Complete versus culprit-only revascularisation in ST elevation myocardial infarction with multi-vessel disease.

BACKGROUND: Multi-vessel coronary disease in people with ST elevation myocardial infarction (STEMI) is common and is associated with worse prognosis after STEMI. Based on limited evidence, international guidelines recommend intervention on only the culprit vessel during STEMI. This, in turn, leaves other significantly stenosed coronary arteries for medical therapy or revascularisation based on inducible ischaemia on provocative testing. Newer data suggest that intervention on both the culprit and non-culprit stenotic coronary arteries (complete intervention) may yield better results compared with culprit-only intervention. OBJECTIVES: To assess the effects of early complete revascularisation compared with culprit vessel only intervention strategy in people with STEMI and multi-vessel coronary disease. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, World Health Organization International Clinical Trials Registry Platform Search Portal, and ClinicalTrials.gov. The date of the last search was 4 January 2017. We applied no language restrictions. We handsearched conference proceedings to December 2016, and contacted authors and companies related to the field. SELECTION CRITERIA: We included only randomised controlled trials (RCTs), wherein complete revascularisation strategy was compared with a culprit-only percutaneous coronary intervention (PCI) for the treatment of people with STEMI and multi-vessel coronary disease. DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of each trial using the Cochrane 'Risk of bias' tool. We resolved the disagreements by discussion among review authors. We followed standard methodological approaches recommended by Cochrane. The primary outcomes were long-term (one year or greater after the index intervention) all-cause mortality, long-term cardiovascular mortality, long-term non-fatal myocardial infarction, and adverse events. The secondary outcomes were short-term (within the first 30 days after the index intervention) all-cause mortality, short-term cardiovascular mortality, short-term non-fatal myocardial infarction, revascularisation, health-related quality of life, and cost. We analysed data using fixed-effect models, and expressed results as risk ratios (RR) with 95% confidence intervals (CI). We used GRADE criteria to assess the quality of evidence and we conducted Trial Sequential Analysis (TSA) to control risks of random errors. MAIN RESULTS: We included nine RCTs, that involved 2633 people with STEMI and multi-vessel coronary disease randomly assigned to either a complete (n = 1381) versus culprit-only (n = 1252) revascularisation strategy. The complete and the culprit-only revascularisation strategies did not differ for long-term all-cause mortality (65/1274 (5.1%) in complete group versus 72/1143 (6.3%) in culprit-only group; RR 0.80, 95% CI 0.58 to 1.11; participants = 2417; studies = 8; I2 = 0%; very low quality evidence). Compared with culprit-only intervention, the complete revascularisation strategy was associated with a lower proportion of long-term cardiovascular mortality (28/1143 (2.4%) in complete group versus 51/1086 (4.7%) in culprit-only group; RR 0.50, 95% CI 0.32 to 0.79; participants = 2229; studies = 6; I2 = 0%; very low quality evidence) and long-term non-fatal myocardial infarction (47/1095 (4.3%) in complete group versus 70/1004 (7.0%) in culprit-only group; RR 0.62, 95% CI 0.44 to 0.89; participants = 2099; studies = 6; I2 = 0%; very low quality evidence). The complete and the culprit-only revascularisation strategies did not differ in combined adverse events (51/2096 (2.4%) in complete group versus 57/1990 (2.9%) in culprit-only group; RR 0.84, 95% CI 0.58 to 1.21; participants = 4086; I2 = 0%; very low quality evidence). Complete revascularisation was associated with lower proportion of long-term revascularisation (145/1374 (10.6%) in complete group versus 258/1242 (20.8%) in culprit-only group; RR 0.47, 95% CI 0.39 to 0.57; participants = 2616; studies = 9; I2 = 31%; very low quality evidence). TSA of long-term all-cause mortality, long-term cardiovascular mortality, and long-term non-fatal myocardial infarction showed that more RCTs are needed to reach more conclusive results on these outcomes. Regarding long-term repeat revascularisation more RCTs may not change our present result. The quality of the evidence was judged to be very low for all primary and the majority of the secondary outcomes mainly due to risk of bias, imprecision, and indirectness. AUTHORS' CONCLUSIONS: Compared with culprit-only intervention, the complete revascularisation strategy may be superior due to lower proportions of long-term cardiovascular mortality, long-term revascularisation, and long-term non-fatal myocardial infarction, but these findings are based on evidence of very low quality. TSA also supports the need for more RCTs in order to draw stronger conclusions regarding the effects of complete revascularisation on long-term all-cause mortality, long-term cardiovascular mortality, and long-term non-fatal myocardial infarction.

