Effect of pacing mode on health-related quality of life in the Canadian Trial of Physiologic Pacing

Background Both “physiologic” (dual-chamber or atrial only) or ventricular-pacing-only permanent pacemakers provide chronotropic competence, with unknown health-related quality of life (QOL) differences between these options. The QOL studies within the Canadian Trial of Physiologic Pacing were performed to assess whether QOL differences exist in patients randomized to these 2 pacing modes. Methods Two QOL protocols were performed: 1) a substudy of 269 patients with detailed QOL measures (The Medical Outcomes Study, Short-Form [SF-36], the Pacemaker Syndrome Scale, an activity scale, and a pacemaker-specific scale) at baseline and 6 months after implantation; and 2) a parent study assessment of QOL in 1721 patients with a 12-item QOL instrument package (SF-6, “ladder of life,” and pacemaker syndrome scale) given 6 months after implantation only. Results In the substudy, pacing was associated with an average significant (P < .05) 0.36 SD unit improvement in QOL across all domains (SF-36: 38 ± 9 to 41 ± 11 for physical scores, 47 ± 11 to 52 ± 9 for mental health scores, both P < .001). Similar improvements were seen with the pacemaker-specific scales. There were no significant differences in the absolute or relative improvement in QOL between assigned pacing modes. The parent study similarly showed no differences in QOL between pacing modalities. Presyncope occurred in 31% of patients in the physiological pacing group, compared with 38% of the patients in the ventricular pacing group (P < .01). No other symptoms were different between the 2 groups. Pacemaker dependency, defined as an escape heart rate <50 beats per minute, did not influence the lack of difference in QOL scores between the 2 assigned pacing modes. Conclusion In this largest randomized assessment of QOL in patients with pacemakers, with the instruments used, there was no significant health-related QOL difference seen between “physiologic” pacing and ventricular pacing. (Am Heart J 2003;145:430-7.)     

Low settings of the ventricular pacing output in patients dependent on a pacemaker: are they really safe?

Background It is generally acknowledged that pacemaker output must be adjusted with a 100% voltage safety margin above the pacing threshold to avoid ineffective pacing, especially in patients dependent on pacemakers. Aims The aim of this prospective crossover study was to assess the beat-to-beat safety of low outputs in patients who are dependent on a pacemaker between 2 follow-up examinations. Methods The study included 12 patients who had received a DDD pacemaker with an automatic beat-to-beat capture verification function. The ventricular output at 0.4 milliseconds pulse duration was programmed independently of the actual pacing threshold in a crossover randomization to 1.0 V, 1.5 V, and 2.5 V for 6 weeks each. At each follow-up, the diagnostic counters were interrogated and the pacing threshold at 0.4 milliseconds was determined in 0.1-V steps. The diagnostic pacemaker counters depict the frequency of back-up pulses delivered because of a loss of capture. During the randomization to 1.0-V output, we evaluated whether the adjustment of the output under consideration of the >100% voltage safety margin reduced the frequency of back-up pulses. Results Pacing thresholds at the randomization to 1.0-V, 1.5-V, and 2.5-V output were not significantly different, with 0.7 ± 0.3 V at 2.5-V output, 0.6 ± 0.2 V at 1.5-V output, and 0.6 ± 0.2 V at 1.0-V output. The frequency of back-up pulses was similar at 2.5-V and 1.5-V output, 2.2% ± 1.9% and 2.0% ± 2.0%, respectively. The frequency of back-up pulses significantly increased at 1.0-V output to 5.8% ± 6.4% (P < .05). Back-up pulses >5% of the time between the 2 follow-ups were observed in no patient at 2.5 V, in 1 patient at 1.5 V, and in 5 patients at 1.0 V. At the randomization to the 1.0-V output, 6 patients had pacing thresholds of 0.5 V or less, and 6 patients had pacing thresholds >0.5 V. The frequency of back-up pulses in the 2 groups was not significantly different, 6.4% ± 8.6% and 5.7% ± 2.6%. Conclusions The frequency of back-up pulses was significantly higher at 1.0-V output than at 1.5-V and 2.5-V output. This also applied to patients with pacing thresholds of ≤0.5 V. Fixed low outputs seem not to be absolutely safe between 2 follow-ups in patients who are dependent on a pacemaker, even when the output has a 100% voltage safety margin above the pacing threshold. When patients with pacemakers programmed to a low ventricular output have symptoms of ineffective pacing, an intermittent increase of the pacing threshold should be carefully ruled out. (Am Heart J 2002;143:1009-11.)     

