Feasibility of Patient-Reported Outcomes Measurement Information System (PROMIS®) computerized adaptive tests in systemic lupus erythematosus outpatients.

Objective The aims of this study were to assess the feasibility of administering Patient-Reported Outcomes Measurement Information System (PROMIS®) computerized adaptive tests (CATs) to outpatients with systemic lupus erythematosus (SLE). Methods Adults with SLE were recruited during routine outpatient visits at an SLE Center of Excellence. Participants completed 14 PROMIS CATs and provided feedback on their experience. Differences in socio-demographic and clinical characteristics between participants and non-participants were evaluated. Results A total of 204 (86%) of 238 socioeconomically and racially diverse SLE patients completed PROMIS CATs. There were no significant differences between participants and non-participants. Time constraints were cited most frequently as reasons for non-participation. More than 75% of individuals submitted positive comments, including approval of the content and format of questions, and the survey's promotion of self-reflection. A minority of participants cited challenges, most often related to question phrasing (8%) and technical difficulties (6%). Conclusions The administration of PROMIS CATs was feasible and positively received in a diverse cohort of SLE outpatients. Neither socio-demographic nor disease characteristics were significant barriers to successful completion of PROMIS CATs. PROMIS CATs have great potential for efficiently measuring important patient-centered outcomes in routine clinical care of a wide range of SLE patients.

Assisted reproductive technology in SLE and APS.

Assisted reproductive technology (ART) procedures, which include in vitro fertilization (IVF), are performed frequently and may be considered for patients with systemic lupus erythematosus and antiphospholipid syndrome. These procedures do not appear to increase the risk of disease flare or thrombosis in these patients. In addition, the presence of antiphospholipid antibodies (aPL) does not independently predict the outcome of IVF pregnancies. As with pregnancies that are achieved naturally, candidates for ART should have quiescent disease for at least 6 months prior to attempting pregnancy for the best possible outcome for mother and child.

The efficacy and safety of bazedoxifene in postmenopausal women by baseline kidney function status.

INTRODUCTION: Two global, double-blind, placebo- and active-controlled, phase-3 studies (2-year prevention (n = 1583) and 3-year treatment (n = 7492)) have shown that bazedoxifene (BZA) is safe and effective for prevention and treatment of postmenopausal osteoporosis. OBJECTIVE: To evaluate the efficacy/safety of BZA according to baseline kidney function. METHODS: Data for the BZA 20- and 40-mg and placebo groups from both studies were integrated for assessment of bone turnover markers (BTMs), bone mineral density (BMD), and fracture incidence (treatment study only). Safety was assessed using integrated data for the BZA, placebo, and raloxifene 60-mg groups from both studies. Baseline glomerular filtration rate (GFR) was estimated by the Modification of Diet in Renal Disease Study equation; among subjects with baseline GFR, renal function categories were defined by GFR (ml/min per 1.73 m(2)): normal (GFR ≥ 90; n = 1982), mild impairment (60 ≤ GFR < 90; n = 6032), or moderate/severe impairment (GFR < 60; n = 723). RESULTS: Demographics were similar across treatment groups and within GFR subgroups. Across GFR subgroups, BZA 20 and 40 mg reduced BTM levels and improved lumbar spine and total hip BMD versus placebo. At month 24, there were significant treatment-by-GFR (p = 0.003) and treatment-by-serum creatinine (p = 0.034) interactions for the increase in lumbar spine BMD versus placebo. Fracture incidence was lower with BZA than placebo across all GFR categories, with no treatment-by-GFR interaction. There were no significant differences among treatment groups in incidences of overall, serious, or renal-related adverse events across GFR subgroups. CONCLUSIONS: Mild to moderate kidney impairment did not affect the efficacy and safety of BZA in postmenopausal women.

Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled phase 3 trial.

