Yuzo Hirota

Left ventricular midwall mechanics in systemic arterial hypertension. Myocardial function is depressed in pressure-overload hypertrophy.

BackgroundLeft ventricular (LV) midwall geometry has been described conventionally as the sum of the chamber radius and half of the wall thickness; this convention is based on the assumption of uniform transmural thickening during systole. However, theoretical considerations and experimental data indicate that the inner half (inner shell) of the LV wall thickens more than the outer half (outer shell). Thus, an end-diastolic circumferential midwall fiber exhibits a relative migration toward the epicardium during systole. As a result, the conventional method provides an overestimate of the extent of the midwall fiber shortening. Methods and ResultsWe developed an ellipsoidal model with a concentric two-shell geometry (nonuniform thickening) to assess midwall fiber length transients throughout the cardiac cycle. This modified midwall method was used in the analysis of LV cineangiograms from 15 patients with systemic arterial hypertension and 14 normal subjects. Study groups were classified according to LV mass index (LVMI): 14 normal subjects (group I), eight hypertensive patients with a normal LVMI (group II), and seven hypertensive patients with an increased LVMI (group III). There were no significant differences in LV end-diastolic pressure or volume among the three groups; the ejection fraction was slightly greater in group 11 (70 + 5%) than in groups I (65±8%) and III (664±4%), but this trend did not achieve statistical significance. Values for endocardial and conventional midwall fractional shortening (FS) were also similar in the three groups. By contrast, FS by the concentric two-shell geometry (modified midwall method) in group III (16±2%) was significantly less than that seen in groups I and II (21±4% and 21 + 5%, respectively; both p < 0.05). This difference achieves greater importance when it is recognized that mean systolic circumferential stress was lower in group III (151±22 g/cm2) than in groups I and 11 (244±37 g/cm2 and 213+38 g/cm2, respectively; both p<0.01). The midwall stressshortening coordinates in six of the seven group III patients were outside the 95% confidence limits for the normal (group I) subjects. Thus, despite a normal ejection fraction, systolic function is subnormal in hypertensive patients with LV hypertrophy. ConclusionsChamber dynamics provide an overestimate of myocardial function, especially when LV wall thickness is increased. This is due to a relatively greater contribution of inner shell thickening in pressure-overload hypertrophy.

Serum and urinary human heart fatty acid-binding protein in acute myocardial infarction

A competitive enzyme immunoassay (C-EIA) was developed for the measurement of serum and urinary levels of human heart fatty acid-binding protein (hh-FABP), and the appearance and time-course changes of hh-FABP levels were evaluated in patients with acute myocardial infarction (AMI). Control serum and urinary hh-FABP levels, which were determined in 86 serum and 42 urine samples from 86 patients without AMI, were found to range between 0 and 2.8 ng/mL. Serial determinations performed on 11 patients with AMI demonstrated that hh-FABP levels were significantly elevated in the first serum and urine samples obtained within 14 h of the onset of clinical symptoms. Two serum and 2 urine samples obtained only 1.5 h after the onset of symptoms already showed elevated hh-FABP levels, while in the same serum samples the activity of the myocardial-specific isoenzyme of creatine kinase (CK-MB) was still normal. Maximal serum and urinary hh-FABP levels appeared between 5 and 10 h after symptoms developed, and fell sharply towards normal thereafter. The hh-FABP levels in serum and urine both peaked earlier than the elevation of CK-MB activity in serum. The presence of hh-FABP in serum and/or urine seems to be a marker for myocardial damage and could be used as a useful tool for the early diagnosis of AMI.

