International Journal of Cardiology - Articles in Press

Androgens and atrial fibrillation: Friends or foes? - Corrected Proof

Tong Liu, Michael Shehata, Guangping Li, Xunzhang Wang — 2010-03-10

Abstract: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. The prevalence of AF increases with age, and this age-specific prevalence is higher in men than in women. However, the mechanisms of aging-induced AF have not been fully elucidated, and this may be related to decline of testosterone with advancing age. On the other hand, anabolic steroid abuse may precipitate the occurrence of AF. Until now, the possible relationship between androgens and AF was not comprehensively reviewed. We intend to review some recent evidence on this issue and propose some potential mechanisms.

Catheter-induced in-stented segment coronary dissection - Corrected Proof

Luiz Fernando Ybarra, Cristiano F. Souza, Valter C. Lima — 2010-03-10

Abstract: Coronary angiography can lead to different kinds of complications. Catheter-induced coronary dissection is one of the most feared of them. It is uncommonly reported and may result in ischemic events ranging from angina to death. We report a case of a woman admitted to the hospital due to progressive effort angina who had a complication during percutaneous coronary intervention not previously reported. It is a usual thinking that a coronary artery stented segment would not be prone to dissect either spontaneously or catheter-induced. This report describes a catheter-induced in-stented segment coronary dissection and a discussion if the dissection line involving the left anterior descending coronary artery stented segment occurred between the stent and the intimal hyperplasia or between the stent and the adventitia.

Identification of an up-regulated anti-apoptotic network in the internal thoracic artery - Corrected Proof

2010-03-08

Abstract: Background: The radial artery (RA) is known as an atherosclerosis-prone vessel in contrast to the atherosclerosis-resistant internal thoracic artery (ITA). The purpose of the present study was to compare the gene expression profile of these arteries from the same patient in order to identify genes involved in atherogenesis or intimal hyperplasia.Methods: Paired specimens of RA and ITA (n=6) were analyzed by histomorphometry and whole genome microarray. The microarray data underwent pathway analysis to identify biological networks. Laser microdissection (LMD) was used to identify the cellular expression of candidate genes in the intimal or medial layer of the ITA and RA.Results: Histomorphometric analyses revealed a significantly higher degree of intimal hyperplasia in the RA compared to the ITA. 552 genes were differentially expressed in the ITA and RA. qRT-PCR confirmed a significant up-regulation of six anti-apoptotic genes. p21 (11.8-fold, p=0.011), CCL2 (5.4-fold, p=0.034), SOCS3 (7.2-fold, p=0.002), IER3 (4.1-fold, p=0.048), MCL-1 (2.6-fold, p=0.025) and IL-6 (17.8-fold, p=0.046) were up-regulated in the ITA. LMD confirmed that cells of the intimal layer of the ITA consistently expressed higher levels of all six candidate genes than those of the RA.Conclusions: Microarray analysis and qRT-PCR identified significantly up-regulated genes in the ITA involved in an anti-apoptotic network. LMD revealed a higher expression of all anti-apoptotic genes in the intimal area of the ITA. These genes may play an important role in protecting the intima of the ITA from developing hyperplasia and atherosclerosis.

Reply to Yaman et al.'s Red cell distribution width and coronary artery disease - Corrected Proof

Erdal Cavusoglu — 2010-03-08

Abstract: Red blood cell distribution width (RDW), a numerical measure of the variability in size of circulating erythrocytes, has recently been shown to be a strong predictor of adverse outcomes in a variety of patient populations, including those with known or suspected coronary artery disease. In this reply, we provide data as to why it is highly unlikely that the association between RDW and mortality is related to, or confounded by, nutritional deficiencies and/or other hematologic coefficients. We make the case that elevated RDW is indeed an independent predictor of poor outcomes.

Risk-prediction models for mortality after coronary artery bypass surgery: Application to individual patients - Corrected Proof

Pankaj Madan, MacArthur A. Elayda, Vei-Vei Lee, James M. Wilson — 2010-03-08

Abstract: Introduction: We derived a risk-assessment model for predicting mortality after coronary artery bypass surgery from patient data from the 1990s and examined the model's accuracy in predicting early mortality in more contemporary patients. We also examined the accuracy of a completely new model and an older model recalibrated with newer data.Materials and methods: Three mortality-prediction models were derived: an “old” model from 8959 patients treated during 1993–1999, a “new” model from 5281 patients treated during 2000–2004, and a version of the old model “recalibrated” with the 2000–2004 data. Each model's discriminatory ability was assessed by computing area under receiver–operator characteristic (ROC) curves, and precision was estimated by comparing observed and predicted mortality rates. To test the temporal applicability of the old model, we applied it to the 2000–2004 data and to data from 1879 patients operated on during 2005–2007. To compare the recalibration and remodeling strategies, the new and recalibrated models were applied to the 2005–2007 data.Results: The old model showed good discrimination (ROC, 0.80) and concordance between observed and predicted mortality for the 2000–2004 patients but overpredicted mortality for the 2005–2007 patients. The new and recalibrated models had good discriminatory ability (ROC, 0.81 and 0.79) and showed similarly good concordance between observed and predicted mortality when applied to the 2005–2007 data.Conclusions: Predictive models for mortality after cardiac surgery lose precision within a few years after development. Recalibrating old models and creating new models (i.e., remodeling) are equally good strategies for predicting outcomes in contemporary patient cohorts.

The underlying causes of chordae tendinae rupture: A systematic review - Corrected Proof

Uri Gabbay, Chaim Yosefy — 2010-03-08

Abstract: Background: The underlying causes of chordae tendinae rupture (CTR) and their frequencies vary. Different publications reached conflicting conclusions due to diverse definitions, different detection measures, and morbidity trends over time.Methods: Systematic literature review of unselected CTR series and underlying cause frequencies reanalysis.Results: Primary CTR overall rates before and since 1985 remain considerable (52.5% vs. 51.2%), yet median decreased (35% and 14%). Sub-acute endocarditis (SBE) and rheumatic heart disease (RHD) were the most frequent causes before 1985 (54.4% and 42.1%, respectively); since 1985 SBE and RHD have dropped sharply to 37.4% and 24.8%, respectively. Since 1985, mitral valve prolapse (MVP) and myxomatous degeneration (MD) have caused 44.5% and 11.7%, respectively. All other causes were almost not evident.Conclusions: “Primary CTR” remains significant. MD may be underestimated, as microscopic evaluation was not routinely performed. MD is probably the most frequent underlying cause given it is also the underlying cause of MVP. MVP may be overestimated due to detection criteria and misinterpretation of leaflet prolapse. SBE, frequently coexistent with other underlying causes, may be overestimated either due to detection bias or being a consequence rather than CTR cause. RHD is expected to further decline, following rheumatic fever. Previous significant underlying causes proved to be episodic if at all causative, e.g., blunt chest trauma, generalized connective tissue disorder, ischemic heart disease, and other heart and valvular diseases. CTR can occur in apparently healthy subjects having no atypical appearance and who may be unaware of carrying risk.

Epicardial application of an amiodarone-releasing hydrogel to suppress atrial tachyarrhythmias - Corrected Proof

2010-03-08

Abstract: Background: Amiodarone is currently the most effective antiarrhythmic drug for sinus rhythm maintenance. However, due to serious extracardiac adverse effects, prophylactic amiodarone therapy is only appropriate for patients at high risk for postoperative atrial fibrillation (AF). We hypothesized that epicardial application of an amiodarone-releasing hydrogel would produce therapeutic myocardial drug concentrations, while systemic levels would remain low.Methods: Goats were fitted with right atrial epicardial patch electrodes. A poly(ethylene glycol)-based hydrogel with amiodarone (1mg/kg bw) (n=10) or without drug (n=6) was applied to the right atrial epicardium. Atrial effective refractory period (AERP), conduction time and atrial response to burst pacing (rapid atrial response, RAR) were assessed up to 28days in awake goats. Myocardial, plasma and extracardiac tissue amiodarone concentrations were analysed by high-performance liquid chromatography.Results: The amiodarone-loaded hydrogel produced therapeutic drug concentrations in the right atrium up to 21days after application. In this period, AERP and conduction time were prolonged, while RAR inducibility was reduced (P<0.05) compared to animals treated with drug-free hydrogel. Mean amiodarone concentrations in the right atrium were 1 order of magnitude higher than in other heart chambers and 2 orders of magnitude higher than in extracardiac tissues. Plasma amiodarone levels remained below the detection limit (<10ng/mL) during the 28-day follow-up.Conclusions: Epicardial application of an amiodarone-releasing hydrogel reduces atrial vulnerability to tachyarrhythmias up to 3weeks, while extracardiac drug levels remain low. Therefore, amiodarone-releasing hydrogel could be applied during cardiac surgery to prevent postoperative AF at minimal risk for extracardiac adverse side effects.

