Background:Little is known about the effect of the coronavirus disease 2019 (COVID-19) pandemic and the outbreak response measures on door-to-balloon time (D2B). This study examined both D2B and ...clinical outcomes of patients with STEMI undergoing primary percutaneous coronary intervention (PPCI).Methods and Results:This was a retrospective study of 303 STEMI patients who presented directly or were transferred to a tertiary hospital in Singapore for PPCI from October 2019 to March 2020. We compared the clinical outcomes of patients admitted before (BOR) and during (DOR) the COVID-19 outbreak response. The study outcomes were in-hospital death, D2B, cardiogenic shock and 30-day readmission. For direct presentations, fewer patients in the DOR group achieved D2B time <90 min compared with the BOR group (71.4% vs. 80.9%, P=0.042). This was more apparent after exclusion of non-system delay cases (DOR 81.6% vs. BOR 95.9%, P=0.006). Prevalence of both out-of-hospital cardiac arrest (9.5% vs. 1.9%, P=0.003) and acute mitral regurgitation (31.6% vs. 17.5%, P=0.006) was higher in the DOR group. Mortality was similar between groups. Multivariable regression showed that longer D2B time was an independent predictor of death (odds ratio 1.005, 95% confidence interval 1.000–1.011, P=0.029).Conclusions:The COVID-19 pandemic and the outbreak response have had an adverse effect on PPCI service efficiency. The study reinforces the need to focus efforts on shortening D2B time, while maintaining infection control measures.
Cardiovascular magnetic resonance (CMR) sequences are commonly used to obtain a complete description of the function and structure of the heart, provided that accurate measurements are extracted from ...images. New methods of extraction of information are being developed, among them, deep neural networks are powerful tools that showed the ability to perform fast and accurate segmentation. Iq1n order to reduce the time spent by reading physicians to process data and minimize intra- and inter-observer variability, we propose a fully automatic multi-scan CMR image analysis pipeline.
Sequence specific U-Net 2D models were trained to perform the segmentation of the left ventricle (LV), right ventricle (RV) and aorta in cine short-axis, late gadolinium enhancement (LGE), native T1 map, post-contrast T1, native T2 map and aortic flow sequences depending on the need. The models were trained and tested on a set of data manually segmented by experts using semi-automatic and manual tools. A set of parameters were computed from the resulting segmentations such as the left ventricular and right ventricular ejection fraction (EF), LGE scar percentage, the mean T1, T1 post, T2 values within the myocardium, and aortic flow. The Dice similarity coefficient, Hausdorff distance, mean surface distance, and Pearson correlation coefficient R were used to assess and compare the results of the U-Net based pipeline with intra-observer variability. Additionally, the pipeline was validated on two clinical studies.
The sequence specific U-Net 2D models trained achieved fast (≤ 0.2 s/image on GPU) and precise segmentation over all the targeted region of interest with high Dice scores (= 0.91 for LV, = 0.92 for RV, = 0.93 for Aorta in average) comparable to intra-observer Dice scores (= 0.86 for LV, = 0.87 for RV, = 0.95 for aorta flow in average). The automatically and manually computed parameters were highly correlated (R = 0.91 in average) showing results superior to the intra-observer variability (R = 0.85 in average) for every sequence presented here.
The proposed pipeline allows for fast and robust analysis of large CMR studies while guaranteeing reproducibility, hence potentially improving patient's diagnosis as well as clinical studies outcome.
Single nucleotide polymorphism rs6903956 has been identified as one of the genetic risk factors for coronary artery disease (CAD). However, rs6903956 lies in a non-coding locus on chromosome 6p24.1. ...We aim to interrogate the molecular basis of 6p24.1 containing rs6903956 risk alleles in endothelial disease biology.
We generated induced pluripotent stem cells (iPSCs) from CAD patients (AA risk genotype at rs6903956) and non-CAD subjects (GG non-risk genotype at rs6903956). CRISPR-Cas9-based deletions (Δ63-89bp) on 6p24.1, including both rs6903956 and a short tandem repeat variant rs140361069 in linkage disequilibrium, were performed to generate isogenic iPSC-derived endothelial cells. Edited CAD endothelial cells, with removal of ‘A’ risk alleles, exhibited a global transcriptional downregulation of pathways relating to abnormal vascular physiology and activated endothelial processes. A CXC chemokine ligand on chromosome 10q11.21, CXCL12, was uncovered as a potential effector gene in CAD endothelial cells. Underlying this effect was the preferential inter-chromosomal interaction of 6p24.1 risk locus to a weak promoter of CXCL12, confirmed by chromatin conformation capture assays on our iPSC-derived endothelial cells. Functionally, risk genotypes AA/AG at rs6903956 were associated significantly with elevated levels of circulating damaged endothelial cells in CAD patients. Circulating endothelial cells isolated from patients with risk genotypes AA/AG were also found to have 10 folds higher CXCL12 transcript copies/cell than those with non-risk genotype GG.