Catecholaminergic Polymorphic Ventricular Tachycardia: Clinical Characteristics, Diagnostic Evaluation and Therapeutic Strategies.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe hereditary arrhythmia syndrome predominantly affecting children and young adults. It manifests through bidirectional or polymorphic ventricular arrhythmia, often culminating in syncope triggered by physical exertion or emotional stress which can lead to sudden cardiac death. Most cases stem from mutations in the gene responsible for encoding the cardiac ryanodine receptor (RyR2), or in the Calsequestrin 2 gene (CASQ2), disrupting the handling of calcium ions within the cardiac myocyte sarcoplasmic reticulum. Diagnosing CPVT typically involves unmasking the arrhythmia through exercise stress testing. This diagnosis emerges in the absence of structural heart disease by cardiac imaging and with a normal baseline electrocardiogram. Traditional first-line treatment primarily involves ß-blocker therapy, significantly reducing CPVT-associated mortality. Adjunctive therapies such as moderate exercise training, flecainide, left cardiac sympathetic denervation and implantable cardioverter-defibrillators have been utilized with reasonable success. However, the spectrum of options for managing CPVT has expanded over time, demonstrating decreased rates of arrhythmic events. Furthermore, ongoing research into potential new therapies including gene therapies has the potential to further enhance treatment paradigms. This review aims to succinctly encapsulate the contemporary understanding of the clinical characteristics, diagnostic approach, established therapeutic interventions and the promising future directions in managing CPVT.

Life-threatening hyperkalemia: a potentially lethal drug combination.

Hyperkalemia is commonly seen in the elderly and is occasionally fatal. Inadvertently combining potassium sparing medications can result in profound hyperkalemia which may result in cardiac dysrhythmias, especially in the setting of chronic kidney disease. An 85 year-old woman on a drug regimen of sotalol, valsartan, spironolactone, and trimethoprim-sulfamethoxazole presented to the emergency department with hypotension and bradycardia. Presumptive treatment for hyperkalemia was started based on her initial electrocardiogram. This diagnosis was later confirmed with a serum potassium value of 10.1 mmol/L. Following pharmacologic treatment, emergency hemodialysis was performed and the patient subsequently recovered. It is known that several drug classes can cause hyperkalemia, with elderly patients at a higher risk of developing this side effect. It is believed that this was a major contributor to the degree of hyperkalemia seen in this patient.

Does choice of antidiabetes therapy influence macrovascular outcomes?

Despite a clear epidemiologic relationship between hemoglobin A(1c) levels and the risk of cardiovascular (CV) disease in patients with type 2 diabetes mellitus (T2DM), prospective studies examining the benefit of intensive glucose lowering in reducing CV events have yielded conflicting results. Controversy over the choice of antidiabetic therapy for lowering macrovascular events has existed for nearly four decades, beginning with the potential risk of increased CV mortality with sulfonylurea use. Although sulfonylureas were subsequently felt to be safe, a more recent controversy was raised as to whether rosiglitazone use was associated with an increased risk of CV events. Additionally, early positive results for metformin in reducing macrovascular events have not been clearly substantiated. Because a typical patient with T2DM may live 20 to 40 years with the disease, long-term prevention of CV events is very important. An evidenced-based review of choice of antidiabetic therapy to reduce CV events in T2DM is discussed below.

Determining the Significance of Coronary Plaque Lesions: Physiological Stenosis Severity and Plaque Characteristics.

