Coronary Stents in Diabetic Patients: State of the Knowledge.

PURPOSE OF REVIEW: This review article aims to summarize the findings of the most relevant research that compared the use of paclitaxel vs. "limus" based drug eluting stent (DES) in diabetic patients and to define the current state of knowledge with new stent technologies in this patient population. RECENT FINDINGS: Since drug eluting stents (DES) were introduced, it has been of great interest to establish whether paclitaxel or sirolimus eluting stents have the same safety and efficacy features for patients with coronary artery disease. The answer to this question is particularly relevant for diabetic patients. Several randomized trials, registry-based studies, and meta-analyses have assessed the performance of these different DES in diabetic patients. The most recently published data favors limus over paclitaxel DES in diabetic patients, but most of these studies compared first vs. second generation DES with the inherent caveats of comparing different platforms, alloys, and drug delivery vehicles. In this literature review, we found that there is robust evidence favoring the use of DES over bare metal stents in diabetic patients with coronary artery disease. We also found that the current state of knowledge is that the everolimus eluting stents have better safety and efficacy than paclitaxel eluting stents in diabetic patients and hence should be the preferred choice. New revascularization strategies including bio-absorbable scaffolds, polymer free stents, and bio-degradable polymers are being studied in diabetic patients with encouraging results.

The significance of transient ischemic dilation in the setting of otherwise normal SPECT radionuclide myocardial perfusion images.

BACKGROUND: Transient ischemic dilation (TID) in the setting of an abnormal SPECT radionuclide myocardial perfusion imaging (MPI) study is considered a marker of severe and extensive coronary artery disease (CAD). However, the clinical significance of TID and its association with CAD in patients with an otherwise normal MPI study is unclear. METHODS: From a database of patients who underwent MPI over a 9-year period, 96 without known cardiac history who had normal image perfusion patterns, and who underwent coronary angiography within 6 months, were identified. TID quantitative values were derived. To adjust for varying stress and image protocols, a TID index based on published threshold values was derived for each patient, with >1 considered as TID. We examined the relationship of TID to the presence/extent of CAD, and to a CAD prognostic index. TID was also correlated with patient survival. To address referral bias, survival in a separate cohort of 3,691 patients with a normal perfusion MPI who did not undergo angiography in the 6-month interval was correlated with the presence and severity of TID. RESULTS: For 28 (29.2%) patients with normal MPI perfusion patterns but with TID, there was no increased incidence of CAD, multivessel or left main disease, or a higher prognostic index compared with no TID. In addition, there was no increased mortality associated with TID in both the angiography cohort and in the patients who did not undergo immediate angiography. CONCLUSIONS: TID in patients with an otherwise normal SPECT MPI study does not increase the likelihood of CAD, its extent or severity, and is not associated with worsened patient survival.

Gadolinium-based coronary angiography in a patient with prior known anaphylaxis to iodine-based dye.

Gadodiamide is a gadolinium-based chemical element that is considered safe and well tolerated in patients without renal dysfunction and is therefore routinely used as a contrast agent in magnetic resonance imaging. Although radio-opaque, it is not frequently used for coronary angiography due to its less than optimal image quality and prohibitive cost. Our center's previous experience was less than satisfactory but the addition of a power injection system yielded good quality diagnostic images. We report a case of 63 years old male with a known history of severe, life-threatening anaphylactic reaction to previous iodinated dye presenting with persistent angina despite optimal medical therapy. Coronary and bypass graft angiography was performed using 24 cc of undiluted Gadodiamide (OMNISCAN) with a power injector (ACIST®) without any incidents or premedication with an interpretable angiogram.

Cardiovascular risk, obesity, and myocardial blood flow in postmenopausal women.

