Time course of markers of tissue repair after ablation of atrial fibrillation and their relation to left atrial structural changes and clinical ablation outcome

Background

Radiofrequency ablation of atrial fibrillation (AF) creates left atrial (LA) tissue damage with a subsequent healing process. We sought to prospectively assess the time course of biomarkers of tissue repair after ablation and to evaluate their association with clinical variables.

Methods

30 consecutive patients (57.9 ± 1.7 yrs, 63% males) with paroxysmal AF underwent a CARTO-guided LA circumferential ablation, Lasso-guided segmental pulmonary vein isolation and ablation of complex fractionated atrial electrograms. Matrix metalloproteinase-9 (MMP-9) and transforming growth factor-β1 (TGF-β1), both key regulators of tissue repair, and the aminoterminal propeptide of type III procollagen (PIIINP), reflecting collagen synthesis, were determined in blood samples before and 6 h, 1, 2, 7, 30, 90 and 180 days post-ablation.

Results

All markers showed a significant ablation-induced up-regulation (MMP-9: 1.8 ± 0.1-fold, TGF-β1: 2.4 ± 0.4-fold, PIIINP: 1.3 ± 0.1-fold). MMP-9 was significantly up-regulated until day 90, TGF-β1 only on day 2. PIIINP increased from day 2 to 7. The area under the curve (AUC) of MMP-9 and TGF-β1 correlated with the ablation-induced reduction of LA volume (both p < 0.05). The AUC of MMP-9 was additionally associated with the amount of radiofrequency energy delivered during ablation (p < 0.05). At 12 months of follow-up 57% of patients were free of AF off antiarrhythmic drugs. The AUC of PIIINP independently predicted recurrent AF (p < 0.05).

Conclusions

Markers of healing showed a significant up-regulation after AF ablation detectable for up to 90 days. A more pronounced up-regulation of MMP-9 or TGF-β1 is associated with a greater reduction of LA size. High PIIINP levels after ablation predict a poor ablation outcome.     

The Role of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Duchenne Muscular Dystrophy Cardiomyopathy

Background

Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Standard cardiac biomarkers are poor indicators of DMD cardiovascular disease. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate collagen turnover. Given the cardiac fibrosis seen in DMD, we hypothesized that MMPs and TIMPs correlate with severity of DMD cardiomyopathy.

Association of diabetes mellitus with myocardial collagen accumulation and relaxation impairment in patients with dilated cardiomyopathy

Aims

To assess the effects of diabetes mellitus (DM) on myocardial collagen accumulation, myocardial relaxation, and prognosis in patients with dilated cardiomyopathy (DCM).

Methods

A total of 102 consecutive DCM patients with a New York Heart Association functional class of I or II were enrolled. Patients were allocated to two groups on the basis of the presence (DCM + DM group, n = 30) or absence (DCM − DM group, n = 72) of DM. Cardiac catheterization performed and left ventricular pressure were measured in all patients. The pressure half-time (T_1/2) was determined as an index of myocardial relaxation function. Endomyocardial specimens were subjected to histological analysis.

Results

The T_1/2 was significantly longer (P < 0.001) and the collagen volume fraction was significantly greater (P = 0.018) in the DCM + DM group than in the DCM − DM group. Multivariate analysis showed that DM was significantly associated with increased incidence of cardiac events (hazard ratio, 3.7; 95% confidence interval, 1.05 to 13.16; P = 0.03).

Conclusions

The prognosis of DCM patients with DM was worse than that of those without DM. Impairment of myocardial relaxation, increased myocardial fibrosis, and mitochondrial degeneration associated with DM may underlie this difference.     

Effects of Sacubitril/Valsartan on Biomarkers of Extracellular Matrix Regulation in Patients With HFrEF

Background

Myocardial fibrosis is an important pathophysiological mechanism underlying the development of heart failure (HF). Given the biochemical targets of sacubitril/valsartan, we hypothesized that circulating biomarkers reflecting the mechanisms that determine extracellular matrix (ECM) homeostasis, including collagen synthesis, processing, and degradation, are altered by sacubitril/valsartan in comparison to enalapril.

