Heart Failure Score Research Articles

Long-Term Outcomes in High-Risk Symptomatic Patients With Hypertrophic Cardiomyopathy Undergoing Alcohol Septal Ablation

We sought to assess outcomes of alcohol septal ablation (ASA) in high-risk patients. Because surgical myectomy is the preferred treatment in patients with symptomatic hypertrophic obstructive cardiomyopathy (HOCM) at our institution, we perform ASA in patients who are at high risk for surgery. We studied 55 symptomatic HOCM patients (mean age 63 +/- 13 years, 67% women, mean follow-up 8 +/- 1 years), at high risk for surgery (as the result of age/comorbidities) who had ASA between 1997 and 2000. The following were recorded at baseline, 3 months, and 1 year: septal thickness, maximal (resting or provocable) left ventricular outflow tract gradient, Minnesota living with heart failure questionnaire score, and the presence of a permanent pacemaker. All-cause mortality was recorded. No patients died at 48 h, 2 died at 1 year, 7 died at 5 years, and 13 died at 10 years. Only age >65 years at time of ASA predicted long-term mortality (log-rank p = 0.03). Mean maximal left ventricular outflow tract gradient (104 +/- 35 mm Hg vs. 49 +/- 28 mm Hg), septal thickness (2.4 +/- 0.4 cm vs. 1.8 +/- 0.6 cm), and Minnesota living with heart failure score (63 vs. 25) improved at 3 months, compared with baseline (all p < 0.001), with no significant changes at 1 year. New permanent pacemaker was present in 26% of patients. In symptomatic HOCM patients who are at high risk for surgery, ASA is associated with symptomatic improvement and low short-term mortality; with long-term mortality only associated with older age at time of procedure. In symptomatic HOCM patients at high-risk for surgery, ASA is a viable option.

Venlafaxine versus clonidine for the treatment of hot flashes in breast cancer patients: a double-blind, randomized cross-over study

Breast cancer patients with treatment-induced menopause experience frequent and severe hot flashes (HF). We compared venlafaxine and clonidine for the treatment of HF with regard to side effects, efficacy, quality of life and sexual functioning. In a double-blind, cross-over study, 60 breast cancer patients experiencing HF were randomized to 8 weeks venlafaxine followed by 2 weeks wash-out, and 8 weeks clonidine or vice versa. HF frequency and severity, side effects, quality of life and sexuality were assessed. Thirty patients started with venlafaxine and 30 with clonidine. Premature discontinuation for toxicity occurred in 14/59 during venlafaxine and 5/53 during clonidine (P = .038). Venlafaxine induced more side effects. Median reduction in HF score was 49% for venlafaxine and 55% for clonidine (ns). Venlafaxine and clonidine are equally, but moderately effective in HF reduction. Side effects are the main reason for drug discontinuation, occurring more often with venlafaxine.

Identifying subpopulations for subgroup analysis in a longitudinal clinical trial

Background In a typical clinical trial treatment effects will not be expected to be the same on all of the study participants. As a result, investigators are often tempted to look at the effects of a given treatment in subgroups of patients in order to determine who will benefit the most or the least, especially when the treatment effect in the total sample is insignificant or borderline. This paper aims at demonstrating the application of random effect models as one approach to identify subpopulations suitable for subgroup analysis in a longitudinal study. Methods Data collected from a double-blind randomized controlled trial were used to demonstrate how multilevel modeling using random effects can be used to identify subgroups of postmenopausal women who benefit the most from nonhormonal treatment (gabapentin) of their hot flashes. Results We estimated subject-specific treatment effects and correlated these effects with patient characteristics at baseline. We found that women with a higher severity of hot flashes score at baseline were more likely to have the greatest reduction in hot flashes score from the treatment. Also, women who had a serum creatinine level higher than the median level at baseline demonstrated a greater response to gabapentin compared to the placebo group. Conclusion Our proposed method can help researchers identify patient factors that are associated with differential effect. Those factors are potential areas for further clinical investigation or for constructing subgroups for sub-analysis.

