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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.

BACKGROUND: Cardiogenic shock is a morbid complication of heart disease that claims the lives of more than 1 in 3 patients presenting with this syndrome. Supporting a unique collaboration across clinical specialties, federal regulators, payors, and industry, the American Heart Association volunteers and staff have launched a quality improvement registry to better understand the clinical manifestations of shock phenotypes, and to benchmark the management patterns, and outcomes of patients presenting with cardiogenic shock to hospitals across the United States. METHODS: Participating hospitals will enroll consecutive hospitalized patients with cardiogenic shock, regardless of etiology or severity. Data are collected through individual reviews of medical records of sequential adult patients with cardiogenic shock. The electronic case record form was collaboratively designed with a core minimum data structure and aligned with Shock Academic Research Consortium definitions. This registry will allow participating health systems to evaluate patientlevel data including diagnostic approaches, therapeutics, use of advanced monitoring and circulatory support, processes of care, complications, and in-hospital survival. Participating sites can leverage these data for onsite monitoring of outcomes and benchmarking versus other institutions. The registry was concomitantly designed to provide a high-quality longitudinal research infrastructure for pragmatic randomized trials as well as translational, clinical, and implementation research. An aggregate deidentified data set will be made available to the research community on the American Heart Association's Precision Medicine Platform. On March 31, 2022, the American Heart Association Cardiogenic Shock Registry received its first clinical records. At the time of this submission, 100 centers are participating. CONCLUSIONS: The American Heart Association Cardiogenic Shock Registry will serve as a resource using consistent data structure and definitions for the medical and research community to accelerate scientific advancement through shared learning and research resulting in improved quality of care and outcomes of shock patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the cost-effectiveness of implantable cardioverter defibrillators (ICDs), cardiac resynchronisation therapy pacemakers (CRT-Ps) and combination therapy (CRT-D) in patients with heart failure with reduced ejection fraction based on a range of clinical characteristics.Methods: Individual patient data from 13 randomised trials were used to inform a decision analytical model. A series of regression equations were used to predict baseline all-cause mortality, hospitalisation rates and health-related quality of life and device-related treatment effects. Clinical variables used in these equations were age, QRS duration, New York Heart Association (NYHA) class, ischaemic aetiology and left bundle branch block (LBBB). A UK National Health Service perspective and a lifetime time horizon were used. Benefits were expressed as quality-adjusted life-years (QALYs). Results were reported for 24 subgroups based on LBBB status, QRS duration and NYHA class.Results: At a threshold of £30 000 per QALY gained, CRT-D was cost-effective in 10 of the 24 subgroups including all LBBB morphology patients with NYHA I/II/III. ICD is cost-effective for all non-NYHA IV patients with QRS duration <120 ms and for NYHA I/II non-LBBB morphology patients with QRS duration between 120 ms and 149 ms. CRT-P was also cost-effective in all NYHA III/IV patients with QRS duration >120 ms. Device therapy is cost-effective in most patient groups with LBBB at a threshold of £20 000 per QALY gained. Results were robust to altering key model parameters.Conclusions: At a threshold of £30 000 per QALY gained, CRT-D is cost-effective in a far wider group than previously recommended in the UK. In some subgroups ICD and CRT-P remain the cost-effective choice. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a global phenomenon, and the overall incidence and prevalence of the condition are steadily increasing. Medical therapies have proven efficacious, but only a small number of pharmacological options are in development. When patients cease to respond adequately to optimal medical therapy, cardiac resynchronization therapy has been shown to improve symptoms, reduce hospitalizations, promote reverse remodelling, and decrease mortality. However, chalienges remain in identifying the ideal recipients for this therapy. The field of mechanical circulatory support has seen immense growth since the early 200Os, and left ventricular assist devices (LVADs) have transitioned over the past decade from large, pulsatile devices to smaller, more-compact, continuous41ow devices. Infections and haematological issues are still important areas that need to be addressed. Whereas LVADs were once approved only for 'bridge to transplantation', these devices are now used as destination therapy for critically ill patients with HF, allowing these individuals to return to the community. A host of novel strategies, including cardiac contractility modulation, implantable haemodynamic-monitoring devices, and phrenic and vagus nerve stimulation, are under investigation and might have an impact on the future care of patients with chronic HF. [ABSTRACT FROM AUTHOR]

The article focuses on the study "CRT Produces Long-Term Improvements in Disease Progression in Mildly Symptomatic Heart Failure Patients," by Cecilia Linde et al. The purpose of the research is to examine the effects of cardiac resynchronization therapy (CRT) with or without an ICD on disease progression in patients with asymptomatic and mildly symptomatic heart failure and ventricular dysynchrony. The end points of the main study are outlined.

