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James D Fett

Publications and source records attributed to James D Fett.

18 recordsLinked to original sources
PubMed2006

Brief communication: Outcomes of subsequent pregnancy after peripartum cardiomyopathy: a case series from Haiti.

BACKGROUND: Maternal risks with pregnancies after an index diagnosis of peripartum cardiomyopathy (PPCM) are inadequately understood. OBJECTIVE: To describe the clinical outcomes of subsequent pregnancy in Haitian women with PPCM. DESIGN: Prospectively identified cases from a defined population base, 2000-2005. SETTING: Hôpital Albert Schweitzer, Deschapelles, Haiti. PATIENTS: 15 patients with PPCM and subsequent pregnancies among 99 prospectively identified patients with PPCM. MEASUREMENTS: Clinical and echocardiographic parameters. RESULTS: Fifteen women with PPCM had 16 subsequent pregnancies after the index pregnancies. Eight of these patients experienced worsening heart failure; of these, 1 died and 1 regained normal left ventricular systolic function. Seven patients tolerated pregnancy without worsening heart failure, and ventricular function recovered in these patients within 30 months after the subsequent pregnancy. LIMITATIONS: The results may not apply to non-Haitian women, and power was insufficient to identify factors that might predict recovery (n = 15). CONCLUSIONS: Half of the women with subsequent pregnancy after PPCM experienced worsening heart failure and long-term systolic dysfunction, while the other half experienced no deterioration and regained normal left ventricular systolic function.

Adult↗
PubMed2005

Inflammation and virus in dilated cardiomyopathy as indicated by endomyocardial biopsy.

Polymerase chain reaction (PCR) testing of "quick-freeze" endomyocardial biopsy tissue for identification of evidence of viral presence is an important new tool in the investigation of unexplained dilated cardiomyopathy patients; and particularly those who are not improving with conventional treatment. Alternate therapeutic measures, including anti-viral treatment and immunosuppressive therapy, offer promise in contributing to left ventricular systolic function improvement. It is important to include PCR testing for a broad spectrum of cardiotropic viruses prior to the application of immunosuppressive therapy.

Biopsy↗
PubMed2005

Peripartum cardiomyopathy: inflammatory markers as predictors of outcome in 100 prospectively studied patients.

AIMS: Peripartum cardiomyopathy (PPCM) is a disorder of unknown aetiology with a course and outcome that is largely unpredictable. We evaluated the prognostic role of multiple inflammatory markers in the plasma of a large cohort of African patients with PPCM. METHODS AND RESULTS: The study of 100 patients with newly diagnosed PPCM was single-centred, prospective, and longitudinal. Clinical assessment, echocardiography, and blood analysis were done at baseline and after 6 months of standard therapy. Inflammatory markers were measured at baseline only. Fifteen patients died. Left ventricular ejection fraction (LVEF) improved from 26.2+/-8.2 to 42.9+/-13.6% at 6 months (P<0.0001). However, normalization of LVEF (>50%) was only observed in 23%. Baseline levels of C-reactive protein correlated positively with baseline LV end-diastolic (rs=0.33, P=0.0026) and end-systolic (rs=0.35, P=0.0012) diameters and inversely with LVEF (rs=-0.27, P=0.015). Patients who died presented with significantly lower mean EF and higher Fas/Apo-1 plasma values (P<0.05). Fas/Apo-1 and New York Heart Association functional class (NYHA FC) predicted mortality at baseline. CONCLUSION: Plasma markers of inflammation were significantly elevated and correlated with increased LV dimensions and lower LVEF at presentation. Baseline Fas/Apo-1 and higher NYHA FC were the only predictors of mortality. Normalization of LVEF was only observed in 23% of this African cohort.

Adolescent↗
PubMed2005

Inhibition of progenitor dendritic cell maturation by plasma from patients with peripartum cardiomyopathy: role in pregnancy-associated heart disease.

Dendritic cells (DCs) play dual roles in innate and adaptive immunity based on their functional maturity, and both innate and adaptive immune responses have been implicated in myocardial tissue remodeling associated with cardiomyopathies. Peripartum cardiomyopathy (PPCM) is a rare disorder which affects women within one month antepartum to five months postpartum. A high occurrence of PPCM in central Haiti (1 in 300 live births) provided the unique opportunity to study the relationship of immune activation and DC maturation to the etiology of this disorder. Plasma samples from two groups (n = 12) of age- and parity-matched Haitian women with or without evidence of PPCM were tested for levels of biomarkers of cardiac tissue remodeling and immune activation. Significantly elevated levels of GM-CSF, endothelin-1, proBNP and CRP and decreased levels of TGF-beta were measured in PPCM subjects relative to controls. Yet despite these findings, in vitro maturation of normal human cord blood derived progenitor dendritic cells (CBDCs) was significantly reduced (p < 0.001) in the presence of plasma from PPCM patients relative to plasma from post-partum control subjects as determined by expression of CD80, CD86, CD83, CCR7, MHC class II and the ability of these matured CBDCs to induce allo-responses in PBMCs. These results represent the first findings linking inhibition of DC maturation to the dysregulation of normal physiologic cardiac tissue remodeling during pregnancy and the pathogenesis of PPCM.

