Automated characterization of coronary artery disease, myocardial infarction, and congestive heart failure using contourlet and shearlet transforms of electrocardiogram signal

MAJOR perioperative cardiac events in patients undergoing noncardiac surgery continue to be a significant source of perioperative morbidity with ranges from 1.4% in relatively unselected patients1to 6% in patients older than 70 yr with cardiac disease.2Moreover, perioperative myocardial infarction (PMI) is one of the most important predictors of short- and long-term morbidity and mortality associated with noncardiac surgery.3–6The actual rate of PMI varies between studies in part because of the definition used and the method of surveillance. Part of the definition depends on the biomarkers (e.g. , creatine kinase [CK], lactate dehydrogenase, and troponin) used to define PMI. This article will review the evolution in the use of biomarkers and how more specific biomarkers have increased the rate of PMI detected.7According to the traditional definition, at least two of the three criteria must be fulfilled to diagnose myocardial infarction (MI): (i) typical ischemic chest pain; (ii) increased serum concentration of CK-MB (myocardial band) isoenzyme; and (iii) typical electrocardiographic findings, including development of pathologic Q waves. The advent of sensitive and specific serologic biomarkers has resulted in a major shift in the classic paradigms for diagnosing infarction.Devereaux et al. 8suggest that only 14% of patients experiencing a PMI will have chest pain and only 53% will have a clinical sign or symptom that may trigger a physician to consider an MI. The large proportion of clinically unrecognized MIs can be explained by several factors present in the immediate postoperative period: analgesics, intubation and sedation, and a host of more common explanations for potential signs and symptoms, such as atelectasis, pneumonia, hypovolemia, and bleeding.Electrocardiography plays a key role in the diagnostic workup of suspected MI. The changes in the ST-T waveforms and the Q waves potentially allow the clinician to date the event, to suggest the infarct-related artery, and to estimate the amount of myocardium at risk. Electrocardiography criteria for diagnosis of acute MI in the absence of left ventricular hypertrophy and left bundle branch block are ST elevation MI—new ST elevation at the J-point in two contiguous leads with the cutoff points: more than or equal to 0.2 mV in men or more than or equal to 0.15 mV in women in leads V2–V3and/or more than or equal to 0.1 mV in other leads; non-ST elevation MI (ST depression and T-wave changes)—new horizontal or down-sloping ST depression more than or equal to 0.05 mV in two contiguous leads; and/or T inversion more than or equal to 0.1 mV in two contiguous leads with prominent R wave or R/S ratio more than 1.However, the electrocardiogram by itself is often insufficient to diagnose acute myocardial ischemia or infarction because ST deviation may be observed in other conditions such as acute pericarditis, left ventricular hypertrophy, left bundle branch block, Brugada syndrome, and early repolarization patterns. Furthermore, in cardiomyopathy, for example, Q waves may occur due to myocardial fibrosis.9A more complete review can be found elsewhere.10Measurement of cardiac markers in blood has been the mainstay for diagnosis of acute MI for nearly 50 yr.A loss of cellular integrity of the sarcolemma results in the release of a number of proteins into the circulation that can be used as biochemical markers of acute myocardial necrosis. CK, SGOT (more recently known as AST), lactate dehydrogenase, myoglobin, and troponins are some of these markers. The timing of their appearance and disappearance in blood is mainly dependent on quantity of release, molecular size, and solubility (fig. 1). The first practical test used for biochemical detection of myocardial damage was the measurement of transaminases described in 1954.11Having wide tissue distribution, AST and lactate dehydrogenase are less specific for myocardial necrosis and offer no advantage over CK isoenzymes. Myoglobin, a heme-related protein abundant in cardiac and skeletal muscle, is an early marker of myocardial necrosis. It is detectable in the plasma 1–2 h after the onset of chest pain, with a peak at 3–8 h. With the availability of assays for CK isoenzymes, these tests were gradually abandoned, at least for an early diagnosis of MI.CK is the enzyme responsible for catalyzing the transfer of high-energy phosphate from creatine phosphate to adenosine triphosphate. CK is known to rise within 4–8 h after an acute MI and to decline to normal levels within 3–4 days. In 1960, Dreyfus et al. 12demonstrated markedly increased plasma CK activity in patients with MI. Total CK found in the normal circulation varies tremendously, and CK is a well-recognized marker of rhabdomyolysis. The problem of multiple etiologies makes interpretation of CK release more difficult in the surgical population.In 1966, van der Veen and Willebrands13demonstrated that CK-MB is a highly specific marker of MI. In the 1970s, it became evident that CK-MB was to be the standard for the diagnostic and quantitative assessment of MI. CK isoenzyme analysis substantially increased the sensitivity of this test for the diagnosis of acute MI. However, other types of myocardial injury, such as myocarditis, trauma, and cardiac surgery, also cause the release of CK-MB.14A variety of techniques were developed to further improve the sensitivity and rapidity of assaying for CK-MB. In the mid-1980s, the development of an antibody specific for CK-MB15marked the beginning of the era of immunologic detection of biomarkers. This technique of mass assay offered the advantage of measuring protein concentration over enzymatic activity. With direct analysis of CK-MB irrespective of total activity, it was quickly recognized that the myocardium is not the only tissue containing large amounts of CK-MB as