Usefulness of low-dose dobutamine stress echocardiography for evaluating reversibility of brain death–induced myocardial dysfunction

Many of the myocardial wall motion abnormalities in heart donors are reversible after transplantation, indicating that the presence of wall motion abnormalities should not automatically lead to the exclusion of donor hearts. The present study observes the natural course of brain death-induced myocardial dysfunction, and investigates whether low-dose dobutamine stress echocardiography could identify reversible myocardial dysfunction in brain-dead patients. We prospectively measured the serial changes of left ventricular fractional shortening (FS) using echocardiography and cardiac troponin T from admission to the time of cardiac standstill in 30 brain-dead patients. Patients were divided into 2 groups according to FS at the time of brain death; group I (FS > or =30%) and group II (FS <30%). Dobutamine stress echocardiography was performed in group II. Twenty-three patients were in group I and 7 patients were in group II. Four patients among 7 patients in group II showed dobutamine-nonresponsive wall motion (group IIa) and the remaining 3 patients showed dobutamine-responsive wall motion (group IIb). Troponin T at the time of brain death was markedly higher in group IIa than in groups I and IIb (5.13+/-3.79 vs 0.23+/-0.20, 0.22+/-0.16 ng/ml, p <0.0001, respectively). FS remained normal and troponin T was not increased until cardiac standstill in group I. FS remained decreased and troponin T remained elevated until cardiac standstill in group IIa, whereas FS became normal at 7 days after brain death with no change in troponin T in group IIb. Thus, some brain death-induced myocardial dysfunction is reversible and low-dose dobutamine stress echocardiography may identify reversible myocardial dysfunction.

Circadian variations of onset of acute myocardial infarction and efficacy of thrombolytic therapy

OBJECTIVESnThe present study investigated whether the onset of acute myocardial infarction and resistance to thrombolysis have similar circadian variations.nnnBACKGROUNDnCircadian variations of the onset of acute myocardial infarction and resistance to thrombolysis in the early morning have been reported. Some studies have also reported a secondary peak incidence in late evening; however, it is not known whether the resistance to thrombolysis has a similar circadian variation in these patients.nnnMETHODSnSix hundred eight Japanese patients with an acute myocardial infarction were the subjects of the study. Two hundred forty-four of the 608 patients were treated with thrombolysis within 12 h of the onset of symptoms. One hundred thirteen patients received urokinase, and 131 patients received tissue-type plasminogen activator (t-PA) over 60 min. Patency of the infarct-related artery, the primary end point of the study, was evaluated at 60 min after the initiation of thrombolytic therapy, and Thrombolysis in Myocardial Infarction (TIMI) grade 0, 1 or 2 was defined as resistant to thrombolysis.nnnRESULTSnThe onset of acute myocardial infarction and resistance to thrombolysis showed circadian variations with early morning and late evening peaks (p<0.001 and p<0.05, respectively). These circadian patterns showed similar distributions as evaluated with Spearmans method (r=0.70, p<0.05), although resistance to thrombolysis showed a phase difference of about 2 h earlier than the infarction incidence. The circadian variation of the resistance to thrombolysis was independent of the types of thrombolytic agents (urokinase or t-PA).nnnCONCLUSIONSnThese findings suggest that adjustment of treatment based on the time of the onset of symptoms may be warranted for the patients with acute myocardial infarction.

Natural History and Left Ventricular Response in Chronic Aortic Regurgitation

This study was aimed at clarifying the natural history and left ventricular response in aortic regurgitation using M-mode echocardiography. We analyzed the history and echocardiographic data on 94 patients, who were divided into 4 stages according to symptoms. The duration of the asymptomatic period, which represents pure volume overload, is long, and the period of minimal symptoms, combined volume and pressure overload, is relatively short. Patients with overt heart failure due to impaired contractility can survive longer than is usually believed, and the factor that predicted the onset of heart failure was a decrease in fractional shortening > 3.8 percentage points.

