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Biomedical subjects

P W Willis

Publications and source records attributed to P W Willis.

At least 19 recordsLinked to original sources
PubMed2001

Adjunctive therapies in the cath lab. Successful medical therapy of left main thrombosis: value of serial coronary angiography.

Acute coronary syndromes (ACS), including unstable angina, non-Q wave myocardial infarctions (MI) and Q-wave MIs, are usually the result of plaque rupture and subsequent thrombus formation. Commonly, patients with ACS have significant underlying coronary artery disease (CAD) demonstrable by coronary angiography and are candidates for prompt revascularization. In many cases, however, ACS are due to coronary thrombosis in the absence of obstructive CAD and therefore aggressive medical therapy may be sufficient. Coronary angiography is an invaluable resource for individualized treatment decisions. We describe a patient with thrombosis of the left main coronary artery successfully treated with aggressive and prolonged antiplatelet and anticoagulant therapy under the guidance of serial coronary angiography.

Aged↗
PubMed1997

Effects of long-term infusion of prostacyclin (epoprostenol) on echocardiographic measures of right ventricular structure and function in primary pulmonary hypertension. Primary Pulmonary Hypertension Study Group.

BACKGROUND: Right heart failure is an important cause of morbidity and mortality in primary pulmonary hypertension. In a recent prospective, randomized study of severely symptomatic patients, treatment with prostacyclin (epoprostenol) produced improvements in hemodynamics, quality of life, and survival. This article describes the echocardiographic characteristics of participants in this trial; the relationship of echocardiographic variables to hemodynamic parameters, exercise capacity, and quality of life; and the echocardiographic changes associated with prostacyclin therapy. METHODS AND RESULTS: The 81 patients enrolled in this multicenter trial were randomized to treatment with a long-term infusion of prostacyclin in addition to conventional therapy (n = 41) or conventional therapy alone (n = 40) for 12 weeks. Echocardiograms and assessments of hemodynamics, exercise capacity, and quality of life were performed before and after the treatment phase. On baseline evaluation, patients had marked right ventricular dilatation and dysfunction, abnormal septal curvature, and significant tricuspid regurgitation with a high regurgitant velocity. Pericardial effusions were common. More pronounced abnormalities in right heart structure and function were associated with higher pulmonary arterial and mean right atrial pressures, lower cardiac index, and impaired exercise capacity but had no predictable relationship to quality-of-life indicators. The 12-week infusion of prostacyclin had beneficial effects on right ventricular size, curvature of the interventricular septum, and maximal tricuspid regurgitant jet velocity. CONCLUSIONS: The echocardiographic manifestations of severe primary pulmonary hypertension reflect abnormalities in hemodynamics and exercise capacity. Prostacyclin has beneficial effects on right heart structure and function that may contribute to the clinical improvement and prolonged survival observed with this drug.

Adult↗
PubMed1997

Role of cytokines in the mechanism of action of amlodipine: the PRAISE Heart Failure Trial. Prospective Randomized Amlodipine Survival Evaluation.

OBJECTIVES: We sought to determine whether the beneficial effects of amlodipine in heart failure may be mediated by a reduction in tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels. We postulated that TNF-alpha and IL-6 levels may also have predictive value in patients with congestive heart failure (CHF). BACKGROUND: The molecular mechanism for progression of CHF may involve cytokine overexpression. The effect of amlodipine on cytokine levels in patients with CHF is unknown. METHODS: In the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) trial, we used enzyme-linked immunosorbent assay to measure plasma levels of TNF-alpha in 92 patients and IL-6 in 62 patients in New York Heart Association functional classes III and IV randomized to receive amlodipine (10 mg/day) or placebo. Blood samples were obtained for cytokine measurement at baseline and at 8 and 26 weeks after enrollment. RESULTS: The baseline amlodipine and placebo groups did not differ in demographics and cytokine levels. Mean (+/- SD) plasma levels of TNF-alpha were 5.69 +/- 0.32 pg/ml, and those of IL-6 were 9.23 +/- 1.26 pg/ml at baseline. These levels were elevated 6 and 10 times, respectively, compared with those of normal subjects (p < 0.001). Levels of TNF-alpha did not change significantly over the 26-week period (p = 0.69). However, IL-6 levels were significantly lower at 26 weeks in patients treated with amlodipine versus placebo (p = 0.007 by the Wilcoxon signed-rank test). An adverse event-CHF or death-occurred more commonly in patients with higher IL-6 levels. CONCLUSIONS: Amlodipine lowers plasma IL-6 levels in patients with CHF. The beneficial effect of amlodipine in CHF may be due to a reduction of cytokines such as IL-6.

Aged↗
PubMed1996

Ethnic differences in forearm vasodilator capacity.

