International Journal of Cardiology - Articles in Press

Atrial fibrillation, complete atrioventricular block and escape rhythm with bundle-branch block morphologies: An exceptional presentation of Lyme carditis - Corrected Proof

Nathalie Wenger, Cyril Pellaton, Philippe Bruchez, Jürg Schläpfer — 2012-02-03

We report the case of a 51year old patient without significant past medical history admitted to the emergency department with complaints of generalized fatigue, shortness of breath and chest pain. He was a former endurance sport athlete and remains physically very active. On admission, the patient was afebrile with a blood pressure of 130/68mm Hg and a regular heart rate of 45bpm. Cardiovascular, pulmonary, and neurological examinations were normal; no skin lesion was observed. The initial ECG revealed atrial fibrillation, complete atrio-ventricular (AV) block and a wide QRS (140ms) escape rhythm of 45bpm with left or right bundle branch block morphology ().

Dual non-responsiveness to antiplatelet treatment is a stronger predictor of cardiac adverse events than isolated non-responsiveness to clopidogrel or aspirin - Corrected Proof

2012-02-03

Abstract: Background: High platelet reactivity (HPR) under treatment with clopidogrel or aspirin is associated with adverse outcome. We aimed to investigate whether high platelet reactivity (HPR) to both aspirin and clopidogrel is a stronger predictor of adverse events compared to isolated HPR to clopidogrel or aspirin.Methods: In this prospective cohort study platelet reactivity to adenosine diphosphate (ADP) and arachidonic acid (AA) was assessed by Multiple Electrode Aggregometry (MEA) in 403 patients undergoing percutaneous coronary intervention. The rates of the composite of cardiac adverse events (acute coronary syndrome, stent thrombosis, stroke, death and revascularization) were recorded during 12-month follow-up.Results: The composite endpoint of cardiovascular adverse events occurred more often in patients with high platelet reactivity (HPR) to both agonists ADP and AA (37.5%) than in those with isolated HPR to ADP (33.3%), AA (25.6%) or without any HPR (18.6%; p=0.003). Classification tree analysis indicated that any HPR emerged as an independent predictor influencing outcome, which was associated with a 1.75 higher risk of cardiac adverse events (OR=1.75: 95%CI=1.1–2.9). Interestingly, the predictive value of HPR tended to be greater among patients with diabetes mellitus (OR=2.18; 95%CI=1.20–3.95). C-reactive protein and diabetes mellitus were independent predictors of high platelet reactivity to both agonists.Conclusions: Dual low responsiveness to clopidogrel and aspirin is a strong predictor of cardiac adverse events, especially in patients with diabetes mellitus, which underlines the need for personalized antiplatelet treatment.

The presence of an atrial electromechanical delay in idiopathic atrial fibrillation as determined by tissue Doppler imaging - Corrected Proof

2012-02-03

Atrial fibrillation (AF) derives from a complex continuum of predisposing factors. However, the true ‘scene of calamity’ is the atrium. Increased left atrial (LA) size is associated with increased risk of AF onset and recurrence, other cardiovascular disease and mortality . Both atrial conduction slowing and atrial dilatation will favour AF as it results in increased total atrial conduction time, which is the time elapsed between the initiation of atrial depolarisation and the last depolarisation of the same activation front . A prolonged total atrial conduction time may reflect the electro-anatomical substrate for AF since it is associated with underlying cardiovascular disease and age . It can be easily and non-invasively determined by means of transthoracic echocardiography assessing the electromechanical PA interval with tissue Doppler imaging (PA-TDI) . Idiopathic AF refers to AF in the absence of a cardiovascular or pulmonary disease generating the pathophysiological substrate for the arrhythmia. Herein, we study the electrophysiologic properties of the atria in patients with idiopathic AF using tissue Doppler imaging.

Circulating carboxy-terminal propeptide of type I procollagen is increased in rheumatic heart disease - Corrected Proof

2012-02-03

Mitral valve is mostly affected in rheumatic heart disease which is prevalent in developing countries and thousands of new cases are being diagnosed worldwide every year . It is known that extensive fibrosis occurs in the rheumatic valve . Serum carboxy-terminal propeptide of type I procollagen (PICP), the marker of collagen synthesis was reported as a marker of extracellular matrix (ECM) remodelling in various heart diseases . We therefore, measured the levels of circulating PICP to explore the severity of ECM remodelling in rheumatic heart disease.

A bleeding conundrum - Corrected Proof

2012-02-03

A 33-year-old woman with complex congenital heart disease (CHD) presented with acute pleuritic chest pain, dyspnoea and hypoxia. The patient was pyrexial, tachycardic and hypotensive with only bilateral scattered crackles. Haematinics showed haemoglobin 7∙8g/dl and a white cell count of 5∙5×109/l. Her C-reactive protein was elevated at 259 and her INR was 4∙3 (coumadin).

Successful primary angioplasty in patient with ST-segment elevation myocardial infarction caused by large septal branch occlusion - Corrected Proof

Artur Dziewierz, Andrzej Wiśniewski, Tomasz Rakowski, Dariusz Dudek — 2012-02-01

We report a rare case of septal ST-segment elevation myocardial infarction (STEMI) caused by isolated, thrombotic occlusion of a large septal branch successfully treated with drug-eluting stent (DES) implantation.

Increase in cardiac M2-muscarinic receptor expression is regulated by GATA binding protein 4 (GATA-4) in streptozotocin-induced diabetic rats - Corrected Proof

2012-02-01

Abstract: Background: An increase in cardiac M2-muscarinic receptor (M2-mAChR) expression in diabetic rats has been observed, but the molecular mechanism of this increase remains unclear. The transcriptional activity of GATA binding protein 4 (GATA-4) has been documented to regulate the expression of M2-mAChR genes. In this study, we were interested in identifying the role of GATA-4 in the increase in M2-mAChR in diabetic rats and a primary culture of cardiomyocytes.Methods: Streptozotocin-induced diabetic rats (STZ-rats) and high-glucose (D-glucose 30mM, 24h)-treated primary cultures of cardiomyocytes from neonatal rats were used to investigate the role of GATA-4 in the change in M2-mAChR. The protein expression was determined by Western blot analysis. Phlorizin (Na+-glucose co-transport inhibitor), insulin, tiron (radical scavenger), PD98059 (ERK inhibitor) and SB203580 (p38 inhibitor) were used. We also silenced GATA-4 by RNAi to investigate the changes in M2-mAChR expression.Results: The cardiac output was reduced in STZ-rats with a higher expression of M2-mAChR or phosphorylated GATA-4 in the heart. These changes were reversed after correction of the blood sugar level. In cardiomyocytes, high glucose treatment also increased M2-mAChR expression and GATA-4 phosphorylation. These changes were reversed by tiron (ROS scavenger) or PD98059 (MEK/ERK inhibitor). However, an increase in M2-mAChR expression was not observed when GATA-4 was silenced by small interfering RNA (siRNA) in cardiomyocytes.Conclusions: We suggest that hyperglycemia can cause a higher expression of M2-mAChR in cardiomyocytes mainly through ROS to enhance MEK/ERK for phosphorylation of GATA-4.

Is there a role for coronary angiography in the early detection of the vulnerable plaque? - Corrected Proof

Kim Hoe Chan, Martin K.C. Ng — 2012-01-31

Abstract: The identification of the coronary “vulnerable plaque” that is prone to disruption and thrombosis remains a “holy grail” in the treatment of coronary artery disease. The widespread use of coronary angiography for the identification of coronary atherosclerotic disease has led to numerous earlier studies exploring the role of angiography in the early detection of the vulnerable plaque. Some of the angiographic features explored for risk of plaque rupture include the degree of luminal stenosis, presence of plaque calcification, complex lesions with plaque disruption and thrombosis, and coronary artery movement patterns. However, a major limiting factor with coronary angiography is that it is a “luminogram”, and provides little characterization of plaque morphology or vessel wall, both of which play an important role in the development of plaque vulnerability. Newer intravascular imaging techniques have been developed to permit more detailed interrogation of plaque morphology and vessel wall, potentially allowing for more accurate detection of plaque vulnerability. Whilst coronary angiography may be increasingly superseded by these advances in imaging technologies, it is likely that it will continue to play an important complementary role in the quest for the early detection of the vulnerable plaque. The prospective identification of the vulnerable plaque currently remains elusive, as definitive tools for its detection do not exist. Hence, further prospective studies on the natural history of the atherosclerotic plaque, as well as validation of imaging modalities in clinical studies are needed before the notion of early detection of the vulnerable plaque becomes a clinical reality.

