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Objectives: The purpose of this study was to assess whether medical management may alter the severity of functional mitral regurgitation (FMR) and its prognosis in patients who have heart failure with reduced ejection fraction (HFrEF)., Background: FMR in patients who have HFrEF is associated with a worse prognosis. It is uncertain to what extent medical management may alter the severity of FMR and its prognosis., Methods: The extent of FMR was assessed at baseline and after a median follow-up period of 50 months in 163 consecutive HFrEF patients (left ventricular ejection fraction <40%). Severe FMR was defined as mitral regurgitation (MR) grade 3-4. All of the patients received the maximal tolerable doses of their heart failure (HF) medications. Major adverse cardiac events were defined as a composite of all-cause death and the need for heart transplantation or hospitalization for HF and/or malignant arrhythmias., Results: A total of 50 (31%) patients had severe MR at baseline. During the follow-up period, 38% of the severe FMR patients showed an improvement to nonsevere FMR (MR grade <3), whereas 18% of the nonsevere FMR patients developed severe FMR despite optimal HF treatment. Cox regression analysis revealed that the presence of sustained severe FMR or worsening of FMR was the most important independent prognostic determinant with an adjusted odds ratio of 2.5 (95% confidence interval: 1.5 to 4.3, major adverse cardiac events 83% vs. 43%). In addition, those patients showed a 13% increase in left ventricular end-diastolic volume index (LVEDVI), whereas the patients with improvement in their severe MR showed a 2% decrease in LVEDVI (p = 0.01)., Conclusions: Severe FMR was successfully treated with medication in almost 40% and was associated with prevention of left ventricular adverse remodeling and with an improved long-term prognosis., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE)., Methods: Two hundred sixty-one patients with left ventricular ejection fraction ≤35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE. Thereafter, patients were encouraged to continue exercising on their own. Clinical assessments were performed at baseline, after the intervention, and at follow-up after 52 weeks. Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks., Results: Groups did not differ in age (median, 60 years), sex (19% women), ischemic pathogenesis (59%), or medication. Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT ( P =0.45); left ventricular end-diastolic diameter changes compared with RRE were -2.8 mm (-5.2 to -0.4 mm; P =0.02) in HIIT and -1.2 mm (-3.6 to 1.2 mm; P =0.34) in MCT. There was also no difference between HIIT and MCT in peak oxygen uptake ( P =0.70), but both were superior to RRE. However, none of these changes was maintained at follow-up after 52 weeks. Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks (HIIT, 39%; MCT, 25%; RRE, 34%; P =0.16). Training records showed that 51% of patients exercised below prescribed target during supervised HIIT and 80% above target in MCT., Conclusions: HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity, and its feasibility remains unresolved in patients with heart failure., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046., (© 2017 The Authors.)

Background: To contribute to the protocol development of exercise training in LVAD supported patients by reviewing the exercise programs for those patients in the ESC affiliated countries., Methods: A subset of data from 77 (26 countries) LVAD implanting centers that participated in the Extra-HF survey (170 centers) was analyzed., Results: Of the 77 LVAD implanting centers, 45 (58%) reported to have a functioning exercise training program (ETP) for LVAD patients. In 21 (47%) of the 45 ETP programs in LVAD implanting centers, patients begin their ETP during their in-hospital post-operative recovery period. Most centers (71%) have an early post-discharge program for their patients, and 24% of the centers offer a long-term maintenance program. The professionals involved in the ETPs are mainly physiotherapists (73%), psychologists, cardiac rehab nurses (22%), or cardiologists specialized in rehabilitation (22%). Not all programs include the treating cardiologist or surgeons. Most of the ETPs (84%) include aerobic endurance training, mostly cycling (73%), or walking (62%) at low intensity intervals. Some programs apply resistance training (47%), respiratory muscle training (55%), or balance training (44%). Reasons for the absence of ETPs are referral of patients to another center (14 centers) and lack of resources (11 centers)., Conclusion: There is a great variance in ETPs in LVAD implanting centers. Not all the implanting centers have an ETP, and those that do have adopted a local protocol. Clear guidance on ETP supplied by LVAD implanting centers to LVAD supported patients and more evidence for optimal modalities are needed., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aims: In heart failure (HF), exercise training programmes (ETPs) are a well-recognized intervention to improve symptoms, but are still poorly implemented. The Heart Failure Association promoted a survey to investigate whether and how cardiac centres in Europe are using ETPs in their HF patients., Methods and Results: The co-ordinators of the HF working groups of the countries affiliated to the European Society of Cardiology (ESC) distributed and promoted the 12-item web-based questionnaire in the key cardiac centres of their countries. Forty-one country co-ordinators out of the 46 contacted replied to our questionnaire (89%). This accounted for 170 cardiac centres, responsible for 77,214 HF patients. The majority of the participating centres (82%) were general cardiology units and the rest were specialized rehabilitation units or local health centres. Sixty-seven (40%) centres [responsible for 36,385 (48%) patients] did not implement an ETP. This was mainly attributed to the lack of resources (25%), largely due to lack of staff or lack of financial provision. The lack of a national or local pathway for such a programme was the reason in 13% of the cases, and in 12% the perceived lack of evidence on safety or benefit was cited. When implemented, an ETP was proposed to all HF patients in only 55% of the centres, with restriction according to severity or aetiology., Conclusions: With respect to previous surveys, there is evidence of increased availability of ETPs in HF in Europe, although too many patients are still denied a highly recommended therapy, mainly due to lack of resources or logistics., (© 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.)