Adolescent↗
PubMed2005

Five-year prospective study of the incidence and prognosis of peripartum cardiomyopathy at a single institution.

OBJECTIVE: To determine the incidence and prognosis of peripartum cardiomyopathy (PPCM) in rural Haiti. PATIENTS AND METHODS: Prospectively identified patients with PPCM treated at the Hospital Albert Schweitzer (HAS), Deschapelles, Haiti, were included in this study. Patients who presented to HAS from February 1, 2000, to January 31, 2005, were identified through a search of the HAS PPCM Registry. Clinical and serial echocardiographic data were collected on these patients. RESULTS: The 5-year experience confirms the high incidence of PPCM in this area, approximately 1 case per 300 live births, which is severalfold the estimated incidence in the United States (estimated 1 case per 3000 to 4000 live births). In this population, the ratio of PPCM deaths for the 5-year period was 47.1 per 100,000 births compared with the US ratio of 0.62 per 100,000 births. The mortality rate was 15.3% (15 deaths of 98 patients), and the mean follow-up was 2.2 years (range, 1 month to 5 years). Five years after the initiation of the HAS PPCM Registry search, 26 (28%) of 92 patients with PPCM observed for at least 6 months had regained normal left ventricular function. The difference in left ventricular echocardiographic features at diagnosis between deceased patients and survivors was not statistically significant: mean end-diastolic dimension (6.2 vs 5.8 cm; P=.08), ejection fraction (22% vs 25%; P=.12), and fractional shortening (16% vs 15%; P=.46). Left ventricular echocardiographic features at diagnosis were unable to predict individually who would eventually recover, although a statistically significant difference occurred at diagnosis between the recovered group and nonrecovered group for mean ejection fraction (28% vs 23%; P<.001) and fractional shortening (17% vs 14%; P=.004). CONCLUSION: Peripartum cardiomyopathy occurs significantly more commonly in rural Haiti on a per capita basis than in the United States. Patients with PPCM have a higher mortality rate and a poorer return of normal ventricular function.

Adolescent↗
PubMed2002

Peripartum cardiomyopathy: a selenium disconnection and an autoimmune connection.

BACKGROUND: Increased incidence and prevalence of peripartum cardiomyopathy (PPCM) have been documented in the Hospital Albert Schweitzer (HAS) District of Haiti. Although the basis for this increased incidence of PPCM remains unclear, there is growing evidence for an underlying autoimmune process. One potential risk factor for increased autoreactivity is a micronutrient deficiency. In Africa, low plasma selenium (Se) level has been reported as a possible risk factor for PPCM. This report details results of initial studies to test the hypothesis that plasma levels of Se and/or other micronutrients may be related to PPCM risk in this population. METHODS: Under the direction of the Institutional Review Board (HAS Ethics Committee) and with informed consent, levels of Se and other micronutrients were measured in plasma samples obtained from PPCM mothers and parity-matched control mothers from the HAS District of Haiti. RESULTS: Mean plasma Se level in 18 PPCM patients was 110 ng/ml (range 67-145) compared to mean plasma Se level in 34 control mothers of 121 ng/ml (range 98-172) (P=0.1748). These levels are substantially greater than those reported for pediatric patients with Keshan cardiomyopathy, which can be prevented by Se prophylaxis. No deficiency or significant difference was found in any other micronutrient tested (Vitamin A (retinol), Vitamin B(12), Vitamin C, Vitamin E, and B-Carotene) for these PPCM and control mothers. CONCLUSION: Although there are several possible mechanisms by which Se could play a role in the pathobiology of PPCM, there is no evidence that Se deficiency is a cause of PPCM or a risk factor for the development of PPCM in this district of Haiti. The results of this investigation indicate that future studies of PPCM in this population should focus on other potential etiologic and risk factors.

Antioxidants↗
PubMed2002

Is peripartum cardiomyopathy an organ-specific autoimmune disease?

Peripartum cardiomyopathy (PPCM) is a rare and serious heart disease that exclusively afflicts women during childbearing years. Symptoms include rapid onset of cardiovascular insufficiency occurring during pregnancy, initiated anytime between the third trimester until 5 months post-partum in the absence of any other signs or history of heart disease. The rare incidence of PPCM and the absence of any relevant animal models have limited research and understanding of the pathogenic mechanisms involved. Several compelling sets of data support the view that PPCM is a form of autoimmune IDCM. However, PPCM differs from autoimmune IDCM in that (a) it is associated with unique sets of autoantibodies and autoantigens, (b) it has a relatively rapid onset, and (c) it exclusively affects pregnant women. Furthermore, the etiology of PPCM is dependent on the interaction of pregnancy associated factors, e.g. increased hemodynamic stress, vasoactive hormones and fetal microchimerism, that co-operate in the context of essential immune and genetic environments for disease progression. Our model of PPCM attempts to represent how multiple factors, e.g. pregnancy, genetics, immune dysregulation, and fetal microchimerism are held in a complex dynamic balance that can co-operate towards the maintenance of cardiovascular health or disease in the mother (Fig. 1). A more thorough study of the precise nature of the cardiac tissue autoantigens may lead to the identification of the mechanisms of breakdown of self-tolerance and perhaps also the putative etiologic agent(s). Further studies of the precise nature of the cardiac tissue autoantigens and the specific factors governing the balance between tolerance and autoimmunity in the periphery, e.g. expression of PD-L1 on cardiac tissues and the role of regulatory T cells, may help to elucidate the autoimmune mechanisms of PPCM.