How easily can omission of patients, or selection amongst poorly-reproducible measurements, create artificial correlations? Methods for detection and implications for observational research design in cardiology - Corrected Proof

Darrel P. Francis — 2012-01-30

Abstract: Background: When reported correlation coefficients seem too high to be true, does investigative verification of source data provide suitable reassurance? This study tests how easily omission of patients or selection amongst irreproducible measurements generate fictitious strong correlations, without data fabrication.Method and results: Two forms of manipulation are applied to a pair of normally-distributed, uncorrelated variables: first, exclusion of patients least favourable to a hypothesised association and, second, making multiple poorly-reproducible measurements per patient and choosing the most supportive.Excluding patients raises correlations powerfully, from 0.0±0.11 (no patients omitted) to 0.40±0.11 (one-fifth omitted), 0.59±0.08 (one-third omitted) and 0.78±0.05 (half omitted). Study size offers no protection: omitting just one-fifth of 75 patients (i.e. publishing 60) makes 92% of correlations statistically significant.Worse, simply selecting the most favourable amongst several measurements raises correlations from 0.0±0.12 (single measurement of each variable) to 0.73±0.06 (best of 2), and 0.90±0.03 (best of 4). 100% of correlation coefficients become statistically significant.Scatterplots may reveal a telltale “shave sign” or “bite sign”. Simple statistical tests are presented for these suspicious signatures in single or multiple studies.Conclusion: Correlations are vulnerable to data manipulation. Cardiology is especially vulnerable to patient deletion (because cardiologists ourselves might completely control enrolment and measurement), and selection of “best” measurements (because alternative heartbeats are numerous, and some modalities poorly reproducible). Source data verification cannot detect these but tests might highlight suspicious data and – aggregating across studies – unreliable laboratories or research fields. Cardiological correlation research needs adequately-informed planning and guarantees of integrity, with teeth.

Severity of the cardiac impairment determines whether digitalis prolongs or reduces survival of rats with heart failure due to myocardial infarction - Corrected Proof

2012-01-30

Abstract: Background: The aim of the present study was to evaluate if the influence of digitalis on survival depends on the severity of cardiac dysfunction in heart failure (HF).Methods and results: Doppler echocardiogram (DE) parameters were analyzed in 84 Wistar control (C) and 80 Wistar rats treated with 0.1mg/100g/day of digitoxin (D) five days after coronary occlusion. The DE variables correlated with the survival of the animals were: myocardial infarction size, left chamber dimensions, fractional area change and E/A ratio. The animals were observed for up to 280days. Mortality was worsened in rats in the D group with a myocardial infarction (MI)<37% and with better DE predictors of survival. Digitoxin was found to prolong survival in rats with an MI≥37% and worse DE predictors.Conclusion: For the first time our study has shown experimentally that the action of digitalis glycosides can positively or negatively influence survival during treatment of HF. It prolongs survival of those in advanced state and compromises survival when there is less severity of the disease. In fact, the greater benefits occur when digitoxin was used in heightened ventricular dilatations and worse ventricular performance.

Copeptin as a prognostic factor for major adverse cardiovascular events in patients with coronary artery disease - Corrected Proof

2012-01-30

Abstract: Background: C-terminal portion of provasopressin (copeptin) has recently been discussed as a novel biomarker for the early rule-out of acute myocardial infarction (AMI). The aim is to investigate the prognostic value of copeptin with regard to mortality and morbidity in patients with symptomatic coronary artery disease (CAD).Methods: We consecutively recruited a cath lab cohort of 2,700 patients (74.1% male; AMI, n=1316; stable angina pectoris, n=1384) presenting to the emergency department of a large primary care hospital. All patients received coronary angiography. Copeptin and other laboratory markers were sampled at the time of presentation or in the cath lab. Clinical outcomes were assessed by hospital chart analysis and telephone interviews. 2621 patients (97.1%) have been successfully followed-up at three months. The primary endpoint was a combined endpoint of rehospitalization for cardiovascular events, stroke, and all-cause death.Results: Using receiver operating characteristic curves, we calculated areas under the curve of 0.703 (95%confidence interval(CI):0.681–0.725) for the composite endpoint after three months (myocardial reinfarction, stroke, all-cause death;n=183), and 0.770 (95%CI:0.736–0.803) for all-cause death (n=76) for copeptin. A cutoff value of 21.6pmol/L for the composite endpoint yielded a sensitivity of 56.3% and a specificity of 78.6%. The predictive performance of copeptin was independent of other clinical variables or cardiovascular risk factors, and superior to that of troponin I or other cardiac biomarkers (all:P<0.0001).Conclusions: Copeptin may help in the prediction of major adverse cardiovascular events in patients with symptomatic CAD. Further studies should substantiate the findings and support the suggested cutoff value of the present study.

A case of reversible cardiomyopathy associated with sorafenib in advanced hepatocellular carcinoma - Corrected Proof

Hyekyong Park, Seung-Hee Han, Hyojin Kang, Kyungil Park — 2012-01-30

Sorafenib, the oral multikinase inhibitor, is now widely used in patients with advanced hepatocellular carcinoma and advanced renal cell carcinoma. In general, it rarely induces cardiomyopathy or heart failure. We recently met a patient who had a severe symptomatic, as yet reversible, cardiomyopathy associated with sorafenib. Careful monitoring may be required to evaluate the persistence of reversibility in sorafenib-induced cardiomyopathy.

Predictive value of glycosylated hemoglobin for mortality of patients with acute myocardial infarction undergoing percutaneous coronary intervention - Corrected Proof

2012-01-30

Elevated glycosylated hemoglobin (HbA1c) has been associated with increased cardiovascular risk in patients both with and without diabetes mellitus (DM). Previous several reports showed an association between elevated admission HbA1c and poor outcome in non-DM patients with acute myocardial infarction (AMI) underwent percutaneous coronary intervention (PCI) . In contrast, other studies have assessed the association between HbA1c levels and mortality in AMI and found no association . In patients with DM, reducing plasma HbA1c levels by tight glycemic control lowers the risk of subsequent microvascular diseases, but the relation of reduced HbA1c levels with macrovascular outcomes is less clear .

Cardioprotective effect of dipeptidyl peptidase-4 inhibitor during ischemia–reperfusion injury - Corrected Proof

2012-01-30

Abstract: Background: Dipeptidyl peptidase-4 (DPP-4) inhibitor is a new anti-diabetic drug for type-2 diabetes mellitus patients. Despite its benefits on glycemic control, the effects of DPP-4 inhibitor on the heart during ischemia–reperfusion (I/R) periods are not known. We investigated the effect of DPP-4 inhibitor on cardiac electrophysiology and infarct size in a clinically relevant I/R model in swine and its underlying cardioprotective mechanism.Methods: Fourteen pigs were randomized to receive either DPP-4 inhibitor (vildagliptin) 50mg or normal saline intravenously prior to a 90-min left anterior descending artery occlusion, followed by a 120-min reperfusion period. The hemodynamic, cardiac electrophysiological and arrhythmic parameters, and the infarct size were determined before and during I/R. Rat cardiac mitochondria were used to study the protective effects of DPP-4 inhibitor on cardiac mitochondrial dysfunction caused by severe oxidative stress induced by H2O2 to mimic the I/R condition.Results: Compared to the saline group, DPP-4 inhibitor attenuated the shortening of the effective refractory period (ERP), decreased the number of PVCs, increased the ventricular fibrillation threshold (VFT) during the ischemic period, and also decreased the infarct size. In cardiac mitochondria, DPP-4 inhibitor decreased the reactive oxygen species (ROS) production and prevented cardiac mitochondrial depolarization caused by severe oxidative stress.Conclusions: During I/R, DPP-4 inhibitor stabilized the cardiac electrophysiology by preventing the ERP shortening, decreasing the number of PVCs, increasing the VFT, and decreasing the infarct size. This cardioprotective effect could be due to its prevention of cardiac mitochondrial dysfunction caused by severe oxidative stress during I/R.