The relationship between exercise capacity, as assessed by peak oxygen consumption, and outcome is well established in heart failure (HF), but the predictive value of cardiopulmonary exercise testing (CPET) has been recently questioned, for two main reasons. First, the decisional power of CPET in the selection of heart transplantation candidates has diminished, since newer therapeutic options and the shortage of donor hearts have restricted this curative option to extremely advanced HF patients, frequently not able to perform a symptom-limited CPET. Secondly, the use of CPET has become more complex and sophisticated, with many promising new prognostic indexes proposed each year. Thus, a modern interpretation of CPET calls for selective expertise that is not routinely available in all HF centres. This position paper examines the history of CPET in risk stratification in HF. Throughout five phases of achievements, the journey from a single CPET parameter (i.e. peak oxygen consumption) to a multiparametric approach embracing the full clinical picture in HF-including functional, neurohumoral, and laboratory findings-is illustrated and discussed. An innovative multifactorial model is proposed, with CPET at its core, that helps optimize our understanding and management of HF patients., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)

A single air dive causes transient endothelial dysfunction. Endothelial progenitor cells (EPCs) and circulating angiogenic cells (CAC) contribute synergistically to endothelial repair. In this study (1) the acute effects of diving on EPC numbers and CAC migration and (2) the influence of the gas mixture (air/nitrox-36) was investigated. Ten divers performed two dives to 18 meters on Day (D) 1 and D3, using air. After 15 days, dives were repeated with nitrox-36. Blood sampling took place before and immediately after diving. Circulating EPCs were quantified by flow cytometry, CAC migration of culture was assessed on D7. When diving on air, a trend for reduced EPC numbers is observed post-dive, which is persistent on D1 and D3. CAC migration tends to improve acutely following diving. These effects are more pronounced with nitrox-36 dives. Diving acutely affects EPC numbers and CAC function, and to a larger extent when diving with nitrox-36. The diving-induced oxidative stress may influence recruitment or survival of EPC. The functional improvement of CAC could be a compensatory mechanism to maintain endothelial homeostasis.

Background: Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising due to an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesise that a comprehensive cardiac rehabilitation programme can improve physical capacity and self-assessed mental health and reduce hospitalisation and healthcare costs after heart valve surgery., Methods: A randomised clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients, 1:1 intervention to control group, using central randomisation, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise, and a psycho-educational intervention comprising five consultations. Primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. Secondary outcome is self-assessed mental health measured by the standardised questionnaire Short Form 36. Also, long-term healthcare utilisation and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design is used to evaluate qualitative and quantitative findings encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study., Discussion: The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015)., Trial Registration: ClinicalTrials.gov (http://NCT01558765).

In a previous paper, as the first of a series of three on the importance of characteristics and modalities of physical activity (PA) and exercise in the management of cardiovascular health within the general population, we concluded that, in the population at large, PA and aerobic exercise capacity clearly are inversely associated with increased cardiovascular disease risk and all-cause and cardiovascular mortality and that a dose–response curve on cardiovascular outcome has been demonstrated in most studies. More and more evidence is accumulated that engaging in regular PA and exercise interventions are essential components for reducing the severity of cardiovascular risk factors, such as obesity and abdominal fat, high BP, metabolic risk factors, and systemic inflammation. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit for each separate risk factor. The present paper, therefore, will review and make recommendations for PA and exercise training in the management of cardiovascular health in individuals with cardiovascular risk factors. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and individual members of the public. Based on previous and the current literature overviews, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and regarding appropriate risk evaluation during exercise in individuals with cardiovascular risk factors.

