bluuebunny/crossref_metadata_2025 huggingface dataset:
3254Manifestations of myocardial fibrosis in the standard 12-lead electrocardiogram
Authors: Holmstrom L , Kentta T , Haukilahti A , Pakanen L , Huikuri H , Junttila M J
Published: October 2019

Background

Myocardial fibrosis has substantial role in sudden cardiac deaths (SCD). Major challenge in preventing SCDs is early recognition of vulnerable patients with fibrotic cardiomyopathy. Our aim was to find manifestations of myocardial fibrosis in 12-lead electrocardiogram (ECG).

Methods

Study population is based on the Fingesture study, which has gathered data from 5,869 consecutive autopsied SCD victims between 1998 and 2017 in Finland. The degree of fibrosis was determined based on the histological samples taken from the heart during autopsy and was categorized into four groups; 1) no fibrosis, 2) scattered mild fibrosis, 3) moderate patchy fibrosis and 4) substantial fibrosis. We were able to collect pre-mortem 12-lead ECGs from 1,100 SCD victims. Ischemic cardiomyopathy was the cause of death in 689 cases and 411 had nonischemic cardiomyopathy at autopsy in the group where ECG was available.

Results

Mean age of the study subjects was 66±13 years and 75% were male. At least some amount of myocardial fibrosis was present in 92% of the victims. QRS duration in ECG correlated with the degree of fibrosis in autopsy as follows; 96±21ms in group 1 (n=93), 97±20ms in group 2 (n=357), 103±26ms in group 3 (n=506) and 108±27ms in group 4 (n=144; p<0.001, β=0.153). Prevalence of fragmented QRS complex was higher among victims with severe fibrosis (40% in group 1, 43% in group 2, 60% in group 3 and 65% in group 4; p<0.001). Additionally, inferolateral T-wave inversions were more common in groups with increasing amount of myocardial fibrosis (5.4% in group 1, 13.2% in group 2, 20.4% in group 3 and 31.9% in group 4; p<0.001). Associations were visible in both ischemic and nonischemic SCDs but reached statistical significance only among ischemic SCD victims. Heart rate corrected JT interval and Sokolow-Lyon index had no linear correlation with the degree of fibrosis.

Conclusions

Myocardial fibrosis was associated with QRS prolongation, T-wave inversions and QRS fragmentation among SCD victims. Fibrosis did not manifest as clearly in ECG among patients with nonischemic cardiomyopathies as among ischemic SCD victims. The results may explain the increased risk for SCD in patients with abnormal QRS complex or inverted T waves providing means for recognizing patients with underlying fibrotic cardiomyopathy.

Acknowledgement/Funding

Sigrid Juselius Foundation, Foundation of Cardiac Research, Paavo Nurmi Foundation and Paulo foundation, Finland
3293Atherothrombotic risk and outcomes following guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome:a post-hoc analysis of the TROPICAL-ACS trial
Authors: Rizas K , Farhan S , Huczek Z , Merkely B , Hein-Rothweiler R , Vogel B , Massberg S , Huber K , Aradi D , Sibbing D
Published: October 2019

Background

A de-escalation of P2Y12-inhibitor treatment guided by platelet function testing (PFT) has been identified as a safe and alternative treatment strategy in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). However, no specific data are available on the efficacy of such strategy in patients with high atherothrombotic risk (ATR).

Purpose

To investigate the safety and efficacy of guided de-escalation of P2Y12-inhibitor treatment in patients with low- vs. high-ATR.

Methods

The TROPICAL-ACS trial randomized 2,610 biomarker-positive ACS patients 1:1 to either conventional treatment with prasugrel for 12 months (control group) or to a PFT guided de-escalation treatment strategy (guided de-escalation group). The primary endpoint was defined as the composite of cardiovascular mortality (CVM), myocardial infarction (MI), stroke, and clinically overt bleeding (bleeding ≥ grade 2 according to the BARC criteria). The ischemic endpoint was defined as the composite of CVM, MI or stroke. We used semi-parametric Cox regression analysis and interaction testing to assess the effect of low- vs. high-ATR on the primary and ischemic endpoints. High-ATR was defined as one of the following: (i) age ≥65 years or (ii) age <65 and either history of peripheral artery disease or at least two of the following risk-factors: diabetes mellitus, current smoking or renal dysfunction.

Results

Patients with high- (n=990) versus low-ATR (n=1,620) exhibited a higher risk for the primary endpoint (11.0% vs. 6.7%; HR 1.67; 95% CI 1.28–2.18; p<0.001). Guided de-escalation was non-inferior to conventional treatment for the primary endpoint in both patients with high- (10.5% vs. 11.5%; pnon-inferiority = 0.029; Figure 1A) and low-ATR (5.6% vs. 7.7%; pnon-inferiority=0.001; Figure 1B). Moreover, there was no significant interaction in the prognostic value of guided de-escalation between high- and low-ATR groups for both the primary (HR 0.90 [0.61–1.32]; p=0.586 in patients with high-ART vs. 0.71 [0.48–1.04; p=0.082 in patients with low-ATR; pinteraction= 0.394) and combined ischemic endpoints (HR 0.83 [0.44–1.56]; p=0.567 in patients with high-ATR vs. 0.68 [0.35–1.34]; p=0.262 in patients with low-ATR; pinteraction =0.666).

Kaplan-Meier curves

Conclusion

A guided DAPT de-escalation strategy appears to be safe and effective in ACS patients regardless of the atherothrombotic risk. Further studies are needed for refining antiplatelet treatment strategies in ACS patients with varying levels of atherothrombotic risk.

