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Biomedical subjects

William T Abraham

Publications and source records attributed to William T Abraham.

At least 19 recordsLinked to original sources
PubMed2026

Subgroups and Special Populations in Heart Failure Clinical Trials: Insights From the HFC-ARC Expert Consensus Panel.

In the evolving landscape of heart failure (HF) management, the identification and analysis of subgroups and special populations within clinical trials are crucial for enhancing clinical decision-making, guiding further research, and understanding heterogeneity in study outcomes. This expert consensus document results from the collaborative efforts of the Heart Failure Collaboratory and the Heart Failure Collaboratory Academic Research Consortium, which brought together stakeholders from academia, industry, the U.S. Food and Drug Administration, and patient representatives. The purpose of this assembly was to propose standardized definitions and critical endpoint considerations essential for shaping the design and conduct of clinical trials for drugs and devices in the field of HF. In this context, we propose definitions and endpoints for specific subgroups and special populations in the spectrum of HF. We enhanced the precision, efficacy, and applicability of clinical research and promote more "personalized" approaches to interpretation of clinical trials. Furthermore, we explore the burgeoning field of gene therapy as a promising avenue for addressing the genetic basis of certain cardiomyopathies within these specialized patient groups. We focus especially on methodological considerations for subgroup analyses in large-scale trials, highlighting the importance of proper interpretation of subgroups and best practices for identifying heterogeneity suggestive of differential treatment effects, including when these analyses should be considered hypothesis-generating and requiring subsequent validation. We advocate for a methodical approach to clinical trial design, one that prioritizes the strategic identification of subgroups and employs appropriate statistical methodologies to ensure the reliability and clinical relevance of findings. Through this lens, we envision a pathway toward more personalized and effective treatments for HF, ultimately aiming to improve patient outcomes by leveraging the insights garnered from meticulously designed and comprehensively analyzed clinical trials.

Humans↗
PubMed2007

Association between performance measures and clinical outcomes for patients hospitalized with heart failure.

CONTEXT: Assessment of quality of care in heart failure has focused on the development and use of process-based performance measures, with the presumption that these processes are associated with improved clinical outcomes. However, this link remains largely untested. OBJECTIVE: To examine the relationship between current American College of Cardiology/American Heart Association (ACC/AHA) performance measures for patients hospitalized with heart failure and relevant clinical outcomes. DESIGN, SETTING, AND PATIENTS: The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure, a registry and performance improvement program for patients hospitalized with heart failure. Sixty- to ninety-day postdischarge follow-up data were prospectively collected from 5791 patients at 91 US hospitals in a prespecified 10% sample between March 2003 and December 2004. Mean patient age was 72.0 years, 51% were male, 78% were white, and 42% had ischemic etiology. Multivariable and propensity-adjusted analyses were performed to assess the process-outcome relationship for each performance measure in eligible patients. Additionally, we evaluated the process-outcome link of a potential performance measure for beta-blockade at discharge among eligible patients hospitalized with heart failure. MAIN OUTCOME MEASURES: Sixty- to ninety-day mortality and combined mortality/rehospitalization rates. RESULTS: Mortality during follow-up was 8.6% and mortality/rehospitalization was 36.2%. None of the 5 ACC/AHA heart failure performance measures was significantly associated with reduced early mortality risk, and only angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use at discharge was associated with 60- to 90-day postdischarge mortality or rehospitalization. Beta-blockade at the time of hospital discharge, currently not a heart failure performance measure, was strongly associated with reduced risk of mortality (hazard ratio, 0.48; 95% confidence interval, 0.30-0.79; P = .004) and mortality/rehospitalization during follow-up. CONCLUSIONS: Current heart failure performance measures, aside from prescription of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at discharge, have little relationship to patient mortality and combined mortality/rehospitalization in the first 60 to 90 days after discharge. Additional measures and better methods for identifying and validating heart failure performance measures may be needed to accurately assess and improve care of patients with heart failure.