Does efficacy of non-estrogenic therapies for hot flashes among women vary by breast cancer history and tamoxifen use? A pooled analysis

9595 Background: Various non-estrogenic therapies have been found to be effective in mitigating hot flashes. However, it is unclear whether the efficacy of these therapies is different among women with breast cancer, and/or those taking tamoxifen, as compared to the counterparts. Methods: All clinical trials (pilot and randomized trials) conducted by a group of investigators at Mayo Clinic and the North Central Cancer Treatment Group (NCCTG) that evaluated the efficacy of any non-estrogenic agent for hot flashes, and had information on breast cancer history and/or tamoxifen use, were eligible for this analysis. All these trials had similar study methodology, including design and measurement tools. Hot flash scores were computed as the daily frequency of hot flashes times the average hot flash severity. The analysis was done using patient level data. Statistically significant changes from the 4th treatment week versus the baseline week were assessed using the Student’s t-test. Forest plots as well as stepwise linear regression models were created to assess the differences among subgroups. A p-value of 0.05 was considered significant. Results: A total of 1,415 women from 20 hot flash studies were eligible for analysis. Among the patients with available information, 80% had a history of breast cancer and 53% were using tamoxifen. Overall, patients without breast cancer had similar percentage of baseline hot flash score at week four, as did those with breast cancer (53% versus 50%, p=0.92). Patients without a history of tamoxifen use had a significantly lower percentage of hot flash score at week four, as compared to those who used tamoxifen (54% versus 61%, p =0.01). However, further analysis showed that this was due to a higher reduction of hot flashes in the placebo arms among patients not receiving tamoxifen. The percentage reduction in hot flash score at week 4 (from baseline) by the therapy arms over placebo arms in the randomized trials, and by the therapies in pilot trials, was similar among tamoxifen users and non- users. Conclusions: The efficacy of non-estrogenic therapies on hot flashes is similar among women with or without a history of breast cancer, as well as among patients taking tamoxifen versus non-users. No significant financial relationships to disclose.

A phase III trial evaluating three doses of citalopram for hot flashes: NCCTG trial N05C9

9538 Background: Hot flashes are experienced by up to 75% of women and can negatively impact quality of life. Estrogen treatment has fallen out of favor, so new options are needed. Based on encouraging pilot data, this trial was designed to evaluate three doses of citalopram for effects on hot flashes. Methods: A randomized trial evaluated citalopram at doses of 10, 20 or 30 mg/day versus placebo for 6 weeks. Women recorded hot flashes for one week before starting treatment, then were titrated up to their assigned dose. The primary endpoint was change from baseline in hot flash score (frequency × severity) per a prospective daily hot flash diary. Secondary endpoints included hot flash frequency and activity interference. Toxicities were evaluated with a self-report questionnaire and NCI common terminology criteria. Eligibility included postmenopausal women with at least 14 bothersome hot flashes per week for the past month. A total of 50 patients per arm (N=200), provided 80% power for a two-sample t-test...

Phase I study of acupuncture as treatment of hot flashes for men with prostate cancer

