Impact of converting enzyme inhibition on progression of chronic heart failure: results of the Munich Mild Heart Failure Trial.

Kleber, Franz X.; Niemöller, Lisa; Doering, W.

doi:10.1136/hrt.67.4.289

Cited by 111 publications

(35 citation statements)

References 31 publications

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“…Complications were defined according to Table 1. [26][27][28][29][30][31] The prevalence of other elements that could modify the rate of morbidities (family history of cardiovascular or endocrine disease, acquired or inherited thrombophilia, anticoagulant or antiplatelet use for reasons other than overt thrombosis, malignancy, orthopedic surgery, hepatitis C or B virus infection) was low and these elements were not, therefore, included in further analysis.…”

Section: Design and Methodsmentioning

confidence: 99%

Elevated liver iron concentration is a marker of increased morbidity in patients with thalassemia intermedia

Musallam¹,

Cappellini²,

Wood³

et al. 2011

Haematologica

166

130

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The online version of this article has a Supplementary Appendix. BackgroundPatients with β thalassemia intermedia can have substantial iron overload, irrespectively of their transfusion status, secondary to increased intestinal iron absorption. This study evaluates whether iron overload in patients with β thalassemia intermedia is associated with morbidity. Design and MethodsThis was a cross-sectional study of 168 patients with β thalassemia intermedia treated at two centers in Lebanon and Italy. Data on demographics, splenectomy status, transfusion status, and presence of co-morbidities were retrieved. Laboratory values of serum ferritin, fetal and total hemoglobin levels, as well as platelet and nucleated red blood cell counts were also obtained. Iron burden was determined directly by measuring liver iron concentration using magnetic resonance imaging. Patients were subdivided according to transfusion and splenectomy status into groups with phenotypes of different severity. ResultsThe mean age of the patients was 35.2±12.6 years and 42.9% of them were male. The mean liver iron concentration was 8.4±6.7 mg Fe/g dry weight. On multivariate logistic regression analysis, after adjusting for age, gender, splenectomy status, transfusion status, and laboratory indices, an increase in 1 mg Fe/g dry weight liver iron concentration was independently and significantly associated with higher odds of thrombosis, pulmonary hypertension, hypothyroidism, osteoporosis, and hypogonadism. A liver iron concentration of at least 7 and at least 6 mg Fe/g dry weight were the best thresholds for discriminating the presence and absence of vascular and endocrine/bone morbidities, respectively (area under the receiver-operating characteristic curve: 0.72, P<0.001). Elevated liver iron concentration was associated with an increased rate of morbidity in patients with phenotypes of all severity, with a steeper increase in the rate of vascular morbidity being attributed to aging, and an earlier appearance of endocrine and bone disease. ConclusionsElevated liver iron concentration in patients with β thalassemia intermedia is a marker of increased vascular, endocrine, and bone disease.

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Section: Design and Methodsmentioning

confidence: 99%

Elevated liver iron concentration is a marker of increased morbidity in patients with thalassemia intermedia

Musallam¹,

Cappellini²,

Wood³

et al. 2011

Haematologica

166

130

View full text Add to dashboard Cite

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“…27 Previous studies in such patients Figure 1. Kaplan-Meier curve for the time to first hospitalization for heart failure during first 30 days after randomization, according to study group.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure

et al. 2015

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Packer et al Angiotensin Neprilysin Inhibition in Heart Failure 55Background-Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. Methods and Results-We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensinconverting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-Btype natriuretic peptide and troponin) versus enalapril. Conclusions-Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255. (Circulation. 2015;131:54-61.

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“…Complications were defined according to Table 1. [18][19][20][21][22][23] The prevalence of other elements (family history of cardiovascular or endocrine disease, acquired or inherited thrombophilia, anticoagulant or antiplatelet use for reasons other than overt thrombosis, malignancy, orthopedic surgery, hepatitis C or B virus infection) in the patients' medical history that could modify the rate of complications was low; and hence, these parameters were not included in further analysis.…”

Section: Methodsmentioning

confidence: 99%

Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study

Taher

Musallam

Karimi

et al. 2010

Blood

332

413

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Despite recent advances in understanding the pathophysiologic mechanisms behind the thalassemia intermedia (TI) phenotype, data on the effects of treatment are deficient. To provide such data, we evaluated 584 TI patients for the associations between patient and disease characteristics, treatment received, and the rate of complications. The most common disease-related complications were osteoporosis, extramedullary hematopoeisis (EMH), hypogonadism, and cholelithiasis, followed by thrombosis, pulmonary hypertension (PHT), abnormal liver function, and leg ulcers. Hypothyroidism, heart failure, and diabetes mellitus were less frequently observed. On multivariate analysis, older age and splenectomy were independently associated with an increased risk of most disease-related complications. Transfusion therapy was protective for thrombosis, EMH, PHT, heart failure, cholelithiasis, and leg ulcers. However, transfusion therapy was associated with an increased risk of endocrinopathy. Iron chelation therapy was in turn protective for endocrinopathy and PHT. Hydroxyurea treatment was associated with an increased risk of hypogonadism yet was protective for EMH, PHT, leg ulcers, hypothyroidism, and osteoporosis. Attention should be paid to the impact of age on complications in TI, and the beneficial role of splenectomy deserves revisiting. This study provides evidence that calls for prospective evaluation of the roles of transfusion, iron chelation, and hydroxyurea therapy in

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Impact of converting enzyme inhibition on progression of chronic heart failure: results of the Munich Mild Heart Failure Trial.

Abstract: Objective-Neurohormonal activation has major impact on the patho-

Cited by 111 publications

References 31 publications

Elevated liver iron concentration is a marker of increased morbidity in patients with thalassemia intermedia

Elevated liver iron concentration is a marker of increased morbidity in patients with thalassemia intermedia

Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure

Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study

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