The classical M. Riesz theorem on the boundedness of the conjugation operator for harmonic functions and Kolmogorov's weak-type inequality are proved in the framework of the octonion-valued monogenic functions.

The classical theorem of M. Riesz about the conjugate harmonic functions is extended onto octonion-valued monogenic functions.

Abstract. Objectives. This study sought to determine recent trends over time in heart failure (HF) hospitalization, patient characteristics, treatment, rehospitalization, and mortality within the Veterans Affairs health care system. Background. Use of recommended therapies for HF has increased in the United States; however, it is unclear to what extent hospitalization rates and the associated mortality have improved. Methods. We compared rates of hospitalization for HF, 30-day rehospitalization for HF, and 30-day mortality following discharge from 2002–2006 in the Veterans Affairs health care system. Odds ratios for outcome were adjusted for patient diagnoses within the past year, laboratory data, and clustering of patients within hospitals. Results. We identified 50,125 patients with a first hospitalization for HF from 2002–2006. Mean age did not change (70 years), but increases were noted for most comorbidities (mean Charlson score increased from 1.72 to 1.89; P <.0001). HF admission rates remained constant at about 5 per 1000 veterans. Mortality at 30 days decreased (7.1%–5.0%; P <.0001), whereas rehospitalization for HF at 30 days increased (5.6%–6.1%; P =.11). After adjustment for patient characteristics, the odds ratio for rehospitalization in 2006 (vs 2002) was 0.54 (95% confidence interval [CI], 0.47–0.61) for mortality, but 1.21 (95% CI, 1.04–1.41) for HF rehospitalization at 30 days. Conclusions. Recent mortality and rehospitalization rates in the Veterans Affairs health care system have trended in opposite directions. These results have implications for using rehospitalization as a measure of quality of care.— Heidenreich PA, Sahay A, Kapoor JR, et al. Divergent trends in survival and readmission following a hospitalization for heart failure in the Veterans Affairs health care system 2002 to 2006. J Am Coll Cardiol. 2010;56:362–368.

Abstract. Primary percutaneous coronary intervention (PCI) and intra-aortic balloon pump counterpulsation (IABP) are established treatment modalities in acute myocardial infarction complicated by cardiogenic shock. We hypothesized that the insertion of the IABP before primary PCI might result in better survival of patients with cardiogenic shock compared with postponing the insertion until after primary PCI. We, therefore, retrospectively studied 48 patients who had undergone primary PCI with IABP because of cardiogenic shock complicating acute myocardial infarction (26 patients received the IABP before and 22 patients after primary PCI). No significant differences were present in the baseline clinical characteristics between the 2 groups. The mean number of diseased vessels was greater in the group of patients treated with the IABP before primary PCI (2.8±0.5 vs 2.3±0.7, P =.012), but the difference in the number of treated vessels was not significant. The peak creatine kinase and creatine kinase-MB levels were lower in patients treated with the IABP before primary PCI (median, 1077; interquartile range, 438–2067 vs median, 3299; interquartile range, 695–6834; P =.047 and median, 95; interquartile range, 34–196 vs median, 192; interquartile range, 82–467; P =.048, respectively). In-hospital mortality and the overall incidence of major adverse cardiac and cerebrovascular events were significantly lower in the group of patients receiving the IABP before primary PCI (19% vs 59% and 23% vs 77%, P =.007 and P =.0004, respectively). Multivariate analysis identified renal failure (odds ratio, 15.2; 95% confidence interval, 3.13–73.66) and insertion of the IABP after PCI (odds ratio, 5.2; 95% confidence interval, 1.09–24.76) as the only independent predictors of in-hospital mortality. In conclusion, the results of the present study suggest that patients with cardiogenic shock complicating acute myocardial infarction who undergo primary PCI assisted by IABP have a more favorable in-hospital outcome and lower in-hospital mortality than patients who receive IABP after PCI. Abdel-Wahab M, Saad M, Kynast J, et al. Comparison of hospital mortality with intra-aortic balloon counterpulsation insertion before versus after primary percutaneous coronary intervention for cardiogenic shock complicating acute myocardial infarction. Am J Cardiol. 2010;105:967–971.

