Endothelial progenitor cells in diabetic patients with myocardial infarction - can statins improve their function?

The effect of statins on endothelial progenitor cells (EPCs) function derived from diabetic patients (DMpts) with acute myocardial infarction (AMI) is unknown. In this study we assess the response of early and late EPCs from diabetic versus non-diabetic patients (NDMpts) with AMI to statins. EPCs were obtained from 10 diabetic and 10 age-matched non-diabetic male patients with AMI. For each patient, cultures of early and late EPCs were performed under 4 different conditions: normal glucose concentration (control); high glucose concentration; normal glucose concentration with atorvastatin supplementation and normal glucose concentration with pravastatin supplementation. To compare the effect of these treatments on EPC function in DMpts versus NDMpts, we performed in vitro: EPC colony-forming units (CFU) assay; cell cycle analysis; viability assessment and expression of the surface markers CXCR4, CD133, CD34 and KDR. Under control conditions, CFU numbers were reduced in DMpts-derived EPCs when compared to those of NDMpts (1.4±0.8 vs 2.6±1.2 CFU/well, P=0.021). When early EPCs from DMpts were cultured in the presence of statins, CFU capacity was restored, surmounting that of NDMpts under control conditions. Statins significantly improved viability of early EPCs and delayed the onset of late EPCs senescence, even in cells from DMpts. In addition, statins induced approximately a 2-fold increase in the proportion of late EPCs in S-phase of the cell cycle (P<0.05). Statins have a beneficial effect on both early and late EPCs from DMpts with AMI. Despite the functional impairment of EPCs from DMpts, they exhibit similar responsiveness to statins as equivalent cells from NDMpts.

Impact of prior chronic statin therapy and high-intensity statin therapy at discharge on circulating endothelial progenitor cell levels in patients with acute myocardial infarction: a prospective observational study.

BACKGROUND: Endothelial progenitor stem cells (EPCs) are mobilized to the peripheral circulation in response to myocardial ischemia, playing a crucial role in vascular repair. Statins have been shown to stimulate EPCs. However, neither the impact of previous statin therapy on EPC response of acute myocardial infarction (AMI) patients nor the effect of post-AMI high-intensity statin therapy on the evolution of circulating EPC levels has yet been addressed. Therefore, we aimed to compare circulating EPC levels between patients receiving long-term statin therapy before the AMI and statin-naive patients and to assess the impact of high-intensity statin therapy at discharge on the evolution of circulating EPCs post-AMI. METHODS: This is a prospective observational study of 100 AMI patients. Circulating EPCs (CD45dimCD34 + KDR + cells) and their subpopulation coexpressing the homing marker CXCR4 were quantified by the high-performance flow cytometer FACSCanto II in whole blood, in two different moments: within the first 24 h of admission and 3 months post-AMI. Patients were followed up clinically for 2 years. RESULTS: Patients previously treated with statins had significantly higher levels of EPCs coexpressing CXCR4 (1.9 ± 1.4 vs. 1.3 ± 1.0 cells/1,000,000 events, p = 0.031) than statin-naive patients. In addition, the subanalysis of diabetics (N = 38) also revealed that patients previously on statins had significantly greater numbers of both CD45dimCD34 + KDR + CXCR4+ cells (p = 0.024) and CD45dimCD34 + KDR + CD133+ cells (p = 0.022) than statin-naive patients. Regarding the evolution of EPC levels after the AMI, patients not on a high-intensity statin therapy at discharge had a significant reduction of CD45dimCD34 + KDR + and CD45dimCD34 + KDR + CXCR4+ cells from baseline to 3 months follow-up (p = 0.031 and p = 0.005, respectively). However, patients discharged on a high-intensity statin therapy maintained circulating levels of all EPC populations, presenting at 3 months of follow-up significantly higher EPC levels than patients not on an intensive statin therapy. Moreover, the high-intensity statin treatment group had significantly better clinical outcomes during the 2-year follow-up period than patients not discharged on a high-intensity statin therapy. CONCLUSION: Chronic statin therapy prior to an AMI strongly enhances the response of EPCs to myocardial ischemia, even in diabetic patients. Furthermore, high-intensity statin therapy after an AMI prevents the expected decrease of circulating EPC levels during follow-up. These results reinforce the importance of an early and intensive statin therapy in AMI patients.

Reduced levels of circulating endothelial progenitor cells in acute myocardial infarction patients with diabetes or pre-diabetes: accompanying the glycemic continuum.

