Eplerenone improves prognosis in postmyocardial infarction diabetic patients with heart failure: results from EPHESUS

Background:  The Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) trial demonstrated that selective aldosterone blockade with eplerenone significantly reduced total mortality by 15%, combined cardiovascular (CV) mortality/CV hospitalization by 13%, CV mortality by 17% and sudden cardiac death by 21%, vs. placebo when added to standard care in patients with left ventricular systolic dysfunction (LVSD) and signs of congestive heart failure (CHF) following acute myocardial infarction (AMI). We retrospectively evaluated the effect of eplerenone vs. placebo in a subset of 1483 diabetic patients with LVSD and signs of CHF following AMI.
Methods:  Diabetic status was determined from medical histories at screening. Analyses were based on time to first occurrence of an event. Results were based on a Cox's proportional hazards regression model stratified by region with treatment, subgroup and treatment-by-subgroup interaction as factors. The 95% confidence intervals for the risk ratios were based on the Wald's test.
Results:  Treatment with eplerenone in diabetic patients with CHF following AMI reduced the risk of the primary endpoint, a composite of CV mortality or CV hospitalization, by 17% (p = 0.031). The absolute risk reduction of the primary endpoint was greater in the diabetic cohort (5.1%) than in the non-diabetic cohort (3%). Hyperkalaemia occurred more often with eplerenone than with placebo (5.6 vs. 3%, p = 0.015). Among the diabetic cohorts, the prespecified endpoint of 'any CV disorder' occurred in 28% of the eplerenone group and 35% of the placebo group (p = 0.007).
Conclusion:  Eplerenone treatment may reduce adverse CV events in diabetic patients with LVSD and signs of CHF following AMI.     

The Prognostic Significance of Bundle Branch Block in High-Risk Chronic Stable Vascular Disease Patients: A Report from the HOPE Trial

Objective: The prognostic significance of left and right bundle branch block (LBBB and RRBB) in patients with chronic stable cardiovascular (CV) disease is not well characterized and was evaluated in the Heart Outcomes Prevention Evaluation (HOPE) study cohort.
Design: Observational analysis of data prospectively collected in the HOPE trial.
Setting and Patients: HOPE was a multicenter, international trial, which evaluated ramipril and vitamin E in 9,541 patients aged ≥55 years with CV disease or diabetes with ≥1 CV risk factor(s) but without heart failure (HF) or known left ventricular systolic dysfunction. Follow-up extended for a median of 4.5 years. Electrocardiograms were obtained at baseline in all study participants and were read centrally.
Main Outcome Measures: Major CV events (defined as CV death, myocardial infarction, or stroke), heart failure, CV death, all-cause death, and sudden death.
Results: Baseline LBBB was present in 246 (2.6%) patients and was associated with increased risk for major CV events (HR = 1.54; 95% CI, 1.18–2.02), CV death (HR 2.29; 95% CI, 1.63–3.20), heart failure (HR 2.99; 95% CI, 2.31–3.87), sudden death (HR 3.17; 95% CI, 2.13–4.73), and all-cause death (HR = 2.10; 95% CI, 1.59–2.77). In multivariate models, LBBB remained an independent predictor of heart failure, sudden death, CV death, and all-cause death (P ≤ 0.002 for all). Baseline RBBB was present in 428 (4.5%) of patients and was not associated with increased CV risk.
Conclusions: In patients with stable chronic CV disease, LBBB but not RBBB is an independent predictor of heart failure, sudden death, CV death, and all-cause death.     

Change of thyroid function in 50 patients with aplastic anemia.

The serum thyroid hormones were measured in 50 patients with aplastic anemia (AA). Serum T3 and T4 levels were significantly lower, especially in the elderly and in those in chronic AA, while they were normal in acute AA. There was no obvious difference with thyroid-stimulating hormone (TSH). It was suggested that the result may be caused by euthyroid sick syndrome, a protective adaptation that helps in classifying and evaluating the prognosis of the disease.     

