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Biomedical subjects

R W Nesto

Publications and source records attributed to R W Nesto.

At least 19 recordsLinked to original sources

Use of exercise test parameters to predict presence and duration of ambulatory ischemia in patients with coronary artery disease.

Myocardial ischemia is an indicator of adverse prognosis. In patients with stable angina and positive exercise tests, prolonged cumulative ischemia on ambulatory electrocardiographic monitoring identifies a high-risk group with severe coronary artery disease and poor survival. To determine whether features of the exercise test can accurately (1) predict the occurrence of ambulatory ischemia, and (2) classify patients into subgroups at varying levels of risk for ambulatory ischemia, we studied 48 patients with a history of angina and documented coronary disease who underwent the standard Bruce protocol and ambulatory monitoring. All patients had a positive exercise treadmill test, and 26 had ischemia on Holter monitoring (total of 2,922 minutes, 173 episodes, 94% with silent ischemia). The remaining 22 patients did not have ischemia. The exercise test parameters showing significant differences between the 2 groups were (1) time to > or = 1 mm ST-segment depression (p < 0.0003), (2) maximal ST-segment depression (p < 0.004), and (3) exercise capacity (p < 0.037). These data were used to develop a model for predicting the presence and the severity of ambulatory ischemia. Time to onset of > or = 1 mm ST-segment depression and maximal ST-segment depression on exercise treadmill testing can be used to determine the likelihood of mild (1 to 5 episodes or lasting < or = 60 minutes) or severe prolonged (> 5 episodes or lasting > 60 minutes) ambulatory ischemia. Patients with a very high or very low probability of ischemia on Holter monitoring can be identified by certain exercise test parameters and may not need to undergo monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Triggers, acute risk factors and vulnerable plaques: the lexicon of a new frontier.

A neglected area of cardiovascular research--study of the mechanisms of acute disease onset-is receiving increased attention. The new interest is based on the undisputed findings that onset of myocardial infarction and sudden cardiac death are more likely soon after awakening, indicating that activities of the patient frequently trigger the diseases. Triggering may occur when stressors produce hemodynamic, vasoconstrictive and prothrombotic forces--acute risk factors--that, in the presence of a vulnerable atherosclerotic plaque, cause plaque disruption and thrombosis. Triggering research may clarify mechanisms and suggest measures to sever the linkage between a potential trigger and its pathologic consequence.

Acute Disease

Effect of autonomic nervous system dysfunction on the circadian pattern of myocardial ischemia in diabetes mellitus.

OBJECTIVES: The aim of this study was to determine the prevalence and characteristics of ambulatory myocardial ischemia in patients with diabetes mellitus and to delineate the relation between the presence and severity of autonomic nervous system dysfunction and the incidence and time of onset of myocardial ischemia. BACKGROUND: Conflicting data exist with regard to the circadian pattern of myocardial infarction and other cardiovascular events, such as ambulatory ischemia, in diabetes. METHODS: We performed ambulatory electrocardiographic monitoring in 60 patients with diabetes and coronary artery disease. Autonomic nervous system testing was performed in a subgroup of 25 patients with myocardial ischemia after discontinuation of all antianginal medications. RESULTS: Thirty-eight of 60 patients had evidence of ambulatory ischemia; 91% of all ischemic episodes were asymptomatic. The 25 patients with ambulatory ischemia who underwent autonomic nervous system testing had a peak incidence of ischemia between 6 AM and noon (46 of 133 ischemic episodes, p < 0.007), compared with the other three 6-h periods. Fifteen of the 25 patients had no or mild autonomic nervous system dysfunction and demonstrated a similar peak incidence of ischemia between 6 AM and noon (p = 0.0009). However, the 10 patients with moderate to severe autonomic nervous system dysfunction did not experience a morning peak of ischemia, and the number of ischemic episodes was distributed evenly throughout the day (p = 0.4). CONCLUSIONS: Silent ischemia is highly prevalent among patients with diabetes and coronary artery disease. Time of onset of ischemia in diabetic patients follows a circadian distribution, with a peak incidence in the morning hours. However, patients with significant autonomic nervous system dysfunction did not demonstrate such a peak, suggesting that alterations in sympathovagal balance may have an effect on the circadian pattern of cardiovascular events.

