Empagliflozin Effects on Pulmonary Artery Pressure in Patients With Heart Failure: Results From the EMBRACE-HF Trial.

BACKGROUND: Sodium glucose cotransporter 2 inhibitors (SGLT2 inhibitors) prevent heart failure (HF) hospitalizations in patients with type 2 diabetes and improve outcomes in those with HF and reduced ejection fraction, regardless of type 2 diabetes. Mechanisms of HF benefits remain unclear, and the effects of SGLT2 inhibitor on hemodynamics (filling pressures) are not known. The EMBRACE-HF trial (Empagliflozin Evaluation by Measuring Impact on Hemodynamics in Patients With Heart Failure) was designed to address this knowledge gap. METHODS: EMBRACE-HF is an investigator-initiated, randomized, multicenter, double-blind, placebo-controlled trial. From July 2017 to November 2019, patients with HF (regardless of ejection fraction, with or without type 2 diabetes) and previously implanted pulmonary artery (PA) pressure sensor (CardioMEMS) were randomized across 10 US centers to empagliflozin 10 mg daily or placebo and treated for 12 weeks. The primary end point was change in PA diastolic pressure (PADP) from baseline to end of treatment (average PADP weeks 8-12). Secondary end points included health status (Kansas City Cardiomyopathy Questionnaire score), natriuretic peptides, and 6-min walking distance. RESULTS: Overall, 93 patients were screened, and 65 were randomized (33 to empagliflozin, 32 to placebo). The mean age was 66 years; 63% were male; 52% had type 2 diabetes; 54% were in New York Heart Association class III/IV; mean ejection fraction was 44%; median NT-proBNP (N-terminal pro B-type natriuretic peptide) was 637 pg/mL; and mean PADP was 22 mm Hg. Empagliflozin significantly reduced PADP, with effects that began at week 1 and amplified over time; average PADP (weeks 8-12) was 1.5 mm Hg lower (95% CI, 0.2-2.8; P=0.02); and at week 12, PADP was 1.7 mm Hg lower (95% CI, 0.3-3.2; P=0.02) with empagliflozin versus placebo. Results were consistent for PA systolic and PA mean pressures. There was no difference in mean loop diuretic management (daily furosemide equivalents) between treatment groups. No significant differences between treatment groups were observed in Kansas City Cardiomyopathy Questionnaire scores, natriuretic peptide levels, and 6-min walking distance. CONCLUSIONS: In patients with HF and CardioMEMS PA pressure sensor, empagliflozin produced rapid reductions in PA pressures that were amplified over time and appeared to be independent of loop diuretic management. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03030222.

Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction: The DEFINE-HF Trial.

BACKGROUND: Outcome trials in patients with type 2 diabetes mellitus have demonstrated reduced hospitalizations for heart failure (HF) with sodium-glucose co-transporter-2 inhibitors. However, few of these patients had HF, and those that did were not well-characterized. Thus, the effects of sodium-glucose co-transporter-2 inhibitors in patients with established HF with reduced ejection fraction, including those with and without type 2 diabetes mellitus, remain unknown. METHODS: DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients with HF with Reduced Ejection Fraction) was an investigator-initiated, multi-center, randomized controlled trial of HF patients with left ventricular ejection fraction ≤40%, New York Heart Association (NYHA) class II-III, estimated glomerular filtration rate ≥30 mL/min/1.73m2, and elevated natriuretic peptides. In total, 263 patients were randomized to dapagliflozin 10 mg daily or placebo for 12 weeks. Dual primary outcomes were (1) mean NT-proBNP (N-terminal pro b-type natriuretic peptide) and (2) proportion of patients with ≥5-point increase in HF disease-specific health status on the Kansas City Cardiomyopathy Questionnaire overall summary score, or a ≥20% decrease in NT-proBNP. RESULTS: Patient characteristics reflected stable, chronic HF with reduced ejection fraction with high use of optimal medical therapy. There was no significant difference in average 6- and 12-week adjusted NT-proBNP with dapagliflozin versus placebo (1133 pg/dL (95% CI 1036-1238) vs 1191 pg/dL (95% CI 1089-1304), P=0.43). For the second dual-primary outcome of a meaningful improvement in Kansas City Cardiomyopathy Questionnaire overall summary score or NT-proBNP, 61.5% of dapagliflozin-treated patients met this end point versus 50.4% with placebo (adjusted OR 1.8, 95% CI 1.03-3.06, nominal P=0.039). This was attributable to both higher proportions of patients with ≥5-point improvement in Kansas City Cardiomyopathy Questionnaire overall summary score (42.9 vs 32.5%, adjusted OR 1.73, 95% CI 0.98-3.05), and ≥20% reduction in NT-proBNP (44.0 vs 29.4%, adjusted OR 1.9, 95% CI 1.1-3.3) by 12 weeks. Results were consistent among patients with or without type 2 diabetes mellitus, and other prespecified subgroups (all P values for interaction=NS). CONCLUSIONS: In patients with heart failure and reduced ejection fraction, use of dapagliflozin over 12 weeks did not affect mean NT-proBNP but increased the proportion of patients experiencing clinically meaningful improvements in HF-related health status or natriuretic peptides. Benefits of dapagliflozin on clinically meaningful HF measures appear to extend to patients without type 2 diabetes mellitus. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02653482.