Abstract. Objectives. We studied the association of clopidogrel with mortality in acute myocardial infarction (AMI) patients with heart failure (HF) not receiving percutaneous coronary intervention (PCI). Background. Use of clopidogrel after AMI is low in patients with HF, despite the fact that clopidogrel is associated with absolute mortality reduction in AMI patients. Methods. All patients hospitalized with first-time AMI (2000 through 2005) and not undergoing PCI within 30 days from discharge were identified in national registers. Patients with HF treated with clopidogrel were matched by propensity score with patients not treated with clopidogrel. Similarly, 2 groups without HF were identified. Risks of all-cause death were obtained by the Kaplan–Meier method and Cox regression analyses. Results. We identified 56,944 patients with first-time AMI. In the matched cohort with HF (n=5050) and a mean follow-up of 1.50 years (SD=1.2), 709 (28.1%) and 812 (32.2%) deaths occurred in patients receiving and not receiving clopidogrel treatment, respectively ( P =.002). The corresponding numbers for patients without HF (n=6092), with a mean follow-up of 2.05 years (SD=1.3), were 285 (9.4%) and 294 (9.7%), respectively ( P =.83). Patients with HF receiving clopidogrel demonstrated reduced mortality (hazard ratio, 0.86; 95% confidence interval, 0.78–0.95) compared with patients with HF not receiving clopidogrel. No difference was observed among patients without HF (hazard ratio, 0.98; 95% confidence interval, 0.83–1.16). Conclusions. Clopidogrel was associated with reduced mortality in patients with HF who do not undergo PCI after their first-time AMI, whereas this association was not apparent in patients without HF. Further studies of the benefit of clopidogrel in patients with HF and AMI are warranted.— Bonde L, Sorensen R, Fosbol EL, et al. Increased mortality associated with low use of clopidogrel in patients with heart failure and acute myocardial infarction not undergoing percutaneous coronary intervention: a nationwide study. J Am Coll Cardiol. 2010;55:1300–1307.

Abstract. Objectives. The authors sought to investigate the effect of β-blocker (BB) therapy on survival in patients with severe aortic regurgitation (AR) Background BBs are thought to be contraindicated in patients with AR because a slower heart rate increases the duration of diastole, during which AR occurs. But AR also causes neuroendocrine activation similar to a heart failure state, for which BBs are potentially beneficial. Methods This is an observational study. An echocardiographic database was screened for patients with severe AR. Detailed chart reviews were performed for clinical, demographic, and therapeutic data. Mortality data were obtained from the Social Security Death Index and analyzed as a function of BB therapy. Results Overall, 355 (47%) of the 756 patients with severe AR were taking a BB, mean age was 61±18 years, and mean ejection fraction was 54%±19%. Over a mean follow-up of 4.5 years, BB therapy was associated with a higher survival rate (1- and 5-year survival rates of 90% and 70%, respectively) compared with those without (1- and 5-year survival rates of 75% and 55%, respectively) ( P =.0009). The Cox regression model showed that BB therapy was an independent predictor of better survival after adjusting for age, sex, heart rate, hypertension, coronary artery disease, diabetes mellitus, heart failure, renal insufficiency, ejection fraction, and aortic valve replacement (hazard ratio, 0.74; 95% confidence interval, 0.58–0.93; P =.01). The survival benefit of BB therapy was further supported by propensity score analysis. Conclusions This observational study strongly suggests that BB therapy is associated with a survival benefit in patients with severe AR.

Abstract. Background. Indications for implantable cardioverter-defibrillators (ICDs) in heart failure (HF) are expanding and may include more than 1 million patients. This study examined patient expectations from ICDs for primary prevention of sudden death in HF. Methods and Results . Study participants (n=105) had an ejection fraction <35% and symptomatic HF without history of ventricular tachycardia/fibrillation or syncope. Participants completed a written survey about perceived ICD benefits, survival expectations, and circumstances under which they might deactivate defibrillation. Mean age was 58 years, mean left ventricular ejection fraction was 21%, 40% had New York Heart Association class III or IV disease, and 65% already had a primary prevention ICD. Most patients anticipated more than 10 years’ survival despite symptomatic HF. Nearly 54% expected an ICD to save ≥50 lives per 100 during 5 years. ICD recipients expressed more confidence that the device would save their own lives compared with those without an ICD ( P <.001). Despite understanding the ease of deactivation, 70% of ICD recipients indicated they would keep the ICD on even if dying of cancer, 55% even if having daily shocks, and none would inactivate defibrillation even if experiencing constant dyspnea at rest. Conclusions. HF patients anticipate long survival, overestimate survival benefits conferred by ICDs, and express reluctance to deactivate their devices even for end-stage disease.— Stewart GC, Weintraub JR, Pratibhu PP, et al. Patient expectations from implantable defibrillators to prevent death in heart failure. J Card Fail. 2010;16:106–113.

Abstract. Objectives. This study sought to evaluate the use of a continuous-flow rotary left ventricular assist device (LVAD) as a bridge to heart transplant Background LVAD therapy is an established treatment modality for patients with advanced heart failure. Pulsatile LVADs have limitations in design precluding their use for extended support. Continuous-flow rotary LVADs represent an innovative design with potential for small size and greater reliability by simplification of the pumping mechanism. Methods In a prospective multicenter study, 281 patients urgently listed (United Network for Organ Sharing status 1A or 1B) for heart transplant underwent implant of a continuous-flow LVAD. Survival and transplant rates were assessed at 18 months. Patients were assessed for adverse events throughout the study and for quality of life, functional status, and organ function for 6 months. Results Of 281 patients, 222 (79%) underwent transplant or LVAD removal for cardiac recovery or had ongoing LVAD support at 18-month follow-up. Actuarial survival on support was 72% (95% confidence interval, 65%–79%) at 18 months. At 6 months, there were significant improvements in functional status and 6-minute walk test results (from 0% to 83% of patients in New York Heart Association functional class I or II and from 13% to 89% of patients completing a 6-minute walk test) and in quality of life (mean values improved 41% with Minnesota Living With Heart Failure and 75% with Kansas City Cardiomyopathy questionnaires). Major adverse events included bleeding, stroke, right heart failure, and percutaneous lead infection. Pump thrombosis occurred in 4 patients. Conclusions A continuous-flow LVAD provides effective hemodynamic support for at least 18 months in patients awaiting transplant, with improved functional status and quality of life.