Previous studies have demonstrated significant ethnic differences in left ventricular structure in both normotensive and hypertensive subjects. To determine if these differences in ventricular geometry are associated with differences in vascular structure, we measured the minimum forearm vascular resistance in 30 healthy young African-American adults and in 30 whites matched for age, gender, and blood pressure. Average daytime blood pressure was determined by ambulatory monitoring during a typical work day. Minimum forearm vascular resistance was measured by plethysmography after 10 minutes of forearm ischemia. Indexed left ventricular mass and relative wall thickness were measured by 2-dimensional-directed M-mode echocardiography. The mean (+/-SD) ambulatory pressure was 126 +/- 11/79 +/- 8 mm Hg in African-Americans and 126 +/- 11/79 +/- 7 mm Hg in whites. The 2 groups were similar in body mass index and in family history of hypertension. African-Americans had a higher minimum forearm vascular resistance than did whites (2.39 +/- 0.75 vs 2.03 +/- 0.55 mm Hg, p <0.05). There was a trend toward a greater left ventricular relative wall thickness in African-Americans (0.38 +/- 0.07 vs 0.35 +/- 0.06, p=0.09). These results suggest that early vascular remodeling is present in African-Americans who do not have established hypertension, and that this ethnic difference in vascular structure is associated with a difference in ventricular geometry.

Adult↗
PubMed1996

Apoptosis as a possible cause of gradual development of complete heart block and fatal arrhythmias associated with absence of the AV node, sinus node, and internodal pathways.

BACKGROUND: Gradually progressive development of complete heart block in young people often is associated with cardiac arrhythmia and sudden death, but the pathogenesis remains unexplained. METHODS AND RESULTS: A young woman with complete heart block died suddenly. Her mother had serological but no clinical evidence of antiphospholipid syndrome. Five brothers of another family had arrhythmia and heart block. Three died suddenly; the other two have automatic defibrillators and are alive. The hearts from the young woman and two of the three brothers who died were available for our histological examination of their cardiac conduction systems. In two of the three hearts, the AV node was absent; in the third heart, only fragments of the AV node remained. In all three hearts, the sinus node was nearly destroyed by a noninflammatory degeneration with no abnormal fibrosis or infiltrate. In each heart, the interatrial and internodal pathways were similarly involved, and in the young woman, there were no myocardial cells in which these pathways normally exist. CONCLUSIONS: In these three subjects with progressive development of complete heart block and various arrhythmias, all of whom died suddenly, the histological abnormalities of their cardiac conduction systems are best interpreted as resulting from apoptosis. Programmed cell death is a logical explanation for the pathogenesis of this puzzling clinical picture.

Adolescent↗
PubMed1996

Adverse effects of enalapril in the Studies of Left Ventricular Dysfunction (SOLVD). SOLVD Investigators.

In the Studies of Left Ventricular Dysfunction (LVD), enalapril or placebo was administered in a double-blind fashion to 6797 participants with ejection fraction < or = 0.35. During 40 months' average follow-up, 28.1% of participants randomized to enalapril reported side effects compared with 16.0% in the placebo group (p < 0.0001). Enalapril use was associated with a higher rate of symptoms related to hypotension (14.8% vs 7.1%, p < 0.0001), azotemia (3.8% vs 1.6%, p < 0.0001), cough (5.0% vs 2.0%, p < 0.0001), fatigue (5.8% vs 3.5%, p < 0.0001), hyperkalemia (1.2% vs 0.4%, p = 0.0002), and angioedema (0.4% vs 0.1%, p < 0.05). Side effects resulted in discontinuation of blinded therapy in 15.2% of the enalapril group compared with 8.6% in the placebo group (p < 0.0001). Thus enalapril is well tolerated by patients with LVD; however, hypotension, azotemia, cough, fatigue, and other side effects result in discontinuation of therapy in a significant minority of patients.

Aged↗
PubMed1996

Obesity, adiposity, and lengthening of the QT interval: improvement after weight loss.