Heterogeneity in platelet cyclooxygenase inhibition by aspirin in coronary artery disease - Corrected Proof

2010-03-08

Abstract: Background: Platelets, long believed to be incapable of de novo protein synthesis, may retain their ability to form the cyclooxygenase (COX) enzyme once it has been inactivated by aspirin. This may explain the inefficacy of the drug to induce sustained platelet inhibition in certain patients. We evaluated the stability of platelet inhibition following once-daily enteric-coated aspirin administration.Methods: Platelet responsiveness to aspirin was evaluated in 11 stable coronary artery disease patients on chronic aspirin therapy before and 1, 3, 8, and 24h after observed ingestion of 80-mg enteric-coated aspirin. Inhibition of the COX pathway was measured pharmacologically through plasma thromboxane (Tx) B2 levels, and functionally by light transmission aggregometry in response to arachidonic acid. COX-independent platelet activity was measured in response to adenosine diphosphate, epinephrine and collagen.Results: Plasma TxB2 levels showed profound inhibition of TxA2 formation, which was stable throughout 24h, in all but 1 subject. This subject had optimal response to aspirin (inhibition of platelet TxA2 production within 1h), but recovered the ability to synthesize TxA2 within 24h of aspirin ingestion. Arachidonic acid-induced platelet aggregation closely mirrored TxB2 formation in this patient, portraying a functional ability of the platelet to aggregate within 24h of aspirin ingestion. COX-independent platelet aggregation triggered TxA2 production to a similar extent in all patients, likely through signal-dependent protein synthesis.Conclusions: COX-dependent platelet activity is recovered in certain individuals within 24h of aspirin administration. Further research should consider increasing aspirin dosing frequency to twice daily, to allow sustained inhibition in such subjects.

Nickel allergy, Kounis syndrome and intracardiac metal devices - Corrected Proof

2010-03-08

Abstract: Metal-induced allergic reactions are not rare in every day practice but nickel, cobalt and chromium are the most common offenders. Other metal anions and metal alloys represent also emerging causes for hypersensitivity reaction in humans. The metal struts of endovascular and intracardiac devices are usually alloys containing nickel and constitute causes for allergic reactions with possible intracardiac and intracoronary mast cell activation resulting in the Kounis hypersensitivity coronary syndrome. Newer intracoronary stents avoid nickel thus making them less allergenic. It is advisable that, before any device implantation, careful history of any metal allergy should be taken and efforts should be made for the development of new devices with better biocompatibility.

Treatment of Kounis syndrome - Corrected Proof

Cihan Cevik, Kenneth Nugent, Goutam P. Shome, Nicholas G. Kounis — 2010-03-08

Abstract: Kounis syndrome is potentially a life-threatening medical emergency with both a severe allergic reaction and acute coronary syndrome. Most of the information about this syndrome has come from the case reports. The management of these patients may be challenging for clinicians, and unfortunately guidelines have not been established yet. In this article, we review the current guidelines of acute coronary syndromes and anaphylaxis along with the published cases with Kounis syndrome secondary to beta-lactam antibiotics. We have summarized our recommendations for the work-up and treatment of Kounis syndrome from available data. Obviously, larger prospective studies are needed to establish definitive treatment guidelines for these patients.

Accuracy of Doppler-derived pulmonary artery hypertension to predict heart failure with normal ejection fraction - Corrected Proof

2010-03-08

Abstract: Recent advances have highlighted the clinical relevance of pulmonary artery hypertension in terms of diagnosis and prognosis in heart failure with normal ejection fraction. We addressed the usefulness of Doppler-derived pulmonary artery systolic pressure to predict heart failure with normal ejection fraction in stable patients with exertional dyspnea. 25 patients referred for clinically indicated catheterism with evidence of heart failure according to the European diagnostic flowchart on “how to diagnose heart failure with normal ejection fraction” and 12 controls referred for clinically indicated catheterism without this condition according to the diagnostic flowchart on “how to exclude heart failure with normal ejection fraction” were included. None of the patients presented with Doppler-derived pulmonary vascular resistance >2.5WU. By logistic regression analysis, pulmonary artery systolic pressure predicted heart failure with normal ejection fraction (p=0.006), with an optimal cut-off value of 35mmHg (area under the ROC curve of 0.80 [0.64–0.92], p<0.001; sensitivity 76%, specificity 75%). Positive and negative predictive values were 93 and 50% for the cut-off value of 40mmHg. Doppler-derived pulmonary artery hypertension is a landmark of heart failure with normal ejection fraction in patients without severely increased pulmonary vascular resistance and deserves further attention in upcoming international recommendations.

Informed consent and transesophageal echocardiography: A review of patient responses - Corrected Proof

Timothy E. Paterick, Zachary R. Paterick, Gerald Fletcher — 2010-03-08

Abstract: Objective: To identify whether our pre-procedure discussion of the risks of transesophageal echocardiography (TEE) as well as documentation in the electronic medical record (EMR) met the standard of care for informed consent.Methods: Questionnaires were mailed to 500 patients who underwent a TEE at the Mayo Clinic Florida (MCF) requesting responses to questions that would identify how well the risks of the TEE procedure were discussed.Results: A positive response to the questions regarding the risks of TEE ranged from 75 to 95% and adequate documentation in the EMR revealed a 66% compliance rate.Conclusions: Individual physician and institutional commitment to informed consent at MCF is reflected in the very positive response to our questionnaire for meeting the criteria of informed consent; however, the documentation of the procedure discussion fell below the desired rate.

Ignoring lack of association of heart rate variability with cardiovascular disease and risk factors: Response to the manuscript “The relationship of autonomic imbalance, heart rate variability cardiovascular disease risk factors” by Julian F. Thayer, Shelby S. Yamamoto, Jos F. Brosschot - Corrected Proof

A. Kluttig, O. Kuss, K.H. Greiser — 2010-03-08

Abstract: A reduced heart rate variability (HRV) is a marker of autonomic dysfunction and has been shown to be associated with an increased risk of cardiovascular morbidity and mortality. However, especially regarding the association of HRV with cardiovascular risk factors the literature is rather inconsistent. We therefore critically discuss the review of Thayer et al. concerning the relationship between autonomic imbalance, heart rate variability and cardiovascular disease risk factors.

Hydrotherapy to heart failure patients - Corrected Proof

Vitor Oliveira Carvalho, Guilherme Veiga Guimarães — 2010-03-08

Exercise training is a well-established nonpharmacological method to increase exercise capacity, an important prognostic variable , and to restore quality of life in heart failure patients . Despite this, new methods (like hydrotherapy and interval exercise training) have been proposed with the aim of potentiate the well known benefits of the conventional rehabilitation.

Ultrafiltration does not affect certain predictors of outcome in heart failure - Corrected Proof

Amir Kazory — 2010-03-08

Abstract: Ultrafiltration as a therapeutic option for heart failure has been of more recent interest due to a proposed physiologic basis for its mechanism of action and the development of newer technology. Several studies have so far demonstrated its efficacy in rapid removal of fluid and improvement in congestive symptoms. However, there is currently no data on its impact on long-term outcomes of patients with heart failure. Moreover, evidence extracted from available studies does not support any beneficial impact on established predictors of mortality in this setting (i.e. blood urea nitrogen and serum sodium levels). This observation coupled with previous data indicating lack of expected beneficial effect on renal function highlights the emergent need for robust long-term outcome studies prior to expansion of the implementation of this complicated and costly therapy.