Endogenous nitric oxide prevents myocardial ischemia in patients with hypertension and left ventricular hypertrophy

Background Left ventricular hypertrophy (LVH) caused by chronic pressure overload is associated with increased risk of myocardial ischemia without epicardial coronary artery disease. We aimed to test the hypothesis that endogenous nitric oxide (NO) prevents myocardial ischemia in patients with LVH. Methods Epicardial coronary blood flow (Doppler wire and quantitative coronary arteriography) and myocardial lactate metabolism (paired arterial and coronary sinus blood sampling) were measured in 12 patients with hypertension, LVH, and angiographically normal epicardial coronary arteries and in 7 control subjects. Measurements were done under 3 pacing protocols: with no treatment (control), with intracoronary N^G-monomethyl-L-arginine (L-NMMA; NO synthesis inhibitor), and with intracoronary L-arginine (NO substrate). Results In control subjects the myocardial lactate extraction ratio was normal and stable during the 3 pacing protocols. In contrast, lactate uptake was significantly decreased from 0.21 ± 0.05 to 0.10 ± 0.06 (P <.05) during L-NMMA pacing in patients with LVH; in 6 of them, lactate production was demonstrated. After L-arginine administration, the lactate extraction ratio during pacing was normalized (0.18 ± 0.04) and lactate production was not observed in any patient. The level of myocardial lactate uptake at peak pacing after L-NMMA was correlated with that under untreated condition (P <.0001). Conclusions In patients with hypertension, LVH, and angiographically normal coronary arteries, inhibition of endogenous NO synthesis in the coronary circulation unmasked myocardial ischemia during tachycardia, and L-arginine reversed the adverse effects of L-NMMA. Although the precise mechanism remains to be determined, our results suggest that constitutive NO in the coronary circulation plays an anti-ischemic role in this population. (Am Heart J 2002;143:684-9.)     

Beta blockers normalize QT hysteresis in long QT syndrome

Objectives This study was performed to evaluate the impact of beta blockers on QT adaptation to heart rate during the exercise and recovery phases of exercise testing in long QT syndrome. Background Long QT syndrome is characterized by familial syncope and sudden death in the context of sudden heart rate changes. QT hysteresis has been proposed as a phenotypic marker of long QT syndrome, suggesting altered QT adaptation to changes in heart rate. Methods Fourteen patients with long QT syndrome (aged 26 ± 16 years, 6 male) and 10 healthy volunteers (aged 37 ± 11 years, 9 male) underwent graded exercise testing with continuous lead II electrocardiographic monitoring. Long QT patients underwent repeat assessment after 1 month of beta blockade. QT intervals at matching heart rates were compared during exercise and recovery to determine the effect of beta blockade on QT hysteresis, defined as the recovery QT peak interval subtracted from the exercise QT peak interval. Results In the 14 long QT syndrome patients, beta blockers slowed the resting heart rate without affecting the corrected QT interval (502 ± 52 ms baseline vs 481 ± 40 ms beta blocker, P = .17). The increase in heart rate with exercise was similar in the 3 groups (P = .73). Exaggerated hysteresis of the QT interval was seen in the patients with long QT syndrome at baseline compared with controls (46 ± 19 ms vs 19 ± 11 ms 1 minute into recovery, P = .006). Beta blockers had minimal effect on the QT interval but markedly reduced hysteresis with minimal separation of the exercise and recovery QT/RR curves (25 ± 35 ms 1 minute into recovery, P = .027). The combined curve separation at all 6 time points analyzed was 165 ± 95 ms in patients with long QT syndrome at baseline, 40 ± 131 ms after beta blockade, and 29 ± 30 ms in control subjects (P = .002). Comparison of the beta blocker effect on hysteresis in the 2 genotypes suggested a greater reduction in hysteresis in the 3 patients with long QT syndrome 1 compared with the 11 patients with long QT syndrome 2. Conclusions Beta blockers reduce QT hysteresis in patients with long QT syndrome to values seen in normal patients. This improved QT adaptation to changes in heart rate may explain the clinical benefit of beta blockers in long QT syndrome. (Am Heart J 2002;143:528-34.)     

