Francisco Rocha-Gonçalves

Prognostic Value of High-Sensitivity C-Reactive Protein in Heart Failure: A Systematic Review

BACKGROUND Several studies have suggested that high-sensitivity C-reactive protein (hsCRP) is a strong independent predictor of acute myocardial infarction and cardiovascular death. In the specific heart failure (HF) context, a low-grade inflammatory state can contribute to HF progression. AIMS To perform a systematic review on the current knowledge about low-grade inflammation, as assessed by hsCRP, in the prediction of HF in general and in high-risk populations as well as its prognostic value in established HF. METHODS We used a computerized literature search in the Medline database using the following key words: C-Reactive Protein, Heart Failure, Cardiomyopathy, Cardiac Failure, Prognosis, and Death. Articles were selected if they had measurements of hsCRP in different patient samples and reference to outcomes in terms of morbidity and mortality. RESULTS hsCRP is associated with incident HF in general and high-risk populations and provides prognostic information in HF patients. In almost all studies, the association of hsCRP with clinical events was independent of other baseline variables known to influence morbidity and mortality. Very different cutoffs have been proposed in each context across studies. CONCLUSIONS The prognostic power of hsCRP, whether we consider incident HF or adverse outcomes in established HF, is consistent in different patient populations.

Prognostic information provided by serial measurements of brain natriuretic peptide in heart failure

BACKGROUND Brain natriuretic peptide (BNP) levels predict prognosis in heart failure patients. We aimed to evaluate if serial measurements of BNP can give additional prognostic information. METHODS Eighty-four patients with systolic dysfunction had two measurements of BNP with an interval of 8 to 12 months and were followed in order to register the occurrence of death. The study was observational and prospectively designed. During follow-up, patients were treated according to state of the art. Physicians were kept blind to BNP levels. RESULTS The median follow-up was 1190 days. The median initial BNP level was 260.4 pg/ml and decreased to 123 pg/ml in the second measurement (P=0.001). The decrease in BNP was significantly associated with ACE-i dosage and with the use of a beta-blocker. All-cause mortality was 20.2%. Patients whose initial BNP level was above the median had a significantly higher hazard of dying (HR 2.96, 95% CI 1.06-8.26). The same was observed for those whose BNP increased between the first and the second measurement (HR 2.64, 95% CI 1.00-7.00). In multivariable analysis, baseline BNP above the median and increasing BNP were associated with shorter survival. CONCLUSIONS Higher baseline BNP and the increasing levels during follow-up were independently associated with mortality. The decrease in BNP levels was proportional to ACE-i dosage and larger among patients on beta-blockers. These results confirm the prognostic information provided by BNP determination and suggest that serial measurements give additional prognostic information.

Adiponectin is increased in cardiac cachexia irrespective of body mass index

Cardiac cachexia (CC) is a complication of chronic heart failure (CHF). Little is known about the mechanisms leading to CC. Adiponectin, leptin, and ghrelin are important regulators of energy metabolism and body weight. Previous studies of CHF and CC had great differences in body mass index (BMI) between cachectic and non‐cachectic patients. To assess serum adiponectin, leptin, and ghrelin concentrations in cachectic and non‐cachectic patients.

Nutritional markers and prognosis in cardiac cachexia

BACKGROUND Cachexia frequently complicates chronic heart failure (CHF) and predicts an ominous prognosis. Hormonal and inflammatory environment differ between cachectic and non-cachectic patients. Nutritional markers of cardiac cachexia and prognostic predictors in this context are not completely understood. OBJECTIVES To study biochemical markers of nutritional status in cardiac cachexia and to investigate variables associated with worse prognosis. METHODS A total of 94 ambulatory patients--38 cachectics and 56 non-cachectics--were recruited. Cardiac cachexia was defined as a weight loss of ≥ 7.5%. An anthropometric evaluation was performed in all patients and blood was collected for several laboratory determinations: haemoglobin, lymphocytes, albumin, transferrin, pre-albumin, cholesterol and triglycerides. Patients were included in a prospective cohort study. RESULTS Cachectics had lower albumin and pre-albumin levels. They also had lower haemoglobin, lymphocytes and triglycerides. Levels of high-sensitivity C-reactive protein, and catabolic hormones were higher in the cachectic group. Low pre-albumin was the only nutritional marker independently associated with cardiac cachexia. (OR = 1.08, CI: 1.01-1.17). During a follow-up of 16.2 ± 5.2 months, 15 (39.4%) cachectic patients and 6 (10.7%) non-cachectics died. In the cachectic group, lower cholesterol was independently associated with worse outcome (HR = 1.32, CI: 1.11-1.57). CONCLUSIONS Pre-albumin seems to be the best laboratory marker of undernutrition in CHF. Low cholesterol independently associates with worse outcome in cardiac cachexia.

B‐type natriuretic peptide is related to cardiac function and prognosis in hospitalized patients with decompensated cirrhosis

Background: B‐type natriuretic peptide (BNP) concentrations are high in cirrhosis, possibly related to volume status and cirrhotic cardiomyopathy. The prognostic significance of BNP in cirrhosis is unknown.

