138 research outputs found
859148_supp_mat – Supplemental material for Multi-disciplinary palliative care is effective in people with symptomatic heart failure: A systematic review and narrative synthesis
No full textSupplemental material, 859148_supp_mat for Multi-disciplinary palliative care is effective in people with symptomatic heart failure: A systematic review and narrative synthesis by Sushma Datla, Cornelia Antonia Verberkt, Angela Hoye, Daisy J.A. Janssen and Miriam J Johnson in Palliative Medicine</p
Do clinically relevant differences in outcomes exist between women and men undergoing treatment for cardiovascular disease?
No full textIntroductionThroughout my own clinical practice, I became aware that differences may exist between men and women in the decisions for treatment and the outcomes after intervention for cardiovascular disease. Clinical trials have corroborated this with women typically presenting at an older age and studies have suggested there are innate differences between the sexes with women believed to have worse outcomes than men. However, historically women have been poorly represented in clinical trials, which has led to biased result interpretation, despite cardiovascular disease remaining the leading cause of death in women. Therefore, extrapolation of results to women may lead to differences in expected outcomes.The aim of this thesis was to explore the question: ‘Do outcomes differ between women and men in the treatment of cardiovascular disease?’MethodsThe over-arching research question was addressed by integrating results from 5 individual datasets. Following the literature review, the areas identified for investigation were: 1) The role of female sex in the treatment of the left main coronary artery; 2) Bleeding risk in women undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction; 3) Does sex play a role in the activated clotting time during angioplasty; 4) The role of sex on outcomes following transcatheter aortic valve implantation; and 5) Sex differences in the perceived intensity of symptoms in patients with aortic stenosis.Each of these studies involved observational data from real world patients and allowed for assessment of matched populations to allow for a comparison when appropriate. The datasets were then analysed utilising the constructivist paradigm to identify themes that contribute to robust and generalisable new knowledge in this field.ResultsThe treatment of the complex left main coronary artery is first addressed and demonstrates no differences between the sexes in those undergoing percutaneous coronary intervention, however there was an advantage in women undergoing coronary artery bypass grafting. In patients presenting with ST-elevation myocardial infarction, women have more episodes of bleeding, however despite this have the same good outcome as men in hospital and therefore require the same access to treatment. The anti-coagulation regime during percutaneous coronary intervention is then considered and demonstrates that for a similar dose of unfractionated heparin, women are more likely to have a very high activated clotting time which may explain the increased risk of bleeding in the prior chapter.In the assessment of aortic stenosis, in symptomatic patients undergoing transcatheter aortic valve implantation, women again appear to have an advantage over men, with male sex a predictor of mortality at long-term follow-up. However, finally addressing the symptomatology of aortic stenosis, there were no differences between sexes in the symptoms of breathlessness or in NT-pro-BNP levels.ConclusionsThe analysis demonstrated that despite an older presentation in women who underwent treatment, women can do as well as men (in coronary artery disease) or even fare better (for transcatheter aortic valve implantation) despite more bleeding and vascular complications. This may impact significantly regarding the multi-disciplinary discussion regarding intervention for these patients and needs to be considered by the clinicians involved in the treatment of cardiovascular disease.The limitations of the studies are that the data are non-randomised and in 2 of the data sets there are small sample sizes. Additionally, there are the difficulties associated with the analysis of mixed methods research in analysing quantitative data qualitatively.In summary, when determining if patient sex should be a factor when deciding upon the management of acquired cardiovascular disease, the triangulation of data from across a number of data sets in this thesis suggests that sex should not be the primary consideration. Further research is needed to refine clinical understanding of which factors should be taken into account
Chronic total coronary occlusions, distal collateral supply and implications of recanalisation
