Polish thread in the history of circulatory physiology.

A review of the most outstanding achievements in physiology of circulation done by scientists and physicians from Poland and evaluation of their contribution to the world knowledge in this matter is presented in the paper. The authors associate the beginnings of the Polish history of studying heart and its diseases with the brilliant physician from the XIV(th) century - Thomas of Wroclaw, and then in the XVI(th) century, with the most eminent physician of Polish Renaissance, the expert on pulse, Joseph Strus. The attempts to address the issues related to the circulatory system over historical period of early ages, through baroque and the blooming period in medicine of the XIX(th), up to our times, were presented. The memories of the exceptional and the more or less known in the world cardiologic ancestors, associated with Poland, were recalled, such as: Adam.Ch. Thebesius, Robert Remak, Edward Korczynski, Oscar Widmann, Napoleon Cybulski, Joseph Pawinski, Andrew Klisiecki, Adolph Beck, Leon Popielski, Wieslaw Holobut and many others. The analysis of Polish achievements in the field of diagnosing and treatment of the ischaemic heart disease, starting from beginnings of the XIX(th) century, was performed. The authors also tried to recapitulate the achievements of the last 50 years in cardiological diagnostics, modern interventional cardiology, cardiac surgery along with transplantology and the scientific programmes concerning these issues. The examples of the greatest scientific achievements related to the circulatory system and to myocardial physiology and pathology over the period of recent decade were described.

Randomized trial of candesartan cilexetil in the treatment of patients with congestive heart failure and a history of intolerance to angiotensin-converting enzyme inhibitors.

BACKGROUND: Many patients with congestive heart failure do not receive the benefits of angiotensin-converting enzyme (ACE) inhibitors because of intolerance. We sought to determine the tolerability of an angiotensin II receptor blocker, candesartan cilexetil, among patients considered intolerant of ACE inhibitors. METHODS: Patients with CHF, left ventricular ejection fraction less than 35%, and history of discontinuing an ACE inhibitor because of intolerance underwent double-blind randomization in a 2:1 ratio to receive candesartan (n = 179) or a placebo (n = 91). The initial dosage of candesartan was 4 mg/d; the dosage was increased to 16 mg/d if the drug was tolerated. A history of intolerance of ACE inhibitor was attributed to cough (67% of patients), hypotension (15%), or renal dysfunction (11%). RESULTS: The study drug was continued for 12 weeks by 82.7% of patients who received candesartan versus 86.8% of patients who received the placebo. This 4.1% greater discontinuation rate with active therapy was not significant; the 95% confidence interval ranged from 4.8% more discontinuation with placebo to 13% more with candesartan. Titration to the 16-mg target dose was possible for 69% of patients who received candesartan versus 84% of those who received the placebo. Frequencies of death and morbidity were not significantly different between the candesartan and placebo groups (death 3.4% and 3.3%, worsening heart failure 8.4% and 13.2%, myocardial infarction 2.8% and 5.5%, all-cause hospitalization 12.8% and 18.7%, and death or hospitalization for heart failure 11.7% and 14.3%). CONCLUSIONS: Candesartan was well tolerated by this population. The effect of candesartan on major clinical end points, including death, remains to be determined.

Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group.

