Coronary Angiography Complicated by Acute Ischaemic Stroke and the Use of Thrombolysis: a Cardiology Perspective and Narrative Review of Current Literature.

PURPOSE OF REVIEW: Coronary angiography-associated acute ischaemic stroke (CAAIS) is an uncommon event but is associated with significant mortality and morbidity. The incidence of CAAIS has increased with a rise in the volume of coronary angiography (CA) and percutaneous coronary intervention (PCI) performed. Intravenous thrombolysis (IVT) is utilized in the general management of acute ischaemic stroke; however, it is associated with a higher risk of intracranial hemorrhage (ICH). As CA or PCI is performed more often in an aging population or high-risk patients that also carry an increased risk of ICH, it is vital to minimize additional complications from the treatment of CAAIS. This article aims to review the pathophysiological mechanisms for CAAIS, clarify the current evidence regarding IVT use in this setting, and thus assist cardiologists in the management of CAAIS. RECENT FINDINGS: The pathophysiology for CAAIS may be different from acute ischaemic stroke in the general population. Embolic phenomena from dislodgement of calcium or other debris during manipulation of instrumentation during CA or PCI are likely mechanisms. This may contribute to altered thrombus composition, which affects the efficacy of IVT as suggested in recent studies. Furthermore, IVT in the management of CAAIS has not been evaluated specifically. The utilization of IVT should be carefully considered in CAAIS given a paucity of evidence demonstrating safety and efficacy in this setting. A multidisciplinary pathway that emphasizes the involvement of cardiologists in the treatment decision-making process would aid in thoughtful risk-benefit evaluation for IVT use in CAAIS and reduce adverse patient outcomes. Future studies to assess the impact of this pathway on CAAIS outcomes would be beneficial.

Effects of aromatase inhibitor therapy on adiposity and cardiometabolic health in postmenopausal women: a controlled cohort extension study.

Purpose: We previously demonstrated that 12 months of aromatase inhibitor (AI) treatment was not associated with a difference in body composition or other markers of cardiometabolic health when compared to controls. Here we report on the pre-planned extension of the study. The pre-specified primary hypothesis was that AI therapy for 24 months would lead to increased visceral adipose tissue (VAT) area when compared to controls. Methods: We completed a 12-month extension to our prospective 12-month cohort study of 52 women commencing AI treatment (median age 64.5 years) and 52 women with breast pathology not requiring endocrine therapy (63.5 years). Our primary outcome of interest was VAT area. Secondary and exploratory outcomes included other measures of body composition, hepatic steatosis, measures of atherosclerosis and vascular reactivity. Using mixed models and the addition of a fourth time point, we increased the number of study observations by 79 and were able to rigorously determine the treatment effect. Results: Among study completers (AI = 39, controls = 40), VAT area was comparable between groups over 24 months, the mean-adjusted difference was -1.54 cm2 (95% CI: -14.9; 11.9, P = 0.79). Both groups demonstrated parallel and continuous increases in VAT area over the observation period that did not diverge or change between groups. No statistically significant difference in our secondary and exploratory outcomes was observed between groups. Conclusions: While these findings provide reassurance that short-to-medium-term exposure to AI therapy is not associated with metabolically adverse changes when compared to controls, risk evolution should be less focussed on the AI-associated effect and more on the general development of cardiovascular risk over time.

Retinal microvascular function predicts chronic kidney disease in patients with cardiovascular risk factors.

BACKGROUND AND AIMS: Endothelial dysfunction is a precursor to atherosclerosis and is implicated in the coexistence between cardiovascular disease (CVD) and chronic kidney disease (CKD). We examined whether retinal microvascular dysfunction is present in subjects with renal impairment and predictive of long-term CKD progression in patients with CVD. METHODS: In a single centre prospective observational study, 253 subjects with coronary artery disease and CVD risk factors underwent dynamic retinal vessel analysis. Retinal microvascular dysfunction was quantified by measuring retinal arteriolar and venular dilatation in response to flicker light stimulation. Serial renal function assessment was performed over a median period of 9.3 years using estimated GFR (eGFR). RESULTS: Flicker light-induced retinal arteriolar dilatation (FI-RAD) was attenuated in patients with baseline eGFR <90 mL/min/1.73 m2, compared to those with normal renal function (eGFR ≥90 mL/min/1.73 m2) (1.0 [0.4-2.1]% vs. 2.0 [0.8-3.6]%; p < 0.01). In patients with normal renal function, subjects with the lowest FI-RAD responses exhibited the greatest annual decline in eGFR. In uni- and multivariable analysis, among subjects with normal renal function, a 1% decrease in FI-RAD was associated with an accelerated decline in eGFR of 0.10 (0.01, 0.15; p = 0.03) and 0.07 mL/min/1.73 m2 per year (0.00, 0.14; p = 0.06), respectively. FI-RAD was not predictive of CKD progression in subjects with baseline eGFR <90 mL/min/1.73 m2. CONCLUSIONS: Retinal arteriolar endothelial dysfunction is present in patients with CVD who have early-stage CKD, and serves as an indicator of long-term CKD progression in those with normal renal function.

