Treatment of advanced heart failure

The incidence of chronic heart failure has increased, with a corresponding increase in morbidity and mortality, and has made a substantial financial impact on our society. Improved therapy for heart failure has resulted in a significant prolongation of survival, a decreased number of hospitalizations, and an enhanced quality of life for many patients. It can reasonably be expected, therefore, that adherence to a rational medical regimen for these patients might decrease costs as well. Management of patients with severe heart failure begins with identifying the etiology and educating the patients and their families. Angiotensin-converting enzyme inhibitors are the cornerstone of therapy but only after diagnostic tests are performed to establish the etiology and extent of myocardial dysfunction. Because cardiac transplantation is a therapeutic option for only a limited number of patients, other surgical and medical therapies have to be viewed as the mainstay of a treatment strategy.     

Prevalence of neutralizing antibodies against California and Bunyamwera serogroup viruses in deer from mountainous areas of California

Plaque reduction-serum dilution neutralization was used to evaluate the status of bunyavirus activity in deer in mountainous areas of California. Antibodies against 9 bunyaviruses were measured in 337 mule deer (Odocoileus hemionus hemionus, O. hemionus californicus, and O. hemionus inyoensis) and black-tailed deer (O. hemionus columbianus). More deer from high mountainous areas had neutralizing antibodies against Jamestown Canyon virus than did deer from low mountainous areas (23% vs. 9%; P less than 0.01). This finding is consistent with transmission by snow pool Aedes mosquitoes. Results for Jerry Slough virus were nearly identical to those for Jamestown Canyon virus, which is further evidence that these are strains of the same virus. Neutralizing antibodies against Northway virus were present in 26% of deer from high mountainous areas and 23% of deer from low mountainous areas, suggesting the involvement of a widespread vector, such as Culiseta inornata. Northway virus is not known to occur outside of Alaska and northwestern Canada. Low prevalences of antibodies were detected in deer to California encephalitis, La Crosse, and snowshoe hare viruses of the California serogroup; and Cache Valley, Lokern, and Main Drain viruses of the Bunyamwera serogroup.     

Hip fracture incidence in nursing home residents and community-dwelling older people,Washington State, 1993-1995

OBJECTIVES: To establish and validate a method of linking data from the Minimum Data Set (MDS) and Medicare hospital claims, to estimate hip fracture incidence rates for Medicare beneficiaries aged 65 and older in Washington State, and to compare the incidence rates of hip fractures in nursing home and non-nursing home residents. DESIGN: Retrospective analysis of Medicare population-based enrollment, hospital claims, and nursing home administrative data sets. SETTING: Nursing home and non-nursing home setting. PARTICIPANTS: Medicare beneficiaries in Washington State residing in the community or in skilled nursing facilities. MEASUREMENTS: Crude age- and sex-specific and standardized age- and sex-adjusted hip fracture incidence for persons residing and not residing in nursing homes. RESULTS: From October 1, 1993, through September 30, 1995, 7,812 Medicare beneficiaries aged 65 or older were hospitalized for hip fractures (6,566 fractures for 1,155,234 person-years of exposure in non-nursing home residents and 1,246 fractures for 42,986 person-years of exposure in nursing home residents). The standardized age- and sex-adjusted hip fracture rate of nursing home residents (23.0 per 1,000 person-years) substantially exceeded that of non-nursing home residents (5.7 per 1,000 person-years) (incidence rate ratio = 4.0, 95% confidence interval = 3.7-4.5). CONCLUSION: The incidence of hip fracture in nursing home residents far exceeds that in noninstitutionalized older people. Linkage of MDS and Medicare hospital claims data is a useful tool for epidemiological surveillance regarding events in nursing homes that are likely to result in hospitalization.     