BACKGROUND: Diabetic patients have a significantly worse prognosis after an acute myocardial infarction (AMI) than their counterparts. Previous studies have shown that the number of circulating endothelial progenitor cells (EPCs) significantly increase early after an AMI in normoglycemic patients. However, it is well known that type 2 diabetes mellitus (DM) is associated with impaired function and reduced circulating EPCs levels. Nonetheless, few studies have analyzed EPCs response of diabetics to an AMI and the EPC response of pre-diabetic patients has not been reported yet. Therefore, we hypothesized that in the acute phase of an AMI, diabetic and pre-diabetics have lower circulating EPCs levels than patients with normal glucose metabolism. We also evaluated the possible capacity of chronic antidiabetic treatment in the recovery of EPCs response to an AMI in diabetics. METHODS: One-hundred AMI patients were prospectively enrolled in the study. Using the high-performance flow cytometer FACSCanto II, circulating EPCs (CD45dimCD34+KDR+ and CD45dimCD133+KDR+ cells) were quantified, within the first 24 hours of admission. In addition, as an indirect functional parameter, we also analyzed the fraction of EPCs coexpressing the homing marker CXCR4. RESULTS: We found that in the acute phase of an AMI, diabetic patients presented significantly lower levels of circulating CD45dimCD34+KDR+ and CD45dimCD133+KDR+ EPCs by comparison with nondiabetics, with a parallel decrease in the subpopulations CXCR4+ (p < 0.001). Indeed, this study suggests that the impaired response of EPCs to an AMI is an early event in the natural history of DM, being present even in pre-diabetes. Our results, also demonstrated that numbers of all EPCs populations were inversely correlated with HbA1c (r = -0.432, p < 0.001 for CD45dimCD34+KDR+ cells). Finally, this study suggests that previous chronic insulin therapy (but not oral antidiabetic drugs) attenuate the deficient response of diabetic EPCs to an AMI. CONCLUSION: This study indicates that there is a progressive decrease in EPCs levels, from pre-diabetes to DM, in AMI patients. Moreover, glycemic control seems to be determinant for circulating EPCs levels presented in the acute phase of an AMI and chronic insulin therapy may probably attenuate the deficit in EPCs pool seen in diabetics.

Circulating endothelial progenitor cells as a predictor of response to cardiac resynchronization therapy: the missing piece of the puzzle?

BACKGROUND: It would be important to better identify heart failure (HF) patients most likely to respond to cardiac resynchronization therapy (CRT). Because endothelial progenitor cells (EPCs) play a crucial role in the maintenance of vascular endothelium integrity, we hypothesize that patients who have higher circulating EPCs levels have greater neovascularization potential and are more prone to be responders to CRT. METHODS: Prospective study of 30 consecutive patients, scheduled for CRT. Echocardiographic evaluation was performed before implant and 6 months after. Responders to CRT were defined as patients who were still alive, have not been hospitalized for HF management, and demonstrated ≥15% reduction in left ventricular end-systolic volume (LVESV) at the 6-month follow-up. EPCs were quantified before CRT, from peripheral blood, by flow cytometry using five different conjugated antibodies: anti-CD34, anti-KDR, anti-CD133, anti-CD45, and anti-CXCR4. We quantified five different populations of angiogenic cells: CD133(+) /CD34(+) cells, CD133(+) /KDR(+) cells, CD133(+) /CD34(+) /KDR(+) cells, CD45(dim) CD34(+) /KDR(+) cells, and CD45(dim) CD34(+) /KDR(+) /CXCR4(+) cells. RESULTS: The proportion of responders to CRT at the 6-month follow-up was 46.7%. Responders to CRT presented higher baseline EPCs levels than nonresponders (0.0003 ± 0.0006% vs 0.0001 ± 0.0002%, P = 0.04, for CD34(+) /CD133(+) /KDR(+) and 0.0006 ± 0.0005% vs 0.0003 ± 0.0003%, P = 0.009, for CD45(dim) CD34(+) /KDR(+) /CXCR4(+) cells). In addition, baseline levels of CD45(dim) CD34(+) /KDR(+) /CXCR4(+) cells were positively correlated with the reduction of LVESV verified 6 months after CRT (r = 0.497, P = 0.008). CONCLUSIONS: High circulating EPCs levels may identify the subset of HF patients who are more likely to undergo reverse remodeling and benefit from CRT. Addition of EPCs levels assessment to current selection criteria may improve the ability to predict CRT response.

