Tianyao Huo

Is Aspiration Thrombectomy Beneficial in Patients Undergoing Primary Percutaneous Coronary Intervention? Meta-Analysis of Randomized Trials

Background—It is unclear whether intravenous glycoprotein IIb/IIIa inhibitors or ischemic time might modify any clinical benefits observed with aspiration thrombectomy before primary percutaneous coronary intervention (PCI) in patients with ST-segment–elevation myocardial infarction. Methods and Results—Electronic databases were searched for trials that randomized ST-segment–elevation myocardial infarction patients to aspiration thrombectomy before PCI versus conventional PCI. Summary estimates were constructed using a DerSimonian-Laird model. Seventeen trials with 20 960 patients were available for analysis. When compared with conventional PCI, aspiration thrombectomy was not associated with a significant reduction in the risk of mortality 2.8% versus 3.2% (risk ratio [RR], 0.89; 95% confidence interval [CI], 0.76–1.04; P=0.13), reinfarction 1.3% versus 1.4% (RR, 0.93; 95% CI, 0.73–1.17; P=0.52), the combined outcome of mortality or reinfarction 4.1% versus 4.6% (RR, 0.90; 95% CI, 0.79–1.02; P=0.11), or stent thrombosis 0.9% versus 1.2% (RR, 0.82; 95% CI, 0.62–1.08; P=0.15). Aspiration thrombectomy was associated with a nonsignificant increase in the risk of stroke 0.6% versus 0.4% (RR, 1.45; 95% CI, 0.96–2.21; P=0.08). Meta-regression analysis did not identify a difference for the log RR of mortality, reinfarction, and the combined outcome of mortality or reinfarction with intravenous glycoprotein IIb/IIIa inhibitors (P=0.17, 0.70, and 0.50, respectively) or with ischemic time (P=0.29, 0.66, and 0.58, respectively). Conclusions—Aspiration thrombectomy before primary PCI is not associated with any benefit on clinical end points and might increase the risk of stroke. Concomitant administration of intravenous glycoprotein IIb/IIIa inhibitors and ischemic time did not seem to influence any potential benefits observed with aspiration thrombectomy.

Cardiovascular and Mortality Risk of Apparent Resistant Hypertension in Women With Suspected Myocardial Ischemia: A Report From the NHLBI-Sponsored WISE Study

Background Women are more likely than men to develop resistant hypertension, which is associated with excess risk of major adverse outcomes; however, the impact of resistant hypertension in women with ischemia has not been explicitly studied. In this Womens Ischemia Syndrome Evaluation (WISE) analysis, we assessed long‐term adverse outcomes associated with apparent treatment‐resistant hypertension (aTRH) among women with suspected myocardial ischemia referred for coronary angiography. Methods and Results Women (n=927) were grouped according to baseline blood pressure (BP): normotensive (no hypertension history, BP <140/90 mm Hg, no antihypertensive drugs); controlled (BP <140/90 mm Hg and a hypertension diagnosis or on 1 to 3 drugs); uncontrolled (BP ≥140/90 mm Hg on ≤2 drugs); or aTRH (BP ≥140/90 mm Hg on 3 drugs or anyone on ≥4 drugs). Adverse outcomes (first occurrence of death [any cause], nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure or angina) were collected over 10 years of follow‐up. Apparent treatment‐resistant hypertension prevalence was 10.4% among those with hypertension. Women with aTRH had a greater incidence of adverse outcomes, compared with normotensive women (adjusted hazard ratio [HR], 3.25; 95% confidence interval [CI], 1.94 to 5.43), and women with controlled (HR, 1.77; 95% CI, 1.26 to 2.49) and uncontrolled (HR, 1.62; 95% CI, 1.15 to 2.27) hypertension; outcome differences were evident early in follow‐up. Risk of all‐cause death was greater in the aTRH group, compared to the normotensive women and women with controlled and uncontrolled hypertension. Conclusions In this cohort of women with evidence of ischemia, aTRH was associated with a profoundly increased long‐term risk of major adverse events, including death, that emerged early during follow‐up.

