Background— Left atrial (LA) dilation precedes or appears early after the onset of atrial fibrillation (AF) and factors in perpetuating the arrhythmia. Angiotensin receptor blockers were proposed for reversing LA remodeling. We evaluated the effect of valsartan on LA remodeling in patients with a recent episode of AF and the effect of LA size on AF recurrence (AFr). Methods and Results— LA and left ventricular (LV) echocardiographic variables were measured at baseline and 6 and 12 months in 340 patients from GISSI-AF, a trial testing valsartan prevention of AFr. Reversal of remodeling was considered as a decrease in LA size over 12 months. Changes in patients with and without recurrence and the relationship to duration of AFr were analyzed. Patients were 68.4±8.8 years old, with history of hypertension (85.3%) and cardioversion in the previous 2 weeks (87.4%) or ≥2 AFr in the previous 6 months (40.4%). Baseline LA maximal volume (LAVmax) was severely increased (>40 mL/m 2 ); LV dimensions and function were relatively normal. Over 12 months, 54.4% of patients had AFr. LAVmax was unchanged by rhythm, time, or randomized treatment. Higher baseline LAVmax and lower LA emptying fraction were linearly related to increasing AFr duration during follow-up. Conclusions— GISSI-AF patients in sinus rhythm and history of AF showed severely increased LAVmax with mostly normal LV volume, mass, and systolic and diastolic function. Valsartan for 1 year did not reverse LA remodeling or prevent AFr. Half of the patients without AFr had severe LA dilation; therefore, mechanisms other than structural remodeling triggered recurrence. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00376272.

Objective: The identification of echocardiographic predictors of recurrence of atrial fibrillation (AF) may represent a valuable step towards its prevention. This study was undertaken in an effort ...

BACKGROUND:Chronic obstructive pulmonary disease (COPD) and heart failure are major causes of death and disability. Because little information is available about the population of patients with both syndromes, we assessed the characteristics and the independent contribution of COPD to outcomes in patients with stable chronic heart failure. METHODS:The clinical, neurohormonal, and echocardiographic characteristics of the 5010 patients enrolled in the Valsartan Heart Failure Trial were compared in patients with or without COPD. The prognostic value of COPD was tested by multivariate Cox proportional hazard models. RESULTS:Patients with COPD were older, more symptomatic, and less likely to be receiving beta-blocker therapy, and had a higher mortality (27.4% vs. 18.4%, P < .0001). Echocardiographic parameters were not different, and brain natriuretic peptide was only minimally increased. Norepinephrine, inflammatory markers, cardiac troponin T, and creatinine values were significantly higher. After adjustment, COPD no longer predicted all-cause mortality but remained predictive of noncardiovascular mortality (hazard ratio 2.50; 95% confidence interval: 1.58-3.96; P < .0001) and hospitalizations, especially noncardiovascular (hazard ratio 1.71; 95% confidence interval; 1.43-2.06; P < .0001). CONCLUSIONS:Patients with COPD are more symptomatic and have worse outcomes that are not explained by poorer left ventricular function. After adjustment for demographic, clinical, biohumoral, and treatment variables, COPD is a weak predictor of all-cause mortality but a strong predictor of noncardiovascular events. Awareness and optimized treatment of heart failure and COPD may reduce the clinical burden of these patients.

BACKGROUND:Clinical trials emphasize mortality and morbidity endpoints.AIMS:To bring relevance of trial results to point of care by examining the prognostic and therapeutic value of individual signs and symptoms (S&S).METHODS:We analysed data from 5010 patients with stable chronic heart failure and left ventricular dysfunction who were participants in the Val-HeFT study. Individual S&S were stratified by severity. Treatment differences between valsartan and placebo were analysed by S&S strata at baseline and endpoint by logistical regression, and an overall S&S score by ANCOVA. Hazard ratios of S&S strata were calculated for mortality and heart failure hospitalisation. Prognostic contributions of S&S to other variables were determined by multivariate analysis.RESULTS:At endpoint, there were significantly fewer valsartan and more placebo patients with severe symptoms. Over time, improvement in the S&S overall score was significantly more favourable for valsartan than placebo. S&S strata were significantly predictive of risk for hospitalisation and death. S&S were each independent and incremental predictors of mortality compared to other variables. Symptom strata separated out moderately symptomatic patients with a mortality rate which was intermediate between that for NYHA Class II and III.CONCLUSION:Risk stratification of individual S&S defined prognosis, identified patients with an intermediate mortality between Class II and III, and treatment benefits of valsartan over placebo.