20678 Background: Up to 80% of men treated with androgen deprivation for prostate cancer suffer from hot flashes. Insomnia, fatigue, and irritability are often associated with hot flashes and adversely affect the quality of life for these patients. Several pharmacologic interventions can reduce hot flash frequency and intensity but have the potential for adverse effects. Acupuncture, a 23 century-old treatment modality, has been reported to substantially reduce hot flash frequency in postmenopausal women. We investigated the benefit of acupuncture in a group of men with hot flashes due to hormonal therapy for prostate cancer. Methods: Eight men with prostate cancer experiencing hot flashes more than three times/day were enrolled in an IRB approved protocol. The hot flashes were scored using 3 nationally accredited scoring systems; Hot Flash Score (HFS), Hot Flash Related Daily Interference Scale (HFRDIS) and Pittsburgh Sleep Quality Index (PSQI). Hot flashes were assessed on weekly basis and at one month post intervention. Interventions were given twice weekly for 4 consecutive weeks and once a week for the following 6 weeks. Pre- and post-acupuncture serum Serotonin is obtained. Results: Four patients completed the protocol with one month follow up. The mean pre-intervention hot flashes score was 12 for HFS, 59.2 for HFRIDS and 5 for PSQI. The post treatment scores were 4, 36.7 and 2.3 respectively. The overall mean reduction in hot flashes was 53%. The mean pretreatment serotonin level was 226 compared to 183 in post therapy estimation. No immediate adverse effects could be observed. Conclusions: The use of acupuncture reduced the intensity and frequency of hot flashes in men with prostate cancer secondary to androgen ablation by 53%. The intervention was safe with no immediate adverse effects. The study is still accruing patients. ClinicalTrials.gov ID#NCT00421902 No significant financial relationships to disclose.

Newer antidepressants and gabapentin for hot flashes: An individual subject pooled analysis

9537 Background: Non-hormonal treatment options have been investigated as treatments for hot flashes, a major clinical problem in many women. Starting in 2000, a series of 10 individual double-blind, placebo-controlled studies involving newer antidepressants and gabapentin have evaluated these non-hormonal agents for decreasing hot flashes from a no-treatment baseline period, inclusive of all known such published trials through 2007. Methods: Individual patient data were collected. Between-study heterogeneity was tested via chi- square tests prior to a pooled analyses. The change in hot flash activity from baseline to week 4 for each agent was calculated via both weighted and unweighted approaches using the size of the study as the weight. The effect size was recalculated using an unweighted approach to test the sensitivity of the results relative to the influence of individual study sample sizes. Regression models and linear random effects were used to adjust for age, breast cancer history, and tamoxifen usage on hot flash activity. Results: Data from 1,341 patients indicated that paroxetine (2 studies), venlafaxine (1 study), fluoxetine (1 study), and sertraline (3 studies) decreased absolute hot flash scores by 41%, 33%, 13%, and 3%-18% more than did their corresponding placebo arms, respectively. As a group, the antidepressants decreased absolute hot flash scores by 26 % more than was seen with their corresponding placebo arms (P= 0.0001). The three gabapentin trials decreased absolute hot flashes by 35–38% more than did their corresponding placebo arms (P= 0.0001). Results were similar for the weighted and unweighted effect size approaches. Age, breast cancer history, and tamoxifen usage did not impact the findings. Conclusions: Newer antidepressants, as a group, and gabapentin decrease hot flashes significantly more than do placebos. There may be efficacy differences among the different antidepressants. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Concert Pharmaceuticals, JDS Pharmaceuticals, Wyeth

Effects of stellate-ganglion block on hot flushes and night awakenings in survivors of breast cancer: a pilot study

