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C J Pepine

Publications and source records attributed to C J Pepine.

At least 19 recordsLinked to original sources
PubMed1992

New insights in measurement of myocardial ischemia.

Myocardial ischemia may be defined as myocellular dysfunction resulting from hypoxia usually due to limited coronary blood flow. The methods commonly used to make a diagnosis of myocardial ischemia employ either clinical findings (e.g., angina, myocardial infarction) or signals from laboratory tests. Since ischemia is often clinically silent and since clinical events related to ischemia may be catastrophic (i.e., myocardial infarction and sudden death), physicians are dependent on tests using various targeted signals. These signals, however, do not actually provide quantitative measurements of the degree of ischemia or related myocardial dysfunction. Nevertheless, the functional abnormalities reflected by these signals can identify patients at high or low risk for adverse outcomes related to ischemia. So, in this sense, these signals can be used to support the diagnosis of ischemia as well as evaluate its importance in a given patient. The most commonly used signal is an ST-segment shift evident on the electrocardiogram (ECG). When this is horizontal or downsloping and > or = 10 mm, this is often, but not always, due to myocardial ischemia. Although assessment of the exercise-stress ECG offers several advantages over assessment of the resting ECG, the standard Bruce protocol is associated with notable shortcomings that become apparent when an attempt is made to assess the effects of a treatment on the ST-segment signal. These might be surmounted by use of a continuous ramp-type protocol. Ambulatory ECG monitoring is growing in importance in the wake of increasing awareness of the different daily life circumstances that are associated with ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiography↗
PubMed1992

Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions.

An association between raised renin levels and myocardial infarction has been reported. We studied the effects of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, on the development of myocardial infarction and unstable angina in 6797 patients with ejection fractions < or = 0.35 enrolled into the two Studies of Left Ventricular Dysfunction (SOLVD) trials. Patients were randomly assigned to placebo (n = 3401) or enalapril (n = 3396) at doses of 2.5-20 mg per day in two concurrent double-blind trials with the same protocol. Patients with heart failure entered the treatment trial (n = 2569) and those without heart failure entered the prevention trial (n = 4228). Follow-up averaged 40 months. In each trial there were significant reductions in the number of patients developing myocardial infarction (treatment trial: 158 placebo vs 127 enalapril, p < 0.02; prevention trial: 204 vs 161 p < 0.01) or unstable angina (240 vs 187 p < 0.001; 355 vs 312, p < 0.05). Combined, there were 362 placebo group patients with myocardial infarction compared with 288 in the enalapril group (risk reduction 23%, 95% CI 11-34%; p < 0.001). 595 placebo group patients developed unstable angina compared with 499 in the enalapril group (risk reduction 20%, 95% CI 9-29%, p < 0.001). There was also a reduction in cardiac deaths (711 placebo, 615 enalapril; p < 0.003), so that the reduction in the combined endpoint of deaths, myocardial infarction, and unstable angina was highly significant (20% risk reduction, 95% CI 14-26%; p < 0.0001). Enalapril treatment significantly reduced myocardial infarction, unstable angina, and cardiac mortality in patients with low ejection fractions.

Angina, Unstable↗
PubMed1992

Daily life ischemia and nitrate therapy.

