Uremic cardiomyopathy is responsible for high morbidity and mortality rates among patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD); however, the early implementation of hemodialysis may halt its progression. Nonconventional hemodialysis, such as frequent hemodialysis, appears to have an advantage over conventional hemodialysis. Kidney transplantation has been shown to reverse uremic cardiomyopathy and to confer a significant survival advantage over hemodialysis. Targeting future therapies at the underlying cellular mechanisms of uremic cardiomyopathy may finally start to reduce the burden of uremic cardiomyopathy in the CKD and ESRD population.

Resynchronization therapy has become standard of care in patients with left bundle branch block (LBBB), congestive heart failure (CHF), and low ejection fraction (EF). In order to characterize the left ventricular (LV) function evolution in patients with LBBB and baseline preserved LVEF, records of all patients who visited an academic echocardiography laboratory during a period of 4 years were retrospectively investigated. Patients were included if they had a baseline EF >50%, LBBB on surface electrocardiography, and at least one follow-up echocardiogram no earlier than 3 months after the baseline study. The endpoint was the occurrence of EF deterioration to values ≤40%. Clinical variables associated with this outcome were identified. Forty-nine patients satisfied the entry criteria. Over a mean 13±8.5 months of follow-up (range 3 to 36), 8 patients (16%) experienced EF deterioration ≤40%. History of CHF prior to baseline echocardiogram and LV mass >300 g were associated with this phenomenon (P=.004 and P=.015, respectively), with a negative predictive value of 100% and 92%, respectively. Our data profiles a risk-stratification methodology in patients with LBBB and baseline EF >50% and possibly a triage strategy toward resynchronization therapy in this population.

The aim of the present study was to investigate whether vitamin D supplementation could improve biochemical findings and functional capacity of patients with heart failure (HF). One hundred patients with New York Heart Association (NYHA) class I through III HF were included in this prospective study and their 25-hydroxyvitamin D levels were evaluated. Only 6% of the participants had a sufficient serum concentration of 25(OH) D >30 nmol/L. Patients with insufficient or deficient serum levels of 25(OH) D (<30 ng/mL and <20 ng/mL, respectively) received oral vitamin D₃ (cholecalciferol) for a total period of 4 months. Vitamin D supplementation increased mean serum concentration of 25(OH) D from 12.63±7.60 nmol/L to 54.49±18.01 nmol/L (P<.001). After vitamin D supplementation, the serum level of pro-brain natriuretic peptide markedly decreased (P<.001). Cholecalciferol significantly decreased high-sensitivity C-reactive protein level (P<.001). Restoration of serum 25(OH) D level was also associated with substantial improvement in NYHA class (P<.001) and 6-minute walk distance (P<.001).

Cognitive impairment is common in heart failure (HF) and believed to be the result of cerebral hypoperfusion and subsequent brain changes including white matter hyperintensities (WMHs). The current study examined the association between cerebral blood flow and WMHs in patients with HF and the relationship between WMHs and cognitive impairment. Sixty-nine patients with HF completed the Mini-Mental State Examination (MMSE) and underwent echocardiography, transcranial Doppler sonography for cerebral blood flow velocity of the middle cerebral artery, and brain magnetic resonance imaging. Multivariable hierarchical regression analyses controlling for medical and demographic characteristics as well as intracranial volume showed reduced cerebral blood flow velocity of the middle cerebral artery was associated with greater WMHs (β=−0.34, P=.02). Follow-up regression analyses adjusting for the same medical and demographic factors in addition to cerebral perfusion also revealed marginal significance between increased WMHs and poorer performance on the MMSE (β=−0.26, P=.05). This study suggests that reduced cerebral perfusion is associated with greater WMHs in older adults with HF. These findings support the widely proposed mechanism of cognitive impairment in HF patients and prospective studies are needed to confirm these results.

