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Biomedical subjects

J B Young

Publications and source records attributed to J B Young.

At least 73 records · Page 4Linked to original sources
PubMed2000

Heart failure is a fever: the cytokine connection.

Inflammation probably contributes to the development and progress of heart failure. Proteins called cytokines, which are produced by damaged tissues and leukocytes as part of the inflammatory response, affect the heart both directly and indirectly. They exacerbate hemodynamic imbalances, act as negative inotropes, stimulate left ventricular hypertrophy, and promote the production of still more cytokines, which continue the cycle. Several medications counter these effects in vitro, and some are in clinical testing.

Cytokines↗
PubMed2000

The HOPE study. Ramipril lowered cardiovascular risk, but vitamin E did not.

The Heart Outcomes Prevention Evaluation (HOPE) study found that the ACE inhibitor ramipril can lower the risk of atherosclerotic disease events and death in patients without heart failure but with known atherosclerosis or with diabetes plus at least one cardiovascular risk factor. This benefit was independent of ramipril's effect on blood pressure. Additional benefits were a reduced risk of diabetic nephropathy in diabetic patients, and a lower likelihood of newly diagnosed diabetes. On the other hand, vitamin E in the doses and duration studied (400 IU/day for 4.5 years) did not lower risk significantly.

Aged↗
PubMed2000

Exercise hemodynamic findings in patients with exertional dyspnea.

To determine whether upright bicycle exercise could provide useful information about disabling exertional dyspnea in the absence of severe abnormalities (as shown by traditional testing methods), we evaluated 13 such patients. There were 3 men and 10 women with a mean age of 49+/-15 (SD) years. We used pulmonary artery catheterization at rest and during upright bicycle exercise to evaluate these patients. All patients had normal left ventricular function except for 1, who had an ejection fraction of 45%. The mean duration to peak exercise was 9+/-6 minutes. Normal systolic pulmonary artery pressure was defined as 25+/-5 mmHg. Four patients had normal systolic pulmonary pressure, and 9 exhibited pulmonary hypertension with exercise. In those 9, the mean mixed pulmonary venous oxygen saturation at rest was 61%+/-9% and fell to 32%+/-9% at peak exercise. Six of the 9 patients also had some degree of resting pulmonary hypertension that worsened with exercise: their mean pulmonary artery systolic pressure at rest was 47+/-14 mmHg and rose to 75+/-25 mmHg at peak exertion (P = 0.01). The other 3 patients showed no pulmonary hypertension at rest; their mean pulmonary artery systolic pressure was 27+/-6 mmHg. However, this level rose to 53+/-4 mmHg at peak exertion (P = 0.04). In this pilot study of patients with dyspnea, 9 of 13 (69%) displayed marked pulmonary hypertension with exercise. The resting hemodynamic levels were normal in 3 (33%) of those with exercise pulmonary hypertension. We conclude that hemodynamic data from bicycle exercise tests can provide additional information regarding the mechanisms of exertional dyspnea.

Catheterization, Swan-Ganz↗
PubMed1999

Ventilatory and heart rate responses to exercise : better predictors of heart failure mortality than peak oxygen consumption.

BACKGROUND: An abnormally low chronotropic response and an abnormally high ventilatory response (V(E)/V(CO2)) to exercise are common in patients with severe heart failure, but their relative prognostic impacts have not been well explored. METHODS AND RESULTS: Consecutive patients with heart failure referred for metabolic stress testing who were not taking beta-blockers or intravenous inotropes (n=470) were followed for 1.5 years. The chronotropic index was calculated while peak V(O2) and V(E)/V(CO2) were directly measured. Chronotropic index and peak V(O2) were considered abnormal if in the lowest 25th percentiles of the patient cohort, whereas V(E)/V(CO2) was considered abnormal if in the highest 25th percentile. For comparative purposes, a group of 17 healthy controls underwent metabolic testing as well. Compared with controls, heart failure patients had markedly abnormal ventilatory and chronotropic responses to exercise. In the heart failure cohort, there were 71 deaths. In univariate analyses, predictors of death included high V(E)/V(CO2) low chronotropic index, low V(O2), low resting systolic blood pressure, and older age. Nonparametric Kaplan-Meier plots demonstrated that by dividing the population according to peak V(E)/V(CO2) and peak V(O2), it is possible to identify low, intermediate, and very high risk groups. In multivariate analyses, the only independent predictors of death were high V(E)/V(CO2) (adjusted relative risk [RR] 3.20, 95% CI 1.95 to 5.26, P<0.0001) and low chronotropic index (adjusted RR 1.94, 95% CI 1.18 to 3.19, P=0.0009). CONCLUSIONS: The ventilatory and chronotropic responses to exercise are powerful and independent predictors of heart failure mortality.