Daily life ischemia has generated considerable interest because most of it is silent and associated with increased risk of adverse outcome. Coronary vasomotion, as well as increases in myocardial oxygen demand, seem important in the pathogenesis of this form of ischemia, so treatment with nitrates seems rational. Administration of sublingual nitroglycerin hourly, over 12 hours, was shown to decrease both silent and painful ischemic episodes in patients with effort angina. Subsequently, isosorbide dinitrate or mononitrate, given either as an intravenous infusion or orally, was shown to decrease both silent and painful ischemic episodes in patients with unstable rest angina and in those with severe angina. More recently, 6 studies have reported using transdermal nitroglycerin for daily life ischemia. Three of these reported open-label uncontrolled observations and suggested that ischemia frequency may be reduced approximately 60-80% during treatment with doses of 10-30 mg/day, with a duration of treatment ranging from 1 hour to 14 days. In 2 of these reports the duration of ischemia also decreased. The other 3 studies were randomized, double-blind, placebo-controlled studies with a total enrollment of 86 patients. These studies provided mixed results. One suggested that evidence for partial tolerance develops within 1 day of treatment, using large continuous or intermittent doses (mean, 52 mg/day). Another suggested that no tolerance develops to intermittent dosing (18 mg/16 hr out of 24 hr) during exercise testing but no effect is seen on daily life ischemia. The remaining study suggested that tolerance does not develop using small doses (15 mg/day) continuously over 14 days for ischemia during daily life, and that this response is different from that observed using the calcium antagonist nifedipine. These limited observations and conflicting results underscore a need for additional larger controlled trials, employing topical nitrate therapy in low intermittent doses for daily life ischemia.

Activities of Daily Living↗
PubMed1992

Advisory group reports on silent myocardial ischemia, acute intervention after myocardial infarction, and postinfarction management.

Three advisory groups of the Council for Myocardial Ischemia and Infarction regularly review current knowledge concerning the following clinical contexts: silent ischemia, acute intervention, and postmyocardial infarction. This article represents the most recent findings of each Advisory Group--the areas of agreement and those of disagreement. What is emphasized here is that ongoing research is critical to refining the therapeutic approach to ischemia and the postmyocardial infarction patient. What seems rational is the stratification of patients into risk groups--high and low--that dictate whether intervention should be aggressive or conservative.

Algorithms↗
PubMed1992

Biology of restenosis and therapeutic approach.

Numerous attempts have been made to prevent restenosis after successful transluminal dilation of an atherosclerotic vessel using a variety of pharmacologic and mechanical approaches. This article reviews the pathobiology of the restenosis process, offers a hypothesis as to its cause, reviews attempts to modify the process, and outlines therapeutic approaches to future treatment.

Angioplasty, Balloon↗
PubMed1992

Ventricular/vascular interaction in health and heart failure.

In summary, the concept of aortic input impedance, which has been examined in detail, requires evaluation of the flow and pressure pulsations within the ascending aorta to determine an input impedance spectrum. This function describes the load imposed on the ejecting left ventricle by the systemic vasculature in terms of pulsatile and steady-flow components and is independent of changes in ventricular performance. The components contain information about the mechanical properties of the large vessels (elastance), arteriolar bed (resistance), and waves reflected (reflectance) within the arterial system. Our investigations indicate that in health the mechanical characteristics of the vasculature appear to minimize pulsatile and steady-flow loading components. The optimal loading pattern is influenced by aging and hypertension so that elastance is increased. This alteration increases the pulsatile flow component of loading, which has the potential to limit left ventricular responses to exercise. In patients with heart failure, the vascular system presents an increase in pulsatile and steady-flow load to the diseased left ventricle. Here the altered loading pattern is due to increased resistance, elastance, and reflectance. The left ventricle has a markedly diminished response to power output in the face of this altered vascular load. With vasorelaxation, all components of vascular loading decrease and result in markedly improved generation of left ventricular power and cardiac output. Recent evidence suggests that agents inducing vasorelaxation can influence various regions of the aorta and large vascular beds in a different manner. This would result in the ability to alter elastance, resistance, and reflectance selectively to affect pulsatile and steady-flow components of load.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗
PubMed1992

Determinants of isolated systolic hypertension in the elderly.

