bluuebunny/crossref_metadata_2025 huggingface dataset:
3226The impact of cardiovascular risk factors on global longitudinal strain over a ten-year period in the general population: The Copenhagen City Heart Study
Authors: Skaarup K G , Lassen M C H L , Biering-Soerensen S R B S , Joergensen P G J , Appleyard M A , Berning J B , Hoest N H , Jensen G B J , Schnohr P S , Soegaard P S , Gislason G H G , Moegelvang R M , Biering-Soerensen T B S
Published: October 2019

Background

Global longitudinal strain (GLS) of the left ventricle (LV) has proved to be a strong predictor of cardiovascular morbidity and mortality. GLS declines throughout adult-life as the LV remodels and adapts. Information on the impact of cardiac risk factors such as male sex, obesity, smoking status, hypertension, hypercholesterolemia, and diabetes on GLS through time has not yet been investigated.

Purpose

The aim of the present study was to investigate the impact of age, sex, body mass index (BMI), smoking status (current and previous vs never), mean arterial blood pressure (MAP), total plasma cholesterol (TPC), and HbA1c on GLS in the general population over a 10-year period.

Method

A total of 689 citizens recruited from the general population participated in the 4th and 5th Copenhagen City Heart Study (CCHS4 and CCHS5) a prospective longitudinal study. At CCHS4 the mean age was 51 years and 45% were male. The average decline in GLS during the follow-up period was −0.65%. All participants underwent two echocardiographic examinations median 10.4 [IQR: 10.2, 10.9] years apart along with thorough health examinations. All analyses were adjusted for baseline GLS value (CCHS4 value).

Results

In regression models, increasing age, male sex, increasing BMI, MAP, hypertension, increasing HbA1c, and diabetes proved to be significantly associated with increased decline in GLS. Relationship between significant continuous cardiovascular risk factors and ΔGLS are displayed in restricted spline curves (Figure 1). In a multivariable regression model including all the investigated cardiovascular risk factors, estimated glomerular filtration rate, plasma pro B-type natriuretic peptide, heart rate, and previous ischemic heart disease, age (standardized β-coef. = −0.10, P=0.005), male sex (standardized β-coef. = −0.16, P<0.001), and MAP (standardized β-coef. = −0.07, P=0.009) remained independent predictors of an accelerated decline in GLS during a 10-year period.

Restricted cubic spline curves

Conclusion

In the general population increasing age, male sex, and increasing MAP are all independently associated with an accelerated decline in GLS over a 10-year period.
3255Characterization of the arrhythmogenic substrate with multimodality imaging in ischemic patients undergoing VT ablation: relationship between cardiac computed tomography and magnetic resonance
Authors: Zucchelli G , Soto Iglesias D , Jauregui B , Teres C , Penela D , Barletta V , Bongiorni M G , Berruezo A
Published: October 2019

Background

Cardiac magnetic resonance (CMR)-aided ventricular tachycardia (VT) substrate ablation has shown to improve VT recurrence-free survival, through a better identification of the arrhythmogenic substrate. However, the access to CMR may be limited in certain centers or sometimes Its use can be contraindicated in patients with cardiac implantable electronic device. Cardiac computed tomography (CT) has shown to improve the results of substrate ablation, correlating with low-voltage areas and local abnormal ventricular activity, and identifying ridges of myocardial tissue (CT-channels) that may be appropriate target sites for ablation.

Purpose

To evaluate the correlation between CT and CMR imaging in identifying anatomical heterogeneous tissue channels (CMR-channels) or CT-channels in ischemic patients undergoing VT substrate ablation.

Methods

The study included 30 post-myocardial infarction (MI) patients (mean age 69±10; 94% male, left ventricular ejection fraction 35±10%), who underwent both CMR and cardiac CT before VT substrate ablation. Using a dedicated post-processing software, the myocardium was segmented in 10 layers from endocardium to epicardium both for the CMR and CT, characterizing the presence of CMR-channels and CT-channels, respectively, by two blinded operators, assigned either to CMR or CT analysis. CMR-channels were classified as endocardial (CMR-channels in layer <50%), epicardial (CMR-channels in layers ≥50%) or transmural (in both endo and epicardial layers). Presence and location of CT and CMR-channels were compared.

Results

In 26/30 patients (86.7%) 91 CT-channels (mean 3.0±1.9 per patient) were identified while 30/30 (100%) showed CMR-channels (n=76; mean 2.4±1.2 per patient). We found 190 CT-channel entrances (mean 6.3±4.1 per patient), and 275 CMR-channel entrances (mean 8.9±4.9 per patient) on cardiac CT and CMR, respectively. There were 47/91 (51.6%) true positive CT-channels. On the contrary, 44/91 (48.4%) CT-channels were considered false positives [19/91 (20.9%) identified out of CMR scar], and 29/76 (38.2%) CMR-channels could not be identified on CT. Thirty-six out of 76 (47.4%) CMR-channels were considered as non-endocardial (epi- or transmural). Twenty-nine out of 36 (80.5%) non-endocardial CMR-channels were coincident with CT-channels.

CT and CMR Channels

Conclusion

CT shows a modest sensitivity in identifying CMR-channels and fails in ascertain their complexity, underestimating the number of entrances; however, channels location at CT fit well with CMR for those classified as transmural or epicardial.
3259Next-generation sequencing to confirm clinical FH in The Netherlands
Authors: Reeskamp L , Zuurbier L C , Hovingh G K , Defesche J C
Published: October 2019

Background

Pathogenic variants in the genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B100 (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9)) are known to cause familial hypercholesterolemia (FH), a disease characterized by high LDL-C levels. We set out to investigate which proportion of patients with extremely elevated LDL-C levels, who were referred for molecular analysis, carry a mutation in any of the three FH genes or other, putative FH genes.

