Simple point-of-care risk stratification in acute coronary syndromes: the AMIS model.

BACKGROUND: Early risk stratification is important in the management of patients with acute coronary syndromes (ACS). OBJECTIVE: To develop a rapidly available risk stratification tool for use in all ACS. DESIGN AND METHODS: Application of modern data mining and machine learning algorithms to a derivation cohort of 7520 ACS patients included in the AMIS (Acute Myocardial Infarction in Switzerland)-Plus registry between 2001 and 2005; prospective model testing in two validation cohorts. RESULTS: The most accurate prediction of in-hospital mortality was achieved with the "Averaged One-Dependence Estimators" (AODE) algorithm, with input of seven variables available at first patient contact: age, Killip class, systolic blood pressure, heart rate, pre-hospital cardiopulmonary resuscitation, history of heart failure, history of cerebrovascular disease. The c-statistic for the derivation cohort (0.875) was essentially maintained in important subgroups, and calibration over five risk categories, ranging from <1% to >30% predicted mortality, was accurate. Results were validated prospectively against an independent AMIS-Plus cohort (n = 2854, c-statistic 0.868) and the Krakow-Region ACS Registry (n = 2635, c-statistic 0.842). The AMIS model significantly outperformed established "point-of-care" risk-prediction tools in both validation cohorts. In comparison to a logistic regression-based model, the AODE-based model proved to be more robust when tested on the Krakow validation cohort (c-statistic 0.842 vs 0.746). Accuracy of the AMIS model prediction was maintained at 12-month follow-up in an independent cohort (n = 1972, c-statistic 0.877). CONCLUSIONS: The AMIS model is a reproducibly accurate point-of-care risk stratification tool for the complete range of ACS, based on variables available at first patient contact.

The impact of statin treatment on presentation mode and early outcomes in acute coronary syndromes.

OBJECTIVES: The role of statin use in the treatment of acute coronary syndromes (ACS) is not clear. The aim of our study was to evaluate the role of statins in ACS. METHODS: Using data from the Acute Myocardial Infarction in Switzerland (AMIS Plus) Project, we compared the effects of chronic statin use, statin therapy after admission and no statin therapy on presentation mode and outcomes in ACS. RESULTS: Available data from the period 2001-2006 including 11,603 patients were analyzed. Major cardiac event rates and in-hospital mortality were more common in statin-naive patients compared to patients who received statins. CONCLUSIONS: Our results support the importance of statin treatment in ACS. Chronic statin therapy seems to alter the initial presentation of ACS but it is questionable whether it provides an additional effect on early outcomes compared to the establishment of statin therapy after admission in statin-naive patients.

Quality of life and exercise capacity in patients with prolonged PQ interval and dual chamber pacemakers: a randomized comparison of permanent ventricular stimulation vs intrinsic AV conduction.

AIMS: The aim of this study was to assess quality of life (QoL) and exercise capacity during permanent ventricular stimulation (PVS) compared with intrinsic atrioventricular conduction (IAVC) in patients with dual chamber pacemakers (PMs) and an intrinsic PQ interval >210 ms. Dual chamber PMs in patients with atrioventricular (AV) block are usually programmed to PVS in VDD or DDD mode, although IAVC is preserved, but prolonged. This results in PVS, although long periods of IAVC may occur. METHODS AND RESULTS: Fourteen consecutive patients (age 76 +/- 6 years; intermittent high degree AV block in six patients, binodal disease in eight patients) were enroled in a prospective, randomized, single blind, crossover study of IAVC vs PVC. To permit IAVC, programmed AV delays were prolonged. At the end of each phase, QoL scores were assessed using a questionnaire and echocardiography and cardiopulmonary stress tests were performed. During the study period with IAVC, 95 +/- 10% of the beats were conducted intrinsically. QoL scores (28.3 +/- 11 vs 29.3 +/- 13; P = 0.68), peak exercise capacity (5.4 +/- 2.4 vs 5.2 +/- 2.9 METs; P = 0.35) and peak oxygen uptake (19.8 +/- 4.5 vs 18.8 +/- 5.2 ml/kg/min; P = 0.16) were comparable during IAVC and PVS, respectively. Similar echocardiographic values were found for left ventricular (LV) ejection fraction (50 +/- 9% vs 51 +/- 10%; P = 0.67) and velocity time integral at the left ventricular outflow tract (24 +/- 5 vs 22 +/- 6 cm; P = 0.20), respectively. CONCLUSIONS: We conclude that in patients with dual chamber PMs and intermittent high degree AV block neither PVS nor IAVC is superior with respect to QoL or exercise capacity. Therefore, pulse generators may be programmed to IAVC to extend their longevity.