Abstract. Objectives . This study sought to determine whether serial measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in com-munity-dwelling elderly people would provide additional prognostic information to that from traditional risk factors. Background . Accurate cardiovascular risk stratification is challenging in elderly people. Methods . NT-proBNP was measured at baseline and 2 to 3 years later in 2975 community-dwelling older adults free of heart failure in the longitudinal Cardiovascular Health Study (CHS). This investigation examined the risk of new-onset heart failure (HF) and death from cardiovascular causes associated with baseline NT-proBNP and changes in NT-proBNP levels, adjusting for potential confounders. Results . NT-proBNP levels in the highest quintile (>267.7 pg/mL) were independently associated with greater risks of HF (hazard ratio [HR], 3.05; 95% confidence interval [CI], 2.46–3.78) and cardiovascular death (HR, 3.02; 95% CI, 2.36–3.86) compared with the lowest quintile (<47.5 pg/mL). The inflection point for elevated risk occurred at NT-proBNP 190 pg/mL. Among participants with initially low NT-proBNP (<190 pg/mL), those with a >25% increase on follow-up to >190 pg/mL (21%) were at greater adjusted risk for HF (HR, 2.13; 95% CI, 1.68–2.71) and cardiovascular death (HR, 1.91; 95% CI, 1.43–2.53) compared with those with sustained low levels. Among participants with initially high NT-proBNP, those with a >25% increase (40%) were at higher risk for HF (HR, 2.06; 95% CI, 1.56–2.72) and cardiovascular death (HR, 1.88; 95% CI, 1.37–2.57), whereas those with a >25% decrease to ≤190 pg/mL (15%) were at lower risk for HF (HR, 0.58; 95% CI, 0.36–0.93) and cardiovascular death (HR, 0.57; 95% CI, 0.32–1.01) compared with those with unchanged high values. Conclusions . NT-proBNP levels independently predict HF and cardiovascular death in older adults. NT-proBNP levels frequently change over time, and these fluctuations reflect dynamic changes in cardiovascular risk. deFilippi CR, Christenson RH, Gottdiener JS, et al. Dynamic cardiovascular risk assessment in elderly people. The role of repeated N-terminal pro-B-type natriuretic testing . J Am Coll Cardiol. 2010; 55: 441-450.

Abstract. Objectives. The purpose of this study was to examine the long-term incidence of heart failure (HF) in elderly patients with myocardial infarction (MI).  Background. In-hospital HF is common after MI and is associated with poor short-term prognosis. Limited data exist concerning the long-term incidence or prognosis of HF after MI, particularly in the era of coronary revascularization.  Methods. A population-based cohort of 7733 patients 65 years and older hospitalized for a first MI ( International Classification of Diseases, 9th Revision Clinical Modification code 410.x) and without a prior history of HF was established between 1994 and 2000 in Alberta, Canada, and followed up for 5 years.  Results. During the index MI hospitalization, 2831 (37%) MI patients were diagnosed with new HF and 1024 (13%) died. Among hospital survivors who did not have HF during their index hospitalization (n=4291), an additional 3040 patients (71%) developed HF by 5 years, 64% of which occurred in the first year. In total, 5871 (76%) elderly patients who survived their first MI developed HF over 5 years. Among those who survived the index hospitalization, the 5-year mortality rate was 39.1% for those with HF during the index MI hospitalization compared with 26.7% among those without HF ( P <.0001) during the index MI hospitalization. Over the study period, the 5-year mortality rate after MI decreased by 28%, whereas the 5-year rate of HF increased by 25%.  Conclusions. In this large cohort of elderly patients without a history of HF, HF developed in three-quarters in the 5 years after their first MI; this proportion increased over time as peri-MI mortality rates declined. New-onset HF significantly increases the mortality risk among these patients.— Ezekowitz JA, Kaul P, Bakal JA, et al. Declining in-hospital mortality and increasing heart failure incidence in elderly patients with first myocardial infarction. J Am Coll Cardiol. 2009;53(1):21–23.