Pre-hospital heparin use for ST-elevation myocardial infarction is safe and improves angiographic outcomes.

AIMS: This study aims to evaluate if pre-hospital heparin administration by paramedics is safe and improves clinical outcomes. METHODS AND RESULTS: Using the multicentre Victorian Cardiac Outcomes Registry, linked with state-wide ambulance records, we identified consecutive patients undergoing primary percutaneous coronary intervention for STEMI between January 2014 and December 2018. Information on thrombolysis in myocardial infarction (TIMI) flow at angiography was available in a subset of cases. Patients receiving pre-hospital heparin were compared to those who did not receive heparin. Findings at coronary angiography and 30-day clinical outcomes were compared between groups. Propensity-score matching was performed for risk adjustment. We identified a total of 4720 patients. Of these, 1967 patients had TIMI flow data available. Propensity-score matching in the entire cohort yielded 1373 matched pairs. In the matched cohort, there was no observed difference in 30-day mortality (no-heparin 3.5% vs. heparin 3.0%, P = 0.25), MACCE (no-heparin 7% vs. heparin 6.2%, P = 0.44), and major bleeding (no-heparin 1.9% vs. heparin 1.4%, P = 0.64) between groups. Propensity-score analysis amongst those with TIMI data produced 552 matched pairs. The proportion of cases with TIMI 0 or 1 flow in the infarct-related artery (IRA) was lower among those receiving pre-hospital heparin (66% vs. 76%, P < 0.001) compared to those who did not. CONCLUSION: In this multicentre, propensity-score matched study, the use of pre-hospital heparin by paramedics was safe and is associated with fewer occluded IRAs in patients presenting with STEMI.

Impaired retinal microvascular function predicts long-term adverse events in patients with cardiovascular disease.

AIMS: Endothelial dysfunction is a precursor to the development of symptomatic atherosclerosis. Retinal microvascular reactivity to flicker light stimulation is a marker of endothelial function and can be quantified in vivo. We sought to determine whether retinal microvascular endothelial dysfunction predicts long-term major adverse cardiovascular events (MACE). METHODS AND RESULTS: In a single-centre prospective observational study, patients with coronary artery disease (CAD) or cardiovascular risk factors underwent dynamic retinal vessel assessment in response to flicker light stimulation and were followed up for MACE. Retinal microvascular endothelial dysfunction was quantified by measuring maximum flicker light-induced retinal arteriolar dilatation (FI-RAD) and flicker light-induced retinal venular dilatation (FI-RVD). In total, 252 patients underwent dynamic retinal vessel assessment and 242 (96%) had long-term follow-up. Of the 242 patients, 88 (36%) developed MACE over a median period of 8.6 years (interquartile range 6.0-9.1). After adjustment for traditional risk factors, patients within the lowest quintile of FI-RAD had the highest risk of MACE [odds ratio (OR) 5.21; 95% confidence interval (CI) 1.78-15.28]. Patients with lower FI-RAD were also more likely to die (OR 2.09; 95% CI 1.00-4.40, per standard deviation decrease in FI-RAD). In Kaplan-Meier analysis, patients with FI-RAD responses below the cohort median of 1.4% exhibited reduced MACE-free survival (55.5 vs. 71.5%; log-rank P = 0.004). FI-RVD was not predictive of MACE. CONCLUSION: Retinal arteriolar endothelial dysfunction is an independent predictor of MACE in patients with CAD or cardiovascular risk factors. Dynamic retinal vessel analysis may provide added benefit to traditional risk factors in stratifying patients at risk for cardiovascular events.

Plasma endothelin-1 and adrenomedullin are associated with coronary artery function and cardiovascular outcomes in humans.

