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PubMed1999

Swelling-activated chloride current is persistently activated in ventricular myocytes from dogs with tachycardia-induced congestive heart failure.

The hypothesis that cellular hypertrophy in congestive heart failure (CHF) modulates mechanosensitive (ie, swelling- or stretch-activated) anion channels was tested. Digital video microscopy and amphotericin-perforated-patch voltage clamp were used to measure cell volume and ion currents in ventricular myocytes isolated from normal dogs and dogs with rapid ventricular pacing-induced CHF. In normal myocytes, osmotic swelling in 0.9T to 0.6T solution (T, relative osmolarity; isosmotic solution, 296 mOsmol/L) was required to elicit ICl,swell, an outwardly rectifying swelling-activated Cl- current that reversed near -33 mV and was inhibited by 1 mmol/L 9-anthracene carboxylic acid (9AC), an anion channel blocker. Block of ICl,swell by 9AC simultaneously increased the volume of normal cells in hyposmotic solutions by up to 7%, but 9AC had no effect on volume in isosmotic or hyperosmotic solutions. In contrast, ICl,swell was persistently activated under isosmotic conditions in CHF myocytes, and 9AC increased cell volume by 9%. Osmotic shrinkage in 1.1T to 1.5T solution inhibited both ICl,swell and 9AC-induced cell swelling in CHF cells, whereas osmotic swelling only slightly increased ICl,swell. The current density for fully activated 9AC-sensitive ICl,swell was 40% greater in CHF than normal myocytes. In both groups, 9AC-sensitive current and 9AC-induced cell swelling were proportional with changes in osmolarity and 9AC concentration, and the effects of 9AC on current and volume were blocked by replacing bath Cl- with methanesulfonate. CHF thus altered the set point and magnitude of ICl,swell and resulted in its persistent activation. We previously observed analogous regulation of mechanosensitive cation channels in the same CHF model. Mechanosensitive anion and cation channels may contribute to the electrophysiological and contractile derangements in CHF and may be novel targets for therapy.

Animals↗
PubMed2006

Subcellular remodeling as a viable target for the treatment of congestive heart failure.

It is now well known that congestive heart failure (CHF) is invariably associated with cardiac hypertrophy, and changes in the shape and size of cardiomyocytes (cardiac remodeling) are considered to explain cardiac dysfunction in CHF. However, the mechanisms responsible for the transition of cardiac hypertrophy to heart failure are poorly understood. Several lines of evidence both from various experimental models of CHF and from patients with different types of CHF have indicated that the functions of different subcellular organelles such as extracellular matrix, sarcolemma, sarcoplasmic reticulum, myofibrils, mitochondria, and nucleus are defective. Subcellular abnormalities for protein contents, gene expression, and enzyme activities in the failing heart become evident as a consequence of prolonged hormonal imbalance, metabolic derangements, and cation maldistribution. In particular, the occurrence of oxidative stress, development of intracellular Ca2+ overload, activation of proteases and phospholipases, and alterations in cardiac gene expression result in changes in the biochemical composition, molecular structure, and function of different subcellular organelles (subcellular remodeling). Not only does subcellular remodeling appear to be intimately involved in the transition of cardiac hypertrophy to heart failure, the mismatching of the function of different subcellular organelles leads to the development of cardiac dysfunction. Although blockade of the renin-angiotensin system, sympathetic nervous system, and various other hormonal actions have been reported to produce beneficial effects on cardiac remodeling and heart dysfunction in CHF, the actions of various cardiac drugs on subcellular remodeling have not been examined extensively. Some recent studies have indicated that both the angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists attenuate changes in sarcolemma, sarcoplasmic reticulum, and myofibril enzyme activities, protein contents, and gene expression, and partly improve cardiac function in the failing hearts. It is suggested that subcellular remodeling is an excellent target for the development of improved drug therapy for CHF. Furthermore, extensive studies should investigate the effects of different agents individually or in combination on reverse subcellular remodeling, cardiac remodeling, and cardiac dysfunction in various experimental models of CHF.

Animals↗
PubMed2002

Noninvasive assessment of cardiac pumping capacity during exercise predicts prognosis in patients with congestive heart failure.