The evaluation of coronary lesions has evolved in recent years. Physiologic-guided revascularization (particularly with pressure-derived fractional flow reserve (FFR)) has led to superior outcomes compared to traditional angiographic assessment. A greater importance, therefore, has been placed on the functional significance of an epicardial lesion. Despite the improvements in the limitations of angiography, insights into the relationship between hemodynamic significance and plaque morphology at the lesion level has shown that determining the implications of epicardial lesions is rather complex. Investigators have sought greater understanding by correlating ischemia quantified by FFR with plaque characteristics determined on invasive and non-invasive modalities. We review the background of the use of these diagnostic tools in coronary artery disease and discuss the implications of analyzing physiological stenosis severity and plaque characteristics concurrently.

Potential of glucose-lowering drugs to reduce cardiovascular events.

Although a clear relationship exists between glycosylated hemoglobin and cardiovascular (CV) disease in individuals with type 2 diabetes mellitus (T2DM) in epidemiologic studies, data from prospective studies are less clear. Earlier prospective studies examining intensive glucose lowering suffered from a lack of statistical power to show CV event reduction, as well as a lack of durable glycemic control and relatively poor control of associated CV risk factors. Although recent CV outcome trials comparing intensive glycemic compared with standard glycemic control have been disappointing, CV event rates appear to be declining substantially in T2DM individuals in the setting of aggressive global CV risk factor modification. No single hypoglycemic agent or combination of agents was associated with increased CV events or mortality. A comprehensive strategy of multifactorial intervention including aggressive and durable glycemic blood pressure, and lipid lowering, aspirin usage, and lifestyle modifications is beneficial in reducing macrovascular and microvascular events in T2DM individuals.

Invasive Evaluation of the Microvasculature in Acute Myocardial Infarction: Coronary Flow Reserve versus the Index of Microcirculatory Resistance.

Acute myocardial infarction (AMI) is one of the most common causes of death in both the developed and developing world. It has high associated morbidity despite prompt institution of recommended therapy. The focus over the last few decades in ST-segment elevation AMI has been on timely reperfusion of the epicardial vessel. However, microvascular consequences after reperfusion, such as microvascular obstruction (MVO), are equally reliable predictors of outcome. The attention on the microcirculation has meant that traditional angiographic/anatomic methods are insufficient. We searched PubMed and the Cochrane database for English-language studies published between January 2000 and November 2019 that investigated the use of invasive physiologic tools in AMI. Based on these results, we provide a comprehensive review regarding the role for the invasive evaluation of the microcirculation in AMI, with specific emphasis on coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR).

The role of aspirin resistance in the treatment of acute coronary syndromes.

The TIMI Risk Score recognizes prior aspirin use as an independent risk factor for adverse outcomes in subjects presenting with an acute coronary syndrome. The etiology of this increased risk awaits clarification, but prior aspirin use may be associated with altered thrombus composition which is more resistant to current treatment modalities as compared to thrombus formation in subjects without prior aspirin use. Post hoc analysis of acute coronary syndrome trials has shown that prior aspirin users treated with unfractionated heparin are at particularly high risk. The addition of glycoprotein IIb/IIIa receptor inhibitor to unfractionated heparin or substitution of low-molecular-weight heparin significantly improves outcomes in prior aspirin users. The prognostic significance of prior aspirin use in acute coronary syndromes has important implications not only in clinical practice, but also in the design and interpretation of clinical trials.

Mechanism by which hyperglycemia plays a role in the setting of acute cardiovascular illness.

Acute hyperglycemia is associated with excess morbidity and mortality in acute cardiovascular illness in both diabetic and nondiabetic patients. Hyperglycemia is associated with altered myocardial energetics, but abnormalities in glucose oxidation and glycolysis do not fully account for this excess risk. Hyperglycemia leads to a pro-oxidative/proinflammatory state that is associated with endothelial dysfunction, diminished coronary vasodilatory reserve, and a prothrombotic state. Hyperglycemia negates the protective effect of ischemic preconditioning and, most importantly, appears to interfere with the salutary effects of insulin in acute cardiovascular illness. Aggressive therapy with continuous infusion of insulin seems to improve a host of metabolic and physiologic effects associated with acute hyperglycemia and appears warranted if euglycemia can be maintained.