Myocardial revascularization with combined arterial grafts utilizing the internal mammary and the gastroepiploic arteries

Coronary artery bypass grafting with a combined arterial graft using both the internal mammary artery and the right gastroepiploic artery was performed in 22 patients during a 21-month period. There were 17 men and 5 women ranging in age from 34 to 73 years (mean age, 53.4 years). Three patients were having a reoperation, and 2 patients had no segment of long saphenous vein available. Twelve patients were less than 55 years old. The mean number of distal anastomoses including vein grafts was 3.2 and the mean number of arterial grafts was 2.5 per patient. The mean aortic cross-clamp time was 63.8 minutes and the mean cardiopulmonary bypass time was 116.7 minutes. There was 1 early and 1 late death. The other 20 patients are alive without angina. Studied within 3 postoperative months, graft patency was 95% (19/20) in internal mammary artery and 93% (14/15) in gastroepiploic artery grafts. It is concluded that the combined arterial graft can be used safely and effectively, and its application facilitates complete revascularization with more arterial and fewer vein grafts.

Clinical observation of spontaneous anginal attacks and multivessel spasm in variant angina pectoris with normal coronary arteries: evaluation by 24-hour 12-lead electrocardiography with computer analysis

OBJECTIVESnUsing a new, computerized 24-h 12-lead electrocardiographic (ECG) recording and analysis system (the EAGLE system), we sought to evaluate the clinical manifestations of ischemic episodes in patients with variant angina and normal coronary arteries.nnnBACKGROUNDnAlthough the prognosis of variant angina without significant organic stenosis is generally good, the incidence of multivessel spasm, a major prognostic factor, is surprisingly high in provocation tests.nnnMETHODSnA total of 122 patients with suspected variant or unstable angina underwent 24-h examination with the EAGLE system and two-channel Holter monitoring. Thirty patients in this group were diagnosed as having variant angina with normal or nearly normal coronary arteries. Twenty-two (73%) of these 30 patients developed anginal attacks with ST segment elevation during monitoring and were enrolled in the study.nnnRESULTSnThe 22 patients had a total of 138 episodes of transient ST segment elevation and 13 episodes of ST segment depression. No arrhythmias were observed during ST segment depression, but 26 episodes of ST segment elevation (19%) were associated with arrhythmias: 7 with premature ventricular contractions, 3 with ventricular bigeminy, 3 with complete atrioventricular (AV) block, 1 with complete AV block and couplets of premature ventricular contractions and 12 with marked sinus bradycardia (< 45 beats/min). Ten (45%) of the 22 patients had multivessel spasm. We observed three different patterns of multivessel spasm: 1) spasm at a different site on different occasions (migratory spasm); 2) spasm that sequentially affected two different sites; 3) simultaneous spasm at more than one site. The duration of ST segment elevation was much longer in patients with sequential and simultaneous spasm than in those with single-vessel spasm, and arrhythmias were more frequent during these two types of multivessel spasm.nnnCONCLUSIONSnAlthough the prognosis of multivessel spasm is believed to be poor, this may not necessarily be so. Anginal attacks due to sequential and simultaneous multivessel spasm seem to be more dangerous than those involving single-vessel spasm or migratory multivessel spasm.

Improvement in left ventricular diastolic function during intravenous and oral diltiazem therapy in patients with hypertrophic cardiomyopathy: An echocardiographic study

M-mode echocardiography was used to evaluate the acute effect of intravenously administered diltiazem, 10 mg, and the chronic effects of oral diltiazem, 180 mg/day, and propranolol, 60 to 120 mg/day, administered for 2 weeks on left ventricular (LV) systolic and diastolic function in 13 patients with hypertrophic cardiomyopathy. Intravenous injection of diltiazem reduced isovolumic relaxation time from 114 +/- 26 to 99 +/- 21 ms (p less than 0.01) and the time to peak rate of LV dimensional lengthening from 166 +/- 17 to 133 +/- 10 ms (p less than 0.01), without significant changes of LV dimensions or fractional shortening. No significant changes were observed in LV dimensions or fractional shortening, but a significant increase in peak rate of LV dimensional lengthening (from 4.1 +/- 1.5 to 4.8 +/- 1.6/s, p less than 0.05) and a reduction in isovolumic relaxation time (from 105 +/- 26 to 77 +/- 23 ms, p less than 0.01) and the time to peak rate of LV dimensional lengthening (from 156 +/- 23 to 124 +/- 20 ms, p less than 0.01) occurred during the oral administration of diltiazem. In contrast, propranolol caused no significant changes in these values. Thus, diltiazem improves LV relaxation and diastolic filling without altering LV systolic function in patients with hypertrophic cardiomyopathy.