initially believed.16CK-MB has been found in the small intestine, tongue, diaphragm, uterus, and prostate. Skeletal muscles also contain CK-MB in small amounts. In the surgical setting, the use of the CK-MB fraction is complicated by increased levels of both total CK and noncardiac CK-MB.The shift from transaminases and dehydrogenases to isoenzymes of the latter and then to CK, CK-MB, and CK-MB mass improved test precision, resulting in greater sensitivity and specificity in the diagnosis of MI over time and better case classifications. However, these tests still did not allow the definite distinction of skeletal and cardiac muscle injuries. This lack of cardiospecificity accelerated the desire for a more specific test than CK-MB.CK-MB was considered the benchmark for MI diagnosis from the 1980s through the late 1990s. The diagnostic sensitivity of both CK-MB (activity or mass) and the troponins markedly increases with time. Sampling to at least 10 h yields approximately 90% diagnostic sensitivity with either biomarker.17In a meta-analysis by Balk et al. ,18CK-MB showed a rather low cumulative sensitivity of 79% and a cumulative specificity of 96% in emergency department patients. It could be argued, however, that inclusion of studies that mixed results of assays, different cutoff strategies, and less than ideal sampling almost certainly led to underestimation of diagnostic sensitivity. Wu and Lane19limited inclusion to studies that used CK-MB mass assays in samples collected over the appropriate timeframe of 12–24 h after the onset of symptoms. Their meta-analysis reported a cumulative sensitivity of 97% and cumulative specificity of 90%.The cardiac troponins are regulatory proteins with both cytosolic and structural pools that are released because of necrosis. The troponin complex is located on the thin filament of striated muscle and consists of three subunits: troponin T, a binding protein that attaches the troponin complex to tropomyosin; troponin I, which modulates the interaction of actin and myosin by acting as an inhibitor of actomyosin adenosine triphosphatase activity; and troponin C, the calcium-binding subunit of the troponin complex. The cardiac forms are designated cardiac troponin I (cTnI) and cardiac troponin T (cTnT). Cardiac troponin has nearly absolute myocardial tissue specificity and high clinical sensitivity.20Several large studies of patients with acute coronary syndrome support the clinical efficacy of troponin over the previous gold standard: the CK and its MB fraction.Although there is only one assay for cTnT, there is a multiplicity of assays for cTnI with substantial heterogeneity of assay sensitivities.21Manufacturers are now developing a new generation of high-sensitivity cTn assays that are more precise at low concentrations and measure cTn concentration at less than 1 ng/l. Of note, cTn assays are neither standardized nor harmonized. Different assays are composed of different antibody configurations recognizing different epitopes of cTnI, suggesting that specific assays may detect slightly different groups of patients, depending on the nature and timing of cTn release.22The performance of assays and the release kinetics and plasma clearance of both troponin T and I have been described elsewhere.23–25An increased value for cardiac troponin is defined as a measurement exceeding the 99th percentile of a normal reference population (upper reference limit). Detection of a rise and/or fall of troponin is essential to the diagnosis of acute MI. Blood samples for measurement of troponin should be drawn on first assessment and 6–9 h later. The above-mentioned discriminatory percentile is designated as the decision level for the diagnosis of MI and must be determined for each specific assay with appropriate quality control. It has also been recommended that optimal test reproducibility should be defined as less than or equal to 10% imprecision at the 99th percentile upper reference limit for each assay.One of the biggest issues apart from the problem of selecting relevant reference subjects is the current practice of the Food and Drug Administration of approving assays based on higher receiver-operating characteristic-optimized cutoffs. In a recent issue of clinical chemistry, Apple26introduced his concept of a scorecard approach to decide which assays are acceptable for use in clinical practice. He proposed a two-tier system using both the 99th percentiles and imprecision values at the 99th percentile based on a young, healthy reference population that is diversified by sex, race, and ethnicity.The first major study to evaluate the perioperative use of cTnI was conducted by Adams et al. 27The authors compared electrocardiogram, total CK, CK-MB, and cTnI with the gold standard (new akinesia or dyskinesia on postoperative transthoracic echocardiography) for detection of perioperative infarction in 108 patients undergoing vascular or spine surgery. Blood samples were obtained every 6 h for a least the first 36 h after surgery. In this population, a PMI as defined by new abnormalities of wall motion was diagnosed in 8 patients (8%). The sensitivity of cTnI was 100% and that of CK-MB was 75%. The difference between the specificity of cTnI (99%) and that of CK-MB (81%) was significant (P < 0.005). Thus, these data did not establish the superior sensitivity of cTnI compared with CK-MB, only its superior specificity for the detection of perioperative infarction.Lee et al. 28evaluated the diagnostic performance of cTnT as a marker for myocardial injury in 1,175 patients aged 50 yr or older and undergoing major noncardiac surgery. CK-MB and electrocardiographic criteria were used to define acute MI. cTnT was measured in the recovery room after surgery and on the next two postoperative mornings. Acute MI was diagnosed in 17 patients (1.4%). cTnT increases occurred in 87% of patients with MI and in 16% of patients without MI, yielding a sensitivity of 87% and a specificity of 84%. The receiver-operating