Javier A. Valle

Nonobstructive coronary artery disease and risk of myocardial infarction.

IMPORTANCE Little is known about cardiac adverse events among patients with nonobstructive coronary artery disease (CAD). OBJECTIVE To compare myocardial infarction (MI) and mortality rates between patients with nonobstructive CAD, obstructive CAD, and no apparent CAD in a national cohort. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of all US veterans undergoing elective coronary angiography for CAD between October 2007 and September 2012 in the Veterans Affairs health care system. Patients with prior CAD events were excluded. EXPOSURES Angiographic CAD extent, defined by degree (no apparent CAD: no stenosis >20%; nonobstructive CAD: ≥1 stenosis ≥20% but no stenosis ≥70%; obstructive CAD: any stenosis ≥70% or left main [LM] stenosis ≥50%) and distribution (1, 2, or 3 vessel). MAIN OUTCOMES AND MEASURES The primary outcome was 1-year hospitalization for nonfatal MI after the index angiography. Secondary outcomes included 1-year all-cause mortality and combined 1-year MI and mortality. RESULTS Among 37,674 patients, 8384 patients (22.3%) had nonobstructive CAD and 20,899 patients (55.4%) had obstructive CAD. Within 1 year, 845 patients died and 385 were rehospitalized for MI. Among patients with no apparent CAD, the 1-year MI rate was 0.11% (n = 8, 95% CI, 0.10%-0.20%) and increased progressively by 1-vessel nonobstructive CAD, 0.24% (n = 10, 95% CI, 0.10%-0.40%); 2-vessel nonobstructive CAD, 0.56% (n = 13, 95% CI, 0.30%-1.00%); 3-vessel nonobstructive CAD, 0.59% (n = 6, 95% CI, 0.30%-1.30%); 1-vessel obstructive CAD, 1.18% (n = 101, 95% CI, 1.00%-1.40%); 2-vessel obstructive CAD, 2.18% (n = 110, 95% CI, 1.80%-2.60%); and 3-vessel or LM obstructive CAD, 2.47% (n = 137, 95% CI, 2.10%-2.90%). After adjustment, 1-year MI rates increased with increasing CAD extent. Relative to patients with no apparent CAD, patients with 1-vessel nonobstructive CAD had a hazard ratio (HR) for 1-year MI of 2.0 (95% CI, 0.8-5.1); 2-vessel nonobstructive HR, 4.6 (95% CI, 2.0-10.5); 3-vessel nonobstructive HR, 4.5 (95% CI, 1.6-12.5); 1-vessel obstructive HR, 9.0 (95% CI, 4.2-19.0); 2-vessel obstructive HR, 16.5 (95% CI, 8.1-33.7); and 3-vessel or LM obstructive HR, 19.5 (95% CI, 9.9-38.2). One-year mortality rates were associated with increasing CAD extent, ranging from 1.38% among patients without apparent CAD to 4.30% with 3-vessel or LM obstructive CAD. After risk adjustment, there was no significant association between 1- or 2-vessel nonobstructive CAD and mortality, but there were significant associations with mortality for 3-vessel nonobstructive CAD (HR, 1.6; 95% CI, 1.1-2.5), 1-vessel obstructive CAD (HR, 1.9; 95% CI, 1.4-2.6), 2-vessel obstructive CAD (HR, 2.8; 95% CI, 2.1-3.7), and 3-vessel or LM obstructive CAD (HR, 3.4; 95% CI, 2.6-4.4). Similar associations were noted with the combined outcome. CONCLUSIONS AND RELEVANCE In this cohort of patients undergoing elective coronary angiography, nonobstructive CAD, compared with no apparent CAD, was associated with a significantly greater 1-year risk of MI and all-cause mortality. These findings suggest clinical importance of nonobstructive CAD and warrant further investigation of interventions to improve outcomes among these patients.

Association of Coronary Stent Indication With Postoperative Outcomes Following Noncardiac Surgery

IMPORTANCE Current guidelines for delaying surgery after coronary stent placement are based on stent type. However, the indication for the stent may be an important risk factor for postoperative major adverse cardiac events (MACE). OBJECTIVE To determine whether the clinical indication for a coronary stent is associated with postoperative MACE. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study in patients at US Veterans Affairs hospitals who had a coronary stent placed between January 1, 2000, and December 31, 2010, and underwent noncardiac surgery within the following 24 months. The association between the indication for stent and postoperative MACE rates was examined using logistic regression to control for patient and procedure factors. EXPOSURES Three subgroups of stent indication were examined: (1) myocardial infarction (MI); (2) unstable angina; and (3) revascularization not associated with acute coronary syndrome (non-ACS). MAIN OUTCOMES AND MEASURES Composite 30-day postoperative MACE rates including all-cause mortality, MI, or revascularization. RESULTS Among 26 661 patients (median [IQR] age, 68 [61.0-76.0] years; 98.4% male; 88.1% white) who underwent 41 815 surgical procedures within 24 months following coronary stent placement, the stent indication was MI in 32.8% of the procedures, unstable angina in 33.8%, and non-ACS in 33.4%. Postoperative MACE rates were significantly higher in the MI group (7.5%) compared with the unstable angina (2.7%) and non-ACS (2.6%) groups (P < .001). When surgery was performed within 3 months of percutaneous coronary intervention, adjusted odds of MACE were significantly higher in the MI group compared with the non-ACS group (odds ratio [OR] = 5.25; 95% CI, 4.08-6.75). This risk decreased over time, although it remained significantly higher at 12 to 24 months from percutaneous coronary intervention (OR = 1.95; 95% CI, 1.58-2.40). The adjusted odds of MACE for the unstable angina group were similar to those for the non-ACS group when surgery was performed within 3 months (OR = 1.11; 95% CI, 0.80-1.53) or between 12 and 24 months (OR = 1.08; 95% CI, 0.86-1.37) from stent placement. Stent type was not significantly associated with MACE regardless of indication. CONCLUSIONS AND RELEVANCE Surgery in patients with a coronary stent placed for MI was associated with increased postoperative MACE rates compared with other stent indications. The risk declined over time from PCI, and delaying surgery up to 6 months in this cohort of patients with stents may be important regardless of stent type.

