ECG pattern of left ventricular hypertrophy in nonobstructive hypertrophic cardiomyopathy: the significance of the mid-precordial changes.

A review of electrocardiograms from 33 patients with nonobstructive hypertrophic cardiomyopathy was made. In 22 patients there was noted a high QRS voltage, depression of the ST segment, and inversion of the T wave, satisfying the diagnostic criteria of left ventricular hypertrophy with the abnormal changes not only extending to the midprecordial leads but showing the most striking abnormal changes in Lead V4 in 20 patients. The frontal plane electrical axis was normal (around 60 degrees), with the most remarkable changes in Lead II. In the VCG, the magnitude of the QRS loop was increased and directed anteriorly and to the left, and the T loop was deviated posteriorly and to the right opposite the QRS loop. The asymmetric septal and apical hypertrophy was noted on echocardiography and/or angiocardiography. The coronary arteries were normal without significant obstruction in selective coronary angiography. It was postulated that the asymmetric septal and apical hypertrophy was reflected in this ECG pattern. The recognition of this ECG pattern provides pertinent information in the clinical detection of nonobstructive HCM.     

HL-A and hypertrophic cardiomyopathy.

HL-A antigens were determined in 26 unrelated Japanese patients with hypertrophic cardiomyopathy. Several antigens were more common in patients compared with controls, but statistically significant differences were not evidenced. We also studied two families in which many had a hypertrophic cardiomyopathy. All the affected individuals revealed HL-A-A9 and B7, while none among the unaffected family members had HL-A-B7. Our findings suggest that the HLA-A system may play some role in the pathogenesis of hypertrophic cardiomyopathy with familial occurrence.     

HLA-DRW4 antigen linkage in patients with hypertrophic obstructive cardiomyopathy

To determine the association of histocompatibility (HLA) genes in patients with hypertrophic cardiomyopathy, we determined HLA-A, HLA-B, HLA-C, and HLA-DR specificities in 33 Japanese patients (15 with the obstructive type of hypertrophic cardiomyopathy, and 18 with the nonobstructive type). HLA-DRW4 was found in 73% of patients with hypertrophic obstructive cardiomyopathy, as compared to 33% of 144 normal controls (p < 0.005). HLA-DRW4 occurred in 33% of those with hypertrophic nonobstructive cardiomyopathy, and there was no significant difference as compared with controls. Thus, hypertrophic obstructive cardiomyopathy is associated with genes in the HLA-DR region and immunogenetic factors linked to HLA appear to play a role in the pathogenesis. This work is the first attempt at demonstration of HLA-DR antigen in hypertrophic cardiomyopathy.     

Number and size of myocytes and amount of interstitial space in the ventricular septum and in the left ventricular free wall in hypertrophic cardiomyopathy

The wall thickness of the myocardium depends on 3 variables: the number of muscle layers, the mean size of myocytes and the percent area of interstitial space. To clarify the pathogenesis of asymmetric septal hypertrophy (ASH) in hypertrophic cardiomyopathy (HC), these 3 variables and wall thickness were measured in the ventricular septum (VS) and in the left ventricular (LV) posterior wall. The $\text{VS}\text{LV}$ ratio of wall thickness was correlated with the $\text{VS}\text{LV}$ ratios of the 3 variables in the hearts of 10 patients in HC with ASH and in 37 control patients without ASH (25 with no cardiac disease and 12 with systemic hypertension). The $\text{VS}\text{LV}$ ratios (mean ± standard deviation) in hearts with HC were 1.6 ± 0.2 for wall thickness, 1.8 ± 0.3 for the number of transmural muscle layers, 0.9 ± 0.1 for mean size of myocytes and 1.1 ± 0.1 for percent area of transmural interstitial space. The $\text{VS}\text{LV}$ ratios in control hearts were 1.0 ± 0.1 for wall thickness, 1.0 ± 0.1 for number of transmural muscle layers, 1.0 ± 0.1 for mean size of myocytes and 1.0 ± 0.1 for percent area of interstitial space. The $\text{VS}\text{LV}$ ratios of wall thickness and transmural muscle layers correlated well. In hearts with ASH in HC, the number of muscle layers was greater in the VS (630 ± 80) and smaller in the LV free wall (360 ± 70) than in the control hearts (500 ± 60 and 480 ± 50, respectively). Thus, the pathogenetic factor of ASH in HC is an increased $\text{VS}\text{LV}$ ratio of the number of muscle layers, and the degree of ASH is determined by the combined abnormalities in the numbers of transmural muscle layers in the VS and the LV free wall.     