Methods

Targeted next-generation sequencing of 28 genes involved in lipid metabolism was performed in 1475 clinical FH patients with LDL-C levels >5mmol/L (corresponding with possible, probable and definite FH score according to the Dutch Lipid Clinic Network criteria) and triglyceride levels <4.5 mmol/L. Genetic variants and copy number variants were curated consecutively using specialist analysis software. (Likely) pathogenic variants in LDLR, APOB, or PCSK9 were annotated as FH-causing variants.

Results

14.3% of the 1475 patients with clinical FH were heterozygous carriers of a mutation in LDLR, APOB, or PCSK9. This number ranged from 8% in the lowest LDL-C group (5–5.99 mmol/L) to 56% in patients with the highest LDL-C levels (>8 mmol/L). Patients with LDLR, APOB, or PCSK9 variants had median LDL-C levels of 6.8 [5.7–7.9], 6.2 [5.1–7.0], and 6.4 [5.7–6.8] mmol/L [interquartile range], respectively. Mutation-negative FH patients had median LDL-C levels of 5.8 [5.2–6.5] mmol/L. Of the FH mutation-negative patients 7.4% had a (likely) pathogenic variant in the gene encoding lipoprotein lipase (LPL) and 1.3% in the apolipoprotein E (APOE) gene. The proportion of FH mutation-negative patients carrying an APOE variant increased from 1.2% in the lowest LDL-C group to 7.5% in patients with LDL-C >8 mmol/L. Mutation-positive FH patients were significantly younger (41.61±17.53 years vs 52.62±13.28 years P<0.001) and had a significant lower BMI (25.86±4.87 vs 26.55±4.07kg/m2, P=0.02) compared to mutation negative patients.

Figure 1

Conclusions

A genetic defect in LDLR, APOB or PCSK9 is identified in only 14.3% of the patients with a clinical FH phenotype (defined as LDL-C >5 mmol/L) referred for molecular testing in the Netherlands. Mutations in LPL and APOE were found in a minor proportion of the FH mutation-negative patients. Our finding that a mutation is only found 56% of patients who present with LDL-C levels above 8 mmol/L indicates that either misclassification of FH and/or other genetic defects may be present in this group.

Acknowledgement/Funding

Grant [016.156.445] from The Netherlands Organisation for Scientific Research (NWO)
3296Clinical application of the fourth universal definition of myocardial infarction
Authors: Hartikainen T , Soerensen N A , Haller P M , Gossling A , Blankenberg S , Westermann D , Neumann J T
Published: October 2019

Background

The recently released fourth version of the Universal Definition of Myocardial Infarction (UDMI) introduced substantial changes such as the implementation of the categories acute and chronic myocardial injury. It further recommends the use of sex-specific troponin cut-offs and consideration of absolute rather than relative changes of troponin concentrations for diagnosis of myocardial infarction (MI). Our aim was to apply the updated UDMI in patients with suspected MI to investigate its effect on diagnosis and prognosis.

Methods

We included 2'304 patients presenting to the emergency department with suspected MI. The final diagnosis was first adjudicated according to the 3rd UDMI by two physicians in a blinded fashion using all available medical records, laboratory findings including high-sensitivity troponin T results as well as clinical and imaging findings. Thereafter all patients were re-adjudicated based on the 4th UDMI, again all available information was used. Included patients were followed up to 4 years to assess all-cause mortality, incident nonfatal MI, revascularization and rehospitalization. Hazard ratios (HR) were calculated to investigate the effect of the diagnoses based on the 4th UDMI on prognosis.

Results

Out of 2'304 included patients, 708 got reclassified by the 4th UDMI. 442 (19.2%) were diagnosed as having MI compared to 504 (21.9%) based on the 3rd UDMI. Out of 1'862 non-MI patients, 74 (3.97%) patients had acute and 583 (31.3%) chronic myocardial injury (Figure 1). Patients with acute or chronic injury were older, more often female and had worse renal function than other non-MI patients. The most common causes for acute myocardial injury were heart failure, pulmonary embolism and takotsubo cardiomyopathy. For chronic myocardial injury hypertension, heart failure and non-obstructive coronary artery disease were the most frequent reasons. In cox regression analyses unadjusted HR for all-cause mortality in patients with acute or chronic myocardial injury was considerably higher when compared to patients with non-cardiac chest pain (HR 13.2 (confidence interval (CI) 6.7–26.3) (p<0.001) for acute myocardial injury and 7.2 (CI 4.2–12.5) (p<0.001) for chronic myocardial injury). After adjustment for age and gender, acute and chronic myocardial injury still strongly predicted a poorer outcome and higher rate of cardiovascular events compared to other non-MI patients. Patients with acute or chronic myocardial injury showed equally poor outcome as patients with MI.

Figure 1. Re-adjudication

Conclusion

By introducing the categories of acute and chronic myocardial injury the 4th UDMI succeeds to identify non-MI patients with higher risk for cardiovascular events and poorer outcome and thus seems to improve risk assessment in this heterogeneous population. Prevention strategies for this specific population are yet to be investigated.
3304High sensitive cardiac troponin i at admission and 30 minutes later to rule-in or rule-out acute myocardial infarction - Preliminary results from the RACING-MI trial
Authors: Bang C , Hansen C , Glerup Lauridsen K , Alcaraz Frederiksen C , Schmidt M , Jensen T , Hornung N , Loefgren B
Published: October 2019

Introduction

Current ESC guidelines have introduced a 0h/1h algorithm for accelerated rule-in or rule-out of acute myocardial infarction (MI) when using assay specific high-sensitive cardiac troponin I (hs-cTnI). Several studies have investigated the diagnostic performance and safety of this approach using different hs-cTnI assays. However, little is known of the diagnostic performance of a 0h/30min algorithm.

Purpose

To evaluate the diagnostic accuracy of early rule-in or rule-out of MI after 30 minutes by applying assay specific hs-cTnI cut-off values from a recently validated 0h/1h algorithm.