Rationale, design, and methods for a pivotal randomized clinical trial for the assessment of a cardiac support device in patients with New York health association class III-IV heart failure

BACKGROUND: Heart failure remains a progressive disease with incremental morbidity and mortality despite optimal medical therapy. A growing body of evidence suggests that progressive left ventricular (LV) remodeling is directly related to a deterioration in LV performance and untoward clinical outcomes for heart failure patients. Preclinical and early phase I clinical studies with the CorCap Cardiac Support Device (CSD), a passive cardiac support device that prevents cardiac remodeling, have shown that it is safe and is associated with improvements in LV structure and function, as well as patient symptomatology. METHODS AND RESULTS: The Acorn Pivotal Trial is a pivotal prospective, randomized, evaluation of the CorCap CSD in patients with New York Heart Association class III-IV heart failure. Patients will be enrolled into one of two different strata. Patients who require a mitral valve repair/replacement (MVR) will fall into the "MVR stratum" and will be randomized to either treatment (MVR surgery plus the CSD) or control (MVR surgery alone). Patients who do not have a clinical indication for MVR surgery will fall into the "no-MVR stratum" and will also be randomized to either treatment (CSD implant plus optimal medical therapy) or control (optimal medical therapy alone). A total of 300 patients (150 treatment and 150 control) will be enrolled. The primary endpoint of the trial is the change in clinical status from baseline to the end of the efficacy phase (1 year), as determined by a clinical composite score. Patients will be classified as improved, worsened, or unchanged based upon patient vital status, the occurrence of a major cardiac procedure indicative of heart failure progression, and a change in the assessment of New York Heart Association functional class. CONCLUSIONS: The Acorn Pivotal Trial will formally test the hypothesis that preventing LV remodeling using a passive cardiac support device will favorably impact the untoward natural history of heart failure and thus represents an important departure from all previous medical and device studies that have been reported to date.     

A multicenter, randomized, double-blind, placebo-controlled trial of pimobendan, a new cardiotonic and vasodilator agent, in patients with severe congestive heart failure.

Pimobendan, a new oral cardiotonic and vasodilator agent, increases myocardial contractile force through specific inhibition of phosphodiesterase type III and increased calcium sensitivity of the myocardial contractile elements. The effects of pimobendan on left ventricular performance and maximal exercise capacity were studied in a multicenter, randomized, double-blind, placebo-controlled trial involving 52 patients with severe congestive heart failure despite diuretics, digoxin, and angiotensin-converting enzyme inhibitors. The acute hemodynamic evaluation included three single doses of 2.5, 5.0, and 10.0 mg of oral pimobendan, which was subsequently administered at a daily dose of 5 or 10 mg for 4 weeks. Acute administration of pimobendan significantly increased the resting cardiac index and lowered pulmonary capillary wedge pressure in a dose-dependent manner, whereas heart rate and systemic arterial pressure were not substantially altered. Patients receiving pimobendan, 5 and 10 mg daily, had a significantly greater increase in maximal exercise duration than those receiving placebo, that is, 144 +/- 30 and 124 +/- 33 seconds versus 58 +/- 25 seconds (p = 0.05). Peak oxygen uptake increased by 1.7 +/- 0.8 and 2.2 +/- 1.3 ml/kg/min in patients receiving pimobendan at a daily dose of 5 and 10 mg, respectively, whereas it decreased by 0.1 +/- 0.6 ml/kg/min in patients receiving placebo (p = 0.06). Thus pimobendan acutely improves resting left ventricular performance and chronically increases exercise duration and peak oxygen uptake in patients with severe congestive heart failure concomitantly treated with digoxin, diuretics, and angiotensin-converting enzyme inhibitors.     

Ghrelin secretion in humans is sexually dimorphic,suppressed by somatostatin,and not affected by the ambient growth hormone levels

We studied plasma ghrelin and GH concentrations over a 24-h period in young healthy men and women and in patients with acromegaly. Healthy subjects were restudied after administration of GH-lowering agents, octreotide or GHRH antagonist. Ghrelin concentrations in women studied during the late follicular stage of the cycle were about 3-fold higher than in men. Suppression of GH secretion by GHRH antagonist did not alter ghrelin concentration profiles. In the presence of high GH levels (acromegaly), ghrelin levels were similar to those found in healthy men. Administration of somatostatin analog octreotide suppressed both GH and ghrelin concentration profiles. We conclude that: 1) ghrelin secretion is sexually dimorphic in humans, with women in the late follicular stage having higher levels than men; 2) ghrelin secretion is suppressed by somatostatin; and 3) GH has no influence over ghrelin secretion.