bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute vasoreactivity testing for severe pulmonary hypertension associated with lung disease
Authors: Takano R , Fujisaki S , Endo H , Nishi N , Hayashi H , Kiko T , Asano R , Ueda J , Aoki T , Tsuji A , Ogo T
Published: October 2024

Background

Pulmonary hypertension results in clinical deterioration and increases mortality risk in patients with lung disease (LD), including chronic obstructive pulmonary disease, interstitial lung disease and combined pulmonary fibrosis and emphysema. Though acute vasoreactivity testing predicts long term-survival of patients with pulmonary arterial hypertension (PAH), its clinical impact for patients with pulmonary hypertension associated with LD (LD-PH) remains unknown.

Purpose

The purpose of this study is to clarify the clinical impact of acute vasoreactivity testing using inhaled nitric oxide for severe LD-PH.

Methods

We retrospectively reviewed 65 consecutive patients with LD-PH between January 2014 and December 2022; 48 patients (73 [68–78] years; males, 81%; median follow-up period 23 [7–35] months) with severe pulmonary hypertension who underwent acute vasoreactivity testing were included. We divided the patients based on a median pulmonary vascular resistance (PVR) response (−15%) in acute vasoreactivity testing into the high-responder (PVR response ≦−15%) and the low-responder (PVR response >−15%) groups.

Results

Acute vasoreactivity testing significantly decreased mean pulmonary arterial pressure (mPAP) (from 41 [34–48] to 36 [31–40] mmHg, P<0.01) and PVR (from 10.7 [8.3–13.8] to 8.9 [6.6–11.4] Wood units, P<0.01). The high-responder group had better long-term survival than the low-responder group (P = 0.03). Univariate Cox regression analysis showed that the prognostic factors for better survival included younger age, high-responder to acute vasoreactivity testing, and PAH-specific therapy (P <0.01, 0.04, 0.03, respectively). There were correlations between the PVR response at acute vasoreactivity testing and improvement in mPAP (R=0.40, P=0.03) or PVR (R = 0.47, P <0.01) with PAH-specific therapy.

Conclusions

PVR response at acute vasoreactivity testing was associated with better long-term survival and haemodynamic improvement with PAH-specific therapy. Acute vasoreactivity testing may be useful to predict the responders to PAH-specific therapy and long-term survival in patients with severe LD-PH.
Prognosis in patients with residual pulmonary hypertension after transcatheter edge-to-edge repair for secondary mitral regurgitation
Authors: Tsubata H , Nakanishi N , Zen K , Nagai T , Matsubara Y , Yamano M , Yamano T , Nakamura T , Matoba S
Published: October 2024

Background

Pulmonary hypertension (PH) is an independent prognostic predictor in patients with heart failure (HF). Recently, transcatheter edge-to-edge repair (TEER) for secondary mitral regurgitation (MR) has been reported to reduce HF hospitalizations and mortality. Elevated pulmonary artery pressure (PAP) before TEER is associated with a poor prognosis; however, the impact of residual PH after TEER on clinical events has not been investigated.

Purpose

The purpose of this study is to clarify whether residual PH influences outcomes in patients with HF treated by TEER for secondary MR.

Methods

We included 63 patients who underwent TEER for severe secondary MR and post-procedural right heart catheterization in our institute from January 2016 to August 2023. Mean PAP after TEER was categorized as increased (>20mmHg) versus not increased (≤20mmHg), and we investigated the clinical outcomes between the two groups. The primary endpoint is a composite outcome of all-cause mortality and HF hospitalization.

Results

Among 63 patients, the average age was 78 years, and 60.3% were male. All patients had Secondary MR, and 52 patients (82.6%) had ventricular Secondary MR—right heart catheterization after TEER revealed a mean PAP of 21.6±7.7 mmHg, pulmonary vascular resistance (PVR) of 2.7±1.4 wood unit (WU), and pulmonary artery wedge pressure (PAWP) of 12.2±5.9 mmHg. Patients with residual PH had higher composite outcome rates of death from any cause or HF hospitalization compared to those without PH (56.1% vs. 19.5%; hazard ratio: 2.62; 95% confidence interval: 1.1 to 6.9; p=0.03). Multivariate Cox regression analysis showed that residual PH and higher PAWP after TEER were associated with higher mortality (hazard ratio: 1.14; 95% confidence interval: 1.03 to 1.28; p=0.01).

Conclusion

Our results suggest that patients with residual PH after TEER have a poor prognosis. Residual PH and high PAWP after TEER are associated with mortality.
The pregnant patient with pulmonary arterial hypertensionand her offspring in the current era. Time to take into account the vasoreactive profile
Authors: Segura De La Cal T , Perez-Olivares C , Luna R , Martin De Miguel I , Cruz Utrilla A , Villar O , Barreiro P , Munoz P , Lopez-Gude M J , Sarnago F , Escribano-Subias P
Published: October 2024

Background and aims

Pregnancy impose physiological changes that may be difficult to accomplish for women with pulmonary arterial hypertension (PAH). This study evaluates the impact that pregnancy carries in a PAH population managed in a timely manner and whether patients responders to calcium channel blockers (CCB) deserve specific recommendations because of a different prognosis.