Impact of Practice-Based Management of Pulmonary Artery Pressures in 2000 Patients Implanted With the CardioMEMS Sensor.

BACKGROUND: Elevated pulmonary artery (PA) pressures in patients with heart failure are associated with a high risk for hospitalization and mortality. Recent clinical trial evidence demonstrated a direct relationship between lowering remotely monitored PA pressures and heart failure hospitalization risk reduction with a novel implantable PA pressure monitoring system (CardioMEMS HF System, St. Jude Medical). This study examines PA pressure changes in the first 2000 US patients implanted in general practice use. METHODS: Deidentified data from the remote monitoring Merlin.net (St. Jude Medical) database were used to examine PA pressure trends from the first consecutive 2000 patients with at least 6 months of follow-up. Changes in PA pressures were evaluated with an area under the curve methodology to estimate the total sum increase or decrease in pressures (mm Hg-day) during the follow-up period relative to the baseline pressure. As a reference, the PA pressure trends were compared with the historic CHAMPION clinical trial (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association [NYHA] Functional Class III Heart Failure Patients). The area under the curve results are presented as mean±2 SE, and P values comparing the area under the curve of the general-use cohort with outcomes in the CHAMPION trial were computed by the t test with equal variance. RESULTS: Patients were on average 70±12 years old; 60% were male; 34% had preserved ejection fraction; and patients were followed up for an average of 333±125 days. At implantation, the mean PA pressure for the general-use patients was 34.9±10.2 mm Hg compared with 31.3±10.9 mm Hg for CHAMPION treatment and 32.0±10.5 mm Hg for CHAMPION control groups. The general-use patients had an area under the curve of -32.8 mm Hg-day at the 1-month time mark, -156.2 mm Hg-day at the 3-month time mark, and -434.0 mm Hg-day after 6 months of hemodynamic guided care, which was significantly lower than the treatment group in the CHAMPION trial. Patients consistently transmitted pressure information with a median of 1.27 days between transmissions after 6 months. CONCLUSIONS: The first 2000 general-use patients managed with hemodynamic-guided heart failure care had higher PA pressures at baseline and experienced greater reduction in PA pressure over time compared with the pivotal CHAMPION clinical trial. These data demonstrate that general use of implantable hemodynamic technology in a nontrial setting leads to significant lowering of PA pressures.

Dapagliflozin Improves Heart Failure Symptoms and Physical Limitations Across the Full Range of Ejection Fraction: Pooled Patient-Level Analysis From DEFINE-HF and PRESERVED-HF Trials.