BACKGROUND: Endothelin-1 (ET-1) is a vasoconstrictor associated with cardiovascular disease, whereas adrenomedullin (ADM) is a vasorelaxant with cardioprotective properties. We sought to determine the relationship between plasma ET-1 and ADM with coronary circulatory function and long-term major adverse cardiovascular events (MACE). METHODS: Thirty-two patients undergoing coronary angiography for chest pain were recruited. Baseline plasma ET-1 and ADM levels were measured. The index of microcirculatory resistance (IMR), coronary flow mediated dilatation (cFMD) and coronary flow reserve (CFR) were measured in a non-obstructed coronary artery. Patients were assessed for MACE over a median period of 8.8 years. RESULTS: Plasma ET-1 levels correlated with IMR (r = 0.57; p < 0.01) and ADM levels correlated with CFR (r = 0.50; p = 0.04) and cFMD (r = 0.62; p = 0.01). After adjustment for age, gender and cardiovascular risk factors, the association between ADM and cFMD (ß = 0.79; p < 0.01) and between ET-1 and IMR (ß = 5.7; p = 0.01) remained significant. IMR was higher, although not statistically significant, in patients with long-term MACE (17.9 ±â€¯5.3 vs. 13.1 ±â€¯6.0 units; p = 0.14). In patients free of MACE, cFMD (9.3 ±â€¯7.6 vs. 2.8 ±â€¯5.0%; p = 0.01) and plasma ADM levels (7.6 ±â€¯5.3 vs. 4.0 ±â€¯1.9 pmol/L; p = 0.07) were higher. CONCLUSIONS: Plasma ET-1 and ADM were associated with measures of coronary microvascular and coronary conduit vessel function, respectively. Increased cFMD and elevated plasma ADM were associated with a cardioprotective effect.

Usefulness of retinal microvascular endothelial dysfunction as a predictor of coronary artery disease.

Endothelial dysfunction is a key feature of atherosclerosis. Retinal microvascular endothelial function can be assessed using noninvasive dynamic vessel imaging techniques. Whether it is impaired in subjects with coronary artery disease (CAD) is unknown. The aim of this study was to examine the relation of retinal microvascular endothelial function with CAD. Vascular studies were performed in 197 prospectively recruited subjects divided into 2 groups: those without CAD but ≥2 cardiovascular risk factors (non-CAD controls; n = 119) and those with stable CAD (n = 78). Retinal microvascular endothelial dysfunction was assessed by measuring retinal arteriolar and venular dilatation to flicker light, a nitric oxide-dependent phenomenon, expressed as percentage increase over baseline diameter. Fingertip pulse-volume amplitude was measured to calculate reactive hyperaemia index and brachial artery flow-mediated dilatation assessed as measures of peripheral microvascular and conduit vessel endothelial function, respectively. Mean retinal arteriolar dilatation was attenuated in patients with CAD compared with non-CAD controls (1.51 ± 1.51% vs 2.37 ± 1.95%, p = 0.001). Retinal arteriolar dilatation was independently associated with CAD after adjustment for age, gender, cardiovascular risk factors, and medication use (odds ratio 1.60, 95% confidence interval 1.14 to 2.25, p = 0.007). Reactive hyperaemia index and flow-mediated dilatation were not different. In conclusion, the capacity of retinal arterioles to dilate in response to flicker light is an independent predictor of the presence of CAD and suggests that retinal microvascular endothelial dysfunction is a marker for underlying CAD.

Retinal microvascular structure and function in patients with risk factors of atherosclerosis and coronary artery disease.

OBJECTIVE: Retinal microvascular signs are markers of cardiovascular disease risk. There are limited data, on relationships between retinal microvascular signs and retinal microvascular endothelial function. We sought to determine the relationship of retinal vascular signs with retinal microvascular endothelial function in patients with or at high risk of coronary artery disease. METHODS: Participants with atherosclerosis risk factors and coronary disease (n=258; mean age 57±11 years) were recruited to have static and dynamic retinal vascular assessment. Retinal arteriolar dilatation in response to flicker light (FI-RAD) was measured using the Digital Vessel Analyser and expressed as percentage increase over baseline diameter. Static retinal photographs were acquired utilising a digital fundus camera for measurement of central retinal artery and vein equivalent (CRAE and CRVE), arteriovenous nicking (AVN) and focal arteriolar narrowing (FAN). RESULTS: Intra-class correlation coefficient was 0.82 for flicker-light induced retinal arteriolar dilatation. There were modest associations in retinal vascular measurements between eyes. For each 10 µm decrease in retinal arteriolar diameter, the absolute increase in FI-RAD was 0.28% (95% CI 0.11, 0.45; p=0.002) independent of age, gender and atherosclerosis risk factors. AVN and FAN were associated with attenuated FI-RAD (ß=-0.67%; 95% CI -1.20, -0.15; p=0.012) and (ß=-0.83%; 95% CI -1.44, -0.23; p=0.007) respectively after adjustment for age and gender. CONCLUSION: Assessment of retinal microvascular endothelial function is reproducible and correlated with retinal microvascular structure and signs, independent of atherosclerosis risk factors. Assessment of retinal vascular structure and function may provide insights into atherosclerotic disease.

Contemporary outcomes in women undergoing percutaneous coronary intervention for acute coronary syndromes.