UNLABELLED: Findings from this 5-year phase 3 study of postmenopausal women with osteoporosis showed that bazedoxifene was associated with an overall favorable safety and tolerability profile, with no evidence of endometrial or breast stimulation. Overall, the results at 5 years were consistent with those seen at 3 years. INTRODUCTION: We report safety and tolerability findings from a 5-year randomized, double-blind, phase 3 study of bazedoxifene in postmenopausal women with osteoporosis. METHODS: In the core study, healthy postmenopausal women with osteoporosis (N=7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. During the 2-year study extension, the raloxifene 60-mg treatment arm was discontinued after the 3-year database was finalized, and subjects receiving bazedoxifene 40 mg were transitioned in a blinded manner to bazedoxifene 20 mg (bazedoxifene 40-/20-mg group) after 4 years. Safety and tolerability data are reported for subjects in the bazedoxifene 20- and 40-/20-mg and placebo groups; efficacy findings are reported elsewhere. RESULTS: A total of 3,146 subjects in the bazedoxifene 20- and 40-mg and placebo groups were enrolled in the extension study (years 4 and 5). Overall, the 5-year incidence of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar among groups. The incidence of hot flushes and leg cramps was higher with bazedoxifene compared with placebo. Venous thromboembolic events, primarily deep vein thrombosis, were more frequently reported in the bazedoxifene groups compared with the placebo group. Reports of cardiac disorders and cerebrovascular events were few and evenly distributed among groups. Bazedoxifene showed a neutral effect on the breast and endometrium. CONCLUSION: Bazedoxifene was associated with an overall favorable safety and tolerability profile in postmenopausal women with osteoporosis over 5 years of therapy, consistent with findings at 3 years.

Neurotoxicity produced by dibromoacetic acid in drinking water of rats.

An evaluation of potential adverse human health effects of disinfection byproducts requires study of both cancer and noncancer endpoints; however, no studies have evaluated the neurotoxic potential of a common haloacetic acid, dibromoacetic acid (DBA). This study characterized the neurotoxicity of DBA during 6-month exposure in the drinking water of rats. Adolescent male and female Fischer 344 rats were administered DBA at 0, 0.2, 0.6, and 1.5 g/l. On a mg/kg/day basis, the consumed dosages decreased greatly over the exposure period, with average intakes of 0, 20, 72, and 161 mg/kg/day. Weight gain was depressed in the high-concentration group, and concentration-related diarrhea and hair loss were observed early in exposure. Testing with a functional observational battery and motor activity took place before dosing and at 1, 2, 4, and 6 months. DBA produced concentration-related neuromuscular toxicity (mid and high concentrations) characterized by limb weakness, mild gait abnormalities, and hypotonia, as well as sensorimotor depression (all concentrations), with decreased responses to a tail-pinch and click. Other signs of toxicity at the highest concentration included decreased activity and chest clasping. Neurotoxicity was evident as early as one month, but did not progress with continued exposure. The major neuropathological finding was degeneration of spinal cord nerve fibers (mid and high concentrations). Cellular vacuolization in spinal cord gray matter (mostly) and in white matter (occasionally) tracts was also observed. No treatment-related changes were seen in brain, eyes, peripheral nerves, or peripheral ganglia. The lowest-observable effect level for neurobehavioral changes was 20 mg/kg/day (produced by 0.2 g/l, lowest concentration tested), whereas this dosage was a no-effect level for neuropathological changes. These studies suggest that neurotoxicity should be considered in the overall hazard evaluation of haloacetic acids.

Dobutamine as bridge to angiotensin-converting enzyme inhibitor-nitrate therapy in endstage heart failure.