Abstract. Background. Screening for asymptomatic left ventricular dysfunction (ALVD) in patients at risk for heart failure (HF) can affect clinical management. The aim of the present study is to examine the role of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in the diagnosis of ALVD in patients with hypertension and diabetes from primary care. Methods and Results. A total of 1012 patients with hypertension and/or diabetes and no symptoms or signs of HF were assessed by NT-pro-BNP assay and echocardiography. Diastolic dysfunction was present in 368 of 1012 patients (36.4%): 327 (32.4%) with mild diastolic dysfunction and 41 (4%) with a moderate to severe diastolic dysfunction. Systolic dysfunction was present in 11 of 1012 patients (1.1%). NT-pro-BNP levels were 170±206 and 859±661 pg/mL, respectively, in diastolic and systolic dysfunction and 92±169 in healthy patients ( P <.0001). Pooling moderate to severe diastolic with systolic dysfunction, a total of 52 patients (5.1%) were obtained: the best cutoff of NT-pro-BNP was 125 pg/mL (men younger than 67 years: sensitivity, 87.5%; specificity, 92.7%; negative predictive value [NPV], 99.5%; positive predictive value [PPV], 33.3%; women younger than 67 years: sensitivity, 100%; specificity, 84.1%; NPV, 100%; PPV, 33.3%; men 67 years or older: sensitivity, 100%; specificity, 77.1%; NPV, 100%; PPV, 32.5%; women 67 years or older: sensitivity, 100%; specificity, 59.9%; NPV, 100%; PPV, 23%). Conclusions. The prevalence of ALVD in patients at risk for HF is 5.1%. Because of its excellent NPV, NT-pro-BNP assessment can be used by general practitioners to rule out ALVD in hypertensive or diabetic patients.— Betti I, Castelli G, Barchielli A, et al. The role of N-terminal Pro-brain natriuretic peptide and echocardiography for screening asymptomatic left ventricular dysfunction in a population at high risk for heart failure. The PROBE-HF study . J Card Fail. 2009;15:377–384.

Abstract. Background. In heart failure (HF), renal dysfunction is associated with an adverse prognosis. Impaired renal perfusion from left ventricular dysfunction is thought to be a principal underlying mechanism. Less is known about the influence of venous congestion, including the potential contribution of tricuspid regurgitation (TR). Methods and Results.   Echocardiograms and a simultaneous (±1 day) blood sample from 196 HF patients were analyzed. Patients with at least moderate TR (n=78) had larger right-sided cardiac cavities, higher right ventricular systolic pressure, lower estimated glomerular filtration rate (eGFR), higher serum urea nitrogen (SUN) level, and SUN/creatinine ratio than patients with less than moderate TR (n=118). In multivariate linear regression analysis, TR severity ( P =.003), older age ( P <.001), and loop diuretic use ( P =.008) were independently associated with lower eGFR, and use of inhibitors of the renin-angiotensin-aldosterone system was associated with higher eGFR ( P =.001). TR severity ( P <.001) and older age ( P <.001) were independently associated with higher SUN value. TR severity ( P =.004) and smaller left ventricular end-diastolic diameter ( P =.048) were independent predictors of a higher SUN/creatinine ratio ( P =.004). Conclusions.  Although a causal relationship cannot be proven, we suggest that significant TR contributes to renal dysfunction in HF patients, probably by elevation of central and renal venous pressure.— Maeder MT, Holst DP, Kaye DM. Tricuspid regurgitation contributes to renal dysfunction in patients with heart failure . J Card Fail. 2008;14:824 – 830 .

Abstract. Objectives. The aim of the current study was to evaluate echocardiographic parameters after 6 months of cardiac resynchronization therapy (CRT) as well as long-term outcome in patients with the left ventricular (LV) lead positioned at the site of latest activation (concordant LV lead position) as compared with that seen in patients with a discordant LV lead position. Background. A nonoptimal LV pacing lead position may be a potential cause for nonresponse to CRT. Methods. The site of latest mechanical activation was determined by speckle tracking radial strain analysis and related to the LV lead position on chest x-ray in 244 CRT candidates. Echocardiographic evaluation was performed after 6 months. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. Results. Significant LV reverse remodeling (reduction in LV end-systolic volume from 189±83 mL to 134±71 mL, P <.001) was noted in the group of patients with a concordant LV lead position (n=153, 63%), whereas patients with a discordant lead position showed no significant improvements. In addition, during long-term follow-up (32±16 months), less events (combined for heart failure hospitalizations and death) were reported in patients with a concordant LV lead position. Moreover, a concordant LV lead position appeared to be an independent predictor of hospitalization-free survival after long-term CRT (hazard ratio: 0.22, P =.004). Conclusions. Pacing at the site of latest mechanical activation, as determined by speckle tracking radial strain analysis, resulted in superior echocardiographic response after 6 months of CRT and better prognosis during long-term follow-up.