OBJECTIVES: To determine the prevalence of QT interval prolongation in patients referred to an outpatient clinic for treatment of obesity; and to describe the change in the QT interval during rapid weight loss with a very-low-calorie diet. DESIGN: Retrospective and prospective review of charts and electrocardiograms. SUBJECTS: Five hundred twenty-two obese patients (411 female, 112 males) with a mean age 44 (18-78 y) and a mean initial weight of 116 kg (63-285 kg) completing 26 weeks of treatment between September, 1989 through to December, 1993. MEASUREMENTS: We reviewed the EKGs of all patients and serially monitored the QTc if greater than 0.44 s or if more than 23 kg was lost during treatment. The QTc interval was calculated with Bazzett's formula using both a manual method and an automated software program. In some patients, body composition was measured by hydrodensitometry. RESULTS: The QTc interval before treatment was 0.42 +/- 0.026 s by manual measurement and 0.41 +/- 0.021 s by automated measurement. Forty-one to 53% of patients showed a QTc interval of greater than 0.42 s and 10-24% demonstrated moderate prolongation (> 0.44 s). In those patients for whom repeat EKG were performed, QTc showed shortening with weight loss by both methods (mean +/- s.e. of 0.42 +/- 0.003 to 0.41 +/- 0.003 s, P < 0.01 manually and 0.41 +/- 0.003 to 0.40 +/- 0.003 s, p < 0.005 by automated program). Analyses were repeated excluding 179 patients with a cardiovascular-related diagnosis or intraventricular block and the results were similar. By regression analysis, gender and fat mass (FM) percentage above normal predicted the QTc. CONCLUSIONS: QT Interval prolongation is common in obesity. For each 50% increase in FM% above normal, there is a 5 ms increase in the QTc above a 'normal' upper limit of 0.40 and 0.38 s in women and men, respectively. Moreover, the QT interval shortens with weight loss. This change may represent an additional benefit of weight loss along with the improvement in other cardiovascular risk factors.

Adipose Tissue↗
PubMed1995

Patients with borderline elevated blood pressure have enhanced left ventricular contractility.

Recent analyses of midwall left ventricular mechanics have demonstrated that patients with established hypertension and ventricular hypertrophy have depressed myocardial contractility. In this study, myocardial performance was assessed in subjects with borderline blood pressure elevations by relating the velocity of circumferential midwall fiber shortening to end-systolic stress in young men and women who were classified as normotensive (n = 92) or as having marginally elevated blood pressure (n = 43) based on daytime ambulatory systolic blood pressure. On average, velocity of midwall fiber shortening in those with higher blood pressure was 8% greater than predicted from results of normotensive controls. These results suggest that young patients with borderline blood pressure elevations have enhanced left ventricular contractility.

Adult↗
PubMed1992

Racial differences in left ventricular structure in healthy young adults.

Racial differences in cardiac structure and function were evaluated in 62 black and 71 white healthy young adults. Left ventricular (LV) mass index, relative wall thickness, fractional shortening, resting cardiac index and resting systemic vascular resistance index were estimated using M-mode echocardiography. Pulsed Doppler interrogation of transmitral flow was used to characterize LV filling. Average daytime blood pressure (BP) was determined by ambulatory monitoring during a typical work or school day. Ambulatory daytime BP averaged 127 +/- 12/80 +/- 7 mm Hg in black subjects, and 127 +/- 9/80 +/- 6 mm Hg in white subjects (p = not significant). The 2 groups were also similar in resting BP, age and gender composition. Relative wall thickness was significantly greater in black than in white subjects (0.37 +/- 0.06 vs 0.34 +/- 0.05; p less than 0.01). This difference was found in both men and women. Black subjects also had a higher resting systemic vascular resistance index (2,110 +/- 570 vs 1,920 +/- 500 dynes.s.cm-5.m2; p less than 0.05) and lower resting cardiac index (3.14 +/- 0.84 vs 3.46 +/- 0.85 L/min/m2; p less than 0.05). There were no significant differences between black and white subjects in LV mass index, fractional shortening and normalized peak filling velocity. These results suggest that racial differences in LV structure and systemic hemodynamics exist even in patients without sustained hypertension. In our study population, the greater relative wall thickness in black subjects was not accompanied by significant differences in LV systolic function or diastolic filling.

Adolescent↗
PubMed1992

Gender differences in left ventricular structure and function in young adults with normal or marginally elevated blood pressure.

Gender differences in left ventricular structure and function were evaluated in 68 male and 69 female young adults (mean age 30 +/- 7 years) with normal or marginally elevated blood pressure. Left ventricular mass index was greater in men than in women, even after controlling for blood pressure. There were no significant gender differences in left ventricular systolic function. Doppler indices of diastolic filling were also similar in men and women. Thus, men have a significantly greater left ventricular mass index than women, but this difference in ventricular size is not associated with differences in systolic or diastolic function.

Adult↗
PubMed1991

Left ventricular mass index and diastolic filling. Relation to blood pressure and demographic variables in a healthy biracial sample.

