A.J. Peters

Hemostatic risk factors in patients with coronary artery disease and type 2 diabetes - a two year follow-up of 243 patients

BackgoundThrombosis is regarded to be a key factor in the development of acute coronary syndromes in patients with coronary artery disease (CAD). We hypothesize, that hemostatic and rheological risk factors may be of major relevance for the incidence and the risk stratification of these patients.MethodsIn 243 patients with coronary artery disease and stable angina pectoris parameters of metabolism, hemostasis, blood rheology and endogenous fibrinolysis were assessed. Patients were prospectively followed for 2 years in respect to elective revascularizations and acute coronary syndromes.ResultsDuring follow-up 88 patients presented with cardiac events, 22 of those were admitted to the hospital because of acute events, 5 Patients were excluded due to non- cardiac death. Patients with clinical events were found to be more frequently diabetic and presented with a more progressed coronary atherosclerosis. Even though patients with diabetes mellitus demonstrated a comparable level of multivessel disease (71% vs. 70%) the rate of elective revascularization was higher (41% vs. 28%, p < 0.05). The results were also unfavorable for the incidence of acute cardiovascular events (18% vs. 8%, p < 0.01). In comparison to non-diabetic patients diabetics demonstrated significantly elevated levels of fibrinogen (352 ± 76 vs. 312 ± 64 mg/dl, p < 0.01), plasma viscosity (1.38 ± 0.23 vs. 1.31 ± 0.16 mPas, p < 0.01), red blood cell aggregation (13.2 ± 2.5 vs. 12.1 ± 3.1 E, p < 0.05) and plasmin-activator-inhibitor (6.11 ± 3.4 vs. 4.7 ± 2.7 U/l, p < 0.05).ConclusionPathological alterations of fibrinogen, blood rheology and plasminogen-activator-inhibtor as indicators of a procoagulant state are of major relevance for the short-term incidence of cardiac events, especially in patients with diabetes mellitus type 2, and may be used to stratify patients to specific therapies.

In vitro Bleeding Test with PFA-100TM—Aspects of Controlling Individual Acetylsalicylic Acid Induced Platelet Inhibition in Patients with Cardiovascular Disease

AbstractObjectives: This study investigated the usefulness and practicability of a platelet function analyzer (PFA-100TM, DADE-Behring, Germany) to determine individual platelet inhibition in patients treated with acetylsalicylic acid (ASA). Background: Patients with coronary artery disease (CAD) routinely and during angioplasty (PTCA) receive standard doses of ASA to avoid acute coronary syndromes and abrupt vessel closures without information of the individual efficacy of platelet inhibition. Methods: With the PFA-100TM a standardized bleeding time is measured. Whole-blood anticoagulated with 3.2% sodium citrate is aspirated through a capillary (⊘ 200μm) and through an aperture (⊘ 147μm). The time until occlusion of the aperture (closure time, CT) by a stable platelet plug induced by shear stress, collagen and epinephrine (COLL/EPI-CT) or shear stress, collagen and adenosine 5′-diphosphate (COLL/ADP-CT) is determined. To examine the usefulness of the PFA-100TM as a rapid bedside test and the individual effect of ASA, closure time was measured in healthy individuals (n=17), in patients with stable CAD (n=19) and in patients undergoing PTCA (n=8). Results: Patients with stable CAD and regular medication with 100mg ASA per day for at least 3 month showed shorter COLL/ADP-CT in comparison to healthy individuals who took only one single dose of 100mg ASA. Of the patients with CAD 63% had a COLL/EPI-CT within normal range suggesting a low or no response to ASA. Also only 50% of the patients undergoing PTCA reached the expected COLL/EPI-CT>300s after an additive single dose of 500mg ASA intravenously. Neither heparin, phenprocoumon, sex nor different blood sampling methods seem to influence the measurements relevantly. Conclusions: This pilot study indicates that with the PFA-100TM test device a simple and quick measurement of an in vitro bleeding time is possible. It is able to detect an increase in the bleeding time after a single dose of ASA 100mg in healthy subjects, reflecting a sensitive detection of ASA induced changes in platelet inhibition respective activation. Differences in the individual response to ASA could be observed in healthy subjects, patients with stable CAD and patients undergoing PTCA. Further studies should validate the PFA-100TM with standard methods to determine ASA response in patients with cardiovascular disease and investigate implications for treatment and outcome in this patient group.

