Myocardial perfusion abnormality in the area of ventricular septum-free wall junction and cardiovascular events in nonobstructive hypertrophic cardiomyopathy.

Myocardial perfusion abnormality in the left ventricle is known to be prognostic in patients with hypertrophic cardiomyopathy (HCM). Magnetic resonance imaging and necropsy studies on HCM hearts revealed myocardial lesions predominating in the area of ventricular septum-free wall junction. We assessed perfusion abnormality in this area and correlated it with the prognosis of HCM patients. We performed exercise Tc-99m tetrofosmin myocardial scintigraphy in 55 patients with nonobstructive HCM. Perfusion abnormalities were semiquantified using a 5-point scoring system in small areas of anterior junctions of basal, mid, and apical short axis views in addition to a conventional 17-segment model. All patients were prospectively followed for sudden death, cardiovascular death and hospitalization for heart failure or stroke associated with atrial fibrillation. Cardiovascular events occurred in 10 patients during an average follow-up period of 5.7 years. Stress and rest scores from anterior junction, and conventional summed stress score were significantly higher in patients with cardiovascular events than without (all P < 0.05). Anterior junction stress score of >2 produced a sensitivity of 50% and a specificity of 98% for cardiovascular events and was an independent predictor (hazard ratio 8.33; 95% confidence interval, 1.61-43.5; P = 0.01), with rest scores producing similar values, which were higher than summed stress score of >8 (5.68; 1.23-26.3; P = 0.03). The absence of myocardial perfusion abnormality in the narrow area of anterior junction differentiated HCM patients with low-risk.

Three-layer ultrasonic tissue characterization of the ventricular septum is predictive of prognosis in patients with non-obstructive hypertrophic cardiomyopathy.

AIMS: A necropsy study of patients with hypertrophic cardiomyopathy (HCM) who died at a young age exhibited marked disarray and fibrosis in the mid-wall layer of the left ventricular (LV) myocardium. We assessed ultrasonic tissue characteristics in the three layers of the ventricular septum (VS), and correlated the result with long-term prognosis in HCM. METHODS AND RESULTS: The magnitude of cyclic variation of integrated backscatter (CV-IB) was calculated in the three layers of the VS and the whole aspect of the LV posterior wall in 58 non-obstructive HCM patients and 20 healthy controls. All HCM patients were prospectively followed for an average period of 7.1 years for the occurrence of cardiac death or hospitalization due to heart failure. Each CV-IB of four regions was lower in HCM patients than in controls (all P < 0.01). CV-IB of the VS mid-wall layer was lower in 14 HCM patients with cardiac events than in patients without (5.4 ± 0.6 vs. 7.4 ± 0.5 dB, P = 0.033) although CV-IB of three other regions did not differ between the two groups. The optical cut-off point of %CV-IB <90%, i.e. the ratio of CV-IB in the VS mid-wall layer to the mean value in the layers on both sides, was an independent predictor of cardiac events (hazard ratio, 6.12; 95% confidence interval, 1.62-66.6; P = 0.013), with a positive predictive value of 44% and particularly with a high negative predictive value of 91%. CONCLUSION: Patients with non-obstructive HCM are not likely to undergo cardiac events in the near future, when the CV-IB value is not significantly lower in the VS mid-wall layer than in the layers on both sides.

Chronotropic incompetence and autonomic dysfunction in patients without structural heart disease.