Acknowledgement/Funding

Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.
3301A novel high-sensitivity cardiac troponin i assay for early diagnosis of acute myocardial infarction
Authors: Boeddinghaus J , Nestelberger T , Twerenbold R , Koechlin L , Wussler D , Badertscher P , Puelacher C , Du Fay De Lavallaz J , Rubini Gimenez M , Zimmermann T , Miro O , Martin-Sanchez F J , Keller D I , Reichlin T , Mueller C
Published: October 2019

Background

Lately, the novel high-sensitivity cardiac troponin I (hs-cTnI) Access assay was developed. Its clinical performance in patients presenting with chest pain to the emergency department (ED) is unknown.

Purpose

To clinically validate the novel hs-cTnI-Access assay and to derive and validate an assay specific 0/1h-algorithm accordingly to the European Society of Cardiology (ESC) recommendations.

Methods

In a prospective international multicentre study we enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by two independent cardiologists including all clinical information including cardiac imaging twice: first, using serial hs-cTnT (Elecsys, primary analysis) and second, using hs-cTnI (Architect, secondary analysis) measurements in addition to the clinically used (hs)-cTn. Hs-cTnI-Access was measured at presentation and at 1h. Primary objective was a direct comparison of diagnostic accuracy as quantified by the area under the receiver-operating-characteristic curve (AUC) of hs-cTnI-Access versus the two established hs-cTn assays (hs-cTnT-Elecsys, hs-cTnI-Architect). Secondary objectives included the derivation and internal validation of an hs-cTnI-Access specific 0/1h-algorithm.

Results

AMI was the adjudicated final diagnosis in 243/1579 (15.4%) patients. The AUC at presentation for hs-cTnI-Access was 0.95 (95% CI, 0.94–0.96), significantly higher as hs-cTnI-Architect (0.92 [95% CI, 0.91–0.94; p<0.001]), and comparable to hs-cTnT-Elecsys (0.94 [95% CI, 0.93–0.95; p=0.12]) Applying the derived hs-cTnI-Access 0/1h-algorithm (derivation cohort n=686) to the internal validation cohort (n=680), 60% of patients were ruled-out (sensitivity 98.9% [95% CI, 94.3–99.8]), and 15% of patients were ruled-in (specificity 95.9% [95% CI, 94.0–97.2]). Patients ruled-out by the 0/1h-algorithm had a survival rate of of 100% after 30-days and 98.4% after two years of follow up. Findings were confirmed in the secondary analyses using the adjudication including serial measurements of hs-cTnI (Architect).

Performance of the 0/1h-algorithm

Conclusions

Diagnostic accuracy of the novel hs-cTnI-Access assay is excellent and at least comparable to the two established hs-cTn assays. The assay-specific 0/1h-algorithm allows a safe rule-out and accurate rule-in of MI in about 75% of patients within 1-hour after presentation to the ED. Survival of patients ruled-out by the 0/1h-algorithm was very high.

Acknowledgement/Funding

Swiss National Science Foundation, the Swiss Heart Foundation, the KTI, the European Union, the Stiftung für kardiovaskuläre Forschung Basel
3308The critical roles of coagulation factors in inducing brown adipose tissue dysfunction and systemic metabolic disorder in obesity
Authors: Hayashi Y , Shimizu I S , Yoshida Y Y , Ikegami R I , Katsuumi G K , Suda M S , Fujiki S F , Minamino T M
Published: October 2019

Obese individuals are predisposed to cardio-metabolic disorders. Brown adipose tissue (BAT) is an active metabolic organ abundant with mitochondria, and studies suggest a potential role of BAT in the maintenance of metabolic health in rodents and humans. Metabolic stress causes BAT dysfunction, but the underlying mechanisms are largely unknown. Coagulation factor Xa (FXa) is critically involved in a coagulation cascade, and it is also known to mediate biological effects by the activation of protease-activated receptor (PAR)-signaling. Accumulating evidence shows that PAR1 contributes to tissue remodeling in cardiovascular system. Here we show a previously unknown role of FXa-PAR signaling in promoting BAT dysfunction and systemic metabolic disorder in a murine dietary obese model. Imposing a high fat diet (HFD) on C57BL/6NCr mice led to a marked increase in tissue factor (TF), coagulation factor VII and FXa in BAT. TF-FVIIa (activated form of FVII)-FXa complex is known to activate PAR1, and we found a significant increase in PAR1 expression in BAT upon metabolic stress. Administration of a FXa inhibitor ameliorated BAT whitening, improved thermogenic response and systemic glucose intolerance upon dietary obesity. In contrast, administration of warfarin did not show any phenotype in BAT. BAT specific TF and PAR1 over-expression model showed significant whitening of this tissue, which was associated with systemic glucose intolerance. BAT specific PAR1 KO mice improved glucose intolerance and thermogenic response under a metabolically stressed condition. In differentiated brown adipocytes, FXa markedly increased mitochondrial reactive oxygen species (ROS) and reduced mitochondrial membrane potential. Inhibition of PAR1 ameliorated FXa-induced mitochondrial ROS production and reduction in membrane potential. We also found that plasma FXa level did not increase in obese mice as well as in obese individuals. These results suggest the previously unknown role of coagulation systems in promoting BAT dysfunction, leading to systemic metabolic disorders. Maintenance of BAT homeostasis through the suppression of FXa-PAR1 signaling would become a new therapeutic target for obesity and diabetes.
3327Increasing incidence of cardiac device related endocarditis over the past ten years: a single center analysis
Authors: Vervaecke A , Van De Vyver G , Scott B , Vermeersch P
Published: October 2019

Background

Cardiac device related infective endocarditis (CDIE) is an increasing problem in the current cardiology practice, related to high mortality and morbidity. Recent trends have shown an increase in cardiac device placement, which remains a risk factor for developing CDIE. We performed a retrospective analysis of all patients admitted to our hospital. The aim of our study was to identify a possible correlation between the amount of device placements and the incidence of CDIE.