Long-term thyroid hormone administration reshapes left ventricular chamber and improves cardiac function after myocardial infarction in rats

Thyroid hormone (TH) is critical for tissue differentiation at early stages of development, induces physiological hypertrophy and regulates the expression of important contractile proteins such as myosin heavy chain (MHC) isoform and calcium cycling proteins. Furthermore, TH seems to control the response to stress by regulating important cardioprotective molecules such as heat shock proteins (HSPs). Thus, the present study investigated whether TH administration immediately after acute myocardial infarction can favourably remodel the post-infarcted myocardium. Acute myocardial infarction was induced in rats by coronary artery ligation (AMI, n=10), while SHAM-operated animals served as controls (SHAM, n = 8). TH was administered for 13 weeks (AMI-THYR, n = 9). Cardiac contractile function and left ventricular (LV) chamber remodelling was assessed by serial echocardiography and in Langendorff heart preparations. AMI significantly reduced LV ejection fraction (EF%); 30.0 (s.e.m, 2.3) Vs. 73.8 (1.8) in SHAM, P < 0.05. In addition, +dp/dt and -dp/dt (in mmHg/s) were 4,051 (343) and 2,333 (118) respectively for SHAM Vs. 2,102 (290) and 1,368 (181) for AMI, P < 0.05. With TH treatment, EF% was increased to 49.5 (2.7) in AMI-THYR, P < 0.05, while +dp/dt and -dp/dt (in mmHg/s) were 3,708 (231) and 2,035 (95) for AMI-THYR, P < 0.05 Vs. AMI. A marked elevation of the expression of beta-MHC and a reduced ratio of SERCA/Phospholamban were found in viable myocardium of AMI hearts, which was prevented by TH. Furthermore, heat shock protein 70 myocardial content was decreased in AMI hearts and was significantly increased after TH treatment. An ellipsoidal reshaping of LV chamber was observed with TH; cardiac sphericity index, (ratio of long/short axis, SI), was 1.98 (0.03) for SHAM, 1.52 (0.05) for AMI and 1.72(0.02) for AMI-THYR, P < 0.05. In conclusion, long-term TH administration immediately after AMI results in sustained improvement of cardiac haemodynamics.     

糖尿病急性心肌梗死后易发心力衰竭的机制

在糖尿病的患者,如果不合并冠心病心肌缺血,基本均处于亚临床状态的心肌损害,心功能表现为早期舒张功能不全以及晚期合并收缩功能不全,其机制是心肌能量代谢的异常导致一系列的病理生理学改变,包括糖类代谢紊乱、脂肪酸的氧化和心肌脂质聚集等,也就是目前常说的糖尿病心肌病。对于严重的糖尿病患者如果遭遇心肌缺血的打击,其更加容易发生心力衰竭和死亡,拥有明显更差的预后,其机制是什么呢？现将详细加以阐述。     

Clinicopathological and biochemical findings of thyroid amyloid in hereditary transthyretin amyloidosis with and without liver transplantation

Hereditary transthyretin (TTR) amyloidosis is a fatal disease causing systemic organ dysfunctions. Histopathological studies revealed that thyroid glands are major target tissues. However, details about thyroid functions remain to be fully elucidated in this disease. For patient treatment, liver transplantation (LT) reportedly prolongs patient survival, but thyroid gland function after LT still remains poorly understood. In this study, we investigated the thyroid functions in 101 patients with hereditary TTR amyloidosis and the effects of LT on thyroid functions in those patients. In addition, we investigated histopathological and biochemical findings of thyroid specimens obtained at autopsy. Disease duration and age at examination inversely correlated with serum levels of free triiodothyronine (fT3) in hereditary TTR amyloidosis. On the contrary, in patients who underwent transplantation, time from disease onset to transplantation and age at transplantation clearly correlated with serum fT3and thyroid stimulating hormone (TSH) levels. In autopsy studies, amounts of thyroid amyloid deposits in patients with transplantation were significantly lower than those in patients without transplantation. Mass spectrometric analyzes also revealed that proportions of wild-type (WT) TTR in thyroid amyloid deposits in patients with hereditary TTR amyloidosis who underwent transplantations were higher than those in patients without transplantation. Thyroid hormone functions may diminish according to the disease progression. LT could prevent thyroid dysfunction in hereditary TTR amyloidosis.     