Methods

We prospectively enrolled chest pain patients suggestive of MI admitted to the Emergency Department. Patients underwent serial hs-cTnI measurements at admission (0 hour) and after 3 hours according to clinical practice. In addition, hs-cTnI measurements were performed after 30 minutes. The assay specific cut-off values from the 0h/1h algorithm were applied to the 30 minute cohort (figure 1). Final diagnosis was adjudicated independently by two physicians.

Results

In total, 943 patients were included. MI was the final diagnosis in 67 (7.1%) patients. Overall, absolute hs-cTnI values after 30 minutes were significantly higher in the MI group than in the non-MI group (19.2 (Q1:Q3) 2.7–75.3) ng/L versus 0.1 (0.2–0.7) ng/L, p<0.001). When applying the assay-specific hs-cTnI cut-off valuesfor the 0h/1h algorithmto the 30 minute patient cohort, 52.4% of patients were classified as rule-out with a negative predictive value of 100% (95% CI: 99.2–100). In total, 8.5% were classified as rule-in with a positive predictive value of 83.8% (95% CI: 74.2–90.3). Sensitivity was 100% (95% CI: 94.6–100) and specificity was 97.4% (95% CI: 95.7–98.6). Overall, 39.1% were assigned to the observational zone with a 3.5% prevalence of MI.

Conclusions

The use of assay specific hs-cTnI measurement at admission (0h) and 30 min later can be used to safely rule-out MI. This indicates that it might be safe to develop a 0h/30min algorithm and hereby reduce time to diagnosis even further. NCT03634384.

Acknowledgement/Funding

Randers Regional Hospital, A.P Møller Foundation, Boserup Foundation, Korning Foundation, Højmosegård Grant, Siemens Healthcare (TNIH assays), etc.
4036The knowledge as the determinant of the adherence to antihypertensive treatment
Authors: Swiatoniowska N , Bartosiak E , Szymanska-Chabowska A , Mazur G , Jankowska-Polanska B
Published: October 2019

Introduction

The education of the patients with cardio-vascular diseases aims to modify the present risk factors and to increase the aware participation in the therapy. Arterial hypertension is one of the most common modifiable risk factors of cardio-vascular diseases. However, the knowledge of the self-care and adherence to therapeutic recommendations are highly disappointing. Understanding people's levels of knowledge on cardiovascular risk factors and its relation to level of adherence in antihypertensive treatment might contribute effectively to medical staff efforts to prevent, treat and control the disease.

The aim of the study was analysis of the knowledge of the cardio-vascular risk factors and the adherence to therapeutic recommendations.

Material and methods

101 patients (mean age 57.5±13.2) with arterial hypertension (stage I and II according to ESC) were enrolled into the study. The following questionnaires were used: Morisky's Self-Reported Measure of Medication Adherence (MMAS-8-Item), Hill-Bone Compliance to High Blood Pressure Therapy Scale (Hill-Bone Scale) and The Cardiovascular Disease Risk Factors Knowledge Level Scale (CARRF).

Results

41% of the patients had worse knowledge of the cardio-vascular risk factors. In comparative analysis there were the significant differences in adherence to treatment with regards to the knowledge according to CRRRF questionnaire. The patients with better knowledge had the best adherence, which diminished along with worsening the knowledge (19.0±3.5 vs 18.3±3.7 vs 16.6±4.1). The increase of the knowledge by one point in scale CARRF-KL was accompanied by the increase of the adherence by 0.14 point (mean). The relations between knowledge and adherence was observed in terms of the treatment (8.3±2.0 vs 10.1±5.0 vs 8.9±3.5; p=0.003) and the global results of Hill-Bone questionnaire (19.5±4.4 vs 22.7±7.3). The relation between the knowledge and the adherence in terms of salt intake or control check-ups was not proved. In multiple regression analysis the knowledge was significant independent determinant, which influenced the adherence in terms of the treatment MMAS (b= 0.253; p=0.0004)

Conclusions

Adherence to therapeutic recommendations is related to the knowledge of the cardio-vascular risk factors, i.e. the better knowledge, the better adherence. The knowledge is the independent predictor of adherence to treatment in patients with arterial hypertension. The identification of knowledge deficits as a factor contributing to lack of adherence and poor hypertension control remains a key challenge for clinicians caring for patients with hypertension.
4070Clinical impact of mitral regurgitation before or following transcatheter aortic valve replacement in patients with aortic stenosis: a nationwide multivariable analysis
Authors: Fauchier L , Bernard A , Bisson A , Lacour T , Herbert J , Ivanes F , Bourguignon T , Clerc J M , Quilliet L , Guillon Grammatico L , Angoulvant D , Saint Etienne C , Babuty D
Published: October 2019

Patients undergoing transcatheter aortic valve replacement (TAVR) may have concomitant mitral regurgitation (MR). The impact of MR at baseline or after TAVR on subsequent prognosis remains to be more precisely determined. We analysed the impact of MR before or after TAVR on prognosis in the systematic analysis of patients treated with TAVR at a nationwide level.

Methods

Based on the French administrative hospital-discharge database, the study collected information for all consecutive patients with aortic stenosis treated with transfemoral TAVR in France between 2008 and 2018. Cox regression was used for the analysis of predictors of events during follow-up.

Results

A total of 47,872 patients with transfemoral TAVR were included in the analysis (mean age 83±7 years). Moderate/severe MR was present at baseline (MRb) in 9.5% of the patients. Few patients (1.6%) revealed moderate/severe MR post-TAVR (MRpt). Mean follow-up was 1.31±1.61 years. MRb was associated with an increased cardiovascular mortality (Hazard ratio 1.29, 95% CI 1.20–1.39) and total mortality (Hazard ratio 1.15, 95% CI 1.10–1.21). However, MRb was not an independent predictor in multivariable analysis, neither for cardiovascular mortality (adjusted HR 1.06, 95% CI 0.98–1.14) nor for total mortality (adjusted HR 1.01, 95% CI 0.96–1.07). MRpt was not a predictor of cardiovascular or total mortality. Older age, male sex, history of pulmonary edema/cardiogenic shock, atrial fibrillation, myocardial infarction, diabetes, renal failure, liver disease, pulmonary disease, previous cancer and anemia at baseline independently predicted mortality during follow-up. All of them (but history of cancer) were also independent predictor of cardiovascular death.

