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Cardiac hypertrophy is a common response to hemodynamic stress in the heart and can progress to heart failure. To investigate whether the transcription factor cardiovascular basic helix-loop-helix factor 1/hairy/enhancer of split related with YRPW motif 2 (CHF1/Hey2) influences the development of cardiac hypertrophy and progression to heart failure under conditions of pressure overload, we performed aortic constriction on 12-wk-old male wild-type (WT) and heterozygous (HET) mice globally underexpressing CHF1/Hey2. After aortic banding, WT and HET mice showed increased cardiac hypertrophy as measured by gravimetric analysis, as expected. CHF1/Hey2 HET mice, however, demonstrated a greater increase in the ventricular weight-to-body weight ratio compared with WT mice (P < 0.05). Echocardiographic measurements showed a significantly decreased ejection fraction compared with WT mice (P < 0.05). Histological examination of Masson trichrome-stained heart tissue demonstrated extensive fibrosis in HET mice compared with WT mice. TUNEL staining demonstrated increased apoptosis in HET hearts (P < 0.05). Exposure of cultured neonatal myocytes from WT and HET mice to H202 and tunicamycin, known inducers of apoptosis that work through different mechanisms, demonstrated significantly increased apoptosis in HET cells compared with WT cells (P < 0.05). Expression of Bid, a downstream activator of the mitochondrial death pathway, was expressed in HET hearts at increased levels after aortic banding. Expression of GATA4, a transcriptional activator of cardiac hypertrophy, was also increased in HET hearts, as was phosphorylation of GATA4 at [Ser.sup.105]. Our findings demonstrate that CHF1/Hey2 expression levels influence hypertrophy and the progression to heart failure in response to pressure overload through modulation of apoptosis and GATA4 activity. hypertrophy; cardiomyopathy; transcription factor; aortic banding; knockout mouse; cardiovascular basic helix-loop-helix factor 1/hairy/ enhancer of split related with YRPW motif 2 doi: 10.1152/ajpheart.00747.2009.

In congestive heart failure (CHF), exaggerated sympathetic activation is observed during exercise, which elicits excess peripheral vasoconstriction. The mechanisms causing this abnormality are not fully understood. Central command is a central neural process that induces parallel activation of motor and cardiovascular systems. This study was undertaken to determine whether central command serves as a mechanism that contributes to the exaggerated sympathetic response to exercise in CHF. In decerebrated rats, renal and lumbar sympathetic nerve responses (RSNA and LSNA, respectively) to 30 s of fictive locomotion were examined. The fictive locomotion was induced by electrical stimulation of the mesencephalic locomotor region (MLR). The study was performed in control animals (fractional shortening > 40%) and animals with myocardial infarctions (MI; fractional shortening < 30%). With low stimulation of the MLR (current intensity = 20 [micro]A), the sympathetic responses were not significantly different in the control (RSNA: +18 [+ or -] 4%; LSNA: +3 [+ or -] 2%) and MI rats (RSNA: + 16 [+ or -] 5%; LSNA: +8 [+ or -] 3%). With intense stimulation of the MLR (50 [micro]A), the responses were significantly greater in MI rats (RSNA: +127 [+ or -] 15%; LSNA: +57 [+ or -] 10%) than in the control rats (RSNA: +62 [+ or -] 5%; LSNA: +21 [+ or -] 6%). In this study, the data demonstrate that RSNA and LSNA responses to intense stimulation of the MLR are exaggerated in MI rats. We suggest that intense activation of central command may play a role in evoking exaggerated sympathetic activation and inducing excessive peripheral vasoconstriction during exercise in CHF. congestive heart failure; mesencephalic locomotor region; renal sympathetic nerve activity; lumbar sympathetic nerve activity

A study was conducted to explore 24-hour ambulatory blood pressure characteristics as predictors of congestive heart failure (CHF) incidence and to investigate whether altered diurnal blood pressure patterns confer any additional risk information beyond that provided by conventional office blood pressure measurements. It was found that nighttime blood pressure appears to convey additional risk information about CHF beyond office-measured blood pressure and other established risk factors for CHF.

Studies were conducted to explore whether insulin resistance predicts congestive heart failure (CHF) and provide the link between obesity and CHF. The findings indicate that insulin resistance predicted CHF incidence independently of established risk factors including diabetes in large community-based sample of elderly men.

The hormone erythropoietin (EPO), which modulates a broad array of cellular processes, has applicability in a variety of disorders including chronic congestive heart failure. The unique and significant biological role of EPO and its receptor as a cytoprotective agent in both neuronal and vascular systems is described.