Methods

All patients, aged 18 years or above, diagnosed and treated for IE in our hospital in the 11 years between January 1st 2007 and December 31st 2017 were retrospectively identified. The amount of cardiac device placements was meticulously kept up to date by the administrative department. Due to the retrospective nature of our study no approval of the local ethics committee was required.

Results

A total of 33 patients with proven CDIE were identified There were no CDIE documented in 2007,2009 and 2010. 2008 showed 2 CDIE (16.7%) whereas the last 4 years of the study showed a mean incidence of 5.75 IE per year. Our population was predominantly male (84.8%) and nearly a third of the population died during hospital stay. The mean age of the population was 73.9 years old. Three quarters of the population underwent surgery and 24 patients out of these underwent device removal, the remaining 2 patients underwent valve replacement or catheter removal.

Half of the patients had early-onset or procedure-related IE (<12 months post procedure). The remaining cases were defined as late onset IE. Overall, 80% of CDIE developed within 3 years after the procedure.

The most prevalent causative organisms in our CDIE population were Staphylococci (68%) followed by Streptococci (20%). Eight out of 33 cases appeared to be culture negative (24.2%).

We sought to correlate these findings to the amount of cardiac device procedures (de novo implantations and replacements) as of 2004 (to compensate for the possible 3-year delay). The number of CD procedures increased by nearly 400% over the course of these 14 years.

Patient demographics

Conclusions

The incidence of CDIE has increased in our population over the past 11 years. This increase runs parallel with the expansion of the number of devices implanted. About half of CDIE occur within 1 year of the procedure defined as early onset CDIE, but the presence of a cardiac device remains a risk factor for IE even thereafter. Causative organisms in our study for CDIE specifically appear to coincide with the results from other studies done in more general populations, with Staphylococci remaining the most prevalent organisms. As patients with cardiac devices implanted appear to be at increased risk for IE, one might add these to the group of patients requiring IE-prophylaxis, especially because of the high mortality rate of IE, which appears to be even higher for CDIE.
3331Impact of baseline hemoglobin level and white blood cell count in real-world patients undergoing contemporary percutaneous coronary intervention: insights from the GLOBAL LEADER study
Authors: Chichareon P , Modolo R , Tomaniak M , Kogame N , Fontos G , Lantelme P , Barraud P , Hamm C , Steg G , Juni P , Vranckx P , Valgimigli M , Windecker S , Onuma Y , Serruys P W
Published: October 2019

Introduction

The impact of hemoglobin (Hb) level and white blood cell count (WBC) on the outcomes in all-comers PCI patients is unknown.

Purpose

We sought to assess the association between baseline Hb level, WBC count on 2-year outcomes after PCI in all-comers patients in the GLOBAL LEADERS study. We compared the outcomes between anemic and non-anemic patients according to WHO definition.

Methods

GLOBAL LEADERS study assessed the efficacy and safety of two antiplatelet strategies in 15,991 patients undergoing PCI. The primary endpoint was all-cause mortality or new Q wave myocardial infarction (MI) at 2 years. Secondary safety endpoint was BARC 3 or 5 bleeding at 2 years.

The association between WBC count, Hb level and outcomes at 2 years were assessed in the multivariable Cox model adjusted for age, diabetes, ejection fraction and renal impairment. For Hb level, patients were categorized according to the WHO definition of anemia (Hb <12 g/dL in women, Hb <13 g/dL in men).

Results

Of 15991 patients randomized in the GLOBAL LEADER study, baseline WBC count and Hb levels were available in 14960 (93.7%) patients and 15215 (95.3%) patients, respectively.

Hb level had an inverse association with adverse events after PCI. In the multivariable Cox model, Hb level was an independent predictor for ischemic and bleeding outcomes at 2 years while the WBC count was not (see table).

Compared with non-anemic patients, anemic patients had significantly higher risk of primary endpoint (adjusted HR 2.07, 95% CI 1.72–2.49), BARC 3 or 5 bleeding (adjusted HR 1.49 95% CI 1.14–1.96), all-cause mortality (adjusted HR 2.33, 95% CI 1.89–2.86), any MI (adjusted HR 1.41, 95% CI 1.11–1.80), and any revascularization (adjusted HR 1.20, 95% CI 1.03–1.39).

Hb level, WBC count and 2-year outcomes Outcomes at 2 years Hemoglobin level (mg/dL) WBC count (109/L) HR (95% CI) P value HR (95% CI) P value All-cause mortality or new Q wave MI 0.87 (0.82–0.91) <0.0001 1.00 (0.999–1.002) 0.33 All-cause mortality 0.82 (0.78–0.87) <0.0001 1.00 (0.999–1.002) 0.37 Any myocardial infarction 0.93 (0.87–0.99) 0.0165 1.00 (0.996–1.001) 0.23 Any revascularization 0.96 (0.93–1.00) 0.0302 1.00 (1.00–1.001) 0.25 BARC 3 or 5 bleeding 0.85 (0.79–0.91) <0.0001 1.00 (0.997–1.002) 0.76

Conclusion

In the all-comers patients undergoing PCI, the baseline Hb level was significantly associated with the ischemic and bleeding outcomes at 2 years whereas baseline WBC count was not. Baseline WBC count may not be useful as a prognostic factor after PCI.
4033A way forward for cardiac rehabilitation - Nurse clinics with active holistic patient management
Authors: Gasparini C G , Marshall W M , Reed S R , Johansen Y V , Benatar J R B
Published: October 2019

Background

Early cardiac rehabilitation (CR) nurse follow up clinics 2- 3 weeks post hospital discharge have been instituted at our Hospital for all patients with established coronary artery disease to improve patient engagement and adherence. In the last 2 years these clinics have increased in attendance rates and patient complexity. These now have medical supervision, allowing for active management of patients. Patients are seen multiple times to maximize evidence based treatments by the same nurse. Risk factors are addressed in these clinics and patients are invited into cardiac rehabilitation education classes and individualized prescribed exercise programmes.

