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result(s) for
"Keeble, Thomas R"
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Neuropsychological outcome after cardiac arrest: results from a sub-study of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
by
Cronberg, Tobias
,
Grejs, Anders M.
,
Bro-Jeppesen, John
in
Analysis
,
Anxiety
,
Applied Psychology (including Clinical Psychology, Psychotherapy)
2023
Background
Cognitive impairment is common following out-of-hospital cardiac arrest (OHCA), but the nature of the impairment is poorly understood. Our objective was to describe cognitive impairment in OHCA survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA.
Methods
This was a prospective case–control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. At approximately 7 months post-event, we administered an extensive neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes.
Results
Of 184 eligible OHCA survivors, 108 were included, with 92 MI controls enrolled. Amongst OHCA survivors, 29% performed
z
-score ≤ − 1 (at least borderline–mild impairment) in ≥ 2 cognitive domains, 14% performed
z
-score ≤ − 2 (major impairment) in ≥ 1 cognitive domain while 54% performed without impairment in any domain. Impairment was most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = − 0.37, 95% confidence intervals [− 0.61, − 0.12]), verbal (MD = − 0.34 [− 0.62, − 0.07]), and visual/constructive functions (MD = − 0.26 [− 0.47, − 0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, executive functions (MD = − 0.44 [− 0.82, − 0.06]) were also worse following OHCA. Diabetes, symptoms of anxiety, depression, and fatigue were significantly associated with worse cognitive performance.
Conclusions
In our study population, cognitive impairment was generally mild following OHCA. OHCA survivors performed worse than MI controls in 3 of 6 domains. These results support current guidelines that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue.
Trial registration
ClinicalTrials.gov, NCT03543371. Registered 1 June 2018.
Journal Article
Speed of cooling after cardiac arrest in relation to the intervention effect: a sub-study from the TTM2-trial
by
Young, Paul J.
,
Taccone, Fabio Silvio
,
Grejs, Anders M.
in
Artificial respiration
,
Body temperature
,
Cardiac arrest
2022
Background
Targeted temperature management (TTM) is recommended following cardiac arrest; however, time to target temperature varies in clinical practice. We hypothesised the effects of a target temperature of 33 °C when compared to normothermia would differ based on average time to hypothermia and those patients achieving hypothermia fastest would have more favorable outcomes.
Methods
In this post-hoc analysis of the TTM-2 trial, patients after out of hospital cardiac arrest were randomized to targeted hypothermia (33 °C), followed by controlled re-warming, or normothermia with early treatment of fever (body temperature, ≥ 37.8 °C). The average temperature at 4 h (240 min) after return of spontaneous circulation (ROSC) was calculated for participating sites. Primary outcome was death from any cause at 6 months. Secondary outcome was poor functional outcome at 6 months (score of 4–6 on modified Rankin scale).
Results
A total of 1592 participants were evaluated for the primary outcome. We found no evidence of heterogeneity of intervention effect based on the average time to target temperature on mortality (
p
= 0.17). Of patients allocated to hypothermia at the fastest sites, 71 of 145 (49%) had died compared to 68 of 148 (46%) of the normothermia group (relative risk with hypothermia, 1.07; 95% confidence interval 0.84–1.36). Poor functional outcome was reported in 74/144 (51%) patients in the hypothermia group, and 75/147 (51%) patients in the normothermia group (relative risk with hypothermia 1.01 (95% CI 0.80–1.26).
Conclusions
Using a hospital’s average time to hypothermia did not significantly alter the effect of TTM of 33 °C compared to normothermia and early treatment of fever.
