Elisabeth Lassnig

Arterial stiffness, wave reflections, and the risk of coronary artery disease.

Background—Increased arterial stiffness, determined invasively, has been shown to predict a higher risk of coronary atherosclerosis. However, invasive techniques are of limited value for screening and risk stratification in larger patient groups. Methods and Results—We prospectively enrolled 465 consecutive, symptomatic men undergoing coronary angiography for the assessment of suspected coronary artery disease. Arterial stiffness and wave reflections were quantified noninvasively using applanation tonometry of the radial artery with a validated transfer function to generate the corresponding ascending aortic pressure waveform. Augmented pressure (AP) was defined as the difference between the second and the first systolic peak, and augmentation index (AIx) was AP expressed as a percentage of the pulse pressure. In univariate analysis, a higher AIx was associated with an increased risk for coronary artery disease (OR, 4.06 for the difference between the first and the fourth quartile [1.72 to 9.57; P <0.01]). In multivariate analysis, after controlling for age, height, presence of hypertension, HDL cholesterol, and medications, the association with coronary artery disease risk remained significant (OR, 6.91; P <0.05). The results were exclusively driven by an increase in risk with premature vessel stiffening in the younger patient group (up to 60 years of age), with an unadjusted OR between AIx quartiles I and IV of 8.25 (P <0.01) and a multiple-adjusted OR between these quartiles of 16.81 (P <0.05). Conclusions—AIx and AP, noninvasively determined manifestations of arterial stiffening and increased wave reflections, are strong, independent risk markers for premature coronary artery disease.

Pulse waveform characteristics predict cardiovascular events and mortality in patients undergoing coronary angiography.

Objectives Pulse waveform characteristics (Augmentation Index – AIx and pulse wave transit time) are measures of the timing and extent of arterial wave reflections. Although previous studies reported an independent association with cardiovascular morbidity, it remains to be established that waveform characteristics, derived from noninvasive pulse waveform analysis, predict cardiovascular outcomes independent of and additional to brachial blood pressure. Methods We prospectively assessed AIx, heart-rate corrected AIx, and pulse wave transit time, using radial applanation tonometry and a validated transfer function to generate the aortic pressure curve, in 520 male patients undergoing coronary angiography. Primary endpoint was a composite of all-cause mortality, myocardial infarction, stroke, cardiac, cerebrovascular, and peripheral revascularization. Results During a follow-up of 49 months, 170 patients reached the primary endpoint. On the basis of Cox proportional hazards regression models, all pressure waveform characteristics predicted the primary endpoint. A 10% increase of AIx and heart-rate corrected AIx was associated with a 20.5% (95% confidence interval 6.5–36.4, P = 0.003) and 31.4% (95% confidence interval 13.2–52.6, P = 0.0004) increased risk of the primary endpoint, respectively. A 10-ms increase of pulse wave transit time was associated with a 20.8% (95% confidence interval 10.8–29.6, P = 0.0001) lower risk of the primary endpoint. In multiple adjusted models, AIx, heart-rate corrected AIx, and pulse wave transit time were independently associated with the combined endpoint even after adjustments for brachial blood pressure, age, extent of coronary artery disease, clinical characteristics, and medications. Conclusion The study provides evidence that pulse waveform characteristics consistently and independently predict cardiovascular events in coronary patients.

Pheochromocytoma crisis presenting with shock and tako-tsubo-like cardiomyopathy

Pheochromocytoma usually presents with hypertension but it may also be an unusual aetiology of cardiogenic shock in order to catecholamine induced myocardial dysfunction. We report the devastating course of a patient with tako-tsubo like apical cardiomyopathy during pheocytoma crisis who presented with classical transient left ventricular apical ballooning 6 months before.

Ability of neuron-specific enolase to predict survival to hospital discharge after successful cardiopulmonary resuscitation.

