bluuebunny/crossref_metadata_2025 huggingface dataset:
3149Regional strain patterns according to hypertension and left ventricular hypertrophy in the general population
Authors: Frimodt-Moeller K E , Olsen F J , Biering-Soerensen S R , Moegelvang R , Jespersen T , Schnohr P , Gislason G , Biering-Soerensen T
Published: October 2019

Background

A pattern of reduced basal longitudinal strain (BLS) is often observed in hypertension (HT) and with altered left ventricular (LV) geometry. Whether this pattern is associated with poor outcome is unclear. We hypothesized that BLS becomes incrementally more impaired in the transition from HT to LV hypertrophy (LVH) and is a predictor of outcome.

Methods

We investigated 1,096 participants from a community-based cohort study who had an echocardiogram with speckle tracking performed. Regional strain was calculated as: BLS, midventricular and apical strain. The participants were stratified by LV geometry: LVH vs. non-LVH (LVH defined as left ventricular mass index >116 g/m2 for men and >96g/m2 for women). Outcome was major adverse cardiovascular events (MACE) defined as incident myocardial infarction, heart failure, and cardiovascular death.

Results

BLS and midventricular strain were significantly reduced when comparing normal participants without HT to participants with HT, whereas only BLS was reduced when comparing participants with HT to those with LVH (figure). Overall, patients with LVH showed both reduced BLS and midventricular strain (BLS: −17.5 vs −19.2%, p<0.001; midventricular strain: −19.2 vs. −19.9%, p=0.007 for LVH and non-LVH, respectively) compared to non-LVH, whereas apical strain was similar between groups.

During a median follow-up of 12.9 years (13.5; 14.9 years) there were 139 events. Only BLS was reduced in patients with MACE (BLS: −18.0 vs −19.1%, p=0.002) compared to patients without outcome. Both BLS and midventricular strain were univariable predictors of MACE in patients with LVH (BLS: HR=1.20 [1.04; 1.20], p=0.002; midventricular strain: HR=1.08 [1.00; 1.17], p=0.049) but not in patients without LVH (BLS: HR=1.02 [0.97; 1.08], p=0.46; midventricular strain: HR=1.01 [0.94; 1.07], p=0.88). Both measures were independent predictors after multivariable adjustment for clinical risk factors: age, gender, smoking, hypertension, and cholesterol (BLS: HR=1.08 [1.00; 1.16, p=0.048; midventricular strain: HR=1.10 [1.00; 1.20], p=0.049).

Regional strain by HT and LV geometry

Conclusion

BLS and midventricular strain, but not apical strain, becomes incrementally impaired in the transition from normal to LVH, and is associated with poor outcome. In regional strain analyses, BLS provides the highest predictive value for outcome in patients with LVH.

Acknowledgement/Funding

None
3224Incremental benefit of left ventricular global longitudinal strain over clinical and left atrial parameters for predicting new-onset atrial fibrillation
Authors: Kawakami H , Ramkumar S , Pathan F , Wright L , Marwick T H
Published: October 2019

Background

Although LV hypertrophy and dysfunction are associated with atrial fibrillation (AF), AF often occurs in the absence of LV hypertrophy or reduced ejection fraction. The effect of subclinical LV dysfunction on AF has not been fully studied.

Purpose

We sought the association between subclinical LV dysfunction (measured with global longitudinal strain, GLS) and new-onset AF.

Methods

This observational study evaluated 531 consecutive patients (median age, 67 years [interquartile range, 56 to 78]; 56% male), without a history of AF who underwent strain echocardiography after cryptogenic stroke. The CHARGE-AF score was used to calculate the 5-year risk of developing AF. Standard echocardiographic parameters were measured, and speckle-tracking was used to measure LA (reservoir strain, pump strain, and conduit strain) and LV strain (GLS). A strain analysis was conducted using a dedicated software package, using R-R gating. The baseline clinical and echocardiographic parameters of the patients who developed AF and those who did not were compared.

Results

Over 2.5 years of follow-up, 61 patients (11%) had new-onset AF. Patients who developed AF were older, had a higher CHARGE-AF score, larger LA volume, worse LA strain, and worse GLS than those who did not. Areas under the receiver-operating curve for GLS (0.84) was comparable to CHARGE-AF (0.79), LA pump strain (0.83), and LA reservoir strain (0.85). In the nested Cox models, GLS demonstrated an independent and incremental predictive value over the clinical and LA parameters (Figure). Moreover, adding GLS to the combined clinical and LA parameters model resulted in a significantly improved reclassification (net reclassification improvement, 0.32; p=0.016). Importantly, the predictive value of GLS was confirmed in patients with abnormal LA volumes (LA volume index≥34ml/m2) but not in patients with normal LA volumes.

Figure 1

Conclusion

GLS is associated with new-onset AF, especially in patients with abnormal LA volumes. This effect is independent of and incremental to the clinical and LA parameters.
3285Impact of intravascular ultrasound-guided percutaneous coronary intervention in patients with diabetes mellitus and chronic kidney disease
Authors: Sato R , Sakamoto K , Yamashita T , Nagamatsu S , Motozato K , Sueta D , Oshima S , Nakako K , Fujimoto K , Shimomura H , Tsunoda R , Hokimoto S , Kaikita K , Tsujita K
Published: October 2019

Background

Several studies have shown favorable results using IVUS-guided PCI. Nevertheless, patient background in which use of IVUS is effective is not well elucidated. Patients with diabetes mellitus (DM) or chronic kidney disease (CKD) tend to have complex coronary artery lesions. We sought to assess the impact of IVUS guidance on clinical outcomes in these patients.

