptor (LDLR) function. PCSK9 inhibitors lower Lp(a) by 20–30%, whereas statins do not lower Lp(a). The mechanism by which PCSK9 inhibitors lower Lp(a) is unclear. We assessed the role of the LDLR in Lp(a) reductions produced by inclisiran, an siRNA which prevents hepatic synthesis of PCSK9.

Methods

ORION-1 was a phase 2 trial of inclisiran in subjects at high ASCVD risk with elevated LDL-C on optimized statin therapy. Subjects received one dose of inclisiran (200, 300, or 500 mg) or two doses at days 1 and 90 (100, 200, or 300 mg). We assessed the correlations between % change in Lp(a) and LDL-C at Day 180 for the inclisiran groups using Spearman correlation coefficients. We additionally assessed the correlation between % change in Lp(a) and absolute change in LDL-C as a proxy for LDLR expression. Lp(a) was measured using an isoform-independent assay and LDL-C with β-quantification.

Results

ORION-1 included 501 subjects; mean age 63; 65% male; 73% on statins. Median baseline Lp(a) was 37.0 nmol/l (IQR: 11.5–142.0 nmol/l), median LDL-C was 117.0 (IQR: 92.5–149.5 mg/dL). Inclisiran dose-dependently lowered Lp(a) by 14% to 26%. Overall, there was a significant but weak correlation between % change in Lp(a) LDL-C (Spearman coefficient 0.35, p<0.001). This correlation appeared to be stronger at higher inclisiran doses and with repeat dosing (table), as well as in statin-users versus non-users (Spearman coefficient 0.37 vs. 0.21). The correlation between % Lp(a) change and absolute LDL-C change was weaker (0.27, p<0.001).

Correlation coefficients LDL-C – Lp(a) Single-dose groups Two-dose groups Inclisiran overall 200 mg (n=60) 300 mg (n=60) 500 mg (n=60) 100 mg (n=59) 200 mg (n=60) 300 mg (n=59) Lp(a) ∼ % change LDL-C 0.22 0.26 0.22 0.29 0.47 0.51 0.35 Lp(a) ∼ absolute change LDL-C 0.35 0.12 0.04 0.22 0.45 0.24 0.27 Lp(a) ∼ % change LDL-C - Statin users 0.16 0.28 0.28 0.31 0.45 0.55 0.37 Lp(a) ∼ % change LDL-C - Non statin users 0.80 -0.08 0.09 0.10 0.63 0.09 0.21

Conclusion

The dose-dependent correlation between % changes in LDL-C and Lp(a) suggests that the LDLR may be partially responsible for Lp(a) reductions produced by inclisiran. The numerically stronger correlation in statin-users supports the idea that LDL-C may compete with Lp(a) for LDLR binding especially at low LDL-C levels.

Acknowledgement/Funding

The Medicines Company
4949Diverging secular trends in cardiovascular disease 21-year incidence in Swedish men born in 1950–1978
Authors: Aberg D , Adiels M , Lindgren M , Nyberg J , Kuhn G , Schaufelberger M , Toren K , Aberg M , Rosengren A
Published: October 2019

Background

Cardiovascular disease (CVD) mortality is decreasing in Western countries, including Sweden. However, there are reports of increases in incidence in young people with respect to heart failure (HF) and atrial fibrillation (AF). The magnitude and causes of these changes are only partly known.

Aims

We investigated secular trends in incidence in CVD outcomes and their attenuation by changes in body mass index (BMI). The outcomes were risk of acute myocardial infarction (AMI), heart failure (HF) and atrial fibrillation (AF) as well as cardiovascular and all-cause death in a population of Swedish adolescents.

Methods

We followed a cohort of Swedish men enrolled for military service conscription in 1969–1996 (n=1,326,082; mean age=18.3) until December 2016, collected from the national inpatient (IPR) and outpatient registries (OPR). Cox-proportional hazard models were used to analyse the longitudinal change in incidence by with respect to early (0–21 years) of follow-up for subgroups with conscription 1968–1971, 1971–1976, 1976–1981, 1981–1986, 1986–1991, 1991–1996 (with the group born 1971–1976 as reference). Adjustments for potential confounders including BMI were performed.

Results

We found that CVD and all-cause mortality and MI decreased progressively during the follow-up with hazard ratios (HR) of 0.51, 95% confidence interval (CI) 0.43–0.62, HR 0.51 CI 0.57–0.62, and 0.60 CI 0.50–0.72, respectively. In contrast, we found increases in the incidence of HF (HR 1.86, CI 1.48–2.33], and AF (HR 8.26, CI 6.87–9.92). Adjustments for changes in BMI partly attenuated the changes in secular trends. Cubic spline models showed where the changes in secular trends were most prominent.

Conclusion

The incidences of cardiovascular outcomes show diverging secular changes. While MI and cardiovascular mortality are continually decreasing, there is an increase in HF and AF. The associations appear to be partly explained by changes in index BMI over time.

Acknowledgement/Funding

grants from the Swedish Government and the county councils, the ALF–GBG-719761, ALFGBG-751111, Swedish Stroke Association, Göteborg Medical Society
4970Validation of ESC/ERS 2015 guidelines risk score in patients with scleroderma associated pulmonary arterial hypertension (SSc-PAH)
Authors: Fayed H , Ahmad M , Abdelkhalek R , Kotecha T , Brown J , Okonkwo N , Knight D S , Marino P , Schreiber B , Handler C , Denton C P , Coghlan J G
Published: October 2019

Background

The ESC/ERS 2015 guidelines presented a comprehensive risk assessment model with three risk categories based on different clinical and biomarkers data. Low, intermediate and high risk were defined with one-year mortality of <5%, 5–10% and >10%. Different groups suggested different methods of risk assessment based on this model.