Congest Heart Fail. 2011;17:220-226. © 2011 Wiley Periodicals, Inc. Despite evidence based medical and pharmacologic advances the management of heart failure remains challenging, especially in the ambulatory setting. There is an urgent need to develop strategies to reduce hospitalizations and re-admission rates for heart failure in general. This focused review illustrates the potential role for remote telemonitoring and implantable hemodynamic devices to address this significant issue. We also explore the growth of cardiac resynchronization therapy and how it has evolved into another tool in our armamentarium for hemodynamic monitoring. [ABSTRACT FROM AUTHOR]

Congest Heart Fail. The long-term impact of cardiac resynchronization therapy (CRT)-induced acute improvement in left ventricular (LV) function is largely unknown. The goal of this study was to evaluate the significance of acute improvement in LV function resulting from CRT in patients with chronic heart failure (HF). The authors compared 6-month clinical composite score (CCS) and LV end-systolic (ESV) reduction (≥15% from baseline) response rates of CRT-treated patients enrolled in the Predictors of Response to CRT (PROSPECT) trial who showed an acute increase (≥15% from baseline) in LV ejection fraction (EF) vs those who did not show a similar change in EF. Of the 396 patients who had pre-implant and post-implant EF measurements, 78 (19.7%) had an increase in EF and 318 (80.3%) did not. Acute reduction of mitral regurgitation by at least one grade occurred in 26% and 23% of patients with and without an acute increase in EF, respectively. Patients with an acute increase in EF had significantly lower baseline EF and smaller LV volumes but otherwise similar characteristics. At 6 months, LVEF and LV volumes were significantly higher and lower in the increased EF group, respectively; however, CCS improvement (70.5% vs 69.5%) and LVESV reduction (57.1% vs 54.9%) response rates were comparable in the two groups. An acute ≥15% increase in LVEF with CRT does not predict 6-month effects of CRT on patient outcomes or LV reverse remodeling. That such findings occur in patients with smaller LV volumes, however, may provide additional insight into the mechanisms responsible for CRT-induced long-term improvement in LV function and clinical benefit. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) is an effective treatment for patients suffering from advanced heart failure and electrical dyssynchrony. Limited data suggest that patients may benefit from routine optimization of the atrioventricular (AV) and interventricular (VV) delays; however, there is scarce information available on how and when optimization should be performed. Objective: The objective of this survey was to characterize the current international standard of care for optimization of the AV and VV delays in CRT devices recipients. Methods: Centers participating in the Frequent Optimization Survey Using the QuickOpt Method (FREEDOM) study completed surveys probing into their optimization of AV and VV delays procedures. Probes focused on the methods used to optimizing the delays, visits at which optimization of the delays was performed, percentage of patients that underwent optimization, and factors that limited centers from optimizing the CRT systems. Results: Few of the 118 investigators from 16 countries who responded to the survey routinely optimized the delays in all patients. At follow-up visits and during hospitalizations, a trend was observed to optimize the delays more often in nonresponders than in responders to CRT. Standard echocardiography was the most common method of optimization. Time availability and lack of qualified staff were the main factors limiting the optimization of CRT systems. Conclusions: In real-world practice, AV and VV optimization was not performed in a high proportion of patients. A less time-consuming and easier optimization method might enable a more systematic optimization of the AV and VV delays at routine follow-up visits in all recipients of CRT systems. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine the effects of cardiac resynchronization therapy (CRT) in New York Heart Association (NYHA) functional class II heart failure (HF) and NYHA functional class I (American College of Cardiology/American Heart Association stage C) patients with previous HF symptoms. Background: Cardiac resynchronization therapy improves left ventricular (LV) structure and function and clinical outcomes in NYHA functional class III and IV HF with prolonged QRS. Methods: Six hundred ten patients with NYHA functional class I or II heart failure with a QRS ≥120 ms and a LV ejection fraction ≤40% received a CRT device (±defibrillator) and were randomly assigned to active CRT (CRT-ON; n = 419) or control (CRT-OFF; n = 191) for 12 months. The primary end point was the HF clinical composite response, which scores patients as improved, unchanged, or worsened. The prospectively powered secondary end point was LV end-systolic volume index. Hospitalization for worsening HF was evaluated in a prospective secondary analysis of health care use. Results: The HF clinical composite response end point, which compared only the percent worsened, indicated 16% worsened in CRT-ON compared with 21% in CRT-OFF (p = 0.10). Patients assigned to CRT-ON experienced a greater improvement in LV end-systolic volume index (−18.4 ± 29.5 ml/m2 vs. −1.3 ± 23.4 ml/m2, p < 0.0001) and other measures of LV remodeling. Time-to-first HF hospitalization was significantly delayed in CRT-ON (hazard ratio: 0.47, p = 0.03). Conclusions: The REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) trial demonstrates that CRT, in combination with optimal medical therapy (±defibrillator), reduces the risk for heart failure hospitalization and improves ventricular structure and function in NYHA functional class II and NYHA functional class I (American College of Cardiology/American Heart Association stage C) patients with previous HF symptoms. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT00271154). [Copyright &y& Elsevier]

