The current role of amiodarone in patients with congestive heart failure

Amiodarone in low to moderate doses is generally safe in controlling arrhythmias in patients with congestive heart failure (CHF). However, its role is uncertain, because it did not affect the overall mortality rate in three out of four large-scale studies. Whether some subgroups might benefit is a matter of speculation. In patients with sustained ventricular tachycardia, or in those who have survived an episode of sudden death, implantation of a cardioverter-defibrillator may be a better strategy.     

Left ventricular volume in patients with heart failure and Cheyne-Stokes respiration during sleep

In patients with congestive heart failure (CHF), elevated, left ventricular (LV) volume might lead to pulmonary congestion and hypocapnia, which would create a predisposition to the development of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA). In addition, because LV volume affects cardiac output, it should influence the lengths of hyperpneas. We therefore evaluated LV volumes and transcutaneous PCO2 (PtcCO2) during wakefulness and stage 2 sleep in 16 patients with CHF due to nonischemic dilated cardiomyopathy (NIDC). Data were then compared between those with (n = 7) and those without CSR-CSA (n = 9). LV end-diastolic volume (LVEDV) was significantly higher in patients with than those without CSR-CSA (585 +/- 118 versus 312 +/- 41 ml, p < 0.05). Compared with patients without CSR-CSA, those with CSR-CSA had lower mean stage 2 sleep PtcCO2 (36.3 +/- 2.2 versus 41.2 +/- 1.2 mm Hg, p < 0.05) and a lesser change in PtcCO2 from wakefulness to stage 2 sleep (-0.4 +/- 0.3 versus 2.0 +/- 0.4 mm Hg, p < 0.001). Among patients with CSR-CSA, hyperpnea length was inversely related to LVEDV (R = 0.769, p = 0.043) owing to the direct relationship of cardiac output to LVEDV (R = 0.791, p = 0.034). We conclude that CSR-CSA in patients with CHF due to NIDC is associated with increased LV volumes possibly through the direct or indirect influence of LV volume on PaCO2 and cardiac output.     

The treatment of ischemic heart disease in patients with chronic kidney failure

An analysis of the initial type of central hemodynamics and the postoperative period in 177 patients aged older than 70 years having calculous cholecystitis has shown that surgical treatment of patients with the normo- and hyperdynamic types of circulation even with concomitant diseases can give positive results. The least favourable regimen of blood circulation proved to be the hypodynamic type characteristic of patients with pronounced disturbances of homeostasis and/or with recent myocardial infarction.     

The role of myocardial apoptosis in the development of heart failure

Heart failure can result from a variety of causes, including volume or pressure overload and contractile disturbances of the myocardium. Loss of myocytes is an important mechanism in the development of cardiac failure. In general, myocyte death resulting in progressive deterioration of myocardial function is attributed to necrosis, but recently the involvement of programmed cell death (mainly apoptosis) has been suggested. The authors review the possible role of myocardial apoptosis in developing of heart failure. Subcellular genetic regulatory processes as well as the pharmacological susceptibility of programmed cell death are also discussed. In heart failure, significant amount of cardiac myocytes undergoes apoptosis, that unlike necrosis can be prevented. Specific inhibition of this process could mean a considerable part of cardioprotection after thorough understanding of the underlying cellular mechanisms.     

Effect of oxygen on sleep quality, cognitive function and sympathetic activity in patients with chronic heart failure and Cheyne-Stokes respiration

BACKGROUND: Cheyne-Stokes respiration disrupts sleep, leading to daytime somnolence and cognitive impairment. It is also an independent marker of increased mortality in heart failure. This study evaluated the effectiveness of oxygen therapy for Cheyne-Stokes respiration in heart failure. METHODS: Eleven patients with stable heart failure and Cheyne-Stokes breathing were studies. Oxygen and air were administered for 4 weeks in a double-blind, cross-over study. Sleep and disordered breathing was assessed by polysomnography. Symptoms were assessed using the Epworth Sleepiness Scale, visual analogue and quality of lift scores. Cognitive function was assessed by neuropsychometric testing. Overnight urinary catecholamine excretion was used as a measure of sympathetic nerve activity. RESULTS: Ninety-seven percent of apnoeas were central in origin. Oxygen therapy reduced the central apnoea rate (18.4 +/- 4.1 vs 3.8 +/- 2.1 per hour; p = 0.05) and periodic breathing time (33.6 +/- 7.4 vs 10.7 +/- 3.9% of actual sleep time; p = 0.003). Oxygen did not improve sleep quality, patient symptoms or cognitive failure. Oxygen reduced urinary noradrenaline excretion (8.3 +/- 1.5 vs 4.1 +/- 0.6 nmol.mmol-1 urinary creatinine; p = 0.03). CONCLUSION: Oxygen stabilized sleep disordered breathing and reduced sympathetic activity in patients with heart failure and Cheyne-Stokes respiration. We were unable to demonstrate an effect on either patient symptoms or cognitive function.     

