Hyperglycemia in Acute Heart Failure: An Opportunity to Intervene?

In patients with acute heart failure (AHF) syndromes, little data are so far available on the relation between glucose values and insulin resistance and mortality, both in the short and long term. The present review is aimed at summarizing available evidence on the prognostic role of hyperglycemia in acute heart failure syndromes. Despite the fact that glucose values are widely measured, inexpensive, and easy to interpret, hyperglycemia in AHF patients still appears to be (or at least to have been) a neglected factor. Scarce information is available on incidence of admission hyperglycemia (especially in nondiabetic AHF patients) and data on in-hospital and discharge glucose values are lacking. Overall, the scarcity of data and the unanswered questions conjure up the need for trials investigating the clinical and prognostic role of glucose abnormalities (hyperglycemia and acute insulin resistance) on admission and during hospital stay in AHF patients. Preliminary evidence suggests that hyperglycemia is an important prognostic factor in AHF; however, whether targeting hyperglycemia via an aggressive versus permissive glycemic management strategy influences AHF outcomes remains unknown.     

Risk Stratification With the Use of Serial N-Terminal Pro–B-Type Natriuretic Peptide Measurements During Admission and Early After Discharge in Heart Failure Patients: Post Hoc Analysis of the PRIMA Study

ObjectiveThe aim of this work was to assess the prognostic value of absolute N-terminal-pro–B-type natriuretic peptide (NT-proBNP) concentration in combination with changes during admission because of acute heart failure (AHF) and early after hospital discharge.BackgroundIn AHF, readmission and mortality rates are high. Identifying those at highest risk for events early after hospital discharge might help to select patients in need of intensive outpatient monitoring.Methods and resultsWe evaluated the prognostic value of NT-proBNP concentration on admission, at discharge, 1 month after hospital discharge and change over time in 309 patients included in the PRIMA (Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) study. Primary outcome measures were mortality and the combined end point of heart failure (HF) readmission or mortality. In a multivariate Cox regression analysis, change in NT-proBNP concentration during admission, change from discharge to 1 month after discharge, and the absolute NT-proBNP concentration at 1 month after discharge were of independent prognostic value for both end points (hazard ratios for HF readmission or mortality: 1.71, 95% confidence interval [CI] 1.13–2.60, Wald 6.4 [P = .011] versus 2.71, 95% CI 1.76–4.17, Wald 20.5 [P < .001] versus 1.81, 95% CI 1.13–2.89, Wald 6.1 [P = .014], respectively.ConclusionsKnowledge of change in NT-proBNP concentration during admission because of AHF in combination with change early after discharge and the absolute NT-proBNP concentration at 1 month after discharge allows accurate risk stratification.     

Cardiology department hospitalization costs in patients with acute heart failure vary according to the etiology of the acute heart failure: Data from the AHEAD Core registry 2005–2009

BackgroundTo assess the distribution of costs associated with Cardiology Unit hospitalization due to acute heart failure (AHF) and evaluate, from the perspective of the healthcare payer, the heterogeneity of resources use according to AHF etiology in patients from 2005 to 2009.MethodsThe type and etiology of AHF was determined upon hospital admission. The cost of in-patient care was based on the individual hospital account of each patient (1759 patients in total; 58.7% male; mean age 71 years).ResultsThe median hospital stay was 7 days and the mean total cost of in-patient care was €3364. A Coronary Care Unit (CCU) stay was recorded in 67.4% patients (median 3 days). Significantly higher costs were found in de-novo AHF patients (mean €3678) with a greater need for CCU care, a longer stay in the CCU and a greater need for intervention (particularly that of percutaneous coronary intervention (PCI)), than in patients with acute decompensation of chronic heart failure (mean cost €2878; p<0.001). Acute coronary syndrome was a major precipitating factor, with the highest costs (€4429) resulting from having received PCI (63.3% of patients) and CCU admission (91.7% of patients). Variations in length of stay according to AHF etiology were minor (median, 6–8 days). In-hospital mortality was 15.0%.ConclusionsHospitalization costs as they relate to AHF are high, particularly in new-onset AHF patients. The heterogeneity of resources use is largely a reflection of interventions undertaken, particularly if revascularization or anti-arrhythmic therapy is provided.     

Acute heart failure associated with high admission blood pressure — A distinct vascular disorder?