BACKGROUND: Uncertainty remains as to whether females benefit as much as males from percutaneous coronary intervention (PCI) in the setting of an acute coronary syndrome (ACS). METHODS: We compared 802 women with 2151 men presenting with ACS, undergoing PCI from April 2004 to October 2006 from the Melbourne Interventional Group registry. Clinical characteristics, in-hospital, 30-day and 1-year outcomes were compared. RESULTS: Women were older (69.6 ± 11.6 vs. 62.17 ± 12.3 years, p<0.001), and had more diabetes (27.1% vs. 19.6%, p<0.001) and hypertension (70.3% vs. 53.9%, p<0.001) than men. Women were less likely to present with ST-elevation myocardial infarction (30.5% vs. 37.9%, p<0.001). Bleeding (3.6% vs. 0.8%, p<0.001) was higher among women. Thirty-day mortality (4.7 vs. 2.4%, p<0.001) and MACE (10.1 vs. 6.4%, p<0.001) were higher in women. Gender was an independent predictor of overall MACE at 30 days (OR 1.45, 95% CI 1.04-2.02, p=0.03) but not death. At 12 months, there were no significant differences in mortality (6.4% vs. 4.8%, p=0.09), myocardial infarction (5.5% vs. 5.0%, p=0.64), target vessel revascularization (7.9% vs. 7.0%, p=0.42) and MACE (16.3% vs. 14%, p=0.13) between women and men. CONCLUSIONS: There is an early hazard amongst women undergoing PCI for ACS, but not at 12 months. These data suggest that gender should not affect the decision to offer PCI but further gender specific studies are warranted.

Are retinal microvascular caliber changes associated with severity of coronary artery disease in symptomatic cardiac patients?

OBJECTIVES: Recent population-based studies have shown that retinal vascular caliber may predict the risk of clinical coronary artery disease (CAD) events. Whether this association is related to macro- or microvascular mechanisms remains unknown. We investigated the relationship of retinal vascular caliber with severity and extent of CAD in symptomatic cardiac patients. MATERIALS AND METHODS: Overall, 98 patients attending diagnostic coronary angiography were recruited. Coronary angiography was used to assess for the severity and extent of CAD. Digital retinal photography was performed immediately prior to cardiac catheterization, and retinal vascular caliber was measured from these photographs by using a computer program and summarized as central retinal arteriolar (CRAE) and venular (CRVE) equivalents. RESULTS: Retinal arteriolar and venular calibers were not associated with increasing severity of CAD, as assessed by Leaman scores (CRAE/CRVE: P for trend=0.17/0.57), presence of clinically significant CAD (CRAE/CRVE: P=0.35/0.32), or number of diseased vessels (CRAE/CRVE: P for trend=0.18/0.69). CONCLUSIONS: Retinal vascular caliber changes are not associated with the severity of obstructive CAD in symptomatic patients. These data suggest that the association of retinal vascular caliber with clinical CAD seen in epidemiological studies may not be applicable to clinical symptomatic patients and may be related to microvascular, rather than macrovascular, mechanisms.

Outcomes after percutaneous coronary intervention in contemporary Australian practice: insights from a large multicentre registry.

OBJECTIVE: To examine short- and medium-term outcomes of percutaneous coronary interventions (PCIs), with a focus on comparing drug-eluting stents (DESs) with bare-metal stents (BMSs). DESIGN, SETTING AND PARTICIPANTS: Retrospective analysis of data from the Melbourne Interventional Group (MIG) registry, a large multicentre Australian registry. The study cohort consisted of 6364 consecutive patients undergoing 7167 PCIs between April 2004 and August 2007. MAIN OUTCOME MEASURES: Clinical events including death, myocardial infarction (MI), target lesion revascularisation (TLR), target vessel revascularisation (TVR) and major adverse cardiac events (MACE) (a composite of death, MI and TVR), at 30 days and at 12 months. RESULTS: The cohort was predominantly male (74%), with a mean age of 64.7 years (SD, 12.0 years). DESs were used in 3482 (51.4%) of PCIs. In the overall cohort, rates of clinical events were low at 30 days: mortality (1.9%), MI (2.4%), TLR (2.0%), TVR (2.4%) and MACE (5.7%). At 12 months, event rates were: mortality (5.2%), MI (6.0%), TLR (5.8%), TVR (8.2%) and MACE (16.2%). Patients receiving DESs had similar mortality rates to those receiving BMSs (4.0% v 6.0%; P = 0.62 [propensity score-adjusted]); late thrombosis rates were also similar in the two groups (0.8% v 1.1%; P = 0.38). The proportion of patients receiving DESs fell significantly over time, from 54.9% in the first 24 months to 44.7% in the last 15 months of the study period (P < 0.01). Independent predictors of 12-month mortality included diabetes, renal failure, ST-segment-elevation MI and cardiogenic shock. CONCLUSION: Our clinical event rates were comparable with international registry outcomes. Rates of mortality and stent thrombosis were no higher in patients with DESs than those with BMSs. Although DESs were used in about half the procedures (preferentially for higher-risk lesions), recent trends suggest their use is in decline.