Efficacy of primary preventive ICD therapy in an unselected population of patients with reduced left ventricular ejection fraction.

AIMS: International guidelines advocate an implantable cardioverter and defibrillator (ICD) in patients with reduced left ventricular ejection fraction (LVEF) to prevent sudden death (SCD). Previous data suggest that the benefit of ICD therapy in real life may be lower than expected from the results of controlled studies and side-effects are not negligible. It is also unclear whether women benefit from treatment to the same extent as men. The aim of this study was to investigate the balance between benefits and complications of ICD therapy in a real-life population of patients with heart failure. METHODS AND RESULTS: We studied 865 consecutive patients with reduced LVEF treated with ICDs for primary prevention of SCD in 2006-11 in four tertiary care hospitals in Sweden (age 64 ± 11 years, 82% men, 62% ischaemic). The patients' medical records were scrutinized as regards appropriate therapies, complications related to the defibrillator, all-cause mortality, and gender differences. Mean follow-up was 35 ± 18 months. During follow-up 155 patients (18%) received appropriate ICD therapy, 61 patients (7%) had inappropriate shocks, 110 patients (13%) had at least one complication that required reoperation and 213 patients (25%) died. Men were twice as likely to receive ICD treatment compared with women (20 vs. 9%, P < 0.01), but neither total mortality nor complication rates differed. CONCLUSIONS: Ventricular arrhythmias necessitating ICD therapy are common (6% annually). Women are less likely to have correct ICD treatment, but have the same degree of treatment complications, thus reducing the net benefit of their treatment.

The HLA locus contains novel foetal susceptibility alleles for congenital heart block with significant paternal influence.

OBJECTIVE: The main aim of this study was to identify foetal susceptibility genes on chromosome six for Ro/SSA autoantibody-mediated congenital heart block. SUBJECTS AND DESIGN: Single nucleotide polymorphism (SNP) genotyping of individuals in the Swedish Congenital Heart Block (CHB) study population was performed. Low-resolution HLA-A, -Cw and -DRB1 allele typing was carried out in 86 families comprising 339 individuals (86 Ro/SSA autoantibody-positive mothers, 71 fathers, 87 CHB index cases and 95 unaffected siblings). RESULTS: A case-control comparison between index cases and population-based out-of-study controls (n = 1710) revealed association of CHB with 15 SNPs in the 6p21.3 MHC locus at a chromosome-wide significance of P < 2.59 × 10(-6) (OR 2.21-3.12). In a family-based analysis of association of SNP markers as well as distinct MHC class I and II alleles with CHB, HLA-DRB1*04 and HLA-Cw*05 variants were significantly more frequently transmitted to affected individuals (P < 0.03 and P < 0.05, respectively), whilst HLA-DRB1*13 and HLA-Cw*06 variants were significantly less often transmitted to affected children (P < 0.04 and P < 0.03). We further observed marked association of increased paternal (but not maternal) HLA-DRB1*04 transmission to affected offspring (P < 0.02). CONCLUSIONS: HLA-DRB1*04 and HLA-Cw*05 were identified as novel foetal HLA allele variants that confer susceptibility to CHB in response to Ro/SSA autoantibody exposure, whilst DRB1*13 and Cw*06 emerged as protective alleles. Additionally, we demonstrated a paternal contribution to foetal susceptibility to CHB for the first time.

Cardiac resynchronization therapy: a breakthrough in heart failure management.

Heart failure is now considered an epidemic. In patients with heart failure, electrical and mechanical dyssynchrony, evident primarily as prolongation of the QRS-complex on the surface electrocardiogram, is associated with detrimental effects on the cardiovascular system at several levels. In the past 10 years, studies have demonstrated that by stimulating both cardiac ventricles simultaneously, or almost simultaneously [cardiac resynchronization therapy (CRT)], the adverse effects of dyssynchrony can be overcome. Here, we provide a comprehensive overview of different aspects of CRT including the rationale behind and evidence for efficacy of the therapy. Issues with regard to gender effects and patient follow-up as well as a number of unresolved concerns will also be discussed.

