C. Esposito

B-type natriuretic peptide-guided versus symptom-guided therapy in outpatients with chronic heart failure: a systematic review with meta-analysis.

Purpose It has been asserted that serial measurements of natriuretic peptides, specifically B-type natriuretic peptide (BNP) or the amino-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP), may serve as an objective practical guide to better tailor the drug treatment for patients with chronic heart failure (CHF), and especially to detect the cases of subclinical congestion that would require an increase in drug dosing. However, considerable uncertainty remains about the alleged useful role of natriuretic peptide-guided therapy in this context. Therefore, we decided to execute a meta-analysis of published randomized controlled trials (RCTs) to test the hypothesis that an improvement of clinical outcomes in outpatients with CHF may be achieved by adjustment of pharmacologic dosing performed according to natriuretic peptide determinations. Methods The relevant studies were collected through a search across the PubMed database (January 1996 to September 2012). For our meta-analysis, parallel-group RCTs were eligible for inclusion if they met the following criteria: they enrolled patients with CHF, they randomized patients to a strategy of titrating drug therapy based on the level of a circulating natriuretic peptide (BNP or NT-proBNP) compared to a parallel control group treated according to the clinical conventional criteria, and they reported all-cause mortality. In addition, it was established that each RCT to be incorporated in the evaluation should have included more than 60 participants and its follow-up should have been longer than 90 days. The primary endpoint of the meta-analysis was all-cause mortality and hospitalization related to heart failure (combined endpoint). Results In the six pooled RCTs subjected to final meta-analysis (total of included patients = 1775), natriuretic peptide-guided therapy for outpatients with CHF was shown to be associated with a decreased risk of death and heart failure hospitalizations during follow-up (odds ratio – random effect model: 0.64; 95% confidence interval: 0.43–0.95; P = 0.026). Conclusion This meta-analysis supports the hypothesis that natriuretic peptide-guided therapy is superior to symptom-guided therapy for improving clinical outcomes in CHF outpatients. However, some large RCTs failed to document significant clinical improvement in terms of mortality and morbidity using a natriuretic peptide-guided strategy; thus, any attempt to clarify this still unresolved issue by means of further basic and clinical research is recommended in the future.

Hypertonic saline plus i.v. furosemide improve renal safety profile and clinical outcomes in acute decompensated heart failure

