Aortic dissection is an acute cardiovascular disease associated with high mortality and morbidity. Although uncommon, recent studies have shown that the incidence of this catastrophic disease is steadily increasing. Unfortunately, the disease is still not well recognized on clinical presentation due to lack of specific signs and symptoms. As early diagnosis and initial management are critical for survival, we focused on developing a biochemical diagnostic approach for this disease given its meritorious properties in use in the acute clinical situation and additional projected combined use with established imaging modalities. Studies using an assay developed against smooth muscle myosin heavy chain, a protein which is released from the aortic medial smooth muscle cells on insult to the aortic wall, showed promising results for use of this assay in the diagnosis of aortic dissection. The background of this pioneering assay in addition to its clinical use are discussed in this review.

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It is not known whether changes in coronary hemodynamics may antedate the development of restenosis after percutaneous coronary transluminal angioplasty (PTCA). The purpose of this study was to evaluate the early change in coronary microvascular function in patients with late restenosis after PTCA. Coronary hemodynamics were studied in series before, immediately after, 2 weeks and 3 months after successful PTCA in 12 male patients with a single lesion of the left anterior descending coronary artery. In each patient, great cardiac venous flow (GCVF) and oxygen content were measured both at baseline and during hyperemia induced by adenosine infusion. The sequential changes of coronary hemodynamics were compared between patients with and without restenosis at 3 months after PTCA. Basic characteristics did not differ between the patients with (n = 6) and those without restenosis (n = 6). Luminal diameter stenosis (in percentage) was also similar between the two groups both before (79.2 ± 18.4% vs 83.0 ± 9.6%, p = NS) and up to 2 weeks after PTCA (25.8 ± 10.9% vs 28.5 ± 7.9%, p = NS). In patients without restenosis, basal and hyperemic GCVF was unchanged up to 2 weeks after PTCA. There was a significant increase in CFR 3 months after PTCA. In patients with restenosis, basal GCVF was significantly increased and hyperemic GCVF was unchanged immediately after PTCA. However, 2 weeks after PTCA, basal GCVF was decreased while luminal diameter was still preserved. In comparison with those without restenosis, patients with restenosis had significantly lower CFR before (1.98 ± 0.42 vs 2.69 ± 0.46, p = 0.019), immediately after (1.47 ± 0.27 vs 2.24 ± 0.47, p = 0.006) and 3 months after PTCA (1.51 ± 0.32 vs 3.40 ± 0.54, p = 0.001). In patients without restenosis, the recovery of coronary microvascular function was delayed up to 3 months after PTCA. In patients with late restenosis, basal coronary microvascular tone was altered within 2 weeks after PTCA suggesting early deterioration of coronary microvascular function before the development of angiographic restenosis.

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The time course and clinical significance of hyperkinetic wall motion(HWM) in a noninfarcted area in direct percutaneous transluminal coronary angioplasty(PTCA) has not been clearly demonstrated in patients with acute myocardial infarction(AMI). The objectives of this study were to examine the change in HWM during one-month follow-up after direct PTCA and determine its impact on the recovery of global left ventricular function. A total of 61 patients with first anteroseptal AMI and one vessel disease were evaluated. The paired left ventriculograms in the 30° right anterior oblique view taken both at baseline and follow-up were analyzed by the centerline and area length methods. The severity of hypokinesis was expressed by mean regional wall motion (standard deviation/chord) in most hypocontractile 50% of chords respondable to left anterior descending coronary artery area and HWM by mean regional wall motion in most hypercontractile 50% of chords of noninfarcted area. HWM increased from 0.18±1.07 to 0.48±1.30 (p=0.0608). The delta global ejection fraction (global ejection fraction at follow-up minus global ejection fraction at baseline) was correlated with both delta infarcted wall motion (infarcted wall motion at follow-up minus infarcted wall motion at baseline) and delta HWM (HWM at follow-up minus HWM at baseline) (r=0.576, p<0.0001, r=0.383, p=0.0036, respectively) during follow-up. Further, the delta global ejection fraction showed better correlation with delta (HWM + infarcted wall motion) [(HWM plus infarcted wall motion at follow-up) minus (HWM plus infarcted wall motion at baseline)] (r=0.593, p<0.0001). Direct PTCA resulted in the enhancement of HWM, which contributed to the increase in the global ejection fraction with the recovery of infarcted wall motion.