Letter regarding the article “Transradial access compared with femoral puncture closure devices in percutaneous coronary procedures”: An underestimated revolution - Corrected Proof

Bernardo Cortese — 2010-03-08

Abstract: We comment on the results of a recently published study that shows how the transradial approach for coronary procedures is safer and is preferred by patients. We comment on the possibility of using a stronger antithrombotic treatment in case of high risk percutaneous interventions. Is scientific evidence regarding the transradial approach enough to warrant its widespread use?

Prevalence of interatrial block in patients with Friedreich's Ataxia - Corrected Proof

2010-03-08

Abstract: Interatrial block is a predictor of atrial arrhythmias. Aim of the present study was to estimate the prevalence of interatrial block (IAB) in Friedreich's Ataxia (FA) compared to controls and correlate it with echocardiographic and genetic features.Methods: IAB, defined as an electrocardiographic (ECG) derived P-wave duration >120ms, echocardiographic variables and genetic markers were evaluated in 23 FA patients with no manifestation of cardiac involvement and were compared to 23 sex- and age-matched controls.Results: IAB was significantly more frequent among FA patients compared to controls (11/23 vs 1/23, p<0.005 respectively). However, no correlations with echocardiographic parameters or Guanine–Adenine–Adenine (GAA) trinucleotide repeat lengths could be established.Conclusion: Early recognition of IAB could allow the identification of asymptomatic FA patients who are prone to develop potentially life-threatening arrhythmias.

Phentermine cardiovascular safety II: Response to Yosefy Int J Cardiol. 2009 Epub Mar 19 - Corrected Proof

Richard B. Rothman, Ed J. Hendricks — 2010-03-08

Abstract: This is the fourth in a series of letters-to-the-editor discussing phentermine and cardiovascular safety. Yosefy et al., in reporting a case of aortic cusp tear in a 28year-old woman with a bicuspid aortic valve, attributed the tear to previous phentermine therapy. Evidence of mitral and tricuspid valve thickening was noted at echocardiography. In replying we pointed out that phentermine-induced valvular heart disease has not been reported and suggested that, since the reference cited for support referred to fenfluramine-induced valvulopathy, the attribution of the cusp tear to phentermine was incorrect.Yosefy replied, asserting that since the patient had no other cardiac risk factor, the tear had to be due to phentermine. In support of his presumption that phentermine therapy can induce cardiac risk he cited only the PDR warnings for phentermine. In this reply we point out that a congenital biscupid valve should not be ignored as a cardiac risk factor, that aortic valve cusp tears have been associated with bicuspid valves but never with phentermine or with valve thickening no matter the etiology, and that there is no published data implicating phentermine as a cause of valve thickening (or any other valve pathology). Evidence of phentermine safety in the peer-reviewed medical literature is discussed in the context of the cardiovascular warnings for phentermine in the PDR.

Bundle branch block patterns and long-term outcomes in heart failure - Corrected Proof

Husam M. Abdel-Qadir, Jack V. Tu, Peter C. Austin, Julie T. Wang, Douglas S. Lee — 2010-03-04

Abstract: Background: The prognostic value of left and right bundle branch blocks (LBBB and RBBB) in hospitalized heart failure (HF) patients is unclear. We sought to determine the prognostic value of bundle branch blocks in patients hospitalized with heart failure.Methods: The associations of BBB type with death, HF hospitalizations or cardiovascular hospitalizations over a five year follow-up were examined within the EFFECT study of hospitalized patients fulfilling the Framingham criteria for acute heart failure. Multinomial logistic regression was used to determine associations with BBB type, and survival was assessed using multiple Cox regression analysis.Results: Among 9082 patients (16.3% with LBBB; 7.2% with RBBB), LBBB was independently associated with lower systolic pressure, tachycardia and hyponatremia (odds ratio [OR] of 0.93 per 10mmHg, 1.04 per 10beats/min, and 0.84 per 10mmol/L, respectively). Men and diabetics (OR of 2.11 and 1.35, respectively) had greater odds of RBBB. After multiple covariate adjustment (n=7319), patients with LBBB had increased risk of HF hospitalization with adjusted hazard ratio [HR] of 1.32 (95% CI; 1.20–1.46, p<0.001) and cardiovascular hospitalization with HR of 1.13 (95% CI; 1.04–1.23, p=0.003). LBBB was associated with increased mortality with adjusted HR of 1.10 (95% CI, 1.02–1.18; p=0.011) in 7910 analysed patients. RBBB did not predict significantly increased risk of either death or hospitalization.Conclusions: Heart failure patients presenting with LBBB had greater clinical severity of heart failure at presentation and greater risk of death and hospitalization for heart failure or cardiovascular disease than those without BBB. In contrast, RBBB did not independently predict worse outcomes.

Assessment of ischemia-modified albumin levels for emergency room diagnosis of acute coronary syndrome - Corrected Proof

Xiao-li Shen, Cai-jing Lin, Li-li Han, Lin Lin, Leng Pan, Xiao-dong Pu — 2010-03-04

Abstract: Background: The aim of this study was to retrospectively evaluate the utility of assessing ischemia-modified albumin (IMA) levels for diagnosing acute coronary syndrome (ACS) in patients presenting to the emergency room (ER) with chest pain.Methods: The records of patients admitted to the ER with chest pain between August 2006 and December 2008 were examined. Those subsequently diagnosed with ACS were included in the study. Serum IMA and cardiac troponin I (cTnI) concentrations were determined in blood samples obtained from patients within 3h of ER admission and on days 1, 3, 7 and 14. IMA and cTnI cut-off values for diagnosis of ACS were employed and the successful diagnosis rates were compared.Results: Of the patients diagnosed with ACS following ER presentation with acute chest pain, the correct diagnosis rate was significantly higher as determined by assessment of IMA vs. cTnI concentrations within 3h of ER presentation (81.02% vs. 42.34%, P<0.01). Thereafter there were no between marker differences in rates of successful diagnosis.Conclusions: These findings support the notion that IMA may be a useful biochemical marker for the early diagnosis of ACS, particularly in patients presenting to the ER with acute chest pain.

Defects in myoglobin oxygenation in KATP-deficient mouse hearts under normal and stress conditions characterized by near infrared spectroscopy and imaging - Corrected Proof

2010-03-04

Abstract: Background: Disruption of ATP-sensitive potassium (KATP) channel activity results in the development of dilated cardiomyopathy in response to different forms of stress, likely due to the underlying metabolic defects. To further understand the role of Kir6.2-containing channels in the development of cardiac disease, we analysed the left ventricular (LV) wall oxygenation and the physiologic responses induced by acute stress in non-dilated Kir6.2−/− hearts.Methods: Control (C57BL6) and Kir6.2−/− mouse hearts were perfused in constant flow Langendorff mode with Krebs–Henseleit buffer. Myocardial oxygenation was evaluated using a newly developed technique, near infrared spectroscopic imaging (NIRSI) of the myoglobin (Mb) oxygen saturation parameter (OSP, ratio of oxy- to total Mb).Results: 2,4-dinitrophenol (DNP, 50-µM) and isoproterenol (0.1-µM) failed to produce a transient vasodilatory response and caused a significant diastolic pressure increase in Kir6.2−/− hearts. DNP strongly suppressed contractile function in both groups and induced severe mean OSP decreases in Kir6.2−/− hearts. Isoproterenol-induced decreases in OSP were similar despite the lack of contractile function stimulation in the Kir6.2−/− group. The index of OSP spatial heterogeneity (relative dispersion, RD) was lower by 15% in the Kir6.2−/− group at the baseline conditions. Recovery after stress caused reduction of RD values by 20% (DNP) and 8% (isoproterenol) in controls; however, these values did not change in the Kir6.2−/− group.Conclusions: 1) NIRSI can be used to analyse 2-D dynamics of LV oxygenation in rodent models of cardiomyopathy; 2) Kir6.2-containing KATP channels play an important role in maintaining myocardial oxygenation balance under acute stress conditions and in post-stress recovery.

