Effectiveness of β-Blockers in Heart Failure With Left Ventricular Systolic Dysfunction and Chronic Kidney Disease

BackgroundEstablishing medication effectiveness outside of a randomized trial requires careful study design to mitigate selection bias. Previous observational studies of β-blockers in patients with chronic kidney disease and heart failure have had methodologic limitations that may have introduced bias. We examined whether initiation of β-blocker therapy was associated with better outcomes among patients with chronic kidney disease and newly diagnosed heart failure with left ventricular systolic dysfunction.Methods and ResultsWe identified 668 adults in the Kaiser Permanente Northern California system from 2006 to 2008 with chronic kidney disease, incident heart failure, left ventricular systolic dysfunction, and no previous β-blocker use. We defined chronic kidney disease as estimated glomerular filtration rate <60 mL min^?1 1.73 m^?2 or proteinuria, and we excluded patients receiving dialysis. We used extended Cox regression to assess the association of treatment with death and the combined end point of death or heart failure hospitalization. Initiation of β-blocker therapy was associated with a significantly lower crude risk of death (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.35–0.63), but this association was attenuated and no longer significant after multivariable adjustment (HR 0.75, CI 0.51–1.12). β-Blocker therapy was significantly associated with a lower risk of death or heart failure hospitalization even after adjustment for potential confounders (HR 0.67, CI 0.51–0.88).Conclusionsβ-Blocker therapy is associated with lower risk of death or heart failure hospitalization among patients with chronic kidney disease, incident heart failure, and left ventricular systolic dysfunction.     

GFR in Patients with β-Thalassemia Major

Background and objectives

Patients with β-thalassemia major (TM) may have tubular dysfunction and glomerular dysfunction, primarily hyperfiltration, based on eGFR. Assessment of GFR based on serum creatinine concentration may overestimate GFR in these patients. This study sought to determine GFR by using inulin clearance and compare it with measured creatinine clearance (Ccr) and eGFR.

Design, setting, participants & measurements

Patients followed up in an Israeli thalassemia clinic who had been regularly transfused for years and treated with deferasirox were included in the study. They were studied by inulin clearance, Ccr, the CKD Epidemiology Collaboration and the Modification of Diet in Renal Disease equations for eGFR, and the Cockcroft–Gault estimation for Ccr. Expected creatinine excretion rate and tubular creatinine secretion rate were calculated.

Results

Nine white patients were studied. Results, given as medians, were as follows: serum creatinine was 0.59 mg/dl (below normal limits); GFR was low (76.6 ml/min per 1.73 m²) and reached the level of CKD; Ccr was 134.9 ml/min per 1.73 m², higher than the GFR because of a tubular creatinine secretion rate of 30.3 ml/min per 1.73 m² (this accounted for 40% of the Ccr); and eGFR calculated by the CKD Epidemiology Collaboration and Modification of Diet in Renal Disease equations and Cockcroft–Gault–estimated Ccr were 133, 141, and 168 ml/min per 1.73 m², respectively. These latter values were significantly higher than the GFR, reaching the hyperfiltration range, and indicated that the estimation techniques were clinically unacceptable as a method for measuring kidney function compared with the GFR according to Bland and Altman analyses.

Conclusions

Contrary to previous reports, patients in this study with TM had normal or reduced GFR. The estimating methods showed erroneous overestimation of GFR and were clinically unacceptable for GFR measurements in patients with TM by Bland and Altman analysis. Therefore, more accurate methods should be used for early detection of reduced GFR and prevention of its further decline toward CKD in these patients.     