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The slow pathway potential or the slow potential serves as a useful marker in catheter ablation of the slow pathway. However, an anatomical approach without recording of these potentials is also an effective way to cure atrioventricular nodal reentrant tachycardia(AVNRT). Moreover, the origin of these potentials is a matter of controversy. We compared 2 approaches to ascertain whether or not recording of these potentials is necessary in eliminating the slow pathway and to estimate the usefulness of the simple anatomical approach. The study population consisted of 24 patients with a conventional approach (Group P) and 19 patients with an anatomical approach (Group A). In group A, the ablation site was determined by fluoroscopy, which was the lowest one-third of the area between the His bundle electrogram recorded position and the coronary sinus orifice at the right anterior oblique view, and just in front of and above the coronary sinus orifice also posterior to the His catheter at the left anterior oblique view where the His catheter was seen tangentially. The slow pathway was successfully ablated in all patients without any complications, including more than first-degree AV block. Although there were no significant differences in total energy or number of applications between the 2 groups, the procedure time was significantly shorter in group A (p<0.01). In conclusion, recording of the slow pathway potential or the slow potential is not always necessary for slow pathway ablation in the treatment of AVNRT. Because our anatomical approach was performed simply, effectively and safely, it is recommended for the slow pathway ablation of AVNRT.

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The purpose of the present study was to determine whether coronary microvascular function is impaired in patients with symptomatic mitral valve prolapse (MVP) and whether ischemia-like ECG, if present, is related to coronary microvascular dysfunction. Twenty chest pain patients with normal coronary angiograms and MVP proven by echocardiogram were included. Both treadmill exercise test (TET) and coronary hemodynamic study were done in each patient. Coronary flow reserve (CFR) was determined by measuring coronary sinus flow (CSF) or great cardiac venous flow (GCVF) both at baseline and after dipyridamole 0.56 mg/kg IV for 4 minutes (maximum). All patients were divided into 2 groups with either negative (TET-) or positive results of TET (TET+). Another 10 subjects with atypical chest pain, normal coronary angiograms, echocardiogram and TET were used as controls. There were no differences in GCVF, either at baseline or after dipyridamole infusion, among the 3 groups. Calculated CFR using GCVF was similar among the 3 groups. However, baseline CSF was higher in the TET+ group (TET- vs TET+ vs control: 77 ± 24 vs 96 ± 31 vs 75 ± 12 ml/min, p < 0.05) and maximum CSF was lower in the TET- group (TET- vs TET+ vs control: 167 ± 25 vs 219 ± 85 vs 238 ± 80 ml/min, p < 0.05). Calculated CFR using CSF was significantly reduced in both the TET- (2.26 ± 0.4) and TET+ groups (2.31 ± 0.7) as compared with the control subjects (3.18 ± 0.95, p < 0.01). There were no differences in any of the hemodynamic parameters between the TET- and TET+ groups. Coronary microvascular function could be impaired in patients with symptomatic MVP. Such impairment, when presented, was probably regional and outside the territory of the left anterior descending coronary artery. However, it was irrelevant to the presence of ischemic-like ECG during exercise.