characteristic curves indicated that the two tests had similar diagnostic performance in detecting MI but that cTnT was superior for prediction of complications.Metzler et al. 29conducted a study with the aim of examining the perioperative pattern of changes in troponin. Blood sampling was performed daily from the day before surgery until the fifth postoperative day (POD) in 67 patients with cardiac risk undergoing elective noncardiac surgery. Eight of the 13 patients (12%) with increased cTnT concentrations had an adverse outcome. In seven patients, CK-MB and troponin increases were discordant. With a cTnT cutoff at 0.2 ng/ml, the positive and negative predictive values for adverse outcome were only 62% and 100%, respectively. By choosing a higher cutoff of 0.6 ng/ml, the positive and negative predictive values for adverse outcome were 88% and 98%.Haggart et al. 30compared the value of cTnI and CK/CK-MB ratios for detection of myocardial injury in 59 patients undergoing either emergency (24) or elective aortic surgery. More than half the patients undergoing emergency surgery and more than a quarter of those having elective surgery suffered myocardial necrosis as determined by detectable cTnI levels. This was accompanied by an increased CK-MB/CK ratio in less than one-fifth of patients.The use of cTnI in diagnosing PMI in the setting of orthopedic surgery was evaluated by Jules-Elysee et al. 31in 85 patients with risk factors for coronary artery disease. In this population, cTnI seemed to be as sensitive as and more specific than the CK-MB index.Martinez et al. 32evaluated surveillance strategies for the diagnosis of PMI using TnI in a cohort of 467 patients at high risk who required noncardiac surgery, with the goal of identifying the highest diagnostic yield. The diagnosis of myocardial injury was determined by biomarkers combined with either postoperative changes on 12-lead electrocardiogram or one of three clinical symptoms consistent with MI (chest pain, dyspnea, or requirement for hemodynamic support). The incidence of MI was 9.0% by the criterion of cTnI greater than or equal to 2.6 ng/ml, 19% by TnI greater than or equal to 1.5 ng/ml, 13% by CK-MB mass, and 2.8% by CK-MB ratio. The specificity of TnI greater than or equal to 2.6 ng/ml as an indicator of MI was 98%, and its positive predictive value was 85%. Using this cutoff, the strategy with the highest diagnostic yield was surveillance on PODs 1, 2, and 3.Le Manach et al. 33used cTnI surveillance after abdominal aortic surgery in 1,136 patients to better evaluate the incidence and timing of PMI (TnI ≥ 1.5 ng/ml) or myocardial damage (abnormal cTnI < 1.5 ng/ml). Abnormal cTnI concentrations were noted in 163 patients (14%), of whom 106 (9%) had myocardial damage and 57 (5%) had PMI. In 34 patients (3%), PMI was preceded by a prolonged (>24 h) period of increased cTnI, and in 21 patients (2%) the increase in cTnI lasted less than 24 h. Abnormal but low postoperative cTnI was associated with increased mortality and could lead to MI. The authors concluded that they had identified two different types of PMI, early and delayed (fig. 2).The fact that, in the cohort studied by Lee et al. ,2890% of patients with cTnT increases did not have clinical complications during the perioperative follow-up raised the question whether these values were false-positive results or evidence of subclinical myocardial injury. To address this issue, Lopez-Jimenez et al. 34collected 6-month follow-up data on a subcohort of 772 patients from the previous study. During the follow-up period, there were 19 (2.5%) major cardiac complications. A cTnT value more than 0.1 ng/ml was an independent correlate of cardiac events, whereas CK-MB was not correlated with postdischarge cardiac events.Badner et al. 35intensively monitored isoenzyme and electric activity of the heart for the first 7 postoperative days in 323 patients with ischemic heart disease, aged 50 yr or older, and undergoing noncardiac surgery. After surgery, patients had daily clinical assessments, electrocardiograms, and measurements of CK, CK-MB, and cTnT (not used in the first 92 patients) on the operative night, twice daily on PODs 1–4, and then daily on days 5–7. The criteria for PMI diagnosis were designed to require the presence of an indicator of high sensitivity (increased total CK) and at least two indicators of high specificity (increased CK-MB, increased cTnT, Q waves, or a positive result of a pyrophosphate scan). The authors observed a 6% incidence for PMI using these criteria. With 14 of 18 events occurring during the first postoperative night, they corroborated the finding that PMI is an early postoperative event in patients with known ischemic heart disease. Use of TnT increase as a sole criterion for the diagnosis of PMI would have nearly doubled the incidence and moved the peak of event occurrence to the first POD. Interestingly, 1-year follow-up suggested that patients with silent PMIs have similar short-term outcomes as those with symptomatic PMIs.Neill et al. 36evaluated the changes in cardiac protein concentrations (CK-MB, cTnT, and cTnI) after vascular or major orthopedic surgery in 80 patients older than 45 yr. The authors compared these changes as markers of postoperative cardiac complications with the incidence of ambulatory electrocardiographic changes for silent myocardial ischemia. Eight patients (10%) had major and 21 patients (27%) had minor postoperative complications. Both cTnT and cTnI showed high specificity for major complications, 96% and 97% respectively, but sensitivity was only 43% for cTnT and 29% for cTnI. There were no associations between postoperative ischemia and cardiac protein concentrations. At 3-month follow-up, cTnT correlated best with complications.The ideal discrimination value of cTnI between the "complicated and uncomplicated" patient groups was investigated by Godet et al. 37in 329 patients undergoing infrarenal aortic surgery. cTnI was measured at recovery and on PODs 1–3. MI was