Methods

Kumamoto Intervention Conference Study is a multicenter registry which has enrolled consecutive patients who underwent PCI in 16 centers in Japan. Between August 2008 and March 2014, 11,195 consecutive patients were enrolled in this registry. To elucidate the efficacy of IVUS usage in DM and CKD patients, 10,822 consecutive subjects with 1-year follow-up data were analyzed. In this patient population, 69.2% (n=7,493) of patients were treated with IVUS-guided PCI. Patients were divided into 4 groups: the No Risk Group, the DM only Group, the CKD only Group, and the DM+CKD Group.

Results

Maximum stent diameter, post dilatation rate, usage of distal protection device, and rotational atherectomy rate were significantly higher in the IVUS-guided PCI patients in all 4 groups. 1-year MACE (cardiovascular death, non-fatal myocardial infarction, and MI with stent thrombosis) was significantly lower in the IVUS-guided PCI patients than angiography-guided PCI patients in each subset, except for the No Risk Group. In contrast to angiography-guided PCI patients, there were no significant differences among the 4 groups as regards 1-year MACE in the IVUS-guided PCI patients except for the DM+CKD Group. In multiple regression analysis, IVUS usage was an independent negative predictor for 1-year MACE in the DM only Group (HR=0.374, 95% CI 0.194–0.719, p=0.003) and in the CKD only Group (HR=0.604, 95% CI 0.379–0.962, p=0.010). When the No Risk Group was used as a reference, the HR has increased according to increased risk factors in the angiography-guided PCI patients, but such tendency was not necessarily observed in the IVUS-guided PCI patients (Table).

Risk Stratification of DM and CKD Variable IVUS-Guided PCI Angiography-Guided PCI HR 95% CI P HR 95% CI P The No Risk Group Reference – – Reference – –   vs. the DM only Group 0.627 0.321–1.227 0.173 2.036 1.090–3.804 0.026   vs. the CKD only Group 1.334 0.795–2.237 0.275 2.730 1.541–4.836 0.001   vs. the DM+CKD Group 2.114 1.287–3.474 0.014 2.225 1.160–4.266 0.016

Conclusion

The efficacy of IVUS usage as regards 1-year MACE was confirmed in DM and CKD patients, but not observed in patients without them or in the combination of DM and CKD patients.

Acknowledgement/Funding

None
3286Fractional flow reserve-guided treatment strategy for left main coronary artery stenoses. Ten-year clinical outcome
Authors: Di Gioia G , Fournier S , Milkas A , Colaiori I , Hamilos M , Muller O , Bartunek J , Vanderheyden M , Wyffels E , Barbato E , De Bruyne B
Published: October 2019

Background

Revascularization decisions regarding left main (LM) coronary stenoses are often very challenging. Non-invasive tests can yield false negative results. On the other hand, some technical aspects of fractional flow reserve (FFR) measurement, as well as the interpretation of their results, are less codified than for other coronary segments.

Purpose

To investigate the 10-year clinical outcome of patients with isolated angiographically intermediate LM coronary stenosis in whom the treatment strategy was based on Fractional Flow Reserve (FFR) measurements.

Methods

From 1999 to 2009 we included 96 patients with isolated intermediate LM coronary disease (DS% 30–70%) evaluated with FFR measurement. When FFR was >0.80, patients were deferred to medical therapy (Deferral-group, n=71). When FFR was ≤0.8, surgical revascularization therapy was proposed (Revascularization-group, n=25). Death, the occurrence of myocardial infarction (MI) and the need for target vessel revascularization (TVR) were evaluated in both groups.

Results

There were no significant differences in clinical characteristics between the 2 groups. Mean DS% was 35% in the Deferral-group and 43% in the Revascularization-group (p<0.01). Average FFR was 0.88 in the Deferral-group and 0.71 in the Revascularization-group (p<0.01). In the latter, the 10-year survival estimate was 72% while it was 77% in the Deferral group (HR [95% CI]: 1.28 [0.53–3.10]; p=NS). No difference was found between the 2 groups in terms of MI (4.5% vs. 1.6%; HR [95% CI]: 3.5 [0.22–56.0]; p=NS) or TVR (9% vs. 12%; HR [95% CI]: 0.94 [0.20–4.43]; p=NS).

Conclusions

The use of FFR to defer revascularization in patients with non-significant isolated LM stenosis is safe and is associated with favourable clinical outcome at 10 years.
3302Effects of implementation of the ESC 0/1-hour algorithm on efficiacy and safety of discharge after rule-out in a consecutive cohort of patients with suspected acute coronary syndrome - RAPID-CPU study
Authors: Stoyanov K M , Hund H , Biener M , Gandowitz J , Riedle C , Loehr J , Mueller-Hennessen M , Vafaie M , Katus H A , Giannitsis E
Published: October 2019

Aims

The feasibility, efficacy and safety of ESC 0/1- and 0/3-hour algorithms using high-sensitivity troponin T (hsTnT) were evaluated in an all-comer cohort with suspected acute coronary syndrome, based on a broad spectrum of symptoms.

Methods

During 12 months, 2,525 eligible patients were enrolled. In a pre-implementation period of 6 months, prevalence of protocols, disposition, lengths of emergency department (ED) stay and treatments were registered. Implementation of ESC 0/1-hour protocol was monitored for another 6 months. Primary endpoints comprised the change of diagnostic protocols, and all-cause mortality at 30 days following direct discharge from the ED. Secondary endpoints included length of ED stay, hospital discharge, and 1-year mortality.