Adrenergic beta-Antagonists↗
PubMed2007

Carvedilol use at discharge in patients hospitalized for heart failure is associated with improved survival: an analysis from Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF).

BACKGROUND: The IMPACT-HF trial demonstrated that carvedilol use at the time of heart failure (HF) hospital discharge significantly increased 90-day postdischarge treatment rates. Whether there is an early survival benefit associated with this therapeutic approach in patients hospitalized for HF is unknown. We examined the early effects on mortality and rehospitalization of carvedilol use at discharge in patients hospitalized for HF and left ventricular systolic dysfunction (LVSD) compared with outcomes in patients who are eligible for, but do not receive, beta blockers before discharge. METHODS: The OPTIMIZE-HF program enrolled 5791 patients admitted with HF in a web-based registry at 91 hospitals participating with prespecified 60- to 90-day follow-up from March 2003 to December 2004. Outcomes data were prospectively collected on patients eligible for beta-blocker therapy and analyzed according to predischarge beta-blocker use. RESULTS: The mean age was 69.7 years; 63% were male, etiology was ischemic in 52%, and mean left ventricular ejection fraction was 24.3%. A total of 2720 patients had LVSD, among whom 2373 (87.2%) were eligible to receive a beta blocker at discharge and carvedilol was prescribed in 1162 (49.0%). Discharge use of carvedilol was associated with a significant reduction in mortality risk at 60 to 90 days (hazard ratio 0.46, P = .0006) and mortality or rehospitalization (odds ratio 0.71, P = .0175) compared to no predischarge beta blocker. Predischarge use of carvedilol was well tolerated with high rates of continued therapy at 60 to 90 days follow-up. Similar findings were observed for other evidence-based beta blockers. CONCLUSIONS: Carvedilol use at the time of HF hospital discharge is well tolerated, improves treatment rates, and is associated with an early survival benefit. These findings provide further support for guideline recommendations that carvedilol or other evidence-based beta blocker should be initiated before hospital discharge in stable patients with HF and LVSD.

Adrenergic beta-Antagonists↗
PubMed2007

Cardiac resynchronization treatment of heart failure.

Cardiac resynchronization therapy (CRT) is well established as a treatment for patients with moderate to severe heart failure on optimal medical therapy. Early studies demonstrated improved functional capacity and evidence of reverse remodeling; more recently, CRT has been associated with a survival benefit in advanced heart failure both with and without a defibrillator. We review the eight landmark trials in CRT. To date, criteria have focused on electrical delay, but echocardiographic parameters emphasize the importance of mechanical delay or ventricular dyssynchrony. With the exponential rise in implants, new issues have emerged, such as optimal device programming, identifying appropriate candidates, and accounting for cases without clinical benefit from CRT.

Cardiac Pacing, Artificial↗
PubMed2006

Initial United States experience with the Paracor HeartNet myocardial constraint device for heart failure.

OBJECTIVE: This study was undertaken to review the initial results and surgical safety data for the US Food and Drug Administration safety and feasibility trial of the Paracor HeartNet (Paracor Medical, Inc, Sunnyvale, Calif.) myocardial constraint device. METHODS: Patients with New York Heart Association functional class II or III heart failure underwent device implantation (n = 21) through a left minithoracotomy. RESULTS: The average age was 53 years (31-72 years). There were 18 men and 3 women, and 17 patients had nonischemic etiology of heart failure. Mean heart failure duration was 8.3 years (1.4-18.8 years). Average ejection fraction was 22% (11%-33%), with an average left ventricular end-diastolic dimension of 74 mm (55-94 mm). Previous medical therapy included angiotensin-converting enzyme inhibitors, beta-blockers, diuretics, digoxin, and aldosterone receptor blockers. At implantation, 17 patients had implantable electronic devices: 1 biventricular pacemaker, 11 biventricular pacemakers with cardioverter-defibrillators, and 5 implantable cardioverter-defibrillators. Patient comorbidities included hypertension in 10 cases, diabetes mellitus in 8, myocardial infarction in 1, and ventricular tachycardia in 8. Mean operative time was 68 minutes (42-102 minutes), and implantation time averaged 15 minutes (5-51 minutes). The average time to ambulation was 1.6 days (1-4 days). The intensive care unit stay averaged 3.3 days (1-16 days), and hospital stay averaged 6.3 days (4-16 days). Atrial fibrillation occurred in 2 patients, and there were 2 in-hospital deaths. CONCLUSIONS: The Paracor device can be implanted in patients with heart failure and reduced left ventricular function with a high degree of success. Significant surgical complications were infrequent. The initial US experience supports the conduct of a randomized, controlled, pivotal trial.