defined as new Q wave or prolonged ST-T depression for more than 2 days. Thirteen patients (4%) developed 19 relevant cardiac complications (cardiac failure, MI, and cardiac death) in the postoperative period. A cTnI level greater than 0.54 ng/ml was correlated with the occurrence of postoperative cardiac complications in the period until discharge. That cutoff yielded a sensitivity of 75% and a specificity of 89%. Late cardiac complications occurring in the first year after aortic surgery were not correlated with cTnI.Kim et al. 38found that increased cTnI levels were associated with a significantly increased risk of PMI and 6-month mortality in a group of 229 patients after major vascular surgery. They further reported a dose–response relation between cTnI concentration and mortality.According to the new universal definition of MI, any of the following criteria meets the diagnosis for MI: detection of rise or fall of cardiac biomarkers (preferably troponin) with at least one value above the 99th percentile of the upper reference limit together with evidence of myocardial ischemia with at least one of the following: symptoms of ischemia; electrocardiogram changes indicative of new ischemia (new ST-T changes or new left bundle branch block); development of pathologic Q waves in the electrocardiogram; and imaging evidence of new loss of viable myocardium or new regional wall motion abnormality.39However, it is important to keep in mind that nearly all the well-accepted studies of clinical risk stratification are based at least in part on diagnosis of PMI using adaptations of the World Health Organization definition, which requires any two of three criteria: ischemic symptoms, electrocardiographic changes, and increased CK-MB levels.In summary, the available studies highlight the difficulty of using cardiac-specific troponin to distinguish myocardial damage from infarction. Commonly, troponin increase alone is mistakenly equated with the diagnosis of MI. However, many conditions may be associated with increased troponin levels, including neurologic injury, brain death, hemorrhagic shock, cardiac trauma, sepsis, hypotension, renal insufficiency, pulmonary embolism, heart failure, and any other condition with increased ventricular wall stress.40–44Furthermore, although recently any increase in troponin in the appropriate clinical setting had been considered indicative of myocardial necrosis rather than ischemia, results from the Protein Markers of Ischemia using Proteomic Testing—TIMI 35 study showed that transient stress-induced myocardial ischemia is associated with a quantifiable increase in circulating troponin that is detectable with a novel, ultrasensitive cTnI assay.45Another issue that remains to be addressed is use in terms of guiding aggressiveness of care. Even if we believe that there is value in perioperative surveillance looking for troponin leakage in the absence of other criteria for MI, the question remains whether early therapy could affect outcome in terms of morbidity and mortality either in the perioperative period or after discharge.The new generation of hs cTn-assays has been shown to be superior to the standard troponin assays for early diagnosis of MI in two recently published studies.46,47However, these studies did not assess the effect of the sensitive troponin assays on clinical management. Furthermore, it remains to be proven whether the results from a group of patients with a high pretest probability can be translated to postsurgical conditions.Consistently performing better than traditional clinical risk scores and preoperative diagnostic tests, the natriuretic peptides clearly hold promise as a relatively cheap and noninvasive risk stratification tool, perhaps both pre- and postoperatively.48Hs C-reactive protein has been shown to be predictive of both immediate postoperative outcome49and significantly decreased overall survival50in the setting of coronary artery bypass surgery.Another interesting approach may be the simultaneous measurement of multiple biomarkers. Goei et al. recently demonstrated that both hs C-reactive protein and NT-pro-brain natriuretic peptide have additional value in the prediction of postoperative cardiac events in vascular surgery patients to cardiac risk factors alone. The integrated use of both NT-pro-brain natriuretic peptide and hs C-reactive protein was able to improve cardiac risk stratification.51Fellahi et al. 52assessed the multiple marker approach in cardiac surgery. Their recently published study showed that simultaneous measurement of cTnI, brain natriuretic peptide, and C-reactive protein improves the risk assessment of long-term adverse cardiac outcome after cardiac surgery.The evidence to guide the rational use of perioperative cardiac monitoring, electrocardiograms, and troponins is limited, and further evaluation regarding the optimal strategy is required. On the basis of the current evidence, in patients without documented coronary artery disease, surveillance should be restricted to those who develop perioperative signs of cardiovascular dysfunction. In patients with high or intermediate clinical risk who have known or suspected coronary artery disease and who are undergoing high- or intermediate-risk surgical procedures, serial 12-lead electrocardiograms should be obtained at baseline, immediately after the surgical procedure and on PODs 1 and 2. Consideration should be given to the use of cardiac-specific troponins for the first 4 days after surgery.In light of all the areas of uncertainty concerning the clinical value of measuring troponin leakage, the 2007 update of the American College of Cardiology/American Heart Association Perioperative Evaluation Guidelines the for postoperative troponin measurement to patients with electrocardiographic changes or chest pain typical of acute coronary syndrome of of Guidelines for preoperative cardiac risk assessment and perioperative cardiac in noncardiac surgery that were published in not sampling to cardiac

