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PubMed2004

Effect of age on atrial contribution to ventricular filling after balloon mitral valvuloplasty in mitral stenosis.

OBJECTIVE: Ventricular filling takes place during the conduit and pump functions of the atrium. While studying whether relief of mitral valve obstruction improves atrial filling, the effect of age on atrial contribution to ventricular filling was studied before and after balloon mitral valvuloplasty (BMV) and on follow-up at 1 year. METHODS: Patients with mitral stenosis (MS) and sinus rhythm (n = 59) were divided into group I (< 18 years, n = 13), group II (< 30 years, n = 29) and group III (> 30 years, n = 17). Two-dimensional mitral valve area (MVA in cm2), transmitral mean gradient (MG in mm Hg), velocity time integral (VTI in cm) of mitral valve flow, VTI contributed by atrial systole (A-VTI), difference between total VTI and A-VTI (E-VTI), percentage contribution of A-VTI to the total VTI (A-%) and difference between A-% before and after BMV (delta-A-%) were noted. Follow-up data was obtained at 1 year. The change in A-% at follow-up (A-%-FU) was calculated as the difference between A-% before BMV and A-% at follow-up. RESULTS: There was a similar increase in MVA with a reduction in MG among the three groups. Among the three groups, total VTI and E-VTI before and after BMV were similar. Before BMV, in all the groups, A-VTI and A-% were similar. After BMV, there was increase in A-VTI and A-% in all the groups with a trend to be more in younger patients. A-VTI was significantly higher in group I only. But E-VTI had decreased significantly in all groups and tended to be less in younger patients. In younger patients, delta-A-% after BMV was significantly higher (13.2 +/- 7.6, 7.9 +/- 5.1 and 6.5 +/- 4.5, respectively, in groups I, II and III; p < 0.01). Correlation coefficient of age against delta-A-% was -0.55 (p < 0.01). Correlation coefficients of delta-A-% against post-BMV-MVA and MG were not good. At follow-up of 11.3+/-1.2 months, changes achieved in total VTI, A-VTI, E-VTI and A-% were maintained. Total VTI, A-VTI, E-VTI and A-% were similar at the time of follow-up on comparing the three groups. But younger patients had significantly higher A-%-FU (12.1 +/- 5.8, 9.4 +/- 4.6 and 7.3 +/- 3.1, respectively, in groups I, II and III; p < 0.01). CONCLUSIONS: Prior to BMV, there is an age related reduction in atrial contribution to ventricular filling that improves with relief of MS. Advancing age reduces the immediate and late recovery of atrial contribution after BMV. This may be due to increasing left atrial fibrosis with age that prevents an improvement in atrial pump function. The differential improvement in atrial function in younger patients warrants earlier intervention in MS to achieve better recovery of atrial function.

Adolescent↗
PubMed2001

Effects of chronic cardiac decentralization on functional properties of canine intracardiac neurons in vitro.

Although intrinsic cardiac neurons display ongoing activity after chronic interruption of extrinsic autonomic inputs to the heart, the effects of decentralization on individual neurons remain unknown. The objective of this study was to determine the effects of chronic (3-4 wk) surgical decentralization on intracellular properties of, and neurotransmission among, neurons contained within the canine intrinsic right atrial ganglionated plexus in vitro. Properties of neurons from decentralized hearts were compared with those of neurons from sham-operated hearts (controls). Two populations of neurons were identified by their firing behavior in response to intracellular current injection. Fifty-nine percent of control neurons and 72% of decentralized neurons were phasic (discharged one action potential on excitation). Forty-one percent of control neurons and 27% of decentralized neurons were accommodating (multiple discharge with decrementing frequency). After chronic decentralization, input resistance of phasic neurons increased, whereas the duration of afterhyperpolarization of accommodating neurons decreased. Postsynaptic responses to interganglionic nerve stimulation were evoked in 89% of control neurons and 83% of decentralized neurons; the majority of these responses involved nicotinic receptors. These results show that, after chronic decentralization, intrinsic cardiac neurons 1) undergo changes in membrane properties that may lead to increased excitability while 2) maintaining synaptic neurotransmission within the intrinsic cardiac ganglionated plexus.