Outpatient management program of patients with chronic heart failure

Hospitalization of patients with heart failure is often caused by poor adherence to drug therapy, by suboptimal utilization of ACE inhibitors and beta-blockers, and by the lack of systematic monitoring of patients after discharge. The aim of the study is to verify the impact of an outpatient management program on the hospitalization rate and functional status of patients with chronic heart failure. Over a five-year period, 435 patients entered our outpatient management program, which includes adjustment in medical therapy, patient education and visits timed according to the patient's status. Fifty-six percent of the patients were in New York Heart functional class I-II; 74% were male; mean age was 62 +/- 11 years. Heart failure was due to coronary heart disease in 42%, dilated cardiomyopathy in 35%, hypertensive heart disease in 13%, other etiologies in 10%. The following changes in medical therapy were made compared to the period before referral: ACE inhibitors in 88% of the patients vs 70% (p < 0.05), mean dose of enalapril and captopril respectively 18 +/- 6 mg vs 11 +/- 4 mg (p < 0.05) and 89 +/- 28 mg vs 61 +/- 34 mg (p < 0.05); digoxin in 71 vs 70% (NS); furosemide in 90 vs 87%; beta-blockers in 16 vs 6% (p < 0.05); amiodarone in 24 vs 16% (p < 0.05); oral anticoagulants in 22 vs 12% (p < 0.05); calcium channel blockers in 10 vs 16% (p < 0.05). During the follow-up period (35 +/- 11 months), there were 111 hospital admissions compared to 518 during the year before recruitment (p < 0.05). Seventy-two patients died (65 for cardiac causes) and four patients underwent cardiac transplantation. Functional status improved (301 patients in I-II functional class and 56 in III-IV after referral compared to 225 and 132 before referral, respectively). Our results were obtained through adjustment in pharmacological therapy, intensive patient education and therapeutic continuity made possible by our outpatient heart-failure clinic organization. It is likely that the increase in costs due to therapeutic adjustment and to the increase in the number of visits is counterbalanced by the reduced rate of hospital admissions.     

Long-term clinical effect of nilvadipine in patients with chronic heart failure: a double-blind placebo-controlled study

The long-term effect of calcium channel blockers on chronic heart failure is disappointing, probably because of reflex sympathetic activation through arterial vasodilation. However, nilvadipine may be beneficial for treatment of chronic heart failure since this drug has minimal effects on sympathetic activation. In this study, the effects of 12-week administration of nilvadipine or placebo on symptoms of heart failure and cardiac function were investigated in 23 patients with mild-to-moderate chronic heart failure in a double-blind trial. The patients were randomly assigned to either a nilvadipine group (16 mg daily) or a placebo group. Intergroup comparisons did not show significant differences in any parameters. Serious adverse effects were not observed during the study. Thus, this study failed to show any beneficial effect of nilvadipine in the long-term treatment of patients with chronic heart failure. We conclude that the long-term administration of nilvadipine (16 mg daily) is neither effective nor harmful in the treatment of patients with chronic heart failure.     

A possible role for saliva as a diagnostic fluid in patients with chronic pain

Magnetic resonance (MR) imaging of the joints with routine pulse sequences can show the three main categories of osteochondral and chondral injuries: osteochondral fractures, osteochondritis dissecans, and chondral fractures. Detecting acute osteochondral fractures, which frequently accompany ligament tears, may modify patient treatment and ultimately may prove important in long-term prognostication. Staging osteochondritis dissecans lesions is possible with MR imaging and can be used to guide therapy, both surgical and nonsurgical. Specific treatment for chondral fractures is evolving; preoperative diagnosis using MR imaging is advantageous because these lesions often are not initially suspected, they are radiographically occult, and they clinically mimic other internal derangements, for which therapy differs. The MR imaging finding that these traumatic lesions share is the frequent presence of an abnormality in the subchondral bone. Fat-suppressed images are the key to detecting subtle areas of subchondral edema, which in turn may draw attention to a defect in the overlying articular surface.     