BACKGROUND: Although blood pressure (BP) is elevated in patients with acute heart failure (AHF), first admission BP has not been meticulously recorded before treatment in previous studies. METHODS: During three consecutive months, all AHF admissions (335 patients) to a city hospital which provides the sole inpatient medical service for approximately 500,000 people were registered. First BP was recorded before treatment at the first patient encounter in the ambulance or the emergency room. RESULTS: Mean BP at admission was 164+/-38/88+/-22 mm Hg. Mean BP in the highest quartile was 212+/-22/115+/-13 mm Hg. Patients with higher baseline BP had higher ejection fraction (highest versus lowest quartile 48+/-13% vs. 33+/-14%, p<0.001), less atrial fibrillation (18% vs. 42%, p=0.001) as well as lower mean urea and higher mean haemoglobin. The apparently more favourable baseline characteristics in patients with higher admission BP did not translate into lower morbidity - the rate of worsening heart failure - was not related to admission BP. However, 6 month mortality was lower in patients with higher admission BP (4% vs. 19.3%, p=0.002). CONCLUSIONS: Blood pressure is elevated substantially at the onset of AHF. The different characteristics and outcome of patients admitted with high-BP associated AHF suggest that this presentation may be a specific disorder related to a distinct yet unknown pathophysiological mechanism.     

Characteristics, outcomes, and predictors of 1-year mortality in patients hospitalized for acute heart failure.

AIMS: Acute heart failure (AHF) is associated with poor prognosis and requires recurrent hospitalizations. However, studies on AHF characteristics, treatment, and prognostic factors are few. Our aim was to investigate the characteristics, treatment, and 1-year prognosis of AHF and identify prognostic factors in different clinical groups. METHODS AND RESULTS: We conducted a prospective multicentre study with 620 patients hospitalized due to AHF; mean age 75.1 (10.4) years, 50% male. Half of the patients had new-onset heart failure. Acute congestion (63.5%) and pulmonary oedema (26.3%) were the most common clinical presentations. Left ventricular ejection fraction (LVEF) was reported in two-thirds of patients. Half of these had preserved systolic function (LVEF> or =45%). At discharge, 86% of patients had beta-blockers and 76% either ACE-inhibitors or angiotensin receptor blockers in use. The 12-month all-cause mortality was 27.4%. We identified several clinical and biochemical prognostic risk factors in univariate analysis. Independent predictors of 1-year mortality were older age, male gender, lower systolic blood pressure (SBP) on admission, C-reactive protein, and serum creatinine >120 micromol/L. CONCLUSION: We present the characteristics and prognosis of an unselected population of AHF patients. One-year mortality is high, and independent clinical risk factors include age, male gender, lower SBP on admission, C-reactive protein, and renal dysfunction.     

The Daily Incidence of Acute Heart Failure Is Correlated With Low Minimal Night Temperature: Cold Immersion Pulmonary Edema Revisited?

BackgroundPrevious studies suggested a higher incidence of acute heart failure (AHF) during cold months in regions with cold climate. We examined the daily incidence of AHF by same-day trough temperature and humidity in a warmer region.Methods and ResultsAll admissions for AHF (340 patients) to a city hospital, providing the sole emergency medical care to a geographical region of approximately 500,000 people were recorded. Patients were followed through admission and for 6 months after discharge. Low minimal trough temperature was associated with an increase in the same-day AHF incidence. Lowest tercile trough night temperatures were associated with higher AHF incidence (3.5 ± 2.1 versus 2.4 ± 1.6, events/24 hours, P = .012). This association was mainly from increased AHF events in nights with the predetermined trough temperature of <7°C (4 ± 2.1 versus 2.5 ± 1.7, events/24 hours, P = .0013). This association persisted even after excluding the coldest consecutive 30 days from the analysis. Humidity was not associated with increased AHF event rate. In a post-hoc analysis we have observed doubling of 6-month mortality in patients admitted with AHF during days with lower trough night temperature, despite no apparent worse baseline characteristics or disease severity at admission.ConclusionsAHF rate is increased during days with lower trough night temperature. If confirmed, these results may have implications on issues related to climate control in houses of the elderly or patients susceptible to heart failure.     

Acute Heart Failure with Preserved Ejection Fraction: Unique Patient Characteristics and Targets for Therapy

Currently, there are 1.0 million annual hospital discharges for acute heart failure (AHF). The total cost of heart failure (HF) care in the United States is projected to increase to $53 billion in 2030, with the majority of costs (80 %) related to AHF hospitalizations. Approximately 50 % of AHF episodes occur in patients with preserved ejection fraction (HFpEF). There is a dearth of evidence-based guidelines for the management of AHF in HFpEF patients. Here, we briefly review the epidemiology, pathophysiology, and treatment of AHF patients with HFpEF.     