Thyroid Hormone Replacement Therapy Attenuates Atrial Remodeling and Reduces Atrial Fibrillation Inducibility in a Rat Myocardial Infarction–Heart Failure Model

BackgroundHeart failure (HF) is associated with increased atrial fibrillation (AF) risk. Accumulating evidence suggests the presence of myocardial tissue hypothyroidism in HF, which may contribute to HF development. In a recent report we demonstrated that hypothyroidism, like hyperthyroidism, leads to increased AF inducibility. The present study was designed to investigate the effect of thyroid hormone (TH) replacement therapy on AF arrhythmogenesis in HF.Methods and ResultsMyocardial infarction (MI) was produced in rats by means of coronary artery ligation. Rats with large MIs (>40%) were randomized into L-thyroxine (T₄; n = 14) and placebo (n = 15) groups 2 weeks after MI. Rats received 3.3 mg T₄ (in 60-day release form) or placebo pellets for 2 months. Compared with the placebo, T₄ treatment improved cardiac function and decreased left ventricular internal diameters as well as left atrial diameter. T₄ treatment attenuated atrial effective refractory period prolongation (45 ± 1.5 ms in placebo group vs 37 ± 1.6 ms in T₄ group; P < .01) and reduced AF inducibility (AF/atrial flutter/tachycardia were inducible in 11/15 rats [73%] in the placebo- vs 4/14 rats [29%] in the T₄-treated group; P < .05). Arrhythmia reduction was associated with decreased atrial fibrosis but was not associated with connexin 43 changes.ConclusionsTo our knowledge this is the first study demonstrating that TH replacement therapy in HF attenuates atrial remodeling and reduces AF inducibility after MI-HF. Clinical studies are needed to confirm such benefits in human patients.     

Previously known and newly diagnosed atrial fibrillation: a major risk indicator after a myocardial infarction complicated by heart failure or left ventricular dysfunction

AIMS: To characterize the relationship between known and newly diagnosed atrial fibrillation (AF) and the risk of death and major cardiovascular (CV) events in patients with acute myocardial infarction (MI) complicated by heart failure (HF) and/or left ventricular systolic dysfunction (LVSD). METHODS: The VALIANT trial enrolled 14,703 individuals with acute MI complicated by HF and/or LVSD. AF was assessed at presentation and at randomization (median 4.9 days after symptom onset). Primary outcomes were risk of death and major CV events 3 years following acute MI. RESULTS: A total of 1812 with current AF (AF between presentation and randomization), 339 patients with prior AF (history of AF without current AF), and 12,509 without AF were enrolled. Patients with AF were older; had more prior HF, angina, and MI, and received beta-blockers and thrombolytics less often than those without AF. Three-year mortality estimates were 20% in those without AF, 37% with current AF, and 38% with prior AF. Compared with patients without AF, the multivariable adjusted HR of death was 1.25 (1.03-1.52; p=0.03) for prior AF and 1.32 (1.20-1.45; p<0.0001) for current AF. HR for major CV events was 1.15 (0.98-1.35; p=0.08) and 1.21 (1.12-1.31; p<0.0001). CONCLUSION: AF is associated with greater long-term mortality and adverse CV events with acute MI complicated by HF or LVSD.     