Effect of ramipril on heart rate variability in digitalis-treated patients with chronic heart failure

Bilharzial-related bladder carcinoma (BBC) is the most common malignant neoplasm in Egypt, also occurring with a high incidence in other regions of the Middle East and East Africa. The clinical and pathological features of BBC are different than those described for the conventional transitional cell carcinoma of the bladder, including the high incidence of squamous cell carcinoma reported in BBC and the fact that over 90% of BBC cases at presentation are advanced-stage tumors (P3 and P4). This study was conducted to better define the phenotypic alterations associated with BBC affecting the p53 cell cycle control pathway, including altered patterns of expression of downstream effector proteins such as mdm2 and p21/WAF1. A well-characterized cohort of 125 patients affected with bilharzial-related bladder tumors was studied. Tumors were classified as squamous carcinomas (n = 68), transitional cell carcinomas (n = 55), or adenocarcinomas (n = 2). The products encoded by TP53, mdm2, and p21/WAF1 genes were analyzed by immunohistochemistry. Furthermore, the patterns of expression of these molecules were correlated with the Ki67 proliferative index. In addition, the microanatomical distribution of programmed cell death was assessed in a subset of tumors, using the so-called terminal deoxynucleotidyl transferase-mediated nick end labeling method. p53 nuclear overexpression was identified in 25 (20%) of 125 cases. Nuclear overexpression of mdm2 was detected in 74 (59.2%) of 125 cases. There was a statistically significant association between coexpression of both p53 and mdm2 and detection of lymph node metastases (P = 0.04). p21/WAF1 expression was detected in 87 (72%) of 121 evaluable cases. A high Ki67 proliferative index was observed in 99 (86%) of 115 evaluable cases. There was a statistically significant association between high Ki67 proliferative index and mdm2-positive phenotype (P = 0.005) and deep muscle invasion (P3b; P = 0.026) as well as lymph node metastases (P = 0.039). Apoptosis was observed in terminally differentiated tumor cells identified in the superficial layers of well-differentiated squamous carcinoma or exfoliating cells in transitional lesions. However, only rare apoptotic tumor cells were found in basal or suprabasal layers as well as in the invasive elements of the neoplasms studied. These results suggest that the frequency of p53 nuclear overexpression in BBC is lower than that reported for conventional transitional cell carcinoma. Nevertheless, tumors with p53 alterations have a greater propensity to progress. The prominent number of cases displaying an mdm2-positive phenotype suggests that this may be an early incident in BBC and should be regarded as a potential oncogenic phenomenon. This is supported by the significant correlation between high Ki67 proliferative index and mdm2 overexpression. The association of an aggressive clinical course with the coexpression of both p53 and mdm2 products might be viewed as a cooperative effect that develops in tumor progression.     

Hemodynamic response to oxygen administration in chronic heart failure: role of chemoreflexes