Action Potentials↗
PubMed1991

Mathematical modelling for biomagnetic localization.

Non-invasive biomagnetic measurements are feasible for obtaining functional information concerning the electrical activity of the human heart and brain. These methods have turned out to be promising in localizing various bioelectric sources in the body. For example, in magnetocardiographic studies of localizing arrhythmogenic tissue and both normal and abnormal conduction pathways between the atrial and the ventricles, the best accuracies reported are comparable to the results obtained by the invasive methods. We consider here basic principles of biomagnetic source localization methods, focusing on the magnetocardiographic mapping.

Action Potentials↗
PubMed1993

Generation and propagation of ectopic beats induced by spatially localized Na-K pump inhibition in atrial network models.

A biophysically detailed two-dimensional network model of the cardiac atrium has been implemented on the Thinking Machines massively parallel CM-5 supercomputer. The model is used to study the effects of spatially localized inhibition of the Na-K pump. Na overloading produced by pump inhibition can induce spontaneous, propagating ectopic beats within the network. At a cell-to-cell coupling value yielding a realistic plane wave conduction velocity of 0.6 m s-1, pump inhibition in roughly 1000 cells can induce propagating ectopic beats in a 512 x 512 lattice of cells.

Action Potentials↗
PubMedDate not supplied

The Maze procedure for the treatment of atrial fibrillation: a minimally invasive approach.

OBJECTIVES: The standard Maze procedure has proven to be extremely effective in curing atrial fibrillation in thousands of patients worldwide. Until now it has required a median sternotomy and cardiopulmonary bypass. In order to simplify the standard approach, a minimally invasive technique was developed. We have recently applied this minimally invasive Maze procedure in 72 patients. METHODS: The technique is dependent on the use of cryosurgery and the total number of atriotomies has been decreased from twelve to four. In addition to performing the Maze procedure, 32% of patients have had concomitant surgery via the minimally invasive approach including mitral valve repair/replacement and tricuspid valve repair. RESULTS: Perioperative morbidity is improved following the minimally invasive approach in comparison to the standard approach with the incidence of temporary perioperative arrhythmias being decreased by 50%. The long-term recurrence of atrial fibrillation is 2.4% following the minimally invasive Maze procedure and 2.2% following the standard Maze procedure. The incidence of pacemaker requirements following the standard Maze procedure is 20% but only 6% following the minimally invasive Maze procedure. Both right atrial and left atrial transport function have been documented in 100% of patients following the minimally invasive Maze procedure. CONCLUSIONS: We believe that the minimally invasive Maze procedure is a substantial improvement over the standard approach in terms of patient morbidity while preserving the effectiveness of the Maze procedure in curing atrial fibrillation.

Adult↗
PubMed1981

Endurance training in the rat. II. Performance of isolated and intact heart.

The effects of isotonic physical training and detraining on cardiac function were studied in young and adult male rats trained by graded treadmill running and compared with sedentary controls. Absolute left ventricular mass was not increased, and ventricular compliance was not altered by training. Ventricular function curves that plotted peak systolic pressure, maximum rate of rise of left ventricular pressure, cardiac output, coronary flow, or stroke work as a function of atrial filling height in the isolated perfused heart did not demonstrate a training effect in either age group. The cardiac response to hypoxia was also comparable in the trained and sedentary rats. The base-line heart rate of anesthetized rats, in which in situ cardiac function was studied, was lower in the trained rats (321 +/- 14 vs. 377 +/- 8, P less than 0.005). Resting hemodynamics and left ventricular function curves generated from pressure-flow data during volume infusion did not differentiate between the hearts of trained and sedentary rats. In conclusion, a moderate level of endurance training did not enhance cardiac contractility when this was assessed under nonexercise conditions in both the isolated perfused heart and intact in situ heart preparations.