BACKGROUND: This study was designed to determine whether overweight or obese status is independently associated with myocardial flow reserve (MFR), an established predictor of cardiovascular mortality, in a group of postmenopausal women with no previous cardiovascular disease. Postmenopausal women are the largest group of overweight and physically inactive individuals in the United States. Increased body mass index (BMI) is consistently associated with increased cardiovascular mortality in this population. Whether this is because of obesity itself or the accompanying increase in cardiovascular risk factors (CRFs) remains controversial. METHODS: We examined the relationship of myocardial blood flow (MBF), coronary vascular resistance, and MFR to BMI in 60 postmenopausal women with no coronary heart disease. Subjects underwent dynamic N-13 ammonia positron emission tomography for the measurement of MBF and MFR. Baseline demographics, CRF, and hemodynamic parameters were recorded for each subject. Datasets were divided into 3 groups according to BMI: normal (18 to 24), overweight (25 to 29), and obese (>or=30). RESULTS: The overweight and obese groups showed significantly higher resting MBF and lower MFR than the normal-weight group (both P < .001), even after adjusting for CRF. A further analysis of subjects without any CRF (n = 35) showed that the MFR remained significantly lower in the obese compared with normal-weight subjects (P = .05). Levels of known markers of vascular inflammation (high-sensitivity C-reactive protein and homocysteine) and high-density lipoprotein cholesterol levels correlated with declining MFR. CONCLUSIONS: These findings provide a mechanistic link between obesity and coronary heart disease in this population.

A prior myocardial infarction: how does it affect management and outcomes in recurrent acute coronary syndromes?

BACKGROUND: Despite improved secondary prevention efforts, acute coronary syndrome (ACS) recurrence among patients with prior history of coronary events remains high. The differences in presentation, management, and subsequent clinical outcomes in patients with and without a prior myocardial infarction (MI) and presenting with another episode of ACS remain unexplored. METHODS: A total of 3,624 consecutive patients admitted to the University of Michigan with ACS from January 1999 to June 2006 were studied retrospectively. In-hospital management, outcomes, and postdischarge outcomes such as death, stroke, and reinfarction in patients with and without a prior MI were compared. RESULTS: Patients with a prior MI were more likely to be older and have a higher incidence of diabetes mellitus, hypertension, hyperlipidemia, and peripheral vascular disease. In-hospital outcomes were not significantly different in the 2 groups, except for a higher incidence of cardiac arrest (4.3% versus 2.5%, p < 0.01) and cardiogenic shock (5.7% versus 3.9%, p = 0.01) among patients without a prior MI. However, at 6 mo postdischarge, the incidences of death (8.0% versus 4.5%, p < 0.0001) and recurrent MI (10.0% versus 5.1%, p < 0.0001) were significantly higher in patients with a prior history of MI compared with those without. CONCLUSION: Patients with prior MI with recurrent ACS remain at a higher risk of major adverse events on follow-up. This may be partly explained by the patients not being on optimal medications at presentation, as well as disease progression. Increased efforts must be directed at prevention of recurrent ACS, as well as further risk stratification of these patients to improve their overall outcomes.

Temporal trends in antiplatelet/antithrombotic use in acute coronary syndromes and in-hospital major bleeding complications.

Antithrombotic and antiplatelet agents are essential for the management of patients with acute coronary syndromes (ACSs). These pharmacologic agents have the potential for increased risk of bleeding. It is not clear if the increased uptake of these therapies has resulted in a clinically evident increase in bleeding complications over time. In this study, we included 3,193 consecutive patients who were admitted to the University of Michigan with an ACS (unstable angina or myocardial infarction) between January 1999 and December 2004. These patients were analyzed for temporal trends in antithrombotic and antiplatelet agent use, thrombolytic therapy, cardiac catheterizations, percutaneous coronary interventions, and major bleeding complications (including gastrointestinal, vascular access, and intracranial hemorrhage). We found a decreasing temporal trend in the incidence of major in-hospital bleeding complications (p <0.001) despite an increasing use of ticlopidine/clopidogrel (p <0.0001), unfractionated heparin (p <0.01), glycoprotein IIb/IIIa inhibitors (p <0.0001), and percutaneous coronary intervention (p <0.0001) in the management of patients with ACSs. In conclusion, major bleeding remains a significant complication of ACS management but has decreased significantly over time. We believe that this decreasing bleeding trend may be because of better identification of higher risk patients, attention to correct dosing, appropriate monitoring, and incorporation of various periprocedural strategies in routine clinical practice.

