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Biomedical subjects

A Marmor

Publications and source records attributed to A Marmor.

At least 19 recordsLinked to original sources
PubMed2001

Endothelin release: a marker for the severity of exercise-induced ischemia.

Elevated endothelin-1 levels were found in exercise-induced ischemia. To our knowledge, no attempt has been made to correlate the presence of the elevated endothelin levels with severity of ischemia. In the present study, we attempt to correlate the severity of ischemia, quantified using a bullseye visual display of scintigraphic ischemic score on SPECT technetium 99m sestamibi, with presence of endothelin at peak exercise. Twenty seven patients with documented effort angina were included in the study. All subjects underwent stress technetium 99m sestamibi and ischemic scores were evaluated on the polar map image divided into 13 segments. Endothelin levels were measured at baseline and at peak exercise. In 13 patients with elevated endothelin-1 levels, there were 88 ischemic segments, 26 of which showed severe ischemia. In the remaining 14 patients with no endothelin-1 elevation, there were 80 ischemic segments of which only four showed severe ischemia. The amount of severe ischemic segments per patient was 2+/-2.2 in the elevated endothelin positive group and 0.28+/-0.6 in the endothelin negative (P< or =0.011). When looking at ischemia as detected by sestamibi SPECT as a gold standard, we found that of 331 segments, 168 were without ischemia, 143 had mild to moderate ischemia, and 30 has severe ischemia. Endothelin levels were 1.2+/-0.6, 2.2+/-0.5, 6.2+/-0.7 pg/l (P<0.01), respectively. Thus, endothelin-1 is a marker of severity of ischemia rather than ischemia itself, and as such, may have prognostic value.

Aged↗
PubMed2001

Tezosentan (an intravenous endothelin receptor A/B antagonist) reduces peripheral resistance and increases cardiac power therefore preventing a steep decrease in blood pressure in patients with congestive heart failure.

OBJECTIVE: This study investigated the effect of tezosentan (an intravenous endothelin-1 receptor antagonist) on vascular resistance and cardiac function and determined the dose response in patients with stable congestive heart failure (CHF) due to left ventricular systolic dysfunction. METHODS: In a double-blind fashion, tezosentan or placebo were administered in ascending doses (5, 20, 50, 100 mg h(-1)) to 38 CHF (NYHA class III) patients with ejection fraction or=15 mmHg. Systemic vascular resistance index (SVRi) was estimated as mean arterial blood pressure [(MAP-right atrial pressure)/cardiac index (CI)]. Cardiac function was assessed as cardiac power index (Cpi), calculated as pressure x flow (MAP x CI), where MAP represents pressure and CI represents cardiovascular flow. RESULTS AND DISCUSSION: Compared to the placebo, tezosentan induced a dose-dependent decrease in SVRi (-32%), an increase in Cpi (+20%) and a small decrease in MAP (-9%). By contrast, patients treated with nitrate vasodilators or nesiritide (a natriuretic peptide) showed a decrease in SVRi not accompanied by a significant increase in Cpi leading to a steep decrease in MAP. CONCLUSIONS: The use of Cpi in the assessment of the hemodynamic effects of tezosentan, provides a useful alternative characterization of the complex influences of vasodilators on cardiac function in patients with CHF.

Adult↗
PubMed2000

Effect of mibefradil, a T-type calcium channel blocker, on morbidity and mortality in moderate to severe congestive heart failure: the MACH-1 study. Mortality Assessment in Congestive Heart Failure Trial.