Inspiratory muscle training and quality of life in patients with heart failure: Systematic review of randomized trials - Corrected Proof

2012-01-30

Patients with chronic heart failure (CHF) may present abnormalities in cardiovascular, musculoskeletal and respiratory systems , and these abnormalities may have important implications for quality of life as well as in their poor prognosis . Thus, a primary objective in the management of these patients is to improve quality of life, and the assessment of this variable should be an important and useful outcome measure for evaluating benefits of medical and physical therapy interventions . Randomized clinical trials (RCTs) have focused on the effects of inspiratory muscle training (IMT) on inspiratory muscle strength and endurance, which leads to improvement on quality of life in these patients . However, the studies analysing these benefits are small and discordant. Therefore, we performed a systematic review comparing IMT to control groups [placebo-IMT (the same regimen as the IMT group, except that the treatment was performed with a lower inspiratory load or with no inspiratory load) or another intervention] on quality of life in patients with CHF.

A meta-analytic overview of thrombectomy during primary angioplasty - Corrected Proof

Giuseppe De Luca, Eliano Navarase, Harry Suryapranata — 2012-01-27

Abstract: Introduction: Even though primary angioplasty restores TIMI 3 flow in more than 90% of STEMI patients, the results in terms of myocardial perfusion are still unsatisfactory in a relatively large proportion of patients. Great interest has been focused in the last years on distal embolization as major determinant of poor reperfusion and clinical outcome after primary angioplasty. The aim of this article is to perform an updated meta-analysis of thrombectomy devices in STEMI patients undergoing primary angioplasty.Methods: The literature was scanned by formal searches of electronic databases (MEDLINE, Pubmed) from January 1990 to December 2010, the scientific session abstracts (from January 1990 to December 2010) and oral presentation and/or expert slide presentations (from January 2002 to December 2010) (on TCT, AHA, ESC, ACC and EuroPCR websites). No language restrictions were enforced.Results: A total of 21 randomized trials were finally included in the meta-analysis, involving 4514 patients (2270 or 50.3% randomized to thrombectomy and 2244 or 49.7% to standard angioplasty). Overall thrombectomy did not reduce 30-day mortality, with more benefits observed only with manual thrombectomy. No difference was observed in the 30-day reinfarction rate, whereas a trend in higher risk of stroke was observed with thrombectomy (p=0.06). Manual but not mechanical thrombectomy significantly improved postprocedural TIMI 3 flow, however, both devices significantly improved myocardial reperfusion as evaluated by ST-segment resolution.By meta-regression analysis a linear relationship was observed between benefits from thrombectomy in ST-segment resolution and in the presence of thrombus at baseline angiography (p=0.0016).Conclusions: The present meta-analysis has demonstrated that, among patients with STEMI, manual thrombectomy significantly improved myocardial perfusion, with a trend in short-term mortality benefits, whereas mechanical thrombectomy, despite the benefits in myocardial perfusion, did not impact on short-term survival. However, the benefits in myocardial perfusion were significantly related to prevalence of coronary thrombus. In light of the observed higher risk of stroke, thrombectomy cannot be routinely recommended, but should be used in case of evident intracoronary thrombus. Mechanical thrombectomy devices may be considered as well to further improve reperfusion and facilitate optimal stent implantation, especially in the presence of large thrombus burden.

The functional right ventricle and tricuspid regurgitation in Ebstein's anomaly - Corrected Proof

2012-01-27

Abstract: Background: The size of the functional right ventricle of patients with Ebstein's anomaly is, according to contemporary opinion, small. However, the in vivo size of the functional right ventricle in patients with Ebstein's anomaly is unknown. Furthermore, it is unknown how the apical displacement and regurgitant fraction of the tricuspid valve in Ebstein's anomaly affects the size of the functional right ventricle. Therefore the primary aim of this study was to determine the volume of the functional right ventricle in patients with Ebstein's anomaly. The secondary aim of this study was to assess correlation of the volume of the functional right ventricle to the apical displacement and regurgitant fraction of the tricuspid valve.Methods: Thirty-two consecutive patients with Ebstein's anomaly without previous cardiac surgery or shunts were studied prospectively by cardiovascular magnetic resonance. Functional right ventricle, left ventricle, and atrialized right ventricle volumes and tricuspid valve regurgitation were measured.Results: Functional right ventricle end diastolic volumes were median 127ml/m² (range: 76–339ml/m²) and were median 2.5 (range: 1.3–8.8) times larger than the left ventricle volumes. Furthermore, functional right ventricle volumes correlated in a strong positive fashion with tricuspid valve regurgitation (p<0.001, R2=0.65) and modestly with the atrialized right ventricle volumes (p=0.027, R2=0.16).Conclusion: Patients with untreated Ebstein's anomaly have large functional right ventricles. The size of the enlarged functional right ventricle seems to depend on the degree of tricuspid valve regurgitation and not on the size of the atrialized right ventricle or the age of the patient.

Diffuse multi-vessel coronary artery spasm: Incidence and clinical prognosis - Corrected Proof

2012-01-27

Abstract: Background: The incidence and clinical prognosis of diffuse and multivessel coronary spasm has not been reported.Methods: Patients with suspected vasospastic angina were prospectively enrolled. Left and right coronary angiogram was performed simultaneously after intravenous ergonovine injection. Spasm (>70% luminal narrowing) was sub-classified as diffuse (more than 20mm length), multivessel (more than 2 epicardial arteries). Clinical characteristics and prognosis were analyzed.Results: Patients (96 consecutive patients, 56 males, mean age 48years) were divided into 3 groups: diffuse-multivessel spasm (group I, n=16, 16.7%), other types of spasm (group II, n=12, 12.5%) and control group (group III, n=68, 70.8%). The rates of males, alcohol drinkers and the mean triglyceride were higher, and high density lipoprotein was lower in group I compared to group III (all p<0.05), but similar to group II (all p=NS). Hard cardiovascular event rates did not differ among groups (one cardiac arrest but successful resuscitation in group I, one non-fatal myocardial infarction in group III) during follow up periods (mean, 41.2±13.7months). Chest pain free survivals during 1year were lower in group I (66.7%) compared to group III (90%), but similar to group II (58.3%) (group I vs III, p<0.05 and group I vs II, p=NS)Conclusions: Diffuse-multivessel spasm was not rare in patients with vasospastic angina and its prognosis is pretty good similar to patients with previously known variant angina with recommended medical treatment.

The peri-operative management of anti-platelet therapy in elective, non-cardiac surgery - Corrected Proof

2012-01-25

Abstract: Background: Cardiovascular complications are important causes of morbidity and mortality in patients undergoing elective non-cardiac surgery, with adverse cardiac outcomes estimated to occur in approximately 4% of all patients. Anti-platelet therapy withdrawal may precede up to 10% of acute cardiovascular syndromes, with withdrawal in the peri-operative setting incompletely appraised.Objectives: The aims of our study were to determine the proportion of patients undergoing elective non-cardiac surgery currently prescribed anti-platelet therapy, and identify current practice in peri-operative management. In addition, the relationship between management of anti-platelet therapy and peri-operative cardiac risk was assessed.Methods: We evaluated consecutive patients attending elective non-cardiac surgery at a major tertiary referral centre. Clinical and biochemical data were collected and analysed on patients currently prescribed anti-platelet therapy. Peri-operative management of anti-platelet therapy was compared with estimated peri-operative cardiac risk.Results: Included were 2950 consecutive patients, with 516 (17%) prescribed anti-platelet therapy, primarily for ischaemic heart disease. Two hundred and eighty nine (56%) patients had all anti-platelet therapy ceased in the peri-operative period, including 49% of patients with ischaemic heart disease and 46% of patients with previous coronary stenting. Peri-operative cardiac risk score did not influence anti-platelet therapy management.Conclusions: Approximately 17% of patients undergoing elective non-cardiac surgery are prescribed anti-platelet therapy, the predominant indication being for ischaemic heart disease. Almost half of all patients with previous coronary stenting had no anti-platelet therapy during the peri-operative period. The decision to cease anti-platelet therapy, which occurred commonly, did not appear to be guided by peri-operative cardiac risk stratification.