Anemia, a common comorbidity in older adults with heart failure and a preserved ejection fraction (HFPEF), is associated with worse outcomes. The authors quantified the effect of anemia treatment on left ventricular (LV) structure and function as measured by cardiac magnetic resonance (CMR) imaging. A prospective, randomized single-blind clinical trial (NCT NCT00286182) comparing the safety and efficacy of epoetin alfa vs placebo for 24 weeks in which a subgroup (n=22) had cardiac magnetic resonance imaging (MRI) at baseline and after 3 and 6 months to evaluate changes in cardiac structure and function. Pressure volume (PV) indices were derived from MRI measures of ventricular volume coupled with sphygmomanometer-measured pressure and Doppler estimates of filling pressure. The end-systolic and end-diastolic PV relations and the area between them as a function of end-diastolic pressure, the isovolumic PV area (PVAiso), were calculated. Patients (75±10 years, 64% women) with HFPEF (EF=63%±15%) with an average hemoglobin of 10.3±1.1 gm/dL were treated with epoetin alfa using a dose-adjusted algorithm that increased hemoglobin compared with placebo (P<.0001). As compared with baseline, there were no significant changes in end-diastolic (−7±8 mL vs −3±8 mL, P=.81) or end-systolic (−0.4±2 mL vs −0.7±5 mL, P=.96) volumes at 6-month follow-up between epoetin alfa compared with placebo. LV function as measured based on EF (−1.5%±1.6% vs −2.6%±3.3%, P=.91) and pressure volume indices (PVAiso-EDP at 30 mm Hg, −5071±4308 vs −1662±4140, P=.58) did not differ between epoetin alfa and placebo. Administration of epoetin alfa to older adult patients with HFPEF resulted in a significant increase in hemoglobin, without evident change in LV structure, function, or pressure volume relationships as measured quantitatively using CMR imaging.

In heart failure (HF), longitudinal changes in ventricular ejection fraction are poorly studied. The authors' objective was to document the dynamic changes in systolic function of both ventricles during acute HF and after a 3-month follow-up period, and to identify factors associated with ventricular improvement. A limited access dataset from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial provided by The National Heart, Lung, and Blood Institute was analyzed. In patients admitted to the hospital with acute HF, both ventricles were evaluated by echocardiography on admission, at discharge, and at 3 months. From baseline to 3 months, left ventricular ejection fraction (LVEF) increased in 43.4% of patients, decreased in 23.9%, and remained unchanged in 32.7%. Similarly, right ventricular systolic function improved in 40.9%, deteriorated in 25.0%, and remained stable in 34.1%. Weight loss during index admission and cardiac index/cardiac output increase were the only factors associated with LVEF improvement from baseline to month 3. There was no difference between ischemic and nonischemic etiology. In acute HF, ischemic or nonischemic, systolic function of the ventricles improved during 3 months in about 40% of patients and remained unchanged or deteriorated in the rest. Weight loss and increase in cardiac index/output during hospitalization was associated with improvement in LVEF.

Despite current therapies and disease management approaches, rates of heart failure (HF) rehospitalization remain high. New tools are needed to assess preclinical (asymptomatic) pulmonary congestion to enable outpatient management. Hence, a novel monitoring system based on noninvasive remote dielectric sensing (ReDS) technology was developed. Validation of the ReDS technology was conducted in preclinical and clinical studies. In a porcine HF model, acute fluid overload followed by administration of diuretics were performed. Changes in ReDS values were correlated to serial computed tomographic (CT) assessments of lung fluid concentrations. In hospitalized decompensated HF patients, changes in ReDS values were correlated to net fluid balance changes. A nearly linear pattern between the changes in ReDS and CT fluid concentration values was observed in 6 discrete experiments (Intraclass correlation=0.95). Results from 24 patients demonstrated a reduction in ReDS values of 17.53%±11% throughout hospitalization, consistent with a reduction in pulmonary congestion. This finding strongly correlated with changes in net fluid balance (Pearson correlation=0.86; 95% confidence interval, 0.68–0.94; R²=0.74). These findings suggest that ReDS technology accurately quantifies lung fluid concentration and has potential for monitoring HF patients through hospitalization and possibly at home.