Natural history of small and medium-sized side branches after coronary stent implantation

Objective Our purpose was to identify angiographic and procedural predictors for acute and late side branch occlusion after coronary stent implantation. Methods We evaluated 185 patients with 185 lesions with 255 side branches with a mean reference diameter of 1.45 ± 0.38 mm; the lesions were covered by 240 stents. Angiographic follow-up was completed in 99 patients with 133 side branches 206 ± 120 days after stent implantation and clinical follow-up was available in 136 patients. Side branch occlusion (SBO) was defined as a Thrombolysis In Myocardial Infarction (TIMI) flow ≤1. Results Acute SBO affected 54 side branches in 49 patients and was not associated with death or Q-wave infarction. By logistic regression, independent predictors for acute SBO were (1) the reference side branch diameter (RLD) at baseline (OR [odds ratio] 0.217, 95% CI 0.07-0.67, P = .008); (2) an ostial side branch stenosis before stenting (OR 2.96, 95% CI 1.26-6.95, P = .013); (3) the involvement of the side branch origin within the lesion of the parent vessel (OR 2.77, 95% CI 1.17-6.57, P = .021); and (4) the balloon-to-artery ratio (OR 4.66, 95% CI 1.18-18.42, P = .028). Among the initially occluded side branches, 81.8% were spontaneously reperfused at follow-up. Late SBO involved 12% of the side branches without impaired antegrade flow after stenting and was predicted by the initial RLD of the side branch (OR 0.07, 95% CI 0.01-0.8, P = .032). Chronic SBO occurred in 13.5% of cases and was also predicted by the baseline RLD (OR 0.13, 95% CI 0.02-0.8, P = .028). Conclusions Acute SBO after stenting occurred in 21.2% of cases and had a benign course. Most acutely occluded side branches underwent late spontaneous reperfusion. A baseline side branch diameter >1.4 mm predicted a preserved antegrade flow immediately after stent implantation, as well as during follow-up. (Am Heart J 2002;143:627-35.)     

Beneficial effects of metoprolol on myocardial sympathetic function: Evidence from a randomized,placebo-controlled study in patients with congestive heart failure

Background We sought to investigate whether β-blockers exert a presynaptic effect in the myocardium as measured by ¹²³I-metaiodobenzylguanidine. Methods The study comprised 59 patients with congestive heart failure, New York Heart Association class II or III, and left ventricular ejection fraction <35%. After an open label titration phase, patients were randomized to their maximal tolerable dose of metoprolol or placebo. Myocardial MIBG uptake was measured before the titration phase and after 6 months of treatment. Other parameters were maximal oxygen consumption, 6-minute walking test, plasma neurohormones, and echocardiographic parameters. Results We found a 21.9% increase in mean myocardial MIBG uptake after 6 months of treatment with metoprolol. In contrast, MIBG uptake decreased by 7.8% in the placebo group (P = 0.03 compared with metoprolol). Left ventricular end-diastolic diameter decreased from 74 ± 11 mm to 67 ± 10 mm (P < .05, within-group comparison) and LVEF increased from 25.3% ± 7.4% to 32.6% ± 9.6% (P < .05, within-group comparison) in the metoprolol group. Placebo-treated patients showed no significant changes. Comparison of changes in left ventricular end-diastolic diameter and LVEF between metoprolol and placebo did not reach statistical significance (P = 0.2). Conclusions This randomized, placebo-controlled study demonstrates that metoprolol has a presynaptic effect as measured by myocardial MIBG scintigraphy in both ischemic and nonischemic cardiomyopathy. (Am Heart J 2002;144:e3.)     

Coronary stent implantation in patients older than 75 years of age: clinical profile and initial and long-term (3 years) outcome

Objective The objective of this study was to compare the initial and long-term outcome of elderly and younger patients after coronary stent implantation. Methods The evolutions of 76 patients aged >75 years and of 860 patients aged ≤75 years who underwent consecutive stenting (from June 1991 to June 1997) were compared in a cohort study. Results The elderly patients had lower left ventricular ejection fractions (0.58 ± 0.14 vs 0.61 ± 0.13; P = .03) and more frequently had unstable angina (78.9% vs 55.3%; P <.0001), previous heart failure (10.5% vs 4.9%; P = .03), and multivessel disease (68.4% vs 58.3%; P = .08). After the procedure, the elderly patients showed a higher inhospital mortality rate (6.6% vs 2.4%; P = .03) and myocardial infarction rate (5.3% vs 1.7%; P = .04). The long-term follow-up period (mean, 3.2 ± 1.4 years; median, 3.0 years) showed in the elderly a higher mortality rate (15.4% vs 5.8%; P = .006), a lower rate of repeat revascularization (9.2% vs 19.7%; P = .04), and a similar incidence rate of major adverse cardiac events (27.7% vs 28.2%; P = .93). Multivariate analysis of the elderly group identified female gender (hazard ratio, 2.19; 95% CI, 1.18 to 4.06; P = .012) and presence of multivessel disease (hazard ratio, 2.35; 95% CI, 1.05 to 5.26; P = .037) as independent predictors of further events. Conclusion Patients aged >75 years have a less favorable baseline profile and higher inhospital and 3-year mortality rates. However, the incidence rate of major adverse cardiac events in the long term is acceptable and similar to that of younger patients. (Am Heart J 2002;143:620-6.)     