AIMS: An attenuated heart rate response to exercise, termed chronotropic incompetence (CI), has been reported to be an independent predictor of cardiovascular mortality. We examined the change in autonomic function during exercise testing and correlated the results with CI. METHODS AND RESULTS: Exercise testing using a bicycle ergometer was performed in 172 patients who had no evidence of cardiac disease. Chronotropic incompetence was defined as the failure to achieve 85% of the age-predicted maximum heart rate, heart rate reserve <80%, or chronotropic response index <0.80. We analysed the relationship between CI and the change in two components of heart rate variability during exercise testing: high-frequency (HF) component (0.15-0.40 Hz) as an index of vagal modulation and the ratio of low-frequency (LF) component (0.04-0.15 Hz) to HF component as an index of sympathovagal balance. Heart rate variability indexes before exercise were similar in patients with and without CI. Percentage changes after exercise in the ratio of LF to HF component were higher in patients with CI than in those without CI (84 +/- 15 vs. 41 +/- 16%, P < 0.05), whereas percentage changes in an HF component were similar in the two groups. CONCLUSION: Our data suggested that CI in patients without structural heart disease was mainly caused by a pathophysiological condition in which sympathetic activation was not well translated into heart rate increase. Further study is needed to determine the post-synaptic sensitivity of the beta-adrenergic receptor pathway in relation to CI.

Vagal enhancement as evidence of residual ischemia after inferior myocardial infarction.

BACKGROUND: Acute inferior myocardial infarction (MI) often induces transient sinus bradycardia through vagal enhancement, known as Bezold-Jarisch reflex, which is explained by preferential distribution of vagal nerve in the inferior wall. We examined vagal activity in relation to the occurrence of residual ischemia in patients with old inferior MI and assessed its diagnostic usefulness. METHODS: Exercise myocardial scintigraphy was performed in 15 patients with old inferior MI, 19 angina pectoris (AP) patients with inferior ischemia but no MI, and 32 control subjects who had no evidence of cardiac disease. We analyzed the connection of residual ischemia in old MI with ST-segment response to exercise and with vagal activity as determined by coefficient of component variance of high frequency (CCV(HF)). RESULTS: Exercise-induced percentage change in CCV(HF) was higher in patients with old MI and residual ischemia (18.8 +/- 13.5%) and AP (5.5 +/- 9.7%) than old MI but no residual ischemia (-24.1 +/- 4.9%) or control (-22.8 +/- 4.5%, P = 0.006). Percentage change in CCV(HF) > -5% had a good diagnostic value for the detection of residual ischemia in patients with old inferior MI with sensitivity of 83%, specificity of 89%, accuracy of 87%, and positive likelihood ratio of 7.50, which was higher than that of ST-segment depression (67%, 50%, 56%, and 1.33). CONCLUSIONS: Vagal enhancement was associated with residual ischemia in old inferior MI as well as inferior AP. Measurement of CCV(HF) is useful in improving the diagnostic reliability of exercise electrocardiography in patients with old inferior MI.

Septal Q wave as a marker of septal ischemia in hypertrophic cardiomyopathy.

BACKGROUND: Small Q waves in the left lateral leads are termed septal q waves, and their response to exercise has been reported to be a marker of septal ischemia in coronary artery disease. Patients with hypertrophic cardiomyopathy (HCM) sometimes develop septal ischemia in the absence of coronary stenosis, but little data are available concerning the association of the septal q wave response with septal ischemia. METHODS AND RESULTS: Exercise electrocardiography and Tc-99m-tetrofosmin myocardial scintigraphy were recorded to detect myocardial ischemia in 29 HCM patients with asymmetric septal hypertrophy. The septal q wave amplitude was summed up in V(5) and V(6) during exercise testing, and the results were correlated with septal ischemia defined as a regional septal ischemia or a part of diffuse subendocardial ischemia. A decrease in the sum of the septal q wave amplitude during exercise testing yielded a sensitivity of 100% and specificity 33% for regional septal ischemia, and a sensitivity of 100% and specificity of 43% for diffuse subendocardial ischemia, although an absent septal q wave at rest provided a low sensitivity for the detection of regional septal ischemia (43%) and diffuse subendocardial ischemia (33%). CONCLUSIONS: The septal q wave response to exercise is a useful marker of septal ischemia in HCM with asymmetric septal hypertrophy.

R-wave amplitude response to myocardial ischemia in hypertrophic cardiomyopathy.