Purpose

To assess rates of adherence and intervention in CR nurse clinics.

Methods

The CR team at our Hospital has prospectively recorded rates of adherence and interventions at Nurse Specialist clinics over a 12 month period.

Results

718 (94%) patients attended CR nurse clinics following discharge. Of these 413 (57%) patients had an intervention in clinic: up titration was 38% for RAAS/beta blocker, 11% for statin and 18% for antianginal and BP medication. A further 21% were referred for further investigations or treatments including admission to hospital. 48% (Standard deviation 11%) attended a cardiac rehabilitation programme in addition to these 1 hour clinics.

Interventions in clinic

Conclusion

Nurse Specialist clinics with medical supervision that are scheduled early post discharge provide a safety net for patients who are discharged following short hospital stays. They also lead to increased prescription of secondary prevention medication and ensure patients have appropriate investigations and referrals. These clinics have resulted in change in practice with routine doctor follow up clinics now cancelled. Long term follow-up for patients is now rationalized and has freed up doctor clinics for more complex patients. Early and intensive engagement with patients is also associated with higher uptake of cardiac rehabilitation programs.

Acknowledgement/Funding

None
4079The future of recurring restenosis prediction - Urinary cysteinyl leukotriene e4
Authors: Maga M , Wachsmann A , Maga P
Published: October 2019

Background

Peripheral artery disease (PAD) is one of the common atherosclerosis manifestations. However endovascular treatment (percutaneous transluminal angioplasty - PTA) remains the most frequently applied treatment method, it is less successful in patients with recurrent restenosis. Even though the influence of cysteinyl eicosanoids on atherosclerosis progression is well-known, their role in restenosis after endovascular treatment has not been studied yet.

Purpose

The aim of this study was to establish prognostic features of urinary leukotrienes E4 (uLtE4) in occurrence of restenosis.

Methods

180 patients admitted for PTA with lower limbs ischemia on 3 or 4 stage of Rutherford scale were recruited in this prospective innovative study. Urine samples were collected before intervention as well as 2 hours after and day after it. During control visits were performed 1,3,6 and 12 months after PTA including uLtE4 level measurement, evaluation of treatment success and complex assessment of restenosis basing on ankle-brachial index, Doppler ultrasound and general condition of patient. To perform the analysis all of patients were divided into 2 groups basing on presence of complications on each follow-up meeting: A-without restenosis; B-with restenosis.

Results

Significant differences in level of uLtE4 were observed between group A and B on 3-month (85.57 vs 157.64, p<0.002) 6-month (83.17 vs 158.28, p<0.001) and 12-month (76.81 vs 150.25, p<0.001) follow-up visits (Fig1). Patients with increased uLtE4 level in 1month had higher risk of restenosis in 3-month observation (OR=3.57, p=0.002) and elevated uLtE4 in 3-month follow-up increased the risk of restenosis in 6 months (OR=2.38, p=0.016). The same trend was observed in 6 months uLtE4 levels regarding 12-months restenosis however it wasn't statistically significant (OR=1.82, p=0.1). However post-operative uLtE4 were significantly higher compared to the pre-operative ones, they did not correlated with future restenosis in none of the follow-ups.

Figure 1

Conclusions

Our study shows that, elevated level of uLtE4 correlates with increased risk of restenosis occurrence in PAD patients after EVT. Leukotrienes rise can also predict the restenosis in the following months. These results confirms the role of inflammatory mediators in atherosclerosis and let us believe, that one day uLtE4 level may become the significant biomarker of complications after lower limbs endovascular treatment.

Acknowledgement/Funding

Grant of Polish Ministry of Science and Higher Education - “Best of the best 2.0” (S/FS0/0267)
4095Exercise and vascular ageing: a cross-sectional and randomized controlled trial
Authors: Streese L , Deiseroth A , Hanssen H
Published: October 2019

Background

Vascular ageing can be quantified at subclinical stages by use of sensitive vascular biomarkers of the macro- and microcirculation. Detection of vascular impairments enables initiation of timely treatment strategies to counteract development of CV disease and improve CV outcome.

Purpose

To (a) compare large artery stiffness and retinal microvascular diameters in healthy life-long active and healthy sedentary older adults with CV risk patients, and (b) to assess the effects of short-term high-intensity exercise training on vascular health in these patients.

Methods

Seven hundred and eighty-three participants were screened for their CV risk and physical activity profile. We included 38 healthy active (HA, mean age 60±7 years) and 36 healthy sedentary (HS, mean age 60±7 years) as well as 84 sedentary patients with ≥2 CV risk factors (SR, mean age 59±6 years) in the cross-sectional approach. SR were randomized to a 12-week high-intensity interval training (HIIT) or physical activity recommendations after the baseline assessment. Carotid-femoral PWV (cfPWV) was measured as a marker of large artery stiffness and the central retinal arteriolar (CRAE) and venular (CRVE) diameters as well as the retinal arteriolar-to-venular diameter ratio (AVR) were measured as a marker of the microcirculation. Standard procedures of anthropometric measurements were implemented.