Morbidity and mortality remain high in heart failure despite considerable progress achieved with medical therapy and electrical devices. A multidisciplinary approach is actually strongly recommended. In order to provide optimal care to the ever-growing population of patients with heart failure, telemonitoring has been proposed as a modality to improve usual care. The aim of this review is to provide an overview of the existing evidence on telemonitoring in HF. Despite two major meta-analyses with favourable results, two recent, large, multicentre, randomized controlled trials, one with a sophisticated technical remote telemonitoring approach (TIM-HF) in stable chronic HF and the other with a comprehensive telephone-based interactive voice-response monitoring (Tele-HF) in patients recently hospitalized for heart failure, have been performed and both failed to demonstrate a clinical benefit for telemonitoring. Newer technologies or other modalities, such as collaboration between a general practitioner and a heart failure clinic facilitated by telemonitoring should be further evaluated. Dedicated telemonitoring for heart failure may be a practical adjunct in selective centres and patients, on top of usual care, including education and a multidisciplinary approach. However, prior to being accepted as a standard of care, more evidence from large, randomized clinical trials is required.

Background: The large randomized controlled multicentre clinical trial, HF-ACTION, recently demonstrated that a programme of recommendation of regular exercise training at moderate intensity is safe, improves quality of life, and reduces the combined endpoint of all-cause death and hospitalization in patients with chronic heart failure. However, the size of beneficial effects was modest compared to results published in smaller single studies and meta-analyses., Objective: Based on results of a pilot study, the objective of the present investigation is to test the hypothesis that a programme comprising interval training at high relative intensity would yield significantly larger effects in terms of left ventricular remodelling compared to moderate continuous exercise training., Study Design: In a three-armed randomized multicentre study of stable heart failure patients with left ventricular ejection fraction ≤35%, the effects of a 12-week programme of high-intensity interval training (HIT; 85-90% of peak oxygen uptake, VO(2peak)) will be compared to actual practice in Europe, represented by either an isocaloric programme of moderate continuous training (MCT; 50-60% of VO(2peak)) and a recommendation of regular exercise (RE) of the individual patients' own preference based on clinical practice at the local centre. The primary endpoint is reverse remodelling, defined as change in left ventricular end-diastolic diameter assessed by echocardiography. Secondary endpoints include peak oxygen uptake (VO(2peak)), biomarkers, quality of life, and level of physical activity assessed by questionnaires. In addition, long-term maintenance of effects after the supervised training period will be determined. Assessments will be made at baseline, after the 12-week intervention programme, and at 1-year follow up. A total number of 200 patients on treatment per protocol, randomized to the three groups in a 1 : 1 : 1 manner, is estimated to detect clinically relevant differences in effect with HIT vs. MCT and RE (p < 0.05; statistical power 0.90) for the primary endpoint. Inclusion of patients started May 2009 and will run until total number has been reached.

Background: Heart failure is associated with frequent hospitalizations, often resulting from volume overload. Measurement of intrathoracic impedance with an implanted device with an audible patient alert may detect increases in pulmonary fluid retention early. We hypothesized that early intervention could prevent hospitalizations and affect outcome., Methods and Results: We studied 335 patients with chronic heart failure who had undergone implantation of an implantable cardioverter-defibrillator alone (18%) or with cardiac resynchronization therapy (82%). All devices featured a monitoring tool to track changes in intrathoracic impedance (OptiVol) and other diagnostic parameters. Patients were randomized to have information available to physicians and patients as an audible alert in case of preset threshold crossings (access arm) or not (control arm). The primary end point was a composite of all-cause mortality and heart failure hospitalizations. During 14.9±5.4 months, this occurred in 48 patients (29%) in the access arm and in 33 patients (20%) in the control arm (P=0.063; hazard ratio, 1.52; 95% confidence interval, 0.97-2.37). This was due mainly to more heart failure hospitalizations (hazard ratio, 1.79; 95% confidence interval, 1.08-2.95; P=0.022), whereas the number of deaths was comparable (19 versus 15; P=0.54). The number of outpatient visits was higher in the access arm (250 versus 84; P<0.0001), with relatively more signs of heart failure among control patients during outpatient visits. Although the trial was terminated as a result of slow enrollment, a post hoc futility analysis indicated that a positive result would have been unlikely., Conclusion: Use of an implantable diagnostic tool to measure intrathoracic impedance with an audible patient alert did not improve outcome and increased heart failure hospitalizations and outpatient visits in heart failure patients. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT 00480077.