No full textThe optimal treatment for patients with a chronic total coronary occlusion (CTO) is controversial, both in terms of the decision whether to revascularise and with respect to the physiological effect of recanalisation on revascularisation strategy.Physiological lesion assessment in the form of fractional flow reserve (FFR) is now well established for the purpose of guiding multi-vessel revascularisation. CTOs are frequently associated with multi-vessel disease and the collateral dependent myocardium distal to the occlusion is often supplied by a collateral supply from another epicardial coronary. The haemodynamic effect of collateral donation upon collateral donor vessel flow may have important implications for the vessel’s FFR; rendering it unreliable at predicting ischaemia should the CTO be revascularised. These haemodynamic changes along with the changes in the target vessel after recanalisation of the occlusion are not well described.The ability to form a functional collateral supply varies considerably between individuals. As arteriogenesis is an endothelium dependent process we hypothesised that biomarkers of endothelial health might be associated with the degree of functional collateralisation measured invasively in the coronary vessel segment distal to a CTO.In this series of studies, I first compare long-term outcomes between patients with a chronic total coronary occlusion treated electively by medical therapy or CTO PCI. I go on to study the haemodynamic changes associated with CTO PCI. Firstly, the associated changes in physiology in the non-CTO vessels and how these changes might influence best revascularisation strategy. Secondly, the haemodynamics in the recently recanalised CTO vessel and the effect that might have on physiological optimization of the PCI result. Finally, I compare coronary haemodynamics taken at the time of CTO PCI with biomarkers of endothelial health to investigate a link between their levels and degree of functional collateralisation. The over-arching goal of this thesis is to add to our understanding of how best to manage patients with a chronic total coronary occlusion
Do clinically relevant differences in outcomes exist between women and men undergoing treatment for cardiovascular disease?
No full textIntroductionThroughout my own clinical practice, I became aware that differences may exist between men and women in the decisions for treatment and the outcomes after intervention for cardiovascular disease. Clinical trials have corroborated this with women typically presenting at an older age and studies have suggested there are innate differences between the sexes with women believed to have worse outcomes than men. However, historically women have been poorly represented in clinical trials, which has led to biased result interpretation, despite cardiovascular disease remaining the leading cause of death in women. Therefore, extrapolation of results to women may lead to differences in expected outcomes.The aim of this thesis was to explore the question: ‘Do outcomes differ between women and men in the treatment of cardiovascular disease?’MethodsThe over-arching research question was addressed by integrating results from 5 individual datasets. Following the literature review, the areas identified for investigation were: 1) The role of female sex in the treatment of the left main coronary artery; 2) Bleeding risk in women undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction; 3) Does sex play a role in the activated clotting time during angioplasty; 4) The role of sex on outcomes following transcatheter aortic valve implantation; and 5) Sex differences in the perceived intensity of symptoms in patients with aortic stenosis.Each of these studies involved observational data from real world patients and allowed for assessment of matched populations to allow for a comparison when appropriate. The datasets were then analysed utilising the constructivist paradigm to identify themes that contribute to robust and generalisable new knowledge in this field.ResultsThe treatment of the complex left main coronary artery is first addressed and demonstrates no differences between the sexes in those undergoing percutaneous coronary intervention, however there was an advantage in women undergoing coronary artery bypass grafting. In patients presenting with ST-elevation myocardial infarction, women have more episodes of bleeding, however despite this have the same good outcome as men in hospital and therefore require the same access to treatment. The anti-coagulation regime during percutaneous coronary intervention is then considered and demonstrates that for a similar dose of unfractionated heparin, women are more likely to have a very high activated clotting time which may explain the increased risk of bleeding in the prior chapter.In the assessment of aortic stenosis, in symptomatic patients undergoing transcatheter aortic valve implantation, women again appear to have an advantage over men, with male sex a predictor of mortality at long-term follow-up. However, finally addressing the symptomatology of aortic stenosis, there were no differences