Debilitating hot flushes and sleep dysfunction often affect survivors of breast cancer, most notably in those taking anti-oestrogen medications. Conventional treatments have been only partially effective in diminishing these issues, and some have serious risks. We did a pilot study to investigate our hypothesis that stellate-ganglion block can be a safe and effective treatment for hot flushes and sleep dysfunction in this patient population. 13 survivors of breast cancer (in remission) with severe hot flushes and night awakenings were treated with stellate-ganglion block at the anterolateral aspect of the C6 vertebra on the right side under fluoroscopy. Patients recorded hot flushes in a daily diary by use of the Hot-Flash Score, devised by Sloan and colleagues, and night awakenings by use of the Pittsburgh Sleep Quality Index. Both instruments were used 1 week before the procedure [A40] and then weekly after the procedure for 12 weeks. We used the generalised-estimating-equations method to analyse the longitudinal measurements of the number of hot flushes and night awakenings over time. This method is a popular approach to analysing datasets that have repeated measures from the same person, and is robust because it does not need the complete distribution of the outcomes to be specified. This trial is registered on the International Standard Randomised Controlled Trial Number register (ISRCTN14318565). There were no adverse events resulting from the stellate-ganglion block, although patients had temporary Horner's syndrome indicating the effectiveness of the block. Five patients had only one stellate-ganglion block and eight had two stellate-ganglion blocks. The total number of hot flushes decreased from a mean of 79.4 (SD 37.4) per week before the procedure to a mean of 49.9 (SD 39.9) per week during the first 2 weeks after the procedure (p=0.0002). The total number of hot flushes continued to decrease over the remaining follow-up period (weeks 3-12), and stabilised at a mean of 8.1 (SD 5.6) per week (p<0.0001). The number of very severe hot flushes was decreased to near zero by the end of the follow-up period (week 12; p<0.0001). Night awakenings decreased from a mean of 19.5 (SD 14.8) per week before the procedure to a mean of 7.3 (SD 7.1) per week during the first 2 weeks after the procedure (p<0.0001). The total number of night awakenings continued to decrease over the remaining follow-up period (weeks 3-12) and stabilised at a mean of 1.4 (SD 1.2) per week (p<0.0001). The findings of this study suggest that stellate-ganglion block can provide survivors of breast cancer with relief from hot flushes and sleep dysfunction with few or no side-effects. Long-term relief of symptoms has the potential to improve overall quality of life and increase compliance with anti-oestrogen medications for breast cancer.

Gabapentin for the treatment of menopausal hot flashes

To compare the effectiveness and tolerability of gabapentin with placebo for the treatment of hot flashes in women who enter menopause naturally. A randomized, double-blind, placebo-controlled trial was conducted across the greater Toronto area between March 2004 and April 2006 in the community and primary care settings. Eligible participants were 200 women in natural menopause, aged 45 to 65 years, having at least 14 hot flashes per week. Study participants were randomized to receive gabapentin 300 mg oral capsules or placebo three times daily for 4 weeks. The primary outcome measure was the mean percentage change from baseline to week 4 in daily hot flash score, determined from participant diaries. Secondary outcome measures included changes in weekly mean hot flash scores and frequencies, quality of life, and adverse events. Of the 197 participants, 193 (98%) completed the study. Analysis was by intention to treat. Hot flash scores decreased by 51% (95% CI: 43%-58%) in the gabapentin group, compared with 26% (95% CI: 18%-35%) on placebo, from baseline to week 4. This twofold improvement was statistically significant (P < 0.001). The Menopause-Specific Quality-of-Life vasomotor score decreased by 1.7 (95% CI: 1.3-2.1; P < 0.001) in the gabapentin group. These women reported greater dizziness (18%), unsteadiness (14%), and drowsiness (12%) at week 1 compared with those taking placebo; however, these symptoms improved by week 2 and returned to baseline levels by week 4. Gabapentin at 900 mg/day is an effective and well-tolerated treatment for hot flashes.

Worldwide surgical experience with the Paracor HeartNet cardiac restraint device

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. 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. 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. 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.

Mixed total anomalous pulmonary venous connection: Anatomic variations, surgical approach, techniques, and results

The purpose of this study was to identify the morphologic characteristics and other risk factors that may predispose patients with mixed totally anomalous pulmonary venous connection to continuing high mortality after surgery. Fifty-seven consecutive patients aged 15 days to 18 years (median, 6 months) underwent rechanneling of mixed totally anomalous pulmonary venous connection. Twenty-three patients had "2+2" pattern (I category), 29 had "3+1" pattern (II category), and 5 patients had pulmonary venous connections of different combinations (III category). Obstructive patterns involving one or more pulmonary veins were present in 19 (33.3%) patients. Operative and late mortality rates were 19.3% and 4.3%, respectively. At a mean follow-up of 63.26 +/- 58.47 months, actuarial survival was 86.9% +/- 0.07% in category I, 86.2% +/- 0.06% in category II, and 20.0% +/- 0.18% in category III (log-rank, P = .001), respectively. At their last follow-up, all survivors (n = 43) had a Ross clinical heart failure score of 0 to 2. Patients with a "2+2" pattern of mixed totally anomalous pulmonary venous connection constitute the safe anatomic category for rechanneling, followed by the "3+1" variety. Cross-sectional echocardiography and/or computed tomographic angiography are mandatory to provide necessary diagnostic information and define the anatomy. Patients aged 2 months or younger, obstructive totally anomalous pulmonary venous connection, and perioperative pulmonary hypertensive crises were significant risk factors for death by logistic regression analysis. The risk of death was 5.85 times higher (95% confidence interval: 1.46-35.68; P = .02) in patients with category III of mixed TAPVC. The precise technique adopted in an individual patient depends on the pattern of anatomic drainage, and an individualized surgical approach is recommended.