Changes of hemostasis, endogenous fibrinolysis, platelet activation and endothelins after percutaneous transluminal coronary angioplasty in patients with stable angina.

OBJECTIVES This study investigated parameters of endogenous fibrinolysis, activation of coagulation and platelets, and endothelin levels before and after elective percutaneous transluminal coronary angioplasty (PTCA) in patients with stable coronary artery disease (CAD). BACKGROUND Abrupt vessel closure is a serious short-term complication after PTCA and is often unforeseeable. Detailed insight into the effect of PTCA on hemostasis, platelets and the release of vasoconstrictive substances, which are among the mainly discussed mechanisms of abrupt vessel closure, is needed to enhance the safety of coronary intervention. METHODS Plasma levels of markers of platelet activity, coagulation, endogenous fibrinolysis and endothelins were determined in 20 patients with stable CAD undergoing elective PTCA. The blood specimens were drawn before, immediately after, 1 h after intervention and on the next morning. RESULTS All patients showed an initially uncomplicated PTCA. Regarding the efficacy of anticoagulation after receiving 15.000 IU heparin during PTCA, two groups were compared. In eight patients with ineffective anticoagulation production of thrombin and platelet activation directly after and 1 h after PTCA was significantly higher compared with 12 patients with effective anticoagulation. Despite the strong activation of coagulation, only a low fibrinolytic response could be observed. Endothelins rose significantly after PTCA in both groups but stayed longer on higher levels in patients with distinct thrombin generation. Three of the eight patients without sufficient heparin treatment suffered abrupt vessel closure. CONCLUSIONS Initially uncomplicated dilation of coronary arteries leads to systemically measurable activation of coagulation and platelets in patients with ineffective doses of heparin and release of endothelins in all patients. Therefore, individual adjustment of anticoagulation and platelet inhibition in combination with effective antivasospastic substances are needed in every patient before, during and after initially uncomplicated PTCA to prevent this serious complication.

Relevance of hemostatic risk factors on coronary morphology in patients with diabetes mellitus type 2.

ObjectiveThe influence hemostatitc parameters on the morphological extent and severity of coronary artery disease were studied in patients with and without DM type 2.BackgroundIt is known that patients with diabetes (DM) have abnormal metabolic and hemostatic parametersMethodsOf 150 consecutive patients with angiographically proven coronary artery disease 29 presented with DM. Additionally to parameters of lipid-metabolism fibrinogen, tissue-plasminogenactivator (t-PA), plasminogen-activator-inhibitor (PAI), plasmin-a-antiplasmin (PAP), prothrombin-fragment 1+2 (F1+2), thrombin-antithrombin (TAT), von-willebrand-factor (vWF), platelet factor 4 (PF4), glykomembranproteine 140 (GMP140) and the rheologic parameters plasma viscosity and red blood cell aggregation were evaluated. The extent and severity of CAD was evaluated according to the criteria of the American Heart Association.ResultsPatients with DM presented with a higher number of conventional risk factors as compared to non-diabetic patients. Additionally there were significant differences for F1+2, red blood cell aggregation and PAI. Diabetic patients showed a more severe extent of coronary arteriosclerosis, which also could be found more distally. A significant relationship between blood-glucose, thrombocyte-activation (vWF), endogenous fibrinolysis (PAI) and the severity of CAD and a more distal location of stenoses could be found (r = 0.6, p < 0.001).ConclusionPatients with coronary artery disease and DM type 2 showed marked alterations of metabolic, hemostatic, fibrinolytic and rheologic parameters, which can produce a prothrombogenic state. A direct association of thrombogenic factors on coronary morphology could be shown. This can be the pathophysiologic mechanism of more severe and distal pronounced coronary atherosclerosis in these patients.