BACKGROUND: Calcium antagonists have proved disappointing in long-term congestive heart failure (CHF) studies. Mibefradil, a new calcium antagonist that selectively blocks T-type calcium channels, has been shown to be an effective antihypertensive, antianginal, and anti-ischemic agent, and because of its different mechanism of action, it may be beneficial as adjunct therapy in CHF patients. METHODS AND RESULTS: This multicenter, randomized, double-blind study compared mibefradil with placebo as adjunct to usual therapy in 2590 CHF patients (NYHA class II to IV; left ventricular fraction <35%). The initial 50-mg daily dose of mibefradil was uptitrated to 100 mg after 1 month and continued up to 3 years. Patients were monitored at 1 week; 1, 2, and 3 months; and every 3 months thereafter. All-cause mortality, cardiovascular mortality, and cardiovascular morbidity/mortality were analyzed by use of the log-rank test (alpha=0.05). Substudies included exercise tolerance, plasma hormone and cytokines, echocardiography, and quality of life. Total mortality was similar between mibefradil- and placebo-treated patients (P=0.151). The 14% increased risk of mortality with mibefradil in the first 3 months was not statistically significant (P=0.093). Treatment groups had similar cardiovascular mortality (P=0.246), cardiovascular morbidity/mortality (P=0.783), and reasons for death or hospitalization. Patients comedicated with mibefradil and antiarrhythmics (class I or III), including amiodarone, had a significantly increased risk of death. Substudies demonstrated no significant differences between treatments. CONCLUSIONS: When used as adjunct therapy, mibefradil did not affect the usual outcome of CHF. The potential interaction with antiarrhythmic drugs, especially amiodarone, and drugs associated with torsade de pointes may have contributed to poor outcomes early in the study.

Aged↗
PubMed1999

Effectiveness of nifedipine GITS in combination with atenolol in chronic stable angina.

Nifedipine gastrointestinal therapeutic system (GITS) is a once-daily formulation of nifedipine that provides stable plasma concentrations over the entire 24 h dosing interval. Two-hundred and one patients with Canadian Cardiovascular Society class II to III angina who were on 50 mg of atenolol yet still experiencing angina symptoms were randomized to receive either placebo or nifedipine GITS 30, 60 or 90 mg/day. After four weeks of treatment, the changes in time from baseline to onset of 1 mm ST segment depression in the 183 eligible patients were 26.7+/-10.2 s, 40.9+/-11.3 s, 63.2+/-12.9 s and 70.3+/-12.6 for the placebo, and 30, 60 and 90 mg/day groups, respectively. These differences were significant (P<0.05) for the 60 and 90 mg/day groups compared with placebo and for the 60 mg/day group compared with the 30 mg/day group. The times to onset of pain and termination of exercise showed similar prolongation but did not achieve statistical significance. During the one-year open label phase of the study, patients exhibited statistically significant improvements in the time to onset of ST segment depression, time to anginal pain and time to termination of exercise at a mean dose of 52.3 mg/day of nifedipine GITS. Adverse events were primarily vasodilatory in nature. This study supports the use of nifedipine GITS in patients with chronic stable angina inadequately controlled on beta-blocker alone.

Adrenergic beta-Antagonists↗
PubMed1998

Adding the new calcium antagonist mibefradil to patients receiving long-term beta-blocker therapy results in improved antianginal and antiischemic efficacy.

OBJECTIVE: The objective of this study was to evaluate the efficacy, tolerability, and safety of mibefradil, a new selective T-type calcium channel blocker, in patients with chronic stable angina pectoris receiving concomitant beta-blocker therapy. DESIGN: This was a multicenter, double-blind, placebo-controlled study. METHODS: Ninety-five patients receiving a stable dose of beta-blockers, which was not changed for the purpose of the study, were administered either 50 mg mibefradil once daily for 2 weeks, then 100 mg once daily for 2 weeks, or matching placebo. Efficacy was evaluated by treadmill exercise tolerance testing 24 hours after dose and by diary registration of anginal episodes and nitroglycerin consumption. RESULTS: Two weeks of treatment with 50 mg mibefradil resulted in a significant increase in symptom-limited exercise duration and a significant delay in the onset of persistent 1 mm ST-segment depression (placebo-corrected treatment effect: 23.2 and 51.7 seconds, respectively). Treatment with the 100 mg dose for 2 additional weeks resulted in a larger improvement in treadmill exercise tolerance testing duration and onset of ischemia (placebo-corrected treatment effect: 52.7 and 75.8 seconds, respectively). In addition, a significant decrease in weekly anginal episodes was observed with the 100 mg dose of mibefradil compared with the effect in the placebo group (-53% vs - 12%, p = 0.037). CONCLUSIONS: The combined treatment of mibefradil and beta-blockers was well tolerated, and the overall incidence of adverse events was no different from that with beta-blockers alone. The results indicate that adding mibefradil to chronic beta-blocker treatment is associated with significant improvement in efficacy, which is not achieved at the expense of tolerability.