The relationship of retinopathy, a marker of systemic microvascular disease, to risk of congestive heart failure (CHF) is determined. It is found that retinopathy is an independent predictor of CHF, and that microvascular disease might play an important role in the development of heart failure in the general population.

People who have elevated blood homocysteine levels may have a greater risk of developing congestive heart failure, according to a study of 2,491 men and women participating in the Framingham Heart Study who were followed for up to eight years. Men and women who had higher than normal homocysteine levels were twice as likely to develop congestive heart failure as those with normal levels. Homocysteine is a naturally occurring substance in the body that has been linked to cardiovascular disease when present in greater than normal amounts.

An increase in the size of the left ventricle of the heart appears to be a risk factor for congestive heart failure even in people who have never had a heart attack. Researchers used echocardiography to measure the dimensions of the left ventricle in 4,744 people with no history of heart attack and no symptoms of heart failure. During the 11-year study, 74 people developed congestive heart failure. An increase in the size of the left ventricle increased the risk of heart failure. The risk of heart failure increased as the size of the heart increased.

Chronic hypertension appears to be a strong risk factor for congestive heart failure (CHF). Researchers followed 5,143 men and women participating in the Framingham Heart Study and the Framingham Offspring Study for up to 20 years. Half of the participants had hypertension at the start of the study. During the study, 392 participants developed CHF. Ninety-one percent had hypertension at the start of the study. Eighty-two percent of the female CHF patients and 76% of the male CHF patients had stage 2 hypertension at the start of the study. Men with hypertension at the start of the study had twice the risk of CHF and women with hypertension had three times the risk. Half of the men and one-third of the women had a history of heart attack at the start of the study. Diabetes, enlargement of the left ventricle of the heart and heart valve disease at the start of the study also increased the risk of developing CHF., Objectives. - To study the relative and population-attributable risks of hypertension for the development of congestive heart failure (CHF), to assess the time course of progression from hypertension to CHF, and to identify risk factors that contribute to the development of overt heart failure in hypertensive subjects. Design. - Inception cohort study. Setting. - General community. Participants. - Original Framingham Heart Study and Framingham Offspring Study participants aged 40 to 89 years and free of CHF. To reflect more contemporary experience, the starting point of this study was January 1, 1970. Exposure Measures. - Hypertension (blood pressure of at least 140 mm Hg systolic or 90 mm Hg diastolic or current use of medications for treatment of high blood pressure) and other potential CHF risk factors were assessed at periodic clinic examinations. Outcome Measure. - The development of CHF. Results. - A total of 5143 eligible subjects contributed 72422 person-years of observation. During up to 20.1 years of follow-up (mean, 14.1 years), there were 392 new cases of heart failure; in 91% (357/392), hypertension antedated the development of heart failure. Adjusting for age and heart failure risk factors in proportional hazards regression models, the hazard for developing heart failure in hypertensive compared with normotensive subjects was about 2-fold in men and 3-fold in women. Multivariable analyses revealed that hypertension had a high population-attributable risk for CHF, accounting for 39% of cases in men and 59% in women. Among hypertensive subjects, myocardial infarction, diabetes, left ventricular hypertrophy, and valvular heart disease were predictive of increased risk for CHF in both sexes. Survival following the onset of hypertensive CHF was bleak; only 24% of men and 31% of women survived 5 years. Conclusions. - Hypertension was the most common risk factor for CHF, and it contributed a large proportion of heart failure cases in this population-based sample. Preventive strategies directed toward earlier and more aggressive blood pressure control are likely to offer the greatest promise for reducing the incidence of CHF and its associated mortality.