Worsening renal function (WRF) during treatment of acute decompensated heart failure (ADHF) is generally associated with adverse outcomes. An increase ≥0.3 mg/dL in creatinine level is widely used as the definition of WRF. The authors sought to determine the level of agreement between WRF based on changes in creatinine and changes in cystatin C (CysC) by analyzing data from 121 ADHF patients with available admission and day 3 creatinine and CysC levels. Admission creatinine and CysC levels were 1.39 (0.98–2.11) mg/dL and 1.95 (1.42–2.69) mg/L, respectively, and correlated well (r=0.81). On average, creatinine (−0.04±0.40 mg/dL) and CysC (0.001±0.34 mg/L) changed minimally from admission to day 3. Although the correlation between both markers on day 3 was still good (r=0.79), the correlation between changes therein was only modest (r=0.43). From the 14 and 15 patients who had WRF based on a ≥0.3 mg/dL increase in creatinine and ≥0.3 mg/L increase in CysC, respectively, only four (about 30%) met both definitions. These observations, together with recent insights in the inconsistencies of creatinine-defined concept of worsening renal function and outcomes, raises the need to research more reliable measures of renal function during treatment of ADHF.

High levels of B-type natriuretic peptide in cancer patients are poorly studied. Previously published data suggest that they are not related to fluid overload and are encountered mostly in solid cancers. The authors investigated the distribution of amino terminal pro-brain natriuretic peptide (NT-proBNP) between hematologic and solid organ malignancies and the relationship of NT-proBNP with volume status in oncologic patients. A total of 145 consecutive patients with at least one occurrence of NT-proBNP exceeding the upper normal range 10-fold were identified. The authors retrospectively reviewed their records including clinical, laboratory, and radiological data and echocardiograms. More than 70% of patients had hematologic malignancies. Patients with NT-proBNP >50,000 pg/mL had only hematologic malignancies, primarily multiple myeloma. There was no association between M-spike proteins and NT-proBNP. About 80% of patients had signs of fluid overload. The magnitude of NT-proBNP elevation was similar between those with and without heart failure or volume overload, as well as with solid cancers vs hematologic malignancies. Contrary to prior reports, it was found that very high NT-proBNP in cancer patients is usually encountered in the context of fluid overload and most often in hematologic malignancies.

Many proven heart failure (HF) therapies decrease N-terminal pro B-type natriuretic peptide (NT-proBNP) values over time, yet some patients have an NT-proBNP >1000 pg/mL following treatment, which is associated with poor outcomes. A total of 151 patients with left ventricular systolic dysfunction were treated with aggressive HF therapy in the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study. Clinical characteristics and NT-proBNP were measured at each visit during 10 months. In this post hoc analysis, biomarker nonresponse was defined as an NT-proBNP >1000 pg/mL and its relationship with echocardiographic and clinical characteristics and outcomes were explored. A risk model predictive of nonresponse was derived and externally validated. A rising NT-proBNP over time was associated with increased cardiovascular event rates while a decreasing NT-proBNP was associated with better clinical outcomes (58.2% vs 27.6%, P=.001). A higher percentage of time in biomarker response was associated with lower event rates (P<.001). Importantly, responders showed improved left ventricular remodeling parameters (all P<.001), while nonresponders did not. A risk model for predicting nonresponse had a C statistic of 0.82 (P<.001) and predicted outcomes well. Using data from the NT-proBNP–Assisted Treatment to Lessen Serial Cardiac Readmissions and Death (BATTLESCARRED) cohort, the risk score was validated for its ability to predict nonresponse (C statistic 0.73, P<.001). Serial changes in NT-proBNP inform risk for adverse outcome and are associated with prognostically meaningful metrics. Prediction of future NT-proBNP nonresponse to HF therapy is possible.