A Hospital-Randomized Controlled Trial of an Educational Quality Improvement Intervention in Rural and Small Community Hospitals in Texas Following Implementation of Information Technology

Rural and small community hospitals typically have few resources and little experience with quality improvement (QI) and, on average, demonstrate poorer quality of care than larger facilities. Formalized QI education shows promise in improving quality, but little is known about its effect in rural and small community hospitals. The authors describe a randomized controlled trial assigning 47 rural and small community Texas hospitals to such a program (n = 23) or to the control group (n = 24), following provision of a Web-based quality benchmarking and case review tool. Centers for Medicare and Medicaid Services Core Measures composite scores for congestive heart failure (CHF) and community-acquired pneumonia (CAP), using Texas Medical Foundation data collected via the QualityNet Exchange system, are compared for the groups, for 2 years postintervention. Given the estimated baseline rates for the CHF (68%) and CAP (66%) composites, the cohort enables the detection of 14% and 11% differences (alpha = .05; power = 0.8), respectively.

Comparison of Menopausal Symptoms During the First Year of Adjuvant Therapy With Either Exemestane or Tamoxifen in Early Breast Cancer: Report of a Tamoxifen Exemestane Adjuvant Multicenter Trial Substudy

Hormonal breast cancer treatment increases menopausal symptoms in women. This study investigated differences between the symptoms associated with either adjuvant tamoxifen or exemestane. Ten common symptoms were assessed by self-report questionnaire administered to 1,614 consecutive patients at baseline and every 3 months during the first year of a double-blind, randomized trial of postmenopausal women with early hormone receptor-positive breast cancer. Symptoms were categorized as none, mild, moderate, or severe. A hot flash score was calculated at each time point. Symptoms were analyzed by repeated-measures analysis of variance. Each time period was tested repeatedly against the baseline; an overall P value was assigned for each reported symptom. Compliance was excellent, with 7,286 questionnaires analyzed. Baseline symptom prevalence ranged from 2% (vaginal bleeding) to 60% to 70% (bone/muscle aches and low energy). There were no significant differences in vaginal bleeding, mood alteration, or low energy. Patients receiving tamoxifen had significantly more vaginal discharge (P < .0001). Exemestane patients reported more bone/muscle aches (P < .0001), vaginal dryness (P = .0004), and difficulty sleeping (P = .03). In both groups, the hot flash score peaked at 3 months and decreased thereafter. At 12 months, patients receiving tamoxifen had a significantly higher mean hot flash score (P = .03), with daily hot flashes increasing from baseline by 33% compared with a 7% increase from baseline with exemestane. At 12 months, exemestane was associated with fewer hot flashes and less vaginal discharge than tamoxifen, but with more vaginal dryness, bone/muscle aches, and difficulty sleeping. Symptoms were common in both groups.