Methods

A retrospective, longitudinal cohort study. All PAH pregnant patients managed at our institution between February 2010 and December 2023 were included. Clinical characteristics at baseline were recorded. Mortality, major complications (maternal death and cardiogenic shock requiring mechanical circulatory support -MCS- or inotropes) and minor complications (hospital admissions for cardiac reason, PAH therapy uptitration and oxygen prescription) were evaluated over the pregnancy course. Long-term follow-up was also assessed. Gestational age, neonatal weight and complications in the new-born (invasive and non-invasive ventilation, inotropic support and neonatal death) were studied. Data were compared between vasoreactive and non-vasoreactive patients.

Results

29 patients were studied (median age 31.5, 27-32.7). 8 underwent early termination of pregnancy and 21 decided to proceed. From the latter group, 7 were responders to CCB and none presented complications over the pregnancy course. From the remaining 14 non-respo

nders who completed their pregnancy, 13 (92.9%) presented minor complications: 11 (79%) were started on the prostacyclin pathway, 5 (35.7%) required inotropic support, 5 (35.7%) oxygen prescription; and 5 (35.7%) experienced major complications: 2 (14.3%) required MCS, 5 (35.7%) inotropic support, and one patient died (7%). Over a median follow-up period of 5 years (1.2-8.5), 2 patients died from the non-responder cohort (1.4%); while no patient responder to CCB experienced complications; moreover, none lost her vasoreactive response. All the new-borns from non-vasoreactive patients were delivered prematurely; while those from vasoreactive patients reached week 37 in the 85,7% of the cases. One of the new-borns from the non-vasoreactive cohort died, and there was a non-significant trend towards a fewer rate of complications in the vasoreactive offspring (42.9 Vs. 84.6, p = 0.054).

Conclusions

In spite of the continuous advances in PAH management, pregnancy still associates high maternal and neonatal morbidity. Nevertheless, vasoreactive PAH patients presented a completely different maternal and neonatal prognosis which may prompt specific recommendations for this particular subgroupOutcomes by vasoreactivity profilePregnancy course for the 21 PAH patients
Feasibility of quantitative evaluation of hemodynamics using SPECT/CT in patients with chronic thromboembolic pulmonary hypertension
Authors: Miyagi A , Shimokawahara H , Takahashi K , Ogawa A , Matsubara H
Published: October 2024

Background

A ventilation/perfusion (V/Q) lung scan is recommended in the diagnostic work-up of patients with newly diagnosed pulmonary hypertension to rule out chronic thromboembolic pulmonary hypertension (CTEPH). V/Q single-photon emission computed tomography (SPECT) is considered the method of choice for diagnosis in CTEPH because it allows more precise evaluation than planar imaging. However, the evaluation of lung perfusion using V/Q SPECT imaging remains mainly a qualitative evaluation, and no quantitative method has been established. We hypothesized that the standardized uptake value (SUV) technique in Positron Emission Tomography (PET)-CT, a nuclear imaging technique well suited for quantitative of tumor biology, could be applied to quantitative assessment of lung perfusion.

Purpose

The purpose of this study was to evaluate the correlation between pulmonary perfusion distribution and hemodynamic data in Tc-labeled large-assembly albumin (99mTc-MAA) SPECT images in order to determine the feasibility of SPECT/CT for quantitative assessment of lung perfusion.

Methods

Twenty-five patients with CTEPH who underwent BPA and received SPECT-CT were included. Since the injected 99mTc-MAA selectively accumulates only in the lungs, SUV normalization was conducted using each patient’s lung volume, calculated by SPECT/CT and defined as SUV lung volume (LV) . The percentage of lung volume below each SUVLV value in total lung volume on SPECT/CT was examined before BPA, after two procedures of BPA, and six months after a series of BPA, and the correlations with hemodynamic parameters on right heart catheterization at each time point were evaluated.

Results

The Percent lung volume below SUVLV of 0.7 in total lung volume before BPA, after two procedures of BPA, and six months after a series of BPA had the strongest correlation with mean pulmonary artery pressure (mPAP) (rs; 0.727, p<0.001, Figure 1). The percent lung volume below SUVLV of 0.7 decreased with the BPA procedure in each patient with CTEPH (Figure 2). Furthermore, receiver operating characteristic analysis revealed that a threshold for the percent lung volume below SUVLV of 0.7 of 50.3% or greater could identify mPAP greater than 21 mmHg for right heart catheterization (area under the curve = 0.86, 95% CI 0.78-0.94, p<0.001).

Conclusion

Percent lung volume below SUVLV of 0.7 in total lung volume using SPECT/CT might reflect the severity of hemodynamics in patients with CTEPH. This method would be feasible for quantitative assessment of lung perfusion, even inter-patient and intra-patient.Figure 1Figure 2
Serial quantitative stress perfusion cardiac magnetic resonance in patients undergoing coronary artery bypass grafting; prediction of symptomatic benefit
Authors: Akbari T , Mach L , Hammersley D , Hatipoglu S , Owen R , Kellman P , Wong J , Pennell D J , Halliday B P , Jones R E , Prasad S K
Published: October 2024

Background

Serial multiparametric cardiovascular magnetic resonance (CMR) in patients undergoing coronary artery bypass grafting (CABG) may provide mechanistic insight into dynamic and persistent abnormalities of the myocardium in patients with stable coronary artery disease (CAD).

Objectives

To assess for dynamic CMR markers of myocardial hypoperfusion and cardiac remodelling in patients undergoing CABG.

Methods

Patients with CAD awaiting elective CABG were recruited into an observational cohort study. Baseline evaluation included bloods, Seattle Angina Questionnaire-7, and adenosine stress perfusion CMR. Automated fully quantitative stress and rest myocardial blood flow was calculated, alongside assessment of the visual ischaemic burden. Native and post-contrast septal T1 indices were also measured. Repeat evaluation at 6-12 months post CABG was performed.

