27 years of experience
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Stanford University Hosp
300 Pasteur Dr
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Education ?

Medical School Score Rankings
Columbia University (1983)
  • Currently 4 of 4 apples
Top 25%

Awards & Distinctions ?

Stanford Hospital & Clinics
American Board of Internal Medicine

Affiliations ?

Dr. Vagelos is affiliated with 3 hospitals.

Hospital Affilations



  • Stanford Hospital and Clinics
    300 Pasteur Dr, Stanford, CA 94305
    • Currently 3 of 4 crosses
    Top 50%
  • Lucile Salter Packard Children's Hospital @ Stanford
    725 Welch Rd, Palo Alto, CA 94304
    • Currently 1 of 4 crosses
  • Stanford Medical Center
  • Publications & Research

    Dr. Vagelos has contributed to 25 publications.
    Title Measurement Precision in the Optimization of Cardiac Resynchronization Therapy.
    Date July 2010
    Journal Circulation. Heart Failure

    Cardiac resynchronization therapy improves morbidity and mortality in appropriately selected patients. Whether atrioventricular (AV) and interventricular (VV) pacing interval optimization confers further clinical improvement remains unclear. A variety of techniques are used to estimate optimum AV/VV intervals; however, the precision of their estimates and the ramifications of an imprecise estimate have not been characterized previously.

    Title Angina Associated with Left Main Coronary Artery Compression in Pulmonary Hypertension.
    Date July 2009
    Journal The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation

    Chest pain is a common complaint in patients with pulmonary arterial hypertension (PAH). Left main coronary artery (LMCA) compression by an enlarged pulmonary artery trunk (PAT) has been associated with angina, but appropriate diagnostic and treatment approaches remain poorly defined. We present two cases of angina caused by LMCA compression from an enlarged pulmonary artery, one of which also presented with new, severe left ventricular systolic dysfunction attributed to myocardial ischemia. Diagnosis of LMCA stenosis was made via coronary angiography followed by computed tomography-gated coronary angiography (CT-CA), which confirmed pulmonary artery enlargement as the source of extrinsic compression. Restoring LMCA patency with percutaneous intervention and/or aggressive treatment of pulmonary hypertension led to significant improvement in angina, cardiac function and quality of life. Given the negative impact on cardiac function, prompt diagnosis and treatment of extrinsic LMCA compression should be considered a priority.

    Title Effect of Rapamycin Therapy on Coronary Artery Physiology Early After Cardiac Transplantation.
    Date May 2008
    Journal American Heart Journal

    BACKGROUND: Rapamycin has been shown to reduce anatomical evidence of cardiac allograft vasculopathy, but its effect on coronary artery physiology is unknown. METHODS: Twenty-seven patients without angiographic evidence of coronary artery disease underwent measurement of fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR) within 8 weeks and then 1 year after transplantation using a pressure sensor/thermistor-tipped guidewire. Measurements were compared between consecutive patients who were on rapamycin for at least 3 months during the first year after transplantation (rapamycin group, n = 9) and a comparable group on mycophenolate mofetil (MMF) instead (MMF group, n = 18). RESULTS: At baseline, there was no significant difference in FFR, CFR, or IMR between the 2 groups. At 1 year, FFR declined significantly in the MMF group (0.87 +/- 0.06 to 0.82 +/- 0.06, P = .009) but did not change in the rapamycin group (0.91 +/- 0.05 to 0.89 +/- 0.04, P = .33). Coronary flow reserve and IMR did not change significantly in the MMF group (3.1 +/- 1.7 to 3.2 +/- 1.0, P = .76; and 27.5 +/- 18.1 to 19.1 +/- 7.6, P = .10, respectively) but improved significantly in the rapamycin group (2.3 +/- 0.8 to 3.8 +/- 1.4, P < .03; and 27.0 +/- 11.5 to 17.6 +/- 7.5, P < .03, respectively). Multivariate regression analysis revealed that rapamycin therapy was an independent predictor of CFR and FFR at 1 year after transplantation. CONCLUSION: Early after cardiac transplantation, rapamycin therapy is associated with improved coronary artery physiology involving both the epicardial vessel and the microvasculature.

