Quality of life and chronic heart failure therapy guided by natriuretic peptides: results from the ProBNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) study.

BACKGROUND: Heart failure (HF) treatment guided by amino-terminal pro-B type natriuretic peptide (NT-proBNP) may reduce cardiovascular event rates compared to standard-of-care (SOC) management. Comprehensive understanding regarding effect of NT-proBNP guided care on patient-reported quality of life (QOL) remains unknown. METHODS: One hundred fifty-one subjects with HF due to left ventricular systolic dysfunction were randomized to either SOC HF management or care with a goal to reduce NT-proBNP values ≤1000 pg/mL. Effects of HF on QOL were assessed using the Minnesota Living with HF Questionnaire (MLHFQ) quarterly, with change (Δ) in score assessed across study procedures and as a function of outcome. RESULTS: Overall, baseline MLHFQ score was 30. Across study visits, QOL improved in both arms, but was more improved and sustained in the NT-proBNP arm (repeated measures P = .01); NT-proBNP patients showing greater reduction in MLHFQ score (-10.0 vs -5.0; P = .05), particularly in the physical scale of the questionnaire. Baseline MLHFQ scores did not correlate with NT-proBNP; in contrast, ∆MLHFQ scores modestly correlated with ∆NT-proBNP values (ρ = .234; P = .006) as did relative ∆ in MLHFQ score and NT-proBNP (ρ = .253; P = .003). Considered in tertiles, less improvement in MLHFQ scores was associated with a higher rate of HF hospitalization, worsening HF, and cardiovascular death (P = .001). CONCLUSIONS: We describe novel associations between NT-proBNP concentrations and QOL scores among patients treated with biomarker guided care. Compared to SOC HF management, NT-proBNP guided care was associated with greater and more sustained improvement in QOL (Clinical Trial Registration: www.clinicaltrials.govNCT00351390).

Heart failure outcomes and benefits of NT-proBNP-guided management in the elderly: results from the prospective, randomized ProBNP outpatient tailored chronic heart failure therapy (PROTECT) study.

BACKGROUND: Elderly patients with heart failure (HF) have a worse prognosis than younger patients. We wished to study whether elders benefit from natriuretic peptide-guided HF care in this single-center study. METHODS AND RESULTS: A total of 151 patients with HF resulting from left ventricular systolic dysfunction (LVSD) were treated with HF treatment by standard-of-care (SOC) management or guided by N-terminal pro-B type natriuretic peptide (NT-proBNP) values (with a goal to lower NT-proBNP ≤1000 pg/mL) over 10 months. The primary end point for this post-hoc analysis was total cardiovascular events in 2 age categories (<75 and ≥75 years). In those ≥75 years of age (n = 38), NT-proBNP values increased in the SOC arm (2570 to 3523 pg/mL, P = .01), but decreased in the NT-proBNP-guided arm (2664 to 1418 pg/mL, P = .001). Elderly patients treated with SOC management had the highest rate of cardiovascular events, whereas the elderly with NT-proBNP management had the lowest rate of cardiovascular events (1.76 events per patient versus 0.71 events per patient, P = .03); the adjusted logistic odds for cardiovascular events related to NT-proBNP-guided care for elders was 0.24 (P = .008), whereas in those <75 years (n = 113), the adjusted logistic odds for events following NT-proBNP-guided care was 0.61 (P = .10). CONCLUSIONS: Natriuretic peptide-guided HF care was well tolerated and resulted in substantial improvement in cardiovascular event rates in elders (ClinicalTrials.Gov #00351390).

Role of Cardiopulmonary Exercise Testing in Predicting Perioperative Outcomes in Cancer Patients Undergoing Thoracoabdominal Surgeries; An Observational Cohort Study.