Results

Use of the ESC 0/1-hour algorithm increased by 270% at the cost of the standard 0/3-hour protocol. Median follow-up times were 400 (316–459) days, with vital status available for 98.7%. After rule-out (1,588 patients), 1,309 patients (76.1%) were discharged directly from the ED, with an all-cause mortality of 0.08% at 30 days (1 death due to lung cancer). Median lengths of stay were 2.9 (1.9–3.8) and 3.2 (2.7–4.4) hours using a single hsTnT below limit of detection (LoD) (5 ng/L) at presentation and the ESC 0/1-hour algorithm, respectively, as compared to 5.3 (4.7–6.5) hours using the ESC 0/3-hour rule-out protocol. Discharge rates increased from 53.9% to 62.8% (p<0.0001), without excessive use of diagnostic resources within 30 days.

Mortality by diagnostic rule

Conclusion

Implementation of the ESC 0/1-hour algorithm seems feasible and safe. It is associated with shorter ED stays than the ESC 0/3-hour protocol and a further increase of discharge rates.

Acknowledgement/Funding

Roche Diagnostics International Ltd.
3303Classification of patients with acute chest pain by analytical benchmarks and subsequent management recommendations - A comparison of three highly-sensitivity troponin assays in the ROMICAT trials
Authors: Karady J , Mayrhofer T , Ferencik M , Udelson J E , Fleg J L , Peacock W F , Januzzi Jr J L , Nagurney J T , Koenig W F , Hoffmann U
Published: October 2019

Background

Concordance of different highly-sensitive troponin (hsTn) assays in stratifying acute chest pain (ACP) patients according to analytical benchmarks and subsequent emergency department (ED) management recommendations are unknown.

Methods

We included patients enrolled in the ROMICAT (Rule Out Myocardial Infarction/Ischemia Using Computer-Assisted Tomography) I and II trials (n=624; 39.1% female; 52.8±10.0 years), who presented to the ED and were referred to further non-invasive diagnostic testing. In ROMICAT I, blood was obtained at 4 hours, and in ROMICAT II at ED presentation, and at 2 and 4 hours and was tested with three state-of-the-art hsTn assays (Roche Diagnostics, Elecsys 2010; Abbott ARCHITECT i2000SR; Siemens Diagnostics, HsVista). In a per sample analysis, we compared the concordance of assays for analytic benchmarks (below the level of detection (LOD)/LOD to 99th percentile/99th percentile to myocardial infarction (MI)/above MI). In a per patient analysis of serial hsTn testing in ROMICAT II, we determined concordance of management recommendations (rule out/observe/rule in) based on 2015ESC guidelines, results of coronary CT angiography and stress myocardial perfusion, and adjudicated endpoints of ACS.

Results

Overall, only 34.4% (353/1027) of samples were classified into the same benchmark category by all assays (table 1). In a per patient analysis, all assays agreed on the same of management recommendation in 25.3% (49/242) patients after the 1st hsTn, mostly driven by differences in discharge (6.6%, 21.1%, and 61.2%; respectively; all p<0.001). The concordance of management recommendations improved significantly to 67.4% (163/242; p<0.001) after the 2nd hsTn measurement but the final agreement for “observe” and “rule in” remained limited (13/90 and 5/18). Among patients in whom discharge was recommended, at least 18.8% (range: 18.8–21.0% across assays) had a positive imaging/stress test and at least 2.9% (range: 2.9–3.4%) had ACS.

Table 1. Classification of measurements from three hsTn assays in 1027 samples of patients with ACP according to analytical benchmarks <LOD LOD – 99th %tile* 99th %tile* – AMI** AMI**< Roche Elecsys, n (%) 578 (56.3) 328 (31.9) 95 (9.3) 26 (2.5) Abbott ARCHITECT, n (%) 176 (17.1) 788 (76.7) 14 (1.7) 49 (4.8) Siemens Vista, n (%) 96 (9.4) 861 (83.9) 33 (3.2) 37 (3.6) *Assay specific 99th percentiles; **as per ESC 2015 guidelines.

Conclusion

Differences in hsTn assay concordance for analytical benchmarks and subsequent ED management recommendations in patients with ACP are substantial raising concerns about the lack of uniform management.

Acknowledgement/Funding

Fulbright Visiting Student Researcher Grant
3305Validation of a novel high-sensitivity cardiac troponin i assay for early diagnosis of acute myocardial infarction
Authors: Boeddinghaus J , Twerenbold R , Nestelberger T , Koechlin L , Wussler D , Wildi K , Puelacher C , Du Fay De Lavallaz J , Rubini Gimenez M , Walter J E , Zimmermann T , Miro O , Martin-Sanchez F J , Keller D I , Mueller C
Published: October 2019

Background

The novel high-sensitivity cardiac troponin I (hs-cTnI)-Vitros assay was developed recently. Before its possible implementation into routine clinical care for triage of chest pain patients, its performance needs clinical validation.

Purpose

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

Methods

In a prospective international multicentre study (12 centres in 5 European countries) 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-Vitros was measured at presentation and at 1h in a blinded fashion. Primary objective was direct comparison of diagnostic accuracy as quantified by the area under the receiver-operating-characteristic curve (AUC) of hs-cTnI-Vitros versus the two established hs-cTn assays (hs-cTnT-Elecsys, hs-cTnI-Architect). Secondary objectives included the derivation and validation of a hs-cTnI-Vitros specific 0/1h-algorithm.

Results

AMI was the adjudicated final diagnosis in 158/1231 (13%) patients. The AUC at presentation for hs-cTnI-Vitros was 0.95 (95% CI, 0.93–0.96), and significantly higher as hs-cTnT-Elecsys (0.94 [95% CI, 0.92–0.95; p=0.01]) and hs-cTnI-Architect (0.92 [95% CI, 0.90–0.94; p<0.001]). Applying the derived hs-cTnI-Vitros 0/1h-algorithm (derivation cohort n=519) to the validation cohort (n=520), 53% of patients were ruled-out (sensitivity 100% [95% CI, 98.6–100]), and 14% of patients were ruled-in (specificity 95.6% [95% CI, 93.4–97.2]). Patients ruled-out by the 0/1h-algorithm had a survival rate of 99.8% at 30-days and 98.7% at 2-years. Findings were confirmed in the secondary analyses using the adjudication including serial measurements of hs-cTnI (Architect).

