Hemodynamic and hormonal effects of quinaprilat in patients with congestive heart failure.

OBJECTIVE: To assess the pharmacodynamic activity and safety of rising single and multiple doses of intravenous quinaprilat compared with placebo in patients with New York Heart Association (NYHA) class III and IV congestive heart failure who were receiving digitalis or diuretic therapy or both. METHODS: Patients were randomly assigned to three treatment groups to receive low (0.5 to 1.0 mg), medium (1.0 and 2.5 mg), or high (5.0 and 10.0 mg) single intravenous doses of quinaprilat or placebo on day 1. On the basis of responses observed on day 1, the three treatment groups received stable multiple intravenous doses of either quinaprilat or placebo every 6 hours on days 2 and 3. Hemodynamic measurements, hormonal assessments, and safety were evaluated before and at specified intervals during the study. RESULTS: Compared with placebo, single and multiple doses of quinaprilat increased cardiac index and reduced pulmonary capillary wedge pressure, mean arterial pressure, systemic vascular resistance, and right atrial pressure in a dose-related manner. No clinically important change in heart rate was observed. Hemodynamic changes after multiple-dose quinaprilat administration were similar to those observed after single doses and were generally sustained during the 6-hour dosing interval. Relative to placebo, quinaprilat reduced plasma angiotensin converting enzyme (ACE) activity, angiotensin II concentration, and aldosterone concentration and increased plasma renin activity; no prominent changes in plasma catecholamine and atrial natriuretic peptide concentrations were observed. There were no clinically important drug-related changes in the safety parameters. CONCLUSIONS: Single and multiple intravenous doses of 0.5 to 10 mg quinaprilat are well-tolerated and produce favorable dose-dependent hemodynamic effects and hormonal changes consistent with those expected of an ACE inhibitor in patients with NYHA class III and IV congestive heart failure.

Coronary thrombolysis during acute myocardial infarction by intravenous BRL 26921, a new anisoylated plasminogen-streptokinase activator complex.

The safety and fibrinolytic efficacy of a new anisoylated plasminogen-streptokinase activator complex (APSAC) was tested in 50 patients with acute myocardial infarction (AMI) less than 4 hours in duration. APSAC (30 mg) was given intravenously as a bolus injection 151 +/- 47 minutes after clinical symptoms. Coronary angiography was then performed to assess coronary artery patency: 28 patients had an inferior AMI and 22 an anterior AMI. A patent infarct-related artery was found in 32 patients (64%) on first coronary angiography 66 +/- 21 minutes after administration of APSAC. Subsequent reperfusion was observed in 10 patients after 74 +/- 16 minutes (84%). Bleeding complications or hematomas were observed in 18 patients, of whom 3 required blood transfusions. Marked hypofibrinogenemia was observed within 24 hours in most patients. A control coronary angiogram was recorded in 37 patients (74%) after 25 +/- 19 days and showed reocclusion in 5 patients.

Early clinical evaluation of the intravenous treatment of acute myocardial infarction with anisoylated plasminogen streptokinase activator complex.

50 consecutive patients with acute myocardial infarction and symptoms of less than 4 hours duration were treated with anisoylated plasminogen streptokinase activator complex (APSAC) 30U intravenously as a bolus injection over 5 minutes. An open infarct-related artery was found in 32 patients (64%) when the first coronary angiography was taken 66 +/- 21 minutes after APSAC. Complete reperfusion was subsequently seen in 10 of 18 patients with an occluded infarct-related artery 74 +/- 16 minutes after injection of APSAC. Thus, a patient infarct-related artery was seen in 42 patients (84%) within 68 +/- 20 minutes. A control coronary angiography was performed in 37 patients (74%) after 25 +/- 19 days. Reocclusion was found in 5 patients. The minimal cross-sectional area of the residual coronary stenosis increased from 1.3 +/- 0.9 mm2 to 1.8 +/- 1.9 mm2. Patients with residual thrombi after coronary thrombolysis (n = 13) demonstrated an increase of the minimal cross-sectional area of the residual stenosis from 1.2 +/- 0.8 to 2.6 +/- 2.3 mm2, whereas those without residual thrombi showed only minor changes of the minimal cross-sectional area (1.3 +/- 0.9 to 1.2 +/- 1.2 mm2). Thus, APSAC demonstrated a high patency rate and a low reocclusion rate after intravenous administration. The prolonged fibrinolytic activity of APSAC leads to a further regression of the residual coronary stenosis among patients with coronary thrombi after reperfusion.