Adrenergic beta-Antagonists↗
PubMed1998

Symptom-oriented nitrate administration and survival after acute myocardial infarction. Israeli Thrombolytic Survey Group.

The effect of nitrates during evolving myocardial infarction is controversial. While previous studies showed that nitrates improve left ventricular function and have a beneficial effect on survival, two recent randomized megatrials showed that nitrates did not alter mortality after acute myocardial infarction (AMI). The present study analyzes the use of nitrates in clinical practice and their impact on mortality in a cohort of unselected consecutive AMI patients admitted to all 25 coronary care units operating in Israel during 2 months in 1994. Among 966 patients in Killip class I-III on admission, 81% (n = 783) received nitrate therapy by intravenous infusion or orally. Baseline characteristics of patients treated with or without nitrates were quite similar. Seven-day mortality was markedly reduced in the nitrate-treated group (5 and 11 %, p < 0.001) in comparison with those who did not receive nitrates. After adjustment for pertinent variables the 7-day relative risk (RR) of mortality was 0.51 [95% confidence interval (CI) 0.25-1.07; p = 0.08], whereas, the 7-day to 1-year mortality after AMI was not altered by nitrate use (RR = 0.97; 95% CI 0.56-1.68; p = 0.92). Nitrate therapy remains a widespread and a valid symptom-oriented therapeutic approach, especially early after AMI, in the community.

Aged↗
PubMed1997

Prognostic value of noninvasively obtained left ventricular contractile reserve in patients with severe heart failure.

OBJECTIVES: The present study sought to evaluate the prognostic value of contractile reserve measured noninvasively during dobutamine infusion in patients with severe heart failure. BACKGROUND: In patients with severe heart failure there is a great need for objective criteria to define candidates for heart transplantation or intensive medical treatment. Cardiac pumping performance reserve has been shown to have excellent prognostic value in patients with cardiogenic shock. METHODS: Cardiac peak power, an afterload-independent contractility index, was measured noninvasively at rest and at peak dobutamine inotropic stimulation. Contractile reserve was defined as the difference between maximal cardiac power at peak dobutamine dose and baseline value. Maximal cardiac power was calculated from the maximal product of validated central arterial pressure and aortic flow. RESULTS: Results were obtained from 52 subjects (42 patients, 10 control subjects). Twenty-two patients were in New York Heart Association functional classes III and IV. Of nine patients with a contractile reserve < 1.5 W/ml, eight died during the 3-year follow-up period. In contrast, all survivors had a contractile reserve > 1.5 W/ml. Using multiple logistic regression analysis, contractile reserve was shown to be the only predictor of survival. CONCLUSIONS: Contractile reserve measured noninvasively during dobutamine infusion is a valuable prognostic indicator in patients with severe heart failure, with added value to ejection fraction.

Aged↗
PubMed1996

Evaluation of contractile reserve by dobutamine echocardiography: noninvasive estimation of the severity of heart failure.

Functional status in chronic heart failure is evaluated in general by subjective means, such as the New York Heart Association class, or by invasive techniques difficult to use routinely. The aim of this study was to evaluate noninvasively the contractile reserve in cases of heart failure as a means to define the functional status of the patients. Cardiac peak power, a new noninvasively obtained afterload-independent index of contractility, was calculated from online Doppler and central arterial blood pressure estimated noninvasively in 35 patients with heart failure and 10 healthy subjects during dobutamine infusion. Cardiac output increased in all patients to the same extent, without differentiation among the functional classes. Contractile reserve, as assessed by peak power, was found to be a good marker of functional class: it was significantly higher in functional class 1 than in functional classes 2 through 4. A correlation of r = 0.99 and probability of p < 0.001 was found with the functional status. This new, noninvasive contractility index, peak power, allows an objective evaluation of the severity of heart failure.