Purpose

We applied three different methods to validate the ESC/ERS risk prediction model for one-year survival in SSc-PAH.

Methods

309 patients with SSc-PAH have been diagnosed and managed in our institution from 2006 to 2017. We used three different risk assessment models that have been previously suggested.

1. Suggested by the Swedish group 1: Having a score of 1 (low risk), 2 (intermediate risk) or 3 (high risk) resulting from the average of the sum obtained after grading each of the variables (whichever available) from 1 to 3 according to ESC/ERS guidelines cut-offs for WHO-functional class (FC), 6-minute walking distance (6MWD), NT-Pro BNP, right atrial pressure (RAP) and cardiac index (CI).

2. Suggested by the French group 2: Having none, 1, 2, 3 or 4 of the following low-risk criteria of; FC, 6MWD, RAP and CI.

3. Instead of the invasive data, The French group also suggested the use of a non-invasive model including NT-Pro BNP.

Patients were divided into different risk groups according to data obtained at baseline and at their 6-month follow-up. Survival analysis over a 5-year period was performed using Kaplan-Meier analysis.

Results

Overall median follow-up was 33.3 months. One year survival was significantly different between the risk groups (p<0.001) using either baseline or follow-up data. Applying the French group non-invasive model, almost two thirds of the population ended up in the higher risk group. Whilst applying the Swedish model, two thirds of the population ended up in the intermediate risk group. In all the models used, there were significantly less number of patients in the lower risk groups at onset with improvement of risk profile at follow up. An important advantage of the Swedish model, that it can be calculated even in the presence of missing data, a problem commonly encountered. The French models are easier to calculate but they cannot be applied when there is missing data.

5-year survival with different models

Conclusion

All models used were valuable in risk prediction of SSc-PAH both at onset and at follow up. However, each model has some caveats which should be considered. In all the methods used, the prevalence of high risk criteria is higher amongst the SSc-PAH population which indicates the higher risk profile at the time of diagnosis in comparison to other PAH populations, which could explain the poorer outcome.
5037Drug treatment with beta-blockers and long-term outcome in patients with takotsubo syndrome: results from the takotsubo Italian network
Authors: Silverio A , Citro R , Bossone E , Bellino M , Zito C , Provenza G , Prota C , Iuliano G , Radano I , Polito M V , Baldi C , Novo G , Antonini-Canterin F , Galasso G , Parodi G
Published: October 2019

Background

Although generally considered a benign disease, Takotsubo syndrome (TTS) has recently been associated to a substantially comparable long-term outcome than acute coronary syndrome (ACS). The use of beta-blockers (BB) has been advocated in these patients for secondary prevention after the index event, considering the presumed role of catecholamine in TTS pathophysiology. However, the effect of BB on long-term outcome remains controversial due to the paucity of data and the lack of evidence from randomized studies.

Purpose

To investigate the impact of BB therapy on long-term outcome in patients with TTS.

Methods

The study included all TTS patients enrolled in the Takotsubo Italian Network multicenter registry. Patients were divided in two study groups according to the BB therapy after discharge. The following major adverse cardiac events (MACE) were assessed at the longest available follow-up: cardiac death, TTS recurrence, rehospitalization for cardiac cause, acute or worsening heart failure (HF) and ACS. Also, the composite of cardiac death and rehospitalization as well as the overall MACE were analyzed

Results

The study population included 548 patients (mean age 68.7±11.4 years; 44 males, 8%). Among them, BB treatment was reported in 368 (BB group, 67.2%) and 180 (no-BB group, 32.8%) patients, respectively. The baseline clinical characteristics were substantially comparable among groups with the only exception of COPD, which was prevalent in the no-BB group (10.3% vs 21.7%, p=0.001).

During follow-up (median 18 months 25–75% c.i. 6–29), TTS recurrence was reported in 26 patients (4.7%), ACS in 10 (1.8%), acute or worsening HF in 39 (7.1%), cardiac hospitalization in 71 (13.0%) and cardiac death in 18 (3.3%). The rate of TTS recurrence and ACS was comparable between groups. Conversely, no-BB patients experienced more frequently acute or worsening HF (5.4% vs 10.6%, p=0.034), cardiac rehospitalization (10.9% vs 17.2%, p=0.042) and cardiac death (1.9% vs 6.1, p=0.018) than BB patients. Therefore, the MACE composite endpoint was significantly prevalent in the no-BB group (12.0% vs 20.6%, p=0.010).

Kaplan-Meier curves for the composite of cardiac death and rehospitalization showed a statistically lower survival in the no-BB patients compared to the BB group (p=0.006). Moreover, landmark analysis showed a wider survival benefit in the BB patients after 2 years.