PURPOSE:B-type natriuretic peptide is one of the most sensitive and specific biohumoral markers of heart failure. We hypothesized that B-type natriuretic peptide changes during treatment of heart failure may provide independent information on disease progression and outcome in patients enrolled in the Val-HeFT trial. METHODS:Patients were divided into four groups according to concentrations of B-type natriuretic peptide at baseline versus 4 months (n = 3740) or 12 months (n = 3343), with respect to the baseline median (97 pg/mL): low-->low (stable below median, 44%-46%), high-->high (stable above median, 32%-37%), high-->low (above to below median, 12%-14%), and low-->high (below to above median, 6%-9%). Cox multivariate regression analysis was used to assess the risk of death and morbidity, with adjustment for baseline B-type natriuretic peptide concentrations. RESULTS:Patients who improved their B-type natriuretic peptide at 4 months (high-->low) had a similar risk for mortality (hazard ratio = 1.191, 95% confidence interval [CI] 0.870-1.631, P =.2746) compared with the low-->low patients. Conversely, patients who worsened in their B-type natriuretic peptide (low-->high) had a risk for mortality (hazard ratio 2.578, CI, 1.861-3.571, P <.0001) higher than patients in the low-->low group, and indistinguishable from the high-->high group. Worsening of B-type natriuretic peptide (low-->high) was associated with 0.03 cm/m2 increase in left ventricular end-diastolic diameter, whereas it decreased by 0.10 cm/m2 in high-->low and low-->low groups (P <.001). CONCLUSIONS:Changes in B-type natriuretic peptide over time with respect to a threshold value of 97 pg/mL convey an independent and additional prognostic value compared with a single determination of B-type natriuretic peptide in a large population of patients with chronic symptomatic heart failure and might be helpful in the management of these patients.

Symptomatic heart failure interferes with a patient's quality of life (QOL) by limiting his or her ability to perform physical tasks and daily activities and by lowering his or her sense of psychological well‐being. Therefore, in addition to decreasing mortality and morbidity, improving QOL should be an important goal when selecting pharmacotherapy. QOL questionnaires, both generic and disease specific, are used widely, but in randomized controlled trials of heart failure treatments, QOL has not been a routine study end point. Beta blockers and angiotensin‐converting enzyme inhibitors, medications widely used in the management of heart failure and hypertension—one of the most common causes of heart failure—have been associated with negative, neutral, and modestly positive QOL effects. Angiotensin receptor blockers, combined with other therapy, including angiotensin‐converting enzyme inhibitors (usually with a diuretic) and/or β blockers in heart failure, have produced improvements in QOL. Patients with hypertension whose blood pressure has been lowered have also experienced an improvement in QOL scores. With current heart failure regimens prolonging life, improving QOL becomes an even more essential end point in assessing the effectiveness of new medications, whether used alone or in combination with standard therapy.

by initial treatment strategy (MED, PCI, CABG) using SF-36 physical function, health utility and Seattle angina questionnaire. Linear modeling to predict 1 year physical function (SF-36 PF) included pt characteristics and treatment strategy. Results: PCI was the initial treatment strategy in 41%, CABG 22% and MED 37% I” elderly CAD pts. Survival at 1 yr was highest among pts undergolng CABG (60% CABG, 72% PCI, 50% MED). Pts undergoing CABG also had less angina, higher health utility rating, and better physical functioning at 1 yr than those treated with either PCI or MED (Table). CABG remained a significant predlctor (p=O.OOl) of higher 1 yr physical function (PF) even after adjusting for baseline PF. age, gender, education, prior MI, DM, PVD, EF, CAD severity and other predictors. In contrast, pts undergoing PCI had a non-significant trend toward better physical functioning at 1 year. Conclusions: After adjusting for potential confounders, CABG still affords elderly pts significantly better angma relief and funchonal outcomes at 1 year than either MED or IO:45 a.m.

Background: Brain natriuretic peptide (BNP), norepinephrine (NE) and left ventricular (LV) remodeling are important determinants of mortality and morbidity in heart failure (HF). Whether changes in LV remodeling correspond to similar changes in BNP and NE has not been studied. Val-HeFT evaluated BNP, NE, ejection fraction (EF) and LV internal diameter in diastole (LVIDd) in 5010 HF patients (23 month mean duration), showing significant improvements with valsartan (V) on all 4 variables. Methods: The overall population was subgrouped into quartiles by changes in EF and LVIDd from baseline to endpoint. Changes in BNP and NE from baseline to endpoint were analyzed by ANCOVA across quartiles, for V and placebo (P) groups separately, and within quartiles for V vs P. Results: Due to V's benefit on EF and LVIDd, there was a slightly disproportionate representation of V and P patients in some quartiles. Quartiles of changes in EF and LVIDd showed a significant and corresponding change in BNP (V: p<0.0001, p<0.0001; P: p<0.0001, p<0.0001, respectively). As compared to patients with decreased EF (Q1) and increased LVIDd (Q4), patients who had no change or increase in EF (Q2-Q4) and patients who had no change or decrease in LVIDd (Q3-Q1) had a quartile dependent decrease in BNP. Such a relationship was not seen between LV remodeling and NE. V caused a significantly greater suppression of BNP compared to P within each quartile of EF and LVIDd. Conclusion: These data confirm a strong relationship between change in BNP and LV remodeling in HF, regardless of treatment. The mechanism for the decrease in BNP by valsartan compared to placebo, independent of LV remodeling remains unknown but is consistent with the improvement in morbidity seen with V in Val-HeFT.