Our study reveals the trans-acting impact of 6p24.1 with another CAD locus on 10q11.21 and is associated with intensified endothelial injury.
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•6p24.1 locus containing rs6903956 is related to endothelial activation pathways.•Chromosomes 6p24.1 and 10q11.21 are spatially organized in endothelial cells.•6p24.1 is in close genomic proximity to a weak promoter of CXCL12 that resides on 10q11.21•Risk allele ‘A’ of rs6903956 is associated with endothelial injury in CAD patients.
An increasing proportion of patients with acute myocardial infarction (AMI) are presenting without standard modifiable risk factors (SMuRFs) of hypertension, hypercholesterolemia, diabetes, and ...smoking, but with an unexpectedly increased mortality. This study examined the SMuRF-less patients presenting with AMI in a multiethnic Asian population.
We recruited patients presenting with AMI from 2011 to 2021 and compared the prevalence, clinical characteristics, and outcomes of SMuRF-less and SMuRF patients. Multivariable analysis was used to compare the outcomes of 30-day cardiovascular mortality, all-cause mortality, readmission, cardiogenic shock, stroke, and heart failure. Kaplan-Meier curves were constructed for 30-day cardiovascular mortality, with stratification by ethnicity, gender and AMI type, and 10-year all-cause mortality.
Standard modifiable risk factor-less patients, who made up 8.6% of 8,680 patients, were significantly younger with fewer comorbidities that include stroke and chronic kidney disease, but higher rates of ventricular arrhythmias and inotropic or invasive ventilation requirement. Multivariable analysis showed higher rates of cardiovascular mortality (HR 1.48, 95% CI: 1.09-1.86,
= 0.048), cardiogenic shock (RR: 1.31, 95% CI: 1.09-1.52,
= 0.015), and stroke (RR: 2.51, 95% CI: 1.67-3.34,
= 0.030) among SMuRF-less patients. A 30-day cardiovascular mortality was raised in the SMuRF-less group, with similar trends in men, patients with ST-segment elevation myocardial infarction (STEMI), and the three Asian ethnicities. All-cause mortality remains increased in the SMuRF-less group for up to 5 years.
There is a significant proportion of patients with AMI without standard risk factors in Asia, who have worse short-term mortality. This calls for greater focus on the management of this unexpectedly high-risk subgroup of patients.
Androgen dependent tissue factor pathway inhibitor regulating protein (ADTRP) is a novel protein associated with coronary artery disease (CAD) susceptibility, and reduced mRNA expression of ADTRP was ...shown to be associated with increased CAD risk. This study aimed to determine and compare circulating ADTRP levels between CAD patients and controls, and to test the performance of plasma ADTRP as a biomarker for CAD. We measured plasma ADTRP, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and high sensitivity-C reactive protein (hs-CRP) levels in 362 CAD patients, 150 angiographically negative CAD controls, and 83 healthy adults with no known clinical or medical conditions using commercial ELISA. Statistical analyses were performed using receiver operator characteristic (ROC) curves, quantile regression and logistic regression, with adjustments for age, gender, ethnicity and BMI. CAD patients had significantly lower plasma ADTRP levels 1,545 (1,087-2,408) pg/ml as compared to CAD controls 2,259 (1,533-3,778) pg/ml and healthy adults 3,904 (2,732-5,463) pg/ml. Plasma ADTRP outperformed the other three inflammatory biomarkers (TNF-alpha, IL-6 and hs-CRP) for CAD (Area under ROC curve: 0.67, Odds ratio (OR): 0.907). Our study has shown for the first time that ADTRP is present in circulation, and that plasma ADTRP may be a novel independent biomarker for CAD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A sizeable number of patients without standard modifiable cardiovascular risk factors (SMuRFs), such as hypertension, diabetes, hypercholesterolemia and smoking, suffer from acute coronary syndrome ...(ACS). These SMuRF-less patients have high short-term morbidity and mortality. We compared both short- and long-term outcomes of SMuRF-less and SMuRF ACS patients in a multi-ethnic Asian cohort.