Conclusions

Although in absence of a secondary preventive effect on TTS recurrence, BB may improve the long-term cardiac outcome in patients with TTS. Prospective randomized studies are advisable to confirm these findings.
5195Growth differentiation factor-15 and mortality in suspected or known coronary heart disease patients with diabetes: a subanalysis of the ANOX study
Authors: Unoki T , Suzuki M , Matsuda M , Ajiro Y , Shinozaki T , Sakagami S , Yonezawa K , Shimizu M , Funada J , Takenaka T , Morita Y , Abe M , Akao M , Hasegawa K , Wada H
Published: October 2019

Background

Diabetes is a risk factor for coronary heart disease (CHD), but further risk stratification in patients with diabetes is necessary to improve the prediction and prevention of cardiovascular events and deaths. Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine, which plays an important role in the regulation of the inflammatory response, growth and cell differentiation. Elevated GDF-15 was found in various diseases including diabetes and stable CHD, and was reported to predict mortality and cardiovascular events in general or established CHD population. However, the prognostic value of GDF-15 in suspected or known CHD patients with diabetes is unknown.

Methods

Serum GDF-15 levels were measured in 1,087 suspected or known CHD patients with diabetes undergoing elective coronary angiography, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict cardiovascular events (ANOX) study, and followed up for 3 years. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.

Results

During the follow-up, 147 patients died from any cause, 47 died from cardiovascular disease, and 94 developed MACE. After adjustment for established risk factors, GDF-15 levels were significantly associated with all-cause death (hazard ratio [HR] for 1-SD increase, 1.66; 95% confidence interval [CI], 1.48–1.86), cardiovascular death (HR, 1.63; 95% CI, 1.34–1.99), and MACE (HR, 1.41; 95% CI, 1.20–1.65). Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of GDF-15 levels further improved the prediction of all-cause death (continuous net reclassification improvement [NRI], 0.344; 95% CI, 0.172–0.517; P<0.001; integrated discrimination improvement [IDI], 0.049; 95% CI, 0.026–0.072; P<0.001), but not that of cardiovascular death (NRI, −0.013; 95% CI, −0.300–0.274; P=0.931; IDI, 0.023; 95% CI, 0.003–0.043; P=0.026) or MACE (NRI, 0.059; 95% CI, −0.151–0.268; P=0.583; IDI, 0.005; 95% CI, −0.004–0.015; P=0.244).

Conclusions

In suspected or known CHD patients with diabetes undergoing elective coronary angiography, elevated GDF-15 levels may predict all-cause mortality independent of established risk factors and cardiovascular biomarkers.

Acknowledgement/Funding

The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization.
5200Incidental Ventricular Tachycardia: Short and Long-term Prognosis
Authors: Sajadieh G , Sajadieh A
Published: October 2019

Background

The prognostic significance of incidental non-sustained ventricular tachycardia (NSVT) in subjects without manifest heart disease is unknown.

Aim

We aimed to evaluate the short- and long-term prognosis of NSVT.

Methods

Data from 678 subjects from Copenhagen Holter study were analyzed. All had at least 48 hours of Holter recording. NSVT was defined as runs of at least three premature ventricular complexes. All were followed up to 16 years. The primary end-point was defined as a combination of cardiovascular mortality, acute myocardial infarction, coronary revascularization, or stroke.

Results

72 (10.6%) had at least one event of VT. The primary end-point occurred more frequently in patients with NSVT: 38.3 versus 17.7 events per 1000 patient-years: HR and 95% CI: 2.06 (1.37–3.20) after relevant adjustments. In a shorter-term follow-up period of up to two-year there were few events: HR and 95% CI: 1.9 (0.69–5.24). The prognosis in subjects with NSVT was not dependent of the length of the VT (p for interaction 0.9), but of the background risk profile.

Table 1. Results of the Cox proportional Hazard models showing risk of cardiovascular events in different groups of subjects with incidental ventricular tachycardia on ambulatory ECG recording Model 1 p Model 2 p Interaction All VT 2.02 (1.32–3.10) 0.001 1.95 (1.2–3.02) 0.003 VT (3 complexes) 1.79 (0.98–3.27) 0.057 1.84 (1.0–3.38) 0.04 0.91 VT (4–9 complexes) 1.94 (1.13–3.32) 0.016 1.78 (1.06–3.22) 0.029 VT and high risk score* 2.84 (1.79–4.49) <0.0001 2.35 (1.46–3.79) 0.0004 0.22 VT and low-risk score 0.70 (0.26–1.90) 0.49 0.93 (0.34–2.57) 0.88 Model 1: adjusted for sex and age. Model 2: adjusted for sex, age, smoking, diabetes mellitus, systolic blood pressure, LDL cholesterol and NT-proBNP. *Framingham riskscore ≥10 vs <10.

Conclusions

Incidental NSVT in subjects without manifest heart disease is associated with increased risk of mortality and CV-events, however the increased risk is not imminent but with a slow pace over time.

Acknowledgement/Funding

Danish Heart Foundation
5206SICD registry in European paediatric and adult patients with congenital heart defects: preliminary results of the SIDECAR project
Authors: Silvetti M S , Kornyei L , Kwiatkowska J , Tamburri I , Saputo F A , Pazzano V , Fesus G , Di Mambro C , Albanese S , Lovecchio M , Valsecchi S , Drago F
Published: October 2019

Aim

Use of the subcutaneous implantable cardioverter-defibrillator (S-ICD) to prevent sudden cardiac death is increasing. Few data exist on S-ICD in young patients. We report preliminary data from a multicenter European registry of paediatric and young adult patients who underwent S-ICD implantation

Methods

Observational, prospective, non-randomized, standard-of-care study on S-ICD implantation/follow-up in young patients with inherited arrhythmias (IA), cardiomyopathies, and congenital heart defects (CHD).