ROC Curves for the 3 hs-cTn assays at 0h

Conclusions

The novel hs-cTnI-Vitros assay has even higher diagnostic accuracy as the current gold-standards hs-cTnT and hs-cTnI. The hs-cTnI-Vitros specific 0/1h-algorithms allows a safe rule-out and accurate rule-in of AMI in about 70% of patients within 1h after presentation to the ED.

Acknowledgement/Funding

Swiss National Science Foundation, the Swiss Heart Foundation, the KTI, the European Union, the Stiftung für kardiovaskuläre Forschung Basel
3312Thrombomodulin expressed on vascular smooth muscle cell influences arterial injury-induced neointima formation in mouse
Authors: Li Y H , Wang K C , Chen P S , Chung H C , Wu H L
Published: October 2019

Background

Thrombomodulin (TM) is a cell membrane-bound anticoagulant protein that only expresses on endothelial cells in normal artery. Vascular smooth muscle cells (SMCs) start to exhibit TM after arterial injury. Our previous study demonstrated that vascular SMC-bound TM expression was associated with SMC synthetic phenotype. TM knockdown not only attenuated aortic SMCs proliferation but also reduced aortic SMC-mediated inflammation. In this study, we investigated the effect of vascular SMC-bound TM on arterial injury-induced neointima formation in mouse.

Methods and results

Because complete loss of TM in TM knockout transgenic mice causes embryonic lethality, we generated vascular SMC-specific TM-deficient mice (SM22-cretg/TMflox/flox) and their wild-type controls (SM22-cretg/TM+/+) using the Cre-loxP system to explore the role of vascular SMC membrane-bound TM in vivo. The blood pressure and body weight were similar between SM22-cretg/TMflox/flox mice and their wild-type controls. Carotid ligation caused neointima formation in mice. Immunofluorescence staining showed that there was large amount TM expression in the medial and neointimal cells at 4 weeks in SM22-cretg/TM+/+ mice after carotid ligation, but there was no TM staining could be found in SM22-cretg/TMflox/flox mice. There was a progressively increased neointima area from 2 to 4 weeks after carotid ligation both in SM22-cretg/TMflox/flox mice and SM22-cretg/TM+/+ mice, but the neointima area and neointima/media area ratio were significantly smaller in SM22-cretg/TMflox/flox mice than SM22-cretg/TM+/+ mice. Immunofluorescence staining showed that there were less Ki67-positive cells in the media and neointima in SM22-cretg/TMflox/flox mice indicating less proliferating cells in the arterial wall of TM-deficient mice. The α-smooth muscle actin-positive staining area was also larger in the SM22-cretg/TMflox/flox mice, suggesting TM deficiency of SMCs in medial lesion exhibited a more contractile status after carotid ligation.

Conclusions

Our results indicated that vascular SMC-bound TM not only mediated vascular SMC phenotype change and cell behavior but also significantly influenced arterial injury-induced neointima formation.

Acknowledgement/Funding

This study was sponsored by grants 104-2314-B-006-083-MY2 and 106-2314-B-006-045-MY3 from the Ministry of Science and Technology, Taipei, Taiwan.
3325Incidence, outcomes and microbiology in patients with infective endocarditis
Authors: Shah A , McAllister D , Astengo F , Perez J , Lee K K , Gallacher P , Hall J , Bing R , Anand A , Newby D , Mills N , Cruden N
Published: October 2019

Introduction

Despite recent improvements in management, infective endocarditis remains associated with high morbidity and mortality. Over the last few decades, several factors have impacted on both the incidence and outcomes following infective endocarditis.

Purpose

Using a national linkage approach, we describe the changing age- and sex-stratified incidence and outcomes of infective endocarditis in Scotland over the last 25 years.

Methods

We conducted a consecutive retrospective individual patient linkage study across multiple national databases. Using data extracted from the Scottish hospital discharge dataset held by the Information Services Division of NHS National Services Scotland, we extracted episodes for all patients aged 20 years or older who were admitted with infective endocarditis between January 1, 1990, and December 31, 2014 in Scotland, UK. Patient episodes with infective endocarditis were linked to national prescribing and microbiology databases. The primary outcome was 1-year mortality following the index presentation. Generalised additive models were constructed to estimate the crude and age- and sex-stratified incidence rates (using a poison distribution) as well as trends in mortality (using a binomial distribution) adjusted for age, sex and comorbidity.

Results

Across 12,446 individual patients, there were a total of 12,667 hospitalisations (mean age 68±17 years, 55% females) with infective endocarditis using a 5-year look back period. The estimated crude rate of hospitalisation increased from 7.38 per 100,000 (95% CI 6.58 to 8.28) in 1990 to 15.09 per 100,000 (95% CI 13.90 to 16.39) in 2014 (p<0.001). Over the period of the study, 31% (3,877/12,667) of people admitted to hospital with infective endocarditis died within one year of admission. Case fatality fell markedly in both men and women from 1990 to 2014 (Figure). Microbiology was status was available for 34% of all hospitalisations with staphylococcus cultures associated with worse outcomes.

Conclusions

Despite the crude incidence of infective endocarditis doubling over the last 25 years and case fatality remaining high, the risk of death has markedly fallen over the last two decades. Staphylococcus cultures remain an independent marker of poor prognosis in this cohort.

