Prospective cohort study of elderly patients with coronary artery disease: impact of frailty on quality of life and outcome.

BACKGROUND: Elderly, frail patients are often excluded from clinical trials so there is lack of data regarding optimal management when they present with symptomatic coronary artery disease (CAD). OBJECTIVE: The aim of this observational study was to evaluate an unselected elderly population with CAD for the occurrence of frailty, and its association with quality of life (QoL) and clinical outcomes. METHODS: Consecutive patients aged ≥80 years presenting with CAD were prospectively assessed for frailty (Fried frailty phenotype (FFP), Edmonton frailty scale (EFS)), QoL (Short form survey (SF-12)) and comorbidity (Charlson Comorbidity Index (CCI)). Patients were re-assessed at 4 months to determine any change in frailty and QoL status as well as the clinical outcome. RESULTS: One hundred fifty consecutive patients with symptomatic CAD were recruited in the study. The mean age was 83.7±3.2 years, 99 (66.0%) were men. The clinical presentation was stable angina in 68 (45.3%), the remainder admitted with an acute coronary syndrome including 21 (14.0%) with ST-elevation myocardial infarction. Frailty was present in 28% and 26% by FFP and EFS, respectively, and was associated with a significantly higher CCI (7.5±2.4 in frail, 6.2±2.2 in prefrail, 5.9±1.6 in those without frailty, p=0.005). FFP was significantly related to the physical composite score for QoL, while EFS was significantly related to the mental composite score for QoL (p=0.003). Treatment was determined by the cardiologist: percutaneous coronary intervention in 51 (34%), coronary artery bypass graft surgery in 15 (10%) and medical therapy in 84 (56%). At 4 months, 14 (9.3%) had died. Frail participants had the lowest survival. Cardiovascular symptom status and the mental composite score of QoL significantly improved (52.7±11.5 at baseline vs 55.1±10.6 at follow-up, p=0.04). However, overall frailty status did not significantly change, nor the physical health composite score of QoL (37.2±11.0 at baseline vs 38.5±11.3 at follow-up, p=0.27). CONCLUSIONS: In patients referred to hospital with CAD, frailty is associated with impaired QoL and a high coexistence of comorbidities. Following cardiac treatment, patients had improvement in cardiovascular symptoms and mental component of QoL.

No-reflow phenomenon and comparison to the normal-flow population postprimary percutaneous coronary intervention for ST elevation myocardial infarction: case-control study (NORM PPCI).

INTRODUCTION: No-reflow (NR) phenomenon is characterised by the failure of myocardial reperfusion despite the absence of mechanical coronary obstruction. NR negatively affects patient outcomes, emphasising the importance of prediction and management. The objective was to evaluate the incidence and independent predictors of NR in patients presenting with ST-elevation myocardial infarction (STEMI). METHODS: This was a single-centre prospective case-control study. Cases were subjects who suffered NR, and the control comparators were those who did not. Clinical outcomes were documented. Salient variables relating to the patients and their presentation, history and angiographical findings were compared using one-way analysis of variance or χ2 test. Multiple regression determined the independent predictors, and a risk score was established based on the ß coefficient. RESULTS: Of 173 consecutive patients, 24 (13.9%) suffered from NR, with 46% occurring post stent implantation. Patients with NR had increased risk of in-hospital death (OR 7.0, 95% CI 1.3 to 36.7, p=0.022). From baseline variables available prior to percutaneous coronary intervention, the independent predictors of NR were increased lesion complexity, admission systolic hypertension, weight of <78 kg and history of hypertension. Continuous data were transformed into best-fit binary variables, and a risk score was defined. Significant difference was demonstrated between the risk score of patients with NR (4.1±1) compared with controls (2.6±1) (p<0.001), and the risk score was considered a good test (area under the curve=0.823). A score of ≥4 had 75% sensitivity and 76.5% specificity. CONCLUSION: Patients with NR have a higher rate of mortality following STEMI. Predictors of NR include lesion complexity, systolic hypertension and low weight. Further validation of this risk model is required.

Cardiogoniometry Compared to Fractional Flow Reserve at Identifying Physiologically Significant Coronary Stenosis: The CARDIOFLOW Study.