Clinicopathologic study of abnormal Q waves in Kawasaki disease (mucocutaneous lymph node syndrome): An infantile cardiac disease with myocarditis and myocardial infarction

A correlative study of abnormal Q waves and pathologic findings was performed on 15 hearts from children with Kawasaki disease. Gross pathologic study revealed acute angiitis with pericarditis, acute myocarditis and coronary heart disease as the result of angiitis.Three hearts in infants with abnormal Q waves in leads I and aVL and chest leads had gross transmural fibrosis in the anteroseptal-lateral walls of the left ventricle. Coagulation necrosis (acute myocardial infarction) or fibrosis, or both, in more than 30 percent of the wall thickness in the posterior ventricular wall was found in four of five hearts in infants with abnormal Q waves in leads II, III and aVF. Seven of the 15 infants had no abnormal Q waves, and only 2 of the 7 had myocardial damage in over 30 percent of the wall thickness.In 9 of the 15 hearts there were 11 gross areas of fibrosis; in these hearts there was a corresponding severe stenosis of more than 90 percent due to organization in the major coronary arteries supplying these areas. In three hearts with coagulation necrosis, the coronary occlusion was caused by fresh large thrombi. In the six hearts without sizable fibrosis, the grade of stenosis due to organization was less than 75 percent in each of the major coronary arteries.Coronary aneurysm due to angiitis was seen in 12 of the 15 hearts, and at autopsy fresh large thrombi were seen in each aneurysm. Ten of the 12 hearts exhibited sizable areas of myocardial damage. Three hearts without aneurysm manifested angiitis with mild stenosis of less than 25 percent, but there were no macroscopic fresh thrombi in any of the major coronary arteries.Thus, abnormal Q waves in children with Kawasaki disease almost always reflect myocardial damage in over 30 percent of the wall thickness of the left ventricle. Electrocardiograms are useful to determine the anterior or posterior localization of the damage. Nevertheless, the possibility of transmural and nontransmural areas of damage cannot be excluded in the absence of abnormal Q waves.     

Noninvasive assessment of T-wave abnormalities on precordial electrocardiograms in middle-aged professional bicyclists

Six middle-aged, active, professional bicyclists with T-wave abnormalities on precordial ECGs were studied noninvasively. Twenty-five age-matched bicyclists without T-wave abnormalities served as the control subjects.Increased voltage of SV1 + RV5 was demonstrated in all subjects. A 5-year follow-up study revealed that these abnormalities of T-wave inversion became more pronounced with age, except in one case. VCGs showed enlargement of anterior QRS loop and discordant T loop, in all cases. On echocardiography, thickness of both the interventricular septum and the left ventricular posterior wall, and left ventricular mass were significantly increased compared with the control group. ²⁰¹Tl myocardial scintigraphy at rest and during exercise revealed no regional perfusion defects of the tracer in either case.We conclude that: (1) T-wave abnormalities of precordial ECGs in six middle-aged athletes were progressive in nature; and (2) these electrocardiographic abnormalities seem to be related to left ventricular hypertrophy induced by steady and strenuous training rather than to coronary artery disease.     