Adult↗
PubMed2006

Systolic blood pressure at admission, clinical characteristics, and outcomes in patients hospitalized with acute heart failure.

CONTEXT: The association between systolic blood pressure (SBP) at admission, clinical characteristics, and outcomes in patients hospitalized for heart failure who have reduced or relatively preserved systolic function has not been well studied. OBJECTIVE: To evaluate the relationship between SBP at admission, clinical profile, and outcomes in patients hospitalized for acute heart failure. DESIGN, SETTING, AND PATIENTS: Cohort study using data from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry and performance-improvement program for patients hospitalized with heart failure at 259 US hospitals between March 2003 and December 2004. Patients were divided into quartiles by SBP at hospital admission (<120, 120-139, 140-161, and >161 mm Hg). In-hospital outcomes were based on 48,612 patients aged 18 years or older with heart failure. Of the 41,267 patients with left ventricular function assessed, 21,149 (51%) had preserved left ventricular function. Postdischarge outcomes were based on a prespecified subgroup (n = 5791, 10% of patients) with follow-up data assessed between 60 and 90 days. MAIN OUTCOME MEASURES: In-hospital and postdischarge mortality. RESULTS: Patients with higher SBP were more likely to be female and black and to have preserved systolic function. Fifty percent of the patients had SBP higher than 140 mm Hg at admission. Patients with lower SBP at admission had higher in-hospital and postdischarge mortality rates. Higher SBP at admission was associated with lower in-hospital mortality rates: 7.2% (<120 mm Hg), 3.6% (120-139 mm Hg), 2.5% (140-161 mm Hg), and 1.7% (>161 mm Hg) (P<.001 for overall difference). Postdischarge mortality rates in the follow-up cohort by SBP at admission were 14.0%, 8.4%, 6.0%, and 5.4%, respectively (P<.001 for overall difference). CONCLUSIONS: Systolic hypertension is common in patients hospitalized for heart failure. Systolic blood pressure is an independent predictor of morbidity and mortality in patients with heart failure with either reduced or relatively preserved systolic function. Low SBP (<120 mm Hg) at hospital admission identifies patients who have a poor prognosis despite medical therapy. These findings may have important therapeutic implications because characteristics and outcomes differ greatly among patients with heart failure with varying SBP.

Acute Disease↗
PubMed2006

Predictors of clinical outcomes in patients given carvedilol for heart failure.

Risk factors for outcomes in heart failure (HF) were derived from populations in clinical trials, at hospital discharge, or in localized geographic or socioeconomic strata before the widespread use of beta blockers. This study observed 4,280 patients in a community-based HF registry for 1 year after completing carvedilol titration. Independent risk factors for death, hospitalization for HF, or hospitalization for cardiovascular reasons other than HF were first identified by age-, gender-, and race-adjusted analyses, then by multivariate analysis adjusted simultaneously for all factors. Over this period, 7% of patients died, 11% were hospitalized for HF, 12% were hospitalized for other cardiovascular reasons, and 27% had > or =1 of these events. The most significant outcome predictors were New York Heart Association class III or IV, history of hospitalization for HF or other cardiovascular reasons, and angina pectoris, all associated with increased odds of having an adverse outcome (all p < or =0.001). The left ventricular ejection fraction was not a significant outcome predictor by multivariate analysis. The odds ratio for an adverse outcome was significantly reduced for patients with hypertensive or idiopathic causes of HF and for those whose physicians had graduated from medical school > or =24 years earlier compared with <14 years earlier (all p <0.005). In conclusion, easily obtained historical information predicts clinical outcomes in patients with HF in the year after initiating carvedilol. In this unselected community population, these historical factors were better predictors of risk than the left ventricular ejection fraction.