Whereas effective strategies are available to treat acute cellular cardiac rejection, humoral rejection, also called vascular or antibody-mediated rejection, is more difficult to manage. Antibody-mediated (non-cellular) rejections (AMR) are rare and few successfully treated cases have been described in the literature. We report on a female patient, diagnosed with humoral rejection, leading to severe ventricular dysfunction and haemodynamic compromise, two months after transplantation. The patient received a combination therapy, consisting of plasmapheresis and immunoglobulins, which resulted in complete resolution of immunohistochemical signs of AMR. In this report, we will overview AMR and discuss several treatment modalities.

The European Society of Cardiology heart failure guidelines firmly recommend regular physical activity and structured exercise training (ET), but this recommendation is still poorly implemented in daily clinical practice outside specialized centres and in the real world of heart failure clinics. In reality, exercise intolerance can be successfully tackled by applying ET. We need to encourage the mindset that breathlessness may be evidence of signalling between the periphery and central haemodynamic performance and regular physical activity may ultimately bring about favourable changes in myocardial function, symptoms, functional capacity, and increased hospitalization-free life span and probably survival. In this position paper, we provide practical advice for the application of exercise in heart failure and how to overcome traditional barriers, based on the current scientific and clinical knowledge supporting the beneficial effect of this intervention.

Everolimus is a recently developed immunosuppressive drug for patients following solid organ transplantation. Its mechanism of action, independent of calcineurin, is different from that of ciclosporin and tacrolimus and because of its lack of nephrotoxicity, it is a good alternative for calcineurin inhibitors in patients with renal dysfunction. In this paper we describe the case report of a 66-year-old caucasian female who underwent heart transplantation in December 2006. After induction with rabbit anti-thymocytic globulin, her immunosuppressive therapy comprised the combination of tacrolimus, mycophenolate mofetil (MMF) and steroids. Because of renal dysfunction, tacrolimus was changed for everolimus after 6 months. Unfortunately our patient developed severe stomatitis with aphthous ulcerations, shortly after the switch. Despite oral therapy (local anaesthetics), severe pain and malnourishment prompted interruption of everolimus and MMF and therapy was changed to ciclosporin and azathioprine. In addition, thalidomide was added. During the following weeks, there was progressive healing of the ulcerations. MMF was re-introduced and thalidomide was stopped after 6 weeks, without recurrent lesions after 4 months of follow-up.

Background: The SENIORS trial demonstrated that nebivolol has beneficial effects in patients with heart failure. However, the role of beta-blocker therapy in patients with heart failure and preserved left ventricular ejection fraction (HFPEF) is still unsettled., Objective: To assess the long-term effects of administration of nebivolol, compared to placebo, on the clinical symptoms, exercise capacity and parameters of left ventricular (LV) function in patients with HFPEF., Methods: The Effect of Long-term Administration of Nebivolol on clinical symptoms, exercise capacity and left ventricular function in patients with Diastolic Dysfunction (ELANDD) study is a prospective multicenter European trial in 120 patients with HFPEF randomised to nebivolol or placebo. HFPEF is defined as symptoms or signs of heart failure, a LV ejection fraction >45% and evidence of diastolic LV dysfunction by Doppler echocardiography. Procedures include a baseline clinical examination, 6-min walk test (6MWT), electrocardiography, Doppler echocardiography and Minnesota QoL questionnaire. Nebivolol or placebo is started at 2.5 mg/day and gradually uptitrated to 10 mg/day. After initiation of the study, patients are assessed at 1, 2, 5 and 6 weeks (titration phase) and at weeks 12 and 26. The primary endpoint is the change from baseline in the 6MWT distance with nebivolol versus placebo. Sample size calculations are based on an anticipated 15% difference (70 m) in the 6MWT distance between nebivolol and placebo-treated patients. This study will allow the collection of data regarding the possible clinical benefits and the effects on LV function of nebivolol administration in patients with HFPEF.

We present two case reports of young women with Takayasu arteritis and cardiovascular complications. The first case is a female patient suffering from significant aortic valve regurgitation, the second case is a woman who presents with amaurosis fugax and develops acute chest pain with heart failure. In this report we review cardiac involvement in Takayasu arteritis.