    Title Predictive Value of the Index of Microcirculatory Resistance in Patients with St-segment Elevation Myocardial Infarction.
    Date February 2008
    Journal Journal of the American College of Cardiology

    OBJECTIVES: The objective of this study is to evaluate the predictive value of the index of microcirculatory resistance (IMR) in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Despite adequate epicardial artery reperfusion, a number of patients with STEMI have a poor prognosis because of microvascular damage. Assessing the status of the microvasculature in this setting remains challenging. METHODS: In 29 patients after primary PCI for STEMI, IMR was measured with a pressure sensor/thermistor-tipped guidewire. The Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade, TIMI frame count, coronary flow reserve, and ST-segment resolution were also recorded. RESULTS: The IMR correlated significantly with the peak creatinine kinase (CK) (R = 0.61, p = 0.0005) while the other measures of microvascular dysfunction did not. In patients with an IMR greater than the median value of 32 U, the peak CK was significantly higher compared with those having values <or=32 U (3,128 +/- 1,634 ng/ml vs. 1,201 +/- 911 ng/ml, p = 0.002). The IMR correlated significantly with 3-month echocardiographic wall motion score (WMS) (R = 0.59, p = 0.002) while the other measures of microvascular function did not. The WMS at 3-month follow-up was significantly worse in the group with an IMR >32 U compared with <or=32 U (28 +/- 7 vs. 20 +/- 4, p = 0.001). On multivariate analysis, IMR was the strongest predictor of peak CK and 3-month WMS. The IMR was the only significant predictor of recovery of left ventricular function on the basis of the percent change in WMS (R = 0.50, p < 0.01). CONCLUSIONS: Compared to standard measures, IMR appears to be a better predictor of microvascular damage after STEMI, both acutely and in short term follow-up.

    Title Impact of Nesiritide on Renal Function in Patients with Acute Decompensated Heart Failure and Pre-existing Renal Dysfunction a Randomized, Double-blind, Placebo-controlled Clinical Trial.
    Date December 2007
    Journal Journal of the American College of Cardiology

    OBJECTIVES: Our purpose was to evaluate the impact of nesiritide on renal function in patients with acute decompensated heart failure and baseline renal dysfunction. BACKGROUND: Although nesiritide is approved for the treatment of acute decompensated heart failure, retrospective analyses have raised concerns that it may cause worsened renal function. To date, no randomized clinical trials have prospectively evaluated this issue. METHODS: Consecutive patients with acute decompensated heart failure and baseline renal dysfunction were enrolled in this randomized, double-blind, placebo-controlled clinical trial. Subjects were randomized to receive nesiritide (0.01 microg/kg/min with or without a 2-microg/kg bolus) or placebo (5% dextrose in water) for 48 h in addition to their usual care. Predefined primary end points of the trial were a rise in serum creatinine by > or =20% and change in serum creatinine. RESULTS: Seventy-five patients were enrolled (39 nesiritide, 36 placebo). The groups had similar baseline age (74.9 vs. 75.5 years, respectively), blood pressure (123/64 vs. 125/64 mm Hg) and serum creatinine (1.82 vs. 1.86 mg/dl). There were no significant differences in the incidence of a 20% creatinine rise (23% vs. 25%) or in the change in serum creatinine (-0.05 vs. +0.05 mg/dl). There were no significant differences in the secondary end points of change in weight (-2.19 vs. -1.58 kg), intravenous furosemide (125 vs. 107 mg), discontinuation of the infusion due to hypotension (13% vs. 6%), or 30-day death/hospital readmission (33% vs. 25%). CONCLUSIONS: In this randomized, double-blind, placebo-controlled clinical trial, nesiritide had no impact on renal function in patients with acute decompensated heart failure. (BNP-CARDS trial;; NCT00186329).

    Title Changes in Coronary Anatomy and Physiology After Heart Transplantation.
    Date August 2007
    Journal The American Journal of Cardiology

    Cardiac allograft vasculopathy (CAV) is a progressive process involving the epicardial and microvascular coronary systems. The timing of the development of abnormalities in these 2 compartments and the correlation between changes in physiology and anatomy are undefined. The invasive evaluation of coronary artery anatomy and physiology with intravascular ultrasound, fractional flow reserve, coronary flow reserve, and the index of microcirculatory resistance (IMR) was performed in the left anterior descending coronary artery during 151 angiographic evaluations of asymptomatic heart transplant recipients from 0 to >5 years after heart transplantation (HT). There was no angiographic evidence of significant CAV, but during the first year after HT, fractional flow reserve decreased significantly (0.89 +/- 0.06 vs 0.85 +/- 0.07, p = 0.001), and percentage plaque volume derived by intravascular ultrasound increased significantly (15.6 +/- 7.7% to 22.5 +/- 12.3%, p = 0.0002), resulting in a significant inverse correlation between epicardial physiology and anatomy (r = -0.58, p <0.0001). The IMR was lower in these patients compared with those > or =2 years after HT (24.1 +/- 14.3 vs 29.4 +/- 18.8 units, p = 0.05), suggesting later spread of CAV to the microvasculature. As the IMR increased, fractional flow reserve increased (0.86 +/- 0.06 to 0.90 +/- 0.06, p = 0.0035 comparing recipients with IMRs < or =20 to those with IMRs > or =40), despite no difference in percentage plaque volume (21.0 +/- 11.2% vs 20.5 +/- 10.5%, p = NS). In conclusion, early after HT, anatomic and physiologic evidence of epicardial CAV was found. Later after HT, the physiologic effect of epicardial CAV may be less, because of increased microvascular dysfunction.

