Real world clinical outcomes and health-related quality of life following revascularisation for left main coronary artery disease

Percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) disease has emerged as a viable alternative to coronary artery bypass graft (CABG) surgery in specific patterns of coronary involvement. Recent evidence suggests it is best utilised in patients with limited overall coronary disease burden and complexity, yet in current practice it is often employed for those with high surgical risk. While there are published data on outcomes following ULMCA PCI is selected groups of patients, there are limited data describing current real-world practice. Current revascularisation guidelines apply data from randomised studies using traditional outcome measures to stratify the appropriate use of treatment modalities. Although measures of health-related quality of life (HRQOL) are recognised to be important to patients, they are rarely taken into consideration in contemporary guidelines or clinical decision making. While there is limited knowledge surrounding the HRQOL outcomes from randomised studies of LMCA revascularisation, no published studies have assessed HRQOL outcomes in the ‘real world’ population treated for LMCA disease, including those who are medically managed. Methods: First, we undertook a retrospective analysis of patients undergoing PCI for ULMCA at a single cardiac centre in the UK. We identified a retrospective cohort of patients who received LMCA PCI between March 2005 and March 2013. We applied Cox proportional hazards model to identify the major predictors of poor survival and clinical outcomes. The primary composite outcome was major adverse cardiac and cerebrovascular events (MACCE), comprising all-cause mortality, myocardial infarction, stroke and repeat revascularisation. In separate analyses, we excluded patients with cardiogenic shock, while other subgroups analysed included LMCA bifurcation cohorts and octogenarians. Second, we recruited a prospective cohort of patients with LMCA disease managed conservatively or by PCI or CABG and applied an HRQOL questionnaire at 4 times points over the course of 1 year follow-up. Multilevel modelling using linear mixed models was used to conduct longitudinal analyses of HRQOL outcomes. Results: The Kaplan-Meier estimate of MACCE at 1 year was 26.2% and at the median (IQR) follow-up of 584 (1036) days it was 41.8%. Significant factors associated with MACCE include SYNTAX score(SS) [ Hazard ratio (HR) 1.01; 95% Confidence Interval (CI): 1.00 - 1.02; p<0.05], presentation in cardiogenic shock [adjusted Hazard Ratio (aHR) 5.88, 95% CI 3.81-9.06, p<0.05], previous MI [aHR 1.94, 95% CI 1.37-2.75, p<0.05] and a history of diabetes [aHR 1.61, 95% CI 1.12-2.31, p<0.05] after long term follow-up. With a separate analysis excluding patients with cardiogenic shock we found SS [aHR 1.02, 95% CI 1.00- 1.04, p<0.05], previous MI [aHR 1.89, 95% CI 1.28-2.80, p<0.05], peripheral vascular disease [aHR 1.68, 95% CI 1.09-2.61, p<0.05] and renal impairment [aHR 1.89, 95% CI 1.05-3.43, p<0.05] were significantly associated with MACCE; for every 10 unit increase in SS there was a 2% increase in the risk of MACCE. In a separate analysis of patients with ‘True’ LMCA bifurcation disease, there was no difference in survival from a single or two stent strategy. Residual coronary disease amongst octogenarians was assessed using the residual SS, each 10 unit increase in rSS was associated with a 3% increase in all-cause mortality (aHR 1.03; 95% CI, 1.00-1.06; p=0.04]. HRQOL was found to deteriorate significantly over 1 year for patients managed conservatively, while despite earlier improvement in HRQOL following PCI, the HRQOL for patients treated with CABG overtook these and showed greater and more sustained improvement over 1 year. Conclusion: This database describes a real world cohort of patients with LMCA, with significantly greater coronary disease burden and comorbidity than most published studies. While cardiogenic shock was a strong predictor of poor outcomes, the SS was also associated with poor outcomes. Other measures of coronary disease burden, such as ‘True’ bifurcation disease are significant predictors of poor outcomes. Diabetes is a predictor of outcome, yet after excluding cardiogenic shock, the association is no longer evident. After adjusting for the sequelae of the diabetes, such as renal impairment and burden of atheromatous disease (SS and PVD), these variables become significant predictors of poor outcomes.. Residual SS following PCI was associated with poor outcomes in this long-lived population, suggesting that untreated coronary disease is undesirable, although it is not clear that more aggressive revascularisation is indicated. HRQOL measures suggest that, despite selection bias, patients currently selected for conservative management for LMCA may benefit from some form of targeted revascularisation despite limited prognostic benefit

