Predictive models of syncope causes in an outpatient clinic.

UNLABELLED: The investigation of unexplained syncope remains a challenging clinical problem. In the present study we sought to evaluate the diagnostic value of a standardized work-up focusing on non invasive tests in patients with unexplained syncope referred to a syncope clinic, and whether certain combinations of clinical parameters are characteristic of rhythmic and reflex causes of syncope. METHODS AND RESULTS: 317 consecutive patients underwent a standardized work-up including a 12-lead ECG, physical examination, detailed history with screening for syncope-related symptoms using a structured questionnaire followed by carotid sinus massage (CSM), and head-up tilt test. Invasive testings including an electrophysiological study and implantation of a loop recorder were only performed in those with structural heart disease or traumatic syncope. Our work-up identified an etiology in 81% of the patients. Importantly, three quarters of the causes were established non invasively combining head-up tilt test, CSM and hyperventilation testing. Invasive tests yielded an additional 7% of diagnoses. Logistic analysis identified age and number of significant prodromes as the only predictive factors of rhythmic syncope. The same two factors, in addition to the duration of the ECG P-wave, were also predictive of vasovagal and psychogenic syncope. These factors, optimally combined in predictive models, showed a high negative and a modest positive predictive value. CONCLUSION: A standardized work-up focusing on non invasive tests allows to establish more than three quarters of syncope causes. Predictive models based on simple clinical parameters may help to distinguish between rhythmic and other causes of syncope.

Implantation of cardiac resynchronization therapy systems in the CARE-HF trial: procedural success rate and safety.

AIMS: To assess procedural characteristics and adjudicated procedure-related (300 cm(3); and, influence of the participating study-centres. Implantation was attempted in 404/409 patients assigned to CRT, and in 65/404 patients assigned to medical therapy. Among these 469 patients, 450 (95.9%) received a successfully implanted and activated device. Complications occurred within 24 h in 47 patients (10.0%), mainly lead dislodgments (n = 10, 2.1%) and coronary sinus dissection/perforation (n = 10, 2.1%), and between 24 h and 30 days in 26 patients (5.5%), mainly lead dislodgment (n = 13, 2.8%). Mean LV lead stimulation threshold was significantly higher than at the right atrium or right ventricle, though remained stable, delivering effective, and reliable CRT. Implanting experience was the only predictor of procedural outcome. CONCLUSION: Transvenous CRT system implantation, using a CS lead designed for long-term LV pacing, was safe and reliable. As implanting centres become more experienced, this success rate is expected to increase further.

Gene transfer of RANTES and MCP-1 chemokine antagonists prolongs cardiac allograft survival.

Vascularized organ allografts are rapidly destroyed by host immune cells that are recruited along chemokine gradients. Among chemokines, Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) CC chemokine ligand (CCL5) and monocyte chemoattractant protein (MCP)-1 (CCL2) are upregulated in rejecting cardiac allografts. To antagonize these chemokines, we constructed adenoviral vectors expressing NH(2)-terminal deletion (8ND) mutants of the respective genes. Using the F344-to-LEW rat model, intragraft gene transfer of chemokine analogs prolonged cardiac allograft survival from 10.1+/-0.7 and 10.4+/-0.7 days using non-coding adenovirus and vehicle alone, respectively, to 17.0+/-0.7 days for 8ND-RANTES (P<0.001) and 14.2+/-0.8 days for 8ND-MCP-1 (P<0.01). 8ND-RANTES reduced graft infiltration by monocytes/macrophages, cluster of differentiation (CD) 8alpha(+) and T-cell receptor alphabeta(+) cells, while 8ND-MCP-1 reduced monocytes/macrophages. In mixed leukocyte reactions in vitro, proliferation of host lymphocytes from regional lymph nodes in response to donor splenocytes was unaffected by 8ND-RANTES gene transfer. Using a two-gene approach, the contribution of 8ND-MCP-1 was negligible, consistent with available evidence that 8ND-RANTES inhibits both RANTES and MCP-1 activities. 8ND-RANTES gene transfer and a short course of low-dose cyclosporine A synergistically prolonged graft survival to 37.8+/-5.5 vs 15.4+/-0.5 days with cyclosporine alone (P<0.001). These results suggest a role for anti-chemokine gene therapy as an adjuvant therapy in heart transplantation.

[Surgical options for terminal heart failure]. / Options chirurgicates pour l'insuffisance cardiaque terminale.

