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Objectives. We sought to determine the prognostic value of the admission electrocardiogram (ECG) in patients with unstable angina and non–Q wave myocardial infarction (MI).Background. Although the ECG is the most widely used test for evaluating patients with unstable angina and non–Q wave MI, little prospective information is available on its value in predicting outcome in the current era of aggressive medical and interventional therapy.Methods. ECGs with the qualifying episode of pain were analyzed in patients enrolled in the Thrombolysis in Myocardial Ischemia (TIMI) III Registry, a prospective study of patients admitted to the hospital with unstable angina or non–Q wave MI.Results. New ST segment deviation ≥1 mm was present in 14.3% of 1,416 enrolled patients, isolated T wave inversion in 21.9% and left bundle branch block (LBBB) in 9.0%. By 1-year follow-up, death or MI occurred in 11% of patients with ≥1 mm ST segment deviation compared with 6.8% of patients with new, isolated T wave inversion and 8.2% of those with no ECG changes (p < 0.001 when comparing ST with no ST segment deviation). Two other high risk groups were identified: those with only 0.5-mm ST segment deviation and those with LBBB, whose rates of death or MI by 1 year were 16.3% and 22.9%, respectively. On multivariate analysis, ST segment deviation of either ≥1 mm or ≥0.5 mm remained independent predictors of death or MI by 1 year.Conclusions. The admission ECG is very useful in risk stratifying patients with non–Q wave MI. The new criteria of not only ≥1-mm ST segment deviation but also ≥0.5-mm ST segment deviation or LBBB identify high risk patients, whereas T wave inversion does not add to the clinical history in predicting outcome.(J Am Coll Cardiol 1997;30:133–40)

In 2005, the Canadian Cardiovascular Society established an ad hoc working group that was charged with writing a commentary to bring together many of the issues that have arisen in the past few years surrounding physician human resources in cardiac sciences. These issues cover the supply side of the workforce (eg, physician shortages, excessive workloads and possible changes to the training of medical specialists) and the recently developed projections of the growth in demand for these services. The present commentary also notes factors that contribute to fundamental shifts in the balance between demand and supply, particularly the potential challenges that our specialists will face with the introduction of wait time targets for key services and procedures. It should come as no surprise to any health care provider that the burden of cardiovascular disease on the Canadian health care system is increasing. Advances in technology, treatment and health care delivery have improved outcomes in patients with cardiovascular illness. As a result, cardiac patients are living longer, often with greater comorbidities. This burden will continue to increase, because approximately 24% of the population will be older than 65 years of age by the year 2030. The pressure is being felt at every level of the health care delivery platform – from the community cardiologist to the subspecialist in a tertiary care centre. Cardiologists, on average, work 57 h a week, more than the average of 52 h for all specialists. In addition, they have an average of 106 h of on-call responsibilities every month (1). The heavy workload is not new; similar workloads were reported in the specialist physician workforce survey conducted by the Canadian Cardiovascular Society in 2001 (2). The continued high workload is taking its toll. In 2004, 31% of cardiologists reported that they were somewhat or very dissatisfied with the balance between personal and work commitments. Female cardiologists (44%) and all cardiologists younger than 45 years of age (37%) were even more likely to be dissatisfied with this balance (1). Despite this work effort, cardiologists cannot keep up with the need for their services. In the same survey, 21% of cardiologists reported that a new patient with a nonurgent condition would wait longer than three months for a first consultation. Urgent patients have more timely access to initial consults (64% of cardiologists reported a wait time of one week or less). In the words of a participant in one of the Canadian Medical Association’s focus groups on access to care, “the quality of health care in Canada is good once you get in” (3). However, for the nonurgent patient, ‘getting in’ is the real challenge, and the risk is that the nonurgent patient will wait and ultimately enter the system as an urgent referral or through the emergency room. With the introduction – and, we hope, the eventual adoption – of wait time benchmarks for key cardiovascular services and procedures (3), the demand for timely care will intensify. Recently published wait time benchmarks for cardiovascular care (4) suggest that elective consults should be seen within six weeks and urgent consults within seven days. Longer working hours are not an option; we need more trained health care providers within cardiovascular medicine. Indications are that the situation is not likely to improve any time soon. Just as the general population is aging, so is the cardiologist workforce. In 2003, 29% of cardiologists were 55 years of age and older, compared with only 22% in 2001 (5). Even if current training programs could replace the number of retiring cardiologists, the demographic mix and subspecialty choice of medical graduates is causing some concern. In 2004, 53.4% of all medical school graduates were female (6). Female physicians prefer, on average, a shorter work week than their male colleagues. This creates two problems for physician human