Adolescent↗
PubMed1999

Refractory heart failure.

Managing patients with heart failure is rooted in appropriate recognition of the syndrome and subsequent tailoring of therapies to individual patients based on the stage of the disease. An individual with asymptomatic left ventricular dysfunction (the earliest stage of heart failure) is treated quite differently than a patient with more advanced heart failure manifested by problematic fluid retention, peripheral organ hypoperfusion with dysfunction, and several comorbidities. The latter patient requires aggressive pharmacologic intervention coupled with other creative strategies that are individually tailored to each individual"s unique clinical circumstance. The therapies available include long-term administration of parenteral inotropic therapy, dialysis, insertion of a ventricular assist device, cardiac transplantation, dynamic skeletal myoplasty, volume reduction surgery, or more standard (but higher risk) operative procedures. New drugs are constantly undergoing evaluation and may lead to additional therapeutic improvements in patients with advanced heart failure. The key is recognizing the appropriate place for more radical therapies.

Adrenergic beta-Antagonists↗
PubMed1999

Preoperative risk factors for right ventricular failure after implantable left ventricular assist device insertion.

BACKGROUND: Implantable left ventricular assist device (LVAD) insertion complicated by early right ventricular (RV) failure has a poor prognosis and is generally unpredictable. METHODS: To determine preoperative risk factors for perioperative RV failure after LVAD insertion, patient characteristics and preoperative hemodynamics were analyzed in 100 patients with the HeartMate LVAD (Thermo Cardiosystems, Inc, Woburn, MA) at the Cleveland Clinic. RESULTS: RV assist device support was required for 11 patients (RVAD group). RVAD use was significantly higher in younger patients, female patients, smaller patients, and myocarditis patients. There was no significant difference in the cardiac index, RV ejection fraction, or right atrial pressure between the two groups preoperatively. The preoperative mean pulmonary arterial pressure (PAP) and RV stroke work index (RV SWI) were significantly lower in the RVAD group (p = 0.015 and p = 0.011, respectively). Survival to transplant was poor in the RVAD group (27%) and was 83% in the no-RVAD group. CONCLUSIONS: The need for perioperative RVAD support was low, only 11%. Preoperative low PAP and low RV SWI were significant risk factors for RVAD use.

Adult↗
PubMed1999

A randomized, multicenter comparison of tacrolimus and cyclosporine immunosuppressive regimens in cardiac transplantation: decreased hyperlipidemia and hypertension with tacrolimus.

BACKGROUND: Tacrolimus-based immunosuppression seems safe and effective in liver and kidney transplantation. To assess the safety and efficacy of tacrolimus (TAC)-based immunosuppression after cardiac transplantation as well as the relative impact of tacrolimus on immunosuppression-related side effects such as hypertension and hyperlipidemia, we conducted a prospective, randomized, open-label, multicenter study of otherwise identical tacrolimus- and cyclosporine-based immunosuppressive regimens in adult patients undergoing cardiac transplantation. METHODS: Eighty-five adult patients (pts) at six United States cardiac transplant centers, undergoing their first cardiac transplant procedure, were prospectively randomized to receive either TAC-based (n = 39) or cyclosporine (CYA)-based (n = 46) immunosuppression. All pts received a triple-drug protocol with 15 pts (18%) receiving peri-operative OKT3 to delay TAC/CYA due to pre-transplant renal dysfunction. Endomyocardial biopsies were performed at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 24, and 52. The study duration was 12 months. RESULTS: Patients were mostly male (87%) Caucasian (90%) with a mean age of 54 years and primary diagnoses of coronary artery disease (55%) and idiopathic dilated cardiomyopathy (41%). There were no significant demographic differences between groups. Patient and allograft survival were not different in the two groups. The probability and overall incidence of each grade of rejection, whether treated or not, and the types of treatment required did not differ between the groups. At baseline and through 12 months of follow-up, chemistry and hematology values were similar between the groups except serum cholesterol was higher in the CYA group at 3, 6, and 12 months (239 vs 205 mg/dL, 246 vs 191 mg/dL, 212 vs 186 mg/dL, respectively, p < 0.001). Likewise, LDL-cholesterol, HDL-cholesterol and triglycerides were significantly higher in the CYA group. More CYA patients received therapy for hypercholesterolemia (71% vs 41% at 12 months, p = 0.01). There were no significant differences in renal function, hyperglycemia, hypomagnesemia, or hyperkalemia during the first 12 months. More CYA patients developed new-onset hypertension requiring pharmacologic treatment (71% vs 48%, p = 0.05). The incidence of infection was the same for the two groups (2.6 episodes/pt/12 month follow-up). CONCLUSION: Tacrolimus-based immunosuppression seems effective for rejection prophylaxis during the first year after cardiac transplantation and is associated with less hypertension and hyperlipidemia and no difference in renal function, hyperglycemia or infection incidence when compared to cyclosporine-based immunosuppression.

