Background Previous studies have not extensively examined the association of hyperuricemia and adverse outcomes in systolic heart failure (HF) in relation to xanthine oxidase inhibitor therapy. ...Methods The Prospective Randomized Amlodipine Survival Evaluation study included New York Heart Association class IIIB or IV patients with left ventricular ejection fraction <30%. For analysis, the population was divided into uric acid quartiles among nonallopurinol users (2.2-7.1, >7.1-8.6, >8.6-10.4, >10.4 mg/dL) and those using allopurinol. Multivariate Cox regression modeling was performed to identify predictors of mortality. Uric acid quartile and allopurinol groups were referenced to the lowest uric acid quartile. Results A total of 1,152 patients were included. In general, patients in the allopurinol group and in the highest uric acid quartile had indicators of more severe HF, including worse renal function and greater proportion of New York Heart Association class IV patients, and greater diuretic use. The allopurinol group and highest uric acid quartile had the highest total mortality (41.7 and 42.4 per 100 person-years, respectively) and combined morbidity/mortality (45.6 and 51.0 per 100 person-years, respectively). Allopurinol use and highest uric acid quartile were independently associated with mortality (hazard ratio HR 1.65, 95% CI 1.22-2.23, P = .001 and HR 1.35, 95% CI 1.07-1.72, P = .01, respectively) and combined morbidity/mortality (uric acid quartile 4 vs 1: HR 1.32, 95% CI 1.06-1.66, P = .02; allopurinol use: HR 1.48, 95% CI 1.11-1.99, P = .008). Conclusion Elevated uric acid level was independently associated with mortality in patients with severe systolic HF, even when accounting for allopurinol use.
Limited information is available about gender and ethnic differences in red cell distribution width (RCDW) with regard to its relation to mortality in a population free of cardiovascular (CV) disease ...and diabetes. To assess gender and ethnic differences in RCDW and their effect on the association between RCDW and mortality, the Third National Health and Nutritional Examination Survey (n = 15,460, 1988 to 1994) data were examined. Multivariate adjusted Cox proportional hazard analysis was performed to assess effect of gender and ethnicity on the association between RCDW and mortality (total, CV disease, and coronary heart disease CHD). RCDW (mean ± SE) was greater in black women (13.1 ± 0.03) and men (13.4 ± 0.02) compared to women of white (12.9 ± 0.02) and other (13.0 ± 0.07) ethnicities and men of white (13.3 ± 0.02) and other (13.3 ± 0.07) ethnicities, respectively (p <0.001). The interaction between RCDW and gender was statistically significant for all study outcomes (p <0.001) but nonsignificant for RCDW and ethnicity. After adjusting for key variables, RCDW in women was associated with adjusted hazard ratios of 1.22 (95% confidence interval CI 1.14 to 1.31) for all-cause mortality, 1.17 (95% CI 1.07 to 1.28) for CV deaths, and 1.18 (95% CI 1.03 to 1.35) for CHD deaths; in men, adjusted hazard ratios were 1.29 (95% CI 1.20 to 1.38) for all-cause mortality, 1.27 (95% CI 1.17 to 1.37) for CV deaths, and 1.25 (95% CI 1.13 to 1.39) for CHD deaths (p <0.05 for all). In conclusion, blacks and men have significantly greater RCDWs compared to whites and women. Greater RCDW is associated with a greater risk of mortality in men compared to women, whereas no effect modification is observed by ethnicity.
Substantial evidence suggests that anemia is an independent risk factor for worse outcomes in patients with heart failure (HF). The Study of Anemia in Heart Failure Trial (STAMINA-HeFT) is the ...largest multicenter, randomized, double-blind, placebo-controlled trial to date evaluating the effect of treating anemia in HF.
Patients (N=319) with symptomatic HF, left ventricular ejection fraction < or = 40%, and hemoglobin > or = 9.0 g/dL and < or = 12.5 g/dL were randomized (double-blind) to placebo (N=157) or darbepoetin alfa (N=162) subcutaneously every 2 weeks for 1 year (target hemoglobin, 14.0+/-1.0 g/dL). The primary end point was change from baseline to week 27 in treadmill exercise time. Secondary end points were change from baseline in New York Heart Association class and quality of life at week 27. An additional prespecified efficacy analysis included the time to death by any cause or first HF-related hospitalization by 1 year. At baseline, the median (interquartile range) hemoglobin was 11.4 (10.9, 12.0) g/dL. At week 27, darbepoetin alfa treatment increased median (interquartile range) hemoglobin by 1.8 (1.1, 2.5) g/dL (placebo, 0.3 -0.2, 1.0 g/dL; P<0.001). Of the patients treated with darbepoetin alfa, 85% achieved 2 consecutive hemoglobin levels of 14.0+/-1.0 g/dL during the study and experienced a hemoglobin increase of > or = 1.0 g/dL from baseline. By intent-to-treat analysis, darbepoetin alfa treatment did not significantly improve exercise duration, New York Heart Association class, or quality of life score compared with placebo. A nonsignificant trend was observed toward a lower risk of all-cause mortality or first HF hospitalization in darbepoetin alfa-treated patients compared with placebo (hazard ratio, 0.68; 95% CI, 0.43, 1.08; P=0.10). Occurrences of adverse events were similar in both treatment groups.