Pioglitazone ameliorates systolic and diastolic cardiac dysfunction in rat model of angiotensin II-induced hypertension - Corrected Proof

2012-01-25

Abstract: We previously showed that administration of angiotensin II to rats causes fibrosis and lipid accumulation in the heart. In the current study, we examined the effect of pioglitazone, an agonist of peroxisome proliferator activated receptor-γ, on angiotensin II-induced intracardiac lipid accumulation and cardiac dysfunction. Pioglitazone, given orally at a dose of 2.5mg/kg/d, reduced cardiac triglyceride content and suppressed lipid deposition in the heart of angiotensin II-induced hypertensive rats without affecting angiotensin II-induced upregulation of lipogenic gene expression. Histological examination showed that pioglitazone reduced the area of cardiac fibrosis and iron deposition in the heart of angiotensin II-treated rats. Expression of an antioxidative molecule, heme oxygenase-1, was increased by angiotensin II infusion, and pioglitazone treatment preserved expression of HO-1. Angiotensin II increased the superoxide signals detected by dihydroethidium staining in myocardial cells with lipid deposition, and this increase was suppressed by pioglitazone. Cardiac function was analyzed in an ex vivo isolated cardiac perfusion system. It was found that pioglitazone improved both the systolic and diastolic cardiac performance, which was weakened by angiotensin II infusion, after transient ischemia and reperfusion. These findings collectively suggest that pioglitazone treatment ameliorated the histological and functional cardiac damage induced by angiotensin II infusion, the mechanism of which may be related to the antioxidative action of pioglitazone.

Dihydrotestosterone—a culprit in left ventricular hypertrophy - Corrected Proof

Carolin Zwadlo, Jürgen Borlak — 2012-01-24

Independent clinical studies have demonstrated a relationship between testosterone and cardiac mass with Hayward et al. being the first to report the idea that sex hormones are involved in cardiac hypertrophy . There is clear evidence to suggest testosterone to induce cardiac hypertrophy and left ventricular hypertrophy which is an important risk factor for cardiovascular morbidity and mortality . Indeed, the male heart is hypertrophied relative to the premenopausal female heart, even when corrected for body weight . However, with age, ventricular mass increases in women but remains constant or rather decreases in men . Thus, in recent years the role of androgens on cardiac mass and function has become the subject of intensive research. The exact role of androgens in cardiac physiology is still not fully understood. However, preclinical and clinical findings suggest testosterone supplementation at supraphysiological concentrations to be associated with structural and morphological changes of the heart, resulting in an increased cardiovascular morbidity and mortality . Conversely, androgen deficiency is also linked to cardiovascular mortality, therefore suggesting that a fine balance in testosterone cardiac tissue levels exists with low levels of testosterone being a risk factor for cardiovascular events . Importantly, testosterone metabolism is significantly changed in left ventricular hypertrophy with levels of metabolites like androstendione and dihydrotestosterone being increased . These changes return to normal by adding finasteride, a 5α-reductase inhibitor to cultures of cardiomyocytes isolated from hypertrophic hearts of spontaneously hypertensive rats (SHR). Furthermore, in experimental studies, addition of testosterone reduced expression of the stress marker atrial natriuretic peptide (ANP) and improved expression of cardiomyocyte differentiation markers, e.g. the homeodomain protein Nkx 2·5 and the zinc-finger protein GATA4 both of which function as transcription factors in the control of gene expression as well as α-myosin heavy chain (α-MHC) . These results suggest that testosterone at certain concentrations maintains physiologic cardiac morphology and function while abnormal testosterone levels in either way seem to result in cardiac impairment. Here we present evidence whereby metabolism of testosterone in hypertrophic myocardium leads to exaggerated levels of dihydrotestosterone and we hypothesize that unlike testosterone itself dihydrotestosterone plays an essential role in mediating responses to exacerbate pathologic left ventricular hypertrophy. Moreover, we postulate that reduction of dihydrotestosterone production via inhibition of the 5α-reductase protects the heart, at least in part, from pathologic remodeling.

Is angiotensin-converting enzyme inhibitor appropriate for contrast-induced nephropathy? A meta-analysis about this field - Corrected Proof

Ximing Li, Tingting Li, Naikuan Fu, Yuecheng Hu, Hongliang Cong — 2012-01-24

Contrast-induced nephropathy (CIN) is the third leading cause of in-hospital acute renal failure . The role of angiotensin-converting enzyme inhibitors (ACEIs) in CIN is controversial . There are evidences both for and against a renoprotective effect of ACEIs in the development of CIN. Some studies pointed out that it was effective in the prevention of CIN , while some concluded that it was a risk for the development of CIN . Our aim is to conduct a meta-analysis of these trials to assess the effect of ACEIs on CIN.

Erythrocytes from patients with carotid atherosclerosis fail to control dendritic cell maturation - Corrected Proof

2012-01-24

Evidence indicates that erythrocytes can represent a potent atherogenic stimulus. In physiological conditions they display an immunomodulatory activity by promoting T cell survival and controlling slan dendritic cell (DC) maturation . In pro-oxidant microenvironments such as atherosclerotic lesions, erythrocytes change their functional features . We have recently demonstrated that erythrocytes from patients with carotid atherosclerosis impact T lymphocyte integrity and function . This study was undertaken to investigate whether the inflammatory and pro-oxidant microenvironment of the atherosclerotic lesions could impair the ability of erythrocytes to control DC maturation, an event implicated in atherosclerotic plaque progression and destabilization . Using immunochemical and cytofluorimetric analysis we determined the phenotype and functions of monocyte-derived DCs cocultured with erythrocytes from patients or from healthy subjects. The study groups consist of 11 consecutive patients with carotid atherosclerosis undergoing carotid endarterectomy at the Sapienza University of Rome, and 11 sex- and age-matched healthy subjects without ultrasonographically evident carotid atherosclerotic disease as controls. The inclusion and exclusion criteria, examination and tests, electrocardiogram and color-Doppler echocardiogram were described in our previous manuscript . Erythrocytes were evaluated for redox and aging markers as described in our previous manuscript . The study protocol was approved by the local Ethic Committee (Rif.1442/11.09.08) and informed consent was obtained from all participants. All the statistical procedures were performed by GraphPad Prism software (San Diego, CA, USA). Based on outcome from our previous research , to detect a difference on DC maturation (% of CD83+ cells) of 30% and using a standard deviation of 20% for 6 treatment groups, 11 patients per group were required to achieve a statistical power of 80%. P values<.05 were considered statistically significant.

Relationship between baseline ET-1 plasma levels and outcome in patients with idiopathic pulmonary hypertension treated with bosentan - Corrected Proof

2012-01-24

Abstract: Objectives: To address if baseline endothelin-1 (ET-1) plasma levels might predict clinical worsening (CW) in patients with idiopathic pulmonary hypertension (IPAH) treated with bosentan.Methods: Forty-four consecutive patients with IPAH (WHO classes II–III) were included in this study. After an initial assessment (clinical status, pulmonary hemodynamics, samples for adrenomedullin (ADM), ET-1 and brain natriuretic peptide (BNP) plasma levels), patients were treated with bosentan and followed-up for CW.Results: We observed CW in 24 patients. Actuarial rates of freedom from CW were 74% at 1year, 56% at 2years, and 43% at 3years. Patients with CW had a worse WHO functional class (II/III; no-CW 14/6 vs CW 5/19, p=0.002), six-minute walk-test distance (no-CW 439+94m vs CW 385+82m, p=0.04), mean pulmonary artery pressure (no-CW 47.4+10.6mm Hg vs CW 56+12.6mm Hg, p=0.02) and pulmonary vascular resistance (PVR no-CW 12.5+4.8 WU vs CW 16.4+6.3 WU, p=0.03) than the no-CW group. Moreover ET-1 (no-CW 14.1+4.2pg/ml vs CW 21.3+6.3pg/ml, p=0.0001), ADM (no-CW 14.9+7pg/ml vs CW 21.5+10.4pg/ml p=0.002) and BNP (no-CW 82.8+35.3pg/ml vs CW 115.4+39.6pg/ml, p=0.007) plasma levels were significantly higher in the CW group than in the no-CW group. The multivariate Cox proportional hazards model identified WHO class III (RR 4.6, 95%CI 14.6–1.45), ET-1 plasma levels (RR 1.1, 95%CI 2.05–1.01) and PVR (RR 1.2, 95%CI 1.3–1.03) as independent risk factors for CW.Conclusions: These data confirm the high rate of CW in patients with IPAH treated with bosentan and document the impact of the endothelin system on CW of these patients.

Osteopontin (OPN) improves risk stratification in pulmonary hypertension (PH) - Corrected Proof

2012-01-24

Osteopontin (OPN) was found upregulated in several heart failure models and appears to play an important role in myocardial remodeling . Moreover, our group demonstrated that OPN plasma level are elevated in patients with left sided heart failure and correlate with an adverse prognosis . Since right ventricular dysfunction is an important predictor of mortality in patients with pulmonary hypertension (PH), we now evaluated the diagnostic and prognostic power of OPN in this patient group.