[Non-invasive methods of investigation cardiology (author's transl)]. / Nichtinvasive Untersuchungsverfahren in der Kardiologie.

Non-invasive assessment of heart and chamber size employs various techniques which yield different information. Overall size as estimated by biplane chest roentgenogram in the upright or - better - supine position is a valuable quantitative method. Correlation with individual chamber size is, however, only fair. Information on wall thickness can currently be obtained only by ultrasound echocardiography. ECG and vectorcardiography as a means for determining ventricular hypertrophy have remained semi-quantitative techniques, but can probably be developed into more quantitative information by means of computer analysis. A method of predicting left ventricular muscle mass using the Frank orthogonal lead system is described. Regional disorder of contraction and contractility have been difficult to assess non-invasively. Kymographic techniques describe only motion of the lateral wall. Ultrasound techniques, even using a two-dimensional approach, rarely include the ventricular apical region. Systolic time intervals and radionuclide minimal transit times have remained of limited importance. The value of ECG-gated computertomography cannot be assessed as yet. The greatest promise can be expected from radionuclide techniques with gated blood pool scanning and myocardial scintigraphic techniques.

[The potential significance of early effort myocardial scintigraphy following PTCA]. / Aussagemöglichkeiten der frühen Belastungsmyokardszintigraphie nach PTCA.

Exercise 201Tl scintigraphy before and after successful PTCA was evaluated in 69 patients with coronary stenosis > 60%. Mean luminal stenosis was found reduced from 74 +/- 10% to 31 +/- 11% (58% reduction). Scintitomographic examination within 3 weeks following intervention showed a reduction of the exercise perfusion defect from 17.00 +/- 14.6 to 5.8 +/- 7.8 arbitrary units (66% reduction). Angiographically, re-stenosis was identified in 22/41 patients (54%) after 6 months. Unexpectedly, re-stenosis could not be predicted by early 201Tl scintigraphy (positive and negative predictive value in patients with single-vessel disease: 61% and 41%, resp.). Nevertheless, evaluation of PTCA results was possible (sensitivity 83%). However, postinterventional transient defects, indicating ischemia, were often seen (all patients: 43/69; patients with single-vessel disease: 31/55) and not indicative of failure of the intervention. Thus, post-PTCA scintigrams should be compared with scintigrams recorded before the intervention to ensure reliable follow-up control.

Hemodynamics and myocardial oxygen metabolism of pulsus alternans in patients with dilative cardiomyopathy.

The hemodynamic and myocardial energetic changes due to pulsus alternans were investigated by left and right heart catheterization and by oxygen consumption measurements in three patients with dilative cardiomyopathy. In all three patients, pulsus alternans developed after intravenous administration of the phosphodiesterase inhibitor enoximone. Following enoximone (Patients 1/2/3), left ventricular peak systolic pressure was reduced, in the respective patients, from 100/103/115 mmHg (normal beat) to 91/96/94 mmHg (strong beat) and further to 59/80/85 mmHg (weak beat); left ventricular end-diastolic pressure was reduced from 24/23/22 mmHg (normal beat) to 5/10/6 mmHg (strong beat) and further to 3/7/4 mmHg (weak beat). Cardiac output increased by an average of 16%. Heart rate increased by an average of 12%. Stroke work (during pulsus alternans mean between strong and weak beats) did not change (less than 5%) in any of the three patients. Arterial-coronary-sinus oxygen content difference decreased by 5%/13%/22, respectively. Myocardial oxygen consumption per beat decreased in Patient 1 by 8%, in Patient 2 by 8% and remained unchanged in Patient 3. It is concluded that pulsus alternans occurred in consequence of alternating systolic performance. The alternation in systolic performance most probably resulted from a disturbance in excitation-contraction coupling induced by enoximone. The pronounced reduction of left ventricular preload following administration of enoximone may have augmented further the differences between the strong and the weak beat. A disturbance in myocardial oxygen metabolism was ruled out as the cause of pulsus alternans in these patients.