Introduction: The cancer patients are at a high risk of developing perioperative complications. Cardiopulmonary exercise testing (CPET) is a non-invasive, perioperative risk stratification tool that predicts perioperative morbidity and mortality. Prior literature has concluded that CPET has a valuable role in predicting post-operative complications in major surgical procedures. However, the data on the effectiveness of CPET in evaluating the perioperative risk in cancer-specific populations are limited. This study assessed the usefulness of CPET in perioperative risk stratification of patients with thoracoabdominal cancer who underwent elective major thoracoabdominal surgeries. Materials and Methods: A retrospective observational cohort study was conducted on cancer patients that underwent pre-operative CPET at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from September 2017 to September 2019. All adult male and female patients with a significant medical history for cancer of the thoracoabdominal region who underwent CPET before a major thoracoabdominal surgery were included in the study. Results: A total of 32 patients were included in the present investigation. The mean age of the sample was 62.75 ± 10.18 years, and the majority of the participants were female. Following surgery, 53% of the participants had post-operative complications in terms of morbidity and mortality. Fifteen participants had an anaerobic threshold (AT) of ≥11.0 ml/ kg/min. Among these, 12 participants had an uneventful surgery. On the contrary, among 17 participants that were considered to have a high risk (<11.0 ml/kg/min) for surgery, 14 subjects (82%) had at least one complication (including mortality). The sensitivity and specificity of CPET to anticipate complications during oncological surgery were calculated to be 82% and 80%, respectively. The mean AT of participants with uneventful surgery was calculated to be 11.83 ± 1.01 ml/kg/min. This was statistically greater than the AT of subjects that had morbidity (9.86 ± 1.20 ml/kg/min) or mortality (8.95 ± 0.35 ml/kg/min) (P < 0.001). Conclusion: CPET, when using AT alone as an indicator, can provide a good-excellent prediction of perioperative outcome among oncology patients undergoing major thoracoabdominal surgical procedures.

Design and methods of the Pro-B Type Natriuretic Peptide Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study.

BACKGROUND: Serial measurements of N-terminal pro-B type natriuretic peptide (NT-proBNP) provide prognostic information in patients with chronic heart failure (HF). Changes in NT-proBNP concentrations parallel prognosis; however, it remains unclear whether HF care with a goal to maximize medical therapy and also lower NT-proBNP concentrations is superior to standard HF care alone. AIMS: The aim of the study was to evaluate the hypothesis that an HF strategy guided by NT-proBNP reduces cardiovascular events compared to standard of care HF management. METHODS: In a prospective randomized single-center trial, subjects with New York Heart Association class II to IV systolic HF (left ventricular ejection fraction < or =40%) will be enrolled. Both groups will receive standard HF management (with a goal for minimizing HF symptoms and achieving maximal dosages of therapies with proven mortality benefit in HF), whereas one group ("NT-proBNP") will also have treatment adjustments to reduce NT-proBNP concentrations < or =1,000 pg/mL. The primary end point of the trial is total cardiovascular events for a 1-year period; secondary end points will include effects of NT-proBNP-guided care on cardiac structure and function, quality of life, and total costs of care. RESULTS: Enrollment began in 2006; of the original 300 planned, thus far, 151 subjects have been randomized. Interim analysis in November 2009 indicated significant reduction of events in the NT-proBNP arm. Full results are expected in 2010. CONCLUSIONS: The Pro-B Type Natriuretic Peptide Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study will test the hypothesis that therapy guided by NT-proBNP concentrations will be superior to standard of care HF management (www.clinicaltrials.gov identifier NCT00351390).

Relative value of amino-terminal pro-B-type natriuretic peptide testing and radiographic standards for the diagnostic evaluation of heart failure in acutely dyspneic subjects.

To define more clearly the relationship between the information provided by the chest radiograph (CXR) and the natriuretic peptide (NT-proBNP) test as part of the evaluation of dyspneic patients presenting to the emergency department with suspected acute heart failure (HF), we evaluated the PRIDE cohort of 599 patients with and without HF, focusing on blinded NT-proBNP and unblinded CXR information. Clinical characteristics and diagnostic performance for each test were compared. We found that NT-proBNP measurement is superior to routine CXR interpretation for diagnosis or exclusion of acute HF and that normal CXR results should not be used to exclude HF in this population.

Independent and incremental prognostic value of multimarker testing in acute dyspnea: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study.

BACKGROUND: Acute dyspnea is common in the emergency department (ED) and is associated with mortality. Biomarkers may help stratify risk in this setting. METHODS: Among 577 dyspneic subjects we identified 5 candidate biomarkers with prognostic value: amino terminal B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), the interleukin family member ST2, hemoglobin and blood urea nitrogen (BUN); these were assessed using both receiver operating characteristic curve and Cox proportional hazards analyses. Results were validated in a population of dyspneic patients from a distinct cohort. RESULTS: At 1 y follow up, 93 (16.1%) patients had died. Independent predictive ability was established in an age-adjusted Cox model containing all markers: NT-proBNP (HR=1.89); CRP (HR=1.95); ST2 (HR=7.17); hemoglobin (HR=1.68); BUN (HR=2.06) (all P<.05). Following categorical assessment based on number of abnormal markers, the 1-y risk of death increased in a monotonic fashion with mortality rates of 0%, 2.0%, 7.8%, 22.3%, 29.3%, and 57.6% respectively; similar results were seen in the validation set. CONCLUSION: Simultaneous assessment of pathophysiologically diverse markers in acute dyspnea provides powerful, independent and incremental prognostic information.