Animals↗
PubMed1977

Behavior of cardiac receptors with nonmyelinated vagal afferents during spontaneous respiration in cats.

Activity from left atrial and left ventricular receptors with nonmyelinated vagal afferents (mean conduction velocity, 1.2 m/sec) was recorded in 13 closed-chest spontaneously breathing cats anesthetized with alpha-chloralose. The anatomic position of each receptor was determined by probing the opened heart at the conclusion of the experiment. Three of eight left atrial receptors and four of five left ventricular receptors were silent under resting conditions. The mean discharge frequency under resting conditons for the six receptors displaying spontaneous activity was 1.0 +/- 0.15 impulse/sec. Thus cardiac receptors with vagal nonmyelinated afferent have a low resting discharge in spontaneously breathing cats. The frequency and pattern of discharge of atrial but not of ventricular receptors was altered during spontaneous respiration. The atrial receptors discharged with cardiac rhythmicity during end inspiration and early expiration when transmural pressure was greatest and were silent for the remainder of the respiratory cycle. Whe respiration was augmented by CO2 breathing or blood volume was increased, the rate of discharge was a linear function of atrial transmural pressure. Eleven ventricular receptors with nonmyelinated afferents (mean conduction velocity, 1.0 m/sec) were exposed to graded volume expansion and phenylephrine infusion in eight open-chest and three spontaneously breathing cats. Raising left ventricular end-diastolic pressure alone increased the frequency of discharge, and a concomitant increase in systolic pressure caused a further increase in firing.

Animals↗
PubMedDate not supplied

Predictors of failure to cure atrial fibrillation with the mini-maze operation.

BACKGROUND: Maze-III is a complex surgical procedure designed to treat chronic atrial fibrillation. A reduction in the number of right and left atrial incisions could decrease the operative time. The aim of this study was to assess the results of a mini-maze operation and to define predictors of its failure. METHODS: Between 1995 and 2000, 72 patients (mean age 64 +/- 9 years) undergoing cardiac surgery had a concomitant mini-maze operation for symptomatic chronic atrial fibrillation. Three and 12 months post-operatively, heart rhythm and left atrial transport functions were assessed by electrophysiology, echocardiography, and magnetic resonance imaging. Multivariate analysis was performed to identify predictors of failure of the mini-maze operation. RESULTS: Operative mortality was 1.4% (1/72). Death during follow-up occurred in 5.6% of patients (4/71), in one due to chronic heart failure. After 1 year, 80% of patients (48/60) were either in sinus rhythm (n = 43; 72%) or had a pacemaker (n = 5; 8%) implanted due to sick sinus syndrome. Intermittent and chronic atrial fibrillation was found in 20% of patients (12/60). Preoperative duration of atrial fibrillation (p = 0.05), preoperative left atrial diameter (p = 0.001), preoperative right atrial diameter (p = 0.02), a reduced left ventricular ejection fraction (p = 0.03), an increased left ventricular end-diastolic diameter (p = 0.04), and the presence of mitral valve stenosis (p = 0.001) were found to be univariate predictors of failure of the mini-maze operation 1 year postoperatively. Multivariate analysis defined preoperative diagnosis of mitral valve stenosis (p = 0.005; OR 117.5), longer duration of preoperative atrial fibrillation (p = 0.01; OR 1.33), and increased preoperative left ventricular end-systolic diameter (p = 0.02; OR 1.2) as incremental independent risk factors for failure of the mini-maze operation to cure chronic atrial fibrillation. CONCLUSION: The mini-maze operation is a safe procedure with similar results to that of Cox's Maze-III operation. The less-invasive mini-maze operation could be applicable even to patients with severely reduced left ventricular function, in whom complex cardiac surgery has to be performed concomitantly as well as in those presenting severe comorbidities.