Cardiogoniometry (CGM) is method of 3-dimensional electrocardiographic assessment which has been shown to identify patients with angiographically defined, stable coronary artery disease (CAD). However, angiographic evidence of CAD, does not always correlate to physiologically significant disease. The aim of our study was to assess the ability of CGM to detect physiologically significant coronary stenosis defined by fractional flow reserve (FFR). In a tertiary cardiology centre, elective patients with single vessel CAD were enrolled into a prospective double blinded observational study. A baseline CGM recording was performed at rest. A second CGM recording was performed during the FFR procedure, at the time of adenosine induced maximal hyperaemia. A significant CGM result was defined as an automatically calculated ischaemia score < 0 and a significant FFR ratio was defined as < 0.80. Measures of diagnostic performance (including sensitivity and specificity) were calculated for CGM at rest and during maximal hyperaemia. Forty-five patients were included (aged 61.1 ± 11.0; 60.0% male), of which eighteen (40%) were found to have significant CAD when assessed by FFR. At rest, CGM yielded a sensitivity of 33.3% and specificity of 63.0%. At maximal hyperaemia the sensitivity and specificity of CGM was 71.4 and 50.0% respectively. The diagnostic performance of CGM to detect physiologically significant stable CAD is poor at rest. Although, the diagnostic performance of CGM improves substantially during maximal hyperaemia, it does not reach sufficient levels of accuracy to be used routinely in clinical practice.

Effect of PSI-697, a novel P-selectin inhibitor, on platelet-monocyte aggregate formation in humans.

BACKGROUND: Platelet activation is central to the pathogenesis of acute coronary syndromes. Surface expression of P-selectin on activated platelets induces formation of platelet-monocyte aggregates and promotes vascular inflammation and thrombosis. P-selectin antagonism may represent a novel therapeutic strategy in vascular disease. We aimed to investigate the effects of the novel P-selectin antagonist PSI-697 on platelet-monocyte aggregate formation in humans. METHODS AND RESULTS: In a double-blind, randomized, placebo-controlled crossover study, healthy smokers were randomized to receive either oral PSI-697 600 mg or matched placebo. The sequence of treatment was also randomized, with all subjects receiving both PSI-697 and placebo. Platelet-monocyte aggregates were measured by flow cytometry at 4 and 24 hours in the presence and absence of thrombin receptor-activating peptide (TRAP; 0.1 to 1.0 µm/L). The ex vivo addition of TRAP caused a concentration-dependent increase in platelet-monocyte aggregates from 8.2% to 94.8% (P<0.001). At 4 and 24 hours, plasma concentrations of PSI-697 increased to 1906 and 83 ng/mL, respectively (P<0.001). PSI-697 had no demonstrable effect on either stimulated or unstimulated platelet-monocyte aggregates at 4 or 24 hours (P>0.05). P-selectin-blocking antibody (CLB-Thromb6), but not PSI-697, inhibited both stimulated and unstimulated platelet-monocyte aggregate formation in vitro (P<0.001). CONCLUSIONS: The novel small-molecule P-selectin antagonist PSI-697 did not inhibit basal or stimulated platelet-monocyte aggregate formation in humans at the dose tested. Its clinical efficacy remains to be established. CLINICAL TRIAL REGISTRATION: URL: http://EudraCT.ema.europa.eu Unique identifier: 2007-005695-14.

Clopidogrel: an updated and comprehensive review.

The risk of adverse events in patients with acute coronary syndrome remains substantial despite the use of regular aspirin. The addition of clopidogrel to regular aspirin therapy has been shown to be associated with significantly better outcomes in a variety of clinical settings within the spectrum of acute coronary syndromes. In this article, the evidence and therapeutic implications for the use of clopidogrel in patients with non-ST-elevation and ST elevation acute coronary syndromes is discussed, and also in those undergoing percutaneous coronary intervention. The use of clopidogrel in combination with other antithrombotics in the acute setting is considered, including glycoprotein IIb/IIIa receptor antagonists and direct thrombin inhibitors. Clopidogrel has changed the way in which patients with non-ST-elevation and, more recently, ST elevation acute coronary syndromes are treated.