Terminal heart failure can be the cause or the result of major dysfunctions of the organisms. Although, the outcome of the natural history is the same in both situations, it is of prime importance to differentiate the two, as only heart failure as the primary cause allows for successful mechanical circulatory support as bridge to transplantation or towards recovery. Various objective parameters allow for the establishment of the diagnosis of terminal heart failure despite optimal medical treatment. A cardiac index <2.0 l/min, and a mixed venous oxygen saturation <60%, in combination with progressive renal failure, should trigger a diagnostic work-up in order to identify cardiac defects that can be corrected or to list the patient for transplantation with/without mechanical circulatory support.

Evaluation of ablation patterns using a biophysical model of atrial fibrillation.

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. Surgical/Radiofrequency (RF) ablation is a therapeutic procedure that consists of creating lines of conduction block to interrupt AF. The present study evaluated 13 different ablation patterns by means of a biophysical model of the human atria. In this model, ablation lines were abruptly applied transmurally during simulated sustained AF, and success rate, time to AF termination and average beat-to-beat interval were documented. The gold standard Cox's Maze III procedure was taken as reference. The effectiveness of twelve less invasive patterns was compared to it. In some of these incomplete lines (entailing a gap) were simulated. Finally, the computer simulations were compared to clinical data. The results show that the model reproduces observations made in vivo: (1) the Maze III is the most efficient ablation procedure; (2) less invasive patterns should include lines in both right and left atrium; (3) incomplete ablation lines between the pulmonary veins and the mitral valve annulus lead to uncommon flutter; (4) computer simulations of incomplete lines are consistent with clinical results of non-transumural RF ablation. Biophysical modeling may therefore be considered as a useful tool for understanding the mechanisms underlying AF therapies.

[What do we actually know about out-of-hospital cardiac arrest?]. / Arrêt cardiaque extrahospitalier: la situation actuelle.

Each year at least 300,000 people in the United States and 8000 to 10,000 people in Switzerland suffer from out-of-hospital cardiac arrest, mostly due to ventricular fibrillation. Early defibrillation provides definitive treatment for most of cardiac arrest victims. Semi-automatic external defibrillators are easy to handle devices allowing to deliver an early electric shock and can be successfully used by lay people following minimal training. Newer strategies of defibrillation designed to respond faster to out-of-hospital cardiac arrest, including public access defibrillation, as well as improvement of each link of the chain of survival appears as the best strategy for the management of out-of-hospital cardiac arrest.

[Cardiology]. / Cardiologie.

The therapeutic acquisition to be retained for 2004 are: 1. The elderly patients with heart failure also should receive beta blocker treatment. The correction of anaemia, aggravating factor in heart failure, improves symptoms and survival of the patient. 2. It remains to prove that the treatment of sleep apnea, which seems to be an additional factor for mortality in cardiovascular diseases, is able to reduce the risk. 3. The interventions in the endocanabinoïd system which regulates weight and metabolic processes might be a promising new therapeutic acquisition. 4. Prevention of coronary disease with lipid lowering drugs is still a major topic, and the trend goes the lower the better. The problems observed with Rofecoxybe and other drug interactions reminds us to be conscious when prescribing multiple drugs. 5. The implantable defibrillator seems to be a life insurance in the event of ventricular fibrillation. However, it is not so easy to identify the patient who might really benefit.

Baseline characteristics of patients recruited into the CARE-HF study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a promising new treatment for patients with heart failure and cardiac dyssynchrony. The CARE-HF study is a morbidity/mortality trial designed to provide conclusive evidence of the effects of CRT in patients with moderate to severe heart failure. METHODS: A description of the baseline characteristics of patients randomised in the CARE-HF trial. RESULTS: 813 Patients with predominantly NYHA class III (94%) heart failure were randomised in 82 centres. Their mean age was 65 (interquartile range [IQR] 59 to 72) years, 34% were aged >70 years and 27% were women. Thirty-eight percent of the patients had ischaemic heart disease. Mean heart rate was adequately controlled at 70 (IQR 60 to 78) bpm consistent with the use of beta-blockers. Supine systolic blood pressure was low at 117 (IQR 105 to 130) mm Hg. Eighty-eight percent of patients had a QRS > or =150 ms. Mean LV ejection fraction was 26% (IQR 22 to 29) and end-diastolic dimension was 7.2 (IQR 6.4 to 7.8) cm. Ninety-four percent of patients were receiving loop diuretics, 95% an ACE inhibitor or angiotensin receptor blocker (ARB), 72% a beta-blocker and 56% were taking spironolactone. CONCLUSIONS: The patients enrolled in CARE-HF had moderately severe heart failure and cardiac dysfunction with evidence of cardiac dyssynchrony. The population appears at high risk of events despite pharmacological therapy and therefore appropriate for a trial of CRT.

