NT-proBNP (N-Terminal pro-B-Type Natriuretic Peptide)-Guided Therapy in Acute Decompensated Heart Failure: PRIMA II Randomized Controlled Trial (Can NT-ProBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?).

BACKGROUND: The concept of natriuretic peptide guidance has been extensively studied in patients with chronic heart failure (HF), with only limited success. The effect of NT-proBNP (N-terminal probrain natriuretic peptide)-guided therapy in patients with acute decompensated HF using a relative NT-proBNP target has not been investigated. This study aimed to assess whether NT-proBNP-guided therapy of patients with acute decompensated HF using a relative NT-proBNP target would lead to improved outcomes compared with conventional therapy. METHODS: We conducted a prospective randomized controlled trial to study the impact of in-hospital guidance for acute decompensated HF treatment by a predefined NT-proBNP target (>30% reduction from admission to discharge) versus conventional treatment. Patients with acute decompensated HF with NT-proBNP levels >1700 ng/L were eligible. After achieving clinical stability, 405 patients were randomized to either NT-proBNP-guided or conventional treatment (1:1). The primary end point was dual: a composite of all-cause mortality and HF readmissions in 180 days and the number of days alive out of the hospital in 180 days. Secondary end points were all-cause mortality within 180 days, HF readmissions within 180 days, and a composite of all-cause mortality and HF readmissions within 90 days. RESULTS: Significantly more patients in the NT-proBNP-guided therapy group were discharged with an NT-proBNP reduction of >30% (80% versus 64%, P=0.001). Nonetheless, NT-proBNP-guided therapy did not significantly improve the combined event rate for all-cause mortality and HF readmissions (hazard ratio, 0.96; 95% confidence interval, 0.72-1.37; P=0.99) or the median number of days alive outside of the hospital (178 versus 179 days for NT-proBNP versus conventional patients, P=0.39). Guided therapy also did not significantly improve any of the secondary end points. CONCLUSIONS: The PRIMA II trial (Can NT-ProBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?) demonstrates that the guidance of HF therapy to reach an NT-proBNP reduction of >30% after clinical stabilization did not improve 6-month outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR3279.

Rationale and design of PRIMA II: A multicenter, randomized clinical trial to study the impact of in-hospital guidance for acute decompensated heart failure treatment by a predefined NT-PRoBNP target on the reduction of readmIssion and Mortality rAtes.

BACKGROUND: Hospital admissions for acute decompensated heart failure (ADHF) are frequent and are accompanied by high percentages of mortality and readmissions. Brain natriuretic peptide (BNP) and the inactive N-terminal fragment of its precursor proBNP (NT-proBNP) are currently the best predictors of prognosis in heart failure (HF) patients. In the setting of chronic HF, studies that performed guidance of therapy by NT-proBNP have had only limited success. For patients with ADHF, retrospective studies have shown that a reduction in NT-proBNP of ≤30% during admission is a significant predictor of HF readmissions and mortality. These data suggest a role for NT-proBNP guidance in the setting of ADHF admissions. STUDY DESIGN: The PRIMA II is an investigator-initiated, multicenter, randomized, controlled, prospective 2-arm trial that investigates the impact of inhospital guidance for ADHF treatment by a predefined NT-proBNP target (>30% reduction during admission) on the reduction of readmission and mortality rates within 180 days. Consenting ADHF patients with NT-proBNP levels of >1,700 ng/L are eligible. After achieving clinical stability, a total of 340 patients are randomized to either NT-proBNP-guided or conventional treatment (1:1). The primary end point is dual, that is, a composite of all-cause mortality and readmission for HF in 180 days and the number of days alive out of hospital in 180 days. Secondary end points are readmissions and/or mortality in 180 days, cost effectiveness of hospitalization days in 180 days, readmissions and mortality in 90 days, and quality of life. CONCLUSION: The PRIMA II trial aims at providing scientific evidence for the use of NT-proBNP-guided therapy compared with conventional treatment in patients admitted for ADHF.

Outpatient treatment of worsening heart failure with intravenous diuretics: first results from a multicentre 2-year experience.