Results

Of 43 patients who underwent serial evaluation with CMR (mean age 62.1±9.3, median LVEF 68% [IQR: 62-73%]), there was improvement in the median visual ischaemic burden (18% [IQR: 11-21] vs 42% [IQR: 27-51], P<0.001), mean global stress myocardial blood flow (1.5±0.5 ml/min/g vs 1.3±0.5 ml/min/g, P=0.002) and median global myocardial perfusion reserve (2.4 [IQR: 1.7-2.8] vs 1.7 [IQR: 1.4-2.2], P=0.002) following CABG. Greater improvement in the SAQ-7 summary score was associated with a larger visual ischaemic burden at baseline (ρ=0.44, P=0.004) and a greater decrease in the visual ischaemic burden following CABG (ρ=-0.38, P=0.02). Quantitative MBF metrics did not associate with baseline or change in SAQ-7 summary score. Mean LV extracellular matrix volume decreased following CABG (16.6±3.6ml/m2 vs 18.2±4.6ml/m2, P=0.009).

Conclusion

Multiparametric CMR identifies dynamic changes in markers of myocardial perfusion and interstitial fibrosis in patients following CABG. Visual assessment of inducible myocardial hypoperfusion may identify patients who will derive the most symptomatic benefit from CABG. The results, however, suggest an important degree of residual inducible ischaemia and an unclear clinical role for CMR-derived MBF calculations.Serial CMR perfusion dataAssociation of SAQ with perfusion
Does the presence of severe pulmonary hypertension affect survival at 5 years follow-up in patients who underwent TAVI for severe aortic stenosis?
Authors: Mohiaddin H , Mohee K , Ambrogetti R , Roberts E , Bhandari S S , Kovac J
Published: October 2024

Background

Pulmonary hypertension (PH) is common in patients with severe aortic stenosis (AS) and is associated with increased mortality after transcatheter aortic valve implantation (TAVI) as well as surgical aortic valve replacement (SAVR). Preprocedural systolic pulmonary artery pressure (sPAP) often improves after TAVI because the most common type of PH is postcapillary PH secondary to left-sided heart disease, which potentially improves after treatment for AS. However, there are limited data regarding the prognostic impact on outcomes after TAVI and their predictors.

Purpose

The aim of this study is to compare survival at 5 years between patients with severe PH against those who did not have severe PH who underwent TAVI.

Methods

Between January 2012 until December 2022, we carried out a retrospective study of all patients who underwent TAVI at our hospital. Severe PH was defined as the presence of sPAP >40mmHg on echocardiography. Patients with aortic regurgitation and mixed aortic valve disease were excluded. Co-morbid pulmonary disease was defined as the presence of any significant pulmonary disease including COPD and Asthma. Co-morbid neurological disease was defined as the presence of any significant neurological disease including CVA/ TIA. Diabetes mellitus was defined as per WHO and included patients who were diet, medication and insulin controlled. Survival status and date of death were ascertained from our electronic health records. Counts and incidence rates of clinical outcomes at 5-year follow-up were computed from Kaplan-Meier analysis (See Figure 1). A Cox proportional hazards model was used to compute HRs and 95% CIs for the study outcomes.

Results

Of the 274 patients available for analysis, 115 (14%) patients had severe PH. The mean age was 84 years in both cohorts whilst patients in the severe PH cohort were frailer by Katz Index Score. Death occurred in 67 patients out of 115 patients who had severe PH and in 87 out of 158 patients who did not have severe PH after a median follow-up time of 4.1 years (58% vs 55%; adjusted HR: 1.04; 95% CI: 0.71-1.51; P = 0.86).

Conclusion

Our data shows that presence of severe pulmonary hypertension in severe aortic disease patients who had undergone TAVI did not affect survival at 5 years follow up compared to patients without severe pulmonary hypertension undergoing TAVI. Determining predictors of mortality in this high-risk cohort is likely to be complex and multifactorial, owing to the severe multi-comorbidity precluding them from SAVR.
Developing a multi-center registry of peripheral artery disease using natural language processing: unlocking the power of the electronic health record
Authors: Girotra S , Li Q , Vaughan-Sarrazin M , Nathani R , Al-Garadi M , Gobbel G
Published: October 2024

Background

Although peripheral artery disease (PAD) is common and associated with a high risk of mortality, contemporary PAD research remains limited due to poor accuracy of diagnosis codes in the electronic health record (EHR). We previously developed and validated a novel natural language processing (NLP) algorithm that can extract ankle brachial index (ABI) and toe-brachial index (TBI) values from clinical documents and identify patients with PAD with high accuracy (positive predictive value 92.4%).

Purpose

Scale the NLP system for developing a nationwide registry of PAD in the Veterans Health Administration (VHA), the largest integrated health system in the U.S. that provides care to ~9 million Veterans across 130 sites. Describe the baseline characteristics and mortality outcomes among participants and identify predictors of long-term mortality.

Methods

A total of 1,182,025 documents from vascular and radiology procedures during 2013-2020 were processed by the NLP system. After excluding non-ABI vascular studies, patients with a known diagnosis of PAD prior to 2015, patients younger than 40 years of age, and those who do not regularly follow-up in the VHA, we identified 107,711 patients with newly diagnosed PAD during 2015-2020. Patients were followed longitudinally using the VA’s electronic health record data. The primary outcome was all-cause mortality. We used Cox proportional hazards regression to examine predictors of long-term mortality.

