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Biomedical subjects

M B Fowler

Publications and source records attributed to M B Fowler.

At least 37 records · Page 2Linked to original sources
PubMed1995

Selecting candidates for cardiac transplantation. How to assess exclusion criteria and predict who will benefit.

The fundamental indication for cardiac transplantation is advanced heart failure that is unresponsive to medical therapy in patients with coronary artery disease or dilated cardiomyopathy. Other potential indications include advanced valvular or congenital heart disease and, more rarely, hypertrophic or restrictive cardiomyopathy, sarcoidosis, myocarditis, and primary unresectable cardiac tumors. Determining which patients have symptoms that are truly refractory to medical therapy is difficult. Ejection fraction or clinical status during acute decompensation is not a sufficient criterion for candidacy.

Cardiac Output, Low↗
PubMed1995

Spontaneous reversibility of catecholamine-induced cardiotoxicity in rats.

In order to evaluate the chronic in vivo effects of excessive catecholamine levels, and the potential for spontaneous reversibility of these effects, we employed a chronic two-week infusion of epinephrine in rats. Epinephrine infusion resulted in myocyte hypertrophy, left ventricular fibrotic degenerative changes, diminished response to adrenergic stimuli, and enhanced left ventricular papillary contractile responses to calcium. Two weeks after cessation of the epinephrine infusion, left ventricular fibrotic degenerative changes were reduced, and responses to adrenergic stimuli were partially restored. However, myocyte hypertrophy and the enhanced responses to calcium persisted in these animals. This study indicates the potential for spontaneous reversal of some of epinephrine's toxic effects, and further implies that the loss in adrenergic sensitivity in epinephrine-treated animals may be a desensitization phenomenon, while the alterations in calcium response are less readily reversed.

Adenylyl Cyclases↗
PubMed1994

Incidence of myocarditis in peripartum cardiomyopathy.

Peripartum cardiomyopathy (PC), an uncommon cause of peripartum heart failure, is defined as a cardiomyopathy presenting in the last trimester of pregnancy or the first 6 months postpartum, without evidence of preexisting cardiovascular disease. The etiology of PC and idiopathic dilated cardiomyopathy (IDC) remains uncertain. Several reports have addressed possible differences in clinical presentation and prognosis between these groups. A relatively high incidence of myocarditis has been recently reported in patients with PC, raising the possibility that this may represent a distinct difference between this condition and IDC. A retrospective review of endomyocardial biopsy specimens from 34 patients fulfilling the criteria for a diagnosis of PC was therefore performed to further evaluate this finding. Results indicate a lower incidence of myocarditis (8.8%, 3 of 34) than that reported in other studies. This incidence was comparable to that found in an age- and sex-matched control population undergoing transplantation for IDC (9.1%, 2 of 22). Factors that may influence the diverse range in the reported incidence of myocarditis are discussed.

Adult↗
PubMed1994

Long-term outcome after heart transplantation for peripartum cardiomyopathy.

To elucidate the long-term outcome and frequency of complications after heart transplantation for peripartum cardiomyopathy (PPCM), we compared the courses of eight consecutive patients undergoing transplantation for PPCM with those of nine female age-matched control subjects undergoing transplantation for idiopathic dilated cardiomyopathy (IDCM). No significant differences could be found in baseline variables between the two groups with the exception of the number of pregnancies (2.5 +/- 1.5 vs 0, p = 0.0002). Two patients in each group died during the first 6 months after transplantation, and one in each group died later. Actuarial survival rates were 75% +/- 15% and 78% +/- 14% (p = NS) at 1 year and 60% +/- 18% and 78% +/- 14% (p = NS) at 5 years in PPCM and IDCM patients, respectively. Linearized rejection rates during the first 3 months were 1.85 +/- 0.56 and 1.91 +/- 0.49 (p = NS) and during the second 3 months were 0.18 +/- 0.18 and 0.45 +/- 0.26 (p = NS), respectively. Similarly no significant differences in linearized infection rates were found. Among patients surviving more than 6 months after transplantation, after a mean follow-up period of 4.5 +/- 3.1 years for those with PPCM and 7.8 +/- 3.2 years for those with IDCM, 83% and 100%, respectively, were rehabilitated; hemodynamic findings were normal in all patients and the frequency of other transplant-associated complications was similar in both groups. In conclusion, heart transplantation is a valuable option for patients with PPCM and severe congestive heart failure that is unresponsive to conventional treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1994

Cardiac transplantation: the Stanford experience in the cyclosporine era.