Background: Intrathoracic impedance monitoring is a new diagnostic tool for patients with heart failure that may aid early identification of decompensation and pulmonary congestion., Methods and Results: The Sensitivity of the InSync Sentry feature for the Prediction of Heart Failure (ie, SENSE-HF) trial is a prospective multicenter international study designed to evaluate the sensitivity and positive predictive value (PPV) of the intrathoracic impedance diagnostic tool, OptiVol, present in Medtronic implantable devices. A total of 500 patients will be enrolled in the trial, with follow-up for up to 24 months. The study has 3 phases. Phase I is double-blind, and evaluates retrospectively the sensitivity and PPV of the intrathoracic impedance data for the prediction of hospitalization with the signs and/or symptoms of pulmonary congestion. At 6 months, the patient enters Phase II, which evaluates the clinical utility of the nominal "alarm" threshold value for identification of episodes of decompensation. The patient enters the final phase (Phase III) after an episode of decompensation correctly identified by the Fluid Trend data ("true" positive alarm), with data collection on how physicians use the Fluid Trend data to influence management. An end point committee adjudicates health care utilizations events (hospitalizations and doctor visits) for their association with signs and/or symptoms of pulmonary congestion., Conclusions: The study completed recruitment during 2008.

Cogan's syndrome is a rare idiopathic chronic inflammatory disease of the eye and the inner ear in young adults. Cogan's syndrome can be associated with large vessel vasculitis. We report a young female, with a history of interstitial keratitis and audiovestibular disease, who presents with large vessel vasculitis with left main coronary artery occlusion and develops heart failure. Cogan's syndrome was diagnosed on the basis of the presence of large vessel vasculitis with the typical inner ear and ocular involvement.

Background: Chronic heart failure is associated with frequent hospitalisations which are often due to volume-overload decompensation. Monitoring of intrathoracic impedance, measured from an implanted device, can detect increases in pulmonary fluid retention early and facilitate timely treatment interventions., Objective: The DOT-HF trial is designed to investigate if ambulatory monitoring of intrathoracic impedance together with other device-based diagnostic information can reduce morbidity and mortality in patients with chronic heart failure who are treated with cardiac resynchronization therapy (CRT) and/or an implantable defibrillator (ICD)., Methods: Approximately 2400 patients will be randomised in a 1:1 fashion to a management strategy with access to the diagnostic information from the implantable device ("access arm"), or a "control arm", where this information is not made available. Study subjects fulfil standard indications for CRT and/or ICD as outlined in current guidelines. In the access arm, a fluid alert algorithm is used to give early warning of decreasing intrathoracic impedance indicating a high risk of an impending volume-overload decompensation. The primary endpoint of DOT-HF is the composite of all-cause mortality or heart failure hospitalisation. Secondary and exploratory endpoints include all-cause mortality, the impact on total health care utilization, quality of life and cost effectiveness. The study is expected to close recruitment during 2010 and to report in 2012.

Study Design and Setting: Two case reports, University Hospital of Antwerp, tertiary referral hospital of the University of Antwerp, Edegem, Belgium., Methods and Results: Two women were transferred to our hospital because of acute cardiorespiratory failure due to amniotic fluid embolism during the peripartal period. Both required intensive supportive treatment and invasive monitoring. Haemodynamic data revealed primary left ventricular failure confirming the clinical picture of cardiogenic pulmonary oedema. Review of the literature provides data that do not support obstruction of the pulmonary vasculature by amniotic fluid as the only primary pathophysiological event. However, despite several case reports stressing left ventricular failure as the dominant clinical event, pathophysiological mechanisms are merely speculative., Conclusions: The diagnosis of amniotic fluid embolism remains a clinical challenge, but can be supported by the presence of amniotic cells in the pulmonary artery, aspirated through a pulmonary artery catheter. The treatment is still not causative but supportive. An overview of cases in the literature with predominant left heart failure during amniotic fluid embolism is given.

The pathophysiological insights into the chronic heart failure (CHF) syndrome and, consequently, the management of patients with CHF have dramatically changed over the past few decades. Antagonists of the activated neurohormonal pathways are now a mainstay in the therapeutic arsenal. It seems, however, that a neurohormonal ceiling might have been reached. Other humoral mal-adaptations have recently gained importance. One of them is the presence of a low-grade inflammatory status characterising patients with moderate to severe CHF. The presence, both at tissue level and in the circulation, of increased levels of pro-inflammatory cytokines suggests that immune activation might be a relevant mechanism contributing to cardiac as well as peripheral manifestations of the disease. Whereas targeted anti-cytokine treatment has proven unsuccessful in the CHF population, the concept of immune modulation is still intensively studied.