Complete versus culprit-only revascularization in patients with multi-vessel disease undergoing primary percutaneous coronary intervention: A meta-analysis of randomized trials

BACKGROUND The best approach for revascularization of multi-vessel coronary disease in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) is controversial. METHODS We searched the Medline and Web of Science databases, the Cochrane Register of Controlled Trials, and major conference proceedings for clinical trials that randomized STEMI patients with multi-vessel disease to a complete versus culprit-only revascularization strategy. Random effects summary risk ratios (RR) were constructed using a DerSimonian-Laird model. RESULTS A total of 6 trials met our selection criteria, which yielded 1,190 patients. The mean follow-up duration was 20.5 months. The incidence of major adverse cardiac events was significantly reduced in the complete revascularization group versus the culprit-only revascularization group (RR 0.57, 95% confidence interval (CI) 0.41-0.78, p < 0.001). This was due to a lower risk of urgent revascularization with complete revascularization (RR 0.55, 95% CI 0.35-0.86, p = 0.01). A non-significant reduction was observed with complete versus culprit-only revascularization for the combined outcome of mortality or myocardial infarction (RR 0.56, 95% CI 0.30-1.04, p = 0.06). CONCLUSION Complete revascularization of significant coronary lesions at the time of primary PCI in patients with STEMI and multi-vessel disease was associated with better outcomes. This was primarily due to a reduction in the need for urgent revascularization. Larger trials are needed to determine if complete revascularization reduces death or myocardial infarction.

Efficacy and safety of angiotensin receptor blockers in older patients: a meta-analysis of randomized trials.

BACKGROUND The efficacy and safety of angiotensin receptor blockers (ARBs) in the older population is unclear. OBJECTIVES To determine the efficacy and safety of ARBs in older patients. METHODS Randomized trials that compared ARBs to control and reported clinical outcomes in patients with a mean age of 65 years or older were included. Random-effects summary risk ratios (RRs) were constructed. RESULTS A total of 16 trials met our selection criteria, which yielded 113,386 patients. ARBs were associated with a marginal increased risk of all-cause mortality (RR: 1.03, 95% confidence interval (CI): 1.00-1.06, P = 0.05), a nonsignificant increased risk of myocardial infarction (RR: 1.04, 95% CI: 0.96-1.12, P = 0.36), a marginal reduction in heart failure hospitalization (RR: 0.86, 95% CI: 0.74-1.00, P = 0.06), and a significant reduction in the risk of stroke (RR: 0.93, 95% CI: 0.87-0.99, P = 0.03). ARBs were associated with an increased risk of acute kidney injury (RR: 1.48, 95% CI: 1.24-1.77, P < 0.001), hypotension (RR: 1.56, 95% CI: 1.24-1.97, P < 0.001), and hyperkalemia (RR: 1.57, 95% CI: 1.13-2.19, P = 0.008). On the sensitivity analysis including placebo-controlled trials, the risk of all-cause mortality was no longer significant (P = 0.2), while the remainder of the outcomes did not change. CONCLUSION In older patients, the benefit of ARBs compared with control was strongest for stroke reduction, with no (or weak) associations for all-cause mortality, myocardial infarction, and heart failure hospitalization. Benefit was offset by an increased risk of acute kidney injury, hypotension, and hyperkalemia. Thus, ARBs should be used with caution in older patients when clinically indicated.

Critical Appraisal of Bivalirudin versus Heparin for Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Trials

Percutaneous coronary intervention with bivalirudin plus bail-out glycoprotein IIb/IIIa inhibitors has been shown to be as effective as unfractionated heparin plus routine glycoprotein IIb/IIIa inhibitors in preventing cardiac ischemic events, but with a lower bleeding risk. It is unknown whether bivalirudin would have the same beneficial effects if compared with heparin when the use of glycoprotein IIb/IIIa inhibitors was similar between treatment arms. We searched the MEDLINE, Web of Science, and Cochrane databases from inception until March 2015 for randomized trials that compared bivalirudin to heparin in patients undergoing percutaneous coronary intervention. We required that the intended use of glycoprotein IIb/IIIa inhibitors was similar between the study groups. Summary estimates were principally constructed by the Peto method. Fifteen trials met our inclusion criteria, which yielded 25,824 patients. Bivalirudin versus heparin was associated with an increased hazard of stent thrombosis (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.15-1.92, P = .002, I2 = 16.9%), with a similar hazard of myocardial infarction (OR 1.09, 95% CI 0.98-1.22, P = .11, I2 = 35.8%), all-cause mortality (OR 0.88, 95% CI 0.72-1.08, P = .21, I2 = 31.5%) and major adverse cardiac events (OR 1.04, 95% CI 0.94-1.14, P = .46, I2 = 53.9%). Bivalirudin was associated with a reduced hazard of major bleeding (OR 0.80, 95% CI 0.70-0.92, P = .001, I2 = 63.5%). The dose of heparin in the control arm modified this association; when the dose of unfractionated heparin in the control arm was ≥ 100 units/kg, bivalirudin was associated with a reduction in major bleeding (OR 0.55, 95% CI 0.45-0.68, P < .0001), but when the dose of unfractionated heparin was ≤ 75 units/kg, bivalirudin was not associated with reduction in bleeding (OR 1.09, 95% CI 0.91-1.31, P = .36). Among patients undergoing PCI, bivalirudin was associated with an increased hazard of stent thrombosis. Bivalirudin may be associated with a reduced hazard of major bleeding; however, this benefit was no longer apparent when compared with a dose of unfractionated heparin ≤ 75 units/kg.

