Effect of aprindine on heart rate variability indices in patients with ischemic heart disease

BACKGROUND: Decreased heart rate variability indices (HRV) are associated with untoward outcome of patients with ischemic heart disease (IHD). Most class I antiarrhythmic agents decrease HRV, but aprindine (a new class I antiarrhythmic agent) is reported to increase HRV in patients without ischemia. HYPOTHESIS: The study was undertaken to determine whether apridine might increase HRV in patients with IHD. METHODS: To investigate the effect of aprindine on HRV in patients with IHD, we performed 24-h ambulatory electrocardiogram (ECG) at the end of placebo and aprindine (60 mg daily) treatment phases on 38 patients with IHD and at least isolated premature ventricular contractions (PVC). The study protocol utilized a single blind, 4-week, placebo-controlled design. Heart rate variability from ambulatory ECG included SDNN (ms), SDANN (ms), SD (ms), rMSSD (ms), pNN50 (%); frequency analysis of HRV consisting of total (ms, 0.01-1.00 Hz), low (ms, 0.04-0.15 Hz), and high (ms, 0.15-0.40 Hz) components. RESULTS: Study patients were divided into three groups according to the severity of IHD and antiarrhythmic efficacy of aprindine. Group 1 consisted of 15 patients with angina with single-vessel disease, and Group 2 was composed of 10 patients with either multivessel disease or post myocardial infarction; PVCs decreased in both groups as result of aprindine treatment. Group 3 consisted of 13 patients who showed no decreased PVC after aprindine treatment. RMSSD increased, and pNN50 and high-frequency spectra tended to increase in Group 1, while SD, rMSSD, pNN50, and total and low-frequency spectra decreased in Group 3; no significant changes were observed in Group 2. Aprindine significantly augments vagal activity, as reflected by the increase of rMSSD, pNN50, and high-frequency spectra in mild IHD. CONCLUSION: These salutary effects are less in more severe IHD, but aprindine does not aggravate HRV. Thus, if there are salutary effects on arrhythmias and no proarrhythmic effects, aprindine could be prescribed to patients with IHD without concern about decreasing HRV.     

Predictors of prognosis after angioplasty in the unprotected left main coronary artery

OBJECTIVES: The short-term and long-term predictors of outcome after coronary angioplasty in the unprotected left main coronary artery were investigated. METHODS: The procedure was performed in 122 consecutive patients for de novo lesions without myocardial infarction in our hospital between April 1986 and October 1998, including 16 emergency cases. Procedures were directional coronary atherectomy (73 patients), balloon angioplasty (31 patients), and stent implantation (18 patients). There were 101 males and mean age was 68 +/- 10 years. Follow-up angiography was performed in 98% of discharged patients, and all patients were clinically followed up for more than 1 year. Clinical and angiographic predictors of in-hospital and long-term outcome were evaluated. RESULTS: The in-hospital mortality was 5.7% (7 of 122 patients). Multivariate analysis revealed that more patients were admitted as emergency cases (57% vs 10%, p = 0.0088), with left ventricular ejection fraction < or = 35% (57% vs 22%, p = 0.029) and renal failure (43% vs 3%, p = 0.0004) finally died. Mean follow-up period was 3.5 years. Estimated survival rate was 77.1%, and cardiac-death free survival rate was 81.0% at 5 years by the Kaplan-Meier method. Univariate analysis showed that the predictors of cardiac death were emergency angioplasty, renal failure, decreased left ventricular ejection fraction, multivessel disease and unstable angina and/or congestive heart failure. Cox's regression model showed that renal failure (p = 0.0004) and multivessel disease (p = 0.0075) were significant predictors of long-term prognosis. CONCLUSIONS: Renal failure was the strongest predictor of outcome after unprotected left main coronary artery angioplasty.     

Effect of diltiazem on silent ischemic episodes, plasma bradykinin and prostaglandin metabolism.

Plasma bradykinin and prostaglandin metabolism are related to the anginal pain modulating system in patients with ischemic heart disease. We carried out a placebo controlled single blind test of diltiazem (30 mg three times a day) in 15 patients with chronic stable angina. The effect of diltiazem was evaluated by exercise treadmill testing and 48-h ambulatory electrocardiographic monitoring. Plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels were determined by radioimmunoassay prior to and during diltiazem therapy. Diltiazem significantly increased the exercise time and reduced episodes of angina. Diltiazem, however, did not appreciably improve either the frequency of silent myocardial ischemic episodes or the total duration of the silent myocardial ischemic episodes. Diltiazem also tended to decrease plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels. When ischemic episodes on ambulatory electrocardiographic monitoring are categorized according to heart rate change at the onset of episode (type A, preceded by heart rate increase > or = 5 beats/min; type B, no preceding heart rate increase), diltiazem was only effective on type A ischemic episodes as well as on symptomatic ischemia. Further, bradykinin was significantly decreased by diltiazem only in patients with exercise-induced silent ischemia or no exercise-induced ischemia, while the thromboxane B2/6-keto-prostaglandin F1 alpha ratio was unaffected by the administration of diltiazem. Thus, silent and symptomatic ischemia may be associated with different bradykinin and prostaglandin responses.     

Comparison of the self-expanding Radius stent and the balloon-expandable Multilink stent for elective treatment of coronary stenoses: a serial analysis by intravascular ultrasound.