CONTEXT: Results from recent studies on the effects of beta1-blockade in patients with heart failure demonstrated a 34% reduction in total mortality. However, the effect of beta1-blockade on the frequency of hospitalizations, symptoms, and quality of life in patients with heart failure has not been fully explored. OBJECTIVE: To examine the effects of the beta1-blocker controlled-release/extended-release metoprolol succinate (metoprolol CR/XL) on mortality, hospitalization, symptoms, and quality of life in patients with heart failure. DESIGN: Randomized, double-blind controlled trial, preceded by a 2-week single-blind placebo run-in period, conducted from February 14, 1997, to October 31, 1998, with a mean follow-up of 1 year. SETTING: Three hundred thirteen sites in 14 countries. PARTICIPANTS: Patients (n = 3991) with chronic heart failure, New York Heart Association (NYHA) functional class II to IV, and ejection fraction of 0.40 or less who were stabilized with optimum standard therapy. INTERVENTIONS: Patients were randomized to metoprolol CR/XL, 25 mg once per day (NYHA class II), or 12.5 mg once per day (NYHA class III or IV), titrated for 6 to 8 weeks up to a target dosage of 200 mg once per day (n = 1990); or matching placebo (n = 2001). MAIN OUTCOME MEASURES: Total mortality or any hospitalization (time to first event), number of hospitalizations for worsening heart failure, and change in NYHA class, by intervention group; quality of life was assessed in a substudy of 741 patients. RESULTS: The incidence of all predefined end points was lower in the metoprolol CR/XL group than in the placebo group, including total mortality or all-cause hospitalizations (the prespecified second primary end point; 641 vs 767 events; risk reduction, 19%; 95% confidence interval [CI], 10%-27%; P<.001); total mortality or hospitalizations due to worsening heart failure (311 vs 439 events; risk reduction, 31%; 95% CI, 20%-40%; P<.001), number of hospitalizations due to worsening heart failure (317 vs 451; P<.001); and number of days in hospital due to worsening heart failure (3401 vs 5303 days; P<.001). NYHA functional class, assessed by physicians, and McMaster Overall Treatment Evaluation score, assessed by patients, both improved in the metoprolol CR/XL group compared with the placebo group (P = .003 and P = .009, respectively). CONCLUSIONS: In this study of patients with symptomatic heartfailure, metoprolol CR/XL improved survival, reduced the need for hospitalizations due to worsening heart failure, improved NYHA functional class, and had beneficial effects on patient well-being.

Contemporary management of patients with left ventricular systolic dysfunction. Results from the Study of Patients Intolerant of Converting Enzyme Inhibitors (SPICE) Registry.

AIMS: The reported prevalence of angiotensin-converting enzyme (ACE) inhibitor use in patients with heart failure varies considerably. Recent reports suggest that many patients who could benefit from such therapy are not receiving ACE inhibitors. The Study of Patients Intolerant of Converting Enzyme Inhibitors (SPICE) Registry was established to understand better the demographics, characteristics, and contemporary use of ACE inhibitors in an international registry. METHODS AND RESULTS: Between August 1996 and April 1997, each of 105 study centres from eight countries in North America and Europe was invited to review retrospectively the medical records of 100 consecutive patients with left ventricular ejection fractions

Multicenter randomized trial and a systematic overview of lidocaine in acute myocardial infarction.

BACKGROUND: More than 20 randomized trials and 4 meta-analyses have been conducted on the use of prophylactic lidocaine in acute myocardial infarction (MI). The results suggest that lidocaine reduces ventricular fibrillation (VF) but increases mortality rates in acute MI. METHODS AND RESULTS: Patients with ST-elevation MI who were examined <6 hours after symptom onset (n = 903) were randomly assigned to either lidocaine or no lidocaine and to either streptokinase and heparin or heparin alone. Lidocaine was given as 4 boluses of 50 mg each every 2 minutes, then an infusion of 3 mg/min for 12 hours, then 2 mg/min for 36 hours. We compared the incidence of in-hospital death and ventricular arrhythmias. We then performed a meta-analysis of prophylactic lidocaine in acute MI that included these and prior trial results. The rates of VF and death with and without lidocaine were calculated for each trial, then odds ratios (OR) with confidence intervals (CI) were calculated for the risk of these events overall with and without lidocaine. Patients given lidocaine in the randomized study had significantly less VF (2.0% vs 5.7% without lidocaine, P =.004) and a trend toward increased mortality rates (9.7% vs 7.0%, P =.145). Meta-analysis revealed nonsignificant trends toward reduced VF (OR 0.71, 95% CI 0.47 to 1. 09) and increased mortality rates (OR 1.12, 95% CI 0.91 to 1.36) with lidocaine. CONCLUSIONS: Lidocaine reduces VF but may adversely affect mortality rates. The routine use of prophylactic lidocaine in acute MI is not recommended.