Conclusion

Baseline MR was associated with increased cardiovascular and totality mortality following TAVR but was not an independent predictor of any of them. By contrast, several other predictors of cardiovascular and total mortality were identified. This suggests that MR should not be directly considered to establish the strategy for TAVR decision or for avoiding TAVR-related futility.
4094Microvascular dysfunction in takotsubo syndrome visualized at stress and rest using 82-rubidium PET imaging
Authors: Kildevang Jensen J , Bentsen S , Bang L E , Holmvang L , Ripa R , Hasbak P , Kjaer A
Published: October 2019

Introduction

Takotsubo Syndrome (TTS) is recognized as the acute onset of reversible heart failure, often mimicking acute coronary syndrome with ECG changes and rise in cardiac biomarkers, but with no apparent coronary obstruction. The pathophysiological mechanisms of TTS are not yet fully understood, but it is well established that microvascular dysfunction and constriction plays a crucial role in the pathogenesis of TTS.

Positron emission tomography (PET) using the radioactive tracer Rubidium-82 (Rb-82) is routinely used to asses myocardial perfusion and microvascular function in a wide array of cardiological conditions.

Purpose

The purpose of this study was to evaluate myocardial perfusion and flow reserve in patients with TTS using Rb-82 positron emission tomography (PET) molecular imaging during rest and pharmacologically induced stress, in the acute phase and after 3 months of follow-up.

Methods

A total of 8 patients were diagnosed with TTS due to acute onset of symptoms, rise in cardiac biomarkers, absence of significant coronary obstruction and apical ballooning of the left ventricle. Subsequently the patients underwent Rb-82 PET scan in the acute phase (1–4 days after onset), and again at 3 months of follow-up. Rb-82 PET scans were performed both during resting conditions and during pharmacologically induced stress with infusion of adenosine. Myocardial blood flow (MBF) and total perfusion defect (TPD) were quantified during rest and stress, and the coronary flow reserve (CFR) was calculated. The AHA-17 segment model was used to determine summed rest scores (SRS) and summed stress scores (SSS). Data are presented as means ± SEM

Results

MBF during stress was significantly lower in the acute phase than at 3 months follow-up (2.99±0.35 vs. 3.82±0.19 ml/g/min, P=0.016) as opposed to resting MBF, which did not differ significantly (1.33±0.14 vs. 1.45±0.09 ml/g/min, P=0.309). The CFR of the patients was not significantly different in the acute phase compared to 3 months follow-up (2.33±0.25 vs 2.65±0.12, P=0.11), though 4 of the patients had a CFR <2.0 in the acute phase, which was normalized at follow-up. TPD was significantly lower at follow-up compared to the acute phase at both rest (21.6±5.86 vs. 0.75±0.61%, P=0.009) and stress (25.3±6.01 vs. 1.25±0.31%, P=0.006). SRS (12.6±3.24 vs. 0.75±0.59, P=0.01) and SSS (19.9±3.39 vs. 1.38±0.59, P=0.001) was significantly higher in the acute phase compared to follow-up. At follow up, all values were normalized.

Figure 1

Conclusion

These results supports the evidence that TTS is partly caused by microvascular dysfunction and constriction during the acute phase. Further studies are needed to uncover the exact mechanisms behind.
4183New onset atrial fibrillation in acute coronary syndrome: early vs late onset
Authors: Alves Guimaraes J , Goncalves F M , Borges S , Monteiro J J , Mateus P S , Trigo J , Moreira J I
Published: October 2019

Background

The prognostic impact of the timing where new-onset Atrial Fibrillation (AF) occurs in Acute Coronary Syndrome (ACS) patients isn't well studied.

Objective

Evaluate the predictors and prognostic impact of early-onset AF (EAF) and late-onset AF (LAF) in ACS patients.

Methods

We analysed 17016 patients with ACS enrolled in a national multicenter registry from October 2010 to January 2019. Patients with history of valvular disease, valve replacement, AF present at hospital admission or those who died in the first 48 hours were excluded. EAF was defined as AF in the first 48 hours of hospitalization and LAF after 48 hours. The primary endpoint was a composite of death and readmission from cardiovascular causes at 1 year.

Results

The mean age was 65±13 years; 74% were males and 42% had STEMI). 324 (1.9%) had EAF and 344 (2.0%) had LAF.

The predictors of EAF were age ≥75 years (OR 2.04, 95% CI 1.53–2.70, p<0.001); history of heart failure (OR 1.82, 95% CI 1.09–3.02, p=0.022), STEMI diagnosis (OR 2.74, 95% CI 2.06–3.61, p<0.001), admission Killip class (KK)≥2 (OR 2.70, 95% CI 1.98–3.69, p<0.001).

The predictors of LAF were age ≥75 years (OR 3.15, 95% CI 2.36–4.19, p<0.001), history of stable angina (OR 1.42, 95% CI 1.06–1.90, p=0.018), cerebrovascular disease (OR 1.68, 95% CI 1.14–2.46, p=0.008), COPD (OR 2.33, 95% CI 1.58–3.44, p<0.001), STEMI diagnosis (OR 2.31, 95% CI 1.77–3.03, p<0.001), admission KK ≥2 (OR 2.06, 95% CI 1.54–2.76, p<0.001) and stress hyperglycemia (OR 1.54, 95% CI 1.15–2.05, p=0.003)

In STEMI patients only those with LAF had higher symptoms time (245 (IQR 165–400) minutes vs 284 (IQR 200–425) min; p=0.02).

During hospitalization, LAF patients had a worse prognosis with a higher rate of heart failure, re-infarction, stroke, major bleeding and death (Table 1).