    Title Recurrent Spontaneous Coronary Artery Dissection with Transient Left Ventricular Systolic Dysfunction.
    Date March 2007
    Journal International Journal of Cardiology

    Spontaneous coronary artery dissection (SCAD) is a potentially life-threatening entity with a variety of clinical presentations. We report a patient who presented with chest pain and angiographic evidence of coronary dissection. Due to the rapid resolution of symptoms and benign-appearing nature of the dissection, no intervention was pursued and the patient was maintained on medical therapy. She represented 2 days later with substernal chest pain, dynamic EKG changes, positive cardiac biomarkers and a transient depression of her left ventricular function.

    Title Screening for Coronary Artery Disease After Mediastinal Irradiation for Hodgkin's Disease.
    Date January 2007
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology

    PURPOSE: Incidental cardiac irradiation during treatment of thoracic neoplasms has increased risks for subsequent acute myocardial infarction or sudden cardiac death. Identifying patients who have a high risk for a coronary event may decrease morbidity and mortality. The objective of this study was to evaluate whether stress imaging can identify severe, unsuspected coronary stenoses in patients who had prior mediastinal irradiation for Hodgkin's disease. PATIENTS AND METHODS: We enrolled 294 outpatients observed at a tertiary care cancer treatment center after mediastinal irradiation doses 35 Gy for Hodgkin's disease who had no known ischemic cardiac disease. Patients underwent stress echocardiography and radionuclide perfusion imaging at one stress session. Coronary angiography was performed at the discretion of the physician. RESULTS: Among the 294 participants, 63 (21.4%) had abnormal ventricular images at rest, suggesting prior myocardial injury. During stress testing, 42 patients (14%) developed perfusion defects (n = 26), impaired wall motion (n = 8), or both abnormalities (n = 8). Coronary angiography showed stenosis 50% in 22 patients (55%), less than 50% in nine patients (22.5%), and no stenosis in nine patients (22.5%). Screening led to bypass graft surgery in seven patients. Twenty-three patients developed coronary events during a median of 6.5 years of follow-up, with 10 acute myocardial infarctions (two fatal). CONCLUSION: Stress-induced signs of ischemia and significant coronary artery disease are highly prevalent after mediastinal irradiation in young patients. Stress testing identifies asymptomatic individuals at high risk for acute myocardial infarction or sudden cardiac death.

    Title Emerging Therapies for the Management of Decompensated Heart Failure: from Bench to Bedside.
    Date January 2007
    Journal Journal of the American College of Cardiology

    While pharmaceutical innovation has been highly successful in reducing mortality in chronic heart failure, this has not been matched by similar success in decompensated heart failure syndromes. Despite outstanding issues over definitions and end points, we argue in this paper that an unprecedented wealth of pharmacologic innovation may soon transform the management of these challenging patients. Agents that target contractility, such as cardiac myosin activators and novel adenosine triphosphate-dependent transmembrane sodium-potassium pump inhibitors, provide inotropic support without arrhythmogenic increases in cytosolic calcium or side effects of more traditional agents. Adenosine receptor blockade may improve glomerular filtration and diuresis by exerting a direct beneficial effect on glomerular blood flow while vasopressin antagonists promote free water excretion without compromising renal function and may simultaneously inhibit myocardial remodeling. Urodilatin, the renally synthesized isoform of atrial natriuretic peptide, may improve pulmonary congestion via vasodilation and enhanced diuresis. Finally, metabolic modulators such as perhexiline may optimize myocardial energy utilization by shifting adenosine triphosphate production from free fatty acids to glucose, a unique and conceptually appealing approach to the management of heart failure. These advances allow optimism not only for the advancement of our understanding and management of decompensated heart failure syndromes but for the translational research effort in heart failure biology in general.

    Title Discordant Changes in Epicardial and Microvascular Coronary Physiology After Cardiac Transplantation: Physiologic Investigation for Transplant Arteriopathy Ii (pita Ii) Study.
    Date July 2006
    Journal The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation

    BACKGROUND: Investigating changes in coronary physiology that occur after cardiac transplantation has been challenging. Simultaneous and independent assessment of the epicardial artery by measuring fractional flow reserve (FFR) and of the microvasculature by calculating the index of microvascular resistance (IMR) with a single coronary pressure wire may be useful. METHODS: Twenty-five asymptomatic patients with normal coronary angiograms underwent FFR, thermodilution-derived IMR and coronary flow reserve (CFR) and intravascular ultrasound (IVUS) evaluation soon after cardiac transplantation and 1 year later. RESULTS: FFR significantly worsened (0.90 +/- 0.05 at baseline to 0.85 +/- 0.06 at 1 year, p = 0.004). FFR correlated strongly with percent plaque volume as measured by IVUS (r = -0.58, p < 0.0001). IMR improved significantly (29.2 +/- 15.9 at baseline to 19.3 +/- 7.6 units at 1 year, p = 0.007). CFR increased, but not significantly (2.6 +/- 1.4 at baseline to 3.2 +/- 1.2 at 1 year, p = not significant). Diabetes and donor heart ischemic time independently predicted baseline IMR. Treatment with rapamycin independently predicted FFR at 1 year. CONCLUSIONS: New coronary physiologic measures, FFR and IMR, show that epicardial artery physiology worsens and correlates with anatomic changes, whereas microvascular physiology improves during the first year after cardiac transplantation. CFR, the traditional method for evaluating coronary circulatory physiology, did not identify these changes.