BACKGROUND: Patients with heart failure (HF) have a high burden of symptoms and physical limitations, regardless of ejection fraction (EF). Whether the benefits of SGLT2 (sodium-glucose cotransporter-2) inhibitors on these outcomes vary across the full range of EF remains unclear. METHODS: Patient-level data were pooled from the DEFINE-HF trial (Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction) of 263 participants with reduced EF (≤40%), and PRESERVED-HF trial (Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With Preserved Ejection Fraction Heart Failure) of 324 participants with preserved EF (≥45%). Both were randomized, double-blind 12-week trials of dapagliflozin versus placebo, recruiting participants with New York Heart Association class II or higher and elevated natriuretic peptides. The effect of dapagliflozin on the change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) at 12 weeks was tested with ANCOVA adjusted for sex, baseline KCCQ, EF, atrial fibrillation, estimated glomerular filtration rate, and type 2 diabetes. Interaction of dapagliflozin effects on KCCQ-CSS by EF was assessed using EF both categorically and continuously with restricted cubic spline. Responder analyses, examining proportions of patients with deterioration, and clinically meaningful improvements in KCCQ-CSS were conducted using logistic regression. RESULTS: Of 587 patients randomized (293 dapagliflozin, 294 placebo), EF was ≤40, >40-≤60, and >60% in 262 (45%), 199 (34%), and 126 (21%), respectively. Dapagliflozin improved KCCQ-CSS at 12 weeks (placebo-adjusted difference 5.0 points [95% CI, 2.6-7.5]; P<0.001). This was consistent in participants with EF≤40 (4.6 points [95% CI, 1.0-8.1]; P=0.01), >40 to ≤60 (4.9 points [95% CI, 0.8-9.0]; P=0.02) and >60% (6.8 points [95% CI, 1.5-12.1]; P=0.01; Pinteraction=0.79). Benefits of dapagliflozin on KCCQ-CSS were also consistent when analyzing EF continuously (Pinteraction=0.94). In responder analyses, fewer dapagliflozin-treated patients had deterioration and more had small, moderate, and large KCCQ-CSS improvements versus placebo; these results were also consistent regardless of EF (all Pinteractionvalues nonsignificant). CONCLUSIONS: In patients with HF, dapagliflozin significantly improves symptoms and physical limitations after 12 weeks of treatment, with consistent and clinically meaningful benefits across the full range of EF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT02653482 and NCT03030235.

Effect of Dapagliflozin on 6-Minute Walk Distance in Heart Failure With Preserved Ejection Fraction: PRESERVED-HF.

BACKGROUND: Heart failure with preserved ejection fraction is associated with significant functional limitations, yet treatments for improving exercise performance have been elusive. We sought to explore the association between prespecified patient characteristics and changes in 6-minute walk distance that constitute a clinically significant response to dapagliflozin. METHODS: We performed a responder analysis to understand patient characteristics associated with clinically meaningful improvement in 6-minute walk test (6MWT) distance ≥15 m among patients randomized to 12 weeks of dapagliflozin versus placebo in the double-blind PRESERVED-HF trial (Effects of Dapagliflozin on Biomarkers, Symptoms and Functional Status in Patients With Preserved Ejection Fraction Heart Failure). RESULTS: A total of 289 randomized patients had 6MWT distance completed at baseline and 12 weeks. Patients randomized to dapagliflozin improved walking distance by ≥15 m more frequently than those on placebo (n=64, 44% versus n=48, 34%). After adjusting for baseline covariates, patients randomized to dapagliflozin were more likely to experience a clinically meaningful improvement in 6MWT distance compared with those that received placebo (adjusted odds ratio, 1.66 [95% CI, 1.00-2.75]; P=0.05). Dapagliflozin-treated patients were also less likely to have a ≥15 m reduction in 6MWT distance compared with placebo-treated patients (adjusted odds ratio, 0.56 [95% CI, 0.33-0.94]; P=0.03). These results were consistent across all prespecified subgroups (all P values for interaction were not significant). CONCLUSIONS: Compared with those on placebo, patients with heart failure with preserved ejection fraction randomized to dapagliflozin were more likely to experience a clinically meaningful improvement and less likely to experience a deterioration in physical function over 12 weeks as measured by 6MWT distance. Beneficial response to dapagliflozin was consistent across prespecified subgroups. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03030235.

The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial.