Objectives. Preexisting data sets were used to investigate the association between hospital admissions for congestive heart failure and air pollutants. Methods. Medicare hospital admissions data, ambient air pollution monitoring data, and meteorological data were used to create daily values of hospital admissions for congestive heart failure, maximum hourly temperature, and maximum hourly levels of carbon monoxide, nitrogen dioxide, sulfur dioxide, and ozone. Data were compiled for each of seven cities (Chicago, Detroit, Houston, Los Angeles, Milwaukee, New York, and Philadelphia) for 1986 through 1989. Single-pollutant and multipollutant models with adjustments for temperature, seasonal effects, and weekly cycles were used in conducting negative binomial regression analyses. Results. Ambient carbon monoxide levels were positively associated with hospital admissions for congestive heart failure in the single-pollutant and multipollutant models for each of the seven cities. The relative risk of hospital admission for congestive heart failure associated with an inerease of 10 ppm in carbon monoxide ranged from 1.10 in New York to 1.37 in Los Angeles. Conclusions. Hospital admissions for congestive heart failure exhibited a consistent association with daily variations in ambient carbon monoxide. This association was independent of season, temperature, and other major gaseous pollutants. (Am J Public Health. 1995;85:1361-1365), Carbon monoxide concentration in the air appears to be associated with increased hospital admissions for congestive heart failure. Researchers correlated air pollution data between 1986 and 1989 with Medicare hospital admissions for congestive heart failure in Chicago, Detroit, Houston, Los Angeles, Milwaukee, New York, and Philadelphia. An increase in carbon monoxide levels was associated with an increase in hospital admissions in all seven cities. The increase persisted after taking into account the season, temperature, and the concentrations of the air pollutants nitrogen dioxide, sulfur dioxide, and ozone. Carbon monoxide was associated with 11% of admissions for congestive heart failure in Los Angeles, 4.5% in Chicago, 4% in Detroit and New York, 3.5% in Milwaukee, 3% in Philadelphia, and 2% in Houston. Carbon monoxide may cause heart failure in susceptible persons by directly poisoning the heart muscle or by placing additional demands on the heart to pump more blood to compensate for lower available oxygen levels.

Adverse cardiac events appear to increase among children infected with HIV as the disease progresses. Heart function was assessed among 81 young children infected with HIV. Elevated heart rate, which was seen in 52 (64%) of the children, was the most common heart abnormality. An abnormally slow heart rate was noted in nine (11%) of the children. Fifteen of the children had high blood pressure, and 16 had low blood pressure. Dysrhythmia, which is an abnormality in the heart rhythm, occurred in 28 (35%) of the children. Seven children experienced cardiac arrest, and eight had congestive heart failure. Heart abnormalities were more severe and more frequent in children with advanced HIV disease. Heart dysfunction was associated with death in 10 of the 37 children who died. Encephalopathy, which is degeneration of the brain, was the strongest predictor of cardiac arrest, and infection with Epstein-Barr virus was the strongest predictor of the development of congestive heart failure., Objective.--Dysrhythmias, hemodynamic instability, congestive heart failure, and sudden death are serious complications of human immunodeficiency virus (HIV) infection that, to our knowledge, have not been studied systematically. We sought to determine the cumulative incidence and clinical predictors of these adverse events in a cohort of HIV-infected children. Design.--Historical cohort study. Setting.--University-affiliated, primary and tertiary care pediatric hospital and ambulatory care center. Participants.--Eighty-one HIV-infected children who had one or more cardiac evaluations between 1984 and 1991 form the study cohort. The initial cardiac evaluation occurred at a median age of 1.5 years, and children were followed up to a median age of 3.6 years. Main Outcome Measures.--Mortality (related to cardiac dysfunction as well as noncardiac causes), tachycardia, bradycardia, hypertension, hypotension, marked sinus arrhythmia, cardiac arrest, and chronic congestive heart failure. Results.--Hemodynamic abnormalities and dysrhythmias occurred frequently. Eight unexpected cardiorespiratory arrests occurred in seven children (9%). Chronic congestive heart failure was noted in 10% of patients. Thirty children died, 10 with significant cardiac dysfunction. As HIV-infected children progressed from acquired immunodeficiency syndrome (AI DS)-related complex to AI DS, significant cardiac problems were more likely to occur. Both nonneurologic AIDS and encephalopathy were strongly associated with most severe cardiac outcomes. However, encephalopathy was the strongest correlate of cardiorespiratory arrest (P=-.002). Epstein-Barr virus coinfection was the strongest correlate of chronic congestive heart failure (P Conclusions.---Cardiac morbidity and mortality are more common with advanced HIV infection. The presence of encephalopathy or Epstein-Barr virus coinfection identifies HIV-infected children at especially high risk for adverse cardiac outcomes. (JAMA. 1993;269:2869-2875)

Elderly patients who have a history of congestive heart failure (CHF) and elevated blood levels of atrial natriuretic peptide (ANP) have a high risk of developing CHF. ANP is a hormone produced by the heart in response to increased blood volume. A total of 310 elderly patients in a nursing home had a history and physical, and their blood ANP was measured. The patients were followed for one year. When they were grouped according to their blood ANP levels, 36% of the group with the highest levels had an episode of CHF during the year, compared to two percent of the group with the lowest levels. An ANP level of 200 picomoles per liter was found to be the value that would best predict who would have an episode of CHF. Using previous history of CHF and ANP levels, the patients could be divided into three groups: those who had a low risk of CHF, those who had a moderate risk and those who had a high risk.

More than half the number of patients suffering from congestive heart failure (CHF) die by ventricular tachycardia. Most patients do not survive beyond a year after receiving the diagnosis.