Objectives: This study ascertains the relationship between continuation or withdrawal of beta-blocker therapy and clinical outcomes in patients hospitalized with systolic heart failure (HF). Background: Whether beta-blocker therapy should be continued or withdrawn during hospitalization for decompensated HF has not been well studied in a broad cohort of patients. Methods: The OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) program enrolled 5,791 patients admitted with HF in a registry with pre-specified 60- to 90-day follow-up at 91 academic and community hospitals throughout the U.S. Outcomes data were prospectively collected and analyzed according to whether beta-blocker therapy was continued, withdrawn, or not started. Results: Among 2,373 patients eligible for beta-blockers at discharge, there were 1,350 (56.9%) who were receiving beta-blockers before admission and continued on therapy, 632 (26.6%) newly started, 79 (3.3%) in which therapy was withdrawn, and 303 (12.8%) eligible but not treated. Continuation of beta-blockers was associated with a significantly lower risk and propensity adjusted post-discharge death (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.37 to 0.99, p = 0.044) and death/rehospitalization (odds ratio: 0.69; 95% CI: 0.52 to 0.92, p = 0.012) compared with no beta-blocker. In contrast, withdrawal of beta-blocker was associated with a substantially higher adjusted risk for mortality compared with those continued on beta-blockers (HR: 2.3; 95% CI: 1.2 to 4.6, p = 0.013), but with similar risk as HF patients eligible but not treated with beta-blockers. Conclusions: The continuation of beta-blocker therapy in patients hospitalized with decompensated HF is associated with lower post-discharge mortality risk and improved treatment rates. In contrast, withdrawal of beta-blocker therapy is associated with worse risk and propensity-adjusted mortality. (Organized Program To Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure [OPTIMIZE-HF]; NCT00344513) [Copyright &y& Elsevier]

Objectives: We sought to examine the characteristics, quality of care, and clinical outcomes for a large cohort of African-American patients hospitalized with heart failure (HF) in centers participating in a quality improvement initiative. Background: Heart failure in African Americans is characterized by variations in natural history, lesser response to evidence-based therapies, and disparate health care. We hypothesized that a performance improvement program will achieve similar adherence to quality measures in African Americans admitted with HF compared with non–African Americans. Methods: The OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure) registry-based performance-improvement program includes a pre-specified 10% subgroup with 60- to 90-day follow-up. Data on quality of care measures and outcomes were analyzed for 8,608 African-American patients compared with 38,501 non–African-American patients. Results: African Americans were significantly younger and more likely to receive evidence-based medications but less likely to receive discharge instructions and smoking cessation counseling. In multivariable analyses, African-American race was an independent predictor of lower in-hospital mortality (odds ratio 0.71; 95% confidence interval 0.57 to 0.87; p < 0.001) but similar hospital length of stay. After multivariable adjustment, post-discharge outcomes were similar for American-American and non–African-American patients, but African-American race was associated with higher angiotensin-converting enzyme inhibitor prescription and left ventricular function assessment; no other HF quality indicators were influenced by race. Conclusions: In the context of a performance-improvement program, African Americans with HF received similar or better treatment with evidence-based medications, less discharge counseling, had better in-hospital survival, and similar adjusted risk of follow-up death/repeat hospital stay. (Organized Program to Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure [OPTIMIZE-HF]; NCT00344513) [Copyright &y& Elsevier]

The Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study is a randomized controlled trial currently assessing the safety and efficacy of cardiac resynchronization therapy in patients with asymptomatic left ventricular (LV) dysfunction with previous symptoms of mild heart failure. This paper describes the baseline characteristics of randomized patients; 610 patients with New York Heart Association (NYHA) class II (82.3%) heart failure or asymptomatic (NYHA class I) LV dysfunction with previous symptoms (17.7%) were randomized in 73 centers. The mean age was 62.5±11.0 years, the mean LV ejection fraction was 26.7%±7.0%, and the mean LV end-diastolic diameter was 66.9±8.9 mm. A total of 97% of patients were taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and 95.1% were taking β-blockers, which were at the target dose in 35.1% of patients. Compared with previous randomized cardiac resynchronization therapy trials, REVERSE patients are on better pharmacologic treatment, are younger, and have a narrower QRS width despite similar LV dysfunction. [ABSTRACT FROM AUTHOR]

Objective: An elastic ventricular restraint device has been developed for patients with heart failure who remain symptomatic despite treatment with standard therapies. The safety and efficacy of this device are under clinical investigation. Six-month data for the first 51 patients treated worldwide are reported. We hypothesize that the Paracor HeartNet device (Paracor Medical, Sunnyvale, Calif), placed through a minithoracotomy in patients with severe dilated cardiomyopathy, improves clinical and functional status. Methods: Fifty-one patients with an ejection fraction of 35% or less, with a New York Heart Association class II or III, and receiving optimal medical therapy for at least 3 months, were selected at 15 sites (3 in Europe, 12 in the United States) to undergo implantation of the HeartNet device through a minithoracotomy. Patients were evaluated at baseline and at 6-month follow-up by echocardiography, the 6-minute walk test, cardiopulmonary exercise testing (partial oxygen pressure in mixed venous blood), New York Heart Association class, and (in the United States) the Minnesota Living with Heart Failure questionnaire. Results: The average age was 52 years (30–73 years), with a preponderance of men and nonischemic cause of heart failure. Implantation was accomplished in 50 of 51 patients (98%). Adverse events included 2 in-hospital deaths secondary to pulmonary complications (4%), additional pulmonary complications in 7 patients (14%), arrhythmia in 14 patients (27%), epicardial laceration in 2 patients (4%), and empyema in 1 patient (2%). Six-month data demonstrated significant improvement in the 6-minute walk test (+65.7, P = .002) and Minnesota Living with Heart Failure scores (−15.7, P = .002) and improvement in echocardiographic findings. Conclusion: The Paracor HeartNet device can be reliably implanted in patients with heart failure and marked reduction of left ventricular function. These data suggest a functional and clinical benefit, with a trend toward reverse remodeling, and support the conduct of a randomized controlled pivotal trial. [Copyright &y& Elsevier]

