BACKGROUND: Percutaneous coronary intervention (PCI) has witnessed rapid technological advancements, resulting in improved safety and effectiveness over time. Little, however, is known about the temporal impact on patient-reported symptoms and quality of life after PCI. METHODS AND RESULTS: Temporal trends in post-PCI symptoms were analyzed using 8879 consecutive patients enrolled in the National Heart, Lung, and Blood Institute-sponsored Dynamic Registry (wave 1: 1997 [bare metal stents], wave 2: 1999 [uniform use of stents], wave 3: 2001 [brachytherapy], wave 4, 5: 2004, 2006 [drug eluting stents]). Patients undergoing PCI in the recent waves were older and more often reported comorbidities. However, fewer patients across the waves reported post-PCI angina at one year (wave 1 to 5: 24%, 23%, 18%, 20%, 20%; P(trend)<0.001). The lower risk of angina in recent waves was explained by patient characteristics including use of antianginal medications at discharge (relative risk [95% CI] for waves 2, 3, 4 versus 1: 1.0 [0.9 to 1.2], 0.9 [0.7 to 1.1], 1.0 [0.8 to 1.3], 0.9 [0.7 to 1.1]). Similar trend was seen in the average quality of life scores over time (adjusted mean score for waves 1 to 5: 6.2, 6.5, 6.6 and 6.6; P(trend)=0.01). Other factors associated with angina at 1 year included younger age, female gender, prior revascularization, need for repeat PCI, and hospitalization for myocardial infarction over 1 year. CONCLUSIONS: Favorable temporal trends are seen in patient-reported symptoms after PCI in routine clinical practice. Specific subgroups, however, remain at risk for symptoms at 1 year and thus warrant closer attention.

BACKGROUND: The recent recognition that coronary-artery stenting has improved the short- and long-term outcomes of patients treated with angioplasty has made it necessary to reevaluate the relative benefits of bypass surgery and percutaneous interventions in patients with multivessel disease. METHODS: A total of 1205 patients were randomly assigned to undergo stent implantation or bypass surgery when a cardiac surgeon and an interventional cardiologist agreed that the same extent of revascularization could be achieved by either technique. The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at one year. The costs of hospital resources used were also determined. RESULTS: At one year, there was no significant difference between the two groups in terms of the rates of death, stroke, or myocardial infarction. Among patients who survived without a stroke or a myocardial infarction, 16.8 percent of those in the stenting group underwent a second revascularization, as compared with 3.5 percent of those in the surgery group. The rate of event-free survival at one year was 73.8 percent among the patients who received stents and 87.8 percent among those who underwent bypass surgery (P<0.001 by the log-rank test). The costs for the initial procedure were $4,212 less for patients assigned to stenting than for those assigned to bypass surgery, but this difference was reduced during follow-up because of the increased need for repeated revascularization; after one year, the net difference in favor of stenting was estimated to be $2,973 per patient. CONCLUSION: As measured one year after the procedure, coronary stenting for multivessel disease is less expensive than bypass surgery and offers the same degree of protection against death, stroke, and myocardial infarction. However, stenting is associated with a greater need for repeated revascularization.

BACKGROUND: Previous studies have examined medication use among patients with coronary artery disease who have suffered an acute myocardial infarction (MI). However, little is known about medication use among patients with coronary artery disease who undergo percutaneous coronary intervention (PCI). OBJECTIVE: To examine the patterns of use of medical therapy among patients who undergo PCI; and to examine the determinants of medical therapy in these patients. METHODS: The Routine versus Selective Exercise Treadmill Testing after Angioplasty (ROSETTA) registry is a prospective multicentre study examining the use of functional testing after PCI. The medication use was examined among 787 patients who were enrolled in the ROSETTA registry at 13 clinical centres in five countries. RESULTS: Most patients were men (mean age 61+/-11 years, 76% male) who underwent single vessel PCI (85%) with stent implantation (58%). At admission, discharge and six months, rates of acetylsalicylic acid use were 77%, 96% and 93%, respectively (discharge versus six months, P<0.0001). Rates of use of other oral antiplatelet agents were 11%, 59% and 2% (P=0.02). For individual anti-ischemic medications, rates of use were as follows: beta-blockers 49%, 58% and 59% (P<0.0001); calcium antagonists 34%, 43% and 42% (P<0.0001); and nitrates 42%, 56% and 43% (P<0.0001). Rates of use of combination anti-ischemic medications were as follows: triple therapy 7%, 9% and 9% (P<0.0001); double therapy 34%, 47% and 38% (P<0.0001); monotherapy 36%, 36% and 41% (P<0.0001); and no anti-ischemic therapy 23%, 8% and 12% (P<0.0001). Rates of use of angiotensin-converting enzyme inhibitors were 25%, 33% and 32% (P<0.0001), and rates of use of lipid lowering agents were 41%, 52% and 61% (P<0.0001). CONCLUSIONS: Trials and guidelines statements have favourably affected the rates of use of acetylsalicylic acid and other antiplatelet agents after PCI. However, in spite of patients undergoing a successful revascularization procedure, physicians do not reduce the use of anti-ischemic medical therapy.