AIMS: The aim of this study is to examine the safety and efficacy of outpatient treatment of worsening heart failure (WHF) with intravenous diuretics. METHODS AND RESULTS: This is a multicentre retrospective observational research study. Patients with all types of heart failure (HF) were included: heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF). Patients included in this study were 18 years or older, had symptoms of WHF, had weight gain of more than 2 kg, and were not responding to uptitrating of oral diuretic therapy. Patients were treated for one or more days at the outpatient department with administration of intravenous loop diuretics with or without a bolus. In this study, 259 patients were included (mean age of 76 years, mean left ventricular ejection fraction of 41%). Rehospitalization rates for HF were 30.5% and 53.3%, respectively, at 30 days and 1 year. All-cause mortality was 5.8% and 26.3%, respectively, at 30 days and 1 year. Rehospitalization rates for HF and all-cause mortality were highest in patients with HFrEF. In a total of 322 individual outpatient treatments with intravenous diuretics, only one adverse event was registered. CONCLUSIONS: Outpatient treatment with intravenous diuretics of patients with WHF is a safe alternative strategy compared with the same treatment in hospitalized patients. However, only non-randomized data are available and rehospitalization rates for this group with WHF are high. No data are available on the best selection criteria and the cost-effectiveness of outpatient treatment with intravenous diuretics.

External Validation of the ELAN-HF Score, Predicting 6-Month All-Cause Mortality in Patients Hospitalized for Acute Decompensated Heart Failure.

Background Our aim was to calibrate and externally revalidate the ELAN-HF (European Collaboration on Acute Decompensated Heart Failure) score, to confirm and improve on a previous external validation of the risk score. Methods and Results The ELAN-HF score predicts 6-month all-cause mortality in patients hospitalized for acute decompensated heart failure using absolute and percentage change of NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels in addition to clinical variables. For the external validation, we used the PRIMA II (Can NT-proBNP-Guided Therapy During Hospital Admission for Acute Decompensated Heart Failure Reduce Mortality and Readmissions?) trial. For both data sets, observed versus predicted mortality was compared for the 4 risk categories; and the mean predicted mortality was plotted against the observed mortality with calculation of a correlation coefficient and SEE. The model discriminant ability was determined by comparing the C-statistics for both data sets. The predicted versus actual 6-month mortality values in the derivation cohort were 3.7% versus 3.6% for the low-risk category, 9.4% versus 9.2% for the intermediate-risk category, 24.2% versus 23.5% for the high-risk category, and 54.2% versus 51.1% for the very-high-risk category. The correlation between predicted and observed mortality by deciles was 0.92, with an SEE of ±4%. In the validation cohort, predicted versus actual 6-month mortality values were 3.0% versus 2.2% for the low-risk category, 9.4% versus 8.2% for the intermediate-risk category, 25.0% versus 22.9% for the high-risk category, and 56.8% versus 53.6% for the very-high-risk category. The correlation between predicted and actual mortality by quintiles was 0.99, with an SEE of ±2%. There was no significant difference in C-statistic between the derivation cohort (0.78; 95% CI, 0.74-0.82) and the validation cohort (0.77; 95% CI, 0.69-0.84; P=0.693). Conclusions Our study confirms that the ELAN-HF score predicts accurately 6-month mortality in patients hospitalized for acute decompensated heart failure with the use of easily obtained characteristics.

Transcranial Doppler blood flow assessment in patients with mild heart failure: correlates with neuroimaging and cognitive performance.

Cardiac output and cerebral perfusion are reduced in patients with advanced stages of heart failure. Our aim was to determine whether cerebral blood flow velocity measured by transcranial Doppler ultrasonography was reduced in outpatients with mild heart failure in comparison to controls and, if so, whether this reduction was related to cognitive performance and abnormalities of the brain diagnosed by magnetic resonance imaging.

Clinical results of far-field R-wave reduction with a short tip-ring electrode.

BACKGROUND: Far-field R-wave (FFRW) sensing of the atrial lead of AAI or DDD pacemakers causes incorrect mode switches and remains a problem in patients with atrial arrhythmias in whom low voltage sensing is essential. We studied a pacing electrode with a short tip-ring distance (1.1 mm). We compared our findings with recordings from a conventional electrode with a larger tip-ring distance (10 mm). METHODS: Thirty-six consecutive patients with an indication for DDD pacing were implanted with the short tip-ring electrode. Another 23 patients received the conventional electrode. FFRW and P-wave amplitudes during pacing and intrinsic ventricular depolarization were measured at implantation. Measurements were repeated before hospital discharge and at follow-up between 10 and 14 days after implantation. RESULTS: P-wave amplitude was slightly smaller in the short tip-ring group (2.71+/-1.04 vs 3.17+/-1.30 mV in the conventional group, respectively, P=NS). All P-waves exceeded 1.2 mV. FFRW during pacing was 0.07+/-0.05 in the short tip-ring group and 0.54+/-0.32 mV in the conventional group (P<0.001). FFRW during intrinsic rhythm was 0.08+/-0.04 and 0.55+/-0.31 mV, respectively (P<0.001). The ratio between P-wave and FFRW was 48.6+/-27.2 in the short tip-ring group and 7.3+/-4.4 in the conventional group (P<0.001). FFRW and P-wave amplitudes did not change at hospital discharge or during follow-up. CONCLUSION: FFRW can be suppressed without compromising P-wave sensing by using a pacing electrode with a short tip-ring distance. Whether reduced FFRW amplitude results in clinical endpoints remains to be determined.