Acknowledgement/Funding

British Heart Foundation
3329Renal pathologic findings and clinical associations in patients with infective endocarditis
Authors: Povalyaev N , Pisaryuk A , Sorokina M , Teterina M , Balatskiy A , Belomyttsev S , Kotova E , Karaulova Y , Efremovtseva M , Malkov P , Milto A , Ratchina S , Kobalava Z
Published: October 2019

Background

Kidney involvement in infective endocarditis (IE) has a huge contribution in failure of the antimicrobal therapy and in rejection of the surgical treatment. Frequency of kidney lesions is still high and is diagnosed in 50–80% cases intravitaly, and in 91,6% post-mortem.

Materials/Methods

28 patients with verified IE (DUKE 2009, 2015), hospitalized and treated in clinical hospital from 2010 to 2018, were included in the study. Kidney function was assessed using CKD-EPI formula. Acute kidney injury (AKI) was diagnosed according to current guidelines (KDIGO 2012). Intravital nephrobiopsy was performed in 2 (7,1%) patients, in 26 patients (92,9%) morphological assessment was made on the autopsy tissue specimens. Autopsy material was assessed grossly and microscopically with H&E staining. Morphological changes in kidney were estimated based on standart histological criteria.

Results

Majority of patients with IE (92.9%) had structural changes in kidney tissue: 3 (12%), 16 (64%) and 6 (24%) patients had respectively isolated glomerular, tubular and mixed lesions. Significantly higher is rate of tubular lesion than glomerular (p=0.014). Main pattern in glomerular damage was mesangial proliferation, we didn't found any cases of crescentic GN. Herewith, proliferation was mainly diffuse (87.5%) rather than focal (12.5%). Glomerular damage in subacute IE (>56 days) appears more often than in acute IE (<56 days) (p=0.057 χ2=3.63). When studying the influence of various factors on the involvement of the glomeruli or tubules, no statistically significant group differences were obtained, except for the gram-negative flora as the causative agent, in which the tubules are significantly more likely to be affected (p=0.019)

Morphological diagnosis n (%) Morphological diagnosis n (%) Glomerulonephritis 8 (28.6) Tubulointerstitial nephritis 3 (10.7) Membranoproliferative glomerulonephritis 3 (10.7) Allegrgic tubulointerstitial nephritis 2 (7.2) Mesangioproliferative glomerulonephritis 5 (17.9) Infective tubulointerstitial nephritis 1 (3.6) Extracapillar crescentic glomerulonephritis 0 (0) Kidney abscess 3 (10.7) Acute tubular necrosis 22 (78.6) Kidney infarction 1 (3.6) Acute tubular necrosis (ischaemic) 11 (39.3) Renal artery embolism 1 (3.6) Acute tubular necrosis (toxic) 11 (39.3) Shock kidney 4 (14.3)

Conclusions

A morphological study of patients with IE revealed a wide range of kidney damage, however, the frequency of tubular lesions, mediated by nephrotoxic drugs and hemodynamic disorders significantly exceeds the frequency of immune complex glomerular lesions, as previously thought.
3334Updated meta-analysis of biodegradable polymer drug-eluting stent versus second-generation durable polymer drug-eluting stent implantations
Authors: Choe J C , Cha K S , Shin J Y , Ahn J , Park J S , Lee H W , Oh J H , Choi J H , Lee H C , Hong T J
Published: October 2019

Background

Data regarding clinical outcomes of biodegradable polymer drug-eluting stent (BP-DES) versus second-generation durable polymer drug-eluting stent (DP-DES) in patients undergoing percutaneous coronary intervention (PCI) are inconclusive.

Purpose

We aimed to perform a meta-analysis to investigate the clinical outcomes of BP-DES compared with second-generation DP-DES in patients who have undergone PCI.

Methods

We searched PubMed, MEDLINE, EMBASE, and Cochrane databases through January 2019 for randomized controlled trials comparing BP-DES with second-generation DP-DES in patients treated with PCI. All-cause death, cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), target lesion revascularization (TLR), definite/probable stent thrombosis (ST) were compared between the groups. Additionally, a landmark analysis with the landmark set at 1 year and a subgroup analysis according to stent characteristics were performed.

Results

Data from 23 trials including 28802 randomized patients were analyzed. At a median follow up of 3.1 years, no significant differences were found in terms of all-cause death (odds ratio [OR] 1.05, 95% confidence interval [CI] 0.95–1.16), cardiac death (OR 1.01, 95% CI 0.87–1.17), MI (OR 0.92, 95% CI 0.82–1.03), TVR (OR 0.97, 95% CI 0.86–1.11), TLR (OR 0.97, 95% CI 0.85–1.11), and definite/probable ST (OR 0.86, 95% CI 0.70–1.07) between the groups. Landmark analysis showed that there were similar risks in all-cause death (OR 1.04, 95% CI 0.93–1.17), cardiac death (OR 1.11, 95% CI 0.92–1.36), MI (OR 0.94, 95% CI 0.79–1.13), TVR (OR 0.95, 95% CI 0.73–1.23), TLR (OR 1.00, 95% CI 0.80–1.24), and definite/probable ST (OR 0.92, 95% CI 0.67–1.28) between the groups. The similar tendency of any study endpoints between the groups was consistent in the subgroup, including stent platform (stainless steel vs. alloy), the drug coating distribution (abluminal vs. circumferential), the polymer degradation period (<6 months vs. >6 months), or the drug release duration (<6 months vs. >6 months) of BP-DES, or the DAPT duration (≥6 months vs. ≥12 months). However, the uses of BP-DES with sirolimus-eluting (OR 0.84, 95% CI 0.72–0.98) or ultrathin strut (defined as <70μm; OR 0.81, 95% CI 0.68–0.97) were predictive for lower risk of MI.