BACKGROUND Accurate prediction of survival to hospital discharge in patients who achieve return of spontaneous circulation after cardiopulmonary resuscitation (CPR) has significant ethical and socioeconomic implications. We investigated the prognostic performance of serum neuron-specific enolase (NSE), a biochemical marker of ischemic brain injury, after successful CPR. METHODS In-hospital or out-of-hospital patients with nontraumatic normothermic cardiac arrest who achieved return of spontaneous circulation (ROSC) following at least 5 minutes of CPR were eligible. Neuron-specific enolase levels were assessed immediately, 6 hours, 12 hours and 2 days after ROSC. Subjects were followed to death or hospital discharge. RESULTS Seventeen patients (7 men, 10 women) were enrolled during a 1-year period. Median (range) NSE levels in survivors and non-survivors respectively were as follows: immediately after ROSC: 14.0 microg/L (9.1-51.4 microg/L) versus 25.9 microg/L (10.2-57.5 microg/L); 6 hours after ROSC: 15.2 microg/L (9.7-30.8 microg/L) versus 25.6 microg/L (12.7-38.2 microg/L); 12 hours after ROSC: 14.0 microg/L (8.6-32.4 microg/L) versus 28.5 microg/L (11.0-50.7 microg/L); and 48 hours after ROSC: 13.1 microg/L (7.8-29.5 microg/L) versus 52.0 microg/L (29.1-254.0 microg/L). Non-survivors had significantly higher NSE levels 48 hours after ROSC than surivors (p = 0.04) and showed a trend toward higher values during the entire time course following ROSC. An NSE concentration of >30 microg/L 48 hours after ROSC predicted death with a high specificity (100%: 95% confidence interval [CI] 85%-100%), and a level of 29 microg/L or less at 48 hours predicted survival with a high specificity (100%: 95% CI 83%-100%). CONCLUSIONS Serum NSE levels may have clinical utility for the prediction of survival to hospital discharge in patients after ROSC following CPR over 5 minutes in duration. This study is small, and our results are limited by wide confidence intervals. Further research on ability of NSE to facilitate prediction and clinical decision-making after cardiac arrest is warranted.

Prognostic significance of immune activation after acute coronary syndromes

We read with great interest the study by Maekawa et al. [(1)][1]in a recent issue of the Journal . The article reports that the peripheral peak monocyte count is associated with adverse cardiac outcome during a 33-month follow-up period. The authors could demonstrate that peripheral monocytosis

Lack of association between plasma lipoprotein(a) concentrations and the presence or absence of coronary atherosclerosis.

BACKGROUND Findings from previous studies relating lipoprotein(a) [Lp(a)] as an independent risk factor for coronary atherosclerosis and the presence of angiographically detectable coronary atherosclerotic lesions are not consistent. This study was performed to determine whether the plasma concentration of Lp(a) is associated with coronary atherosclerosis asessed by coronary angiography. METHODS We studied a total of 100 men and women (41 women, 59 men, age 63.7 +/- 11.0 years) who were referred for coronary angiography. Base-line data collection comprised conventional risk factors for coronary artery disease, lipids, fasting total homocysteine, and clinical characteristics. The relation between plasma Lp(a) levels and the presence or absence of coronary lesions was studied. The coronary angiograms were evaluated in a blinded manner. Any coronary stenosis was considered as coronary artery disease (CAD). RESULTS From the 100 patients, 40 were found to have no CAD and 60 had CAD assessed by coronary angiography. Estimates of the relative risk of coronary heart disease for the fifth quintile of plasma Lp(a) as compared with the first quintile were 0.87 (95 percent confidence interval, 0.66 to 1.34). After adjustment for age, sex, lipoproteins, and homocysteine levels, estimates of the relative risk of coronary heart disease for the fifth quintile of plasma Lp(a) as compared with the first quintile were 1.06 (95 percent confidence interval, 0.81 to 1.39). The presence of angiographic CAD was associated with patient age (p=0.048), male sex (p<0.01), high LDL-cholesterol levels (p=0.02), low HDL-cholesterol levels (p=0.02), high plasma fibrinogen levels (p<0.01) and high fasting total homocysteine levels (p=0.04). CONCLUSION These results suggest that the plasma concentration of Lp(a) is not associated with the presence of coronary artery disease in patients referred for coronary angiography.Background — Findings from previous studies relating lipoprotein(a) [Lp(a)] as an independent risk factor for coronary atherosclerosis and the presence of angiographically detectable coronary atherosclerotic lesions are not consistent.This study was performed to determine whether the plasma concentration of Lp(a) is associated with coronary atherosclerosis asessed by coronary angiography. Methods — We studied a total of 100 men and women (41 women, 59 men, age 63.7±11.0 years) who were referred for coronary angiography. Base-line data collection comprised conventional risk factors for coronary artery disease, lipids, fasting total homocysteine, and clinical characteristics.The relation between plasma Lp(a) levels and the presence or absence of coronary lesions was studied. The coronary angiograms were evaluated in a blinded manner. Any coronary stenosis was considered as coronary artery disease (CAD). Results — From the 100 patients, 40 were found to have no CAD and 60 had CAD assessed by coronary angiography. Estimates of the relative risk of coronary heart disease for the fifth quintile of plasma Lp(a) as compared with the first quintile were 0.87 (95 percent confidence interval, 0.66 to 1.34). After adjustment for age, sex, lipoproteins, and homocysteine levels, estimates of the relative risk of coronary heart disease for the fifth quintile of plasma Lp(a) as compared with the first quintile were 1.06 (95 percent confidence interval, 0.81 to 1.39).The presence of angiographic CAD was associated with patient age (p=0.048), male sex (p<0.01), high LDL-cholesterol levels (p=0.02), low HDL-cholesterol levels (p=0.02), high plasma fibrinogen levels (p<0.01) and high fasting total homocysteine levels (p=0.04). Conclusion — These results suggest that the plasma concentration of Lp(a) is not associated with the presence of coronary artery disease in patients referred for coronary angiography.