[Acute coronary syndrome and myocardial infarct--new definitions]. / Akutes Koronarsyndrom und Myokardinfarkt--neue Definitionen.

Until recently a general consensus existed for the clinical entity diagnosed as myocardial infarction using the world health organisation (WHO) definition. According to the WHO definition myocardial infarction was defined by a combination of two of three typical characteristics: typical symptoms, rise of cardiac enzymes (CK, CK-MB), and a typical ECG pattern involving the development of Q waves. New insights into the development of acute myocardial infarction, the superiority of the biochemical characteristics of cardiac troponin assays over CK and CK-MB measurements in blood, and new therapeutic concepts made a new definition of myocardial infarction, e.g. of the acute myocardial infarction, necessary. Timing of the diagnosis of myocardial necrosis is of outmost importance relative to the time of observation (acute, evolving, healing, healed MI), as is the classification of the extent of myocardial damage (microscopic, small, medium or large). The term "acute coronary syndrome" (ACS) has been established as a working diagnosis for choosing the appropriate therapeutic strategy. In patients with ACS and ST elevation ischemia (STEMI ACS, true posterior ischemia inclusive) as well as in patients with presumably new LBBB, immediate reperfusion therapy should be performed (primary PTCA or thrombolytic therapy), whereas in patients with ECG changes other than ST elevation or new LBBB (NSTEMIACS) additional antiplatlet therapy on top of aspirin and heparin is indicated. In contrast to the acute phase of infarction when troponin in blood often is not detectable yet, the diagnosis of definitive myocardial infarction is based primarily on troponin elevation. Hard criteria for established infarction are the development of pathologic Q waves or healing or healed myocardial necrosis in pathology; troponin may be normal then, depending of time relapsed.

Sudden cardiac death after coronary artery bypass grafting is not predicted by signal-averaged ECG.

BACKGROUND: Sudden cardiac death (SCD) is a major cause of death despite successful revascularization in patients with coronary artery disease. The signal-averaged ECG (SAECG) is a sensitive predictor of SCD and could be used in the screening strategy to select patients for prophylactic cardioverter implantation. METHODS: The SAECG was recorded in 561 patients (mean age: 60 +/- 8.8 years) within 10 days of coronary artery bypass grafting. Signal-averaged ECG was performed with a bandpass filtering of 40 to 250 Hz for more than 250 beats until a noise level of 0.6 microV was achieved. All patients were followed for 5.5 +/- 1.2 years after the procedure. RESULTS: Preoperative angiographic ejection fraction was at least 60% in 393 patients (72%), 40% to 60% in 126 patients (23%), and 40% or less in 28 patients (5%). There were 34 deaths, 10 of which were SCD. Late potentials were found in a total of 150 patients (27%) and were equally frequent preoperatively and postoperatively and among patients with (30%) and without (27%) SCD. The only predictors for overall mortality were age and a reduced ejection fraction. CONCLUSIONS: Signal-averaged ECG did not predict prognosis in low-risk patients undergoing coronary artery bypass grafting.

Elevation of troponin I in sepsis and septic shock.

OBJECTIVE: To detect myocardial damage in severe systemic inflammation by cTnI measurements in patients without acute coronary syndromes. DESIGN: Prospective case control study. SETTING: Tertiary referral center. PARTICIPANTS: Twenty patients with sepsis, septic shock, and systemic inflammatory response syndrome (SIRS) were examined and compared to controls without coronary artery disease or myocarditis. MEASUREMENTS AND RESULTS: cTnI levels were assessed in patients with SIRS, sepsis, and septic shock. Eight patients (two female/six male) suffered from septic shock, nine (three female/six male) from sepsis without shock, and three (three male) from SIRS. Seventeen patients (85%) showed elevated cTnI (median 0.57 microg/l; 0.17-15.4), whereas no patient in the control group showed elevated cTnI (P < 0.0001). Six patients (30%),--three with septic shock and three with sepsis--died during hospitalization, five of them with elevated cTnI. Four out of five autopsies showed normal coronary arteries. Coronary angiography, autopsy, and stress echocardiography ruled out significant coronary artery disease in ten cTnI-positive patients (59%). In 41 % of cTnI-positive patients, Streptococcus pneumoniae could be cultured, whereas no cTnI-negative or control patient showed signs of infection due to S. pneumoniae. CONCLUSION: Cardiac troponin I was elevated in 85% of patients with sepsis, septic shock or SIRS in our study. A high percentage showed infection caused by S. pneumoniae. In what way microorganisms cause cTnI elevations is not yet understood.

