Rocco Lagioia

Cardiovascular and noncardiovascular comorbidities in patients with chronic heart failure

A broad spectrum of concomitant disorders may complicate heart failure adding further morbidity and mortality risk. Comorbidities may be subdivided into cardiovascular and noncardiovascular. The first group includes hypertension, coronary artery disease, peripheral artery disease, cerebrovascular disease, arrhythmias and valvular heart disease. Noncardiovascular comorbidities include respiratory, endocrine, metabolic, nutritional, renal, hematopoietic, neurological as well as musculoskeletal conditions. In recent years, advances in the treatment of heart failure have not been attended by important changes in management of its comorbidities. They now seem to be major causes of the poor prognosis of heart failure patients. In this review we provide an updated summary of the epidemiological, pathophysiological and clinical characteristics of comorbidities as well as their potential impact for heart failure treatment.

Percent achieved of predicted peak exercise oxygen uptake and kinetics of recovery of oxygen uptake after exercise for risk stratification in chronic heart failure

To investigate whether percent achieved of predicted peak exercise oxygen uptake (%VO2max) and recovery of oxygen consumption after exercise may provide prognostic information in chronic heart failure (CHF), we prospectively studied 196 patients with mild to moderate CHF. The following variables were examined: age, etiology of CHF, functional class, ejection fraction (EF), peak exercise oxygen uptake normalized for body weight (VO2max), %VO2max, time to reach 50% of the peak oxygen uptake after exercise (T1/2VO2max), presence of nonsustained ventricular tachycardia (NSVT) and inability to take ACE-inhibitors. VO2max was the most powerful predictor of cardiac death (P<0.0001). Other independent predictors of death were EF, T1/2VO2max, NSVT and inability to take ACE-inhibitors. The discriminatory accuracy of VO2max for cardiac death was not significantly greater than that of %VO2max. In conclusion, the determination of %VO2max does not enhance risk stratification in CHF whereas the kinetics of oxygen consumption after exercise can provide prognostic information.

Clinical utility of N-terminal pro-B-type natriuretic peptide for risk stratification of patients with acute decompensated heart failure. Derivation and validation of the ADHF/NT-proBNP risk score

BACKGROUNDnNT-proBNP has been associated with prognosis in acute decompensated heart failure (ADHF). Whether NT-proBNP provides additional prognostic information beyond that obtained from standard clinical variables is uncertain. We sought to assess whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) determination improves risk reclassification of patients with ADHF and to develop and validate a point-based NT-proBNP risk score.nnnMETHODSnThis study included 824 patients with ADHF (453 in the derivation cohort, 371 in the validation cohort). We compared two multivariable models predicting 1-year all-cause mortality, including clinical variables and clinical variables plus NT-proBNP. We calculated the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI). Then, we developed and externally validated the NT-proBNP risk score.nnnRESULTSnOne-year mortalities for the derivation and validation cohorts were 28.3% and 23.4%, respectively. Multivariable predictors of mortality included chronic obstructive pulmonary disease, estimated glomerular filtration rate, sodium, hemoglobin, left ventricular ejection fraction, and moderate to severe tricuspid regurgitation. Adding NT-proBNP to the clinical variables only model significantly improved the NRI (0.129; p=0.0027) and the IDI (0.037; p=0.0005). In the derivation cohort, the NT-proBNP risk score had a C index of 0.839 (95% CI: 0.798-0.880) and the Hosmer-Lemeshow statistic was 1.23 (p=0.542), indicating good calibration. In the validation cohort, the risk score had a C index of 0.768 (95% CI: 0.711-0.817); the Hosmer-Lemeshow statistic was 2.76 (p=0.251), after recalibration.nnnCONCLUSIONSnThe NT-proBNP risk score provides clinicians with a contemporary, accurate, easy-to-use, and validated predictive tool. Further validation in other datasets is advisable.

Ivabradine, coronary artery disease, and heart failure: beyond rhythm control

Elevated heart rate could negatively influence cardiovascular risk in the general population. It can induce and promote the atherosclerotic process by means of several mechanisms involving endothelial shear stress and biochemical activities. Furthermore, elevated heart rate can directly increase heart ischemic conditions because of its skill in unbalancing demand/supply of oxygen and decreasing the diastolic period. Thus, many pharmacological treatments have been proposed in order to reduce heart rate and ameliorate the cardiovascular risk profile of individuals, especially those suffering from coronary artery diseases (CAD) and chronic heart failure (CHF). Ivabradine is the first pure heart rate reductive drug approved and currently used in humans, created in order to selectively reduce sinus node function and to overcome the many side effects of similar pharmacological tools (ie, β-blockers or calcium channel antagonists). The aim of our review is to evaluate the role and the safety of this molecule on CAD and CHF therapeutic strategies.

