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.

Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men.

AIMS: There is a significant uncertainty regarding the effect of testosterone replacement therapy (TRT) on cardiovascular (CV) outcomes including myocardial infarction (MI) and stroke. The aim of this study was to examine the relationship between normalization of total testosterone (TT) after TRT and CV events as well as all-cause mortality in patients without previous history of MI and stroke. METHODS AND RESULTS: We retrospectively examined 83 010 male veterans with documented low TT levels. The subjects were categorized into (Gp1: TRT with resulting normalization of TT levels), (Gp2: TRT without normalization of TT levels) and (Gp3: Did not receive TRT). By utilizing propensity score-weighted Cox proportional hazard models, the association of TRT with all-cause mortality, MI, stroke, and a composite endpoint was compared between these groups. The all-cause mortality [hazard ratio (HR): 0.44, confidence interval (CI) 0.42-0.46], risk of MI (HR: 0.76, CI 0.63-0.93), and stroke (HR: 0.64, CI 0.43-0.96) were significantly lower in Gp1 (n = 43 931, median age = 66 years, mean follow-up = 6.2 years) vs. Gp3 (n = 13 378, median age = 66 years, mean follow-up = 4.7 years) in propensity-matched cohort. Similarly, the all-cause mortality (HR: 0.53, CI 0.50-0.55), risk of MI (HR: 0.82, CI 0.71-0.95), and stroke (HR: 0.70, CI 0.51-0.96) were significantly lower in Gp1 vs. Gp2 (n = 25 701, median age = 66 years, mean follow-up = 4.6 years). There was no difference in MI or stroke risk between Gp2 and Gp3. CONCLUSION: In this large observational cohort with extended follow-up, normalization of TT levels after TRT was associated with a significant reduction in all-cause mortality, MI, and stroke.

Mechanisms of coronary thrombosis in cigarette smoke exposure.

Acute rupture or erosion of a coronary atheromatous plaque and subsequent coronary artery thrombosis cause the majority of sudden cardiac deaths and myocardial infarctions. Cigarette smoking is a major risk factor for acute coronary thrombosis. Indeed, a majority of sudden cardiac deaths attributable to acute thrombosis are in cigarette smokers. Both active and passive cigarette smoke exposure seem to increase the risk of coronary thrombosis and myocardial infarctions. Cigarette smoke exposure seems to alter the hemostatic process via multiple mechanisms, which include alteration of the function of endothelial cells, platelets, fibrinogen, and coagulation factors. This creates an imbalance of antithrombotic/prothrombotic factors and profibrinolytic/antifibrinolytic factors that support the initiation and propagation of thrombosis.

Femoral micropuncture or routine introducer study (FEMORIS).

OBJECTIVES: The Micropuncture® 21-gauge needle may reduce complications related to vessel trauma from inadvertent venous or posterior arterial wall puncture. METHODS: This was a single-center, multiple-user trial. Four hundred and two patients undergoing possible or definite percutaneous coronary intervention (PCI) were randomized 1:1 to an 18-gauge versus a 21-gauge needle. Patients and personnel pulling the sheaths and performing the follow-up were blinded. The primary end point was a composite of access bleeding. Events were tabulated following sheath removal, ≤ 24 h after the procedure and at the follow-up (at 1-2 weeks). End points were blindly adjudicated. RESULTS: The event rate overall was 12.4% and did not differ significantly between groups, although the 21-gauge needle was found to reduce events by more than one third. An exploratory subgroup analysis of prespecified variables indicated that: patients who did not undergo PCI or elective procedures, female patients and those with a final sheath size of ≤ 6 Fr all had a significant or near-significant reduction of complications with Micropuncture. CONCLUSIONS: Although no significant differences between the use of the 18- and 21-gauge needles were observed, there was a 50-75% reduction with Micropuncture in several subgroups. The study was terminated prematurely. Access site complications may be reduced by the use of the 21-gauge needle, particularly when the risk of bleeding is not high. Further multicenter data will be required to confirm these hypothesis-generating observations.

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.

Acute myocardial infarction and the five-chambered heart.

The case of a patient presenting with acute inferior ST-elevation myocardial infarction is described. Emergent coronary angiography of the right coronary artery revealed what appeared to be the abrupt drainage of contrast into a large, peculiar cavity or chamber. Echocardiography and cardiac computed tomography demonstrated a giant right coronary aneurysm in the right coronary artery that gave the impression of a "fifth heart chamber." The patient underwent successful surgical resection of the aneurysm. Diagnostic and treatment approaches to giant coronary aneurysms are discussed.