Aged

Comparative efficacy of nifedipine gastrointestinal therapeutic system versus diltiazem when added to beta blockers in stable angina pectoris.

To determine the relative efficacy of nifedipine gastrointestinal therapeutic system (GITS) and diltiazem, 20 patients with angina pectoris and coronary artery disease were studied in a double-blinded, placebo-controlled randomized crossover trial. All patients were taking concomitant beta blockers. Efficacy was assessed by symptoms, exercise treadmill testing, and ambulatory ST-segment monitoring at baseline and after 6 weeks on each medication. Mean daily dose was titrated to 119 +/- 7 mg (nifedipine GITS) and 342 +/- 59 mg (diltiazem). The addition of either nifedipine GITS or diltiazem resulted in a significant reduction in angina frequency, improvement in exercise treadmill duration (7 vs 7 and 8 minutes; baseline vs nifedipine GITS and diltiazem), time to angina onset (4 vs 7 and 7 minutes; baseline vs nifedipine GITS and diltiazem), and time to ST-segment depression (5 vs 6 and 7 minutes; baseline vs nifedipine GITS and diltiazem). There was no significant difference between nifedipine GITS and diltiazem with respect to the magnitude of improvement in anginal symptoms or exercise test parameters. Both nifedipine GITS and diltiazem reduced the overall frequency and duration of ischemic episodes on ambulatory monitoring, but this reduction was not statistically different. Thus, nifedipine GITS and diltiazem at maximally tolerated doses were equally effective at reducing angina and increasing exercise tolerance as beta blockers alone.

Adrenergic beta-Antagonists

Usefulness of left ventricular size and function in predicting survival in chronic dialysis patients with diabetes mellitus.

To identify patients at high risk for sudden death, a group of stable patients on maintenance dialysis with diabetes mellitus were studied for up to 135 months to determine if there were clinical, laboratory or echocardiographic predictors of high risk. Eighty-two patients on maintenance dialysis who underwent clinical, laboratory evaluation and echocardiography were enrolled and followed for a mean of 25 months for cardiac and noncardiac complications. Thirty-seven patients with normal wall motion and left ventricular (LV) internal diameter had a mean survival of 35.8 months; 28 patients survived greater than 12 months. Seven patients with normal LV wall motion and dilated LV cavities had a mean survival of 45.7 months; 7 patients survived greater than 12 months. Fifteen patients with abnormal LV wall motion and normal internal LV dimensions had a mean survival of 17 months; 7 patients survived greater than 12 months. Twenty-three patients with both abnormal LV wall motion and dilated LV cavities had a mean survival of 7.8 months; 5 patients survived greater than 12 months. Although echocardiographic abnormalities predicted cardiac mortality at 6 and 12 months, the combination of an abnormal standard electrocardiogram at baseline, clinical history of angina pectoris, and prior documented myocardial infarction or congestive heart failure did not. When the study group was divided by mode or duration of dialysis, presence or absence of diabetes, or use of cardioactive drugs, echocardiographic LV wall motion abnormalities remained the most important determinant of survival.

Adult

Preoperative evaluation for diabetic renal transplantation: impact of clinical, laboratory, and echocardiographic parameters on patient and allograft survival.