Efficacy and safety of thyroxine therapy on patients with heart failure and subclinical hypothyroidism: A protocol for systematic review and meta-analysis

Background:Subclinical hypothyroidism (SCH) can increase the risk of heart failure (HF) clinically. However, thyroxine therapy for patients with HF and SCH has the risk of developing tachyarrhythmias. At present, there is no sufficient evidence-based medical evidence for levothyroxine in the therapy of this situation, and the treatment issue is still controversial. Therefore, our meta-analysis aims to assess the effectiveness and safety of thyroxine therapy for patients with HF and SCH.Methods:We searched the related randomized controlled trials that have been published in the following 7 electronic databases: PubMed, Cochrane Library, EMBASE, Chongqing VIP, China National Knowledge Infrastructure, Chinese biomedical literature database, and Wan Fang database. The treatment group was treated with routine HF therapy plus thyroxine, while the control group was treated with HF routine therapy. Main outcome measures effective rate and New York Heart Association classification; Secondary outcome measures included: left ventricular ejection fraction, quality of life score, brain natriuretic peptide / N-terminal pro brain natriuretic peptide, 6-minute walk test, and adverse events. After screening studies and extracting data, we will use Cochrane collaborative tools to evaluate the risk of bias to assess the methodological quality of the included randomized controlled trials. We will use STATA 14.0 software for data synthesis and statistical analysis. Both subgroup analysis and sensitivity analysis will be used to detect potential sources of heterogeneity. In addition, we will use sensitivity analysis to test the stability of the outcomes. If possible, we will perform a funnel chart and Eggers test evaluate publication bias. The quality of the evidence will be evaluated through the grades of recommendations assessment, development, and evaluation system.Results:Our findings will be published in peer-reviewed journals.Conclusion:This research will provide evidence about the efficacy and safety of thyroxine in the treatment of patients with HF and SCH. Objective to provide evidence-based medicine basis for thyroxine treatment of patients with SCH and HF.Registration number:INPLASY2020100062.     

Post-myocardial infarction ventricular remodeling: Animal and human studies

Summary Segmental alterations in left ventricular function are generally present in patients who suffer an acute myocardial infarction. Regional wall motion abnormalities in left ventricular systolic function can be identified in the hyperacute period and generally persist in patients who complete a myocardial infarction. Through the process of infarct expansion, the infarcted territory may thin and lengthen in the short term following a myocardial infarction. Some infarct survivors are also prone to further progressive alterations in the shape and size of the left ventricle, a process that has been termedpostinfarction ventricular remodeling. Although left ventricular remodeling appears to represent an adaptive process serving to preserve stroke volume (and cardiac output) following myocardial injury, the enlargement process may have undesirable long-term effects on global left ventricular function and on clinical prognosis. Fortunately, recent experimental and clinical evidence demonstrates that ventricular remodeling and its deleterious consequences may be preventable.     

Five‐year incidence and progression of thyroid dysfunction in an older population

Background: Very few studies have assessed both the incidence and progression of thyroid dysfunction in a single older population‐based cohort. In this study, we aimed to assess the 5‐year incidence, progression and risk factors for development of thyroid dysfunction in an older Australian population. Methods: The Blue Mountains Eye Study is a longitudinal population‐based cohort study. During 1997–1999, 1768 participants (≥55 years) had thyroid function assessed. After excluding participants reporting any form of treatment for their thyroid condition at baseline, 951 participants (91.4%) without thyroid dysfunction and 54 (5.4%) with thyroid dysfunction were re‐examined 5 years later. Thyroid dysfunction was defined using serum thyrotropin (thyroid stimulating hormone (TSH)) screen, followed by serum free T4 assessment. Results: The overall 5‐year incidence of thyroid dysfunction was 4.7% (95% confidence interval (CI) 3.4–6.1). Obesity (body mass index ≥ 30 kg/m²) and serum TSH > 2 mIU/L at baseline predicted incident overt hypothyroidism (odds ratio (OR) 4.05, CI 1.74–9.41) and (OR 5.46, CI 1.16–25.67) respectively. The 5‐year incidence of subclinical hypothyroidism was significantly higher in women than in men, 2.5% versus 0.7% (P= 0.03). Progression to overt hypothyroidism was observed in 17.9% of subjects with subclinical hypothyroidism over 5 years. Conclusions: The 5‐year incidence of thyroid dysfunction in this older population was relatively low, and was associated with obesity and serum TSH level > 2 mIU/L at baseline. Over one in six persons with subclinical hypothyroidism progressed to overt thyroid dysfunction over the 5‐year period. Our findings highlight the need for appropriate management of subclinical hypothyroidism among older people.     