Journal Article
Acute Coronary Occlusion in NSTEMI Patients: Prevalence, Clinical Characteristics and the Potential Role of Artificial Intelligence
by
Dragona, Vassiliki-Maria
,
Pappas, Christos
,
Varlamos, Charalampos
in
acute coronary occlusion
,
Aged
,
Angiography
2026
Background and Objectives: The electrocardiogram (ECG)–based STEMI/NSTEMI classification determines the urgency of invasive management in acute myocardial infarction. However, it often underestimates the presence of acute coronary occlusion (ACO) in patients presenting with non-ST-elevation myocardial infarction (NSTEMI). Artificial intelligence (AI)-assisted ECG interpretation has emerged as a potential tool to improve early recognition of ACO. This study aimed to determine the prevalence of ACO among NSTEMI patients, to compare clinical characteristics between patients with and without ACO and to explore the potential role of AI in earlier recognition of ACO. Materials and Methods: All consecutive NSTEMI patients undergoing coronary angiography between September 2022 and December 2024 were included. Contrary to other studies that included TIMI flow grades 0–1, 0–2, or 0–3, ACO in our study was defined strictly as a culprit lesion with TIMI flow grade 0 at index coronary angiography. Clinical characteristics were compared between ACO and non-ACO patients. Admission 12-lead ECGs from ACO patients were retrospectively analysed using a clinically validated AI-based ECG interpretation model and classified according to the urgency of invasive management. Results: Among 520 NSTEMI patients, 49 (9.4%) had angiographically confirmed ACO. Within the non-ACO group, 7.0% of patients had TIMI flow grade 1 on index coronary angiography (6.3% of the total population). Therefore, 15.7% of the study population had TIMI flow grade 0/1. ACO patients were younger (60.9 ± 12.8 vs. 66.3 ± 12.0 years, p = 0.0065). Clinical characteristics did not differ between the groups, except for dyslipidemia, which was more prevalent in non-ACO patients (38.8% vs. 53.9%, p = 0.043). Revascularisation rates were higher in the ACO group (93.9% vs. 82.2%, p = 0.037). Culprit vessel distribution differed markedly between the groups (p < 0.0001). In multivariable logistic regression analysis, age was independently associated with ACO (OR 0.96, 95% CI 0.93–0.99, p = 0.007). AI-assisted ECG analysis was performed in 42 ACO patients; 57.1% were classified as requiring immediate invasive management. Conclusions: A significant proportion of NSTEMI patients have ACO. AI-assisted ECG interpretation may support earlier identification of ACO, although its clinical impact requires further validation. Future studies are warranted to confirm these findings.
Journal Article
Ultrasound-Guided Femoral Vascular Access for Percutaneous Coronary and Structural Interventions
by
Karamasis, Grigoris V.
,
Varlamos, Charalampos
,
Keeble, Thomas R.
in
Cardiac catheterization
,
Cardiology
,
Comparative analysis
2023
Radial access has largely substituted femoral access for coronary interventions. Nevertheless, the femoral artery remains indispensable for gaining access to structural and complex percutaneous coronary interventions such as transcatheter aortic valve implantation and chronic total occlusion interventions, respectively. Ultrasound-guided femoral puncture is a broadly available, inexpensive, and relatively easy-to-learn technique. According to the existing evidence, ultrasound guidance for gaining femoral access has improved the effectiveness and safety of the technique. In the present paper, we sought to review the current literature in order to provide the reader with up-to-date data regarding the benefits of ultrasound-guided femoral access compared with the conventional technique as well as describing the state-of-the-art technique for gaining femoral access under ultrasound guidance.
Journal Article
The challenges of a randomised placebo-controlled trial of CTO PCI vs. placebo with optimal medical therapy: The ORBITA-CTO pilot study design and protocol
by
Simpson, Rupert
,
Mohdnazri, Shah
,
Robertson, Craig
in
Anaerobic threshold
,
Angina pectoris
,
Cardiovascular disease
2023
Percutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) has been performed for the improvement of symptoms and quality of life in patients with stable angina. The ORBITA study demonstrated the role of the placebo effect in contemporary PCI in non-CTO chronic coronary syndromes. However, the benefit of CTO PCI beyond that of a placebo has not been demonstrated.
The ORBITA-CTO pilot study will be a double-blind, placebo-controlled study of CTO PCI randomising patients who have: (1) been accepted by a CTO operator for PCI; (2) experienced symptoms due to a CTO; (3) evidence of ischaemia; (4) evidence of viability within the CTO territory; and (5) a J-CTO score ≤3.