Background: We determined whether low-dose oral enoximone could wean patients with ultra-advanced heart failure (UA-HF) from intravenous (IV) inotropic support. Chronic parenteral inotropic therapy in UA-HF is costly and requires an indwelling catheter. An effective and safe oral inotrope would have value. Methods: In this placebo-controlled study, 201 subjects with UA-HF requiring IV inotropic therapy were randomized to enoximone or placebo. Subjects receiving intermittent IV inotropes were administered study medication of 25 or 50 mg 3 times a day (tid). Subjects receiving continuous IV inotropes were administered 50 or 75 mg tid for 1 week, which was reduced to 25 or 50 mg tid. The ability of subjects to remain alive and free of inotropic therapy was assessed for up to 182 days. Results: Thirty days after weaning, 51 (51%) subjects on placebo and 62 (61.4%) subjects in the enoximone group were alive and free of IV inotropic therapy (unadjusted primary end point P = 0.14, adjusted for etiology P = .17). At 60 days, the wean rate was 30% in the placebo group and 46.5% in the enoximone group (unadjusted P = .016) Kaplan-Meier curves demonstrated a trend toward a decrease in the time to death or reinitiation of IV inotropic therapy over the 182-day study period (hazard ratio 0.76 [95% CI 0.55-1.04]) and a reduction at 60 days (0.62 [95% CI 0.43-0.89], P = .009) and 90 days (0.69 [95% CI 0.49-0.97], P = .031) after weaning in the enoximone group. Conclusions: Although there was no benefit over placebo in weaning patients from IV inotropes from 0 to 30 days, the EMOTE data suggest that low-dose oral enoximone can be used to wean a modest percentage of subjects from IV inotropic support for up to 90 days after initiation of therapy. [Copyright &y& Elsevier]

Early intervention and prevention of hospitalizations would reduce the burden of heart failure on the healthcare system while improving the quality of life of affected patients. Traditional methods of patient assessment, including physical examination and patient report of symptoms, have a low sensitivity for detecting elevations in left ventricular filling pressure, a major precursor of pulmonary congestion and heart failure decompensation. Intrathoracic fluid accumulation during pulmonary congestion leads to decreased impedance across the lung. The OptiVol® system in the InSync Sentry® cardiac resynchronization therapy-defibrillator, Concerto® cardiac resynchronization therapy-defibrillator and Virtuoso® implantable cardioverter-defibrillator devices monitors intrathoracic impedance and is intended to recognize early signs of volume accumulation before physical symptoms appear. Through a recent clinical trial, the default setting for the OptiVol system functioned as a predictor of hospitalization with 76.9% sensitivity. Intrathoracic impedance monitoring is not intended to replace careful frequent clinical evaluation of the heart failure patient, but instead aims to complement traditional heart failure management practices. [ABSTRACT FROM AUTHOR]

Background: Community patients with heart failure (HF) are older, less often treated by HF specialists, and have more comorbidity than those in randomized clinical trials. These differences might affect β-blocker prescribing in HF. Methods: To explore patterns of β-blocker prescribing for HF in the community and their association with outcomes, we determined carvedilol doses at end titration in 4113 patients from a community-based β-blocker HF registry according to physician and patient characteristics, HF severity, and rates of hospitalization and death. Results: Female sex, age ≥65 years, and left ventricular ejection fraction ≥35% were associated with lower β-blocker doses. Average daily dose of β-blocker was lower with worse baseline New York Heart Association class. More patients of cardiologists achieved carvedilol doses ≥25 mg twice daily, whereas in those of noncardiologists lower doses were more common. Relative risk of HF hospitalizations or all-cause death was significantly lower with higher doses of β-blocker. Conclusions: β-Blocker dosing in community HF appears lower than in randomized clinical trials, especially when prescribed by noncardiologists. At all doses, patients taking the β-blocker carvedilol have a lower incidence of death and HF hospitalization than those discontinuing it, regardless of physician type in the community setting. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

The authors present the results of a study that determined that heart failure performance measures, with the exception of the prescription of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at hospital discharge, have little relationship to patient mortality and the combination of mortality or rehospitalization in the first 60 to 90 days after hospital discharge. Performance measures studied included discharge instructions, evaluation of left ventricular systolic function, smoking cessation, anticoagulant administration and the use of angiotensin-converting enzyme inhibitors.

Women and the elderly are underrepresented in clinical trials of heart failure (HF). The authors analyzed, by sex and age groups, a registry of 4280 community patients initiating carvedilol for HE Women (n=1485) were older than men (n=2793) and had worse functional class with higher left ventricular ejection fraction and blood pressure. Women also had more HF hospitalizations, less use of angiotensin-converting enzyme inhibitors, and lower doses of carvedilol. Nevertheless, during 1-year follow-up, both groups experienced greater than 40% reductions in HF hospitalizations (P<.O01), with mortality of 7.3% in women vs 9.1% in men (P=.085). With increasing age, left ventricular ejection fraction, blood pressure, and functional class increased, whereas angiotensin-converting enzyme inhibitor use and carvedilol doses decreased. HF hospitalizations fell at least 40% in all age groups after starting carvedilol (P<.001). Characteristics of women and the elderly with HF in the community suggest increased risk, but both populations respond well after initiating carvedilol. [ABSTRACT FROM AUTHOR]