Mitral valve disease in sarcoidosis diagnosed by cardiovascular magnetic resonance

An 81-year-old man was referred to our clinic with a 1-year history of shortness of breath on exertion. The patient also had a history of cryptogenic liver cirrhosis and idiopathic pulmonary fibrosis

Day case discharge of patients treated with drug coated balloon only angioplasty for de novo coronary artery disease:A single center experience

Objective: To report our initial experience with Drug Coated Balloon (DCB) only angioplasty and propose a protocol to achieve this safely. Background: There are no articles published in the literature currently regarding the safety of same day discharge in patients treated with DCB-only angioplasty. Methods: Retrospective review of all our patients treated with DCB-only angioplasty from Sept 2017 to April 2018 with identification of potential complications relating to same day discharge. Results: A total of 100 consecutive patients who underwent elective DCB-only angioplasty for de novo coronary artery disease and were discharged on the same day as the procedure were included. In 99% no cardiac symptoms relating to the procedure requiring urgent hospitalisation or urgent investigations were identified. One patient was readmitted the next day requiring stenting of the previously treated lesion. Our 30 day mortality was zero. Some 97 hospital bed days were saved with 100 patients treated. Conclusion: Elective day-case DCB-only angioplasty according to our local protocol is safe and cost-effective and should be considered for the majority of the patients

Long-term safety of paclitaxel drug-coated balloon-only angioplasty for de novo coronary artery disease: the SPARTAN DCB study

Objectives: We aimed to investigate long-term survival of paclitaxel DCB for percutaneous coronary intervention (PCI). Background: Safety concerns have been raised over the use of paclitaxel devices for peripheral artery disease recently, following a meta-analysis suggesting increased late mortality. With regard to drug-coated balloon (DCB) angioplasty for coronary artery intervention however, there is limited data to date regarding possible late mortality relating to paclitaxel. Methods: We compared all-cause mortality of patients treated with paclitaxel DCB to those with non-paclitaxel second-generation drug-eluting stents (DES) for stable, de novo coronary artery disease from 1st January 2011 till 31st December 2018. To have homogenous groups allowing data on safety to be interpreted accurately, we excluded patients with previous PCI and patients treated with a combination of both DCB and DES in subsequent PCIs. Data were analysed with Kaplan–Meier curves and Cox regression statistical models. Results: We present 1517 patients; 429 treated with paclitaxel DCB and 1088 treated with DES. On univariate analysis, age, hypercholesterolaemia, hypertension, peripheral vascular disease, prior myocardial infarction, heart failure, smoking, atrial fibrillation, decreasing estimated glomerular filtration rate (eGFR) [and renal failure (eGFR < 45)] were associated with worse survival. DCB intervention showed a non-significant trend towards better prognosis compared to DES (p = 0.08). On multivariable analysis age, decreasing eGFR and smoking associated with worse prognosis. Conclusion: We found no evidence of late mortality associated with DCB angioplasty compared with non-paclitaxel second-generation DES in up to 5 years follow-up. DCB is a safe option for the treatment of de novo coronary artery disease

Circulating intermediate monocytes CD14++CD16+ are increased after elective percutaneous coronary intervention

Aim Inflammation plays a central role in the pathogenesis of atherosclerosis and in the sequelae of percutaneous coronary intervention (PCI). Previous work demonstrated that intermediate monocytes (CD14++CD16+) are associated with adverse cardiovascular events, yet monocyte subset response following elective PCI has not been described. This article explores the changes in monocyte subset and humoral response after elective PCI. Methods This prospective study included 30 patients without inflammatory diseases being referred for elective PCI. We included patients treated with drug coated balloons or 2nd generation drug eluting stents. Patients underwent blood tests at baseline (prior to PCI), four hours, two weeks and two months later. Analyses were performed in terms of monocyte subsets (classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++), gene expression of CD14+ leucocytes and humoral biomarkers. Results Intermediate monocytes decreased significantly four hours after PCI, were recovered at two weeks, and increased significantly at two months post elective, uncomplicated PCI. They remain significantly elevated in the DES group but not in the DCB group. Gene expression analysis of CD14+ leucocytes showed IL18 had decreased expression at two weeks, CXCR4 and IL1β decreased at two months, while pentraxin 3 increased at two weeks and two months. In terms of humoral biomarkers, hsTnI remains elevated up to two weeks post PCI while IL6 and TNFα remain elevated till two months post PCI. Conclusion Intermediate monocytes increase significantly two months following elective, uncomplicated PCI. They remain significantly elevated in the DES group but not in the DCB group suggesting that the PCI strategy could be one of the ways to modulate the inflammatory response post PCI