Natriuretic peptides for guiding heart failure therapy.

Use of natriuretic peptide to guide heart failure therapy represents a promising option. Although natriuretic peptides provide accurate diagnostic and independent incremental prognostic information, their use to gauge and titrate therapy is not yet fully realized.

Comparison of modified anchored "hang-back technique (HBT)" with conventional HBT in bimedial rectus recession.

PURPOSE: We conducted a retrospective study to establish whether bimedial rectus recession (BMR) using a modified "hang-back technique" (HBT) is comparable with conventional HBT. METHODS: Consecutive patients younger than the age of 16 underwent BMR during 1999 and 2000 with at least a 6-month postoperative follow-up period were included. In 1999, all patients had operations performed with conventional HBT, whereas those in 2000 were conducted with modified HBT. Angles of strabismus were measured preoperatively and at 2 weeks, 2 months, and 6 months postoperatively. RESULTS: Thirty-nine and 43 patients underwent BMR using conventional and modified HBT respectively. Preoperative angles for near and distance were 43.6 (PD) versus 43.5 PD and 36.4 PD versus 36.8 PD. At 6 months' postop, the mean angles for near and distance were 6.4 PD Eso (range, 35 PD Eso - 40 PD Exo) and 5.4 PD Eso (range, 35 PD Eso - 35 PD Exo) in the conventional group: 8.1 PD Eso (range, 35 PD Eso - 20 PD Exo) and 6.3 PD Eso (range, 35 PD Eso - 25 PD Exo) in the modified group. The overall success rate (alignment to within 10 PD of orthotropia for distance and near) was similar between the two groups (conventional HBT:69.2% vs. modified HBT: 67.4%, P = 0.352). However, modified HBT was found to be associated with significantly lower consecutive exotropia rate postoperatively at 6 months (4.7% vs. 20.5%, P = 0.031). CONCLUSION: BMR using modified HBT is as effective as conventional HBT but with a significantly lower consecutive exotropia rate.

Improvement in structural and functional echocardiographic parameters during chronic heart failure therapy guided by natriuretic peptides: mechanistic insights from the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study.

AIMS: We sought to determine if heart failure (HF) care with a goal to lower N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations, compared with standard of care (SOC) management, is associated with improvement in echocardiographic parameters of cardiac structure and function. METHODS AND RESULTS: Of 151 subjects with HF due to left ventricular systolic dysfunction (LVSD) prospectively randomized to NT-proBNP-guided vs. SOC HF care, 116 had serial echocardiographic data. Endpoints in this echocardiographic study included the relationship between change in NT-proBNP and LV reverse remodelling, as well as associations between biomarker-guided therapy and measures of diastolic function, right ventricular (RV) size and function, estimates of LV filling pressure and RV systolic pressure (RVSP), and the degree of mitral regurgitation (MR). After a mean of 10 months of study procedures, in adjusted analyses, final NT-proBNP concentrations predicted risk of remodelling [hazard ratio (HR) ↑LV end-diastolic volume index = 1.43, 95% confidence interval (CI) 1.10-1.86, P = 0.007; HR ↑LV end-systolic volume index = 1.54, 95% CI 1.10-1.91, P = 0.01; HR ↓LV ejection fraction (LVEF) = 1.53, 905% CI 1.12-1.89, P = 0.02]. In addition to greater improvement in LVEF and reductions in LV volume, compared with SOC, NT-proBNP-guided patients showed significant decreases in the ratio of early transmitral peak velocity to early diastolic peak annular velocity (E/E'), pulmonary vein peak S velocity, RV fractional area change, RVSP, and MR severity. CONCLUSION: NT-proBNP concentrations may serve as a non-invasive indicator of the state of cardiac structure and function in HF due to LVSD. Multiple, prognostically meaningful echocardiographic variables improved more significantly in patients treated with NT-proBNP-guided care vs. SOC.

Characterization and prediction of natriuretic peptide "nonresponse" during heart failure management: results from the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) and the NT-proBNP-Assisted Treatment to Lessen Serial Cardiac Readmissions and Death (BATTLESCARRED) study.