Percutaneous coronary revascularization in patients with formerly "refractory angina pectoris in end-stage coronary artery disease" – Not "end-stage" after all

BackgroundPatients with refractory angina pectoris in end-stage coronary artery disease represent a severe condition with a higher reduction of life-expectancy and quality of life as compared to patients with stable coronary artery disease. It was the purpose of this study to invasively re-evaluate highly symptomatic patients with formerly diagnosed refractory angina pectoris in end-stage coronary artery disease for feasible options of myocardial revascularization.MethodsThirty-four Patients formerly characterized as having end stage coronary artery disease with refractory angina pectoris were retrospectively followed for coronary interventions.ResultsOf those 34 patients 21 (61.8%) were eventually revascularized with percutaneous interventional revascularization (PCI). Due to complex coronary morphology (angulation, chronic total occlusion) PCI demanded an above-average amount of time (66 ± 42 minutes, range 25–206 minutes) and materials (contrast media 247 ± 209 ml, range 50–750 ml; PCI guiding wires 2.0 ± 1.4, range 1–6 wires). Of PCI patients 7 (33.3%) showed a new lesion as a sign of progression of atherosclerosis. Clinical success rate with a reduction to angina class II or lower was 71.4% at 30 days. Surgery was performed in a total of8 (23.5%) patients with a clinical success rate of 62.5%. Based on an intention-to-treat 2 patients of originally 8 (25%) demonstrated clinical success. Mortality during follow-up (1–18 months) was 4.8% in patients who underwent PCI, 25% in patients treated surgically and 25% in those only treated medically.ConclusionThe majority of patients with end-stage coronary artery disease can be treated effectively with conventional invasive treatment modalities. Therefore even though it is challenging and demanding PCI should be considered as a first choice before experimental interventions are considered.

Long-term urokinase therapy and isovolemic hemodilution: A clinical and hemodynamic comparison in patients with refractory angina pectoris

Antiischemic effectiveness of long-term urokinase therapy and isovolemic hemodilution therapy has been reported in patients with symptomatic coronary artery disease, but both interventions have never been compared. In patients with refractory angina pectoris and end-stage coronary artery disease (clinical functional class III), isovolemic hemodilution (n=9) (hydroxyethyl starch solution 6%, 1–2 times/week), and urokinase therapy (n=11) (500,000 U urokinase per i.v. injection, 3 times a week) were performed over a period of 12 weeks, each additionally to maximal conventional treatment. Apart from the assessment of clinical symptoms and rheologic parameters, invasive hemodynamic measurements were carried out at rest and during exercise testing before and after treatment. After treatment with urokinase, patients showed a significant reduction of clinical symptoms (from 19.8±6.5 to 5.0±4.3 anginal events/week,p<0.001), fibrinogen (from 410±88 to 238±40 mg/dl,p<0.001), plasma viscosity (from 1.45±0.10 to 1.33±0.03 mPa×s−1,p<0.01), and no changes of hematocrit (from 0.45±0.02 to 0.45±0.02) and whole blood viscosity (from 4.7±0.5 to 4.4±0.7 mPa × s−1); however, hemodilution resulted in a decrease of hematocrit (from 0.46±0.01 to 0.39±0.01,p<0.001) and whole blood viscosity (from 4.7±0.5 to 4.0±0.3 mPa×s−1,p<0.001) and no changes of initially comparable levels of clinical symptoms, fibrinogen, and plasma viscosity. Hemodynamic parameters at rest improved after urokinase therapy with a reduction of pulmonary capillary wedge pressure (from 9.1±5.1 to 5.5±2.8 mmHg,p<0.05) at comparable levels of systemic vascular resistance (from 1510±340 to 1420±510 dyn×s×cm−5). Hemodilution did not result in any significant hemodynamic changes. Apart from clinical symptoms, long-term intermittent urokinase therapy reduces pulmonary capillary wedge pressure at rest. This may reflect an improved diastolic function due to a rheological enhancement of myocardial perfusion at the level of the coronary microcirculation. Isovolemic hemodilution seems to be of no benefit.