BACKGROUND: In patients with coronary artery disease who receive metallic drug-eluting coronary stents, adverse events such as late target-lesion failure may be related in part to the persistent presence of the metallic stent frame in the coronary-vessel wall. Bioresorbable vascular scaffolds have been developed to attempt to improve long-term outcomes. METHODS: In this large, multicenter, randomized trial, 2008 patients with stable or unstable angina were randomly assigned in a 2:1 ratio to receive an everolimus-eluting bioresorbable vascular (Absorb) scaffold (1322 patients) or an everolimus-eluting cobalt-chromium (Xience) stent (686 patients). The primary end point, which was tested for both noninferiority (margin, 4.5 percentage points for the risk difference) and superiority, was target-lesion failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization) at 1 year. RESULTS: Target-lesion failure at 1 year occurred in 7.8% of patients in the Absorb group and in 6.1% of patients in the Xience group (difference, 1.7 percentage points; 95% confidence interval, -0.5 to 3.9; P=0.007 for noninferiority and P=0.16 for superiority). There was no significant difference between the Absorb group and the Xience group in rates of cardiac death (0.6% and 0.1%, respectively; P=0.29), target-vessel myocardial infarction (6.0% and 4.6%, respectively; P=0.18), or ischemia-driven target-lesion revascularization (3.0% and 2.5%, respectively; P=0.50). Device thrombosis within 1 year occurred in 1.5% of patients in the Absorb group and in 0.7% of patients in the Xience group (P=0.13). CONCLUSIONS: In this large-scale, randomized trial, treatment of noncomplex obstructive coronary artery disease with an everolimus-eluting bioresorbable vascular scaffold, as compared with an everolimus-eluting cobalt-chromium stent, was within the prespecified margin for noninferiority with respect to target-lesion failure at 1 year. (Funded by Abbott Vascular; ABSORB III ClinicalTrials.gov number, NCT01751906.).

Persistence or recurrence of angina after successful percutaneous coronary intervention (PCI) represent an important clinical issue involving from one fifth to one third of patients undergoing myocardial revascularization at one-year follow-up. A systematic approach to this syndrome is strongly needed. Precision medicine is particularly important in addressing angina after successful PCI because of the multiple underlying causes. Restenosis or coronary atherosclerosis progression explain symptom recurrence after successful PCI in some patients, while functional causes, including vasomotor abnormalities of epicardial coronary arteries and/or coronary microvascular dysfunction, explain symptoms in the remaining patients. In this review, we summarize the mechanisms of persistent or recurrent angina after PCI, proposing a diagnostic algorithm and a systematic therapeutic approach.