Many proven heart failure (HF) therapies decrease N-terminal pro B-type natriuretic peptide (NT-proBNP) values over time, yet some patients have an NT-proBNP >1000 pg/mL following treatment, which is associated with poor outcomes. A total of 151 patients with left ventricular systolic dysfunction were treated with aggressive HF therapy in the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study. Clinical characteristics and NT-proBNP were measured at each visit during 10 months. In this post hoc analysis, biomarker nonresponse was defined as an NT-proBNP >1000 pg/mL and its relationship with echocardiographic and clinical characteristics and outcomes were explored. A risk model predictive of nonresponse was derived and externally validated. A rising NT-proBNP over time was associated with increased cardiovascular event rates while a decreasing NT-proBNP was associated with better clinical outcomes (58.2% vs 27.6%, P=.001). A higher percentage of time in biomarker response was associated with lower event rates (P<.001). Importantly, responders showed improved left ventricular remodeling parameters (all P<.001), while nonresponders did not. A risk model for predicting nonresponse had a C statistic of 0.82 (P<.001) and predicted outcomes well. Using data from the NT-proBNP-Assisted Treatment to Lessen Serial Cardiac Readmissions and Death (BATTLESCARRED) cohort, the risk score was validated for its ability to predict nonresponse (C statistic 0.73, P<.001). Serial changes in NT-proBNP inform risk for adverse outcome and are associated with prognostically meaningful metrics. Prediction of future NT-proBNP nonresponse to HF therapy is possible.

Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction.

OBJECTIVES: The aim of this study was to evaluate whether chronic heart failure (HF) therapy guided by concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is superior to standard of care (SOC) management. BACKGROUND: It is unclear whether standard HF treatment plus a goal of reducing NT-proBNP concentrations improves outcomes compared with standard management alone. METHODS: In a prospective single-center trial, 151 subjects with HF due to left ventricular (LV) systolic dysfunction were randomized to receive either standard HF care plus a goal to reduce NT-proBNP concentrations ≤1,000 pg/ml or SOC management. The primary endpoint was total cardiovascular events between groups compared using generalized estimating equations. Secondary endpoints included effects of NT-proBNP-guided care on patient quality of life as well as cardiac structure and function, assessed with echocardiography. RESULTS: Through a mean follow-up period of 10 ± 3 months, a significant reduction in the primary endpoint of total cardiovascular events was seen in the NT-proBNP arm compared with SOC (58 events vs. 100 events, p = 0.009; logistic odds for events 0.44, p = 0.02); Kaplan-Meier curves demonstrated significant differences in time to first event, favoring NT-proBNP-guided care (p = 0.03). No age interaction was found, with elderly patients benefitting similarly from NT-proBNP-guided care as younger subjects. Compared with SOC, NT-proBNP-guided patients had greater improvements in quality of life, demonstrated greater relative improvements in LV ejection fraction, and had more significant improvements in both LV end-systolic and -diastolic volume indexes. CONCLUSIONS: In patients with HF due to LV systolic dysfunction, NT-proBNP-guided therapy was superior to SOC, with reduced event rates, improved quality of life, and favorable effects on cardiac remodeling. (Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting; NCT00351390).

Characteristics of the novel interleukin family biomarker ST2 in patients with acute heart failure.

OBJECTIVES: The purpose of this study was to examine the patient-specific characteristics of the interleukin-1 receptor family member ST2 in patients with acute heart failure (HF). BACKGROUND: ST2 signaling is involved in the process of cardiac fibrosis and hypertrophy. METHODS: In all, 346 patients with acute HF had ST2 measured. Associations between ST2 and demographics, severity/type of HF, and other biomarkers were examined. Receiver-operator characteristic curves and multivariable Cox proportional hazards analyses evaluated the prognostic ability of ST2. RESULTS: The ST2 values correlated with the severity of HF (p < 0.001), left ventricular ejection fraction (r = -0.134; p = 0.014), creatinine clearance (r = -0.224; p < 0.001), B-type natriuretic peptide (r = 0.293; p < 0.001), amino terminal B-type natriuretic peptide (r = 0.413; p < 0.001), and C-reactive protein (r = 0.429; p < 0.001). ST2 was not associated with age, prior HF, or body mass index. The ST2 levels at presentation were higher among patients who died by 1 year. The area under the receiver-operator characteristic for death at 1 year was 0.71 (p < 0.001). In a multivariable Cox model containing established clinical and biochemical predictors (including natriuretic peptides), ST2 remained a predictor of mortality (hazard ratio: 2.04, 95% confidence interval: 1.30 to 3.24, p = 0.003), and was equally predictive in patients with HF and preserved or impaired systolic function. When both ST2 and natriuretic peptides were elevated, the highest rates of death were observed in cumulative hazard analysis (p < 0.001). In the presence of a low ST2 level, natriuretic peptides did not predict mortality. CONCLUSIONS: Consistent with its proposed role in a myocardial-specific response to stretch, ST2 has strong clinical and biochemical correlates in patients with acute HF. Prognostically, ST2 is powerful in acute HF and is synergistic with natriuretic peptides for this use.

