Cardiovascular and Noncardiovascular Prescribing and Mortality After Takotsubo Comparison With Myocardial Infarction and General Population.

Background: Takotsubo syndrome is an increasingly common cardiac emergency with no known evidence-based treatment. Objectives: The purpose of this study was to investigate cardiovascular mortality and medication use after takotsubo syndrome. Methods: In a case-control study, all patients with takotsubo syndrome in Scotland between 2010 and 2017 (n = 620) were age, sex, and geographically matched to individuals in the general population (1:4, n = 2,480) and contemporaneous patients with acute myocardial infarction (1:1, n = 620). Electronic health record data linkage of mortality outcomes and drug prescribing were analyzed using Cox proportional hazard regression models. Results: Of the 3,720 study participants (mean age, 66 years; 91% women), 153 (25%) patients with takotsubo syndrome died over the median of 5.5 years follow-up. This exceeded mortality rates in the general population (N = 374 [15%]; HR: 1.78 [95% CI: 1.48-2.15], P < 0.0001), especially for cardiovascular (HR: 2.47 [95% CI: 1.81-3.39], P < 0.001) but also noncardiovascular (HR: 1.48 [95% CI: 1.16-1.87], P = 0.002) deaths. Mortality rates were lower for patients with takotsubo syndrome than those with myocardial infarction (31%, 195/620; HR: 0.76 [95% CI: 0.62-0.94], P = 0.012), which was attributable to lower rates of cardiovascular (HR: 0.61 [95% CI: 0.44-0.84], P = 0.002) but not non-cardiovascular (HR: 0.92 [95% CI: 0.69-1.23], P = 0.59) deaths. Despite comparable medications use, cardiovascular therapies were consistently associated with better survival in patients with myocardial infarction but not in those with takotsubo syndrome. Diuretic (P = 0.01), anti-inflammatory (P = 0.002), and psychotropic (P < 0.001) therapies were all associated with worse outcomes in patients with takotsubo syndrome. Conclusions: In patients with takotsubo syndrome, cardiovascular mortality is the leading cause of death, and this is not associated with cardiovascular therapy use.

Succinobucol-eluting stents increase neointimal thickening and peri-strut inflammation in a porcine coronary model.

OBJECTIVE: The aim of this study was to assess the efficacy of stent-based delivery of succinobucol alone and in combination with rapamycin in a porcine coronary model. BACKGROUND: Current drugs and polymers used to coat coronary stents remain suboptimal in terms of long term efficacy and safety. Succinobucol is a novel derivative of probucol with improved antioxidant and anti-inflammatory properties. METHODS: Polymer-free Yukon stents were coated with 1% succinobucol (SucES), 2% rapamycin (RES), or 1% succinobucol plus 2% rapamycin solutions (SucRES) and compared with a bare metal stent (BMS). RESULTS: The in vivo release profile of SucES indicated drug release up to 28 days (60% drug released at 7 days); 41 stents (BMS, n = 11; SucES, n =10; RES, n = 10; SucRES, n = 10) were implanted in the coronary arteries of 17 pigs. After 28 days, mean neointimal thickness was 0.31 ± 0.14 mm for BMS, 0.51 ± 0.14 mm for SucES, 0.19 ± 0.11 mm for RES, and 0.36 ± 0.17 mm for SucRES (P < 0.05 for SucES vs. BMS). SucES increased inflammation and fibrin deposition compared with BMS (P < 0.05), whereas RES reduced inflammation compared with BMS (P < 0.05). CONCLUSION: In this model, stent-based delivery of 1% succinobucol using a polymer-free stent platform increased neointimal formation and inflammation following coronary stenting.

Cardiovascular disease behavioural risk factors in rural interventions: cross-sectional study.