between sexes in the symptoms of breathlessness or in NT-pro-BNP levels.ConclusionsThe analysis demonstrated that despite an older presentation in women who underwent treatment, women can do as well as men (in coronary artery disease) or even fare better (for transcatheter aortic valve implantation) despite more bleeding and vascular complications. This may impact significantly regarding the multi-disciplinary discussion regarding intervention for these patients and needs to be considered by the clinicians involved in the treatment of cardiovascular disease.The limitations of the studies are that the data are non-randomised and in 2 of the data sets there are small sample sizes. Additionally, there are the difficulties associated with the analysis of mixed methods research in analysing quantitative data qualitatively.In summary, when determining if patient sex should be a factor when deciding upon the management of acquired cardiovascular disease, the triangulation of data from across a number of data sets in this thesis suggests that sex should not be the primary consideration. Further research is needed to refine clinical understanding of which factors should be taken into account
Chronic total coronary occlusions, distal collateral supply and implications of recanalisation
No full textThe optimal treatment for patients with a chronic total coronary occlusion (CTO) is controversial, both in terms of the decision whether to revascularise and with respect to the physiological effect of recanalisation on revascularisation strategy.Physiological lesion assessment in the form of fractional flow reserve (FFR) is now well established for the purpose of guiding multi-vessel revascularisation. CTOs are frequently associated with multi-vessel disease and the collateral dependent myocardium distal to the occlusion is often supplied by a collateral supply from another epicardial coronary. The haemodynamic effect of collateral donation upon collateral donor vessel flow may have important implications for the vessel’s FFR; rendering it unreliable at predicting ischaemia should the CTO be revascularised. These haemodynamic changes along with the changes in the target vessel after recanalisation of the occlusion are not well described.The ability to form a functional collateral supply varies considerably between individuals. As arteriogenesis is an endothelium dependent process we hypothesised that biomarkers of endothelial health might be associated with the degree of functional collateralisation measured invasively in the coronary vessel segment distal to a CTO.In this series of studies, I first compare long-term outcomes between patients with a chronic total coronary occlusion treated electively by medical therapy or CTO PCI. I go on to study the haemodynamic changes associated with CTO PCI. Firstly, the associated changes in physiology in the non-CTO vessels and how these changes might influence best revascularisation strategy. Secondly, the haemodynamics in the recently recanalised CTO vessel and the effect that might have on physiological optimization of the PCI result. Finally, I compare coronary haemodynamics taken at the time of CTO PCI with biomarkers of endothelial health to investigate a link between their levels and degree of functional collateralisation. The over-arching goal of this thesis is to add to our understanding of how best to manage patients with a chronic total coronary occlusion
Intravenous versus intracoronary bolus of glycoprotein IIb/IIIa inhibitor administration during primary percutaneous coronary intervention on long-term left ventricular systolic and diastolic function.
No full textIn primary percutaneous coronary intervention (PCI), glycoprotein (GP) IIb/IIIa inhibitors are often given in order to attain and maintain better myocardial perfusion. We tested the hypothesis that intracoronary (IC) bolus of GP IIb/IIIa inhibitors might produce a greater improvement in left ventricular (LV) systolic and diastolic function than an intravenous(IV) bolus.Seventy seven patients undergoing primary PCI for their first ST elevation myocardial infarction (STEMI) were randomly assigned to either an IC or IV bolus of GP IIb/IIIa inhibitor, followed by IV infusion. Compared with the echocardiographic findings within 3 days after PCI, LV ejection fraction was higher at 1 year, with no significant differences between the IV and IC groups (IV: 44\% vs. 49\%, p = 0.001; IC: 43\% vs. 48\%,p < 0.001). LV diastolic function (E/E') did not significantly change at 1 year by either approach.LV systolic function improved by a similar magnitude following primary PCI, with either IC or IV bolus administration of GP IIb/IIIa inhibitor therapy. However, no significant changes were observed in LV diastolic function
Acute coronary syndromes, platelets and the endothelium