Results

The mean age was 70.5 years; 97.3% were males, and 18.5% were of Black race. The mean ABI value was 0.78 (SD: 0.26) and the mean TBI value was 0.51 (SD: 0.19). There was a high prevalence of hypertension (83.6%), heart failure (20.8%), diabetes (53.6%), renal failure (22.1%) and chronic obstructive pulmonary disease (32.4%, Table 1). At 1-year, 9.6% of patients had died and this proportion increased to 25.4% at 3 years. Although nearly all patient variables were significantly associated with mortality, older age, severe PAD at diagnosis, diabetes, heart failure, renal failure and COPD were the strongest predictors of long-term mortality. Black race was associated with lower hazard of long-term mortality.

Conclusions

Using a previously validated novel NLP algorithm that extracts ABI and TBI values from clinical documents, we have successfully developed a registry of newly diagnosed PAD in the VHA. Ongoing studies from our cohort will yield important insights into the association between clinical management of PAD and clinical outcomes, with the goal of identifying opportunities for improving care.
Diagnostic performance of the fragmented QRS complex on electrocardiogram for detecting myocardial scars assessed by 3.0 Tesla cardiac magnetic resonance imaging
Authors: Viriyanukulvong K , Theerasuwipakorn N , Wongcharoen W , Kosum P , Chokesuwattanaskul R
Published: October 2024

Background

Fragmented QRS complex (f-QRS) on a 12-lead electrocardiogram (EKG) with a 100 Hz low-pass filter is known to be related to ischemic myocardial scars. Cardiac magnetic resonance (CMR) imaging enhances tissue characterization capability resulting in a better myocardial scar assessment over other noninvasive imaging modalities. However, the diagnostic values of f-QRS on non-ischemic scars and f-QRS from EKG with a 40 Hz low-pass filter (routine filter in clinical practice) are unknown. Therefore, this study aims to evaluate the diagnostic performance of f-QRS (from EKG with 40 Hz and 100 Hz low-pass filters) for detecting any myocardial scars assessed by 3.0 Tesla CMR.

Methods

This cross-sectional study included patients who underwent a 3.0 Tesla CMR scan from May 2020 to May 2023. A 12-lead EKG with 0.15-40 and 0.15-100 Hz low-pass filters, performed on the same day of the CMR scan, was assessed for the presence of f-QRS. The ECG leads were divided into 3 categories (e.g., anteroseptal leads V1-V4; lateral leads I, aVL, V5-V6; and inferior leads II, III, aVF). The f-QRS was defined as the presence of R’ wave or notching in the nadir of the S wave in 2 contiguous leads. The primary outcome was the diagnostic performance of f-QRS from EKG in myocardial scar detection in the corresponding left ventricle (LV) segments. The secondary outcomes were to compare diagnostic performance between f-QRS from EKG with 0.15-40 and 0.15-100 Hz low-pass filters.

Results

The study involved 1,692 participants with a median age of 67 (IQR: 59-85) years old and 52.5% males. Myocardial scars were found in 826 (49%) participants. Male, history of CAD, and myocardial scars were significantly more frequent in the participants with f-QRS (59.4% vs 46%, 26.4% vs 20.6%, and 48.9% vs 37.3%, respectively). The sensitivity, specificity, positive predictive value, negative predictive value, and AUC of f-QRS from EKG with 0.15-100 Hz low-pass filter for detecting myocardial scars were 25.6%, 88.7%, 45.1%, 76.8%, and 0.57 for anteroseptal segments; 22.1%, 91.5%, 36.8%, 84.1%, and 0.57 for lateral segments; and 42.9%, 63.4%, 36.9, 68.9%, and 0.53 for inferior segments. The f-QRS from 0.15-100 Hz showed a higher sensitivity but lower specificity and PPV for all LV segments. NPV and AUC were not significantly different between the two filters.

Conclusion

This study demonstrates a high specificity and negative predictive value of f-QRS from a 12-lead EKG with 0.15-40 and 0.15-100 Hz low-pass filters in diagnosing myocardial scars when correlated to the corresponding LV segments.central illustrationbaseline charateristic
Mapping 18F-FDG PET uptake in the aortic wall and thrombus
Authors: Bragulat-Arevalo M , Ferrer-Cornet M , Dux-Santoy L , Olivero-Soldevila R , Carrasco-Poves A , Teixido-Tura G , Garrido-Oliver J , Galian-Gay L , Lopez-Gutierrez P , Morales-Galan A , Catala-Santarrufina A , Solsona J , Ferreira-Gonzalez I , Rodriguez-Palomares J , Guala A
Published: October 2024

Background

Positron Emission Tomography (PET) uptake allows for the assessment of molecular activity, being 18F-FDG uptake indicative of glucose metabolism. PET uptake is commonly quantified manually by drawing regions of interest, which is subjective, poorly-reproducible and may miss relevant information.

Purpose

To develop and test an image analysis method to quantify and map 18F-FDG uptake on the whole aortic wall and thrombus.

Methods

PET-MRI was acquired in patients with thoracic or abdominal aortic aneurysms. The aorta was semi-automatically segmented in the MR angiography using 3DSlicer, generating a surface mesh that was expanded by 3 mm inward and outward. PET uptake was interpolated over this volume with a uniform spatial resolution of 1 mm. By means of 9 reference points, the aortic wall was discretized into 52 (thoracic) or 80 (thoraco-abdominal) standardized regions (i.e. wall patches). For each aortic patch and for the whole thrombus volume, the target to background Ratio (TBR) was calculated by dividing the uptake by a reference uptake in the left atrium. Two observers segmented the aorta and thrombus, located the anatomical reference points and quantified TBR. Inter-observer agreement for segmentation and aortic wall discretization was evaluated in terms of the 95% Hausdorff Distance (HD) and Dice Score Coefficient (DSC), while both median and 95% TBR in each region were tested via intra-class correlation coefficient (absolute value, single measure).