Impact of Pre-Procedural Beta Blockade on Inpatient Mortality in Patients Undergoing Primary Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction

Early use of β blockers (BBs) in acute myocardial infarction remains controversial, with some studies demonstrating benefit and others harm. The aim of this study was to assess the association between pre-percutaneous coronary intervention (PCI) BB use and in-hospital outcomes in patients who underwent primary PCI for ST-segment elevation myocardial infarction between 2007 and 2009 at institutions participating in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC-2). Inverse propensity score weighting was used to account for the nonrandomized use of pre-PCI BBs. The cohort comprised 7,667 patients, with 4,769 (62%) receiving pre-PCI BBs. These patients were older, with higher rates of diabetes mellitus, hypertension, and previous myocardial infarction, PCI, or coronary artery bypass grafting. In adjusted models, pre-PCI BB use was associated with lower rates of intraprocedural ventricular tachycardia or ventricular fibrillation (odds ratio [OR] 0.58, p <0.01) and lower in-hospital mortality (OR 0.65, p = 0.022), with increases in rates of emergent coronary artery bypass grafting (OR 1.56, p <0.01) and repeat PCI (OR 1.93, p <0.01). There were no significant increases in rates of cardiogenic shock and congestive heart failure. In conclusion, pre-PCI BB use in this population was associated with decreased arrhythmia and mortality, without increasing rates of cardiogenic shock and heart failure but with higher rates of repeat PCI and emergent coronary artery bypass grafting, suggesting that there may yet remain a role for early BB use in pre-PCI patients with ST-segment elevation myocardial infarctions.

Duration of resuscitation efforts for in-hospital cardiac arrest by predicted outcomes: Insights from Get With The Guidelines − Resuscitation

BACKGROUND The duration of resuscitation efforts has implications for patient survival of in-hospital cardiac arrest (IHCA). It is unknown if patients with better predicted survival of IHCA receive longer attempts at resuscitation. METHODS In a multicenter observational cohort of 40,563 adult non-survivors of resuscitation efforts for IHCA between 2000 and 2012, we determined the pre-arrest predicted probability of survival to discharge with good neurologic status, categorized into very low (<1%), low (1-3%), average (>3%-15%), and above average (>15%). We then determined the association between predicted arrest survival probability and the duration of resuscitation efforts. RESULTS The median duration of resuscitation efforts among all non-survivors was 19min (interquartile range 13-28min). Overall, the median duration of resuscitation efforts was longer in non-survivors with a higher predicted probability of survival with good neurologic status (median of 16, 17, 20, and 23min among the groups predicted to have very low, low, average, and above probabilities, respectively; P<0.001). However, the duration of resuscitation was often discordant with predicted survival, including longer than median duration of resuscitation efforts in 40.4% of patients with very low predicted survival and shorter than median duration of resuscitation efforts in 31.9% of patients with above average predicted survival. CONCLUSIONS The duration of resuscitation efforts in patients with IHCA was generally consistent with their predicted survival. However, nearly a third of patients with above average predicted outcomes received shorter than average (less than 19min) duration of resuscitation efforts.

Postdischarge Bleeding After Percutaneous Coronary Intervention and Subsequent Mortality and Myocardial Infarction

Background—Bleeding after hospital discharge from percutaneous coronary intervention (PCI) is associated with increased risk of subsequent myocardial infarction (MI) and death; however, the timing of adverse events after these bleeding events is poorly understood. Defining this relationship may help clinicians identify critical periods when patients are at highest risk. Methods and Results—All patients undergoing PCI from 2004 to 2007 who survived to hospital discharge without a bleeding event were identified from the HMO Research Network-Stent (HMORN-Stent) Registry. Postdischarge rates and timing of bleeding-related hospitalizations, MI, and death were defined. We then assessed the association between postdischarge bleeding–related hospitalizations with death and MI using Cox proportional hazards models. Among 8137 post-PCI patients surviving to hospital discharge without in-hospital bleeding, 391 (4.8%) had bleeding-related hospitalization after discharge, with the highest incidence of bleeding-related hospitalizations occurring within 30 days of discharge (n=79, 20.2%). Postdischarge bleeding–related hospitalization after PCI was associated with subsequent death or MI (hazard ratio, 3.09; 95% confidence interval, 2.41–3.96), with the highest risk for death or MI occurring in the first 60 days after bleeding-related hospitalization (hazard ratio, 7.16; confidence interval, 3.93–13.05). Conclusions—Approximately 1 in 20 post-PCI patients are readmitted for bleeding, with the highest incidence occurring within 30 days of discharge. Patients having postdischarge bleeding are at increased risk for subsequent death or MI, with the highest risk occurring within the first 60 days after a bleeding-related hospitalization. These findings suggest a critical period after bleeding events when patients are most vulnerable for further adverse events.