Results

29 patients (12 CHD, 14 Cardiomyopathies, and 3 IA), mean age 17±6 years, 13 of them <18 years, with body mass index (BMI) 23±4, underwent S-ICD implantation (primary prevention 66%). The first 8 patients underwent a three-incision procedure, the following 21 (72%) a two-incision procedure. No intraoperative complications occurred. Over 19 months median follow-up (25th–75th percentiles, 5–37) 5 patients (17%) received appropriate and 2 (7%) inappropriate shocks. Four patients (14%) had device-related complications requiring surgical intervention: three skin erosions at the superior parasternal incision, one pocket infection. A higher risk of complications was seen in patients who underwent standard procedures [hazard ratio (HR) 14.7, 95% confidence interval (CI) 2.34 to 93.03; P=0.001] and those with BMI <20 (HR 11.06, 95% CI 1.01–121.07; P=0.008).

Conclusion

These preliminary results of a multicenter European paediatric registry suggest that S-ICD is safe and effective with low rates of inappropriate shocks. Improvement of implantation techniques seems associated with better outcome.
5226The majority of 30-day survivors of in-hospital cardiac arrest are alive one-year post-arrest without anoxic brain damage, admission to nursing home or need of in-home care
Authors: Yonis H , Bundgaard K , Noermark Mortensen R , Wissenberg M , Gislason G , Koeber L , Torp-Pedersen C , Mosgaard Larsen J , Hay Kragholm K
Published: October 2019

Background

Survivors of in-hospital cardiac arrest are at risk of anoxic brain damage that can lead to admission to nursing home or need of in-home care. However, studies on long-term outcomes after in-hospital cardiac arrest are scarce with previous research focusing on short term measures such as survival-to-discharge.

Purpose

This study aimed to investigate the composite endpoint of nursing home admission or anoxic brain damage among 30-day survivors of in-hospital cardiac arrest within the first-year post-arrest. As a sub analysis, we also investigated the additional need of in-home care.

Methods

All in-hospital cardiac arrests in 13 Danish hospitals during 2013–2015 were identified from the DANARREST register. Inclusion criteria were indication for a resuscitation attempt and survival to day 30. Patients who, prior to arrest, already lived in a nursing home, and/or had anoxic brain damage were excluded. In the sub analysis patients who received in-home care prior to arrest were also excluded. The DANARREST data was linked to nationwide registries including the National Patient Register and administrative nursing home and home care registries using the Danish Civil Registration Number, a unique personal identification number that is given to every citizen in Denmark.

Results

The primary study population comprised of 454 (26.3%) 30 day-survivors out of 1723 eligible patients. Median age was 67 (Q1-Q3 57–75); 301 (66.9%) were men. In this group, the 1-year risk of anoxic brain damage or nursing home admission was 4.6% (95% CI 2.7%- 6.6%) with a competing risk of death of 15.6% (95% CI 12.3%-19.0%), leaving 79.8% alive without anoxic brain damage or nursing home admission at one-year follow-up (see Figure 1A).

The sub study population comprised of 343 30-day survivors with a 1-year risk of anoxic brain damage, nursing home admission or need of in-home care of 23.6% (95% CI 19.1%-28.1%). The competing risk of death was 7.6% (95% CI 4.8%-10.4%), leaving 68.8% alive without anoxic brain damage, nursing home admission or need of in-home care at one-year follow-up (see Figure 1B).

Figure 1

Conclusion

The majority of 30-day survivors of in-hospital cardiac arrest were alive at one-year follow-up without being diagnosed with anoxic brain damage, admitted to nursing home or without need of in-home care.
5228Identification of reliable clinical variables for early prediction of outcome after out-of-hospital cardiac arrest using algorithm-based machine learning statistical methods
Authors: Johnsson J , Hoerberg S , Holm A , Gustafzelius S , Dankiewicz J , Nielsen N
Published: October 2019

Background

Several factors are known to influence both survival and long-term neurologic function after out-of-hospital cardiac arrest (OHCA). Previous studies have indicated that both pre-hospital circumstances as well as patients' history and clinical status on hospital admission are variables strongly associated with later outcome. This study aimed to identify and evaluate clinical variables for early prediction of outcome for unconscious survivors after OHCA using machine learning statistics analysis.

Methods

The Target Temperature Management (TTM) trial randomized 939 international patients with OHCA of presumed cardiac cause to TTM at 33°C or 36 °C for 24 h in intensive care units (ICUs). Patient outcome were survival and neurological function defined by the Cerebral Performance Category (CPC) scale. This multicentre cohort was used for a post hoc analysis using machine learning statistical analysis.

A Conditional Interference decision forest algorithm was designed for training on the TTM-dataset to perform early prediction of outcome at 180 days.

Results

After ranking all available variables in the TTM-dataset based on their importance for the algorithm to make predictions, we could identify a slimmed list with eleven clinical predictors of a poor outcome including older age, low motor score on Glasgow Coma Scale (GCS), increasing doses of adrenaline, first monitored rhythm not shockable, longer duration of low flow, longer time from cardiac arrest to advanced life support, high BMI (Body Mass Index), low pH, bilateral absence of corneal and pupillary reflex, low initial body temperature and cardiac arrest location at home. Age was overall the most important variable for prediction. Our slimmed prediction model performed slightly worse with an AUC of 0.813 (0.741–0.916) compared to an extended model with all available variables included, AUC = 0.839 (0.778 – 0.886). When using all variables in a comparing logistic regression analysis the mean AUC was a corresponding 0.830 (0.792–0.882).

