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.

WITHDRAWN: Enlargement of the Right Atrium - Diverticulum or Aneurysm?

The publisher regrets that this was an accidental duplication of an article that has already been published in Eur. J. Echocardiogr., 4 (2003) 223-225, . The duplicate article has therefore been withdrawn.

Endothelial cell senescence.

The wear and tear processes that are thought to contribute to human ageing may play an important role in the development of vascular diseases. One such process is cellular senescence. In endothelial cells the senescent phenotype can be induced by a number of factors, including telomere damage, oxidative stress and sustained mitogenic stimulation. Several lines of evidence indicate that endothelial cell senescence maybe relevant to vascular disease. In this chapter we examine the causes, mechanisms and regulation of endothelial cell senescence as they emerge from studies in cell culture. We also describe the senescent phenotype and discuss its pathophysiological implications. We review the evidence for the occurrence of endothelial cell senescence in vivo and examine findings in animal models of ageing and human genetic disorders that argue for and against a role of endothelial cell senescence in age-related vascular pathology. Finally, we address the particular case of endothelial progenitor cell senescence and discuss the relevance of this phenomenon for angiogenesis and vascular repair.

Idiopathic enlargement of the right atrium: 23 year follow up of a familial cluster and their unaffected relatives.

OBJECTIVE: To evaluate the long term outcome of familial idiopathic enlargement of the right atrium (IERA) and the risk of developing this disorder among unaffected offspring. DESIGN: 23 year follow up study. PATIENTS: 14 members (eight men, mean age 54 years, range 40-78) of a pedigree with familial IERA. METHODS: All patients were examined clinically and echocardiographically in 1979 and 2002. Normal cross sectional dimensions of the right atrium were derived from echocardiographic evaluation of 100 people (47% men) with no structural or haemodynamic signs of heart disease. The 90th centile was chosen as the upper normal limit. IERA was defined as an increased right atrial long axis indexed to body surface area (RALAX(i), men > 2.6 cm/m2, women > 2.8 cm/m2) in the absence of other cardiac abnormalities. Severe IERA was defined arbitrarily as RALAX(i) > or = 4 cm/m2. RESULTS: The course of the two index patients with severe IERA diagnosed in 1979 was complicated by atrial fibrillation, systemic embolism, and symptoms of heart failure without systolic dysfunction, resulting in the death of one man (77 years old). One of two patients with initially mild forms progressed to severe IERA. All of the initially unaffected offspring (n = 9) remained asymptomatic, although four of them had developed mild IERA. CONCLUSIONS: During 23 years' follow up, severe IERA induced atrial fibrillation, systemic embolism, and symptoms of heart failure without systolic dysfunction in all cases in this family. Mild IERA seems to become manifest during middle age and may be followed by gradual progression to clinically relevant disease.

Aberrant tendinous chords with tethering of the tricuspid leaflets: a congenital anomaly causing severe tricuspid regurgitation.

OBJECTIVE: To define the entity of tricuspid regurgitation caused by tethering of the tricuspid valve leaflets by aberrant tendinous chords. DESIGN: Retrospective study. SETTING: Tertiary care centre (university teaching hospital). PATIENTS: 10 patients with unexplained severe tricuspid regurgitation. METHODS: The last 13 500 echocardiographic studies from our facility were reviewed to identify patients with severe unexplained tricuspid regurgitation. Tethering was defined by the presence of aberrant tendinous chords to the tricuspid valve leaflets limiting the mobility of the tricuspid leaflet and resulting in incomplete coaptation and apical displacement of the regurgitant jet origin. Aberrant tendinous chords were defined as those inserting at the clear zone of the tricuspid leaflet and not originating from the papillary muscle. Patients fulfilling the diagnostic criteria for Ebstein's anomaly were excluded. RESULTS: 10 patients with aberrant tendinous chords tethering one or more tricuspid valve leaflets were identified. There were short non-aberrant tendinous chords in seven patients, five of whom also had right ventricular or tricuspid annulus dilatation. CONCLUSIONS: Tethering of the tricuspid valve leaflets by aberrant tendinous chords can be the sole mechanism of congenital tricuspid regurgitation. It is often associated with short non-aberrant tendinous chords, which may develop secondary to right ventricular or tricuspid annulus dilatation. Awareness of tethering as a cause of tricuspid regurgitation may be important in planning reconstructive surgery.

Enlargement of the right atrium--diverticulum or aneurysm?

Diverticula and aneurysms are rare congenital anomalies of the right atrium. Here, we report a case of a giant congenital diverticulum of the right atrium in a 27-year-old female and discuss the morphological characteristics distinguishing diverticula and aneurysms.

Cellular senescence after single and repeated balloon catheter denudations of rabbit carotid arteries.