AIM: To study the determinants (or mechanisms) of isolated systolic hypertension in the elderly. METHODS: Pulsatile blood pressure and flow (multisensor catheter) were measured in the ascending aorta and impedance spectra were calculated in 18 subjects undergoing cardiac catheterization. Nine subjects (mean +/- SEM age 58 +/- 1.4 years) had increased aortic systolic (166 +/- 2.3 mmHg, P < 0.001), mean (116 +/- 2.1 mmHg, P < 0.02) and pulse blood pressure (83 +/- 2.1 mmHg, P < 0.001) and normal diastolic blood pressure (84 +/- 2.0 mmHg, NS) and constituted the isolated systolic hypertension group. The other nine age-matched (58 +/- 1.1 years) subjects had normal aortic systolic and diastolic blood pressure and constituted the normotensive control group. RESULTS: Both static (peripheral vascular resistance) and dynamic (characteristic impedance and wave reflection) components of left ventricular external load (aortic input impedance) were elevated in the isolated systolic hypertensives compared to the normotensive subjects; peripheral vascular resistance was 44% higher (P < 0.001), characteristic impedance (index of aortic stiffness) was 107% higher (P < 0.001), the first harmonic of impedance moduli (index of wave reflection) was 57% higher (P < 0.004) and the first impedance moduli minimum was shifted to a higher frequency (from 3.4 +/- 0.2 Hz to 4.2 +/- 0.13 Hz, P < 0.008) in the group with isolated systolic hypertension. CONCLUSIONS: The changes in impedance spectra in the isolated systolic hypertensives indicate that the cross-sectional area of the peripheral vascular bed was reduced and that the aorta and large arteries were stiffer, producing an increased pulse wave velocity and an early return of pulse wave reflection in systole. The marked increase in arterial stiffness in isolated systolic hypertension offset the increase in diastolic blood pressure that would have been expected from an increase in peripheral vascular resistance alone, and early return of the reflected pressure wave augmented aortic pressure throughout systole and accounted for the large increase observed in systolic and pulse pressure in the aorta.

Aged↗
PubMed1992

Intervention therapy for coronary artery disease in the elderly.

The central aim of this review was to examine the application of intervention therapy for CAD in the elderly population. The data reviewed indicates that it is no longer appropriate to use age 70 or 75 as the upper limit of eligibility for thrombolytic intervention in patients with acute myocardial infarction. Elderly who are physiologically active without contraindications to thrombolytic therapy should be considered eligible. Additional controlled trials specifically targeted at the elderly population are needed to better define the precise dosing regimen and the magnitude and extent of bleeding complications in this group. Nevertheless, it appears appropriate to recommend thrombolytic intervention for most eligible elderly patients presenting with acute myocardial infarction. This recommendation is based on the fact that the higher mortality in the elderly results in more lives saved per patient treated than for younger patients. It is important to reemphasize that this recommendation is for treating elderly patients with acute infarction as suggested by ST-segment elevation and/or Q waves, without contraindications to thrombolytic therapy. Those with non-Q-wave infarctions, hypertension, recent stroke, history of bleeding, or other contraindications are not candidates. Regarding intervention therapy in other elderly patients with acute and chronic manifestations of coronary disease, results also appear very encouraging. Elderly patients appearing to tolerate PTCA include those with all forms of angina from chronic stable angina to unstable angina. Although only observational data are on hand at present, our review suggests these elderly patients tolerate PTCA well and indeed may benefit. The elderly patients who have co-morbid factors that adversely influence the application of CABG for revascularization may be the best candidates for PTCA. At present, the challenge for the physician is to carefully assess each elderly patient on an individual basis for intervention therapy. This evaluation should be aimed at identifying factors that may permit application of intervention treatment to the elderly patients who are most likely to receive the greatest benefit.

Age Factors↗
PubMed1991

Effects of atenolol alone, nifedipine alone and their combination on ambulant myocardial ischemia.