Results

Anthropometric parameters differed between the groups according to the inclusion criteria. cfPWV was highest in SR (8.2±1.4m/s) compared to HS (7.5±1.6m/s) and HA (7.0±1.1 m/s). HA had a lower cfPWV compared to HS (p<0.05) and SR (p<0.001). HA had wider CRAE (179±14μm) and narrower CRVE (204±17μm) compared to HS (CRAE: 172±11 μm; CRVE: 209±11 μm) resulting in a higher AVR in HA (0.88±0.05) compared to HS (0.83±0.04, p<0.001). By contrast, SR showed narrower CRAE (171±14 μm) and wider CRVE (218±16μm, p<0.05) compared to HS resulting in a lower AVR (0.79±0.05, p<0.001) compared to HS and HA. HIIT in SR improved most classic CV risk factors. Additionally, CRAE increased (pre: 175±14μm vs post: 181±13μm, p=0.001) and CRVE decreased (pre: 222±14μm vs post: 220±14μm, p=0.007) in the HIIT group without changes in the cfPWV. PWV was significantly but moderately associated with AVR (r=−0.2, p=0.01).

Conclusions

Life-long physical activity and fitness were associated with lower arterial stiffness and favourable retinal vessel diameters in healthy individuals. CV patients had higher arterial stiffness and lower AVR. Short-term HIIT improved retinal microvascular phenotype without changes in large artery stiffness. Retinal vessel diameters are sensitive diagnostic tool for CV risk stratification and subclinical vascular disease monitoring in CV patients. Short-term HIIT may postpone development of small vessel disease in older patients.

Acknowledgement/Funding

Swiss National Science Foundation, Nora van Meeuwen-Häfliger Stiftung
4097Validation of seven different exercise treadmill stress testing protocols in a large 25-year stress testing registry
Authors: Harb S , Menon V M , Wu W U , Cremer P C , Cho L C , Gulati M G , Jaber W A J
Published: October 2019

Background

While the Bruce protocol has been extensively validated, other modified exercise protocols with less workload burden are commonly used, though their prognostic value is not well established.

Purpose

We sought to assess whether exercise capacity (or workload achieved in metabolic equivalents of task [METs]) remains predictive of mortality across various exercise stress testing protocols.

Methods

In a 25-year stress testing registry spanning from 1991 to 2015, we identified 120,705 patients who underwent 7 different standardized symptom-limited exercise stress testing protocols: Bruce, Modified Bruce, Cornell 0%, Cornell 5%, Cornell 10%, Naughton, and modified Naughton. The choice of the protocol was dependent on the supervising exercise physiologist according to purpose of the test and the individual patient. The primary outcome was all-cause mortality.

Results

Mean age was 53.3±12.5 years and 59% were male. There were 74953 Bruce, 8368 modified Bruce, 2648 Cornell 0%, 9972 Cornell 5%, 20425 Cornell 10% 1226 Naughton, and 3113 modified Naughton individual protocols. A total of 8426 death occurred over 8.7 years of mean follow-up duration. Figure 1 shows that there was an inverse relationship between peak METs achieved and mortality across all 7 protocols. On multivariable analysis, increasing METs remained protective against death [adjusted HR of 0.46; 95% CI (0.44 - 0.48); p<0.001] even after adjusting for the protocol chosen, age, gender, hypertension, diabetes, coronary disease, end-stage renal disease, smoking, and statin use.

METS vs. mortality by protocol

Conclusion

Across 7 different exercise protocols with various workloads, the predicted exercise capacity remained predictive of mortality irrespective of the protocol chosen, patients' demographics and comorbidities. Different testing choices likely represent different estimated functional capacity.
4102QT interval duration, long QT pattern and changes over time in children practicing sport
Authors: D'Ascenzi F , Anselmi F , Graziano F , Berti B , Franchini A , Bacci E , Ceccon C , Capitani M , Bonifazi M , Mondillo S
Published: October 2019

Background

Twelve-lead electrocardiogram (ECG) is an established tool in the evaluation of adult athletes, providing information about life-threatening cardiovascular diseases such as long-QT syndrome. However, changes induced by development challenge the interpretation of ECG in the paediatric population, particularly for the repolarisation phase. The aim of this prospective, longitudinal study was to determinate the distribution of QT interval in children practicing sport and to evaluate changes in QT duration during preadolescence.

Methods

A final population of 1473 children practising sport (mean age: 12.0±1.8 years, interval 7–15 years) was analysed. Each athlete was evaluated at baseline, mid-term and end of the study with a mean follow-up of 3±1 years. QT interval was corrected with Bazett (B) and Fridericia (F) formulae.

Results

At baseline QTcB was 412±25ms and QTcF 387±21ms, with no changes during follow-up. Ten children (0.68%) had an abnormal QTc. In children with QTc ≥480ms confirmed both by Bazett and Fridericia formulae, QT duration persisted abnormal during the follow-up and children were disqualified. Conversely, children with borderline QTc intervals (>460 and <480ms) were not disqualified and we found a normalization of QT interval during the development. Mean difference in the calculation of QT between the two formulae was 25±11ms, p<0.0001. For HR values higher than 80 bpm, the QTcF resulted with low fluctuations around the mean was independent from HR values. Conversely, the QTcB revealed significant growing trend as the HR increased and showed higher variability than Fridericia correction.