Myocardial catecholamines in hypertrophic and dilated (congestive) cardiomyopathy: a biopsy study

A high performance liquid chromatographic method was used to determine myocardial norepinephrine and epinephrine concentrations in 66 biopsy specimens obtained from the right or left ventricle during routine diagnostic cardiac catheterization of 45 patients with dilated (congestive) or hypertrophic cardiomyopathy, or with heart disease other than cardiomyopathy, such as acute perimyocarditis, postmyocarditis and constrictive pericarditis. The validity of catecholamine determination in a 2 to 6 mg biopsy specimen to assess overall ventricular myocardial catecholamines was demonstrated. Norepinephrine concentrations in the myocardium were inversely correlated with the grade of hypertrophy in patients with congestive cardiomyopathy or heart disease other than cardiomyopathy, but not in patients with hypertrophic cardiomyopathy. The fact that the myocardial norepinephrine concentration was always lower in the left than in the right ventricle of the same patient may be explained by the simple dilution of sympathetic nerve endings in the left ventricle. There were some cases of hypertrophic cardiomyopathy in which the concentration of myocardial norepinephrine was exceptionally high, although its mean value was not significantly higher than that in patients with other types of heart disease who served as a control group without cardiomyopathy. Some patients with dilated cardiomyopathy had lower levels of myocardial norepinephrine than would be expected for the degree of interstitial fibrosis and the severity of heart failure. The mean plasma norepinephrine and epinephrine levels were significantly elevated in patients with dilated cardiomyopathy.     

Prostacyclin therapy in patients with congestive heart failure

The acute hemodynamic effects of intravenous prostacyclin (PGI₂), in doses of 22 ± 11 ng/kg per min were studied in nine patients with severe congestive heart failure refractory to digitalis and diuretic drugs. After prostacyclin infusion, mean (±standard deviation) pulmonary capillary wedge pressure decreased from 21.0 ± 7.9 to 15.0 ± 6.6 mm Hg (p < 0.001), mean arterial pressure from 98.9 ± 12.8 to 76.2 ± 7.0 mm Hg (p < 0.001), systemic vascular resistance from 2,574 ± 384 to > 1,368 ± 283 dynes s cm^?5 (p < 0.001), pulmonary vascular resistance from 1,008 ± 451 to 443 ± 135 dynes s cm^?5 (p < 0.001) and pulmonary arteriolar resistance from 330 ± 111 to 189 ± 73 dynes s cm^?5 (p < 0.001). Heart rate increased from 78 ± 21 to 82 ± 24 beats/min (p = not significant [NS]), cardiac index from 2.0 ± 0.37 to 3.2 ± 0.59 liters/min per m² (p < 0.001) and stroke index from 27.6 ± 8.69 to 42.0 ± 0.62 cc/m² (p < 0.001). With prostacyclin, moreover, coldness of the limbs and face disappeared, and patients felt warmth and mild flushing of the face. After prostacyclin, plasma norepinephrine levels, renin activity and aldosterone concentrations rose from 824 ± 375 to 880 ± 468 pg/ml (NS), 0.68 ± 1.36 to 0.95 ± 1.21 ng/ml per h (NS), and 6.64 ± 2.50 to 6.38 ± 2.88 ng/dl (NS), respectively, while plasma epinephrine increased from 140 ± 80 to 250 ± 154 pg/ml (p < 0.025).     

Electrocardiographic findings in experimental myocarditis in DBA/2 mice: complete atrioventricular block in the acute stage, low voltage of the QRS complex in the subacute stage and arrhythmias in the chronic stage