This was a retrospective study of patients with first ACS from 2011 to 2017. The primary outcome was long-term all-cause mortality. Secondary outcomes were 30-day all-cause mortality, cardiac-mortality, unplanned cardiac readmission, cardiogenic shock, heart failure, and stroke. Subgroup analysis was carried out by sex and ACS type.
Of 5400 patients, 8.6% were SMuRF-less. The median follow-up time was 6.3 years (interquartile range IQR 4.2–8.2 years). SMuRF-less patients were younger and tended to present with ST-segment elevation myocardial infarction (STEMI). They were more likely to require inotropic support, intubation, and have cardiac arrest. At 30 days, SMuRF-less patients had higher rates of all-cause mortality, cardiac-related mortality and cardiogenic shock, but lower rates of heart failure. At 6 years, all-cause mortality was similar in both groups (18.0% versus 17.1% respectively, p = 0.631). Kaplan–Meier curves showed increased early mortality in the SMuRF-less group, but the divergence in survival curves was no longer present in the long-term. The absence of SMuRF was an independent predictor of mortality, regardless of sex or ACS type.
In a multi-ethnic cohort of patients with ACS, SMuRF-less patients were observed to have higher mortality than SMuRF patients during the early stages which was attenuated over time.
The pandemic has led to adverse short-term outcomes for patients with ST-segment elevation myocardial infarction (STEMI). It is unknown if this translates to poorer long-term outcomes. In Singapore, ...the escalation of the outbreak response on February 7, 2020 demanded adaptation of STEMI care to stringent infection control measures. A total of 321 patients presenting with STEMI and undergoing primary percutaneous coronary intervention at a tertiary hospital were enrolled and followed up over 1-year. They were allocated into three groups based on admission date—(1) Before outbreak response (BOR): December 1, 2019–February 6, 2020, (2) During outbreak response (DOR): February 7–March 31, 2020, and (3) control group: November 1–December 31, 2018. The incidence of cardiac-related mortality, cardiac-related readmissions, and recurrent coronary events were examined. Although in-hospital outcomes were worse in BOR and DOR groups compared to the control group, there were no differences in the 1-year cardiac-related mortality (BOR 8.7%, DOR 7.1%, control 4.8%, p = 0.563), cardiac-related readmissions (BOR 15.1%, DOR 11.6%, control 12.0%, p = 0.693), and recurrent coronary events (BOR 3.2%, DOR 1.8%, control 1.2%, p = 0.596). There were higher rates of additional PCI during the index admission in DOR, compared to BOR and control groups (p = 0.027). While patients admitted for STEMI during the pandemic may have poorer in-hospital outcomes, their long-term outcomes remain comparable to the pre-pandemic era.
Background:
Infectious control measures during the COVID-19 pandemic have led to the propensity toward telemedicine. This study examined the impact of telemedicine during the pandemic on the ...long-term outcomes of ST-segment elevation myocardial infarction (STEMI) patients.
Methods:
This study included 288 patients admitted 1 year before the pandemic (October 2018–December 2018) and during the pandemic (January 2020–March 2020) eras, and survived their index STEMI admission. The follow-up period was 1 year. One-year primary safety endpoint was all-cause mortality. Secondary safety endpoints were cardiac readmissions for unplanned revascularisation, non-fatal myocardial infarction, heart failure, arrythmia, unstable angina. Major adverse cardiovascular events (MACE) was defined as the composite outcome of each individual safety endpoint.
Results:
Despite unfavorable in-hospital outcomes among patients admitted during the pandemic compared to pre-pandemic era, both groups had similar 1-year all-cause mortality (11.2 vs. 8.5%, respectively,
p
= 0.454) but higher cardiac-related (14.1 vs. 5.1%,
p
< 0.001) and heart failure readmissions in the pandemic vs. pre-pandemic groups (7.1 vs. 1.7%,
p
= 0.037). Follow-up was more frequently conducted via teleconsultations (1.2 vs. 0.2 per patient/year,
p
= 0.001), with reduction in physical consultations (2.1 vs. 2.6 per patient/year,
p
= 0.043), during the pandemic vs. pre-pandemic era. Majority achieved guideline-directed medical therapy (GDMT) during pandemic vs. pre-pandemic era (75.9 vs. 61.6%,
p
= 0.010). Multivariable Cox regression demonstrated achieving medication target doses (HR 0.387, 95% CI 0.164–0.915,
p
= 0.031) and GDMT (HR 0.271, 95% CI 0.134–0.548,
p
< 0.001) were independent predictors of lower 1-year MACE after adjustment.