It has been assumed that less intense levels of care for managing heart failure result in a lowering of the overall costs for this care in the United States. The objective of this review was to determine whether this assumption is correct. A systematic review was performed using Medline, technology assessment Web sites, and relevant cardiovascular and heart failure journals from the year 2000 to the present. US randomized controlled trials where costs were evaluated as one of the endpoints were included. Data were collected using Cochrane Review characteristics of included studies and risk of bias assessment forms. Cost data from each trial were converted to a uniform cost definition and year. Meta-analysis was performed where appropriate. Ten trials were identified evaluating costs at various time points (3, 6, and 12 months). Meta-analysis of trials demonstrated no difference in costs for care, no matter the patient condition or settings. In high-quality trials examining costs, there may be a shifting in costs from more expensive care settings to less expensive care settings without savings to the healthcare system. Larger and longer-term trials should be undertaken to understand this issue.

Self-management intervention is a good method to improve self-care ability, as such, to promote quality of life. However, the research focused on self-management intervention in heart failure patients in Taiwan is very limited. Therefore, the purposes of this study were to test the effectiveness of self-management intervention in patients with heart failure in Taiwan and examine the relationship between self-care ability and quality of life. A quasi-experimental design was used in this study with convenience sampling. Of the 82 subjects participating in this study, 40 of them chose to join the experimental (self-management intervention plus usual care) and 42 of them chose to join control (usual care) group. Three questionnaires were used to collect the data, which were the demographic questionnaire, the self-care questionnaire (Self-Care of HF Index V 6), and the quality of life questionnaire (Minnesota Living with Heart Failure Questionnaire). To examine the effectiveness of the intervention, self-care ability and quality of life were measured, using a pretest, 1- and 2-month follow-up assessment. Generalized estimation equations (GEE) were used to compare changes over time among groups for outcomes to ensure the effectiveness of the intervention. This study confirmed the effectiveness of the self-management intervention. The clinical provider should increase the awareness of the importance of self-management skills and self-care ability especially for heart failure patients. The designated disease-specific self-management patient book and individualize intervention should be dispensing and implementing.

Iron insufficiency has been associated with heart failure, but the impact of a reduction of hemoglobin content in the erythrocytes as estimated by mean corpuscular hemoglobin concentration (MCHC) to myocardial structure, performance, and long-term clinical outcomes has not been well-established. The authors examined hematologic data and long-term outcomes of 197 ambulatory patients with chronic systolic and symptomatic heart failure who underwent comprehensive echocardiographic evaluation. The authors observed that relative hypochromia (defined as low MCHC) was associated with higher natriuretic peptide levels (NT-proBNP, r =−0.40, P<.0001) and lower estimated glomerular filtration rate (eGFR; r = 0.45, P <. 0001) and correlated modestly with indices of left and right ventricular diastolic dysfunction (all P<.05), but were not related to left ventricular ejection fraction (LVEF, r=0.17, P=.079). After 5 years of follow-up, lower MCHC levels were associated with higher risk of death, transplant, or heart failure hospitalization after adjusting for age, LVEF, eGFR, and New York Heart Association class (hazard ratio, 1.34; 95% confidence interval, 1.04–1.72; P=.025), particularly in those with above-median hemoglobin (>13.8 g/dL; hazard ratio, 2.02; 95% confidence interval, 1.44–2.81, P<.0001). Taken together, the observations imply that physicians should take notice of the presence of relative hypochromia particularly in the absence of anemia in the setting of chronic systolic heart failure.

