The Benefits of Early Combination Treatment of Carvedilol and an ACE-Inhibitor in Mild Heart Failure and Left Ventricular Systolic Dysfunction. The Carvedilol and ACE-Inhibitor Remodelling Mild Heart Failure Evaluation Trial (CARMEN)

Remme, Willem J.; Riegger, G. A. J.; Hildebrandt, Per; Komajda, Michel; Jaarsma, Wybren; Bobbio, Marco; Soler‐Soler, Jordi; Scherhag, Armin; Lutiger, Beatrix; Rydén, Lars

doi:10.1023/b:card.0000025756.32499.6f

Cited by 130 publications

(89 citation statements)

References 26 publications

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“…Furthermore, the institution of anti-congestive medication involved in remodelling (ie, ACE inhibitors and b-blockers) to asymptomatic mutation carriers with only a slight left ventricular function impairment is believed to preserve left ventricular function and extend the asymptomatic state as seen in large randomized trials. 41,42 However, concerning both strategies involving modification of lifestyle and treatment options, the clinical utility must be assessed in prospective clinical trials. Furthermore, the clinical utility of screening DCM patients for sarcomere gene mutations may be less obvious in other populations with a lower frequency of disease-associated genetic variants.…”

Section: Discussionmentioning

confidence: 99%

The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy

et al. 2009

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We investigated a Danish cohort of 31 unrelated patients with idiopathic dilated cardiomyopathy (IDC), to assess the role that mutations in sarcomere protein genes play in IDC. Patients were genetically screened by capillary electrophoresis single strand conformation polymorphism and subsequently by bidirectional DNA sequencing of conformers in the coding regions of MYH7, MYBPC3, TPM1, ACTC, MYL2, MYL3, TNNT2, CSRP3 and TNNI3. Eight probands carried disease-associated genetic variants (26%). In MYH7, three novel mutations were found; in MYBPC3, one novel variant and two known mutations were found; and in TNNT2, a known mutation was found. One proband was double heterozygous. We find evidence of phenotypic plasticity: three mutations described earlier as HCM causing were found in four cases of IDC, with no history of a hypertrophic phase. Furthermore, one pedigree presented with several cases of classic DCM as well as one case with left ventricular non-compaction. Disease-causing sarcomere gene mutations were found in about one-quarter of IDC patients, and seem to play an important role in the causation of the disease. The genetics is as complex as seen in HCM. Thus, our data suggest that a genetic work-up should include screening of the most prominent sarcomere genes even in the absence of a family history of the disease.

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Section: Discussionmentioning

confidence: 99%

The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy

et al. 2009

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“…It is well known that an important characteristic of an overloaded heart is progressive ventricular remodeling, which appears to be a key contributor to morbidity and mortality of congestive heart failure (10,28). Angiotensin-converting enzyme inhibitor and ␤-blocker therapy were proven to be remarkably effective in improving left ventricular remodeling (10) and reducing morbid events (28).…”

Section: Discussionmentioning

confidence: 99%

“…Angiotensin-converting enzyme inhibitor and ␤-blocker therapy were proven to be remarkably effective in improving left ventricular remodeling (10) and reducing morbid events (28). Diabetic bladder remodeling might lead to some local neurogenic and myogenic changes that result in altered bladder function.…”

Section: Discussionmentioning

confidence: 99%

Temporal diabetes- and diuresis-induced remodeling of the urinary bladder in the rat

