Advantages of exercise echocardiography in comparison to dobutamine echocardiography in the diagnosis of coronary artery disease in hypertensive subjects.

OBJECTIVE: The aim of the study was to compare the efficacy and safety of two stress echocardiography methods, exercise and dobutamine, in the diagnosis of coronary artery disease in hypertensive patients with angina. PATIENTS AND METHODS: A total of 197 treated hypertensive patients, age 53 +/- 9 years (65 women) with no history of myocardial infarction referred for coronary angiography were prospectively investigated with exercise electrocardiography (ECG), exercise and dobutamine echocardiography. RESULTS: Sensitivity of the exercise ECG, exercise echocardiography and dobutamine echocardiography did not differ (77%, 82% and 75%). Negative predictive value of exercise ECG was significantly lower than exercise echocardiography (64% vs 79%, P < 0.01). Specificity and positive predictive value of exercise ECG were markedly lower than exercise and dobutamine echocardiography (57%, 96%, 98% and 72%, 97%, 98%, P < 0.0001 for both stress echocardiography vs ECG). Specificity and sensitivity of diagnostic methods were not influenced by the presence of echocardiographic left ventricular hypertrophy. Dobutamine infusion in comparison to exercise was more often associated with substantial arterial blood pressure rise or fall (7% vs 2%, P < 0.05) and with simple ventricular ectopy (15,7% vs 6,1%, P < 0.05). CONCLUSIONS: In hypertensive patients with the symptoms of angina, both stress echo methods are significantly more specific than the exercise ECG test. Maximal exercise is associated with less frequent side effects than infusion of dobutamine, so exercise echocardiography may be preferred in the diagnosis of angina in hypertensive patients.

[Is application of electrocardiographic exercise test always usefull in the diagnosis of coronary artery disease? Advantages and limitations of this method]. / Czy zawsze warto wykonywac elektrokardiograficzna próbe wysilkowa w rozpoznawaniu choroby wiencowej? Zalety i organiczenia metody.

UNLABELLED: To determine the diagnostic value of the electrocardiographic exercise testing (EET) in 551 patients with chest pain regarded as definite or probable stable angina pectoris (CAD), results of performed EET were compared with coronary angiography. All patients underwent exercise testing according to the Bruce protocol. The criterion for a positive exercise ST-segment response was > or = 1 mm of horizontal or down sloping depression 80 msec after J-point. The indications for cardiac catheterization in each patient were determined at the discretion of the attending physician. Clinically important coronary artery disease was defined as > 50 per cent narrowing of the diameter of at least one major vessel or > or = 50 per cent of the left main coronary artery. RESULTS: The sensitivity and specificity of EET for detection of CAD were for the entire group, in women and men respectively: 93%, 91%, 94% and 21%, 16%, 27%. CONCLUSION: 1. Indications for EET should be based on prior probability of coronary artery disease. 2. Application of higher than conventional ST depression criteria (> or = 2 mm) lowers sensitivity but increases specificity of EET. 3. Variables determining false positive results are as follows: age, sex (female), low probability of CAD, ST-segment depression in leads: II, III, aVF and mitral valve prolapse. 4. Variables determining false negative results are as follows: high probability of CAD, sex (male) and one vessel disease.

[How efficacy of antianginal drugs should be evaluated]. / Jak oceniac skutecznosc leków wiencowych.

This article studies the different methods of antianginal drug evaluation in the long-term treatment of ischemic heart disease. Subjective and objective methods are discussed with their limitations. The authors review serial ECG stress testing, this being the most frequently used method of antianginal pharmacotherapy evaluation. Safety, selected topics related to bioethics and statistical analysis in the clinical evaluation of drugs are discussed. Meta-analyses and clinical multicenter mega-trials, which are currently gaining in popularity and are likely to play an important role in the complex process of therapeutic decision making in the future, are discussed in the final section of this paper.

[Comparative evaluation of antianginal efficacy of isosorbide dinitrate in various doses in patients with stable angina]. / Porównawcza ocena aktywnosci przeciwdlawicowej róznych dawek dwuazotanu izosorbitolu u chorych ze stabilna choroba wiencowa.