OBJECTIVES:The objective of the study was to evaluate the effect of an angiotensin receptor blocker on left ventricular (LV) structure and function when added to prescribed heart failure therapy.BACKGROUND:The clinical benefit derived from heart failure therapy is attributed to the regression of LV remodeling.METHODS:At 302 multinational sites, 5,010 patients in New York Heart Association (NYHA) classification II to IV heart failure taking angiotensin-converting enzyme inhibitor (ACEI) and/or beta-blocker (BB) were randomized into valsartan and placebo groups and followed for a mean of 22.4 months. Serial echocardiographic measurements of left ventricular internal diastolic diameter (LVIDd) and ejection fraction (EF) were recorded. Total study reproducibility calculated to 90% power at 5% significance defined detectable differences of 0.09 cm for LVIDd and 0.86% for EF.RESULTS:Baseline LVIDd and EF for valsartan and placebo groups were similar: 3.6 +/- 0.5 versus 3.7 +/- 0.5 (cm/m(2)) and 26.6 +/- 7.3 versus 26.9 +/- 7.0 (%). Mean group changes from baseline over time were compared. Significant decrease in LVIDd and increase in EF began by four months, reached plateau by one year, and persisted to two years in valsartan compared with placebo patients, irrespective of age, gender, race, etiology, NYHA classification, and co-treatment therapy. Changes at 18 months were -0.12 +/- 0.4 versus -0.05 +/- 0.4 (cm/m(2)), p < 0.00001 for LVIDd, and +4.5 +/- 8.9 versus +3.2 +/- 8.6 (%), p < 0.00001 for EF. The exception occurred in patients taking both ACEI and BB as co-treatment, in whom the decrease in LVIDd and increase in EF were no different between valsartan and placebo groups.CONCLUSIONS:The Val-HeFT echocardiographic substudy of 5,010 patients with moderate heart failure demonstrated that valsartan therapy taken with either ACEI or BB reversed LV remodeling.

Objective: To qualify 302 multinational echocardiography sites to record and read serial studies and to monitor quality in 5010 patients randomized into Valsartan in Heart Failure Trial (Val-HeFT).Background: Decentralized echocardiography reading is unprecedented in large clinical trials.Methods: Single and duplicate recordings, and triplicate readings of echocardiographic variables were submitted to 3 core laboratories. Quality of recording was defined with a 16-point scoring system; accuracy of reading by agreement with core readings; reproducibility by agreement between the duplicate studies.Results: Seventy-five percent of initial submissions were approved for recording, and 50% for reading. Resubmissions were evaluated until approval. initial scores of sites approved with 1 versus 2 submissions differed, 13.8 +/- 1.4 versus 10.6 +/- 2.0, P < .001; final score was similar, 13.4 +/- 1.6, P = ns. Initial score of sites approved after 3 or more submissions differed, 9.5 +/- 1.9, P < .001; final score improved to 12.7 +/- 1.9, but remained lower, P < .001. Expressed as 95% limits of agreement (mean difference +/- 1.96 x SD), accuracy = -0.04 +/- 0.74 cm for left ventricular internal end-diastolic diameter (LVIDd); -0.29 +/- 14.3% for ejection fraction (EF); reproducibility 0.00 +/- 0.53 cm for LVIDd; -0.25 +/- 8.3% for EF. Quality of random sampling at baseline, 4, 12, and 18 months showed recording scores of 11.7 +/- 2.7, 12.3 +/- 2.4, 12.1 +/- 2.2, and 11.4 +/- 2.0, P = .24. Power analysis revealed differences of 0.09 cm for LVIDd, and 0.86% for EF detectable with a power of 90% and alpha of 5%.Conclusion: The qualifying process improved echocardiography recording and reading to bring 95% of the sites to an equivalent level of quality. Monitoring quality found that recording quality and reading accuracy were maintained 18 months into the trial. Reproducibility, given the large sample size, will be able to detect small changes in LVIDd and EF.