CHADS(2) and CHA(2)DS(2)VASc scores as predictors of cardioembolic sources in secondary stroke prevention.

INTRODUCTION AND OBJECTIVES: Cardioembolism is one of the most common causes of ischemic stroke, with an estimated prevalence of 20-30%, and correct diagnosis is essential given the therapeutic implications. Although stroke risk scores (CHADS2 and more recently CHA2DS2-VASc) have been validated in heterogeneous populations of patients with atrial fibrillation, their accuracy has not been ascertained for secondary stroke prevention. We set out to assess the sensitivity and specificity of the CHADS2 and CHA2DS2-VASc stroke risk scores as predictors of cardioembolic sources, documented by transesophageal echocardiography (TEE) in a population with ischemic stroke. METHODS: The CHADS2 and CHA2DS2-VASc scores were applied to all patients admitted to the stroke unit/neurology ward of a Portuguese tertiary hospital with atrial fibrillation (diagnosed previously or during or after admission) who underwent TEE between January and August 2011. The presence of a cardioembolic source was defined as the observation by TEE of spontaneous echo contrast in the left atrium and atrial appendage or thrombi in the left cardiac chambers. RESULTS: We studied 94 patients, 66.0% male, mean age 64.4 years (standard deviation 14.2). A cardioembolic source was detected in 20 patients. ROC curve analysis identified as predictors of cardioembolic source CHADS2 score ≥4 (sensitivity of 75.0%, specificity of 66.0%, p=0.014) and CHA2DS2-VASc score ≥5 (sensitivity of 83.3%, specificity of 58.0%, p=0.009). CONCLUSIONS: Both scores showed acceptable sensitivity as predictors of embolic risk in the context of secondary prevention of cardioembolic stroke. The CHA2DS2-VASc score has higher sensitivity than CHADS2 but lower specificity.

Digoxin in advanced heart failure patients: a question of rhythm.

BACKGROUND: The impact of digoxin on outcomes of patients with advanced heart failure (HF) remains uncertain and its effect may be different for patients in atrial fibrillation (AF) or sinus rhythm (SR). OBJECTIVES: To determine the impact of digoxin on outcomes of advanced HF patients and to assess whether prognosis differs in patients in AF and SR. METHODS: A total of 268 consecutive patients admitted to an intensive care unit with decompensated HF were evaluated. Patients were divided into two groups: A - patients with AF (n=89), and B - patients in SR (n=179). For each group we compared patients medicated and not medicated with digoxin. A mean follow-up of 3.3 years was performed. RESULTS: Addition of digoxin to contemporary standard HF therapy showed no impact on mortality of patients in group B (all-cause mortality in follow-up: 19.1% vs. 22.5%, p=0.788). Regarding group A, we observed significantly lower medium-term mortality for patients on digoxin therapy (18.6% vs. 46.6%, p=0.048). Digoxin therapy did not influence readmissions for decompensated HF. Among AF patients, no differences were found regarding demographic, clinical, echocardiographic and laboratory variables between patients medicated and not medicated with digoxin. CONCLUSIONS: Digoxin therapy may improve the prognosis of advanced HF patients with AF under optimal medical therapy. However, no benefit of digoxin was demonstrated for patients in SR. These results may help to improve patient selection for digoxin therapy.

One-shot diagnostic and prognostic assessment in intermediate- to high-risk acute pulmonary embolism: the role of multidetector computed tomography.

INTRODUCTION: Contrast-enhanced multidetector computed tomography (MDCT) is useful for the diagnosis of pulmonary embolism (PE). However, current guidelines do not support its use for risk assessment in acute PE patients. OBJECTIVES: We compared the prognostic impact of MDCT-derived indices regarding medium-term mortality in a population of intermediate- to high-risk PE patients, mostly treated by thrombolysis. METHODS: Thirty-nine consecutive patients admitted to an intensive care unit with acute PE were studied. All patients had a pulmonary MDCT on admission to the emergency room as part of the diagnostic algorithm. We assessed the following MDCT variables: right ventricular/left ventricular diameter (RV/LV) ratio, arterial obstruction index, pulmonary artery-to-aorta diameter ratio and azygos vein diameter. A 33-month follow-up was performed. RESULTS: Mean age was 59.1±19.6 years, with 80% of patients receiving thrombolysis. Follow-up all-cause mortality was 12.8%. Of the MDCT-derived variables, only the RV/LV ratio had significant predictive value, being higher in patients who suffered the endpoint (1.6±0.5 vs. 1.9±0.4, p=0.046). Patients with an RV/LV ratio ≥1.8 had 11-fold higher medium-term all-cause mortality (3.8% vs. 38.8%, p<0.001). Regarding this endpoint, the c-statistic was 0.78 (95% CI, 0.60-0.96) for RV/LV ratio and calibration was good (goodness-of-fit p=0.594). No other radiological index was predictive of mortality. CONCLUSIONS: MDCT gives the possibility, in a single imaging procedure, of diagnosing and assessing the prognosis of patients with intermediate- to high-risk PE. Although further studies are needed, the simple-to-calculate RV/LV ratio has good discrimination and calibration for predicting poorer outcomes in patients with acute PE.