Liberalization of stringent guidelines regarding donor selection is acceptable in the case of critical recipient condition. Few cardiac allografts with preexisting accessory atrioventricular pathways have been implanted. We describe the successful radiofrequency modification of the atrioventricular node and ablation of an accessory pathway after cardiac transplantation. Although the previously healthy donor had no history of arrhythmia, the recipient's postoperative course was characterized by multiple bouts of reentry tachycardia. The highly successful catheter-based ablation techniques available to cure this condition favor the use of donor hearts with a preexisting accessory pathway.

Aims: Familial dilated cardiomyopathy (FDCM) is associated with mutations in more than 10 genes, but genes mutation frequencies and associated clinical features remain largely unknown. Here, we performed a mutation analysis of four genes involved in FDCM in a population of idiopathic DCM., Methods and Results: A SSCP and sequencing mutation screening of all the exons coding for beta myosin heavy chain (MYH7 gene), cardiac T troponin (TNNT2 gene), phospholamban (PLN gene), and the cardio-specific exon of metavinculin (VCL gene) were performed in 96 independent patients (54 familial and 42 sporadic). It led to the identification of eight heterozygous mutations, seven new ones in MYH7, and the already described R141W mutation in TNNT2. MYH7 mutations (in five familial and two sporadic cases) substitute residues located either in the head (I201T, T412N, A550V) or tail domains (T1019N, R1193S, E1426K, R1634S) of the protein. DCM was not associated with skeletal myopathy or conduction defects in any patients. Contrasting clinical features were observed between MYH7 and TNNT2 mutations carriers. In MYH7 vs. TNNT2, mean age at diagnosis was late (P<0.03), penetrance was incomplete in adults (56 vs. 100%), and mean age at major cardiac event was higher (P<0.04)., Conclusion: We have identified seven mutations in MYH7, one in TNNT2, and none in PLN or in the VCL cardio-specific exon. MYH7 appears as the most frequently mutated gene in our FDCM population (approximately 10%), and mutation carriers present with delayed onset, in contrast to TNNT2.

The gap between the number of potential recipients of a cardiac graft and the availability of donor hearts is still growing. A proper selection of heart transplant candidates is mandatory to ensure that patients in critical need, who are likely to benefit from this procedure, are identified. The work-up of a patient with terminal chronic heart failure includes a comprehensive cardiac and systemic evaluation. Critical in the decision is the exclusion of irreversible pulmonary hypertension. Furthermore, underlying diseases that could compromise short- and long-term prognosis after transplantation should be carefully assessed. The mortality on the waiting list and the growing pool of patients with chronic heart failure that is excluded from transplantation has stimulated the search for alternative treatment modalities. Besides a pharmacologic approach, the last few years have witnessed a tremendous evolution in so-called mechanical devices, designed to improve both morbidity and mortality of these patients. Although several of these devices have only just entered the clinical phase, internal cardioverter defibrillators, left ventricular assist devices and biventricular pacemakers can no longer be viewed as experimental tools.

Gout is a common co-morbidity in patients with chronic heart failure and its treatment is complex. We report the case of a 58-year-old man with chronic severe heart failure who developed rhabdomyolisis after short-term intake of colchicine. Although colchicine is a highly effective therapy for acute gouty arthritis, the dosage should be carefully titrated in patients with chronic heart failure, especially if renal or liver disease are also present.

Aims: Physical reconditioning of patients with chronic heart failure (CHF) improves exercise capacity and restores endothelial function and skeletal muscle changes. The effects of 4 months combined endurance/resistance exercise training on cytokines and cytokine receptors in patients with CHF were studied. In addition, changes in submaximal and maximal exercise performance were addressed., Methods and Results: Twenty-three patients with stable CHF due to coronary artery disease (CAD, n=12) or idiopathic dilated cardiomyopathy (IDCM, n=11) were trained for 4 months. Blood sampling for measurement of plasma concentrations (ELISA) of interleukin (IL)-6, tumour necrosis factor (TNF)-alpha, soluble TNF receptor 1 (sTNFR1) and 2 (sTNFR2), as well as cardiopulmonary exercise testing were performed at baseline and after 4 months. Training induced a significant decrease in sTNFR1 (P=0.02) for the total population, and in both sTNFR1 (P=0.01) and sTNFR2 (P=0.02) concentrations for the CAD group only. IL-6 and TNF-alpha levels were not altered. Cytokine concentrations remained unchanged in an untrained age- and sex-matched control group. NYHA functional class, submaximal and maximal workrate were significantly improved in both patient groups. Oxygen uptake at the anaerobic threshold (P=0.002) and at peak exercise increased in the CAD patients only (P=0.008)., Conclusion: Besides an overall beneficial effect on exercise capacity, combined endurance/resistance exercise training has an anti-inflammatory effect in patients with CHD and CAD., (Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd.)