In a randomized, double-blind, placebo (P) controlled with cross-over design study 38 male patients with stable angina and angiographically proven coronary artery disease, received isosorbide dinitrate (ISDN) in various single doses: 10 mg, 20 mg, 20 mg slow-release (-SR), 40 mg-SR, 80 mg-SR and 120 mg-SR. Evaluation of antianginal efficacy and the effect of ISDN on the simple hemodynamic parameters was performed by analysis of walking times on the treadmill: total, to angina and to ischemia (WTI) as well as: heart rate and systolic blood pressure at rest and during exercise. Exercise stress tests on the treadmill were performed: preceding drug administration, 2 hours and 6 h after. 6 h after taking the drug all doses of ISDN improved significantly all three analysed walking times on the treadmill, for example WTI in comparison to P (p < 0.001): 10 mg by 34.6%, 20 mg by 49.6%, 20 mg-SR by 42.9%, 40 mg-SR by 52.5%, 80 mg-SR by 66.0%, and 120 mg-SR by 58.4%. ISDN 20 mg was more active antianginally than 10 mg, but was connected with more severe orthostatic hypotension and headaches. ISDN 20 mg-SR was weaker in the improvement of coronary reserve than ISDN 20 mg, but it gave less adverse effects. The elevation of ISDN-SR dose was effective in the improvement of coronary reserve up to 80 mg-SR (without further benefits after 120 mg-SR). The antianginal efficacy of doses: 40 mg-SR, 80 mg-SR and 120 mg-SR was not significantly different.

What intervals in oral therapy of isosorbide dinitrate in various doses are sufficient to prevent nitrate tolerance?

INTRODUCTIONS: The organic nitrates are effective anti-anginal drugs during initial treatment, but their therapeutic value is compromised by the rapid development of tolerance during sustained therapy. The only widely accepted method of preventing tolerance is the use of intermittent administration, but without specifying to what extent the length of interval is dependent on type and dose of nitrate. The aim of this study was to evaluate how long periods free of nitrates are sufficient to prevent tolerance in long-term therapy with oral sustained-release isosorbide dinitrate (ISDN). MATERIAL AND METHODS: In a double-blind study, 38 patients with stable angina, received ISDN: 40 mg, 80 mg and 120 mg or placebo in the first ingestion (1st) and in long-term therapy in four 7 day phases: 4-times-daily (4x), 3-times-daily (3x) with 12 h nitrate-free interval, twice-daily (2x) with 18 h interval and once-daily (1x). After 1st and on the last day of each long-term phases, exercise tests with the analysis of walking times: total, to angina and to ischaemia (WTI) were performed: preceding ingestion, 2 h and 6 h after. RESULTS: Six hours after 1st all doses WTI improved significantly in comparison to placebo (p < 0.0001): 40 mg by 52.5%, 80 mg by 66.0% and 120 mg by 58.4%. None of the ISDN doses improved significantly WTI in 4x phase; in 3x, only 40 mg by 12.1% (p < 0.05); in 2x, only 80 mg by 22.3% (p < 0.05) and in once-daily, 80 mg by 27.2% and 120 mg by 36.2% (p < 0.01). CONCLUSION: 12 h nitrate-free interval is sufficient in order to prevent tolerance in long-term treatment of sustained-release ISDN with 40 mg dose, 18 h with 80 mg and 24 h with 120 mg doses.

[Evaluation of antianginal efficacy of long-term therapy with low dose isosorbide dinitrate in patients with stable angina pectoris]. / Ocena skutecznosci przeciwdlawicowej terapii przewleklej nizszymi dawkami dwuazotanu izosorbitolu u chorych ze stabilna choroba wiencowa.