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3-9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0-9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7-10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6-34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1-7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05-2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01-1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF.

Effect of cardiac resynchronization therapy on myocardial gene expression in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves echocardiographic measures of ventricular structure and function in the failing heart. To determine whether or not these changes are representative of true biologic reverse ventricular remodeling or simply an artifact of an improved contraction pattern, we evaluated changes in myocardial gene expression typical of reverse remodeling before and after chronic CRT. METHODS AND RESULTS: Optimally medically treated patients with nonischemic heart failure meeting standard clinical criteria for CRT were enrolled. Before implantation of a CRT device, baseline echocardiogram and endomyocardial biopsies were obtained. These studies were repeated after 6 months of CRT. Using quantitative reverse-transcriptase polymerase chain reaction, the amount of messenger RNA for selected genes regulating contractile function (sarcoplasmic reticulum Ca2+ ATPase, alpha- and beta-myosin heavy chain [MHC] isoforms, phospholamban [PLB]), and pathologic hypertrophy (beta-MHC and atrial natriuretic peptide [ANP]) was determined from biopsy samples. Changes in gene expression (baseline to 6 months) were determined and correlated to changes in echocardiographic remodeling parameters. Ten patients were enrolled in the study, with 7 completing both baseline and follow-up biopsies and echocardiograms. On average, a significant increase was observed in alpha-MHC and PLB gene expression from baseline to 6 months (P = .016 for both). Beta-MHC levels tended to decrease with CRT (P = .078). Increased alpha-MHC levels correlated best with decreases in left ventricular end-diastolic dimension (P = .073, r = -0.71) and reductions in mitral regurgitation. No significant correlation between ejection fraction and gene expression was found. CONCLUSIONS: These changes in myocardial gene expression support the occurrence of reverse remodeling during chronic CRT. The changes are similar to those reported previously with beta-blockade, but were seen on top of standard drug therapies for heart failure.

B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study.

BACKGROUND: We sought to determine the degree to which B-type natriuretic peptide (BNP) adds to clinical judgment in the diagnosis of congestive heart failure (CHF). METHODS AND RESULTS: The Breathing Not Properly Multinational Study was a prospective diagnostic test evaluation study conducted in 7 centers. Of 1586 participants who presented with acute dyspnea, 1538 (97%) had clinical certainty of CHF determined by the attending physician in the emergency department. Participants underwent routine care and had BNP measured in a blinded fashion. The reference standard for CHF was adjudicated by 2 independent cardiologists, also blinded to BNP results. The final diagnosis was CHF in 722 (47%) participants. At an 80% cutoff level of certainty of CHF, clinical judgment had a sensitivity of 49% and specificity of 96%. At 100 pg/mL, BNP had a sensitivity of 90% and specificity of 73%. In determining the correct diagnosis (CHF versus no CHF), adding BNP to clinical judgment would have enhanced diagnostic accuracy from 74% to 81%. In those participants with an intermediate (21% to 79%) probability of CHF, BNP at a cutoff of 100 pg/mL correctly classified 74% of the cases. The areas under the receiver operating characteristic curve were 0.86 (95% CI 0.84 to 0.88), 0.90 (95% CI 0.88 to 0.91), and 0.93 (95% CI 0.92 to 0.94) for clinical judgment, for BNP at a cutoff of 100 pg/mL, and for the 2 in combination, respectively (P<0.0001 for all pairwise comparisons). CONCLUSIONS: The evaluation of acute dyspnea would be improved with the addition of BNP testing to clinical judgment in the emergency department.

B-type natriuretic peptide levels in patients in the emergency department with possible heart failure and previous stable angina pectoris and/or healed myocardial infarction.

We examined the relation between B-type natriuretic peptide (BNP) levels and a history of stable angina pectoris and/or healed myocardial infarction in 1,240 patients who were evaluated in the emergency department for possible heart failure. In patients who had heart failure, there was no relation between BNP levels and previous stable angina pectoris and/or healed myocardial infarction. However, in patients who did not have heart failure, there was a relation between BNP levels and previous stable angina pectoris and/or healed myocardial infarction but no significant independent relation in multiple regression analysis.