Abstract 1614: Sequential Analysis of Immunosuppressive Therapy in Autoreactive Myocarditis - Sequential Analysis from ESETCID

In the European Study on Epidemiology and Treatment of Cardiac Inflammatory Disease (ESETCID) pts with autoreactive (virus-negative) myocarditis (AM) and an ejection fraction &lt;45% were randomised for 6 months of treatment with azathioprin (2mg/kg BW/day for 1 m and 0.85mg/kg BW/day for 5 m) + prednisolone (1.25mg/kg BW/ for 1 m and 0.3mg/kg BW/day for 5 m) or placebo on top of their heart failure treatment and followed-up for up to 8 years. Patients: 3149 pts with dilated cardiomyopathy were screened, 103 pts (mean age 47± 9 years, 81 male, 22 female) with AM and an EF 14 infiltrating cells/mm 2 ), persistence of viral or bacterial genomes for Parvo B19, coxsackie-, influenza-, adeno-, cytomegalo-, HHV 6, EBV, chlamydia and borrelia were excluded from the analysis. 56 pts (45 m) with AM were treated with verum, 47 pts ( 38m) with placebo. MACE are defined as cardiac death, heart transplantation, ICD implantation or hospitalisation for cardiac decompensation. Time to MACE is given in days to the event. Results: Inflammation was eradicated in 63% in the treatment group, but it also vanished spontaneously in 40% in the placebo arm(p&lt;0,05). After 12 months the Kaplan Mayer MACE curves began to diverge. At 4 years freedom from MACE was 50% in the verum and 40% in the placebo group. Respective data at 8 years were 40% and 20% freedom from MACE. NYHA-association class and Minnesota Heart Failure Score improved in treatment and placebo arms to a similar extend. Ejection fraction by echo and radioventriculography improved in both arms with a trend for immunosuppression(IS). Independent from IS pts with no inflammation in the follow-up biopsy (n=45) showed a better NYHA-class (p&lt;0,05), ejection fraction and superior long term freedom from MACE than those with persistent inflammation.. Conclusion: Immunosuppression is superior to conventional heart failure treatment in the acute eradication of the inflammatory infiltrate iDCM patients and bears better long-term prognosis. Results

Abstract 1753: Transcriptomic based Biomarkers Contain Diagnostic and Prognostic Information about Patients with new onset Heart Failure

INTRODUCTION: One of the clinical dilemmas in cardiology is to accurately diagnose the etiology of patients with new onset heart failure such as to differentiate between potentially reversible myocarditis from idiopathic dilated cardiomyopathy (IDCM). Furthermore, it is difficult to predict the clinical trajectory of patients with IDCM. We hypothesized that the transcriptomic signatures generated from endomyocardial biopsies, obtained from patients at first presentation of heart failure, could serve as novel biomarkers to distinguish between myocarditis and IDCM as well as to predict the prognosis of patients classified as having IDCM. METHODS AND RESULTS: Endomyocardial biopsy samples were collected from 68 patients with new onset heart failure due to IDCM (n=49) and myocarditis (n=19). The average follow-up was 5 years and included information on mortality, need for left ventricular assist device (LVAD), or heart transplant. We used the U133 Plus 2.0 microarray (Affymetrix) and data analysis was performed with Significance Analysis of Microarrays (SAM) and Prediction Analysis of Microarrays (PAM). First, we identified a molecular signature of 39 genes in our training cohort (n=25 IDCM and n=8 myocarditis). When tested in independent patients (myocarditis: n=11; IDCM: n=11), this signature performed with 97% accuracy. Next, we identified a transcriptomic signature of 45 genes in a group of patients with IDCM that delineated between patients classified as having a good prognosis (event free survival &gt; 5 years; n=18) vs a bad prognosis (death or requirement for insertion of LVAD or tx within 2 years of presentation; n=12). We tested this biomarker in independent samples and were able to predict prognosis with 87% accuracy. The transcriptomic biomarker was substantially more accurate in assigning prognosis than the Seattle Heart Failure Score (p=0.011). CONCLUSION: Together these findings illustrate the potential utility of using transcriptomic biomarkers generated from a single endomyocardial biopsy to improve the accuracy of diagnosis and prognosis in patients with new onset heart failure. This creates novel modalities to enhance management and identification of patients at highest risk for complications of heart failure in the short term.