Association of homocysteine with peripheral neuropathy in Chinese patients with type 2 diabetes

Aim

To explore the relationship between plasma total homocysteine concentration and diabetic neuropathy in Chinese patients with type 2 diabetes.

Methods

Chinese patients with type 2 diabetes (n = 249) were enrolled in a cross-sectional hospital based study. Diabetic neuropathy status was documented by presence of clinical signs and confirmed by electromyography. Plasma total homocysteine concentration was measured using fluorescence polarization immunoassay. Traditional risk factors for diabetic neuropathy were obtained from fasting blood samples and interviewer-questionnaire.

Results

Plasma total homocysteine levels were higher in subjects with diabetic neuropathy than without (12.8 (9.2-14.8) μmol/l vs. 8.0 (7.7-9.1) μmol/l, p = 0.005). The association of homocysteine with diabetic neuropathy was independent of major traditional risk factors for diabetic neuropathy (duration of diabetes, HbA1c) and determinants of higher homocysteine concentration (age, gender, serum folate and vitamin B12, renal status, and Biguanide use) (OR: 1.12 (1.00-1.25), p = 0.042). Furthermore, per increase of 4.0 μmol/l plasma homocysteine was related to neuropathy, after controlling for per unit increase of other factors (OR: 1.17 (0.94-1.33), p = 0.045).

Conclusion

Plasma total homocysteine concentration was independently associated with occurrence of diabetic neuropathy in Chinese people. Future prospective studies are warranted to clarify the relationship.     

Primary human acute myelogenous leukemia cells release matrix metalloproteases and their inhibitors: release profile and pharmacological modulation

Objectives: Angiogenesis seems important for both leukemogenesis and chemosensitivity in acute myelogenous leukemia (AML). Angiogenesis is regulated by the balance between pro‐ and antiangiogenic cytokines, which also indicates an important role of matrix metalloproteases (MMPs) and their natural inhibitors, tissue inhibitors of metalloproteases (TIMPs). We investigated the constitutive release of MMPs and TIMPs for a large group of consecutive AML patients. Methods: AML cells were cultured in vitro either alone or together with microvascular endothelial cells, and levels of MMPs and TIMPs were determined in culture supernatants. Results: AML cells showed constitutive release of several MMPs and TIMPs. For all patients, detectable MMP‐10 release was observed, and most patients showed detectable release of at least one additional MMP, usually MMP‐9 or MMP‐2. A significant correlation was found between MMP‐9 and TIMP‐1 release and the release of several CCL and CXCL chemokines. MMP‐9 release was higher for AML cells with monocytic differentiation corresponding to the FAB‐subtype M4/M5 AML; it was mainly released in its inactive form, but endogenously active MMP‐9 could be detected even in the presence of the constitutively released TIMP‐1/2. Endothelial cells released relatively high levels of MMP‐10, and these levels were further increased by coculture with AML cells. Patients achieving complete hematological remission after only one induction cycle showed relatively low constitutive MMP‐2 release. Conclusion: We conclude that primary human AML cells show constitutive release of both MMPs and TIMPs, and this release may be important for leukemogenesis and possibly also for chemosensitivity.     

Calponin1 inhibits dilated cardiomyopathy development in mice through the εPKC pathway

Background

Calponin1 (CNN1) is involved in the regulation of smooth muscle contraction in physiological situation and it also expresses abnormally in a variety of pathological situations. We found that the expression of CNN1 decreased significantly in the heart tissue of a cTnT^R141W transgenic dilated cardiomyopathy (DCM) mouse model and an adriamycin (ADR)-induced DCM mouse model, suggesting that CNN1 is involved in the pathogenesis of DCM. However, the role of CNN1 on cardiac function, especially on pathogenesis of DCM, has not been clarified. In this study, we tested whether rescued expression of CNN1 could prevent the development of DCM and investigated its possible mechanisms.

Methods and results

The DCM phenotypes were significantly improved with the transgenic expression of CNN1 in the cTnT^R141W × CNN1 double transgenic (DTG) mice, which was demonstrated by the survival, cardiac geometry and function analyses, as well as microstructural and ultrastructural observations based on echocardiography and histology examination. The expression of CNN1 could also resist the cardiac geometry breakage and dysfunction in the ADR-induced DCM mice model. Meanwhile, the epsilon isoform of protein kinase C (εPKC) activator and inhibitor could reverse the activation of εPKC/ERK/mTOR pathway and DCM phenotypes in the cTnT^R141W and cTnT^R141W × CNN1 double transgenic (DTG) mice.