[Influence of nitrates on red blood cell deformability and clinical parameters in patients with silent ischemia]. / Wplyw azotanów na odksztalcalnosc krwinek czerwonych i parametry kliniczne chorych z niemym niedokrwieniem.

In 30 patients after myocardial infarctum with actual silent ischemia (no pain during last 12 months) mononitrate (Olicard 40) was administered and red blood cell deformability was determined. Clinical improvement and decrease of aforementioned deformability were observed after mononitrate therapy.

Lack of effect of amiodarone on survival after extensive infarction. Polish Amiodarone Trial.

BACKGROUND: The purpose of this study was to elucidate whether the reduction of mortality with amiodarone after myocardial infarction depended on ejection fraction. METHODS: The data from the Polish Amiodarone Trial were analysed retrospectively. Patients with acute myocardial infarction and contraindications to beta-blockers were randomized on days 5-7 after admission to receive amiodarone (n = 305) or placebo (n = 308). Short and long-term (46 months) mortality were analysed comparing the groups with impaired (ejection fraction < 40%) and preserved (ejection fraction > or = 40%) left ventricular function. A subset of patients (n = 523) with available echocardiograms were subjected to this analysis. RESULTS: Long-term and sudden cardiac mortality were significantly reduced with amiodarone in the group of patients with ejection fraction > or = 40% (amiodarone versus placebo, respectively: 9.1 versus 16.5%, P < 0.05; 3.4 versus 8.2, P < 0.05). No beneficial effect of amiodarone was observed in the group with low ejection fraction (cardiac and sudden cardiac mortality: amiodarone versus placebo, 20.8 versus 19.3% and 7.8 versus 5.7% respectively). One-year mortality also revealed a favourable trend only in amiodarone-allocated patients with ejection fraction > or = 40%. CONCLUSION: Amiodarone decreased long-term and sudden cardiac mortality after myocardial infarction only in patients with preserved left ventricular function. No benefit was observed in patients with decreased ejection fraction.

[Assessment of outcome in treatment of cardiac shock after myocardial infarction with intravenous streptokinase]. / Ocena wyników leczenia wstrzasu zawalowego dozylnym wlewem streptokinazy.

In 1986 a prospective randomized study coordinated by the Institute of Cardiology in Warsaw was started in 10 teaching cardiology hospitals in Poland for assessment of the results of treatment with intravenous streptokinase infusion in acute myocardial infarction. The studied population comprised 927 patients admitted to intensive treatment units within 6 hours after the onset of infarction pain. For the groups treated with streptokinase or heparin 752 patients were selected at random. In 175 cases the administration of streptokinase was contraindicated. These patients received conventional treatment and served as controls. The age of the patients was from 38 to 70 years, mean age 57.6 +/- 9.3 years. In 105 out of 927 cases cardiac shock was diagnosed. In the groups of early shock during hospitalization the death rate was 82%. No statistically significant difference was found in the death rates between patients with cardiac shock treated with heparin or with streptokinase.

[Localization of myocardial infarction with the help of EKG and two-dimensional echocardiography. Controversies]. / Lokalizacja zawalu serca za pomoca ekg i echokardiografii dwuwymiarowej. Kontrowersje.