BACKGROUND: Prognostic parameters in patients with congestive heart failure (CHF) are important for guiding therapeutic options. Maximal oxygen uptake (O(2)max) is a widely used parameter for prognostic assessment in patients with CHF and correlates with exercise cardiac output; however, afterload is not taken into account. METHODS: The concept of a noninvasive surrogate of cardiac power output combines exercise systolic BP (SBP), as an estimate of afterload, with O(2)max, as an estimate of exercise cardiac output neglecting preload. Thus, a variable termed exercise cardiac power (ECP) is defined as the product of O(2)max (expressed as a percent predicted value) and SBP (ECP, expressed as %mm Hg, is the product of O(2)max, expressed as percentage of predicted maximum, times systolic pressure. The prognostic value of ECP obtained during routine treadmill ergospirometry was assessed in patients referred to our heart failure clinic. Patients undergoing heart transplantation were censored at the time of transplantation. RESULTS: One hundred fifty-four patients were followed prospectively for a mean (+/- SE) duration of 625 +/- 32 days. Thirty-two patients (21%) died. ECP was the most powerful predictor of mortality, was the combined end point of mortality or hospitalization for worsening heart failure (all p < 0.001), and was an independent predictor in multivariate analysis. An ECP of < 5,000 %mm Hg indicated a poor prognosis with a 1-year mortality rate of 37%, whereas only 2% of the patients having an ECP of > 9,000 %mm Hg died during the first year. CONCLUSION: The integration of afterload and O(2)max improves the prognostic value of each indicator, and provides an easily available and independent predictor of mortality and morbidity in CHF patients. This integrative concept of cardiac hydraulic performance is superior to O(2)max and can be used in routine ergospirometry.

Analysis of Variance↗
PubMed1997

Congestive heart failure in elderly patients.

The prevalence of congestive heart failure (CHF) is increasing. Most patients with CHF are elderly, and CHF is the most common dismissal diagnosis in elderly hospitalized patients. As many as 50% of elderly patients with heart failure may have normal systolic function and isolated diastolic heart failure. Assessment and management of elderly patients are complicated by comorbidities, increased susceptibility to side effects, and concerns about the appropriate use of costly and invasive procedures. The basics of the approach to the evaluation and management of heart failure in elderly patients are reviewed.

Age Distribution↗
PubMed2004

Renal dysfunction in congestive heart failure, pathophysiological and prognostic significance.

AIMS: Many congestive heart failure (CHF) patients suffer from various comorbidities, which may aggravate CHF or independently increase mortality risk. Renal failure (RF) is one of them. We defined bedside clinical, laboratory and electrocardiographic parameters characterizing CHF patients with and without concomitant RF, and analyzed their impact on mortality. METHODS: We studied symptomatic unselected consecutive furosemide-treated CHF patients hospitalized for various acute conditions. On admission, history taking, physical examination, chest x-ray, ECG and routine laboratory tests were performed. Subsequently, patients were divided into 2 subgroups, those with serum creatinine > or = 1.5 mg/dl (RF) and those with lower values. Following discharge, information concerning mortality and circumstance of death was obtained from hospital records and outpatient death certificates. RESULTS: Included were 398 patients, 163 (40.9%) with RF and 235 free of RF. Prevailing in the RF subgroup were older age (mean age 75.5 vs 70.8, p < 0.001), male gender (p < 0.001), admission pulmonary edema (p = 0.007), cardiac arrhythmias (p = 0.05), cardiac conduction disturbances (p = 0.002), severe CHF (p = 0.005), lower ejection fraction (p = 0.03), anemia (p = 0.009), higher furosemide maintenance dosages (p < 0.001), insulin treatment (p = 0.03) and receiving less ACE inhibitors (p = 0.006). On median follow-up of 43 months, mortality was 54.9% in the RF vs 31.9% in the non-RF subgroup (p < 0.001), RF being the parameter most significantly associated with low survival (OR 1.97, p < 0.001). In the RF subgroup older age (p < 0.02), female gender (p < 0.003) and not using ACE inhibitors (p = 0.04) or drugs with antiarrhythmic effects (p < 0.005), emerged significantly associated with low survival, while diabetes mellitus (DM) and admission pulmonary edema tended to be so associated (p < 0.2). Using multivariate analysis in the RF subgroup, older age, female gender and DM proved most significantly associated with poorer survival (p = 0.004, OR 1.5, p = 0.03, OR 1.72, p = 0.04, OR 1.28, respectively). In the non-RF subgroup, only older age (p = 0.005) and DM (p = 0.05) were significantly associated with low survival. Sudden death occurred in 21 patients, 14 (8.6%) in the RF and 7 (3%) in the non-RF subgroup (p < 0.001). CONCLUSIONS: RF is a marker of severity in CHF. Its full-blown deleterious prognostic effect is already manifested at serum creatinine 1.5 mg/dl. Older age, DM and female gender most significantly heralded a shorter survival. Such patients require special care.