Comparison of 2-dimensional echocardiography and myocardial perfusion imaging for diagnosing myocardial infarction in emergency department patients

Background Both 2-dimensional echocardiography and myocardial perfusion imaging (MPI) with technetium-99m based agents have been used to identify patients in the emergency department with myocardial infarction (MI). However, the inclusion of small numbers of patients in prior studies limits the accurate assessment of sensitivity of the 2 techniques. Methods Gated MPI was used as part of the initial triage process in patients initially considered at low to moderate risk for acute coronary syndromes (no ST elevation or depression). Patients diagnosed with MI also underwent echocardiography. MPI results were considered positive if there was a perfusion defect associated with abnormal wall motion or thickening, and echocardiographic results were considered positive if there were segmental wall motion abnormalities or ejection fraction of less than 40%. Results Both tests were performed on 141 patients. The sensitivities for MI for echocardiography (91%; 95% CI, 86%-95%) and MPI (89%; 95% CI, 83%-94%) were similar. Patients who had either negative echocardiographic results (peak creatine kinase level [CK], 325 ± 206 vs 582 ± 614 U/L; P = .003) or negative MPI results (peak CK, 313 ± 227 vs 590 ± 620 U/L; P = .001) had smaller MIs as estimated with peak CK values. Ejection fraction was highly correlated between the 2 techniques (r = 0.82; P <.001). Conclusion Both echocardiography and MPI have a high sensitivity for identifying patients in the emergency department who have MI. False negative studies with either technique were associated with small MIs. (Am Heart J 2002;143:659-67.)     

Effect of atorvastatin and pravastatin on serum C-reactive protein

Background Extra-lipid effects of statins, such as anti-inflammatory actions, may contribute to their clinical benefit. These effects, with important implications for the concept of a statin “class effect,” may be drug specific or may be related to the extent of lipid lowering. Methods We randomized 130 patients to treatment with either atorvastatin (80 mg daily, n = 63) or pravastatin (40 mg daily, n = 67), and measured serum lipids, C-reactive protein, and fibrinogen at baseline and after 3 months of therapy. Results Mean C-reactive protein (CRP) levels were significantly reduced in both groups, with a 36% reduction in the atorvastatin group (0.39 ± 0.36 to 0.25 ± 0.27, P = .001) and a 22% reduction observed in the pravastatin group (0.40 ± 0.33 to 0.31 ± 0.32, P = .003). A reduced or unchanged CRP level was seen in 67.2% of pravastatin-treated patients (45/67) and 73% of atorvastatin- treated patients (46/63) (P = .47). There was no difference between drugs in either the absolute or relative reductions in CRP levels. However, whereas the reduction of CRP with pravastatin was unrelated to the degree of low-density lipoprotein reduction (r = −.05, P = .69), atorvastatin-induced CRP reductions correlated directly to the change in low-density lipoprotein-C (r = .33, P = .009). Conclusions High-dose atorvastatin and pravastatin both reduce CRP levels. However, whereas pravastatin's effect on CRP is independent of lipid-lowering efficacy, these data suggest that lipid-dependent mechanisms are, at least in part, active in atorvastatin-treated patients. (Am Heart J 2003;145:e8.)     

Implantation of CD133 Stem Cells in Patients Undergoing Coronary Bypass Surgery: IMPACT-CABG Pilot Trial

Background

The Implantation of Autologous CD133⁺ Stem Cells in Patients Undergoing CABG (IMPACT-CABG) trial is investigating the feasibility, safety, and efficacy of intramyocardial injections of autologous CD133⁺ stem cells during coronary artery bypass grafting (CABG) in patients with chronic ischemic cardiomyopathy. We are reporting the results of the first 5 open-label patients.