Background The role of endothelial dysfunction in predicting angina recurrence after percutaneous coronary intervention is unknown. Design We assessed the role of peripheral endothelial dysfunction measured by reactive-hyperaemia peripheral-artery tonometry (RH-PAT) in predicting recurrence of angina after percutaneous coronary intervention. Methods We enrolled consecutive patients undergoing percutaneous coronary intervention with second-generation drug-eluting stents. RH-PAT was measured at discharge. The endpoint was repeated coronary angiography for angina recurrence and/or evidence of myocardial ischaemia at follow-up. Patients with in-stent restenosis and/or significant de novo stenosis were defined as having angina with obstructed coronary arteries (AOCA); all other patients as having angina with non-obstructed coronary arteries (ANOCA). Results Among 100 patients (mean age 66.7 +/- 10.4 years, 80 (80.0%) male, median follow-up 16 (3-20) months), AOCA occurred in 14 patients (14%), ANOCA in nine patients (9%). Repeated coronary angiography occurred more frequently among patients in the lower RH-PAT index tertile compared with middle and upper tertiles (14 (41.2%) vs. 6 (18.2%) vs. 3 (9.1%), p = 0.006, respectively). ANOCA was more frequent in the lower RH-PAT index tertile compared with middle and upper tertiles. In the multivariate regression analysis, the RH-PAT index only predicted angina recurrence. The receiver operating characteristic curve of the RH-PAT index to predict the angina recurrence demonstrated an area under the curve of 0.79 (95% confidence interval: 0.69-0.89; p < 0.001), with a cut-off value of 1.705, having sensitivity 74% and specificity 70%. Conclusions Non-invasive assessment of peripheral endothelial dysfunction using RH-PAT might help in the prediction of recurrent angina after percutaneous coronary intervention, thus identifying patients who may need more intense pharmacological treatment and risk factor control.

BACKGROUND: Recurrent angina (RA) after percutaneous coronary intervention (PCI) remains a challenging problem that confronts cardiologists in routine clinical practice. In patients without epicardial coronary causes, RA is commonly speculated as resulting from coronary microvascular dysfunction. The aim of this study was to investigate the coronary microvascular function in patients with RA late after successful PCI and without epicardial stenosis at the time of repeat angiography. METHODS: We studied 39 consecutive patients with RA in whom PCI was successfully performed 6 to 12 months previously because of angina and single-vessel disease and without restenosis and disease progression at the time of repeat angiography. Twelve subjects without RA were recruited as the control group. Thermodilution-derived coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured using a pressure-temperature sensor-tipped coronary wire. The exercise treadmill test was performed according to the Bruce protocol. RESULTS: Patients with RA showed significantly higher IMR and lower CFR than control subjects, in the target arteries and in the reference vessels (P < 0.05). The hyperemic IMR was more remarkably increased in the target arteries than in the reference vessels (29.3 +/- 11.7 vs 24.4 +/- 9.7; P = 0.008). The hyperemic IMR was increased and the CFR was impaired more significantly in patients with a positive exercise treadmill test (P < 0.05). CONCLUSIONS: Using an intracoronary thermodilution method, to our knowledge, we have for the first time confirmed that, in patients who underwent successful coronary stenting and without epicardial stenosis at repeat angiography late after PCI, coronary microvascular dysfunction was responsible for the RA.

OBJECTIVES: We investigated whether coronary microvascular dysfunction predicts major adverse outcomes during follow-up among women with signs and symptoms of ischemia. BACKGROUND: Altered coronary reactivity occurs frequently in women evaluated for suspected ischemia, and the endothelium-dependent component is linked with adverse outcomes. Possible links between endothelium-independent microvascular coronary reactivity and adverse outcomes remain uncertain. METHODS: As part of the National Heart, Lung and Blood Institute-sponsored WISE (Women's Ischemia Syndrome Evaluation), we investigated relationships between major adverse outcomes and baseline coronary flow reserve (CFR) after intracoronary adenosine in 189 women referred to evaluate suspected ischemia. RESULTS: At a mean of 5.4 years, we observed significant associations between CFR and major adverse outcomes (death, nonfatal myocardial infarction, nonfatal stroke, or hospital stay for heart failure). An exploratory receiver-operator characteristic analysis identified CFR <2.32 as the best discriminating threshold for adverse outcomes (event rate 26.7%; and >or=2.32 event rate 12.2%; p = 0.01). Lower CFR was associated with increased risk for major adverse outcomes (hazard ratio: 1.16, 95% confidence interval: 1.04 to 1.30; p = 0.009). This held true among the 152 women without obstructive coronary artery disease (CAD) (hazard ratio: 1.20, 95% confidence interval: 1.05 to 1.38; p = 0.008). The CFR significantly improved prediction of adverse outcomes over angiographic CAD severity and other risk conditions. CONCLUSIONS: Among women with suspected ischemia and atherosclerosis risk factors, coronary microvascular reactivity to adenosine significantly improves prediction of major adverse outcomes over angiographic CAD severity and CAD risk factors. These findings suggest that coronary microvessels represent novel targets for diagnostic and therapeutic strategies to predict and limit adverse outcomes in women. (Women's Ischemia Syndrome Evaluation [WISE]; NCT00000554).