The dual endothelin receptor antagonist tezosentan acutely improves hemodynamic parameters in patients with advanced heart failure.

BACKGROUND: Endothelin-1, a potent vasoconstrictor, is elevated in congestive heart failure and is postulated to play a major role in the pathogenesis of the disease. Endothelin receptor antagonism may be a specific therapeutic approach. This study was designed to determine the effective dosage range, hemodynamic effects, and tolerability of tezosentan, an intravenous dual endothelin receptor antagonist, in patients with advanced heart failure. METHODS: This randomized, double-blind, placebo-controlled multicenter trial enrolled 38 patients with symptomatic stable heart failure (New York Heart Association class III, left ventricular ejection fraction <35%) undergoing right heart catheterization. Patients were equally randomized to a 4-hour intravenous infusion of placebo or tezosentan in ascending doses (5, 20, 50, and 100 mg over 1 hour each). Angiotensin-converting enzyme inhibitors and diuretics were withheld 24hours before the study. Hemodynamics were measured during and for 4 hours after the infusion. RESULTS: Compared with placebo, tezosentan treatment produced a significant increase in cardiac index (treatment difference 0.59 L/min/m(2), P =.0001) and decreases in pulmonary and systemic vascular resistances (P

Hemodynamic effects of bosentan in patients with chronic heart failure.

A role of the potent and long-acting vasoconstrictor peptide endothelin-1 and the pathophysiology of chronic human heart failure has been postulated based upon indirect evidence such as elevated plasma endothelin-1 levels and their with the degree of hemodynamic impairment. The advent of specific of endothelin-1 receptor antagonists has provided the opportunity not only to directly evaluate its pathophysiological role but also to assess its potential role as a new approach to heart failure therapy. This brief review summarizes the evidence linking endothelin-1 to the pathophysiology of chronic heart failure and the clinical results obtained in patients during acute, intravenous and more prolonged, oral administration with bosentan, a mixed ET(A)/ET(B)-receptor antagonist. Bosentan acutely and during short-term oral therapy markedly improved hemodynamics in patients in addition to standard heart failure therapy, including an ACE-inhibitor. These effects were associated with a reduced responsiveness of the renin-angiotensin system to diuretic therapy and reduced basal plasma aldosterone levels. Although the hemodynamic and neurohumoral profile of short-term bosentan therapy looks promising for the treatment of patients with chronic heart failure appropriate trials will have to be performed to document clinical benefit during long-term therapy. Finally, the question remains open whether mixed endothelin-1 receptor antagonists like bosentan will have similar effects as compared to antagonists which block the ET(A) receptor only.

Rationale and perspective of endothelin-1 antagonism in acute heart failure.

A role of the potent and long-acting vasoconstrictor peptide endothelin (ET)- I in the pathophysiology of chronic human heart failure has been postulated, based upon indirect evidence such as elevated plasma ET-1 levels and their relationship to the degree of haemodynamic impairment. Acute heart failure shares many features of chronic heart failure, albeit in an exaggerated fashion. As both the mixed ETA/ETB-receptor antagonist bosentan and the selective ETA receptor antagonist BQ 123 acutely improved the haemodynamics of chronic heart failure patients, there seems to be good reason to believe that ET-1 receptor antagonism may also be of benefit in the setting of acute heart failure. However, appropriate trials will have to be performed to document the clinical benefit of such an approach. Finally, the question remains open as to whether mixed ET-1 receptor antagonists like bosentan will prove better, worse or equal to antagonists that block the ETA, receptor only.

A prospective randomized trial comparing stenting to internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis: the SIMA trial. Stenting vs Internal Mammary Artery.

OBJECTIVE: To compare coronary artery bypass grafting (CABG) with percutaneous transluminal coronary angioplasty (PTCA) in patients with proximal, isolated de novo left anterior descending coronary artery disease and left ventricular ejection fraction of 45%. PATIENTS AND METHODS: In the multicenter Stenting vs Internal Mammary Artery (SIMA) study, patients were randomly assigned to PTCA and stent implantation or to CABG (using the internal mammary artery). The primary clinical composite end point was event-free survival, including death, myocardial infarction, and the need for additional revascularization. Secondary end points were functional class, antianginal treatment, and quality of life. Analyses were by intention to treat. RESULTS: Of 123 patients who accepted randomization, 59 underwent CABG, and 62 were treated with stent implantation (2 patients were excluded because of protocol violation). At a mean +/- SD follow-up of 2.4+/-0.9 years, a primary end point had occurred in 19 patients (31%) in the stent group and in 4 (7%) in the CABG group (P<.001). This significant difference in clinical outcome is due to a higher incidence of additional revascularization in the stent group, the incidence of death and myocardial infarction being similar (7% vs 7%, respectively; P=.90). The functional class, need for antianginal drug, and quality-of-life assessment showed no significant differences. CONCLUSIONS: Both stent implantation and CABG are safe and highly effective treatments to relieve symptoms in patients with isolated, proximal left anterior descending coronary artery stenosis. Both are associated with a low and comparable incidence of death and myocardial infarction. However, similar to PTCA alone, a percutaneous approach using elective stent placement remains hampered by a higher need for repeated intervention because of restenosis.

