Radiation dose reduction of 50% in dynamic myocardial CT perfusion with skipped beat acquisition: a retrospective study.

BACKGROUND: Dynamic myocardial computed tomography perfusion (CTP) is a novel imaging technique that increases the applicability of CT for cardiac imaging; however, the scanning requires a substantial radiation dose. PURPOSE: To investigate the feasibility of dose reduction in dynamic CTP by comparing all-heartbeat acquisitions to periodic skipping of heartbeats. MATERIAL AND METHODS: We retrieved imaging data of 38 dynamic CTP patients and created new datasets with every fourth, third or second beat (Skip1:4, Skip1:3, Skip1:2, respectively) removed. Seven observers evaluated the resulting images and perfusion maps for perfusion deficits. The mean blood flow (MBF) in each of the 16 myocardial segments was compared per skipped-beat level, normalized by the respective MBF for the full dose, and averaged across patients. The number of segments/cases whose MBF was <1.0 mL/g/min were counted. RESULTS: Out of 608 segments in 38 cases, the total additional number of false-negative (FN) segments over those present in the full-dose acquisitions and the number of additional false-positive cases were shown as acquisition (segment [%], case): Skip1:4: 7 (1.2%, 1); Skip1:3: 12 (2%, 3), and Skip1:2: 5 (0.8%, 2). The variability in quantitative MBF analysis in the repeated analysis for the reference condition resulted in 8 (1.3%) additional FN segments. The normalized results show a comparable MBF across all segments and patients, with relative mean MBFs as 1.02 ± 0.16, 1.03 ± 0.25, and 1.06 ± 0.30 for the Skip1:4, Skip1:3, and Skip1:2 protocols, respectively. CONCLUSION: Skipping every second beat acquisition during dynamic myocardial CTP appears feasible and may result in a radiation dose reduction of 50%. Diagnostic performance does not decrease after removing 50% of time points in dynamic sequence.

Multireader image quality evaluation of dynamic myocardial computed tomography perfusion imaging with a novel four-dimensional noise reduction filter.

BACKGROUND: Dynamic myocardial computed tomography perfusion (CTP) is a novel technique able to depict cardiac ischemia. PURPOSE: To evaluate the impact of a four-dimensional noise reduction filter (similarity filter [4D-SF]) on image quality in dynamic CTP imaging, allowing for substantial radiation dose reduction. MATERIAL AND METHODS: Dynamic CTP datasets of 30 patients (16 women) with suspected coronary artery disease, acquired with a 320-slice CT system, were retrieved, reconstructed with the deep learning-based algorithm of the system (DLR), and filtered with the 4D-SF. For each case, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in six regions of interest (33-38mm2) were calculated before and after filtering, in four-chamber and short-axis views, and t-tested. Furthermore, six radiologists of different expertise evaluated subjective image preference by answering five visual grading analysis-type questions (regarding acceptable level of noise, absence of artifacts, natural appearance, cardiac contour sharpness, diagnostic acceptability) using a 5-point scale. The results were analyzed using visual grade characteristics (VGC) and intraclass correlation coefficient (ICC). RESULTS: Mean SNR in four-chamber view (unfiltered vs. filtered) were: septum=4.1 ± 2.1 versus 7.6 ± 5.6; lateral wall=4.5 ± 2.0 versus 8.0 ± 4.9; CNRseptum=16.6 ± 8.9 versus 31.7 ± 28; lateral wall=16.2 ± 8.9 versus 31.3 ± 28.9. Similar results were obtained in short-axis view. The perceived filtered image quality indicated decreased noise (VGCAUC=0.96) and artifacts (0.65), improved natural appearance (0.59), cardiac contour sharpness (0.74), and diagnostic acceptability (0.78). The inter-observer variability was excellent (ICC=0.79). All results were statistically significant (P < 0.05). CONCLUSION: Similarity filtering after DLR improves image quality, possibly enabling dose reduction in dynamic CTP imaging in patient with suspected chronic coronary syndrome.

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.

Prognosis and NT-proBNP in heart failure patients with preserved versus reduced ejection fraction.