Clinical outcomes

Conclusions

In our updated meta-analysis, BP-DES implantation was associated with comparable clinical outcomes compared with second-generation DP-DES implantation. However, PCI with ultrathin biodegradable polymer sirolimus-eluting stent could reduce the risk of MI.
4071Early changes in quality of life after transcatheter aortic valve replacement: One-year results from the 3M TAVR Study
Authors: Lauck S , Wood D A , Baron S J , Borregaard B , Wijeysundera H , Asgar A , Hawkey M , Keegan P , Natarajan M , Masson J B , Humphries K , Welsh R , Cairns J , Webb J G , Cohen D
Published: October 2019

Background

In patients with severe calcific aortic stenosis, transcatheter aortic valve replacement (TAVR) has been shown to significantly improve quality of life (QOL). However, changes in QOL at early follow-up (<1 month), and following next-day discharge are poorly understood.

Methods

A total of 411 patients at 13 centers were enrolled in the Multimodality, Multidisciplinary but Minimalist TAVR (3M TAVR) study in 2015–2017. QOL was evaluated using the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) in participants with a baseline score and at least one score at 2 weeks, 30 days and 1 year. Study endpoints were change in (1) KCCQ-Overall Summary Score (KCCQ-OS) and (2) minimal clinically important differences (MCID). Mixed effects models were used to explore patterns of change from baseline, with fixed terms for time, status at 1-year and their interaction terms, and a random intercept for subject to account for within subject correlation. Descriptive statistics were used to report MCID.

Results

Data were available for 358 (87.1%) participants. 216 (60.3%) were men with a median age 84.0 and STS 5.0 There was significant increase in QOL 2 weeks after TAVR (p≤0.01), and further significant improvement at the 1-month timepoint (p<0.01) for participants who were alive at 1 year. Sex, age category, and STS score category did not have a significant effect on the change in QOL (p>0.05). In the first 2 weeks, moderate (10–20 points) and large (>20 points) improvements were observed in 19.9% and 49.0% of the surviving patients, respectively; at 1-year, similar MCID were seen in 14.6% and 64.0% respectively.

Figure 1

Conclusion

This is the first study to report significant increase in QOL 2 weeks after TAVR, with sustained improvement during the first year in patients treated with the Vancouver TAVR Clinical Pathway with a goal of next-day discharge. Further studies are necessary to determine whether alternative TAVR clinical pathways yield similar findings.

Acknowledgement/Funding

Investigator-initiated unrestricted research grant, Edwards
4099High intensity endurance and strength training in water polo Olympic team players: impact on arterial wall properties
Authors: Oikonomou E , Siasos G , Marinos G , Zaromitidou M , Athanasiou D , Foundoulakis P , Tsalamandris S , Antonopoulos A , Mistakidi C V , Vlachopoulos C , Tousoulis D
Published: October 2019

Background

Regular physical activity is recommended for health improvement. However the upper intensity threshold associated with best health outcome is difficult to determine. Water polo (WP) Olympic athletes present unique characteristics with very high intensity work, long training sessions and a combination of endurance and strength training.

Purpose

To examine how long term, intense mixed endurance and strength training affect peripheral and central hemodynamics and biomarkers of cardiovascular health.

Methods

The study population consisted of 20 WP Olympic team player's, 20 matched recreational active subjects (RA) and 20 sedentary control subjects (Cl). Reflected waves were assessed with the Augmentation index (AIx), central aortic stiffness with pulse wave velocity (PWV) and endothelial function with flow mediated dilation (FMD).

Results

From Cl subjects to RA active subjects and to WP players there was a stepwise decrease in aortic systolic pressure (116±16 mmHg vs. 107±14 mmHg vs. 106±6 mmHg, p=0.03) while there was no difference in branchial systolic pressure (p=0.52). There was also a stepwise improvement in AIx (−4.22±9.97% vs. −6.97±11.28% vs. −12.14±6.62%, p=0.03) and FMD (6.61±1.78% vs. 7.78±1.98% vs. 8.3±2.05%, p=0.04) according to the intensity of exercise and WP players had lower AIx and higher FMD compared to RA subjects and to Cl subjects.

Conclusions

In young WP Olympic team players intense mixed endurance and strength training has no adverse impact on arterial wall properties and endothelial function with a parallel improvement in central hemodynamics. These findings highlight that there are no definitive data to support on any adverse vascular related impact of ultra-endurance training while mixed endurance and strength training may be associated with a favorable vascular profile.
4112Risk factors and clinical outcomes in chronic CAD and PAD: an analysis of the randomized, double-blind COMPASS trial
Authors: Vanassche T , Verhamme P , Anand S , Bosch J , Eikelboom J
Published: October 2019

Background

Patients with coronary artery disease (CAD) and peripheral artery disease (PAD) are at high risk for cardiovascular death and ischemic events. Secondary prevention requires both optimal control of modifiable cardiovascular risk factors and antithrombotic therapy. The COMPASS study showed a reduction in ischemic events in patients treated with the combination of low-dose rivaroxaban and aspirin, compared with aspirin alone. However, the impact of intensifying antithrombotic therapy by baseline risk factor control is not well studied.

Objective

To study the association between baseline risk factor status and outcomes, and the effects of treatment with low-dose rivaroxaban and aspirin compared with aspirin alone according to baseline risk factors, in a large contemporary population of patients with CAD or PAD.

Methods

We studied ischemic events (cardiovascular death, stroke, or MI) in participants from the randomised, double blind COMPASS trial in relation to baseline blood pressure, smoking status, cholesterol level, presence of diabetes, body mass index, and level of physical activity, as well as by the number of cardiovascular risk factors (0–1, 2, 3, 4, or 5–6). Within each risk factor category, we compared rates and hazard ratios of patients treated with rivaroxaban plus aspirin vs aspirin alone and tested for interaction between the treatment effect of rivaroxaban and risk factor status.