Patients will undergo medication optimisation that will ensure they are on at least a minimum amount of anti-anginals and complete questionnaires. Patients will record their symptoms on an app daily throughout the study. Patients will undergo randomisation procedures, including an overnight stay, and be discharged the following day. All anti-anginals will be stopped after randomisation and re-initiated on a patient-led basis during the 6-month follow-up period. At follow-up, patients will undergo repeat questionnaires and unblinding, with a further 2-week unblinded follow-up.
The co-primary outcomes are feasibility (blinding) in this cohort and angina symptom score using an ordinal clinical outcome scale for angina. Secondary outcomes include changes in quality-of-life measures, Seattle Angina Questionnaire (SAQ), peak VO2, and anaerobic threshold on the cardiopulmonary exercise test.
The feasibility of a placebo-controlled CTO PCI study will lead to future studies assessing efficacy. The impact of CTO PCI on angina measured using a novel daily symptom app may provide improved fidelity in assessing symptoms in patients with CTO's.
Journal Article
Coronary artery height differences and their effect on fractional flow reserve
by
Aggarwal, Rajesh K.
,
Keeble, Thomas R.
,
Kabir, Alamgir M.
in
Angina pectoris
,
Cardiology
,
Cardiovascular disease
2021
Fractional flow reserve (FFR) uses pressure-based measurements to assess the severity of a coronary stenosis. Distal pressure (Pd) is often at a different vertical height to that of the proximal aortic pressure (Pa). The difference in pressure between Pd and Pa due to hydrostatic pressure, may impact FFR calculation.
One hundred computed tomography coronary angiographies were used to measure height differences between the coronary ostia and points in the coronary tree. Mean heights were used to calculate the hydrostatic pressure effect in each artery, using a correction factor of 0.8 mmHg/cm. This was tested in a simulation of intermediate coronary stenosis to give the \"corrected FFR\" (cFFR) and percentage of values, which crossed a threshold of 0.8.
The mean height from coronary ostium to distal left anterior descending (LAD) was +5.26 cm, distal circumflex (Cx) -3.35 cm, distal right coronary artery-posterior left ventricular artery (RCA-PLV) -5.74 cm and distal RCA-posterior descending artery (PDA) +1.83 cm. For LAD, correction resulted in a mean change in FFR of +0.042, -0.027 in the Cx, -0.046 in the PLV and +0.015 in the PDA. Using 200 random FFR values between 0.75 and 0.85, the resulting cFFR crossed the clinical treatment threshold of 0.8 in 43% of LAD, 27% of Cx, 47% of PLV and 15% of PDA cases.
There are significant vertical height differences between the distal artery (Pd) and its point of normalization (Pa). This is likely to have a modest effect on FFR, and correcting for this results in a proportion of values crossing treatment thresholds. Operators should be mindful of this phenomenon when interpreting FFR values.
Journal Article
Assessing the Impact of Prolonged Averaging of Coronary Continuous Thermodilution Traces
by
Rupert F. G. Simpson
,
Sarosh A. Khan
,
Emanuele Gallinoro
in
Accuracy
,
Angina pectoris
,
Arrhythmia
2024
Continuous Thermodilution is a novel method of quantifying coronary flow (Q) in mL/min. To account for variability of Q within the cardiac cycle, the trace is smoothened with a 2 s moving average filter. This can sometimes be ineffective due to significant heart rate variability, ventricular extrasystoles, and deep inspiration, resulting in a fluctuating temperature trace and ambiguity in the location of the “steady state”. This study aims to assess whether a longer moving average filter would smoothen any fluctuations within the continuous thermodilution traces resulting in improved interpretability and reproducibility on a test–retest basis. Patients with ANOCA underwent repeat continuous thermodilution measurements. Analysis of traces were performed at averages of 10, 15, and 20 s to determine the maximum acceptable average. The maximum acceptable average was subsequently applied as a moving average filter and the traces were re-analysed to assess the practical consequences of a longer moving average. Reproducibility was then assessed and compared to a 2 s moving average. Of the averages tested, only 10 s met the criteria for acceptance. When the data was reanalysed with a 10 s moving average filter, there was no significant improvement in reproducibility, however, it resulted in a 12% diagnostic mismatch. Applying a longer moving average filter to continuous thermodilution data does not improve reproducibility. Furthermore, it results in a loss of fidelity on the traces, and a 12% diagnostic mismatch. Overall, current practice should be maintained.