BackgroundIn advanced congestive heart failure (CHF), intravenous (i.v.) inotropic agents, i.v. diuretics, ultrafiltration, and hemodialysis have been shown to not yield better clinical outcomes. In this scenario, the simultaneous administration of hypertonic saline solution (HSS) and furosemide may offer a more effective therapeutic option with a good safety profile.MethodsTherefore, a meta-analysis was performed to compare combined therapy, consisting of i.v. furosemide plus concomitant administration of HSS, with i.v. furosemide alone for acute decompensated heart failure (ADHF). The outcomes we chose were all-cause mortality, risk of re-hospitalization for ADHF, length of hospital stay, weight loss, and variation of serum creatinine.ResultsBased on five randomized controlled trials (RCTs) involving 1,032 patients treated with i.v. HSS plus furosemide vs. 1,032 patients treated with i.v. furosemide alone, a decrease in all-cause mortality in patients treated with HSS plus furosemide was proven [RR = 0.57; 95 % confidence interval (CI) = 0.44–0.74, p = 0.0003]. Likewise, combined therapy with HSS plus furosemide was shown to be associated with a reduced risk of ADHF-related re-hospitalization (RR = 0.51; 95 % CI = 0.35–0.75, p = 0.001). Besides, combined therapy with HSS plus furosemide was found to be associated with a reduced length of hospital stay (p = 0.0002), greater weight loss (p < 0.00001), and better preservation of renal function (p < 0.00001).ConclusionHSS as an adjunct to i.v. furosemide for diuretic-resistant CHF patients led to a better renal safety profile and improved clinical endpoints such as mortality and heart failure-related hospitalizations.ZusammenfassungHintergrundBei fortgeschrittener kongestiver Herzinsuffizienz (CHF) haben intravenös (i.v.) applizierte inotrope Substanzen, i.v.-Diuretika, Ultrafiltration und Hämodialyse nachgewiesenermaßen nicht zu besseren klinischen Ergebnissen geführt. Im vorliegenden Szenario stellen die gleichzeitige Gabe von hypertoner Kochsalzlösung (HSS) und Furosemid möglicherweise eine wirksamere therapeutische Option mit gutem Sicherheitsprofil dar.MethodenDaher wurde eine Metaanalyse durchgeführt mit dem Ziel, die kombinierte Therapie aus Furosemid i.v. plus begleitender Gabe von HSS mit der Gabe von Furosemid i.v. allein bei akut dekompensierter Herzinsuffizienz (ADHF) zu vergleichen. Die gewählten Endpunkte waren Mortalität aus sämtlichen Ursachen, Risiko der Wiederaufnahme ins Krankenhaus wegen ADHF, Krankenhausverweildauer, Gewichtsabnahme und Veränderung des Serumkreatinins.ErgebnisseAuf der Grundlage von 5 randomisierten kontrollierten Studien mit 1032 Patienten, die mit HSS plus Furosemid i.v. behandelt wurden, versus 1032 Patienten, die mit Furosemid i.v. allein behandelt wurden, wurde eine Abnahme der Mortalität aus sämtlichen Ursachen bei Patienten mit der Gabe von HSS plus Furosemid nachgewiesen (RR = 0,57; 95%-Konfidenzintervall, 95%-KI: 0,44–0,74; p = 0,0003). Gleichermaßen wurde gezeigt, dass die kombinierte Therapie aus HSS plus Furosemid mit einem verminderten Risiko einer stationären Wiederaufnahme wegen ADHF einherging (RR = 0,51; 95%-KI: 0,35–0,75; p = 0,001). Außerdem stellte sich heraus, dass die kombinierte Therapie aus HSS plus Furosemid mit einer geringeren Krankenhausverweildauer (p = 0,0002), größerer Gewichtsabnahme (p < 0,00001) und besserer Aufrechterhaltung der Nierenfunktion (p < 0,00001) assoziiert war.SchlussfolgerungMit HSS zusätzlich zu Furosemid bei diuretikaresistenten CHF-Patienten wurde eine Verbesserung des renalen Sicherheitsprofils und klinischer Endpunkte wie Mortalität und herzinsuffizienzbedingte stationäre Aufnahme wahrscheinlich.

Ultrasound evaluation of the inferior vena cava collapsibility index in congestive heart failure patients treated with intravenous diuretics: new insights about its relationship with renal function: An observational study

OBJECTIVE In chronic heart failure (CHF), collapsibility index of the inferior vena cava (IVCCI) is used for noninvasive ultrasonographic appraisal of central venous pressure, but it also may be related both to estimated glomerular filtration rate (eGFR) and renal outcome. METHODS On the basis of retrospective observational cohort study, we analyzed 49 patients with right or biventricular CHF in III NYHA class, who had undergone intravenous intensive treatment with furosemide. Aggravated renal dysfunction (ARD) was defined by serum creatinine (Cr) increase of ≥0.3 mg/dL from baseline. IVCCI was categorized in three layers (IVCCI ≤15%, IVCCI 16-40% and IVCCI >40%). The predictors of ARD were searched for as well as any relation between basal IVCCI and both eGFR at admission and occurrence of ARD. RESULTS Overall, 15 cases and 34 controls were compared. Multivariate predictors of ARD were a lower basal eGFR (HR: 0.82 CI: 0.72-0.94 p=0.0045) and intravenous furosemide daily mean dose >80 mg (HR: 48.62 CI: 1.62-3841.5 p=0.0430). A very significant positive correlation was found between IVCCI at admission ≤ 15% and basal eGFR (r=0.96 p<0.0001), while a negative correlation with eGFR was detected in the IVCCI highest (>40%) range (r=-0.696 p=0.0013). Furthermore, the category with basal IVCCI >40% showed a higher rate of ARD compared to that with basal IVCCI 16-40% (p<0.05). CONCLUSION On the basis of the demonstrated u-shaped relationship between IVCCI and eGFR both the stratum with the highest (>40%) and the one with the lowest (≤15%) basal IVCCI may be associated with increased risk of ARD.