Conclusion

This algorithm with eleven clinical variables predicted outcome almost as good as a corresponding large model with cardiac arrest patients from the TTM-trial and could be a powerful clinical decision tool for early prediction of outcome after cardiac arrest.
5937Natural history of functional tricuspid regurgitation: implications of quantitative doppler assessment
Authors: Bartko P E , Arfsten H , Frey M , Heitzinger G , Pavo N , Cho A N N A , Neuhold S , Tan T , Strunk G , Hengstenberg C , Huelsmann M , Goliasch G
Published: October 2019

Objectives

To establish the prognostic value of quantitative measures of functional tricuspid regurgitation (TR) severity i.e. effective regurgitant orifice area (EROA) and regurgitant volume.

Methods

382 patients with HFrEF on guideline-directed medical therapy were enrolled and TR EROA as well as regurgitant volume by Doppler/2D-echocardiography were assessed. All-cause mortality was defined as the primary study endpoint.

Results

Quantitative metrics of TR severity were consistently associated with mortality with a HR of 1.27 (95% CI 1.13–1.42, P<0.001) for the EROA and of 1.29 (95% CI 1.14–1.45, P<0.001) for the regurgitant volume (Figure 1, Panels A and B). Results remained unchanged after bootstrap- or clinical confounder-based adjustment. A spline curve pattern illustrates the association with mortality with thresholds for the EROA≥0.2cm2, and the regurgitant volume≥20ml with sustained excess mortality thereafter (Figure 1 Panels C-D).

Figure 1. Panels A–D

Conclusions

This large-scale study demonstrates the prognostic value of quantitative measures of TR severity in HFrEF. Thresholds for EROA and TR regurgitant volume associated with mortality fall within current ranges defining non-severe TR. This may potentially impact therapeutic decision making particularly timing of intervention.
5939Perioperative shift in right ventricular mechanical pattern in patients undergoing mitral valve surgery: a predictor of right ventricular failure?
Authors: Tokodi M , Lakatos B K , Kispal E , Toser Z , Racz K , Soltesz A , Szigeti S Z , Hartyanszky I , Nemeth E , Merkely B , Kovacs A
Published: October 2019

Background

Severe mitral regurgitation (MR) induces significant changes not only in the left, but also in the right ventricular (RV) morphology and function. Early treatment of MR is recommended, however, surgical procedure disrupts the native RV contractile pattern and predisposes the at-risk ventricle to develop postoperative RV failure (RVF) which is associated with poor outcomes.

Purpose

Accordingly, the PREPARE-MVR study (PRediction of Early PostoperAtive Right vEntricular failure in Mitral Valve Replacement/Repair patients) aims to explore the alterations of RV contraction pattern in patients undergoing MVR and to investigate the association of preoperative echocardiographic findings with early postoperative RVF.

Methods

We prospectively enrolled 70 patients (62±12 years, 67% males) undergoing open heart MVR. Thirty age and gender matched healthy volunteers served as control group. Transthoracic 3D echocardiography was performed preoperatively and at intensive care unit discharge. Furthermore, focused 2D echocardiogram was also obtained during the ICU stay. Forty-three patients also completed 6 months follow-up. 3D model of the RV was reconstructed and end-diastolic volume index (EDVi) along with RV ejection fraction (RVEF) were calculated. For in-depth analysis of RV mechanics, we decomposed the motion of the RV to compute longitudinal (LEF) and radial ejection fraction (REF). Right heart catheterization was performed to monitor RV stroke work index (RVSWi).

Results

RV morphology as assessed by EDVi was unaffected by surgery (preoperative vs postoperative; 73±17 vs 71±16 mL/m2, p=NS). RVEF was slightly decreased after MVR (52±6 vs 48±7%, p<0.05), whereas RV contraction pattern has changed notably. Before MVR, the longitudinal shortening was the main contributor to global systolic function (LEF/RVEF vs REF/RVEF; 0.53±0.10 vs 0.43±0.12; p<0.001), whereas in controls the longitudinal and radial shortening contributed equally to RVEF (0.47±0.07 vs 0.43±0.09; p=NS). Postoperatively, the radial motion became dominant (0.35±0.08 vs 0.47±0.09; p<0.001). However, this shift was only temporary as 6 months later the contraction pattern became similar to controls showing equal contribution of the two components (0.44±0.10 vs 0.42±0.11; p=NS). Postoperative RVF (defined as RVSWi <300 mmHg*mL/m2 or ICU TAPSE <10 mm) was detected in 14 [20%] patients. Preoperative LEF was associated with postoperative RVSWi (r=−0.61, p<0.001) and it was an independent predictor of postoperative RVF (OR=1.16 [1.03–1.35], p<0.05).

Conclusion

Severe MR induces a significant shift in the RV mechanical pattern which may influence the development of postoperative RV dysfunction and failure after MVR. Advanced indices of RV mechanics are associated with invasively measured parameters of RV contractility and may predict postoperative RVF.
5947Predictive role of C-reactive protein levels in patients with ST-segment elevation acute myocardial infarction for heart failure related events
Authors: Van Tassell B , Trankle C R , Kadariya D , Canada J M , Carbone S , Buckley L F , Wohlford G F , Dixon D L , Christopher S , Vo C , Mankad P , Dell M , Shah K B , Kontos M C , Abbate A
Published: October 2019

Background

ST-segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). C-reactive protein (CRP) is the inflammatory biomarker most commonly used for risk stratification in patients with cardiovascular diseases. CRP levels are known to rise and fall during STEMI in response to myocardial injury. In this study, we analyzed whether admission CRP or delayed CRP (measured at 72 hours after admission) held a greater predictive value for adverse HF events in patients with STEMI.