Heterogeneity of heart failure (HF) phenotypes indicates contributions from underlying common polymorphisms. We considered polymorphisms in the β1-adrenergic receptor (β1AR), a β-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, β1-Arg-389 had respective 2.8 ± 0.3- and 4.3 ± 2.1-fold greater agonist-promoted contractility vs. β1-Gly-389, defining enhanced physiologic coupling under relevant conditions of endogenous expression and HF. The β-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 β1AR-389 variation alters signaling in multiple models and affects the β-blocker therapeutic response in HF and, thus, might be used to individualize treatment of the syndrome. [ABSTRACT FROM AUTHOR]

Optimization of pacemaker settings for cardiac resynchronization therapy (CRT) remains challenging and problematic. Several noninvasive methods are offered to customize the programmed parameters for individual patients, but so far only echocardiographic imaging has established itself as an accepted method. The authors examined the value of acoustic cardiography as a fast and more cost-efficient alternative to established echocardiographic imaging techniques for the optimization of CRT devices. The atrioventricular delay in 22 subjects with implanted CRT devices was independently optimized using echocardiography (Doppler transmitral flow) as well as acoustic cardiography, and the recommended settings from each method were later compared. Doppler echocardiography and acoustic cardiography recommendations matched within a mean value ± SD of 17±16 milliseconds and gave a correlation coefficient of r=0.90 (p<0.001). In 17 of the 22 cases (77.3%), the difference between echocardiographic and acoustic cardiogram CRT optimization results was ≤20 milliseconds. Furthermore, the echocardiographic transmitral flow pattern was not significantly different for the setting independently chosen by the echocardiographic expert and the acoustic cardiographer for the cases with a difference of ≥20 milliseconds (22.7%). In addition, it took less time for the acoustic cardiogram to collect sufficient information to make a recommendation, and it was found that the acoustic cardiogram data trend is easier to interpret. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

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 ≥130 milliseconds, were included for this analysis. Patients with an improvement of ≥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 ≥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. [Copyright &y& Elsevier]

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 ≥120 milliseconds, left ventricular ejection fraction ≤0.40, and left ventricular end-diastolic diameter ≥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. [Copyright &y& Elsevier]

Continuous measurement of spontaneous heart rate variability is now possible from permanently implanted devices and may contain information useful in the chronic management of patients with congestive heart failure. Since heart rate variability semi-quantifies autonomic control of the heart, changes noted from continuous measurement provide insight into cardiac control system status, which may reflect clinical status of the patient. This review outlines clinical evidence supporting the use of heart rate variability derived from implanted electronic devices and suggests a practical application in an every day clinical setting for its use. Changes in continuously measured heart rate variability coupled with the absolute value of the standard deviation of the atrial-to-atrial activation period predict subsequent risk for decompensation and hospitalization. Prospective clinical trials will evaluate this approach and the use of such markers on health care utilization in populations of patients with long-term chronic heart failure. [ABSTRACT FROM AUTHOR]

Objectives: We sought to compare the in-hospital mortality of patients with acute decompensated heart failure (ADHF) who were receiving parenteral treatment with one of four intravenous vasoactive medications. Background: There are limited data regarding the effects of the choice of intravenous vasoactive medication on in-hospital mortality in patients hospitalized with ADHF. Methods: This was a retrospective analysis of observational patient data from the Acute Decompensated Heart Failure National Registry (ADHERE), a multicenter registry designed to prospectively collect data on each episode of hospitalization for ADHF and its clinical outcomes. Data from the first 65,180 patient episodes (October 2001 to July 2003) were included in this analysis. Cases in which patients received nitroglycerin, nesiritide, milrinone, or dobutamine were identified and reviewed (n = 15,230). Risk factor and propensity score-adjusted odds ratios (ORs) for in-hospital mortality were calculated. Results: Patients who received intravenous nitroglycerin or nesiritide had lower in-hospital mortality than those treated with dobutamine or milrinone. The risk factor and propensity score-adjusted ORs for nitroglycerin were 0.69 (95% confidence interval [CI] 0.53 to 0.89, p ≤ 0.005) and 0.46 (94% CI 0.37 to 0.57, p ≤ 0.005) compared with milrinone and dobutamine, respectively. The corresponding values for nesiritide compared with milrinone and dobutamine were 0.59 (95% CI 0.48 to 0.73, p ≤ 0.005) and 0.47 (95% CI 0.39 to 0.56, p ≤ 0.005), respectively. The adjusted OR for nesiritide compared with nitroglycerin was 0.94 (95% CI 0.77 to 1.16, p = 0.58). Conclusions: Therapy with either a natriuretic peptide or vasodilator was associated with significantly lower in-hospital mortality than positive inotropic therapy in patients hospitalized with ADHF. The risk of in-hospital mortality was similar for nesiritide and nitroglycerin. [Copyright &y& Elsevier]

The article focuses on the diagnostic procedure applied to patients who underwent echocardiography. The aim of the study is to assess the diagnostic performance of B-type natriuretic peptide testing and echocardiogram assessment of left ventricular systolic function, separately and combined, for the identification of congestive heart failure in patients who present acute dyspnea. The result of the study is presented as well as its recommendations.