BNP at discharge in acute heart failure patients: Is it all about volemia? A study using impedance cardiography to assess fluid and hemodynamic status

BACKGROUND Besides hemodynamic parameters, several other variables have been associated to B-type natriuretic peptide (BNP) levels. Limited knowledge on BNP determinants in acute heart failure (HF) can undermine the interpretation of BNP levels. METHODS AND RESULTS To identify predictors of BNP levels, we evaluated 163 hospitalized acute HF patients. Thoracic fluid content (TFC) and hemodynamic parameters were measured by impedance cardiography at discharge. Patients were followed-up for 60 days for the occurrence of death/hospital admission. Median discharge BNP levels were 659.3 pg/ml. In multivariable linear regression analysis, TFC (β=0.043, 95% CI 0.024-0.062 per U/kΩ, p<0.001) was a powerful predictor of BNP levels, independently of known markers of HF severity like severe systolic dysfunction and discharge New York Heart Association class. Other independent predictors were: new onset HF, albumin, and body mass index. Sex, left cardiac work index, stroke index, hemoglobin, renal failure and discharge furosemide and lisinopril doses were associated to BNP only in univariate analysis. During follow-up, 45 (27.6%) patients were hospitalized or died. TFC (HR=1.047 (1.016-1.080) per U/kΩ increase, p=0.003) and BNP (HR=1.003 (1.001-1.004) per 10 pg/ml increase, p<0.001) were univariate predictors of the outcome, but in multivariate Cox regression analysis, only BNP was independently associated with prognosis. CONCLUSION Discharge BNP levels in acute HF patients reflected volemia and disease severity. Persistently high BNP levels during hospitalization should raise the possibility of remaining congestion, which could negatively influence prognosis. The utility of BNP as prognostic marker in HF may reside on its ability to reflect multiple underlying pathophysiological disturbances.

New cardiovascular biomarkers: clinical implications in patients with valvular heart disease

Valvular heart disease (VHD) is characterized by an ongoing, inflammatory cellular response which results in a left ventricular hemodynamic stress change in response to valvulopathy. The current inflammatory hypothesis suggests that as the heart valve disease progresses the inflammatory cytokine response is activated causing continuation of deleterious effects on the heart and vasculature. This can lead to progression of heart failure and left ventricular dysfunction. Over the last 10 years, a number of biologically active molecules, termed biomarkers, have been discovered in VHD. These can be used to detect the progression and pathogenesis of heart failure and to assess the severity of inflammation (e.g., C-reactive protein). Brain natriuretic peptide (BNP) can diagnose underlying cardiac systolic and diastolic dysfunction. In high-risk patients BNP is also considered to be a useful tool for assisting in the diagnosis and monitoring the progression of VHD. Patients with symptomatic VHD benefit from aortic valve surgery; however, management in the absence of symptoms remains challenging. While the lack of symptoms can delay aortic valve replacement, unselected premature aortic valve replacement may be associated with unbalanced risks of cardiac surgery. This review summarizes the current and emerging clinical and potential research application of specific biomarkers of VHD.

Heart failure and sleep apnoea: To sleep perchance to dream

Heart failure and sleep apnoea are major health problems with an increasingly recognized association; evidence suggests that sleep apnoea may play a role in the progression of heart failure. However, confounding factors such as obesity, hypertension and coronary heart disease make this relationship uncertain and an independent correlation remains unproven.

Inhalatory pentamidine therapy and the duration of the QT interval in HIV-infected patients

We evaluated the effect of chronic Pneumocystis carinii pneumonia (PCP) prophylaxis, with a once a month dose of 300 mg of inhalatory pentamidine isethionate, on QT interval duration. We included 22 human immunodeficiency virus (HIV)-infected patients: 11 were on this medication and 11 were not. The two groups were matched for age, sex and HIV infection stage. No patient had any clinical condition or was under any medication known to affect the duration of the QT interval. The heart rate-corrected QT (QTc) was obtained by averaging the observations of three independent observers. QTc duration was similar in both groups. The time separating pentamidine administration and the performance of the ECG did not influence the results, neither did the duration of inhalatory pentamidine therapy. Our results suggest that inhalatory pentamidine does not prolong the QT interval duration and so, as opposed to what has been reported concerning intravenous pentamidine therapy, does not seem to induce an increased risk of torsades de pointes.

New understanding about calcific aortic stenosis and opportunities for pharmacologic intervention.

Purpose of review This review article will discuss aortic stenosis, the evolving studies defining the cellular mechanisms and the potential for medical therapies for the treatment of this disease. Recent findings Currently, the only therapy for these patients is surgical valve replacement. In the past decade there has been a change in the paradigm towards our understanding of the cellular biology of this disease process. Studies in laboratories across the world have demonstrated that this disease has an active biology and that this biology may be targeted with medical therapies similar to that of vascular atherosclerosis. Summary Calcific aortic stenosis is the third most common form of cardiovascular disease in the USA. It has replaced rheumatic heart disease in prevalence in western countries due to improved access to healthcare and the widespread use of antibiotics.