An uncommon cause of recurrent strokes: Tropheryma whippelii endocarditis.

BACKGROUND: Cardiac involvement in Whipple's disease is not an uncommon phenomenon in autopsies, but its clinical occurrence is often overshadowed by gastrointestinal symptoms. We report a very atypical manifestation of this disorder. SUMMARY OF REPORT: An extraordinary presentation of an extremely long-lasting, culture-negative endocarditis caused by Tropheryma whippelii is described, the clinical consequence of which has become apparent in recurrent strokes. CONCLUSIONS: Cardiac involvement of Whipple's disease should always be considered in culture and serologically negative endocarditis. The polymerase chain reaction technique may be a useful tool to confirm a presumed diagnosis of T whippelii endocarditis and consequently to apply an effective treatment regimen.

Myocardial infarction caused by a large coronary artery aneurysm.

A large coronary aneurysm, originating from a side branch of the right coronary artery, caused recurrent ischemia resulting in myocardial infarction. Successful surgical excision, without concomitant coronary artery bypass grafting, is described.

The acute effects of transvenous biventricular pacing in a patient with congestive heart failure.

The management of congestive heart failure remains an issue of great interest. Encouraging data emerged over the last 2 years supporting the use of multisite pacing in patients with severe congestive heart failure and intraventricular conduction delay. We present a case of acute biventricular pacing in a 81-year old man with dilated cardiomyopathy and symptomatic congestive heart failure. This novel form of pacemaker treatment resulted in a rapid hemodynamic and clinical improvement.

[Pharmacoeconomic evaluation of pravastatin in coronary secondary prevention in patients with myocardial infarct or unstable angina pectoris. An analysis based on the LIPID Study]. / Pharmakoökonomische Bewertung von Pravastatin in der koronaren Sekundärprävention bei Patienten mit Myokardinfarkt oder instabiler Angina Pectoris. Eine Analyse auf der Grundlage der LIPID-Studie.

BACKGROUND: Secondary coronary prevention with lipid lowering drugs have become a major issue in health policy formulation due to the large upfront investment in drug therapy. The recently completed LIPID trial with pravastatin in secondary prevention immediately raise the question whether pravastatin might be cost-effective in Switzerland. METHODS: We conducted a cost-effectiveness analysis from the perspective of third party payers. The following costs were included in the analysis: daily treatment costs of pravastatin, non fatal myocardial infarction, coronary bypass operations and stroke. Life years gained was obtained by applying the declining exponential approximation of life expectancy. All calculations were standardized to 1000 treated patients. RESULTS: The net costs of treating 1000 patients (i.e. drug costs minus the costs of sequelae and interventions) are Fr. 3.6 Mio. In addition, a total of 430 life-years may be saved through treatment. The corresponding cost-effectiveness of pravastatin treatment is Fr. 8341 (nominal) Fr. 6985 (discounted). CONCLUSIONS: The results suggest that the cost-effectiveness of pravastatin in secondary prevention lie well within the threshold of other commonly accepted medical interventions and may be considered an economically viable approach for secondary coronary prevention.

Regulation of aldosterone secretion in patients with chronic congestive heart failure by endothelins.

We studied acute (day 1) and long-term (day 14) effects of endothelin (ET) receptor blockade with the mixed ET(A/B) antagonist bosentan (1 g twice daily; n = 18) or placebo (n = 12) on plasma angiotensin II and aldosterone in 30 patients with symptomatic chronic heart failure taking angiotensin-converting enzyme inhibitors, diuretics, and digoxin. Hormones were determined before and 3 hours after morning doses of diuretics and digoxin and the double-blind study drug, respectively, on days 1 and 14. On day 1, angiotensin II increased from 16.1+/-17.9 to 27.6+/-5.6 ng/L (p <0.05) with bosentan and similarly with placebo (15.5+/-9.3 and 36.0+/-49.1 ng/L, p = 0.06) after the morning dose of diuretics and digoxin. Aldosterone tended to increase from 322+/-239 to 362+/-254 pmol/L (bosentan) and from 271+/-70 to 297+/-136 pmol/L (placebo). On day 14, before drug intake, angiotensin II was unchanged compared with day 1 in both groups. However, aldosterone was lower than on day 1 with bosentan (213+/-124 vs. 322+/-239 pmol/L, p<0.05) and remained below baseline values 3 hours after drug intake, whereas it was unchanged with placebo. Thus, short-term ET(A/B) receptor antagonism decreases basal aldosterone secretion independently of angiotensin II, suggesting that ET participates in the regulation of aldosterone in patients already treated with angiotensin-converting enzyme inhibitors and diuretics.