Statin use for nonrheumatic calcific aortic valve stenosis: a review with meta-analysis.

Aims To synthesize by meta-analysis the findings of recent experimental studies focusing on possible therapeutic effectiveness of statins for nonrheumatic calcific aortic stenosis Methods Observational studies and randomized controlled trials (RCTs) were selected from the Pubmed database to evaluate the hemodynamic progression of aortic stenosis in statin-treated patients compared with controls (i.e. patients with aortic stenosis taking placebo or no treatment). The endpoints were the annualized changes in one or more of the following ultrasonographic measurements: peak aortic valve jet velocity, peak aortic valve pressure gradient, mean aortic valve pressure gradient aortic valve area (AVA). For estimating the overall effect of statin therapy on each of the above-mentioned continuous variables across the considered studies, we used the weighted mean difference (WMD) as effect size measure. In addition, we calculated the odds of aortic valve replacement surgery and cardiovascular death in both statin-treated patients and controls for subsequently estimating the appropriate odds ratios. Results Nine studies were selected. A lower annualized increase in peak aortic valve jet velocity was found in statin-treated patients compared with controls (overall WMD: −0.09 m/s per year, 95% CI −0.16, −0.01 P = 0.018). Similarly, a smaller annualized increase in peak aortic valve pressure gradient was found in the statin group (overall WMD: −2.04 mmHg/year 95% CI: −3.56, −0.52, P = 0.0085). However, the overall effects in statin-treated patients on both annualized increases in mean aortic valve pressure gradient and decreases in AVA were not significantly different from those found in controls. Moreover, there was no significant difference in cardiovascular outcomes in the statin groups compared with placebo groups in each of the three analyzed RCTs and overall. Conclusion Significant benefit of statin therapy in retarding hemodynamic deterioration was identified by favorable effects concerning annualized changes in peak aortic valve jet velocity and peak aortic valve pressure gradient; on the contrary, in statin-treated patients with aortic stenosis, no significant improvement was found for annualized changes in mean aortic valve pressure gradient and AVA and clinical outcomes.

Hypertonic saline plus i.v. furosemide improve renal safety profile and clinical outcomes in acute decompensated heart failure@@@Besseres renales Sicherheitsprofil und klinische Ergebnisse durch hypertone Kochsalzlösung plus Furosemid i.v. bei akuter dekompensierter Herzinsuffizienz: A meta-analysis of the literature@@@Eine Metaanalyse der Literatur