Adrenergic beta-Antagonists↗
PubMed2006

A polymorphism within a conserved beta(1)-adrenergic receptor motif alters cardiac function and beta-blocker response in human heart failure.

Heterogeneity of heart failure (HF) phenotypes indicates contributions from underlying common polymorphisms. We considered polymorphisms in the beta(1)-adrenergic receptor (beta(1)AR), a beta-blocker target, as candidate pharmacogenomic loci. Transfected cells, genotyped human nonfailing and failing ventricles, and a clinical trial were used to ascertain phenotype and mechanism. In nonfailing and failing isolated ventricles, beta(1)-Arg-389 had respective 2.8 +/- 0.3- and 4.3 +/- 2.1-fold greater agonist-promoted contractility vs. beta(1)-Gly-389, defining enhanced physiologic coupling under relevant conditions of endogenous expression and HF. The beta-blocker bucindolol was an inverse agonist in failing Arg, but not Gly, ventricles, without partial agonist activity at either receptor; carvedilol was a genotype-independent neutral antagonist. In transfected cells, bucindolol antagonized agonist-stimulated cAMP, with a greater absolute decrease observed for Arg-389 (435 +/- 80 vs. 115 +/- 23 fmol per well). Potential pathophysiologic correlates were assessed in a placebo-controlled trial of bucindolol in 1,040 HF patients. No outcome was associated with genotype in the placebo group, indicating little impact on the natural course of HF. However, the Arg-389 homozygotes treated with bucindolol had an age-, sex-, and race-adjusted 38% reduction in mortality (P = 0.03) and 34% reduction in mortality or hospitalization (P = 0.004) vs. placebo. In contrast, Gly-389 carriers had no clinical response to bucindolol compared with placebo. Those with Arg-389 and high baseline norepinephrine levels trended toward improved survival, but no advantage with this allele and exaggerated sympatholysis was identified. We conclude that beta(1)AR-389 variation alters signaling in multiple models and affects the beta-blocker therapeutic response in HF and, thus, might be used to individualize treatment of the syndrome.

Adrenergic beta-Antagonists↗
PubMed2006

Beta-blocker use and outcomes among hospitalized heart failure patients.

OBJECTIVES: The purpose of this study was to determine the effect of beta-blocker therapy on outcomes of hospitalized heart failure (HF) patients enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization (ESCAPE). BACKGROUND: The effect of beta-blocker therapy on outcomes among hospitalized HF patients is not well documented. METHODS: We studied the association between beta-blocker therapy and outcomes among 432 hospitalized HF patients in the ESCAPE trial. RESULTS: A total of 268 patients (62%) were on beta-blockers before admission. These patients had a shorter length of stay (7.9 +/- 6.3 days vs. 9.4 +/- 6.7 days; p < 0.01) and a lower six-month mortality rate (16% vs. 24%; p = 0.03) compared with those who were not on beta-blockers. Of the patients who were on admission beta-blockers and were discharged alive (n = 263), beta-blockers were discontinued in 54 and significantly modified (>50% dose reduction or changed to alternative beta-blocker) in 28 patients during hospitalization. Factors associated with discontinuation of beta-blockers during hospitalization included respiratory rate >24 breaths/min (30.8% vs. 16.9%; p = 0.03), heart rate >100 beats/min (19.2% vs. 7.3%; p = 0.01), lower ejection fraction (17.9 +/- 5.4% vs. 20.2 +/- 7.1%; p = 0.04), diabetes (21.2% vs. 37.1%; p = 0.03), and systolic blood pressure <100 mm Hg during hospitalization (70.3% vs. 54.1%; p = 0.03). After adjusting for factors associated with beta-blocker use and those with outcomes, consistent beta-blocker use during hospitalization was associated with a significant reduction in the rate of rehospitalization or death within six months after discharge (odds ratio 0.27, 95% confidence interval 0.10 to 0.71; p < 0.01). CONCLUSIONS: Beta-blocker therapy before and during hospitalization for HF is associated with improved outcomes.