To determine whether arrhythmias persist in the chronic stage of myocarditis, serial electrocardiograms were studied in DBA/2 mice with experimentally induced myocarditis. After baseline electrocardiograms with standard limb and two precordial leads were recorded, 52 mice were inoculated intraperitoneally with 0.1 ml of the myocardiotropic variant of encephalomyocarditis in a viral suspension containing 10(2) TCD50 (50% tissue culture infective dose). Electrocardiograms were recorded every day on days 3 to 18 and, thereafter, once every 10 to 20 days until day 220. The cumulative incidence rate of myocarditis was 90.4% (47 of 52). No arrhythmias were found on baseline electrocardiograms. Serial electrocardiograms showed atrial and ventricular premature complexes and complete atrioventricular (AV) block, respectively, in 6 (12.8%), 8 (17.0%) and 25 (53.2%) of 47 mice with myocarditis. Myocardial lesions were found in the heart of mice with these ectopic complexes. Mononuclear cell infiltrations into the His bundle were noted in the conduction system of mice with complete AV block. Heart rate began to increase after day 11 (638 +/- 105 beats/min, n = 16 versus control rate 557 +/- 57 beats/min, n = 47, mean +/- standard deviation, p less than 0.01) and reached a maximum on day 15 (40 +/- 22 beats/min, n = 8, p less than 0.01). The sum of QRS voltage in eight leads began to decrease after day 6 (62.1 +/- 18.8 mm, n = 24 versus control value 80.0 +/- 14.7 mm, n = 47, p less than 0.01) and reached a minimum on day 13 (32.5 +/- 7.5 mm, n = 8, p less than 0.01) when myocardial necrosis and congestion of the lungs and liver were most prominent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognosis in hypertrophic cardiomyopathy

One hundred thirty-six patients with hypertrophic cardiomyopathy were followed up for 1 to 17 years. Twenty-one patients had died, 14 of them suddenly, two from heart failure, two from cerebral embolism, and three from noncardiac causes. Life table analysis revealed that sudden death was significantly associated with young age less than 20 years (relative risk [rr] = 8.63, when compared with those greater than 40 years) and with positive Master's single two-step test (rr = 3.55). Heart failure was more frequent in patients with positive Master's single test (rr = 4.27) and with left ventricular end-diastolic pressure greater than 20 mm Hg (rr = 2.58). Atrial fibrillation, observed in 15 patients, was a poor prognostic sign, resulting in five cardiac deaths and seven heart failures. In contrast, prognosis was favorable in patients with apical hypertrophy with giant negative T wave. Thus Japanese patients with hypertrophic cardiomyopathy showed a prognosis consistent with Western patients, except for excellent outcome of apical hypertrophy.     

Mean QRS, ventricular gradient and left ventricular mass in patients with eccentric left ventricular hypertrophy.

The spatial ventricular gradient (G) and the mean QRS-T angle were examined in 12 patients with angiographically determined eccentric left ventricular hypertrophy (LVH), as compared with 12 normal control subjects. In these 24 patients, a high significant correlation (r = 0.88) was obtained between the magnitude of the spatial mean QRS and LV mass. Although correlations were obtained between the magnitude of the spatial G or the spatial mean QRS-T angle and LV mass, they were lower (r = 0.56, 0.71 respectively). The magnitude of the spatial G (0.190 +/- 0.049 MVSec) in the eccentric LVH group increased significantly (p less than 0.001) in comparison with the control value (0.105 +/- 0.032 mVSec), while in the eccentric LVH group, decreased G/QRS (p less than 0.02), decreased T/QRS (p less than 0.05), and increased QRS-T angle (p less than 0.02) were observed. Furthermore, decreased G/QRS and widening of the QRS-T angle were observed in cases of LVH only. In cases of mild or moderate LVH, normal G/QRS ratios with definitely increased G magnitude and normal QRS-T angle were observed. It is concluded that the magnitude of the spatial mean QRS closely relates to an increase in LV mass. Therefore, should the magnitude of G increase proportionally to an increase in total muscle volume in ideal hypertrophy, then the widening of the QRS-T angle observed in LVH would be due not only to the large ARS complex but also to an alteration in the ventricular gradient.     