Methods

Bone marrow was harvested from iliac crests and stem cells were isolated using the CliniMACS CD133⁺ Reagent System (Miltenyi Biotec, GmbH, Bergisch Gladbach, Germany). Patients received CABG, followed by CD133⁺ cellular injection in the revascularized hypokinetic myocardium.

Results

Five males New York Heart Association (NYHA) class III patients aged 64 ± 10 years were treated. Immunomagnetic cell processing allowed an average of 100 ± 48-fold enrichment in CD133⁺ cells, with 92 ± 11% recovery after selection. Mean number of CD133⁺ cells injected was 8.4 ± 1.2 million. There were no protocol-related complications during the 18-month follow-up and all patients improved to NYHA class I. Six-month echocardiography showed no significant improvement in left ventricular ejection fraction (34 ± 2% at baseline vs 38 ± 12%: P = 0.50). However, cardiac magnetic resonance showed that systolic wall thickening increased from 15.0 ± 10.5% to 29.0 ± 22.1% (P = 0.01). In addition, mean segmental wall thickness also improved in comparison with baseline (10.7 ± 2.7% to 12.1 ± 4.8%; P < 0.01).

Conclusions

This work represents the first Canadian experience with CD133⁺ stem cells for the treatment of chronic ischemic cardiomyopathy. These results demonstrate the initial safety and feasibility of the IMPACT-CABG pilot trial. Subsequent patients are now being randomized to receive either CD133⁺ stem cell or placebo.     

Left ventricular function in atrial fibrillation during overdrive pacing

Objective Our purpose was to measure the effect of ventricular pacing in patients with atrial fibrillation (AF) on stroke volume and cardiac output. Background Unceasing variation in cycle length in AF decreases stroke volume and cardiac output. Because ventricular-inhibited pacing after atrioventricular node ablation has been reported to improve left ventricular performance, we tested the hypothesis that overdrive pacing would produce a similar benefit by regularizing cycle length. Methods and Results We studied 18 patients with chronic AF and permanent pacemakers. The aortic time velocity integral (TVI) was measured with continuous-wave Doppler and was used as a surrogate measure of stroke volume (stroke volume = TVI × aortic valve area, and aortic valve area is constant whether in AF or during pacing). For each patient, the linear relation between preceding cycle length and TVI in AF was used to estimate relative stroke volume (TVI compared within each patient) at a preceding cycle length of 666 ms in AF, and a similar comparison between AF and pacing was made at the minimum allowable pacing rate. Relative stroke volume in AF was then compared with relative stroke volume at both the fixed cycle (666 ms) and the minimum allowable rate. During pacing at 666 ms, relative stroke volume increased significantly by 18% (t = 2.8, P = .048), but there was no difference in cardiac output during pacing at the minimum possible rate and the corresponding preceding cycle length in AF. Conclusion Our data suggest that regularization of ventricular rhythm by overdrive pacing in patients with AF only improves stroke volume (and by extension, cardiac output) at pacing rates at the outer limit of and above the normal physiologic range. (Am Heart J 2002;143:827-32.)     

Nutritional supplementation with MyoVive repletes essential cardiac myocyte nutrients and reduces left ventricular size in patients with left ventricular dysfunction

Background Congestive heart failure depletes the myocardium of carnitine, coenzyme Q10 (CoQ10), and taurine—substances known to influence mitochondrial function and cell calcium. We hypothesized that feeding patients a nutritional supplement that contained carnitine, CoQ10, and taurine would result in higher myocardial levels of these nutrients and improve left ventricular function. Methods Forty-one patients who underwent aortocoronary artery bypass with an ejection fraction ≤40% at referral were randomly assigned to a double-blind trial of supplement or placebo. Radionuclide ventriculography was performed at randomization and before surgery. Surgical myocardial biopsies, adjusted for protein content, were analyzed for carnitine, CoQ10, and taurine levels. Results The groups were well matched. Minor exceptions were supplement group versus placebo group for digoxin use (7 vs 0, respectively; P = .009) and age (62 ± 11 years vs 69 ± 5 years, respectively; P = .04). There were significantly higher levels in the treated group compared with the placebo group for myocardial levels of CoQ10 (138.17 ± 39.87 nmol/g wet weight and 56.67 ± 23.08 nmol/g wet weight; P = .0006), taurine (13.12 ± 4.00 μmol/g wet weight and 7.91 ± 2.81 μmol/g wet weight; P = .003), and carnitine (1735.4 ± 798.5 nmol/g wet weight and 1237.6 ± 343.1 nmol/g wet weight; P = .06). The left ventricular end-diastolic volume fell by −7.5 ± 21.7 mL in the supplement group and increased by 10.0 ± 19.8 mL in the placebo group (P = .037). Conclusions Supplementation results in higher myocardial CoQ10, taurine, and carnitine levels and is associated with a reduction in left ventricular end-diastolic volume in patients with left ventricular dysfunction before revascularization. Because the risk of death for surgical revascularization is related to preoperative left ventricular end-diastolic volume, supplementation could improve outcomes. (Am Heart J 2002;143:1092-100.)     