Left ventricular mass and risk of cardiovascular events and all-cause death among ethnic Chinese—The Chin-Shan Community Cardiovascular Cohort study - Corrected Proof

2010-03-04

Abstract: Background: We conducted this cohort study involving ethnic Chinese population to explore the association between left ventricular mass and cardiovascular events and all-cause death, and to define the cutoff value of left ventricular mass for risk stratification.Methods: We evaluated 2604 participants aged ≥35years in the Chin-Shan Community Cardiovascular Cohort (CCCC) study who had received echocardiography without previous cardiovascular events. Left ventricular mass was divided by body surface area to obtain left ventricular mass index (LVMI). The end-points were all-cause death and incident cardiovascular events including coronary heart disease and stroke over a median follow-up of 14.4years.Results: By multivariate Cox regression analyses, a linear relationship between LVMI and cardiovascular events was found (adjusted hazard ratio 2.01, 95% CI, 1.11 to 3.63, for the highest quintile of LVMI compared with the lowest quintile, p for trend=0.001). A J-shape relationship between LVMI and all-cause death was observed, with the test for a linear relationship being rejected (p=0.003). The adjusted hazard ratios of all-cause death were significantly lower in the second quintile (0.58, 95% CI, 0.40 to 0.84) and in the third quintile (0.68, 95% CI, 0.47 to 0.96) of LVMI compared with the lowest quintile. The proposed cut-off value of LVMI was 105g/m2 for prediction of cardiovascular events.Conclusion: A linear relationship between LVMI and cardiovascular events, and a J-shape relationship between LVMI and all-cause death were found. The cut-off value derived from our Chinese population was lower than the frequently applied value derived from Caucasian population.

Asymptomatic left ventricular dysfunction in puerperal women: An echocardiographic-based study - Corrected Proof

Daniela V. Vettori, Luis E. Rohde, Nadine Clausell — 2010-03-04

Abstract: Background: Peripartum cardiomyopathy is a rare but significant cause of maternal morbidity and mortality. Identification of silent forms of ventricular dysfunction associated with the peripartum period is challenging, yet necessary to establish specific counseling and therapeutic measures to prevent progression to overt heart failure. Our aims were to determine the prevalence of asymptomatic left ventricular systolic dysfunction in puerperium and compare its progression with that of cases of peripartum cardiomyopathy occurring in the same study period.Methods: Cross-sectional study conducted from September 2002 to April 2005 to determine by echocardiography the prevalence of asymptomatic ventricular dysfunction in early puerperium and a nested cohort study from November 2007 to January 2008 to obtain clinical and echocardiography follow-up data of positively screened patients. All clinically diagnosed cases of peripartum cardiomyopathy occurring in the same study period were also examined.Results: We screened 1182 puerperal women; ten cases (0.85%) of asymptomatic ventricular dysfunction were detected characterized by either decreased left ventricular systolic function and/or increased end-diastolic diameter. Incidence of peripartum cardiomyopathy was 6 cases/10,866 deliveries (1/1811 live births) in the same period. An echocardiogram-based follow-up study performed after a mean of 4.0years (2.9–5.2years), showed significant and similar improvement in parameters of left ventricular function in both groups (p>0.05).Conclusions: Asymptomatic left ventricular dysfunction in puerperal women shows a high prevalence and a pattern of long term echocardiographic changes similar to those found in overt peripartum cardiomyopathy.

Gender differences in variables related to B-natriuretic peptide, left ventricular ejection fraction and mass, and peak oxygen consumption, in patients with heart failure - Corrected Proof

2010-03-04

Abstract: Aim and methods: We assessed gender differences in variables related to B-natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), peak oxygen consumption (peak-VO2), and LV mass (LVM), among patients recently hospitalized for suspected heart failure (HF).Results: Of 930 consecutive patients, 409 accepted follow-up after discharge, 221 of these had definite HF (90 women, mean age 74.5 [9.8]years). In 141 HF patients (61 women) with BNP data, women had lower BNP than men (43.9 [38.1] versus 76.3 [88.9]pmol/L, P=0.0193). LVEF (all HF patients) was higher in women (49.8 [13.4] versus 42.4 [13.9]%, P=0.0004). Peak-VO2 (147 HF patients, 48 women) was lower in women (13.9 [4.3] versus 16.3 [4.2]mL/kg/min, P=0.0093). LVM index (200 HF patients, 78 women) was lower in women (130.4 [46.5] versus 171.7 [57.6]g/m2, P<0.0001).Among HF patients, variables independently related to BNP were body mass index (BMI) and peak-VO2 exclusively among men, mitral regurgitation, respiratory disease and angiotensin receptor blocker treatment only among women. Variables independently related to LVEF were resting heart rate, acetylic salicylic acid use and BNP exclusively among men. No variable was exclusive for women. Variables independently related to peak-VO2 were right ventricular size, BNP, resting and peak heart rate solely among men, BMI and stable angina pectoris exclusively among women. Variables independently related to LVM were left atrial diameter only among men, BMI exclusively among women.Conclusion: Among elderly HF patients, there were some important gender differences in BNP, LVEF, peak-VO2 and LVM, and in variables independently related to these factors.

The effect of intravenous administration of erythropoietin on the infarct size in primary percutaneous coronary intervention - Corrected Proof

2010-03-03

Abstract: Background: After an acute myocardial infarction, the early restoration of coronary blood flow is mandatory for reducing infarct size. However, the process of reperfusion itself may also cause irreversible myocardial injury and contribute to the final infarct size. Recent animal studies have suggested that erythropoietin could protect the myocardium when administered after the onset of reperfusion. We investigated whether the administration of erythropoietin at the time of PCI would limit the size of the infarct during acute myocardial infarction by analysis of MRI and cardiac enzymes in this pilot study.Methods: We randomly assigned 57 patients with acute, anterior wall ST-elevation myocardial infarction who were presented within 12h after the onset of chest pain to one group which was given an intravenous bolus of recombinant human erythropoietin (rhEPO, 50U/kg) immediately before undergoing PCI or the control group without the IV treatment before PCI. Infarct size was assessed by measuring the release of cardiac enzymes (CK, CK-MB) and by performing MRI on day 4 after infarction.Results: The injection of erythropoietin did not result in thrombotic or hypertensive complications. The release of cardiac enzyme was not different between two groups. On day 4, the absolute infarct volume of the area of hyperenhancement on MRI did not differ between two groups (EPO group 52.4±23.6cm3 vs. control group 54.8±28.6cm3, p=0.74). Two groups did not differ in the percentage of total infarct volume over left ventricle volume (EPO group 34.4±11.7% vs. 37.0±13.8%, p=0.50).Conclusions: Intravenous administration of erythropoietin was safe and was not associated with thrombotic or hypertensive side effects. However, it did not reduce the infarct size when assessed by MRI and cardiac enzyme. Further studies about the dose or routes of administration of EPO are needed (ClinicalTrials.gov Identifier NCT00882466).

Biodistribution of bone marrow mononuclear cells in chronic chagasic cardiomyopathy after intracoronary injection - Corrected Proof

2010-03-03

Abstract: Background: Animal and human clinical studies have indicated that bone marrow (BM) mononuclear cell (MNC) therapy for Chagasic Cardiomyopathy (ChC) is feasible, safe and potentially efficacious. Nevertheless, little is known about the retention of these cells after intracoronary (IC) infusion.Methods: Our study investigated the homing of technetium-99m (99mTc) labeled BM MNCs and compared it to thallium-201 (201Tl) myocardial perfusion images using the standard 17-segment model. Six patients with congestive heart failure of chagasic etiology were included.Results: Scintigraphic images revealed an uptake of 5.4%±1.7, 4.3%±1.5 and 2.3%±0.6 of the total infused radioactivity in the heart after 1, 3 and 24h, respectively. The remaining activity was distributed mainly to the liver and spleen. Of 102 segments analyzed, homing took place in 36%. Segments with perfusion had greater homing (58.6%) than those with decreased or no perfusion (6.8%), p<0.0001. There was no correlation between the number of injected cells and the number of segments with homing for each patient (r=−0.172, p=0.774).Conclusions: These results indicate that 99mTc-BM MNCs delivered by IC injection homed to the chagasic myocardium. However, cell biodistribution was heterogeneous and limited, being strongly associated with the myocardial perfusion pattern at rest. These initial data suggest that the IC route may present limitations in chagasic patients and that alternative routes of cell administration may be necessary.