OBJECTIVE: To assess the impact on renal transplant patients and graft survival of clinical, laboratory, and echocardiographic parameters commonly measured prior to surgery. PATIENTS: Forty-seven consecutive diabetics with preoperative echocardiograms at the time of transplantation. METHODS: Clinical history, standard chest roentgenogram, electrocardiogram, blood tests, echocardiograms, and HLA testing at baseline; follow-up from 2 to 7 years with periodic reassessment of graft function. RESULTS: Patient survival did not appear to be influenced by age, sex, or type of allograft. A history of either myocardial infarction, congestive heart failure, or angina was present in 15 patients with 3-year survival of 50% (72% if not present, p less than 0.05). Histocompatibility testing did not impact on survival. Serum sodium, potassium, calcium, phosphate, and calcium-phosphate product did not discern different survival groups. A hematocrit greater than 30% was present in 15 patients with 3-year survival of 43% (73% if not present, p less than 0.05). Greater than 10% antibody sensitization of the recipient resulted in a 3-year survival of 38% in eight patients (68% if not present, p less than 0.05). Radiologic evidence of cardiomegaly or congestive heart failure and standard electrocardiographic evidence for left ventricular hypertrophy or strain did not impact on survival. Echocardiographic measurements of left ventricular end-diastolic diameter, posterior wall thickness, or ejection fraction were also not predictive. Increased end-systolic diameter (10 patients, 30% 3-year survival versus 69%, p less than 0.05) and decreased velocity of circumferential fiber shortening (11 patients, 45% 3-year survival versus 71%, p less than 0.05) both appeared to be related to survival. Increased accuracy of prediction could be obtained by adding risk factors so that a history of coronary artery disease and increased end-systolic diameter predicted 3-year survival of 42% versus 82% if neither was present. In terms of graft survival, no clinical, radiographic, or electrocardiographic result yielded predictive information. Among the laboratory tests, only highly antibody-sensitized patients (eight patients, 0% 3-year survival versus 66% 3-year survival, p less than 0.001) showed different survival patterns. Echocardiographic elevated end-systolic diameter predicted a significantly (p less than 0.001) decreased graft survival (3-year survival 33% versus 63%). CONCLUSION: Preoperative prediction of patient and graft survival in diabetic renal transplantation may be enhanced by echocardiographic assessment of systolic load and function. For patients with normal systolic function, whose hematocrit is below 30%, with preformed antibodies less than 10%, renal transplantation has an excellent prognosis; invasive cardiac procedures are not likely required. Since these risk factors are likely additive, a high-risk group may be identified. These latter patients should undergo coronary angiography.

Adult

Acute myocardial infarction in the diabetic patient: pathophysiology, clinical course and prognosis.

Although there have been significant advances in the care of many of the extrapancreatic manifestations of diabetes, acute myocardial infarction continues to be a major cause of morbidity and mortality in diabetic patients. Factors unique to diabetes increase atherosclerotic plaque formation and thrombosis, thereby contributing to myocardial infarction. Autonomic neuropathy may predispose to infarction and result in atypical presenting symptoms in the diabetic patient, making diagnosis difficult and delaying treatment. The clinical course of myocardial infarction is frequently complicated and carries a higher mortality rate in the diabetic than in the nondiabetic patient. Although the course and pathophysiology of myocardial infarction differ to some degree in diabetic patients from those in patients without diabetes, much more remains to be known to formulate more effective treatment strategies in this high risk subgroup.

Adult

Attenuation of the circadian patterns of myocardial ischemia with nifedipine GITS in patients with chronic stable angina. N-CAP Study Group.