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)

Actuarial Analysis↗
PubMed1993

Beneficial effects of metoprolol in idiopathic dilated cardiomyopathy. Metoprolol in Dilated Cardiomyopathy (MDC) Trial Study Group.

Several small studies have suggested beneficial effects of long-term beta-blocker treatment in idiopathic dilated cardiomyopathy. Our large multicentre study aimed to find out whether metoprolol improves overall survival and morbidity in this disorder. 383 subjects with heart failure from idiopathic dilated cardiomyopathy (ejection fraction < 0.40) were randomly assigned placebo or metoprolol. 94% were in New York Heart Association functional classes II and III, and 80% were receiving background treatment. A test dose of metoprolol (5 mg twice daily) was given for 2-7 days; those tolerating this dose (96%) entered randomisation. Study medication was increased slowly from 10 mg to 100-150 mg daily. There were 34% (95% CI -6 to 62%, p = 0.058) fewer primary endpoints in the metoprolol than the placebo group; 2 and 19 patients, respectively, deteriorated to the point of needing transplantation and 23 and 19 died. The change in ejection fraction from baseline to 12 months was significantly greater with metoprolol than with placebo (0.13 vs 0.06, p < 0.0001). Pulmonary capillary wedge pressure decreased more from baseline to 12 months with metoprolol than with placebo (5 vs 2 mm Hg, p = 0.06). Exercise time at 12 months was significantly greater (p = 0.046) in metoprolol-treated than in placebo-treated patients. In patients with idiopathic dilated cardiomyopathy, treatment with metoprolol prevented clinical deterioration, improved symptoms and cardiac function, and was well tolerated.

Adolescent↗
PubMed1993

Controlled trials with beta blockers in heart failure: metoprolol as the prototype.

Early studies of acute beta-blocking drug therapy, such as metoprolol and acebutolol, in patients with idiopathic dilated cardiomyopathy (IDC) and survivors of acute myocardial infarction were interpreted to have detrimental or, at best, neutral effects on cardiac and clinical hemodynamics. Subsequent trials of longer duration with metoprolol versus placebo in patients with IDC demonstrated an "exceptional response" to beta-blocker therapy in some individuals. Hemodynamics and patient demographic characteristics appear not to predict those patients who may or may not benefit. Controlled trials with newer beta-adrenoceptor modulating drugs--such as xamoterol, bucindolol, and carvedilol--have been equivocal in some situations. Xamoterol has been associated with progressive heart failure and increased sudden cardiac deaths, whereas bucindolol improved clinical heart failure symptoms and testing hemodynamic parameters, as did treatment with carvedilol, in patients with ischemic cardiomyopathy. The success of these agents in patients with congestive heart failure may be in their ability to modulate the excessive myocardial stimulation of the beta-adrenergic nervous system while benefitting the dynamics of the peripheral system.

Adrenergic beta-Antagonists↗
PubMed1993

Beta-blockers in heart failure: potential of carvedilol.

The excessive or inappropriate response of the neuroendocrine system to impaired cardiac performance has become a major therapeutic target in heart failure. While the benefits of ACE inhibition and vasodilation are now established, and the necessary effects of diuretic therapy accepted, there is increasing evidence that in many patients additional benefit would follow modulation of the sympathetic nervous system. Beta-adrenergic blocking drugs improve survival following myocardial infarction and have improved patients with heart failure. Drugs such as carvedilol, which combine vasodilation mediated through alpha-adrenergic blockade with beta-adrenergic blockade have an attractive profile as they unite these two pharmacological actions in a way that may benefit patients with heart failure.

Adrenergic beta-Antagonists↗
PubMed1993

Protective effect of clentiazem against epinephrine-induced cardiac injury in rats.