While fractional flow reserve (FFR) is a good diagnostic index to assess the myocardial ischemia, coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) can be used to address microvascular status without any significant epicardial disease. The independent predictors for FFR and IMR are totally different and acts differently on the macro- and micro-vascular dysfunction. In high FFR patients, low CFR and high IMR which indicates the presence of overt microvascular disease demonstrated poor prognosis. Thus, comprehensive physiological assessments using FFR, CFR and IMR could improve the ability to discriminate patients at high risk of future events.

INTRODUCTION: Stenting with metal stents can affect microcirculatory function. The impact of BVS on the microvascular network has not been studied. METHODS: A total of 30 patients with bifurcation disease of Medina (X,X,0) scheduled for elective PCI with the ABSORB BVS were studied. Pressure wire studies were performed before and after scaffold implantation and at a mean follow-up of 9 months. At each time point, FFR, IMR, and CFR were calculated using the thermodilution method. RESULTS: Following scaffold implantation, FFR change from pre-PCI, post-PCI and follow-up was 0.76, 0.92 and 0.91, respectively (P < 0.001 from pre to post-PCI and P = 0.91 from post-PCI to follow-up). There was a statistically significant improvement between pre- and post-procedural IMR (median 27.7 to 17.9, P = 0.02) and CFR (median 2.2 to 2.9, P = 0.02). Median IMR at follow-up (23.6) remained numerically lower than pre-procedure but this was not statistically significant (P = 0.05). Similarly, while median CFR at follow-up remained at post-procedural level (2.9), this effect did not reach statistical significance (P = 0.06). CONCLUSION: There is an immediate reduction in microvascular resistance after elective BVS implantation but this effect is not sustained long term.

Since its introduction, the TIMI frame count method has contributed to the understanding of the pathophysiology of coronary artery disease. In this article, the evolution of the TFC method and its applicability in the assessment of various therapeutic modalities are described.

BACKGROUND: This study investigated the effects of the intracoronary injection of nicorandil and tirofiban on myocardial perfusion and short-term prognosis in elderly patients with acute ST-segment elevation myocardial infarction (STEMI) after emergency percutaneous coronary intervention (PCI). METHODS: Seventy-eight STEMI patients with age >65 years who underwent emergency PCI were consecutively enrolled. These patients received conventional PCI and were randomly divided into a control group and a treatment group (n=39 per group). The control group received an intracoronary injection of tirofiban followed by a maintenance infusion for 36 hours after surgery. The treatment group received intracoronary injection of tirofiban and nicorandil, and then intravenous infusion of tirofiban and nicorandil 36 hours after surgery. The following parameters were measured: TIMI grade, corrected TIMI frame count (cTFC), TIMI myocardial perfusion grade (TMPG), ST-segment resolution (STR) rate 2 hours post-operatively, resolution of ST-segment elevation (STR) at 2 hours postoperatively, peak level of serum CK-MB, left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) at 7-10 days postoperatively, and major adverse cardiac events (MACEs) in-hospital and within 30 days post-operatively. RESULTS: Compared with the control group, more patients in the treatment group had TIMI 3 and TMPG 3, and STR after PCI was significantly higher. The treatment group also had significantly lower cTFC, lower infarction relative artery (IRA), lower peak CK-MB, and no reflow ratio after PCI. The treatment group had significantly higher LVEDD and LVEF but lower incidence of MACEs than the control group. CONCLUSION: The intracoronary injection of nicorandil combined with tirofiban can effectively improve myocardial reperfusion in elderly STEMI patients after emergency PCI and improve short-term prognoses.