The Role of Intravenous Vasodilators in Acute Heart Failure Management

Acute heart failure is a major cause of emergency hospital admission, with significant impact on health resources and patient outcomes. With no new treatments for over 20 years, the advent of new innovative therapies may facilitate a radical change in our approach to such patients. In this article, we examine the current evidence for the use of current intravenous vasodilators in AHF management, and review the potential of novel therapies currently in development.     

Acute heart failure in the emergency department: short and long-term outcomes of elderly patients with heart failure

AIMS: Previous epidemiologic studies of acute heart failure (AHF) have involved patients admitted to hospital and fail to account for that unknown proportion discharged directly from the emergency department (ED). We examined discharge rates, and whether outcomes, including mortality, differed based on admission status in AHF. METHODS AND RESULTS: This population-based cohort included all patients > or =65 years presenting to an Alberta ED with HF (ICD9-CM 428.x; 1998 to 2001). Patients were either not admitted (Not-ADM) or directly admitted to hospital (ADM) and followed for one-year. Of 10,415 AHF patients evaluated in the ED, 35% were Not-ADM whereas 65% were ADM. Thirty days after ED presentation the rates of death, re-ED or initial/re-hospitalisation were 3.3%, 44% and 19% for Not-ADM, and 10.9%, 33% and 21% for the ADM patients, respectively (all p<0.0001). At one-year, the rates of death, re-ED or initial/re-hospitalisation were 20%, 82% and 58% for Not-ADM, and 34%, 72% and 60% for ADM, respectively (all p<0.0001). CONCLUSIONS: One third of AHF patients were not immediately admitted after an ED visit but most present again to the ED, two-thirds were hospitalised and 20% died within the first year. Our findings provide new impetus to undertake risk assessment and treatment strategies in the ED for AHF.     

Early Worsening Heart Failure in Patients Admitted for Acute Heart Failure: Time Course,Hemodynamic Predictors,and Outcome

BackgroundThe most common outcome currently assessed in acute heart failure trials (AHF) is dyspnea improvement. Worsening hear failure (WHF) is a new outcome measure that incorporates failure to improve or recurrent symptoms of AHF requiring rescue intravenous therapy, mechanical circulatory or ventilatory support, or readmission because of AHF, occurring within 30 days of AHF admission.Methods and ResultsRetrospective data analysis of 120 patients with AHF requiring hemodynamic monitoring who enrolled in the placebo arm of 2 prospective randomized studies. The incidence of WHF was 42% at 30 days from enrollment. Most WHF events occurred in-hospital during the first 7 days after admission (early WHF). Thirty-day readmission from AHF was an infrequent event in the present cohort (5.0%). The strongest hemodynamic predictors of WHF were cardiac power at baseline and its change during the initial 6 hours of monitoring. Other hemodynamic parameters associated with WHF events were blood pressure and its increase, cardiac output, and pulmonary wedge pressure change during the initial 6 hours of monitoring. WHF was found to be a strong predictor of 6-month mortality.ConclusionsWHF is a common morbid event clustered mostly during the first week of AHF admission and is associated with higher 6-month mortality. The hemodynamic measurements associated with WHF are similar to those predicting adverse outcome in AHF and cardiogenic shock (low cardiac power, higher pulmonary capillary wedge pressure, and vascular resistance), emphasizing the notion that early WHF should become an important AHF-specific outcome measure.     

Heart rate as an independent predictor of long term mortality of acute heart failure patients in sinus rhythm according to their ejection fraction: data from the AHEAD registry

BackgroundHeart rate (HR) at admission in patients with acute heart failure (AHF) has been shown to be an important risk marker of in-hospital mortality. However, its relation with mid and long-term prognosis as well as the impact of Ejection Fraction (EF) is unknown. Our objective was to study the relationship between long-term survival and HR at admission depending on EF in a cohort of patients hospitalized for AHF.MethodsWe analyzed the data of 2335 patients in sinus rhythm hospitalized for AHF from AHEAD registry. Patients with cardiogenic shock and AHF from surgical or non-cardiac etiology were excluded.ResultsSurvival rates at 6 and 12 months were 84.8% and 78% respectively. Increased age, decreased diastolic BP, lack of PCI during hospitalization, increased creatinine level and increased HR (with different cut-offs according to EF categories) were found as predictors whatever the EF at 6 and 12 months. Optimal prognostic cut-offs of heart rate were identified for Heart Failure with reduced EF at 100 bpm, for Heart Failure with mid-range EF at 90 bpm and for Heart Failure with preserved EF at 80 bpm for both 6 and 12 months.ConclusionOur study suggests that HR at admission appears to be an independent prognostic parameter in AHF patients in sinus rhythm irrespective of EF and can be used to classify patients according to the severity of the disease.     