BackgroundIn advanced congestive heart failure (CHF), intravenous (i.v.) inotropic agents, i.v. diuretics, ultrafiltration, and hemodialysis have been shown to not yield better clinical outcomes. In this scenario, the simultaneous administration of hypertonic saline solution (HSS) and furosemide may offer a more effective therapeutic option with a good safety profile.MethodsTherefore, a meta-analysis was performed to compare combined therapy, consisting of i.v. furosemide plus concomitant administration of HSS, with i.v. furosemide alone for acute decompensated heart failure (ADHF). The outcomes we chose were all-cause mortality, risk of re-hospitalization for ADHF, length of hospital stay, weight loss, and variation of serum creatinine.ResultsBased on five randomized controlled trials (RCTs) involving 1,032 patients treated with i.v. HSS plus furosemide vs. 1,032 patients treated with i.v. furosemide alone, a decrease in all-cause mortality in patients treated with HSS plus furosemide was proven [RR = 0.57; 95 % confidence interval (CI) = 0.44–0.74, p = 0.0003]. Likewise, combined therapy with HSS plus furosemide was shown to be associated with a reduced risk of ADHF-related re-hospitalization (RR = 0.51; 95 % CI = 0.35–0.75, p = 0.001). Besides, combined therapy with HSS plus furosemide was found to be associated with a reduced length of hospital stay (p = 0.0002), greater weight loss (p < 0.00001), and better preservation of renal function (p < 0.00001).ConclusionHSS as an adjunct to i.v. furosemide for diuretic-resistant CHF patients led to a better renal safety profile and improved clinical endpoints such as mortality and heart failure-related hospitalizations.ZusammenfassungHintergrundBei fortgeschrittener kongestiver Herzinsuffizienz (CHF) haben intravenös (i.v.) applizierte inotrope Substanzen, i.v.-Diuretika, Ultrafiltration und Hämodialyse nachgewiesenermaßen nicht zu besseren klinischen Ergebnissen geführt. Im vorliegenden Szenario stellen die gleichzeitige Gabe von hypertoner Kochsalzlösung (HSS) und Furosemid möglicherweise eine wirksamere therapeutische Option mit gutem Sicherheitsprofil dar.MethodenDaher wurde eine Metaanalyse durchgeführt mit dem Ziel, die kombinierte Therapie aus Furosemid i.v. plus begleitender Gabe von HSS mit der Gabe von Furosemid i.v. allein bei akut dekompensierter Herzinsuffizienz (ADHF) zu vergleichen. Die gewählten Endpunkte waren Mortalität aus sämtlichen Ursachen, Risiko der Wiederaufnahme ins Krankenhaus wegen ADHF, Krankenhausverweildauer, Gewichtsabnahme und Veränderung des Serumkreatinins.ErgebnisseAuf der Grundlage von 5 randomisierten kontrollierten Studien mit 1032 Patienten, die mit HSS plus Furosemid i.v. behandelt wurden, versus 1032 Patienten, die mit Furosemid i.v. allein behandelt wurden, wurde eine Abnahme der Mortalität aus sämtlichen Ursachen bei Patienten mit der Gabe von HSS plus Furosemid nachgewiesen (RR = 0,57; 95%-Konfidenzintervall, 95%-KI: 0,44–0,74; p = 0,0003). Gleichermaßen wurde gezeigt, dass die kombinierte Therapie aus HSS plus Furosemid mit einem verminderten Risiko einer stationären Wiederaufnahme wegen ADHF einherging (RR = 0,51; 95%-KI: 0,35–0,75; p = 0,001). Außerdem stellte sich heraus, dass die kombinierte Therapie aus HSS plus Furosemid mit einer geringeren Krankenhausverweildauer (p = 0,0002), größerer Gewichtsabnahme (p < 0,00001) und besserer Aufrechterhaltung der Nierenfunktion (p < 0,00001) assoziiert war.SchlussfolgerungMit HSS zusätzlich zu Furosemid bei diuretikaresistenten CHF-Patienten wurde eine Verbesserung des renalen Sicherheitsprofils und klinischer Endpunkte wie Mortalität und herzinsuffizienzbedingte stationäre Aufnahme wahrscheinlich.

Hypertonic saline plus i.v. furosemide improve renal safety profile and clinical outcomes in acute decompensated heart failureBesseres renales Sicherheitsprofil und klinische Ergebnisse durch hypertone Kochsalzlösung plus Furosemid i.v. bei akuter dekompensierter Herzinsuffizienz