The relationships of left ventricular (LV) structure and diastolic filling to ambulatory blood pressure, race, age, and gender were studied in 104 young, generally healthy, untreated subjects with normal or marginally elevated blood pressure. Average daytime systolic blood pressure (r = 0.41, P less than .001), diastolic blood pressure (r = 0.38, P less than .001), male gender (r = 0.49, P less than .001), and age (r = 0.32, P less than .001) were univariate correlates of LV mass index as measured by M-mode echocardiography. In a stepwise multiple regression model, male gender, age, and systolic blood pressure were independent predictors of LV mass index. LV filling rate normalized to mitral stroke volume, a Doppler-derived index of diastolic filling, was inversely related to age (r = -0.47, P less than .001), heart rate (r = -0.27, P less than .01), LV mass index (r = -0.32, P less than .001), and diastolic blood pressure (r = -0.20, P less than .05). Age, heart rate, and LV mass index were predictors of normalized peak filling in a stepwise regression model. Race was not significantly related to either LV mass index or diastolic filling. Our results confirm the importance of demographic variables as well as blood pressure in determining LV mass and filling characteristics in humans prior to the development of sustained essential hypertension. These variables contribute to ventricular mass and diastolic function in varying degrees. Gender is strongly correlated with LV mass, but not with filling indices.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Nonemergent cardiac catheterization and risk-stratified revascularization following thrombolytic therapy for acute myocardial infarction. A critical analysis of therapy in the community setting. University of North Carolina Cardiology Consortium.

We evaluated a strategy for administering thrombolytic therapy without emergent cardiac catheterization to patients with acute myocardial infarction in community hospitals. Fifty-nine patients were treated with intravenous streptokinase and heparin, and referred for elective catheterization. Angioplasty or bypass surgery was performed only in patients judged to be at risk for reinfarction. One or more predetermined criteria for infarct segment viability were present in 47 (80%) of 59 patients. Angina recurred in 24 patients and enzyme-positive reinfarction in 9 patients, but only 2 patients developed new Q waves or a creatine kinase rise to over twice the normal value. Of 18 patients judged to be at low risk for reinfarction, only 1 required urgent angioplasty or bypass surgery. Fourteen-day mortality was 7% and infarct vessel patency was 94%. These data indicate that physicians in small community hospitals with a close relationship to a referral center and with a carefully designed protocol can administer thrombolytic therapy safely and effectively. By subsequent stratification of patients according to the risk of recurrent infarction, 22% of patients eligible for revascularization were spared urgent angioplasty or bypass surgery.

Angioplasty, Balloon↗
PubMed1988

Discrepancy between first-dose converting enzyme inhibition at rest and subsequent inhibition during exercise in chronic heart failure.

Low-dose angiotensin-converting enzyme inhibition is thought to completely block the renin-angiotensin system. This study examined the hemodynamic and hormonal responses to initial low- and higher dose converting-enzyme inhibitor (lisinopril or captopril) at rest compared with the response during subsequent chronic therapy while treadmill exercise testing was performed in nine patients with chronic heart failure. At rest, similar changes in systemic arterial pressure, plasma renin activity, and plasma aldosterone concentration were found with initial low and higher doses. However, after at least 4 weeks of therapy, dose-dependent increases in plasma renin activity and decreases in plasma aldosterone concentration were noted during exercise without significant differences in exercise systemic arterial pressure or heart rate. This discrepancy suggests that initial low-dose converting enzyme inhibition does completely block the enzyme, but higher dose therapy is required for complete blockade during subsequent exercise in chronic heart failure.

Adult↗
PubMed1987

Evolution of regional left ventricular wall motion abnormalities in acute Q and non-Q wave myocardial infarction.

The evolution of segmental wall motion in Q and non-Q wave acute myocardial infarction was studied in detail in 15 patients without known prior ischemic events. Serial two-dimensional echocardiographic studies were performed beginning early after the onset of chest pain and continuing until 10 to 14 days after admission. An area of apparent infarction was identified on each initial study based on later correlation of ECG and echocardiographic findings. Wall motion of infarct-and noninfarct-related areas was graded in a semiquantitative fashion based on the scoring of a visual analysis. Sequential image data demonstrated significant spontaneous improvement in wall motion of the infarct area in non-Q but not in Q wave events. Patients with non-Q wave infarction and improvement in regional function were at high risk for recurrent infarction within 6 months. Improvement in wall motion inside or outside the area of infarction in Q wave events was related to future risk. We concluded that in patients with initial acute myocardial infarction, failure to develop Q waves correlated with return of function in the apparent area of infarction. Improvement in regional wall motion after the initial study suggested risk for future ischemic events in both ECG types of myocardial infarction. Serial echocardiographic imaging may be a means to identify patients at risk for infarct extension in both non-Q and Q wave events.

Echocardiography↗
PubMed1987

The clinical scope of disopyramide seven years after introduction--an overview.

Disopyramide phosphate, seven years after its introduction, has proved to be a useful and effective Type IA oral agent for treatment of ventricular arrhythmias. The experience of these seven years has amplified and more sharply defined the initial efficiency and safety issues related to the use of the agent. This experience now shows that disopyramide is at least as effective as other agents in its class and that it can be used safely in the majority of patients for whom treatment is indicated if therapeutic guidelines are followed. The areas of effectiveness, comparative effectiveness, side effects and toxicity of this agent are summarized and guides to patient selection are presented in this review article.

Anti-Arrhythmia Agents↗