BACKGROUND AND PURPOSE: R-wave amplitude change during exercise has been reported to enhance diagnostic value for myocardial ischemia in coronary heart disease. METHODS: We summed up R-wave amplitude in all the 12 leads during exercise testing and correlated the results with regional myocardial ischemia or diffuse subendocardial ischemia as detected by scintigraphy in 49 patients with hypertrophic cardiomyopathy (HCM) and 16 controls. RESULTS: The sum of R-wave amplitude decreased during exercise in patients with HCM (mean, 12.4 mV to 11.7 mV, P < .01) as well as in controls (8.0 mV to 7.7 mV, P < .05). Percent changes in the sum of R-wave amplitude did not differ between 4 subgroups of patients with HCM: one having both regional and subendocardial ischemia, one only the former, one only the latter, and one neither of them (mean, 6.5%, 7.7%, 4.6%, and 5.1%; P = .79). CONCLUSIONS: R-wave amplitude response to exercise failed to demonstrate myocardial ischemia in our patients with HCM.

Vagal enhancement due to subendocardial ischemia as a cause of abnormal blood pressure response in hypertrophic cardiomyopathy.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) often develop myocardial ischemia in association with abnormal blood pressure response to exercise. Vagal nerves mediate cardioinhibitory stimuli, with little knowledge regarding vagal response to myocardial ischemia in patients with HCM. METHODS: Exercise Tc-99m-tetrofosmin myocardial scintigraphy was performed in 59 HCM patients and 39 controls who had no evidence of cardiac disease. We examined how reversible regional perfusion abnormality and transient left ventricular cavity dilation, a parameter of subendocardial ischemia, are related to vagal modulation as assessed by coefficient of high frequency component variance (CCV(HF)) on heart rate variability. We then correlated the results with abnormal blood pressure response to exercise, defined as failed increase >or=25 mm Hg during exercise. RESULTS: Regional perfusion abnormality and left ventricular cavity dilation were observed in 26 and 21 HCM patients, respectively. The percentage change of CCV(HF) from before to after exercise was higher in HCM patients with left ventricular cavity dilation than without or controls (5.2+/-9.8%, -23.5+/-5.7%, -14.5+/-5.5%, P=0.004). By contrast, the change of CCV(HF) was similar in HCM patients with regional perfusion abnormality, those without, and controls. The change of CCV(HF) was correlated with exercise-induced increase in systolic blood pressure (rho=-0.64, P<0.001); HCM patients with abnormal blood pressure response were characterized by a higher percentage change in CCV(HF) (50.0+/-18.3%). CONCLUSIONS: Subendocardial ischemia provoked vagal enhancement in patients with HCM, which may be related to the development of abnormal blood pressure response to exercise.

Gated single-photon emission computed tomography detects subendocardial ischemia in hypertrophic cardiomyopathy.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) sometimes develop subendocardial ischemia (SEI) in the left ventricle (LV). In the present study it was examined whether volumetric variables obtained by gated single-photon emission computed tomography (SPECT) are useful in detecting exercise-induced SEI in patients with HCM. METHODS AND RESULTS: Exercise 99mTc-tetrofosmin myocardial scintigraphy was performed in 26 HCM patients having non-obstruction and mild hypertrophy with a ventricular septal thickness < or = 20 mm. SEI was quantified using software developed previously, and the results were correlated with volumetric variables obtained using Quantitative Gated SPECT software. Exercise-induced percentage change in LV end-systolic volume was higher in 9 HCM patients with SEI (25.8+/-3.1%) than in 17 patients without (10.0+/-2.5%, p=0.009), although the percentage change in LV end-diastolic volume was similar in the 2 groups. The receiver-operator characteristics curve of the percentage changes in LV end-systolic volume for the detection of SEI showed that the optimal cutoff was 17%. This cutoff point yielded a good diagnostic value for the presence of SEI with a sensitivity of 89%, specificity 82%, and likelihood ratio 5.04. CONCLUSIONS: Gated SPECT technique is useful in detecting SEI during exercise in a select population of HCM patients.