B-type natriuretic peptide and renal function in the diagnosis of heart failure: an analysis from the Breathing Not Properly Multinational Study.

BACKGROUND: Both B-type natriuretic peptide (BNP) and renal function are prognostic indicators of survival in patients with congestive heart failure (CHF). However, relationships between BNP, renal function, and heart failure as an emergency diagnosis are unknown. METHODS: The Breathing Not Properly Multinational Study was a prospectively designed diagnostic test evaluation study conducted in seven centers. Of 1,586 participants who presented with acute dyspnea, 1,452 patients (91.6%) had both BNP level and baseline estimated glomerular filtration rate (eGFR) available. Patients with an eGFR less than 15 mL/min/1.73 m2 and those on dialysis therapy were excluded. The final diagnosis was adjudicated by two independent cardiologists who were blinded to BNP results. RESULTS: The final diagnosis was CHF in 715 patients (49.2%). Raw and log-log transformed correlations between BNP and eGFR values were r = -0.19 and r = -0.17 for those with CHF and r = -0.20 and r = -0.31 for those without CHF (both P < 0.0001 for r not equal 0). Mean BNP levels were 561.6 pg/mL (162.3 fmol/mL), 647.5 pg/mL (187.1 fmol/mL), 745.6 pg/mL (215.5 fmol/mL), and 850.7 pg/mL (245.8 fmol/mL) for those with CHF and 85.4 pg/mL (24.7 fmol/mL), 131.7 pg/mL (38.1 fmol/mL), 297.2 pg/mL (85.9 fmol/mL), and 285.0 pg/mL (82.3 fmol/mL) for those without CHF in eGFR categories of 90 or greater, 89 to 60, 59 to 30, and less than 30 mL/min/1.73 m2, respectively. The area under the receiver operating characteristic curve and optimum cut points for BNP were 0.91 and 70.7 pg/mL (20.4 fmol/mL), 0.90 and 104.3 pg/mL (30.1 fmol/mL), 0.81 and 201.2 pg/mL (58.1 fmol/mL), and 0.86 and 225.0 pg/mL (65.0 fmol/mL) for the eGFR categories of 90 or greater, 89 to 60, 59 to 30, and less than 30 mL/min/1.73 m2, respectively. CONCLUSION: Renal function correlates weakly with BNP and influences the optimal cut point for BNP, particularly in those with an eGFR less than 60 mL/min/1.73 m2.

Prevalence of sleep disordered breathing in a heart failure program.

Recent data show that a high percentage of patients with systolic left ventricular dysfunction have sleep-disordered breathing (SDB), contributing to the incidence of morbidity and mortality in heart failure. This study examines the prevalence of sleep disorders in stable heart failure patients regardless of ejection fraction. On three consecutive days in a heart failure clinic, all patients were asked to participate in a screening for SDB. This screening involved the placement of an outpatient device (ClearPath, Nexan, Inc., Alpharetta, GA), which collects thoracic impedance, oxyhemoglobin saturation, and 2-lead electrocardiogram data. Sixteen patients (42%) had moderate or severe SDB, and 22 patients (55%) had mild or no significant SDB. Fourteen of the 16 patients with moderate or severe SDB subsequently received treatment by confirming SDB and the continuous positive airway pressure in a sleep lab. Forty-two percent of patients with stable heart failure presenting to a heart failure clinic screened positive for SDB, despite receiving optimal standard of care.

Uncovering heart failure in patients with a history of pulmonary disease: rationale for the early use of B-type natriuretic peptide in the emergency department.

