What is the real hospital mortality from acute myocardial infarction? Epidemiological vs clinical view.

AIMS: To examine the general influence of the definition of fatal and non-fatal acute myocardial infarction and coronary deaths on the estimation of in-hospital case-fatality, and to show how the definition of acute myocardial infarction influences time-trends of hospital mortality over 11 years. METHODS AND RESULTS: As part of the World Health Organization's MONICA (multinational Monitoring of Trends and Determinants in Cardiovascular Disease) Project in Augsburg all patients aged 25-74 years with a suspected diagnosis of acute myocardial infarction who were hospitalized in the study region's major clinic were registered prospectively between 1985 to 1995 (n=4889). Patient information, including short-term survival status, was obtained from medical records, by interview of surviving patients, and municipal death certificate files which were validated by an extended identification and validation process. In-hospital case fatality was estimated according to different definitions which closely followed the international MONICA criteria. Epidemiological definitions comprised definite and possible acute myocardial infarction, and events with unclassifiable deaths, while the clinical definition was restricted to definite infarction. Overall, case fatality by the epidemiological definitions was 28 to 29.8% (23.5% of those treated in a coronary care unit) compared to 13.5% using the clinical definition. While over the 11 years, the reduction in case fatality according to the epidemiological definitions was modest, highly significant decreases were observed by applying the clinical definition (from 15.8% in 1985-1988 to 10.8% in 1993-1995, P<0.001 adjusted for age and sex). The discrepancy in case fatality between the definitions is explained by the high proportion of patients who die very early (about 70% of all fatal events during the first 24 h) with the consequence of missing data which may preclude a definite diagnosis of acute myocardial infarction. CONCLUSIONS: Applying a broader definition of acute myocardial infarction reveals that in-hospital mortality is higher than believed until now, and it implies that our efforts must be intensified to reduce overall in-hospital coronary heart disease mortality.

Determinants of short-period heart rate variability in the general population.

Decreased heart rate variability (HRV) is associated with a worse prognosis in a variety of diseases and disorders. We evaluated the determinants of short-period HRV in a random sample of 149 middle-aged men and 137 women from the general population. Spectral analysis was used to compute low-frequency (LF), high-frequency (HF) and total-frequency power. HRV showed a strong inverse association with age and heart rate in both sexes with a more pronounced effect of heart rate on HRV in women. Age and heart rate-adjusted LF was significantly higher in men and HF higher in women. Significant negative correlations of BMI, triglycerides, insulin and positive correlations of HDL cholesterol with LF and total power occurred only in men. In multivariate analyses, heart rate and age persisted as prominent independent predictors of HRV. In addition, BMI was strongly negatively associated with LF in men but not in women. We conclude that the more pronounced vagal influence in cardiac regulation in middle-aged women and the gender-different influence of heart rate and metabolic factors on HRV may help to explain the lower susceptibility of women for cardiac arrhythmias.

[Temporal trends in myocardial infarct morbidity, mortality and 28-day fatalities and medical management. Results of the Augsburg Myocardial Infarct Register 1985 to 1992]. / Zeitliche Trends von Herzinfarktmorbidität, -mortalität, 28-Tage-Letalität und medizinischer Versorgung. Ergebnisse des Augsburger Herzinfarktregisters von 1985 bis 1992.

Between 1985 and 1992 a significant decrease in rates of acute myocardial infarction (AMI; fatal and non fatal, including prehospital cardiac death) from 533 cases per 100,000 population of 455 cases was observed in the 25- to 74-year-old male study population (linear regression model: -13%, p < 0.01). In the corresponding female study population the AMI rate increased from 153 cases per 100,000 population in 1985 to 153 cases in 1992 (linear regression model: +18%, p < 0.05). The decrease was only in 50- to 59-year-old male AMI patients without changes in risk factors (smoking, diabetes, hypertension, recurrent AMI) but with a decrease in patients with a history of angina pectoris, which may have been caused by intensified medical treatment of AMI endangered patients. Over time 34% of the patients died before hospitalization and another 19% died within the first 24 h after hospitalization. The register results show an underestimation of the coronary mortality by the official cause of death statistics. In contrast, the significant increase in treatment with thrombolytics (men from 16% to 38%, women from 8% to 42%), beta-blockers (men from 48% to 69%, women from 45% to 71%), and antiplatelets (men from 55% to 94%, women from 52% to 91%) was not related to any significant changes in 28-day case fatality of the 24-h survivors (men and women 13% to 14%). Without media campaigns, for the increased number of cases hospitalized within 4 h after the event (1985-1987 men 50%, women 42%; 1990-1992 58% and 60%; p < 0.01) thrombolytic treatment shows an increase from 25% in men and 17% in women (1985-1987) to 54% in men and 47% in women (1990-1992; p < 0.01).