This study aims to (1) assess the distribution of variables within the population and the prevalence of cardiovascular disease (CVD) behavioural risk factors in patients, (2) identify target risk factor(s) for behaviour modification intervention, and (3) develop an analytical model to define cluster(s) of risk factors which could help make any generic intervention more targeted to the local patient population. Study patients with at least one CVD behavioural risk factor living in a rural region of the Scottish Highlands. The study used the STROBE methodology for cross-sectional studies. Demographic and clinical data of patients (n = 2025) in NHS Highlands hospital were collected at the point of admission for PCI between 04.01.2016 and 31.12.2019. Collected data distributions were analysed by CVD behavioural risk factors for prevalence, associations, and direction of associations. Cluster definition was measured by assignment of a unit score each for the overall level of prevalence and significance of associations, and general logistics modelling for direction and significance of the risk. The mean (SD) age was 69.47(± 10.93) years [95% CI (68.99-69.94)]. The key risk factors were hyperlipidaemia, hypertension, and elevated body mass index (BMI). Approximately 40% of the population have multiple risk factor counts of two. Analytical measures revealed a population risk factor cluster with elevated BMI [77.5% (1570/2025)] that is mostly either hyperlipidaemic [9.43%, co-eff. (17), P = 0.007] or hypertensive [22.72%, co-eff. (17), P = 0.99] as key risk factor clusters. Carefully modelled analyses revealed clustered risk associated with elevated BMI. This information would support a strategy for targeting risk factor clusters in novel interventions to improve implementation efficiency. Exposure to and outcome of an elevated BMI is linked more to the population's socio-economic outcomes rather than to regional rurality or urbanity.

Using latent class analysis to identify clinical features of patients with occlusive myocardial infarction: Preangiogram prediction remains difficult.

BACKGROUND: Treatment decisions in myocardial infarction (MI) are currently stratified by ST elevation (ST-elevation myocardial infarction [STEMI]) or lack of ST elevation (non-ST elevation myocardial infarction [NSTEMI]) on the electrocardiogram. This arose from the assumption that ST elevation indicated acute coronary artery occlusion (OMI). However, one-quarter of all NSTEMI cases are an OMI, and have a higher mortality. The purpose of this study was to identify features that could help identify OMI. METHODS: Prospectively collected data from patients undergoing percutaneous coronary intervention (PCI) was analyzed. Data included presentation characteristics, comorbidities, treatments, and outcomes. Latent class analysis was undertaken, to determine patterns of presentation and history associated with OMI. RESULTS: A total of 1412 patients underwent PCI for acute MI, and 263 were diagnosed as OMI. Compared to nonocclusive MI, OMI patients are more likely to have fewer comorbidities but no difference in cerebrovascular disease and increased acute mortality (4.2% vs. 1.1%; p < .001). Of OMI, 29.5% had delays to their treatment such as immediate reperfusion therapy. With latent class analysis, while clusters of similar patients are observed in the data set, the data available did not usefully identify patients with OMI compared to non-OMI. CONCLUSION: Features between OMI and STEMI are broadly very similar. However, there was no difference in age and risk of cerebrovascular disease in the OMI/non-OMI group. There are no reliable characteristics therefore for identifying OMI versus non-OMI. Delays to treatment also suggest that OMI patients are still missing out on optimal treatment. An alternative strategy is required to improve the identification of OMI patients.

Radial versus femoral approach for high-speed rotational atherectomy.

OBJECTIVE: The aim of this study was to compare in-hospital outcomes for patients undergoing high-speed rotational atherectomy (HSRA) via the radial and femoral route. BACKGROUND: Transradial access is often avoided for HSRA because of concern over limitations on guide catheter size. No studies have compared a radial and femoral approach for HSRA. METHODS: This is a retrospective comparison of in-hospital outcomes for 151 consecutive patients (75 radial, 76 femoral) undergoing HSRA. RESULTS: Significantly smaller diameter guide catheters (6.3 +/- 0.5 Fr vs. 7.1 +/- 0.8 Fr, P < 0.001) and burrs (1.6 +/- 0.2 mm vs. 1.7 +/- 0.2 mm, P = 0.02) were used in the radial compared with the femoral group. Procedural success (93.3% vs. 94.7%, P = 0.75), procedure time (108.7 +/- 30.5 min vs. 112.8 +/- 35.0 min, P = 0.45), and patient radiation exposure (12125 +/- 8373 vs. 12118 +/- 7831 cGy cm(2), P = 1.00) were similar in radial and femoral groups. There was a trend in favor of radial artery access for major access site bleeding complications (0.0% vs. 5.3%, P = 0.12). The incidence of in-hospital death or myocardial infarction was low in both groups. CONCLUSION: This study shows that radial artery access is a feasible, safe, and effective approach for HSRA. Overall complication rates are low and radial access may be associated with a lower risk of major bleeding complications compared with a femoral approach.