Systolic outward motion of the left ventricular apical wall as detected by magnetic resonance tagging in patients with apical hypertrophic cardiomyopathy.

Patients with apical hypertrophic cardiomyopathy (APH) associated with paradoxic jet flow (ie, diastolic flow away from the apex) may gradually develop an apical aneurysm, which often leads to arrhythmia and mural thrombus formation. We observed systolic outward motion of the left ventricular apical myocardium in patients with APH using a magnetic resonance tagging procedure and examined the relationship of the outward motion to echocardiographic and scintigraphic findings and to cardiac events. Systolic displacement of the myocardial tags of the apical region perpendicular to the long axis in the 4-chamber view was recorded in 31 patients with APH. Of these patients, 14 showed no outward movement of tags (group A), and 17 showed outward movement (group B). In group B, apical hypertrophy was more severe (35 +/- 7 mm vs. 29 +/- 6 mm, p < 0.05), paradoxic jet flow was more frequent (64% vs. 14%, p < 0.05) and the defect score in I-123-beta-methyliodophenylpentadecanoic acid scintigraphy was higher (2.1 +/- 0.7 vs. 1.3 +/- 0.7, p < 0.01). During a mean follow-up period of 55 months, only 1 patient experienced paroxysmal atrial fibrillation in group A. In group B, 1 patient died suddenly, 1 was admitted to hospital because of congestive heart failure, 2 developed angina pectoris, 2 exhibited non-sustained ventricular tachycardia, and 1 showed multifocal premature ventricular contraction; in these 7 patients the outward movement was greater than in the 10 patients in Group B who had no cardiac events (1.00 +/- 0.59 vs. 0.52 +/- 0.40, p < 0.05). Hence, our results show that outward tag displacement is frequently associated with severe apical hypertrophy, paradoxic jet flow, apical ischemia, and cardiac events. The tagging method may be useful in assessing the severity of APH and predicting the occurrence of cardiac events at an early stage.

Resting ST-segment depression predicts exercise-induced subendocardial ischemia in patients with hypertrophic cardiomyopathy.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) sometimes display characteristic electrocardiographic (ECG) findings at rest and develop subendocardial ischemia during exercise in the absence of coronary lesions. However, their relationship has not yet been fully clarified. METHODS: Exercise Tc-99m-tetrofosmin myocardial scintigraphy was performed in 48 patients with non-obstructive HCM. We quantified transient left ventricular cavity dilation (LVCD) on exercise scintigrams, a parameter of subendocardial ischemia, and correlated the results with the ECG findings at rest and during exercise. RESULTS: Transient LVCD occurred during exercise in 17 (35%) patients with HCM. Hemodynamic parameters during exercise did not differ between HCM patients with and without transient LVCD. Multiple logistic regression analysis showed that transient LVCD was significantly associated with ST-segment depression at rest (chi2=5.00, odds ratio=5.70, 95% confidence intervals 1.24-26.18, P=0.025) and a greater total number of leads with resting ST-segment depression (chi2=6.38, odds ratio=1.60, 95% confidence intervals 1.12-2.42, P=0.012). The degree of LVCD was correlated with the total number of leads with ST-segment depression at rest (P=0.002); the optimal cutoff for the diagnosis of transient LVCD was 3 with a sensitivity of 65%, a specificity of 90%, and an accuracy of 81%. CONCLUSIONS: In patients with HCM, ST-segment depression at rest was accompanied by exercise-induced subendocardial perfusion abnormality as detected by myocardial scintigraphy. ST-segment depression at rest suggests that the subendocardium is predisposed to exertional ischemia.