Natriuretic Peptide testing in primary care.

The incidence, as well as the morbidity and mortality associated with heart failure (HF) continue to rise despite advances in diagnostics and therapeutics. A recent advance in the diagnostic and therapeutic approach to HF is the use of natriuretic peptide (NP) testing, including both B-type natriuretic peptide (BNP) and its amino terminal cleavage equivalent (NT-proBNP). NPs may be elevated at an early stage among those with symptoms as well among those without. The optimal approach for applying NP testing in general populations is to select the target population and optimal cut off values carefully. Superior diagnostic performance is observed among those with higher baseline risk (such as hypertensives or diabetics). As well, unlike for acute HF, the cut off value for outpatient testing for BNP is 20-40 pg/mL and for NTproBNP it is 100-150 ng/L. In symptomatic primary care patients, both BNP and NT-proBNP serve as excellent tools for excluding HF based on their excellent negative predictive values and their use may be cost effective. Among those with established HF, it is logical to assume that titration of treatment to achieve lower NPs levels may be advantageous. There are several ongoing trials looking at that prospect.

Natriuretic peptide testing in clinical medicine.

Since the discovery of atrial natriuretic factor in 1981 by de Bold et al, there has been tremendous progress in our understanding of natriuretic peptides (NPs). Recently, testing for brain-type NP (BNP) and its amino terminal cleavage equivalent (NT-proBNP) has been rapidly adopted in clinical medicine for numerous indications, including the diagnosis and exclusion of heart failure (HF). In this regard, logical application of BNP or NT-proBNP testing may not only reduce healthcare costs but also potentially reduce adverse clinical outcomes. With respect to this fact, the potential importance of the concentration of the NPs for prognosis and the response of BNP or NT-proBNP to therapeutic intervention in terms of clinical events has been demonstrated. On the basis of these observations it is reasonable to expect that concentrations of these peptides might be useful for the management of patients with HF, acting as a gauge of therapeutic accuracy and/or stability of disease. Besides HF, the prognostic utility of NPs has been explored in other settings, particularly in ischemic heart disease and those conditions that lead to right ventricular dysfunction.

Randomized controlled clinical trial of beta irradiation as an adjunct to trabeculectomy in open-angle glaucoma.

OBJECTIVE: To assess the effect of a single intraoperative application of 750 cGy of beta irradiation on the outcome of trabeculectomy for uncontrolled open-angle glaucoma. DESIGN: A prospective, randomized, double-blind, placebo-controlled clinical trial. PARTICIPANTS: Sixty-one eyes of 61 Caucasian patients at low risk of filtering surgery failure, with poorly controlled primary or secondary open-angle glaucoma undergoing routine trabeculectomy. METHOD: Patients were randomly assigned to control or beta irradiation groups. All patients underwent standard trabeculectomy with fornix-based conjunctival incision. Eyes assigned to beta irradiation received 750 cGy of beta irradiation directly over the sclerostomy site on completion of conjunctival suturing. An identical but inactive applicator was applied to control eyes, delivering no radiation. Both operator and patient remained masked to the assignment for the 12-month follow-up period. MAIN OUTCOME MEASURES: The main outcome measure was intraocular pressure (IOP) control. Complete success of IOP control was defined as an IOP less than 21 mmHg at 12 months without need for additional medication. Qualified success was defined as an IOP less than 21 mmHg at 12 months where additional medication was required. RESULTS: Complete success of IOP control was achieved in 19 (86%) control eyes and 35 (90%) irradiated eyes (P = 1.0). Qualified success of IOP control was achieved in 21 (95%) control eyes and 39 (100%) irradiated eyes at 12 months follow-up (P = 1.0) CONCLUSIONS: We experienced a very high success rate of filtration surgery in this select population without adjunctive irradiation. Our sample size was too small to show any improvement in success with use of beta irradiation in this group. Other studies would have to be done to determine whether it may have measurable benefit in cases with a high risk of filtration failure.