Compliance with Deferoxamine Therapy and Thyroid Dysfunction of Patients with β-Thalassemia Major in Syria

Abstract

Hypothyroidism is one of the common endocrine complications described in patients with β-thalassemia major (β-TM). Studies have reported its incidence and severity depending on the region, quality of management and treatment protocols. The reported thyroid dysfunction includes overt hypothyroidism, subclinical hypothyroidism and rarely, central hypothyroidism. The main aims of this study were to identify the incidence of hypothyroidism in 82 patients with β-TM in Syria, and also to evaluate the effect of compliance with deferoxamine (DFO) therapy on the patients’ thyroid function. Out of the 82 patients included in this study, 24 had subclinical hypothyroidism (29.27%) and one patient had overt hypothyroidism (1.22%). It was demonstrated by this study that noncompliance with DFO therapy increases the risk of thyroid dysfunction 6.38-times compared to compliance with DFO [risk ratio (RR) = 6.385; 95% confidence interval (95% CI) 2.40-16.95)]. These results emphasize the importance of compliance with chelation therapy to minimize the burden of thyropathy on patients’ quality of life, and also augment the rationale for a routine follow-up and endocrine evaluation for early detection and management of these complications.     

Left Ventricular Dysfunction and Exercise Capacity Trajectory: Implications for Subclinical Heart Failure Staging Criteria

ObjectivesThis study aimed to determine the association of stage B heart failure (SBHF) and its constituent left ventricular (LV) abnormalities with trajectory of exercise capacity over time, and assess whether this association is modified by reversion of these LV abnormalities to normal.BackgroundThe LV abnormalities of SBHF may coincide with a reduction in exercise capacity that precedes the overt exercise intolerance of clinical heart failure (HF). Determining the predictive capacity of established and novel SBHF criteria for exercise capacity decline may improve HF risk stratification.MethodsLV structure/function (echocardiography) and exercise capacity (6-min walk distance [6MWD]) were assessed at baseline and 3-year follow-up in 268 patients from the NIL-CHF (Nurse-led Intervention for Less Chronic Heart Failure) study (all stage A [SAHF] or SBHF). Changes (Δ) in 6MWD were compared between SAHF and SBHF and across each of 4 constituent components of SBHF: LV hypertrophy, regional wall motion abnormality(ies) (RWMA), left ventricular systolic dysfunction (LVSD) (ejection fraction <45%) and elevated early diastolic filling/annular velocity ratio (E/e’ ≥15).ResultsΔ6MWD was similar in those with SAHF (n = 141) and SBHF (n = 127; ?5 m [95% confidence interval (CI): ?21 to +11 m]; covariate-adjusted). However, within the setting of SBHF there was substantive heterogeneity; that is, reductions in 6MWD were observed with persistent elevated E/e’ (?34 m [95% CI: ?62 to ?6 m]) and persistent LVSD (?41 m [95% CI: ?74 to ?8 m]), but not with LV hypertrophy (+17 m [95% CI: ?15 to +49 m) or RWMA (+5 m [?27 to +36 m]), nor in patients whose elevated E/e’ or LVSD reverted to normal by 3 years (p > 0.10).ConclusionsElevated E/e’ is associated with a similar degree of exercise capacity decline to LVSD, supporting that both LV functional criteria be considered in distinguishing SBHF from SAHF. That reversion of either manifestation of LV dysfunction was associated with preserved exercise capacity advocates targeting of these factors by HF preventive interventions.     

Study on Left Ventricular Diastolic Function under Different Left Ventricular Systolic Function

Ithasbecomeincreasinglyclearthatabnormali－tiesofdiastolicfunctionhaveamajorroleinproducingsignsandsymptomsinpatientspresentingwithhearfailure犤１，２犦．Asmanyasone－thirdofpatientswiththediagnosisofheartfailurehavenormalsystolicfunction，whichimplicates     

Comparison of Quality of Life in Patients with β-Thalassemia Intermedia and β-Thalassemia Major in Southern Iran