Localization and quantification of mitral valve prolapse using three-dimensional echocardiography.

AIMS: Mitral valve prolapse is a common source of severe mitral regurgitation in Western countries. Three-dimensional echocardiography can provide views of the entire valve, allowing a complete assessment of the valve leaflets and commissures. It has the potential to precisely locate and quantify mitral valve prolapse. METHODS AND RESULTS: Between January 1997 and December 2000, 91 patients with severe mitral regurgitation due to mitral valve prolapse underwent a transesophageal echocardiography with three-dimensional reconstruction of the mitral valve as part of their pre-operative work-up. The location and extent of the prolapse by echo was compared to the surgical status. The volume of prolapsing leaflet was calculated and compared to the volume of resected tissue whenever a repair was attempted. There was an excellent correspondence between the echographic localization of the prolapse and surgical inspection, and between the volume of prolapsing and surgically resected tissue (r=0.94, p<0.0001). CONCLUSIONS: In patients with severe mitral regurgitation due to mitral valve prolapse, 3D echo allowed a precise localization and an accurate quantification of the prolapsing portion of the leaflets. This technique can provide refinements in the surgical planning of mitral valve repair and in the selection of candidates for this intervention.

[Left ventricular hypertrophy: a marker for patients at risk of arterial hypotension during stress echocardiography with dobutamine?]. / Hypertrophie ventriculaire gauche: un marqueur des patients à risque d'hypotension artérielle durant l'échocardiographie de stress sous dobutamine?

OVERVIEW: Arterial hypotension during stress echocardiography with Dobutamine (ESD) is an occasional complication with no prognostic value, but it sometimes necessitates termination of the investigation. The present study had the aim of elucidating the mechanism responsible for hypotension during ESD and proposing one or several markers for patients at risk for this complication. METHOD: One hundred and twenty consecutive patients referred for stress echocardiography (Dobutamine or cycloergometrine) were analysed. Arterial hypotension induced by Dobutamine was defined as a fall of more than 30 mmHg compared to the arterial pressure before the test or following the preceding level of Dobutamine. Concentric left ventricular hypertrophy (LVH) was defined as a left ventricular mass > 125 g/m2. RESULTS: Among the 89 patients undergoing ESD, 32 (35%) had LVH, 9 of whom (28%) had arterial hypotension, prompting termination of the examination in 4 patients. Among the 57 patients (65%) without LVH, only 2 (3%) had hypotension. All patients with LVH had normal left ventricular function at rest and excellent contractility under stress, with no sign of ischaemia. None of the 31 patients, 5 of whom had LVH, who underwent the test with cycloergometrine had hypotension. CONCLUSION: Hypotension occurring during ESD affects patients more often with LVH (p < 0.001) and excellent systolic function. We postulate that the vigorous contraction of the left ventricle with Dobutamine produces excessive stimulation of the cardiac mechanoreceptors inducing a reflex hypotension. LVH is therefore a marker for patients at risk of hypotension and effort echocardiography is an excellent alternative to this investigation.

Alloimmunity and nonimmunologic risk factors in cardiac allograft vasculopathy.

Graft vasculopathy is an accelerated form of coronary artery disease that occurs in transplanted hearts. Despite major advances in immunosuppression, the prevalence of the disease has remained substantially unchanged during the last two decades. According to the 'response to injury' paradigm, graft vasculopathy is the result of a continuous inflammatory response to tissue injury initiated by both alloantigen-dependent and independent stress responses. Experimental evidence suggests that these responses may become self-sustaining, as allograft re-transplantation into the donor strain at a later stage fails to prevent disease progression. Histological evidence of endothelitis and arteritis, in association with intima fibrosis and atherosclerosis, reflects the central role of alloimmunity and inflammation in the development of arterial lesions. Experimental results in gene-targeted mouse models indicate that cellular and humoral immune responses are both involved in the pathogenesis of graft vasculopathy. Circulating antibodies against donor endothelium are found in a significant number of patients, but their pathogenic role is still controversial. Alloantigen-independent factors include donor-transmitted coronary artery disease, surgical trauma, ischaemia-reperfusion injury, viral infections, hyperlipidaemia, hypertension, and glucose intolerance. Recent therapeutic advances include the use of novel immunosuppressive agents such as sirolimus (rapamycin), HMG-CoA reductase inhibitors, calcium channel blockers, and angiotensin converting enzyme inhibitors. Optimal treatment of cardiovascular risk factors remains of paramount importance.