Results

Data from 20 patients with thoracic or abdominal aneurysms were analysed, 10 of them presented thrombus. The reproducibility of the segmentation of the aorta (median HD 3.16 IQR [2.42 - 3.94] mm, DSC 0.90 [0.89 - 0.92]) and of the thrombus (HD 4.87 [3.51 - 8.45] mm, DSC 0.85 [0.80 - 0.87]) were excellent. The inter-observer agreement in the localization of reference points was good (HD 5.10 [3.29 - 8.73] mm), resulting in excellent overlapping of the standardized aortic wall patches (HD 3.80 [2.44 - 5.08] mm). Inter-observer agreement of median and 95% TBR in each aortic patch were excellent (ICC of 0.90 and 0.93, respectively, Figure 1), with minimal bias (Figure 2). Similarly, excellent interobserver reproducibility was observed for median and 95% TBR in the thrombus (ICC of 0.97 and 0.96, respectively, Figure 2).

Conclusions

A robust and reproducible image analysis method to map PET uptake along the aortic wall was developed, extending the possibilities to study aortic diseases molecular activity and its association with local aortic characteristics.
Comparison of endovascular therapy and open surgical revascularization in patients with acute superior mesenteric artery occlusion
Authors: Yanishi K , Goto D , Ozawa T , Yoshimura J , Kawamata H , Fujioka A , Seki T , Zen K , Matoba S
Published: October 2024

Background

Acute mesenteric ischemia (AMI) is rare, and few large-scale trials have evaluated endovascular therapy (EVT) and open surgical revascularisation (OS). This study aimed to assess clinical outcomes after EVT or OS for acute superior mesenteric artery occlusion (SMAO) and identify predictors of mortality and bowel resection.

Methods

Data from the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination database from April 2012 to March 2020 were retrospectively analyzed. Overall, 746 patients with acute SMAO who underwent revascularisation were classified into two groups: EVT (n=475) or OS (n=271). The primary clinical outcome was in-hospital mortality. The secondary outcomes were bowel resection, bleeding complications (transfusion or endoscopic hemostasis), major adverse cardiovascular events (MACEs), hospitalisation duration, and cost.

Results

The in-hospital death or bowel resection rate was approximately 30%. In-hospital mortality (22.5% vs. 21.4%, p=0.72), bowel resection (8.2% vs. 8.5%, p=0.90), and MACEs (11.6% vs. 9.2%, p=0.32) were comparable between the EVT and OS groups, respectively (Table.1). EVT was advantageous in terms of hospitalisation duration and cost (both p<0.0001). Interaction analyses revealed that EVT and OS had no significant difference in terms of in-hospital death in patients with thromboembolic and atherothrombotic characteristics (Figure.1). Multivariate logistic regression analysis revealed that advanced age, decreased activities of daily living, chronic kidney disease, and old myocardial infarction were significant predictive factors for in-hospital mortality. Diabetes Mellitus was a predictor of bowel resection after revascularisation.

Conclusions

EVT was comparable to OS in terms of clinical outcomes in patients with acute SMAO. Some predictive factors for mortality or bowel resection were obtained.

Clinical implications

EVT may be a feasible alternative to OS, potentially impacting clinical practice as a less invasive option for managing patients with acute SMAO.In-hospital clinical outcomesInteraction effect test for mortality
Plasma levels of sCASP3 predicts carotid intima media thickness progression
Authors: Pan M , Sharify D , Melander O , Melander M , Engstrom G , Nilsson J A N , Goncalves I , Sun J , Edsfeldt A
Published: October 2024

Background

Studies on human atherosclerotic plaques have shown that apoptosis is associated with rupture prone plaques and that apoptosis is a key process for fast plaque progression. In line with this, we showed that circulating levels of soluble Caspase-3 (sCaspase-3) predict atherosclerotic events. However, the relationship between circulating levels of apoptosis markers and plaque progression remains to be explored.

Purpose

Here we aimed to investigate if circulating levels of apoptosis markers could predict mean intima-media thickness in the common carotid artery (IMT-CCA) progression among individuals with atherosclerotic carotid plaques.

Methods

The Malmö Diet and Cancer (MDC) cardiovascular cohort was used. MDC is a prospective population-based cohort study. Baseline variables (blood, clinical information and carotid ultrasound measurements) were collected between 1991-1994 and the right carotid ultrasound re-examinations were performed between 1994-2001. IMT was measured at by ultrasound at baseline as well as at the re-examinations. The Olink Proximity Extension Assay (SciLifeLab, Uppsala, Sweden) was used to analyze plasma levels of sCaspase-3, sFADD, sCaspase-8, sTRAIL-R2 and sTNFR1 at baseline. Correlation and multiple linear regression analyses, adjusted for age, sex, and cardiovascular risk factors, were employed to evaluate the relationships between apoptosis biomarkers and IMT-CCA as well as average annual change in IMT-CCA.