Clinical Evaluation of the CorCap Cardiac Support Device in Patients With Dilated Cardiomyopathy

Left ventricular (LV) remodeling is related to adverse outcomes in heart failure. The CorCap Cardiac Support Device (CSD; Acorn Cardiovascular, Inc, St. Paul, MN) is an implantable device that attenuates LV remodeling. The Acorn trial assessed the safety and efficacy of the CSD in 300 heart failure patients. Patients needing mitral surgery (n = 193) were randomized to mitral surgery alone or mitral surgery plus CSD. Patients who did not need mitral surgery (n = 107) were randomized to medical therapy or medical therapy plus CSD. The primary endpoint was a clinical composite based on changes in patient vital status, the need for major cardiac procedures for worsening heart failure, and a change in New York Heart Association (NYHA) class. The proportional odds ratio for the primary endpoint favored treatment with the CSD (1.73 confidence interval [CI]: 1.07 to 2.79; p = 0.024). The CSD-treated patients received significantly (p = 0.01) fewer cardiac procedures indicative of worsening heart failure and had an improvement in New York Heart Association class (p = 0.049). There was no significant difference in survival between groups (p = 0.85). Treatment with the CSD led to a decrease in LV end-diastolic (p = 0.009) and end-systolic volumes (p = 0.017), an increase in the LV sphericity index (p = 0.026), an improvement in the Minnesota Living with Heart Failure score (p = 0.04), and the Short Form-36 Questionnaire (p = 0.015). There was no evidence for a significant difference (p = 0.43) in serious adverse events between the treatment and control groups. The results of the Acorn trial support the hypothesis that preventing LV remodeling with a CSD favorably impacts the untoward natural history of heart failure.

Sildenafil Improves Exercise Capacity and Quality of Life in Patients With Systolic Heart Failure and Secondary Pulmonary Hypertension

Patients with systolic heart failure (HF) who develop secondary pulmonary hypertension (PH) have reduced exercise capacity and increased mortality compared with HF patients without PH. We tested the hypothesis that sildenafil, an effective therapy for pulmonary arterial hypertension, would lower pulmonary vascular resistance and improve exercise capacity in patients with HF complicated by PH. Thirty-four patients with symptomatic HF and PH were randomized to 12 weeks of treatment with sildenafil (25 to 75 mg orally 3 times daily) or placebo. Patients underwent cardiopulmonary exercise testing before and after treatment. The change in peak VO2 from baseline, the primary end point, was greater in the sildenafil group (1.8+/-0.7 mL x kg(-1) x min(-1)) than in the placebo group (-0.27 mL x kg(-1) x min(-1); P=0.02). Sildenafil reduced pulmonary vascular resistance and increased cardiac output with exercise (P<0.05 versus placebo for both) without altering pulmonary capillary wedge or mean arterial pressure, heart rate, or systemic vascular resistance. The ability of sildenafil treatment to augment peak VO2 correlated directly with baseline resting pulmonary vascular resistance (r=0.74, P=0.002) and indirectly with baseline resting right ventricular ejection fraction (r=-0.64, P=0.01). Sildenafil treatment also was associated with improvement in 6-minute walk distance (29 m versus placebo; P=0.047) and Minnesota Living With Heart Failure score (-14 versus placebo; P=0.01). Subjects in the sildenafil group experienced fewer hospitalizations for HF and a higher incidence of headache than those in the placebo group without incurring excess serious adverse events. Phosphodiesterase 5 inhibition with sildenafil improves exercise capacity and quality of life in patients with systolic HF with secondary PH.

