Identifying and Treating Vulnerable Atherosclerotic Plaques.

Acute coronary syndromes and, in particular, ST-elevation myocardial infarction are usually caused by coronary thrombosis in which the thrombus develops either on a disrupted plaque (usually a thin-capped fibroatheroma) or an eroded atherosclerotic plaque. These thrombus-prone plaques are vulnerable or high-risk. Although, traditionally, cardiologists have concentrated on treating significant coronary obstruction, there has been great interest over the last 2 decades in possibly preventing the thrombotic causes of myocardial infarction/sudden coronary death by mostly identifying and stabilizing these asymptomatic vulnerable or high-risk plaques, which, at least on invasive angiography, are mostly nonobstructive. Computed tomographic angiography and intravascular imaging during invasive coronary angiography have now been shown to identify a majority of these vulnerable or high-risk plaques before symptoms, thus opening up new preventive strategies. In conclusion, this article discusses the identification and management of these thrombus-prone lesions and patients with these lesions either with noninvasive techniques and systemic therapies or possibly through a new and bold interventional paradigm.

In Search of Coronary Thrombosis as the Cause of Myocardial Infarction: Unraveling a 20th-Century Mystery.

For the greater part of the 20th century, the pathophysiology of acute myocardial infarction regarding whether thrombosis was either present or primary was debated until 1973 when pathologists and clinicians met and by consensus, finally decided that the data supported that transmural infarction (what we now refer to as ST elevation myocardial infarction or STEMI) was caused by thrombus in the vessel supplying the infarcted territory. As the data for this consensus came from pathological analysis, it took another 7 years until angiographic and interventional data in humans with acute presentations of transmural infarction convincingly indicated that thrombus was indeed responsible. Subsequently, in patients presenting with either syndromes of unstable angina or nontransmural (later called non-ST elevation) myocardial infarction, it was established through angiographic and other interventional approaches that thrombus formation was also causative in a substantial proportion of these patients. This article reviews the history and this search for causation of myocardial infarction that now has resulted in present therapies that have saved innumerable lives over the last 30 to 40 years.

New Precordial T Wave Inversions in Hospitalized Patients.

BACKGROUND: The incidence of precordial T changes has been described in athletes and in specific populations, while the etiology in a large patient population admitted to the hospital has not previously been reported. METHODS: All electrocardiograms (ECGs) read by the same physician with new (compared to prior ECGs) or presumed new (no prior ECGs) precordial T wave inversions of >1 mm (0.1 mV) in multiple precordial leads were retrospectively reviewed and various ECG, patient-related, and imaging parameters assessed. A total of 226 patients and their ECGs were initially selected for analysis. Of these, 35 were eliminated leaving 191 for the final analysis. RESULTS: Patients and their ECGs were divided into 5 groups based on diagnosis and incidence including Wellens syndrome, takotsubo, type 2 myocardial infarction, other (including multiple diagnoses), and unknown. Although subtle differences including number of T inversion leads, depth of T waves, QTc intervals, and other variables were present between some groups, diagnosis in individual cases required appropriate clinical, laboratory, or imaging studies. For example, although Wellens syndrome was identified in <20% of cases, a presenting history of chest discomfort with precordial T changes either on the admission or next-day ECG was highly sensitive and specific for this diagnosis. In some cases, type 2 myocardial infarction can also have a Wellens-like ECG phenotype without significant left anterior descending disease. CONCLUSIONS: Precordial T wave changes in hospitalized patients have various etiologies, and in individual cases, the changes on the ECG alone cannot easily distinguish the presumptive diagnosis and additional data are required.

Reducing Tobacco-Related Disability in Chronic Smokers.

Tobacco consumption (predominantly cigarettes) is the leading preventable cause of mortality worldwide. Although the major focus of strategies to reduce mortality from tobacco must include prevention of future generations from initially gaining access, some smokers are unwilling or unable to quit. Can the higher risk chronic smoker be identified and can their risk be reduced? The risk of adverse events in cigarette smokers is influenced by the intensity and duration of cigarette smoking or secondhand exposure, associated conventional risk factors, environmental stressors, and certain genetic variants and epigenetic modifiers. Recent data suggest that inflammatory markers such as high-sensitivity C-reactive protein (hs CRP) and targeted imaging can identify some smokers at higher risk. As smoking is prothrombotic, aspirin initiation and expanded statin use might reduce cardiovascular risk in those who do not presently meet criteria for these therapies, but further study is required. Thus, although advocacy for smoking cessation should always be the primary approach, increased efforts are needed to identify and potentially treat those who are unable or unwilling to quit.