Serum glucose and lipid levels in adult congenital heart disease patients

Atherosclerosis has been correlated with known cardiovascular risk factors such as serum glucose or lipid levels. Because congenital heart disease patients tend to survive until adulthood, atherosclerosis has also become a matter of concern in these patients. One hundred fifty-eight congenital heart disease patients and 152 patients selected at random from the population were studied and compared to determine serum glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, and triglycerides levels. Both groups had similar socioeconomic status levels and the same environmental influences. Significant differences were seen between congenital heart disease patients and the control group, after sex, age, and body mass index adjustment, in fasting plasma glucose (97.7 [94.2-101.2] vs 86.9 [83.2-90.7], P < .001), total cholesterol (171.5 [165.7-177.3] vs 199.8 [90.7-206.0], P < .001), LDL cholesterol (103.9 [98.8-108.8] vs 123.8 [118.5-129.1], P < .001), and high-density lipoprotein cholesterol (48.1 [46.2-50.0] vs 54.2 [52.1-56.2], P < .001) levels. Nonsignificant differences were seen in triglycerides concentrations. Those patients with ventricular septal defect, coarctation of the aorta, and cyanosis had the lowest total cholesterol and LDL cholesterol concentrations. Congenital heart disease patients have lower plasma cholesterol concentrations and higher serum glucose levels than noncongenital ones.     

Effectiveness of a novel serotonin blocker,sarpogrelate, for patients with angina pectoris

Background We have recently demonstrated that a single oral administration of sarpogrelate, a 5-HT_2A receptor antagonist, may improve exercise capacity in anginal patients with well-developed collaterals. The aim of the current study was to investigate the effectiveness of 2-week treatment with sarpogrelate on anginal symptoms and exercise capacity in anginal patients. Methods A treadmill exercise test was repeated after a 2-week period with or without sarpogrelate (100 mg 3 times a day) in 20 patients with angiographically proven stable angina. Anginal symptoms and daily physical activity by the specific activity scale (SAS) were also evaluated. Results Treatment with sarpogrelate significantly increased the SAS score and prolonged exercise time to the onset of 0.1-mV ST depression. When data were analyzed in a subgroup of patients (n = 8) with well-developed collaterals, the treatment with sarpogrelate decreased the number of anginal attacks (control vs sarpogrelate, 3.0 ± 2.8 vs 0.9 ± 1.1/2 weeks, P < .05), increased the SAS score (5.2 ± 1.6 vs 6.2 ± 1.3 METS, P < .05), and increased the time to the onset of 0.1-mV ST depression (235 ± 84 vs 295 ± 127 seconds, P < .05). In addition, the double product at the onset of 0.1-mV ST depression increased by 15% (P < .05) after sarpogrelate. In contrast, all parameters were not significantly changed after sarpogrelate treatment in patients (n = 12) without well-developed collaterals. Conclusions These findings indicate the therapeutic effectiveness of sarpogrelate for anginal patients, especially for patients with well-developed collaterals. (Am Heart J 2002;144:e1.)     