In the follow-up, in multivarite analysis, only LAF was a predictor of the primary endpoint (EAF: HR 0.79, 95% CI 0.50–1.25, p=0.314; LAF: HR 1.45, 95% CI 1.05–2.00, p<0.025).

Complications during hospitalization No AF EAF LAF p Death 1.3 6.5 12.5 <0.001 Heart Failure 11.4 38.3 50.3 <0.001 Re-enfarction 1.0 0.9 3.5 <0.001 Stroke 0.5 0.9 3.8 <0.001 Major bleeding 1.3 4.3 4.1 <0.001

Kaplan Meier curve

Conclusion

Patients with EAF and LAF have different characteristics and outcomes with LAF patients having a worse in-hospital and long term prognosis.
4283Exercise right heart catheterization before and after balloon pulmonary angioplasty in inoperable patients with chronic thromboembolic pulmonary hypertension
Authors: Liebetrau C , Kriechbaum S , Rieth A , Ghofrani H A , Haas M , Rolf A , Hamm C W , Guth S , Mayer E , Wiedenroth C B
Published: October 2019

Background

Balloon pulmonary angioplasty (BPA) is an evolving treatment option for inoperable patients with chronic thromboembolic pulmonary hypertension (CTEPH). The main indicator for success is improvement in pulmonary hemodynamics, but outcome data are heterogeneous.

Purpose

The aim of the present study was to evaluate pulmonary hemodynamics not only at rest, but also during exercise before and 6 months after BPA.

Methods

We report a prospective series of 64 consecutive patients with inoperable CTEPH who were treated interventionally with BPA. All patients underwent standardized assessment prior to the first BPA and 6 months after the last intervention. Assessment included WHO FC, Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR), 6-minute walking distance (6MWD), serum levels of the N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP), and exercise RHC.

Results

The mean number of sessions per patient was 5.6 (± 1.3) and the mean number of pulmonary segments targeted in all interventions was 11 (± 3). BPA treatment led to improvements in pulmonary hemodynamics and exercise capacity (6MWD: 416±94 m vs. 463±96 m; p<0.0001) except for CO and CI during RHC at rest; these parameters showed improvements only during exercise RHC. MPAP at rest showed a reduction from 41±9 to 31±9 mmHg (p<0.0001) and PVR at rest decreased from 6.8±2.3 WU to 4.3±1.9 WU (p<0.0001). Further decreases were observed for systolic pulmonary arterial pressure, TPG, PVR, and TPR. Cardiac output (7.0±2.0 L/min vs. 8.3±2.0 L/min; p<0.0001) and cardiac index during exercise RHC (3.8±1.1 L/min/m2 vs. 4.4±1.1 L/min/m2; p<0.0001) improved significantly. Median NT-proBNP concentrations decreased from 741 ng/L (IQR 192–1425 ng/L) to 139 ng/L (IQR 60–266 ng/L) during BPA treatment (p<0.0001). Results from the CAMPHOR questionnaire showed significant improvements in symptoms (11±5.8 vs. 5.5±4.9, p<0.0001), activity limitations (9.2±5.6 vs. 5.2±4.5, p<0.0001), and quality of life (6.4±5.7 vs. 3.5±3.7, p<0.0001).

Conclusion

Significant improvements in pulmonary hemodynamics at rest and during exercise were observed 6 months after BPA. Exercise right heart catheterization offers a more discriminating evaluation of the changes in pulmonary hemodynamics after BPA.
4314Cardiac involvement of Wilsons disease
Authors: Quick S , Reuner U , Weidauer M , Heidrich F M , Mues C , Hempel C , Sveric K , Ibrahim K , Linke A , Speiser U
Published: October 2019

Background

Wilson's disease (WD) is an inherited autosomal recessive disorder resulting from abnormal copper metabolism. Relatively little is known about the effects of copper accumulation on the heart.

Objective

We aimed to determine if patients with Wilson's disease show signs of cardiac involvement and structural heart disease.

Methods

In this prospective trial, we studied 61 patients with Wilson's disease and compared them to 61 age- and gender-matched healthy controls.

Results

While left ventricular function assessed by global longitudinal and global radial strain did not differ significantly between the groups, Wilson's disease patients had significantly reduced global radial strain (table 1).

Wilson's disease patients demonstrated significantly more late gadolinium enhancement than the control patients (4.9±1.4 vs. 1.1±0.2% p<0.001).

The severity of Wilson's disease, based on the Unified Wilson's Disease Rating Scale, was significantly correlated with the extent of late gadolinium enhancement (r=0.53, P=0.001), cardiac troponin (r=0.56, P=0.001), the number of premature ventricular contraction (r=0.66, P=0.001).

Table 1. Myocardial strain and CMR characteristics of patients and controls Parameter Patients (n=61) Controls (n=61) p value Left ventricular parameters   GLS, % −22.8 (4.8) −21.8 (5.1) 0.124   GRS, % 43.2 (13.2) 51.6 (13.8) 0.002   GCS, % −29.2 (5.2) −28.6 (4.7) 0.534 Late gadolinium enhancement   LGE, %* 4.9 (1.4) 1.1 (0.2) 0.003   LGE at RVIP, n (%) 58 (95) 3 (5) <0.001   Midwall LGE, n (%) 11 (18) 0 <0.001 Right ventricular parameters   GLS, % −23.6 (4.9) −26.1 (5) 0.01 Data are presented as mean (SD), median (IQR)*, or n (%) unless otherwise stated. GLS, global longitudinal strain; GRS, global radial strain; GCS, global circular strain; LGE: late gadolinium enhancement; RIVP, right ventricular insertion point.