Clinical significance of cardiac troponins I and T in acute heart failure

BACKGROUND: Elevated cardiac troponin (cTn) levels are relatively common in acute heart failure (AHF). AIMS: To evaluate the prevalence and prognostic significance of elevated cTnI and cTnT in AHF. METHODS: FINN-AKVA is a prospective, multicenter study in AHF. In this analysis, 364 non-ACS patients with measurements of cTnI and cTnT taken on admission and 48 h thereafter were analyzed. RESULTS: Of the 364 AHF patients, 51.1% had cTnI and 29.7% cTnT levels above the cut-off value. Six-month all-cause mortality was 18.7%. Both cTnI (OR 2.0, 95% CI 1.2-3.5, p=0.01) and cTnT (OR 2.6, 95% CI 1.5-4.4, p=0.0006) were associated with adverse outcome. The mortality risk was proportional to the magnitude of cTn release. On multivariable analysis, Cystatin C (OR 6.3, 95% CI 3.2-13, p<0.0001), logNT-proBNP (OR 1.4, 95% CI 1.0-1.8, p=0.03) and systolic blood pressure on admission (/10 mm Hg increase, OR 0.9, 95% CI 0.8-0.9, p=0.0004) were independent risk markers, whereas the troponins were not significantly associated with increased mortality. CONCLUSIONS: cTn elevations are frequent in AHF patients without ACS. cTnI is more often elevated than cTnT. Both cTnI and cTnT elevations are associated with increased mortality proportional to the degree elevation but they do not act as independent risk markers.     

Hyponatraemia and changes in natraemia during hospitalization for acute heart failure and associations with in-hospital and long-term outcomes – from the ESC-HFA EORP Heart Failure Long-Term Registry

Aims

To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post-discharge outcomes.

Methods and results

Of 8298 patients in the European Society of Cardiology Heart Failure Long-Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non-use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers. In-hospital death occurred in 3.3%. The prevalence of hyponatraemia and in-hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in-hospital mortality 6.9%), 11% Yes/No (in-hospital mortality 4.9%), 8% No/Yes (in-hospital mortality 4.7%), and 72% No/No (in-hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In-hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12-month mortality was 19% and adjusted hazard ratios (95% confidence intervals) were for hyponatraemia Yes/Yes 1.60 (1.35–1.89), Yes/No 1.35 (1.14–1.59), and No/Yes 1.18 (0.96–1.45). For death or heart failure hospitalization they were 1.38 (1.21–1.58), 1.17 (1.02–1.33), and 1.09 (0.93–1.27), respectively.

Conclusion

Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced heart failure and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in-hospital and post-discharge outcomes. Hyponatraemia developing during hospitalization (possibly depletional) was associated with lower risk.     

Angiotensin receptor-neprilysin inhibition in patients with acute decompensated heart failure: an expert consensus position paper

Heart Failure Reviews - The short-term mortality and rehospitalization rates after admission for acute heart failure (AHF) remain high, despite the high level of adherence to contemporary practice...     

Underutilization of IV Nitrates in the Treatment of Acute Heart Failure

Acute heart failure (AHF) is a growing public health concern with high inhospital mortality and costs. Clinical practice guidelines, underpinned by positive randomized controlled trials, recommend the early use of intravenous (IV) nitrates in the treatment of AHF. However, the “real‐world” usage of IV nitrates has not been clearly defined. The objective of this study was to examine the use of IV nitrates in the treatment of AHF as recommended by clinical practice guidelines. A case‐record analysis was conducted of all admissions with AHF at a large teaching hospital. Of the 81 AHF patients (mean age 77 ± 11, mean SBP 130 ± 27 mmHg) enrolled for this analysis, only 5 (6%) received IV nitrates at the time of AHF admission. Forty (49%, mean age 77 ± 11, mean SBP 131 ± 27 mmHg) of these 81 patients met the guideline criteria for suitability for IV nitrates and only 5 (12%) of these received them during this admission. Patients who received IV nitrates were more likely to have higher blood pressure and all had myocardial ischemia as a precipitant. Seventy‐five (93%) of the total population received loop diuretics on admission. Overall, this study shows that loop diuretics remain the first‐line therapy in AHF with little use of IV nitrates, despite recommendations from clinical practice guidelines.     