    Title Diastolic Dysfunction After Mediastinal Irradiation.
    Date December 2005
    Journal American Heart Journal

    BACKGROUND: Mediastinal irradiation is known to cause cardiac disease, but its effect on left ventricular diastolic function is unknown. The purpose of this study was to determine the prevalence of diastolic dysfunction and its association with prognosis in asymptomatic patients after mediastinal irradiation. METHODS: We recruited 294 patients who had received at least 35 Gy to the mediastinum for treatment of Hodgkin disease. Each patient underwent resting echocardiography, stress echocardiography, and nuclear scintigraphy. Survival free from cardiac events was determined during 3.2 years of follow-up. RESULTS: The mean age of the included patients was 42 years, and 49% were male. Adequate measurements of diastolic function were obtained in 282 (97%) patients. Diastolic dysfunction was considered mild in 26 (9%) and moderate in 14 (5%). Exercise-induced ischemia was more common in patients with diastolic dysfunction (23%) than those with normal diastolic function (11%, P = .008). After adjustment for patient demographics, clinical characteristics, and radiation history, patients with diastolic dysfunction had worse event-free survival than patients with normal function (hazard ratio 1.66, 95% CI 1.06-2.4). CONCLUSIONS: There is a high prevalence of diastolic dysfunction in asymptomatic patients after mediastinal irradiation, and the presence of diastolic dysfunction is associated with stress-induced ischemia and a worse prognosis. Screening with Doppler echocardiography may be helpful in identifying patients at risk for subsequent cardiac events.

    Title Preoperative Cardiac Evaluation: Mechanisms, Assessment, and Reduction of Risk.
    Date August 2005
    Journal Thoracic Surgery Clinics

    The changing paradigm in cardiovascular disease in which atherosclerotic lesions exist in a spectrum of stable to unstable, the lack of a perfect prediction tool, and the paucity of randomized controlled data on appropriate intervention make protection of cardiac patients undergoing thoracic surgery challenging. Nociception-related sympathetic drive combines with inflammatory stimuli and the cardiodepressant effects of anesthesia to create a window of maximum risk in the early postoperative period (8-24 hours), and although multivariate models have shown that a combination of surgery-specific risk, patient-specific cardiovascular history, and estimated functional capacity best determine the need for further investigation, the optimal choice of investigation is unclear. Exercise or dobutamine stress echocardiography provide the best validated investigations, and in the case of poor images, dobutamine MR imaging is increasingly used. When disease is found, medical and interventional options are available. PCI is often used, but the risk of converting a stable flow-limiting lesion into a less stable non-flow-limiting lesion must be considered, along with a delay for anti-platelet therapy and endothelialization of the stent. Alternatively, medical protection with acute beta-blockade or alpha2-agonists reduces risk (although beta-blockade often is avoided in chronic lung disease, even nonselective agents are safe in patients with non-airways reactive COPD). In addition, it is likely that statin use reduces risk, probably by stabilizing plaques, but patients with cardiac risk are increasingly likely to be taking this medication already. The assessment and management of cardiac risk in the perioperative thoracic surgery patient is challenging. With focused, rational, and individually tailored management; tight monitoring of postoperative pain; and a close working relationship between the surgeon, anesthesiologist, and cardiologist, patient care can be optimized, and risk can be effectively controlled.

    Title Impact of Angiotensin-converting Enzyme Gene Polymorphism on Neurohormonal Responses to High- Versus Low-dose Enalapril in Advanced Heart Failure.
    Date February 2005
    Journal American Heart Journal

    BACKGROUND: The impact of angiotensin-converting enzyme (ACE) gene polymorphism on neurohormonal dose response to ACE inhibitor therapy is unclear. METHODS: ACE Insertion (I) or Deletion (D) genotype was determined in 74 patients with chronic heart failure who were randomly assigned to receive either high-dose or low-dose enalapril over a period of 6 months. Monthly pre-enalapril and post-enalapril neurohormone levels (serum ACE activity (sACE), plasma angiotensin II (A-II), plasma renin activity (PRA), and serum aldosterone (ALDO) were compared between genotype subgroups and between patients who received high- or low-dose enalapril within each genotype subgroup. RESULTS: At baseline, predose/postdose sACE and postdose PRA were significantly higher in the DD genotype. At 6-month follow-up, postdose sACE was reduced in a dose-dependent fashion in all three genotypes (P < .05). However, predose and postdose ALDO and A-II levels did not differ between each genotype subgroup at baseline or by enalapril dose within each genotype subgroup. ALDO escape and A-II reactivation were not affected by ACE genotype or enalapril dosage. CONCLUSIONS: Predose sACE were consistently higher in the DD genotype when compared with ID or II subgroups. Despite a dose-dependent suppression of sACE, there were no observed statistically significant differences in ALDO and A-II suppression or escape with escalating doses of enalapril within each subgroup.