A multicentre study of the localization of myocardial infarction (MI) using ECG and 2-dimensional echocardiography (Echo-2D) was performed on the 21st day of the onset of MI. The study population consisted of 650 pts (mean age 55.0 years), 553 males and 97 females. The purpose of the study was: 1) to compare the site of MI as diagnosed by ECG and Echo-2D, 2) to determine the controversies in the diagnosis between these two methods. Consistent results of both methods were obtained in 408 pts (62.8%) of the group. In 61 pts (9.4%) the diagnosis of MI by ECG and Echo-2D was undefined. In 181 pts (27.8%) the inconsistencies of ECG and Echo-2D evaluations were demonstrated; in 106 pts ECG changes were undefined, but evident Echo-2D changes were found; on the contrary, in 51 pts MI diagnosed by ECG was not confirmed by Echo-2D. In 24 pts entirely inconsistent results were shown. 209 pts (32%) with myocardial contractility disorders in the apical region of the heart diagnosed by Echo-2D showed different MI localisation as determined by ECG: 147 pts had anterior or antero-lateral MI, 28 pts--postero-inferior MI, 12 pts--apical MI and 22 pts--another one. By these findings it has been shown that ECG and Echo-2D are compatible methods but not replaceable ones.

Effect of amiodarone on mortality after myocardial infarction: a double-blind, placebo-controlled, pilot study.

OBJECTIVES: The goal of this study was to evaluate the effect of amiodarone on mortality, ventricular arrhythmias and clinical complications in high risk postinfarction patients. BACKGROUND: No therapy has been shown to reduce sudden death in patients ineligible to receive beta-adrenergic blocking agents after myocardial infarction. METHODS: Patients who were not eligible to receive beta-blockers were randomized to receive amiodarone (n = 305) or placebo (n = 308) for 1 year. RESULTS: There were 21 deaths in the amiodarone group compared with 33 in the placebo group (odds ratio 0.62, 95% confidence interval [CI] 0.35 to 1.08, p = 0.095). There were two noncardiac deaths in the amiodarone group and none in the placebo group; thus, the difference in cardiac mortality (19 vs. 33, respectively) was statistically significant (odds ratio 0.55, 95% CI 0.32 to 0.99, p = 0.048). There was a significant decrease in Lown class 4 ventricular arrhythmias (7.5% vs. 19.7%, respectively, p < 0.001). Adverse effects developed in 30% of amiodarone-treated patients and 10% of placebo-treated patients. Pulmonary toxicity, which was mild and reversible, occurred in only one patient in the amiodarone group but in no patient in the placebo group. CONCLUSIONS: This trial demonstrated a significant reduction in cardiac mortality and ventricular arrhythmias with amiodarone treatment. However, given the wide confidence intervals and borderline statistical significance of our trial, larger trials are needed to confirm or refute this view.

[Aneurysms in acute myocardial infarction (multicenter studies)]. / Tetniaki w ostrym zawale serca. (Badania wieloosrodkowe).

The authors present outcomes concerning frequency of appearance and clinical course of aneurysms after acute myocardial infarction. The study population consisted of 730 patients (mean age 54 +/- 9 years) with acute myocardial infarction, including 579 men and 151 women. The diagnosis was based on the following criteria: 1) coronary artery disease history, 2) physical examination, 3) ECG, 4) 2-dimensional echocardiography, 5) biochemical data. Post-infarction aneurysm was revealed in 42 patients (5.8%, 33 men and 9 women); antero-lateral aneurysm--in 36 patients (85.7%), and inferior-posterior aneurysm--in 6 patients (14.3%). Ventricular arrhythmias in the first day of infarction had a high frequency in both groups; with aneurysm--92.9%, without aneurysm--82.2%. The frequency of arrhythmia in 21-st day of infarction decreased similarly in both groups with aneurysm--40.5%, without aneurysm--38.9%. There was no statistically significant difference among both groups. There was no correlation between localisation of aneurysms and degree of contractility disturbances of the heart muscle (dyskinesis, akinesis). Heart failure--class III and IVK (Killip-Kimball classification) occurred in 19.0% of patients with aneurysm and in 10.4% of patients without aneurysm. That was no essential correlation between localisation of aneurysms and advancement of the heart failure.

[Does the appearance of pro-arrhythmic response to anti-arrhythmic drugs have prognostic significance?]. / Czy wystapienie reakcji proarytmicznej na lek przeciwarytmiczny ma znaczenie prognostyczne?