[Thrombolysis therapy and coronary angiography in acute myocardial infarct in the Augsburg region: results of the Augsburger Heart infarct register 1985-1987]. / Thrombolysetherapie und Koronarangiographie bei akutem Myokardinfarkt in der Region Augsburg: Ergebnisse des Augsburger Herzinfarktregisters 1985-1987.

In the years 1985-87, the Augsburg Coronary Event Register registered 1333 hospitalized patients who had survived an acute myocardial infarction (AMI) for at least 24 h. In 953 patients, data on time intervals in the prehospital phase were documented in addition to the medical records data in a standardized nurse interview. The time from onset of AMI until the patient called for medical attention constituted most of the prehospital time delay. Of the interviewed male and female patients, 67% were hospitalized within 6 h (= time limit). The differences, both in the number of thrombolyses and the number of coronary angiographies performed in men and in women are statistically significant. Thrombolysis was performed in 27% of the male and 12% of the female AMI patients who were admitted to hospital within the time limit. The rate of thrombolytic therapy decreased with increasing age and was less in patients with recurrent AMI (men: 20%, women: 0%) than in patients with first AMI (men: 29%, women: 15%). There was some time-of-day variation in the percentage of thrombolytic therapy which may be attributable to hospital organization. From 1985 to 1987, the coronary angiography rates performed in the medical center doubled, independent of the thrombolytic therapy rates. In this time, angiography rates in thrombolyzed patients increased from 49% to 75%, and from 14% to 31% in patients without thrombolysis. The 28-day case fatality was 4.8% in patients with thrombolysis and 13% in patients without thrombolytic therapy. Controlling for age, sex, and recurrent AMI, this difference is not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

[The myocardial infarct status of a South German population: results of the Augsburg myocardial infarct register l985]. / Zur Herzinfarktsituation in einer süddeutschen Bevölkerung: Ergebnisse des Augsburger Herzinfarktregisters 1985.

The Augsburg Myocardial Infarction Register recorded in 1985, 999 coronary events (734 men, 265 women) occurring in 25-74-year-old residents of the city of Augsburg and the counties of Augsburg and Aichach-Friedberg (study population: 156,489 men and 171,093 women). On average, 444 men and 138 women per 100,000 of the population suffered an acute myocardial infarction (AMI) in 1985. The risk of morbidity increased with age in both men and women, but gained significance for women only after their 55th year of life. The 28-day case fatality was 54% for male AMI cases and 66% for females; 34% of the AMI patients died without ever reaching a hospital. Cardiopulmonary resuscitation (CPR) was attempted by a physician in one-in-three of these out-of-hospital deaths. Although one of two out-of-hospital deaths occurred in the presence of a medical lay person; lay CPR was the exception. Broader population education in CPR techniques may thus constitute one method of reducing the number of early AMI deaths. The median prehospital time for interviewed hospital patients (66%) was 5 h, and approximately 2 h for patients with systemic thrombolysis (n = 71). The combination of fatal coronary events from the official cause-of-death statistics and the results from the Augsburg register were used to estimate AMI morbidity for the whole of the FRG in 1985. This leads to an expected morbidity of 210,000 AMI, of which 141,000 AMI will be fatal (both sexes).

Morbidity and mortality of myocardial infarction in the MONICA study area Augsburg in 1985.

In the year 1985, 998 (734 men, 264 women) cases of acute coronary events were registered among the 25-74 year-old residents of the study area (151,489 men and 171,093 women) of whom 583 (403 men, 180 women) died within 28 days (case fatality). Both AMI as a clinical diagnosis and AMI as a cause of death are validated by defined MONICA diagnostic criteria (acute symptoms, enzyme level, ECG, autopsy diagnosis). The AMI-risk (MONICA diagnostic categories 1, 2, 3, 9) in the study area Augsburg is relatively low (incidence: men 302, women 113; attack rate: men 444, women 138; death rate: men 241, women 92; all per 100,000 for each group). The 28-day case fatality is comparatively high (men 54%, women 67%). A comparison of the Augsburg rates with those of three other centers shows that the Augsburg figures are in the lower range.

The effects of chronic ethanol treatment on oligomycin sensitive ATPase activity in the guinea pig heart.

In an effort to determine the effect of chronic ethanol ingestion on myocardial oligomycin sensitive ATPase, guinea pigs were fed 15% ethanol instead of drinking water for 34 weeks. Mg2+-ATPase activity of isolated mitochondria was determined in control and alcohol fed guinea pigs at 16, 20, 24 and 34 weeks. To prove a possible higher fragility of the mitochondria from alcohol fed animals, the ATPase activity was also determined in the supernatant after the isolation of mitochondria "100 000 g fraction". Mg2+-ATPase activity of the isolated mitochondria was time dependent reduced to 56% of the value obtained in the control animals. In the "100 000 g fraction" the ATPase activity, however, started to increase after 8 weeks and after 34 weeks it was about twice as high than in the control group. The findings of this study document a decrease in oligomycin sensitive ATPase activity and an increase in mitochondrial fragility after chronic ethanol ingestion. It supports in the thesis that chronic alcohol intake affects the activity of the intrinsic membrane enzymes by structural derangements of mitochondrial membrane. The changes may play a role in the development of alcoholic cardiomyopathy.