Hydrogen as additive of HTK solution fortifies myocardial preservation in grafts with prolonged cold ischemia - Corrected Proof

Mengwei Tan, Xiangdong Sun, Long Guo, Cunhua Su, Xuejun Sun, Zhiyun Xu — 2012-01-24

Abstract: Background: Recent evidences indicated that hydrogen (H2) can attenuate organ transplantation induced cold ischemia/reperfusion (I/R) injury if administrated perioperatively. In this study we evaluated whether administrating H2 during the prolonged cold ischemia stage by adding it to Histidine–Tryptophan–Ketoglutarate (HTK) solution fortifies preservation for cardiac grafts.Methods: One hundred and twenty-eight Sprague–Dawley (SD) rats were equally randomized to four groups: three H2-rich HTK-treated groups with H2 of different concentrations and traditional HTK-treated group as the control group. Isolated hearts were mounted on the Langendorff apparatus for aerobic perfusion. Following baseline hemodynamic measurements, grafts were arrested and stored in HTK with or without H2 for 6h at 4°C. After this prolonged cold storage, grafts were reperfused and concerned parameters were examined.Results: Compared with the control group, preservation in H2-rich HTK significantly enhanced the percentage recovery of hemodynamic parameters, which was parallel to the diminished re-beating time and improved microscopic morphology of myocardium. Oxidative stress associated parameters including 8-hydroxy-2′-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) were decreased while myocardial superoxide dismutase (SOD) activity was preserved. Concentrations of inflammatory mediators including tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6), percentage of TUNEL-positive cells, expression of pro-apoptotic molecule Bax, and caspase-3 activity were reduced while Bcl-2 mRNA and protein levels were up-regulated in H2-rich HTK groups. The protective effects of H2 were concentration dependant.Conclusions: Hydrogen as additive of HTK solution fortifies HTK's preservation efficacy for cardiac grafts subjected to prolonged cold ischemia by inhibiting cold ischemia-induced up-regulation of oxidative stress, inflammation mediators, and apoptosis.

Long-term clinical outcomes after percutaneous coronary intervention for unprotected left main coronary artery in heart transplant patients with cardiac allograft vasculopathy - Corrected Proof

2012-01-24

Cardiac allograft vasculopathy (CAV) is a serious disease that adversely affects the long-term survival of patients undergoing successful orthotopic heart transplantation . Cardiac allograft vasculopathy involving left main coronary artery manifests in a different manner from native left main coronary artery disease due to several factors including the nature of vasculopathy involving both epicardial and intra-myocardial arteries in a diffuse manner as well as absence of angina due to denervation of the allograft. Therefore, most of these patients with CAV involving left main coronary artery present with congestive heart failure, sudden cardiac death or various ventricular arrythmias. The only definite treatment for CAV at present is re-transplantation which has several limitations including limited number of donors, ethical considerations and worse survival rates compared to initial transplantation .

High-sensitive troponin T is associated with atrial fibrillation in a general population - Corrected Proof

2012-01-24

Atrial fibrillation (AF) is the most important cause of embolic stroke and deteriorates the quality of life of subjects . AF increases morbidity and mortality even after adjusting for comorbid cardiovascular conditions . Identification of predicting factors, especially biomarkers, for AF is desirable for prediction and risk stratification of AF. Newly developed high-sensitive troponin T (hsTnT) assay has improved early diagnosis of acute coronary syndromes and risk stratification []. Moreover, minor elevation of circulating hsTnT was associated with the incidences of heart failure and cardiovascular death in a community-dwelling elderly population (≥ 65years) without known heart failure []. Elevated hsTnT levels were also associated with risks for all-cause mortality and for morbidities of left ventricular (LV) hypertrophy and LV systolic dysfunction in a population-based cohort []. Thus, elevations of hsTnT are related to cardiac remodeling and may indicate subtle cardiac damage. AF is associated with remodeling of the left atrium (LA). However, little has been known whether hsTnT levels are elevated in AF. Therefore, we investigated the association between circulating hsTnT levels and the incidence of AF in healthy subjects without apparent cardiovascular diseases.

Slow coronary flow in patients undergoing urgent coronary angiography for ST elevation myocardial infarction - Corrected Proof

2012-01-24

The slow coronary flow (SCF), also known as syndrome Y, has been described since 1972 . Slow coronary flow phenomenon is characterized by delayed opacification of epicardial coronary vessels in the absence of stenosis and/or conditions such as coronary ectasia, coronary spasm, valvular and myocardial heart disease . However, previous studies showed SCF may cause unstable angina and non-ST elevation myocardial infarction (non-STEMI), association between SCF and STEMI have not evaluated adequately yet . In this study, we aimed to evaluate in-hospital and long-term (mean 29month) clinical events in SCF patients who were admitted with STEMI in a large population.

Chemical denervation of the renal artery by vincristine in swine. A new catheter based technique - Corrected Proof

2012-01-24

Abstract: Background: Renal sympathetic denervation is a promising technique for the treatment of resistant hypertension. We evaluated a novel method for chemical sympathetic denervation of the renal artery by local delivery of vincristine, an antineoplastic drug with potential for peripheral neurotoxicity, using a dedicated catheter in an animal model.Methods: Local delivery of vincristine by a specially designed catheter, was performed unilaterally in the renal arteries of 14 juvenile Landrace swine. The procedure was then repeated in the contralateral renal artery using a placebo mixture. Animals were euthanized at 28days and histological specimens of renal arteries and perirenal arterial stroma containing renal nerves were extracted and sectioned. The number of uninjured nerves in each histological section was then quantified, following identification by immunohistochemical staining.Results: In all animals delivery of vincristine and placebo mixtures was successful and uncomplicated. Both vincristine- and placebo-treated renal arteries were angiographically patent at the end of the procedure. The mean number of intact nerves in all sections was significantly lower in the group of vincristine (p<0.05).Conclusions: Catheter-based delivery of vincristine in the renal artery of an experimental model is feasible and results in significant reduction in the number of renal nerves. Our findings warrant further confirmation in animal and human studies.

Doppler echocardiography may provide a potentially life-saving screening of anomalous origin of coronary artery in young athletes - Corrected Proof

2012-01-24

Congenital anomalies of the coronary artery are the cause of sudden death in young people. Although cardiac computed tomography (CT) and magnetic resonance images (MRI) are the best methods to diagnose such anomalies, these modalities are not suitable for screening.

Risk of myocardial infarction in women with pelvic inflammatory disease - Corrected Proof

Tsan-Hon Liou, Chin-Wen Wu, Wen-Rui Hao, Ming-I Hsu, Ju-Chi Liu, Hui-Wen Lin — 2012-01-24

Abstract: Background: There is evidence that chronic inflammation may promote atherosclerotic disease. The purpose of this study was to test the hypothesis that pelvic inflammatory disease (PID) is a risk marker for myocardial infarction (MI).Method: Using the Taiwan Longitudinal Health Insurance Database 2005 (LHID2005), this cohort study comprised patients with a recorded diagnosis of PID (N=68,668) between January 1, 2004 and December 31, 2005, with age-matched controls (1:2) (N=136,906). Each patient was followed-up using entry data until the end of 2006. Cox proportional hazard regressions were used to evaluate the up to 3-year MI-free survival rates, after adjusting for known confounding factors.Results: We found that patients with PID were more likely to have MI than the control population after adjusting for potential confounders [adjusted hazard ratio (HR), 1.86, 95% confidence interval (CI), 1.23–2.81]. When stratified by patient's age, the adjusted HR for MI was 2.09 (95% CI, 1.24–3.52) for patients with PID aged over 55years. However, the adjusted HR for MI occurring was not significant for patients with PID aged≤55years.Conclusions: PID is a risk marker for MI that is independent of traditional MI risk factors. Further research in this important area of public health is warranted.