Adult↗
PubMed1975

Functional antagonism between calcium-antagonists and noradrenaline on isolated guinea-pig atria.

In the isolated electrically driven guinea-pig atrium the influence of D 600 and nifedipine on the action of noradrenaline was investigated. 1. The calcium-antagonists caused a dose-dependent negative inotropic effect. 10(-7) M of D 600 or nifedipine inhibited the contractile amplitude by 75 and 55%, respectively. 2. In spite of the pronounced negative inotropic effect evoked by the two calcium-antagonists, the maximal response to noradrenaline was not changed. The sensitivity of the myocardium to noradrenaline was only slightly diminished i.e. by a factor of 4.6 and 3 as calculated from the pD2-values. 3. The functional antagonism between noradrenaline and calcium-antagonists, therefore, offers the possibility to overcome cardiac side-effects of calcium-antagonists.

Animals↗
PubMed2001

Long-term endothelin receptor blockade improves cardiovascular function in diabetes.

To evaluate the potential contribution of endothelin-1 (ET-1) toward the cardiovascular complications of diabetes, the present study examined the effects of chronic ET receptor blockade with bosentan on heart function and vascular reactivity in streptozotocin (STZ)-induced diabetic rats. Wistar rats were divided into four groups: control, control bosentan-treated, diabetic, and diabetic bosentan-treated. After chronic bosentan treatment, cardiac function and vascular reactivity were assessed. Exvivo working heart function was determined in terms of rate of contraction (+dP/dt), rate of relaxation (-dP/dt), and left ventricular developed pressure (LVDP). Contractile responses to ET-1 were determined in isolated superior mesenteric arteries. In addition, ET-1-like immunoreactivity was determined in ventricular and vascular tissues by immunohistochemistry. Cardiac function was depressed in the untreated-diabetic group. Bosentan treatment improved working heart function; hearts from the diabetic bosentan-treated group exhibited improved LVDP and -dP/dt. The contractile responses of mesenteric arteries to ET-1 were exaggerated in the untreated-diabetic group. Long-term bosentan treatment normalized these responses. Immunohistochemical analyses revealed increased ET-1-like immunoreactivity in ventricular and vascular tissues from untreated diabetic rats. These data show the beneficial effects of ET(A/B) receptor blockade on cardiovascular function in STZ-diabetic rats. An altered ET-1 system may contribute toward the pathogenesis of cardiovascular dysfunction in diabetes.

Animals↗
PubMed2000

Ebstein's anomaly in adults: Doppler-echocardiographic evaluation.

A systematic approach and segmental analysis are required for comprehensive assessment including both morphologic and functional abnormalities associated with Ebstein's anomaly. The essence of the disease is an apical displacement of both the septal and the posterior tricuspid leaflets, exceeding 20 mm or 8 mm/m2 in adults. As a consequence, the right heart consists of three components including the true right atrium, the functional right ventricle (RV) and an intervening zone that is anatomically ventricular but functionally right atrial (atrialized RV). The thin wall of the atrialized RV may result in an aneurysm between the anatomic tricuspid annulus and the apically displaced posterior leaflet. The annular attachment of the anterior leaflet is normal, which may be dysplastic and adherent to the RV wall. Tricuspid regurgitation is usually moderate to severe. Size, shape and function of the functional RV must be described. The paradoxical motion of the interventricular septum causes alterations in left ventricular geometry and function. An interatrial communication is frequently present. Echocardiography is the method of choice to diagnose Ebstein's anomaly on its own or in association with other heart defects.

Adult↗
PubMed2000

Myosin light chain replacement in the heart.

