Characteristics Associated with Upper-Range Doses of Beta-Blockers and Angiotensin-Renin Inhibitors in Reduced Ejection Fraction.

BACKGROUND: Heart failure (HF) patients with reduced ejection fraction (HFrEF) are frequently treated with sub-optimal doses of angiotensin converting enzyme-inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and beta blockers (BBs). OBJECTIVES: To determine factors associated with attaining upper-range doses in patients with HFrEF. METHODS: We examined treatment in patients with left ventricular ejection fraction (LVEF) ≤ 40% in a community-based, dedicated heart-failure clinic. Upper-range doses were defined as ≥ 75% of target recommended doses by heart failure society guidelines. RESULTS: The majority of the 215 patients were men (82%); median age at presentation 73 years (interquartile range [IQR] 65-78) and LVEF of 30% (IQR 25-35%). Following the up-titration program, 41% and 35% of patients achieved upper-range doses of ACE-Is/ARBs and BBs, respectively. Higher body mass index (BMI) was the only parameter found to be associated with achieving upper-range doses of ACE-I/ARBs (odds ratio [OR] 1.13, 95% confidence interval [95%CI] 1.05-1.22, P = 0.001). More patients achieved this target as BMI increased, with a sharp decline in the highest obesity category (BMI ≥ 40 m2/kg). Attaining upper-range doses of BBs was associated with pre-existing diabetes mellitus (DM) (OR 2.6, 95%CI 1.34-5.19, P = 0.005); women were associated with attaining lower BBs doses (OR 0.34, 95%CI 0.13-0.90, P = 0.031). CONCLUSIONS: Achieving upper-range doses of ACE-Is/ARBs and BBs in HFrEF outpatients in a treatment up-titration program were associated with greater BMI and DM, respectively. These findings may serve as benchmarks for up-titration programs.

The Effect of Mineralocorticoid Receptor Antagonists on Recruitment and Function of Endothelial Progenitor Cells in Patients with Congestive Heart Failure.

BACKGROUND: Circulating endothelial progenitor cells have an important role in the process of vascular repair. Impaired recruitment and function of endothelial progenitor cells is related to the pathophysiology of congestive heart failure. Endothelial progenitor cells have been shown to express the mineralocorticoid receptor. OBJECTIVES: To investigate the effect of mineralocorticoid receptor antagonists on endothelial progenitor cells in patients with heart failure. METHODS: Twenty-four patients with compensated heart failure, who were not under mineralocorticoid receptor antagonist therapy, were recruited. Either eplerenone (n=8) or spironolactone (n=16) therapy was initiated. Circulating endothelial progenitor cell level, identified as the proportion of mononuclear cells expressing vascular endothelial growth factor receptor 2 (VEGFR-2), CD133, and CD34, was evaluated by flow cytometry at baseline and after 8 weeks. Following 7 days of culture, colonies were counted by microscopy and MTT assay was performed on randomly selected patients (n=12) to estimate viability. RESULTS: Both median CD34+/VEGFR2+ and median CD133+/VEGFR2+ increased significantly (P = 0.04 and 0.02, respectively). However, the number of colonies and viability of the cells after therapy (as assessed by the MTT assay) was not significantly different compared with the baseline. CONCLUSIONS: These preliminary results suggest that mineralocorticoid receptor blockade may enhance endothelial progenitor cells recruitment in patients with compensated heart failure.

Right ventricular function and prognosis in stable heart failure patients.