Plasma triglyceride levels increase the risk for recurrent vascular events independent of LDL-cholesterol or nonHDL-cholesterol - Corrected Proof

2012-01-24

Abstract: Background: Plasma triglyceride (TG) levels are known to confer an increased risk of vascular disease in healthy populations, but data in high-risk patients are scarce. In this study we evaluated the risk on recurrent vascular events conferred by increased plasma TG levels in patients with various clinical manifestations of vascular disease.Methods: Prospective cohort study of 5731 patients with clinically manifest vascular disease.Results: First new vascular events (myocardial infarction, ischemic stroke, vascular death) occurred in 782 subjects during a median follow-up of 4.9years (interquartile range 2.5–8.1years). Patients in the highest plasma TG quintile (>2.24mmol/L) had a higher risk for recurrent vascular events (HR 1.45; 95%CI 1.13–1.86) compared with the lowest plasma TG quintile (<0.97mmol/L) after adjustments for age, gender, body mass index, smoking, lipid-lowering medication and low-density lipoprotein-cholesterol. The increased risk associated with increasing plasma TG levels was irrespective of the presence of type 2 diabetes (T2DM), but only present in patients without the metabolic syndrome. Furthermore, the increased risk was particularly present in patients with coronary artery disease (CAD) (HR 1.45; 95%CI 1.02–2.08) and was not modified by other lipid levels (p-value for interaction >0.05). Plasma TG still contributed to vascular risk when other lipid levels were at target level.Conclusions: Higher plasma TG levels are associated with increased risk for recurrent vascular events, in particular in CAD patients. This increased risk is independent of the presence of T2DM and the use of lipid-lowering medication and is not modified by other lipid levels.

Right ventricular long-axis response to different chronic loading conditions: Its relevance to clinical symptoms - Corrected Proof

2012-01-20

Abstract: Background: The intervention timing in atrial septal defect (ASD) or pulmonary valvular stenosis (PVS) is more dependent on symptoms than right ventricular (RV) damage in clinical practice. RV long-axis function is sensitive in revealing RV myocardial dysfunction. We evaluate the impact of different chronic loading conditions on RV long-axis function and its relationship to patients' symptoms in ASD or PVS.Methods: Transthoracic echocardiography was performed in normals (n=39) and patients with isolated secundum ASD (n=45) or PVS (n=38). RV volume- and pressure-overloading were defined as the ratio of RV/left ventricular end-diastolic dimension ≥0.5 and RV systolic pressure ≥40mmHg, respectively. RV long-axis dysfunction was defined as M-mode tricuspid annular plane systolic excursion (TAPSE) <1.6cm. New York Heart Association (NYHA) functional class and other symptoms (decreased exercise tolerance, palpitation and chest pain) were recorded.Results: Thirty-nine (32.0%) had normal loading (Group 1; 39 normals); 24 (19.6%) had isolated volume-overloading (Group 2; all ASDs); 21 (17.2%) had isolated pressure-overloading (Group 3; 21 PVSs) and 38 (31.1%) had both overloading conditions (Group 4; 21 ASDs and 17 PVSs). RV long-axis dysfunction in abnormal loading groups were zero (0%, Group 2), 21 (100%, Group 3) and 22 (57.8%, Group 4) (χ2=45.9, p<0.001). Group 3 were more symptomatic (NYHA functional class 2.5±0.6 versus 1.6±0.5, p<0.05) and had lower TAPSE (1.6±0.4 versus 3.0±0.7cm, p<0.05) than Group 2. RV long-axis dysfunction was the strongest predictor of the presence of symptoms (odds ratio=9.298, p<0.001).Conclusion: Chronic volume-overloading accentuates while pressure-overloading attenuates RV long-axis excursion and its impairment was associated with the presence of symptoms.

Diagnosis of Cardiobacterium hominis endocarditis: Usefulness of positron emission tomography - Corrected Proof

Imane El Hajjaji, Nicolas Mansencal, Olivier Dubourg — 2012-01-20

Cardiobacterium hominis is a Gram-negative bacilli bacterium in the HACEK group and is an unusual cause of infective endocarditis . Few data are available concerning the characteristics of this specific infective endocarditis [].

Uric acid: A cardiovascular risk factor in patients with recent myocardial infarction - Corrected Proof

2012-01-20

Abstract: Background: To date uric acid (UA) is not considered a cardiovascular risk factor, although evidence about a relationship between UA and cardiovascular diseases has been reported.Methods: Information from 10,840 patients enrolled in the GISSI-Prevenzione trial was used to evaluate the relationship between UA and risk for total mortality and cardiovascular events (CVE). UA levels were categorized in quintiles, as ≤4.5 (Q1), 4.6 to 5.3 (Q2), 5.4 to 6.0 (Q3), 6.1 to 6.8 (Q4) and >6.8 (Q5) mg/dL. Multivariable analysis was used to estimate the relative risks (HR) of outcome measures across categories of UA. The analysis of the area under the receiver operating characteristic curve (AUC), the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI) tests were used to evaluate the incremental prognostic information of UA.Results: During 36,802 person-years of follow-up, 974 deaths and 1120 cardiovascular events occurred. We found a statistically significant association between high UA and total mortality [HR, P value]: Q1 [reference category, 1.00]; Q2 [1.13, 0.267]; Q3 [1.06, 0.619]; Q4 [1.23, 0.063]; Q5 [1.63, <0.0001], test for trend P<0.0001. Similar results were obtained for cardiovascular events [HR, P value]: Q1 [reference category, 1.00]; Q2 [1.12, 0.271]; Q3 [1.19, 0.094]; Q4 [1.25, 0.031]; Q5 [1.38, 0.002], test for trend P=0.0009. The prognostic accuracy of prediction models for CVE was significantly increased by adding UA to classical cardiovascular risk factors (AUC P=0.0041; NRI P=0.0004; IDI P<0.0001).Conclusion: High UA may be considered a risk factor for death and CVE.

Modified criteria for determining cardiometabolic syndrome in Asian Indians living in the USA: Report from the diabetes among Indian Americans national study - Corrected Proof

2012-01-19

The disproportionate burden of cardiovascular disease (CVD) in the Asian Indian (AI) diaspora is well documented but not well understood . Foucan et al. found AIs with type-2 diabetes mellitus (DM) had a 5-fold higher risk of cardiometabolic syndrome (CMetS) than the general US population . Typical risk factors (RFs) like elevated low-density lipoprotein cholesterol (LDL-C) levels do not account for the high CMetS risk. Decreased levels of high-density lipoprotein subfraction 2b (HDL2b) are associated with higher rates of coronary artery disease . Higher levels of abdominal adiposity, visceral fat, dyslipidemia, insulin resistance, and high-sensitivity C-reactive protein (hsCRP) have also been reported as contributory factors . In this study we aimed to propose an explanatory model of CMetS in AIs, controlling for confounders such as demographic variables, traditional risk factors, and novel biomarkers.

Long-term outcome after Cardiac Resynchronization Therapy: A nationwide database - Corrected Proof

2012-01-19

Heart failure (HF) is a complex clinical syndrome that represents a growing public health problem . Cardiac resynchronization therapy (CRT) is one of the surgical procedures proposed to HF treatment. Nevertheless, although its efficacy – both in isolated therapy (CRT-P) and combined with cardiac defibrillators (CRT-D) – has been shown in randomized clinical trials and recently demonstrated for patients with less functional impairment , its effectiveness in the real world should be better evaluated.

Depression and coronary heart disease: Apprehending the elusive black dog - Corrected Proof

Carolina A. Chavez, Chantal F. Ski, David R. Thompson — 2012-01-19

Abstract: Depression is the third leading cause of disease burden worldwide and is predicted to be the leading cause by 2030. Importantly, depression has been identified as an independent risk factor for coronary heart disease (CHD) and both share significant physiological overlap. Identification of depression is complex. Consequently, accurate diagnosis of comorbid depression and CHD is challenging and requires a move toward an interdisciplinary engagement of knowledge transfer. A concerted effort is required utilising translational research to better identify depression in the CHD population. This approach is not meant to categorise patients, rather it is aimed at progressing toward an improved prognosis. Further, this approach should provide health professionals with the confidence to apply the term depression and define its meaning in a more precise and consistent manner.

Correlations between myocardium selective videodensitometric perfusion parameters and corrected TIMI frame count in patients with normal epicardial coronary arteries - Corrected Proof

2012-01-19

TIMI frame count (TFC), was introduced in the early 1990s, as a method to assess the efficacy of thrombolysis and risk stratification in acute myocardial infarction (AMI) . TFC proved to be a simple, reproducible, quantitative and objective method to evaluate epicardial flow not only in acute coronary syndrome settings, but in stable conditions with microvascular dysfunction, as well . Recently, 2 different angiographic methods myocardial blush grade (MBG), and TIMI myocardial perfusion grading (TMP) have been described for direct assessment of myocardial perfusion in AMI . However, these methods are limited inherently by their subjective nature and categorical values, and are not defined in stable patients. Alongside others novel computer-assisted videodensiometric methods have been introduced, which supply additional, objective and quantitative information on myocardial perfusion in AMI . The objective of the present study was to evaluate regional myocardial perfusion assessed by our novel computerized videodensitometric method, and its relation to corrected TFC in non-AMI patients without epicardial coronary stenoses.