Adult↗
PubMed1999

Oral steroid pulse without taper for the treatment of asymptomatic moderate cardiac allograft rejection.

BACKGROUND: The most frequently administered treatment for asymptomatic ISHLT Grade 3A cardiac allograft rejection is intravenous steroids or oral steroid pulse with a taper. This study analyzes the efficacy of 3-day 100-mg course of prednisone without a tapered regimen for the treatment of asymptomatic moderate cardiac allograft rejection. METHODS: All new episodes of asymptomatic ISHLT Grade 3A rejections were treated with oral steroid pulse without taper, consisting of 100 mg of prednisone for 3 consecutive days followed by resuming the pre-rejection steroid dose on the fourth day. We retrospectively reviewed the histologic response of all treated episodes among all cardiac transplant recipients transplanted between January 1995 through December 1997 who were treated with triple therapy consisting of cyclosporine, azathioprine and steroids. Patients receiving additional or alternative immunosuppressives were excluded from the study. The treated episodes were analyzed as responders if the follow-up biopsy were Grade 0, 1A, 1B, or 2; treatment was counted as non-responders if the follow-up biopsy showed Grade 3A or higher. RESULTS: Of 230 cardiac transplant recipients, 100 patients received a 3-day 100 mg course of prednisone without taper for 174 new episodes of asymptomatic ISHLT Grade 3A rejection. The overall response rate was 75% (130/174 rejection episodes). A significant difference in the response rate was observed depending on the number of days post transplant. A comparison of the success rates among rejections which occurred > 90 days post transplant versus < 30 days revealed responses to be 88% versus 70% (p = 0.02); for rejections treated > 60 days post transplant versus < 30 days showed success rates of 84% versus 70% (p = 0.04). The mean age of the recipient revealed a trend to be lower among the non-responder group (49+/-12 years versus 53+/-9 years, p = 0.07). Having left ventricular assist device as a bridge to transplant did not significantly affect the treatment outcome. The response rates were 69% for the patients who required the assist device versus 77% for those not bridged (p = ns). There was no significant difference in the gender or the baseline immunosuppressive doses between the responders and non-responders. The cost of a 3-day outpatient, visiting nurse supervised intravenous steroid therapy versus 3 days of oral prednisone was $861 vs $6.88. CONCLUSION: Oral steroid pulse without taper is an effective and economical way to treat asymptomatic moderate grade cardiac allograft rejection. A 3-day course of 100 mg of prednisone without taper should be considered as first line of therapy for clinically stable form of moderate cardiac allograft rejection occurring > 60 days post transplant.

Administration, Oral↗
PubMed1999

Contemporary management of patients with left ventricular systolic dysfunction. Results from the Study of Patients Intolerant of Converting Enzyme Inhibitors (SPICE) Registry.

AIMS: The reported prevalence of angiotensin-converting enzyme (ACE) inhibitor use in patients with heart failure varies considerably. Recent reports suggest that many patients who could benefit from such therapy are not receiving ACE inhibitors. The Study of Patients Intolerant of Converting Enzyme Inhibitors (SPICE) Registry was established to understand better the demographics, characteristics, and contemporary use of ACE inhibitors in an international registry. METHODS AND RESULTS: Between August 1996 and April 1997, each of 105 study centres from eight countries in North America and Europe was invited to review retrospectively the medical records of 100 consecutive patients with left ventricular ejection fractions </=35%. The median age of the 9580 Registry patients was 66 years, 26% were women, the median ejection fraction was 27%, and the primary aetiology of left ventricular dysfunction was ischaemic (63%). Eighty percent of patients were receiving ACE inhibitors. The most common reason for non-use of ACE inhibitors was intolerance (9%). CONCLUSION: The SPICE Registry provides a contemporary description of the demographics and management of patients with documented left ventricular systolic dysfunction. The contemporary use of ACE inhibitors (80%) appears to be higher than previously reported and the main reason for non-use is perceived intolerance (9%).