Results

In total, 1929 participants (median age 60 years) with an ultrasound confirmed carotid plaque (focal IMT >1.2mm) at baseline were included. Subjects who underwent ultrasound IMT re-examination over a period of >4.5 years were divided into a discovery (n=406) and a validation (n=355) cohort. sCaspase-3 was identified as the marker with the strongest correlation to IMT-CCA at baseline (p=0.02) and upon re-examination (p=0.04), among the five apoptosis markers examined, in both the discovery and validation cohorts. sCaspase-3 also showed a correlation with the average annual change of IMT-CCA (r=0.12, p=8×10-4) in both cohorts. Furthermore, when diving the cohort into tertiles based on plasma levels of sCapase-3, subjects with high levels of sCaspase-3 (3rd tertile) had greater annual changes in IMT-CCA compared to the 1st tertile (p=0.03). Multiple linear regression analyses confirmed that sCapase-3 was associated with the average annual IMT-CCA change in both the discovery (beta=0.14, 95% confidence interval (CI) 0.04–0.24) cohort and the validation cohort (beta=0.11, 95%CI 0.01–0.21).

Conclusion

Using a large, population-based study with repeated IMT measurements, we demonstrated that circulating levels of sCapase-3 were associated with increasing IMT in the CCA. While further studies are warranted, these results suggest that sCapase-3 levels could serve as potential screening marker to identify individuals at higher risk for plaque progression.
The influence of concomitant antiplatelet therapy in venous thromboembolism patients treated with anticoagulants in the DOAC era: insight from the COMMAND VTE Registry-2
Authors: Kaneda K , Yamashita Y , Nishikawa R , Chatani R , Nishimoto Y , Ikeda N , Ono K
Published: October 2024

Background/Introduction

The mainstay of treatment and second prevention of venous thromboembolism (VTE) is anticoagulation therapy, and recently direct oral anticoagulant (DOAC) for VTE have prevailed all over the world as oral anticoagulation therapy. Although concomitant antiplatelet therapy in addition to oral anticoagulation therapy could have an influence on both recurrent VTE and bleeding events, there have been still limited real-world data on the issue in the DOAC era.

Purpose

We aimed to investigate long-term clinical outcomes in VTE patients treated with concomitant antiplatelet therapy in the DOAC era.

Methods

The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. After excluding 407 patients without oral anticoagulation therapy, the current study population was consisted of 4790 VTE patients with oral anticoagulation therapy, who were divided into 374 patients (7.8%) treated with concomitant antiplatelet therapy and 4416 patients (92.2%) treated with only oral anticoagulation therapy.

Results

Patients with concomitant antiplatelet therapy were older (Concomitant antiplatelet therapy: 74.1 vs. Only oral anticoagulation therapy: 67.3 years, P<0.001), were less often women (52% vs 59%, P=0.005) and more frequently had history of major bleeding (9.8% vs 6.0%, P=0.003), myocardial infarction (16% vs 0.9%, P<0.001) and stroke (33% vs 6.8%, P<0.001). The cumulative incidences of recurrent VTE were not significantly different between the 2 groups (5.9% vs 9.6% at 5-year, Log rank P=0.06). Similarly, the cumulative incidences of major bleeding (14.6% vs 13.3% at 5-year, Log rank P=0.11) and stroke (8.3% vs 6.0% at 5-year, Log rank P=0.12) were not significantly different between 2 groups. However, the cumulative incidences of clinically relevant all bleeding (29.0% and 23.0% at 5-year, Log rank P=0.007) were significantly higher in concomitant antiplatelet therapy group, which was statistically significant even after adjusting confounders.

Conclusion

In the current large VTE registry in the DOAC era, concomitant antiplatelet therapy in addition to oral anticoagulation therapy for patients with VTE was not significantly associated with the risks recurrent VTE, major bleeding or stroke, but was associated with an increased risk of clinically relevant all bleeding.Study Flow ChartMain results
Lipoprotein(a) levels in patients with cryptogenic stroke and persistent foramen ovale
Authors: Bernhard J , Galli L , Schrutka L , Haider P , Hengstenberg C , Gabriel H , Krychtiuk K , Speidl W
Published: October 2024

Background

Elevated levels of lipoprotein(a) [Lp(a)] are an independent risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). However, it is not known whether high Lp(a) is associated with cryptogenic stroke.

Methods

We included 478 patients with cryptogenic stroke that underwent closure of a persistent foramen ovale and had Lp(a) measurement available. These patients were matched according to age and gender in a 1:3 ratio to 1434 controls.

Results

Mean age of patients was 49.9 +/-12.9 years and 275 patients (57.4%) were male. Median Lp(a) levels were significantly higher in cases (26 IQR 13 – 87 nmol/L) as compared to controls (16 IQR 2 – 61 nmol/L; p<0.00001). Lp(a) levels > 200 nmol/L were significantly more frequent in patients with cryptogenic stroke as compared to controls (10.0 % vs. 7.0 %; p<0.05). The odds-ratio for an increase of Lp(a) by 50nmol/L was 1.09 (95% CI 1.03 – 1.15) independent of age and gender.

Conclusion

Patients with cryptogenic stroke and persistent foramen ovale showed significantly higher plasma levels of Lp(a) and an increase of Lp(a) was associated with a significant increased risk for cryptogenic stroke. Whether high Lp(a) increases risk for deep vein thrombosis leading to embolization or for arterial thrombosis has to be elucidated in further studies.
Predictors of Ischemic Stroke in a cohort of patients with Chagas Cardiomyopathy: the CLOT-Chagas study
Authors: Echeverria L E , Rojas L Z , Becerra-Motta L P , Cantillo-Reines M , Serrano-Garcia A Y , Botero D R , Gomez-Ochoa S A
Published: October 2024

Introduction

a high risk of embolic events characterizes Chronic Chagas Cardiomyopathy (CCC) due to the presence of structural alterations of the left ventricle, the high incidence of arrhythmias, and intrinsic coagulation disorders. Despite its relevance, there is limited information on factors associated with this type of embolic event in patients with CCC, with most studies designed as case-control studies. This study aimed to prospectively analyze independently associated factors with this population's Ischemic Stroke (IS).