Adrenergic beta-Antagonists↗
PubMed2006

Utility of impedance cardiography for the identification of short-term risk of clinical decompensation in stable patients with chronic heart failure.

OBJECTIVES: This study sought to assess the potential utility of impedance cardiography (ICG) in predicting clinical deterioration in ambulatory patients with heart failure (HF). BACKGROUND: Impedance cardiography uses changes in thoracic electrical impedance to estimate hemodynamic variables, but its ability to predict clinical events has not been evaluated. METHODS: We prospectively evaluated 212 stable patients with HF and a recent episode of clinical decompensation who underwent serial clinical evaluation and blinded ICG testing every 2 weeks for 26 weeks and were followed up for the occurrence of death or worsening HF requiring hospitalization or emergent care. RESULTS: During the study, 59 patients experienced 104 episodes of decompensated HF (16 deaths, 78 hospitalizations, and 10 emergency visits). Multivariate analysis identified 6 clinical and ICG variables that independently predicted an event within 14 days of assessment. These included three clinical variables (visual analog score, New York Heart Association functional class, and systolic blood pressure) and three ICG parameters (velocity index, thoracic fluid content index, and left ventricular ejection time). The three ICG parameters combined into a composite score was a powerful predictor of an event during the next 14 days (p = 0.0002). Visits with a high-risk composite score had 2.5 times greater likelihood and those with a low-risk score had a 70% lower likelihood of a near-term event compared with visits at intermediate risk. CONCLUSIONS: These results suggest that when performed at regular intervals in stable patients with HF with a recent episode of clinical decompensation, ICG can identify patients at increased near-term risk of recurrent decompensation.

Adult↗
PubMed2006

Aquaretic effect of lixivaptan, an oral, non-peptide, selective V2 receptor vasopressin antagonist, in New York Heart Association functional class II and III chronic heart failure patients.

OBJECTIVES: The purpose of this study was to examine the renal effects of a V2 receptor arginine vasopressin (AVP) antagonist in heart failure. BACKGROUND: Arginine vasopressin has been implicated in the renal water retention and dilutional hyponatremia associated with chronic heart failure. METHODS: We examined the effects of the oral, non-peptide, selective V2 receptor antagonist lixivaptan in 42 diuretic-requiring patients with mild-to-moderate heart failure in a randomized, double-blind, placebo-controlled, ascending single-dose study. After overnight fluid deprivation, patients received single-blind placebo on day -1 (baseline) and double-blind study medication (placebo [n = 12] or lixivaptan 10, 30, 75, 150, 250, or 400 mg [n = 5 per dose group]) on day 1, followed by 4 h of continued fluid restriction and additional 20 h with ad libitum fluid intake. RESULTS: At all but the 10-mg dose, lixivaptan produced a significant and dose-related increase in urine volume over 4 h, compared with placebo. During 24 h, increases in urine volume ranged from 1.8 l with placebo to 3.9 l after the 400-mg lixivaptan dose (p < 0.01). These increases in urine volumes were accompanied by significant increases in solute-free water excretion. At higher doses, serum sodium was significantly increased; AVP antagonism was well tolerated in these patients. CONCLUSIONS: These observations confirm a role for AVP in the renal water retention associated with heart failure and suggest that the V2 receptor antagonist lixivaptan may be a promising therapeutic agent for the treatment of heart failure.