Ectopic pacing at physiological rate improves postanoxic recovery of the developing heart.

Recently, rapid and transient cardiac pacing was shown to induce preconditioning in animal models. Whether the electrical stimulation per se or the concomitant myocardial ischemia affords such a protection remains unknown. We tested the hypothesis that chronic pacing of a cardiac preparation maintained in a normoxic condition can induce protection. Hearts of 4-day-old chick embryos were electrically paced in ovo over a 12-h period using asynchronous and intermittent ventricular stimulation (5 min on-10 min off) at 110% of the intrinsic rate. Sham (n = 6) and paced hearts (n = 6) were then excised, mounted in vitro, and subjected successively to 30 min of normoxia (20% O(2)), 30 min of anoxia (0% O(2)), and 60 min of reoxygenation (20% O(2)). Electrocardiogram and atrial and ventricular contractions were simultaneously recorded throughout the experiment. Reoxygenation-induced chrono-, dromo-, and inotropic disturbances, incidence of arrhythmias, and changes in electromechanical delay (EMD) in atria and ventricle were systematically investigated in sham and paced hearts. Under normoxia, the isolated heart beat spontaneously and regularly, and all baseline functional parameters were similar in sham and paced groups (means +/- SD): heart rate (190 +/- 36 beats/min), P-R interval (104 +/- 25 ms), mechanical atrioventricular propagation (20 +/- 4 mm/s), ventricular shortening velocity (1.7 +/- 1 mm/s), atrial EMD (17 +/- 4 ms), and ventricular EMD (16 +/- 2 ms). Under anoxia, cardiac function progressively collapsed, and sinoatrial activity finally stopped after approximately 9 min in both groups. During reoxygenation, paced hearts showed 1) a lower incidence of arrhythmias than sham hearts, 2) an increased rate of recovery of ventricular contractility compared with sham hearts, and 3) a faster return of ventricular EMD to basal value than sham hearts. However, recovery of heart rate, atrioventricular conduction, and atrial EMD was not improved by pacing. Activity of all hearts was fully restored at the end of reoxygenation. These findings suggest that chronic electrical stimulation of the ventricle at a near-physiological rate selectively alters some cellular functions within the heart and constitutes a nonischemic means to increase myocardial tolerance to a subsequent hypoxia-reoxygenation.

Incessant atrioventricular dissociation due to far-field QRS oversensing and recurrent mode switch in a dual chamber pacemaker.

We report the case of a repetitive and incessant activation of mode switch in a dual chamber pacemaker because of the inappropriate sensing by the atrial lead of far-fields signals from the ventricular evoked response. The incidence, consequences and prevention of the oversensing of far-field QRS complexes are discussed.

[Out of hours coronary angiography: changing indications]. / Coronarographies en dehors des heures ouvrables: évolution des indications.

The authors have recently demonstrated that 13% of indications for cardiac catheterisation performed "after hours" (week ends, holidays or from 6 pm to 7 am) are Class III of the AHA/ACC recommendations (i.e. indications not based on recognised medical evidence). In order to limit procedures performed for these unrecognised indications, a consensus of experts has defined a number of local recommendations. The aim of this paper was to study the impact of these recommendations on the indications of "out of hours" cardiac catheterisation. Two patient populations were identified and compared with respect to these recommendations. The first group comprised 157 consecutive patients treated between 1993 and 1994 (average age 58 +/- 13 years; 35% females) and the second one of 148 consecutive patients treated from 1998 to 1999 (average age 57 +/- 13 years; 25% females). The local recommendations were respected in 61% of cases and not applied in 39% of cases. This was a satisfactory result in view of the fact that the local recommendations are more restrictive than international guidelines as they cover emergency indications. In the second group of patients, there were no AHA/ACC Class III indications (30% Class I, 6% Class IIa and 3% Class IIb). There was a significant increase in the number of primary angioplasties for acute myocardial infarction (27 vs 2%; p < 0.001) and an expected reduction in salvage angioplasties (17 vs 7%; p < 0.01). There was no significant change in the indications in patients with unstable angina, the European and American guidelines having been published at the end of data collection. Therefore, the introduction of recommendations for out of hours cardiac catheterisation has limited the number performed for unrecognised indications in favour of evidence based procedures.

Silent single coronary artery anomaly depicted by magnetic resonance angiography.