Conclusions

εPKC/ERK/mTOR pathway activation induced by the rescued expression of CNN1 contributed to the improvement of cardiac dysfunction and pathological changes observed in the DTG mice. CNN1 could be a therapeutic target to prevent the development of DCM and heart failure (HF).     

Impairment of insulin action in non-obese, normal-glucose tolerant, first-degree relatives of Chinese type 2 diabetic patients

Aims

To investigate first-phase insulin release and peripheral insulin sensitivity of non-obese, normal-glucose tolerant, first-degree relatives of Chinese type 2 diabetic patients.

Methods

12 euglycemic first-degree relatives of type 2 diabetic patients (ERDM), 12 newly diagnosed type 2 diabetic patients (DM-2) and 12 healthy individuals (control) participated in the study. All subjects were non-obese (BMI < 25 kg/m²). Intravenous glucose tolerance test and euglycemic hyperinsulinemic clamp test were performed to evaluate first-phase insulin release and quantify insulin sensitivity, respectively.

Results

The first-phase insulin release did not differ between the ERDM and control subjects (p = 0.532), while the acute insulin response was absent in the DM-2 patients (p = 0.001). Peripheral glucose deposit rate (GDR) was significantly lower in the ERDM (10.6 ± 2.1 mg/kg·min, p = 0.000) and DM-2 (9.6 ± 1.1 mg/kg·min, p = 0.000) groups than that in the control group (13.2 ± 1.2 mg/kg·min). There was no statistical difference in GDR between the ERDM and DM-2 groups (p = 0.110). Fasting FFA levels of the ERDM (p = 0.007) and DM-2 (p = 0.000) subjects were significantly higher than those of the controls.

Conclusions

Non-obese, first-degree relatives of type 2 diabetic patients with normal glucose tolerance (NGT) exhibit remarkable impairment of insulin sensitivity and increased FFA levels. Insulin resistance is independent of obesity and blood glucose level. Progression from NGT to type 2 diabetes may mainly be attributed to deterioration of early insulin secretion.     

Lamin A/C mutation is independently associated with an increased risk of arterial and venous thromboembolic complications

Background

Lamin A/C (LMNA) mutation carriers suffer from a variety of clinical phenotypes, including dilated cardiomyopathy (DCM). Although it has been suggested that carriers are at risk for thromboembolic complications, it is unknown whether this risk is higher than can be expected from the underlying cardiac abnormalities. The purpose of this study was to determine whether a LMNA mutation is associated with an increased risk of thromboembolic complications.

Methods

We compared a cohort of 76 LMNA mutation carriers with a cohort of 224 idiopathic DCM patients without a LMNA mutation, with respect to the prevalence of arterial and venous thromboembolic complications. Furthermore, we carried out a case–control study to explore whether a prothrombotic phenotype was present in LMNA mutation carriers without DCM or atrial tachyarrhythmias (n = 14) and compared this with mutation negative relatives (n = 13).

Results

The prevalence of thromboembolic complications was higher in the cohort of LMNA mutation carriers than in DCM patients (22 vs 11%; p < 0.05), after respectively mean follow-up of 42 ± 12 and 49 ± 12 years. After adjustment for possible confounders, including atrial tachyarrhythmias and left ventricular ejection fraction, LMNA mutation carriership was independently associated with an increased risk of thromboembolic complications (HR 4.8, 95% CI: 2.2–10.6). The results of the case–control study suggested a prothrombotic phenotype in LMNA mutation carriers, as reflected by an altered platelet function and increased thrombin generation.

Conclusions

LMNA mutation is independently associated with an increased risk of arterial and venous thromboembolic complications. Laboratory research in LMNA mutation carriers without severe cardiac abnormalities suggests a prothrombotic phenotype.     