Platelet aggregation at discharge: a useful tool in acute coronary syndromes?

INTRODUCTION: Inhibition of platelet aggregation appears two hours after the first dose of clopidogrel, becomes significant after the second dose, and progresses to a steady-state value of 55% by day seven. Low response to clopidogrel has been associated with increased risk of stent thrombosis and ischemic events, particularly in the context of stable heart disease treated by percutaneous coronary intervention. OBJECTIVE: To stratify medium-term prognosis of an acute coronary syndrome (ACS) population by platelet aggregation. METHODS: We performed a prospective longitudinal study of 70 patients admitted for an ACS between May and August 2009. Platelet function was assessed by ADP-induced platelet aggregation using a commercially available kit (Multiplate(®) analyzer) at discharge. The primary endpoint was a combined outcome of mortality, non-fatal myocardial infarction, or unstable angina, with a median follow-up of 136.0 (79.0-188.0) days. RESULTS: The median value of platelet aggregation was 16.0U (11.0-22.5U) with a maximum of 41.0U and a minimum of 4.0U (normal value according to the manufacturer: 53-122U). After ROC curve analysis with respect to the combined endpoint (AUC 0.72), we concluded that a value of 18.5U conferred a sensitivity of 75.0% and a specificity of 68% to that result. We therefore created two groups based on that level: group A - platelet aggregation <18.5U, n=44; and group B - platelet aggregation ≥18.5U, n=26. The groups were similar with respect to demographic data (age 60.5 [49.0-65.0] vs. 62.0 [49.0-65.0] years, p=0.21), previous cardiovascular history, and admission diagnosis. There were no associations between left ventricular ejection fraction, GRACE risk score, or length of hospital stay and platelet aggregation. The groups were also similar with respect to antiplatelet, anticoagulant, proton pump inhibitor (63.6 vs. 46.2%, p=0.15) and statin therapy. The variability in platelets and hemoglobin was also similar between groups. Combined event-free survival was higher in group A (96.0 vs. 76.7%, log-rank p<0.01). Platelet aggregation higher than 18.5U was an independent predictor of the combined event (HR 6.75, 95% CI 1.38-32.90, p=0.02). CONCLUSION: In our ACS population platelet aggregation at discharge was a predictor of medium-term prognosis.

[Fulminant myocarditis]. / Miocardite fulminante - a propósito de um caso clínico.

A 46-year-old woman was admitted due to diplopia because of ophthalmoplegia, which improved with corticosteroid therapy. Eight days later, she was admitted with fulminant myocarditis in cardiogenic shock, with severe left ventricular dysfunction and frequent episodes of nonsustained ventricular tachycardia. As there was no clinical improvement, an endomyocardial biopsy was performed that revealed inflammatory infiltrate, vasculitis, and PCR positive for cytomegalovirus, Epstein-Barr virus, parvovirus B19 and enterovirus. Left ventricular function recovered with heart failure treatment and corticosteroids. Three months later, after progressive withdrawal of prednisolone, there was recurrence of myocarditis and left ventricular dysfunction, which was successfully treated by restarting corticosteroid therapy. One month later she was readmitted with fulminant myocarditis which again responded to steroids. She intermittently presented cutaneous purpura lesions. At this time the provisional diagnosis was vasculitis and she started monthly cycles of cyclophosphamide. Before the second cycle she was admitted with pneumonia and ventricular dysfunction and died.

CYP2C19*2 and prognosis after an acute coronary syndrome: Insights from a Portuguese center.