Methods

We analyzed data from the VCUART3 clinical trial enrolling 99 patients with STEMI within 12 hours of presentation at 3 sites in the United States of America treated with anakinra or placebo. CRP levels were measured with a high-sensitivity assay at time of admission and again at 72 hours later. A dedicated committee composed of individuals not involved in the conduct of the trial adjudicated HF events including a composite endpoint of death from any reason or incidence of HF defined as new-onset HF requiring hospital admission or a new prescription for a loop diuretic (D+HF) and a composite endpoint of death and HF hospitalization (D+HHF) at 1 year. We used a time-dependent Cox-regression analysis to determine the association of CRP at admission or at 72 hours with the outcomes of interest in univariate and multivariate analysis. Data are presented as median and interquartile range. (ClinicalTrials NCT01950299)

Results

CRP levels from admission and 72 hours were available in 90 and 87 subjects respectively and they increased from 4.6 [2.8–8.5] mg/L to 11.6 [4.6–24.5] mg/L (P<0.001). Both admission CRP (CRP0) and CRP at 72 hours (CRP72) were associated with the risk of D+HF (P=0.011 and <0.001, respectively) and of D+HHF (P=0.010 and P<0.001, respectively); however at multivariate analysis, only CRP72 remained significantly associated with the risk of D+HF (P=0.001) and D+HHF (P=0.004) while CRP0 was not. CRP72 significantly correlated with NTproBNP levels at 72 hours (NTproBNP72, Spearman rho R=+0.37, P=0.001). NTproBNP72 predicted D+HF (P=0.030) but not independently of CRP72 (P=0.096 for NTproBNP72 and P=0.007 for CRP72 at multivariate analysis including the 2 variables). NTproBNP72 did not predict D-HHF.

Conclusions

Among contemporary patients with STEMI, the levels of CRP at 72 hours after admission was superior to admission CRP levels for predicting the incidence of HF events, and independent of NTproBNP levels. Our results indicate the importance of the inflammatory response during STEMI, supporting the concept of inhibiting the inflammatory response as a therapeutic strategy.

Acknowledgement/Funding

Funded by NHLBI 1R34HL121402; Drug supply from Swedish Orphan Biovitrum
5964Hybrid PET/MR imaging for the prediction of left ventricular (LV) recovery after revascularisation of chronic total occluded coronaries
Authors: Vitadello T , Rischpler C , Langwieser N , Kunze K , Nekolla S , Laugwitz K L , Schwaiger M , Ibrahim T
Published: October 2019

Background

Percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) represents one of the major challenges in interventional cardiology. Physicians are still reluctant in referring for PCI, assuming non viability of the myocardium subtended by the CTO. Data are controversial in assessing the improvement of left ventricular (LV) wall motion after revascularisation and the prognostic value of viability testing to guide patient selection.

Purpose

The aim of this study was to determine, whether hybrid fluorodeoxyglucose positron emission tomography/magnetic resonance (FDG PET/MR) imaging allows a more accurate prediction of LV regional wall motion recovery after successful PCI of CTOs in comparison to PET or MR alone.

Methods

We enrolled 49 consecutive symptomatic patients with CTO and evidence of wall motion abnormality in the corresponding CTO-territory. All patients underwent hybrid FDG PET/MR imaging as semi-quantitative assessment of myocardial viability - glucose metabolism in PET and late gadolinium enhancement (LGE) transmurality in MR – prior of PCI of the CTO. Follow-up MRI was performed in 23 patients 3–6 months after successful revascularisation to evaluate wall motion changes.

Results

We assessed viability in 124 myocardial segments subtended by a CTO in 23 patients with successful PCI who underwent serial imaging. Segments with wall motion abnormality at baseline (n=80) were analysed. Most of these segments (n=54, 68%) were concordantly assessed viable by PET and MR, conversely only 2 (2%) segments were assessed non-viable by both imaging techniques. However, almost one third of the segments showed discordant patterns of viability either PET not viable/ MR viable (3 (4%) segments) or PET viable/ MR not viable (21 (26%) segments): particularly the latter revealed a significant wall motion improvement (p=0.033).

The combination of PET and MR showed a fair accuracy in predicting myocardial segments with wall motion improvement after CTO revascularisation (PET/MR area under ROC curve (AUC) 0.72, SE 0.07, p=0.002), which was superior to MR-LGE (AUC=0.66, SE 0.09) and FDG-PET (AUC=0.58, SE 0.10) alone (Figure).

Comparisons of ROC curves

Conclusion

Hybrid PET/MR imaging prior to successful CTO showed a better performance than PET or MR alone in predicting regional improvement of disturbed wall motion.