BACKGROUND: Intravenous inotropic intervention in congestive heart failure is generally associated with a poor prognosis and is largely used as a "bridge" to mechanical support or heart transplantation. HYPOTHESIS: We hypothesized that the inotropic support afforded by dobutamine may serve as a bridge to the introduction and intensification of angiotensin-converting enzyme (ACE) inhibitor-nitrate therapy. METHODS: We studied the efficacy of transitioning inotrope-dependent patients in endstage heart failure from intravenous dobutamine to high-dose ACE inhibitor-nitrates, with 1-year follow-up. Forty-nine sequential dobutamine-dependent patients with left ventricular ejection fraction (LVEF) 17+/-17% were treated with increasing lisinopril (1.9+/-1.5 to 46+/-28 mg/day) and isosorbide dinitrate (7+/-6 to 229+/-161 mg/day). Outpatient dobutamine was continued or repeat infusions pursued, as indicated, and dobutamine was tapered when feasible. RESULTS: During the following year, 14 of 49 patients required repeat dobutamine, with home treatment with dobutamine for 6.3+/-3.7 months (n = 5). At 1 year, New York Heart Association (NYHA) classification improved from 3.6+/-0.5 to 1.9+/-1.0, p < 0.0001; yearly hospitalizations fell from 2.7+/-2.3 to 1.2+/-3.0, p = 0.02; and LVEF rose from 17+/-7% to 24+/-11%, p < 0.0001. At 1 year, 14 patients who remained dobutamine dependent had significantly more severe symptoms than dobutamine-independent patients (n = 35). Transplant or death occurred in 7 of 14 patients with follow-up dobutamine, and in 5 of 35 patients free of subsequent dobutamine, p = 0.03. Patients with poor outcome (transplant n = 10, death n = 12) continued to be more limited (NYHA 2.7+/-0.9 vs. 1.7+/-0.9, p = 0.0002), with more follow-up hospitalizations (3.6+/-5.4 vs. 0.6+/-0.8, p = 0.0004), and no improvement in LVEF (17+/-8vs. 28+/-11%, p = 0.003). CONCLUSIONS: Of the patients on dobutamine inotropic support, 70% were successfully transitioned to ACE inhibitor-nitrate therapy, with improved symptoms and LVEF, and with reduced hospitalizations and follow-up dobutamine or transplant. Thirty percent of patients with continued need for dobutamine had a significantly poorer 1-year clinical outcome.

Reversal of heart failure remodeling in women.

Epidemiological studies suggest that women with heart failure differ from men with heart failure in that their survival is better. Therapeutic trials have not clearly demonstrated a survival benefit for women. This study was to determine the tolerance for high doses of angiotensin-converting enzyme (ACE) inhibitor-nitrates in women versus men and to compare their symptomatic response, exercise tolerance, and ventricular functional improvement over 1 year. Eighty-eight sequential patients with heart failure, 54 men and 34 women with left ventricular ejection fraction < or = 35%, were prospectively followed for 1 year. For all patients, ACE inhibitor-nitrate therapy was intensified. Each patient had three 6-monthly echocardiograms at baseline, at 6 months, and at 1 year, and metabolic stress testing. Patients were 57.3 +/- 12.3 years old, with New York Heart Association (NYHA) class severity 2.6 +/- 1.0. Lisinopril dosages were raised from 14 +/- 14 mg/day to 57 +/- 26 mg/day, isosorbide mononitrate from 15 +/- 27 mg/day to 126 +/- 72 mg/day, and carvedilol (n = 34) to 17 +/- 16 mg/day. Women and men were epidemiologically comparable, with similar baseline echocardiographic parameters (left ventricular ejection fraction 19% +/- 7% versus 17% +/- 6%, respectively). Both tolerated up-titration in medical therapy. Final 12-month ejection fractions were equivalent for women and men at 34% +/- 17% and 34% +/- 13%, respectively, with similar improvements in left ventricular diameters. At 1 year, women had higher resting heart rates and remained more symptomatic with lower exercise capacity. However, the relative changes in NYHA status and aerobic capacity were similar for women and men. Thus, both women and men tolerated uptitrated ACE inhibitor-nitrate medical therapy, with comparable reversal of heart failure remodeling. Although women continued to be more symptomatic than men, relative improvements in symptomatic status, in exercise capacity, and in hospitalization rate were equivalent.

Impact of left ventricular size on pharmacologic reverse remodeling in heart failure.