The Nifedipine Gastro-Intestinal Therapeutic System (GITS) Circadian Anti-ischemia Program (N-CAP) was designed to test the effect of nifedipine GITS as monotherapy or in combination with a beta-adrenergic blocking agent on the circadian pattern of angina and silent ischemia in patients with chronic stable angina. At 118 sites in the United States, 1,174 patients were screened for entry into this study. To be eligible for participation patients were required to have at least two episodes of angina a week and at least two episodes of myocardial ischemia during 48-h ambulatory electrocardiographic (ECG) monitoring during the baseline placebo period. A total of 207 patients completed all phases of the study. Beta-blockers were continued in those patients already receiving them. In this 7- to 10-week single-blind placebo withdrawal study, a 1-week placebo run-in was followed by up to 5 weeks of single-blind titration with nifedipine GITS, a 4-week efficacy phase with an established dose and a final single-blind 2-week placebo withdrawal period. Ambulatory ECG monitoring was performed at the end of each placebo phase and at the end of the efficacy phase with a digital monitoring device that was validated in a pilot study. Overall, nifedipine GITS significantly reduced the weekly number of anginal episodes from 5.7 to 1.8 (p = 0.0001) and the number of ischemic events from 7.3 to 4 (p = 0.0001) reported during the 48-h monitoring periods, with a significant increase in both during the placebo withdrawal period. The baseline circadian pattern of ischemia showed an early morning peak and a secondary peak in the afternoon. Nifedipine GITS significantly reduced ischemia during the 48-h period when administered as monotherapy or in combination with a beta-blocker. Patients were also randomized to receive nifedipine GITS in either a morning or an evening dose. The two regimens resulted in equal anti-ischemic benefit. The primary side effect of nifedipine GITS was edema, which was dose related. In summary, nifedipine GITS reduced the number of anginal and ischemic episodes when given alone or in combination with a beta-blocker. Nifedipine GITS had a sustained effect: a single daily dose was effective over 24 h regardless of whether it was administered in the morning or evening. This study also suggests that combination therapy with nifedipine GITS and a beta-blocker is especially efficacious in reducing ischemia.

Adrenergic beta-Antagonists

Angioplasty triggers intracoronary leukotrienes and lipoxin A4. Impact of aspirin therapy.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) is a widely used and important method of reperfusing coronary arteries. However, it is also associated with serious complications such as acute reocclusion and accelerated restenosis. The factors as well as the mechanisms involved in PTCA-associated complications remain to be fully elucidated. Because peptidoleukotrienes and lipoxins are potent vasoactive compounds, the formation of which is not inhibited by aspirin (ASA) treatment in vitro, it is possible that these eicosanoids are involved in PTCA-associated untoward events. To test this, we determined the intracoronary levels of peptidoleukotrienes and lipoxin A4 (LXA4) as well as thromboxane (TX) and 5S,12S-dihydroxyeicosatetraenoic acid (5S,12S-DiHETE; a product of double dioxygenation) after plaque rupture and evaluated the impact of ASA therapy. METHODS AND RESULTS: PTCA was performed on 12 patients with coronary artery disease, six undergoing ASA therapy and six without ASA therapy, for at least 2 weeks before PTCA. By means of a technique that permitted sampling of intracoronary blood at the plaque site in situ, samples were taken immediately before and 10 seconds after initiation of plaque rupture. Lipoxygenase (LO)-derived products, including LXA4 and 5S,12S-DiHETE, and a marker of cyclooxygenase activity, i.e., TXB2, were quantitated after extraction and chromatography using deuterium-labeled internal standards and electron capture negative ion chemical ionization mass spectrometry. Peptidoleukotrienes (LTC4 and LTD4) were quantitated after reverse-phase high-performance liquid chromatography coupled with radioimmunoassay. Intracoronary blood taken before PTCA showed no detectable levels of these eicosanoids (the minimum limits of detection were within the picomole range). In contrast, each of these LO products was detected after PTCA. Patients undergoing ASA treatment showed elevated levels of each LO product examined compared with those not receiving ASA. Eicosanoid levels were (mean +/- SEM): LTC4, 7.10 +/- 1.22 ng/ml (ASA) versus 0.48 +/- 0.10 ng/ml; LTD4, 4.92 +/- 0.56 ng/ml (ASA) versus 1.17 +/- 0.48 ng/ml; LXA4, 24.98 +/- 4.11 ng/ml (ASA) versus 15.83 +/- 2.43 ng/ml; 5S,12S-DiHETE, 19.47 +/- 3.98 ng/ml (ASA) versus 11.98 +/- 1.83 ng/ml; TXB2, complete blockage (ASA) versus 31.04 +/- 7.38 ng/ml (p less than 0.05 for LTC4 and LTD4). To distinguish between dilatation of whole blood versus dilatation of whole blood and atheroma for contribution of eicosanoids, we also monitored their formation in Gore-tex grafts. Upon balloon inflation, TXB2 was generated, but LO products were not detected. In contrast, injection of platelet- and leukocyte-directed agonists within the graft led to both peptidoleukotriene and lipoxin formation. CONCLUSIONS: The results indicate that PTCA triggers the intraluminal release of peptidoleukotrienes and LXA4 and that ASA therapy enhances their appearance in intracoronary blood. In addition, they provide direct evidence for LO products (LTC4, LTD4, and LXA4) in a local milieu in vivo. Moreover, the presence of the double dioxygenation product 5S,12S-DiHETE (a potential marker of 5- and 12-LO interactions) suggests that transcellular metabolic events can contribute to eicosanoid formation in vivo.