Conclusion

Our data demonstrate that cardiac involvement in Wilson's disease is possible and those patients who are severely affected by the disease carry a higher risk of developing structural heart disease.
4323Detection of early inflammation in myocarditis by molecular magnetic resonance imaging of activated platelets
Authors: Maier A , Jakob K , Von Elverfeldt D , Braig M , Bienert T , Peter K , Klingel K , Bode C , Von Zur Muehlen C
Published: October 2019

Introduction

A noninvasive imaging strategy for diagnosis and localization of early myocarditis would be of great clinical interest. However, resolution of current imaging techniques is limited. Platelets play an important role in inflammatory processes but the role in myocarditis is unknown. Therefore, the aim of this project was to examine the role of platelets in myocarditis and establish a sensitive non-invasive molecular MRI in-vivo imaging strategy for diagnosis of myocarditis with a contrast agent against activated platelets in mice.

Methods

Myocarditis was induced by subcutaneous injection of an emulsion of porcine cardiac myosin and complete freud's adjuvant (CFA) in Balb/c mice. Inflammatory activity was targeted with a contrast agent against activated platelets consisting of microparticles of iron oxide (MPIO) conjugated to a single chain antibody directed against ligand-induced binding sites (LIBS) on activated glycoprotein IIb/IIIa (=LIBS-MPIO). In comparison, we applied an unspecific control antibody linked to microparticles of iron oxide (control-MPIO) and injected LIBS-MPIO to mice subjected to incomplete freud's adjuvant (iCFA). All imaging results were correlated to immunohistochemistry findings.

Results

Histological evaluation showed significantly higher binding of LIBS-MPIOs to platelet enriched, CD41-positive inflamed myocardium two days after induction of myocarditis in comparison to later time points (7d, 14d, 21d) (p<0.05) and control-MPIO (p<0.05) injection. In iCFA injected mice no significant LIBS-MPIO binding was found (p<0.05). In 3D in-vivo MRI we could specifically detect focal signal effects in LIBS-MPIO injected mice 2 days after induction of myocarditis, whereas in control-MPIO injected mice no signal effect was visible. Quantification of the myocardial MRI signal confirmed a signal decrease after LIBS-MPIO injection and significant fewer signals in comparison to control-MPIO injection (p<0.05).

As a perspective, we also found CD41 positive areas in histology of human myocarditis specimens.

Conclusions

Platelets are involved in the inflammation of myocarditis. Molecular MRI with LIBS-MPIO can image them at an early time point. This noninvasive imaging strategy is of clinical interest for both diagnostic and prognostic purposes, and highlights the potential of molecular MRI for characterization of cardiovascular pathologies such as myocardial inflammation.
P3100Anti-thrombin nanoparticles limit ischemia-reperfusion injury and no-reflow in myocardial infarction
Authors: Pan H , Lindon A , Grabau R , Dominguez W , Wickline S
Published: October 2019

Introduction

Persistent microvascular thrombosis and thrombin signaling in cardiac ischemia reperfusion injury (IRI) combine to promote infarct expansion and heart failure. We have reported previously that treatment of acute ischemic kidney injury (AKI) in rodents with anti-thrombin perfluorocarbon nanoparticles (PFC NP) limits damage to endothelium, reduces “no reflow”, and hastens recovery of kidney function. In cardiac IRI, we hypothesized that thrombin continues to exert deleterious effects well after reperfusion, but whether this strategy is effective in preserving vascular barrier function and preventing no reflow in cardiac IRI is not known. Accordingly, we postulated that sustained local thrombin inhibition with long acting anti-thrombin nanoparticles might limit vascular damage and barrier disruption that otherwise leads to hemorrhage and no reflow.

Methods

14 Sprague Dawley rats undergoing LAD occlusion for 45 min were pretreated with i.v. injection of anti-thrombin PPACK (D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone)-conjugated PFC NP (∼13,000 PPACK per PFC NP), or saline (control) followed by 2 hours of reperfusion. Sham controls (no LAD ligation) were compared. Simultaneous to treatments, a different and unique nontargeted CE PFC NP (CE: Crown Ether core) was injected for subsequent tracking and spectroscopic quantification of the relative distributions and amounts of PFC NP trapped in non-reperfused myocardium. Hearts were perfused with saline in situ, then extracted for ex vivo 19F (fluorine) MRI and spectroscopy at 7T (Bruker). T2* images were acquired for hemorrhage/edema in the area at risk. 19F MRI was acquired for PFC NP trapping (spin echo: TR 2000ms, TE 4.51 ms, FOV 20x20, 64x64 slice 1mm), along with whole heart 19PFC CE spectroscopy.

Results

Fluorine MRI of an intact heart illustrates the trapping of PFC NP in areas of nonreperfusion (Figure) amidst infarct scar region. Quantification of total heart CE PFC NP signal emanating from trapped NP revealed reduced accumulation (−49%) in the hearts of treated rats (0.47±0.09 vs 0.92±0.19, treated vs control; p<0.05). For sham occlusions, minimal deposition of CE PFC NP was observed irrespective of PPACK PFC NP treatment (n=10 per group). Areas of T2* signal indicative of vascular leakage extended beyond that of the 19F signals (Figure T2*), indicating more severe damage and trapping in central infarct zones than in more peripheral border zones after 2 hours.

Discussion

Continued inhibition of thrombin in cardiac IRI with locally-acting PPACK PFC NP preserved vascular integrity, and limited hemorrhage and No Reflow (less trapping). Because these PPACK PFC NP do not prolong bleeding times or coagulation parameters beyond ∼30–60 min after injection, yet maintain prolonged local surveillance against activated thrombin, they represent a potentially useful therapeutic strategy for cardiac IRI.
P3107Effect of cardiac rehabilitation predicts event-free survival
Authors: Mikkelsen N , Rasmusen H , Reeh J , Cardarso-Suarez C , Lado-Baleato O , Diaz-Louzao C , Prescott E
Published: October 2019

Background

Participation in cardiac rehabilitation (CR) improves prognosis. Whether more effect of exercise training also affects prognosis is unknown.

Purpose

To investigate whether change in VO2peak after CR is a predictor of future cardiovascular disease and/or mortality

Methods

Retrospective analysis on 1237 cardiac patients completing a CR program in Copenhagen in 2011–2017 with a cardiopulmonary exercise test performed at baseline and end of CR. The association between change in VO2peak and future risk of morbidity and mortality through registry linkage was assessed by Cox regression analysis adjusting for age, sex, cardiac diagnosis, comorbidities and baseline VO2peak.