Myosin-actin cross-bridge kinetics are an important determinant for cardiac systolic and diastolic function. We compared the effects of myosin light chain substitutions on the ability of the fibers to contract in response to calcium and in their ability to produce power. Transgenesis was used to effect essentially complete replacement of the target contractile protein isoform specifically in the heart. Atrial and ventricular fibers derived from the various transgenic (TG) lines were skinned, and the force-velocity relationships, unloaded shortening velocities, and Ca(2+)-stimulated Mg(2+)-ATPase activities were determined. Replacement with an ectopic isoform resulted in significant changes in cross-bridge cycling kinetics but without any overt effects on morbidity or mortality. To confirm that this result was not light chain specific, a modified alpha-myosin heavy chain isoform that resulted in significant changes in force development was also engineered. The animals appeared healthy and have normal lifespans, and the changes in force development did not result in significant remodeling or overt hypertrophy. We conclude that myosin light chains can control aspects of cross-bridge cycling and alter force development. The myosin heavy chain data also show that changes in the kinetics of force development and power output do not necessarily lead to activation of the hypertrophic response or significant cardiac remodeling.

Aging↗
PubMed1992

Novel functional M1 selective muscarinic agonists. Synthesis and structure-activity relationships of 3-(1,2,5-thiadiazolyl)-1,2,5,6-tetrahydro-1-methylpyridines .

A series of novel 3-(3-substituted-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro- 1-methylpyridines (substituted-TZTP; 5a-l, 7a-h, 8, 9c-n, 11, 13j) were synthesized and tested for central muscarinic cholinergic receptor affinity by using [3H]-oxotremorine-M (Oxo-M) and [3H]-pirenzepine (Pz) as ligands. The potency and efficacy of the compounds for the pharmacological defined M1 and M2 muscarinic receptors were determined on isolated electrically stimulated rabbit vas deferens and on spontaneously beating isolated guinea pig atria, respectively. Selected compounds were also tested for M3 activity in the isolated guinea pig ileum. The C1-8 alkoxy-TZTP 5a-l analogues all displaced [3H]-Oxo-M and [3H]-Pz with low nanomolar affinity. Depicting chain length against Oxo-M binding and against Pz binding the unbranched C1-8 alkoxy-TZTP (5a-h) derivatives produced U-shaped curves with butoxy- (5d) and (pentyloxy)-TZTP (5e) as the optimum chain length, respectively. This U-shaped curve was also seen in the ability of the compounds 5a-h to inhibit the twitch height in the vas deferens preparation. The (pentyloxy)- (5e) and the (hexyloxy)-TZTP (5f) analogues produced an over 90% inhibition of the twitch height with IC50 values in the low picomolar range. In both the atria and in the ileum preparations 5f had low efficacy and potency. With the (alkylthio)-TZTP (7a-h) analogues the structure-activity relationship was similar to the one observed with the alkoxy (5a-h) analogues, but generally 7a-h had higher receptor affinity and was more potent than the corresponding 5a-h. However, the C3-8 alkyl-TZTP (9c,e,g,h) analogues had 10-100 times lower affinity for the central muscarinic receptors than the corresponding alkoxy and alkylthio derivatives, and their efficacy in the vas deferens preparation was too low to obtain IC50 values. The unsubstituted TZTP (11) compound was a potent but nonselective muscarinic agonist. The two 3-(3-butoxy/(hexyloxy)-1,2,5-oxadiazol-4-yl)-1,2,5,6-tetrahy dro-1- methylpyridines (butoxy/hexyloxy)-OZTP; 19a/b) were also synthesized and tested. Both 19a and 19b had much lower affinity for the central muscarinic receptors than 5d and 5f, and the efficacy of 19a,b was too low to give IC50 values in the vas deferens preparation. Therefore, the C5-6 (alkyloxy)/(alkylthio)-TZTP's represent a unique series of potent functional M1 selective muscarinic agonists.

Animals↗
PubMed2005

Sinus node dysfunction following targeted disruption of the murine cardiac sodium channel gene Scn5a.