The complimentary information derived from both modalities may particularly help to identify small amounts of viable epicardial myocardium within large scars which can improve contractility after CTO-revascularisation.
5965Perimatrial inflammation measured by fluoine-18-fluorodeoxyglucose-positron emission tomography/computed tomography to predict new-onset atrial fibrillation
Authors: Hada Y , Iwamiya S , Hijikata S , Yoshitake T , Sato H , Konishi Y , Sakurai K , Azegami K , Hirao K
Published: October 2019

Background

Fluoine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is a useful modality of inflammatory disease. Epicardial adipose tissue (EAT) contains abundant ganglionated plexi, therefore EAT inflammation may cause atrial arrhythmia, such as atrial premature contraction (APC) and atrial fibrillation (AF). Previous studies have shown that inflammatory activity of EAT has relation to the presence of AF. However, it is unknown whether EAT inflammation contributes to the occurrence of AF.

Methods

Out of 20720 examinees who underwent FDG-PET/CT for screening of cancer in the years 2012–2018, 151 (aged 65.6±12.0 years old, 62 females) had ambulatory electrocardiographic monitoring (Holter ECG) within a year and non-detection of AF. Standardized uptake value (SUV) was measured in fat adjacent to roof of left atrium (ROOF), atrioventricular groove (AV), left main coronary artery (LMT), and right ventricular blood pool (RV). In order to correct for blood pool activity, SUV of ROOF, AV, and LMT were divided by SUV of RV respectively, yielding target-to-background ratio (TBR). As regards to arterial inflammation, measurements were performed with SUV in ascending aorta (A-Ao) and in superior vena cava (SVC) as blood pool. In the same way, SUV of A-Ao was divided by SUV of SVC, yielding TBR.

Results

According to Holter ECG, APC≥100 beats per day was seen in 60 patients (Group A), but not in the other 91 (Group B). In Group A, TBR of ROOF, AV, and LMT were all significantly higher than Group B (p<0.001, p=0.004, and p=0.008, respectively). During a median follow-up of 179 days, new-onset AF was diagnosed in 7 patients (4 in Group A (6.7%), 3 in Group B (3.3%), p=0.046). There was significant difference in TBR of ROOF between patients with and without new-onset AF (p<0.001), but not in TBR of AV and LMT. In addition, no significant difference was observed in TBR of A-Ao between these two groups. In the Cox proportional hazard analysis, TBR of ROOF was found to be an independent predictor of new-onset AF (odds ratio 40.1, 95% confidence interval 6.05 to 265.9, p<0.001).

Conclusions

Although EAT inflammation evaluated by SUV is related to frequent APCs, only in fat adjacent to roof of left atrium is associated with and predicts future occurrence of AF. Arterial inflammation measured by SUV has no relation to atrial arrhythmia.
6067Right ventricular global longitudinal strain predicts cardiovascular mortality and heart failure hospitalization in patients with functional tricuspid regurgitation
Authors: Ochoa-Jimenez R , Guta A C , Previtero M , Palermo C , Aruta P , Badano L P , Muraru D
Published: October 2019

Background

Functional tricuspid regurgitation (FTR) and its increasing severity are well-known factors associated with increased morbidity and mortality in patients with pulmonary artery hypertension or left heart diseases.

Purpose

To assess the main clinical and echocardiographic determinants of outcome in patients with various causes of FTR.

Methods

A total of 140 patients (pts) (72±14 years, 40% men) with FTR of diverse etiologies underwent complete 2D and additional 3D echocardiography acquisitions and were followed for a median of 5.2 years (interquartile range 2.1 - 6.7 years). Severe FTR was defined by ≥2 parameters: (1) coaptation defect; (2) vena contract ≥7; (3) PISA radius >9 mm; (4) hepatic vein systolic flow reversal. The primary composite outcome was defined as death from cardiovascular causes and hospitalization due to right-sided heart failure (HF).

Results

74 pts (53%) developed the primary composite outcome. Death occurred in 31 pts (22%), while hospitalization due to right-sided HF occurred in 66 pts (47%). At baseline, patients who developed the primary composite outcome, compared to those who did not, had more symptoms, more severe FTR, higher pulmonary systolic pressure (60±27 vs 43±16 mmHg), larger right atrium (69±34 vs 51±22 mL/mm2), right ventricular (RV) basal diameter (29±6 vs 24±4 mm/m2), larger RV end-diastolic (102±45 vs 76±25 mL/m2) and end-systolic (62±37 vs 43±17 mL/m2) volumes, larger tricuspid annulus area (7.7±1.8 vs 6.8±1.8 cm2/m2), lower RV systolic function (RVEF [42±11 vs 46±8%], TAPSE [18±4 vs 21±4], S' [11±3 vs 12±2], RV global longitudinal strain (RVGLS) [16±5 vs 19±4], RV free wall longitudinal strain [19±7 vs 23.5]); all p-values <0.03. There were no significant differences in age, body size or comorbidities. After multivariable Cox regression analysis, FTR grade severity (hazard ratio [HR]=2.95, 95% confidence interval [CI] 2.14–4.06, p<0.001) and RVGLS (HR= 0.91, 95% CI 0.86–0.95) were the only independent predictors of mortality. A cutoff of −17.5 for RVGLS had 57% sensitivity, 73% specificity and a HR of 2.34 (95% CI of 1.42–3.88, p-value=0.001). The Kaplan Meier survival curve showed that patients with an RVGLS ≥ −17.5 had a higher probability of developing the primary composite outcome, especially at an earlier phase of the follow up when compared to those with higher LS (log rank test chi-square = 13.0, p<0.001) (Figure). At the end of follow up, 60% of patients with a RVGLS ≥-17.5 did not developed the primary composite outcome vs 29% in the group with a LS lower than −17.5.