We investigated the effects of clentiazem, a 1,5-benzothiazepine calcium antagonist, on epinephrine-induced cardiomyopathy in rats. With 2-week chronic epinephrine infusion, 16 of 30 rats died within 4 days, and severe ischemic lesions and fibrosis of the left ventricles were observed. In epinephrine-treated rats, left atrial and left ventricular papillary muscle contractile responses to isoproterenol were reduced, but responses to calcium were normal or enhanced compared to controls. Left ventricular alpha and beta adrenoceptor densities were also reduced compared to controls. Treatment with clentiazem prevented epinephrine-induced death (P < .05), and attenuated the ventricular ischemic lesions and fibrosis, in a dose-dependent manner. Left atrial and left ventricular papillary muscle contractile responses to isoproterenol were reduced compared to controls in groups treated with clentiazem alone, but combined with epinephrine, clentiazem restored left atrial responses and enhanced left ventricular papillary responses to isoproterenol. On the other hand clentiazem did not prevent epinephrine-induced down-regulation of alpha and beta adrenoceptors. Interestingly, clentiazem, infused alone, resulted in decreased adrenergic receptor densities in the left ventricle. Clentiazem also did not prevent the enhanced responses to calcium seen in the epinephrine-treated animals, although the high dose of clentiazem partially attenuated the maximal response to calcium compared to epinephrine-treated animals. In conclusion, clentiazem attenuated epinephrine-induced cardiac injury, possibly through its effect on the adrenergic pathway.

Animals↗
PubMed1992

Influence of preoperative pulmonary artery pressure on mortality after heart transplantation: testing of potential reversibility of pulmonary hypertension with nitroprusside is useful in defining a high risk group.

Patients with pulmonary hypertension are at risk of developing fatal right heart failure after heart transplantation. To evaluate this risk potential, candidates for heart transplantation are screened by measuring rest right heart pressures and the response to nitroprusside. To test the validity of this approach, the influence of pretransplantation right heart catheterization data on outcome after transplantation was analyzed in 293 of 301 consecutive patients. Patients with a pulmonary vascular resistance greater than 2.5 Wood units measured at baseline study had a 3-month mortality rate of 17.9% compared with 6.9% in patients with resistance less than or equal to 2.5 units (p less than 0.02). Patients with a pulmonary vascular resistance greater than 2.5 units at baseline study could be differentiated further according to their hemodynamic response to nitroprusside; those whose resistance could be reduced to less than or equal to 2.5 units with a stable systemic systolic pressure greater than or equal to 85 mm Hg had a 3-month mortality rate of only 3.8%. In contrast, patients whose pulmonary vascular resistance could not be reduced to less than 2.5 units, and those whose resistance could be reduced to less than or equal to 2.5 units but only at the expense of systemic hypotension (systolic pressure less than or equal to 85 mm Hg) had a 3-month mortality rate of 40.6% and 27.5%, respectively. Furthermore, all 10 patients who died of right heart failure belonged to the latter two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

The influence of preoperative patient characteristics on early and late survival following cardiac transplantation.

In an attempt to identify the preoperative factors that influence survival following cardiac transplantation, we retrospectively analyzed multiple demographic, clinical, and hemodynamic data of 301 consecutive patients who underwent cardiac transplantation between December 1980 and July 1988 (cyclosporine era). Univariate and multivariate regression analyses revealed that the two most deleterious risk factors for premature death following transplantation were pulmonary hypertension not responsive to vasodilator challenge and preoperative requirement of hemodynamic support (intravenous inotropes or mechanical assistance). The combination of these two independent risk factors was an even stronger predictor of mortality (relative risk, 6:1; p less than 0.0001): the 3-month actuarial survival rate of the 20 patients with this combination was 30.3% versus 78.4% of the 47 patients with only pulmonary hypertension, 87.9% of the 42 patients with only the requirement of hemodynamic support, and 95.3% of the 172 patients with neither of these two risk factors. The difference in postoperative mortality between patients with versus those without these two risk factors is due to a higher rate of fatal infectious complications: six of 20 patients (30%) with both risk factors died from infection within 3 months after transplant compared with three deaths among 172 patients (1.7%) with neither of these risk factors. The majority of fatal infections were pulmonary. There were significantly more fatal and nonfatal infectious episodes in patients with one or both of these risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Cardiac transplantation in patients with preexisting neoplastic diseases.