Increased comorbidities in heart failure patients ≥ 85 years but declined from > 90 years: Data from the Swedish Heart Failure Registry

Objectives

Epidemiological studies of elderly heart failure (HF) patients (≥ 85 years) are limited with inconsistent findings. Our objective is to confirm and extend epidemiological study in elderly (≥ 85 years) patients using the Swedish Heart Failure Registry database.

Methods

This retrospective study included 8,347 HF patients aged ≤ 65 years and 15,889 HF patients aged ≥ 85 years. Elderly population was further divided into two subgroups: 11,412 patients were 85–90 years and 4,477 patients were > 90 years.

Results

The ≥ 85 year group was characterized by more women, higher systolic blood pressure (SBP), lower body-mass index (BMI), more than twice as many HF with normal left ventricular ejection fraction (HFNEF), higher incidence of cardiovascular and non-cardiovascular comorbidities and less use of proven therapeutics compared with the ≤ 65 year group. Compared with the 85–90 year subgroup, the > 90 year subgroup had a decline in cardiovascular and non-cardiovascular comorbidities except renal insufficiency and anaemia which continued to increase with ageing (p < 0.01). Tendency was the same regardless of gender but slightly different between systolic HF (SHF) and HFNEF. In the group with HFNEF, there were more women, higher SBP, lower N-terminal pro-B-type natriuretic peptide levels, less ischaemic heart disease, more hypertension and left bundle branch block regardless of age. Atrial fibrillation was more frequent in patients with HFNEF than with SHF in the elderly group (p < 0.01). Patients with HFNEF in the > 90 year subgroup had increasing incidence of ischaemic heart disease compared to 85–90 year group (p < 0.01).

Conclusions

HF patients ≥ 85 years had increased cardiovascular and non-cardiovascular comorbidities but with a decline from > 90 years.     

The role of the matrix metalloproteinases during in vitro vessel formation

Matrix metalloproteinases (MMPs) constitute a large family of extracellular matrix degrading proteases implicated in a number of physiological and pathological processes, including angiogenesis. However, the relative importance of the individual MMPs in vessel formation is poorly understood. Using the three-dimensional rat aortic model, the role of the MMPs in angiogenesis in vitro was investigated both by the use of synthetic MMP inhibitors, and by a study of the expression of nine MMPs and three of their endogenous inhibitors (the TIMPs) during vessel formation. Inhibition of microvessel growth in this model by the MMP inhibitor Marimastat demonstrated the requirement of the MMPs for angiogenesis in both collagen and fibrin matrices (half-maximal inhibition at 5 and 80 nM, respectively). The profile of MMP expression was seen to be modified by both matrix composition and exogenous growth factors. For example, whilst the gelatinase MMP-2 and stromelysin MMP-3 were present at high levels in fibrin culture, the stromelysin MMP-11 and membrane-type-1-MMP were more highly expressed during vessel formation in collagen. The angiogenic basic fibroblast growth factor (bFGF) upregulated the expression of the gelatinases (MMP-2 and MMP-9), the stromelysins (MMP-3, MMP-10 and MMP-11) and the interstitial collagenase MMP-13, whereas vascular endothelial growth factor (VEGF) led to a marked increase in expression of MMP-2 only. Together, the environment-dependent upregulation in expression of a number of MMPs during angiogenesis, and the total inhibition of vessel growth observed at nanomolar concentrations of synthetic MMP inhibitors, suggests a major collective role of these enzymes in angiogenesis, and provides a basis for further development of MMP inhibitors for anti-angiogenic therapy.     

Myocardial alterations and clinical implications associated with recovery of cardiac function in dilated cardiomyopathy with obesity

Background

Obesity is associated with an increased risk of heart failure (HF) but the relationship between changes in cardiac function and the specific pathological features of dilated cardiomyopathy (DCM) with obesity, remains unknown.

Methods

Endomyocardial biopsies from the left ventricle (LV) were obtained from 50 patients with DCM, at the first-onset of decompensated HF. Thirty patients were obese (obese-group: body mass index > 30 kg/m²) and 20 were non-obese (lean-group). Clinical data were acquired at the admission, after one month and one year.