Drospirenone for oral contraception and hormone replacement therapy: are its cardiovascular risks and benefits the same as other progestogens?

The use of combined estrogen/progesterone has been shown to result in an increased cardiovascular risk in randomised double-blinded trials. However, these studies used oral progestogen (progestin) preparations, which lack anti-mineralocorticoid activity and have suboptimal anti-androgenic activity compared with progesterone. Drospirenone is a unique progestogen that has clinically been shown to have anti-mineralocorticoid/anti-androgenic effects. Drospirenone in combination with estrogen is currently being used for oral contraception and hormone replacement therapy, and has been shown to have favourable effects on a number of cardiovascular risk factors. Our review of the literature suggests that because of its anti-mineralocorticoid effects, drospirenone in conjunction with estrogen may prevent the development of cardiovascular disease in both pre- and post-menopausal women.

Angiotensin-converting enzyme inhibitors: a new mechanism of action.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are valuable agents for the treatment of hypertension, heart failure, and other cardiovascular and renal diseases. The cardioprotective effects of ACE inhibitors are mediated by blockade of both conversion of angiotensin (Ang) I to Ang II and kinin hydrolysis. Here, we report a novel mechanism that may explain the cardiac antifibrotic effect of ACE inhibition, involving blockade of the hydrolysis of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP). METHODS AND RESULTS: To study the role of Ac-SDKP in the therapeutic effects of the ACE inhibitor captopril, we used a model of Ang II-induced hypertension in rats treated with the ACE inhibitor either alone or combined with a blocking monoclonal antibody (mAb) to Ac-SDKP. These hypertensive rats had left ventricular hypertrophy (LVH) as well as increases in cardiac fibrosis, cell proliferation, transforming growth factor-beta (TGF-beta) expression, and phosphorylation of Smad2 (P-Smad2), a signaling mediator of the effects of TGF-beta. The ACE inhibitor did not decrease either blood pressure or LVH; however, it significantly decreased LV collagen from 13.3+/-0.9 to 9.6+/-0.6 microg/mg dry wt (P<0.006), and this effect was blocked by the mAb (12.1+/-0.6; P<0.034, ACE inhibitor versus ACE inhibitor+mAb). In addition, analysis of interstitial collagen volume fraction and perivascular collagen (picrosirius red staining) showed a very similar tendency. Likewise, the ACE inhibitor significantly decreased LV monocyte/macrophage infiltration, cell proliferation, and TGF-beta expression, and these effects were blocked by the mAb. Ang II increased Smad2 phosphorylation 3.2+/-0.9-fold; the ACE inhibitor lowered this to 0.6+/-0.1-fold (P<0.001), and the mAb blocked this decrease to 2.1+/-0.3 (P<0.001, ACE inhibitor versus ACE inhibitor+mAb). Similar findings were seen when the ACE inhibitor was replaced by Ac-SDKP. CONCLUSIONS: We concluded that in Ang II-induced hypertension, the cardiac antifibrotic effect of ACE inhibitors is a result of the inhibition of Ac-SDKP hydrolysis, resulting in a decrease in cardiac cell proliferation (probably fibroblasts), inflammatory cell infiltration, TGF-beta expression, Smad2 activation, and collagen deposition.

Predictors, Trends, and Outcomes (Among Older Patients ≥65 Years of Age) Associated With Beta-Blocker Use in Patients With Stable Angina Undergoing Elective Percutaneous Coronary Intervention: Insights From the NCDR Registry.