In this study of patients with symptomatic HF and anemia, treatment with darbepoetin alfa was not associated with significant clinical benefits. Darbepoetin alfa treatment was well tolerated and effectively raised hemoglobin. A trend of lower risk of morbidity and mortality was observed.
Arginine vasopressin (AVP) is a neuropeptide hormone that plays an important role in circulatory and sodium homeostasis, and regulating serum osmolality. Several clinical conditions have been ...associated with inappropriately elevated levels of AVP including heart failure, cirrhosis of the liver and the syndrome of inappropriate secretion of antidiuretic hormone. Three receptor subtypes that mediate the actions of AVP have been identified (V(1A), V(2) and V(1B)). Activation of V(1A) receptors located in vascular smooth muscle cells and the myocardium results in vasoconstriction and increased afterload and hypertrophy. The V(2) receptors located primarily in the collecting tubules mediate free water absorption. The V(1B) receptors are located in the anterior pituitary and mediate adrenocorticotropin hormone release. The cardiovascular and renal effects of AVP are mediated primarily by V(1A) and V(2) receptors. Antagonism of V(1A) receptors results in vasodilatation and antagonism of V(2) receptors resulting in aquaresis, an electrolyte-sparing water excretion. Several non-peptide AVP antagonists (vasopressin receptor antagonists VRAs) also termed 'vaptans' have been developed and are vigorously being studied primarily for treating conditions characterised by hyponatraemia and fluid overload. Conivaptan is a combined V(1A)/V(2)-receptor antagonist that induces diuresis as well as haemodynamic improvement. It has been shown in clinical trials to correct euvolaemic and hypervolaemic hyponatraemia, and has been approved by the US FDA for the treatment of euvolaemic hyponatraemia as an intravenous infusion. Tolvaptan, a selective V(2)-receptor antagonist, has undergone extensive clinical studies in the treatment of hyponatraemia and heart failure. It has been shown to effectively decrease fluid in volume overloaded patients with heart failure and to correct hyponatraemia. A large outcome study (n = 4133 patients) will define its role in the management of heart failure. Lixivaptan and satavaptan (SR-121463) are other selective V(2)-receptor antagonists being evaluated for the treatment of hyponatraemia. In addition, a potential role for the vaptans in attenuating polyuria in nephrogenic diabetes insipidus and cyst development in polycystic kidney disease is being explored. Ongoing clinical trials should further define the scope of the potential therapeutic role of VRAs.
Anemia and heart failure Ghali, Jalal K
Current opinion in cardiology
24, Številka:
2
Journal Article
Recenzirano
The earlier enthusiasm for raising hemoglobin in heart failure has been followed by skepticism and concern of potential harm from using erythropoiesis-stimulating agents (ESAs).
Several recent ...studies have confirmed the high prevalence and prognostic role of anemia and have shown encouraging signals of the safety of using ESAs in heart failure and potential benefit that may be related to nonhematopoietic effects of ESAs. In addition, recent studies have also suggested a potential beneficial role of iron replacement in heart failure.
Despite the encouraging findings of these preliminary studies, the future role of ESAs and iron replacement will be determined by ongoing randomized placebo-controlled studies.
Nearly 1 million hospitalizations for chronic heart failure occur yearly in the United States, with most related to worsening systemic congestion. Diuretic use, the mainstay therapy for congestion, ...is associated with electrolyte abnormalities and worsening renal function. In contrast to diuretics, the vasopressin antagonist tolvaptan may increase net volume loss in heart failure without adversely affecting electrolytes and renal function.
To evaluate the short- and intermediate-term effects of tolvaptan in patients hospitalized with heart failure.
Randomized, double-blind, placebo-controlled, parallel-group, dose-ranging, phase 2 trial conducted at 45 centers in the United States and Argentina and enrolling 319 patients with left ventricular ejection fraction of less than 40% and hospitalized for heart failure with persistent signs and symptoms of systemic congestion despite standard therapy.
After admission, patients were randomized to receive 30, 60, or 90 mg/d of oral tolvaptan or placebo in addition to standard therapy, including diuretics. The study drug was continued for up to 60 days.
In-hospital outcome was change in body weight at 24 hours after randomization; outpatient outcome was worsening heart failure (defined as death, hospitalization, or unscheduled visits for heart failure) at 60 days after randomization.