Aged↗
PubMed1995

A new methodology for non-invasive clinical assessment of cardiovascular system performance and of ventricular-arterial coupling during stress.

The objective of the study was to develop a non-invasive method for the quantitative evaluation of cardiovascular performance and ventricular-arterial (VA) coupling during varying physiological states. VA-coupling was represented by the ratio between the arterial and ventricular elastances-Ea/Ees. Approximate indices of the relative change of Ees and VA-coupling during stress were developed and tested. These indices can be evaluated directly from non-invasive measurements of ejection fraction values (for VA-coupling) and measurements of stroke volumes and systolic and diastolic arterial pressures (for Ees). Additional relative indices can be evaluated from these data (e.g., stroke work, cardiac output) to yield a complete representation of the cardiovascular response to stress. The present methodology was applied to assess the exercise stress response in healthy subjects (H, n = 8) and in patients with left ventricular dysfunction (n = 24). Left ventricular volumes were determined by nuclear angiography and arterial pressures were measured non-invasively by a new, validated method. Using published data obtained invasively, we found that the relative indices of Ees and VA-coupling showed a high correlation with the invasive ones (r > 0.8, P < 0.01). The patients were subgrouped by their maximal exercise capacitance (P2-50W, P3-75W). At rest, the two patient groups had similar ejection fraction values (45 +/- 15% and 48 +/- 16%), which were significantly different from those of the healthy subjects (66 +/- 7%, P < 0.05). During stress, a larger increase in stroke work and cardiac output was found in the healthy subjects. All three groups showed similar relative increases in Ees and heart rate, but relative Ea increased in P2 and decreased in H, while the opposite was found for the end-diastolic volume. The relative VA-coupling index in P2 was significantly larger than that in P3 and H (P < 0.05). The present non-invasively based indices can be used to quantitatively monitor the individual cardiovascular response to stress testing or drug interventions and to evaluate the importance of VA-coupling in the clinical setting.

Arteries↗
PubMed1995

Differences in ischemic threshold and nitrate efficacy between normotensive and hypertensive patients with stable angina pectoris.

The coexistence of ischemic heart disease with hypertension makes antihypertensive therapy essential, since relief of hypertension may ameliorate the coronary disease. On the other hand, the effect of antianginal nitrate therapy in patients with stable angina pectoris and systemic arterial hypertension is not fully understood. This study assessed the effects of hypertension on the ischemic threshold and the time to moderate angina, measured as parameters of nitrate efficacy. In this double-blind, parallel-group study, 141 patients with stable angina pectoris were randomly assigned to receive 5 mg, 10 mg or 20 mg isosorbide-5-mononitrate or matching placebo bid for 21 days. Ninety-three normotensive and 48 hypertensive patients were compared with regard to the time to moderate anginal pain and the ischemic threshold before and after nitrate treatment on the first day of the study. The acute nitrate effect 2 h after drug administration was substantially attenuated in hypertensives at both 10 and 20 mg of isosorbide-5-mononitrate, with the time to moderate anginal pain being significantly shortened. Impaired vasodilatator response of the arterial vasculature to organic nitrates, probably due to impaired biotransformation of organic nitrates to nitric oxide in hypertensive patients, is suggested as a possible mechanism for the diminished nitrate effect. Thus, oral nitrate therapy does not have the same beneficial antianginal effect in hypertensive patients as it does in normotensives. Dose adjustment based on the pretreatment blood pressure, and the administration of higher doses of oral nitrates should therefore be considered in hypertensive patients suffering from stable angina pectoris.