BACKGROUND AND HYPOTHESIS: Although medical therapy may normalize echocardiographic left ventricular (LV) systolic function in selected patients with cardiomyopathy, other patients experience no change or a further deterioration in heart failure remodeling. Our aim was to determine what clinical or echocardiographic parameters predict a beneficial therapeutic response. METHODS: We prospectively followed biannual clinical and echocardiographic assessments in 215 patients. Forty-six of these patients ("Nonresponders") experienced no change or a decline in LV ejection fraction at 6 months. Of the 148 patients who improved LV function, 21 ("Responders") normalized LV systolic function at 6 months. Only Responders (n = 21) and Nonresponders (n = 46) were compared. RESULTS: On average, these 67 patients were 54 +/- 12 years old with 4.5 +/- 3.3 years of heart failure. At 6 months, following up-titration of angiotensin-converting enzyme inhibitors and nitrates, Responder LV ejection fraction rose from 22 +/- 6 to 50 +/- 5% with improvement in New York Heart Association classification (2.6 +/- 0.8 to 1.5 +/- 0.8, p = 0.001). These patients had significantly more favorable clinical and echocardiographic outcomes versus Nonresponders despite comparable medical therapy. All baseline demographic, clinical, and echocardiographic variables were equivalent, except for initial LV end-diastolic diameter which differentiated Nonresponders (7.1 +/- 0.7 cm) from Responders (6.1 +/- 0.8 cm), p = 0.007. CONCLUSION: Thus, although heart failure therapy improves LV systolic function in a majority of patients, with normalization in up to 10% of patients, significant LV enlargement may render remodeling unresponsive to pharmacologic intervention, with a potential future need for alternative mechanical or surgical intervention.

Effects of exercise training on chronotropic incompetence in patients with heart failure.

OBJECTIVE: To describe the effects of exercise training on chronotropic incompetence in patients with stable heart failure, as measured by their inability to achieve a peak exercise heart rate greater than 85% of maximum. BACKGROUND: Exercise intolerance and chronotropic incompetence are characteristic of patients with heart failure. Exercise training improves exercise capacity in these patients; however, to what extent reversal of chronotropic incompetence contributes to such a response remains uncertain. METHODS: Fifty-one patients undergoing standard medical therapy were randomly assigned to a 24-week exercise training program or a no exercise control group. Twenty-one of 26 patients assigned to the exercise group and 22 of 25 control patients completed the study. Peak oxygen consumption, resting and exercise plasma norepinephrine level, and quality of life (Living With Heart Failure Questionnaire) were assessed. RESULTS: A significant (P <.05) increase in peak heart rate was observed in the exercise group (9 +/- 3 beats/min) when compared with the control group (1 +/- 3 beats/min). Among exercise-trained patients with chronotropic incompetence at baseline (n = 14), the increase in peak heart rate at week 24 was 12 +/- 3 beats/min. Peak oxygen consumption was significantly (P <.05) increased in the exercise group (204 +/- 57 mL/min) versus the control group (72 +/- 33 mL/min). Health-related quality of life was not significantly changed with exercise training. Twenty-four weeks of exercise training induced a greater (P <.05) reduction in plasma norepinephrine at rest and during exercise in patients with a nonischemic cardiomyopathy versus those with ischemic cardiomyopathy. CONCLUSIONS: Exercise training results in an increase in peak heart rate and partial reversal of chronotropic incompetence among patients with stable heart failure. These responses contribute, in part, to the exercise training-induced increase in exercise capacity that occurs in these patients.

Pregnancy outcome in patients requiring parenteral nutrition.

OBJECTIVE: The purpose of this retrospective study was to evaluate maternal and perinatal outcomes and complications of parenteral nutrition during pregnancy in our institution. METHODS: This study was a review of medical records of all women who required parenteral nutrition during pregnancy at our institution from 1990-1997. The frequency of maternal and perinatal complications was calculated. RESULTS: Twenty-six pregnancies required parenteral nutrition for the following indications: hyperemesis gravidarum (n = 16), cholecystitis/pancreatitis (n = 3), small bowel obstruction (n = 2), intracranial bleed (n = 2), ulcerative colitis (n = 1), and other (n = 2). The mean gestational age at initiation of therapy was 16.2 weeks and the mean duration of therapy was 30.6 days. Five pregnancies were terminated prior to fetal viability. Of the remaining pregnancies, obstetric complications occurred in 11, including two cases of idiopathic preterm labor resulting in preterm deliveries. Maternal complications resulting from the central venous catheters included four infections, two thromboses, one occlusion, one pneumothorax, and one catheter dislodgment. The complication rate for centrally inserted central catheters (50%) was significantly greater than the rate for peripherally inserted central catheters (9%). CONCLUSIONS: Successful outcomes can be achieved in obstetric patients requiring parenteral nutrition. In this group of patients, the frequency of maternal complications secondary to centrally inserted central venous catheters was greater than that reported in nonpregnant patients. Peripherally inserted central catheters may be preferable when parenteral nutrition is required during pregnancy.