In patients on conventional heart failure therapy including angiotensin-converting enzyme (ACE) inhibitors, the addition of angiotensin receptor blockers (ARBs), direct renin inhibitors (DRIs), or aldosterone antagonists are therapeutic options to further reduce the risk of cardiovascular events. However, whether one is preferable over the other is not known. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched for randomized clinical trials (RCTs), until March 2011, of trials testing either an ARB, DRI, or an aldosterone antagonist in patients with heart failure who were on conventional heart failure therapy with follow-up of at least 3 months. Efficacy (death, cardiovascular death, nonfatal myocardial infarction, heart failure hospitalization and composite of cardiovascular death or heart failure hospitalization) and safety (hyperkalemia, hypotension, renal failure) outcomes were compared. The authors identified 16 RCTs involving 31,429 participants that satisfied the inclusion criteria. When compared with placebo (reference rate ratio [RR] of 1), aldosterone antagonists reduced the rate of death (RR, 0.79; 95% credibility interval [CrI], 0.66–0.98), cardiovascular death (RR, 0.78; 95% CrI, 0.65–0.93), heart failure hospitalization (RR, 0.74; 95% CrI, 0.55–0.94), and the composite of cardiovascular death or heart failure hospitalization (RR, 0.73; 95% CrI, 0.55–0.90) with no difference for other efficacy outcomes. However, ARBs and DRIs did not result in any significant reduction in the rate of any of the efficacy outcomes when compared with placebo. When compared with placebo (RR=1), ARBs increased the rate of hyperkalemia (138% increase), renal failure (126% increase), and hypotension (63% increase). Similarly, aldosterone antagonists resulted in a 110% increase in hyperkalemia and DRIs with a 98% increase in hypotension. In patients with heart failure and reduced systolic function on conventional heart failure medications, the risk benefit ratio favors the addition of aldosterone antagonists over ARBs or DRIs.

Few studies have explored the clinical potentials of combined Cystatin C (Cys) and uric acid (UA) in heart failure (HF). The authors evaluated Cys and UA as predictors of clinical outcomes compared with conventional renal biomarkers. This prospective cohort study included 587 HF patients presenting with dyspnea. At admission, Cys, UA, and other renal measures including serum urea nitrogen (BUN), creatinine (Cr), and glomerular filtration rate (GFR) were obtained. The primary endpoint was the composite of cardiac death and rehospitalization for worsening HF. During a 25-month median follow-up period, 68 patients experienced clinical outcomes: 9 cardiac deaths and 59 HFs. They showed higher BUN and Cr values and lower GFR. Within these parameters, Cys and UA had the most favorable area under the curves, and patients with Cys ≥0.8 mg/L and UA ≥6.6 mg/dL showed more frequent events. The net reclassification improvement analysis showed the combination of Cys and UA had a greater incremental effect for cardiac prognosis. On multivariate Cox hazard analysis, Cys and UA were independent predictive markers for clinical outcomes. In HF patients presenting with dyspnea, Cys and UA appear to be more useful predictors of clinical events than other renal measures.

Diastolic dysfunction can be diagnosed on equilibrium radionuclide angiocardiography (ERNA) by a low peak filling rate (PFR) in the setting of a normal left ventricular ejection fraction (LVEF). The authors evaluated the relationship between diastolic dysfunction, LVEF, and end-diastolic volume (EDV). A total of 408 predominantly asymptomatic patients with an LVEF ≥50% by ERNA were studied. LVEF of patients with a low PFR was compared with the LVEF of patients with a normal PFR. Correlation analyses to evaluate the association between PFR and EDV were also performed. The LVEF of patients with a low PFR was lower than the LVEF of patients with normal PFR (59±7 vs 63%±7%; P<.01). There was no correlation between EDV and PFR (r=−0.04; P=.32). The results did not change when the EDV indices were used. In patients who had repeat scans, there was no correlation between the change in EDV and the change in PFR (r=0.16; P=.2). In asymptomatic patients undergoing ERNA who have normal systolic function, a low PFR can be associated with a lower LVEF, but it is not associated with changes in EDV. This suggests that diastolic dysfunction is associated with mild systolic dysfunction.