Longitudinal Risk of Adverse Events in Patients With Acute Kidney Injury After Percutaneous Coronary Intervention: Insights From the National Cardiovascular Data Registry

Background— Acute kidney injury (AKI) remains a common complication after percutaneous coronary intervention (PCI) and is associated with adverse in-hospital patient outcomes. The incidence of adverse events after hospital discharge in patients having post-PCI AKI is poorly defined, and the relationship between AKI and outcomes after hospital discharge remains understudied. Methods and Results— Using the National Cardiovascular Data Registry CathPCI registry, we assessed the incidence of AKI among Medicare beneficiaries after PCI from 2004 to 2009 and subsequent post-discharge adverse events at 1 year. AKI was defined using Acute Kidney Injury Network (AKIN) criteria. Adverse events included death, myocardial infarction, bleeding, and recurrent kidney injury. Using Cox methods, we determined the relationship between in-hospital AKI and risk of post-discharge adverse events by AKIN stage. In a cohort of 453 475 elderly patients undergoing PCI, 39 850 developed AKI (8.8% overall; AKIN stage 1, 85.8%; AKIN 2/3, 14.2%). Compared with no AKI, in-hospital AKI was associated with higher post-discharge hazard of death, myocardial infarction, or bleeding (AKIN 1: hazard ratio [HR], 1.53; confidence interval [CI], 1.49–1.56 and AKIN 2/3: HR, 2.13; CI, 2.01–2.26), recurrent AKI (AKIN 1: HR, 1.70; CI, 1.64–1.76; AKIN 2/3: HR, 2.22; CI, 2.04–2.41), and AKI requiring dialysis (AKIN 1: HR, 2.59; CI, 2.29–2.92; AKIN 2/3: HR, 4.73; CI, 3.73–5.99). For each outcome, the highest incidence was within 30 days. Conclusions— Post-PCI AKI is associated with increased risk of death, myocardial infarction, bleeding, and recurrent renal injury after discharge. Post-PCI AKI should be recognized as a significant risk factor not only for in-hospital adverse events but also after hospital discharge.

Implications of the PEGASUS-TIMI 54 trial for US clinical practice

Objectives This study aims to determine the proportion of real-world patients with myocardial infarction (MI) who would have been eligible for the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial, to characterise their current use of P2Y12 inhibitors and to explore the estimated costs and ischaemic event consequences of increasing P2Y12 inhibitor use among these patients. Methods In the US national ACTION Registry–GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With The Guidelines), we identified 273 328 patients with MI and determined the proportion that would have met the eligibility criteria for the PEGASUS trial. We described longitudinal P2Y12 inhibitor use among patients eligible for PEGASUS and estimated the cost and ischaemic consequences of increasing P2Y12 use among eligible patients. Results A total of 112 222 (41.1%) patients with MI in ACTION Registry–GWTG met eligibility for the PEGASUS trial. Among 83 871 eligible patients with pharmacy claims data, 23 042 (27.5%) were on a P2Y12 inhibitor at 1 year, 9661 (11.5%) at 2 years and 5246 (6.3%) at 3 years, with the majority (79.2%) of these patients on clopidogrel. The use of ticagrelor in eligible patients not yet on a P2Y12 inhibitor at 1 year post-MI would cost an estimated US

OBESITY PARADOX AMONG SURVIVORS OF ACUTE MYOCARDIAL INFARCTION AND ITS INTERACTION WITH TIME

885 000 per MI, stroke or cardiovascular death averted over a 3-year time horizon, while the use of clopidogrel would cost an estimated US

Patient and lesion-specific characteristics predict risk of major adverse cardiovascular events among patients with previous percutaneous coronary intervention undergoing noncardiac surgery.

19 800 per ischaemic event averted. Conclusion In contemporary clinical practice, a minority of patients are on a P2Y12 inhibitor beyond 1-year post-MI. Applying PEGASUS trial findings to clinical practice would result in a large increase in P2Y12 inhibitor use, with a cost per ischaemic event averted that is strongly influenced by the choice of therapy.

Coronary angiography and failure to rescue after postoperative myocardial infarction in patients with coronary stents undergoing noncardiac surgery

Obese patients are known to have a lower 1-year mortality after AMI compared to normal weight patients. However, it is unknown whether this obesity paradox persists over time. As metabolic abnormalities in the obese may take longer to display their effects, disparities in outcome may manifest later