Aged↗
PubMed1977

Chronic congestive heart failure in coronary artery disease: clinical criteria.

Congestive heart failure is a frequent and important manifestation of cardiovascular disease, but no uniform clinical criteria are available for use in epidemiologic studies. To develop diagnostic criteria, we related pertinent clinical findings to physiologic measures of left ventricular function in patients with coronary artery disease. When left ventricular end diastolic pressure or arteriovenous oxygen difference was used as the physiologic criterion, the following variables contributed significant (P less than 0.01) information: heart volume, ventricular gallop, heart rate, and blood pressure. The most reliable and valid set of descriptors determined in one group was tested in a second group of 1306 patients who had been followed for 6 to 36 months after initial evaluation. The validity of the descriptors was confirmed, and patients identified as having heart failure by these criteria experienced a worse survival rate (P less than 0.001). These criteria characterize patients likely to have impaired left ventricular function and a greater risk of death.

Alabama↗
PubMed1999

Trends of congestive heart failure epidemiology: contrast with clinical trial results.

Congestive heart failure (CHF) is an important and growing public health problem and the cause of substantial morbidity and mortality. Its increasing incidence and prevalence may be in part explained by the progressive aging of the world population. The improvement in coronary artery disease and hypertension treatment allows the individuals to lie longer and develop CHF. Indeed, the most common etiology of CHF is coronary artery disease, the leading cause of cardiovascular morbidity and mortality worldwide, and the second cause of CHF is hypertension which is still markedly increasing in developing countries. Estimates of prevalence of CHF are 0.4 to 2% of the general population. The number of hospital admissions for CHF has also been steadily increasing. Half of the patients carrying a diagnosis of CHF will die within 4 years and patients with severe CHF will die within 1 year. At present, there is no evidence that the prognosis of heart failure in the community has changed despite the advances in therapy over the past decades, such as the demonstration that angiotensin-converting enzyme inhibitors and other vasodilators improve the clinical signs and symptoms of patients with CHF, reduce mortality and slow the progression of myocardial dysfunction. Nevertheless, the overall mortality from this condition remains very high. It is possible that the results of the trials have not yet been evidenced in the majority of patients with CHF because the ideal conditions, treatment and follow-up in the trials are not yet widely achieved in the population.

Adult↗
PubMed2001

Selenium status, kwashiorkor and congestive heart failure.

UNLABELLED: Selenium deficiency is associated with congestive heart failure (CHF) in geographic areas where dietary selenium intake is low and in individuals receiving total parenteral nutrition. Among 66 children with kwashiorkor (including marasmic-kwashiorkor), those who developed CHF had lower serum selenium concentrations than those who did not (32.9 +/- 8.3 vs 41.1 +/- 11.9 microg/L, mean +/- SD, p = 0.03). This association was independent of serum albumin and selenium status was not associated with severity of symptoms, anthropometric indices or HIV infection. CONCLUSION: This association raises the possibility that selenium may contribute to CHF in washiorkor.

Child↗
PubMed2004

Cardiac matrix remodelling in congestive heart failure: the role of matrix metalloproteinases.

BACKGROUND: Congestive heart failure (CHF), the most frequent reason for hospital admission of elderly patients, is an important and rapidly increasing cause of morbidity and mortality worldwide. Its development is accompanied by left-ventricle (LV) dilatation and pump dysfunction. The extracellular space in the heart is now recognized as an essential element of myocardial structure and function, and a dynamic participant in remodelling. The matrix metalloproteinases (MMPs) are an endogenous enzyme system responsible for extracellular collagen degradation and remodelling. OBJECTIVES: To evaluate the potential role of several MMPs (MMP-1, MMP-3 and MMP-9) in CHF. PATIENTS AND METHODS: We recruited 30 consecutive patients with moderate to severe CHF who presented for heart-failure management, along with 15 age- and sex-matched control participants. Two-dimensional and M-mode echocardiographic studies were used to assess LV size and function and hence assess LV remodelling. MMP-1, -3 and -9 concentrations in serum were measured by ELISA at the time of admission and diagnosis. RESULTS: Serum levels of all 3 metalloproteinases were higher in patients with CHF than in controls; those of MMP-3 were markedly increased in patients with severe CHF. CONCLUSIONS: The association found between LV performance and MMP levels suggests that MMPs are implicated in CHF, that serum concentrations of MMPs may serve as markers for CHF, and that MMPs are a potential novel therapeutic target.