BACKGROUND: Clopidogrel requires oxidation dependent on the cytochrome P450 enzyme 2C19 (CYP2C19) to form its active metabolite. The importance of loss-of-function alleles (particularly CYP2C19*2, 681G>A) in poor platelet response to clopidogrel is well recognized. OBJECTIVE: To investigate the prevalence and prognostic impact of the CYP2C19*2 allele in a local acute coronary syndrome (ACS) population. METHODS: We performed a prospective, longitudinal study of 95 patients admitted for an ACS between March and October 2009 to a single coronary care unit. Patients aged under 75 who survived hospital stay and for whom clopidogrel was prescribed were included. At discharge, CYP2C19 was genotyped using a commercially available kit. Patients were divided into two groups: Group A (non-carriers, normal metabolizers, CYP2C19*1/*1), n=69; and Group B (carriers, slow metabolizers, CYP2C19*2/*1 or *2/*2), n=26. The primary endpoint was a combined outcome of cardiovascular death, non-fatal myocardial infarction or re-admission for unstable angina; median follow-up was 136.0 (79.0-188.0) days. RESULTS: The median age of the population was 62.0 (51.0-68.0) years, and 83.2% were male. The CYP2C19*2 (A) allele had a frequency of 14.2%. There were no differences between the groups with respect to demographic data or history of cardiovascular disease. Coronary anatomy, left ventricular ejection fraction and renal function were also similar. The groups were also homogenous with respect to GRACE risk score (118.0 (95.0-136.5) vs. 115.0 (96.0-133.0), p=0.68), medical treatment and percutaneous revascularization during hospital stay. Event-free survival was higher for Group A (94.0% vs. 75.0%, log-rank p=0.010). Three readmissions for MI were documented, all in the slow metabolizers group. CONCLUSION: In our ACS population, the CYP2C19*2 allele was a medium-term prognostic marker.

[Emery-Dreifuss muscular dystrophy: case report]. / Distrofia muscular de Emery-Dreifuss: a propósito de um caso clínico.

Emery-Dreifuss muscular dystrophy type 1 (EDMD1) is a familial disease with X-Linked recessive transmission, caused by a mutation in a nuclear envelope protein, emerin. Clinical manifestations usually occur in adolescence and include contractures, muscle atrophy and weakness, and cardiac conduction disturbances. We describe the case of a young male, aged 16, with first-degree atrioventricular (AV) block and limited extension of both forearms. He had elevated CK, and cardiac monitoring showed severe conduction tissue disease, with significant sinus pauses, chronotropic incompetence and periods of AV dissociation during exercise. Immunohistochemical staining using an emerin antibody showed absence of the protein in a fragment of muscle tissue and genetic study identified a mutation associated with EDMD1. Study of his brother, aged 21, also established a diagnosis of EDMD1. Both individuals received a permanent pacemaker but musculoskeletal manifestations at that time did not warrant any other intervention: Screening for certain genetic diseases, including muscular dystrophies, is mandatory following identification of conduction abnormalities in young people.

Mean pulmonary arterial pressure after percutaneous mitral valvuloplasty predicts long-term adverse outcomes.

INTRODUCTION AND AIM: Percutaneous mitral valvuloplasty (PMV) is an effective treatment option for mitral stenosis (MS), but its success is assessed on the basis of clinical and echocardiographic outcomes in studies with relatively short follow-up. We aimed to characterize a cohort of patients undergoing PMV with long-term follow-up and to determine independent predictors of post-PMV mitral re-intervention and event-free survival. METHODS: We studied 91 consecutive patients with MS who underwent PMV with a median clinical follow-up duration of 99 months. Two endpoints were considered: post-PMV mitral re-intervention (PMV or mitral surgery) and a composite clinical events endpoint including cardiovascular death, mitral valve re-intervention and hospital admission due to decompensated heart failure. We compared patients who required post-PMV mitral re-intervention with those who did not during follow-up. RESULTS: The study population included 83.5% females and mean age was 48.9±13.9 years. The 1-, 3-, 5-, 7- and 9-year rates of clinical event-free survival were 93.0±2.8%, 86.0±3.9%, 81.0±4.4%, 70.6±5.6%, and 68.4±5.8%, respectively. The 1-, 3-, 5-, 7- and 9-year rates of mitral re-intervention-free survival were 98.8±1.2%, 97.5±1.7%, 92.1±3.1%, 85.5±4.5%, and 85.5±4.5%, respectively. The median time to mitral re-intervention was 6.2 years. Patients who required mitral re-intervention during follow-up were younger (43.3 vs. 51.2 years, p=0.04) and had higher pre- and post-PMV mitral gradient (14.9 vs. 11.5 mmHg, p=0.02 and 6.4 vs. 2.1 mmHg, p<0.001) and higher post-PMV mean pulmonary artery pressure (mPAP) (30.0 vs. 23.2 mmHg, p=0.01). In a Cox proportional hazards model, mPAP ≥25 mmHg was the sole predictor of both mitral re-intervention (HR 5.639 [1.246-25.528], p=0.025) and clinical events (HR 3.622 [1.070-12.260], p=0.039). CONCLUSION: In our population, immediate post-PMV mPAP was the sole predictor of post-PMV mitral intervention. These findings may help identify patients in need of closer post-PMV follow-up.