    Title "tako-tsubo-like Left Ventricular Dysfunction": a Clinical Entity Mimicking Acute Myocardial Infarction with a Favorable Prognosis.
    Date January 2005
    Journal The American Journal of Geriatric Cardiology

    An emotionally-distressed, elderly Caucasian woman presented with chest pain and hypertension. Electrocardiogram showed inferior ST-segment elevation, and an urgent cardiac catheterization was performed. Coronary angiography revealed normal appearing coronary arteries; however, left ventriculography showed extensive left ventricular apical akinesis. The patient had a mild rise in cardiac enzyme levels indicative of myocardial injury. She was discharged after an uncomplicated in-hospital course. One month later, the left ventricular wall motion abnormality had improved. In this report, the authors discuss this compilation of findings known as tako-tsubo-like left ventricular dysfunction.

    Title Simultaneous Assessment of Fractional and Coronary Flow Reserves in Cardiac Transplant Recipients: Physiologic Investigation for Transplant Arteriopathy (pita Study).
    Date October 2003
    Journal Circulation

    BACKGROUND: The utility of measuring fractional flow reserve (FFR) to assess cardiac transplant arteriopathy has not been evaluated. Measuring coronary flow reserve (CFR) as well as FFR could add information about the microcirculation, but until recently, this has required two coronary wires. We evaluated a new method for simultaneously measuring FFR and CFR with a single wire to investigate transplant arteriopathy. METHODS AND RESULTS: In 53 cases of asymptomatic cardiac transplant recipients without angiographically significant coronary disease, FFR and thermodilution-derived CFR (CFRthermo) were measured simultaneously with the same coronary pressure wire in the left anterior descending artery and compared with volumetric intravascular ultrasound (IVUS) imaging. The average FFR was 0.88+/-0.07; in 75% of cases, the FFR was less than the normal threshold of 0.94; and in 15% of cases, the FFR was < or =0.80, the upper boundary of the gray zone of the ischemic threshold. There was a significant inverse correlation between FFR and IVUS-derived measures of plaque burden, including percent plaque volume (r=0.55, P<0.0001). The average CFRthermo was 2.5+/-1.2; in 47% of cases, CFRthermo was < or =2.0. In 14%, the FFR was normal (> or =0.94) and the CFR was abnormal (<2.0), suggesting predominant microcirculatory dysfunction. CONCLUSIONS: FFR correlates with IVUS findings and is abnormal in a significant proportion of asymptomatic cardiac transplant patients with normal angiograms. Simultaneous measurement of CFR with the same pressure wire, with the use of a novel coronary thermodilution technique, is feasible and adds information to the physiological evaluation of these patients.

    Title Early Use of Statins in Acute Coronary Syndromes.
    Date May 2003
    Journal Current Atherosclerosis Reports

    This review examines the use of statin medications early in the clinical course of acute coronary syndrome (ACS). Available data demonstrate that there are clear clinical benefits to this practice. Numerous previous studies have documented the primary and secondary benefits of statins in the prevention of coronary events. Recent trials show that when statins are used during hospital admissions for ACS, patients experience decreased recurrent myocardial infarction, lower death rates, and fewer repeat hospitalizations for ischemia or revascularization. Several studies suggest that the positive effects of statins on plaque stabilization, inflammation, thrombosis, and endothelial function may be independent of lipid levels. There is also an emerging view that beneficial lipid-lowering with statins in high-risk patients has no lower limit. This information suggests that all patients admitted for ACS should be treated with statins, regardless of cholesterol levels.

    Title Early Use of Statins in Acute Coronary Syndromes.
    Date September 2002
    Journal Current Cardiology Reports

    This review examines the use of HMG-CoA reductase inhibitor (statin) medications early in the clinical course of acute coronary syndrome. Available data demonstrate that there are clear clinical benefits to this practice. Numerous previous studies have documented the primary and secondary benefits of statins in the prevention of coronary events. Recent trials show that when statins are used during hospital admissions for acute coronary syndrome (ACS), patients experience decreased recurrent myocardial infarction, lower death rates, and fewer repeat hospitalizations for ischemia or revascularization. Several studies suggest that the positive effects of statins on plaque stabilization, inflammation, thrombosis, and endothelial function may be independent of lipid levels. There is also an emerging view that beneficial lipid-lowering with statins in high-risk patients has no lower limit. This information suggests that all patients admitted for ACS should be treated with statins, regardless of cholesterol levels.