Context Estimation of mortality risk in patients hospitalized with acute decompensated heart failure (ADHF) may help clinicians guide care. Objective To develop a practical user-friendly bedside tool for risk stratification for patients hospitalized with ADHF. Design, Setting, and Patients The Acute Decompensated Heart Failure National Registry (ADHERE) of patients hospitalized with a primary diagnosis of ADHF in 263 hospitals in the United States was queried with analysis of patient data to develop a risk stratification model. The first 33 046 hospitalizations (derivation cohort; October 2001-February 2003) were analyzed to develop the model and then the validity of the model was prospectively tested using data from 32 229 subsequent hospitalizations (validation cohort; March-July 2003). Patients had a mean age of 72.5 years and 52% were female. Main Outcome Measure Variables predicting mortality in ADHF. Results When the derivation and validation cohorts are combined, 37 772 (58%) of 65 275 patient-records had coronary artery disease. Of a combined cohort consisting of 52 164 patient-records, 23 910 (46%) had preserved left ventricular systolic function. In-hospital mortality was similar in the derivation (4.2%) and validation (4.0%) cohorts. Recursive partitioning of the derivation cohort for 39 variables indicated that the best single predictor for mortality was high admission levels of blood urea nitrogen (≥43 mg/dL [15.35 mmol/L]) followed by low admission systolic blood pressure (<115 mm Hg) and then by high levels of serum creatinine (≥2.75 mg/dL [243.1 μmol/L]). A simple risk tree identified patient groups with mortality ranging from 2.1% to 21.9%. The odds ratio for mortality between patients identified as high and low risk was 12.9 (95% confidence interval, 10.4-15.9) and similar results were seen when this risk stratification was applied prospectively to the validation cohort. Conclusions These results suggest that ADHF patients ... [ABSTRACT FROM AUTHOR]

Background: The ADHERE is designed to study characteristics, management, and outcomes in a broad sample of patients hospitalized with acute decompensated heart failure. Heart failure is a leading cause of hospitalization for adults older than 65 years in the United States. Most available data on these patients are limited by patient selection criteria and study design of clinical trials and single-center studies. Methods: Participating hospitals identify patients with a primary or secondary discharge diagnosis of heart failure. Medical history, management, treatments, and health outcomes data are collected through review of medical records and entered into a database via secure web browser technology. Results: As of January 2004, data on 107362 patients have been received from 282 participating hospitals. Of enrollees with available analyzable data (N = 105388 from 274 hospitals), the mean age was 72.4 (±14.0), and 52% were women. The most common comorbid conditions were hypertension (73%), coronary artery disease (57%), and diabetes (44%). Evidence of mild or no impairment of systolic function was found in 46% of patients. Inhospital mortality was 4.0% and the median hospital length of stay was 4.3 days. Conclusions: The ADHERE demonstrates both the feasibility and significant implications of gathering representative data on large numbers of patients hospitalized with heart failure. Initial data provided important insights into the clinical characteristics and patterns of care of these patients. Ongoing registry work will provide the framework for improved treatment strategies for patients hospitalized with decompensated heart failure. [ABSTRACT FROM AUTHOR]

Heart Rhythm 2004, the 25th Annual Scientific Sessions of the Heart Rhythm Society (formerly the North American Society of Pacing and Electrophysiology), met in San Francisco in May 2004. The meeting is the world''s premier forum for the presentation of research and the exchange of state-of-the-art information in cardiac electrophysiology and pacing. Major new research findings were presented on the value of implantable cardioverter-defibrillator therapy, noninvasive methods for risk stratification, treatment of vasovagal syncope, radiofrequency ablation for atrial fibrillation, resynchronization therapy for heart failure, and new insights from basic science into the mechanisms of cardiac arrhythmias. [Copyright &y& Elsevier]

Objective: Diabetes has been implicated in reduced myocardial compliance and changes in the intercellular matrix of the myocardium. We determined the effect of diabetes on B-type natriuretic peptide (BNP) concentrations in patients presenting to the emergency department with dyspnea.Research Design and Methods: The Breathing Not Properly Multinational Study was a prospective evaluation of 1,586 patients. A subset of 922 patients was obtained and subdivided into the following groups: group 1 (n = 324), neither diabetes nor heart failure; group 2 (n = 107), diabetes and no heart failure; group 3 (n = 247), no diabetes and heart failure; group 4 (n = 183), both diabetes and heart failure; group 5 (n = 41), heart failure history with no diabetes; and group 6 (n = 20), heart failure history with diabetes. Patients from groups 1, 3, and 5 were matched to groups 2, 4, and 6, respectively, to have the same mean age, sex distribution, BMI, renal function, and New York Heart Association (NYHA) classification (for heart failure).Results: There was no significant difference in median BNP levels between diabetes and no diabetes among no heart failure patients (32.4 vs.32.9 pg/ml), heart failure patients (587 vs. 494 pg/ml), and those with a heart failure history (180 vs. 120 pg/ml). Receiver-operating characteristic curve analysis of the area under the curve for BNP was not different in diabetic versus nondiabetic patients (0.888 vs. 0.878, respectively). However, in a multivariate model, diabetes was an independent predictor of a final diagnosis of heart failure (odds ratio 1.51, 95% CI 1.03-2.02; P < 0.05).Conclusions: History of diabetes does not impact BNP levels measured in patients with acute dyspnea in the emergency department. Despite the impact of diabetes on the cardiovascular system, diabetes does not appear to confound BNP levels in the emergency department diagnosis of heart failure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In patients with chronic heart failure, detecting signs and symptoms of worsening congestion early enough to prevent hospitalization is an ongoing challenge. Intrathoracic impedance monitoring is a new, device-based method for detecting fluid accumulation in the lungs. Small clinical trials have shown that it may provide an early warning of impending decompensation and may be useful when used in conjunction with routine clinical assessment in guiding diuresis during hospitalization. Additional large-scale, prospective, randomized clinical trials are currently underway to further evaluate its clinical utility. This review discusses the basic concepts underlying intrathoracic impedance monitoring, the clinical evidence supporting its use, and some common pitfalls to avoid when interpreting intrathoracic impedance data. [ABSTRACT FROM AUTHOR]