A population-based investigation of the autoantibody profile in mothers of children with atrioventricular block.

The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.

Comparative effects of permanent biventricular and right-univentricular pacing in heart failure patients with chronic atrial fibrillation.

BACKGROUND: One third of chronic heart failure patients have major intraventricular conduction and uncoordinated ventricular contraction. Non-controlled studies suggest that biventricular pacing may improve haemodynamics and well-being by reducing ventricular asynchrony. The aim of this trial was to assess the clinical efficacy and safety of this new therapy in patients with chronic atrial fibrillation. METHODS: Fifty nine NYHA class III patients with left ventricular systolic dysfunction, chronic atrial fibrillation, slow ventricular rate necessitating permanent ventricular pacing, and a wide QRS complex (paced width >or=200 ms), were implanted with transvenous biventricular-VVIR pacemakers. This single-blind, randomized, controlled, crossover study compared the patients' parameters, as monitored during two 3-month treatment periods of conventional right-univentricular vs biventricular pacing. The primary end-point was the 6-min walked distance, secondary end-points were peak oxygen uptake, quality-of-life, hospitalizations, patients' preferred study period and mortality. RESULTS: Because of a higher than expected drop-out rate (42%), only 37 patients completed both crossover phases. In the intention-to-treat analysis, we did not observe a significant difference. However, in the patients with effective therapy the mean walked distance increased by 9.3% with biventricular pacing (374+/-108 vs 342+/-103 m in univentricular;P =0.05). Peak oxygen uptake increased by 13% (P=0.04). Hospitalizations decreased by 70% and 85% of the patients preferred the biventricular pacing period (P<0.001). CONCLUSION: As compared with conventional VVIR pacing, effective biventricular pacing seems to improve exercise tolerance in NYHA class III heart failure patients with chronic atrial fibrillation and wide paced-QRS complexes. Further randomized controlled studies are required to definitively validate this therapy in such patients.

Reduction of hospital days by biventricular pacing.

The health care costs for heart failure are substantial. Studies indicate that hospital treatment constitutes 65-75% of these. The aim of this study was to assess total and heart failure related hospital days as well as safety and efficacy of biventricular pacing in 16 patients with severe heart failure and delayed intraventricular conduction (QRS duration >150 ms). They were implanted with a biventricular pacemaker and followed by NYHA class, 6-min walk test and quality of life for a mean of 291+/-76 days. Total number of hospital days and the need for hospitalisations were monitored. Thirteen responders improved by at least one functional class. After 6 months of pacing the 6-min walk test improved from 375+/-83 m to 437+/-73 m (P<0.001) and Minnesota Living with Heart Failure quality of life score from 41+/-19 to 24+/-17 (P<0.001) compared to baseline. The need for hospital care decreased significantly after biventricular pacing. The total number of hospital days in all patients was 253 the year before compared to 45 the year after biventricular pacing (P<0.01). For heart failure related hospital days the corresponding figures were 183 and 39 days, respectively (P<0.01). Biventricular pacing improved 13/16 patients with severe heart failure and wide QRS complexes in this open study. The improvement resulted in a reduced need for hospital care.

[Biventricular pacing as a new therapeutic method in heart failure. An alternative for patients with intraventricular conduction disorders]. / Biventrikulär pacing ny behandlingsmetod vid hjärtsvikt. Alternativ för patienter med intraventrikulära retledningsrubbningar.

Patients with severe heart failure often have interventricular conduction disturbances indicated by wide QRS complexes. The resulting uncoordinated contraction pattern leads to impaired systolic and diastolic function which might be overcome by a new technique, biventricular pacing. The first Swedish clinical trial is reported, an open study where 13 out of 16 patients improved in terms of functional class, walking test and quality of life after six months of treatment. The number of hospital days was markedly reduced after pacemaker implantation.

Significant improvement of quality of life following atrioventricular synchronous pacing in patients with hypertrophic obstructive cardiomyopathy. Data from 1 year of follow-up. PIC study group. Pacing In Cardiomyopathy.