Aged↗
PubMed1999

Inappropriate use of digoxin in the elderly: how widespread is the problem and how can it be solved?

Cardiovascular disease is ubiquitous within the elderly population and requires treatment with multiple types of medications. As with any cardiovascular pharmaceutical regimen, the risk versus the benefit of each medication must be strongly considered. This is particularly true where, for various reasons, adverse effects are more often prevalent and pronounced. Over the years, it has been documented that digoxin is a frequently prescribed medication in elderly populations. Although this drug can be beneficial when used in the appropriate setting, recent data would suggest that inappropriate administration of digoxin is common and not without potentially serious consequences. Currently, the use of digoxin can be advocated to control heart failure in atrial fibrillation and when added to ACE inhibitors and diuretics in those patients with symptomatic heart failure related to systolic left ventricular dysfunction. It is likely that the excessive use of digoxin in elderly populations as discussed in this review is perhaps based on the prevalence of diastolic heart failure in the elderly as well as other co-morbid conditions that may mimic heart failure signs and symptoms. Since the elderly appear to be at high risk for digoxin toxicity, the inappropriate use of this medication to treat these conditions could result in significant and unnecessary morbidity. It is proposed that echocardiography should be performed in most elderly patients when congestive heart failure is suspected. This simple diagnostic tool, along with a careful history and medical examination, would hopefully prevent the misinterpretation of confusing clinical findings and would help to identify the patients with normal systolic function or valvular disease such as critical aortic stenosis, where digoxin treatment would not be warranted. If it is necessary to administer digoxin, then the likelihood of significant toxicity can be greatly reduced by using an algorithm to calculate the appropriate dosage, which takes into consideration the patient's gender, bodyweight and creatinine clearance. Although it is probable that the indications for digoxin use to treat congestive heart failure will continue to evolve, at the present time most would recommend using this agent in symptomatic heart failure related to a reduction in left ventricular systolic function or when associated with atrial fibrillation.

Aged↗
PubMed1999

Cardiac transplantation at the Cleveland Clinic Foundation.

The past 15 years has seen a significant evolution of heart transplant patient selection criteria, definition of suitable donors, immunosuppressive strategies, infection prophylaxis and treatment, and post-transplant patient surveillance. Primarily important has been broadening of the donor suitability definition and an evolution toward transplanting more ill and hemodynamically unstable patients. Despite "pushing the envelope" with both patient and donor selection and with transplanted patients generally being more ill, we believe our outcomes at the Cleveland Clinic Foundation are exemplary. The one- and 3-year survival rates for 265 heart transplants performed during 1996-1998 were 88% and 81%, respectively. Key to the success of our program has been close interdisciplinary working relationships and respect, broad and expert consultative support services, a desire to investigate clinical challenges, and dedication to excellence. Of additional importance is the realization that no matter how difficult we believe our difficulties are, we realize that those of our patients are vastly greater.

Adult↗
PubMed1998

Development of transplantation vasculopathy and progression of donor-transmitted atherosclerosis: comparison by serial intravascular ultrasound imaging.

BACKGROUND: Transplant coronary artery disease is a combination of atherosclerosis transmitted from the donor and new lesions of allograft vasculopathy. We sought to determine the morphological characteristics of allograft vasculopathy and differentiate it from donor-transmitted atherosclerosis with serial intravascular ultrasound. METHODS AND RESULTS: Intravascular ultrasound examination was performed in 93 patients at 27.2+/-15.0 and 369. 7+/-23.9 days after transplantation. The maximally and minimally diseased sites were selected in each segment as defined by Coronary Artery Surgery Study classification. For each matched site, maximal plaque thickness was measured. Lesions (maximum plaque thickness >/=0.5 mm) present at baseline examination were defined as donor lesions. On follow-up, lesions that developed at previously normal sites were defined as de novo lesions. The distribution and severity of donor and de novo lesions were similar in proximal, mid, and distal segments. The de novo lesions were less focal (43% vs 74%) and more circumferential (69% vs 45%) compared with the donor lesions, but there was significant morphological heterogeneity. Similar numbers of patients with and those without donor lesions developed de novo lesions. Moreover, progression of donor lesions was not associated with the presence or absence of de novo lesions. CONCLUSIONS: Differentiation between early allograft vasculopathy from conventional atherosclerosis by distribution and morphology of lesions alone is difficult. Serial intravascular ultrasound imaging with early baseline examination is necessary to make this distinction. This distinction is important because the progression of donor lesions and the development of de novo lesions are independent of each other.

Adolescent↗