OBJECTIVES: This study sought to examine predictors, trends, and outcomes associated with ß-blocker prescriptions at discharge in patients with stable angina without prior history of myocardial infarction (MI) or systolic heart failure (HF) undergoing elective percutaneous coronary intervention (PCI). BACKGROUND: The benefits of ß-blockers in patients with MI and/or systolic HF are well established. However, whether ß-blockers affect outcomes in patients with stable angina, especially after PCI, remains uncertain. METHODS: We included patients with stable angina without prior history of MI, left ventricular systolic dysfunction (left ventricular ejection fraction <40%) or systolic HF undergoing elective PCI between January 2005 and March 2013 from the hospitals enrolled in the National Cardiovascular Data Registry (NCDR) CathPCI registry. These patients were retrospectively analyzed for predictors and trends of ß-blocker prescriptions at discharge. All-cause mortality (primary endpoint), revascularization, or hospitalization related to MI, HF, or stroke at 30-day and 3-year follow-up were analyzed among patients ≥65 years of age. RESULTS: A total of 755,215 patients from 1,443 sites were studied, and 71.4% population of our cohort was discharged on ß-blockers. At 3-year follow-up among patients ≥65 years of age with CMS data linkage (16.3% of the studied population), there was no difference in adjusted mortality rate (14.0% vs. 13.3%; adjusted hazard ratio [HR]: 1.00; 95% confidence interval [CI]: 0.96 to 1.03; p = 0.84), MI (4.2% vs. 3.9%; adjusted HR: 1.00; 95% CI: 0.93 to 1.07; p = 0.92), stroke (2.3% vs. 2.0%; adjusted HR: 1.08; 95% CI: 0.98 to 1.18; p = 0.14) or revascularization (18.2% vs. 17.8%; adjusted HR: 0.97; 95% CI: 0.94 to 1.01; p = 0.10) with ß-blocker prescription. However, discharge on ß-blockers was associated with more HF readmissions at 3-year follow-up (8.0% vs. 6.1%; adjusted HR: 1.18; 95% CI: 1.12 to 1.25; p < 0.001). Results at 30-day follow-up were broadly consistent as well. During the period between 2005 and 2013, there was a gradual increase in prescription of ß-blockers at the index discharge in our cohort (p < 0.001). CONCLUSIONS: Among patients ≥65 years of age with history of stable angina without prior MI, systolic HF or left ventricular ejection fraction <40% undergoing elective PCI, ß-blocker use at discharge was not associated with any reduction in cardiovascular morbidity or mortality at 30-day and at 3-year follow-up. Over time, ß-blockers use at discharge in this population has continued to increase.

Left Ventricular Outflow Tract Pseudoaneurysm after Aortic Valve Replacement.

Left ventricular outflow tract pseudoaneurysm is an uncommon complication following aortic valve replacement (AVR), occurring most frequently secondary to endocarditis. We present a case of a 47-year-old female with a history of intravenous drug abuse and a past surgical history of two AVRs (2001 and 2009 with aortic root replacement for endocarditis) who presented with symptoms of lower extremity weakness. Subsequent radiologic imaging revealed the presence of a left ventricular outflow tract pseudoaneurysm, which was surgically managed with a homologous conduit.

Changes in myocardial infarction guideline adherence as a function of patient risk: an end to paradoxical care?