Impact of geographic miss on adjacent coronary artery segments in diffuse in-stent restenosis with beta-radiation therapy: angiographic and intravascular ultrasound analysis

Background The impacts of geographic miss on edge restenosis have not been sufficiently evaluated. Methods β-Radiation therapy with rhenium 188-filled balloon after rotational atherectomy for diffuse in-stent restenosis was performed in 50 patients. We evaluated the impacts of geographic miss on adjacent coronary artery segments beyond the stent by angiographic (QCA) and intravascular ultrasound (IVUS) analysis in 50 irradiated lesions and 100 edges. Serial IVUS and QCA comparisons between postradiation and 6 months' follow-up were available in 44 and 47 of 50 patients, respectively. QCA measurements of minimal lumen diameter (MLD) and IVUS analysis were performed in the reference and radiation segments. Edges that were touched by the angioplasty balloon but were not adequately covered by radiation constituted the geographic miss edges. Results Geographic miss was observed in 55.6% and 52.6% in QCA and IVUS analysis, respectively. Edge restenosis after radiation therapy in 3 patients was associated with geographic miss. In contrast to uninjured edges (postradiation 2.9 ± 0.6 mm to follow-up 2.8 ± 0.6 mm, P = .292), MLD in the radiation segment by QCA analysis significantly decreased from 2.7 ± 0.4 mm to 2.4 ± 0.6 mm in geographic miss edges (P = .002). IVUS analysis showed that significant positive remodeling in the radiation segment occurred in uninjured edges (vessel area from 15.4 ± 4.4 mm² to 15.8 ± 4.4 mm², P = .001) but not in geographic miss edges (vessel area from 12.8 ± 3.6 mm² to 13.0 ± 3.6 mm², P = .119). Conclusion The geographic miss might be one of the predictors, which resulted in decreased MLD at follow-up in β-radiation therapy. Sufficient lesion coverage with radiation might be associated with positive remodeling in the radiation segment. (Am Heart J 2002;143:327-33.)     

Cardiac troponin I: a potential marker of exercise intolerance in patients with moderate heart failure

Background In severe heart failure, increased values of cardiac troponins have been detected during decompensation. In this study, we investigated whether an increase of cardiac troponin I can be observed after symptom-limited exercise and after an exercise training session in patients with moderate heart failure. Methods Twenty-seven patients with moderate heart failure (New York Heart Association II-III, ejection fraction 31% ± 8%) were compared with 9 patients with mild heart failure and 10 subjects without heart failure. They underwent a symptom-limited exercise test and a bicycle exercise training session at >80% of maximal heart rate over 20 to 30 minutes. Plasma cTnI levels were measured at baseline, after symptom-limited exercise (hourly for 5 hours), and after training (4 and 10 hours). Results Patients with moderate heart failure showed an increase of cTnI from 37 ± 49 pg/mL to 73 ± 59 pg/mL (P < .001) after symptom-limited exercise. Four patients with moderate and 1 with mild heart failure and normal cTnI values at rest showed an increase of cTnI above 100 pg/mL after acute exercise but not after training. Subjects without heart failure had lower cTnI levels at rest and significantly lower values after symptom-limited exercise and training (P < .05 for each). Conclusion Patients with symptomatic heart failure reveal an increase of cTnI after symptom-limited exercise at levels that indicate minor myocardial damage. The prognostic impact of this finding should, therefore, be further investigated. (Am Heart J 2002;144:351-8)     

Cardiac dimension and function in patients with childhood onset growth hormone deficiency,before and after growth hormone retreatment in adult age

Background Growth hormone (GH) replacement during childhood has been shown to increase stature; however, there is little information on its long-term effect on the heart is not yet clear. The aim of this study was to assess cardiac size and function in patients with childhood-onset GH deficiency in whom GH treatment had been stopped at the achievement of final height and the effect of a second course of GH replacement in adult age. Methods Cardiac dimensions and function, obtained with echocardiography, of 21 patients (5 women and 16 men, mean age 28 ± 8 years), all of whom were treated during childhood, were compared with 21 age- and sex-matched healthy control subjects. Eight of these patients (2 women and 6 men, mean age 28 ± 8 years) were given a second course of GH replacement therapy for 15 ± 3 months. Results The stature and all cardiac dimensions of patients with GH deficiency who were treated during childhood were significantly smaller than those of the control subjects. After the second course of GH in adulthood, the only significant change observed was an increase in left ventricular (LV) mass (93 ± 21 vs 106 ± 24 g, P = .007) and LV mass index (59 ± 12 vs 66 ± 13 g/body surface area, P = .005). Conclusion The stature and cardiac dimensions of patients with childhood-onset GH deficiency measured in adult age were smaller than those of control subjects, despite long-term GH replacement therapy during childhood. A second course of GH treatment during adulthood caused a significant increase in the estimated LV mass index in patients with both isolated and multiple pituitary hormone deficiency. (Am Heart J 2003;145:549-53.)     