Aged↗
PubMed1994

[Isosorbide-5-mononitrate in angina pectoris: its efficacy and absence of tolerance and rebound with an eccentric type of administration].

UNLABELLED: 214 patients with angina pectoris were randomized to placebo or isosorbide-5-mononitrate (ISMN) rapid release 5, 10 or 20 mg b.i.d. at 8 a.m. and 3 p.m. Exercise tests were performed between 8 a.m. and 10 p.m., before and 2 and 7 h after each dose on days 2 and 14 and before and 2 h after the morning dose on days 7 and 21. All doses of ISMN increased exercise duration significantly more than placebo, and this effect lasted throughout most of the day. It was maximal (73 s; 24%) 2 h after the morning dose, slightly attenuated but still significant at 7 h, increased 2 h after the second dose and attenuated but still greater than with placebo at 7 h. The increase was even greater at 3 weeks (99 s; 29%), perhaps due to a training effect. Similar improvement was observed in other exercise parameters. There was no significant dose response. There were 100% more anginal attacks in the placebo than in the 20-mg treatment group. No rebound (assessed by comparing exercise duration before the morning dose between the groups) was observed. CONCLUSION: ISMN b.i.d. eccentrically has an antianginal effect throughout most of the day, peaking at 2 h. This effect is sustained during chronic therapy, without tolerance or rebound.

Adult↗
PubMed1994

Ventricular systolic assessment in patients with dilated cardiomyopathy by preload-adjusted maximal power. Validation and noninvasive application.

BACKGROUND: Noninvasive cardiac-specific analysis of contractile function in patients with dilated heart failure remains problematic. This study tests whether maximal power divided by the square of end-diastolic volume (PWRmx/EDV2, or preload-adjusted PWRmx) can provide such assessment. METHODS AND RESULTS: To validate the load insensitivity of the PWRmx index and determine its response to contractile change, 24 subjects with chronic dilated cardiomyopathy underwent invasive pressure-volume catheterization study using the conductance catheter technique. Preload was transiently reduced by 30% using balloon occlusion of the inferior vena cava, and afterload impedance was lowered by 50%, induced by a bolus injection of nitroglycerin. Contractile state was varied by intravenous dobutamine, verapamil, or esmolol. PWRmx was calculated from the simultaneous product of ventricular pressure and rate of volume change (dV/dt), the latter derived from the volume catheter signal. PWRmx varied directly with preload but was minimally influenced by afterload. However, PWRmx/EDV2 was not significantly altered by either loading change. PWRmx/EDV2 did vary with contractility, correlating closely with changes in the end-systolic pressure-volume relation (r = .91, P < .001). To test the noninvasive application of this index, 12 additional patients were studied, with PWRmx/EDV2 derived from nuclear ventriculography combined with a novel method to measure central arterial pressures. Subjects received intravenous nitroprusside or dobutamine in random order. Ejection fraction increased similarly with both agents (+42.9 +/- 8.9% for dobutamine and +29.4 +/- 5.3% for nitroprusside, both P < .01). In contrast, PWRmx/EDV2 did not significantly change with nitroprusside but increased by 126 +/- 16.1% with dobutamine (P < .01). CONCLUSIONS: Preload-adjusted PWRmx is a steady-state index of ventricular systolic function that is sensitive to inotropic state and minimally influenced by physiological changes in afterload impedance or volume load. It appears useful for noninvasive cardiac-specific analysis of acute drug effects.

Cardiac Catheterization↗
PubMed1993

Effect of contrast material osmolality on the electrocardiogram during intrauterine injection.