resource planning. First, if a higher number of female physicians were attracted to cardiology, more physicians would be needed to provide the same service capacity. Second, cardiology has not been very successful in recruiting female medical graduates, likely in part due to the workload conditions. Although one-half of all medical school graduates are female, in 2006, only 30% of cardiologists younger than 35 years of age were female, according to the Canadian Medical Association Masterfile (7). It is possible that the high workload and challenges in balancing work and family life in this profession have been, and will continue to be, real barriers to attracting top candidates into the profession. Advances in treatment are also contributing to pressures on the existing workforce. Over the past decade, the rapid adoption of new procedures (such as angioplasty) and technological advances (such as drug-eluting stents), which have made these procedures the first choice for the majority of revascularizations, has increased the demand for interventional cardiologists. Similarly, expanding indications for implantable cardioverter defibrillators, which are now indicated for primary prevention of sudden cardiac death in patients with depressed left ventricular function, will increase the demand for electro-physiologists needed for related consultations, procedures (including device implantations) and follow-up. The epidemic of heart failure and proven impact of disease management programs on outcomes will result in a greater need for physicians with training in heart failure. This subspecialization of our profession is competing with the need to promote the training of more generalist community cardiologists, who are the most appropriate first point of access to cardiovascular care for the majority of patients. In addition to all of these factors, the Canadian population is aging, and elderly Canadians are living longer. We expect the number of people who have had an acute myocardial infarction, or heart attack, in 2001, to almost triple by the year 2021 (J Tepper, personal communication). For the same period, it has been projected that the number of people living with chronic heart failure will double (S Schultz, personal communication). In short, at present we are already understaffed, and the Canadian population is consequently underserviced by cardiovascular specialists; with current trends, this will only get worse. We cannot afford to reduce the number of medical graduates who choose to train in cardiology. However, that is exactly what The Association of Faculties of Medicine of Canada Postgraduate Medical Education (AFMC PGME) Standing Committee proposed in an undated position paper entitled, “The internal medicine R4 match: Time for a change. A position paper of the AFMC PGME Committee”. The AFMC PGME proposed to assign a defined portion of the postgraduate year 4 spots to general medicine to increase the number of generalists and decrease the number of subspecialists. Although we are sympathetic with the shortage of general internists, we must not allow this problem to be corrected at the expense of cardiology trainee positions. Although general practitioners and internal medicine specialists play an important role in the delivery of basic cardiovascular care in some communities, they are not an acceptable substitute for cardiologists. Studies have shown that cardiologists have the greatest propensity to provide cardiovascular disease prevention services (8), higher referral rates for important diagnostic services such as angiography (9) and are more likely to prescribe the Heart Failure Society of America-recommended medications for congestive heart failure patients on admission and at discharge (10). A recent Canadian study of 38,702 heart failure patients (11) confirmed that cardiologist care was associated with higher adjusted rates of invasive interventions and postdischarge prescriptions of heart failure medications. These services translate into improved outcomes. The study also found a lower one-year risk-adjusted mortality for patients attended by cardiologists compared with those who were attended by general internists, family practitioners or other physicians. This difference in outcomes is not specific to the Canadian context (12,13). The current shortage of cardiologists, and the resulting workloads and wait times, cannot be solved over the short term. At a minimum, we need to maintain the number of cardiology training positions, and preferably, expand our ranks to meet current and projected demands for cardiology services. Perhaps it is time to adopt the two-track approach to training in cardiology that the American College of Cardiology is proposing: a combined three-year plus two-year internal medicine and cardiology program for community cardiologists, and a combined two-year plus three-year internal medicine and cardiology program for those planning a career in academic cardiology or cardiology in tertiary centres with cardiology-only call schedules. This approach would double the number of cardiology graduates for the year that the first graduates of the five-year program enter practice in the same year as the last graduates of the current six-year program. After years of lobbying for more cardiology training positions, we still have not solved the long-term problem of too many patients and too few cardiologists to meet the needs of their services and procedures. What we need now are innovative approaches to recruit and train our next generation of cardiologists and cardiovascular health care providers. This is absolutely essential if we are to ensure that Canadians will always have access to quality and timely cardiovascular care if and when they need it.