Pro-healing drug-eluting stents: a role for antioxidants?

Current strategies to lower the incidence of ISR (in-stent restenosis) following PCI (percutaneous coronary intervention) are aimed at modifying arterial healing after stent injury. This can impair endothelial recovery and render the vessel prone to acute thrombosis. As early restoration of endothelial integrity inhibits neointimal growth and thrombosis, alternative approaches which encourage this process may provide a more effective long-term result after PCI. Oxidative stress is enhanced after PCI and participates in the regulation of endothelial regeneration and neointimal growth. Moreover, evidence suggests antioxidants improve re-endothelialization and inhibit ISR. By promoting, rather than blocking, the healing process, antioxidant and other therapies may offer an alternative or additional approach over the antiproliferative approaches common to many current devices.

Radial Versus Femoral Access for Rotational Atherectomy: A UK Observational Study of 8622 Patients.

BACKGROUND: Rotational atherectomy (RA) is an important interventional tool for heavily calcified coronary lesions. We compared the early clinical outcomes in patients undergoing RA using radial or femoral access. METHODS AND RESULTS: We identified all patients in England and Wales who underwent RA between January 1, 2005, and March 31, 2014. Eight thousand six hundred twenty-two RA cases (3069 radial and 5553 femoral) were included in the analysis. The study primary outcome was 30-day mortality. Propensity scores were calculated to determine the factors associated with treatment assignment to radial or femoral access. Multivariable logistic regression analysis, using the calculated propensity scores, was performed. Thirty-day mortality was 2.2% in the radial and 2.3% in the femoral group (P=0.76). Radial access was associated with equivalent 30-day mortality (adjusted odds ratio [OR], 1.06; 95% confidence interval [CI], 0.77-1.46; P=0.71), procedural success (OR, 1.04; 95% CI, 0.84-1.29; P=0.73), major adverse cardiac and cerebrovascular events (OR, 1.05; 95% CI, 0.80-1.38; P=0.72), and net adverse clinical events (OR, 0.90; 95% CI, 0.71-1.15; P=0.41), but lower rates of in-hospital major bleeding (OR, 0.62; 95% CI, 0.40-0.98; P=0.04) and major access site complications (OR, 0.05; 95% CI, 0.01-0.38; P=0.004), compared with femoral access. CONCLUSIONS: In this large real-world study of patients undergoing RA, radial access was associated with equivalent 30-day mortality and procedural success, but reduced major bleeding and access site complications, compared with femoral access.

Hybrid Instantaneous Wave-Free Ratio-Fractional Flow Reserve versus Fractional Flow Reserve in the Real World.

BACKGROUND: The instantaneous wave-free ratio (iFR) is a novel method to assess the ischemic potential of coronary artery stenoses. Clinical trial data have shown that iFR has acceptable diagnostic agreement with fractional flow reserve (FFR), the reference standard for the functional assessment of coronary stenoses. This study compares iFR measurements with FFR measurements in a real world, single-center setting. METHODS AND RESULTS: Instantaneous wave-free ratio and FFR were measured in 50 coronary artery lesions in 42 patients, with FFR ≤ 0.8 classified as functionally significant. An iFR-only technique, using a treatment cut-off value, iFR ≤ 0.89, provided a classification agreement of 84% with FFR ≤ 0.80. Use of a hybrid iFR-FFR technique, incorporating FFR measurement for lesions within the iFR gray zone of 0.86-0.93, would improve classification agreement with FFR to 94%, with diagnosis achieved without the need for hyperemia in 57% patients. CONCLUSION: This study in a real-world setting demonstrated good classification agreement between iFR and FFR. Use of a hybrid iFR-FFR technique would achieve high diagnostic accuracy while minimizing adenosine use, compared with routine FFR.

The relationship between oxidised LDL, endothelial progenitor cells and coronary endothelial function in patients with CHD.