Propionil-L-carnitine: a new compound in the metabolic approach to the treatment of effort angina

The effects of propionyl-L-carnitine on exercise tolerance of 12 patients with stable exertional angina were assessed in a double-blind, placebo-controlled, cross-over protocol using serial exercise tests. Compared to placebo, propionyl-L-carnitine significantly increased total work from 514 +/- 199 to 600 +/- 209 W (P less than 0.05) (17%) and prolonged exercise time and time to ischemic threshold from 515 +/- 115 to 565 +/- 109 sec (P less than 0.05) (10%) and from 375 +/- 102 to 427 +/- 93 sec (P less than 0.01) (14%), respectively. ST segment depression at the highest common work level was significantly reduced from 0.19 +/- 0.08 to 0.15 +/- 0.08 mV (P less than 0.05) (21%). No significant changes in heart rate, systolic blood pressure, and rate-pressure product at rest, at the highest common work level, on appearance of the ischemic threshold, or at peak exercise were observed after propionyl-L-carnitine treatment. No side effects were observed under propionyl-L-carnitine treatment. This study shows that propionyl-L-carnitine can significantly improve exercise tolerance in patients with stable angina. Our data seem to confirm that propionyl-L-carnitine most likely exerts its protective action via the metabolic pathway.

The ADHF/NT-proBNP risk score to predict 1-year mortality in hospitalized patients with advanced decompensated heart failure

BACKGROUNDnThe acute decompensated heart failure/N-terminal pro-B-type natriuretic peptide (ADHF/NT-proBNP) score is a validated risk scoring system that predicts mortality in hospitalized heart failure patients with a wide range of left ventricular ejection fractions (LVEFs). We sought to assess discrimination and calibration of the score when applied to patients with advanced decompensated heart failure (AHF).nnnMETHODSnWe studied 445 patients hospitalized for AHF, defined by the presence of severe symptoms of worsening HF at admission, severely depressed LVEF, and the need for intravenous diuretic and/or inotropic drugs. The primary outcome was cumulative (in-hospital and post-discharge) mortality and post-discharge 1-year mortality. Separate analyses were performed for patients aged ≤ 70 years. A Seattle Heart Failure Score (SHFS) was calculated for each patient discharged alive.nnnRESULTSnDuring follow-up, 144 patients (32.4%) died, and 69 (15.5%) underwent heart transplantation (HT) or ventricular assist device (VAD) implantation. After accounting for the competing events (VAD/HT), the ADHF/NT-proBNP scores C-statistic for cumulative mortality was 0.738 in the overall cohort and 0.771 in patients aged ≤ 70 years. The C-statistic for post-discharge mortality was 0.741 and 0.751, respectively. Adding prior (≤6 months) hospitalizations for HF to the score increased the C-statistic for post-discharge mortality to 0.759 in the overall cohort and to 0.774 in patients aged ≤ 70 years. Predicted and observed mortality rates by quartiles of score were highly correlated. The SHFS demonstrated adequate discrimination but underestimated the risk. The ADHF/NT-proBNP risk calculator is available at http://www.fsm.it/fsm/file/NTproBNPscore.zip.nnnCONCLUSIONSnOur data suggest that the ADHF/NT-proBNP score may efficiently predict mortality in patients hospitalized with AHF.

Detection and prognostic impact of renal dysfunction in patients with chronic heart failure and normal serum creatinine