Prognostic value of heart rate variability in patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) have been reported to display impaired heart rate variability, although little is known regarding its prognostic value. By using fast Fourier transformation of 24-hour Holter recordings in 73 HCM patients at a stable clinical condition, we computed 4 spectral components: very low frequency, low frequency, high frequency, and total power. During 28 months, 7 HCM patients experienced death or acquired hospitalization for heart failure. Sudden death did not occurred. High frequency component was lower in HCM patients with cardiac events than that in patients without cardiac events (3.78 +/- 0.66 vs. 4.43 +/- 0.92 In(ms(2)), P =.045). There were no significant differences in other heart rate variability variables between HCM patients with and without cardiac events. In multivariate analysis, high frequency component remained to be an independent predictor of cardiac events (relative risk=0.10, 95% CI 0.01-0.73, P =.023). Heart rate variability analysis is predictive of heart failure in our cohort of HCM patients, whereas its predictive value of sudden death remains unclear.

Heart rate turbulence and clinical prognosis in hypertrophic cardiomyopathy and myocardial infarction.

Short-term fluctuations in sinus cycle length after a single ventricular premature complex (VPC) have attracted considerable interest and has been termed heart rate turbulence (HRT). The onset and slope of HRT have each been reported to be independent and powerful predictors of clinical prognosis in patients with myocardial infarction (MI), but there are no data available for patients with hypertrophic cardiomyopathy (HCM). Thus the present study analyzed the 2 HRT variables to determine their prognostic value in HCM patients. Holter monitoring data were obtained from 104 HCM patients, 44 MI patients and 56 normal controls, from which singular VPCs followed by >or=20 normal sinus beats were isolated and the HRT onset and slope were automatically calculated. HRT onset and slope were abnormal in MI patients, but not in HCM patients, as compared with normal control subjects (onset -1.1+/-2.9, -2.1+/-3.4, -1.4+/-5.1%; slope 10.6 +/-8.6, 18.0+/-13.9, 16.6+/-9.7 ms/beat, respectively). During the follow-up period of 27+/-10 months, 7 HCM patients and 10 MI patients either died from cardiac death or were hospitalized for congestive heart failure. In MI patients, HRT onset was higher and the HRT slope was lower in patients with cardiac events than in patients without (onset 1.1+/-2.7 vs -1.7+/-2.7%, p=0.011; slope 5.7+/-4.3 vs 12.0+/-9.0 ms/beat, p=0.028). In HCM patients, however, the HRT onset and slope were similar between patients with and without cardiac events (onset -2.0+/-2.0 vs -2.1 +/-3.5%, p=0.98; slope 18.1+/-10.9 vs 18.0+/-14.0 ms/beat, p=0.68). In conclusion, unlike MI patients, the HRT variables in selected HCM patients were not abnormal and failed to predict the clinical prognosis.

Sustained cavity obliteration and apical aneurysm formation in apical hypertrophic cardiomyopathy.

OBJECTIVES: In patients with apical hypertrophic cardiomyopathy (ApHCM), we estimated the severity of cavity obliteration (CO) in the apical potion of the left ventricle and correlated it with various clinical findings including apical aneurysm. BACKGROUND: Apical hypertrophic cardiomyopathy sometimes develops apical aneurysm. The apical CO is often exhibited in ApHCM along with apical hypertrophy and ischemia. It remains unclear, however, how the CO and others are related to aneurysm. METHODS: In 46 patients with ApHCM, we measured CO time on M-mode echocardiography and corrected it by the R-R interval (cCOT). We divided the 46 patients into the following groups: 17 with cCOT 200 to 350 ms (severe CO group). We then compared apical aneurysm, hypertrophy, ischemia, QT interval, and the like between the three groups. RESULTS: The severe CO group exclusively comprised 11 patients having apical aneurysm and paradoxic jet flow. Of the 11 patients, 10 exhibited irreversible defects on exercise single photon emission computed tomography with thallium-201. All with moderate CO showed reversible defects, and none with no/mild CO showed any defects. Left ventricular hypertrophy and the corrected QT interval (QTc) were largest in the severe CO group. There were high correlations between the cCOT, hypertrophy, ischemia, and QTc. Of the 11 patients with severe CO, 6 had nonsustained ventricular tachycardia and 1 had mural thrombus. CONCLUSIONS: In ApHCM, sustained CO is an important pathophysiologic condition as well as hypertrophy, ischemia, and prolonged QTc, which are considered jointly related to the development of aneurysm through interactions.

