Israel Medical Association Journal

Experimental and clinical data suggest a causal relationship between immunological and inflammatory processes and heart failure. Inflammatory processes may be involved in the pathogenesis of heart failure and may play a role in the progression of ventricular dysfunction. In the last decade several immunological methods were developed that tried to address these questions and overcome the inflammatory and immunological insults. We hope that the present review will increase awareness of new treatment options and encourage researchers and physicians to investigate this novel approach to treat patients with heart failure.
 

Ten years ago we published a review updating current knowledge on heart failure. We summarized that heart failure is a neuro-humoral and inflammatory syndrome, and that pro-inflammatory cytokines are involved in cardiac depression and in the complex syndrome of heart failure. We suggested that understanding the involvement of these cytokines may enable us to reverse cardiac depression and heart failure. Now we know that there are several mechanisms involved in this syndrome, including inflammation, nitric oxide-dependent pathways, apoptosis, reactive oxygen species, and mitochondrial energy metabolism. This review will focus on the up-to-date mechanistic aspects of heart failure, including clinical trials that have contributed to our better understanding of this entity.

Background: Myeloperoxidase levels were shown to reflect endothelial dysfunction, inflammation, atherosclerosis and oxidative stress.

Objectives: To examine the role of circulating myeloperoxidase, a leukocyte-derived enzyme, as a predictor of mortality in patients with congestive heart failure.

Methods: Baseline serum MPO[1] levels were measured in 285 consecutive CHF[2] patients and 35 healthy volunteers. N-terminal pro-brain natriuretic peptide and high sensitivity C-reactive protein concentrations were also measured. The primary outcome endpoint was overall mortality.

Results: MPO levels were significantly elevated in patients with CHF compared to healthy volunteers (P = 0.01). During a mean follow-up of 40.9 ± 11.3 months there were 106 deaths. On a univariate Cox regression analysis MPO levels were of marginal value (P = 0.07) whereas NT-proBNP[3] was of considerable value (P < 0.0001) in predicting all-cause mortality. By dividing our cohort according to NT-proBNP levels into high, intermediate and low risk groups a clear difference in mortality was shown. By further dividing the patient cohort according to MPO levels above or below the median (122.5 ng/ml), mortality prediction improved in the patients with intermediate NT-proBNP values.

[1] MPO = myeloperoxidase

[2] CHF = congestive heart failure

[3] NT-proBNP = N-terminal pro-brain natriuretic peptide

Background: Cardiac computed tomography scans influde several extra-cardiac structures such as mediastinum, lung parenchyma and upper abdominal organs. A variety of abnormalities in those structures might be clinically important and in some cases might explain the patient's complaints.

Objectives: To analyze consecutive cardiac computed tomography examinations for the prevalence and clinical significance of extra-cardiac findings.

Methods: Cardiac CT scans of 134 sequential patients (104 males, 30 females) aged 20–77 years (mean 54 years) with suspected coronary artery disease were prospectively and independently reviewed by a consensus of two radiologists for the presence of lung, mediastinal, pleural, upper abdominal and skeletal abnormalities. CT scans with extra-cardiac abnormalities were divided into two groups: group A – defined as "clinically significant" or "potentially significant findings" – consisted of patients requiring further evaluation or follow-up, and group B – "clinically non-significant findings."

Results: Extra-cardiac abnormalities were found in 103 of the 134 patients (76.8%). Group A abnormalities were found in 52/134 patients (39%), while group B abnormalities were seen in 85/134 (63%). The most common abnormalities in group A were non-calcified lung nodules (> 4 mm) noted in 17/134 patients (13%), followed by enlarged mediastinal lymph nodes (> 10 mm) in 14/134 (10%), diaphragmatic hernia (2 cm) in 12/134 (9%), moderate or severe degenerative spine disease in 12/134 (9%), and emphysema and aortic aneurysm in 6 patients each (4.5%). A malignant lung tumor was noted in one patient.

Conclusions: There is a high prevalence of non-cardiac abnormalities in patients undergoing CCT[1]. Clinically significant or potentially significant findings can be expected in 40% of patients who undergo CCT, and these will require further evaluation and follow-up. The reporting radiologist should be experienced in chest imaging and aware of the large variety of non-cardiac findings in CCT that might explain the patient's complaints. 

Background: Heart rate variability is a sensitive marker of cardiac sympathetic activity.

Objectives: To determine whether long-term hyperthyroidism induced by thyroxine suppressive therapy affects HRV[1].

Methods: Nineteen patients treated with suppressive doses of thyroxin for thyroid cancer and 19 age-matched controls were enrolled. Thyroid function tests and 1 minute HRV were performed on all subjects and the results were compared between the groups. The 1 minute HRV was analyzed during deep breathing and defined as the difference in beats/minute between the shortest and the longest heart rate interval measured by eletrocardiographic recording during six cycles of deep breathing.