BACKGROUND: We assessed the prognostic significance of absolute and percentage change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients hospitalised for acute decompensated heart failure with preservedejection fraction (HFpEF) versus heart failure with reduced ejection fraction (HFrEF). METHODS: Patients with left ventricular ejection fraction ≥50% were categorised as HFpEF (n=283), while those with <40% as were categorised as HFrEF (n=776). Prognostic values of absolute and percentage change in NT-proBNP levels for 6 months all-cause mortality after discharge were assessed separately in patients with HFpEF and HFrEF by multivariable adjusted Cox regression analysis. Comorbidities were compared between heart failure groups. RESULTS: Discharge NT-proBNP levels predicted outcome similarly in HFpEF and HFrEF: for any 2.7-factor increase in NT-proBNP levels, the HR for mortality was 2.14 for HFpEF (95% CI 1.48 to 3.09) and 1.96 for HFrEF (95% CI 1.60 to 2.40). Mortality prediction was equally possible for NT-proBNP reduction of ≤30% (HR 4.60, 95% CI 1.47 to 14.40 and HR 3.36, 95% CI 1.93 to 5.85 for HFpEF and HFrEF, respectively) and for >30%-60% (HR 3.28, 95% CI 1.07 to 10.12 and HR 1.79, 95% CI 0.99 to 3.26, respectively), compared with mortality in the reference groups of >60% reductions in NT-proBNP levels. Prognostically relevant comorbidities were more often present in patients with HFpEF than patients with HFrEF in low (≤3000 pg/mL) but not in high (>3000 pg/mL) NT-proBNP discharge categories. CONCLUSIONS: Our study highlights-after demonstrating that NT-proBNP levels confer the same relative risk information in HFpEF as in HFrEF-the possibility that comorbidities contribute relatively more to prognosis in patients with HFpEF with lower NT-proBNP levels than in patients with HFrEF.

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.

Targeting N-Terminal Pro-Brain Natriuretic Peptide in Older Versus Younger Acute Decompensated Heart Failure Patients.

OBJECTIVES: The aim of this study was to analyze the prognostic value and attainability of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in young and elderly acute decompensated heart failure (ADHF) patients. BACKGROUND: Less-effective NT-proBNP-guided therapy in chronic heart failure (HF) has been reported in elderly patients. Whether this can be attributed to differences in prognostic value of NT-proBNP or to differences in attaining a prognostic value is unclear. The authors studied this question in ADHF patients. METHODS: Our study population comprised 7 ADHF cohorts. We defined absolute (<1,500 ng/l, <3,000 ng/l, <5,000 ng/l, and <15,000 ng/l) and relative NT-proBNP discharge cut-off levels (>30%, >50%, and >70%). Six-month all-cause mortality after discharge was studied for each level in Cox regression analyses, and compared between elderly (age >75 years) and young patients (age ≤75 years). Thereafter, we compared percentages of elderly and young patients attaining NT-proBNP levels (= attainability). RESULTS: A total of 1,235 patients (59% male, 45% >75 years of age) was studied. Admission levels of NT-proBNP were significantly higher in elderly versus younger patients. The prognostic value of absolute and relative NT-proBNP levels was similar in elderly and young patients. Attainability was significantly lower in elderly patients for all absolute levels and a >50% relative reduction, but not for >30% and >70%. For absolute levels, attainability differences between age groups were decreased to a large extent after correction for admission NT-proBNP and anemia at discharge. For relative levels, attainability differences disappeared after correction for HF etiology and anemia at discharge. CONCLUSIONS: In young and elderly ADHF patients, it is not the prognostic value of absolute and relative NT-proBNP levels that is different, but the attainability of these levels that is lower in the elderly. This can largely be attributed to factors other than age.

Competing Risk of Cardiac Status and Renal Function During Hospitalization for Acute Decompensated Heart Failure.