Placenta accreta: comparison of cases managed with and without pelvic artery balloon catheters.

OBJECTIVE: To describe our experience with the use of prophylactic pelvic artery balloon catheters in cases of placenta accreta diagnosed by antenatal ultrasound and to compare these cases with contemporary controls. METHODS: In this prospective study, all patients seen at our institution between January 1994 and August 1997 with the antenatal sonographic diagnosis of placenta accreta were offered prophylactic preoperative pelvic artery balloon catheterization. Patients who were delivered by cesarean hysterectomy for unsuspected placenta accreta in our institution during the same time interval served as controls. Five patients with the sonographic diagnosis of placenta accreta underwent prophylactic pelvic artery balloon catheterization. Surgical outcomes in patients who received balloon catheters were compared with those managed without them. Statistical analysis was performed using the Mann-Whitney U test. RESULTS: Five patients with placenta accreta or one of its variants were correctly identified with antenatal ultrasonography. Of the five patients who underwent pelvic artery balloon catheterization, all had placenta accreta and four required cesarean hysterectomy. The mean estimated blood loss, transfusion requirement, and length of hospitalization in patients undergoing hysterectomy managed with and without the balloon catheters was not different (P > 0.06). CONCLUSIONS: Antenatal sonographic diagnosis of placenta accreta enables preoperative planning. In our experience, use of pelvic artery balloon occlusion catheters in patients requiring a cesarean hysterectomy for placenta accreta did not improve surgical outcomes compared with patients managed without them. These preliminary findings are based on a small number of patients; therefore, further investigation is needed.

Angiotensin converting enzyme inhibitor-induced angioedema more prevalent in transplant patients.

BACKGROUND: Angioedema in association with angiotensin converting enzyme inhibitor (ACEI) use is rare, but serious. Which patients are predisposed to the reaction and whether it involves an immune mechanism remain unclear. OBJECTIVES: To determine the frequency of ACEI angioedema in immunosuppressed cardiac and renal transplant patients. METHODS: This was a retrospective chart review of all adult cardiac (n = 156) and renal (n = 341) transplant patients followed at our hospital (years 1985 to 1995). RESULTS: Of 105 cardiac and 91 renal transplant patients on a combination of immunosuppressive and ACEI therapy, 5 (4.8%) cardiac and 1 (1%) renal patients developed angioedema. This prevalence of ACEI angioedema among cardiac and renal transplant patients is 24 times and 5 times higher, respectively, than that observed in the general population (0.1% to 0.2%). Reactions often appeared after prolonged ACEI use (average 19 months; range 3 days to 6.3 years). African-Americans were significantly more likely to experience ACEI-associated angioedema (P = .034), especially among the cardiac patients where 4 of 5 reactors were African-American. CONCLUSIONS: For unclear reasons, ACEI-induced angioedema (often late-onset) is more prevalent among immunosuppressed cardiac and renal transplant patients. Additionally, African-Americans are over-represented among those developing the reaction.

Effects of high-dose lisinopril-isosorbide dinitrate on severe mitral regurgitation and heart failure remodeling.

In long-term, 1-year follow-up, uptitration of angiotensin-converting enzyme inhibitor and nitrate therapy over established doses can further improve severe functional mitral regurgitation in patients with dilated cardiomyopathy due to a reversal of heart failure-related left ventricular remodeling. With marked left ventricular enlargement, >6.8 cm end-diastolic diameter, heart failure remodeling may be irreversible and resistant to further medical intervention.

The impact of beta-receptor blocker addition to high-dose angiotensin-converting enzyme inhibitor-nitrate therapy in heart failure.