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The aim of the present study was to analyze the incidence, clinical features and prognosis of patients with hypertrophic cardiomyopathy (HCM) which evolved into dilated phase HCM. The medical records of 43 patients with HCM followed up for at least 10 years were analyzed retrospectively. The patients were divided into two groups: group A consisting of patients with dilated-phase HCM defined by a left ventricular end diastolic dimension (LVDD) of 55 mm or more and a left ventricular ejection fraction (LVEF) of less than 50% obtained by echocardiography, and group B, consisting of patients with HCM that did not evolve into dilated phase HCM. During the mean follow-up of 16.7 years, 10 patients (23.3%) evolved into dilated phase HCM (group A) while the remaining 33 patients (76.7%) did not (group B). Ventricular tachycardia (VT) occurred in 7 of the 10 patients (70.0%) in group A and in 5 of the 33 patients (15.2%) in group B (p < 0.001). An increase in LVDD and decreases in LVEF and SV1 + RV5 in the electrocardiogram were observed during the early phase of the follow-up period in group A, while these changes were gradual in group B. Cardiac death occurred in 5 (50.0%) of the 10 patients in group A and in 2 (6.1%) of the 33 patients in group B (p < 0.001). In conclusion, dilated-phase HCM is characterized by decreases in LVEF and SV1 + RV5 and an increase in LVDD during the early phase of follow-up period, and is associated with an increased incidence of VT and a poor prognosis.

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Polymorphism in the angiotensin-converting enzyme (ACE) gene has been found to be associated with left ventricular hypertrophy (LVH) in patients with essential hypertension (EHT) in certain populations. We sought to evaluate, in a Japanese population, whether ACE genotype is related to left ventricular mass, or to the geometry of LVH in EHT. Eighty-seven patients with EHT were examined. Their relative wall thickness (RWT) and left ventricular mass index (LVMI), determined by echocardiogram, were used to divide them into 4 groups: normal (normal RWT and LVMI, n = 35); concentric remodeling (increased RWT but normal LVMI, n = 10); eccentric hypertrophy (increased LVMI but normal RWT, n = 20); and concentric hypertrophy (increased LVMI and RWT, n = 22). Genetic analysis for ACE genotypes was performed on peripheral leukocytes using PCR techniques. Interventricular septal thickness and RWT were significantly greater in the patients with the DD genotype than in those with the II genotype, but LVMI did not differ among the three ACE genotypes. The frequency of the DD genotype was higher in the concentric hypertrophy group than in each of the other groups, and the frequency of the II genotype was lower in the concentric hypertrophy group than in either the normal or eccentric hypertrophy group. The geometric pattern of hypertensive LVH was associated with ACE genotype in a Japanese population. The DD genotype may contribute to concentric hypertrophy, but not to eccentric hypertrophy.

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Right atrial appendage (RAA) blood flow pattern was analyzed in 42 normal subjects without cardiovascular disease (aged 30 to 48 years, mean 40 ± 6) who underwent transesophageal echocardiography. RAA flow pattern was demonstrated to be bi-, tri- or quadriphasic and heart rate dependent (p < 0.01) in this study. In 15 subjects (36%), a biphasic pattern was observed. A triphasic pattern was observed in 12 subjects (28%). Fifteen subjects (36%) had a quadriphasic pattern. In these subjects, we observed a pattern consisting of two diastolic forward flow waves, each followed by a backward flow wave. Mean heart rates among subjects with bi-, tri- and quadriphasic patterns were 110 ± 6, 91 ± 4 and 72 ± 13 beats/min, respectively. In the triphasic pattern, the onset of superior vena cava diastolic forward flow began 18 ± 4 ms after the onset of tricuspid E wave, whereas the first diastolic forward flow wave in the RAA began 40 ± 7 ms after onset of the tricuspid E wave. A similar relation was also noted in the quadriphasic pattern. This sequence was constant and independent of heart rate (p < 0.05), suggesting a temporal relation between right ventricular relaxation and the first diastolic forward flow wave in the RAA. In normal subjects, the RAA flow pattern is heart rate dependent and three distinct flow patterns can be differentiated. Right ventricular relaxation appears to induce both the superior vena cava diastolic forward flow wave and the first diastolic forward flow wave of the RAA. These results can be used for comparison with patterns found in disease states.