Increased life expectancy in patients with β-thalassemia (β-thal) requires healthcare professionals to give greater attention to improving their quality of life (QoL). We aimed to evaluate health-related QoL (HRQoL) and its determinants in patients with β-thal intermedia (β-TI) compared with β-thal major (β-TM). In this cross sectional study, 118 patients with β-TI, referred to the Thalassemia Clinic of Shiraz University of Medical Sciences, Shiraz, Iran, were investigated by convenience sampling from January to June 2014 in southern Iran. A Short Form-36 (SF36) questionnaire was used. We had previously conducted a similar study in 101 patients with β-TM (12 to 38 years). Compared data of the two studies were analyzed. Mean age was 26.5?±?6.5 (12 to 48) years in β-TI and 19.5?±?4.4 (12–38) years in the β-TM group. The best scales of HRQoL were physical functionin (PF) (76.8?±?26.6) and bodily pain (BP) (70.1?±?24.8) in the β-TI group. Males had significantly better score only in vitality dimension compared to females (p?=?0.020). Higher education (p?=?0.023) in univariate analysis and age ≤20 years (B coefficient?=?13, p?=?0.008) in multivariate analysis showed significant relationships with higher total HRQoL score in β-TI. Comparison of β-TI and β-TM, after adjusting for covariates, total HRQoL was similar between the two groups. In evaluating the subscales, only PF showed a better condition in patients with β-TM [adjusted mean difference?=?12.5, 95% confidence interval (95% CI): 5.6–19.3, p?相似文献   

Right Ventricular Failure—A Continuing Problem in Patients with Left Ventricular Assist Device Support

The discrepancy between the limited availability of donor hearts and the ever-increasing number of patients with heart failure has led to the increasing use of left ventricular assist devices (LVAD) as a bridge to transplant. One of the main complications inherent following institution of LVAD therapy is right ventricular (RV) failure, manifested by the need for inotropic and/or nitric oxide support >14 days after LVAD implant and/or the need for right-sided mechanical circulatory support. RV failure is a major contributor of significant morbidity and mortality after LVAD placement. The complex pathophysiology of RV failure, which could potentially be related to RV myocardial dysfunction, interventricular dependence, and RV afterload, has led to inconsistencies in predicting risk factors for RV dysfunction. Several strategies have evolved over the years of experience with mechanical circulatory support that have aimed to avoid as well as reduce the incidence of RV failure. It is imperative that patients who definitely need biventricular support are identified. Despite the numerous risk factors identified in many studies as well as the development of risk factor profile scores, this continues to be a challenging problem. However, the lower incidence of RV failure following LVAD in the current era is encouraging, suggesting a favorable relationship between RV unloading and function, and continuous-flow physiology.     

Marital Status and Fertility in Adult Iranian Patients with β-Thalassemia Major

Expecting a family is an important component and a great goal for better quality of life for most of adults with β-thalassemia major. The aim of the present study was to examine the marital status of adults with β-thalassemia major. This cross-sectional study examined the marital status of patients with transfusion-dependent β-thalassemia aged over 15 years. Patients’ demographic characteristics including age, gender, marital status, duration of marriage, divorce, having or not having children and spouse’s health status were recorded. Information about the disease including cardiac and endocrine complications, ferritin level, splenectomy and viral hepatitis were also recorded. Of 228 patients with transfusion-dependent β-thalassemia major aged over 15 years who were treated at this medical center, 32 (14 %) were married. The mean age of married patients was 25.18 ± 4.74 years. Among the married patients, 8 (25 %) were females and 24 (75 %) patients were males. The mean age of marriage was 22.76 ± 4.16 years. The minimum and maximum marriage age was 15 and 33 years, respectively. The median duration of marriage was one year with the range from 3 months to 11 years. Only 8 (25 %) patients (one female and seven males) had children. Therapeutic advances have led to significantly increased survival and improved quality of life and fertility of patients with β-thalassemia major. According to the results, 14 % of patients over 15 years were married which was slightly higher as compared with other similar studies.     

Epidemiology of Left Ventricular Systolic Dysfunction and Heart Failure in the Framingham Study: An Echocardiographic Study Over 3 Decades

Objectives

The purpose of this study was to describe the temporal trends in prevalence of left ventricular systolic dysfunction (LVSD) in individuals without and with heart failure (HF) in the community over a 3-decade period of observation.