BACKGROUND: The natural history of heart failure is one of continued worsening of cardiac function. Beta-receptor blocker therapy has been effective in improving clinical status and left ventricular function in patients with heart failure. Similarly, high doses of angiotensin-converting enzyme (ACE) inhibitors with nitrates partially reverse the ventricular remodeling of heart failure. HYPOTHESIS: We tested the hypothesis that beta-blocker therapy added to high-dose ACE inhibitor-nitrates would potentiate the reversal of heart failure. METHODS: Thirteen patients, aged 52 +/- 8 years, with moderate to severe heart failure, 12 of whom were referred for transplant consideration, with heart failure duration of 4.8 +/- 2.2 years, were prospectively followed for 12 months. Baseline echocardiographic ejection fraction was 19 +/- 8%, and presenting New York Heart Association class was 2.9 +/- 0.7. Angiotensin-converting enzyme inhibitors and nitrates were uptitrated over 6 months to a final dose of lisinopril 53 +/- 31 mg/day, and isosorbide dinitrate 217 +/- 213 mg/day. At 6 months, beta-blocker therapy with atenolol was initiated and titrated to a final dose of 46 +/- 23 mg/day. Two-dimensional Doppler echocardiography and metabolic stress testing were performed at baseline, at 6 months on lisinopril-nitrates only, and at 12 months on combined ACE inhibitor-nitrate and beta-blocker therapy. RESULTS: New York Heart Association classification improved from 2.9 +/- 0.7 to 1.8 +/- 0.8 on lisinopril-nitrates (p < 0.05), and to 1.5 +/- 0.5 with the addition of beta blockade (p = NS). On follow-up, peak oxygen consumption rose from 17 +/- 7 ml O2/kg/min at baseline to 21 +/- 5 ml O2/kg/min at 6 months on lisinopril-nitrates (p = 0.06) without further change on beta blockade. Ejection fraction rose from 19 +/- 8 to 33 +/- 14% on lisinopril-nitrates at 6 months (p = 0.005) and to 36 +/- 18% on beta blockade at 12 months (p = NS). CONCLUSION: High-dose ACE inhibitor-nitrate therapy significantly improved patient clinical status and left ventricular systolic function in heart failure. The addition of beta-receptor blockade over and above high-dose ACE inhibitor-nitrates was well tolerated but had no further impact on symptomatic status, exercise tolerance, or left ventricular systolic function. The potential for pharmacologic reversal of heart failure remodeling may be finite despite the use of complementary therapies. Larger placebo-controlled and randomized trials of beta-receptor blockade added to high-dose ACE inhibitor-nitrate therapy are needed to confirm these observations.

Undetected cardiogenic shock in patients with congestive heart failure presenting to the emergency department.

The purpose of this study was to examine the use of lactic acid levels and continuous central venous oxygen saturation (central venous oximetry) to stratify and treat patients with acutely decompensated end-stage chronic congestive heart failure (CHF) presenting to the emergency department. This prospective, convenience, non-outcome study was performed at an urban tertiary care hospital. Patients with end-stage CHF with an ejection fraction <30% presenting in decompensated CHF were eligible for the study. Patients were assessed using the Killip classification and New York Heart Association criteria. After lactic acid levels were obtained, patients were managed according to a standardized protocol guided by central venous oximetry. The patients were divided into high lactic acid (n = 22), low lactic acid (n = 5), and control groups (stable patients presenting to a cardiology clinic, n = 17) for comparison. There was no statistical difference in vital signs, or Killip and New York Heart Association criteria among the 3 groups. Central venous oxygen saturation was significantly lower in the high lactic acid group (32 +/- 12%) than in the normal lactic acid (51 +/- 13%) and control groups (60 +/- 6%) (p < 0.001). After treatment there was a significant decrease in lactic acid (-3.65 +/- 3.65 mM/L) and an increase in central venous oxygen saturation (32 +/- 13%) in the high lactic acid group compared with the normal lactic acid group (p < 0.001). A significant subset of patients with decompensated end-stage CHF present to the emergency department in occult shock and are clinically indistinguishable from patients with mildly decompensated CHF and stable CHF. Once identified, these patients require aggressive alternative management and disposition. Further study is necessary to identify whether this intervention impacts morbidity, mortality, and health care resource consumption.

Reproductive health in diabetic women. A report of two cases demonstrating the importance of preconception care.

BACKGROUND: Optimal glycemic control prior to and during early pregnancy is essential in diabetic women. CASES: Two cases of fetal anencephaly occurred in diabetic women who conceived with medical technical assistance but did not receive preconception counseling. Both women had poor glycemic control periconceptually, as evidenced by elevated glycosylated hemoglobin determinations in the early first trimester. Targeted sonographic evaluations in the second trimester revealed both fetuses to be anencephalic. Both women terminated their pregnancies. CONCLUSION: Women with diabetes should be encouraged to seek preconceptual counseling and achieve tight glycemic control prior to attempting pregnancy. Health care providers play a vital role in stressing the importance of preconception care to these patients.