Results

1237 patients were included, mean was age 64 (±11) years and 75% were males. 30% of the patients did not improve in VO2peak. There were 166 events and 76 deaths during a median follow-up of 2.3 years. Both baseline VO2peak and change in VO2peak were significantly associated with risk after multivariable adjustment.

Change in VO2peak: MACE and mortality

Conclusion

Improvement in VO2peak during a CR program is a strong predictor of subsequent prognosis in cardiac patients.
P3124Predictive value of the residual SYNTAX score following primary PCI in multivessel patients with MI-related cardiogenic shock - a CULPRIT SHOCK sub-analysis
Authors: Barthelemy O , Rouanet S , Brugier D , Vignoles N , Bertin B , Zeitouni M , Guedeney P , Overtchouk P , Hage G , Hauguel-Moreau M , Akin I , Desch S , Vicaut E , Thiele H , Montalescot G
Published: October 2019

Background

Complete revascularization (CR) – assessed by the residual SYNTAX score (rSS) – following PCI is associated with a better prognosis – in stable coronary disease, acute coronary syndrome and myocardial infarction (MI). Whether, the completeness of revascularization impacts the prognosis of patients in cardiogenic shock (CS) remains unclear.

Aim

Assess the prognosis value of rSS following primary PCI in multivessel patients undergoing MI-related CS.

Methods

The CULPRIT SHOCK trial – the largest randomized trial (n=706) to date in CS – compared an immediate multivessel PCI (MVPCI) strategy to a culprit lesion only PCI (with possible staged revascularization) strategy in multivessel patients with MI-related CS. The rSS were retrospectively assessed following last PCI (either index or staged) by a central core laboratory and patients were allocated in 4 different groups according to rSS: CR (rSS=0), 0< rSS ≤5, 5< rSS ≤14, rSS >14. The prognostic impact of rSS on the 30-day composite endpoint (mortality and/or severe renal failure) and 30-day and 1-year mortality were assessed using multivariate logistic regression.

Results

Among the 604 patients with last rSS available, aged 68.2±11.4, the median rSS was 9.0 [4.0–17.0]. CR was achieved in 75 (25%) patients in the MVPCI strategy and in 31 (10.2%) in the culprit lesion only PCI strategy. One hundred and six (17.5%), 102 (16.9%), 198 (32.8%) and 198 (32.8%) patients had a rSS=0, 0< rss ≤5, 5< rSS ≤14 and rSS >14, respectively. Patients with a higher rSS were older, less active smoker, had more triple vessel disease, chronic total occlusion, post-PCI culprit coronary TIMI flow <3 and require more mechanical circulatory support and catecholamine. Univariate analysis shows a stepwise increase in adverse events according to rSS: patients with 5< rss ≤14 and rSS >14 had higher rates of 30-day primary endpoint (OR [95% CI]: 2.02 [1.24; 329] and 2.75 [1.69; 4.49]), 30-day mortality (OR [95% CI]: 2.13 [1.29; 3.51] and 3.14 [1.90; 5.18]) and 1-year mortality (OR [95% CI]: 2.39 [1.46; 3.90] and 3.47 [2.11; 5.71]) compared to patients with CR. After multiple adjustment, rSS – tested as continuous variable – was independently associated with 30-day primary endpoint, 30-day and one-year mortality (Figure)

Conclusion

Among multivessel patients with MI-related cardiogenic shock, 1) complete revascularization is achieved only in one fourth of the patients using a MVPCI strategy and, 2) the residual SYNTAX score is independently associated with early and late mortality.

Acknowledgement/Funding

Funded by the European Union 7th Framework Program and others
P3125Five-year impact of immediate invasive strategy on clinical outcomes in patients with non-ST-segment elevation myocardial infarction: RIDDLE-NSTEMI study
Authors: Milosevic A , Milasinovic D , Vasiljevic Z , Vukcevic V , Dikic M , Matic D , Stefanovic B , Asanin M , Stankovic G
Published: October 2019

Background

Most of the previous studies evaluated the impact of early versus delayed invasive intervention on clinical outcomes in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) in one-year period.

Purpose

The aim of this study was to assess whether the immediate invasive intervention influences the occurrence of death and new myocardial infarction (MI), specifically in patients with non-ST segment MI (NSTEMI) in long-term follow-up.

Methods

In The Randomized Study of Immediate Versus Delayed Invasive Intervention in Patients With Non ST-segment Elevation Myocardial Infarction (RIDDLE-NSTEMI) 323 patients with NSTEMI were randomized to either immediate (median time to intervention was 1.4 hours) or delayed invasive strategy (61.0 hours). The incidence of primary outcome -death or new MI at 30 days was lower in patients assigned to the immediate (n=162) than in patients assigned to the delayed (n=161) invasive intervention group (4.3% vs. 13%, respectively; p=0.008). Long-term follow-up of 5 years was available for 96.90% of the patients.

Results

At 5 years, the immediate invasive intervention was associated with lower rate of death or new MI, compared with delayed invasive strategy (15.8% vs 32.9%, respectively; p=0.00). The observed benefit of the immediate intervention was mainly due to an increased early reinfarction risk with the delayed strategy (2.5% vs 9.9%, p=0.001) with similar new MI rates beyond 30 days (5.9% in the immediate and 10.7% in the delayed group, p=0.130). Five-year mortality was 12.0% in the immediate invasive intervention strategy group, and 18.1% in the delayed strategy group (p=0.135).