Coronary artery disease occurs when plaque is accumulated in the walls of the artery. This causes the artery to narrow, reducing blood flow to the heart. Coronary artery disease is globally identified as the most predominant and lethal cardiovascular disease. Furthermore, undiagnosed coronary artery disease may progress and lead to complications such as myocardial infarction and congestive heart failure. Hence there is a compelling need for the prompt and unerring detection of coronary artery disease, myocardial infarction, and congestive heart failure using automated systems. The electrocardiogram (ECG) is the most preferred method of detecting cardiovascular diseases as it is easily available and economical compared to imaging methods. Hence, this thesis describes the development of advanced models using ECG signals for the detection of coronary artery disease, myocardial infarction, and congestive heart failure, focusing on the detection of myocardial infarction. Also, this thesis contributes to the medical field as this offers some level of explainability of the inner workings of the deep models that clinicians may relate to. The reliability of the developed deep model used in healthcare applications such as emergency diagnosis of different types of myocardial infarction contributes significantly to clinicians. The thesis has three contributing chapters, which are given below. In the first chapter, the development of convolutional neural network (CNN) and GaborCNN (with a unique Gabor layer) models for rapidly classifying coronary artery disease, myocardial infarction, congestive heart failure, and healthy ECG signals is discussed. The ECG signals which were acquired from the Physikalisch- Technische Bundesanstalt database, were fed to the two models for classification. The GaborCNN was affirmed to be the better model for the classification task due to its high overall accuracy of 98.74% and lower computational demand. This is the first study to integrate the Gabor filter into the CNN model to automatically classify normal, coronary artery disease, myocardial infarction, and congestive heart failure classes using ECG signals. Despite the surge in the development of robust models for the automated detection of cardiovascular diseases, these are often not trusted by clinicians due to the lack of explainability of models’ mechanisms. Hence, in the second chapter, the development of the CNN and DenseNet models with the application of an advanced and unique GRAD- CAM technique to both models’ output is discussed. ECG beats were extracted from the healthy and ten myocardial infarction classes using the R peak detection algorithm and fed to the developed CNN and DenseNet models. Application of the GRAD-CAM technique enabled visualization of ECG leads and portions of ECG waves that influenced the models’ predictive decisions. DenseNet was identified as a better model due to its low computational complexity and higher classification accuracy of 98.9% due to feature reusability. Lead V4 was the most activated lead in both models. The DenseNet model with the Grad-CAM technique enables clinicians to determine the type of myocardial infarction based on explainability and, thus, has the potential to boost clinicians’ confidence in using it in hospital settings. This is the first study to report features that influenced the classification decisions of deep models for multi-class classification of myocardial infarction and healthy ECGs. Current diagnostic models for cardiovascular diseases have been primarily developed using public databases and are thus unsuitable for hospital settings, where the uncertainty of models is predominant. In the third chapter, a unique Dirichlet DenseNet model was trained with pre-processed myocardial infarction ECG signals and tested with noisy myocardial infarction signals. The predictive entropy was used as an uncertainty measure to determine the misclassification of normal and myocardial infarction signals. The misclassification of signals was determined based on the computation of four uncertainty metrics; uncertainty sensitivity, specificity, accuracy and precision. The proposed method demonstrates that the developed model is reliable as it is able to convey when it is not confident in the diagnostic information its presenting, having the potential to make a significant contribution to clinicians, especially in emergencies such as urgent diagnosis of myocardial infarction. This is the first work to have explored uncertainty quantification of a deep model using multi-class myocardial infarction ECG signals. In summary, the models proposed in the three chapters have great potential to contribute significantly to healthcare in areas such as the emergency diagnosis of acute myocardial infarction.