Background. Mild hyponatremia is relatively common in patients with heart failure (HF). The associations of outcomes have not been evaluated in the context of in-hospital clinical course including central hemodynamics and changes in serum sodium level. Methods. The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) was a randomized controlled study designed to evaluate the utility of a pulmonary artery catheter plus clinical assessment vs clinical assessment alone in guiding therapy in patients hospitalized with New York Heart Association class IV HF due to systolic dysfunction (left ventricular ejection fraction <30%). A Cox proportional hazard model with baseline serum sodium as a continuous variable was used to examine the association of serum sodium levels with 6-month postdischarge mortality, HF rehospitalization, and death or rehospitalization. A categorical analysis was also performed, comparing persistent and corrected hyponatremia. Results. A total of 433 hospitalized patients with HF were enrolled in ESCAPE. Hyponatremia (Na <135 mmol/L) was present in 103 patients (23.8%). Of these, 71 patients (68.9%) had persistent hyponatremia. Hyponatremia was associated with higher 6-month mortality after covariate adjustment (hazard ratio [HR] for each 3-mEq/L decrease in sodium level, 1.23; 95% confidence interval, 1.05–1.43; P=.01). After controlling for baseline variables and clinical response, we found that patients with persistent hyponatremia had an increased risk of all-cause mortality (31% vs 16%; HR, 1.82; P=.04), HF rehospitalization (62% vs 43%; HR, 1.52; P=.03), and death or rehospitalization (73% vs 50%; HR, 1.54; P=.01), compared with normonatremic patients. Conclusions. Persistent hyponatremia was an independent predictor of mortality, HF rehospitalization, and death or rehospitalization despite clinical and hemodynamic improvements that were similar to those in patients without hyponatremia. —Gheorghiade M, Rossi JS, Cotts W, et al. Characterization and prognostic value of persistent hyponatremia in patients with severe heart failure in the ESCAPE Trial. Arch Intern Med. 2007;167(18):1998–2005. Previous studies have identified hyponatremia as an independent predictor of mortality in patients with decompensated HF. Hyponatremia in HF results from vasopressin released in response to hypovolemia from diuretic therapy and hypotension from low cardiac output and vasodilators. Water and sodium retention in HF are further mediated by the sympathetic stimulation of the renin-angiotensin-aldosterone system. Initially, it was thought that hyponatremia simply resulted from the volume overload in these patients, although it is now suggested that it is an effect of the neurohormonal milieu that is disturbed in HF. The distinction is relevant because both ESCAPE and the Acute and Chronic Therapeutic Impact of a Vasopressin 2 Antagonist (Tolvaptan) in Congestive Heart Failure (ACTIV-CHF) trial both demonstrate no improvement in mortality with manipulation of sodium levels in HF. Correction of hyponatremia, however, from the removal of free water, was obviously associated with improved quality of life and decreased HF rehospitalization, despite the lack of reduction in mortality. ESCAPE is limited by the small number of hyponatremic patients (103) and of those in whom hyponatremia was corrected with treatment (32). Nonetheless, it lends more weight to the observation that hyponatremic HF patients do worse than those with normal sodium levels. It would be useful to see the posttreatment sodium levels of the normonatremic patients (n=327) to determine the incidence of drug-induced decreases in sodium vs levels that remained unchanged, then comparing those Hrs. Further, the increased use of diuretics and spironolactone identified in the hyponatremic population are also associated with decreased sodium levels. Thus, hyponatremia is a marker of more severe HF, because of either the more intensive treatment of these patients or the disease activity itself.

Objective. The purpose of this study was to evaluate the impact of nesiritide on renal function in patients with acute decompensated heart failure (ADHF) and baseline renal dysfunction. Background. Although nesiritide is approved for the treatment of ADHF, retrospective analyses have raised concerns that it may cause worsened renal function. To date, no randomized clinical trials have prospectively evaluated this issue. Methods. Consecutive patients with ADHF and baseline renal dysfunction were enrolled in this randomized, double-blind, placebo-controlled clinical trial. Patients were randomized to receive nesiritide (0.01 μg/kg/min with or without a 2-μg/kg bolus) or placebo (5% dextrose in water) for 48 hours in addition to their usual care. Predefined primary end points of the trial were a rise in serum creatinine by ≥20% and change in serum creatinine. Results. Seventy-five patients were enrolled (39 nesiritide, 36 placebo). The groups had similar baseline age (74.9 vs 75.5 years, respectively), blood pressure (123/64 vs 125/64 mm Hg), and serum creatinine (1.82 vs 1.86 mg/dL). There were no significant differences in the incidence of a 20% creatinine rise (23% vs 25%) or in the change in serum creatinine (−0.05 vs +0.05 mg/dL). There were no significant differences in the secondary end points of change in weight (−2.19 vs −1.58 kg), intravenous furosemide (125 vs 107 mg), discontinuation of the infusion due to hypotension (13% vs 6%), or 30-day death/hospital readmission (33% vs 25%). Conclusions. In this randomized, double-blind, placebo-controlled clinical trial, nesiritide had no impact on renal function in patients with ADHF.—Witteles RM, Kao D, Christopherson D, et al. Impact of nesiritide on renal function in patients with acute decompensated heart failure and pre-existing renal dysfunction. J Am Coll Cardiol. 2007;50:1835-1840. This small study contradicts the conclusion posited by the 2005 meta-analysis, “Risk of Worsening Renal Function With Nesiritide in Patients With Acutely Decompensated Heart Failure” published in the Journal of the American Medical Association, stating that “nesiritide significantly increases the risk of worsening renal function in patients with ADHF.” Notable in this study is that patients received the recommended starting dose of 0.01 μg/kg/min of nesiritide with or without a 2-μg/kg bolus dependent on their presenting blood pressure and clinical status. Higher dosages, up to 0.06 μg/kg/min of nesiritide, and an indiscriminate use of a drug bolus in hypotensive patients used in some of the studies included in the aforementioned meta-analysis are associated with a higher incidence of hypotension, a strong predictor of worsening renal function. Further, all participants in this study received nesiritide within 12 hours of admission, before “excessive” diuresis could occur, presumably reducing the risk of hypotension. Nesiritide used in the conditions specified in this study did not aversely affect renal function. Whether this translates to a reduction in mortality, readmission rates, and quality of life improvement compared with conventional treatment remains to be seen. The ongoing and larger Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial should better address these questions when completed.