Administration, Oral↗
PubMed2006

Sustained reverse left ventricular structural remodeling with cardiac resynchronization at one year is a function of etiology: quantitative Doppler echocardiographic evidence from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE).

BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective therapy for patients with moderate to severe heart failure and prolonged QRS duration. The purpose of this study was to determine whether reverse left ventricular (LV) remodeling and symptomatic benefit from CRT were sustained at 12 months, and if so, in what proportion of patients this occurred. METHODS AND RESULTS: Serial Doppler echocardiograms were obtained at baseline and 6 and 12 months after CRT in 228 patients enrolled in the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial. Measurements were made of LV end-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction, LV mass, severity of mitral regurgitation (MR), peak transmitral velocities during early (E wave) and late (A wave) diastolic filling, and myocardial performance index. At both 6 and 12 months, respectively, CRT was associated with reduced LV EDV (P<0.0001 and P=0.007) and LV ESV (P<0.0001 and P<0.0001), improved ejection fraction (P<0.0001 and P<0.0001), regression of LV mass (P=0.012 and P<0.0001), and reduced MR (P<0.0001 and P<0.0001). LV filling time, transmitral E/A ratio, and myocardial performance index all improved at 12 months compared with baseline (P<0.001, P=0.031, and P<0.0001). Reverse LV remodeling with CRT occurred in more patients at 6 than at 12 months (74% versus 60%, respectively; P<0.05) and was greater in patients with a nonischemic than an ischemic etiology. CONCLUSIONS: Reverse LV remodeling and symptom benefit with CRT are sustained at 12 months in patients with New York Heart Association class III/IV heart failure but occur to a lesser degree in patients with an ischemic versus a nonischemic etiology, most likely owing to the inexorable progression of ischemic disease.

Aged↗
PubMed2006

Diuretic resistance in heart failure.

The use of diuretics for the treatment of heart failure (HF) is ubiquitous in any basic HF medical regimen. Although initially these drugs clearly show benefit by relieving symptomatic episodes of decompensated HF, long-term use of these drugs can lead to a "diuretic-resistant" state and is associated with an increased risk of morbidity and mortality. A number of factors may be responsible for this, including dietary noncompliance, inadequate diuretic dosing or methods of administration, and concomitant use of certain medications. Diuretics themselves may set in motion an iatrogenic cardiorenal syndrome leading to worsening renal function and diuretic resistance. The methods for overcoming this resistance are varied and require a focused approach with emphasis on relieving the congestive symptoms related to HF while attempting to preserve renal function and minimize any untoward systemic effects.

Diuretics↗
PubMed2006

Rationale and design of a randomized controlled trial to assess the safety and efficacy of cardiac resynchronization therapy in patients with asymptomatic left ventricular dysfunction with previous symptoms or mild heart failure--the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms, reduces heart failure (HF)-related hospitalizations, and reverses left ventricular remodeling in some patients with moderate to severe HF and ventricular dyssynchrony defined by a prolonged QRS duration. The effects of CRT on HF outcomes in patients with asymptomatic left ventricular dysfunction (ALVD) or mild HF remain to be determined. METHODS: The REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study is a prospective, multicenter, randomized, double-blind, parallel, controlled clinical trial designed to establish whether CRT combined with optimal medical treatment can attenuate HF disease progression compared with optimal medical treatment alone in patients with ALVD +/- New York Heart Association class I American College of Cardiology/American Heart Association stage C or New York Heart Association class II HF, QRS duration > or =120 milliseconds, left ventricular ejection fraction < or =0.40, and left ventricular end-diastolic diameter > or =55 mm. The primary end point is the HF clinical composite response and left ventricular end-systolic volume index is the first-order secondary end point. Approximately 500 patients from 100 centers in the United States, Canada, and Europe will be randomized to CRT versus no CRT. The follow-up is 5 years in total with the primary and first secondary end points reported at 12 months. Enrollment began in September 2004 and is expected to be completed in 2006. CONCLUSION: REVERSE will assess the safety and efficacy of CRT in patients with ALVD or mild HF and electrocardiographic evidence of ventricular dyssynchrony.