UNLABELLED: Plasma B-type natriuretic peptide (BNP) can reliably identify acute congestive heart failure (CHF) in patients presenting to the emergency department (ED) with acute dyspnea. Heart failure, asthma, and chronic obstructive pulmonary disease (COPD) are syndromes where dyspnea and wheezing are overlapping signs, and hence, these syndromes are often difficult to differentiate. OBJECTIVE: To determine whether BNP can distinguish new-onset heart failure in patients with COPD or asthma presenting with dyspnea to the ED. METHODS: The BNP Multinational Study was a seven-center prospective study of 1,586 adult patients presenting to the ED with acute dyspnea who had blinded BNP levels measured on arrival with a rapid, point-of-care device. This study evaluated the 417 patients with no previous history of heart failure and a history of asthma or COPD as a subgroup from the 1,586 adult patients in the BNP Multinational Study. The reference standard for CHF was adjudicated by two independent cardiologists, also blinded to BNP results, who reviewed all clinical data and standardized CHF scores. RESULTS: A total of 417 subjects (mean age 62.2 years, 64.4% male) had a history of asthma or COPD without a history of CHF. Of these, 87/417 (20.9%, 95% CI = 17.1% to 25.1%) were found to have CHF as the final adjudicated diagnosis. The emergency physicians identified a minority, 32/87 (36.8%), of these patients with CHF. The mean BNP values (+/- SD) were 587.0 +/- 426.4 and 108.8 +/- 221.3 pg/mL for those with and without CHF (p < 0.0001). At a cutpoint of 100 pg/mL, BNP had the following decision statistics: sensitivity 93.1%, specificity 77.3%, positive predictive value 51.9%, negative predictive value 97.7%, accuracy 80.6%, positive likelihood ratio 4.10, and negative likelihood ratio 0.09. If BNP would have been added to clinical judgment (high > or = 80% probability of CHF), at a cutpoint of 100 pg/mL, 83/87 (95.4%) of the CHF subjects would have been correctly diagnosed. Multivariate analysis found BNP to be the most important predictor of CHF (OR = 12.1, 95% CI = 5.4 to 27.0, p < 0.0001). In the 87 subjects found to have CHF, 39.0%, 22.2%, and 54.8% were taking angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers (BBs), and diuretics on a chronic basis, respectively. CONCLUSIONS: The yield of adding routine BNP testing in patients with a history of asthma or COPD in picking up newly diagnosed CHF is approximately 20%. This group of patients presents a substantial therapeutic opportunity for the initiation and chronic administration of ACEI and BB therapy, as well as other CHF management strategies.

Accuracy of the precordial V-Quick patch in persons with cardiac or pulmonary disease.

The aim of this study was to demonstrate the equivalence of 12-Lead Electrocardiograms (EKG) obtained with the new V-Quick patch and traditional tab-style electrodes. Using a within-subject design, a convenience sample of 100 subjects with either cardiac or pulmonary disease underwent two 12-lead EKGs, one with the traditional tab-style electrodes and one with the precordial patch. Computer-generated measurements of waveform axes and amplitude were obtained for both EKGs. Comparison of mean and 95% confidence intervals revealed no significant differences in Q, R or S wave amplitude across the six precordial leads. Furthermore, a four-factor ANOVA found no significant difference (p > 0.05) in the Q, R and S wave amplitude between the type of electrode, gender and type of disease. A subset of 29 EKGs read by three experts found intra- (.90) and inter-rater (.84) reliability to be strong. In conclusion, the precordial V-Quick patch provided equivalent EKGs to those obtained using standard tab-style electrodes.

Future therapies for heart failure.

The treatment of heart failure has changed as the understanding of the disease evolves. Heart failure remains the only cardiovascular disease that continues to rise in both incidence and prevalence, despite recent advances in treating symptoms and thwarting disease progression. Many opportunities exist for improving patient outcomes with pharmaceutical agents and technologies available now or in the near future. This article discusses recently approved drugs and devices and clinical trials that may affect the management of this challenging disease.

Peripherally inserted veno-venous ultrafiltration for rapid treatment of volume overloaded patients.

BACKGROUND: Veno-venous ultrafiltration may benefit patients with acute or chronic circulatory volume overload. Use of conventional systems, however, may be cumbersome, requiring physician placement of a double-lumen central venous catheter and use of a dedicated dialysis technician and apparatus. METHODS: A simplified peripheral ultrafiltration system including a miniaturized disposable circuit was evaluated in patients with volume-overload states. Separate intravenous catheters (16-18 G) for withdrawal and return of blood (blood flow