BACKGROUNDnAccurate identification of renal dysfunction (RD) is crucial to risk stratification in chronic heart failure (CHF). Patients with CHF are at special risk of having RD despite normal serum creatinine (SCr), owing to a decreased Cr generation. At low levels of SCr, the equations estimating renal function are less accurate. This study was aimed to assess and compare the prognostic value of formulas estimating renal function in CHF patients with normal SCr.nnnMETHODSnWe studied 462 patients with systolic CHF and normal SCr. Creatinine clearance was estimated by the Cockcroft-Gault (eCrCl) and glomerular filtration rate by the 4-variable MDRD equation (eGFR); eCrCl normalized for body-surface area (eCrCl(BSA)) was calculated. The primary outcome was all-cause mortality at 2 years.nnnRESULTSnSeventy five patients died. At multivariate Cox regression analysis, only eCrCl(BSA) was significantly associated with mortality (p = 0.006); eGFR (p = 0.24), eCrCl (p = 0.09) and BUN (p = 0.14) were not statistically significant predictors. The patients in the lowest eCrCl(BSA) quartile had an adjusted 2.1-fold (CI: 1.06-4.1) increased risk of mortality, compared with those in the referent quartile. Two-year survival was 70.4% in the lowest eCrCl(BSA) quartile and 89.7% in the referent quartile. Other independent predictors of mortality were ischemic etiology (RR: 2.16 [CI: 1.3-3.5], p = 0.0017), NYHA III/IV class (RR: 2.45 [CI: 1.51-3.97], p = 0.0003), LVEF <0.25 (RR: 3.38 [CI: 1.69-6.75], p = 0.014), and anemia (RR: 1.86 [CI: 1.16-2.99], p = 0.009).nnnCONCLUSIONSnA sizeable proportion of CHF patients have prognostically significant RD despite normal SCr. Such patients represent a high-risk subgroup and can more accurately be identified by the CG formula corrected for BSA than the MDRD.

Systemic Vascular Hemodynamic Changes due to 17-β-Estradiol Intranasal Administration

Purpose: According to the literature, estradiol has a direct vasodilator action by means of endothelium-derived relaxing factor synthesis. The present study aims to evaluate the acute hemodynamic effects of intranasal 17-β-estradiol on cerebral and lower limb arterial circulation in postmenopausal women. Methods: Sixteen healthy women in natural menopause (mean age: 54 ± 3 years) were investigated for at least 6 months, each receiving 300 µg of intranasal 17-β-estradiol. We evaluated the heart rate, systolic/diastolic blood pressure, peak systolic velocity, end-diastolic velocity, and velocity–time integral (VTI) at the level of internal carotid and posterior tibial arteries, before and after 30, 60, and 180 minutes of drug administration. Results: After intranasal 17-β-estradiol administration, the internal carotid artery VTI showed statistically significant (P < .05) variations at all the time intervals after administration of the drug (30, 60, and 180 minutes) when compared with “time zero” (T0, ie, the speed recorded at baseline before drug administration). No significant variation was found at the posterior tibial artery. The systolic/diastolic blood pressure and heart rate did not significantly differ before and after drug administration. Conclusions: The administration of a single intranasal dose of 17-β-estradiol in healthy postmenopausal women increased cerebral perfusions, whereas the effect on peripheral circulation was much more limited.

Inpatient Cardiac Rehabilitation Soon After Hospitalization for Acute Decompensated Heart Failure: A propensity score study.

PURPOSE: Postdischarge management of acute decompensated heart failure (ADHF) remains an ongoing challenge. We sought to assess whether inpatient cardiac rehabilitation (CR) soon after hospitalization for ADHF improves outcome. METHODS: Patients (N = 275) hospitalized for ADHF were enrolled. The primary outcome was a composite of all-cause mortality and urgent heart transplantation (UHT) at 1 year. The followup started at the time of discharge from the acute care setting. Because of the observational nature of the study, a propensity score analysis was used to predict the likelihood of undergoing CR. A multivariable Cox regression analysis adjusted for propensity score was used to assess the effect of CR on the primary outcome. RESULTS: Of the 275 patients, 130 underwent CR. Among the baseline variables of the index hospitalization for ADHF, propensity score derivation identified male gender, New York Heart Association Class IV, refractory HF, moderate to severe mitral or tricuspid regurgitation, nonuse of renin-angiotensin-aldosterone system inhibitors, and daily dosage of furosemide, as being independently associated with the likelihood of undergoing CR. No patient was lost to followup. During the 12-month followup, 74 patients died and 3 underwent UHT. The overall incidence of the primary outcome was 28%. On propensity score–adjusted Cox multivariable analysis, the relative risk of the primary outcome for participants in CR compared with nonparticipants in CR was 0.58 (confidence interval [CI]: 0.34–0.99; P = .04). CONCLUSIONS: Results suggest that the strategy of inpatient CR soon after discharge from the acute care setting improves 1-year UHT-free survival of patients with ADHF.

Predictors of Long‐Term Mortality in Older Patients Hospitalized for Acutely Decompensated Heart Failure: Clinical Relevance of Natriuretic Peptides

Acute heart failure is a common cause of hospitalization among older patients. Optimized risk stratification might improve the outcome for this subgroup of patients. Natriuretic peptides have been used in the diagnosis of heart failure and in evaluating the prognosis of patients hospitalized for heart failure. However, their utility in the elderly is still controversial.