OBJECTIVE: To determine the applicability and safety of an ifosfamide, cisplatin, and etoposide (VIP) regimen as a neoadjuvant chemotherapy to a concomitant thoracic radiotherapy and cisplatin continuous infusion in locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-four patients (stage IIIb in 43 and stage IIIa in 1) entered a study of VIP, followed by concomitant thoracic radiotherapy and cisplatin continuous infusion. Chemotherapy consisted of three courses of cisplatin 25 mg/m2, ifosfamide 1.5 g/m2 (with uroprotection), and etoposide 100 mg/m2 given on days 1 to 4 of a 21-day cycle with hematopoietic support using recombinant human methionyl granulocyte colony stimulating factor. Patients who achieved a response or a stabilization were planned to receive a split-course normofractionated thoracic radiotherapy (first course: 30 Gy/10; 4-week rest period; second course: 25 Gy/10). A continuous cisplatin infusion of 6 mg/m2 daily was administered using an autonomous chemotherapy delivery device. Total plasma platinum titration was performed daily during the two courses in five of the patients. Analyses were done on an intent-to-treat basis. RESULTS: Thirty-nine of the 44 patients received the three-cycle chemotherapy program. Received dose intensity was 82%. Thirty-eight patients received the radiotherapy and, among them, 35 received the complete concomitant continuous cisplatin infusion. Objective (complete) response rates were 48% (7%) at the end of chemotherapy and increased up to 61% (16%) by the end of radiotherapy. At the end of the first radiotherapy cycle, the mean total plasma platinum concentration was twice as high as that of the residual postinduction chemotherapy concentration. During induction chemotherapy, myelosuppression was the limiting toxicity requiring hospital readmission in 23 patients. During radiotherapy, the main toxicity was acute esophagitis. A relatively high rate of pulmonary fibrosis was observed using the subjective objective management analytic--late effects of normal tissue score without life-threatening pulmonary function impairment. None of the patients died from toxic reactions. Probability of survival at 1, 2, and 3 years was 49%, 19%, and 5%, respectively. Primary cause of failure was a local relapse in 63% of the patients, brain metastases in 24%, and hematogeneous metastases to other sites in 13%. CONCLUSION: Neoadjuvant VIP followed by concomitant radiotherapy-chemotherapy is feasible, but the split-course radiotherapy did not prevent a high rate of local recurrences. The high rate of toxic reactions requiring hospital readmission limits further development of such an aggressive regimen in NSCLC.     

Uric acid in chronic heart failure: a marker of chronic inflammation

BACKGROUND: Chronic heart failure is associated with hyperuricaemia and elevations in circulating markers of inflammation. Activation of xanthine oxidase, through free radical release, causes leukocyte and endothelial cell activation. Associations could therefore be expected between serum uric acid level, as a marker of increased xanthine oxidase activity, and markers of inflammation. We have explored these associations in patients with chronic heart failure, taking into account the hyperuricaemic effects of diuretic therapy and insulin resistance. METHODS AND RESULTS: Circulating uric acid and markers of inflammation were measured in 39 male patients with chronic heart failure and 16 healthy controls. All patients underwent a metabolic assessment, which provided a measure of insulin sensitivity (intravenous glucose tolerance tests and minimal modelling analysis). Compared to controls, patients with chronic heart failure had significantly higher levels of circulating uric acid, interleukin-6, soluble tumour necrosis factor receptor (sTNFR)-1, soluble intercellular adhesion molecule-1 (ICAM-1, all P<0.001), E-selectin and sTNFR2 (both P<0.05). In patients with chronic heart failure, serum uric acid concentrations correlated with circulating levels of sTNFR1 (r=0.74), interleukin-6 (r=0.66), sTNFR2 (r=0.63), TNFa (r=0.60) (all P<0.001), and ICAM-1 (r=0.41, P<0.01). In stepwise regression analyses, serum uric acid emerged as the strongest predictor of ICAM-1, interleukin-6, TNF, sTNFR1 and sTNFR2, independent of diuretic dose, age, body mass index, alcohol intake, serum creatinine, plasma insulin and glucose, and insulin sensitivity. CONCLUSIONS: Serum uric acid is strongly related to circulating markers of inflammation in patients with chronic heart failure. This is consistent with a role for increased xanthine oxidase activity in the inflammatory response in patients with chronic heart failure.     

Hemodynamic and autonomic effects of intravenous saterinone in patients with chronic heart failure

In this study, the hemodynamic and neurohumoral/autonomic effects of intravenous saterinone (a selective phosphodiesterase type III inhibitor, with additional alpha 1-blocking properties) were evaluated. In a double-blind, placebo-controlled design, 36 patients with moderate to severe heart failure were studied (saterinone, n = 24; placebo, n = 12). Invasive hemodynamic measurements, by using right-heart catheterization, were performed, as well as measurement of plasma neurohormones and analysis of heart rate variability (HRV), to study drug influences on neurohumoral activation and autonomic tone. Systemic vascular resistance significantly decreased during saterinone infusion, accompanied by a decrease in systemic blood pressure (both p values < 0.05) and an increase in heart rate (p = 0.05). Filling pressures also decreased during saterinone, but this was statistically significant only for pulmonary capillary wedge pressure, whereas the cardiac index remained unaffected. Plasma neurohormones (norepinephrine, epinephrine, and renin activity) were not significantly influenced by saterinone. HRV analysis revealed no significant effect of saterinone on autonomic tone. These results suggest that intravenous saterinone has a significant vasodilating effect in patients with moderate to severe chronic heart failure (CHF), without exerting an adverse effect on the autonomic nervous system, as demonstrated by assessment of plasma neurohormones and HRV analysis.     