The effect of a six-week program of yoga and meditation on brachial artery reactivity: do psychosocial interventions affect vascular tone?

BACKGROUND: Chronic stress is estimated to increase the risk of cardiovascular (CV) events two-fold. Although stress reduction has been linked to a reduction in CV events, little is known regarding its exact mechanism of benefit. HYPOTHESIS: Yoga and meditation will improve parameters of endothelial function. METHODS: We examined the effects of yoga and meditation on hemodynamic and laboratory parameters as well as on endothelial function in a 6-week pilot study. Systolic and diastolic blood pressures, heart rate, body mass index (BMI), fasting glucose, lipids, hs C-reactive protein (CRP), and endothelial function (as assessed by brachial artery reactivity) were all studied at baseline and after 6 weeks of yoga practice. RESULTS: A course in yoga and meditation was given to the subjects for 1.5 h three times weekly for 6 weeks and subjects were instructed to continue their efforts at home. This prospective cohort study included 33 subjects (mean age 55 +/- 11 years) both with (30%) and without (70%) established coronary artery disease (CAD). There were significant reductions in blood pressure, heart rate, and BMI in the total cohort with yoga. None of the laboratory parameters changed significantly with yoga. For the total cohort there was no significant improvement in endothelial-dependent vasodilatation with yoga training and meditation compared with baseline (16.7% relative improvement from 7.2-8.4%; p = 0.3). In the group with CAD, endothelial-dependent vasodilatation improved 69% with yoga training (6.38-10.78%; p = 0.09). CONCLUSION: Yoga and meditation appear to improve endothelial function in subjects with CAD.

Stroke and a valvular lesion in a patient with stage IV non-small cell lung cancer.

The mechanism and severity of stroke varies in the setting of malignancy. We report a case of a 68-year-old man with lung adenocarcinoma, who experienced acute neurological symptoms. Imaging studies showed multiple acute ischaemic infarcts in cerebral and cerebellar hemispheres. Further work up was consistent with non-bacterial thrombotic endocarditis (NBTE). We highlight, through a review of the literature, the importance of transoesophageal echocardiography (TOE) in defining the above diagnosis. The treatment of NBTE consists of systemic anticoagulation and therapy of the underlying malignancy. Enoxaparin is preferred over warfarin to achieve this goal. He received systemic targeted therapy with erlotinib. A TOE performed 8 months later showed complete resolution of the vegetation.

Cardiovascular risk factors in the metabolic syndrome: impact of insulin resistance on lipids, hypertension, and the development of diabetes and cardiac events.

Metabolic syndrome (MS) is associated with excess cardiovascular risk above and beyond the contribution of traditional risk factors. It is a proinflammatory and prothrombotic condition associated with underlying insulin resistance. Hypertension and hyperlipidemia in the setting of MS are also associated with excess cardiovascular risk, as is the development of new onset diabetes during the course of therapy. Although impaired fasting glucose and impaired glucose tolerance (IGT) both predict the development of diabetes mellitus, IGT more strongly predicts CV events because it is associated with a greater degree of insulin resistance. Early recognition and aggressive lifestyle interventions are the cornerstones of treatment, with aggressive pharmacologic therapy introduced when appropriate. It is expected that future studies will more clearly define the early use of insulin-sensitizing agents in MS.

The role of intensive glycemic control in the management of patients who have acute myocardial infarction.

Hyperglycemia is associated with excess mortality in AMI and should be treated aggressively in the intensive care setting. The exact goal of therapy is unclear because different blood glucose targets were used in earlier studies (eg, 215 mg/dL in DIGAMI versus 110 mg/dL in the Belgian study of critically-ill patients). In the setting of AMI, it is prudent to avoid excessive hypoglycemia and, thus, more modest goals for blood glucose may be considered until more definitive data are present. Aggressive therapy with continuous infusion of insulin seems to improve a host of metabolic and physiologic effects that are associated with acute hyperglycemia and improves mortality in the acute setting. Aggressive glycemic control should be coupled with appropriate use of reperfusion therapies, glycoprotein IIb/IIa inhibitors, aspirin, 1-blockers, ACE inhibitors, and antithrombotic agents. The role of intensive chronic glucose control in reducing CV events is less clear but earlier studies were not well-powered; did not achieve aggressive, durable glycemic control; and did not use insulin-sensitizing agents routinely. Given the results of the DIGAMI trial, the goal of therapy postdischarge should include strict glycemic control while future studies help to delineate the role of insulin-sensitizing agents versus insulin-providing agents in reducing recurrent macrovascular events. Careful attention also should be paid to aggressive lifestyle modifications and treatment of hypertension, hyperlipidemia, and left ventricular dysfunction, as well as appropriate use of anti-platelet and antithrombotic agents.