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Circulating intermediate monocytes CD14++CD16+ are increased after elective percutaneous coronary intervention.

Acknowledgements: We would like to thank all staff at the cardiology department at the Norfolk & Norwich University Hospital who facilitated this study.Funder: NIHRFunder: National Institute for Health Research Capability Fund from Norfolk and Norwich University HospitalFunder: Norfolk Heart TrustFunder: B Braun Ltd.AIM: Inflammation plays a central role in the pathogenesis of atherosclerosis and in the sequelae of percutaneous coronary intervention (PCI). Previous work demonstrated that intermediate monocytes (CD14++CD16+) are associated with adverse cardiovascular events, yet monocyte subset response following elective PCI has not been described. This article explores the changes in monocyte subset and humoral response after elective PCI. METHODS: This prospective study included 30 patients without inflammatory diseases being referred for elective PCI. We included patients treated with drug coated balloons or 2nd generation drug eluting stents. Patients underwent blood tests at baseline (prior to PCI), four hours, two weeks and two months later. Analyses were performed in terms of monocyte subsets (classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++), gene expression of CD14+ leucocytes and humoral biomarkers. RESULTS: Intermediate monocytes decreased significantly four hours after PCI, were recovered at two weeks, and increased significantly at two months post elective, uncomplicated PCI. They remain significantly elevated in the DES group but not in the DCB group. Gene expression analysis of CD14+ leucocytes showed IL18 had decreased expression at two weeks, CXCR4 and IL1β decreased at two months, while pentraxin 3 increased at two weeks and two months. In terms of humoral biomarkers, hsTnI remains elevated up to two weeks post PCI while IL6 and TNFα remain elevated till two months post PCI. CONCLUSION: Intermediate monocytes increase significantly two months following elective, uncomplicated PCI. They remain significantly elevated in the DES group but not in the DCB group suggesting that the PCI strategy could be one of the ways to modulate the inflammatory response post PCI

Drug-Coated Balloon vs. Drug-Eluting Stents for De Novo Unprotected Left Main Stem Disease: The SPARTAN-LMS Study

The objective of this study is to compare the outcomes of patients treated with drug-coated balloons (DCBs) or second-generation drug-eluting stents (DESs) for de novo unprotected left main stem (LMS) disease. Previous studies comparing the treatment of LMS disease suggest that the mortality for DES PCI is not worse than CABG. There are limited data from studies investigating the treatment of de novo LMS disease with DCB angioplasty. We compared the all-cause and cardiac mortality of patients treated with paclitaxel DCB to those with second-generation DES for de novo LMS disease from July 2014 to November 2019. Data were analysed using Kaplan–Meier analyses and propensity-matched analyses. A total of 148 patients were treated with either a DCB or DES strategy. There was no significant difference in all-cause mortality in the DCB group (19.5%) compared to the DES group (15.9%) (HR 1.42 [0.61–3.32], p = 0.42). Regarding cardiac mortality, 2 (4.9%) were recorded for the DCB group and 7 (6.5%) for the DES group (HR 1.21 [0.31–4.67], p = 0.786); for target vessel myocardial infarction, there were 0 (0%) for the DCB group and 7 (6.5%) for the DES group; and for target lesion revascularisation, there were 3 (7.3%) in the DCB group and 9 (8.3%) in the DES group (HR: 0.89 [0.24–3.30]). p = 0.86. These remained not significant after propensity score matching. We found no difference in the mortality outcomes with DCB angioplasty compared to second-generation DES, with a median follow-up of 33 months. DCB can therefore be regarded as a safe option in the treatment of LMS disease in suitable patients