Thyroid axis function and dysfunction in critical illness

Acutely ill patients typically present with low circulating T3 and increased reverse T3. When illness is severe and prolonged, also pulsatile TSH secretion and circulating T4 levels are low. This constellation of changes within the thyroid axis is referred to as the low T3 syndrome or non-thyroidal illness syndrome (NTI), and comprises both peripheral and central alterations in the thyroid axis. Acute alterations are dominated by changes in thyroid hormone binding, in thyroid hormone uptake by the cell and in the activity of the type-1 and type-3 deiodinase enzymes. Prolonged critical illness is associated with a neuroendocrine dysfunction characterized by suppressed hypothalamic thyrotropin-releasing hormone (TRH) expression, resulting in reduced stimulation of the thyrotropes whereby thyroidal hormone release is impaired. During prolonged critical illness, several tissue responses could be interpreted as compensatory to low thyroid hormone availability, such as increased expression of monocarboxylate transporters, upregulation of type 2 deiodinase activity and increased sensitivity at the receptor level. Whether the low T3 syndrome should be treated and which compound should be used remains to be further studied.     

Growth hormone and insulin-like growth factor-1 in acute myocardial infarction.

BACKGROUND: Growth hormone therapy after myocardial infarction improves cardiac function and survival in animals. Beneficial effects in humans are reported from studies where patients with idiopathic dilated cardiomyopathy were treated with growth hormone. We have studied the role of the endogenous growth hormone system in myocardial infarction. METHODS AND RESULTS: Fifty-two consecutive patients with acute myocardial infarction were studied during the first 5 days and at follow-up 6 and 12 weeks later. The time from chest pain onset was used in the analyses. The mean growth hormone level within the first 6 h was nearly three times higher (1.1 +/- 0.2 microg. l(-1)) than on the third day (0.4 +/- 0.05 microg. l(-1), P < 0.0002). It remained higher in patients with higher levels of cardiac enzymes, impaired left ventricular function and intense inflammatory response. Insulin-like growth factor-1 (IGF-1) declined slowly but remained within the normal range throughout the whole study period. Patients who died within 2 years had higher levels of growth hormone and lower levels of IGF-1, indicating growth hormone resistance. Endogenous levels of growth hormone or IGF-1 did not correlate with improvement in left ventricular function at 6 weeks. CONCLUSIONS: The growth hormone axis is stimulated early in acute myocardial infarction, particularly in patients with more severe cardiac damage. Whether treatment with growth hormone can be beneficial for patients with heart failure after myocardial infarction remains to be investigated.     

早发冠心病心肌梗死型与非心肌梗死型危险因素差异分析

目的探讨早发冠心病中心肌梗死型与非心肌梗死型的危险因素差异。方法回顾性分析2004年1月至2009年12月在沈阳医学院附属奉天医院心血管内科住院并确诊的45岁及以下冠心病患者165例,分为急性心肌梗死(AMI)组和非AMI组。对两组患者的相关临床资料及危险因素进行统计分析。结果 AMI组吸烟史比例、男性比率、血浆纤维蛋白原及D-二聚体均高于非AMI组,差异有统计学意义(P<0.05),两组的血脂异常率、血小板计数(PLT)、血小板压积、凝血酶原时间(PT)、国际标准化比值(INR)和活化部分凝血活酶时间(APTT)的差异无统计学意义。结论吸烟、男性性别、血脂水平异常是早发冠心病重要危险因素;血浆纤维蛋白原水平增高对于预测早发冠心病心肌梗死可能具有一定的临床意义。     

Congestive heart failure with preserved left ventricular systolic function after acute myocardial infarction: clinical and prognostic implications