Cardiogenic shock due to myocardial infarction caused by coronary vasospasm associated with hyperthyroidism.

A 66-year-old woman who was found to be patient finally died from multi-organic dysfunction hyperthyroid suffered from repeated episodes of due to cardiogenic shock. Autopsy showed repeated angina. Serum thyrotropin (TSH) was 0.01 mU/ml myocardial infarctions and coronary arteries without (normal value 0.4–4 mU/ml), free triiodothyronine any atherosclerotic lesions. (fT3) was 6.48 pg/ml (normal value 2.3–4.0 pg/ml) Coronary vasospasm is characterized by a tranand free thyroxine (fT4) was increased to 43.6 pg/ml sient, marked reduction in the luminal diameter of an (normal value 8.0–14.0 pg/ml). The patient was in a epicardial coronary artery, and therefore leads to clinically hyperthyroid state. Detailed medical history myocardial ischaemia and causes variant angina [1]. did not reveal any other predisposing factors for The reduction in myocardial diameter is focal, usualvasospasm (e.g. ergotism or cocaine abuse). Thyreostatic treatment with thiamazol was started. During a prolonged episode of chest pain, the ECG showed monophasic ST-segment elevations in leads V1 to V6. Even after thrombolytic therapy, symptoms continued. Early on, the patient developed cardiogenic shock conditions. The emergency coronary angiogram showed total occlusion of the left anterior descending artery and circumflex artery due to coronary vasospasm which was completely reversible by injection of intracoronary nitrate (Figs. 1 and 2). The patient was treated with nitrates, anesthetized and mechanically ventilated. Since nitrates were not effective in resolving the vasospasm and because of rapid deterioration of the hemodynamic state, we did not add calcium cannel blockers to the therapeutic regimen. Ongoing ECG monitoring showed recurrent transient ST-segment elevations (Figs. 3 and 4). The

Whipple’s disease: misdiagnosed as sarcoidosis with further tricuspid valve endocarditis and pulmonary embolism – a case report

GH Whipple described a 36-year-old physician in 1907 with gradual loss of weight and strength, stools consisting chiefly of neutral fat and fatty acids, indefinite abdominal signs and a peculiar multiple arthritis. The patient died of this progressive illness. Whipple called it intestinal lipodystrophy since he observed accumulation of large masses of neutral fats and fatty acids in the lymph spaces. It was renamed Whipple’s disease in 1949. An infectious aetiology was suspected as early as Whipple’s initial report. However, successful treatment with antibiotics was not reported until 1952, which resulted in dramatic clinical responses. The cause is now known to be Tropheryma whipplei. Light and electron microscopy of infected tissue identified a gram-positive, non-acid-fast, periodic acid-Schiff (PAS) positive bacillus with a characteristic trilamellar plasma membrane resembling that of gram-negative bacteria. Whipple’s disease is extremely rare. It is a systemic infectious disorder affecting mostly middle-aged white men. The clinical presentation is often non-specific, which may make its diagnosis difficult. The four cardinal clinical manifestations are arthralgias, weight loss, diarrhoea and abdominal pain. The frequently vague articular symptoms can precede the diagnosis of Whipple’s disease by an average of 6–8 years. Lymph nodes and other tissues may present diagnostic problems, since the changes in routinely stained sections may mimic those of sarcoidosis. The detection of PAS-positive histiocytes in the small intestine remains the mainstay of the diagnosis, although Whipple’s disease without gastrointestinal involvement is described. We illustrate a case in which, retrospectively, the clinical presentation would have been typical for Whipple’s disease. However, the clinical presentation and the histological examinations of lymph nodes, liver biopsies and ascites initially were misinterpreted as sarcoidosis with consecutive immunosuppressive therapy and progressive worsening of the patient’s health presenting at least as sepsis with endocarditis.