Materials and Methods

A prospective study was conducted between 2019 and 2023 at a cardiovascular center's Heart Failure and Heart Transplant Clinic. Adult patients diagnosed with CCC were included, recording sociodemographic, clinical, and echocardiographic variables as potential predictors of IS. Patients were followed up for 18 months via telephone for outcome assessment. Multivariate logistic regression models were used to identify factors potentially associated with IS during follow-up.

Results

A total of 232 patients diagnosed with CCC were included (males: 54.9%; median age: 67 years), the majority of whom were receiving anticoagulant therapy (n=144; 62.1%), with DOACs being the most frequently prescribed type of anticoagulants (51%). During follow-up, 16 patients (6.9%) developed an IS. There was a trend towards a lower incidence of IS in patients treated with direct oral anticoagulants (6.8%) compared to those receiving Warfarin (11.5%); however, this difference was not statistically significant (p=0.584). In the multivariate regression analysis including all potential predictors of IS, only the presence of a ventricular aneurysm (RR 5.64; 95% CI 1.61-19.70, p=0.007) and the score obtained when applying the Pfeiffer cognitive impairment questionnaire (RR 0.56; 95% CI 0.42-0.75, p<0.001) were significantly associated with the outcome of IS, even after adjusting for age, sex, NYHA functional class, ejection fraction, and anticoagulant therapy. The model composed of ventricular aneurysms and the Pfeiffer questionnaire score showed adequate performance in predicting IS during follow-up (AUC 0.79).

Conclusions

and Discussion: The incidence of IS in this population was higher than reported in the literature for both CCC patients and those with heart failure from other etiologies. The finding of an association between the presence of ventricular aneurysms and IS has been previously reported; however, the association between the Pfeiffer cognitive test and the development of IS represents a novel observation that deserves validation in future studies for its applicability in the clinical setting.
The incidence and outcome of patients with early cardiovascular complications following intracerebral haemorrhage: An individual patient data pooled analysis from the VISTA database
Authors: Ishiguchi H , Huang B , El-Bouri W K , Dawson J , Lip G Y H , Abdul-Rahim A H
Published: October 2024

Background

Early cardiovascular (CV) complications in patients following intracerebral haemorrhage (ICH) is poorly understood. Such incident CV complications could be part of the so-called stroke-heart-syndrome occurring following ICH (SHS-ICH). We investigated the incidence and outcomes of patients with SHS-ICH.

Methods

Data were sought from the Virtual International Stroke Trials Archive (VISTA), an international repository of clinical trials data. We reviewed relevant adverse events and identified patients based on the incidence of cardiovascular complications within 30 days of post-ICH or ischaemic stroke (acute coronary syndrome [ACS] including acute myocardial injury, heart failure [HF]/left ventricular [LV] dysfunction, atrial fibrillation [AF]/atrial flutter [AFL], other arrhythmia/ ECG abnormalities, and cardio-respiratory arrest [CRA]). We conducted propensity score matching (PSM) to compare the incidence and outcomes of patients with SHS following ICH (SHS-ICH) with patients with SHS following acute ischaemic stroke (AIS). Poor outcome was defined as modified Rankin Scale, mRS ≥2, at 90 days.

Results

We pooled data from 12,438 participants recruited in acute stroke trials (mean age 68±12 years; 56% male), of which 1,171 (9.4%) were patients with ICH. Of the ICH patients, 150 patients (12.8%) had SHS-ICH. Following PSM, a total of 2,342 patients (1,171 for each of the ICH and AIS cohorts) were analysed. The incidence of SHS was not significantly different in the ICH and AIS cohorts (Table 1). The incidence of AF was significantly lower in patients with ICH compared to patients with AIS (1.5% vs. 4.5%, p<0.0001), despite comparable incidences of other arrhythmia/ECG abnormalities (9% vs. 9%, p=0.9). Multivariate-adjusted analysis found that SHS-ICH was associated with poor outcomes (Table 2, odds ratio, OR 1.08 [95%CI: 1.03-1.16], p=0.04, compared to ICH patients without SHS).

Conclusions

Stroke-heart syndrome is common and serves as a crucial prognostic marker in patient with ICH, with outcomes similar to SHS patients related to AIS. The development of SHS-ICH was associated with poorer outcomes compared to ICH patients without SHS.
Association of non-invasive assessed anatomical features with functional testing in coronary artery anomalies - NARCO trial
Authors: Stark A W , Bigler M R , Kakizaki R , Shiri I , Siepe M , Raeber L , Graeni C
Published: October 2024

Introduction

Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital condition believed to carry an increased risk for myocardial ischemia. However, correlation between anatomical characteristics and ischemia remains unclear. Therefore, this study aimed to assess: 1. The difference of invasive fractional flow reserve (FFR) and intravascular ultrasound (IVUS)-based minimal lumen area (MLA) between baseline and stress. 2. The association of coronary computed tomography angiography (CCTA)-based anatomical characteristics to invasively measured hemodynamics and IVUS in AAOCA.