Animals↗
PubMed2002

Peripartum cardiomyopathy in the Hospital Albert Schweitzer District of Haiti.

OBJECTIVE: This report details current epidemiologic information on peripartum cardiomyopathy in 1 district of Haiti and represents the initial report of an ongoing investigation that addresses potential etiologic and prognostic factors. Another goal is to alert the medical community of what appears to be a high-incidence area. STUDY DESIGN: A detailed peripartum cardiomyopathy registry has been implemented to include a review of case records from 1994 to 2000 and subsequently to identify new cases from February 1, 2000, to July 1, 2001. The Hospital Albert Schweitzer District of Haiti is a 600-square mile area with approximately 258,000 population served by a hospital, an associated clinic, and outlying health centers. There are approximately 7740 live births annually. This report details epidemiologic information on the HAS District peripartum cardiomyopathy patients including incidence, mortality rate, complications, and prognostic factors. RESULTS: There were 47 confirmed patients (retrospective cohort, 20 patients; prospective cohort, 27 patients), which was approximately 1 case per 400 live births (compared with an incidence of 1 case per 3000 to 4000 live births in the United States). There were 4 deaths (14% of 29 patients with follow-up), and 7 complications (pulmonary embolism, 1 case; hemiplegia, 1 case; subsequent deterioration of heart function, 5 cases). The prognosis for subsequent pregnancy was 4 of 5 cases (80%) of recurrent congestive heart failure. CONCLUSION: Peripartum cardiomyopathy appears to be relatively common in the Hospital Albert Schweitzer District of Haiti. A core group of patients is identified for ongoing epidemiologic and immunohematologic investigation of risk factors and potential etiologic factors.

Adolescent↗
PubMed2002

Autoimmune mechanisms as the basis for human peripartum cardiomyopathy.

The etiology and mechanisms of pathogenesis of human peripartum cardiomyopathy (PPCM) remain unknown. The incidence and prevalence of this disease is rare in some parts of the world and more common in others. The purpose of this review is to summarize our current knowledge of the factors that have been entertained which may contribute to the pathogenesis of PPCM with special emphasis on more recent data from our laboratory that provide support to the view that this disease is an autoimmune disease with multiple contributing factors and effector mechanisms. This is supported by the fact that sera from PPCM patients contain high titers of auto-antibodies against normal human cardiac tissue proteins of 37, 33, and 25 kD that was not present in the sera of patients with idiopathic cardiomyopathy (IDCM), indicating for the first time that PPCM is distinct from IDCM. In addition to the autoantibodies, the PBMC's from PPCM patients demonstrate a heightened level of fetal microchimerism, an abnormal cytokine profile, decreased levels of CD4+ CD25lo regulatory T cells, and a significant reduction in the plasma levels of progesterone, estradiol and relaxin in PPCM patients as compared with other normal pregnant non-PPCM patients. A potential role for reduced plasma levels of selenium in the pathogenesis of select PPCM patients was also noted. These findings for the first time suggest that such abnormalities may in concert lead to the initiation and perpetuation of an autoimmune process, which leads to cardiac failure and disease. Identification of the precise nature of the cardiac tissue autoantigens (currently in progress) will pave the way for the delineation of mechanism of this autoimmune disease. A working model for the pathogenesis of this disease is also described herein.

Autoimmune Diseases↗
PubMed2002

Peripartum cardiomyopathy. Insights from Haiti regarding a disease of unknown etiology.

Peripartum cardiomyopathy (PPCM) is a disease of unknown etiology characterized by the onset of left ventricular failure during the period of 1 month antepartum to 5 months postpartum. The PPCM Project at Hospital Albert Schweitzer (HAS) in Haiti has identified 78 cases of PPCM since February 1, 2000, representing an incidence of 1 case per 350 to 400 live births, which is severalfold the estimated incidence in the United States. The reasons for this high incidence in Haiti are unknown. Ongoing investigations have identified the presence of several anticardiac antibodies in many women at HAS who have PPCM, suggesting that PPCM is a unique form of dilated cardiomyopathy and supporting the hypothesis that PPCM has an autoimmune basis. Identification of a high-incidence area for PPCM presents a unique opportunity to make progress in defining potential risk factors, identifying high-risk mothers, detecting underlying etiologies, and discovering more effective new treatments of this often-fatal disease.

Autoantibodies↗