[Infection sources in HNO- and jawbone regions in patients before valve replacement surgery].

Hintergrund:Die Endokarditis künstlicher Herzklappen ist ein gefürchtetes Krankheitsbild. Daher wird zumeist routinemäßig vor einer Klappenoperation eine Fokussuche auch beim asymptomatischen Patienten durchgeführt, um potentielle infektiöse Streuherde aufzufinden und noch vor der Operation prophylaktisch zu sanieren.Patienten und Methode:Anhand von 92 Patienten mit bevorstehender Klappenoperation wurde die Inzidenz von Infektionsquellen im Zahn-Kiefer- und HNO-Bereich evaluiert. Als Screeninguntersuchungen wurden Zahnpanoramaschichtaufnahme mit anschließender Begutachtung durch den kieferchirurgischen Facharzt sowie ein Nasennebenhöhlenröntgen durchgeführt. Als dentaler Fokus galten periapikale Beherdung, Zysten und Wurzelreste. Im Nasennebenhöhlenröntgen wurde primär jede Verschattung als pathologisch gewertet und zu einer weiteren Abklärung dem HNO-Facharzt zugeführt.Ergebnisse:49 von 92 Patienten (53,3%) wiesen bei der routinemäßigen Fokussuche einen pathologischen Befund auf. 42 Patienten (45,6%) zeigten einen behandlungsbedürftigen dentalen Infektionsherd, bei 19 Patienten wurden Verschattungen im NNH-Röntgen beschrieben (drei Aspergillome, drei Sinusitiden, die restlichen Verschattungen wurden als chronische, präoperativ nicht behandlungsbedürftige Polyposis befundet). Zwölf Patienten hatten sowohl im Kieferstatus als auch im NNH-Röntgen Auffälligkeiten. Die Blutsenkungsgeschwindigkeit korrelierte weder mit Kiefer- noch mit HNO-Herden. Dentale Foci fanden sich am häufigsten bei Patienten mit geplantem Mitralklappenersatz (MKE) (61%, davon 2/3 mehrere Herde). Von den Patienten mit anstehendem Aortenklappenersatz (AKE) hatten 47%, Mehrfachklappenersatz (MKE) 50%, MKE plus ACB (aortokoronare Bypassoperation) 50% und AKE plus ACB 40% sanierungsbedürftige Foci.Schlussfolgerung:Durch die präoperative Fokussuche bei einem unerwartet hohen Prozentsatz der Patienten konnten bakterielle Herde diagnostiziert werden. Letztendlich fehlen allerdings prospektive Daten, die untermauern, dass durch die Herdsanierung die Inzidenz der Prothesenendokarditis reduziert werden kann.Background:Prosthetic valve endocarditis is a life-threatening complication after valve replacement surgery. Therefore, it is common to perform a screening for potential sources of infection before surgery in order to be able to do a prophylactic treatment.Patients and Method:The incidence of potential infectious sources of bacteremia in the dental, jaw and nasopharyngeal area was evaluated in 92 patients going to have valve replacement surgery. Screening examinations were an X-ray of the paranasal sinuses and a panoramic radiograph of the dental arch. Chronic apical peridontitis, cysts and remaining radices were counted as dental sources. Each shadow in the paranasal sinuses X-ray was seen as pathological and was further investigated by an otorhinolaryngologist.Results:A potential infectious source was found in 49 patients. 42 patients had a dental infectious source with need for treatment. 19 patients showed a pathologic sinus X-ray (three aspergillomas, three sinusitis, the others had a chronical polyposis with no need for treatment). Twelve patients had dental as well as sinusoidal sources. Erythrocyte sedimentation rate did not refer to the appearance of infectious sources. Patients going to have a mitral valve replacement had most dental sources (61%), 47% of the patients with planned aortic valve replacement, 50% of the patients planned to get more than one heart valve replaced, 50% of the patients getting mitral valve replacement and CABG and 40% of the patients waiting for aortic valve replacement and CABG had dental foci.Conclusion:Screening for infectious foci before valve replacement surgery diagnosed foci in a high percentage of the patients. Nevertheless current data concerning whether a prophylactic treatment may reduce the incidence of prosthetic valve endocarditis are conflicting.