The Sirolimus-eluting coronary stent in daily routine practice in Germany: trends in indications over the years. Results from the prospective multi-centre German Cypher Stent Registry.

BACKGROUND: Drugeluting coronary stents (DES) are increasingly used during percutaneous coronary interventions (PCI). Due to limited budgets in Germany, no special reimbursement has been given for their use and therefore they were mainly used in selected patients. METHODS: In order to determine the change in indications in patients treated with a Sirolimus-eluting stent (SES) in daily clinical practice between 2002 and 2005, we analysed data from a prospective multi-centre DES registry, the German Cypher Stent Registry. RESULTS: From April 2002 until September 2005, 11 507 patients at 132 hospitals, who received at least one SES during their PCI, were included. Between 2002 and 2005, the median age of patients increased from 63 years to 66 years (p for trend <0.0001), whereas the prevalence of prior coronary bypass surgery (p<0.0001) and prior PCI (p<0.001) significantly decreased. Initial presentation of patients was stable over time, with a small increase of patients treated for non-ST elevation myocardial infarction (p=0.05). We found a significant increase in the treatment of complex stenoses (p<0.0001) as well as an increase in the proportion of chronic total occlusions (p<0.01). There was a steady increase in the proportion of patients treated for de novo lesions (p<0.0001), which was accompanied by a relative decrease in the proportion of patients treated for in-stent restenosis (p<0.0001). Concerning interventional characteristics a significant increase in the length of SES implanted per lesion, the numbers of SES implanted per lesion as well as an increase of the proportion of patients treated for more than one stenosis during one intervention could be observed (all p<0.0001). There was a significant decrease in the use of glycoprotein II b/IIIa antagonists during the PCI (2002: 26.5 to 14.2% in 2005, p<0.0001). MACE rates until hospital discharge did not change significantly over time. CONCLUSIONS: Between 2002 and 2005 there were two trends in the use of SES: a) a significant increase in the use of SES for de novo lesions and b) a significant trend to use SES for longer lesions, smaller arteries, more complex lesions and more SES per lesion. In summary these findings indicate that still SES are mainly used in patients with lesions that are at high risk for restenosis.

[Predictive value of an ischemia test in men and women with stable angina pectoris in clinical practice. Results of the heart catheter registry of the Working Society of Senior Hospital Cardiologists]. / Prädiktiver Wert eines Ischämietests bei Männern und Frauen mit stabiler Angina pectoris im Klinikalltag. Ergebnisse des Herzkatheter-Registers der ALKK.

BACKGROUND AND OBJECTIVE: Symptoms of coronary artery disease (CAD) and the accuracy of non-invasive tests differ between men and women. This study sought to evaluate the difference between the predictive value of a stress test in clinical practice for the diagnosis of significant coronary heart disease (CHD: stenosis > 50%) between women and men with stable angina. PATIENTS AND METHODS: 143,848 consecutive patients undergoing diagnostic coronary angiography at 99 hospitals during 2002 were included in the prospective cardiac catheter registry of the Working Party of Senior Hospital Cardiologists (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte [ALKK]). All patients with stress test and stable angina CCS class I-III (n=27387; 20.4%) were included, 10,911 (39.8%) of them female. 70.6% of women and 73.2% of men had a positive stress test. RESULTS: In 46.1% of women and 71.5% of men with positive test and stable angina had relevant CHD (p<0,001). Diabetes increased the prevalence of CHD in patients with a positive test both in women (65.5%) and men (80.5%), with CCS class III angina to 63.3% and 85.8%, respectively. CONCLUSIONS: In clinical practice a positive stress test in women with stable angina is associated significantly less often with clinically relevant CHD than in men. The low positive predictive value of 46.1% underlines the need for additional clinical features like diabetes or cardiac symptoms (CCS class) before invasive diagnosis is performed.