Paradoxical hypertension after reversal of heart failure in patients treated with intensive vasodilator therapy.

Hypertension is a major cause of heart failure, evolving from left ventricular hypertrophy to systolic and diastolic dysfunction. Although effective heart failure therapy has been associated with a lowering or no change in systemic arterial blood pressure in long-term follow-up, this study describes the symptomatic, clinical, and left ventricular functional response of a subgroup of heart failure patients with a prior history of hypertension who demonstrated a paradoxical hypertensive response despite high-dose vasodilator therapy. We prospectively identified 45 patients with a past history of hypertension who had become normotensive with symptomatic heart failure. Of these 45 heart failure patients, 12 became hypertensive while receiving therapy in follow-up, with systolic blood pressure > or = 140 mm Hg (Group A). The remaining 33 patients did not have a hypertensive response to therapy (Group B). In the 12 Group A patients, 60+/-10 years old, with symptomatic heart failure for 6.3+/-4.3 years, vasodilator therapy was intensified in the 2.0+/-0.5 years of follow-up, achieving final doses of enalapril 78+/-19 mg and isosorbide dinitrate 293 +/-106 mg per day. New York Heart Association classification improved from 2.9+/-0.8 to 1.3+/-0.5 (P < or = .0001), with a reduction in heart-failure-related hospitalizations. Left ventricular ejection fraction increased from 17+/-6% to 40+/-10% (P < .0001). Follow-up blood pressure at 1 to 3 months was unchanged. However, both systolic and diastolic blood pressure increased at final follow-up, rising from 116+/-14 to 154+/-13 mm Hg (P = .0001) and from 71+/-9 to 85+/-14 mm Hg (P = .004), respectively. Renal function remained unchanged. Although both groups had similar clinical responses, there were more blacks and women in the hypertensive Group A. Effectively, 12 of 45 (27%) heart failure patients with an antecedent history of hypertension demonstrated a paradoxical hypertensive response to vasodilator therapy. The recurrence of hypertension in a significant portion of patients successfully treated for heart failure has important clinical implications.

Reverse remodeling in heart failure with intensification of vasodilator therapy.

BACKGROUND: Heart failure therapy with beta-receptor blockade has been shown to effect a partial reversal of left ventricular (LV) remodeling in heart failure. HYPOTHESIS: We tested the hypothesis that, in the absence of beta blockade, uptitration of angiotensin-converting enzyme (ACE) inhibitor and nitrate therapy over conventional dosages would improve symptoms as well as LV function in patients with severe heart failure. METHODS: For patients with nonischemic or ischemic cardiomyopathy, intensive high-dose angiotensin-converting enzyme inhibitor and nitrate therapy was uptitrated. Echocardiograms were obtained semiannually and evaluated in a blinded fashion. Of 99 patients in the study, aged 55 +/- 13 years, with heart failure for 5.2 +/- 3.1 years, 74 were men, 69 were Caucasian, and 34 had ischemic cardiomyopathy. The final dosage of enalapril was 40 +/- 23 mg/day of isosorbide dinitrate it was 153 +/- 127 mg/day. RESULTS: Initial New York Heart Association classification improved from 2.8 +/- 0.9 to 1.7 +/- 0.9 (p < 0.001) in 2.7 years of follow-up. Of the 99 patients, 72 further improved their ejection fraction. For the whole group, ejection fraction increased from 21 +/- 9% to 30 +/- 13% in 6 months (p < 0.001), with a reduction in LV end-diastolic size from 6.6 +/- 0.9 to 6.3 +/- 1.0 cm (p = 0.002), a decrease in the severity of mitral regurgitation from mild/moderate to only mild. Resting heart rate declined with no change over time in systemic systolic blood pressure. Final ejection fraction for nonischemic patients (n = 65) was 36 +/- 16% versus 23 +/- 9% for the ischemic population. CONCLUSIONS: Uptitration of high-dose ACE inhibitor and nitrate therapy to higher doses is well tolerated in severe heart failure, further improves both clinical status and LV systolic function, and is more effective in nonischemic than in ischemic cardiomyopathy.