BackgroundIn advanced congestive heart failure (CHF), intravenous (i.v.) inotropic agents, i.v. diuretics, ultrafiltration, and hemodialysis have been shown to not yield better clinical outcomes. In this scenario, the simultaneous administration of hypertonic saline solution (HSS) and furosemide may offer a more effective therapeutic option with a good safety profile.MethodsTherefore, a meta-analysis was performed to compare combined therapy, consisting of i.v. furosemide plus concomitant administration of HSS, with i.v. furosemide alone for acute decompensated heart failure (ADHF). The outcomes we chose were all-cause mortality, risk of re-hospitalization for ADHF, length of hospital stay, weight loss, and variation of serum creatinine.ResultsBased on five randomized controlled trials (RCTs) involving 1,032 patients treated with i.v. HSS plus furosemide vs. 1,032 patients treated with i.v. furosemide alone, a decrease in all-cause mortality in patients treated with HSS plus furosemide was proven [RR = 0.57; 95 % confidence interval (CI) = 0.44–0.74, p = 0.0003]. Likewise, combined therapy with HSS plus furosemide was shown to be associated with a reduced risk of ADHF-related re-hospitalization (RR = 0.51; 95 % CI = 0.35–0.75, p = 0.001). Besides, combined therapy with HSS plus furosemide was found to be associated with a reduced length of hospital stay (p = 0.0002), greater weight loss (p < 0.00001), and better preservation of renal function (p < 0.00001).ConclusionHSS as an adjunct to i.v. furosemide for diuretic-resistant CHF patients led to a better renal safety profile and improved clinical endpoints such as mortality and heart failure-related hospitalizations.ZusammenfassungHintergrundBei fortgeschrittener kongestiver Herzinsuffizienz (CHF) haben intravenös (i.v.) applizierte inotrope Substanzen, i.v.-Diuretika, Ultrafiltration und Hämodialyse nachgewiesenermaßen nicht zu besseren klinischen Ergebnissen geführt. Im vorliegenden Szenario stellen die gleichzeitige Gabe von hypertoner Kochsalzlösung (HSS) und Furosemid möglicherweise eine wirksamere therapeutische Option mit gutem Sicherheitsprofil dar.MethodenDaher wurde eine Metaanalyse durchgeführt mit dem Ziel, die kombinierte Therapie aus Furosemid i.v. plus begleitender Gabe von HSS mit der Gabe von Furosemid i.v. allein bei akut dekompensierter Herzinsuffizienz (ADHF) zu vergleichen. Die gewählten Endpunkte waren Mortalität aus sämtlichen Ursachen, Risiko der Wiederaufnahme ins Krankenhaus wegen ADHF, Krankenhausverweildauer, Gewichtsabnahme und Veränderung des Serumkreatinins.ErgebnisseAuf der Grundlage von 5 randomisierten kontrollierten Studien mit 1032 Patienten, die mit HSS plus Furosemid i.v. behandelt wurden, versus 1032 Patienten, die mit Furosemid i.v. allein behandelt wurden, wurde eine Abnahme der Mortalität aus sämtlichen Ursachen bei Patienten mit der Gabe von HSS plus Furosemid nachgewiesen (RR = 0,57; 95%-Konfidenzintervall, 95%-KI: 0,44–0,74; p = 0,0003). Gleichermaßen wurde gezeigt, dass die kombinierte Therapie aus HSS plus Furosemid mit einem verminderten Risiko einer stationären Wiederaufnahme wegen ADHF einherging (RR = 0,51; 95%-KI: 0,35–0,75; p = 0,001). Außerdem stellte sich heraus, dass die kombinierte Therapie aus HSS plus Furosemid mit einer geringeren Krankenhausverweildauer (p = 0,0002), größerer Gewichtsabnahme (p < 0,00001) und besserer Aufrechterhaltung der Nierenfunktion (p < 0,00001) assoziiert war.SchlussfolgerungMit HSS zusätzlich zu Furosemid bei diuretikaresistenten CHF-Patienten wurde eine Verbesserung des renalen Sicherheitsprofils und klinischer Endpunkte wie Mortalität und herzinsuffizienzbedingte stationäre Aufnahme wahrscheinlich.

Use of Natriuretic Peptides as a Guidance for Treating Patients with Chronic Heart Failure: Unresolved Issues and Novel Insights

Abstract: Serial measurements of natriuretic peptides (NPs), i.e. B-type natriuretic peptide (BNP) or amino-terminal fragment of pro B-type natriuretic peptide (NT-pro BNP), may serve as an objective guide to modulate the intensity of drug treatment for individuals with chronic heart failure (CHF). However, considerable uncertainty remains about the alleged useful role of NP-guided therapy in this context. Particularly, which NP level should be assumed as optimal target level for therapy is still matter of debate. Actually, a too low predetermined cut off is encumbered with the risk of inducing a dose escalation perhaps not founded on solid rationale but provided with the potential of propitiating adverse medication effects that may be associated with higher doses. Conversely, a too high predetermined level for NP would entail a poor sensitivity, with the potential of excluding from higher doses of medications, that are proven to increase survival, just the patients who above all would have benefitted from this uptitration. Another much debated issue is constituted by possible age-related differences concerning the effects on clinical endpoints of NP-guided therapy. In addition, some Authors dispute about the possible advantages for the cardiovascular system arising from the functional activation of NPs in CHF patients, so denying that their increased levels have to be per se blamed for hemodynamic upheaval, especially in elder CHF patients. After outlining the main RCTs carried out so far, the Authors stress the above reported issues and discuss the sometime contradictory results of the RCTs exploring NPs use as a guidance for therapy.