Adult

Left ventricular filling abnormalities in asymptomatic morbid obesity.

Indexes of left ventricular (LV) diastolic filling were measured by pulse Doppler echocardiography in 16 asymptomatic morbidity obese patients presenting for bariatric surgery and were compared with an age- and sex-matched lean control population. No patient had concomitant disorders known to affect diastolic function. All patients had normal systolic function. LV wall thickness and internal dimension were measured in order to calculate LV mass. Fifty percent of morbidly obese patients had LV diastolic filling abnormalities as assessed by the presence of greater than or equal to 2 abnormal variables of mitral inflow velocity. The ratio of peak early to peak late (atrial) filling velocity was significantly decreased in obese compared with control patients (1.16 +/- 0.26 vs 1.66 +/- 0.30, p less than 0.001). The peak velocity of early LV diastolic filling was significantly reduced in obese patients (75 +/- 15 vs 98 +/- 19 cm/s, p less than 0.001). The atrial contribution to stroke velocity as assessed by the time-velocity integral of late compared with total LV diastolic filling was significantly increased in obese patients (36 +/- 7 vs 27 +/- 4%, p less than 0.001). Obese patients had significantly increased LV mass (214 +/- 45 vs 138 +/- 37 g, p less than 0.001), even when corrected for body surface area (95 +/- 16 vs 76 +/- 16 g/m2, p less than 0.002). However, increased LV mass did not correlate with indexes of abnormal diastolic filling in obese patients. These data suggest that abnormalities of diastolic function occur frequently in asymptomatic morbidly obese patients and may represent a subclinical form of cardiomyopathy in the obese patient.

Adult

Effect of nifedipine on total ischemic activity and circadian distribution of myocardial ischemic episodes in angina pectoris.

A randomized, double-blind, crossover study was conducted in 10 patients to assess the effect of nifedipine versus placebo on total ischemic activity and circadian distribution of ischemic episodes. After baseline exercise treadmill testing and 48-hour ambulatory electrocardiographic ST-segment monitoring, patients received either nifedipine (mean dose, 80 mg/day) or placebo administered 4 times per day, with the initial dose taken immediately upon arising in the morning. Patients were maintained on a stable dose of each study drug for 7 days, after which they underwent repeat exercise treadmill testing and 48-hour ambulatory electrocardiography. During exercise treadmill testing, greater exercise duration was achieved by patients receiving nifedipine than by those receiving placebo (421 +/- 121 vs 353 +/- 155 seconds, respectively; p less than 0.05). Time to greater than or equal to 1 mm ST depression was significantly greater with nifedipine (282 +/- 146 seconds) than at baseline (130 +/- 72 seconds, p less than 0.003) and with placebo (150 +/- 98 seconds, p less than 0.0005). During ambulatory electrocardiographic monitoring, nifedipine reduced both the total number of ischemic episodes (18 vs 54 at baseline and 63 with placebo; p less than 0.02 for both) and the total duration of ischemia (260 vs 874 at baseline and 927 minutes with placebo; p less than 0.02 for both). The surge of ischemia between 06:00 and 12:00 noted at baseline and during placebo therapy was nearly abolished during nifedipine treatment. Nifedipine at this dosage, administered in this manner, is effective in reducing total ischemic activity and may prevent morning surges of ischemic episodes.