Anatomic or functional testing in stable patients with suspected CAD: contemporary role of cardiac CT in the ISCHEMIA trial era.

One of the foundations of the management of patients with suspected coronary artery disease (CAD) is to avoid unnecessary invasive coronary angiography (ICA) referrals. However, the diagnostic yield of ICA following abnormal conventional stress testing is low. The ability of ischemia testing to predict subsequent myocardial infarction and death is currently being challenged, and more than half of cardiac events among stable patients with suspected CAD occur in those with normal functional tests. The optimal management of patients with stable CAD remains controversial and ischemia-driven interventions, though improving anginal symptoms, have failed to reduce the risk of hard cardiovascular events. In this context, there is an ongoing debate whether the initial diagnostic test among patients with stable suspected CAD should be a functional test or coronary computed tomography angiography. Aside from considering the specific characteristics of individual patients and local availability and conditions, the choice of the initial test relates to whether the objective concerns its role as gatekeeper for ICA, prognosis, or treatment decision-making. Therefore, the aim of this review is to provide a contemporary overview of these issues and discuss the emerging role of CCTA as the upfront imaging tool for most patients with suspected CAD.

Understanding myocardial infarction.

Over the last 40 years, our understanding of the pathogenesis of myocardial infarction has evolved and allowed new treatment strategies that have greatly improved survival. Over the years, there has been a radical shift in therapy from passive healing of the infarction through weeks of bed rest to early discharge usually within 2 to 3 days as a result of immediate reperfusion strategies and other guideline-directed medical therapies. Nevertheless, challenges remain. Patients who develop cardiogenic shock still face a high 30-day mortality of at least 40%. Perhaps even more important is how do we identify and prevent patients from developing myocardial infarction in the first place? This article discusses these milestones of therapy and considers important issues for progress in the future.

Strategies for the Prevention of Coronary Artery Disease Complications: Can We Do Better?

Billions of dollars have been spent over the past 25 years on developing new therapies for the prevention/treatment of adverse cardiac events related to atherosclerotic cardiovascular disease. Although some therapies have been lifesaving, several mega-randomized studies have shown only a <2% absolute reduction in adverse events with a large residual event rate. Is all this money well spent? Atherosclerosis develops decades before an adverse event, and the trials previously alluded to have nearly always been applied to secondary prevention, decades after disease initiation. Will earlier intervention result in a lower incidence of events? Individuals with an absence of the usual cardiac risk factors have a lifelong low incidence of events. Early initiation of strategies against the common cardiovascular risk factors in primary or primordial prevention will lower the incidence of adverse events, although many groups have not been well studied, including individuals younger than 40 years of age. New strategies are required to realize a radical reduction in events, and this article proposes new methods of prevention/treatment for coronary artery disease complications.

Environmental Tobacco Smoke and Cardiovascular Disease.

Environmental tobacco smoke (ETS) and its sequelae are among the largest economic and healthcare burdens in the United States and worldwide. The relationship between active smoking and atherosclerosis is well-described in the literature. However, the specific mechanisms by which ETS influences atherosclerosis are incompletely understood. In this paper, we highlight the definition and chemical constituents of ETS, review the existing literature outlining the effects of ETS on atherogenesis and thrombosis in both animal and human models, and briefly outline the public health implications of ETS based on these data.

In-Hospital Outcomes of Percutaneous Coronary Intervention in America's Safety Net: Insights From the NCDR Cath-PCI Registry.