This study compared the effects of Cardiac Resynchronization Therapy (CRT) in patients with New York Heart Association (NYHA) Class II with those in Class III or IV. CRT was provided to 952 patients (188 in NYHA Class II), who were enrolled in the InSync/InSync ICD Italian Registry. This prospective, observational study enrolled patients with Class II to Class IV heart failure (HF), ejection fraction (EF) of ≤35%, and QRS complex >130 ms. Patients with decompensated HF and myocardial infarction within 3 months were excluded. Clinical outcomes were estimated after 12 months of CRT. Parameters measured included EF, mitral regurgitation, NYHA Class, end systolic and diastolic diameters, QRS width, and hospitalizations per year. All-cause death, heart transplant and, if applicable, ICD firing for ventricular fibrillation were measured. The median follow-up period was 16 months. Fewer major adverse cardiovascular events occurred in NYHA Class II patients compared with Class III and IV, (13 vs 23 per 100 patient-years, P<.001). Fewer patients improved in class status in Class II compared with Class II and IV (34% vs 69%, P<.001), whereas the increase in EF was similar (8±9% vs 9±11%), as was the reduction in end-diastolic diameter (EDD) (−3±8 vs −3±8 mm), and end-systolic diameter (ESD) (−4±10 mm vs −6±10 mm). The Class II group experienced lower all-cause mortality. CRT induced similar improvements in ventricular function in the 2 groups, whereas the improvement in functional status in class II patients was lower than for those in class III or IV. A positive effect of CRT on cardiac dimensions was associated with a long-term beneficial effect on disease progression in patients in class II. —Landolina M, Lunati M, Gasparini M; et al; InSync/InSync ICD Italian Registry Investigators. Comparison of the effects of cardiac resynchronization therapy in patients with class II versus class III and IV heart failure (from the InSync/InSync ICD Italian Registry). Am J Cardiol. 2007;100(6):1007–1012. Comment. This study parallels the findings of the Cardiac Resynchronization in Heart Failure (CARE-HF) study, which demonstrated reductions in hospitalizations and mortality with CRT in NYHA Class III/IV patients with an EF <35% and a widened QRS. In this study, the 2 cohorts (Class II and Class III/IV) are closely matched by baseline EF (29% and 27%, respectively), EDD (69 mm each), ESD (57 mm and 59 mm, respectively), and QRS duration (163 ms and 168 ms, respectively). However, significant differences exist between the Class II and Class III/IV cohorts in ischemic etiology of HF (38% vs 47%), presence of atrial fibrillation (10% vs 18%), use of β-blockers (56% vs 47%) and, not unexpectedly, mitral regurgitation severity (average grade, 1.9 vs 2.3). Empirically, the less symptomatic Class II patients would be expected to derive less clinical benefit than the more afflicted Class III/IV patients, although these differences are not readily explained by the nearly identical improvements in EF, QRS duration, EDD, and ESD data. The most demonstrable difference with CRT between the cohorts is the magnitude of reduction in mitral regurgitation in Class III/IV (mean grade reduction, 0.1 vs 0.4). CRT remains a useful modality in treating advanced HF with dyssynchronous left ventricular contraction and poor EF. Although the Class II patients experienced less functional benefit with CRT, they still had a substantial decline in HF hospitalizations (1.1–0.2/y). Those patients who progressed from Class II to Class II/IV despite CRT had no improvement in left ventricular function. The authors acknowledge the study limitations in suboptimal medical therapy in both cohorts, and potential selection bias of Class II patients who were expected to benefit from CRT in this multicenter study. Whether CRT can arrest decline in NYHA class remains to be seen. A study that matched cohorts more closely in regard to ischemic vs nonischemic HF, pharmacologic therapy, with non-CRT patients with similar baseline characteristics would be useful.