Phase II Evaluation of Desipramine for the Treatment of Hot Flashes

PurposeNewer antidepressants with serotonergic effects reduce hot flashes significantly better than placebo. This pilot study was designed to test the efficacy of desipramine, an older antidepressant targeting norepinephrine, in women desiring therapy for hot flashes and to evaluate the toxicity of desipramine. Patients and MethodsIn this nonrandomized trial, eligible women were required to have reported ≥ 14 bothersome hot flashes per week for ≥ 1 month. After an Initials baseline week in which no study medication was taken, participants started with desipramine 25 mg daily, which was titrated to100 mg daily by week 5. The primary endpoint was change from baseline in hot flash frequency and hot flash score. Statistical methods involved paired t tests for continuous variables and Fisher exact tests for categoric variables. ResultsTwenty-six patients were enrolled on this study between March 2004 and November 2005. The decrease in mean hot flash frequency over 4 weeks of treatment was 23%, with a 31% reduction in hot flash scores. Seven patients (30%) withdrew early because of toxicities consisting of insomnia, nausea, headaches, and/or feeling frightened. ConclusionDesipramine did not reduce hot flashes beyond the 25%–30% reduction that would be expected with placebo, based on previous work. Therefore, data from this trial do not support further study of this agent for treatment of hot flashes. It is of physiologic interest that this older antidepressant, classified as a tricyclic, did not achieve a clinically significant reduction in hot flash scores in this pilot trial.

Surgical Ablation of Atrial Fibrillation in Patients With Congestive Heart Failure

Background Congestive heart failure (CHF) and atrial fibrillation (AF), both of which cause morbidity and mortality, are mutually promoting diseases. We aimed to evaluate surgical AF ablation in CHF. Methods and Results Among 212 patients (age 69 ± 8.8 years, 87% with persistent AF) undergoing concomitant left atrial (LA) ablation, 79 (37.3%) presented CHF (n = 62 with a left ventricular ejection fraction [LVEF] 0.31–0.45, n = 17 with an LVEF ≤ 0.30). Patients with CHF were similar to controls regarding AF duration (61 ± 65.1 months vs. 54 ± 67.2 months, not significant [NS]), LA diameter (49 ± 7.5 mm vs. 50 ± 9.2 mm, NS), and heart rate (78 ± 18.4 min −1 vs. 81 ± 21.3 min −1, NS), but they required more circulatory support (17.7% vs. 1.5%, P < .001) and a longer intensive care unit stay (6 ± 9.5 days vs. 4 ± 10.5 days, P = .032). At follow-up after 13 ± 7.3 months, 42 patients (66%) with CHF and 81 controls (74%, NS) were in sinus rhythm (SR) (55% and 64% without antiarrhythmic drugs, respectively, NS). Univariate and logistic regression analysis revealed that AF duration and LA diameter predicted rhythm outcome but not CHF. In patients with an LVEF of 0.30 or less, SR conversion significantly improved LVEF, New York Heart Association class, and Minnesota Living with Heart Failure score. Kaplan-Meier estimates suggested superior survival of patients with stable SR (100% vs. 73%, log-rank P < .05). Conclusions If patients presenting with CHF and AF require cardiac surgery, concomitant AF ablation should be considered, especially if left ventricular function is severely impaired.

Summary Health Status Measures in Advanced Heart Failure: Relationship to Clinical Variables and Outcome

Background Patient-centered health status measures are important because they capture the patient's perspective on their heart failure, but it is unclear which of these have independent prognostic significance. Methods and Results A total of 142 consecutive subjects from a specialty heart failure clinic were assessed at baseline with a broad array of clinical, laboratory, and self-report measures including four summary measures of health status. The relationships between these measures and their association with the combined end point of transplantation or death over a mean follow-up of 3 years were examined. In unadjusted analyses, the Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score had the strongest association with the combined end point (HR [for each unit score difference] = 0.98 [0.96–0.99], P = .002). In the adjusted Cox proportional hazards model including all 4 summary measures, the Seattle Heart Failure Score, V0 2, systolic blood pressure, and medical comorbidity, only the Standard Gamble utility remained significantly associated with time to the combined end point (HR [for each 0.01 utility score difference] = 0.98 [0.97–0.99], P = .007). Conclusions Our study suggests that summary health status measures are simple and significant indicators of prognosis in advanced heart failure patients. The KCCQ summary score summarizes a wide range of clinical variables from the patient's point of view, whereas the standard gamble utility contains important prognostic information not captured in usual clinical variables.