Cardiac resynchronization therapy in the elderly: a realistic option for an increasing population?

Cardiac resynchronization therapy (CRT) has become a mainstay of heart failure treatment. Since heart failure is a disease primarily affecting older patients it is important to evaluate the performance of CRT in this population. Elderly has been suggested as a subgroup less likely to benefit from CRT. This is an important issue that should be clarified, because most patients with heart failure are old. The present review discusses the available data concerning cardiac resynchronization therapy in the elderly, focusing on efficacy, indication, safety, and impact of co-morbidities.

[Cardio-renal syndrome: the challenge in heart failure treatment]. / Síndrome cardio-renal: os desafios no tratamento da insuficiência cardíaca.

Heart failure is a chronic and progressive disease that is estimated to affect approximately 20 million people worldwide and is one of the major public health problems. Its prevalence is reaching epidemic levels with about 550,000 new cases diagnosed annually, partly due to increased life expectancy in developed countries. And as it is a systemic disease, it can cause dysfunction in various organs, but especially in the kidney. The renal failure is often associated with heart failure and, when present together, make the treatment more complex and the prognosis is worse. This is the cardio-renal syndrome. The definition of cardio-renal syndrome varies according to the working groups, and there isn't a consensus. The exact cause of deterioration of renal function and the mechanism behind this interaction are complex, multifactorial in nature and not fully known at present. The treatment available is the one used for the treatment of heart failure. It is necessary to maintain the normal function of filtration, secretion and reabsorption in kidney to have a real improvement of the clinical condition of the patient. Patients with higher risk of developing nephropathy and those who have diagnosed renal failure should have prescribed drugs that are handled very carefully. But as in many other clinical situations, there aren't perfect drugs available to treat cardio-renal syndrome and the existing ones may have serious side effects in medium/long term causing the deterioration of renal function and possibly an increased mortality. The treatment is truly challenging in patients with severe fluid overload that is refractory to diuretics. This article aims to present the existing definitions of cardio-renal syndrome, its epidemiology, describe the current knowledge about the pathophysiology and its relationship to therapeutic interventions, some actual strategies and future technologies in an attempt to preserve the kidney, mainly during the decompensation of chronic heart failure.

Ascending aortic aneurysm and patent foramen ovale: a rare cause of platypnea-orthodeoxia.

Platypnea-orthodeoxia is a rare syndrome characterized by dyspnea and hypoxia induced by the upright position and relieved by the supine position. Several factors related to atrial anatomy can facilitate shunting through an atrial septal defect; in many cases, the syndrome is associated with patent foramen ovale and right-to-left shunt, and has also been linked to aortic aneurysm. We present a case of platypnea-orthodeoxia syndrome in a 61-year-old woman with patent foramen ovale and ascending aortic aneurysm.

Anemia: only a marker or an independent predictor of mortality in advanced heart failure?