Association of aortic stiffness and wave reflections with coronary flow reserve in women without obstructive coronary artery disease: An ancillary study from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

BACKGROUND Increased aortic stiffness and reduced coronary flow reserve (CFR) independently predict adverse outcomes. But information about relationships between arterial properties and CFR in subjects without obstructive coronary artery disease (CAD) is limited. METHODS CFR was measured (Doppler flow wire and intracoronary adenosine) in 50 women (age 53 ± 11 years) with symptoms and signs of myocardial ischemia without obstructive CAD. Aortic pulse wave velocity (aPWV), a measure of aortic stiffness, was obtained via catheter pullback; radial artery pressure waves were measured by applanation tonometry and central aortic pressure synthesized. RESULTS Overall, CFR (mean 2.61 ± 0.47) was significantly correlated with aPWV (r = -0.51), pulse wave amplification (r = 0.45), augmented pressure (r = -0.48), augmentation index (AIx, r = -0.44), aortic systolic pressure (r = -0.49), left ventricular wasted energy (LVEw, r = -0.47) (all P < .001), systolic pressure time index (r = -0.37, P < .008), and rate pressure product (r = -0.29, P < .04). In the multiple regression model including aPWV, CFR was still significantly correlated with aPWV (P < .008) and aortic systolic pressure (P < .01). No other measures contributed significant additional information. Women with CFR ≤2.5 versus those with CFR >2.5 had greater aPWV (894 ± 117 vs 747 ± 93 cm/s, P < .001), augmented pressure (14 ± 4.9 vs 11 ± 4.1 mmHg, P < .008), AIx (32 ± 6.6 vs 27 ± 6.6%, P < .003), LVEw (30 ± 12 vs 21 ± 10 dyne-s/cm(2) × 10(2), P < .02) and reduced pulse pressure amplification (1.20 ± .07 vs 1.26 ± .10, P < .008) and pressure wave travel time (133 ± 7.3 vs 138 ± 6.9 milliseconds, P < .04). CONCLUSIONS Among symptomatic women without obstructive CAD, CFR was inversely related to aortic systolic pressure and indices of aortic stiffness. These changes in arterial properties increase left ventricular afterload requiring the ventricle to generate additional, but wasted, energy that increases indices of myocardial oxygen demand, reduces CFR and increases vulnerability to ischemia.

Renal function and coronary microvascular dysfunction in women with symptoms/signs of ischemia.

Objectives Chronic kidney disease (CKD) is more prevalent among women and is associated with adverse cardiovascular events. Among women with symptoms and signs of ischemia enrolled in the Women’s Ischemia Syndrome Evaluation (WISE), a relatively high mortality rate was observed in those with no obstructive coronary artery disease. Coronary microvascular dysfunction or reduced coronary flow reserve (CFR) was a strong and independent predictor of adverse outcomes. The objective of this analysis was to determine if renal function was associated with coronary microvascular dysfunction in women with signs and symptoms of ischemia. Methods The WISE was a multicenter, prospective, cohort study of women undergoing coronary angiography for suspected ischemia. Among 198 women with additional measurements of CFR, we determined the estimated glomerular filtration rate (eGFR) with the CKD-EPI equation. We tested the association between eGFR and CFR with regression analysis. Results The median eGFR was 89 ml/min. The eGFR correlated with CFR (r = 0.22; P = 0.002). This association persisted even after covariate adjustment. Each 10-unit decrease in eGFR was associated with a 0.04-unit decrease in CFR (P = 0.04).There was a strong interaction between eGFR and age (P = 0.006): in those ≥60 years old, GFR was strongly correlated with CFR (r = 0.55; P<0.0001). No significant correlation was noted in those <60 years old. Conclusions Reduced renal function was significantly associated with lower CFR in women with symptoms and signs of ischemia. Coronary microvascular dysfunction warrants additional study as a mechanism contributing to increased risk of cardiovascular events in CKD.

An injectable capillary-like microstructured alginate hydrogel improves left ventricular function after myocardial infarction in rats.