The effects of atenolol (100 mg/day) and nifedipine (20 mg 3 times daily) and their combination on ambulant myocardial ischemia were investigated using a randomized, double-blind, placebo-controlled, crossover trial. Eighteen men with symptomatic coronary artery disease, exercise-induced ischemia and minimal symptoms, underwent 4 blinded treatment periods of 2 weeks' duration (2 placebo, 1 atenolol, 1 nifedipine). Those that did not have ischemia eliminated by monotherapy received combination therapy with both drugs. Forty-eight-hour ambulatory electrocardiographic monitoring was used to quantitate ischemic parameters at the end of each period. Both nifedipine and atenolol as monotherapy reduced the number of ischemic episodes and the average duration of each episode compared with placebo (p less than 0.05). Compared with placebo, nifedipine reduced the total duration of ischemia (p less than 0.05) but the effect of atenolol on ischemia duration was of borderline significance (p = 0.066). There were no differences in reduction of ischemic parameters when atenolol was compared with nifedipine (difference not significant). In the 9 patients who continued to have ischemia with monotherapy, combination therapy eliminated it in 2 and reduced the duration by greater than 50% in the remaining patients compared with placebo. In conclusion, monotherapy with nifedipine or atenolol is similarly effective in eliminating or reducing ambulant ischemia. Combination therapy can provide additional benefit in those with continued ischemia.

Adult↗
PubMed1991

Circadian variations in myocardial ischemia. Implications for management.

Extended ambulatory electrocardiographic monitoring in the patient's customary environment provides clear evidence of circadian patterns in myocardial ischemic episodes. In patients with effort angina, the highest activity occurs between 6 AM and noon. This coincides with peaks in diurnal variation of frequency of acute myocardial infarction, stroke, and sudden death. A number of potential underlying common triggering mechanisms, including catecholamine secretion, sympathetic nervous system activity, blood pressure, heart rate, cortisol secretion, and aggregability of platelets, exhibit similar surges. As a result of these coinciding morning peaks, myocardial oxygen demand is increased and oxygen supply reduced after a person arises in the morning. Attention to this vulnerable period is merited in the timing and choice of medication, both to prevent or reduce ischemia and to modify potential disease-triggering mechanisms.

Circadian Rhythm↗
PubMed1991

The prognostic and economic implications of a strategy to detect and treat asymptomatic ischemia: the Atenolol Silent Ischemia Trial (ASIST) protocol.

Although silent ischemia may be linked to increases in cardiovascular morbidity and mortality, the long-term effects of a strategy aimed at the detection and treatment of this asymptomatic condition have not been fully explored. We therefore have developed the Atenolol Silent Ischemia Trial (ASIST), the first multicenter, randomized, prospective study of the prognostic implications of silent ischemia in asymptomatic and minimally symptomatic patients with coronary artery disease. Inclusion criteria for study patients were documented coronary artery disease, evidenced angiographically or by previous myocardial infarction, and transient ischemia, evidenced by abnormalities of regional wall motion, stress thallium-201, or exercise electrocardiogram. The main objective of ASIST is to assess the influence of frequency and duration of symptomatic and asymptomatic ischemic episodes on the occurrence of fatal and nonfatal cardiac events. Atenolol, a beta 1-selective adrenergic blocker, was chosen as the therapeutic intervention because of its potential benefits in treating both symptomatic and asymptomatic ischemia. Ambulatory electrocardiographic monitoring will be used to measure the frequency and duration of ischemic episodes during daily life. The predictive ability of short-term (4-week) effects on long-term (52-week) response to atenolol treatment is also being assessed, along with the economic impact of this diagnostic and therapeutic strategy. Given the current emphasis on reducing morbidity and mortality associated with coronary artery disease, ASIST results should shed light onto the long-term management and prognostic implications of this otherwise asymptomatic condition.

Atenolol↗
PubMed1991

Unrecognized left ventricular dysfunction in an apparently healthy alcohol abuse population.