Effects of intraaortic balloon counterpulsation on regional myocardial function during acute coronary occlusion in the dog

The effects of intraaortic counterpulsation on regional myocardial function were studied using ultrasonic dimension gauges in 24 open chest dogs. Pairs of ultrasonic crystals were implanted in the subendocardium of the left ventricle in control, marginally ischemic and ischemic segments. After coronary arterial occlusion, the end-diastolic length of all three segments was increased. Segment shortening was rapidly replaced by systolic expansion in the ischemic segment. In the marginal segment, active shortening decreased by 53 percent and, in the control segment, shortening was augmented by compensatory operation of the Frank-Starling mechanism. Balloon pumping initiated 10 minutes after coronary occlusion resulted in an increase in mean aortic diastolic pressure from 103 to 115 mm Hg without any significant change in peak systolic pressure. In the marginal segment, end-diastolic length decreased by 3 percent, and previously reduced shortening increased to 82 percent of control value, deteriorating again with discontinuation of counterpulsation. Balloon pumping produced no change in the dyskinetic motion of the ischemic segment but caused compensatory augmentation of shortening of the control segment. Thus, counterpulsation selectively improved segment function of the marginally ischemic segment, presumably as a result of a regional increase in myocardial blood flow and in availability of oxygen due to augmented perfusion pressure. The systolic unloading effect was counterbalanced by improved cardiac performance.     

Influence of acute mechanical overload on dimension and dynamics of interventricular septal thickness in dogs

To evaluate directly septal thickness and related dynamic changes, miniature ultrasonic crystals were Implanted across the Interventricular septum and left ventricular free wall and In the circumferential endocanNal segments of the left and right ventricles In 12 open chest dogs. In the control resting state, end-dlastollc wall thickness of the septum and the left ventricular free wall was 9.4 ± 2.1 and 9.6 ± 2.6 mm, respectively (mean ± standard deviation). Wall thickness Increased during systole by 15 percent In the septum and by 17 percent in the free wall. With constriction of the ascending aorta, left ventricular end-dlastollc segment Increased by 13 percent with reciprocal thinning In the end-dlaslollc thickness of the septum (by ?8.5 percent) and the left ventricular free wall (by ?5.2 percent); there were decreases in percent shortening of the left ventricular segment (from 21.0 to 15.5 percent) and In percent thickening of both the septum (from 14.6 to 11.8 percent) and the free wall (from 16.9 to 13.1 percent).Pulmonary arterial constriction resulted In significant right ventricular chamber enlargement; however, there was no direct change In dimension and dynamics of the septum. When mitral regurgitation was produced by sectioning the chordae tendlneae, left ventricular end-dlastollc segment length Increased (by 23.5 percent) with reciprocal thinning of the enddlastollc thickness of the septum (by ?8.6 percent) and the free wall (by ?6.9 percent). The left ventricular segment shortening and wall thickening of the septum and the free wall were equally augmented (from 18.6 to 37.5, from 16.1 to 31.0 and from 19.8 to 29.3 percent, respectively). Wtth the onset of acute tricuspld regurgitation, right ventricular end-dlastollc segment and its shortening Increased markedly, but there were no direct changes in the septum. Thus, the interventrlcular septum can be regarded as a functional part of the left ventricle, and any form of mechanical loading on the left ventricle will ultimately Induce proportionate changes in the septum and left ventricular free wall.     

Effect of diltiazem on pacing-induced ischemia in conscious dogs with coronary stenosis: Improvement of postpacing deterioration of ischemic myocardial function