BACKGROUND: Although the Thrombolysis in Myocardial Infarction (TIMI) flow grade is valuable and widely used qualitative measure in angiographic trials, it is limited by its subjective and categorical nature. METHODS AND RESULTS: In normal patients and patients with acute myocardial infarction (MI) (TIMI 4), the number of cineframes needed for dye to reach standardized distal landmarks was counted to objectively assess an index of coronary blood flow as a continuous variable. The TIMI frame-counting method was reproducible (mean absolute difference between two injections, 4.7 +/- 3.9 frames, n=85). In 78 consecutive normal arteries, the left anterior descending coronary artery (LAD) TIMI frame count (36.2 +/- 2.6 frames) was 1.7 times longer than the mean of the right coronary artery (20.4 +/- 3.0) and circumflex counts (22.2 +/- 4.1, P < .001 for either versus LAD). Therefore, the longer LAD frame counts were corrected by dividing by 1.7 to derive the corrected TIMI frame count (CTFC). The mean CTFC in culprit arteries 90 minutes after thrombolytic administration followed a continuous unimodal distribution (there were not subpopulations of slow and fast flow) with a mean value of 39.2 +/- 20.0 frames, which improved to 31.7 +/- 12.9 frames by 18 to 36 hours (P < .001). No correlation existed between improvements in CTFCs and changes in minimum lumen diameter (r=-.05, P=.59). The mean 90-minute CTFC among nonculprit arteries (25.5 +/- 9.8) was significantly higher (flow was slower) compared with arteries with normal flow in the absence of acute MI (21.0 +/- 3.1, P < .001) but improved to that of normal arteries by 1 day after thrombolysis (21.7 +/- 7.1, P=NS). CONCLUSIONS: The CTFC is a simple, reproducible, objective and quantitative index of coronary flow that allows standardization of TIMI flow grades and facilitates comparisons of angiographic end points between trials. Disordered resistance vessel function may account in part for reductions in flow in the early hours after thrombolysis.

In 2013 the European Society of Cardiology (ESC) released new guidelines on the management of stable coronary artery disease. These guidelines update and replace the previous ESC guidelines on the management of stable angina pectoris, issued in 2006. There are several new aspects in the 2013 ESC guidelines compared with the 2006 version. This opinion paper provides an in-depth interpretation of the ESC guidelines with regard to these issues, to help physicians in making evidence-based therapeutic choices in their routine clinical practice. The first new element is the definition of stable coronary artery disease itself, which has now broadened from a 'simple' symptom, angina pectoris, to a more complex disease that can even be asymptomatic. In the first-line setting, the major changes in the new guidelines are the upgrading of calcium channel blockers, the distinction between dihydropyridines and non-dihydropyridine calcium channel blockers, and the presence of important statements regarding the combination of calcium channel blockers with beta-blockers. In the second-line setting, the 2013 ESC guidelines recommend the addition of long-acting nitrates, ivabradine, nicorandil or ranolazine to first-line agents. Trimetazidine may also be considered. However, no clear distinction is made among different second-line drugs, despite different quality of evidence in favour of these agents. For example, the use of ranolazine is supported by strong and recent evidence, while data supporting the use of the traditional agents appear relatively scanty.

BACKGROUND: The TIMI risk score for unstable angina and non-ST elevation myocardial infarction is an effective tool for predicting the risk of death and ischemic events among patients with non-ST elevation acute coronary syndromes, as well as for identifying those who are likely to benefit most from low-molecular-weight heparin and glycoprotein IIb/IIIa inhibition. METHODS: To explore the pathobiologic basis for this interaction, we evaluated the relationship between the risk score, assessed at presentation, and angiographic findings among patients with non-ST elevation acute coronary syndromes. Angiographic data regarding thrombus, epicardial flow, and lesion severity were available for 1491 patients from the angiographic substudy of PRISM-PLUS. RESULTS: Patients with risk scores of 5 to 7 (N = 435) were more likely to have a severe culprit stenosis (81% vs 58%, P < .001) and multivessel disease (80% vs 43%, P < .001) compared to those with scores of 0 to 2 (N = 220). The probability of left main disease (P = .01), visible thrombus, and impaired flow in the culprit lesion also increased progressively with rising risk scores (P < .001). Of the risk indicators that comprise the score, history of coronary disease, advanced age, and ST changes showed the strongest association with severe epicardial disease. Positive biomarkers of necrosis, ST changes, and prior aspirin use emerged as stronger correlates of visible thrombus and/or impaired culprit artery flow. CONCLUSIONS: The TIMI risk score identifies patients who are more likely to have intracoronary thrombus, impaired flow, and increased burden of coronary atherosclerosis. These findings likely explain in part the particular benefit of potent antithrombin and antiplatelet agents among patients with higher risk scores.