A double-blind, randomized study of the effect of immediate intravenous nitroglycerin on the incidence of postprocedural chest pain and minor myocardial necrosis after elective coronary stenting.

BACKGROUND: Anginal chest pain without creatine kinase (CK) elevation is frequently observed in the first hours after coronary stenting. Possible causes of ischemic episodes are microembolism, side branch occlusion, coronary vasospasm, and disturbances of microvascular circulation. In a prospective, double-blind, randomized trial, we tested the effect of intravenous nitroglycerin on the incidence of angina and minor myocardial necrosis (MMN), as detected by cardiac troponin I increase, after elective coronary stenting. METHODS AND RESULTS: One hundred patients were randomly assigned to intravenous nitroglycerin (group A: n = 50, goal dose 100 microgram/min) or placebo (group B: n = 50, NaCl 0.9%) during 12 hours after stenting. Patients with acute myocardial infarction, known intolerance to nitrates, and hemodynamic instability during angioplasty were excluded. The 2 groups were comparable in respect to baseline and interventional variables, except for age (group A: 60 +/- 9 years, group B: 56 +/- 10 years; P =.04). The incidence of chest pain was not influenced by nitroglycerin (group A: 18%, group B: 22%; P = not significant). However, the occurrence of MMN was significantly reduced by nitroglycerin (group A: 5%, group B: 19%, P =.036). A rise in CK with significant CK-MB fraction was observed in only 2 patients in group B (both less than twice upper limit). Only 4 of the 10 patients with MMN also had chest pain. CONCLUSIONS: Routine use of intravenous nitroglycerin after coronary stenting significantly reduced the occurrence of minor myocardial necrosis. However, the incidence of postprocedural chest pain remained unchanged.

[Interventional treatment of acute myocardial infarct]. / Interventionelle Behandlung des akuten Myokardinfarkts.

BACKGROUND: Randomised trials have shown that primary percutaneous angioplasty (PTCA) may offer advantages over thrombolysis in treating acute myocardial infarction (vessel patency is achieved more often, mortality and reinfarction rate are lower, cerebrovascular accidents are less frequent). Data from several foreign registries have been less clear. Up to now no registry data have been available for Switzerland. Data from registries are very important in planning optimal treatment under "real world" conditions. METHOD: All patients receiving acute PTCA during the first 24 hours of acute myocardial infarction were prospectively included in a registry at a single centre. We assessed times until revascularisation, as well as clinical, angiographic and outcome data. RESULTS: 503 patients (age 59 +/- 12 years, 15% women) were included from 1. 1. 1995 to 30.6.2000. Primary PTCA was performed in 334 patients, and rescue PTCA in 169. Diabetes mellitus was present in 36% of the total. Multivessel disease was present in 61%, anterior infarction in 36%, and 16% were in cardiogenic shock before intervention. The pre-hospital delay was 2:12 h (median). In-hospital decision delay (hospital admission until contact to cardiologist) in patients with primary PTCA was 31 minutes (median). The time from vessel puncture to recanalisation was 19 minutes (median). 273 patients were transferred for coronary angiography and intervention by other hospitals (218 by ground ambulance, 55 per helicopter transfer). The total transfer time (calculated from time of decision to arrival in the catheterization laboratory) was 57 minutes (median). PTCA was successful angiographically in 97% and TIMI 3 flow was obtained in 93% of all patients. Hospital mortality was low in view of the high proportion of patients in cardiogenic shock prior to PTCA (mortality in shock patients was 33%). Mortality in patients without pre-existing cardiogenic shock was 2%. CONCLUSION: Patients with acute myocardial infarction, especially high-risk patients, can be treated successfully by acute PTCA around the clock in Switzerland, in accordance with the strict international recommendations for time delays. The treatment results are similar to those in randomised trials. Transfer of patients from referral hospital is safe, with acceptable delays. Optimisation of the decision process and transport logistics may further improve outcome by reducing the total ischaemia time.