Is preventive medicine responsible for the increasing prevalence of heart failure?

Myocardial infarction is a major cause of death and disability worldwide. Coronary atherosclerosis is a chronic disease with stable and unstable periods. During unstable periods with activated inflammation in the vascular wall, patients may develop a myocardial infarction. Myocardial infarction may be a minor event in a lifelong chronic disease, it may even go undetected, but it may also be a major catastrophic event leading to sudden death or severe hemodynamic deterioration. A myocardial infarction may be the first manifestation of coronary artery disease, or it may occur, repeatedly, in patients with established disease. Information on myocardial infarction attack rates can provide useful data regarding the burden of coronary artery disease within and across populations, especially if standardized data are collected in a manner that demonstrates the distinction between incident and recurrent events. From the epidemiological point of view, the incidence of myocardial infarction in a population can be used as a proxy for the prevalence of coronary artery disease in that population. Furthermore, the term myocardial infarction has major psychological and legal implications for the individual and society. It is an indicator of one of the leading health problems in the world, and it is an outcome measure in clinical trials and observational studies. With these perspectives, myocardial infarction may be defined from a number of different clinical, electrocardiographic, biochemical, imaging, and pathological characteristics. In the past, a general consensus existed for the clinical syndrome designated as myocardial infarction. In studies of disease prevalence, the World Health Organization (WHO) defined myocardial infarction from symptoms, ECG abnormalities, and enzymes. However, the development of more sensitive and specific serological biomarkers and precise imaging techniques allows detection of ever smaller amounts of myocardial necrosis. Accordingly, current clinical practice, health care delivery systems, as well as epidemiology and clinical trials all require a …