Acute heart failure--intra-aortic balloon: a forgotten treatment.

Acute heart failure (AHF) is a serious clinical condition associated with high morbidity and mortality. The authors present the case of a 61-year-old man, with a past history of idiopathic dilated cardiomyopathy with heart failure, who came to the emergency room due to acute decompensation. During hospital stay he developed cardiogenic shock and inotropic support was initiated, followed by mechanical circulatory assistance with intra-aortic balloon counterpulsation, as a bridge to heart transplantation. The authors discuss theoretical considerations concerning subtypes and etiology of AHF, and indications for the use of mechanical support and heart transplantation.     

Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX‐AHF‐2 study

Patients admitted for acute heart failure (AHF) experience high rates of in‐hospital and post‐discharge morbidity and mortality despite current therapies. Serelaxin is recombinant human relaxin‐2, a hormone with vasodilatory and end‐organ protective effects believed to play a central role in the cardiovascular and renal adaptations of human pregnancy. In the phase 3 RELAX‐AHF trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for AHF. Compared to placebo, serelaxin also reduced worsening heart failure (WHF) by 47% through day 5 and both all‐cause and cardiovascular mortality by 37% through day 180. RELAX‐AHF‐2 ( ClinicalTrials.gov NCT01870778) is designed to confirm serelaxin's effect on these clinical outcomes. RELAX‐AHF‐2 is a multicentre, randomized, double‐blind, placebo‐controlled, event‐driven, phase 3 trial enrolling ～6800 patients hospitalized for AHF with dyspnoea, congestion on chest radiograph, increased natriuretic peptide levels, mild‐to‐moderate renal insufficiency, and systolic blood pressure ≥125 mmHg. Patients are randomized within 16 h of presentation to 48 h intravenous infusions of serelaxin (30 µg/kg/day) or placebo, both in addition to standard of care treatments. The primary objectives are to demonstrate that serelaxin is superior to placebo in reducing: (i) 180 day cardiovascular death, and (ii) occurrence of WHF through day 5. Key secondary endpoints include 180 day all‐cause mortality, composite of 180 day combined cardiovascular mortality or heart failure/renal failure rehospitalization, and in‐hospital length of stay during index AHF. The results from RELAX‐AHF‐2 will provide data on the potential beneficial effect of serelaxin on cardiovascular mortality and WHF in selected patients with AHF.     

急性心力衰竭的流行现状和诊治进展

急性心力衰竭是年龄≥65岁住院患者主要的死亡原因,其早期住院死亡率及再入院率均高,住院期间及出院后涉及预后的影响因素众多。B型利钠肽和肌钙蛋白是独立的急性心力衰竭预后指标,有助于急性心力衰竭患者的危险评估。目前治疗急性心力衰竭的传统药物由于作用单一,应用各有局限性。新的药物奈西立肽、重组人心钠肽和钙增敏剂(左西孟旦)对心力衰竭的治疗已显示出良好的效果,是有望突破急性心力衰竭治疗瓶颈的药物。     

Lower admission blood pressure as an independent predictor of 1-year mortality in elderly patients experiencing a first hospitalization for acute heart failure

BackgroundSystolic blood pressure (SBP) is an acknowledged prognostic factor in patients with heart failure (HF). Admission SBP should be a risk factor for 1-year mortality even in elderly patients experiencing a first admission for HF, and this risk may persist in the oldest subset of patients.DesignMethods: We reviewed the medical records of 1031 patients aged 70 years or older admitted within a 3-year period for a first episode of acute heart failure (AHF). The cohort was divided according to admission SBP values in quartiles. We analyzed all-cause mortality as a function of these admission SBP quartiles.ResultsMean age was 82.2 ± 6 years; their mean admission SBP was 138.6 ± 25 mmHg. A statistically significant association was present between mortality at 30 (p < 0.0001), 90 (p < 0.0001), and 365 days (p < 0.0001) after hospital discharge and lower admission SBP quartiles. One-year mortality ranged from 14.7% for patients within the upper SBP quartile to 41.4% for those in the lowest quartile. The multivariate analysis confirmed this association (HR: 0.884; 95% CI: 0.615-0.76; p = 0.0001), which remained significant when admission SBP was evaluated as a continuous variable (HR: 0.980; 95% CI: 0.975–0.985; p = 0.0001). The association between SBP and 1-year mortality remained when the sample was divided into old (70–82 years) and “oldest-old” (>82 years) patients.ConclusionsLower SBP at admission is an independent predictor of midterm postdischarge mortality for elderly patients experiencing a first admission for AHF.