The article focuses on the use of the combined cardiac resynchronization therapy (CRT) and implantable cardioverter-defibrillator (ICD) to treat asymptomatic and symptomatic heart failure patients. It says that randomized clinical trials were performed in patients with heart failure to compare the effect of the combined process with the use of ICD therapy alone. It reveals that CRT-ICD showed consistency on reducing heart failure and electrocardiographic dyssynchrony.

Neurohormonal activation and increased sympathetic stimulation are among the factors that have been linked to the development and progression of left ventricular dysfunction (LVD) and heart failure (HF) in post–myocardial infarction (MI) patients. Various available pharmacologic therapies can target these factors and improve many aspects of the disease, depending on the degree of LVD. The American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone antagonists because of their proven favorable effects on symptoms, left ventricular function, cardiac remodeling, hospitalization rates, and survival. However, they are not being used in over two thirds of patients with post-MI LVD. This review illustrates the impact of these therapies on post-MI LVD patients using evidence from multiple clinical trials. In addition, current and emerging treatments for acute decompensated HF will be outlined. [Copyright &y& Elsevier]

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, β 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 β-blocker therapy and analyzed according to predischarge β-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 β 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 β 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 β 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 β blocker should be initiated before hospital discharge in stable patients with HF and LVSD. [Copyright &y& Elsevier]

A response by William T. Abraham to letters to the editor about his article focusing on cardiac resynchronization therapy for heart failure in the June 13, 2002 issue is presented.

Background Pulmonary hypertension (PH) associated with left heart disease (World Health Organization [WHO] Group II) has previously been linked with significant morbidity and mortality. However, there are currently no approved therapies or hemodynamic monitoring systems to improve outcomes in WHO Group II PH. Methods We conducted a retrospective analysis of the CHAMPION trial of an implantable hemodynamic monitor (IHM) in 550 New York Heart Association (NYHA) Functional Class III HF patients, regardless of left ventricular ejection fraction (LVEF) or heart failure (HF) etiology. We evaluated clinical variables, changes in medical therapy, HF hospitalization rates and survival in patients with and without WHO Group II PH. Results Data were obtained for 314 patients (59%) who had WHO Group II PH. Patients without PH were at significantly lower risk for mortality than PH patients (hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.19 to 0.52, p < 0.0001). PH patients had higher HF hospitalization rates than non-PH patients (0.77/year vs 0.37/year; HR 0.49, 95% CI 0.39 to 0.61, p < 0.001). In patients with and without PH, ongoing knowledge of hemodynamic data resulted in a reduction in HF hospitalization for PH patients (HR 0.64, 95% CI 0.51 to 0.81, p = 0.002) and for non-PH patients (HR 0.60, 95% CI 0.41 to 0.89, p = 0.01). Among PH patients, there was a reduction in the composite end-point of death and HF hospitalization with ongoing knowledge of hemodynamics (HR 0.74, 95% CI 0.55 to 0.99, p = 0.04), but no difference in survival (HR 0.78, 95% CI 0.50 to 1.22, p = 0.28). Conclusions WHO Group II PH is prevalent and identifies HF patients at risk for adverse outcomes. Ongoing knowledge of hemodynamic variables may allow for more effective treatment strategies to reduce the morbidity of this disease. [ABSTRACT FROM AUTHOR]

The article discusses the advances of telecommunication technologies that provide telemedical care in the medical management of patients with heart failure. It notes several studies that demonstrate the effectiveness of a standardized and appropriate classification of telemedical system in managing chronic heart failure. It also mentions the classification of four generations of telemedicine, which was proven as efficient approach in managing the disease.

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. [Copyright &y& Elsevier]

Background: The role of coronary-artery bypass grafting (CABG) in the treatment of patients with coronary artery disease and heart failure has not been clearly established. Methods: Between July 2002 and May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to medical therapy alone (602 patients) or medical therapy plus CABG (610 patients). The primary outcome was the rate of death from any cause. Major secondary outcomes included the rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes. Results: The primary outcome occurred in 244 patients (41%) in the medical-therapy group and 218 (36%) in the CABG group (hazard ratio with CABG, 0.86; 95% confidence interval [CI], 0.72 to 1.04; P=0.12). A total of 201 patients (33%) in the medical-therapy group and 168 (28%) in the CABG group died from an adjudicated cardiovascular cause (hazard ratio with CABG, 0.81; 95% CI, 0.66 to 1.00; P=0.05). Death from any cause or hospitalization for cardiovascular causes occurred in 411 patients (68%) in the medical-therapy group and 351 (58%) in the CABG group (hazard ratio with CABG, 0.74; 95% CI, 0.64 to 0.85; P<0.001). By the end of the follow-up period (median, 56 months), 100 patients in the medical-therapy group (17%) underwent CABG, and 555 patients in the CABG group (91%) underwent CABG. Conclusions: In this randomized trial, there was no significant difference between medical therapy alone and medical therapy plus CABG with respect to the primary end point of death from any cause. Patients assigned to CABG, as compared with those assigned to medical therapy alone, had lower rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes. (Funded by the National Heart, Lung, and Blood Institute and Abbott Laboratories; STICH ClinicalTrials.gov number, NCT00023595.) N Engl J Med 2011;364:1607-16. [ABSTRACT FROM AUTHOR]