Results

Baseline information on all six risk factors was available in 27,117 (99%) patients. Each risk factor was associated with increased risk of ischemic events (Figure 1, panel A). Patients with 5 or 6 risk factors had more than 2-fold higher rates of ischemic events (HR 2.36; 95% CI: 1.80–3.10) and of cardiovascular death (HR 2.22; 1.48–3.33) compared with patients with 0 or 1 risk factor. The addition of low-dose rivaroxaban on top of aspirin reduced event rates independently of number of risk factors (p for interaction 0.93) (Figure 1, panel B). The largest absolute benefit of low-dose rivaroxaban was seen in patients with the greatest number of risk factors.

Figure 1

Conclusion

More favourable baseline risk factor status and the use of low-dose rivaroxaban were both independently associated with lower risk of ischemic events. Patients at highest risk, based on number of baseline risk factors, derive the largest absolute benefit of the combination of rivaroxaban and aspirin.

Acknowledgement/Funding

The COMPASS trial was sponsored by Bayer AG. The sponsor did not influence the analysis plan, drafting of abstract, or the decision to submit
4117Cardiac surveillance during breast cancer treatment; a snapshot of current practice
Authors: Koop Y , Maas A H E M , Vermeulen H , Atsma F
Published: October 2019

Background

Breast cancer (BC) is the most common type of cancer in women. Over the past decades survival rates increased up to 90% at 5 years and 83% at 10 years. The various BC treatments, such as radiotherapy, chemotherapy and immunotherapy increase cardiotoxicity risk, leading to premature ischemic heart disease and heart failure amongst survivors. Both affect women's daily routine and quality of life. Reducing this adverse risk, by early recognition and (preventive) treatment, is therefore important. Despite, screening for cardiotoxicity is currently insufficiently standardized in daily practice.

A fundamental step in identifying areas of improvement is providing an overview of current practice.

Purpose

This study aims to describe current cardiac surveillance for women with BC during and after cancer treatment, using routinely collected hospital data in the Netherlands.

Methods

An observational study has been performed on Dutch hospital data from 2012 up to 2015, provided by Statistics Netherlands. Information about cardiology and oncology diagnoses, diagnostic procedures, treatments and preventive measures were available. Newly diagnosed female patients with codes malignant neoplasm of the breast (ICD-10, C50.0-C50.9) in 2013 and without any comorbidities since 1–1-2012 were included in the analyses. In follow-up data up to 31–12 2015, we mapped all types of care the patients received for BC and cardiology related indications.

Results

We included 16040 newly diagnosed BC patients in 2013, with a mean age of 65.9 (sd 12.9). A total of 5084 (31.7%) received chemotherapy, 1385 (8.6%) immunotherapy and 7870 (49.1%) radiotherapy. Amongst all included patients, 4376 (27.3%) received any type of cardiac care. Cardiology specific laboratory tests (e.g. Troponin) were performed in 96 (0.6%). Imaging procedures, such as echocardiography and MUGA occurred in 1853 (11.5%) and 1544 (9.6%) patients, respectively.

Of the 5084 patients receiving chemotherapy 1862 (36.6%) received any type of imaging or cardiac care, of the 1385 patients receiving immunotherapy 689 (49.7%), and of the 7870 patients receiving radiotherapy 2401 (31.7%).

Conclusions

This study shows that only a quarter of Dutch women treated for BC receive cardiac surveillance. Diagnostic procedures or laboratory tests to detect cardiotoxicity are not structurally performed in women receiving cardiotoxic cancer treatments (e.g. chemo- and radiotherapy). A more structural approach and individual risk assessment is needed to provide more tailored cardiac care during BC treatment.
4179Feasibility and validation of routine CMR-based phenotyping for the prediction of heart failure admission or death in patients with systolic dysfunction
Authors: Cornhill A , Dykstra S , Mikami Y , Flewitt J , Seib M , Yee K , Faris P , Hansen R , Lydell C , Howarth A , Heydari B , White J
Published: October 2019

Background

Standardized patient phenotyping using cardiovascular magnetic resonance (CMR) imaging has been shown to be of clinical value for prediction of adverse events in patients with heart failure and reduced ejection fraction (HFrEF). Studies have validated the prognostic capacity of function (LV, RV and LA) and replacement fibrosis burden in patients with ischemic and non-ischemic cardiomyopathy. The translation and validation of routine CMR-based phenotyping into clinical practice has yet to be demonstrated in prospective studies.

Purpose

This study was designed to explore feasibility and prognostic value of routine CMR-based patient phenotyping in a high-volume clinical referral center for patients with HFrEF.

Methods

One thousand three hundred and ninety-three consecutive patients with chronic HFrEF were prospectively recruited between January 2015 and June 2018. Chronic HFrEF was defined by LVEF≤50% by CMR, with no recent (within 90 days) acute myocardial infarction or myocarditis diagnosis. Patients with congenital heart disease and those without LGE CMR protocol were excluded. All patients underwent standardized CMR protocols with multi-chamber volumetric analysis and regional myocardial fibrosis coding. Pharmacy, ECG, laboratory and patient reported data was used for statistical modelling. A minimum three-month follow-up was mandated to identify the composite clinical outcome of heart failure hospitalization or death.