Aged↗
PubMed2005

Potential gaps in congestive heart failure management in a rural hospital.

INTRODUCTION: Congestive heart failure (CHF) is increasingly recognized as an important cause of morbidity and mortality. Previous studies in urban settings have shown that patients frequently are not receiving recommended therapy. There is a paucity of studies that have evaluated CHF management in a rural setting. We therefore reviewed hospital and outpatient care in this setting as an initial step toward improving CHF care. METHOD: A retrospective chart review was used to examine the care of all 34 patients hospitalized for CHF from 2000-2001 in a small rural hospital, to assess the need for improved CHF management. RESULTS: The median age of the patients was 78 yr, and a number of them had many co-morbid cardiovascular risks. Similar to other studies, only 23% of patients were prescribed recommended doses of angiotensin-converting enzyme (ACE) inhibitors. Use of beta-blockers was far below expected rates. Although there was follow-up care for nearly all patients (97%), few patients had echocardiography performed (38%) or had their medications altered in the outpatient setting. CONCLUSION: There is a need for improved management of CHF in the rural setting. Approaches to improving CHF care should use the continuity of care advantage provided by primary care physicians to optimize outpatient medical treatment regimens and improve access to diagnostic services such as echocardiography.

Adult↗
PubMed1992

Short-term reproducibility of gas exchange measurements during bicycle exercise in patients with mild to moderate congestive heart failure.

A series of 45 patients with congestive heart failure due to coronary disease had semisupine bicycle exercise tests (ramp protocol, 10 W/min) on two occasions separated by 3 to 7 days in order to determine the short-term reproducibility of gas exchange measurements during symptom-limited exercise. The percentage difference (PD) between each pair of measurements (m1, m2; PD = 100%.(m2-m1): m1) were calculated. The mean PD values (+/- 1 sigma) and the single determination standard deviations (SDSD) for exercise tolerance (ET, W), peak heart rate (pHR, 1/min), peak oxygen uptake (pVO2, ml/min/kg), peak carbon dioxide output (pVCO2, ml/min/kg), and peak minute ventilation (pVE, l/min) were as follows: [table: see text] No patient reached a plateau of oxygen uptake during the last portion of the ramp exercise test. Thus, pVO2 is not an objective endpoint. The single determination standard deviations show that exercise tolerance and peak oxygen uptake do not differ as to their reproducibility. The absolute values of PD were not a function of exercise tolerance for any of the parameters studied. The PD values for ET and pVO2 were normally distributed. The data suggest that a change in ET and pVO2 must exceed 27% and 28% between two sequential studies in an individual patient in order to be significant at the 5% level, respectively. For the one-tailed test situation, the changes in ET or pVO2 must be greater than 23% in order to be significant.

Adult↗
PubMed2006

Efficacy of adaptive servoventilation in patients with congestive heart failure and Cheyne-Stokes respiration.

BACKGROUND: Congestive heart failure (CHF) is associated with Cheyne-Stokes respiration (CSR), which may hasten CHF. Adaptive servoventilation (ASV) is a novel method of ventilatory support designed for removal of CSF in CHF patients. This study compares the efficacy of ASV in patients with CHF and CSR with the efficacy of oxygen therapy. METHODS: Fourteen patients with CHF and CSR were recruited. During sleep, nasal oxygen therapy and ASV treatment were each performed for two weeks. Comparison before and after each treatment was made for the following items: a) parameters of sleep respiration, sleep structure and quality; b) left ventricle ejection fraction (LVEF) and 6-minute walk distance. RESULTS: Compared with the baseline levels of apnoea hypopnoea index of 34.5 +/- 6.1 before treatment, the apnoea hypopnoea index significantly decreased following oxygen therapy to 27.8 +/- 8.2, P < 0.05 and further reduced following ASV treatment to 6.5 +/- 0.8, P < 0.01. The minimal pulse oxygen saturation markedly increased following oxygen therapy from a baseline of (84.3 +/- 2.6)% to (88.6 +/- 3.7)%, P < 0.05 and further increased following ASV treatment (92.1 +/- 4.9)%, P < 0.01. Stages I + II sleep as percentage of total sleep time decreased from (81.9 +/- 7.1)% to (78.4 +/- 6.7)% following oxygen therapy and further to (72.4 +/- 5.0)% following ASV treatment. Stages III + IV sleep as percentage of total sleep time decreased from (8.4 +/- 5.5)% to (6.0 +/- 3.0)% following oxygen therapy and but increased to (11.9 +/- 5.4)% following ASV treatment. The arousal index of 30.4 +/- 8.1 before treatment significantly decreased following oxygen therapy to 25.6 +/- 5.7, P < 0.05 and further declined following ASV treatment to 18.2 +/- 6.1, P < 0.01. No significant difference was shown in above percentages between day 14 of oxygen therapy and before treatment (P > 0.05). LVEF was significantly higher on day 14 of ASV treatment (37.2 +/- 4.1)% than on day 14 of oxygen therapy (33.2 +/- 5.1)% and before treatment (30.2 +/- 4.6)% (all P < 0.05). Six-minute walk distance was the shortest before treatment (226 +/- 28) m, longer on day 14 of oxygen therapy (289 +/- 26) m, and the longest on day 14 of ASV treatment (341 +/- 27) m (all P < 0.01). CONCLUSION: ASV treatment is of better efficacy and greater clinical significance in improvement of CHF by eliminating CSR than oxygen therapy.