UNLABELLED: The aim of this study was to evaluate two ways of long-term therapy with lower doses of oral isosorbide dinitrate (ISDN) in normal tablets and in sustained-release form (SR), in patients with stable angina. METHODS: In double-blind, placebo (PL) controlled with cross-over design study 38 male patients with stable angina and angiographically proven coronary artery disease, received ISDN in normal tablets in two doses: 10 mg and 20 mg, and also two doses SR: 20 mg-SR and 40 mg-SR or PL in the first ingestion and in long-term therapy in two 7 day phases: 4-times-daily (4x) every 6 h and 3-times-daily (3x) with 12 h interval. In 3x patients received ISDN only in doses: 20 mg, 20 mg-SR and 40 mg-SR. After the first ingestion and on the last day of long-term phases, exercise stress tests on the treadmill were performed: preceding ingestion, 2 h and 6 h after. Evaluation of antianginal efficacy of ISDN was performed by analysis of walking times: total, to angina and to ischemia (WTI). RESULTS: 6 h after first ingestion all doses of ISDN improved significantly WTI in comparison to PL: 10 mg by 34.6% (p < 0.01), 20 mg by 49.6% (p < 0.0001), 20 mg-SR by 42.9% (p < 0.001) and 40 mg-SR by 52.5% (p < 0.0001). None of the doses improved significantly WTI in the long-term 4x phase, in 3x--only 40 mg-SR by 12.1% (p < 0.05). CONCLUSIONS: Tolerance to anti-anginal efficacy of ISDN in lower doses in long-term therapy 4-times-daily, every 6 h, was found. A 12-h interval is sufficient to prevent tolerance in long-term treatment of sustained-release ISDN in 40 mg dose. Intermitted dosing of nitrates, as a prevention of tolerance, and the practical results of works using other pharmacologic interventions in a clinical setting are discussed in the final section of this paper.

[How nitrate tolerance be prevented in the treatment of ischemic heart disease?]. / Jak zapobiegac tolerancji azotanów w leczeniu choroby niedokrwiennej serca?

Organic nitrates are widely used for chronic treatment of ischaemic heart disease. However, the clinical value of long-term nitrate therapy is limited by the development of tolerance to their anti-anginal effects. This paper examines the different effects of nitrates, especially cellular effects. The theories put forward to explain nitrate tolerance are examined, including recent work on vascular superoxide and endothelin-1 regulation. Clinically, tolerance can be prevented by intermitted dosing of nitrates. This topic, and the practical results of work using other pharmacologic interventions in a clinical setting are discussed in the final section of this article.

[Is it worthwhile to treat stable angina pectoris with long-acting nitrates?]. / Czy warto leczyc stabilna dlawice piersiowa azotanami dlugo dzialajacymi?

Organic nitrates have been used in the treatment of angina pectoris for over a century. During the last twenty years, their use has also been expanded to include the treatment of unstable angina and congestive heart failure. Although nitrates are among the most often used drugs in coronary artery disease, to date, their long-term use has not been investigated in any large-scale clinical trials. The finding, recently published by Nakamura et al., that long-term nitrate use may be deleterious in ischemic heart disease, may therefore be the start of a critical re-examination of this traditional form of therapy. This paper examines the different effects of nitrates in various clinical situations. The pharmacological and physiological beneficial mechanisms of nitrates in coronary artery disease, and also the potentially harmful mechanisms are discussed in the final section of this article.

[Plasma volume expansion may explain the attenuation of antianginal activity of oral isosorbide dinitrate in long-term therapy]. / Powiekszanie sie objetosci osocza moze tlumaczyc oslabienie aktywnosci przeciwdlawicowej doustnego dwuazotanu izosorbitolu w terapii przewleklej.

UNLABELLED: The aim of the study was to evaluate whether tolerance to oral isosorbide dinitrate in sustained-release form (ISDN-SR) may be related to reduction in hematocrit (HCT)--an indirect indicator of plasma volume expansion. METHODS: In a double blind, cross-over and placebo (P) controlled study 38 men, with mean age 52.5 +/- 7.4 years, with stable angina and angiographically proven coronary artery disease, received ISDN-SR 120 mg or P as initial dose and after 7 days of therapy: 4-times-daily (ISDN-SR 480 mg a day) and once-daily (ISDN-SR 120 mg a day). Venous HCT was measured: before treatment and after each of the 3 long-term phases. Antianginal efficacy of ISDN-SR 120 mg was evaluated by analysis of walking time to ischemia (WTI) on treadmill during stress tests performed 2 and 6 hours after drug ingestion in acute and long-term therapy. RESULTS: 6 hours after first ingestion of ISDN-SR 120 mg the mean walking time to ischaemia WTI was significantly improved in comparison to P by 58.4% (p < 0.0001) and after 7 days of once-daily treatment by 36.2% (p < 0.01) but not after the 4-times-daily period (NS). HCT fell from mean 43.2 +/- 3.6% before and 42.0 +/- 3.4% (NS) after P phase, to 40.5 +/- 3.0% (p < 0.05) after 4-times-daily period, but HCT remained unchanged after one week of once-daily treatment (NS). CONCLUSIONS: Significant reduction in hematocrit--an indirect indicator of plasma volume expansion--during oral ISDN-SR 120 mg in long-term therapy 4-times-daily, when tolerance occurred, but not once-daily (without tolerance), may contribute to the mechanism of attenuation of antianginal activity of nitrates.