Results:  One minute HRV during deep breathing was significantly lower among thyroxine-treated patients compared to healthy controls (25.6 ± 10.5 vs. 34.3 ± 12.6 beats/min, P < 0.05). There were no significant differences in mean, maximal and minimal heart rate between the groups

Conclusions: Thyroxine therapy administered for epithelial thyroid cancer resulted in subclinical hyperthyroidism and significantly decreased HRV due to autonomic dysfunction rather than basic elevated heart rate.

Background: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers improve prognosis in congestive heart failure and are the treatment of choice in these patients; despite this, the rates of ACE-I[1] usage in heart failure patients remain low in clinical practice.

Objectives: To evaluate the rate of ACE-I/ARB[2] treatment in hospitalized patients with CHF[3], and analyze the reasons for non-treatment.

Methods: We prospectively evaluated 362 consecutive patients hospitalized with CHF. Patients were evaluated for ACE-I/ARB usage at discharge and were followed for 1 year.

Results: At hospital discharge 70% of the patients were prescribed ACE-I/ARB treatment. Only 69% received recommended target or sub-target dosages, proven to improve prognosis. This decreased to 63% and 59% at 6 months and 12 months of follow-up respectively, due to a shift from sub-target levels to low dosages. Justified reasons for under-treatment were apparent in only 25% not optimally treated discharged patients and this decreased to 12% and 4% at 6 and 12 months follow-up, respectively. Common reasons for non-treatment at discharge were hyperkalemia and elevation in serum creatinine, while hypotension and cough were more prominent at follow-up. Clinical parameters associated with increased treatment rates were ischemic heart disease and the absence of chronic renal failure. Patients receiving treatment had lower hospitalization and mortality rates.

Conclusions: ACE-I/ARB treatment is still underutilized in patients discharged from hospital with a diagnosis of CHF. Increasing the awareness of the importance of these drugs may increase the number of patients treated.

Background: Despite improved management of heart failure patients, their prognosis remains poor.

Objectives: To characterize hospitalized HF[1] patients and to identify factors that may affect their short and long-term outcome in a national prospective survey.

Methods: We recorded stages B-D according to the American College of Cardiology/American Heart Association definition of HF patients hospitalized in internal medicine and cardiology departments in all 25 public hospitals in Israel.

Results: During March-April 2003, 4102 consecutive patients were recorded. Their mean age was 73 ± 12 years and 57% were males; 75.3% were hypertensive, 50% diabetic and 59% dyslipidemic; 82% had coronary artery disease, 33% atrial fibrillation, 41% renal failure (creatinine ³ 1.5 mg/dl), and 49% anemia (hemoglobin £ 12 g/dl). Mortality rates were 4.7% in-hospital, 7.6% at 30 days, 18.7% at 6 months and 28.1% at 12 months. Multiple logistic regression analysis revealed that increased 1 year mortality rate was associated with New York Heart Association III–IV (odds ratio 2.07, 95% confidence interval 1.78–2.41), age (for 10 year increment) (OR[2] 1.41, 95% CI[3] 1.31–1.52), renal failure (1.79, 1.53–2.09), anemia (1.50, 1.29–1.75), stroke (1.50, 1.21–1.85), chronic obstructive pulmonary disease (1.25, 1.04–1.50) and atrial fibrillation (1.20, 1.02–1.40).

Conclusions: This nationwide heart failure survey indicates a high risk of long-term mortality and the urgent need for the development of more effective management strategies for patients with heart failure discharged from hospitals.

Background: Heart failure with preserved systolic left ventricular function is a major cause of cardiac disability.

Objectives: To examine the prevalence, characteristics and late clinical outcome of patients hospitalized with HF-PSF[1] on a nationwide basis in Israel.

Methods: The Israel nationwide HF survey examined prospectively 4102 consecutive HF patients admitted to 93 internal medicine and 24 cardiology departments in all 25 public hospitals in the country. Echocardiographic LV function measurements were available in 2845 patients (69%). The present report relates to the 1364 patients who had HF-PSF (LV ejection fraction ≥ 40%).

Results: Mortality of HF-PSF patients was high (in-hospital 3.5%, 6 months 14.2%, 12 months 22.0%), but lower than in patients with reduced systolic function (all P < 0.01). Mortality was higher in patients with HF as the primary hospitalization diagnosis (16.0% vs. 12.5% at 6 months, P = 0.07 and 26.2% vs. 18.0% at 12 months, P = 0.0002). Patients with HF-PSF who died were older (78 ± 10 vs. 71 ± 12 years, P < 0.001), more often female (P = 0.05) and had atrial fibrillation more frequently (44% vs. 33%, P < 0.01). There was also a relationship between mortality and pharmacotherapy: after adjustment for age and co-morbid conditions, mortality was lower in patients treated with angiotensin-converting enzyme inhibitors (P = 0.0003) and angiotensin receptor blockers (P = 0.002) and higher in those receiving digoxin (P = 0.003) and diuretic therapy (P = 0.009).

Conclusions: This nationwide survey highlights the very high late mortality rates in patients hospitalized for HF without a decrease in systolic function. The findings mandate a focus on better evidence-based treatment strategies to improve outcome in HF-PSF patients.