Adult↗
PubMed2005

Home peritoneal ultrafiltration in patients with severe congestive heart failure without end-stage renal disease.

Congestive heart failure (CHF), mainly because of ischemic heart disease, is becoming a common medical problem. As CHF worsens and reaches New York Heart Association (NYHA) class IV, many patients can become refractory to medical therapy, especially those who are elderly or who have pre-existing non uremic chronic renal failure. For such patients, quality of life, morbidity, and mortality are expected to be bad. Our objective in the present study was to make a preliminary assessment of the usefulness of icodextrin administered in a single nocturnal peritoneal exchange to patients nonrespondent to the maximal conventional medical therapy. We studied two patients (aged 80 and 87 years), who were affected by severe dilatative cardiomyopathy and moderate-to-severe chronic renal failure. After at least 12 months of treatment, we observed a significant improvement in quality of life and a reduction in morbidity and hospitalization in both patients. Both patients also significantly increased their creatinine clearance. One patient maintained ejection fraction stability (22%-->27%); the other experienced an increase in ejection fraction to 50%from 25%. These preliminary observations suggest that a single nocturnal exchange with icodextrin can be an effective treatment in patients affected by refractory CHF and moderate-to-severe chronic renal failure.

Aged, 80 and over↗
PubMed1990

Nifedipine pharmacodynamics and pharmacokinetics in treatment of congestive heart failure.

In 22 of 27 cases of congestive heart failure (CHF) treated with nifedipine (NIF), significant improvements in resting hemodynamics were noticed. The higher the basal systemic vascular resistance (SVR) and pulmonary artery end diastolic pressure (PAEDP), the greater the magnitude of reduction was achieved (r = 0.84 and 0.77, P less than 0.01, respectively). Exercise hemodynamic investigation showed that NIF lowered SVR, PAEDP and pulmonary vascular resistance (PVR), with an increase in stroke volume (SV) at the serum concentration of 5-10 ng/ml. Maximum effect was observed at the concentration of 20 ng/ml. No further vasodilation was attainable with serum concentrations above 20 ng/ml. No remarkable deviation of NIF pharmacokinetic parameters from the normal ranges was found in CHF patients. The plasma norepinephrine level decreased markedly 2 and 7 hours after the use of NIF. It is concluded that oral NIF is beneficial to severe CHF patients with low cardiac output and high SVR.

Adolescent↗
PubMed1990

Outpatient dobutamine for end-stage congestive heart failure.

Eleven patients with refractory class IV congestive heart failure who were not candidates for cardiac transplantation were given iv dobutamine therapy on an outpatient basis. All patients underwent hemodynamic evaluation to confirm a beneficial response to low dose (5 micrograms/kg.min) dobutamine and to establish arrhythmia control both on and off dobutamine before hospital discharge. Six of the 11 patients could not be weaned from dobutamine in hospital and were discharged on continuous infusion (maximum dose, 5 micrograms/kg.min), while four were discharged with an infusion regimen ranging from 3 to 5 consecutive days/wk. All patients had a chronic venous access placed and were instructed on the use of an external battery-powered infusion pump with a container holding a concentrated solution of dobutamine hydrochloride. All infusions were delivered at home on an ambulatory basis. Intravenous drug support was discontinued gradually over an average of 3.2 months; seven of 11 patients were able to be weaned entirely from iv inotropic therapy and were maintained on oral therapy alone. Seven of the 11 patients (six of whom were maintained on oral therapy alone) required no hospital readmission during the infusion or follow-up period.

Adult↗