BACKGROUND: Right ventricular ejection fraction (RVEF) is a mortality predictor in heart failure (HF) patients. There are controversial results regarding the influence of RVEF on other important prognostic variables. The purpose of this study was to investigate the effect of RVEF on exercise parameters obtained during cardiopulmonary exercise testing (CPET), creatinine and B-type natriuretic peptide (BNP) levels, and a composite outcome of death, heart transplantation, or ventricular assist device implantation in ambulatory HF patients. METHODS AND RESULTS: This retrospective cohort study included 246 ambulatory HF patients with CPET and RVEF evaluated with the use of first-pass radionuclide angiography. We analyzed the impact of RVEF on other prognostic factors with the use of multivariable linear regression. The mean age was 49 ± 12 years. The mean peak VO2 was 16.4 ± 5.7 mL kg(-1) min(-1), mean peak VE/VCO2 34.1 ± 9.1, mean creatinine 1.17 ± 0.40 mg/dL, and median BNP 158 pg/mL (interquartile range 374 pg/mL). The mean left ventricular ejection fraction was 35 ± 12% and the mean RVEF 38 ± 10%. For every 10% decrease in RVEF, peak VO2 decreased 0.97 mL kg(-1) min(-1) (P < .05), creatinine increased 0.12 mg/dL (P < .01), and log BNP increased 0.26 (P < .05). CONCLUSIONS: We found an independent association between RVEF and prognostic markers in HF patients. Worsening RV function may exert its negative effect on prognosis through increasing congestion (elevated BNP), affecting renal blood flow (increased creatinine) and limiting left ventricular preload, thereby reducing exercise tolerance.

Comparison of 18-Month Outcomes of Ambulatory Patients With Reduced (≤40%) Left Ventricular Ejection Fraction Treated in a Community-Based, Dedicated Heart Failure Clinic Versus Treated Elsewhere.

We sought to examine the management and outcomes of ambulatory patients with heart failure and reduced ejection fraction in a community-based, dedicated clinic. Patients with left ventricular ejection fraction (LVEF) ≤40% were actively solicited to attend a community-based, dedicated clinic. Eligible patients who chose to decline constituted our control group. Of 552 patients with LVEF ≤40% (median age 73 years and median LVEF 35%), 304 (55%) agreed to attend the clinic. Patients with worse New York Heart Association class were more likely to attend the clinic (odds ratio 2.07 [1.45, 2.95], p <0.001), whereas women were more likely to decline (odds ratio 0.63 [0.42, 0.93], p <0.022). During 18 months of follow-up, patients in the dedicated clinic significantly improved their functional capacity (56% New York Heart Association 3 to 4 at baseline vs 27% at follow-up, p <0.001) and LVEF (35% [interquartile range 25, 35] at baseline vs 35% (interquartile range 30, 40) at follow-up, p <0.001). In comparison with patients managed routinely, patients treated in a dedicated clinic achieved better guideline-recommended pharmacological treatment (65% vs 85% receiving ß blockers, p <0.001, 65% vs 82% receiving renin-angiotensin inhibitors, p = 0.0006, 31% vs 45% receiving mineralocorticoid receptor antagonists, p <0.001). During follow-up, electrical device implantation was similar (6% vs 7% of dedicated-HF-clinic patients, p = 0.700). Furthermore, overall survival was better in patients treated in the clinic (log rank p = 0.0006), even after censoring the first 4 months to account for potential bias (log rank p = 0.0232). In conclusion, management in a community-based, dedicated clinic compared with routine management was associated with augmented guideline-recommended treatment and improved survival.

Serum NT-proBNP concentrations in the early phase do not predict the severity of systolic or diastolic left ventricular dysfunction among patients with ST-elevation acute myocardial infarction.

The cohort included 55 consecutive patients with first ST elevation acute myocardial infarction (STEAMI) who underwent reperfusion. Blood samples were drawn for N-terminal pro B-type natriuretic peptide (NT-proBNP), highly-sensitive C-reactive protein (hs-CRP), creatinine kinase (CK), cardiac troponin l (cTnl), and white blood cell (WBC) count within 24 hours of admission. Transthoracic echocardiography, performed within the same time frame, assessed left ventricular (LV) systolic function, as well as diastolic function. Variables significantly associated with poor systolic LV dysfunction were hs-CRP, peak CK, cTnl, and WBC. There was no significant correlation between NT-proBNP and systolic function early after STEAMI (p=0.49). Among patients with diastolic dysfunction, there was no significant correlation between NT-proBNP levels and peak mitral E-wave velocity to peak initial A-wave velocity (E/A ratio) (r =0.19, p=0.18) or E-wave deceleration time (r =0.22, p=0.15). Thus, NT-proBNP levels in the early phase after STEAMI were not indicative of systolic or diastolic function.