    Title Neurohormonal and Clinical Responses to High- Versus Low-dose Enalapril Therapy in Chronic Heart Failure.
    Date January 2002
    Journal Journal of the American College of Cardiology

    OBJECTIVES: We sought to compare the neurohormonal responses and clinical effects of long-term, high-dose versus low-dose enalapril in patients with chronic heart failure (CHF). BACKGROUND: Examination of neurohormonal and clinical responses in patients receiving different doses of angiotensin-converting enzyme (ACE) inhibitors may provide insight into the potential for additional suppression with angiotensin II (AT-II) or aldosterone antagonists. METHODS: Seventy-five patients with CHF were randomized to receive either high-dose (40 mg/day, n = 37) or low-dose (5 mg/day, n = 38) enalapril over six months. The results from exercise testing, echocardiography, tissue-specific ACE activity and monthly pre- and post-enalapril neurohormonal levels were compared. RESULTS: Despite greater intra-group improvements in plasma renin activity and serum aldosterone levels in the high-dose group, no statistically significant differences were observed between the two groups in all variables, except for serum ACE activity at the end of study. Elevated serum aldosterone and plasma AT-II levels were observed in 35% and 85% of patients, respectively, at 34 weeks, an inter-group difference that was not statistically significant. A trend toward higher levels of tissue-specific ACE activity in the high-dose group compared with the low-dose group at the end of study was observed (p = 0.054). A predefined composite end point of clinical events had a trend toward better improvement in the high-dose group. CONCLUSIONS: This study could not demonstrate a difference between high- and low-dose enalapril in terms of serum aldosterone and plasma AT-II suppression, despite a dose-dependent reduction in serum ACE activity. Even at maximal doses of enalapril, elevated serum aldosterone and plasma AT-II levels were frequently observed.

    Title Constrictive Pericarditis Due to Coccidiomycosis.
    Date November 1999
    Journal The Annals of Thoracic Surgery

    Coccidiomycosis is a fungal infection that rarely causes cardiac disease. Constrictive pericarditis in the setting of disseminated coccidiomycosis can be fatal, despite antifungal therapy and pericardiectomy. We report on a patient with constrictive pericarditis due to localized infection by Coccidioides immitis. The patient underwent successful surgical pericardiectomy and antifungal chemotherapy, and remains well 1 year later.

    Title Assessment of Left Ventricular Wall Motion Abnormalities with the Use of Color Kinesis: a Valuable Visual and Training Aid.
    Date September 1997
    Journal Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography

    Accurate interpretation of left ventricular segmental wall motion by echocardiography is an important yet difficult skill to learn. Color-coded left ventricular wall motion (color kinesis) is a tool that potentially could aid in the interpretation and provide semiquantification. We studied the usefulness of color kinesis in 42 patients with a history of congestive cardiomyopathy who underwent two-dimensional echocardiograms and a color kinesis study. The expert's reading of the two-dimensional wall motion served as a reference for comparison of color kinesis studies interpreted by the expert and a cardiovascular trainee. Correlation between two-dimensional echocardiography and the expert's and trainee's color coded wall motion scores were r = 0.83 and r = 0.67, respectively. Reproducibility between reviewers and between operators was also assessed. Interobserver variability for color-coded wall motion showed a correlation of r = 0.78. Correlation between operators was also good; r = 0.84. Color kinesis is reliable and appears promising as an adjunct in the assessment of wall motion abnormalities by echocardiography. It is both a valuable visual aid, as well as a training aid for the cardiovascular trainee.

    Title Volume-mediated Pulmonary Responses in Liver Transplant Candidates.
    Date April 1997
    Journal Clinical Transplantation

    Pulmonary hypertension, defined as mean pulmonary artery pressure (mPAP) greater than or equal to 25 mmHg, is a recognized complication of hepatic dysfunction with portal hypertension and is considered a relative contraindication to liver transplantation. To characterize pulmonary hemodynamic responses in OLT candidates without pre-existing primary pulmonary hypertension, 22 consecutive patients referred for OLT at the Stanford University Hospital underwent prospective right heart catheterization with pressure determinations at baseline and following infusion of 11 crystalloid over 10 min. In addition, EKG, chest X-ray and transthoracic echocardiograms were performed as a part of the routine evaluation. Eleven non-cirrhotic patients served as controls. At baseline, 1/22 (4.5%) OLT patients had pulmonary hypertension while 9/22 (41%) developed pulmonary hypertension following volume infusion (p < 0.0001). In contrast, 0/11 controls manifested elevated pulmonary pressures at baseline or following volume challenge. OLT candidates were found to have significant increases in mean pulmonary pressure and capillary wedge pressure (PCWP) compared to controls, suggesting intravascular volume overload or left ventricular dysfunction as potential causes. OLT candidates who manifested volume-dependent pulmonary hypertension (a) had a 2-fold higher baseline PCWP, (b) currently smoked, and (c) had previously undergone portosystemic shunts. Aggregate analysis of EKG, echo and CXR for determination of volume-mediated pulmonary hypertension revealed a sensitivity of 25%, specificity of 75% and a positive predictive value of 40%. Preoperative identification of patients with a predisposition to manifesting elevated pulmonary pressures in the context of rapid volume infusion offers the potential for improved risk stratification and optimized clinical management.