We compared the outcome of the self-expanding Radius stent and the balloon-expandable Multilink stent serially by angiography and intravascular ultrasound. Successful stent deployment was achieved in 66 lesions of 56 stable angina patients (34 lesions with Radius stents and 32 lesions with Multilink stents). At follow-up, there were no significant differences in minimal lumen diameter or percent diameter stenosis between the groups, nor in restenosis rates, although the Radius stent group rate was slightly lower (23.5% vs. 31.3%). In the Radius stent group, stent cross-sectional area (CSA) increased gradually after implantation until the 6-month follow-up (8.37 +/- 1.83 to 10.16 +/- 2.59 mm(2); n = 15), giving a larger CSA (P = 0.03) than the Multilink stent group, which decreased (9.00 +/- 2.05 to 8.27 +/- 2.15 mm(2); n = 17). The lumen CSA was also slightly larger (6.82 +/- 3.06 vs. 5.84 +/- 1.85 mm(2); P = 0.29) in the Radius stent group. These findings indicated that the Radius stent enlarged progressively after implantation, which might be useful for prevention of restenosis.     

Effect of infarcted myocardium on diagnostic accuracy of exercise echocardiography for detecting noninfarct-related coronary artery lesions

Background The utility of exercise echocardiography for evaluating remote ischemia due to noninfarct-related artery (n-IRA) lesions in patients with prior myocardial infarction has not been established.Methods Quantitative coronary angiography and treadmill exercise echocardiography were performed within 2 weeks in 115 patients with prior myocardial infarction (>6 weeks) and 224 patients without myocardial infarction. Coronary lumen diameter stenosis ≥50% (by angiography) and the lack of a hyperdynamic response on exercise echocardiography were considered significant. Myocardial infarction size was defined as the number of myocardial segments with severe hypokinesis, akinesis, or dyskinesis on echocardiography at rest.Results For detection of n-IRA lesions in patients with prior myocardial infarction, the sensitivity of exercise echocardiography was similar (78% vs 79%, P = not significant), however, the specificity was significantly lower (77% vs 91%, P < .01) than for detection of significant stenoses in patients without prior myocardial infarction. Angiographic percent-diameter stenosis, presence of collateral vessel, achieved exercise level, and presence of peri-infarct ischemia did not affect the specificity of exercise echocardiography. However, the specificity of exercise echocardiography was significantly lower (69% vs 84%, P < .05) in patients with echocardiographically large infarction (infarction size ≥2) than in patients with small infarction (infarction size <2).Conclusion In patients with prior myocardial infarction, exercise echocardiography showed low specificity for detection of noninfarct-related artery lesions, especially in patients with echocardiographically large myocardial infarction. These characteristics of treadmill exercise echocardiography should be considered when this technique is applied for patients with healed myocardial infarction. (Am Heart J 2003;145:162-8.)     

Coronary remodeling of proximal and distal stenotic atherosclerotic plaques within the same artery by intravascular ultrasound study

The aim of this intravascular ultrasound study was to compare the type and the degree of vessel remodeling in proximal and distal de novo lesions within the same coronary artery in patients with stable angina pectoris. Seventy-six de novo coronary artery lesions in 38 coronary arteries of 38 patients were imaged by intravascular ultrasound. The vessel area (VA) within the external elastic lamina and the lumen area (LA) were measured, and the wall area (VA-LA) was calculated at the lesion site, and the proximal and distal reference sites. The VA ratio was defined as (lesion VA/average of the proximal and distal reference VAs) to represent the degree of vessel remodeling. The proximal coronary segments showed compensatory enlargement more often (68% vs 29%, p < 0.01) than the distal segments, and the VA ratio at the lesion site was significantly larger (1.1 +/- 0.3 vs 1.0 +/- 0.2, p <0 .01) in proximal segments than in distal segments. The type of coronary remodeling was discordant in 61% and concordant in only 39% of coronary arteries between the proximal and distal segments. The type of coronary remodeling of proximal and distal coronary lesions was inhomogeneous, even within the same vessel. Proximal coronary segments showed more prominent compensatory enlargement than distal segments, which have a similar degree of luminal narrowings.     

Plasma bradykinin and prostaglandin metabolism and exercise testing in patients with silent myocardial ischemia compared with patients with painful myocardial ischemia

Bradykinin, alone or in combination with prostaglandin, is thought to produce pain in patients with coronary heart disease. To elucidate this further, we have investigated and compared serum bradykinin, TXB2 and 6 KPGF1 alpha levels in patients with silent myocardial ischemia (SMI, n = 18), painful myocardial ischemia (PMI, n = 8) and normal subjects (NL, n = 18). In addition, SMI and PMI subjects were given exercise testing and the results then compared. After Holter monitoring for 48 hours, exercise testing was performed. Blood was sampled in the morning between the Holter and exercise regimen. Maximal heart rate, systolic blood pressure and the double products were not significantly different between the SMI and PMI groups. The duration of exercise for the SMI group was 7.08 +/- 2.1 min vs 5.9 +/- 1.9 in the PMI group (p less than 0.10). Plasma bradykinin was 14 +/- 3 pg/ml in the SMI group and 15 +/- 3 in the PMI group (N.S), whereas it was 7 +/- 4 in the NL (p less than 0.05). The TXB2/6KPGF1 alpha for the SMI group was 1.3 +/- 0.3, which was significantly higher than that for the NL group (0.8 +/- 0.3, p less than 0.01), though this did not greatly differ from the PMI group (1.2 +/- 0.3). These results suggest that SMI patients under Holter monitoring who manifest no symptoms but show significant ST segment depressions must receive the same careful attention given to PMI patients. In both group of patients bradykinin and prostaglandin metabolism is similarly changed, as was demonstrated by exercise stress testing.