Abstract: While cardiac resynchronization therapy (CRT) has been shown to reduce morbidity and mortality in heart failure (HF) patients, the fundamental mechanisms for the efficacy of CRT are poorly understood. The lack of understanding of these basic mechanisms represents a significant barrier to our understanding of the pathogenesis of HF and potential recovery mechanisms. Our purpose was to determine cellular mechanisms for the observed improvement in chronic HF after CRT. We used a canine model of chronic nonischemic cardiomyopathy. After 15 months, dogs were randomized to continued RV tachypacing (untreated HF) or CRT for an additional 9 months. Six minute walk tests, echocardiograms, and electrocardiograms were done to assess the functional response to therapy. Left ventricular (LV) midmyocardial myocytes were isolated to study electrophysiology and intracellular calcium regulation. Compared to untreated HF, CRT improved HF-induced increases in LV volumes, diameters and mass (p <0.05). CRT reversed HF-induced prolongations in LV myocyte repolarization (p <0.05) and normalized HF-induced depolarization (p <0.03) of the resting membrane potential. CRT improved HF-induced reductions in calcium (p <0.05). CRT did not attenuate the HF-induced increases in LV interstitial fibrosis. Using a translational approach in a chronic HF model, CRT significantly improved LV structure; this was accompanied by improved LV myocyte electrophysiology and calcium regulation. The beneficial effects of CRT may be attributable, in part, to improved LV myocyte function. [Copyright &y& Elsevier]

Heart failure (HF) in the community differs meaningfully from that in clinical trials, particularly the higher prevalence of patients with preserved left ventricular (LV) ejection fraction (EF) typically excluded from clinical trials, thus limiting knowledge of their responsiveness to β-blocker therapy. From a community-based registry of 4,280 patients with HF starting treatment with the β blocker carvedilol, we compared characteristics, carvedilol titration, and outcomes of patients according to LVEF >40% or <40% (as in clinical trials) and across the spectrum of LVEF <21%, 21% to 30%, 31% to 40%, and >40%. Patients with preserved EF (LVEF >40%) were older and more often women and hypertensive. Lower LVEF was associated with worse functional class and more HF hospitalizations in the previous year. Carvedilol dose decreased with increasing LVEF. Hospitalization rates for HF related inversely to LVEF before starting carvedilol therapy and decreased from the previous year in all LVEF groups during follow-up. Although 1-year mortality rate decreased from 8% with LVEF ≤20% to 6% with LVEF >40%, adjusted hazard ratios were not significantly different across LVEF groups. Thus, characteristics of community patients with HF vary across the spectrum of LVEF. Patients with HF and preserved EF treated with carvedilol in the community improve symptomatically and experience fewer HF hospitalizations after initiating carvedilol. In conclusion, without a control group, the effect of carvedilol on outcomes is not conclusive and trials of carvedilol in patients with HF and preserved EF should be undertaken. [Copyright &y& Elsevier]

Abstract: Purpose: B-type natriuretic peptide is known to correlate with hemodynamic state, presence and severity of congestive heart failure, and prognosis. Although low-range B-type natriuretic peptide less than 100 pg/mL has a high negative predictive value (90%), and high-range B-type natriuretic peptide greater than 500 pg/mL has a high positive predictive value (87%), there remains some ambiguity in the interpretation of results in the medium range (100-500 pg/mL). We hypothesized that taking into account the history of congestive heart failure along with other clinical variables would be helpful in this range of B-type natriuretic peptide levels. Method: The Breathing Not Properly Multicenter Study was an international, 7-center, prospective study including 1475 patients with a mean age of 63 years (57% were male, and 54% were female); 35% of patients with a history of congestive heart failure were enrolled, and a final diagnosis of congestive heart failure was made in 46%. The index criteria was defined as positive if any 2 index findings (ie, history of coronary artery disease, lower extremity edema, pulmonary edema, cephalization of the pulmonary arteries, and cardiomegaly) were present. Results: The interval likelihood ratios (LR) for low, medium, and high B-type natriuretic peptide ranges are 0.13, 1.85, and 8.1, respectively. For medium B-type natriuretic peptide levels a positive history of congestive heart failure makes the diagnosis of congestive heart failure more probable with a cumulative LR of 4.3. Also in this range a positive index criterion was strongly indicative of congestive heart failure even in the absence of a history of congestive heart failure (LR 3.3). Where there are both a positive history of congestive heart failure and a positive index criteria for the medium B-type natriuretic peptide group, the cumulative LR (10.2) is similar to that of a high B-type natriuretic peptide level (8.1). Conclusion: Even in the medium range (100-500 pg/mL), when using the history of congestive heart failure and index criteria, B-type natriuretic peptide can be a powerful diagnostic tool in the hands of clinicians in the emergency department. [Copyright &y& Elsevier]