We sought to determine the prognostic value of the admission electrocardiogram (ECG) in patients with unstable angina and non-Q wave myocardial infarction (MI).Although the ECG is the most widely used test for evaluating patients with unstable angina and non-Q wave MI, little prospective information is available on its value in predicting outcome in the current era of aggressive medical and interventional therapy.ECGs with the qualifying episode of pain were analyzed in patients enrolled in the Thrombolysis in Myocardial Ischemia (TIMI) III Registry, a prospective study of patients admitted to the hospital with unstable angina or non-Q wave MI.New ST segment deviationor = 1 mm was present in 14.3% of 1,416 enrolled patients, isolated T wave inversion in 21.9% and left bundle branch block (LBBB) in 9.0%. By 1-year follow-up, death or MI occurred in 11% of patients withor = 1 mm ST segment deviation compared with 6.8% of patients with new, isolated T wave inversion and 8.2% of those with no ECG changes (p0.001 when comparing ST with no ST segment deviation). Two other high risk groups were identified: those with only 0.5-mm ST segment deviation and those with LBBB, whose rates of death or MI by 1 year were 16.3% and 22.9%, respectively. On multivariate analysis, ST segment deviation of eitheror = 1 mm oror = 0.5 mm remained independent predictors of death or MI by 1 year.The admission ECG is very useful in risk stratifying patients with non-Q wave MI. The new criteria of not onlyor = 1-mm ST segment deviation but alsoor = 0.5-mm ST segment deviation or LBBB identify high risk patients, whereas T wave inversion does not add to the clinical history in predicting outcome.

Background Ligand binding to the platelet membrane receptor glycoprotein (GP) IIb/IIIa, the final and obligatory step to platelet aggregation, can now be inhibited by pharmacological agents. This study was designed to evaluate the potential of lamifiban, a novel nonpeptide antagonist of GP IIb/IIIa, for the management of unstable angina. Methods and Results In a prospective, dose-ranging, double-blind study, 365 patients with unstable angina were randomized to an infusion of 1, 2, 4, or 5 μg/min of lamifiban or of placebo. Treatment was administered for 72 to 120 hours. Outcome events were measured during the infusion period and after 1 month. Concomitant aspirin was administered to all patients and heparin to 28% of patients. Lamifiban, all doses combined, reduced the risk of death, nonfatal myocardial infarction, or the need for an urgent revascularization during the infusion period from 8.1% to 3.3% ( P =.04). The rates were 2.5%, 4.9%, 3.3%, and 2.4% with increasing doses. At 1 month, death or nonfatal infarction occurred in 8.1% of patients with placebo and in 2.5% of patients with the two high doses ( P =.03). The highest dose of lamifiban additionally prevented the need for an urgent intervention. Lamifiban dose-dependently inhibited platelet aggregation. Bleeding times were significantly prolonged with platelet inhibition of >80%. Major (but neither life-threatening nor intracranial) bleedings occurred in 0.8% of patients with placebo and 2.9% with lamifiban. Conclusions The nonpeptide GP IIb/IIIa antagonist lamifiban protected patients with unstable angina from severe ischemic events during a 3- to 5-day infusion and reduced the incidence of death and infarction at 1 month, suggesting considerable promise for this new therapeutic approach.