Background. The present study assessed the efficacy and safety of vernakalant hydrochloride (RSD1235), a novel compound, for the conversion of atrial fibrillation (AF). Methods and results. Patients were randomized in a 2:1 ratio to receive vernakalant or placebo and were stratified by AF duration of 3 hours to 7 days (short duration) and 8 to 45 days (long duration). A first infusion of placebo or vernakalant (3 mg/kg) was given for 10 minutes, followed by a second infusion of placebo or vernakalant (2 mg/kg) 15 minutes later if AF was not terminated. The primary end point was conversion of AF to sinus rhythm for at least 1 minute within 90 minutes of the start of drug infusion in the short-duration AF group. A total of 336 patients were randomized and received treatment (short duration, n=220; long duration, n=116). Of the 145 vernakalant patients, 75 (51.7%) in the short-duration AF group converted to sinus rhythm (median time, 11 minutes) compared with 3 of the 75 placebo patients (4.0%; P<.001). Overall, in the short- and long-duration AF groups, 83 of the 221 vernakalant patients (37.6%) experienced termination of AF compared with 3 of the 115 placebo patients (2.6%; P<.001). Transient dysgeusia and sneezing were the most common adverse effects in vernakalant-treated patients. Four vernakalant-related serious adverse events (hypotension [2 events], complete atrioventricular block, and cardiogenic shock) occurred in 3 patients. Conclusion. Vernakalant demonstrated rapid conversion of short-duration AF and was well tolerated.—Roy D, Pratt CM, Torp-Pedersen C, et al.; Atrial Arrhythmia Conversion Trial Investigators. Vernakalant hydrochloride for rapid conversion of atrial fibrillation: a phase 3, randomized, placebo-controlled trial. Circulation. 2008;117(12):1518–1525. This double-blinded prospective study demonstrated efficacy of vernakalant in converting AF to sinus rhythm when compared with placebo. The highest success rates were inversely proportionate to the duration of the arrhythmia, (62.1% with AF of 3–48 hours, 23.8% with AF of 3–7 days, and 7.9% with AF of 8–45 days), presumably due to atrial electrical remodeling seen with longer durations of AF. The mean time to conversion was 11 minutes, and 74 of the 75 converted patients maintained sinus rhythm at 24 hours. Nonsustained ventricular tachycardia was higher in the placebo group (14.8% vs 6.3%), but this may be in part due to the higher proportion of those in the placebo group using digoxin. Torsade de pointes occurred in 2 patients and was not seen until 32 hours and 16 days of the infusions, though the drug half-life is 2 to 3 hours. Modest increases in QT interval were seen in the trial drug group, but these were resolved by 90 minutes after drug infusion. Heart failure was more common in the placebo and vernakalant group with 8 to 45 days of AF (32% and 24%, respectively) compared with those with a <8-day duration (7% and 10%, respectively). Whether the higher proportion of heart failure patients at baseline in the 8 to 45 days group affected conversion cardioversion rates is unclear. Vernakalant is a novel drug in phase 3 trials that selectively blocks atrial K+ and frequency-dependent Na+ channels, resulting in prolongation of the atrial refractory period with little effect on ventricular refractory periods. Compared with other commonly used antiarrhythmics used in AF (e.g., ibutilide, procainamide, and amiodarone), it is relatively effective, rapid-acting, and apparently well tolerated. Though a small percentage of the trial patients had heart failure, the data suggest that vernakalant could be safely used in converting heart failure with short-duration AF to sinus rhythm, whereas other common antiarrhythmic medications are usually contraindicated for use in this population.

Abstract. Objectives. This study ascertains the relationship between continuation or withdrawal of β-blocker therapy and clinical outcomes in patients hospitalized with systolic heart failure (HF). Background. Whether β-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 Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF) enrolled 5791 patients admitted with HF in a registry with prespecified 60- to 90-day follow-up at 91 academic and community hospitals throughout the United States. Outcomes data were prospectively collected and analyzed according to whether β-blocker therapy was continued, withdrawn, or not started. Results. Among 2373 patients eligible for β-blockers at discharge, there were 1350 (56.9%) who were receiving β-blockers before admission and continued on therapy, 632 (26.6%) were newly started, 79 (3.3%) in whom therapy was withdrawn, and 303 (12.8%) were eligible but not treated. Continuation of β-blockers was associated with a significantly lower risk and propensity-adjusted postdischarge death (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.37–0.99; P =.044) and death/rehospitalization (odds ratio, 0.69; 95% CI, 0.52–0.92; P =.012) compared with no β-blocker. In contrast, withdrawal of β-blocker use in patients was associated with a substantially higher adjusted risk for mortality compared with those continued on β-blockers (HR, 2.3; 95% CI, 1.2–4.6; P =.013) but with similar risk as HF patients eligible but not treated with β-blockers. Conclusions. The continuation of β-blocker therapy in patients hospitalized with decompensated HF is associated with lower postdischarge mortality risk and improved treatment rates. In contrast, withdrawal of β-blocker therapy is associated with worse risk and propensity-adjusted mortality.— Fonarow GC, Abraham WT, Albert NM, et al; for the OPTIMIZE-HF investigators. Influence of beta-blocker continuation or withdrawal on outcomes in patients hospitalized with heart failure: findings from the OPTIMIZE-HF program . J Am Coll Cardiol. 2008;52(3):190–199.