Use of beta-adrenoreceptor antagonists in treatment of patients with chronic heart failure

Chronic heart failure (CHF) is present in 1-10% of the whole population. From the drugs used in CHF so far only angiotensin converting enzyme inhibitors and nitrate with hydralazine improved the survival which was caused by beneficial influence of these drugs on neurohormonal factors. There is growing interest in beta-blockers which are believed to stop the progress of CHF. Although the first attempts of using beta-blockers in the treatment of CHF took place in 70-ties, only recent years brought better understanding of mechanisms of their action. The beneficial effect of beta-blockers in CHF is related to their protective influence on myocardium and to hampering of apoptosis--programmed cell death--the phenomenon which is exaggerated in CHF. The investigations carried out in last years proved that carvedilol which is beta 1-, beta 2- and alpha 1-blocker and has antioxidant properties improved clinical status and reduced mortality in the cohorts of patients with all-cause CHF. At present great trials estimating various beta-blockers and comparing these drug among themselves are being conducted.     

Tumor necrosis factor and steroid metabolism in chronic heart failure: possible relation to muscle wasting

OBJECTIVES: We sought to assess the possible relations between clinical severity of chronic heart failure and catabolic factors, specifically tumor necrosis factor (TNF), soluble TNF receptors 1 and 2 (sTNFR-1 and sTNFR-2), cortisol, testosterone and dehydroepiandrosterone (DHEA). BACKGROUND: Chronic heart failure is associated with loss of muscle bulk that may be related to alteration of the balance between catabolism and anabolism. METHODS: Sixty-three patients (average age +/- SD 60.4 +/- 11.3 years) with stable chronic heart failure and 20 control subjects aged 52.8 +/- 11.4 years were studied. We measured body mass index (BMI) and obtained maximal incremental exercise testing with metabolic gas exchange measurements and measurements of venous levels of TNF, sTNFR-1 and sTNFR-2, cortisol and DHEA. RESULTS: There was no difference in total TNF-alpha levels between patients and control subjects (9.76 +/- 8.59 vs. 6.84 +/- 2.7 pg/ml). sTNFR-1 (128.9 +/- 84.5 vs. 63.6 +/- 23.3 pg/ml, p < 0.003) and sTNFR-2 (250.1 +/- 109.5 vs. 187.9 +/- 92.2 pg/ml, p = 0.03) were higher in patients. DHEA was lower in patients (9.88 +/- 6.94 vs. 15.64 +/- 8.33 nmol/liter, p = 0.004). The ratio of log cortisol to log DHEA correlated with log TNF level (r = 0.50, p < 0.001 for the patients alone; r = 0.48, p < 0.001 for the group as a whole). Peak oxygen consumption correlated with both sTNFR-1 and sTNFR-2 (r = -0.51, p < 0.001 and r = -0.39, p < 0.001, respectively). There was a negative correlation between BMI and TNF levels (r = -0.43, p < 0.001 for the patients) and the cortisol/DHEA ratio (r = -0.32, p = 0.01 for the patients). CONCLUSIONS: There is an increase in TNF and its soluble receptors in chronic heart failure. This increase is associated with a rise in the cortisol/DHEA (catabolic/anabolic) ratio. These changes correlate with BMI and clinical severity of heart failure, suggesting a possible etiologic link.     

The renin-angiotensin-aldosterone system in chronic heart failure

Renin-angiotensin-aldosterone system (RAAS) in patients with rheumatic valve defects clearly tends to activation which in its turn aggravate chronic heart failure (CHF). Plasma renin activity in CHF depends on the cause of the latter, humoral changes in rheumatic heart disease being the most considerable. At the same time activated RAAS was characteristic of patients with rhythm disorders. All this evidence an important role of morphological changes and affected intracardiac haemodynamics in development of humoral vicious circle.