High mortality among heart failure patients treated with antidepressants - Corrected Proof

2010-03-02

Abstract: Background: This study was designed to assess whether pharmacologically treated depression was associated with increased mortality risk in systolic heart failure (SHF) patients.Methods: Patients (n=3346) with SHF (left ventricular ejection fraction≤0.45) and primarily New York Heart Association (NYHA) classes II–III (78%) were recruited from a clinical database used in 20 heart failure clinics in Denmark. The association between pharmacologically treated depression identified by at least one prescription of an antidepressant and mortality risk was evaluated.Results: Follow-up time was 540days (range: 30–1600days). 539 patients died. For 243 patients (7%) an antidepressant had been prescribed at least once. In a Cox Proportional Hazard Model, pharmacologically treated depression was associated with a 49% increased mortality risk (Hazard ratio: 1.49, 95% confidence interval: 1.03–2.16) after adjustment for traditional confounders. Three months after the baseline visit in the heart failure clinic, these patients received lower doses of beta-blockers than patients without antidepressant therapy (p=0.006). Female sex (p<0.001) and NYHA classes III–IV (p=0.007) were associated with the prescription of an antidepressant.Conclusions: Our analyses suggest that pharmacologically treated depression is associated with a 49% increased mortality risk, and that these high-risk patients receive lower doses of beta-blockers than patients with no antidepressant therapy.

Heart failure etiology impacts survival of patients with heart failure - Corrected Proof

2010-03-02

Abstract: Background: The impact of heart failure (HF) etiology on prognosis of HF is not well known.Methods: 3078 patients (median age 75years, 61% male) hospitalized with HF were studied. Patients were classified into six etiology groups: hypertension (HTN, 13.9%), ischemic heart disease (IHD, 42.4%), valvular disease (VHD, 9.5%), dilated cardiomyopathy (DCM, 7.9%), other (11.5%), and unknown etiology (14.8%). Patients with normal left ventricular ejection fraction (LVEF) were also included. Follow-up was up to 5years.Results: In multivariable analysis, with HTN as the reference, VHD showed the highest risk, HR 1.71 (CI: 1.3–2.2, p<0.0001), followed by DCM, HR 1.66 (CI: 1.2–2.3, p=0.002), IHD, HR 1.4 (CI: 1.1–1.7, p=0.001), and unknown etiology, HR 1.4 (CI: 1.1–1.7, p=0.007). For HF of IHD mortality risk was greater for patients with LVEF<30% (HR 2.1, CI: 1.7–2.7, p<0.0001) than for patients with LVEF≥30% (HR 1.3, CI: 1.0–1.5, p=0.03), compared to the reference (p-value for interaction<0.001).Conclusion: HF due to VHD, DCM and IHD carry a worse prognosis than that of HTN. For the IHD the risk increases progressively with lower values of LVEF.

Transcatheter atrial septal defect closure guided by colour flow Doppler - Corrected Proof

2010-03-02

Abstract: Objectives: To describe and assess the use of the maximum colour flow diameter (CFDmax) in guiding transcatheter closure of atrial septal defects (ASDs) and compare it with the standard balloon sizing method.Background: Balloon sizing of ASDs has been the standard method of assessing the size of ASDs and selecting a closure device. However, overestimation of the defect by stretching it may result in complications such as erosion of the atrial wall or aortic root, particularly in the presence of a deficient aortic rim and the long-term effects of oversized defects are unknown.Methods: Retrospective and prospective assessment of 115 consecutive patients who underwent ASD closure during three different time periods, when change in local practice occurred. Fifty patients underwent ASD closure with balloon sizing (period A), 15 with the aid of balloon sizing and additional estimation of the CFDmax (period B) and 50 with sole assessment of the CFDmax (period C).Results: The mean difference between the device used and the 2D defect size decreased from 6.9 to 5.1mm (p<0.01) and the percentage of device oversizing decreased from 38% to 31%. The complication rate decreased from 14% to 2%, (p=0.03), whilst the procedure and screening times decreased from 70 to 43min, (p<0.001) and 14.2 to 8.4min, (p<0.001), respectively.Conclusions: Transcatheter closure of ASDs guided solely by the CFDmax is feasible and safe and results in decreased procedure and screening times, whilst maintaining a low complication rate.

Differential response to resistance training in CHF according to ACE genotype - Corrected Proof

2010-03-02

Abstract: Background: The Angiotensin Converting Enzyme (ACE) gene may influence the risk of heart disease and the response to various forms of exercise training may be at least partly dependent on the ACE genotype. We aimed to determine the effect of ACE genotype on the response to moderate intensity circuit resistance training in chronic heart failure (CHF) patients.Methods: The relationship between ACE genotype and the response to 11weeks of resistance exercise training was determined in 37 CHF patients (New York Heart Association Functional Class=2.3±0.5; left ventricular ejection fraction 28±7%; age 64±12years; 32:5 male:female) who were randomised to either resistance exercise (n=19) or inactive control group (n=18). Outcome measures included , peak power output and muscle strength and endurance. ACE genotype was determined using standard methods.Results: At baseline, patients who were homozygous for the I allele had higher (p=0.02) and peak power (p=0.003) compared to patients who were homozygous for the D allele. Patients with the D allele, who were randomised to resistance training, compared to non-exercising controls, had greater peak power increases (ID p<0.001; DD p<0.001) when compared with patients homozygous for the I allele, who did not improve. No significant genotype-dependent changes were observed in , muscle strength, muscle endurance or lactate threshold.Conclusion: ACE genotype may have a role in exercise tolerance in CHF and could also influence the effectiveness of resistance training in this condition.

Serum calcium, phosphorus and cardiovascular events in post-menopausal women - Corrected Proof

2010-03-02

Abstract: Background: There is increasing evidence linking phosphorus and calcium levels to a higher risk of cardiovascular morbidity and mortality in the general population.Methods: We performed a post hoc data analysis from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial of raloxifene treatment in 7259 postmenopausal women with osteoporosis to test the hypothesis that higher baseline calcium and phosphorus levels are associated with a higher risk of incident cardiovascular events during 4years of follow-up.Results: Baseline mean (SD) values were 2.3 (0.1)mmol/L for serum calcium, 1.2 (0.2)mmol/L for serum phosphorus. Adjusted for multiple covariates including 25(OH)D, parathyroid hormone, and phosphorus, adjusted hazard ratios (AHR) (95% confidence interval (CI)) per SD of calcium were: 1.17(1.01–1.35), p=0.03 for combined cardiovascular outcome, 1.22(0.99–1.49), p=0.06 for cerebrovascular events, 1.12(0.92–1.37), p=0.25 for coronary heart disease, and 1.18(0.94–1.48), p=0.16 for death. While there was some evidence that higher serum phosphorus levels were associated with higher rate of combined cardiovascular outcome (p=0.07) and cerebrovascular events (p=0.03) in pauci-variable analysis, these associations did not persist after adjustment for additional confounders. Adjusted for multiple covariates including 25(OH)D, parathyroid hormone, and calcium, AHR(95% CI) per SD of phosphorus were 0.88(0.77–1.01), p=0.07 for combined cardiovascular outcome, 0.86(0.70–1.06), p=0.15 for ceverbrovascular events, 0.92(0.76–1.10), p=0.35 for coronary heart disease, and 1.00(0.80–1.25) for death.Conclusion: We found an independent association between higher baseline serum calcium levels and higher rate of cardiovascular events. Our findings did not support an independent association between serum phosphorus levels and cardiovascular events.

Hairy-related transcription factor 2 is not potentially related to congenital heart disease in Chinese patients - Corrected Proof

2010-02-25

Abstract: Congenital heart disease (CHD) is the malformation of the heart during embryonic development, contributing to the inadequate function of the heart. A recently suggested gene hairy-related transcription factor 2 (HEY2), is an important determinant of mammalian heart development and functions thereby. We had preformed a direct sequencing within 768 Chinese CHD patients in the HEY2 gene. However, we did not reveal any diagnostic alterations in the coding regions by direct sequencing in HEY2, nevertheless this work expands our knowledge of the causes of CHD in the other way.