INTRODUCTION AND OBJECTIVES: Advanced heart failure (HF) remains a major cause of mortality. Identification of new prognostic risk factors is therefore a priority. Anemia, a frequent comorbidity in HF patients and a recognized trigger of symptoms, has recently received considerable attention in this context. Several studies have demonstrated an association between anemia and increased mortality in stable chronic HF patients. However, the prognostic impact of this comorbidity on the survival of advanced HF patients remains unclear. Our aim was to assess whether anemia is not only a marker of advanced HF, but also an independent predictor of mortality. METHODS: We performed a retrospective study of 391 consecutive patients admitted to a single advanced HF care unit and divided into two groups according to the presence or absence of anemia at admission. Demographic, clinical, laboratory and therapeutic data were compared between the groups. Anemia was defined as hemoglobin at admission of <12 g/dl for women and <13 g/dl for men. Appropriate statistical tests and multivariate analysis were used to identify independent predictors of one-year and overall mortality. Median follow-up was 3.2 years. RESULTS: Group A, anemic patients (n=169, 43.2%), were older (61.7 +/- 14.7 vs. 58.0 +/- 14.5 years, p = 0.01) and included a higher number of patients with ischemic cardiomyopathy (40.7% vs. 28.6%, p = 0.01), but fewer with dilated cardiomyopathy (41.0% vs. 55.8%, p = 0.004). At admission, group A had lower systolic blood pressure (110.1 +/- 24.8 mmHg vs. 115.2 +/- 22.0 mmHg, p = 0.03) and higher mean C-reactive protein (1.90 +/- 3.6 mg/dl vs. 1.19 +/- 2.6 mg/dl, p = 0.004) and creatinine (1.50 +/- 0.9 mg/dl vs. 1.20 +/- 0.5 mg/dl, p < 0.001). Gender, prevalence of cardiovascular risk factors, previous medication and left ventricular ejection fraction were not statistically different between the groups. At discharge, fewer anemic patients received digoxin (71.1% vs. 81.8%, p = 0.03). Mortality rates at 3 months (13.6% vs. 6.7%, p = 0.05), one year (22.9% vs. 11%, p = 0.006) and during follow-up (39.8 % vs. 23.8%, p = 0.002) were significantly higher in Group A. Multivariate analysis demonstrated that anemia was an independent predictor of mortality at one year (p = 0.035) and during median follow-up: (p = 0.014). In the anemic group a linear relationship between hemoglobin levels and mortality was also detected. CONCLUSIONS: In our population, anemia was a frequent comorbidity and had an independent and negative impact on long-term mortality. Its correction could improve outcomes in advanced HF patients.

Predictors of adverse outcome in a diabetic population following acute coronary syndromes.

INTRODUCTION: People with diabetes are at increased risk for heart failure (HF), major adverse cardiovascular events (MACE) and death following acute coronary syndromes (ACS). It is important to recognize the most powerful predictors of these events after an ACS as early as possible, in order to address them more aggressively. This is particularly important considering that various studies have shown that this population is undertreated in the setting of ACS. OBJECTIVES: To characterize a diabetic population presenting with ACS and to determine independent predictors of HF, MACE and mortality on follow-up. METHODS: This was a longitudinal, observational, retrospective study including 471 consecutive diabetic patients, both previously known and newly diagnosed, hospitalized for ACS in a single center between May 2004 and December 2006. A mean 12-month follow-up was conducted. Cox regression analysis was used to determine the independent predictors of HF, MACE and mortality on follow-up, divided into different periods--1 month, 6 months and 1 year. RESULTS: Of the overall diabetic population, 67.3% were male and mean age was 69 +/- 11 years. Mean glomerular filtration rate (GFR) was 62 +/- 22 ml/min and mean left ventricular ejection traction (LVEF) was 50%. diagnosis on admission was ST-elevation myocardial infarction (STEMI) in 31.3%, non-ST elevation myocardial infarction (NSTEMI) in 50.1%, unstable angina (UA) in 14.3% and ACS with left bundle branch block or pacemaker in 4.2%. Cardiac catheterization was performed in 55.6% of the patients during the index hospitalization. Mortality during hospitalization and at 1 year was 6.4% and 10.4%, respectively. The one-year MACE rate was 20.4% and hospitalization for HF occurred in 10.1% of the patients. The independent predictors of HF at 1 year were blood glucose on admission > 184.5 mg/dl, GFR < 63.8 ml/min, LVEF < 46.5% and NSTEMI, while predictors of mortality were LVEF < 40.5% and Killip class on admission > I. Blood glucose on admission > 130.5 mg/dl and LVEF < 49.5% were independent predictors of MACE, whereas cardiac catheterization was a protective factor. CONCLUSION: Following ACS diabetic patients have high rates of mortality, HF and MACE. The low rate of invasive strategy may contribute to this situation. HF during hospitalization, whether by low LVEF or Killip class > I, and higher blood glucose on admission were powerful predictors of poorer outcome. Moreover, the use of recommended cardiovascular agents and procedures were protective factors. These findings suggest that diabetic patients should not be excluded from recommended cardiovascular interventions. Efforts should be made to identify these high-risk patients as early as possible in order to manage them carefully and aggressively to improve their poor prognosis.

Ischemic versus non-ischemic cardiomyopathy--are there differences in prognosis? Experience of an advanced heart failure center.