OBJECTIVES: The aim of this study was to analyze the dynamic changes in renal function in combination with dynamic changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients hospitalized for acute decompensated heart failure (ADHF). BACKGROUND: Treatment of ADHF improves cardiac parameters, as reflected by lower levels of NT-proBNP. However this often comes at the cost of worsening renal parameters (e.g., serum creatinine, estimated glomerular filtration rate [eGFR], or serum urea). Both the cardiac and renal markers are validated indicators of prognosis, but it is not yet clear whether the benefits of lowering NT-proBNP are outweighed by the concomitant worsening of renal parameters. METHODS: This study was an individual patient data analysis assembled from 6 prospective cohorts consisting of 1,232 patients hospitalized for ADHF. Endpoints were all-cause mortality and the composite of all-cause mortality and/or readmission for a cardiovascular reason within 180 days after discharge. RESULTS: A significant reduction in NT-proBNP was not associated with worsening of renal function (WRF) or severe WRF (sWRF). A reduction of NT-proBNP of more than 30% during hospitalization determined prognosis (all-cause mortality hazard ratio [HR]: 1.81; 95% confidence Interval [CI]: 1.32 to 2.50; composite endpoint: HR: 1.36, 95% CI: 1.13 to 1.64), regardless of changes in renal function and other clinical variables. CONCLUSIONS: When we defined prognosis, NT-proBNP changes during hospitalization for treatment of ADHF prevailed over parameters for worsening renal function. Severe WRF is a measure of prognosis, but is of lesser value than, and independent of the prognostic changes induced by adequate NT-proBNP reduction. This suggests that in ADHF patients it may be warranted to strive for an optimal decrease in NT-proBNP, even if this induces WRF.

Serum potassium decline during hospitalization for acute decompensated heart failure is a predictor of 6-month mortality, independent of N-terminal pro-B-type natriuretic peptide levels: An individual patient data analysis.

BACKGROUND: Limited data exist for the role of serum potassium changes during hospitalization for acute decompensated heart failure (ADHF). The present study investigated the long-term prognostic value of potassium changes during hospitalization in patients admitted for ADHF. METHODS: Our study is a pooled individual patient data analysis assembled from 3 prospective cohorts comprising 754 patients hospitalized for ADHF. The endpoint was all-cause mortality within 180 days after discharge. Serum potassium levels and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured at admission and at discharge. RESULTS: A percentage decrease >15% in serum potassium levels occurred in 96 (13%) patients, and an absolute decrease of >0.7 mmol/L in serum potassium levels occurred in 85 (12%) patients; and both were predictors of poor outcome independent of admission or discharge serum potassium. After the addition of other strong predictors of mortality-a 30% change in NT-proBNP during hospitalization, discharge levels of NT-proBNP, renal markers, and other relevant clinical variables-the multivariate hazard ratio of serum potassium percentage reduction of >15% remained an independent predictor of 180-day mortality (hazard ratio 2.06, 95% CI 1.14-3.73). CONCLUSIONS: A percentage serum potassium decline of >15% is an independent predictor of 180-day all-cause mortality on top of baseline potassium levels, NT-proBNP levels, renal variables, and other relevant clinical variables. This suggest that patients hospitalized for ADHF with a decline of >15% in serum potassium levels are at risk and thus monitoring and regulating of serum potassium level during hospitalization are needed in these patients.

N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) Measurements Until a 30% Reduction Is Attained During Acute Decompensated Heart Failure Admissions and Comparison With Discharge NT-proBNP Levels: Implications for In-Hospital Guidance of Treatment.

BACKGROUND: A >30% N-terminal pro-B-type natriuretic peptide (NT-proBNP) reduction at discharge in acute decompensated heart failure (ADHF) predicts a favorable prognosis. To study the feasibility of guiding ADHF treatment by measuring NT-proBNP well before discharge, we assessed at which moment during hospitalization patients attain a NT-proBNP reduction of >30% (target) and whether this target is still attained at discharge. METHODS: Twenty-five consecutive ADHF patients with NT-proBNP >1,700 ng/L were included (original cohort). NT-proBNP was measured daily until the target was attained, at clinical stability, and at discharge and was analyzed as percentages of patients on target. For comparison purposes, the same analysis was performed in individual patient data from 2 other ADHF cohorts (42 and 111 patients, respectively), in which NT-proBNP was measured from admission to day 3 and at discharge. RESULTS: In the original cohort of 25 patients (median age 70 years, 40% male), the cumulative percentage of patients attaining the target increased gradually during admission to 22 patients (88%) in a median of 3 days (interquartile range 2-5). In the comparison cohorts, a similar course was observed in patients attaining the target before discharge. Compared with levels measured at days 2 and 3, rebound NT-proBNP increases to levels off-target at discharge were seen in up to 33% of patients in the original and comparison cohorts. CONCLUSION: A target >30% NT-proBNP reduction is gradually attained before discharge, and rebound NT-proBNP increases to levels off-target occur in up to 33% of ADHF patients who initially attained target early during admission.