OBJECTIVES: This study compared risk-adjusted percutaneous coronary intervention (PCI) outcomes of safety-net hospitals (SNHs) and non-SNHs. BACKGROUND: Although risk adjustment is used to compare hospitals, SNHs treat a disproportionate share of uninsured and underinsured patients, who may have unmeasured risk factors, limited health care access, and poorer outcomes than patients treated at non-SNHs. METHODS: Using the National Cardiovascular Data Registry CathPCI Registry from 2009 to 2015, we analyzed 3,746,961 patients who underwent PCI at 282 SNHs (hospitals where ≥10% of PCI patients were uninsured) and 1,134 non-SNHs. The relationship between SNH status and risk-adjusted outcomes was assessed. RESULTS: SNHs were more likely to be lower volume, rural hospitals located in the southern states. Patients treated at SNHs were younger (63 vs. 65 years), more often nonwhite (17% vs. 12%), smokers (33% vs. 26%), and more likely to be admitted through the emergency department (48% vs. 38%) and to have an ST-segment elevation myocardial infarction (20% vs. 14%) than non-SNHs (all p < 0.001). Patients undergoing PCI at SNHs had higher risk-adjusted in-hospital mortality (odds ratio: 1.23; 95% confidence interval: 1.17 to 1.32; p < 0.001), although the absolute risk difference between groups was small (0.4%). Risk-adjusted bleeding (odds ratio: 1.05; 95% confidence interval: 1.00 to 1.12; p = 0.062) and acute kidney injury rates (odds ratio: 1.01; 95% confidence interval: 0.96 to 1.07; p = 0.51) were similar. CONCLUSIONS: Despite treating a higher proportion of uninsured patients with more acute presentations, risk-adjusted PCI-related in-hospital mortality of SNHs is only marginally higher (4 additional deaths per 1,000 PCI cases) than non-SNHs, whereas risk-adjusted bleeding and acute kidney injury rates are comparable.

Normalization of Testosterone Levels After Testosterone Replacement Therapy Is Associated With Decreased Incidence of Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac dysrhythmia associated with significant morbidity and mortality. Several small studies have reported that low serum total testosterone (TT) levels were associated with a higher incidence of AF. In contrast, it is also reported that anabolic steroid use is associated with an increase in the risk of AF. To date, no study has explored the effect of testosterone normalization on new incidence of AF after testosterone replacement therapy (TRT) in patients with low testosterone. METHODS AND RESULTS: Using data from the Veterans Administrations Corporate Data Warehouse, we identified a national cohort of 76 639 veterans with low TT levels and divided them into 3 groups. Group 1 had TRT resulting in normalization of TT levels (normalized TRT), group 2 had TRT without normalization of TT levels (nonnormalized TRT), and group 3 did not receive TRT (no TRT). Propensity score-weighted stabilized inverse probability of treatment weighting Cox proportional hazard methods were used for analysis of the data from these groups to determine the association between post-TRT levels of TT and the incidence of AF. Group 1 (40 856 patients, median age 66 years) had significantly lower risk of AF than group 2 (23 939 patients, median age 65 years; hazard ratio 0.90, 95% CI 0.81-0.99, P=0.0255) and group 3 (11 853 patients, median age 67 years; hazard ratio 0.79, 95% CI 0.70-0.89, P=0.0001). There was no statistical difference between groups 2 and 3 (hazard ratio 0.89, 95% CI 0.78- 1.0009, P=0.0675) in incidence of AF. CONCLUSIONS: These novel results suggest that normalization of TT levels after TRT is associated with a significant decrease in the incidence of AF.

Normalization of Testosterone Levels After Testosterone Replacement Therapy Is Not Associated With Reduced Myocardial Infarction in Smokers.

OBJECTIVE: To examine the effect of cigarette smoking (CS) status and total testosterone (TT) levels after testosterone replacement therapy (TRT) on all-cause mortality, myocardial infarction (MI), and stroke in male smokers and nonsmokers without history of MI and stroke. PARTICIPANTS AND METHODS: Data from 18,055 males with known CS status and low TT levels who received TRT at the Veterans Health Administration between December 1, 1999, and May 31, 2014, were grouped into (1) current smokers with normalized TT, (2) current smokers with nonnormalized TT, (3) nonsmokers with normalized TT, and (4) nonsmokers with nonnormalized TT. Combined effect of CS status and TT level normalization after TRT on all-cause mortality, MI, and stroke was compared using propensity score-weighted Cox proportional hazard models. RESULTS: Normalization of serum TT levels in nonsmokers was associated with a significant decrease in all-cause mortality (hazard ratio [HR]=0.526; 95% CI, 0.477-0.581; P<.001) and MI (HR=0.717; 95% CI, 0.522-0.986; P<.001). Among current smokers, normalization of serum TT levels was associated with a significant decrease in only all-cause mortality (HR=0.563; 95% CI, 0.488-0.649; P<.001) without benefit in MI (HR=1.096; 95% CI, 0.698-1.720; P=.69). Importantly, compared with nonsmokers with normalized TT, all-cause mortality (HR=1.242; 95% CI, 1.104-1.396; P<.001), MI (HR=1.706; 95% CI, 1.242-2.342; P=.001), and stroke (HR=1.590; 95% CI, 1.013-2.495; P=.04) were significantly higher in current smokers with normalized TT. CONCLUSION: We conclude that active CS may negate the protective effect of testosterone level normalization on all-cause mortality and MI after TRT.