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We studied the effects of potassium channel openers (PCOs) on frequency dependent prolongations of action potential duration (APD), triggered activities and oscillatory action potentials (OSC) induced by E-4031 and dofetilide. The action potentials of canine Purkinje fibers were recorded by a glass microelectrode technique. The effects of E-4031 (10^-6 M) as well as that of additional nicorandil (2×10^-5 M) on the APD were examined. When abnormal automaticitiy was observed under perfusion of E-4031 (10^-5 M) or dofetilide (10^-5 M), action potentials were recorded continuously to estimate the sequential effects of additional perfusion of nicorandil (6×10^-5 M) or Y-26763 (10^-5 M) on triggered activities and OSC. APD prolongation by E-4031 at slower stimulation rates (cycle lengths ≥1000 msec) was suppressed by nicorandil in a dose dependent manner. Both nicorandil and Y-26763 abolished the train of early afterdepolarization (EAD) due to E-4031 or dofetilide with a shifting of the resting membrane potential to a more negative level. PCOs also normalized dofetilide induced abnormal automaticities (EAD, OSC). The antagonistic actions of PCOs on changes in action potential induced by class III antiarrhythmic agents may prevent the development of proarrhythmias produced by these agents.

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The effects of class I antiarrhythmic drugs on epicardial electrograms during regular atrial pacing were investigated in anesthetized, open-chest dogs. Lidocaine, flecainide or disopyramide was infused selectively into the distal site of the left anterior descending artery. Lidocaine produced a dose-dependent elevation of ST segment without changing the amplitude of R wave. Flecainide produced a dose-dependent increase of R-wave amplitude accompanied by the augmentation of negative T. The ST segment was elevated at the high dose. The QRST area did not change at the low dose but significantly increased at the high dose, indicating that the ST-T change at the low dose was secondary to changes in ventricular depolarization. The effects of disopyramide on R wave and ST segment were between those of lidocaine and flecainide. The major action of lidocaine was the acceleration of ventricular repolarization while that of flecainide was the deceleration of ventricular conduction. Disopyramide had an action that was intermediate between the two drugs.

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It remains controversial whether basal nitric oxide (NO) production in coronary resistance vessels in heart failure is enhanced or not. A transonic Doppler flow probe was placed around the left anterior descending coronary artery, and complete atrioventricular block was produced in fifteen dogs. The coronary pressure-flow relationships during long diastole were analyzed without and with pacing-induced heart failure. Three weeks after pacing at 240/min, plasma norepinephrine and renin activity significantly rose. Right atrial pressure and left ventricular end-diastolic pressure increased, and cardiac output and coronary perfusion pressure decreased; however, mean coronary blood flow did not change after pacing (55 ± 5 to 52 ±5 ml/min/100 g, mean ± SEM). The slope of the diastolic coronary pressure-flow relationship became steeper (1.22 ± 0.13 to 1.62 ± 0.09 ml/min/100 g/mmHg, p < 0.05) with a slight increase in the measured zero-flow pressure (29.5 ± 1.1 to 32.8 ± 1.5 mmHg, p < 0.05) after pacing. After pretreatment with indomethacin, administration of N^G-nitro-L-arginine methyl ester caused an equal increase in the zero-flow pressure before (31.4 ± 1.7 to 39.2 ± 2.2 mmHg, p < 0.05) and after heart failure (33.9 ± 2.5 to 41.6 ± 2.2 mmHg, p < 0.05), and more decline of the slope of the coronary pressure-flow relationship in heart failure (1.86 ± 0.22 to 1.20 ± 0.05 ml/min/100 g/mmHg, p < 0.05) than before heart failure (1.11 ± 0.12 to 1.05 ± 0.11 ml/min/100 g/mmHg, N.S.). This indicates that in failing hearts the vasodilatory action of NO in small vessels predominates despite the presence of several vasoconstricting factors. These results suggest that coronary blood flow is maintained despite detrimental hemodynamic and activated neurohumoral factors in the initial stage of heart failure, and that increased basal NO production plays a central role in the maintenance of basal coronary blood flow.