Angina, heart failure with preserved ejection fraction (HFpEF) and coronary microvascular dysfunction (CMD) in the absence of obstructive coronary artery disease (CAD) are more common in women and are associated with adverse cardiovascular prognosis. Cardiac magnetic resonance imaging (CMRI) is established for assessment of left ventricular (LV) morphology and systolic function and is increasingly used to assess myocardial perfusion and diastolic function. Indeed, stress CMRI allows measurement of myocardial perfusion reserve index (MPRI) using semi-quantitative techniques, and quantification of LV volumetric filling patterns provides valuable insight into LV diastolic function. The utility of these two techniques remains limited, because reference control values for MPRI and LV diastolic function in asymptomatic middle-aged, women have not previously been established. To address this limitation, we recruited twenty women, without clinical cardiovascular disease or cardiovascular risk factors, with normal maximal Bruce protocol exercise treadmill testing. Subjects underwent CMRI (1.5 tesla) using a standardized protocol of adenosine stress and rest perfusion and LV cinematic imaging. Commercially available with automated CMRI segmentation was used for calculation of MPRI, LV filling profiles, and ejection fraction. Mean age was 54+/-9 years and mean body mass index was 25+/-4 kg/m(3). The exercise treadmill testing results demonstrated a normotensive group with normal functional capacity and hemodynamic response. We report reference control values for semi-quantitative MPRI as well as measures of LV systolic and diastolic function including ejection fraction, stroke volume, peak filling rate (PFR), PFR adjusted for end-diastolic volume (EDV) and stroke volume, time to PFR, and EDV index. The data herein provide reference values for MPRI and diastolic function in a cohort of healthy, middle-aged of women. These reference values may be used for comparison with a variety of patient populations, including women with CMD and HFpEF.

Women with cardiac chest pain indicated by signs and symptoms of myocardial ischemia in the absence of obstructive CAD are often labelled as cardiac syndrome X (CSX). A subset of patients with CSX may have symptoms of ischemia due to microvascular dysfunction. Angina due to microvascular coronary dysfunction (MCD) is an etiologic mechanism in women with vascular dysfunction. New data provide improve understanding of coronary vascular dysfunction and resultant myocardial ischemia that characterize MCD among patients with cardiac syndrome X. MCD has an adverse prognosis and health care cost expenditure comparable to obstructive CAD. The high prevalence of this condition, particularly in women, adverse prognosis and substantial health care costs, coupled with a lack of evidence regarding treatment strategies, places MCD as a research priority area.

In the original publication of this article [1] Fig. 1 was incorrect due to the use of a colour bar with wrong range in error.

The aim of this present study was to investigate if overweight individuals exhibit signs of vascular dysfunction associated with a high risk for cardiovascular disease (CVD). One hundred lean and 100 overweight participants were recruited for the present study. Retinal microvascular function was assessed using the Dynamic Retinal Vessel Analyser (DVA), and systemic macrovascular function by means of flow-mediated dilation (FMD). Investigations also included body composition, carotid intimal-media thickness (c-IMT), ambulatory blood pressure monitoring (BP), fasting plasma glucose, triglycerides (TG), cholesterol levels (HDL-C and LDL-C), and plasma von Willebrand factor (vWF). Overweight individuals presented with higher right and left c-IMT (p = 0.005 and p = 0.002, respectively), average 24-h BP values (all p < 0.001), plasma glucose (p = 0.008), TG (p = 0.003), TG: HDL-C ratio (p = 0.010), and vWF levels (p = 0.004). Moreover, overweight individuals showed lower retinal arterial microvascular dilation (p = 0.039) and baseline-corrected flicker (bFR) responses (p = 0.022), as well as, prolonged dilation reaction time (RT, p = 0.047). These observations emphasise the importance of vascular screening and consideration of preventive interventions to decrease vascular risk in all individuals with adiposity above normal range.