Dynamic changes in QT interval duration Baseline Mid-term FU Long-term FU p value Intervallo QT 343±25 345±24* 346±25* <0.0001 RR (ms) 599±111 711±111* 721±119*^ <0.0001 QTc Bazett (ms) 412±25 (371–449) 411±25 (367–449) 409±25 (367–446) 0.10 QTc Fredericia (ms) 387±21 (355–418) 387±20 (353–419) 387±20 (353–418) 0.59 FU, follow up; *p<0.0001 vs. baseline; §p<0.0001 vs. mid-term FU; ^p<0.05 vs. mid-term FU.

Conclusions

QT duration does not change over time in children with normal duration. A minority of children has a QT ≥480ms; in these subjects QT interval remains prolonged during the follow-up. Conversely, in children with borderline QT, mid-term follow-up is useful to identify a normalization during the growth. Clinicians should take into account that the use of Bazett and Fridericia correction formulae is not interchangeable and that Fridericia formula should be preferred when resting HR is higher than 80 bpm.
4224Conflict-driven risk factors faced by displaced populations and deterioration of health: Review of Syrian conflict as an example
Authors: Shimony E , Shekhar A C , Narula J
Published: October 2019

Purpose

Conflict yields adverse health effects for those living in afflicted regions. It dramatically exacerbates poverty and creates large numbers of vulnerable refugees. In addition to food scarcity, healthcare disparity, and overwhelming inequality, refugees face extreme emotional trauma and cumulative stress. This could lead to lifestyle modifications – including unhealthy diets, low activity levels, and smoking – that contribute to cardiovascular disease (CVD). The issue of refugees and displaced persons has never been more apparent than in the last decade. There are currently 68.5 million refugees worldwide, including those due to violent conflict in Syria. [i]

Methods

To conceptualize the magnitude of cardiovascular risk refugees face during periods of conflict and resettlement, we reviewed the published literature for the prevalence of behavioral modification in Syrian refugees, including altered diets, smoking, stress, and overall mental health.

Results

Literature review suggests refugees are 10 times more likely to experience post-traumatic stress disorder (PTSD), with lifetime incidence as high as 38.5% as seen in a study of Syrian Kurdish refugees in Iraq.[ii] Syrian refugees in Sweden were found to experience high levels of both depression and anxiety, 40% and 32%, respectively. [iii] The INTERHEART study showed a causal link between elevated levels of stress and CVD. [iv]

In addition to serving as a risk factor for CVD, stress cultivates unhealthy lifestyles. A study of Syrian refugees found an increase of 7.6 cigarettes per day following the war; this data also followed a trend of increasing levels of PTSD, suggesting that the stress of migration and the conflict led to increased cigarette use.[v] In Syrian resettlement areas, Palestinian refugees were found to consume almost twice as many cigarettes as the local population, a trend also true in Lebanon.[vi] Heart-healthy nutrition and diets are often not available to refugees, and a study of Syrian refugees in Lebanon found diets that consisted almost exclusively of carbohydrates with little to no vegetables, fruits, or proteins. Stress, poor diets, and smoking in displaced people may translate into a higher incidence of noncommunicable diseases. In the Lebanese study, hypertension, diabetes, and CVD were reported in refugees at 60%, 47%, and 30%, respectively. [vii]

Conclusions

Improving the health of war-affected displaced subjects is an issue worthy of concern. Conflict results in unhealthy lifestyles and behaviors and must end to restore emotional health and physical well-being.
4252Additional value of stress testing for evaluation of ventricular arrhythmias in athletes undergoing preparticipation screening
Authors: Vessella T , Zorzi A , De Lazzari M , Menegon V , Spagnol R , Merlo L , Pegoraro C , Giorgiano F , Cardillo R , Perazzolo Marra M , Basso C , Corrado D , Sarto P
Published: October 2019

Introduction

The optimal protocol of athletes pre-participation screening is a matter of debate. The aim of this study is to test the additional value of exercise testing (ET) for evaluation of ventricular arrhythmias (VA) in athletes with otherwise normal findings.

Methods

The study included 10,975 competitive athletes who underwent preparticipation screening including ECG and stress testing. Athletes with ≥3 isolated premature ventricular beats or ≥1 repetitive VA underwent second-line investigations (echocardiography and 24-hour ambulatory ECG monitoring with a training session) and, in case of frequent, complex or exercise-induced VA or echocardiographic abnormalities, also cardiac magnetic resonance (CMR).

Results

451 (4,1%) athletes were excluded for abnormalities at history, physical examination and baseline ECG. Among the remaining 10524 athletes, 524 (5%)showed VA at ET, 87 of whom underwent CMR.Echocardiography identified major cardiac abnormalities in 5 athletes and regional ventricular systolic dysfunction in 7, which were confirmed by CMR in 6. Other 12 patients with normal echocardiography had a positive CMR. In particular, in 16 subjects the CMR showed left ventricular late gadolinium enhancement suggesting myocardial fibrosis with a non-ischemic distribution. At multivariate analysis, VA observed at high work load at ET, the presence of complex VA at ET and the presence of a morphology other than infundibular or fascicular predicted an underlying pathological myocardial substrate while the presence of frequent (>500/24-hour) premature ventricular beats did not.