Finding the High-Risk Patient in Primary Prevention Is Not as Easy as a Conventional Risk Score!

Patients with coronary artery disease or its equivalent are an appropriate target for guideline-directed therapy. However, finding and treating the individuals at risk for myocardial infarction or sudden death in primary prevention has been problematic. Most initial cardiovascular events are acute syndromes, and only a minority of these occurs in those deemed high risk by contemporary algorithms. Even newer noninvasive modalities cannot detect a majority of those at risk. Furthermore, accurate and early detection of high risk/vulnerability does not guarantee event prevention. Until new tools can be identified, one should consider a few simplistic solutions. In addition to a greater emphasis on lifestyle, earlier use of statins than currently recommended and a direct assault on tobacco could go a long way in reducing acute syndromes and cardiovascular mortality. To achieve the tobacco goal, the medical community would have to be directly and communally engaged.

Left Atrial Area and Right Ventricle Dimensions in Non-gated Axial Chest CT can Differentiate Pulmonary Hypertension Due to Left Heart Disease from Other Causes.

BACKGROUND: It is unknown whether axial non-gated CT can distinguish World Health Organization Group 2 pulmonary hypertension (pulmonary hypertension due to left heart disease) from non-Group 2 pulmonary hypertension. OBJECTIVE: The study was performed to identity imaging parameters in non-gated chest CT that differentiate Group 2 from non-Group 2 pulmonary hypertension. METHODS: Among 158 patients who underwent right heart catheterization for evaluation of pulmonary hypertension, 112 had sufficient data and chest CT for review. Invasive hemodynamic data and numerous variables obtained from axial CT images (maximum diameters of main, right, left pulmonary arteries, ascending aorta, main pulmonary artery to ascending aorta diameter ratio, right atrial diameter, left atrial area and right ventricular size) were collected. CT variables were validated against hemodynamic data to identify parameters that would allow to differentiate pulmonary hypertension due to left heart disease (Group 2) from non-Group 2 pulmonary hypertension. RESULTS: Based on right heart catheterization data, we identified 53 patients with Group 2 pulmonary hypertension, 50 patients with non-Group 2 pulmonary hypertension, and 9 subjects with no pulmonary hypertension. In patients with a dilated pulmonary artery (n = 84), the ROC curve for left atrial area (area under the ROC curve 0.76 ± 0.06) independently distinguished patients with Group 2 pulmonary hypertension (n = 42) from patients with non-Group 2 pulmonary hypertension (n = 42). A dilated left atrium (>20 mm(2)) in combination with a normal right ventriuclar size had a sensitivity of 77% and specificity of 94% for Group 2 pulmonary hypertension. CONCLUSIONS: In patients with a dilated pulmonary artery on chest CT, left atrial area and right ventricular dimensions may aid to diagnose pulmonary hypertension and to distinguish underlying cardiac disease from other causes.

A Single Controlled Exposure to Secondhand Smoke May Not Alter Thrombogenesis or Trigger Platelet Activation.

INTRODUCTION: Chronic secondhand smoke (SHS) exposure increases cardiovascular events, particularly acute thrombotic events. There are little human data on acute SHS exposure. The aim of this study was to determine whether a single controlled exposure of humans to SHS increased thrombogenesis. METHODS: After 6-8 hours fast, subjects (n = 50) were exposed to constant dose SHS (particulate level of 500 µg/m(3)) for 120 minutes in a temperature-regulated and ventilated, simulated bar environment. Blood was drawn before and immediately after SHS exposure for thromboelastography (TEG) and flow cytometry. Maximum clot strength (MA) was measured using TEG and platelet leukocyte aggregates (LPA) were measured as an index of platelet activation. Anti-CD 14 antibodies were used as leukocyte markers and anti-CD 41 antibodies as platelet markers for cytometry. Data were analyzed using students' t test for paired samples. RESULTS: There was no effect of acute exposure to SHS on platelet activation or thrombogenesis. Also, intra group (smokers [n = 19] and nonsmokers [n = 31]) comparisons of LPA and TEG parameters did not show changes with SHS exposure. CONCLUSIONS: While there are abundant data showing enhanced thrombogenesis and platelet activation following repeated exposure to SHS, our study suggests that a single exposure does not appear to significantly alter thrombin kinetics nor result in platelet activation. The effects of SHS on thrombogenesis might be nonlinear.