The hypothesis that increased cellular proliferation in the vasculature may lead to replicative senescence has been tested in a model of neointima formation. We have used a biomarker of replicative senescence, senescence-associated beta-galactosidase (SA-beta-gal), to detect senescence in rabbit carotid arteries subjected to single and double balloon denudations. We found an accumulation of senescent cells in the neointima and media of all injured vessels, in contrast to the near absence of such cells in control vessels. The relative area occupied by SA-beta-gal-positive cells was higher in vessels subjected to double denudation than in those subjected to single denudation, both in the neointima (0.99% versus 0.06%, respectively; P:<0.001) and in the media (0.11% versus 0.01%, respectively; P:<0.02). The majority of SA-beta-gal-positive cells were vascular smooth muscle cells, and a minority were endothelial cells. SA-beta-gal-positive cells showed no evidence of apoptosis by use of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling. Our results indicate that the proliferative response that follows intraluminal injury to the artery leads to the emergence of senescent endothelial and smooth muscle cells. The demonstration that vascular cell senescence can occur in vivo suggests that this process may be involved in cardiovascular pathologies that have a proliferative component.

Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells.

Senescence-associated (beta)-galactosidase is widely used as a biomarker of replicative senescence. However, it remains unknown whether this is a distinct enzyme active at pH 6, and differentially expressed in senescence, or a manifestation of an increase in the classic acid lysosomal (beta)-galactosidase. Here we have investigated the origin of senescence-associated-(beta)-galactosidase activity by modifying the intracellular and lysosomal pH of young and senescent human umbilical vein endothelial cells and examining the effect of these manipulations on the levels of activity, using a flow cytometric assay. Lysosomal alkalinisation with chloroquine or bafilomycin A(1), as well as equilibration of the intracellular milieu to pH 6 with nigericin, caused a profound (92-99%) inhibition of the total intracellular (beta)-galactosidase activity. However, independent of pH alterations, senescent cells showed levels of (beta)-galactosidase activity three- to sixfold higher than young cells. This increase in activity occurred in parallel to an increase in (beta)-galactosidase protein levels. Acridine Orange staining revealed an increase in lysosomal content with replicative age, which correlated with the increase in (beta)-galactosidase. These findings demonstrate that senescence-associated (beta)-galactosidase is a manifestation of residual lysosomal activity at a suboptimal pH, which becomes detectable due to the increased lysosomal content in senescent cells.

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.

Epicardial, biatrial synchronous pacing for prevention of atrial fibrillation after cardiac surgery.

About 30% of patients develop AF after open heart surgery. Biatrial synchronous pacing (BSP) has been shown to promote sinus rhythm in patients with paroxysmal AF refractory to drug therapy. We conducted a prospective, randomized study to test the effect of BSP via epicardial electrodes on the incidence of AF after heart surgery, as compared to conventional therapy. To apply BSP, we attached two epicardial electrodes to the right and one to the left atrium. Immediately following surgery, BSP was initiated in the AAI-Mode at a rate of 10 beats/min above the underlying rhythm (maximum 110 beats/min) and continued for 3 days, during which the rhythm was continually monitored. After 21 (age 63 +/- 9 years) of the planned 200 patients, the study was prematurely aborted because of the proarrhythmic effect of BSP: 6 of the 12 patients treated with BSP developed sensing failure (P amplitude < 1 mV), which provoked AF in 5 of these 6 patients. BSP was discontinued due to diaphragmal stimulation in two patients and due to ventricular stimulation by a dislocated left atrial electrode in one patient. Two patients in the control group (n = 9) developed AF. Using the available standard technology, BSP via epicardial electrodes is not suitable to suppress AF after heart surgery, primarily due to postoperative deterioration of atrial sensing and its profibrillatory effect. In patients requiring atrial pacing after heart surgery, sensing thresholds must be closely monitored to prevent induction of AF.

[After care of acute myocardial infarct: what are the 4 most important points?]. / Nachbehandlung des akuten Myokardinfarktes: Was sind die vier wichtigsten Punkte?

The variable prognosis after myocardial infarction necessitates an individual tailoring of follow-up treatment. Therapeutic decisions must be based on a complete risk stratification including assessment of persisting ischemia, left ventricular function, rhythmic instability and cardiovascular risk factor profile. High risk patients (prognostic indication) as well as symptomatic patients (symptomatic indication) should be referred for coronary angiography to assess the need for revascularisation procedures (PTCA, CABG). The individual risk profile also defines drug therapy for secondary prevention (not more than 3-4 drugs): anti-platelet agents or anticoagulation in every patient; beta blockers in all but the lowest risk group; ACE-inhibitors in heart failure or asymptomatic, substantial left ventricular dysfunction; liberal use of cholesterol-reducing drugs. Life style alterations should be encouraged in almost every patient. Information about the necessary measures to be taken upon occurrence of angina at rest or other cardiac symptoms must be repeatedly given to all patients.