Coronary thrombosis related to use of Xenadrine RFA.

Recently, ephedra was removed from the U.S. marketplace due to a heightened concern that dietary supplements containing ephedra may present "an unreasonable risk of illness or injury." This is the 1st time the U.S. Food and Drug Administration has banned an herbal supplement, and the ban sheds light on the potential harm of nutritional supplements that are used for weight loss or as a boost to athletic performance. We report the case of a body builder who used Xenadrine RFA, an ephedra-containing supplement, at recommended doses for nearly a year; he then experienced an acute myocardial infarction, which was documented to be secondary to thrombosis in situ. We ruled out other possible causes of myocardial infarction, as well a hypercoagulable state. There was no evidence of illicit drug use. Our report serves as a poignant reminder of the potential dangers of herbal supplementation, especially when used to heighten athletic performance.

Plaque disruption and thrombus in Ambrose's angiographic coronary lesion types.

Lesion eccentricity with irregularities on coronary angiography is associated with ruptured plaques and thrombus based on postmortem and clinical angiographic studies. However, the predictive value of such angiographic markers of plaque disruption and thrombus remains to be determined in vivo. The purpose of this study was to establish whether Ambrose's angiographic coronary lesion types and other angiographic criteria predict the presence of disrupted plaques and thrombus using intracoronary angioscopy. Angioscopy was performed before angioplasty in 60 patients with various coronary syndromes and culprit lesions that were not totally occlusive. Lesions were classified angiographically according to Ambrose's criteria as concentric, type I and II eccentric, and multiple irregularities, or as complex or noncomplex, and then compared with the corresponding angioscopic findings. Disruption and/or thrombus were seen in 17 of 19 type II eccentric lesions and 21 of 23 angiographically complex lesions and had the highest positive predictive value to detect complicated atherosclerotic plaques (type II eccentric lesions: positive predictive value 89%, 95% confidence intervals 67% to 99%; complex lesions: 91%, 95% confidence intervals 72% to 99%). We conclude that Ambrose's type II eccentric stenoses and angiographically complex lesions are strongly associated with disrupted plaques and/or thrombus as assessed by angioscopy in patients and represent unstable plaque substrates.

Treating the diabetic patient: appropriate care for glycemic control and cardiovascular disease risk factors.

Diabetes, a leading cause of morbidity and mortality in the United States, is associated with a 2- to 4-fold increase in the risk of coronary artery disease. As the population in the United States has aged, the incidence of obesity, hypertension, glucose intolerance, and dyslipidemia has increased significantly, culminating in the current epidemic of type 2 diabetes mellitus. Strict glycemic control must, therefore, be accompanied with proven therapies (such as antihypertensives and lipid-lowering agents) to reduce cardiovascular events. Patients with type 2 diabetes have average low-density lipoprotein (LDL) levels but have an increased number of small, dense LDL particles, which are associated with a 3-fold increase in cardiovascular disease. Type 2 diabetes mellitus is also associated with increased triglyceride rich atherogenic particles, which trigger inflammation. In addition to glycemic control and drug therapy, lifestyle modifications (eg, diet, weight loss, and exercise) also play an important role in managing diabetes. Therefore, strict glycemic control, pharmacologic therapy, and lifestyle modifications are parts of a comprehensive strategy to prevent both microvascular and macrovascular events in patients with type 2 diabetes.