Conclusion

Immediate invasive intervention in the patients with NSTEMI significantly reduces the early risk of new MI. However, the timing of invasive intervention appears not to have significant impact on the clinical outcome beyond 30 days.
P3132Methylenetetrahydrofolate reductase A1298C as a risk factor for rheumatic heart disease in indonesian population
Authors: Nauphar D , Pratamawati T M , Sanif M E
Published: October 2019

Introduction

Rheumatic heart disease (RHD) is a chronic condition causing damage in cardiac valvular tissues due to acute rheumatic fever (ARF) post Streptococcus pyogenes or Group A β hemolytic Streptococcus (GABHS) infection. The damage to the valve tissue within the heart can lead to congestive heart failure, strokes, endocarditis, and death. However, only 3–6% of post-streptococcal infection individuals develop ARF, suggesting host susceptibility in the pathogenesis of ARF. Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) may be linked to the genetic susceptibility of the host that results in abnormal autoimmune response to the infection.

Purpose

This study aims to look at MTHFR A1298C polymorphism as a risk factor for rheumatic heart disease in Indonesian population.

Methods

This was an observational analytical study with case control approach. Blood samples were obtained from 36 Indonesian RHD patients with confirmed diagnosis of RHD using echocardiography and 36 healthy controls. Patients DNA were isolated and then amplified using polymerase chain reaction followed by restriction fragment length polymorphism analysis using MboII restriction enzyme.

Results

We observed a significant difference between genotypic distribution between cases and controls (OR = 4.6, 95% CI = 1.697–12.469, p=0.002). The genotype frequency of MTHFR A1298C AA (wild type) was 36.1%, heterozygous AC was 47.2%, and 16.7% of CC in the cases group. In the control group, the genotype frequency of the wild type AA was 72.2%, AC was 27.8%, and homozygous CC was 2.8%.

Conclusion

Compared with the CC frequency in the control population, the frequency of MTHFR CC was 5 times higher in individuals with rheumatic heart disease (p=0.002), suggesting that MTHFR A1298C gene variant may contribute to the pathogenesis of RHD. Individuals with MTHFR 1298C have a risk of 4.6 times higher to develop ARF post streptococcal infection.
P3139Transvenous lead extraction: lead age threshold to predict the success of the procedure
Authors: Giannotti Santoro M , Segreti L , Fiorentini F , Bernini G , Barletta V , Della Tommasina V , Cellamaro T , Soldati E , Di Cori A , Zucchelli G , De Lucia R , Viani S , Paperini L , Pedrinelli R , Bongiorni M G
Published: October 2019

Introduction

Transvenous lead extraction is a safe and effective procedure. The dwell time of the leads, with other factors, is associated with poor outcome of the procedure. However, a precise estimation of the success of the procedure is not available.

Purpose

The aim of this study is to identify a lead's age threshold able to predict the success of the transvenous lead extraction (TLE) procedure.

Methods

All patients who underwent TLE in our center from January 2009 to December 2017 were retrospectively analyzed. The primary endpoint was the clinical success of the procedure. The optimal cut-off threshold was determined by the analysis of Receiver-Operating Characteristics (ROC) curves, using the Youden index.

Results

We analyzed 1210 consecutive patients that required transvenous removal of 2343 leads (686 ICD leads, 1657 pacemaker leads, 322 coronary sinus leads). Clinical success was achieved in 1168 patients (96.5%). Dwelling time median of the oldest lead for a patient was 66 months (interquartile range 27.0–115.0). The oldest lead completely removed was 32 years old. ROC curve analysis showed a dwell time threshold of 107 months – 8,92 years - for clinical success (Positive Predictive Value: 99.5%; Negative Predictive Value: 7.8%) and the area under the curve (AUC) was 0.879. Comparison of ROC for dwelling time and the 0.5 curve was assessed as statistically significative (p<0.0001).

Conclusions

Transvenous lead extraction is an effective procedure. The best cut-off threshold to predict a very high clinical success is 107 months.
P3341Micro and macrovascular damage across the glycemic spectrum among women and men from general population
Authors: Roos M , Aribas E , Chaker L , Klaver C , Ahmadizar F , Kavousi M
Published: October 2019

Background

Type 2 diabetes mellitus (T2DM) is a global epidemic that is strongly associated with micro- and macrovascular complications. Head to head comparisons of micro- and macrovascular dysfunction across the glycaemic spectrum among women and men from large population-based cohorts are sparse.

Purpose

To investigate associations of impaired serum fasting glucose (IFG) and T2DM with markers of micro- and macrovascular damage among women and men from general population.

Methods

We included 10,920 women and men (>45 years) from a large prospective population-based study. We applied linear and logistic regression analyses to examine the cross-sectional associations between IFG and T2DM with markers of micro- and macrovascular damage including estimated glomerular filtration rate (eGFR), retinopathy, carotid intima-media thickness (cIMT), carotid plaque (CP), carotid-femoral pulse-wave velocity (PWV), and ankle-brachial index (ABI), adjusted for cardiovascular risk factors.

Results

Mean age was 65.09±10.0 years, 11.8% had IFG and 12.2% were T2DM patients. The majority of population were women (57.2%). In the fully adjusted models, compared to individuals with normal glucose levels (<6.1 mmol/l), IFG was independently associated with PWV (β; 95% CI: 0.011; 0.002–0.021) among men. T2DM was independently associated with larger burden of CP (Odds ratio (OR); 95% CI: 1.57; 1.13–2.17), and higher eGFR (β; 95% CI: 2.17; 0.62–3.72) among women and with larger burden of retinopathy (OR; 95% CI: 1.92; 1.30–2.85), higher cIMT (β; 95% CI: 0.010; 0.01–0.02), and PWV (β; 95% CI: 0.03; 0.01–0.04) among men.

Conclusions

IFG and T2DM were associated with micro- and macrovascular damage. Compared to non-diabetics, diabetic men had larger burden for markers of microvascular damage including retinopathy while diabetic women had larger burden of macrovascular damage including CP. Both IGF and T2DM were also associated with age-related macrovascular markers such as cIMT and PWV. Proper screening of macrovascular changes at earlier stages of dysglycemia and before the overt T2DM is crucial for prevention and early treatment of end-organ damage