Effects of cigarette smoke exposure on clot dynamics and fibrin structure: an ex vivo investigation.

OBJECTIVE: The purpose of this study was to examine the effect of cigarette smoke exposure (CSE) on clot dynamics and fibrin architecture and to isolate the relative contribution of platelets and fibrinogen to clot dynamics. METHODS AND RESULTS: From young healthy males smokers (n=34) and nonsmokers (n=34) a baseline blood was drawn, and smokers had another blood draw after smoking 2 regular cigarettes. Using thromboelastography (TEG) the degree of platelet-fibrin interaction was measured. In additional experiments, abciximab (20 microg/mL) was added to the smokers samples (n=27) to reduce the effects of platelet function from the TEG parameters. The maximum clot strength (G) obtained with abciximab measured mainly the contribution of fibrinogen to clot strength (GF). By subtracting GF from G, the contribution of platelets to clot strength (GP) was presumed. A significant difference was found for all TEG parameters between nonsmokers versus postsmoking and pre- versus postsmoking samples. Postsmoking both GF and GP were significantly higher as compared to presmoking. On electron microscopy and turbidity analysis, postsmoking fibrin clots were significantly different compared to presmoking and nonsmoking samples. CONCLUSIONS: Acute CSE changes clot dynamics and alters fibrin architecture. Both functional changes in fibrinogen and platelets appear to contribute to heightened thrombogenicity after acute CSE.

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.

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.

Preventing future acute coronary events: is the target the so-called vulnerable plaque or the high-risk or vulnerable patient?

PURPOSE OF REVIEW: Heart disease still remains the leading cause of mortality in the USA in spite of recent reductions in the death rate; complications of coronary artery disease and its sequelae are the most common mechanism of demise. Although there have been great advances in the prevention and treatment of acute myocardial infarction, greater emphasis on prevention will likely be needed to reduce acute coronary complications further. RECENT FINDINGS: The literature is replete with articles on the attempted localization of so-called vulnerable plaques and vulnerable, or high-risk patients. They emphasize the importance of the identification of that high-risk plaque or high-risk individual prior to a subsequent coronary event. This article highlights the breakthroughs into the pathophysiology of acute coronary syndromes in the past few decades and presents a perspective on current treatments, improved risk stratification and potential technological advances that may impact diagnosis and management. SUMMARY: Unfortunately, the search for the so-called vulnerable plaque is hampered by the lack of both natural history studies and proven local or regional therapies for these otherwise asymptomatic plaques. Thus, emphasis on the vulnerable or high-risk patient is appropriate, but identifying these individuals in primary prevention is also fraught with difficulty. No specific recommendations can be made at present, as more data are needed in both areas. However, guidelines for future advances are proposed.

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.

Impact of completeness of percutaneous coronary intervention revascularization on long-term outcomes in the stent era.

BACKGROUND: The importance of completeness of revascularization by percutaneous coronary intervention in patients with multivessel disease is unclear in that there is little information on the impact of incomplete revascularization outside of randomized trials. The objective of this study is to compare long-term mortality and subsequent revascularization for percutaneous coronary intervention patients receiving stents who were completely revascularized (CR) with those who were incompletely revascularized (IR). METHODS AND RESULTS: Patients from New York State's Percutaneous Coronary Interventions Reporting System were subdivided into patients who were CR and IR. Then subsets of IR patients were contrasted with CR patients. Differences in long-term survival and subsequent revascularization for CR and IR patients were compared after adjustment for differences in preprocedural risk. A total of 68.9% of all stent patients with multivessel disease who were studied were IR, and 30.1% of all patients had total occlusions and/or > or =2 IR vessels. At baseline, the following patients were at higher risk: those who were older and those with more comorbid conditions, worse ejection fraction, and more renal disease and stroke. After adjustment for these baseline differences, IR patients were significantly more likely to die at any time (adjusted hazard ratio=1.15; 95% confidence interval, 1.01 to 1.30) than CR patients. IR patients with total occlusions and a total of > or =2 IR vessels were at the highest risk compared with CR patients (hazard ratio=1.36; 95% confidence interval, 1.12 to 1.66). CONCLUSIONS: IR with stenting is associated with an adverse impact on long-term mortality, and consideration should be given to either achieving CR, opting for surgery, or monitoring percutaneous coronary intervention patients with IR more closely after discharge.

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 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.