Challenging the two concepts in determining the appropriate pre-discharge N-terminal pro-brain natriuretic peptide treatment target in acute decompensated heart failure patients: absolute or relative discharge levels?

AIMS: NT-proBNP is a strong predictor for readmissions and mortality in acute decompensated heart failure (ADHF) patients. We assessed whether absolute or relative NT-proBNP levels should be used as pre discharge treatment target. METHODS AND RESULTS: Our study population was assembled from seven ADHF cohorts. We defined absolute (<1500, <3000, <5000, and <15 000 ng/L) and relative NT-proBNP targets (>30, >50, and >70%). Population attributable risk fraction (PARF) is the proportion of all-cause 6-month mortality in the population that would be reduced if all patients attain the NT-proBNP target. PARF was determined for each target as well as the percentage of patients attaining the NT-proBNP target. Attainability was investigated by logistic regression analysis. A total of 1266 patients [age 74 (64-80), 60% male] was studied. For every absolute NT-proBNP level, a corresponding percentage reduction was found that resulted in similar PARFs. The highest PARF (∼60-70%) was observed for <1500 or >70%, but attainability was low (27% and 22%, respectively). The strongest predictor for not attaining these targets was admission NT-proBNP. In admission NT-proBNP tertiles, PARFs were significantly different for absolute, but not for relative targets. CONCLUSION: In an ADHF population, pre-discharge absolute or relative NT-proBNP targets may both be useful as they have similar effects on PARF. However, depending on admission NT-proBNP, absolute targets show varying PARFs, while PARFs for relative targets were similar. A relative target is predicted to reduce mortality consistently across the whole spectrum of ADHF patients, while this is not the case using a single absolute target.

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.

A novel discharge risk model for patients hospitalised for acute decompensated heart failure incorporating N-terminal pro-B-type natriuretic peptide levels: a European coLlaboration on Acute decompeNsated Heart Failure: ELAN-HF Score.

BACKGROUND: Models to stratify risk for patients hospitalised for acute decompensated heart failure (ADHF) do not include the change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels during hospitalisation. OBJECTIVE: The aim of our study was to develop a simple yet robust discharge prognostication score including NT-proBNP for this notorious high-risk population. DESIGN: Individual patient data meta-analyses of prospective cohort studies. SETTING: Seven prospective cohorts with in total 1301 patients. PATIENTS: Our study population was assembled from the seven studies by selecting those patients admitted because of clinically validated ADHF, discharged alive, and NT-proBNP measurements available at admission and at discharge. MAIN OUTCOME MEASURES: The endpoints studied were all-cause mortality and a composite of all-cause mortality and/or first readmission for cardiovascular reason within 180 days after discharge. RESULTS: The model that incorporated NT-proBNP levels at discharge as well as the changes in NT-proBNP during hospitalisation in addition to age ≥75 years, peripheral oedema, systolic blood pressure ≤115 mm Hg, hyponatremia at admission, serum urea of ≥15 mmol/L and New York Heart Association (NYHA) class at discharge, yielded the best C-statistic (area under the curve, 0.78, 95% CI 0.74 to 0.82). The addition of NT-proBNP to a reference model significantly improved prediction of mortality as shown by the net reclassification improvement (62%, p<0.001). A simplified model was obtained from the final Cox regression model by assigning weights to individual risk markers proportional to their relative risks. The risk score we designed identified four clinically significant subgroups. The pattern of increasing event rates with increasing score was confirmed in the validation group (BOT-AcuteHF, n=325, p<0.001). CONCLUSIONS: In patients hospitalised for ADHF, the addition of the discharge NT-proBNP values as well as the change in NT-proBNP to known risk markers, generates a relatively simple yet robust discharge risk score that importantly improves the prediction of adverse events.