The digestion of a human IgG1 K myeloma protein with pepsin in the presence of 8M-urea was observed to produce a fragment, designated Fb′2, which differed from the products of aqueous peptic digestion and from other characteristic immunoglobulin digestion products. 2. Fragment Fb′s was also found when two other IgG1/K proteins were treated similarly. 3. Sedimentation-equilibrium studies showed the mol.wt. of fragment Fb′2 to be 56800. 4. On reduction, two equivalents of each of three peptides were released from fragment Fb′s; these were characterized by N- and C-terminal determinations and by amino acid sequencing. 5. Fragment Fb′2 was shown to consist of the constant regions of both light chains, from residue Ile-117 to the C-terminus, and the CH1 domains and hinge region of the heavy chains, from residue Val-113 to residue Met-252, with a gap of five residues within the intrachain disulphide loop, between residues Leu-174 and Tyr-180.

Goblet-cell mucin (mucin 1) was isolated and purified from human small-intestinal scrapings. After application of mucin 1 to DEAE-Bio-Gel (A) columns, most of the glycoprotein (76–94% of hexoses) was eluted in the first peak (designated mucin 2). Minor amounts of acidic glycoproteins were eluted with 0.2m- and 0.4m-NaCl in later peaks. Analyses of mucin 1 and mucin 2 revealed mucin 2 to be a monodisperse highly glycosylated glycoprotein containing 6.3% by wt. of protein, N-acetylgalactosamine, N-acetylglucosamine, galactose and fucose. Mucin 1 was similar in composition, but was polydisperse and contained more protein (12.3% by wt.) as well as N-acetylneuraminic acid. Analytical CsCl-gradient ultracentrifugation showed both mucin 1 and mucin 2 to have a major component with an average buoyant density of 1.47000g/ml. Mucin 1 also contained a slightly less-dense minor glycoprotein component. After exhaustive reduction and alkylation mucin 1 retained its major component, but partly dissociated into two lighter glycoprotein components. Mucin 2, in contrast, did not change its density distribution after reduction. Band ultracentrifugation in 2H2O-containing iso-osmotic buffers showed that mucin 1 contained a major fast-sedimenting component (so=37±2S), and a minor amount of a slower-sedimenting component. After reduction there was an increased quantity of the latter component, for which an so value of 14.5S was calculated. In contrast, mucin 2 was unaltered by reduction (so=33±2S). These findings indicate that the major component of goblet-cell mucin (mucin 2) does not dissociate after S–S-bond reduction, and thus does not apparently rely for its polymeric structure on the association of subunits through covalent disulphide bonds. However, the effects of reduction on mucin 1 suggest that in the native mucin intramolecular disulphide bonds in the minor glycoproteins may stabilize their structure, permitting secondary non-covalent interactions to develop with the major dense mucin (mucin 2) protein.

Spectral properties of pig intestinal Ca2+-binding protein (CaBP) and its apoprotein have been examined by fluorescence, absorption and c.d. Direct fluorescence from some of the five phenylalanine residues is observed and excitation spectra show that there is also energy transfer from some phenylalanine residues to the tyrosine. Absorption and c.d. spectra show that the tyrosine hydroxy group does not ionize significantly below pH 12. Tyrosine fluorescence is reversibly quenched by a lysine residue with a pK of 10.05 in the Ca2+ form. At low pH the tyrosine fluorescence is enhanced with transitions with pK values of approx. 4.2. The c.d. spectrum of the Ca2+ form shows a decrease of the ellipticity band at 276nm with a transition similar to that of the fluorescence titration. The apoprotein, however, shows an additional transition with a pK of about 6. The results are interpreted in terms of the recently published structure of the cow intestinal CaBP [Szebenyi, Obendorf & Moffat (1981) Nature (London) 294, 327-332]. The single tyrosine has a very high pK, although it apparently lies on the surface of the protein molecule.