Cardiac Output, Low↗
PubMed2006

Clinical predictors and timing of New York Heart Association class improvement with cardiac resynchronization therapy in patients with advanced chronic heart failure: results from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) and Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE-ICD) trials.

BACKGROUND: Based on current patient selection criteria, a significant proportion of recipients of cardiac resynchronization therapy (CRT) do not respond to treatment. The purpose of this analysis is to identify predictors and characterize the timing of response to CRT in patients with advanced heart failure. METHODS: Patients randomized to receive CRT in the MIRACLE and MIRACLE-ICD trials, designed to assess the benefit of CRT compared with standard medical therapy in patients with advanced heart failure, left ventricular ejection fraction <0.35, and QRS > or =130 milliseconds, were included for this analysis. Patients with an improvement of > or =1 New York Heart Association (NYHA) class from baseline to the 6-month follow-up were considered responders and those who had no change or worse NYHA class or died were classified as nonresponders. Responders were subdivided into early (within 1-3 months) and late (6 months). RESULTS: One hundred forty-three (64%) of 224 and 190 (61%) of 313 patients in the MIRACLE and MIRACLE-ICD trials, respectively, responded to therapy, with 81 (57%) of 143 and 100 (53%) of 190 responding early. Several but differing factors predicted CRT response and timing in the two trials with a high sensitivity (89%-90%) but, owing to a low specificity (31%-49%), a modest predictive accuracy (66%-75%). CONCLUSIONS: Based on improvement of > or =1 NYHA class, less than two thirds of patients enrolled in the MIRACLE or MIRACLE-ICD trials responded to CRT, with just more than half responding within the first month. Several factors predicted CRT response and timing, but given their modest predictive accuracy, comparable for both studies, additional methods for selecting candidates most likely to benefit from CRT are needed.

Aged↗
PubMed2006

How obesity affects the cut-points for B-type natriuretic peptide in the diagnosis of acute heart failure. Results from the Breathing Not Properly Multinational Study.

BACKGROUND: B-type natriuretic peptide (BNP) is valuable in diagnosing heart failure (HF), but its utility in obese patients is unknown. Studies have suggested a cut-point of BNP > or = 100 pg/mL for the diagnosis of HF; however, there is an inverse relation between BNP levels and body mass index. We evaluated differential cut-points for BNP in diagnosing acute HF across body mass index levels to determine whether alternative cut-points can improve diagnosis. METHODS: The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who presented to the Emergency Department with acute dyspnea. B-type natriuretic peptide was measured on arrival. Height and weight data were available for 1368 participants. The clinical diagnosis of HF was adjudicated by 2 independent cardiologists who were blinded to BNP results. RESULTS: Heart failure was the final diagnosis in 46.1%. Mean BNP levels (pg/mL) in lean, overweight/obese, and severely/morbidly obese patients were 643, 462, and 247 for patients with acute HF, and 52, 35, and 25 in those without HF, respectively (P < .05 for all comparisons except 35 vs 25). B-type natriuretic peptide cut-points to maintain 90% sensitivity for a HF diagnosis were 170 pg/mL for lean subjects, 110 pg/mL for overweight/obese subjects, and 54 pg/mL in severely/morbidly obese patients. CONCLUSIONS: Body mass index influences the selection of cut-points for BNP in diagnosing acute HF. A lower cut-point (BNP > or = 54 pg/mL) should be used in severely obese patients to preserve sensitivity. A higher cut-point in lean patients (BNP > or = 170 pg/mL) could be used to increase specificity.

Acute Disease↗