OBJECTIVE: The balance between coronary endothelial dysfunction and repair is influenced by many protective and deleterious factors circulating in the blood. We studied the relationship between oxidised low-density lipoprotein (oxLDL), circulating endothelial progenitor cells (EPCs) and coronary endothelial function in patients with stable coronary heart disease (CHD). METHODS: 33 patients with stable CHD were studied. Plasma oxLDL was measured using ELISA, coronary endothelial function was assessed using intracoronary acetylcholine infusion and EPCs were quantified using flow cytometry for CD34(+)/KDR(+) cells. RESULTS: Plasma oxLDL correlated positively with the number of EPCs in the blood (r=0.46, p=0.02). There was a positive correlation between the number of circulating EPCs and coronary endothelial function (r=0.42, p=0.04). There was no significant correlation between oxLDL and coronary endothelial function. CONCLUSIONS: Plasma levels of oxLDL are associated with increased circulating EPCs in the blood of patients with CHD, which may reflect a host-repair response to endothelial injury. Patients with stable CHD had a high prevalence of coronary endothelial dysfunction, which was associated with lower numbers of circulating EPCs, suggesting a mechanistic link between endothelial dysfunction and the pathogenesis of atherosclerosis.

Thrombus aspiration during primary percutaneous coronary intervention for acute myocardial infarction: A review of clinical evidence and guidelines.

Acute ST segment elevation myocardial infarction (STEMI) is characterized by complete thrombotic occlusion of a major coronary artery. Early recanalization of the infarct-related artery is most efficiently delivered by primary percutaneous coronary intervention (PPCI), however this does not always restore normal myocardial perfusion, mainly due to distal embolization of the thrombus and microvascular obstruction. Early evidence for manual thrombus aspiration during PPCI was promising and this was once considered an important aspect of the procedure, especially in patients with a high thrombus burden. However, a large body of evidence from recent major randomized controlled trials (notably TASTE and TOTAL) does not support the routine use of manual thrombus aspiration in patients with STEMI undergoing PPCI.

The effect of reactive oxygen species on whole blood aggregation and the endothelial cell-platelet interaction in patients with coronary heart disease.

BACKGROUND: The effect of reactive oxygen species (ROS) on platelet function in coronary heart disease (CHD) is complex and poorly defined. Platelet aggregation studies in healthy volunteers have demonstrated contrasting results when platelets are exposed to ROS. We investigated the effect of ROS on whole blood aggregation (WBA) and the endothelial cell-platelet interaction in patients with CHD. METHODS AND RESULTS: ROS generated by xanthine and xanthine oxidase caused a concentration-dependent inhibition of WBA in blood from healthy donors and patients with CHD. In patients with CHD, 100 µM xanthine and 100 mU/ml xanthine oxidase inhibited WBA in response to 3 µg/ml collagen by 28.9% (95% CI 15.9%-41.8%, p<0.001) and in response to 5 µM ADP by 36.0% (95% CI 9.6%-62.4%, p=0.005). Using nitrotyrosine expression, platelets isolated from patients with CHD were found to be susceptible to peroxynitrite damage. The addition of 1 × 10(5) cultured endothelial cells inhibited WBA in response to 3 µg/ml collagen by 31.2% (95% CI 12.2%-50.2%, p<0.05) and in response to 5 µM ADP by 31.6% (95% CI 2.5-60.7%, p<0.05). Addition of xanthine and xanthine oxidase did not alter this effect, however pre-treatment of endothelial cells with a nitric oxide synthase inhibitor (L-NAME) partly reversed the inhibition. CONCLUSION: ROS inhibit WBA in blood from patients with CHD. Whilst endothelial cells also inhibit WBA, the effect is attenuated by L-NAME, suggesting that nitric oxide is likely to remain an important protective mechanism against thrombosis in CHD.

Quantifying power output during cycling through measuring strain energy in a bicycle frame.

Quantifying power output is becoming more popular in training and competition for cycling. This popularity comes from the fact that power is a direct means of measuring intensity, which is considered by many to be the most important variable in a successful training program. Although other methods are available for measuring power output, there is no frame that is available that uses strain to quantify power output. Using a frame may prove superior to currently available products. Additionally, strain may prove useful for cycling technique analysis, another critical factor for success. In this study, a cyclocross bicycle frame was instrumented with six strain gages to determine if strain energy in the frame correlates with power output. For pilot data, an 85 kg subject rode the bike on rollers with a fork stand at 250 watts and a cadence of 90 rpm. Although more data needs to be collected and analyzed to find a correlation with power output, initial pilot data shows that the strain in the frame is cyclic in nature when pedaling and has a corresponding frequency with the pedaling cadence. It is hypothesized that the strain in the frame will have a high correlation with power output. While this application is specific to cycling, correlating strain to power output may prove useful in other applications.