Cardiac transplantation has traditionally been reserved for individuals with end-stage congestive heart failure (CHF) in whom there is no history of other life-threatening systemic disorders. In most transplant centers, patients with a history of malignancy and severe heart failure have not been considered acceptable candidates for cardiac transplantation. In the last 4 years at Stanford University Medical Center, 8 cardiac transplants have been performed in 7 patients with a history of neoplastic disease. Six of these patients had already received treatment for lymphoproliferative disorders and in 1 case, a patient underwent a transplant after treatment for adenocarcinoma of the colon. Six of the 7 patients were discharged from the hospital and in that group, the 1-year posttransplant survival rate was 71%. This was comparable to an overall 1-year survival rate of 80% for patients undergoing a cardiac transplant at our center during the same period of time. At follow-up averaging over 2 years, there has been 1 case of recurrent neoplasia. One patient with evidence of radiation-induced pulmonary damage died of respiratory failure 2 days after transplantation. One patient required retransplantation because of intractable rejection and subsequently died from infectious complications. Immunosuppressive therapy in these patients has not been associated with an increased risk for neoplastic recurrence or for the development of posttransplant lymphoproliferative disorders. The current study demonstrates that in a carefully selected group, previously treated neoplastic disease should not represent a contraindication to cardiac transplantation.

Adolescent↗
PubMed1990

Cardiac adrenoceptors in the failing heart: effect of intervention.

The sympathetic nervous system is chronically activated in heart failure. This results in a reduction in numbers and sensitivity of beta-receptors, making the heart less responsive to the actions of catecholamines. This is specific to beta-receptors, the adenycyclase system being largely unaffected. Sympathomimetic agents are still used in patients with heart failure to augment cardiac contractility, but tachyphylaxis limits their long-term usefulness, and they may actually cause further myocardial damage. On the other hand, beta-blockade can improve sensitivity to catecholamines and cardiac action in some patients with severe left ventricular dysfunction, although this treatment can be hazardous and cannot yet be routinely recommended. Partial beta-agonists are theoretically useful since they can provide baseline sympathetic drive while protecting the heart against excessive sympathetic stimulation and down-regulation of beta-receptors. Xamoterol, a partial agonist with half the sympathetic activity of isoprenaline, has been shown to be superior to placebo and to digoxin in patients with mild to moderate heart failure.

Adrenergic beta-Agonists↗
PubMed1990

Selection of patients for cardiac transplantation.

In order to appropriately allocate the precious resource of donor organs for cardiac transplantation, one must adequately assess the prognosis of the prospective recipient with or without transplantation. This requires knowledge of the natural history of heart failure as well as those parameters by which it is evaluated. It also requires knowledge of those factors that make patients appropriate versus inappropriate surgical candidates. This article approaches both these necessary areas of patient evaluation.

Age Factors↗
PubMed1989

Frequency of familial nature of dilated cardiomyopathy and usefulness of cardiac transplantation in this subset.

A familial etiology was identified on the basis of family history in 16 (8.75%) of 184 patients undergoing cardiac transplantation at Stanford for endstage dilated cardiomyopathy (DC). These 16 patients, from 11 families, included 5 sibling pairs. To help determine optimal management of such patients, their case histories and posttransplant courses were reviewed. Mean age of patients at presentation was 23 +/- 15 years. In sibling pairs, duration of symptoms from onset to diagnosis was 14 +/- 5 weeks for the first sibling, but only 4 +/- 2 weeks for the second. Progressive cardiac enlargement was documented radiographically in siblings of transplant recipients in 2 families before the onset of symptoms. The posttransplant course with regard to rejection incidence, infectious complications, coronary artery disease and malignancy was similar to that of the 168 patients with nonfamilial DC. Actuarial survival at 5 years after transplantation was 80%. Thirteen patients (including all sibling pairs) are alive 1 to 11 years after transplantation. Sepsis was the cause of death in 3 patients, occurring during the early postoperative period in 2 and following retransplantation for graft atherosclerosis 7 years after the initial transplant in the third patient. Thus, diagnosis of DC in childhood or adolescence mandates evaluation and surveillance of family members, because this disease can progress rapidly. The favorable results of cardiac transplantation for familial DC suggest that it should be promptly considered for such patients with end-stage disease.

Adolescent↗