Median (interquartile range) body weight at 24 hours after randomization decreased by -1.80 (-3.85 to -0.50), -2.10 (-3.10 to -0.85), -2.05 (-2.80 to -0.60), and -0.60 (-1.60 to 0.00) kg in the groups receiving tolvaptan 30, 60, and 90 mg/d, and placebo, respectively (P< or =.008 for all tolvaptan groups vs placebo). The decrease in body weight with tolvaptan was not associated with changes in heart rate or blood pressure, nor did it result in hypokalemia or worsening renal function. There were no differences in worsening heart failure at 60 days between the tolvaptan and placebo groups (P =.88 for trend). In post hoc analysis, 60-day mortality was lower in tolvaptan-treated patients with renal dysfunction or severe systemic congestion.
Tolvaptan administered in addition to standard therapy may hold promise for management of systemic congestion in patients hospitalized for heart failure.
Here We Go Again Ghali, Jalal K., MD
Journal of the American College of Cardiology,
07/2013, Letnik:
62, Številka:
5
Journal Article
Recenzirano
Odprti dostop
...would the authors care to speculate on a potential mechanism for the suggested synergistic effect of carvedilol in patients with left bundle branch block?
Heart failure with reduced ejection fraction (HFrEF) is defined as the presence of typical symptoms of heart failure (HF) and a left ventricular ejection fraction ≤ 40%. HFrEF patients constitute ...approximately 50% of all patients with clinical HF. Despite breakthrough discoveries and advances in the pharmacologic management of HF, HFrEF patients continue to pose a significant economic burden due to a progressive disease characterized by recurrent hospitalizations and need for advanced therapy. Although there are effective, guideline-directed medical therapies for patients with HFrEF, a significant proportion of these patients are either not on appropriate medications’ combination or on optimal tolerable medications’ doses. Since the morbidity and mortality benefits of some of the pharmacologic therapies are dose-dependent, optimal medical therapy is required to impact the burden of disease, quality of life, prognosis, and to curb health care expenditure. In this review, we summarize landmark trials that have impacted the management of HF and we review contemporary pharmacologic management of patients with HFrEF. We also provide insight on general considerations in the management of HFrEF in specific populations. We searched PubMed, Scopus, Medline and Cochrane library for relevant articles published until April 2019 using the following key words “heart failure”, “management”, “treatment”, “device therapy”, “reduced ejection fraction”, “guidelines”, “guideline directed medical therapy”, “trials” either by itself or in combination. We also utilized the cardiology trials portal to identify trials related to heart failure. We reviewed guidelines, full articles, review articles and clinical trials and focused on the pharmacologic management of HFrEF.
This study sought to understand prognostic implications of increased baseline left ventricular (LV) mass and geometric patterns in a high risk acute myocardial infarction.
The LV hypertrophy and ...alterations in LV geometry are associated with an increased risk of adverse cardiovascular events.
Quantitative echocardiographic analyses were performed at baseline in 603 patients from the VALIANT (VALsartan In Acute myocardial iNfarcTion) echocardiographic study. The left ventricular mass index (LVMi) and relative wall thickness (RWT) were calculated. Patients were classified into 4 mutually exclusive groups based on RWT and LVMi as follows: normal geometry (normal LVMi and normal RWT), concentric remodeling (normal LVMi and increased RWT), eccentric hypertrophy (increased LVMi and normal RWT), and concentric hypertrophy (increased LVMi and increased RWT). Cox proportional hazards models were used to evaluate the relationships among LVMi, RWT, LV geometry, and clinical outcomes.
Mean LVMi and RWT were 98.8 +/- 28.4 g/m(2) and 0.38 +/- 0.08. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, heart failure, stroke, or resuscitation after cardiac arrest was lowest for patients with normal geometry, and increased with concentric remodeling (hazard ratio HR: 3.0; 95% confidence interval CI: 1.9 to 4.9), eccentric hypertrophy (HR: 3.1; 95% CI: 1.9 to 4.8), and concentric hypertrophy (HR: 5.4; 95% CI: 3.4 to 8.5), after adjusting for baseline covariates. Also, baseline LVMi and RWT were associated with increased mortality and nonfatal cardiovascular outcomes (HR: 1.22 per 10 g/m(2) increase in LVMi; 95% CI: 1.20 to 1.30; p < 0.001) (HR: 1.60 per 0.1-U increase in RWT; 95% CI: 1.30 to 1.90; p < 0.001). Increased risk associated with RWT was independent of LVMi.
Increased baseline LV mass and abnormal LV geometry portend an increased risk for morbidity and mortality following high-risk myocardial infarction. Concentric LV hypertrophy carries the greatest risk of adverse cardiovascular events including death. Higher RWT was associated with an increased risk of cardiovascular complications after high-risk myocardial infarction.
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