Incidental congenital coronary artery vascular fistulas in adults: Evaluation with adenosine-13N-ammonia PET-CT.

AIM: To assess the functionality of congenital coronary artery fistulas (CAFs) using adenosine stress 13N-ammonia positron emission tomography computed tomography (PET-CT). METHODS: Congenital CAFs were incidentally detected during coronary angiography (CAG) procedures in 11 adult patients (six males and five females) with a mean age of 64.3 years (range 41-81). Patients were collected from three institutes in the Netherlands. The characteristics of the fistulas (origin, pathway and termination), multiplicity of the origins and pathways of the fistulous vessels were assessed by CAG. Five patients underwent adenosine pharmacologic stress 13N-ammonia PET-CT to assess myocardial perfusion and the functional behavior of the fistula. RESULTS: Eleven patients with 12 CAFs, 10 unilateral and one bilateral, originating from the left anterior descending coronary artery (n = 8), right coronary artery (n = 2) and circumflex (n = 2). All fistulas were of the vascular type, terminating into either the pulmonary artery (n = 11) or coronary sinus (n = 1). The CAG delineated the characteristics of the fistula (origin, pathway and termination). Multiplicity of the origins and pathways of the fistulous vessels were common in most fistulas (8/12, 67% and 9/12, 75%, respectively). Multiplicity was common among the different fistula components (23/36, 64%). Adenosine pharmacologic stress 13N-ammonia PET-CT revealed normal myocardial perfusion and ejection fraction in all but one patient, who showed a reduced ejection fraction. CONCLUSION: PET-CT may be helpful for assessing the functional status of congenital CAFs in selected patients regarding clinical decision-making. Studies with a larger patient series are warranted.

Cognitive impairment in heart failure: a systematic review of the literature.

BACKGROUND: Heart failure (HF) and cognitive impairment are common medical conditions that are becoming increasingly prevalent in the aging Western population. They are associated with frequent hospitalisation and increased mortality, particularly when they occur simultaneously. Evidence from a number of studies suggests that HF is independently associated with impairment in various cognitive domains. AIMS: This systematic literature review evaluates the relation between cognitive deterioration and heart failure. METHODS: We searched electronic databases from 1966 to May 2006 for studies that investigated cognitive function in HF patients. Twenty-two controlled studies that met the inclusion criteria were selected for analysis. Study characteristics and data on global cognitive performance, memory scores, psychomotor speed and depression scores were extracted and analysed using the Cochrane Review Manager software. RESULTS: Pooled analysis shows diminished neuropsychological performance in HF patients, as compared to control subjects. In a pooled sample of 2937 heart-failure patients and 14,848 control subjects, the odds ratio for cognitive impairment was 1.62 (95% confidence interval:1.48-1.79, p<0.0001) among subjects with HF. CONCLUSION: This review confirms the relationship between HF and cognitive impairment, but it also stresses the need for additional systematic neuropsychological data and adequate neuro-imaging from representative populations of HF patients.

Brain magnetic resonance imaging abnormalities in patients with heart failure.

BACKGROUND: Although heart failure (HF) is a common cardiovascular disorder, to date little research has been conducted into possible associations between HF and structural abnormalities of the brain. AIMS: To determine the frequency and pattern of magnetic resonance imaging (MRI) abnormalities in outpatients with chronic HF, and to identify any demographic and clinical correlates. METHODS: Brain MRI scans were compared between a sample of 58 HF patients, 48 controls diagnosed with cardiovascular disease uncomplicated by HF (cardiac controls) and 42 healthy controls. Deep, periventricular and total white matter hyperintensities (WMH), lacunar and cortical infarcts, global and medial temporal lobe atrophy (MTA) were investigated. RESULTS: Compared to cardiac and healthy controls, HF patients had significantly more WMH, lacunar infarcts and MTA, whereas cardiac controls only had more MTA, compared to healthy controls. Age and left ventricular ejection fraction (LVEF) were independently associated with total WMH. Age and systolic hypotension were associated with MTA in HF patients and cardiac controls. CONCLUSION: Our results suggest that cardiac dysfunction contributes independently to the development of cerebral MRI abnormalities in patients with HF. Age and low LVEF are the principal predictors of cerebral WMH in patients with HF and in cardiac controls.