Minor elevations in troponin T values enhance risk assessment in emergency department patients with suspected myocardial ischemia: analysis of novel troponin T cut-off values.

BACKGROUND: A consensus document developed by a joint committee of the European Society of Cardiology and the American College of Cardiology redefines myocardial infarction (MI) using an increase of troponin I or T as compared to a reference control population (i.e., troponin T (TnT) of 0.01 microg/l). A clinical problem arises when an arbitrary cut-off point is selected for determination of MI (i.e., TnT> or =0.1 microg/l), as minor elevations of troponin are associated with increased cardiovascular risk in selected patients with acute coronary syndromes. METHODS: We prospectively studied 420 unselected patients being evaluated for suspected myocardial ischemia in the emergency department (ED). We compared a 99th percentile MI cut-off limit for TnT, determined by constructing a standard receiver operator curve from our ED population in whom an acute coronary syndrome was excluded, to a standard MI cut-off limit of 0.1 microg/l in assessing cardiovascular risk. We also assessed the prognostic value of detectable TnT concentrations below this 99th percentile MI cut-off, but above the upper reference limit of healthy controls. RESULTS: The diagnosis of acute coronary syndromes (ACS) was more frequent in groups with higher TnT concentrations: 16.8% with a normal TnT (<0.03 microg/l), 29.5% with detectable TnT below the 99th percentile MI limit (0.03-0.066 microg/l), 64.3% with detectable TnT between the 99th percentile and standard MI cut-offs (0.067-0.099 microg/l), and 85.4% with TnT> or =0.1 microg/l (p<0.001 for the trend). Thirty-day cardiovascular event rates increased for any detectable concentration of troponin: 1.3% with normal TnT, 4.8% with detectable TnT below the 99th percentile MI limit, 15.4% with TnT between the 99th percentile and standard MI cut-off limits, and 12.5% with TnT> or =0.1 microg/l (p<0.01 for the trend). CONCLUSION: Using an MI cut-off concentration for TnT from a "non-ACS reference" improves risk stratification, but fails to detect a positive TnT in 11.7% of subjects with an acute coronary syndrome.

Value of a single troponin T at the time of presentation as compared to serial CK-MB determinations in patients with suspected myocardial ischemia.

BACKGROUND: Prior studies with cardiac markers have focused predominantly on subjects presenting to the emergency department with chest pain or unstable angina, and have relied on serial markers for the diagnosis of acute myocardial infarction. We evaluated the diagnostic utility of a single cardiac troponin T (cTnT) determination at the time of presentation as compared to serial creatine kinase (CK) MB determinations in a broad spectrum of patients with suspected myocardial ischemia. METHODS: A total of 267 consecutive patients presenting to the emergency department with suspected myocardial ischemia had a single, blinded cTnT determination drawn at the time of presentation to the emergency department in addition to routine serial electrocardiographic and CK-MB determinations. RESULTS: The specificity (93.7% vs. 87.1%; p<0.05) and positive predictive value (80.0% vs. 69.4%; p<0.05) of a single cTnT determination were superior to that of serial CK-MB determinations without compromising sensitivity. Forty-six percent of patients with confirmed myocardial infarction and an abnormal cTnT at presentation had a normal initial CK-MB determination. Conversely, 20% of patients without acute coronary syndromes had an abnormal CK-MB determination in the setting of a normal cTnT. The initial cTnT was abnormal in all patients with confirmed myocardial infarction and a symptom duration of at least 3.5 h. CONCLUSIONS: In a heterogeneous population of patients with suspected myocardial ischemia, the initial cTnT determination drawn at the time of presentation is a powerful diagnostic tool that, when used in context with symptom duration, allows for more rapid and accurate triage of patients than serial CK-MB determinations.

Benzocaine-induced methemoglobinemia: a potentially fatal complication of transesophageal echocardiography.

We describe the cases of 2 patients who developed benzocaine-induced methemoglobinemia after the administration of benzocaine as premedication for transesophageal echocardiography. The use of intravenous methylene blue resolved the cyanosis in both patients. Physicians who perform procedures involving the application of topical anesthesia need to be aware of this side effect to prevent morbidity and mortality.