Effects of exercise training in patients with heart failure: the Exercise Rehabilitation Trial (EXERT)

Background The purpose of this study was to examine the effects of exercise training on functional capacity in patients with heart failure. Methods One hundred eighty-one patients in New York Heart Association class I to III, with ejection fraction <40% and 6-minute walk distance <500 meters, were recruited into a randomized, controlled, single-blind trial comparing 3 months of supervised training, then 9 months of home-based training with usual care. Results There was a significant increase in 6-minute walk distance at 3 and 12 months but no between-group differences. Incremental peak oxygen uptake increased in the exercise group compared with the control group at 3 months (0.104 ± 0.026 L/min vs 0.025 ± 0.023 L/min; P = .026) and 12 months (0.154 ± 0.074 L/min vs 0.024 ± 0.027 L/min; P = .081). Compared with the control group, significant increases were observed in the exercise group for arm and leg strength. No significant changes were observed in cardiac function or quality of life. Adherence to exercise was good during supervised training but reduced during home-based training. Conclusions Exercise training improves peak oxygen uptake and strength during supervised training. Over the final 9 months of the study, there was little further improvement, suggesting that some supervision is required for these patients. There were no adverse effects on cardiac function or clinical events. (Am Heart J 2002;144:23-30.)     

Left atrial thrombus predicts transient ischemic attack in patients with atrial fibrillation

Background Atrial fibrillation (AF) is widely accepted as a direct cause of cardioembolic stroke from left atrial (LA) thrombus formation. However, the relationship between LA thrombus and transient ischemic attack (TIA) in patients with AF is less well established. Methods Two hundred sixty-one adult patients (mean age 66 ± 11 years, 220 men and 41 women) with AF undergoing transesophageal echocardiography (TEE) were prospectively followed up for TIA (mean duration 30.3 ± 20.6 months). Results LA thrombus was present in 18% (n = 46) and LA spontaneous echocardiographic contrast in 50% (n = 131) of the group. Nineteen of 261 patients had TIA during follow-up. Multivariate logistic regression showed congestive heart failure (CHF) as the only predictor of TIA when a model of clinical variables was constructed (odds ratio [OR] 2.7, P = .04). Age, sex, hypertension, and use of warfarin or aspirin were not predictors. When TEE variables were added to the model, LA thrombus became the only predictor of TIA (OR 7.7, P = .0001). Survival free of TIA (Kaplan-Meier) was significantly less (P = .0001) in patients with LA thrombus compared with those without, and the annual TIA event rate was 9.2% per year versus 1.9% per year (P <.0001), respectively. Conclusions To our knowledge, this is the first prospective study documenting an association between LA thrombus and TIA in patients with AF. Other TEE variables, including aortic atheromata, and clinical parameters were not independently predictive. These data support a likely thromboembolic mechanism for TIA from LA thrombus in patients with AF.     

Hepatocyte growth factor as a potential predictor of the presence of atherosclerotic aorto-iliac artery disease

Background Hepatocyte growth factor (HGF), a member of the endothelial-specific growth factors with the greatest mitogenic activity, may play a role in the protection and/or repair of vascular endothelial cells injured by atherosclerosis. As a result, plasma HGF concentration may increase in response to endothelial cell damage. To test this hypothesis, we measured plasma concentrations of HGF in patients with or without aorto-iliac artery atherosclerotic disease. Methods One hundred ten consecutive patients who underwent coronary angiography were enrolled in this study. Abdominal aortography was performed after coronary arteriography to determine whether aorto-iliac artery atherosclerotic disease was present. Peripheral venous blood samples were obtained to measure the plasma HGF concentration. Results Aortography revealed aorto-iliac atherosclerotic disease in 35 patients (32%). The plasma HGF concentration was significantly higher in patients with arteriosclerotic lesions (0.35 ± 0.11 ng/mL) than in patients without atherosclerotic lesions (0.27 ± 0.09 ng/mL, P = .0002). On the basis of multiple logistic regression analysis of the relationships between coronary risk factors, age, sex, severity of coronary artery disease, plasma HGF concentration, and the presence of arteriosclerotic lesions, plasma HGF concentration (P = .0005) and age (P = .035) were found to predict independently the presence of aorto-iliac arteriosclerosis. Conclusion Plasma HGF concentration can be used to predict the presence of arteriosclerotic lesions in the region from the abdominal aorta to the femoral arteries. (Am Heart J 2002;143:272-6.)