Immunological defects precursors of myocarditis and dilated cardiomyopathy?

Anti-virus-antibodies are elevated in a relatively high number of dilated cardiomyopathies, and in myocarditis increasing or decreasing titers can characteristically be observed. In myocarditis as well as in dilated cardiomyopathy the high incidence of antibodies in the serum of the patients against myocardial sarcolemmal and mitochondrial proteins coincides with a low T-cell-suppressor activity. T-lymphocyte-cell-suppressor activity modifies the immunoglobulin synthesis of B-lymphocytes. The T-cell-suppressor activity has been found to be low in myocarditis as well as in congestive cardiomyopathies. This coincidence looks like a pathogenetic link, since a low T-cell-suppressor activity is generally correlated to an increased antibody synthesis of B-lymphocytes. The finding of a low T-cell-suppressor activity in a small group of normal individuals supports the concept that this group has a predisposition to suffer from myocarditis and later on developing dilated cardiomyopathy. Thus there are several indicators of a probably genetically determined immunological defects which can play a pathogenetic role in the development from myocarditis to dilated cardiomyopathy.

Immunological analysis of auto-antibodies against the adenine nucleotide translocator in dilated cardiomyopathy.

We have previously identified the adenine nucleotide translocator (ANT), an intrinsic protein of the inner mitochondrial membrane, as an auto-antigen in dilated cardiomyopathy (DCM). Further immunochemical characterization by crossed immunoelectrophoresis, indirect solid phase radioimmunoassay and immunoadsorption studies on the isolated translocator protein and mitochondria from heart, kidney and liver showed the existence of organ-specific antigenic determinants although partial crossreactivity between the three proteins was observed. Sera from 18 patients with histologically proven dilated cardiomyopathy were studied for their capacity to bind to the translocator protein. Seventeen of 18 patients showed significant binding, while in the sera of patients with coronary heart disease, suspected alcoholic heart disease or healthy blood donors, no anti-ANT antibodies were observed. Further studies showed organ-specific and functionally active autoantibodies, which decreased the ADP/ATP exchange rate from heart mitochondria. A close correlation was found between the antibody-titer and the hemodynamic function. These results give new evidence for autoimmunological events in dilated cardiomyopathy.

The antigenic characteristics and the significance of the adenine nucleotide translocator as a major autoantigen to antimitochondrial antibodies in dilated cardiomyopathy.

To obtain further knowledge of the antigen-antibody system, immunochemical characterization of the adenine nucleotide translocator was achieved by crossed immunoelectrophoresis, immunoreplica technique, radioimmunoassay, immunoabsorption studies, and nucleotide-transport measurements. Sera of 18 patients with proven congestive cardiomyopathy (CCM) were tested. On the adenine nucleotide translocator (ANT) from heart, kidney, and liver, organ-specific antigenic determinants were demonstrable, although a partial cross-reactivity existed. Conformation specificity was also confirmed by experimental studies. Of the patients studied, 17 of 18 with CCM showed a significant binding to the heart ANT, while no or a lower binding was seen on the kidney/liver ANT. In CCM, a correlation exists between the ejection fraction and the anti-ANT titer. These results give new evidence for autoimmunological events in MC and CCM and indicate a possible causal relationship between these two diseases.

Acute myocardial infarction during continuous electrocardiographic ST segment recording. Possible role of bradycardia and hypotension induced by glyceryl trinitrate.

A 62 year old man developed an inferior wall myocardial infarction during ambulatory ST segment monitoring. Before the onset of persistent ST segment elevation he had taken several glyceryl trinitrate tablets, which was followed by bradycardia and symptoms of hypotension. Whether a paradoxical reaction to glyceryl trinitrate may have triggered the development of myocardial infarction in this case is uncertain.

[Immunological examinations in dilated cardiomyopathies]. / Immunologische Untersuchungsbefunde bei dilativen Kardiomyopathien.

Immunological data in dilated cardiomyopathies can differentiate the nosology of these diseases. In nearly one half of these dilated cardiomyopathies, binding of immunoglobuline in myocardial structures (biopsies) can be demonstrated. By immunohistological techniques collagen I in myocardial biopsies has been predominantly shown. In lymphocytes of the diseases patients the T-cell-suppressor activity is low. This phenomenon seems to play an important role in the pathogenesis of dilated cardiomyopathies and can explain numerous humoral immunological findings. As conclusion the hypothesis can be drawn: several cases of dilated cardiomyopathies and myocarditis can be regarded as different stages of a single underlying disease, in which a low T-cell-suppressor activity seems to act as a predisposing factor.