Heart Function Challenged with β-Receptor Agonism or Antagonism in a Heart Failure Model

We have shown that chronic treatment with carteolol, a non-selective -adrenergic receptor antagonist, improved left ventricular (LV) function and survival in an avian model of dilated cardiomyopathy (DCM). The aim of the present study was to compare ex vivo heart function with and without -agonist and antagonist challenge. We investigated whether intracoronary infusion of a -blocker, carteolol or -agonist, isoproterenol decreased contractility. In the DCM group, isoproterenol resulted in a significantly greater increase in heart rate (71% vs. 28% compared to control hearts). To investigate the mechanism for the increase in heart rate, we exposed spontaneously beating neonatal cardiomyocytes to serum immunoglobulin (IgG) isolated from DCM animals. Serum IgG resulted in a significant increase in spontaneous beating rate in neonatal rat cardiomyocytes that was blocked by pre-treatment with a -blocker. Carteolol challenge did not significantly change heart rate but did significantly increase LV peak pressure in DCM hearts (62%) while coronary artery flow remained unchanged (2.7 ± 0.1 vs 2.7 ± 0.5 ml/min/g). These results show that 1) -receptor stimulation results in a greater tachycardic response in DCM animals, and 2) carteolo challenge improves myocardial contractility in hearts from DCM animals independent of heart rate or changes in coronary artery flow.     

The Impact of Left Ventricular Diastolic Dysfunction on Clinical Outcomes After Transcatheter Aortic Valve Replacement

Objectives

This study sought to determine the impact of left ventricular diastolic dysfunction (LVDD) on clinical outcomes in patients undergoing transcatheter aortic valve replacement (TAVR).

Heart Transplantation and Left Ventricular Assist Device Therapy: Two Comparable Options in End‐Stage Heart Failure?

Heart transplantation is the only curative therapy for chronic heart failure, and it plays an important role in the treatment of chronic heart failure with a survival rate of approximately 50% of all patients after 10 years. This has to be kept in mind when alternative therapies enter into our daily routine in treating this patient population. However, the shortage of appropriate donor organs and the expanding pool of patients waiting for heart transplantation have led to growing interest in alternative strategies, particularly in left ventricular assist device (LVAD) therapy. With growing clinical experience and continued technical advances, continuous‐flow pumps are evolving as a bridge to transplantation or as a destination therapy for advanced heart failure. Nevertheless, the importance of this new indication of chronic cardiac support compared to heart transplantation is still completely open and the object of controversial ongoing discussion. This review (1) describes the clinical use and long‐term outcome of a currently available miniaturized LVAD in the context to the standard of care—heart transplantation, (2) provides an outlook of the ongoing process of further optimization of LVADs, and (3) comments on the challenges with assist devices as alternatives to transplantation with a 5‐year outlook.     

Ventricular Ectopy in Patients With Left Ventricular Dysfunction: Should It Be Treated?

Ventricular premature complexes (VPCs) are commonly encountered in patients with congestive heart failure (CHF). Frequent ventricular ectopy can be associated with deterioration of cardiac function and may lead to VPC-induced cardiomyopathy. VPC-induced inter- and/or intraventricular dyssynchrony has been postulated as the main mechanism underlying VPC-induced left ventricular dysfunction. For risk stratification, VPCs in the setting of CHF can not be regarded to be a benign arrhythmia as in an apparently healthy subject. However, any potential survival benefits to be derived from suppression of VPCs or nonsustained ventricular tachycardia in CHF may be offset by the negative inotropic and proarrhythmic effects of antiarrhythmic drugs and may be masked by the risk of death that is already high in this subgroup of patients. β-Blockers are currently considered to be the first-line therapy, with amiodarone as a back-up. Catheter ablation, although invasive and not without procedural risk, avoids the common adverse effects of currently available antiarrhythmic medications. From a standpoint of preventing or reversing left ventricular dysfunction, frequent VPCs should be treated earlier regardless of their site of origin or the presence of associated symptoms, such as palpitations. Catheter ablation may be the preferable approach in selected patients, particularly when β-blocker therapy has been ineffective or not tolerated.