Study was undertaken to assess whether proarrhythmic response to antiarrhythmic drug is a risk factor for cardiac death in patients (pts) with ischaemic heart disease (IHD). In 782 pts with IHD and frequent and/or complex ventricular ectopic beats (VEB) 1041 drug tests guided by 24 hour Holter monitoring were conducted. The following drugs were assessed: propranolol, disopyramide, mexiletine, amiodarone. Pro-arrhythmia was defined according to Velebit: 1/greater than or equal to 4-fold increase in VEBs, 2/greater than or equal to 10-fold increase in repetitive forms of 3/new occurrence of ventricular tachycardia or ventricular fibrillation (VT/VF). Proarrhythmic effect was observed in 8.4% of pts and in 7.9% of drug tests. The frequency with individual drugs ranged from 5.7% to 9%. No drug was completely free of this type of reaction. Antiarrhythmic drugs inducing arrhythmogenic response were eliminated. Pts were followed-up for a mean of 22 months (range 1-49). Chronic antiarrhythmic treatment was conducted. Pts were discharged taking the agent deemed most effective for suppression of arrhythmia. Follow-up visits were made every 6-12 months. All cases of death were verified. In long-term observation cardiac death and sudden death occurred in 53 and 32 pts. With actuarial analysis (Kaplan-Meler method, log rank test) there was significant difference in cardiac death (p less than 0.05) of pro-arrhythmia (+) compared with ++pro-arrhythmia (-) pts at yr (11% v 4%, 7% v 3%) and 3 yr (24% x 11%, 16% v 7%). The relative importance of baseline clinical variables in predicting survival was assessed with a stepwise Cox regression.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of beta adrenergic blocking drugs on the prognostic value of ST-segment depression during exercise electrocardiogram testing]. / Wplyw leków beta adrenolitycznych na wartosc prognostyczna obnizonego odcinka ST w elektrokardiogramie wysilkowym.

Exercise testing has been shown to be predictive for future cardiac events in patients with established diagnosis of coronary heart disease. Exercise test parameters associated with poor prognosis may be unreliable if patient is receiving beta adrenergic agents. The purpose of this study was: 1) to compare the results of exercise testing performed before and during beta blocking therapy, and 2) to determine the role of beta blockers in the prognostic significance of the ST-segment response recorded during exercise testing. The study population consisted of 518 patients (mean age 52 +/- 7 years) with coronary heart disease. The diagnosis was based on the presence of one of the following three criteria: 1) typical history and significant ST-segment depression on resting or exercise electrocardiogram, 2) history of myocardial infarction, 3) significant coronary angiographic abnormalities. In all patients symptom-limited exercise test was performed before and two weeks after the onset of beta blocker therapy. The data from the first and second tests were estimated for significance of differences between the mean values with following results: maximal heart rate--135 +/- 21 and 123 +/- 19 bpm (p less than 0.001), maximal work load achieved--98 +/- 43 and 109 +/- 44 W (p less than 0.001), maximal systolic blood pressure--171 +/- 28 and 163 +/- 26 mmHg (p less than 0.001). Occurrence of characteristic ST-segment depression was more frequent during the first than during the second test (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Proarrhythmic response to antiarrhythmic drug as a risk factor for sudden cardiac death in patients with ischemic heart disease.