Aortic Counterpulsation May Improve Late Patency of the Occluded Coronary Artery in Patients With Early Failure of Thrombolytic Therapy

OBJECTIVESnUsing a prospective, randomized design, we tested our hypothesis that the augmentation of diastolic pressure by intraaortic balloon counterpulsation (IABP) would improve the late patency of the occluded coronary artery in patients with early failure of thrombolytic therapy.nnnBACKGROUNDnRescue angioplasty is often performed in patients in whom thrombolysis has failed, although 30% to 60% of the infarct-related arteries that are closed early after thrombolytic therapy will open later with conservative therapy.nnnMETHODSnThe study included 45 patients in whom thrombolysis had failed, despite treatment with intravenous tissue-type plasminogen activator (alteplase 0.75 mg/kg body weight) delivered over 60 min within 12 h of the onset of symptoms. All patients underwent coronary angiography 60 min after initiation of thrombolytic therapy (baseline), and Thrombolysis in Myocardial Infarction (TIMI) grade 0, 1 or 2 flow was defined as failed thrombolysis. The patients were randomized to groups receiving IABP for 48 h (n = 23) or conservative therapy (n = 22, control subjects) at the end of cardiac catheterization. The late patency of the infarct-related artery, the primary end point of the study, was evaluated 3 weeks after myocardial infarction. Stenosis of the infarct-related artery was measured using a computer-assisted quantitative angiographic system in blinded manner. Data are expressed as mean value +/- SEM.nnnRESULTSnThere was no difference with regard to the baseline value for TIMI flow grade between the groups. However, 3 weeks after myocardial infarction, the patients treated with IABP had a significantly higher frequency of TIMI flow grade 3, lower residual percent stenosis and larger minimal lumen diameter of the infarct-related artery than did the control subjects (74% vs. 32%, p < 0.05; 42 +/- 5% vs. 68 +/- 6%, p < 0.01; and 1.6 +/- 0.1 vs. 0.9 +/- 0.2 mm, p < 0.01, respectively).nnnCONCLUSIONSnThese findings suggest that in patients with early failure of thrombolytic therapy, IABP may improve late patency of the occluded coronary artery, probably due to augmented perfusion pressure.

Hypertrophic nonobstructive cardiomyopathy: A precise assessment of hemodynamic characteristics and clinical implications

A precise assessment of left ventricular function was performed in 20 patients with hypertrophic nonobstructive cardiomyopathy to elucidate the basic pathophysiology, and the data were compared with those in 22 normal subjects. Whereas end-diastolic pressure was high in those with cardiomyopathy, a more accurate index of preload, end-diastolic stress, did not differ from normal value. Afterload was about half the normal value. Both isovolumic indexes [peak positive dP/dt and (dP/dt)/DP40] and ejection phase indexes of contractility (ejection fraction) were in the normal range; however, the end-systolic stress volume ratio was significantly reduced (43% of the normal value). Although the left ventricular minute work index was in the normal range, the unit muscle performance (minute work/mass) was very low (49%). An abnormality of left ventricular relaxation was demonstrated by low peak negative dP/dt (56%) and prolonged time constant T (191%), and a stiff left ventricle was demonstrated by a high diastolic elastic stiffness constant (129%). These observations suggest that the contraction of a unit muscle is inappropriate to produce an adequate contraction of the whole ventricle, and that hypertrophy might be an adaptive process to maintain normal systolic function by increasing mass and reducing afterload.