Platelet Glycoprotein IIb/IIIa Inhibitors in Coronary Artery Disease

Hintergrund: Die Blockade der membranständigen thrombozytären Glykoprotein-(GP-)IIb/IIIa-Rezeptoren stellt eine innovative Strategie in Richtung einer potenten Hemmung der Plättchenaktivität im Bereich der rupturierten Koronarplaque dar. GP-IIb/IIIa-Rezeptoren binden an zirkulierendes Fibrinogen oder Von-Willebrand-Faktor und führen so zu einer Vernetzung von Thrombozyten als eine gemeinsame Endstrecke der Plättchenaggregation. Intravenöse Pharmaka sind gegen diese Rezeptoren gerichtet, wobei einerseits ein chimäres monoklonales Antikörperfragment (Abciximab) und andererseits peptidische (Eptifibatid) und nichtpeptidische (Tirofiban und Lamifiban) Mimetika zur Verfügung stehen. In zahlreichen plazebokontrollierten, groß angelegten klinischen Studien wurden diese Substanzen auf ihre Wirksamkeit überprüft.Ergebnisse: Im Rahmen von perkutanen Koronarinterventionen konnte eine absolute Reduktion des Risikos, innerhalb von 30 Tagen den kombinierten Endpunkt aus Tod und Myokardinfarkt zu erleiden oder eine dringliche neuerliche Revaskularisation zu benötigen, um 1,5–6,5% erreicht werden. Es wurde eine erhebliche Variabiliät des Behandlungseffekts zwischen den einzelnen geprüften Substanzen (Abciximab, Eptifibatid, Tirofiban) nachgewiesen. Ein Behandlungseffekt wurde sehr frühzeitig und mit jeder Art von Koronarintervention gezeigt und konnte bereits über einen Langzeitverlauf (> 3 Jahre) dokumentiert werden. Das erhöhte Blutungsrisikos ist durch eine Reduktion und Gewichtsanpassung der begleitenden Heparinisierung zu reduzieren.Beim akuten Koronarsyndrom ohne ST-Strecken-Hebung im EKG wird das Risiko, innerhalb von 30 Tagen den kombinierten Endpunkt aus Tod und Myokardinfarkt zu erleiden, durch eine 2- bis 4-tägige Behandlungsdauer mit Eptifibatid oder Tirofiban um 1,5–3,2% reduziert. Ein klinischer Vorteil war sowohl während der Behandlungsphase als auch darüber hinaus nachzuweisen. Eine frühzeitige Koronarrevaskularisation steigert die Effektivität der GP-IIb/IIIa-Rezeptor-Blockade. Die Zielsetzung des Einsatzes dieser Substanzen ist eine Stabilisierung vor der Intervention und eine Reduktion der interventionsassoziierten ischämischen Ereignisse.Schlussfolgerung: Somit ist eine Blockade der thrombozytären GP-IIb/IIIa-Rezeptoren als Zusatzbehandlung bei perkutanen Koronarinterventionen und der Behandlung akuter Koronarsyndrome geeignet, ischämische Komplikationen zu reduzieren.Background: Inhibition of platelet activity at the injured coronary plaque is a target for novel therapeutic strategies. One of these mechanisms is the blockade of the platelet surface membrane glycoprotein (GP) IIb/IIIa receptor, which binds circulating fibrinogen or von Willebrand factor and crosslinks platelets as the final common pathway to platelet aggregation. Intravenous agents directed against this receptor include the chimeric monoclonal antibody fragment abciximab, the peptide inhibitor eptifibatide and nonpeptide mimetics tirofiban and lamifiban.Results: During percutaneous coronary intervention, an absolute reduction of 1.5–6.5% in the 30-day risk of death, myocardial infarction or repeat urgent revascularization has been observed, with some variability in treatment effect among the agents tested. Treatment effect is achieved early with every modality of revascularization and maintained over the longterm up to 3 years. Increased bleeding risk may be minimized by reduction and weight adjustment of concomitant heparin dosing.In the acute coronary syndromes without ST segment elevation, absolute 1.5–3.2% reductions in 30-day rates of death or myocardial infarction have been achieved with 2- to 4-day courses of eptifibatide or tirofiban. Clinical benefit accrues during the period of drug infusion and is durable. Treatment effect may be enhanced among patients undergoing early coronary revascularization, with evidence of stabilization before intervention and suppression of postprocedural ischemic events.Conclusion: Thus, blockade of the platelet GP IIb/IIIa receptor reduces ischemic complications when used as an adjunct to percutaneous coronary intervention or the management of acute ischemic syndromes.