Angina Pectoris

Performance characteristics of a new shape of guiding catheter for PTCA of the left coronary artery.

The inability to successfully perform angioplasty commonly involves inadequate guiding catheter performance. We evaluated the use of a new left coronary guiding catheter for angioplasty (PTCA) of lesions in both the left anterior descending and left circumflex arteries. The Nesto guide in two different sizes was used in 100 consecutive PTCA cases as a primary catheter. The catheter successfully cannulated the left main coronary artery in 93 patients and PTCA was successfully performed in 85 patients for target lesions at various locations in either or both vessels. Positive features of this new guiding catheter include superior back-up support and ease of disengagement.

Angioplasty, Balloon, Coronary

Misplaced caval filter and subsequent pericardial tamponade.

Use of the Greenfield filter for partial caval interruption is generally accepted as the most reliable mechanical method of pulmonary embolus prophylaxis. However, there have been reports of a variety of (usually nonfatal) complications. We report here the near-fatal complication of acute pericardial tamponade after misplacement of a Greenfield filter. Because of the filter's unusual location, retrieval required cardiopulmonary bypass, profound hyperthermia, and circulatory arrest.

Adult

Rationale for treatment of silent myocardial ischemia: focus on nifedipine.

The realization that the majority of ischemic episodes in ambulatory patients with coronary artery disease are not associated with angina has raised important questions regarding the medical management of such individuals. Data from studies utilizing ambulatory Holter monitoring of the ST segment suggest that ischemia is likely to be due to a combination of a modest rise in myocardial oxygen demand and a concomitant decrease in coronary perfusion. Patients with ambulatory ischemia may have a poorer survival than those without ischemia during daily activities. This paper will address the potential impact these new findings could have on treatment. A growing body of knowledge regarding the use of nifedipine for silent ischemia will be examined. Enthusiasm to make abolition of ischemia an end point of therapy in patients with coronary artery disease will necessitate a reexamination of drugs that have been assessed largely on their ability to provide symptomatic relief.

Coronary Disease

Silent myocardial ischemia and infarction in diabetics with peripheral vascular disease: assessment by dipyridamole thallium-201 scintigraphy.

We investigated the incidence of silent myocardial ischemia and infarction as assessed by dipyridamole thallium scintigraphy in 30 diabetic patients with peripheral vascular disease and without clinical suspicion of coronary artery disease. Seventeen patients (57%) had thallium abnormalities, with reversible thallium defects compatible with ischemia in 14 patients (47%) and evidence of prior, clinically silent myocardial infarction in 11 patients (37%). Thallium abnormalities were most frequent in patients with concomitant hypertension and cigarette smoking (p = 0.001). These results suggest that unsuspected coronary artery disease is common in this particular group of patients with diabetes mellitus.

Adult

Cardiac conduction defects associated with aortic and mitral valve calcification in dialysis patients.

The prevalence of aortic valve and mitral valve or mitral annular calcification by echocardiography was studied in 66 dialysis patients and correlated with results of 24-h ambulatory and resting ECG data and 12-month survival. The well-known association of mitral valve or mitral annular calcification with cardiac conduction defects was confirmed. Those patients with mitral valve or mitral annular calcification demonstrated a higher prevalence of first-degree atrioventricular block and bundle branch block. Despite advanced age and these conduction defects, those patients with mitral valvular calcification did not show decreased survival at 12 months.

Aortic Valve