Ischemia-reperfusion (IR) injury is a common complication of a variety of cardiovascular diseases, including ischemic stroke and myocardial infarction (MI). While timely re-establishment of blood flow in a thrombosed artery is the primary goal of acute therapy in these diseases, paradoxically, reperfusion of ischemic tissue can cause widespread microvascular dysfunction that significantly exacerbates organ damage. Reperfusion injury is associated with activation of the humoral and cellular components of the hemostatic and innate immune systems and also with excessive reactive oxygen species production, endothelial dysfunction, thrombosis, and inflammation. Platelets are critical mediators of thromboinflammation during reperfusion injury and a hyperactive platelet phenotype may contribute to an exaggerated IR injury response. This is particularly relevant to diabetes which is characteristically associated with hyperactive platelets, significantly worse IR injury, increased organ damage, and increased risk of death. However, the mechanisms underlying vulnerability to IR injury in diabetic individuals is not well defined, nor the role of

BACKGROUND: There is uncertainty regarding the optimal duration of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). Our goal was to evaluate the cost-effectiveness of different durations of DAPT. METHODS: We created a probabilistic patient-level Markov microsimulation model to assess the discounted lifetime costs and quality-adjusted life years (QALYs) of short duration (3-6 months: short-duration group) vs standard therapy (12 months: standard-duration group) vs prolonged therapy (30-36 months: long-duration group) in patients undergoing PCI. RESULTS: The majority of patients in the model underwent PCI for stable angina (47.1%) with second-generation drug-eluting stents (62%) and were receiving clopidogrel (83.6%). Short-duration DAPT was the most effective strategy (7.163 +/- 1.098 QALYs) compared with standard-duration DAPT (7.161 +/- 1.097 QALYs) and long-duration DAPT (7.156 +/- 1.097 QALYs). However, the magnitude of these differences was very small. Similarly, the average discounted lifetime cost was CAN$24,859 +/- $6533 for short duration, $25,045 +/- $6533 for standard duration, and $25,046 +/- $6548 for long duration. Thus, in the base-case analysis, short duration was dominant, being more effective and less expensive. However, there was a moderate degree of uncertainty, because short duration was the preferred option in only approximately 55% of simulations at a willingness to pay threshold of $50,000. CONCLUSIONS: Based on a stable angina cohort receiving clopidogrel with second-generation stents, a short duration of DAPT was marginally better. However, the differences are minimal, and decisions about duration of therapy should be driven by clinical data, patient risk of adverse events, including bleeding, and cardiovascular events.

Resistant hypertension is associated with increased risk for cardiovascular events. Coronary flow reserve (CFR) is impaired in patients with hypertension and an independent predictor of cardiac mortality. However, there are no published data on CFR in the subset of treatment-resistant hypertension. The aim of this study was to assess CFR in patients with resistant hypertension. Twenty-five consecutive patients with primary resistant hypertension, scheduled for renal denervation, 25 matched patients with controlled hypertension, and 25 healthy controls underwent transthoracic colour Doppler echocardiography at rest and during adenosine infusion. Patients with hypertension were pair-matched with regard to age, sex, ischemic heart disease, diabetes mellitus, smoking status, and body-mass index. Healthy controls were selected according to age and sex. Mean flow velocity was measured in the left coronary anterior descending artery. Baseline mean flow velocities were similar in patients with controlled and resistant hypertension. CFR was significantly lower in patients with resistant hypertension as compared to individuals with non-resistant hypertension (2.7 +/- 0.6 vs. 3.1 +/- 0.8; p = 0.03). Systolic office blood pressure was significantly higher in patients with resistant hypertension (169 +/- 20 vs. 144 +/- 21 mm Hg; p < 0.01). Heart rate, ventricular mass, and ejection fraction were similar in the two groups. Healthy controls showed significantly lower baseline velocity, higher CFR, and lower blood pressure as compared to hypertensives. Resistant hypertension was associated with impaired CFR as compared to individuals with non-resistant hypertension indicating impaired cardiac microvascular function which may contribute to the increased risk of adverse outcome in patients with resistant hypertension.