Results

The obese-group had higher systolic blood pressure (142.8 ± 33.9 vs 113.6 ± 18.7 mm Hg; p < 0.001) and serum troponin-T level (0.049 ± 0.07 vs 0.020 ± 0.03 ng/mL; p = 0.022) than the lean-group. LV ejection fraction (LVEF) was not significantly different between groups, but after one year the obese-group had an improved LVEF (57.0 ± 11.4 vs 44.3 ± 17.1; p = 0.003). Light microscopy revealed that the obese-group had larger cardiomyocytes (17.2 ± 1.7 vs 16.4 ± 1.4 μm; p = 0.033) and less myofilament lysis (37 vs 75%; p = 0.008) with a higher density of lipid droplets (1.93 ± 0.8 vs 0.94 ± 0.7 /μm²; p < 0.001). Multivariate regression analysis revealed that independent predictors of LVEF improvement after 12 months were diuretics use, nuclear diameter, and absence of myofilament lysis (p = 0.024, 0.012 and 0.028, respectively).

Conclusions

Cardiac function in most patients with DCM with obesity is reversible and myocardial structural changes are trivial even at the ultrastructural level.     

Coronary artery disease, coronary revascularization, and outcomes in chronic advanced systolic heart failure

Background

Associations between coronary artery disease (CAD) and outcomes in systolic heart failure (HF) and that between coronary artery bypass graft (CABG) surgery and outcomes in patients with HF and CAD have not been examined using propensity-matched designs.

Methods

Of the 2707 patients with advanced chronic systolic HF in the Beta-Blocker Evaluation of Survival Trial (BEST), 1593 had a history of CAD, of whom 782 had prior CABG. Using propensity scores for CAD we assembled a cohort of 458 pairs of CAD and no-CAD patients. Propensity scores for prior CABG in those with CAD were used to assemble 500 pairs of patients with and without CABG. Matched patients were balanced on 68 baseline characteristics.

Results

All-cause mortality occurred in 33% and 24% of matched patients with and without CAD respectively, during 26 months of median follow-up (hazard ratio {HR} when CAD was compared with no-CAD, 1.41; 95% confidence interval {CI}, 1.11-1.81; P = 0.006). HR's (95% CIs) for CAD-associated cardiovascular mortality, HF mortality, and sudden cardiac death (SCD) were 1.53 (1.17-2.00; P = 0.002), 1.44 (0.92-2.25; P = 0.114) and 1.76 (1.21-2.57; P = 0.003) respectively. CAD had no association with hospitalization. Among matched patients with HF and CAD, all-cause mortality occurred in 32% and 39% of those with and without prior CABG respectively (HR for CABG, 0.77; 95% CI, 0.62-0.95; P = 0.015).

Conclusions

In patients with advanced chronic systolic HF, CAD is associated with increased mortality, and in those with CAD, prior CABG seems to be associated with reduced all-cause mortality but not SCD.     

Incidence and mortality of heart failure: A community-based study

Background

Data on the incidence and mortality of heart failure (HF) in community-based populations of developed countries are limited. We estimated the trends of the incidence and, the mortality of HF.

Methods

Prospective population-based study in a white, low-middle class Mediterranean community of 267,231 inhabitants in Spain. Participants were all the patients (= > 14 years), newly diagnosed with HF (4793), according to the Framingham criteria, from January 1, 2000 through December 31, 2007. Main outcome were incidence and mortality following an HF diagnosis.

Results

Incidence of HF increased among both men and women, and among persons with systolic and non-systolic HF. Incidence of HF increased from 296 per 100,000 person-years in 2000 to 390 per 100,000 person-years in 2007 (RR 1.32, CI 95% 1.27-13.7, P < .01). Although, risk-adjusted mortality declined from 2000 to 2007, the prognosis for patients with newly diagnosed HF remains poor. In 2007, risk-adjusted 30-day, 1-year, and 4-years mortality was 12.1%, 28.8%, and 61.4%, respectively. Incidence and mortality of systolic HF were higher than those of non-systolic HF (P < 0.05).

Conclusions

During the last 8 years, in a white, middle class population of the south of Europe, the increased incidence and the decreased mortality of heart failure have resulted in an increased prevalence of heart failure. Incidence and mortality of systolic heart failure were higher than those of non-systolic heart failure.     

The obesity paradox in men with coronary heart disease and heart failure: The role of muscle mass and leptin

Aims

We have investigated the role of muscle mass, natriuretic peptides and adipokines in explaining the obesity paradox.