Kaplan-Meier curve of outcome by RVGLS

Conclusions

In patients with FTR, a decreased RVGLS, with a cutoff of −17.5, proved to be an independent prognostic factor for the development of HF hospitalizations and death from cardiovascular causes.
6071Extent of hypertensive exposure in relation to vascular brain injury and cognitive impairment using heart-brain magnetic resonance imaging; The Heart-Brain Connection Study
Authors: Amier R , Marcks N , Hooghiemstra A M , Nijveldt R , Van Buchem M A , De Roos A , Biessels G J , Kappelle L J , Van Oostenbrugge R J , Bots M L , Niessen W J , Van Osch M J P , Van Der Flier W M , Brunner-La Rocca H P , Van Rossum A C
Published: October 2019

Background

Preserving brain health into advanced age has become one of the great challenges of modern medicine. Hypertension is highly prevalent and considered an independent contributor to cognitive impairment. Vascular brain injury, induced by exposure of the cerebral microcirculation to increased pressure and pulsatility, is the hypothesized link between hypertension and cognitive impairment. Hypertensive exposure can be assessed by cardiovascular magnetic resonance imaging markers, e.g. aortic stiffness by pulse wave velocity (PWV), left ventricular mass index (LVMi) and left ventricular (LV) concentricity by mass-to-volume ratio.

Purpose

To investigate the extent of hypertensive exposure in relation to cerebral small vessel disease (CSVD) and cognitive impairment, using heart-brain magnetic resonance imaging.

Methods

We included 559 participants aged 68±9 years from the Heart-Brain Connection study, consisting of three patient groups (i.e. heart failure, vascular cognitive impairment and carotid occlusive disease) and controls. LVMi, LV mass-to-volume ratio, aortic PWV and CSVD were assessed by 3.0 T heart-brain magnetic resonance imaging. Impairment in ≥1 major cognitive domain was assessed by comprehensive neuropsychological testing. Effect modification for patient groups was investigated by interaction terms; results are reported pooled or stratified accordingly.

Results

Overall prevalence of CSVD was 68.7% and prevalence of cognitive impairment was 26.9%. Figure 1 provides a visual overview of hypertensive exposure markers in relation to brain outcome. Aortic PWV (odds ratio [OR] 1.17, p=0.003 in patient groups only), LVMi (OR in carotid occlusive disease 5.69, p=0.006; OR in other groups 1.30, p=0.017) and LV mass-to-volume ratio (OR 1.81, p<0.001) were all associated with CSVD. Both aortic PWV (OR 1.07, p=0.009) and LV mass-to-volume ratio (OR 1.27, p=0.007) were also associated with cognitive impairment. Relations were independent of sociodemographics and cardiac index, and mostly persisted after correction for systolic blood pressure or medical history of hypertension. The relations of hypertensive exposure markers with cognitive impairment were attenuated when presence of CSVD was added as co-variate, (indirectly) supporting the hypothesis that CSVD is the link between hypertension and cognitive impairment.

Figure 1

Conclusion

Hypertensive exposure markers were independently associated with CSVD and cognitive impairment. Our findings indicate that hypertensive exposure markers relate to brain structure and function beyond clinical blood pressure or medical history.

Acknowledgement/Funding

Netherlands Cardiovascular Research Initiative; Dutch Heart Foundation; NFU; ZonMW; KNAW
6110OCT guidance during primary PCI may increase long-term risk of device oriented events: subanalysis of ROBUST study
Authors: Jakl M , Cervinka P , Kala P , Kanovsky J , Kupec A , Vanek J , Bezerra H G , Schnell A , Costa M A
Published: October 2019

Background

Optical coherence tomography (OCT) guidance in primary percutaneous coronary intervention (pPCI) is expected to be safe in short and mid-term follow-up. Long term merits or risks of OCT guidance are unknown.

Purpose

To assess the possible merits of OCT guidance in pPCI in long-term follow-up.

Methods

201 patients with ST-elevation myocardial infarction (STEMI) were enrolled in this study. Patients were randomized either to pPCI alone (angio-guided group, n=96) or to pPCI with OCT guidance (OCT-guided group, n=105) and also either to biolimus A9 or to everolimus-eluting stent implantation. The OCT study was performed after PCI with C7-XRTM intravascular imaging system employing a non-occlusive technique.

Incidence of Device-oriented Composite Endpoints (DoCE) was compared in both study groups. DoCE were defined as composite of definite or possible cardiovascular death, myocardial infarction and target vessel revascularization. The search for DoCE was performed by means of medical check-ups, repeated telephone contacts, analysis of medical records and search in national population registry.

Results

Mean follow-up was 6.5 (6.5–7.1 years). Of these patients, 2 (1.0%) patients died of cardiovascular reason, 4 patients (2%) suffered myocardial infarction and 7 (3.5%) patients underwent target lesion revascularization. In OCT guided group, number of stents per patient was higher (1.4 vs. 1.2, p=0.03). Risk of DoCE was significantly higher in OCT-guided group (7.6% vs. 2.1%, p=0.023).

Event-free survival in study groups

Conclusion

Our data suggest increased risk of adverse events related to OCT guided tailoring of stent implantation performed after pPCI. These findings should be confirmed by further randomised trials with higher statistical power.

Acknowledgement/Funding

The work was supported by a long-term organization development plan 1011 (FMHS)