    Title Evidence-based, Cost-effective Risk Stratification and Management After Myocardial Infarction. California Cardiology Working Group on Post-mi Management.
    Date March 1997
    Journal Archives of Internal Medicine

    Current management of patients after an acute myocardial infarction (AMI) reflects a variety of approaches ranging from conservative to aggressive. Although each method is appropriate in certain subgroups, their application frequently lacks a scientific basis. Current, clinically relevant, evidence-based practice guidelines are needed for secondary prevention for survivors after an AMI. To meet this need, the California Cardiology Working Group was assembled to evaluate the available data from clinical trials and other published studies and develop evidence-based, cost-effective guidelines for clinicians to use as a basis for patient management after an AMI. The group consisted of 18 members, including cardiologists from academic institutions and physicians working in cardiac intensive care, private practices, and managed care settings, representing a broad spectrum of expertise pertaining to patients who have had an AMI. The members had expertise in cardiac intensive care, interventional cardiology, nuclear cardiology, lipid disorders, echocardiography, and cardiac rehabilitation. The intended audience for these practice guidelines includes all physicians who treat survivors of MI. A literature review of all relevant clinical trials and other published data about the natural history after AMI and the effects of current therapeutic modalities are discussed herein. Case histories served as models for application of the literature-based data. The recommendations for management were reached by consensus vote based on the scientific evidence. When more than 1 management option applied, this was recognized in the recommendations. The recommendations accompany the text.

    Title Transplant Candidates with Severe Left Ventricular Dysfunction Managed with Medical Treatment: Characteristics and Survival.
    Date May 1996
    Journal Journal of the American College of Cardiology

    OBJECTIVES. This study sought to assess the clinical characteristics and survival of patients with symptomatic heart failure who were referred as potential heart transplant candidates, but were selected for medical management. BACKGROUND. Patients with severe left ventricular dysfunction referred for heart transplantation may be considered too well to be placed immediately on an active waiting transplant list. The clinical characteristics of this patient group and their survival have not been well defined. These patients represent a unique group that are characterized by comparatively low age and freedom from significant comorbid conditions. METHODS. We studied 116 consecutive patients with symptomatic heart failure, severe left ventricular dysfunction (left ventricular ejection fraction 20 +/- 7% [mean +/- SD]) and duration of symptoms >1 month referred for heart transplantation, who were acceptable candidates for the procedure but who were not listed for transplantation because of relative clinical stability. These patients were followed up closely on optimal medical therapy. A variety of baseline clinical, hemodynamic and exercise variables were assessed to define this patient group and used to predict cardiac death and requirement later for heart transplantation. RESULTS. During a mean follow-up period of 25.0 +/- 14.8 months (follow-up 99% complete), there were eight cardiac deaths (7%) (seven sudden, one acute myocardial infarction). Only nine patients (8%) were listed for heart transplantation. Actuarial 1- and 4-year cardiac survival rates were 98 +/- 1% and 84 +/- 7% (mean +/- SE), respectively, and freedom from listing for transplantation was 95 +/- 2% and 84 +/- 7% (mean +/- SE), respectively. Patients were mainly in New York Heart Association functional class II or III and had a preserved cardiac index (2.4 liters/min.m2), pulmonary capillary wedge pressure of 16 +/- 9 mm Hg (mean +/- SD) and maximal oxygen consumption of 17.4 +/- 4.3 ml/min per kg (mean +/- SD). By logistic regression analysis, there was no predictor for cardiac death. Longer duration of heart failure (p = 0.013) and mean pulmonary artery (p < 0.05) and pulmonary systolic (p = 0.014) and diastolic (p < 0.05) pressures correlated significantly with listing for heart transplantation by univariate logistic regression. By multivariate logistic regression, only pulmonary artery systolic pressure (p < 0.004) and duration of heart failure (p < 0.015) remained as predictors for need for later transplantation. CONCLUSIONS. In the current treatment era, prognosis is favorable in a definable group of transplant candidates despite severe left ventricular dysfunction. This patient group can be identified after intensive medical therapy by stable symptoms, a relatively high maximal oxygen uptake at peak exercise and a preserved cardiac output.