Incications and complications of invasive diagnostic procedures and percutaneous coronary interventions in the year 2003. Results of the quality control registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte (ALKK).

BACKGROUND: The ALKK registry contains about 20% of the invasive and interventional cardiological procedures performed in Germany. METHODS: In 2003 a total of 82,282 consecutive diagnostic invasive and 30,689 interventional procedures from 75 hospitals were centrally collected and analyzed. RESULTS: The main indication for an invasive diagnostic procedure was coronary artery disease in 92.5% of cases, myocardial disease in 1.6%, impaired left ventricular function in 4.0%, valve disease in 4% and other indications in 1.9%. An acute coronary syndrome was present in 25% of the patients. The rate of severe complications in patients with a lone diagnostic invasive procedure was low (<0.5%). The indication for percutaneous coronary intervention (n=30,689) was stable angina in 44.1%, ST elevation myocardial infarction in 22.3%, non ST elevation myocardial infarction in 14.8%, unstable angina in 10.0%, silent ischemia in 2.2%, prognostic in 5.2% of patients. The majority of interventions were performed directly after the diagnostic procedure (n=23,887=78.6%). The intervention was successful in 94.6% of cases. Stent implantation was performed in 77.2%, with 1 stent in 88.4%, two stents in 7.6% and 3 or more stents in 3.3%. A drug-eluting stent was implanted in 3.6% of the cases. The complication rate after PCI was influenced by the indication for the intervention. The in-hospital mortality in patients with cardiogenic shock was 33%, while in patients with stable angina, silent ischemia and prognostic indication only 0.2% died. CONCLUSION: There is an increase of invasive diagnostic and interventional procedures in patients with acute coronary syndromes, with 47% of PCIs performed in these patient. PCIs were performed in 75% of the cases directly after the diagnostic procedure. The rate of stent implantation seems to have reached a plateau at around 80%, while drug-eluting stents were implanted only in a minority of cases. The complication rate is mainly dependent on the clinical presentation of the patients and the indication for PCI.

Sirolimus-eluting stent treatment for isolated proximal left anterior descending artery stenoses. Results from the prospective multi-center German Cypher Registry.

BACKGROUND: Stenting of isolated proximal LAD stenoses is still a controversial issue since it is associated with higher target vessel revascularization (TVR) rate than both bypass surgery using the internal mammary artery, and stenting of other coronary artery territories. The sirolimus- eluting stent (SES) has been reported to significantly reduce restenosis rates in de novo coronary lesions. Therefore, we compared patients from the German Cypher Registry treated with SES for isolated proximal LAD lesions with those stented for isolated lesions in the proximal LCX or RCA. METHODS: A total of 349 patients treated with SES were analyzed. 249 patients were treated for proximal LAD stenosis, and 100 for proximal LCX/RCA stenoses. The combined clinical endpoint was MACCE (death of any cause, non-fatal MI and non-fatal stroke) and TVR at 6 months. RESULTS: In-hospital events (death, MI and TVR) did not differ significantly between both groups (3.2% for the LAD group vs 2.0% for the LCX/RCA-group, p=0.73). The combined end point of death of any cause, non-fatal MI and non-fatal stroke at six months was 2.6% in the LAD group, and 2.2% in the LCX/RCA group (p=1.0). TVR occurred in 4.8% of the LAD group and in 6.5% of the LCX/RCA group at six months (p=0.58). The percentage of patients free from angina at daily activities was 80.6% in the LAD group, and 77.4% in the LCX/ RCA group (p=0.52). CONCLUSION: SES once implanted into isolated proximal LAD stenoses appears as effective as reported in other vessel territories. Accordingly, stenting of the proximal LAD using SES might prove a suitable alternative to surgery.