To examine effects of chronic alcohol abuse on left ventricular function, 162 otherwise relatively healthy alcohol abusers, having been admitted to a rehabilitation program, underwent cardiac evaluation including chest X-ray, electrocardiogram, and radionuclide angiography after 2 weeks abstinence. Twenty-nine of the 162 alcoholic subjects (18%) with left ventricular dysfunction were identified. Twenty-two had regional wall motion abnormalities, suggesting a localized process, of whom 12 also had depressed ejection fractions. Seven others had a depressed ejection fraction alone with a more global myopathic process. Only 4 of these 29 patients had any history suggesting prior heart disease. Two of the 29 had Q-waves greater than or equal to 0.4 s and 8 had an abnormal cardiothoracic ratio on chest X-ray. Chronic alcohol abusers appear to be at relatively high risk for left ventricular dysfunction; most of which is unrecognized. Routine screening methods failed to identify 85% of our subjects who later were recognized by radionuclide angiography. Since historical and electrocardiographic abnormalities are often absent in this population, detection of left ventricular dysfunction by other methods such as radionuclide angiography must be used.

Adult↗
PubMed1991

Therapeutic implications of circadian variations in myocardial ischemia and related physiologic functions.

Electrocardiographic (ECG) monitoring for long periods documents circadian patterns in myocardial ischemic episodes. The rise begins between 6 AM and 8 AM for patients with effort angina, the zenith of ischemic activity occurs at about noon. Similar peaks occur in the frequency of acute myocardial infarction and sudden death. Triggering mechanisms common to all of these events may include rises in catecholamine secretion, sympathetic nervous system activity, blood pressure, heart rate, cortisol secretion, and aggregability of platelets, as well as a trough in fibrinolytic activity. These coincident peaks and troughs would be expected to increase myocardial oxygen demand and decrease oxygen supply after a person arises in the morning. This vulnerable period merits recognition. Tailoring the dosing and choice of medication to prevent or reduce ischemia may be important if potential disease-activity triggering mechanisms are to be attenuated. By modifying triggering mechanisms, we may be able to modify the frequencies of adverse outcomes such as acute myocardial infarction and sudden death.

Adrenergic beta-Antagonists↗
PubMed1991

ACC/AHA guidelines for cardiac catheterization and cardiac catheterization laboratories. American College of Cardiology/American Heart Association Ad Hoc Task Force on Cardiac Catheterization.

It is evident that the practice of cardiac catheterization has undergone, and continues to undergo, marked change. Most prominent are the recent very rapid proliferation of catheterization laboratories in general and the development of newer types of catheterization laboratory. No uniform definitions exist for these newer laboratories, so meaningful communication is difficult. The new settings are of particular concern because their location, mobility, organization, and ownership raise questions about the quality of patient care. Most difficult to address are the questions about patient safety and physician conflict of interest. There are no objective data in peer-reviewed literature to support the reported safety and cost savings of these newer settings. Through deliberations, surveys, interviews, and correspondence with the cardiology community embraced by the ACC and the AHA, the task force generally found that in freestanding catheterization laboratories, access to emergency hospitalization may be delayed, and appropriate oversight may be lacking. Additionally, opportunities for self-referral may be fostered and the perception of commercialism and entrepreneurial excess in practice created. All of these problems must be avoided. The growth and development of some freestanding facilities, particularly the mobile laboratories, do not seem to have been driven by an increased need in remote communities or for temporary support but rather almost exclusively by a desire to capture market share. Accordingly, a series of definitions, guidelines, and recommendations for the laboratories as well as for patient selection has been developed. The consensus was that a very restrictive and cautious attitude to the newer settings is appropriate at this time. The justification for development or expansion of cardiac catheterization services must be patient need. Documentation of this need must be based on objective estimates of the number of patients with known or suspected cardiac disease who meet generally accepted indications for laboratory study. Concerns about the lack of data from prospective clinical trials of patient safety in such a group necessitate a very cautious attitude toward any new catheterization services, in particular those without in-house cardiac surgical support. In view of the lack of appropriately controlled safety and need data for hospital-based, mobile, or freestanding laboratories operating without on-site (accessible by gurney) cardiac surgery facilities, the task force reaffirms the position that further development of these services cannot be endorsed at this time. In addition, there is reason for major concern that such proliferation in catheterization services may contribute to increasing costs and troubling ethical questions.

American Heart Association↗