No full textABSTRACTBackground: Acute coronary syndromes (ACS) are medical emergencies. Platelet and endothelial function are fundamental to the pathophysiology; and implicated in secondary conditions such as no reflow (NR). Guidelines support the administration of P2Y12 antagonists in ACS treatment, but the broader effects are unclear.Objectives: 1) Assess the impact of P2Y12 inhibition (ticagrelor) on the platelet sensitivity to prostacyclin (PGI2) and nitric oxide (NO) in coronary artery disease (CAD). 2) Review NR and identify at risk patients 3) Outline the optimal P2Y12 antagonist in ACS patients with diabetes.Methods: 1) Platelet and endothelial function assessed at baseline and after 3 days oral ticagrelor in CAD patients. Multiple aspects of platelet activation and sensitivity to PGI2 and NO were examined by flow cytometry. 2) Prospective case-control study of STEMI patients with and without NR. Multiple regression identified independent predictors and a risk score established. 3) Meta-analysis of randomised trials with clinical outcomes for P2Y12 inhibitors in ACS patients with diabetes.Results: Ex vivo studies of CAD patients (n=63) demonstrated that oral ticagrelor induced only modest platelet inhibition in whole blood. However, it enhanced the inhibitory actions of PGI2 and NO. Ticagrelor potently amplified PGI2 inhibition of platelet-leukocyte aggregate formation (a measure of platelet inflammatory function). Ticagrelor improved endothelial reactive hyperaemic index (RHI), which correlated with platelet sensitivity. 24(13.9%) STEMI patients suffered NR, which significantly increased the risk of cardiovascular death. The independent predictors of NR were lesion complexity, systolic hypertension, weight<78kg, and history of hypertension. Systematic review of 7 studies, established newer P2Y12 antagonists (ticagrelor and prasugrel) were optimal for ACS patients with diabetes; with a trend to prasugrel superiority in the reduction of major adverse cardiovascular events.Conclusion: In patients with CAD, P2Y12 antagonism by ticagrelor promotes inhibition of platelet haemostatic and inflammatory function by endogenous regulators; and improves endothelial function
Acute coronary syndromes, platelets and the endothelium
No full textABSTRACTBackground: Acute coronary syndromes (ACS) are medical emergencies. Platelet and endothelial function are fundamental to the pathophysiology; and implicated in secondary conditions such as no reflow (NR). Guidelines support the administration of P2Y12 antagonists in ACS treatment, but the broader effects are unclear.Objectives: 1) Assess the impact of P2Y12 inhibition (ticagrelor) on the platelet sensitivity to prostacyclin (PGI2) and nitric oxide (NO) in coronary artery disease (CAD). 2) Review NR and identify at risk patients 3) Outline the optimal P2Y12 antagonist in ACS patients with diabetes.Methods: 1) Platelet and endothelial function assessed at baseline and after 3 days oral ticagrelor in CAD patients. Multiple aspects of platelet activation and sensitivity to PGI2 and NO were examined by flow cytometry. 2) Prospective case-control study of STEMI patients with and without NR. Multiple regression identified independent predictors and a risk score established. 3) Meta-analysis of randomised trials with clinical outcomes for P2Y12 inhibitors in ACS patients with diabetes.Results: Ex vivo studies of CAD patients (n=63) demonstrated that oral ticagrelor induced only modest platelet inhibition in whole blood. However, it enhanced the inhibitory actions of PGI2 and NO. Ticagrelor potently amplified PGI2 inhibition of platelet-leukocyte aggregate formation (a measure of platelet inflammatory function). Ticagrelor improved endothelial reactive hyperaemic index (RHI), which correlated with platelet sensitivity. 24(13.9%) STEMI patients suffered NR, which significantly increased the risk of cardiovascular death. The independent predictors of NR were lesion complexity, systolic hypertension, weight<78kg, and history of hypertension. Systematic review of 7 studies, established newer P2Y12 antagonists (ticagrelor and prasugrel) were optimal for ACS patients with diabetes; with a trend to prasugrel superiority in the reduction of major adverse cardiovascular events.Conclusion: In patients with CAD, P2Y12 antagonism by ticagrelor promotes inhibition of platelet haemostatic and inflammatory function by endogenous regulators; and improves endothelial function
The role of cardiopulmonary exercise testing for identifying possible silent myocardial ischaemia in people with coronary heart disease