Reduzierte gesundheitsbezogene Lebensqualität bei Patienten mit implantiertem Kardioverter/ Defibrillator, Schockereignissen und Herzinsuffizienz

Summary Implantable cardioverter/defibrillators (ICD) have led to a reduction in cardiac mortality in patients with ventricular tachyarrhythmias. A considerable number of patients experience repeated shocks which may have an impact on the quality of life.In 106 patients with an ICD, who were seen for routine follow-up in an outpatient department, cardiac disease related symptoms, parameters of ICD therapy (e.g., delivered shocks and antitachycardial pacing) and quality of life using a validated questionnaire were assessed (scale 0–4).Patients who experienced shocks (n=17, 1–25 shocks) when compared to the rest of the group demonstrated a reduced quality of life (1.95±0.52 vs. 2.51±0.59, p<0.001). In patients with successful termination of arrhythmias with antitachycardial pacing only (without shocks), quality of life was slightly but not significantly reduced (2.22±0.56 vs. 2.46±0.62, p=0.13). New York Heart Association heart failure Grade III was also associated with a significant reduction in the quality of life scores. The number of outpatient visits or hospital admissions was not significantly increased in the patient group with shocks. Seventy percent of the patients with former or recently delivered shocks were additionally treated with antiarrhythmics.Delivery of shocks in patients with an implanted cardioverter/defibrillator is associated with a severe reduction in various aspects of quality of life which is comparable to patients with refractory angina pectoris. These aspects characterize a disease state which warrants additional medical antiarrhythmic therapy and new treatment modalities including psychological guidance for this patient group.Zusammenfassung Die Implantation von Kardiovertern/Defibrillatoren (ICD) reduziert die kardiovaskuläre Mortalität von Patienten mit ventrikulären Tachyarrhythmien. Die erlittenen Schocks können einen Einfluß auf die Lebensqualität haben.Bei 106 Patienten mit einem ICD wurden bei einer ambulanten Routineuntersuchung die gespeicherten Arrhythmieereignisse, Angaben zu Klinik- und Arztbesuchen in den letzten 12 Wochen sowie die Lebensqualität mittels validiertem Fragebogen („Profil der Lebensqualtiät chronisch Kranker”) erfaßt.Die Patienten mit Schockereignissen (n=17, 1–25 Schocks) hatten im Vergleich zu den Patienten ohne Schockereignisse eine verminderte Lebensqualität (Gesamtpunktwert 1,95±0,52 vs. 2,51±0,59, p<0,001). Die Lebensqualität der Patienten, deren Rhythmusstörungen durch Überstimulation therapiert werden konnten, war nicht signifikant vermindert (Gesamtpunktwert 2,22±0,56 vs. 2,46±0,62 bei den Patienten ohne Ereignisse, p=0,13). Eine Herzinsuffizienzsymptomatik des NYHA-Stadiums III oder eine reduzierte linksventrikuläre Ejektionsfraktion vor Implantation des ICD waren ebenfalls signifikant mit einer Verminderung der Lebensqualität assoziiert. Die Anzahl stationärer oder ambulanter Behandlungen ist in den Patientengruppen mit Schockereignissen und ohne Schockereignisse nicht signifikant unterschiedlich. Siebzig Prozent der Patienten mit aktuellen oder früheren Schockereignissen waren zusätzlich antiarrhythmisch medikamentös therapiert.Schockereignisse bei Patienten mit implantiertem Kardioverter/Defibrillator sind mit einer schweren Beeinträchtigung verschiedener Bereiche der Lebensqualität verbunden, die vergleichbar mit der von Patienten mit therapierefraktärer Angina pectoris ist. Diese Beobachtungen kennzeichnen einen schweren chronischen Krankheitsstatus. Eine Reduktion der Arrhythmieereignisse (z.B. durch Revaskularisation oder medikamentöse Therapie) und eine Behandlung durch Überstimulation ist wünschenswert.