AIMS: Atrioventricular synchronous pacing exerts beneficial effects, including reduction of left ventricular outflow tract gradients, in patients with hypertrophic obstructive cardiomyopathy. The Pacing in Cardiomyopathy study was initiated to explore the effects of pacing in a double-blind randomized crossover fashion. The aims were to ascertain the beneficial effects of pacing in a controlled study and to rule out a placebo effect by pacing. This paper deals with the outcome of pacing on quality of life during 1 year of follow-up. METHODS: Quality of life was evaluated with the Karolinska questionnaire, validated for patients paced for bradyarrhythmias and ischaemic heart disease. Drug-refractory patients with hypertrophic obstructive cardiomyopathy were recruited for the study and after a temporary pacing procedure implanted with permanent pacemakers. Patients were randomized to two study arms defining the sequence of pacemaker programming. In one arm the pacemaker was inactive, in the other active. After 3 months the pacemaker was reprogrammed to the alternate mode and a further 3 months followed. After this period subsequent pacemaker programming corresponded to the mode preferred by the patient. A last assessment was made 1 year after baseline examinations. RESULTS: Eighty patients completed the first crossover period and 75 completed the full 1 year of follow-up. Active pacing induced significant quality of life improvements, in the order of 9-44%, regardless of programming sequence. Discontinuation of pacing after a first active period resulted in the return of symptoms. Fourteen patients requested early reprogramming after having been programmed to inactive pacing after a first period of active pacing. Seventy-six patients preferred active pacing after the crossover period. A further 6 months of pacing induced progressive improvement in symptoms already favourably influenced. CONCLUSION: Atrioventricular synchronous pacing has a profound beneficial effect on most domains of quality of life in patients with hypertrophic obstructive cardiomyopathy refractory to drug treatment.

Placebo effect of pacemaker implantation in obstructive hypertrophic cardiomyopathy. PIC Study Group. Pacing In Cardiomyopathy.

This study evaluated a possible placebo effect by pacemaker implantation. The study design was a 3-month multicenter, double-blind, randomized cross-over study to compare the effects of atrioventricular (AV) synchronous pacing with an optimal AV delay to inactive pacing in patients with obstructive hypertrophic cardiomyopathy (HC). Quality of life and left ventricular (LV) outflow tract obstruction were evaluated after the first study period in 40 patients assigned to inactive pacing. Data were compared with the corresponding results among the 41 subjects assigned to a first study period of active pacing. During inactive pacing, there was a significant improvement in perceived chest pain, dyspnea, and palpitations. Moreover, LV outflow tract gradient decreased from 71 +/- 32 mm Hg to 52 +/- 34 mm Hg (p = 0.04). In patients assigned to active pacing the reduction of the gradient was significantly more pronounced (70 +/- 24 mm Hg to 33 +/- 27 mm Hg; p <0.0001). The difference in gradient reduction between the groups was highly significant (p <0.00001). In the group assigned to active pacing there was also significant improvement in perceived symptoms as well as in alertness, the ability to be self-autonomous, and strenuous physical exercise. The improvements in the latter were significantly greater in those paced actively compared with patients paced inactively, whereas the changes in perceived symptoms did not differ between groups. In conclusion, pacemaker implantation had a placebo effect on objective and subjective parameters in this group of patients with obstructive HC.

Rapid return of left ventricular outflow tract obstruction and symptoms following cessation of long-term atrioventricular synchronous pacing for obstructive hypertrophic cardiomyopathy.