AIMS: To characterise the prevalence, in-hospital complications, management, and long-term outcome of patients with congestive heart failure but preserved left ventricular systolic function after acute myocardial infarction. METHODS: 3166 consecutive patients screened for entry in the Bucindolol Evaluation in Acute Myocardial Infarction Trial with definite acute myocardial infarction and echocardiographic assessment of left ventricular systolic function were included between 1998 and 1999 in this prospective observational study. Main outcome measures were occurrences of in-hospital complications and all cause mortality. RESULTS: Congestive heart failure was seen during hospitalisation in 1464 patients (46%), 717 patients had preserved left ventricular systolic function (wall motion index > or =1.3 corresponding to ejection fraction > or =0.40), and 732 patients had systolic dysfunction (wall motion index <1.3). One year mortality in patients with no heart failure, heart failure with preserved systolic function, and heart failure with systolic dysfunction were 6, 22 and 35%, P<0.0001. Unadjusted risk of death from all causes associated with heart failure and preserved systolic function was 3.3 (95% CI 2.8-4.0), and after adjustment for baseline characteristics and left ventricular systolic function in multivariate Cox proportional hazards analysis the risk was 2.1 (95% CI 1.7-2.6), P<0.0001. CONCLUSIONS: Congestive heart failure is frequently present in patients with preserved left ventricular systolic function, and is associated with increased risk of in-hospital complications and death following acute myocardial infarction.     

Hospital protocols and evidence-based therapies: the importance of integrating aldosterone blockade into the management of patients with post-acute myocardial infarction heart failure

Left ventricular systolic dysfunction (LVSD) and clinical heart failure are common complications of acute myocardial infarction (AMI) and result in substantially increased mortality and morbidity. Evidence-based cardiovascular protective therapies, including angiotensin-converting enzyme inhibitors, beta blockers, antiplatelet agents, and lipid-lowering medications, improve outcomes for these patients. However, this population is significantly undertreated with these guideline-recommended agents. Critical pathways have been demonstrated to improve the quality and consistency of treatment; as such, the new American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of patients with ST-elevation myocardial infarction (STEMI) recommend that critical pathways be implemented for the management of these patients. The recent Eplerenone Post-acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) demonstrates that eplerenone, a selective aldosterone blocker, has incremental benefit in decreasing mortality and morbidity when used with standard care therapies in patients post AMI with heart failure and LVSD. The clinical trial evidence coupled with the national guidelines provides a strong rationale for routine incorporation of aldosterone blockade into new or already established critical pathways for AMI complicated by LVSD and heart failure.     

Defining and managing patients with non-ST-elevation myocardial infarction: Sorting through type 1 vs other types

Advances in cardiovascular (CV) imaging, redefined electrocardiogram criteria, and high-sensitivity CV biomarker assays have enabled more differentiated etiological classification of myocardial infarction (MI). Type 1 MI has a different underlying pathophysiology than type 2 through type 5 MI; type 1 MI is characterized primarily by intracoronary atherothrombosis and the other types by a variety of mechanisms, which can occur with or without an atherosclerotic component. In type 2 MI, there is evidence of myocardial oxygen supply-demand imbalance unrelated to acute coronary atherothrombosis. Types 1 and 2 MI are spontaneous events, while type 4 and type 5 are procedure-related; type 3 MI is identified only after death. Most type 1 and type 2 MI present as non-ST-elevation MI (NSTEMI), although both types can also present as ST-elevation MI. Because of their different underlying etiologies, type 1 and type 2 NSTEMI have different presentation and prognosis and should be managed differently. In this article, we discuss the epidemiology, prognosis, and management of NSTEMI occurring in the setting of underlying type 1 or type 2 pathophysiology. Most NSTEMI (65%–90%) are type 1 MI. Patients with type 2 MI have multiple comorbidities and causes of in-hospital mortality among these patients are not always CV-related. It is important to distinguish between type 1 and type 2 NSTEMI early in the clinical course to allow for the use of the most appropriate treatments that will provide the greatest benefit for these patients.     