Background

The obesity paradox relates to the association between obesity and increased survival in patients with coronary heart disease (CHD) or heart failure (HF).

Methods

Prospective study of 4046 men aged 60–79 years followed up for a mean period of 11 years, during which 1340 deaths occurred. The men were divided according to the presence of doctor diagnosed CHD and HF: (i) no CHD or HF ii), with CHD (no HF) and (iii) with HF.

Results

Overweight (BMI 25–9.9 kg/m²) and obesity (BMI ≥ 30 kg/m²) were associated with lower mortality risk compared to men with normal weight (BMI 18.5–24.9 kg/m²) in those with CHD [hazards ratio (HR) 0.71 (0.56,0.91) and 0.77 (0.57,1.04); p = 0.04 for trend] and in those with HF [HR 0.57 (0.28,1.16) and 0.41 (0.16,1.09; p = 0.04 for trend). Adjustment for muscle mass and NT-proBNP attenuated the inverse association in those with CHD (no HF) [HR 0.78 (0.61,1.01) and 0.96 (0.68,1.36) p = 0.60 for trend) but made minor differences to those with HF [p = 0.05]. Leptin related positively to mortality in men without HF but inversely to mortality in those with HF; adjustment for leptin abolished the BMI mortality association in men with HF [HR 0.82 (0.31,2.20) and 0.99 (0.27,3.71); p = 0.98 for trend].

Conclusion

The lower mortality risk associated with excess weight in men with CHD without HF may be due to higher muscle mass. In men with HF, leptin (possibly reflecting cachexia) explain the inverse association.     

The effects of high glucose and atorvastatin on endothelial cell matrix production.

BACKGROUND: Statins are known to enhance atherosclerotic plaque stability through influences on extracellular matrix homeostasis. Net matrix production reflects the relative balance of matrix production and degradation through enzymes such as matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of MMP (TIMPs). The effects of statins on endothelial cell production of these parameters following co-exposure with a proatherogenic stimulus such as high glucose are not known. METHODS: Human endothelial cells were exposed for 72 h to 5 mm (control) or 25 mm (high) glucose +/- atorvastatin (1 micromol/l). Extracellular matrix homeostasis was assessed by measuring matrix metalloproteinase (MMP)-2 secretion, tissue inhibitor of MMP (TIMP)-1 and -2 secretion and net collagen IV production. Results were expressed as percentage +/- SEM of control values. RESULTS: Exposure to high glucose increased cellular collagen IV expression to 190.1 +/- 11.7% (P < 0.0001) of control levels. No change in MMP-2 secretion (111.6 +/- 5.2%; P > 0.05) was observed but both TIMP-1 and TIMP-2 expression were increased to 136.3 +/- 6.4% and 144.0 +/- 27.5%, respectively (both P < 0.05). The presence of atorvastatin in high glucose conditions reduced collagen IV expression to 136.1 +/- 20.6%. This was paralleled by increased secretion of MMP-2 to 145.8 +/- 7.8% (P < 0.01), increased TIMP-2 expression to 208.0 +/- 21.3% (P < 0.005 compared with high glucose) but no change in TIMP-1 expression (155.1 +/- 14.6%) compared with high glucose alone. The presence of atorvastatin in control conditions did not affect levels of collagen IV expression (114.5 +/- 13.2%). CONCLUSIONS: Endothelial cell exposure to high glucose was associated with a MMP/TIMP profile that increased extracellular matrix production which was attenuated by concurrent exposure to atorvastatin. Consequently, a mechanism by which the atherosclerotic plaque regression that is observed in patients taking these drugs has been demonstrated.     

Impact of body composition, fat distribution and sustained weight loss on cardiac function in obesity

Background

Older age is an independent predictor of all-cause mortality in patients with mild to moderate heart failure (HF). Whether older age is also an independent predictor of mortality in patients with more advanced HF is unknown.

Methods

Of the 2707 Beta-Blocker Evaluation of Survival Trial (BEST) participants with ambulatory chronic HF (New York Heart Association class III/IV and left ventricular ejection fraction < 35%), 1091 were elderly (≥ 65 years). Propensity scores for older age, estimated for each of the 2707 patients, were used to assemble a cohort of 603 pairs of younger and older patients, balanced on 66 baseline characteristics.