INTRODUCTION: Previous studies have associated heart failure (HF) of ischemic etiology with worse prognosis compared to HF from non-ischemic cardiomyopathy. HF treatment has evolved significantly in recent years. Has this evolution had an impact on this prognostic gap? OBJECTIVE: The aim of our study was to compare patients with advanced HF--nonischemic versus ischemic etiology--in terms of baseline characteristics, treatment, and in-hospital and long-term prognosis (including death, heart transplantation and hospital readmission). METHODS: We performed a retrospective study including 286 consecutive patients with systolic HF admitted to an HF unit between January 2003 and June 2006. We compared two groups according to HF etiology: Group A--ischemic cardiomyopathy (n = 109); Group B--non-ischemic cardiomyopathy (n = 177). Mean follow-up was 41 months. RESULTS: Group A were older (62.2 +/- 10.4 vs. 55.9 +/- 15.2 years, p < 0.001), with a higher proportion of males (80.7 vs. 67.8%, p = 0.017), diabetes, anemia, dyslipidemia and smokers; they required more prolonged treatment with inotropic drugs and more frequent treatment with statins, antiplatelet agents and nitrates. On admission, Group B patients presented with lower serum sodium and higher aminotransferase levels. There were no differences in the occurrence of cardiogenic shock or dysrhythmias, baseline ECG rhythm, frequency of left bundle branch block, renal function, BNP, left ventricular ejection fraction, heart rate or implantation of intracardiac devices. Group A had higher in-hospital mortality (11.0 vs. 4.0%, p = 0.020). Multivariate analysis showed that the only predictor of in-hospital mortality was serum sodium < 133 mmol/l and also showed that HF etiology was not a predictor of this endpoint; previous medication with angiotensin-converting enzyme inhibitors was a protective factor. On Kaplan-Meier analysis, it was observed that, in the long-term, there were no significant differences in either survival rates (70.0 vs. 76.8%, p = 0.258), or the combined endpoints of survival free of death or heart transplantation (55.7 vs. 54.5%, p = 0.899) and survival free of death, heart transplantation or hospital readmission (38.0 vs. 32.8%, p = 0.386). CONCLUSIONS: Although in-hospital mortality was higher in ischemic cardiomyopathy, this variable was not an independent predictor of mortality and the difference appears to fade in the long-term, in contrast to what had been reported in older studies, but in agreement with more recent data.

Apolipoprotein E epsilon-4 polymorphism is associated with younger age at referral to a lipidology clinic and a poorer response to lipid-lowering therapy.

BACKGROUND: The risk of coronary heart disease (CHD) is related to environmental factors and genetic variants. Apolipoprotein E (apoE) polymorphisms are heritable determinants of total and low-density lipoprotein cholesterol, with some authors suggesting an association between the ε4 allele and CHD. We investigated the relationship between apoE genotype and age at referral to a specialized lipid clinic by the primary care physician and whether the benefits of treatment with statin differed between genotypes. METHODS: We assessed individual apoE genotypes and lipid blood profile in a total of 463 patients followed at a specialized lipid clinic due to dyslipidemia, with a 3-year median follow-up time. The primary care physician at the time of the referral had no access to the apoE genotyping results. Carriers of apoE ε4/ε2 genotype were excluded. RESULTS: The frequencies of ε2, ε3 and ε4 alleles were 7.8, 78.9 and 13.3%, respectively. There were no significant differences between genders. Although with similar lipid profiles and antidyslipidemic drug usage at baseline, ε4-carriers were referred to the clinic at a younger age (44.2 ± 14.7 years) compared with non-ε4 carriers (50.6 ± 13.8 years) (p < 0.001), with a substantially younger age of referral for homozygous E4/4 and for all genotypes with at least one copy of the ε4 allele (p < 0.001 for trend). Although both ε4 and non-ε4 carriers achieved significant reductions in total cholesterol during follow-up (p < 0.001 vs. baseline), the mean relative decrease in total cholesterol levels was higher in non-ε4 carriers (-19.9 ± 2.3%) compared with ε4 carriers (-11.8 ± 2.3%), p = 0.003. CONCLUSION: Our findings support the concept that there is a reduced response to anti-dyslipidemic treatment in ε4 carriers; this can be a contributing factor for the earlier referral of these patients to our specialized lipid clinic and reinforces the usefulness of apoE genotyping in predicting patients response to lipid lowering therapies.