Conclusion:
The pandemic has led to the wider application of teleconsultation, with increased adherence to GDMT, enhanced medication target dosing. Achieving GDMT was associated with favorable long-term prognosis.
Invasive fractional flow reserve (FFR) is recommended to guide stent deployment. We previously introduced a non-invasive FFR calculation (FFR
B
) based on computed tomography coronary angiography ...(CTCA) with reduced-order computational fluid dynamics (CFD) and resistance boundary conditions. Current study aimed to assess the feasibility and accuracy of FFR
B
for predicting coronary hemodynamics before and after stenting, with invasive FFR as the reference. Twenty-five patients who had undergone CTCA were prospectively enrolled before invasive coronary angiography (ICA) and FFR-guided percutaneous coronary intervention (PCI) on 30 coronary vessels. Using reduced-order CFD with novel boundary conditions on three-dimensional (3D) patient-specific anatomic models reconstructed from CTCA, we calculated FFR
B
before and after virtual stenting. The latter simulated PCI by clipping stenotic segments from the 3D coronary models and replacing them with segments to mimic the deployed coronary stents. Pre- and post-virtual stenting FFR
B
were compared with FFR measured pre- and post-PCI by investigators blinded to FFR
B
results. Among 30 coronary lesions, pre-stenting FFR
B
(mean 0.69 ± 0.12) and FFR (mean 0.67 ± 0.13) exhibited good correlation (
r
= 0.86,
p
< 0.001) and agreement mean difference 0.024, 95% limits of agreement (LoA): −0.11, 0.15. Similarly, post-stenting FFR
B
(mean 0.84 ± 0.10) and FFR (mean 0.86 ± 0.08) exhibited fair correlation (
r
= 0.50,
p
< 0.001) and good agreement (mean difference 0.024, 95% LoA: −0.20, 0.16). The accuracy of FFR
B
for identifying post-stenting ischemic lesions (FFR ≤ 0.8) (residual ischemia) was 87% (sensitivity 80%, specificity 88%). Our novel FFR
B
, based on CTCA with reduced-order CFD and resistance boundary conditions, accurately predicts the hemodynamic effects of stenting which may serve as a tool in PCI planning.
The aim of this study was to evaluate a new analytical method for calculating non-invasive fractional flow reserve (FFR
AM
) to diagnose ischemic coronary lesions. Patients with suspected or known ...coronary artery disease (CAD) who underwent computed tomography coronary angiography (CTCA) and invasive coronary angiography (ICA) with FFR measurements from two sites were prospectively recruited. Obstructive CAD was defined as diameter stenosis (DS) ≥50% on CTCA or ICA. FFR
AM
was derived from CTCA images and anatomical features using analytical method and was compared with computational fluid dynamics (CFD)-based FFR (FFR
B
) and invasive ICA-based FFR. FFR
AM
, FFR
B
, and invasive FFR ≤ 0.80 defined ischemia. A total of 108 participants (mean age 60, range: 30–83 years, 75% men) with 169 stenosed coronary arteries were analyzed. The per-vessel accuracy, sensitivity, specificity, and positive predictive and negative predictive values were, respectively, 81, 75, 86, 81, and 82% for FFR
AM
and 87, 88, 86, 83, and 90% for FFR
B
. The area under the receiver operating characteristics curve for FFR
AM
(0.89 and 0.87) and FFR
B
(0.90 and 0.86) were higher than both CTCA- and ICA-derived DS (all
p
< 0.0001) on per-vessel and per-patient bases for discriminating ischemic lesions. The computational time for FFR
AM
was much shorter than FFR
B
(2.2 ± 0.9 min
vs
. 48 ± 36 min, excluding image acquisition and segmentation). FFR
AM
calculated from a novel and expeditious non-CFD approach possesses a comparable diagnostic performance to CFD-derived FFR
B
, with a significantly shorter computational time.
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