Results

All-cause mortality occurred in 33% and 36% of younger and older matched patients respectively during 4 years of follow-up (hazard ratio {HR} associated with age ≥65 years, 1.05; 95% confidence interval {CI}, 0.87-1.27; P = 0.614). HF hospitalization occurred in 38% and 40% of younger and older matched patients respectively (HR, 1.01; 95% CI, 0.84-1.21; P = 0.951). Among 603 pairs of unmatched and unbalanced patients, all-cause mortality occurred in 28% and 36% of younger and older patients respectively (HR, 1.34; 95% CI, 1.10-1.64; P = 0.004) and HF hospitalization occurred in 34% and 40% of younger and older unmatched patients respectively (HR, 1.24; 95% CI, 1.03-1.50; P = 0.024).

Conclusion

Significant bivariate associations suggest that older age is a useful marker of poor outcomes in patients with advanced chronic systolic HF. However, lack of significant independent associations suggests that older age per se has no intrinsic effect on outcomes in these patients.     

Diabetes in heart failure: prevalence and impact on outcome in the population

Purpose

Little is known on the prevalence and prognostic importance of diabetes mellitus (DM) among individuals with heart failure (HF) in community-based cohorts.

Methods

Within Olmsted County, Minnesota, a random sample of all subjects with a first diagnosis of HF between 1979 and 1999 was validated using Framingham criteria. DM was validated using glycemic criteria.

Results

Among 665 subjects with HF (mean age 77 ± 12 years, 46% male), 20% had prior DM. Subjects with DM were younger, had greater body mass index (BMI), and lower left ventricular ejection fraction than subjects without diabetes. The prevalence of DM increased markedly over time (3.8% per year; 95% confidence interval [CI], 0.8 to 6.9; P = .024), independently of BMI, particularly in older subjects (odds ratio of having DM in 1999 compared with 1979 was 3.93 [95% CI, 1.57 to 9.83] in subjects ≥75 years vs. 1.11 [95% CI, .40 to 3.05] in subjects <75 years). Five-year survival was 37% among subjects with DM versus 46% among subjects without (P = .017). The risk of death associated with DM differed markedly according to clinical coronary artery disease (CAD) (P = .025). Subjects with DM and no CAD had a higher risk of death (relative risk [RR] = 1.79 [95% CI, 1.33 to 2.41]) than those with CAD (RR = 1.11 [95% CI, .81 to 1.51]), independently of age, sex, BMI, renal function, calendar year of HF, comorbidity and EF.

Conclusions

Among community-dwelling patients with HF, the prevalence of DM increased markedly over time. DM is associated with a large increase in mortality, particularly among subjects without clinical CAD, underscoring the importance of aggressive management of DM in HF.     

Event-free survival in adults with heart failure who engage in self-care management

Background

Self-care management in heart failure (HF) involves decision-making to evaluate, and actions to ameliorate symptoms when they occur. This study sought to compare the risks of all-cause mortality, hospitalization, or emergency-room admission among HF patients who practice above-average self-care management, those who practice below-average self-care management, and those who are symptom-free.

Methods

A secondary analysis was conducted of data collected on 195 HF patients. A Cox proportional hazards model was used to examine the association between self-care management and event risk.

Results

The sample consisted of older (mean ± standard deviation = 61.3 ± 11 years), predominantly male (64.6%) adults, with an ejection fraction of 34.7% ± 15.3%; 60.1% fell within New York Heart Association class III or IV HF. During an average follow-up of 364 ± 288 days, 4 deaths, 82 hospitalizations, and 5 emergency-room visits occurred as first events. Controlling for 15 common confounders, those who engaged in above-average self-care management (hazard ratio, .44; 95% confidence interval, .22 to .88; P < .05) and those who were symptom-free (hazard ratio, 0.48; 95% confidence interval, .24 to .97; P < .05) ran a lower risk of an event during follow-up than those engaged in below-average self-care management.

Conclusion

Symptomatic HF patients who practice above-average self-care management have an event-free survival benefit similar to that of symptom-free HF patients.