BACKGROUND A new post-myocardial infarction (MI) therapy is injection of high-water-content polymeric biomaterial gels (hydrogels) into damaged myocardium to modulate cardiac negative remodeling and preserve heart function. METHODS We investigated the therapeutic potential of a novel gelatinized alginate hydrogel with a unique microstructure of uniform capillary-like channels (termed Capgel). Shortly (48h) after induced anterior MI, Sprague Dawley rats received intramyocardial injection of Capgel directly into the antero-septal wall at the infarct border zone (n=12) or no injection (n=10, controls). Echocardiograms were performed at 48h (week 0) and 4weeks (week 4) to evaluate left ventricular function. RESULTS Echocardiograms showed 27% improvement of left ventricular systolic function over time with gel injection: fractional shortening increased from 26±3% at week 0 to 33±2% at week 4 (p=0.001). Capgel was present at the injection site after 4weeks, but was minimal at 8weeks. The remaining gel was heavily populated by CD68(+) macrophages with CD206(+) clusters and blood vessels. An in vitro experiment was performed to assess Angiotensin-(1-7) released from Capgel. Angiotensin-(1-7) was released from the Capgel in a sustained manner for 90days. CONCLUSIONS Use of Capgel, a degradable, bioactive hydrogel composed of gelatinized capillary-alginate gel, appears safe for intramyocardial injection, is associated with improved left ventricular function after MI in rats, and may provide a long-term supply of Angiotensin-(1-7).

Number and Function of Bone-Marrow Derived Angiogenic Cells and Coronary Flow Reserve in Women without Obstructive Coronary Artery Disease: A Substudy of the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE)

Background In women with ischemia and no obstructive coronary artery disease, the Womens Ischemic Syndrome Evaluation (WISE) observed that microvascular coronary dysfunction (MCD) is the best independent predictor of adverse cardiovascular events. Since coronary microvascular tone is regulated in part by endothelium, we hypothesized that circulating endothelial cells (CEC), which reflect endothelial injury, and the number and function of bone-marrow derived angiogenic cells (BMDAC), which could help repair damaged endothelium, may serve as biomarkers for decreased coronary flow reserve (CFR) and MCD. Methods We studied 32 women from the WISE cohort. CFR measurements in response to intracoronary adenosine were taken as an index of MCD. We enumerated BMDAC colonies and CEC in peripheral blood samples. BMDAC function was assessed by assay of migration of CD34+ cells toward SDF-1 and measurement of bioavailable nitric oxide (NO). These findings were compared with a healthy reference group and also entered into a multivariable model with CFR as the dependent variable. Results Compared with a healthy reference group, women with MCD had lower numbers of BMDAC colonies [16 (0, 81) vs. 24 (14, 88); P = 0.01] and NO [936 (156, 1875) vs. 1168 (668, 1823); P = 0.02]. Multivariable regression analysis showed strong correlation of CFR to the combination of BMDAC colony count and CD34+ cell function (migration and NO) (R2 = 0.45; P<0.05). Conclusions The BMDAC function and numbers of BMDAC colonies are decreased in symptomatic women with MCD and are independently associated with CFR. These circulating cells may provide mechanistic insights into MCD in women with ischemia.

Serotonin Transporter Gene Polymorphism in Women With Suspected Ischemia: A Report From the NHLBI-Sponsored WISE

Introduction: Association of serotonin transporter gene (5-HTTLPR) polymorphisms with adverse cardiovascular (CV) events in women with suspected ischemia has not yet been reported. We hypothesized an association of 5-HTTLPR polymorphisms with risk of adverse CV events in women with suspected ischemic heart disease (IHD) referred for coronary angiography enrolled in the Women’s Ischemia Syndrome Evaluation (WISE). Method: We studied clinical and angiographic data and DNA from a cohort of 437 Caucasian women enrolled in the WISE genotyped for the long (L) and short (S) variant of the 5-HTTLPR polymorphism. Women were followed yearly for adverse CV events (defined as first occurrence of all-cause death, myocardial infarction, stroke, or heart failure hospitalization) with data collected at WISE 10-year follow-up. Exploratory analyses compared outcomes between genotype groups. Results: A total of 437 women, with baseline, angiographic, and long-term follow-up data, were successfully genotyped. Their mean age was 58 ± 11 years and body mass index 29 ± 6; 54% had hypertension, 18% diabetes, 50% dyslipidemia, 20% depression history, and only 34% had obstructive CAD. At 8.9 years median follow-up, the SS genotype was associated with significantly increased risk of adverse CV event versus LL + LS (1.93, confidence interval [CI]: 1.03-3.61, P = .03). Results were not significant for all-cause death (hazard ratio: 1.63, CI: 0.91-2.93, P = .09). Conclusion: Among a cohort of Caucasian women with suspected IHD enrolled in the WISE, the SS homozygous genotype for the 5-HTTLPR polymorphism was associated with increased risk of adverse CV outcomes.