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Imidapril, enalapril and quinapril were subcutaneously administered to aortic-banded rats by osmotic minipumps to compare the suppressive actions of these angiotensin converting enzyme (ACE) inhibitors on pressure-induced cardiac hypertrophy. Among the three drugs tested, imidapril was most potent for the prevention of cardiac hypertrophy, although equipotent hypotensive doses were used. Imidapril reduced both serum and cardiac ACE activities, while enalapril reduced only the former. Quinapril also reduced both, however, it was less potent at reducing the former compared to imidapril. Moreover, only imidapril significantly decreased left ventricular end diastolic pressure, which tended to be increased by aortic-banding. The lipophilicity of ACE inhibitors could not explain the more potent suppressive action of imidapril on cardiac hypertrophy because the lipophilicity of imidaprilat, an active metabolite of imidapril, was as low as an active metabolite of enalapril; i.e., much lower than an active metabolite of quinapril. The efficay of ACE inhibitors on pressure-induced cardiac hypertrophy depends not only on an inhibitory effect on cardiac. ACE activity, but also on other actions such as their effect on left ventricular end diastolic pressure.

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A case of atypical AV nodal reentrant tachycardia (AVNRT) with eccentric retrograde left-sided activation, masquerading as tachycardia using a left-sided accessory pathway, is reported. Initially it appeared that the tachycardia was a typical slow-fast form of AVNRT. The earliest retrograde activation, however, was registered at a site approximately 3 cm from the coronary sinus orifice (left atrial free wall), indicating atypical AVNRT. Atrial tachycardia and orthodromic AV reciprocating tachycardia using an accessory AV pathway were excluded. Slow pathway ablation at the posteroseptal right atrium eliminated the tachycardia. It was suggested that the anterograde limb of the tachycardia circuit was a slow AV nodal pathway with typical posteroseptal location, whereas the retrograde limb was a long atrionodal pathway connectting the compact AV node and the left atrial free wall near the mid-coronary sinus.

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A 72-year old male with an old myocardial infarction who had drug-refractory ventricular tachyarrhythmias received an implantable cardioverter-defibrillator(ICD). The patient did no take his prescribed β-blocking agent for two days, following which he experienced six discrete shocks for spontaneous VT while riding his bicycle. Both 5J and 30J cardioversions were ineffective at terminating the VT and accelerated VT developed following the shocks. After admission, an electrophysiological study was performed while he was taking the β-blocking agent, both low and high energy cardioversions reproducibly terminated the clinical VT without showing any accelerated rhythm. These findings suggest that the increase in sympathetic discharge may enhance the proarrhythmic potential of ICDs.

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Ventricular tachycardia with a delta wave-like beginning of the QRS complex is considered to be refractory to endocardial catheter ablation because it originates from the epicardial region. A 45-year-old woman had incessant ventricular tachycardia with a delta wave-like beginning of the QRS complex which was resistant to several antiarrhythmic drugs. The origin of the arrhythmia was at the mitral annulus on the antero-lateral left ventricular wall. The earliest endocardial activation preceded the QRS complex by 18 msec. After 7 sec of endocardial radiofrequency application ventricular tachycardia was terminated. During a 2 year follow-up ventricular tachycardia did not recur and only small numbers of premature ventricular contractions (<100/day) were noted. VT with delta wave-like QRS morphology which originates from the basal region of the ventricle may be treated successfully with radiofrequency catheter ablation using an endocardial approach.

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A 74-year-old male who had received radiotherapy (total 54 Gy) for right lung cancer 7 months earlier developed a symptomatic brady-tachycardia syndrome requiring the implantation of a permanent pacemaker. Chest CT showed a pulmonary tumor of 2-cm diameter in the right lower lobe with direct extension into the surrounding tissue, suggesting the possibility of cardiac invasion. Carbon-11 methionine positron emission tomography (PET) indicated the absence of visible invasion of the heart with lung cancer. The bradytachycardia syndrome, therefore, was considered to be associated with sinus node injury due to radiation. Carbon-11 methionine PET metabolic imaging might play an important role in evaluating noninvasively the cause of the arrhythmia in this patient.

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