Because of the current donor shortage, organ selection criteria are being progressively liberalized. We present a case of carbon monoxide poisoning in a multiorgan donor that led to primary cardiac allograft failure. A biventricular assist device was used as a bridge to recovery.

Objective: The Abiomed BVS 5000 ventricular assist device (VAD) has been approved in Belgium for emergency cardiac support in patients with postcardiotomy failure with the aim of native heart function recovery. Other indications have emerged from world wide experience, but the indication and usefulness of emergency implantation of assist devices is often debated., Methods: To decide which patients benefit most from emergency ventricular assist device implantation, we retrospectively reviewed our results of mechanical circulatory support with Abiomed in 20 patients over a 4-year period. Fifteen patients with mean age 58 +/- 6 years experienced postcardiotomy failure and underwent biventricular assist device (BVAD) implantation (group A), after elective (n = 9) or after emergency coronary artery bypass grafting (CABG) (n = 6). Five patients (group B), with mean age 35 +/- 19 years, had an implantation for other underlying conditions: hypertrophic cardiomyopathy (n = 3), myocarditis (n = 1) and primary cardiac allograft failure (n = 1)., Results: Of these two groups, eight and two patients respectively needed cardiopulmonary resuscitation before VAD implantation. The mean duration of support in both groups was 5.8 (range 12 h-13 days) and 4.4 days (range 2 h-9 days) respectively. Six and two patients could be weaned from the device and nine and one patients respectively, died on the device. Two patients in group B underwent successful heart transplantation and four patients in group A died after weaning. Two patients in the postcardiotomy group and four patients in group B survived (13% and 80%) with an overall survival and discharge rate of 30%., Conclusion: Although sample sizes are small, better survival rates with emergency Abiomed BVS 5000 implantation were obtained in the non postcardiotomy group (group B). For patients in the postcardiotomy group, outcome was negatively influenced by cardiac arrest and resuscitation before urgent CABG. Since death is the only alternative for these patients in cardiogenic shock and organ recovery cannot be predicted, we continue to consider emergency VAD implantation in this patient population.

Background: Intravenous administration of cyclosporine, which contains Cremophor EL (a polyethoxylated castor oil; BASF, Berlin, Germany), has occasionally resulted in an anaphylactic reaction. An apparent hypersensitivity reaction (bronchospasm and decrease in blood pressure) had occurred during heart transplantation in a 59-year-old woman after intravenous infusion of cyclosporine. Subsequent oral administration of cyclosporine precipitated no reaction., Objective: The purpose of this study was to attempt to ascertain the mechanism responsible for the anaphylactic reaction., Methods: Hypersensitivity investigations, including total serum IgE and allergen-specific IgE quantifications, skin testing, and basophil activation tests by flow cytometric determination of CD63 upregulation were undertaken in the study patient and in two healthy control subjects who were free of medication., Results: The results of intradermal testing with Cremophor EL were positive after 15 minutes in the study patient only. Both cyclosporine and Cremophor EL induced considerable activation of the basophils from our study patient, with an upregulation of CD63 expression from 1% to 39% and 55%, respectively. In contrast, the expression of CD63 on basophils from the two control subjects remained essentially unchanged., Conclusions: The negative investigative findings in the control subjects, the patient's clinical manifestations in temporal relationship to the infusion, her positive results on intradermal testing with Cremophor, the basophil activation test results, and her uneventful course after oral administration of cyclosporine strongly support the presence of IgE antibodies to Cremophor EL in our patient.

This report describes the diagnostic difficulty encountered in a young female patient presenting with neurologic symptoms, atrial fibrillation and severe left ventricular systolic dysfunction, eventually leading to cardiac transplantation. The scrutiny used in the evaluation of the particular aspect of the left ventricle, and the integration of the information obtained from echocardiography, angiography and magnetic resonance imaging, led to the diagnosis of a rare and mostly unknown cause of cardiac failure. The correct identification of this entity is mandatory because enhanced risk of thromboembolism and malignant arrhythmia should be anticipated. A review of the literature revealed only 6 patients in whom isolated non-compaction of the left ventricle was treated by heart transplantation.