OBJECTIVES: The goals of this analysis were to determine: 1) whether guideline-based care during hospitalization for a myocardial infarction (MI) varied as a function of patients' baseline risk; and 2) whether temporal improvements in guideline adherence occurred in all risk groups. BACKGROUND: Guideline-based care of patients with MI improves outcomes, especially among those at higher risk. Previous studies suggest that this group is paradoxically less likely to receive guideline-based care (risk-treatment mismatch). METHODS: A total of 112,848 patients with MI were enrolled at 279 hospitals participating in Get With The Guidelines-Coronary Artery Disease (GWTG-CAD) between August 2000 and December 2008. We developed and validated an in-hospital mortality model (C-statistic: 0.75) to stratify patients into risk tertiles: low (0% to 3%), intermediate (3% to 6.5%), and high (>6.5%). Use of guideline-based care and temporal trends were examined. RESULTS: High-risk patients were significantly less likely to receive aspirin, beta-blockers, angiotensin-converting inhibitors/angiotensin receptor blockers, statins, diabetic treatment, smoking cessation advice, or cardiac rehabilitation referral at discharge compared with those at lower risk (all p < 0.0001). However, use of guideline-recommended therapies increased significantly in all risk groups per year (low-risk odds ratio: 1.33 [95% confidence interval (CI): 1.22 to 1.45]; intermediate-risk odds ratio: 1.30 [95% CI: 1.21 to 1.38]; and high-risk odds ratio: 1.30 [95% confidence interval: 1.23 to 1.37]). Also, there was a narrowing in the guideline adherence gap between low- and high-risk patients over time (p = 0.0002). CONCLUSIONS: Although adherence to guideline-based care remains paradoxically lower in those MI patients at higher risk of mortality and most likely to benefit from treatment, care is improving for eligible patients within all risk categories, and the gaps between low- and high-risk groups seem to be narrowing.

Risk Factors in first presentation acute coronary syndromes (ACS): how do we move from population to individualized risk prediction?

Patients with acute coronary syndromes (ACS) have a poor short- and long-term prognosis. We sought to examine the presence of established coronary risk factors in contemporary patients presenting with an ACS for the first time and no known coronary artery disease (CAD) in the past. The study was conducted in 3171 consecutive patients admitted with the diagnosis of ACS. Of these, 941 patients (30%) had the admission as the first occurrence of ACS and no prior history of CAD. We studied the degree to which these first presenters with ACS had 1 or more established risk factors. We found that 98% of patients presenting with an ACS for the first time and no previous CAD had at least 1 established risk factor. Current population-based screening efforts must be improved to allow more effective prevention strategies and more individualized risk prediction.

Impact of duty hours restrictions on quality of care and clinical outcomes.

BACKGROUND: In July 2003, the Accreditation Council for Graduate Medical Education instituted residency duty-hours requirements in response to growing concerns regarding clinician fatigue and the incidence of medical errors. These changes, which limited maximum continuous hours worked and total hours per week, often resulted in increased discontinuity of care. The objective of this study was to assess the impact of the duty-hours restrictions on quality of care and outcomes of patients with acute coronary syndrome. METHODS: We performed a retrospective analysis of 1003 consecutive patients with acute coronary syndrome admitted to the University of Michigan Hospital between July 2002 and June 2004. Patients were stratified by hospital admission during academic year 2002-2003 (pre-duty-hours changes, n=572) and academic year 2003-2004 (post-duty-hours changes, n=431). Main outcome measures included differences in adherence to quality indicators, length of stay, and in-hospital and 6-month adverse events. RESULTS: Post-duty-hours changes, there was an increase in the usage of beta-blockers (85.8% vs 93.8%, P <.001), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (65.7% vs 71.8%, P=.046), and statins (76.2% vs 84.0%, P=.002) at time of discharge. Length of stay decreased from 3.1 days to 2.8 days, P=.002. There was no difference in in-hospital mortality (4.2% vs 2.8%, P=.23). Six-month mortality (8.0% vs 3.8%, P=.007) and risk-adjusted 6-month mortality (odds ratio 0.53, 95% confidence interval, 0.28-0.99, P=.05) decreased after the duty-hours changes. CONCLUSIONS: Implementation of the Accreditation Council for Graduate Medical Education residency duty-hours restrictions on an academic inpatient cardiology service was associated with improved quality of care and efficiency in patients admitted with acute coronary syndrome. In addition, improved efficiency did not adversely impact patient outcomes, including mortality.