Atrioventricular (AV) synchronous pacing reduces left ventricular (LV) outflow tract obstruction and symptoms in patients with obstructive hypertrophic cardiomyopathy (HC). The duration of gradient reduction, if pacing is discontinued for a prolonged period of time, is unknown. This question is addressed in the present randomized double-blind crossover study comparing continued with inactivated pacing. Ten patients, successfully paced for > or = 6 months, were randomized to continue pacing or to have their pacemakers inactivated after baseline examinations, including echo-Doppler imaging, exercise testing, and a quality-of-life questionnaire. When entering the study, the patients were in New York Heart Association functional classes I to II. After pacemaker programming, examinations were repeated at 1, 4, and 12 weeks. At the 12-week follow-up the alternate pacing mode was programmed, and the patient entered the second study arm. Premature pacemaker pacing occurred if severe clinical deterioration or a significant increase of the LV outflow tract obstruction were evident. Three patients started in the inactive mode and 7 patients in the active mode. All patients who started with the pacemaker inactivated required early reprogramming due to return of symptoms after 7, 10, and 13 days, respectively. All 7 patients who started in the active pacing mode completed the first period; however, after reprogramming to the inactive mode they required early activation after 1 to 20 days due to reappearance of intolerable subjective symptoms. The LV outflow tract gradient increased significantly after inactivation of pacing in all patients (22 +/- 21 mm Hg to 47 +/- 21 mm Hg). Thus, AV synchronous pacing effectively relieves symptoms and reduces the LV outflow tract gradient in patients with obstructive HC. This improvement, which is rapidly established with the initiation of cardiac pacing, is not persistent after cessation of pacing. Reinitialization of pacing promptly reduces the LV outflow tract obstruction and relieves symptoms to a preexisting extent.

Clinical progress after randomized on/off pacemaker treatment for hypertrophic obstructive cardiomyopathy. Pacing in Cardiomyopathy (PIC) Study Group.

BACKGROUND: The therapeutic options for hypertrophic obstructive cardiomyopathy (HOCM) classically include medical treatment with beta-blockers and calcium antagonists or myectomy-myotomy as a surgical possibility for refractory cases. The observation that pacemaker activation of the heart in HOCM reduces the subaortic gradient is well known but less well investigated. METHODS: Eighty-three patients (33 female and 50 male) mean age 53 (18-82) years, with symptoms refractory to drug treatment and a resting gradient above 30 mmHg, who responded favourably to temporary pacing, were included in this prospective study and had a pacemaker (DDD) implanted. After an initial double-blind crossover phase of 6 months, patients were reinvestigated at 12 months and followed for a mean of 36 months. RESULTS: As observed during a screening investigation, the obstruction was significantly reduced from 72 +/- 35 mmHg to 29 +/- 24 mmHg (P < 0.01) when the pacemaker was on, while no major effect was seen during the sham phase. The effect was persistent at 1 year with a remaining resting gradient of 28 +/- 24 mmHg. In parallel, we documented an improvement in functional capacity, according to the NYHA classification and by quality of life analysis, and a significant improvement in dyspnoea and angina. Exercise on treadmill improved only in patients with reduced initial tolerance (< 8 min). During the mean follow-up of 36 months, 65 patients remained on pacing alone, with eight patients having additional AV-node ablation and five patients finally having surgery. CONCLUSION: This controlled multicentre study shows that pacemaker treatment is an option for HOCM patients; it is inoffensive and does not exclude alternative methods, but satisfies 79% of patients beyond 3 years.

Modification of atrioventricular conduction as adjunct therapy for pacemaker-treated patients with hypertrophic obstructive cardiomyopathy.

AIMS: Atrioventricular synchronous pacing offers symptomatic relief for patients with drug-refractory hypertrophic obstructive cardiomyopathy. Successful treatment requires complete right ventricular apical pre-excitation. Enhanced atrioventricular conduction renders this difficult in some patients. The aim of this study was to evaluate whether selective prolongation of atrioventricular conduction is a useful tool for optimization of treatment in patients with hypertrophic obstructive cardiomyopathy primarily refractory to cardiac pacing. METHODS: Six patients refractory to pacemaker treatment for 3-19 months underwent radiofrequency modification of atrioventricular conduction. Patients were followed with echo-Doppler, exercise testing and clinical evaluation for 6-12 months after modification. RESULTS: Intrinsic PQ time was significantly prolonged from 175 +/- 18 ms to 253 +/- 22 ms; however, one patient exhibited complete block at one month follow-up. Left ventricular outflow tract obstruction decreased from 74 +/- 17 mmHg to 28 +/- 27 mmHg at the 6-month follow-up. Symptomatic improvement of at least one functional class was recorded in all patients; exercise tolerance remained unchanged, however, less angina and dyspnoea were reported in everyday life. CONCLUSION: Radiofrequency modification of atrioventricular conduction, with persistent prolongation of the PQ interval, enhances the effects of pacing in patients with hypertrophic obstructive cardiomyopathy. This treatment enhances left ventricular outflow tract gradient reduction and improves symptoms.