Background: Prognosis of solid organ cancer in immunosuppressed hosts is generally dismal. Therefore, every effort to identify patients with asymptomatic carcinomas before transplantation should be encouraged., Methods: Sixty-seven patients referred for heart transplantation were examined adhering to the scheme proposed at the 24th Bethesda Conference. To increase the sensitivity of this work-up, the following items were added: tumor marker assays (prostate-specific antigen in males, carcino embryogenic antigen), abdominal ultrasound, CT scan of the abdomen and the thorax, mammography/echography of the breasts, PAP smear, colonoscopy if carcino embryogenic antigen abnormal or occult blood in stool, prostate echography if prostate-specific antigen abnormal or prostate hypertrophy., Results: Carcinoma was detected in 10 of the 67 patients; for 8 patients of this cancer group, transplantation was denied. Importantly, 9 of the 10 malignancies were detected by means of the diagnostic items that were added to the standard screening protocol. There were no significant differences between the cancer and the non-cancer group regarding mean age, sex, etiology of heart failure, and smoking history. Stratifying patients in younger (i.e., < or =54 years) and older (i.e., > or =55 years) age groups showed a significantly greater proportion of older patients in the cancer group (8/10=80%) compared to the non-cancer group (25/57=44%), P=0.04. After a mean follow-up of 34 months, 5 of the 36 transplanted patients developed a malignancy (4 skin carcinomas, 1 non-Hodgkin lymphoma). There have been no malignancy-related deaths until now., Conclusion: The importance of a thorough screening program in the triage of candidates with preexisting malignancies, especially in an older patient population, is illustrated in this report.

We cared for a patient with progressive renal impairment who presented with blurred vision, QRS broadening and cardiac failure due to chronic cibenzoline intoxication. Treatment consisted of catecholamines and repetitive infusions of Ringer lactate. Cardiac function and symptoms recovered completely.

This case report describes the devastating consequences of spontaneous coronary dissection in a 36-year-old female patient. Surgical revascularization was attempted, but diffuse myocardial infarction developed. The patient was bridged to heart transplantation but died secondary to multiple organ failure. To our knowledge, this is the only reported case of spontaneous dissection of the three main coronary arteries due to severe cystic medial necrosis.

Objective: To determine whether coil stents are as effective as tubular stents in improving coronary flow velocity reserve (CFVR) after stent deployment., Methods: Distal CFVR was measured with a 0. 014 inch Doppler guide wire before and after stenting in 33 patients. A coil stent was implanted in 16 patients and a tubular stent was used in 17 patients. Coronary flow velocity within the stent was also recorded during a slow pullback., Results: Following placement of the stents, the percentage diameter stenosis was similar for both the tubular and coil stents (mean (SE) 11 (2)% v 13 (2)%, NS). However, distal CFVR was higher after stenting with a tubular stent compared with a coil stent (2.46 (0.13) v 1.96 (0.14), p < 0.05). Furthermore, pullback through the stent detected a major flow velocity increase within coil stents but not in tubular stents (83 (24)% v 5 (5)%, p < 0.05)., Conclusions: In spite of similar angiographic improvement, placement of coil stents was associated with inferior functional results compared with tubular stents. The flow velocity acceleration within the coil stents suggests the presence of a residual narrowing within the stent, which is not appreciated on angiography.

We report a patient in whom presumed vasospasm of an angiographically normal coronary artery led to severe transmural myocardial ischemia. To our knowledge, this is the first case in which an allergic reaction to locally applied chlorhexidine caused such a severe reaction.

Heart transplantation has become an accepted and successful treatment for end-stage heart disease with survival rates of 80-90% after one year and 70% after 5 years. During the early posttransplant period (6-12 months), patients are subject to two major complications: rejection and infection. Fortunately, a certain degree of graft tolerance develops, allowing the immunosuppressive therapy to be progressively tapered off with a concomitant decrease in infectious problems. Long-term survival, however, is largely dependent on the development of an accelerated atherosclerosis in the graft, which is believed to represent some kind of chronic rejection. This transplant vasculopathy is documented by means of coronary angiography with an incidence of approximately 5 to 10% per year. It is not surprising therefore that major interest has risen concerning risk factors promoting this pathology.