Coronary artery anomalies are rare and usually benign. They are detected by coronary angiograms during invasive catheterization. Single coronary artery anomaly, with the left main artery originating from the proximal right coronary artery, can be responsible for myocardial blood supply insufficiency and causes chest pain or sudden death, especially during physical exercise, as it courses between the aorta and the pulmonary artery. We report a case of a fortuitous diagnosis of single coronary artery anomaly discovered during coronary angiogram and investigated in addition with magnetic resonance angiography. Magnetic resonance imaging can provide a precise description of the coronary artery anomaly and its course between great arteries, allowing accurate surgical planning.

Study of atrial arrhythmias in a computer model based on magnetic resonance images of human atria.

The maintenance of multiple wavelets appears to be a consistent feature of atrial fibrillation (AF). In this paper, we investigate possible mechanisms of initiation and perpetuation of multiple wavelets in a computer model of AF. We developed a simplified model of human atria that uses an ionic-based membrane model and whose geometry is derived from a segmented magnetic resonance imaging data set. The three-dimensional surface has a realistic size and includes obstacles corresponding to the location of major vessels and valves, but it does not take into account anisotropy. The main advantage of this approach is its ability to simulate long duration arrhythmias (up to 40 s). Clinically relevant initiation protocols, such as single-site burst pacing, were used. The dynamics of simulated AF were investigated in models with different action potential durations and restitution properties, controlled by the conductance of the slow inward current in a modified Luo-Rudy model. The simulation studies show that (1) single-site burst pacing protocol can be used to induce wave breaks even in tissue with uniform membrane properties, (2) the restitution-based wave breaks in an atrial model with realistic size and conduction velocities are transient, and (3) a significant reduction in action potential duration (even with apparently flat restitution) increases the duration of AF. (c) 2002 American Institute of Physics.

A computer model of human atria with reasonable computation load and realistic anatomical properties.

Atrial fibrillation is the most frequent arrhythmia, provoking discomfort, heart failure and arterial embolisms. The aim of this work is to develop a simplified anatomical computer model of human atria for the study of atrial arrhythmias and the understanding of electrical propagation mechanisms. With the model we propose, up to 40 s of real-time propagation have been simulated on a single-processor computer. The size and the electrophysiological properties of the simulated atria are within realistic values and information about anatomy has been taken into account in a three-dimensional structure. Besides normal sinus beat, pathological phenomena such as flutter and fibrillation have been induced using a programmed stimulation protocol. One important observation in our model is that atrial arrhythmias are a combination of functional and anatomical reentries and that the geometry plays an important role. This virtual atrium can reproduce electrophysiological observations made in humans but with the advantage of showing in great detail how arrhythmias are initiated and sustained. Such details are difficult or impossible to study in humans. This model will serve us as a tool to evaluate the impact of new therapeutic strategies and to improve them.

The CARE-HF study (CArdiac REsynchronisation in Heart Failure study): rationale, design and end-points.

BACKGROUND: Cardiac resynchronisation is a promising new intervention for patients with heart failure, left ventricular systolic dysfunction and ventricular dyssynchrony. OBJECTIVE: The CARE-HF trial is designed to evaluate the long-term effects of cardiac (atrio-bi-ventricular) resynchronisation on the mortality and morbidity of patients with heart failure due to left ventricular systolic dysfunction already receiving diuretics and optimal medical therapy with ACE inhibitors and beta-blockers (where indicated and tolerated). METHODS AND RESULTS: Approximately 800 patients will be randomised to device therapy or control and followed for a minimum of 18 months. A pragmatic study design has been chosen that does not attempt to conceal allocation from investigators or patients because it is impossible to guarantee maintenance of blinding for the duration of the study. The end-points committee will adjudicate events in a blinded fashion. Since cardiac resynchronisation may alter other aspects of the management of the patient, as would occur in clinical practice, the study should be considered a comparison of strategies rather than simply of a device. The primary end-point is all-cause mortality or unplanned cardiovascular hospitalisation. The study should complete recruitment during 2002 and report in 2004.

[Implantable defibrillator. Update]. / Le défibrillateur implantable. Mise au point.

The implantable cardioverter-defibrillator is a device able to detect and efficiently treat life-threatening ventricular arrhythmias. Its decisive accomplishment in reducing sudden cardiac death and total cardiac mortality, opposed to the insufficient reliability of the traditional therapies explains its present ascendancy. In this review, the working principles and the implant techniques are developed, as well as the complications and the usual problems which could be encountered in implanted patients. Finally, the current indications are discussed in the light of recent clinical trials.