Long-term effects of dual chamber pacing in patients with hypertrophic cardiomyopathy without outflow tract obstruction at rest.

BACKGROUND: Atrioventricular-synchronous pacing is beneficial in patients with hypertrophic obstructive cardiomyopathy. The effects of pacing in patients without significant left ventricular outflow tract obstruction at rest are, however, less well explored. This study compares the long-term outcome of pacing patients with and without significant left ventricular outflow tract obstruction at rest. METHODS: Forty-one patients with hypertrophic obstructive cardiomyopathy were studied, 19 with a left ventricular outflow tract gradient < 40 mmHg at rest, but exceeding 50 mmHg during provocation with isoproterenol (group A), and 22 with a left ventricular outflow tract obstruction > 40 mmHg at rest (group B). Before the implantation of a permanent pacemaker, the patients were studied according to a temporary pacing protocol. This included graded isoproterenol provocation of the left ventricular outflow tract obstruction, which was assessed by echo Doppler. Following permanent pacemaker implantation, the patients were regularly followed up with echo Doppler, exercise testing and monitoring of the clinical condition. RESULTS: Isoproterenol provocation was reproducible and the technique did not cause any clinically important side effects. Left ventricular outflow tract gradient reduction after chronic pacing did not differ between the two groups. In group A, it decreased from 98 +/- 30 mmHg in sinus rhythm to 42 +/- 26 mmHg during pacing. The corresponding values in group B were 87 +/- 40 mmHg to 36 +/- 24 mmHg. The clinical condition improved similarly in the two groups. Exercise capacity increased significantly and perceived dyspnoea and angina pectoris were significantly lower at submaximal levels of exercise after 6 months of pacing. CONCLUSION: Hypertrophic obstructive cardiomyopathy patients who only exhibit significant left ventricular outflow tract obstruction during provocation benefit as much from pacemaker treatment as do patients who already have significant obstruction at rest. Isoproterenol is a safe and reproducible method for pre-pacing evaluation of hypertrophic obstructive cardiomyopathy patients.

Influence of right ventricular pacing site on left ventricular outflow tract obstruction in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVES: This study was designed to show the influence of right ventricular pacing site on left ventricular outflow tract obstruction during pacing treatment of patients with hypertrophic obstructive cardiomyopathy. BACKGROUND: Atrioventricular synchronous pacing has been reported to reduce left ventricular outflow obstruction and symptoms in patients with hypertrophic obstructive cardiomyopathy. A paradoxic septal movement induced by right ventricular pacing has been implicated as the mechanism behind the reduced left ventricular outflow tract obstruction; however, the importance of pacing site has not been clarified. METHODS: Cardiac output, measured invasively, and left ventricular outflow tract gradient, estimated by Doppler echocardiography, were studied in 15 patients with hypertrophic obstructive cardiomyopathy. Measurements were made with the right ventricular electrode in the septal and apical positions during temporary pacing and during sinus rhythm. RESULTS: Right ventricular apical pacing reduced the outflow tract gradient in all 15 patients to a mean +/- SD of 38 +/- 24 mm Hg from 96 +/- 33 mm Hg during sinus rhythm. During high septal pacing the outflow tract gradient was not reduced, remaining at 93 +/- 44 mm Hg. No significant changes in cardiac output were seen when levels during sinus rhythm (6.4 liters/min), apical pacing (6.4 liters/min) and high septal pacing (5.6 liters/min) were compared. CONCLUSIONS: The right ventricular pacing site is of crucial importance for reducing left ventricular outflow tract obstruction when patients with hypertrophic obstructive cardiomyopathy are treated with pacing. Cardiac output is not reduced by apical pacing.

Results of atrioventricular synchronous pacing with optimized delay in patients with severe congestive heart failure.