Gender and coronary disease.

Cardiovascular disease constitutes a burden of epidemic proportion,1 and understanding its determinants is essential to designing effective interventions. Doing so requires the ability to track disease burden at the population level. In the United States, without national registries, community surveillance is the method of choice.2 Community surveillance studies are mostly retrospective by design, rely on diagnostic codes for case finding, and require a defined population in which events can be consistently and reliably captured and validated with standardized approaches. Applied to cardiovascular disease, community surveillance measures its burden in communities by tracking the incidence of events, their severity, and their mortality, thereby enabling the appraisal of the components of cardiovascular diseases in a given population.2 Because of the aforementioned methodological requirements, few surveillance studies exist in the United States. They include the Atherosclerosis Risk in Communities (ARIC) Study,3 the Minnesota Heart Survey,4 the Olmsted County Study,5 and the Worcester Heart Attack Study.6 The data from these studies indicate that, although deaths from coronary disease have declined, the incidence of myocardial infarction in the United States has remained mostly stable. Thus, the decline in mortality can be envisioned as reflecting an improvement in survival, which may be mediated by a declining severity of myocardial infarction. Article p 503 The article by Myerson et al7 in this issue of Circulation specifically addresses this important and understudied issue in ARIC between 1987 and 2002. They examined a large, multiracial population and relied on several indicators, including the composite Predicting Risk of Death in Cardiac Disease Tool (PREDICT) score to conclude that the severity of infarction declined over time. Indeed, the proportion of infarctions with major ECG abnormalities, ST-segment elevation, and Q waves decreased, as did biomarker values and the proportion of persons presenting with shock. …