Association of interleukin-6 circulating levels with coronary artery disease: A meta-analysis implementing mendelian randomization approach - Corrected Proof

Wenquan Niu, Yan Liu, Yue Qi, Zhijun Wu, Dingliang Zhu, Wei Jin — 2012-01-19

Abstract: Background: We aim to investigate whether the association between circulating interleukin 6 (IL-6) levels and the risk for coronary artery disease (CAD) is robust and perhaps even causal by a meta-analysis implementing mendelian randomization approach with IL-6 gene G–174C polymorphism as an instrument.Methods: Data were available from 19 articles encompassing 9417 CAD patients and 15982 controls. A random effects model was applied irrespectively of between-study heterogeneity, and publication bias was examined using a funnel plot and the corresponding statistics.Results: Overall, comparison of IL-6 gene alleles –174C with –174G had 4% increased risk for CAD (95% confidence interval [95% CI]: 0.97–1.10; P=0.285), accompanying marginal heterogeneity (I2=38.3%; P=0.033). This association was potentiated in dominant model as odds ratio (OR) reached 1.08 (95% CI: 0.96–1.22; P=0.204) and heterogeneity was significant (I2=58.4%; P<0.0005). Subgroup analysis by ethnicity indicated that carriers of –174C allele were associated with a 12% increased risk for CAD in prospective studies involving White populations (OR=1.12; 95% CI: 0.95–1.33; P=0.184), whereas the association in East Asians was remarkably reversed with 37–46% reduced risk. Relative to –174GG homozygotes, carriers of –174C allele had an overall 0.24pg/ml high circulating IL-6 levels (P=0.047). The predicted OR for 1pg/ml elevation in IL-6 levels was 1.60 (95% CI: 1.44–1.72; P<0.01) in prospective studies involving White populations. Publication biases were absent for all comparisons (P>0.1).Conclusion: Our findings provided strong evidence on the causal association of circulating IL-6 levels with the development of CAD in White populations.

Elderly, hypotension and presentation of neurologic symptoms are risk factors of mortality in aortic dissection - Corrected Proof

Yu-Jang Su, Yen-Chun Lai, Yu-Hang Yeh, Che-Hung Liu — 2012-01-19

Aortic dissection (AD) is one of the cardiovascular emergencies in the emergency department (ED). An Int. J Cardiol article in the year of 2005 from southern Taiwan described by Dr. Chan, ever mentioned that type A dissection, probable extravasation (pericardial effusion, pleural effusion), visible intimal flap in echocardiography and acute renal deterioration are risk factors in mortality . For presentation, an aortic dissection generally occurs with the sudden onset of chest discomfort, abdominal pain, back pain and neurological symptoms. However, some are painless and atypical AD (17%) and strongly related to altered mental status, stroke, syncope and cardiac tamponade . Although there are some articles describing the prognostic factors of AD patients: elderly, renal dysfunction, with cardiopulmonary resuscitation, and lower extremity ischemia , we made a retrospective review of the five-year AD cases in a northern Taiwan medical center from January 1, 2005 to December 31, 2010 by gathering the data of 132 AD patients including gender, age, episodes of time, season, vital signs (heart rate and systolic blood pressure), symptoms (chest pain, chest tightness, abdominal pain, neurological deficit), D-dimer, DeBakey type classifications, and outcome. Comparisons are made in different sets of AD groups. To prevent from data bias, 49 cases are excluded (2 out-of-hospital cardiac arrest, 9 transferred from another hospital, 36 admitted via outpatient department, 2 transferred to another hospital). A total of 83 cases with complete data are strictly enrolled into our study. Elderly are the patients above 65years old. We define daytime as 7:00a.m. to 19:00p.m., and night time as 19:00p.m. to next day of 7:00a.m. The months during spring season are (March, April, May); summer (June, July, August); autumn (September, October, November) and winter (December, January, February). Hypertension was defined as systolic blood pressure >140mmHg. About the symptoms, chest pain and chest tightness (CP/CT) are all chest symptoms, and limb weakness, headache, syncope, convulsion are classified into cases having neurological symptoms. Mortality cases are defined as in-hospital mortality without survival to discharge. The normal range of D-dimer is within 500ng/ml. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology” . We analyzed the data by commercial statistical software (SPSS for Windows, version 11.0, SPSS Ltd., Chicago, IL). We used χ2 test for statistical analyses, and significance was set at a p value less than 0.05 (2-tailed).

Effects of enalapril in systolic heart failure patients with and without chronic kidney disease: Insights from the SOLVD Treatment trial - Corrected Proof

2012-01-18

Abstract: Background: Angiotensin-converting enzyme inhibitors improve outcomes in systolic heart failure (SHF). However, doubts linger about their effect in SHF patients with chronic kidney disease (CKD).Methods: In the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial, 2569 ambulatory chronic HF patients with left ventricular ejection fraction ≤35% and serum creatinine level ≤2.5mg/dl were randomized to receive either placebo (n=1284) or enalapril (n=1285). Of the 2502 patients with baseline serum creatinine data, 1036 had CKD (estimated glomerular filtration rate <60ml/min/1.73m2).Results: Overall, during 35months of median follow-up, all-cause mortality occurred in 40% (502/1252) and 35% (440/1250) of placebo and enalapril patients, respectively (hazard ratio {HR}, 0.84; 95% confidence interval {CI}, 0.74–0.95; p=0.007). All-cause mortality occurred in 45% and 42% of patients with CKD (HR, 0.88; 95% CI, 0.73–1.06; p=0.164), and 36% and 31% of non-CKD patients (HR, 0.82; 95% CI, 0.69–0.98; p=0.028) in the placebo and enalapril groups, respectively (p for interaction=0.615). Enalapril reduced cardiovascular hospitalization in those with CKD (HR, 0.77; 95% CI, 0.66–0.90; p<0.001) and without CKD (HR, 0.80; 95% CI, 0.70–0.91; p<0.001). Among patients in the enalapril group, serum creatinine elevation was significantly higher in those without CKD (0.09 versus 0.04mg/dl in CKD; p=0.003) during first year of follow-up, but there was no differences in changes in systolic blood pressure (mean drop, 7mm Hg, both) and serum potassium (mean increase, 0.2mEq/L, both).Conclusions: Enalapril reduces mortality and hospitalization in SHF patients without significant heterogeneity between those with and without CKD.

High prevalence of male hypogonadism and sexual dysfunction in long-term clinically stable heart transplantation recipients - Corrected Proof