Journal Article
Stress perfusion cardiovascular magnetic resonance and serial fractional flow reserve assessment of the left anterior descending artery in patients undergoing right coronary artery chronic total occlusion revascularization
by
Kelly, Paul A.
,
Mohdnazri, Shah R.
,
Gedela, Swamy
in
Adenosine
,
chronic total occlusion
,
Clinical Cardiology
2022
Fractional flow reserve (FFR) assessment of remote arteries, in the context of a bystander chronic total occlusion (CTO), can lead to false positive results. Adenosine stress cardiovascular magnetic resonance (CMR) evaluates perfusion defects across the entire myocardium and may therefore be a reliable tool in the work-up of remote lesions in CTO patients. The IMPACT-CTO study investigated donor artery invasive physiology before, immediately post, and at 4 months following right coronary artery (RCA) CTO percutaneous coronary intervention (PCI). The aim of this subanalysis was to assess the concordance between baseline perfusion CMR and serial FFR evaluation of left anterior descending artery (LAD) ischemia in patients from the IMPACT-CTO study.
Baseline adenosine stress CMR examinations from 26 patients were analyzed for qualitative evidence of LAD ischemia. The results were correlated with the serial LAD FFR measurements.
The present findings demonstrated that before RCA CTO PCI, there was 62% agreement between perfusion CMR and FFR (ischemic threshold £ 0.8) in the assessment of LAD ischemia (k = 0.29; fair concordance). At 4 months after revascularization, there was 77% agreement (k = 0.52; moderate concordance) between the index CMR assessment of LAD ischemia and the follow-up LAD FFR. Concordance was improved at a LAD FFR ischemic threshold of £ 0.75.
In this hypothesis generating study, baseline CMR assessment of LAD ischemia correlated better with the 4 months LAD FFR data (threshold £ 0.8) as compared to the FFR measurements taken prior to RCA CTO revascularization.
Journal Article
Intravascular vs. surface cooling in out-of-hospital cardiac arrest patients receiving hypothermia after hospital arrival: a post hoc analysis of the TTM2 trial
2025
Purpose
To compare the performance of targeted temperature management (TTM) at 33 °C using intravascular (IC) vs. surface-cooling (SFC) devices after out-of-hospital cardiac arrest (OHCA).
Methods
A post hoc analysis including OHCA patients randomized to hypothermia in the TTM2-trial (NCT02908308) comparing hypothermia with normothermia. The main outcome was cooling performance, defined as the proportion of patients reaching target temperature < 33.5 °C within 4 h, time outside temperature ranges during maintenance, rewarming rate and post-TTM fever. Exploratory outcomes included survival and good functional outcome, defined as modified Rankin Scale (mRS) scores of 0–3 at 6 months, analyzed using Inverse Probability Treatment Weighting (IPTW).
Results
Among 930 patients randomized to hypothermia, 876 were treated with a cooling device and included in this study. Of those, 27.3% received IC devices, while 72.7% received SFC devices. The proportion reaching target temperature within 4 h was higher with IC (IC: 69.6% vs. SFC: 49.2%;
p
< 0.001). Temperature outside ranges during the cooling period and post-TTM fever were lower with IC compared to SFC (17.2% vs. 39.6%;
p
< 0.001 and 0% vs. 6.3%;
p
< 0.001, respectively). In the exploratory IPTW analysis, 6-month survival rates were 55.2% in the IC group and 50.2% in the SFC group (OR 1.22, 95% CI 0.89–1.68) and survival with good functional outcome at 6 months was 51.1% patients in the IC group and 44.9% in the SFC (OR 1.28, 95% CI 0.93–1.77).
Conclusions
Among OHCA patients randomized to hypothermia in the TTM2 study, intravascular cooling, compared with surface cooling, was associated with better cooling performance.
Journal Article