We have examined sino-atrial node (SAN) function in hearts from adult mice with heterozygous targeted disruption of the Scn5a gene to clarify the role of Scn5a-encoded cardiac Na+ channels in normal SAN function and the mechanism(s) by which reduced Na+ channel function might cause sinus node dysfunction. Scn5a+/- mice showed depressed heart rates and occasional sino-atrial (SA) block. Their isolated peripheral SAN pacemaker cells showed a reduced Na+ channel expression and slowed intrinsic pacemaker rates. Wild-type (WT) and Scn5a+/- SAN preparations exhibited similar activation patterns but with significantly slower SA conduction and frequent sino-atrial conduction block in Scn5a+/- SAN preparations. Furthermore, isolated WT and Scn5a+/- SAN cells demonstrated differing correlations between cycle length, maximum upstroke velocity and action potential amplitude, and cell size. Small myocytes showed similar, but large myocytes reduced pacemaker rates, implicating the larger peripheral SAN cells in the reduced pacemaker rate that was observed in Scn5a+/- myocytes. These findings were successfully reproduced in a model that implicated i(Na) directly in action potential propagation through the SAN and from SAN to atria, and in modifying heart rate through a coupling of SAN and atrial cells. Functional alterations in the SAN following heterozygous-targeted disruption of Scn5a thus closely resemble those observed in clinical sinus node dysfunction. The findings accordingly provide a basis for understanding of the role of cardiac-type Na+ channels in normal SAN function and the pathophysiology of sinus node dysfunction and suggest new potential targets for its clinical management.

Action Potentials↗
PubMed2000

Operation Everest III (Comex '97): modifications of cardiac function secondary to altitude-induced hypoxia. An echocardiographic and Doppler study.

During Operation Everest III (Comex '97), to assess the consequences of altitude-induced hypoxia, eight volunteers were decompressed in a hypobaric chamber, with a decompression profile simulating the climb of Mount Everest. Cardiac function was assessed using a combination of M-mode and two-dimensional echocardiography, with continuous and pulsed Doppler at 5,000, 7,000, and 8,000 m as well as 2 d after return to sea level (RSL). On simulated ascent to altitude, aortic and left atrial diameters, left ventricular (LV) diameters, and right ventricular (RV) end-systolic diameter fell regularly. Heart rate (HR) increased at all altitudes accompanied by a decrease in stroke volume; in total, cardiac output (Q) remained unchanged. LV filling was assessed on transmitral and pulmonary venous flow profiles. Mitral peak E velocity decreased, peak A velocity increased, and E/A ratio decreased. Pulmonary venous flow velocities showed a decreased peak D velocity, a decreased peak S velocity, and a reduction of the D/S ratio. Systolic pulmonary arterial pressure (Ppa) showed a progressive and constant increase, as seen on the elevation of the right ventricular/right atrial (RV/RA) gradient pressure from 19.0 +/- 2.4 mm Hg at sea level up to 40.1 +/- 3.3 mm Hg at 8,000 m (p < 0.05), and remained elevated 2 d after recompression to sea level (SL) (not significant). In conclusion, this study confirmed the elevation of pulmonary pressures and the preservation of LV contractility secondary to altitude-induced hypoxia. It demonstrated a modification of the LV filling pattern, with a decreased early filling and a greater contribution of the atrial contraction, without elevation of LV end-diastolic pressure.

Adult↗
PubMed1996

Thoracic epidural anesthesia improves functional recovery from myocardial stunning in conscious dogs.