The impact of cardiac surgery in native valve infective endocarditis: Can euroSCORE guide patient selection? - Corrected Proof

2010-02-24

Abstract: Background: Decision making regarding surgical intervention in native valve endocarditis (NVE) is often complex and surgery is withheld in a number of patients either because medical treatment is considered the best treatment or because the risk of operation is considered too high. The objective of this study was to investigate the outcome of surgical treatment and to validate the ability of euroSCORE to predict operative mortality in NVE patients.Methods: Prospective cohort study including 323 consecutive NVE patients. Patients were divided into 3 groups based on treatment strategy and indication/contraindication for surgery. The additive and logistic euroSCORE was calculated and the observed and predicted mortality was compared.Results: Cardiac surgery was associated with a good prognosis, in-hospital and after 12months, compared to conservative treatment. After adjustment for confounders surgery was associated with a survival benefit (hazard ratio (HR) 0.45, 95% CI: 0.27–0.76%; p=0.003). When propensity score was used in regression adjustment, cardiac surgery was still associated with a better outcome after 12months (HR 0.41, 95% CI: 0.25–0.68; p<0.001).Observed mortality for patients receiving surgical treatment was 11% compared to a mean logistic euroSCORE mortality of 16% (NS). The discriminating ability of euroSCORE was good, area under the ROC curve 0.74 (95% CI: 0.64–0.84; p<0.001) logistic model and 0.75 (95% CI: 0.65–0.86; p<0.001) additive model.Conclusions: Cardiac surgery was associated with a good prognosis when indicated regardless of euroSCORE, and surgery should only be withheld after thorough consideration. EuroSCORE remains a valuable tool to identify high-risk IE patients when surgery is considered.

Aorta-right ventricular fistulisation following staphylococcal aureus endocarditis of prosthetic aortic valve in a Tetralogy of Fallot patient - Corrected Proof

Bhavik N. Modi, Asmat H.N. Din, Kunjan Bhatt, Michael Henein — 2010-02-22

Perivalvular extension of infection in Prosthetic Valve Endocarditis (PVE) is frequent and associated with high rates of heart failure and death . Patients with PVE due to staphylococcal aureus are particularly prone to increased mortality and complications . Aorto-cavitary fistulisation, however, is a rare complication, the most common involve the right coronary sinus to right ventricle, the non-coronary sinus to right ventricle and the left coronary sinus to the left atrium .

Prognosis and outcomes of elderly (75–84years) patients with acute myocardial infarction 1–2years after the event — AMI-elderly study of the MONICA/KORA Myocardial Infarction Registry - Corrected Proof

2010-02-18

Abstract: Background: With increasing life expectancy the management of acute myocardial infarction (AMI) in patients of an older age is of growing importance. However, long-term data are limited regarding ‘hard’ endpoints and quality of life in unselected elderly patients in ‘real world’ settings.Methods and results: From March 2005 to March 2006 all 75–84-year old patients consecutively hospitalised due to an incident AMI in a large community teaching hospital were analyzed (N=235). Evidence-based therapy included the treatment with aspirin (93%), clopidogrel (65%), betablockers (93%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (84%), and statins (83%). Percutaneous coronary intervention (PCI) was performed in 45.5% and bypass grafting (CABG) in 10.2%. The 28-day-case fatality was 17.4%. Long-term follow-up was obtained in 95.9% of all hospital survivors at a mean of 18.7±6.4months; during this time 19.9% of patients died. After multivariate analysis the only significantly negative predictor for survival and MACCE was diabetes, and the only significantly positive predictor was revascularisation during hospital stay. Patients with PCI/CABG had lower NYHA class (81% vs. 48%; p<0.04). Patients with PCI also had a higher EQ-5D index score (75±18 vs. 67±17, p<0.04) compared to patients not receiving PCI.Conclusion: The positive long-time effect of revascularisation procedures during hospitalisation, not only on ‘hard’ endpoints but also on functional outcome and quality of life emphasizes that invasive therapies should not be considered less valuable in elderly people and that age alone should not preclude aggressive treatment during AMI.

Recommendations for adult and paediatric cardiologists on obtaining additional qualification in “Adults with Congenital Heart Disease” (ACHD) - Corrected Proof

2010-02-16

Abstract: Background: The number of adult congenital heart disease (ACHD) patients will be larger in the medium to long term than that of children and adolescents with congenital heart disease. The present structures for the medical care of ACHD patients are not sufficient and need to be improved. Therefore the Task Force aimed at developing recommendations for adult and paediatric cardiologists to acquire the additional qualification “Adults with Congenital Heart Disease” (ACDH).Methods: The members of the interdisciplinary Task Force were selected on the basis of their special clinical, scientific and organisational expertise. The leading author submitted a draft version, which was revised by a sub-group of the interdisciplinary Task Force. It was subsequently agreed upon and re-circulated by all the members of the Task Force. The recommendations were then presented to the relevant committees of all participating associations and groups and approved following detailed discussion.Results: A training programme for acquiring an additional qualification in the treatment of adults with congenital heart disease was created successfully.Conclusions: The medical care of adults with congenital heart disease is a sub-speciality in the border area between adult cardiology and paediatric cardiology. ACHD cardiologists are to be specially trained experts with appropriate knowledge and special skills and experience in the diagnosis and therapy of congenital heart disease in adults. ACHD cardiologists should be able to recognise and treat problems that occur in adulthood in connection with congenital heart disease.

Balloon valvuloplasty in the treatment of congenital aortic valve stenosis — A retrospective multicenter survey of more than 1000 patients - Corrected Proof

2010-02-12

Abstract: Background: The value of balloon valvuloplasty of the aortic valve in childhood is still under debate.Objective: To evaluate the results of the procedure in a retrospective multicenter survey of a large cohort over a long time interval.Methods: Retrospective analysis of 1004 patients with balloon valvuloplasty of the aortic valve performed between 9/1985 and 10/2006 at 20 centers in Germany, Austria and Switzerland. Amongst others, the following parameters were evaluated before and after the procedure as well as at the end of follow-up or before surgery: clinical status, left ventricular function, transaortic pressure gradient, degree of aortic regurgitation, freedom from re-intervention or surgery.Patients: Patients from 1day to 18years of age with aortic valve stenosis were divided into four groups: 334 newborns (1–28days); 249 infants (29–365days); 211 children (1–10years), and 210 adolescents (10–18years).Results: Median follow-up was 32months (0days to 17.5years). After dilatation the pressure gradient decreased from 65 (±24)mm Hg to 26 (±16)mm Hg and remained stable during follow-up. The newborns were the most affected patients. Approximately 60% of them had clinical symptoms and impaired left ventricular function before intervention. Complication rate was 15% in newborns, 11% in infants and 6% in older children. Independently of age, 50% of all patients were free from surgery 10years after intervention.Conclusions: In this retrospective multicenter study, balloon valvuloplasty of the aortic valve has effectively postponed the need for surgery in infants, children and adolescents up to 18years of age.

Cardiac syndrome X: Current concepts - Corrected Proof

Mukesh Singh, Sarabjeet Singh, Rohit Arora, Sandeep Khosla — 2010-02-08

Abstract: Cardiac syndrome X is a heterogeneous entity, both clinically and pathophysiologically, encompassing a variety of pathogenic mechanisms. Management of this syndrome represents a major challenge to the treating physician. They often seek medical care because of recurring and disabling chest pain, which may imply repetitive and costly invasive and non-invasive investigations. A careful patient evaluation for underlying pathophysiologic mechanism and exclusion of other causes of chest pain along with attention to various psychological aspects is helpful in reducing the stress and suffering of these patients. This article reviews the available literature on the pathophysiology and current controversies surrounding the management of this difficult to treat condition.

Recent advances in the echocardiographic diagnosis of mitral valve prolapse - Corrected Proof

Tsung O. Cheng, Xin-Fang Wang, Jing Zhang, Ming-Xing Xie — 2010-02-08

The entity of mitral valve prolapse (MVP) was originally described clinically and auscultatorily and subsequently documented angiocardiographically nearly half of a century ago. However, it was the widespread use of echocardiography in the l980s that rapidly propelled this entity into its current prominent status of vast worldwide interest as the commonest heart valve disease in the United States , one of the two most common congenital anomalies of the heart , and the commonest cause of mitral regurgitation in developed countries .