    Title Cardiac Transplantation: the Stanford Experience in the Cyclosporine Era.
    Date August 1994
    Journal The Journal of Thoracic and Cardiovascular Surgery

    We analyzed our experience with 496 patients who underwent primary cardiac transplantation since the introduction of cyclosporine immunosuppression (Dec. 16, 1980, to Jan. 7, 1993). There were 388 male and 108 female patients. Mean recipient age was 40 +/- 16 years (range 0.1 to 70 years, median 44 years). Recipient diagnoses included coronary disease in 188, idiopathic cardiomyopathy in 196, viral cardiomyopathy in 35, and congenital heart disease in 28 patients. Donor age was 25 +/- 10 years (range 1 to 53 years, median 24 years). Graft ischemic time was 148 +/- 57 minutes (range 38 to 495 minutes, median 149 minutes). Operative mortality (hospital death) rate was 7.9% +/- 1.3% (70% confidence intervals). Multivariate logistic regression analysis revealed that (higher) pulmonary vascular resistance and gender (female) were the only independent predictors of hospital death (p < 0.05). Actuarial survival estimates for all patients at 1, 5, and 10 years are 82% +/- 1.7% (83% +/- 1.8% adult, 77% +/- 5.2% pediatric), 61% +/- 2.5% (65% +/- 2.5% adult, 64% +/- 6.6% pediatric), and 41% +/- 3.7% (40% +/- 4% adult, 54% +/- 8.6% pediatric), respectively. For 232 patients treated with triple-drug immunosuppression and induction with OKT3 since 1987, survival estimates at 1 and 5 years are 82% +/- 2.6% and 67% +/- 3.7%, respectively. Causes of death for the entire group were rejection in 29 (14% of deaths), infection in 69 (34%), graft coronary disease in 36 (18%), nonspecific graft failure in 6 (3%), malignancy in 19 (10%), stroke in 6 (3%), pulmonary hypertension in 6 (3%), and other causes in 30 (15%) patients. Actuarial freedom from rejection at 3 months, 1 year, and 5 years was 21% +/- 1.9%, 14% +/- 1.7%, and 7.2% +/- 1.5%, respectively (+/- 1 standard error of the mean). Estimates of freedom from rejection-related death at 1, 5, and 10 years were 96% +/- 1%, 93% +/- 1.4%, and 93% +/- 1.4%, respectively. Actuarial freedom from any infection at 3 months and at 1 and 5 years was 40% +/- 2.3%, 27% +/- 2.1%, and 15% +/- 2.0% and from infection-related death, 95% +/- 1.0%, 93% +/- 1.2%, and 85% +/- 1.9%, respectively. Actuarial freedom from (angiographic or autopsy proved) graft coronary artery disease at 1, 5, and 10 years was 95% +/- 1.2%, 73% +/- 2.7%, and 65% +/- 3.6% and from coronary disease-related death or retransplantation 98% +/- 0.7%, 84% +/- 2.2%, and 66% +/- 4.3%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

    Title Abnormalities of Pulmonary Function in Patients with Congestive Heart Failure, and Reversal with Ipratropium Bromide.
    Date March 1994
    Journal The American Journal of Cardiology

    Patients with congestive heart failure (CHF) have baseline restrictive and obstructive abnormalities in pulmonary function. Thus, improvement of respiratory parameters may provide a new method for the treatment of CHF. Ipratropium is an inhaled anticholinergic bronchodilator with no reported cardiac or systemic effect. A pilot study was performed to investigate the acute effects of a 72 micrograms inhaled dose of ipratropium bromide on pulmonary function and pulmonary artery pressures in 18 nonsmokers and 11 smokers with severe (New York Heart Association class 2 or 3), stable CHF who were referred for orthotopic cardiac transplantation. An unmatched group of 10 healthy subjects (5 men and 5 women, mean age 36.8 +/- 1.8 years) were studied with pulmonary function testing alone. Forced expiratory volume in 1 second (FEV1) in 15 of 18 nonsmokers with CHF showed a favorable response with a mean improvement of 5.1% (2.74 +/- 0.20 to 2.89 +/- 0.19 liter after drug treatment; p = 0.0026). Forced expiratory flow between 25 and 75% of the forced vital capacity (FEF25-75) improved by 19% (2.50 +/- 0.25 to 3.09 +/- 0.28 liter/s; p = 0.0013). Eight of 11 smokers with CHF responded with a 9.5% increase in FEV1 (2.32 +/- 0.21 to 2.54 +/- 0.19 liter; p = 0.0006) and a 23.2% increase in FEF25-75 (1.82 +/- 0.38 to 2.37 +/- 0.46 liter/s; p = 0.0029). Pulmonary artery pressures, cardiac output, systemic arterial pressures, and cardiac rate and rhythm were unaffected by administration of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

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