Results

The cohort had a median age of 61 years with 23% being female. The median follow-up was 737 days with 146 patients (10.5%) experiencing the composite outcome. Numerous imaging and non-imaging variables were significantly different between patients with and without the composite outcome, including: median LVEF (32% vs 39%, p<0.0001), RVEF (46% vs 51% p<0.0001), LV mass (77g/m2 vs. 65g/m2, p<0.0001), digoxin (19% vs. 9%, p<0.0001) and diuretic (63% vs 41%, p<0.0001) use. Presence of replacement fibrosis (HR=2.09, p=0.001), particularly midwall striae (HR=2.01, p<0.0001), diffuse (HR=3.88, p<0.0001) and RV insertion site fibrosis (HR=1.54, p=0.022) patterns, were significantly associated with the combined endpoint. A stepwise multivariable model was applied using all eligible variables and resulted in robust accuracy for prediction of the combined outcome with a concordance index of 0.751 (Figure 1).

Conclusions

This study demonstrates the feasibility and prognostic value of automated patient phenotyping that captures patient reported data, imaging, and administrative data for risk prediction modelling in HFrEF. The incremental application of machine learning is being explored.

Acknowledgement/Funding

J White: Early Investigator Award (Heart and Stroke Foundation of Alberta), Calgary Health Trust
4260Loss of Pnn in cardiomyocytes results in impairment of intercalated discs and arrhythmogenic cardiomyopathy in mice
Authors: Leu S , Hsu S Y , Ouyang P
Published: October 2019

Background

Pnn, a multiple functional protein that localizes within nucleus and in the cytoplasmic region of desmosome. Although recent studies have characterized the physiological role of nuclear Pnn in regulating pre-mRNA alternative splicing and gene transcription, the function of Pnn in desmosome, particularly in cardiomyocytes, remains unidentified.

Purpose and methods

In the present study, we applied an inducible cardiomyocyte-specific Pnn depletion mouse model (Myh6-CreERT2, Pnnflox/flox) to observe the impact of loss of Pnn on cardiac structure and function in adult mice.

Results

Six weeks after tamoxifen injection to induce cardiac Pnn depletion, the electrocardiographic abnormalities and decrease of left ventricular ejection fraction (LVEF) were observed. Histopathological examination showed that the proliferation of cardiac fibroblasts and expression of α-smooth muscle actin were increased with Pnn depletion, while the cell-cell connection among cardiomyocytes were impaired. In addition, cellular hypertrophy and decrease of capillary density were also found. Results from Immunofluorescent staining further showed that the distribution pattern of desmosomal proteins and adherent junctional proteins, including desmoglein, desmocollin, plakoglobin, plakophllin, desmoplakin and β-catenin were altered in the cardiomyocytes with Pnn depletion. Both desmosomal and adherent junctional proteins were translocated form cell-cell junction to cytoplasm, indicating the disruption of intercalated discs in Pnn-depleted cardiomyocytes. Microarray data also indicated that loss of cardiac Pnn regulated the mRNA expression of genes responsible for extracellular matrix-receptor interaction, ribosome, and integrin. In addition, expression levels of oxidative stress-associated proteins were significantly regulated by Pnn depletion.

Impairment of intercalated disc

Conclusion

Results from present study indicated that Pnn plays an essential role in the maintenance of intercalated disc integrity of cardiomyocytes, while cardiomyocyte-specific loss of Pnn leads to arrhythmogenic cardiomyopathy in mice.

Acknowledgement/Funding

Ministry of Science and Technology Taiwan, MOST-106-2320-B-182A-010-MY3
4284The combined use of radiofrequency-ablation and balloon-dilation (CURB) in the creation of a stable inter-atrial communication: first-in-man use for patients with severe pulmonary arterial hypertension
Authors: Yan C , Wan L , Pan X , Li H , Li S , Song H
Published: October 2019

Background

Recent preclinical research has suggested that combined use of radiofrequency-ablation and balloon-dilation (CURB) had the potential to create a stable inter-atrial communication. However, the related clinical data is still absent.

Purpose

This study describes the first-in-man use of CURB in the patients with severe pulmonary arterial hypertension (PAH).

Methods

Under the guidance of fluoroscopy and intra-cardiac echocardiography, CURB was attempted in 3 patients with severe PAH (age: 35.0±12.1 years, one idiopathic PAH and two PAH related to repaired congenital heart disease). With the aid of 3D location system, fossae ovalis was ablated with radiofrequency. Then the graded balloon-dilation was performed after transseptal puncture, and radiofrequency-ablation was repeated around the rim of fenestration created with balloon-dilation. The exercise capacity and fenestration-size were followed up.

Results

CURB was performed successfully in all 3 patients, and pulmonary vascular resistance was 30.3±10.9 Wood units. The fenestration size was 5.0±1.0 mm (range: 4–6 mm), and systemic arterial oxygen saturation decreased by 4.7±0.6% (range: 4–5%). World Health Organization functional class increased by 1.6±0.5 (P<0.001) and cardiac index increased by 0.58±0.34 L/min/m2 (P<0.001). In addition, exercise capacity improved significantly (+63.7 meters, P<0.001). Follow-up (6.0±1.0 months; range: 5–7 months) showed that all fenestrations were stable (P=0.808), and no complication occurred.

Figure 1. The combined use of radiofrequency-ablation and balloon-dilation (CURB) was performed in the patient with severe PAH. Left figures showed the procedure of CURB. Middle figures showed the created fenestration with MSCT, and the morphology and size of fenestration was provided in the right-inferior panel. In addition, the sizes of right atrium and ventricle were alleviated with increase of left atrium. Right figures indicated that the fenestration-size was stable during follow-up (one week, one month and six months, respectively).

Conclusions

In patients with severe PAH, CURB is feasible and effective to create a stable inter-atrial communication. Further research was required to evaluate the long-term result of this novel approach.

ClinicalTrials.gov ID: NCT03554330.

Acknowledgement/Funding

National Natural Science Foundation of China (81670283) and Beijing Natural Science Foundation (7162160)