Renal dysfunction and high levels of hsCRP are additively associated with hard endpoints after percutaneous coronary intervention with drug eluting stents - Corrected Proof

2010-02-08

Abstract: Background: Chronic kidney disease (CKD) and high C-reactive protein (CRP) are known risk factors of cardiovascular disease. In the drug eluting stent (DES) era, the relationship among CKD, CRP, and long-term outcomes after percutaneous coronary intervention (PCI) has not yet been demonstrated. We investigated the combined effects of renal dysfunction and CRP on outcomes in patients who underwent PCI using DES.Methods: A total of 1859 patients (mean age 64±10years) who underwent PCI with DES between February 2003 and June 2006, were divided into 4 groups (quartile) according to estimated glomerular filtration rate (eGFR) and hsCRP at admission.Results: The composite of cumulative death and non-fatal myocardial infarction (mortality+MI) during median follow-up of 27months, was significantly higher in the lowest eGFR quartile than in the other three groups (hazard ratio (HR) for mortality+MI: 3.32, 95% CI: 2.21–5.00, P<0.001). Mortality+MI was also significantly higher in the highest hsCRP quartile (HR: 3.29, 95% CI: 2.02–5.37, P<0.001). A combined analysis of mortality+MI on the basis of hsCRP and renal function showed the exaggerated hazard in the combined worst quartile of hsCRP and GFR (HR of the combined worst quartile, 10.876, 95% CI: 3.74–31.63, P<0.001). Furthermore, both the lowest eGFR quartile and the highest hsCRP quartile were significantly associated with increased risk of stent thrombosis. In a multivariate analysis, low GFR and high hsCRP were independent predictors of mortality+MI after PCI with DES along with left ventricular dysfunction, diabetes, and left main disease.Conclusions: In an unselected cohort of patients receiving PCI with DES, poor renal function and high hsCRP were additively associated with a higher risk of hard endpoints and were independent predictors of mortality+MI even after correction for other factors. Our data suggest the importance of systemic factors on mortality even in the DES era.

Minimum-intensity projection of multidetector-row computed tomography for assessment of pulmonary hypertension in children with congenital heart disease - Corrected Proof

2010-02-08

Abstract: Background: The present study aimed to assess the feasibility of minimum-intensity projection (minIP) images for the evaluation of pulmonary hypertension (PH) in children with congenital heart disease (CHD).Methods: A total of 70 consecutive patients (mean age, 4.6±4.4years; range, 6months–16years) underwent multidetector-row computed tomography (MDCT) angiography of the thorax prior to cardiac catheterization and lung perfusion scintigraphy. Contiguous axial, coronal and sagittal minIP images of 5-mm thickness were reconstructed from the contrast-enhanced CT datasets. Two reviewers evaluated the images in consensus and qualitatively graded lung parenchyma attenuation as homogeneous (Class I), slightly heterogeneous lung attenuation that does not conform to the anatomic boundaries of the secondary pulmonary lobule (Class II), and mosaic pattern (Class III). MinIP attenuation grading results were then compared with those of perfusion scintigraphy. Furthermore, the relationships between the results of these modalities and mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) were evaluated.Results: In 51 (73%) patients, concordant findings were observed between the modalities, although minIP showed a higher grade for heterogeneous images than did scintigraphy. mPAP and PVR showed significant difference among the minIP attenuation classes (p<0.0001 for both). High-grade heterogeneous minIP images were associated with high mPAP, high PVR, presence of major aortopulmonary collateral artery, and chromosomal abnormality.Conclusion: MinIP is a promising technique for depicting lung perfusion and can be used as superior alternative to scintigraphy in the evaluation of PH.

The CID Chrono™ cobalt–chromium alloy carbofilm-coated coronary stent system - Corrected Proof

2010-02-08

Abstract: Background: In an attempt to improve the stent's safety, development of bare metal stents (BMS) continues, with new materials and geometry. Chrono™ (CID, Italy) is a thin strut cobalt–chromium (Co–Cr) stent combining the clinical benefits of the bio- and haemo-compatible Carbofilm™ coating.Methods: We assessed the safety and efficacy of percutaneous coronary interventions (PCI) using the new Co–Cr Chrono™ stent in patients undergoing elective PCI for de novo lesions in native coronary vessels. The patients were followed for 12months for the occurrence of major cardiac events (MACE, defined as death, myocardial infarction, repeat PCI and bypass surgery). Patients with complex (B2/C) lesions were compared to those with non-complex lesions (A/B1).Results: A total of 340 consecutive patients were analysed: 155 patients with complex lesions (Complex group) and 185 patients with non-complex lesions (Non-complex group). Dual antiplatelet therapy was maintained >1month in 21% of patients in both Complex and Non-complex group. Stent length was longer in the Complex group (25±10mm versus 17±6mm; p<0.001). Stent diameter <3.0mm was most frequent in the Complex group (35.5% versus 27.5%; p<0.05). During the 12-month follow-up period MACE occurred in 10.6% of the global population (12.3% in the Complex group and 9.2% in the Non-complex group; p=0.43). Repeat PCI was most frequent in the Complex group (9.7% versus 3.8%; p=0.044). The incidence of definite and probable stent thrombosis (ARC criteria) was 1.29% in the Complex group and 1.08% in the Non-complex group (p=1.0).Conclusions: Implantation of the Co–Cr Chrono™ stent results in a good safety and efficacy for both complex and non-complex de-novo coronary artery lesions.

Hyperaldosteronism is associated with a decrease in number and altered growth factor expression of endothelial progenitor cells in rats - Corrected Proof

2010-02-01

Abstract: Background: Aldosterone plays a role in hypertension, the pathogenesis of heart failure and vascular injury. However, little information exists about the possible influence of aldosterone on bone marrow derived endothelial progenitor cells (EPC), which are involved in the repair of damaged endothelium. This study was designed to determine the long- term in vivo influence of aldosterone on the number of EPC.Methods: Male Wistar rats were equipped with a subcutaneous pump which released aldosterone (n=20) or placebo (n=20) over 28days. The animals were either fed with or without the aldosterone antagonist spironolactone (each n=10). EPC were identified by the uptake of ac-LDL and BS-1. The expression of VEGF-2 receptor, VEGF, HGF, SDF1 and the mineralocorticoid receptor (MR) in EPC was assessed by quantitative PCR. Finally, VEGF concentration was measured in the serum of all animals by ELISA.Results: The total number of EPC was significantly lowered by chronic aldosterone treatment. Spironolactone compensated the effect and lead to a 2-fold increase. While the SDF1 mRNA was not affected by aldosterone, HGF, MR2 and VEGF receptor mRNA were significantly downregulated in EPC. Strikingly spironolactone not only leads to increases in the mRNA expression in hyper-aldosteronemic animals but also exhibited significant increases above the control levels.Conclusion: The present data indicate that high levels of aldosterone impair the function and reduce the numbers of EPC and lead to a downregulation of VEGF and the VEGF receptor in vivo. Spironolactone antagonized these effects. MR blockade by spironolactone may therefore represent a future tool to enhance the response to cell based therapy.

Cardiovascular changes after transcatheter endovascular stenting of adult aortic coarctation - Corrected Proof

2010-02-01

Abstract: Background: Longer term data on efficacy and clinical endpoints relating to transcatheter endovascular stenting in adults with aortic coarctation remains limited. We hypothesised that stenting would have effects on blood pressure, presence and extent of collaterals, left ventricular (LV) mass and vascular function.Methods: Eighteen patients mean age 31.6±12.8 years were studied with clinical assessment and cardiovascular magnetic resonance before and after (10.2±2.2 months) aortic coarctation endovascular stenting. Fredriksen coarctation index increased and using this index no patient had significant coarctation (index <0.25) after stenting.Results: Blood pressure decreased (153±17/82±14 versus 130±21/69±13mmHg; p<0.001) unrelated to change in existing anti-hypertensive therapy. LV ejection fraction increased (70±10 versus 74±8%; p=0.01) and LV mass index decreased (91±24 versus 82±20g/m2; p=0.003). Collaterals appeared smaller and the degree of flow through collateral arteries decreased (40±29 versus −1±33%; p<0.001). Distensibility of the ascending aorta increased (4.0±2.5 versus 5.6±3.5×10−3mmHg−1; p=0.04). Unexpectedly, right ventricular mass index decreased (35±7 versus 30±10g/m2; p=0.01).Conclusion: All patients underwent successful relief of coarctation by endovascular stenting. Both cardiac and vascular beneficial outcomes were demonstrated. The reduction in LV mass suggests a potential for reduction in risk of adverse events and warrants further study.