Predictors of underlying pathological myocardial substrate Substrate Univariate Multivariable YES (n=23) NO (n=501) OR (95% IC) P OR (95% IC) P Age 17 [13–43] 15 [14–17] 1.03 [0.98 -1.06] 0.18 – Male gender 15 (65%) 184 (37%) 3.2 [1.3–7.7] <0.001 1.6 [0.7–4.8] 0.28 >500 PVBs/24-hour 7 (30%) 98 (20%) 1.8 [0.7–4.5] 0.21 – VA at high work-load 10 (44%) 78 (16%) 4.2 [1.8–9.8] <0.001 1.6 [1.1–4.7] 0.02 Couplets/NSVT at ET 14 (61%) 117 (23%) 6.2 [2.5–15] <0.001 8.5 [2.5–29] 0.01 PVBs other than infundibular/fascicular 17 (74%) 118 (24%) 6.1 [2.4–16] <0.001 3.9 [1.4–11] 0.008

Conclusions

VA at ET may represent the only sign of a pathological myocardial abnormalities, such as the “isolated nonischemic left ventricular scar”, that could be the substrate for life-threatening ventricular arrhythmias. Addition of ET to baseline ECG may increase the sensitivity of PPE of competitive athletes.
4301Diastolic dysfunction is an independent predictor of adverse events in patients with systolic dysfunction. Insights from the MADIT-CRT trial
Authors: Gori M , Claggett B , Shah A M , Senni M , Goldenberg I , Kutyifa V , Solomon S D
Published: October 2019

Background

Diastolic dysfunction (DD) is common in patients with heart failure with reduced ejection fraction (HFrEF). However, its prognostic relevance in HFrEF, on top of conventional risk factors including natriuretic peptides, is unknown

Purpose

To show the prognostic contribution of DD in HFrEF

Methods

We analyzed 1155 baseline echocardiograms (63% of all available exams) in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) study, comprising HFrEF patients with LVEF≤30%, QRS duration ≥130 ms, and NYHA class I/II. We classified DD according to ASE 2016 classification, based on transmitral Doppler velocities, mitral annular Tissue Doppler velocities, pulmonary venous flow velocities, and left atrial volumes. Using Cox regression and C-statistics we assessed the independent prognostic value of DD for nonfatal HF or death. We also evaluated CART (Classification And Regression Tree) analysis

Results

Patients were 64±11 years-old, 24% females, and mean LVEF was 24±5%. While 45% had impaired relaxation, 33% had pseudo-normal filling, 12% restrictive patter, 6% had indeterminate diastolic function, and 4% were not classifiable due to missing data. During a mean follow-up of 2.1±1.0 years, there were 233 adverse events. After multiple adjustment, compared to patients with impaired relaxation, those with pseudo-normal and restrictive filling had greater risk of HF/death (respectively HR 1.76, 95% CI 1.16–2.66, p=0.007; HR 2.70, 95% CI 1.58–4.60, p<0.001), independently of assigned treatment (p-interaction 0.34). Adding DD to conventional markers of risk improved prediction (C-statistic 0.733, 95% CI 0.689–0.776 versus 0.708, 95% CI 0.663–0.753, p=0.024). Finally, at CART analysis DD was the first parameter to be considered to risk stratify patients (Figure)

Risk stratification tree

Conclusions

DD is a strong independent predictor of death or heart failure in HFrEF patients with mild symptoms and should be considered in assessment of risk in this population
4303Revisiting the weber and ventilatory classifications in heart failure by combining exercise stress echo with gas exchange phenotyping
Authors: Sugimoto T , Bandera F , Alfonzetti E , Guazzi M
Published: October 2019

Background

In heart failure (HF), the Weber and Ventilatory Classes are well acquired landmark reference exercise classifications for quantification of outcome. However, they have not been associated with a thorough hemodynamic phenotyping in the modern HF populations.

Methods

194 HF patients with preserved (N=41), mid-range (N=43), and reduced (N=110) ejection fraction and patients with exercise induced-dyspnea and no HF (nonHF, N=77) underwent CPET combined with Echo-Doppler with special attention for the assessment of left atrial dynamics by strain (LAS) analysis, and right ventricular (RV) to pulmonary circulation (PC) coupling assessed by transticuspid annular plane systolic excursion (TAPSE)/pulmonary arterial systolic pressure (PASP) ratio. They were also evaluated in terms of clinical outcome (mortality and HF hospitalization).

Results

Distribution and variables of interest for Weber Classes were: Class A; n=22 nonHF, no HFpEF, 3 HFmrEF, 3 HFrEF with LAS during exercise of 39±12% and TAPSE/PASP of 0.67±0.21 mm/mmHg; Class B; n=25, 7, 12, 21 with LAS during exercise of 28±14% and TAPSE/PASP of 0.56±0.25 mm/mmHg; Class C: n=27, 25, 20, 48 with LAS during exercise of 24±14% and TAPSE/PASP of 0.46±0.18 mm/mmHg; Class D; n=3, 9, 8, 38 with LAS during exercise of 17±12% and TAPSE/PASP of 0.33±0.14 mm/mmHg and Ventilatory Class I: 59, 24, 22, 39, with LAS during exercise of 31±14% and TAPSE/PASP of 0.55±0.21 mm/mmHg; Class II: 14, 9, 12, 39 with LAS during exercise of 22±13% and TAPSE/PASP of 0.45±0.21 mm/mmHg; Class III: 3, 7, 5, 20 with LAS during exercise of 16±7% and TAPSE/PASP of 0.31±0.09 mm/mmHg; Class IV: 1, 1, 4, 12 with LAS during exercise of 10±6% and TAPSE/PASP of 0.28±0.11 mm/mmHg. Significant differences among each classes in LAS during exercise and peak TAPSE/PASP (P<0.05, respectively) have been observed (Figures A and B). LAS during exercise and peak TAPSE/PASP were positively correlated with peak VO2 (R=0.45 and 0.49, P<0.05, respectively) and also negatively correlated with VE/VCO2 slope (R=−0.49 and −0.55, P<0.05, respectively). Cox proportional hazard regression analyses showed that Weber (HR=3.7, 95% CI 1.7 to 8.0, P<0.001) and Ventilatory Classes (HR=1.7, 95% CI 1.1 to 2.7, P=0.01) were independently associated with the cardiac endpoint after adjustment for age and gender. Clinical stratification according to Weber (A/B or C/D) and Ventilatory (IV or not) Classes clearly differentiated between patients with low and high clinical risk (HR=2.8, 95% CI 1.4 to 5.7, P=0.005, Figure C).