The effects of thoracic epidural anesthesia (TEA) on the contractile performance of ischemic and postischemic myocardium have not been well investigated. The purpose of this investigation was to examine the effects of TEA on severity and duration of myocardial stunning in an experimental model for sublethal acute myocardial ischemia. Seven dogs were chronically instrumented for measurement of heart rate (HR), left atrial (LAP), aortic and left ventricular pressure (LVP), LV dP/dtmax' and myocardial wall-thickening fraction (WTF). An occluder around the left anterior descending artery (LAD) allowed induction of reversible LAD ischemia. TEA was performed with lidocaine 4 mg/kg through a chronically implanted epidural catheter at the second thoracic level. Regional myocardial blood flow was determined with colored microspheres. Two experiments were performed in a cross-over design on separate days: Experiment 1, induction of 10 min of LAD ischemia without TEA; and Experiment 2, induction of 10 min of LAD ischemia with TEA. WTF was measured at baseline (BL) and predetermined time points until complete recovery from ischemic dysfunction occurred. LAD ischemia caused a significant decrease of LAD-WTF with (-28% +/- 5.1% versus BL) and without TEA (-15.5% +/- 5.3% versus BL). After 3 h of reperfusion, WTF as percent of BL values was significantly higher with TEA (P < 0.001). BL values of WTF were reached after 24 h with TEA and after more than 48 h without TEA (P < 0.05). There were no significant differences for mean arterial pressure (MAP), heart rate (HR), LVP, LAP, and LVdP/dtmax between the groups during ischemia and reperfusion. In nonischemic myocardium TEA caused an increase of subendocardial blood flow. During ischemia neither the subendocardial/subepicardial nor the occluded/ normal zone blood flow was affected by TEA. TEA attenuates myocardial stunning in conscious dogs. This finding is consistent with data regarding a reduction of infarct size due to TEA.

Anesthesia, Epidural↗
PubMed2003

Investigation of cardiac function in children with suspected obstructive sleep apnea.

OBJECTIVE: To assess the prevalence of cardiac failure in a group of children with suspected obstructive sleep apnea (OSA) and to assess the need for preoperative electrocardiograms (ECGs) and chest radiographs (CXRs) in children with OSA. DESIGN: Case record review of 271 children having (adeno)tonsillectomy for symptoms of OSA. METHOD: Preoperative ECGs and CXRs were assessed for signs of right atrial or ventricular hypertrophy or failure. Case records were assessed for evidence of cardiac failure during anaesthesia. RESULTS: One child with congenital heart disease had signs of cardiac failure preoperatively. No other cases of atrial or ventricular hypertrophy or failure were found. CONCLUSIONS: Cardiac failure appears to be uncommon in children with symptoms of OSA. Preoperative ECG and CXR are essential in only selected cases.

Adolescent↗
PubMed2006

RAte Control Efficacy in permanent atrial fibrillation: a comparison between lenient versus strict rate control in patients with and without heart failure. Background, aims, and design of RACE II.

BACKGROUND: Recent studies demonstrated that rate control is an acceptable alternative for rhythm control in patients with persistent atrial fibrillation (AF). However, optimal heart rate during AF is still unknown. OBJECTIVE: To show that in patients with permanent AF, lenient rate control is not inferior to strict rate control in terms of cardiovascular mortality, morbidity, neurohormonal activation, New York Heart Association class for heart failure, left ventricular function, left atrial size, quality of life, and costs. METHODS: The RACE II study is a prospective multicenter trial in The Netherlands that will randomize 500 patients with permanent AF (< or = 12 months) to strict or lenient rate control. Strict rate control is defined as a mean resting heart rate < 80 beats per minute (bpm) and heart rate during minor exercise < 110 bpm. After reaching the target, a 24-hour Holter monitoring will be performed. If necessary, drug dose reduction and/or pacemaker implantation will be performed. Lenient rate control is defined as a resting heart rate < 110 bpm. Patients will be seen after 1, 2, and 3 months (for titration of rate control drugs) and yearly thereafter. We anticipate a 25% 2.5-year cardiovascular morbidity and mortality in both groups. RESULTS: Enrollment started in January 2005 in 29 centers in The Netherlands and is expected to be concluded in June 2006. Follow-up will be at least 2 years with a maximum of 3 years. CONCLUSION: This study should provide data how to treat patients with permanent AF.

Anti-Arrhythmia Agents↗