ST-elevation myocardial infarction associated with acute ischemic stroke - Corrected Proof

Salvatore Patanè, Filippo Marte, Concetta Lentini, Sergio Buonamonte — 2010-01-29

Abstract: Randomized clinical studies have demonstrated that tissue plasminogen activator thrombolytic therapy improves functional outcomes. Recently the time window for tissue plasminogen activator thrombolytic therapy has been extended from 3 to 4.5h after ischemic stroke onset, which will allow more ischemic stroke patients to benefit from this treatment. Healthcare providers should also ascertain whether the ST-elevation myocardial infarction (STEMI) patient has also neurological contraindications to fibrinolytic therapy, including any history of intracranial hemorrhage, significant closed head or facial trauma within the past 3months, uncontrolled hypertension, or ischemic stroke within the past 3months (EXCEPT acute ischemic stroke within 3h). History of prior ischemic stroke greater than 3months is a relative contraindication. We present a case of tissue plasminogen activator thrombolytic therapy in a 68-year-old Italian man admitted to the Emergency Department with heart failure, ischemic stroke and ST-elevation myocardial infarction. Also this case focuses attention on regression of ischemic stroke symptoms in STEMI patient treated with tissue plasminogen activator thrombolytic therapy.

Long-term active immunization with a synthetic peptide corresponding to the second extracellular loop of β1-adrenoceptor induces both morphological and functional cardiomyopathic changes in rats - Corrected Proof

2010-01-25

Abstract: Background: β1-Adrenoceptors (β1-ARs) are the predominant receptors in regulating heart functions. β1-ARs contain 7-transmembrane domains (7TM), 3 extracellular loops and 3 intracellular loops. Among these loops, the second extracellular loop of β1-AR (β1-AR-ECII) plays an important role in the pathogenesis of heart failure.Methods: (1) Select the sera-negative rats for antibodies against β1-AR-ECII. (2) Detect the level of antibodies against β1-AR-ECII in the process of active immunization with artificial synthetic peptides according to the sequence of human β1-AR-ECII. (3) Observe its long-term role on cardiac structure and function in vivo by immunizing rats. (4) Detect the changes of T lymphocytes subsets in the process of active immunization.Results: The peptides induced the production of specific autoantibody against β1-AR-ECII. Furthermore, immunization with β1-AR-ECII peptide induced both morphological and functional alterations in the hearts of rats, which potentially results in heart failure. In addition, induction of the autoantibodies against β1-AR-ECII increased the CD4+/CD8 + ratio in the peripheral blood of rats.Discussion: In this study, we determined the effect of anti-β1-AR-ECII autoantibody on morphological and functional cardiomyopathic alterations by immunization of rats with a synthetic peptide corresponding to the β1-AR-ECII for 18months. These results provide further evidence that autoantibody against β1-AR-ECII is involved in the pathogenesis of heart failure. But the underlying mechanisms need further study.

The impact of body mass index on clinical outcomes after acute myocardial infarction - Corrected Proof

2010-01-25

Abstract: Background: Several studies indicated that an elevated body mass index (BMI) is associated with a lower rate of mortality in patients with acute myocardial infarction (AMI). However, the existence of the obesity paradox in AMI patients remains controversial.Methods: We examined the association of BMI and clinical outcomes in 2157 patient with AMI (mean follow-up of 26months). BMI was categorized into 9 groups (<18.5, 18.5 to 20.9, 21.0 to 23.4, 23.5 to 24.9, 25.0 to 26.4, 26.5 to 27.9, 28.0 to 29.9, 30.0 to 34.9, and ≥35.0kg/m2). Cox regression was used to calculate hazard ratios (HR) for the various BMI categories, adjusting for the clinical variables, left ventricular ejection fraction, and hemoglobin level.Results: BMI had a U-shaped association with mortality. Relative to the lowest mortality group (BMI of 26.5 to 27.9kg/m2), the adjusted HRs for mortality were increased only in the lower (HR 2.3; 95% CI 1.3–4.2) and upper (HR 1.8; 95% 1.2–2.9) BMI categories. There was a significant interaction between BMI and anemia (P=0.0003) such that the U-shaped relationship between BMI and mortality was present mainly in patients with anemia. Patients in the lower and upper BMI categories and concomitant anemia had a striking increase in mortality (adjusted HR 5.1, 95% CI 1.9–11.7 and 3.2, 95% CI 1.5–7.0, respectively).Conclusion: Both obesity and underweight are associated with increased mortality in patients with AMI. The risk of mortality is particularly high among underweight and obese patients with anemia.

Left bundle branch block with changing axis deviation - Corrected Proof

Salvatore Patanè, Filippo Marte, Mauro Sturiale — 2010-01-25

Abstract: Changing axis deviation has been reported during atrial fibrillation or atrial flutter. Changing axis deviation has also been reported during acute myocardial infarction associated with atrial fibrillation or at the end of atrial fibrillation during acute myocardial infarction. A left bundle branch block is usually associated with normal or left axis deviation. Rarely the ECG shows a left bundle branch block with changing QRS morphology and changing axis deviation. We present a case of a left bundle branch block with changing axis deviation in a 73-year-old Italian man. Also this case focuses attention on the left bundle branch block with changing axis deviation.

Why did high-dose rosuvastatin not improve cardiac remodeling in chronic heart failure? Mechanistic insights from the UNIVERSE study - Corrected Proof

2010-01-20

Abstract: Background: Statins are often prescribed for prevention of atherosclerotic outcomes in patients who have chronic heart failure (CHF), if this has an ischaemic etiology. These agents may also possess additional properties, independent of effects on blood lipid levels, which may have an effect on cardiac remodeling. However, beneficial effects were not observed in the recent UNIVERSE trial.Methods: We prospectively planned a sub-study of UNIVERSE to explore relevant mechanistic effects of rosuvastatin, including effects on collagen turnover and plasma coenzyme Q10 (CoQ) levels. Additionally, CoQ levels in CHF patients receiving chronic statin therapy were measured.Results: CoQ levels were significantly reduced after 26weeks of rosuvastatin statin therapy (n=32), compared to placebo (n=37) in CHF patients in UNIVERSE trial. Patients with CHF (n=56) matched for age, gender and severity of disease who had been taking statins for 12months or longer had CoQ levels of 847±344nmol/L, significantly lower than 1065.4±394nmol/L in UNIVERSE patients at baseline (p=0.0001). Serum types I and III N-terminal procollagen peptide (PINP and PIIINP), measures of collagen turnover which can contribute to cardiac fibrosis were significantly increased in the rosuvastatin group compared to baseline in UNIVERSE patients (PINP: p=0.03, PIIINP: p=0.001).Conclusion: In conclusion putative beneficial effects of statin therapy on cardiac remodeling in UNIVERSE may have been negated by increases in collagen turnover markers as well as a reduction in plasma CoQ levels in these patients with CHF.

Cardiac troponin I is released following high-intensity short-duration exercise in healthy humans - Corrected Proof

Rob Shave, Peter Ross, David Low, Keith George, David Gaze — 2010-01-15

Abstract: It has been previously shown that cardiac troponin (cTn) is released in response to prolonged endurance exercise. The influence of short-duration high-intensity exercise upon the release of cTn is not known. We examined cardiac troponin I (cTnI) release pre-, during and post-30min of high-intensity running exercise in eight recreationally active males (age 29±3years; VO2peak 53±11mlkgmin−1). Following exercise, cTnI increased in six of the eight participants. Four participants showed a minimal response (<0.05µg/l) post-exercise. In contrast, two participants showed a progressive increase in cTnI (>0.1µg/l) following exercise which peaked 3–4h post-exercise. cTnI returned below the detection limit of the assay in all bar one of the participants 24h post-exercise. These data are the first to show that cTnI can be released following short-duration high-intensity exercise. Clinicians should be aware that exercise-induced release of cTnI is not limited to prolonged endurance activity.