RATIONALE AND OBJECTIVES: In a previous study, intrauterine injection of meglumine-sodium diatrizoate (high osmolar contrast media) during hysterosalpingography was found to induce lengthening of the QTc interval on electrocardiography. To evaluate the relationship between high osmolality and electrocardiographic changes during intrauterine injection, the authors evaluated the effect on QTc of two ionic contrast agents with different osmolality during routine hysterosalpingography. METHODS: Forty-eight women undergoing routine hysterosalpingography were included in the study. Thirty-two women received meglumine-sodium diatrizoate (1500 mOsm/kg) and 16 received meglumine-sodium ioxaglate (600 mOsm/kg). QTc changes were evaluated using a 12 lead computerized electrocardiogram system during all the stages of the procedure. RESULTS: In the meglumine-sodium diatrizoate group, QTc interval was prolonged significantly from 419 +/- 19 msec at baseline to 447 +/- 30 msec during injection of contrast material, P < .001, and returned to baseline values in late phase (416 +/- 18 msec). The meglumine-sodium ioxaglate group showed no change in the QTc interval. CONCLUSION: As the single major difference between the two ionic agents is osmolality, we believe that QTc interval prolongation in the meglumine-sodium diatrizoate group is related to increased osmolality.

Adult↗
PubMed1993

Validation of a method for noninvasive measurement of central arterial pressure.

The goal of this study was to validate a newly improved noninvasive method for calibrated measurement of the ascending portion of the central arterial pressure wave in humans. Noninvasive pressure waveforms were generated by measuring the time delay between the R wave of the electrocardiogram and onset of brachial artery flow (by Doppler) during computer-controlled upper arm cuff deflation. This delay shortens with falling cuff pressure (becoming near constant at and below diastolic pressure), so that a plot of pressure versus time delay yields the ascending portion of the arterial waveform. These waveforms were compared with simultaneous invasive ascending aortic pressures in 57 adult patients (31 by fluid manometer [group A] and 26 by catheter-tipped micromanometer [group B]) during routine cardiac catheterization. Patient age ranged from 26 to 77 years. Eighty percent of group A patients and 40% of group B had coronary artery disease. Noninvasive systolic and diastolic pressures were very similar to invasive values in both groups (Pni = 0.98 x Pi, r = 0.99, p < 0.0001). Instantaneous pressure differences between waveforms were also similar in both groups, averaging between 4.5 and 5.5 mm Hg. Micromanometer and noninvasive pressure data were also obtained before and after intravenous nitroglycerin (n = 5) and isometric handgrip (n = 8) and demonstrated good agreement. A potential application of these pressures is for estimating maximal ventricular power to assess systolic function. This was tested using invasive pressure-volume data from four patients under a variety of conditions (exercise, pacing, etc.).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Left ventricular peak power during exercise: a noninvasive approach for assessment of contractile reserve.

Cardiac peak power, a contractility index based upon instantaneous changes in intracavitary pressure and systolic peak flow, was measured at rest and during supine exercise in 26 patients with coronary artery disease and 8 healthy subjects. The pathophysiological significance of this index was compared with left ventricular ejection fraction (LVEF) during exercise. Cardiac peak power, ejection fraction, end-diastolic volume, stroke volume, cardiac output and systemic vascular resistance were measured at rest, during three stages of supine bicycle ergometry and two stages of recovery. Cardiac peak power increased continuously in healthy subjects, from 5.4 +/- 0.8 W/ml at rest to 11.4 +/- 3.1 W/ml at peak exercise, p < 0.001. In patients, peak power increased initially, reached a plateau in stage 2, and subsequently remained unchanged in stage 3 (5.6 +/- 2 versus 5.6 +/- 1.6 W/ml, p = ns). Ejection fraction demonstrated a flat response during exercise in patients, contrasting with a 42% increase in cardiac peak power. The lack of increase in ejection fraction was attributed to its dependence on afterload. Peak power showed no correlation with systemic vascular resistance (r = 0.01, p = ns). In a subgroup of patients with low resting LVEF (LVEF = 26% +/- 7%), peak power increased 70% during exercise, from 2.0 +/- 0.7 to 3.5 +/- 1.7 W/ml, p < 0.05, in contrast to a flat ejection fraction response. Thus, cardiac peak power, a relatively afterload-independent index of left ventricular performance and contractility can be obtained noninvasively during exercise.

Blood Pressure↗