Sexual function in patients supported with left ventricular assist device and with heart transplant.

AIMS: Sexual dysfunction is common among patients with heart failure (HF) and considered an important hamper to quality of life. While implantation of left ventricular assist device (LVAD) may prolong and improve life in advanced HF, limited data are available on its impact on sexual function. The aim of this study is to evaluate sexual function in LVAD patients and compare this with patients after heart transplantation (HTx). METHODS AND RESULTS: Sexual activity and satisfaction of stable patients with durable LVAD or after HTx were evaluated using a validated questionnaire and visual analogue scale from 0 to 10. Data were collected from 31 patients (mean age 59 ± 12 years, 87% male), 17 after HTx and 14 with LVAD. Pleasure or satisfaction with sex was significantly higher in HTx patients (P = 0.0005). In total, 29% LVAD patients and 71% HTx patients reported content with sexual activity. Recalled satisfaction with sex life pre-operation was comparable between the groups. During support, satisfaction with sex life using visual analogue scale was 7.6 ± 3.1 for HTx versus 3.9 ± 4.0 for LVAD patients (P = 0.017). In total, 11 LVAD patients (79%) reported specific problems in sexual function including erectile dysfunction or vaginal dryness (8, 57%); problems with the LVAD, cable, or batteries (5, 36%); problems with orgasm (4,29%); and other problems such as fear of injury, feeling depressed, partner issues, self-image, and pain (1, 7% each). CONCLUSION: Sexual dysfunction occurs in patients with LVAD support and may be more prominent than after HTx. Problems limiting sexual function related to physiological, psychological, and equipment merit consideration during follow-up.

Outcome of emergency percutaneous coronary intervention for acute ST-elevation myocardial infarction complicated by cardiac arrest.

BACKGROUND: The poor prognosis of primary percutaneous coronary intervention (PCI) in patients resuscitated from cardiac arrest complicating acute ST-segment elevation myocardial infarction (STEMI) may at least partly be explained by the common presence of cardiogenic shock. This study examined the impact of emergency primary PCI on outcome in patients with STEMI not complicated by cardiogenic shock who were resuscitated from cardiac arrest. METHODS AND RESULTS: The study group included 948 consecutive patients without cardiogenic shock who underwent emergency primary PCI from 2001 to 2006 for STEMI. Twenty-one of them were resuscitated from cardiac arrest before the intervention. Data on background, clinical characteristics, and outcome were prospectively collected. There were no differences between the resuscitated and nonresuscitated patients in age, sex, infarct location, or left ventricular function. The total one-month mortality rate was higher in the resuscitated patients (14.3 vs. 3.4%, P=0.033), but noncardiac mortality accounted for the entire difference (14.3 vs. 1.2%, P=0.001), whereas cardiac mortality was similarly low in the two groups (0 vs. 2.0%, P=NS). Predictors of poor outcome in the resuscitated patients were older age (r=0.47, P=0.032), unwitnessed sudden death (r=0.44, P=0.04), longer interval between onset of cardiac arrest and arrival of a mobile unit (r=0.67, P=0.001) or to spontaneous circulation (r=0.65, P=0.001), low glomerular filtration rate (r=-0.50, P=0.02), and the initial thrombolysis in myocardial infarction grade of flow (r=-0.51, P=0.017). CONCLUSION: Emergency PCI for STEMI not associated with cardiogenic shock exerts a similar effect on cardiac mortality in patients who were resuscitated from cardiac arrest and in those without this complication. The higher all-cause mortality rate among resuscitated patients is explained by noncardiac complications.