Liu¹,

Daneshgari²

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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-The natural history of diabetes mellitus-induced remodeling of the urinary bladder is poorly understood. In this study, we examined temporal remodeling of the bladder in diabetic and diuretic rats. Male SpragueDawley rats were divided into three groups: streptozotocin-induced diabetic, 5% sucrose-induced diuretic, and age-matched control. Micturition and morphometric characteristics were evaluated using metabolic cages and light-microscopic examination of the bladder 4 days and 1, 2, 3, and 9 wk after induction. Digital image analysis was used to quantify equatorial cross-sectional areas of bladder tissue and lumen, as well as relative content of the three primary tissue components: smooth muscle, urothelium, and collagen. Diabetes and diuresis caused significant increases in fluid intake, urine output, and bladder weight. In both groups, progressive increases were observed in lumen area from 4 days to 3 wk after induction and in wall area from 2 to 3 wk after induction. Wall thickness decreased within the first 2 wk in the diabetic and diuretic rats but returned to control at 3 and 9 wk. As a percentage of total cross-sectional area, smooth muscle area increased, urothelium area was unchanged, and collagen area decreased in diabetic and diuretic rats after 2-3 wk compared with control rats. In conclusion, diabetes and diuresis induced similar bladder remodeling. Diabetes-induced diuresis caused adaptive physical changes in rat bladder by 4 days after induction; remodeling was observed by 2-3 wk after induction and remained stable from 3 to 9 wk. streptozotocin; morphology; smooth muscle; urothelium; collagen DIABETES MELLITUS (DM) is a metabolic disorder that is characterized by defects in insulin secretion and/or insulin action, resulting in hyperglycemia. The prevalence of DM rose from 4.9% in 1990 to 7.3% in 2000, an increase of 49% (23). DM seriously affects multiple organ systems, including the urinary bladder. It has been reported that 52% of randomly evaluated diabetic patients had urological symptoms, and even many hyperglycemic patients who reported no complications had unrecognized urological symptoms (12). The classic symptoms associated with diabetic bladder dysfunction (DBD) include decreased bladder sensation, increased bladder capacity, and impaired detrusor smooth muscle contractility with resultant increased postvoid residual urine (7). In addition to these functional impairments, we and other investigators showed that diabetes induced alterations in bladder mass and tissue composition, capacity, compliance, and response to pharmacological agents and electrical stimulation (3,19,27). Recently, Pitre et al. (27) examined time-dependent morphological changes in rat bladder after induction of diabetes by streptozotocin (STZ).However, the full spectrum of morphological changes in the urinary bladder of diabetic rats and the role of diuresis remain to be determined.Diuresis, induced by feeding 5% sucrose, instead of water, to animals, causes significant increases in bladder weight but does not af...

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“…26 However, in patients with a new diagnosis, the initiation and increase in dose of three neurohumoral blockers may take many weeks, and there is evidence that reverse remodeling is both dosedependent and greater with multiple drugs than with one or two agents. [27][28][29][30][31] Moreover, a reduction in left ventricular volumes and an increase in the left ventricular ejection fraction may still occur between 6 and 12 months after the initiation of treatment. 32 Consequently, 3 months may be too short a period to wait to see whether there is sufficient recovery of left ventricular function to obviate the need for an ICD.…”

Section: Discussionmentioning

confidence: 99%

Declining Risk of Sudden Death in Heart Failure

2017

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BACKGROUNDThe risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and mineralocorticoid-receptor antagonists. We sought to examine this trend in detail. METHODSWe analyzed data from 40,195 patients who had heart failure with reduced ejection fraction and were enrolled in any of 12 clinical trials spanning the period from 1995 through 2014. Patients who had an implantable cardioverter-defibrillator at the time of trial enrollment were excluded. Weighted multivariable regression was used to examine trends in rates of sudden death over time. Adjusted hazard ratios for sudden death in each trial group were calculated with the use of Cox regression models. The cumulative incidence rates of sudden death were assessed at different time points after randomization and according to the length of time between the diagnosis of heart failure and randomization. RESULTSSudden death was reported in 3583 patients. Such patients were older and were more often male, with an ischemic cause of heart failure and worse cardiac function, than those in whom sudden death did not occur. There was a 44% decline in the rate of sudden death across the trials (P = 0.03). The cumulative incidence of sudden death at 90 days after randomization was 2.4% in the earliest trial and 1.0% in the most recent trial. The rate of sudden death was not higher among patients with a recent diagnosis of heart failure than among those with a longer-standing diagnosis. CONCLUSIONSRates of sudden death declined substantially over time among ambulatory patients with heart failure with reduced ejection fraction who were enrolled in clinical trials, a finding that is consistent with a cumulative benefit of evidence-based medications on this cause of death. (Funded by the China Scholarship Council and the University of Glasgow.)A BS TR AC T

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The Benefits of Early Combination Treatment of Carvedilol and an ACE-Inhibitor in Mild Heart Failure and Left Ventricular Systolic Dysfunction. The Carvedilol and ACE-Inhibitor Remodelling Mild Heart Failure Evaluation Trial (CARMEN)

Cited by 130 publications

References 26 publications

The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy

The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy

Temporal diabetes- and diuresis-induced remodeling of the urinary bladder in the rat

Declining Risk of Sudden Death in Heart Failure

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