The effects of diltiazem on regional myocardial function were examined in conscious dogs subjected to rapid cardiac pacing during coronary arterial stenosis. Ultrasonic dimension gauges were implanted within the left ventricle for measurement of the control and ischemic segment lengths. During coronary stenosis, percent shortening in the ischemic segment decreased by 18 percent. Heart rate was then suddenly increased by rapid cardiac pacing and this resulted in a further reduction of ischemic segmental shortening. On cessation of pacing, there was early potentiation of rate of increase of left ventricular pressure (dP/dt) and of control segmental shortening with subsequent exponential decay in sequential beats. In the ischemic segment, percent shortening returned to the control level in the first postpacing beat, became severely depressed at 5 seconds after pacing and gradually returned to the control level over the subsequent 5 minutes.Twenty minutes after administration of diltiazem, cardiac pacing was repeated in the same manner and there was less marked potentiation of dP/dt of the first postpacing beat. There was no significant change in the postpacing dimension and function of the control segment; however, in the ischemic segment, although shortening of the first beat after termination of the pacing was similar, the post stimulation deterioration of shortening was significantly improved, percent shortening being augmented from 7.4 to 10.6 percent at 5 seconds (p <0.05). These findings indicate that diltiazem exerts protective effects on the ischemic myocardium by promoting a rapid recovery from ischemia.     

Automated method for left ventricular volume measurement by cineventriculography with minimal doses of contrast medium

Cineventriculography is of considerable value in the dimensional analysis of the left ventricular cavity, but conventional methods necessitate injection of large amounts of contrast medium. In this study, small dose left ventriculography, using only 5 ml of dye, was performed in order to minimize the untoward effects of contrast medium. A computer-aided image processing system was also developed to enhance the contrast of the ventricular image by subtracting the reference image to eliminate irrelevant background. The boundary of the left ventricular cavity was automatically determined to calculate the instantaneous volume change throughout the cardiac cycle. With use of this small dose of dye, the elevation of left ventricular end-diastolic pressure that consistently occurred 1 to 3 minutes after injection of conventional large doses could be avoided. (End-diastolic pressure at 1 minute after dye injection averaged 11.8 ± 4.9 [mean ± standard deviation] for small dose and 19.1 ± 6.1 mm Hg for large dose injection.) Values for end-diastolic volume, end-systolic volume and ejection fraction calculated from the two consecutive small and large dose left ventriculograms in 16 patients were similar.Thus, minimal doses of contrast medium permit accurate measurement of left ventricular dimension and function without significant hemodynamic derangement. The optimal projection for regional wall motion analysis can easily be selected by this method with repeated exposure at various degrees of obliquity. With this technique, even noninvasive measurement of left ventricular volume can be provided by intravenous injection of small doses of contrast agent.     

High reliability rates of spatial pattern analysis by vectorcardiogram in assessing the severity of eccentric left ventricular hypertrophy.

In 33 patients, including 12 control subjects and 21 with eccentric LVH, LV mass determined by angiocardiogram was correlated to 26 VCG measurements (Frank system) calculated from the scalar X, Y, and Z leads. The results demonstrated that the most reliable indices of VCG in assessing the severity of eccentric LVH determined by angiocardiogram were the magnitude of the spatial mean QRS vector and the time of the spatial maximal QRS vector ("spatial VAT"), of which correlation coefficients were 0.93 and 0.93, respectively. Such high correlation coefficients have never been obtained with the usual ECG analysis. These findings strongly suggest that (1) increased QRS voltage and usual prolonged QRS duration in eccentric LVH are due to an increase in LV mass, and (2) prolonged VAT observed in eccentric LVH is closely related to an anatomic alteration, namely, the greater distance of intra-ventricular conducting pathways as the result of LV dilatation, as an increase in LV mass is usually paralleled by the grade of the chamber enlargement in this type of LVH. Regarding the T loop, correlations between the LV mass and the VCG measurements were less as compared to those of the QRS loop. In general, T changes in moderate or severe LVH may be also related to a certain altered cardiac muscle state, in addition to an increase in LV mass. Angiocardiographic and light microscopic findings of a patient with eccentric LVH in whom a widened QRS-T angle was demonstrated to an extent much more than that expected with an increase in LV mass are presented and discussed. The spatial pattern analysis by VCG is very useful and reliable in assessing the severity of eccentric LVH.