Pulmonary vascular resistance (PVR) has important prognostic implications in the assessment of patients with pulmonary hypertension. Using echocardiography to measure PVR would have the advantage of being able to follow patients serially and to assess their response to treatment noninvasively. The authors sought to assess whether right ventricular strain rate imaging (SRI) can predict PVR in patients with pulmonary hypertension. The study population consisted of 46 patients referred for right heart catheterization. The inclusion criteria was mean pulmonary artery pressure ≥25 mm Hg in right heart catheterization in patients with pulmonary hypertension including chronic systolic heart failure. Echocardiography was performed to obtain SRI just before right heart catheterization. Mean values of peak systolic longitudinal strain and strain rate obtained from basal and mid-right ventricular free wall were calculated. The control group consisted of 35 healthy adults matched for age and sex. The most significant correlations were between basal right ventricular strain and strain rate (SR) and mean pulmonary arterial pressure (r=0.63, P=.000), transpulmonary gradient (r=0.6, P=.001), and PVR (r=0.5, P=.003). SR was independently correlated with PVR (PVR=26.9−16.9×basal right ventricular SR; r=0.53, P=.003). The present study shows that basal right ventricular free wall strain and SR could be independently correlated with PVR in patients with pulmonary hypertension.

Despite the widespread use of loop diuretics to treat acute decompensated heart failure (ADHF), robust data supporting their role and optimal dosing strategies are scarce. This analysis aimed to compare clinical outcomes of patients admitted with ADHF who received a diuretic dosing protocol with those who received the usual diuretic therapy. We performed an observational medical records review to compare the use of a nurse-driven diuretic dosing protocol with usual diuretic dosing for patients admitted with ADHF during a 1-year period. Using a propensity scoring model, comparisons were made between groups for total weight loss, length of stay (LOS), 30-day readmissions, in-hospital mortality, 30-day mortality, and acute kidney failure. Sixty-eight of the 596 patients admitted with ADHF during the study period received the diuretic protocol. Protocol use was associated with an additional 2.63-kg weight loss (P=.003) but a trend toward increased LOS compared with patients receiving usual care (P=.097). However, patients receiving the protocol had a significantly lower risk of 30-day readmission (odds ratio, 0.46, 95% confidence interval, 0.22–0.95). Protocol use was not associated with significant differences in kidney failure, inpatient mortality, or 30-day mortality. A diuretic dosing protocol for patients admitted with ADHF improves weight loss and may lower 30-day readmissions, at the cost of potentially increasing LOS.

The authors sought to conduct a systematic review comparing the effects of exercise training in heart failure patients taking β-blockers vs those not. A systematic search of exercise training trials in chronic heart failure patients that compared groups who took β-blocker medication or compared selective and nonselective β-blockers during exercise training was conducted. Eight prospective studies met the criteria for the quantitative synthesis, which included data from 236 participants. The increment in peak oxygen consumption (VO₂) was greater in exercising vs control participants, with a mean difference (MD) of 1.27 mL/kg/min (95% confidence interval [CI], 0.85–1.70; P<.00001). In exercising patients, the increment in peak VO₂ was greater in the group taking β-blocker vs those taking placebo (MD, 1.66 mL/kg/min; 95% CI, 0.36–2.97; P=.01). In exercising patients, there was no difference in the increment of peak VO₂ between nonselective β-blocker and selective β-blockers groups (MD, −0.09 mL/kg/min; 95% CI, −1.54–1.36; P=.09). Minnesota Quality of Life Score was significantly better in the exercise group vs sedentary control group (both groups taking β-blockers) (MD, −11.3; 95% CI, −15.9 to −6.8; P<.00001). Our analysis demonstrated that β-adrenergic blocker therapy did not reduce exercise capacity or exercise training adaptations and quality of life in heart failure patients.

©2012 Wiley Periodicals, inc.