Abstract. Background. Thiazolidinediones are associated with fluid retention, often interpreted as worsening cardiac function, limiting their use in patients with heart failure (HF). We compared the effects of pioglitazone and glyburide on cardiac function in patients with type 2 diabetes, systolic dysfunction, and New York Heart Association functional class II or III HF. Methods and Results. Participants received pioglitazone or glyburide (±insulin) for 6 months in this double-blind, randomized, multicenter study. The primary end point was time to HF, a composite of cardiovascular mortality, and hospitalization or emergency department visit for HF. Secondary end points included echocardiographic and functional classification assessments. An earlier time to onset and higher incidence of the primary end point was noted with pioglitazone (13%) vs glyburide (8%) ( P =.024). Hospitalization or emergency department visit occurred in 30 pioglitazone and 15 glyburide participants, 19 and 12 of whom, respectively, continued treatment. Cardiac mortality (5 vs 6 participants, respectively) and cardiac function, as measured by change in ventricular mass index ( P =.959), ejection fraction ( P =.413), or fractional shortening ( P =.280), were similar between treatments. Conclusions. Pioglitazone was associated with a higher incidence of hospitalization for HF without an increase in cardiovascular mortality or worsening cardiac function (by echocardiography).— Giles TD, Miller AB, Elkayam U, et al. Pioglitazone and heart failure: results from a controlled study in patients with type 2 diabetes mellitus and systolic dysfunction. J Card Fail. 2008;14(6):445–452.

Objectives. This study sought to determine the characteristics and long-term prognosis of anemia in ambulatory patients with chronic heart failure. Background. Anemia is prevalent in heart failure and may portend poor outcomes. Methods. We reviewed 6159 consecutive outpatients with chronic stable heart failure at baseline, short-term (3-month) follow-up, and long-term (6-month) follow-up between 2001 and 2006. Clinical, demographic, laboratory, and echocardiographic data were reviewed from electronic medical records. Mortality rates were determined from 6-month follow-up to end of the study period. Results. Prevalence of anemia (hemoglobin <12 g/dL for men, <11 g/dL for women) was 17.2% in our cohort. Diabetes, B-natriuretic peptide, left ventricular ejection fraction, and estimated glomerular filtration rate were independent predictors of baseline anemia. Documented evaluation of anemia was found in only 3% of all anemic patients and better in internal medicine than in cardiology clinics. At 6-month follow-up, new-onset anemia developed in 16% of patients without prior anemia, whereas 43% patients with anemia at baseline had resolution of their hemoglobin levels. Higher total mortality rates were evident in patients with persistent anemia (58% vs 31%; P<.0001) or with incident anemia (45% vs 31%; P<.0001) compared with those with without anemia at 6 months. Conclusions. These observations in a broad unselected outpatient cohort suggest that anemia in patients with heart failure is underrecognized and underevaluated. However, resolution of anemia was evident in up to 43% of patients who presented initially with anemia and did not pose greater long-term risk for all-cause mortality. However, the presence of persistent anemia conferred poorest survival in patients with heart failure when compared with that of incident, resolved, or no anemia.—Tang WH, Tong W, Jain A, et al. Evaluation and long-term prognosis of new-onset, transient, and persistent anemia in ambulatory patients with chronic heart failure. J Am Coll Cardiol. 2008;51(5):569–576. In this retrospective study, when adjusted for ejection fraction, left ventricular diameter, and stable heart failure patients, anemia was associated with higher mortality at a mean follow-up of 3.9 years (47% vs 26%). Baseline characteristics of the anemia population included more diabetics (35% vs 25%), higher creatinine levels (1.79 vs 1.20), and older age (69 vs 65 years). Though ejection fraction and left ventricular end-diastolic diameter were similar in both groups (34%–35% and 6.4 cm, respectively), the anemia group had more evidence of diastolic dysfunction (diastolic stage >2 in 60% vs 46%) and slightly more pulmonary hypertension (43 vs 39 mm Hg), suggesting that cardiac output may have been lower in the anemia group. One would expect a higher incidence of anemia with a decline in renal function and consequent decrease in glomerular filtration rate, though B-natriuretic peptide was a stronger independent predictor of anemia than a glomerular filtration rate <60 mL/min/1.73 m2 (odds ratio, 4.38 vs 3.04, respectively). However, B-natriuretic peptide is normally elevated with renal insufficiency. More telling in this study were the effects on all-cause mortality when anemia was resolved by the follow-up period, as these patients' survival curves were nearly identical to those who were nonanemic. The development of anemia during the follow-up period was associated with higher mortality than nonanemic patients and those with resolved anemia, but less mortality than those with persistent anemia. Disturbing is the observation that anemia prevalence was 17.2% at baseline, though only 3% of HF patients had had a documented anemia evaluation. While mortality was higher in this group of anemic patients, so were rates of diabetes and renal insufficiency, both known predictors of mortality. Nonetheless, the data demonstrate that successful treatment of anemia conferred improved survival in HF patients compared with those with persistent anemia. Whether anemia is a marker of disease (eg, from renal failure) or a mediator deserves more study. Regardless, its diagnosis should be sought, and it should be treated when indicated.