Effects of growth hormone in rats with postinfarction left ventricular dysfunction

Summary Growth hormone may affect cardiac function. In rats, chronic hypersecretion of growth hormone leads to increased maximum isometric contractile force of the left ventricular papillary muscle in vitro. In humans, administration of growth hormone can increase myocardial contractility. However, cardiac effects of growth hormone in heart failure or cardiac dysfunction have not been studied to date. The current study was to evaluate the cardiac effects of growth hormone in conscious rats with postinfarction left ventricular dysfunction and sham controls. Ligation of the left coronary artery or sham operation was performed, then 4 weeks after surgery, recombinant human growth hormone (2 mg/kg/day, SC) or vehicle was administered for 15 days. Catheters were implanted 13 days after treatment with growth hormone or vehicle. Hemodynamic parameters were measured in conscious rats 2 days after catheterization. In vehicle-treated rats, left ventricular systolic pressure, maximum dP/dt, and arterial pressure were significantly decreased and left ventricular end-diastolic pressure was significantly increased in the ligation group compared with sham controls. Growth hormone treatment increased left ventricular systolic pressure (p<0.05) and dP/dt (p<0.05) and reduced left ventricular end-diastolic pressure (p<0.05), significantly in the ligated rats. In sham rats, growth hormone tended to decrease arterial pressure but did not alter ventricular contractility. Neither ligation nor growth hormone significantly altered heart rate and right atrial pressure. These results suggest that growth hormone treatment may improve cardiac function by increasing myocardial contractility in cardiac dysfunction or heart failure.     

Differential prognostic importance of QRS duration in heart failure and acute myocardial infarction associated with left ventricular dysfunction

BACKGROUND/AIMS: Studies of the prognostic importance of QRS duration in patients with heart failure (HF) have shown conflicting results and few studies have estimated the importance after myocardial infarction (MI). METHODS: The Danish Investigations and Arrhythmia ON Dofetilide (DIAMOND) study randomised 3028 patients to dofetilide (class III antiarrhythmic) or placebo. The study consisted of two almost identical trials conducted simultaneously. One trial included 1518 patients with chronic HF and the other trial 1510 patients with a recent MI. All patients had left ventricular dysfunction. Dofetilide did not influence mortality in either trial. QRS duration was systematically measured at randomisation and was available in 2972 patients. RESULTS: Over a 10 year observation period 1037 (70%) patients in the MI study and 1324 (87%) in the HF study died. In the MI study, risk of death increased 6% for each 10 ms increase in QRS duration (HR=1.06/10 ms increase in QRS (CI=1.04-1.09), p<0.0001) whereas QRS duration had no influence in the HF study after multivariable adjustment. The difference between HF and MI was significant (p<0.0004 for interaction). CONCLUSION: QRS duration predicts death in patients with left ventricular dysfunction who have suffered MI. In patients with HF QRS duration is not predictive of mortality.     

Cardiovascular cell therapy and endogenous repair

Cardiovascular disease (CVD) exceeds infection and cancer as the leading cause of death. In the USA alone, approximately a million individuals suffer an acute myocardial infarction (AMI) annually. As the prevalence of CVD risk factors (e.g. hypertension, obesity and type 2 diabetes) rises, CVD is increasing in younger individuals. Fortunately, existing therapies have improved post-AMI mortality, but in turn have increased the prevalence of post-AMI heart failure (HF). Approximately half-a-million new HF cases are diagnosed each year in the USA. In the next 25 years, up to 15% of the population over the age of 65 in the USA is projected to have HF. Therapeutic interventions that prevent/reverse atherosclerosis, prevent post-AMI HF and halt the progressive functional deterioration once HF occurs are all needed. Cell therapy - either via exogenous delivery or by endogenous mobilization of cells - may be able to do so, in part, by improving the body's capacity for repair. To date, primarily bone marrow- or blood-derived cells have been utilized after AMI to prevent left ventricular dysfunction, and skeletal myoblasts have been transplanted into failing myocardium. Preclinical studies are directed at prevention/reversal of atherosclerosis with bone marrow precursors, and ultimately at replacing failing heart with a cell-based bioartificial construct.