The prognostic significance of arrhythmogenic response to an antiarrhythmic drug was studied. In 782 patients with ischemic heart disease (IHD) and frequent and/or complex ventricular premature beats (VPBs), 1,041 drug tests guided by 24-hour Holter monitoring were conducted. The following drugs were assessed: beta blockers, disopyramide, mexiletine, amiodarone. Proarrhythmia was defined as: (1) greater than 4-fold increase in VPBs, (2) greater than 10-fold increase in repetitive forms, or (3) new occurrence of ventricular tachycardia or ventricular fibrillation (VT/VF). During a follow-up of 1-49 months (mean 22) patients were treated with antiarrhythmic drugs found to be safe in control Holter monitoring. Proarrhythmic effects were observed in 8.4% of patients. No drug was completely free of this type of reaction. In long-term observation, cardiac death and sudden death occurred in 53 and 32 patients, respectively. With actuarial analysis (Kaplan-Meier method, log-rank test) there was a significant difference in cardiac death (P less than 0.01) and sudden death rate (P less than 0.05) of proarrhythmia (+) compared with proarrhythmia (-) patients at 1 year (11% vs 4%, 7% vs 3%) and 3 years (24% vs 11%, 16% vs 7%). Proarrhythmic response was an independent risk factor apart from myocardial infarction, VT/VF, ejection fraction less than 40% and QTc greater than 440 msec. Arrhythmogenic response to antiarrhythmic drugs seems to be an additional predictor of sudden death in IHD.

[Transesophageal and classical echocardiography in myocardial infarction and heart valve disease (comparison study)]. / Echokardiografia przezprzelykowa i klasyczna w zawale serca i wadach zastawkowych (badanie porównawcze).

In 85 patients (22 with myocardial infarct and 63 with valvular heart disease) echocardiographical examination simultaneously by classical and transesophageal methods was done. The transesophageal method was better in assessing the aortic valve and similar to the classical method in reference to the mitral valve. Heart contractility assessment was better with the classical method. Transesophageal echocardiography is the method of choice in patients in whom classical echocardiography cannot be done (obesity, emphysema, chest deformation).

[Transesophageal echocardiography--our preliminary experience]. / Echokardiografia przezprzelykowa--wstepne doswiadczenia wlasne.

This study presents the initial experience of our department with transesophageal echocardiography. Transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) were performed simultaneously in 31 clinical patients (16 to 76 years old). 13 pts with aortic (9) and mitral (4) valve disease, 10 pts with ischemic heart disease (including 7 AMI), 3 pts with congestive cardiomyopathy, 2 pts with aortic aneurysm and 3 pts with other heart diseases. The investigations were performed with use of Aloka SSD 650 machine and 7.5 MHz transesophageal convex transducer. The patients were prepared for the examination in the typical way by local anesthesia, administration of sedatives and heart monitoring. The following projections were used: basic short- and long-axis view, four chamber view, and transgastric view. These investigation confirmed the usefulness TEE for evaluation of aortic and mitral valves, especially their morphology, atrial septum and atrial cavities. Contractility and other heart structures were difficult to be evaluated by TEE. It seems to be possible to estimate the proximal sections of the coronary arteries. Only few complications were found: supraventricular (2) and ventricular extrasystoles (8), transient supraventricular tachycardia (3), and bradycardia (3). Late complications were not found.

[Effects of antiarrhythmic drugs on some echocardiographic parameters of left ventricular function in patients with ischemic heart disease]. / Wplyw leków przeciwarytmicznych na niektóre echokardiograficzne wskazniki czynnosci lewej komory u chorych z choroba niedokrwienna serca.

This study was performed to evaluate the effects of antiarrhythmic drugs on left ventricular function in 843 patients with ischaemic heart disease and ventricular arrhythmias (Lown classes 2-5). Rhythm abnormalities were observed by ambulatory electrocardiographic monitoring before and after 2-weeks of antiarrhythmic therapy. Haemodynamic variables such as cardiac output (CO), ejection fraction (EF), stroke volume (SV), and ratio of myocardial contractility (RMC) were derived from the cross sectional echocardiography. Efficacy of the applied drugs was 42-71%. Of these antiarrhythmic agents only propranolol caused the deterioration of left ventricular performance, measured by CO; in mono-therapy propranolol produced significant changes (p less than 0.05), in combination with amiodarone--at point of significance. Mexiletine produced significant improvement in EF and SV (p less than 0.05). There were no significant changes in haemodynamic parameters after treatment with the other drugs.