Großes Pseudoaneurysma des linken Ventrikels nach Posterolateralwandinfarkt

Pseudoaneurysmen des linken Ventrikels sind eine sehr seltene Komplikation nach akutem Myokardinfarkt. Wir berichten über einen 69jährigen Patienten mit ausgedehnten posterolateral gelegenem Pseudoaneurysma, welches durch eine reanimationspflichtige Linksherzdekompensation klinisch manifest wurde. Lokalisation und Ausdehnung des Aneurysmas konnten echokardiographisch und angiographisch sicher quantifiziert werden; koronarangiographisch bestand korrespondierend zur Lokalisation des Aneurysmas ein proximaler Abbruch des Ramus circumflexus. Auf Grund der hohen Rupturgefahr von Pseudoaneurysmen wurde der Patient einer raschen chirurgischen Therapie zugeführt. Pseudoaneurysmus of the left ventricle are rare complications after acute myocardial infarction. We report on a 69 year old patient with a large false aneurysm located in the posterolateral ventricular wall. It became clinically apparent during an episode of severe left heart failure. Echocardiography and left ventriculography allowed an accurate determination of localization and dimension of the pseudoaneurysm; coronary angiography revealed a proximal occlusion of the left circumflex coronary artery. Because of the high risk of rupture, a rapid surgical repair of the false aneurysm was indicated.

Antiischämischer Wirkungsnachweis bei Patienten mit therapierefraktärer Angina pectoris im Endstadium der koronaren Herzkrankheit - Ergebnisse zur chronisch-intermittierenden Urokinasetherapie

Patienten mit therapierefraktärer Angina pectoris im Endstadium der koronaren Herzkrankheit stellen aufgrund der verbesserten Sekundärprävention der koronaren Herzkrankheit eine zunehmende Patientengruppe mit einem hohen Leidensdruck dar. Bei der Indikation und zur Bewertung eines antiischämischen Therapieerfolges sind sensitive nicht-invasive Untersuchungsverfahren neben einer Einschätzung der klinischen Symptomatik von wesentlicher Bedeutung. Es zeigt sich basierend auf eigenen Erfahrungen, daß Verfahren, welche sich wesentlich auf die ergometrische Belastbarkeit von Patienten stützen aufgrund der Symptomlimitierung in der klinischen Routine nur von eingeschränktem Nutzen sein können. Daneben erschwert die diffuse Ischämie bei diesen Patienten insbesondere den elektrokardiographischen und szintigraphischen Ischämienachweis. Vielversprechend hingegen scheint die Auswertung indirekter Ischämieparameter der diastolischen und systolischen Funktion z.B. durch die Doppler-Echokardiographie oder die Radionuklidventrikulographie wie es beispielhaft für die chronisch-intermittierende Urokinasetherapie gezeigt werden konnte. Insgesamt weisen die Befunde zur antiischämischen Wirksamkeit der chronisch-intermittierenden Urokinasetherapie auf eine absolute Verbesserung der Perfusion hin, was sie den anderen kardial-entlastenden, medikamentösen Therapieansätzen im Sinne eines kausal-therapeutischen Ansatzes überlegen macht. Patients with refractory angina pectoris and end-stage coronary artery disease represent an increasing clinical problem. Numbers of these patients will increase in the future for improved survival due to effective secondary prevention of coronary artery disease. Next to the evaluation of clinical symptoms non-invasive objective parameters of myocardial ischemia are of major relevance before initiation of alternative treatment modalities and for verification of antiischemic effectiveness. Based on our own experience it can be shown that in these patients testing which is mainly based on the patients physical exercise capacity is only of limited value due to the early occurence of clinical symptoms. Furthermore diffuse perfusion abnormalities reduce the sensitivity of electrocardiographic and scintigraphic detection of ischemic changes. In contrast indirect measures of ischemia relating to the systolic or diastolic function of the left ventricle like dopplerechocardiography and radionuclide ventriculography seem to be promising approaches. This is confirmed by the results from the application of long-term intermittent urokinase therapy. Long-term intermittent urokinase therapy leads to an absolute enhancement of myocardial perfusion, which makes this approach superior to other medical interventions which are mainly based on a reduction of cardiac work-load.