Cardiovascular News

Plasma brain-type natriuretic peptide (BNP) and amino-terminal proBNP (NTproBNP) provide prognostic information on cardiovascular morbidity and mortality beyond that provided by standard risk factors. Clinical applications of B-type peptides under ongoing research include their use in diagnosing acute heart failure (HF), in risk stratification in both acute and established HF, in acute coronary syndromes (ACS), in asymptomatic populations at cardiovascular risk (older adults and people with hypertension), and as part of a screening strategy for detection of left ventricular impairment and prediction of cardiovascular risk in the general population.1,2 In this issue of Circulation , Campbell and colleagues3 assess the ability of NTproBNP to predict myocardial infarction (MI) in subjects who have experienced a cerebrovascular event. NTproBNP (reflecting cardiac distension) is compared with C-reactive protein (a systemic marker of inflammation) and renin (a marker of sodium status regulated by renal perfusion and delivery of sodium to the renal glomerulus). See p 110 The nested case-control study is from the 6105 participants in the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a placebo-controlled study of converting enzyme inhibitor–based therapy in patients with previous cerebrovascular events.4 Within PROGRESS, 206 subjects incurred an MI during 3.9 years of follow-up. The investigators matched those incurring an MI with control PROGRESS patients avoiding MI from time of randomization to time of case ascertainment. Cases and controls were matched for age, gender, treatment allocation, region, and cerebrovascular qualifying event. The form of matching meant that individual patients may have been controls initially and subsequently became cases on incurring an MI during further follow-up. Matching in this fashion may confuse the interpretation of the nonconditioned analysis of baseline variables. Comparing the 206 cases with 412 controls at randomization, the investigators report that in addition to higher systolic blood pressure, more frequent known coronary disease, …

Brain (B-type) natriuretic peptide (BNP) is a 32 amino acid peptide that is synthesized and released predominantly from ventricular myocardium in response to myocyte stretch. Like atrial natriuretic peptide (ANP), BNP seems to have almost exclusively beneficial physiological properties, including balanced vasodilation, natriuresis, and inhibition of both the sympathetic nervous system and the renin-angiotensin-aldosterone axis. Attempts to exploit these properties for therapeutic benefit has led to the development of recombinant human BNP (nesiritide) for the acute treatment of decompensated heart failure, and also of novel compounds that inhibit neutral endopeptidase, an enzyme that is partially responsible for BNP degradation. See p 2913 In patients with heart failure, the cardiac neurohormonal system is activated, and circulating plasma levels of ANP, BNP, and the N-terminal fragments of their prohormones (N-proANP and N-proBNP) are elevated. Compared with ANP and N-proANP, BNP and N-proBNP undergo a greater proportional rise in disease states (ie, higher “signal-to-noise” ratio), and thus have emerged as the preferred biomarkers for clinical development. With commercially available assays now available, measurement of BNP or N-proBNP can be integrated readily into the care of patients with suspected heart failure. Although data are limited, BNP and N-proBNP seem to provide qualitatively similar information, and for purposes of this editorial, will be referred to interchangeably. Incorporation of BNP measurement into the clinical evaluation facilitates the diagnosis of heart failure due to either left ventricular (LV) systolic or diastolic dysfunction; a normal BNP level virtually rules out the diagnosis of decompensated heart failure, whereas a markedly elevated BNP has a high positive predictive value for heart failure.1 Although BNP levels are correlated with age, sex, intracardiac filling pressures, LV mass and ejection fraction (LVEF), renal function, and symptoms, BNP provides prognostic information in patients with heart failure that is independent of these variables.2 …

The decline in coronary heart disease: Determining the paternity of success

Aspirin in heart failure: don't throw the baby (aspirin) out with the bathwater.

Table of ContentsI. IntroductionA. Development of GuidelinesB. General ApproachC. Preoperative Clinical EvaluationII. Further Preoperative Testing to Assess Coronary RiskA. Clinical MarkersB. Functional CapacityC. Surgery-Specific RiskIII. Management of Specific Preoperative Cardiovascular Condition

Abdominal aortic aneurysm and coronary artery disease: Frequent companions, but an uneasy relationship

Undiagnosed coronary artery disease in long-term type 1 diabetes. The Dialong study

Section 13: Evaluation and Therapy for Heart Failure in the Setting of Ischemic Heart Disease