Although exercise is an important component of heart failure management, optimal regimens, particularly in heart failure with preserved ejection fraction (HFPEF), are uncertain. Tai chi (TC) is a mind-body exercise that may have potential benefits but has not been studied in this population. The authors randomized 16 patients with HFPEF to either 12 weeks TC or aerobic exercise. Assessments included peak oxygen uptake, 6-minute walk, quality of life, echocardiography, mood, and self-efficacy at baseline and at 12 weeks. Cardiorespiratory measures during exercise were obtained to characterize training intensities. Baseline characteristics were as follows: age 66±12 years, E/A ratio 1.3±0.7, and E/e′ ratio 15.9±4.8. Overall, adherence was excellent (89% attendance). Change in peak oxygen uptake was similar between groups after 12 weeks, but 6-minute walk distance increased more after TC (69±46 m vs 10±31 m, P=.02). While both groups had improved Minnesota Living With Heart Failure scores and self-efficacy, Profile of Mood States (POMS)-Depression scores improved more with TC (−1.7±2.8 vs 1.6±3, P=.05). Cardiorespiratory assessment during TC showed lower oxygen uptake (4.3 mL/kg/min vs 9.4 mL/kg/min, P<.01), respiratory rate, and heart rate. TC is feasible and safe in HFPEF. Therepeutic endpoints appear similar with TC relative to aerobic exercise despite a lower aerobic training workload.

Statins do not appear to have a significant benefit in heart failure (HF) as they do in coronary artery disease (CAD). Significant evidence exists that low serum cholesterol levels may be harmful in HF. This study sought to determine the optimal low-density lipoprotein (LDL) level in patients hospitalized with acute HF. Patients were included if they presented to the hospital with acute HF and had a lipid panel drawn during admission. The primary outcome was all-cause mortality, and secondary outcomes were rates of major cardiovascular (CV) events, left ventricular assist device (LVAD) implantation, and orthotopic heart transplantation (OHT). A total of 2428 patients were followed for a mean of 2.9±2.2 years. For the entire cohort, when compared with those with LDL levels >130 mg/dL, all-cause mortality was higher in those with LDL levels <71 mg/dL (hazard ratio, 1.68; 95% confidence interval, 1.31–2.167; P<.01). Results were similar when analyzing patients with LVEF ≤40%, HF of ischemic etiology only, and in statin users. The rates of CV events, LVAD implantation, or OHT in any comparison did not differ. Low LDL levels (<71 mg/dL), similar to low total cholesterol levels, were associated with a poorer prognosis and higher overall mortality in patients with HF, regardless of etiology and systolic function.

©2012 Wiley Periodicals, Inc.

Sildenafil is a selective phosphodiesterase-5 inhibitor and causes vasodilatation, particularly in pulmonary circulation. Since left heart failure may be associated with pulmonary hypertension “out of proportion to left heart disease,” sildenafil may have beneficial effect in such patients. The present investigation was designed as a 12-week, single-center, randomized, double-blind, placebo-controlled study evaluating the effects of sildenafil on mean blood pressure (primary endpoint) in patients with left systolic heart failure. Secondary endpoints included exercise capacity assessed by 6-minute walk test. A total of 106 patients were randomized 1:1 to sildenafil (n=53) or placebo (n=53). Patients received sildenafil 25 mg twice a day or matching placebo for the first 2 weeks and 50 mg 3 times a week for the remainder of the trial. The placebo-corrected effect on mean blood pressure was 1.16 mm Hg (95% confidence interval, −1.6 to 5.1, P >.05), demonstrating that sildenafil did not decrease mean blood pressure. Compared with placebo, sildenafil increased the 6-minute walk test by a nonsignificant treatment effect of 14 m (P=.67). Adverse effects occurred in a comparable proportion of patients taking sildenafil and placebo, and none of the patients needed to discontinue therapy. Sildenafil is well tolerated in left heart failure patients and does not decrease blood pressure. It can be safely added to standard heart failure therapy.