No full textThis thesis investigates the utility of cardiopulmonary exercise testing (CPET) in assessing and managing patients with coronary artery disease (CAD), particularly focusing on the significance of oxygen pulse (O2Pulse) inflections as a marker for myocardial ischemia. The research encompasses a comprehensive analysis of O2Pulse morphology, inflection point identification, and the impact of exercise-based cardiac rehabilitation (exCR) programs, specifically high-intensity interval training (HIIT) and moderate-intensity steady-state (MISS) training, on patients with CHD.Chapter 3 examines the reliability of CPET in detecting suspected myocardial ischemia through O2Pulse and ΔV̇O2/ΔWR inflections in chronic total occlusion (CTO) patients. This study was considerable hampered by poor recruitment and the outbreak of COVID-19. Subsequently only four patients were enrolled, three of whom exhibited no inflections in O2Pulse. In the one patient who did have O2Pulse inflections they occurred at similar work rates (10W) and heart rates (5bpm). Chapter 5 extends the inquiry into the short-term reliability and agreement of O2Pulse curve parameters in a healthy cohort demonstrating that the mean percent minimal detectable change for filtered O2Pulse was 13.5 ± 3.2. Building on these findings, Chapter 6 evaluates the inter- and intra-rater reliability in identifying O2Pulse inflections, comparing subjective assessments with an objective algorithmic method. Almost perfect agreement between the algorithm and human raters was demonstrated, with a Fleiss’ Kappa statistic of 0.89. Chapter 7, a subset analysis from the HIIT or MISS UK trial, delves into the rate of O2Pulse inflections in outpatient cardiac rehabilitation (16%) and how different exercise interventions affect O2Pulse inflections in CAD patients.The results highlight a considerable potential for CPET, particularly O2Pulse inflections, in the diagnosis, treatment, and management of CAD. The research underscores the potential reliability of O2Pulse as a diagnostic tool, the effectiveness of exCR in improving cardiopulmonary fitness, and the relevance of O2Pulse inflections as a surrogate marker for myocardial ischemia. The findings suggest that both HIIT and MISS can positively influence O2Pulse inflections, offering a non-invasive means to monitor and potentially improve the health outcomes of CAD patients.This thesis contributes to the understanding of CPET in clinical settings, advocating for its broader application in cardiac rehabilitation. It identifies areas for further research, including the exploration of different exercise modalities, to optimize exCR programs and enhance patient care
The role of cardiopulmonary exercise testing for identifying possible silent myocardial ischaemia in people with coronary heart disease
No full textThis thesis investigates the utility of cardiopulmonary exercise testing (CPET) in assessing and managing patients with coronary artery disease (CAD), particularly focusing on the significance of oxygen pulse (O2Pulse) inflections as a marker for myocardial ischemia. The research encompasses a comprehensive analysis of O2Pulse morphology, inflection point identification, and the impact of exercise-based cardiac rehabilitation (exCR) programs, specifically high-intensity interval training (HIIT) and moderate-intensity steady-state (MISS) training, on patients with CHD.Chapter 3 examines the reliability of CPET in detecting suspected myocardial ischemia through O2Pulse and ΔV̇O2/ΔWR inflections in chronic total occlusion (CTO) patients. This study was considerable hampered by poor recruitment and the outbreak of COVID-19. Subsequently only four patients were enrolled, three of whom exhibited no inflections in O2Pulse. In the one patient who did have O2Pulse inflections they occurred at similar work rates (10W) and heart rates (5bpm). Chapter 5 extends the inquiry into the short-term reliability and agreement of O2Pulse curve parameters in a healthy cohort demonstrating that the mean percent minimal detectable change for filtered O2Pulse was 13.5 ± 3.2. Building on these findings, Chapter 6 evaluates the inter- and intra-rater reliability in identifying O2Pulse inflections, comparing subjective assessments with an objective algorithmic method. Almost perfect agreement between the algorithm and human raters was demonstrated, with a Fleiss’ Kappa statistic of 0.89. Chapter 7, a subset analysis from the HIIT or MISS UK trial, delves into the rate of O2Pulse inflections in outpatient cardiac rehabilitation (16%) and how different exercise interventions affect O2Pulse inflections in CAD patients.The results highlight a considerable potential for CPET, particularly O2Pulse inflections, in the diagnosis, treatment, and management of CAD. The research underscores the potential reliability of O2Pulse as a diagnostic tool, the effectiveness of exCR in improving cardiopulmonary fitness, and the relevance of O2Pulse inflections as a surrogate marker for myocardial ischemia. The findings suggest that both HIIT and MISS can positively influence O2Pulse inflections, offering a non-invasive means to monitor and potentially improve the health outcomes of CAD patients.This thesis contributes to the understanding of CPET in clinical settings, advocating for its broader application in cardiac rehabilitation. It identifies areas for further research, including the exploration of different exercise modalities, to optimize exCR programs and enhance patient care
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