Methods

Consecutive patients with AAOCA and presence of ≥1 anatomical high-risk features (i.e. intramural course (IM), slit-like ostium, acute take-off angle or proximal narrowing), were systematically evaluated as part of the NARCO trial using CCTA, FFR using adenosine (140 µg/kg/min), dobutamine-volume stress (20-40mcg/kg/min, 0.5-1mg atropine and 3L of saline solution) and IVUS- MLA of IM. Anatomic high-risk features were quantified by CCTA including ostial lumen area and IM-MLA, IM-width, IM-height, IM-elliptic ratio, take-off angle, proximal narrowing and IM length of the anomalous coronary segment.

Results

A total of 94 patients with AAOCA were screened, whereas 48 showed high-risk anatomic features and underwent the complete stress protocol. Mean age was 54±12 years and 36 (75%) were male and 39 (81%) presented with symptoms. FFRstress was significantly lower than FFRadenosine (0.88 [0.81-0.91] vs. 0.91 [0.87-0.94], p<0.001) (Figure 1). FFRadenosine was ≤0.8 in 5 patients (10%), and FFRdobutamine was ≤0.8 in 12 patients (25%), resulting in 7 (15%) with FFRadenosine >0.8 while FFRdobutamine was ≤0.8. IVUS-MLA was decreased from 6.3 (5.4-8.2) mm2 to 5.4 (4.2-7.1) mm2 during stress (p<0.001) (Figure 2), while elliptic ratio increased from 2.6 (2.1-3.4) to 3.3 (2.5-4.4) (p<0.001). Logistic regression analysis for body surface area adjusted CCTA derived high-risk features showed, that only ostial lumen area, IM-MLA, -elliptic ratio and -width could predict FFRstress ≤0.8. Receiver operating curve analysis showed that ostial width had the greatest AUC with 0.86 (accuracy 83%, sensitivity 83%, and specificity 83%). Eight out of 12 (67%) patients with hemodynamic relevance underwent surgery, 2 (17%) underwent stenting and 2 (17%) were treated with medication.

Conclusion

In patients with AAOCA and anatomic high-risk features, only one quarter are hemodynamic relevant. FFR during dobutamine-volume stress showed to be the more sensitive stress modality as compared to FFRadenosine. CCTA derived ostial and IM anatomical severity is associated with ischemia under stress. Comprehensive functional and anatomical assessment of AAOCA helps to optimize patient management and avoid unnecessary revascularization.Figure 1:FFRadenosine vs FFRstressFigure 2:IVUS-MLArest vs IVUS-MLAstress
Cycling coupled to intra-coronary thermodilution to evaluate angina with non-obstructive coronary artery disease
Authors: Zeitouni M , Rahoual G , Procopi N , Beaupre F , Martinez C , Michon M , Sulman D , Guedeney P , Hammoudi N , Vicaut E , Hatem S , Kerneis M , Silvain J , Montalescot G , Collet J P
Published: October 2024

BACKGOUND

Patients with Angina and Non-Obstructive Coronary Artery disease (ANOCA) face misdiagnosis and inadequate treatment. A new continuous thermodilution method enables assessment of absolute coronary blood flow (Q) and microvascular resistance (Rµ). The effectiveness of saline-induced hyperemia in capturing exercise-induced coronary flow regulation remains unknown.

OBJECTIVE

To describe Q and Rµ adaptation during exercise and to explore the correlation between Coronary Flow Reserve (CFR) derived from saline and exercise-induced hyperemia, as well as Microvascular Resistance Reserve (MRR).

Methods

Q, Rµ, CFR and MRR were first assessed using continuous thermodilution with saline infusion at 10 mL/min (rest) and 20 mL/min (hyperemia) in the left anterior descending artery, followed by subsequent stress testing using a dedicated supine cycling ergometer. The microvascular parameters were assessed during incremental workload of 30 watts every two minutes. CFRsaline<2.5 was considered the cutoff for coronary microvascular dysfunction. A minimal sample size of 29 participants was required to detect a hypothesized Spearman coefficient correlation r=0.5 between CFRsaline and CFRexercise using a 80% power and 5% significance level test.

Results

Coronary microvascular dysfunction was observed in 53.3% of the participants with suspected ANOCA (16 out of 30). During cycling, participants with coronary microvascular dysfunction had a lower reduction in Rµ (-109 [32; 286] versus -202 [102; 379] WU per 30 watts, p<0.01) and a lower ability to increase coronary flow (7 [30.5; 103.0] versus 21 [5.8; 45.0] mL/min per 30 watts, p=0.01) compared with those without coronary microvascular dysfunction. In the overall population, average CFRsaline and CFRexercise were 2.70±0.90 and 2.85±1.54, respectively (p=0.46) with an agreement classification of 83.3%. A good correlation between the two techniques was observed for both CFR (Spearman coefficient r=0.73, p<0.0001) and MRR (r=0.76, p<0.0001). Monitoring of CFR and Rµ during exercise unmasked functional coronary microvascular dysfunction priorly labeled as normal by saline induced hyperemia in 13.3% of the study population. These individuals had a moderate and late decrease of Rµ during the early stages of exercise, with a plateau up to 75% of their theoretical workload.

Conclusion

Participants with coronary microvascular dysfunction demonstrated compromised CFR due to impaired reduction of Rµ during physical workload. Saline-induced hyperemia provided a valid surrogate for exercise physiology independently of the absolute level of CFR and MRR, although exercise provided more granularity to evaluate hemodynamic adaptation among participants with functional dysfunction.