2012-01-18

The impact of gonadic and sexual function on male heart transplantation (HTX) recipients has been scarcely investigated so far. The aim of this observational study was a long-term evaluation of the gonadic and sexual function in male HTX recipients. A total of 52 patients, aged 20–78years (mean±SD: 54.2±15.2) were included. The time interval elapsed since HTX was 88±65.3months (range 4–220). All recipients were clinically stable, with a mean left ventricle ejection fraction (LVEF) 57.9±5.8% (range 40–65) and NYHA class I (86.5%) or II (13.5%). Most (88.5%) were on anti-hypertensive drugs and all were treated with immunosuppressive therapy including calcineurin inhibitors (cyclosporine, everolimus), azathioprine or mycophenolate-mofetil. Thirty-four patients were also on low-dose prednisone. Cardiac allograft vasculopathy (CAV)≥grade 1 was detected at coronary artery angiography in 11 patients (21.2%) . Sexual function was evaluated by the International Index of Erectile Function (IIEF) questionnaire . A score <11 was indicative of severe erectile dysfunction (ED). The psychological status was evaluated by The Middlesex Hospital Questionnaire (MHQ) . Total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglyceride were determined. Hormonal assay was also evaluated, including serum prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), sex hormone-binding globulin (SHBG) and free-estimated testosterone (FeT) by Vermeulen's formula . Values <10.4nmol/L of TT or <225pmol/L of FeT were considered indicative of significant hypogonadism (Hypo) . Thirty-seven (71%) of the 52 patients examined had some degree of ED, with 21 (40%) reporting severe, 4 (8%) mild and 12 (23%) light ED. No significant age-dependent trend was observed. ED was not related to the length of time elapsed after HTX or Hypo, but to the presence of ACE-inhibitors therapy (p<0.01), depression (p<0.005) and diabetes (p<0.025). The relationships between the severity of ED and TT, FeT, TC, LDL-C, LVEF, and domains of sexual function are shown in . Severe ED was more frequent in patients treated with everolimus (p<0.025). No significant correlation was found between ED and age, etiology of HF, smoking, hypertension, other anti-hypertensive or antidepressant drugs, as well as MHQ domains or presence and severity of CAV. The prevalence of Hypo, defined as TT<10.4nmol/L, was detected in eighteen patients (34.6%). Hypo was not age-related, but was higher in patients aged 50–59years and more frequent in patients recently transplanted, with a peak of 57% at 2–4years. Fifty-five percent of patients with low TT and 14.7% of those with normal TT had increased (>9.4IU/L) LH levels, suggesting that primary testicular failure was the prevalent cause of Hypo. Patients taking everolimus showed significantly lower TT and FeT levels and significantly higher LH and FSH levels than those taking any other immunosuppressive drug (). On the other hand, cyclosporine blood levels were directly related to FeT levels (124.8±43.6mg/dL vs 198.1±22.4mg/dL, p<0.001). Prednisone daily dose was significantly higher in patients with low than in those with normal serum TT levels (). As also shown in , the presence of a significant androgenic defect was also supported by serum SHBG concentration which was significantly lower in patients with low as compared to normal TT levels. Hypo recipients displayed higher total and LDL-C, triglyceride and body mass index (BMI) values, and lower, although normal, LVEF (). Similarly to ED, also Hypo was related to the presence of glycemic alterations (p<0.025).

Role of vitamin D in the cardiac remodeling induced by tobacco smoke exposure - Corrected Proof

2012-01-18

Animal studies have shown that exposure to tobacco smoke (ETS) leads to inflammation and cardiac remodeling, characterized by heart hypertrophy, higher diastolic dimension of the left ventricle and impaired systolic function . Although the precise mechanisms of smoking-induced alterations remain unclear, the evidence supports the hypothesis that oxidative stress and inflammation provide the pathophysiological link between ETS and heart alterations . In recent years, vitamin D has emerged as an important nutrient for heart health and its deficiency has been linked to increased cardiovascular disease risk . In heart aggression models, vitamin D (VD) supplementation attenuated the cardiac remodeling by influencing the contractility, hypertrophy, renin angiotensin system, fibrosis and inflammation . Given that vitamin D may modulate cardiac alterations following different injuries, the objective of this study was to investigate the effect of vitamin D supplementation on cardiac remodeling induced by tobacco-smoke exposure in rats. Rats were allocated into six groups: 1) VD0-no ETS, without VD supplementation and no ETS, 2)VD1-no ETS, supplementation of 1000IU VD/kg diet and no ETS, 3) VD3-no ETS, supplementation of 3000IU VD/kg, 4) VD0-ETS, ETS without VD supplementation, 5) VD1-ETS, ETS with VD supplementation of 1000IU, and 6) VD3-ETS, ETS with VD supplementation of 3000IU. After two months of tobacco exposure and VD supplementation, the animals underwent blood pressure measure and echocardiography. Collagen volume fraction, myocyte cross-sectional area (MCSA), serum 25-hydroxycholecalciferol, oxidative stress and cytokine production in heart tissue were evaluated.

Preischemic efferent vagal stimulation increases the size of myocardial infarction in rabbits. Role of the sympathetic nervous system - Corrected Proof

2012-01-18

The vagal nerve stimulation (VNS) has been tested for the treatment of chronic heart failure in humans (). However, many of the effects of parasympathetic stimulation in ischemic heart disease are still unknown. Kawada et al. have shown a significant increase in acetylcholine (Ach) levels in the ventricular myocardium subjected to VNS (). Since, Ach has been implicated in the mechanism of ischemic preconditioning (), we can hypothesize that VNS applied before ischemia may reduce myocardial infarct size by a release of Ach. However, under certain experimental conditions, the two divisions of the autonomic nervous system (sympathetic and parasympathetic) can be activated. Therefore, co-activation of the sympathetic nervous system could generate a situation adverse and contrary to the possible beneficial effect expected for VNS.

Coronary aneurysm formation following biodegradable polymer drug-eluting stent implantation - Corrected Proof

Feng Zhang, Juying Qian, Lili Dong, Junbo Ge — 2012-01-18

Coronary aneurysm formation is a rare complication occurring after drug-eluting stent (DES) implantation, but always predisposes to the development of late stent thrombosis. Such abnormal dilatation of stented coronary artery has been documented not only with the first-generation sirolimus-/paclitaxel-eluting stents but also with the second-generation everolimus-eluting stent . Although exact causes of aneurysm formation remain unknown, available pathological evidence supports the hypothesis that persistent hypersensitivity reaction to the permanent polymer coated on these DESs is the most likely mechanism . Recently, several novel DESs with biodegradable polymers, which carry and control the drug release during a proper period of time and after that erode and vanish from the vascular surface, have been developed and used to improve DES safety and efficacy . We report a case of multiple coronary aneurysm formation at 10-month angiographic follow-up after implantation of a biodegradable polymer sirolimus-eluting stent. To the best of our knowledge, this is the first report of coronary aneurysm formation associated with the biodegradable polymer DES.

TRPC6, a potential novel target for enhancing cardiac repair of bone marrow mesenchymal stem cells - Corrected Proof

Jing Zhao, Pengzhou Hang, Yue Li — 2012-01-18

It has been well documented that bone marrow mesenchymal stem cells (BMSCs) therapy has been widely applied in ischemic diseases such as myocardial and hepatic ischemia, through promotion of angiogenesis and suppression of apoptosis . Meanwhile, BMSCs transplantation has been demonstrated to be an effective therapy for cerebrovascular diseases, which could promote endogenous neurogenesis and behavioral recovery . Previous studies have proved that the secretion of neurotrophins, such as nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), and their downstream signal pathways is important for understanding BMSCs transplantation in cerebral diseases . In addition, BDNF modified BMSCs have also been employed to treat cerebral ischemic injury. They found that this therapy could effectively reduce the infarct size and improve the function of injured tissues . Interestingly, a number of recent clinical studies have indicated that serum concentrations of BDNF and NGF were also deregulated in patients suffering from myocardial infarction . Therefore, neurotrophins were indicated to play an important role in myocardial ischemia, which is probably contributable to BMSCs therapy.

Prevalence and spectrum of GATA6 mutations associated with familial atrial fibrillation - Corrected Proof

Yi-Qing Yang, Xin-Hua Wang, Hong-Wei Tan, Wei-Feng Jiang, Wei-Yi Fang, Xu Liu — 2012-01-18

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia, occurring in 1% to 2% of the general population. The prevalence of AF increases with age, ranging from <1% in young adults to nearly 10% of those aged >80years . AF confers a 5-fold risk of stroke, and approximately 15% of all strokes are attributed to this tachycardia . AF is also an independent risk factor for death, with a risk ratio of 1.5 for men and 1.9 for women after adjustment for known risk factors . AF has traditionally been perceived as a complication of various cardiac and systemic disorders, including hypertension, coronary artery disease, valvular heart disease, and hyperthyroidism . However, 30% to 45% of AF occurs in the absence of any traditional risk factors, a condition classified as lone AF , of which at least 15% presents with a positive family history, so termed familial AF . There is accumulating evidence supporting that genetic factors play important roles in the pathogenesis of AF and multiple genes responsible for AF have been identified . Nevertheless, AF is a genetically heterogeneous disorder and presently the genetic basis of AF remains largely unknown .

Survival benefit of new anticoagulants compared with warfarin in patients with atrial fibrillation: A meta-analysis - Corrected Proof

Tong Liu, Panagiotis Korantzopoulos, Lijian Li, Guangping Li — 2012-01-18

Recently published data suggest that new anticoagulants including the direct thrombin inhibitor dabigatran, and the direct factor Xa inhibitors rivaroxaban and apixaban are equivalent or even superior to warfarin in preventing stroke or systemic embolism in the setting of atrial fibrillation (AF) . Of note, there are data showing a trend toward reduction in all-cause mortality while the most recent randomised trial demonstrated a clear reduction in the risk of death. Therefore, we performed a meta-analysis of the randomised controlled trials (RCTs) examining the potential survival benefit of new anticoagulants over warfarin.