To verify that atrioventricular (AV) synchronous pacing (DDD) with short AV delay improves the condition of patients with severe congestive heart failure, we implanted DDD pacemakers in 10 patients with severe heart failure (New York Heart Association [NYHA] class III to IV). One day after pacemaker implantation, the AV delay was optimized by Doppler echocardiographic measurements over the aortic outflow tract. Patients were evaluated regarding NYHA class, stroke volume, cardiac output, ejection fraction, and quality of life at 1, 3, and 6 months after pacemaker implantation. Although the optimized AV delay was associated with short-term improvement in stroke volume and cardiac output (baseline stroke volume = 22 +/- 7 ml, day 1 = 28 +/- 12 ml; p = 0.03: baseline cardiac output = 1.9 +/- 0.6 L/min, day 1 = 2.2 +/- 1.1 L/min; p = 0.10), the mean stroke volume, cardiac output, NYHA class, and ejection fraction did not change significantly after 1, 3, and 6 months of pacing compared with baseline values. Three patients improved in NYHA class during the follow-up. A consistent improvement in stroke volume, cardiac output, NYHA class, and ejection fraction was observed in only 1 patient. In conclusion, we found no beneficial effects of AV-synchronous pacing with optimized AV delay in patients with severe heart failure.

Serum NCA in bone marrow transplant recipients and its metabolism.

Normal colon and granulocyte antigen (NCA) in serum from 24 patients undergoing bone marrow transplantation (BMT), mostly for leukemic disease, was studied for a period of 0-60 days before/after transplantation. Out of the 23 patients with a take, 20 acquired elevated serum NCA. One patient had a rejection of the transplantation and never showed a rise of NCA values. Thirteen patients were studied in detail; 7 of them had an NCA rise 1-4 days before take, 4 at the day of take and 2 patients 1-4 days later. To investigate the rate of NCA turnover, 125I-NCA was injected into Macaca irus monkeys. One hour after injection, 87% of the injected substance had left the circulation. The prime site of accumulation was the liver. Thereafter, blood NCA decreased at a slower and linear rate. Of the substance seen at the beginning of the second phase 50% had been eliminated after 30 hours. The data support the theory that NCA is produced by the myeloid cells in bone marrow, that it has a rapid metabolism and therefore is of interest as a marker of bone marrow activity in health and malignant disease.

Decrease of a normal colon and granulocyte antigen (NCA) in whole lysed blood of myelosuppressed patients.

A normal colon and granulocyte antigen (NCA) is found in large amounts in neutrophil granulocytes. A method combining freeze-thawing and ultrasonication of whole blood proved to be the most efficient in recovery of NCA from separated granulocytes or whole blood. NCA in whole blood was studied in healthy persons and in 8 patients with embryonal carcinoma undergoing chemotherapy, with a myelosuppressive effect. A strong correlation (r = 0.96) between the total number of peripheral granulocytes and the amount of NCA in lysed whole blood was found in both healthy persons and myelosuppressed patients. The NCA content per 10(9) granulocytes was equal in granulocytopenic and healthy persons. NCA measurements therefore give information about the total number of granulocytes in peripheral blood within the limits measured (0.5-6.5 x 10(9) granulocytes/l).

NCA: a differentiation antigen of myelopoietic cells in humans and hominoid monkeys.

NCA, a normal colonic and granulocytic antigen, could be demonstrated in serum and in myelopoietic, but not lymphopoietic or erythropoietic, cells of Homo sapiens and other Primates. The levels of NCA in both serum and myelopoietic cells of Homo and hominoids were higher than those of more distant relatives of the same order. Thus, the classic phylogenetic differences are reflected also by the distribution of NCA. Hyperimmunization of Macaca irus, in which the NCA content of serum and cells is low, led to occurrence of anti-NCA IgG in all animals. The phylogenetic differences may accordingly have to do with slight antigenic NCA differences between Homo and other Primates rather than differences in amount only. Purified NCA did not affect growth and maturation of myelopoietic stem cells in vitro, whereas anti-NCA inhibited development of the majority of myelopoietic clusters and colonies.