[Evaluation of clinical effectiveness and adverse effects of Polnitrin]. / Ocena skutecznosci klinicznej i dzialan niepozadanych preparatu Polnitrin.

In a double-blind, randomized, placebo cross-controlled trial the effectiveness and the adverse effects of two types of buccal tablets containing 5 mg nitroglycerin: Polnitrin produced by Warsaw Pharmaceutical Works POLFA and its analogue of foreign origin, were assessed. The third compared preparation was sublingual nitroglycerin in 0.5 mg tablets. The longest dissolution in the buccal cavity showed Polnitrin (mean 6.6 hours). Polnitrin significantly increased the resting heart rate during 3 hours, and during 6 hours at maximal effort. The foreign analogue decreased significantly the systolic pressure during 3 hours after application. No significant differences were noted in the effects on the basic haemodynamic parameters between the compared buccal tablets. Exercise tolerance and coronary reserve were assessed with repeated exercise tests on moving track (Marquette Case-12). Immediately after being stuck to the gum Polnitrin, its analogue and sublingual nitroglycerin significantly prolonged the marching time: total, till pain, and till ischaemia. After 6 hours the marching time till pain appearance was significantly longer after Polnitrin than after placebo or its analogue. Local adverse effects connected with the presence of the tablet in the oral vestibule may hamper the treatment with Polnitrin in some cases. The most frequent side effect were headaches which are known to occur usually after all nitrates.

[Natural and postoperative course of coronary disease in late observations: prognostic value of clinical indicators and invasive and non-invasive studies]. / Przebieg naturalny i pooperacyjny choroby wiencowej w obserwacjach odleglych: ocena wartosci prognostycznej wskazników klinicznych, badan nieinwazyjnych i inwazyjnych.

The results of a prospective study in 301 patients (pts) with angiographically documented coronary artery disease are presented. The mean follow-up period was 30 +/- 14 months, the mean age of pts was 48 +/- 9 years. A prognostic significance of 37 indicators obtained from clinical, hemodynamical, angiographical and noninvasive studies was investigated. In the group of pts treated medically (n = 202) the natural history of disease was defined by the following indicators: history of myocardial infarction, congestive heart failure, NYHA functional class III and IV, frequent ventricular premature depolarizations (VPD), abnormal ecg at rest, QT greater than QS2 index, left ventricular (LV) ejection fraction less than 50%, elevation of LV end-diastolic pressure and LV end-diastolic volume index LV wall motion abnormalities in particular dyskinesia, left main coronary artery disease and three vessel coronary artery disease. In a multivariate Cox model analysis, the independent correlates of long-term survival were frequency of VPD (p less than 0.001), NYHA functional class III-IV (p less than 0.003), QT greater than QS2 index (p less than 0.01), LV ejection fraction (LVEF) less than 50% (p less than 0.02). The combination of two indicators: LVEF less than 50% and QT greater than QS2 identify pts with high mortality rate (31%) during a two year follow-up period as compared with only 1% in the group with LVEF greater than or equal to 50% and QT less than or equal to QS2. The different clinical and hemodynamical characteristics of both the groups of pts treated medically or surgically made a reliable comparison of those two methods of treatment impossible.

[Activitrax--a pacemaker with a regulated rhythm rate]. / Activitrax--stymulator z regulowana czestoscia rytmu.

In 10 patients: 7--with the complete atrioventricular block and 3 with the sick sinus syndrome the rate responsive activity sensing pacemaker--Activitrax was implanted. Significant increase of rheographically measured cardiac output in a course of rate responsive pacing in comparison with on demand constant frequency rate stimulation was stated during treadmill exercise tests performed 6 and 12 weeks after a pulse generator implantation.