Neuroimaging and correlates of cognitive function among patients with heart failure.

BACKGROUND/AIMS: We purposed to investigate the relationship between cerebral abnormalities detected by magnetic resonance imaging (MRI) and cognitive performance in nondemented outpatients with heart failure (HF). METHODS: In 58 patients with HF neuropsychological assessment was performed including tests of mental speed, executive functions, memory, language and visuospatial functions. Deep, periventricular and total white matter hyperintensities (WMH), lacunar and cortical infarcts, global and medial temporal lobe atrophy (MTA) were investigated on MRI of the brain. Correlations between MRI findings and the cognitive measures were calculated. RESULTS: MTA correlated with memory (r = -0.353, p < 0.01), with executive functions (r = -0.383, p < 0.01) and the Mini Mental State Examination (r = -0.343, p < 0.05). Total WMH and deep WMH were found to correlate with depression and anxiety scores, but not with cognitive measures. Age, estimated premorbid intelligence and MTA were independent predictors of diminished cognitive performance. CONCLUSIONS: In HF patients, MTA was related to cognitive dysfunction, involving memory impairment and executive dysfunction, whereas WMH was related to depression and anxiety.

Female gender and the risk of rupture of congenital aneurysmal fistula in adults.

AIMS: To delineate the risk factors for rupture of congenital aneurysmal fistulas in adult patients. METHODS: We conducted a literature search of the Medline database using Pubmed search interface to identify reports dealing with rupture of congenital aneurysmal fistulas in an adult population. The search included the English and non-English languages between 1963 and 2005. RESULTS: Fourteen adult patients (12 females) with serious and life-threatening complications secondary to aneurysmal fistulas were reported. Mean age was 62.9 years. The ethnic origins of these 14 patients were 9 Asian and 5 Caucasian. Most patients have had no other cardiac malformations. Five patients had a history of hypertension. One patient was asymptomatic. In 13 symptomatic patients, the clinical presentation was cardiac tamponade, pericardial effusion, syncope, heart failure, chest pain, dyspnea, fatigue, distal thromboembolic events with infarction, shock, and/or sudden death. Aneurysmal fistulas were identified in 10 patients; of these 6 were of the saccular type. Rupture occurred in 9 patients (8 females and 1 male). Eleven patients were treated surgically with 1 late death. Two male subjects experienced sudden unexpected cardiac death. CONCLUSION: Rupture of congenital aneurysmal fistulas occurred more often in females. Identified risk factors for rupture, hemopericardium, tamponade, and death were among others saccular aneurysm, Asian ethnic race, origin of the aneurysmal fistulas from the left coronary artery and a history of hypertension may play a role. In this article, we present a literature review of congenital aneurysmal fistulas associated with or without rupture and a case report of a woman with unruptured aneurysmal fistula.

Profile of cognitive impairment in chronic heart failure.

OBJECTIVES: To determine the frequency and pattern of cognitive dysfunction in outpatients with chronic congestive heart failure (CHF) and to identify the corresponding demographic and clinical correlates. DESIGN: Case-control study. SETTING: Outpatient clinic in a community hospital. PARTICIPANTS: Sixty-two outpatients with CHF, 53 controls diagnosed with cardiovascular disease uncomplicated by CHF (cardiac controls), and 42 healthy controls were investigated. MEASUREMENTS: Neuropsychological assessment included tests of mental speed, executive function, memory, language, and visuospatial function. Composite z-scores for five cognitive domains and mean z-score for overall cognitive performance were computed. The cutoff score to indicate cognitive impairment was defined as the overall healthy participants' cognitive z-score minus 2 standard deviations. Independent demographic and clinical predictors of cognitive impairment were identified using linear regression analysis. RESULTS: Patients with CHF showed a pattern of general cognitive impairment, including impairment of executive function, memory, language, mental speed, and attention. Twenty-five percent (P=.04) of patients with CHF were classified as cognitively impaired, compared with 15% of the cardiac controls and 4% of the healthy controls. Independent predictors of cognitive impairment in patients with CHF were estimated intelligence, New York Heart Association class, and presence of the apolipoprotein (Apo)E epsilon4 allele. CONCLUSION: Cognitive dysfunction is relatively common in patients with CHF, with deficits being most prominent in the domains of executive function, memory, language, and mental speed. Disease severity and ApoE genotype are likely to be important determinants for cognitive impairment in patients with chronic CHF.