Conclusions

In patients with HF of any LVEF, Weber and Ventilatory classifications are paralleled by progressive impairment in exercise echo-derived hemodynamic parameters of left atrial function and RV to PC coupling. Peak VO2 and VE/VCO2 slope combine in a strong predictive value irrespective of type of HF.
4304Fast-SENC quantifies segmental right ventricular intramyocardial strain to assess subclinical RV dysfunction prior to changes in RV ejection fraction
Authors: Montenbruck M , Kelle S , Esch S , Andre F , Schwarz A , Korosoglou G , Steen H
Published: October 2019

Right ventricular ejection fraction (RVEF) identifies reduced right-side cardiac function in symptomatic patients. However, alternative metrics are needed to detect subclinical RV dysfunction before cardiac remodeling results in systemic damage. Fast-SENC intramyocardial strain (fSENC) is a unique cardiac magnetic resonance imaging (CMR) modality that measures intramyocardial RV contraction in 1 heartbeat per image plane. This prospective registry compares fSENC and RVEF based on ACC/AHA Heart Failure Stage.

Methods

A single center, prospective registry of MRI scans acquired with a 1.5T scanner were evaluated for conventional CMR diagnostics including RVEF. In addition, fSENC scans were acquired and processed with the MyoStrain software to quantify intramyocardial RV strain. Two short axis scans (basal & midventricular) were used to calculate strain in 6 longitudinal RV segments while two long axis scans (3-chamber & 4-chamber) were used to calculate 5 circumferential RV segments.

CMR and fSENC metrics were compared based on progression of heart failure in which the ACC/AHA Heart Failure stage was determined by CMR findings including LGE in cases in which contrast was injected. HF Stages B and C were separated into different degrees of structural heart disease with “−” representing lower levels and “+” higher levels to provide better delineation of progression of heart dysfunction leading to heart failure.

Results

A total of 977 scans in 779 patients were included in the study. Patients had an average (± stdev) age of 55 (17) yrs and BMI of 26 (5) kg/m2; 48% had arterial hypertension, 12% diabetes mellitus, 33% moderate or severe valvular heart disease, 25% cancer, 7% atrial fibrillation, and 24% coronary artery disease.

Figure 1 shows the relationship between % normal RV myocardium (RV fSENC <−17%) and CMR RVEF in the y-axis versus modified ACC/AHA Heart Failure Stage in the x-axis respectively.

Figure 1

Conclusion

Segmental fSENC detects subclinical RV dysfunction well before changes in RVEF. The ability to directly measure intramyocardial RV strain allows quantification various subclinical right heart diseases, the impact and monitoring of pharmacological therapiesand device interventions on RV function.
4310Left ventricular myocardial mass index is a predictor of clinical outcomes in patients with Fabry disease
Authors: Moiseev S , Karovaikina E , Bulanov N , Moiseev A , Fomin V
Published: October 2019

Fabry disease (FD) is a rare lysosomal storage disorder characterized by severe complications in young patients. The aim of the study was to determine predictors of clinical outcomes in patients with FD.

Methods

The diagnosis of FD was confirmed by enzymatic and genetic studies. The outcomes included death and a composite of end-stage renal disease (ESRD), cardiac (clinically significant arrhythmia and cardioverter/pacemaker implantation) and cerebrovascular (transient ischemic attack, stroke) events. Cox regression model was used to examine the risk of clinical outcomes.

Results

One hundred adult patients (65 males and 35 females, median age 40 [32; 50.8] years) with a definite diagnosis of FD were enrolled in our study. The majority of patients had classic phenotype (94.2%) and missense mutations in the GLA gene (69.0%). Forty-seven patients (38 males and 9 females) experienced clinical outcomes which included arrhythmias in 10 patients (atrial fibrillation in 8 of thems), ESRD in 33 patients, and cerebrovascular events in 8 patients. The median age of the first outcome was 39 (32; 49) years. In males, the outcomes occurred more frequently than in females (58.5% vs. 25.7%, respectively, p=0.002). Eleven males died at the median age of 43 (37; 46) years. All of them had ESRD. The most frequent cause of death was sudden cardiac death (n=9). Left ventricular myocardial mass index (LVMMI) was higher among patients with outcomes than in patients without outcomes (153 g/m2 [102; 203] vs. 92 g/m2 [78; 122], respectively, p<0.0001). However, there was no correlation between LVMMI and cardiac events (p=0.12). Using Cox regression analysis, LVMMI (HR 1.01 [1.002; 1.02], p=0.015), eGFR <60 ml/min/1.73m2 (HR 3.79 [1.87; 7.66], p<0.0001) and albuminuria>300 mg/day (HR 1.29 [1.04; 1.59], p=0.022) were associated with a higher risk of a composite outcome after adjustment for gender and age. Albuminuria>300 mg/day (HR 1.57 [1.05; 2.35], p=0.029) and LVMMI (HR 1.006 [1; 1.012], p=0.038) were predictors of death after adjustment for gender. However, this effect has been lost after adjustment for hemodialysis duration. The type of mutation in the GLA gene was not a predictor of clinical outcomes.

Conclusion

Left ventricular myocardial mass index was a predictor of clinical outcomes in patients with FD. Poor prognosis in our cohort was related to ESRD that accounted for all deaths.