Determinant of QT dispersion in patients with hypertrophic cardiomyopathy.

QT dispersion is thought to reflect a regional difference in repolarization process although QT interval is composed of depolarization and repolarization. This study was designed to investigate the effect of depolarization and repolarization on QT dispersion in hypertrophic cardiomyopathy. Standard 12-lead ECG was recorded in 70 hypertrophic cardiomyopathy patients with anteroseptal wall hypertrophy (HC-As), 8 patients with lateral wall hypertrophy (HC-L), 8 patients with diffuse hypertrophy (HC-D), and 46 normal controls. QRS, JTc, maximum and minimum QTc, and QTc dispersion were compared. The maximum QTc was greater in HC-As and HC-L than in the control; the minimum QTc was similar in all 3 groups; consequently, QTc dispersion was greater in HC-As and HC-L. In HC-D, the maximum QTc and the minimum QTc were greater than the control, which produced QTc dispersion similar to that in the control. JTc did not differ among 4 groups. In hypertrophic cardiomyopathy, both QTc and QRS duration were increased in the leads coinciding with the left ventricular portion of localized hypertrophy. We conclude that QTc dispersion depended on the heterogeneity of QRS duration or depolarization rather than repolarization, which in fact may be ascribed to the regionally different hypertrophy of the left ventricle in hypertrophic cardiomyopathy.

Serum fatty acid levels, dietary style and coronary heart disease in three neighbouring areas in Japan: the Kumihama study.

CHD mortality is extremely low in Japan, particularly in rural districts, when compared with that in Western countries. This has been partly attributed to the difference in dietary lifestyle. We investigated the factors influencing CHD mortality in a rural coastal district of Japan, comprising mercantile, farming, and fishing areas with distinct dietary habits. We prospectively examined the incidence of CHD from 1994 to 1998, as well as coronary risk factors and serum fatty acid concentrations. The incidence of angina pectoris was significantly (P=0.01) lower in the fishing area than in the mercantile and farming areas. Blood pressure, physical activity, prevalence of diabetes, serum levels of uric acid and HDL-cholesterol were similar between the three areas. Total- and LDL-cholesterol levels were significantly lower but the smoking rate was markedly higher in the fishing area than in the other two areas. Serum levels of saturated fatty acids and n-6 polyunsaturated fatty acids (PUFA) were lowest in the fishing area, but n-3 PUFA did not differ significantly. The n-6:n-3 PUFA ratio was lowest and eicosapentaenoic:arachidonic acid was highest in the fishing area. Although many previous studies have emphasized the beneficial effect of n-3 PUFA in preventing CHD, the present study indicated that a lower intake of n-6 PUFA and saturated fatty acids has an additional preventive effect on CHD even when the serum level of n-3 PUFA is high because of high dietary fish consumption.

Fractional flow reserve in a patient with intermediate coronary stenosis and hypertrophic cardiomyopathy.

We discuss the case of a 61-year-old male patient with hypertrophic cardiomyopathy and chest pain on exertion. Coronary angiography and intravascular ultrasound revealed an intermediate stenosis in the proximal site of the left anterior descending artery, while Tc-99m myocardial scintigraphy revealed exercise-induced myocardial ischemia in the anteroseptal wall and apical portion. Flow velocity-derived coronary flow reserve (CFR) and pressure-derived fractional flow reserve (FFRmyo) were both low (1.1 and 0.59), suggesting that the stenosis was functionally significant. Directional coronary atherectomy greatly improved the FFRmyo (0.99), the scintigraphic findings, and anginal pain but did not improve the CFR (1.2). FFRmyo was useful in assessing the functional significance of an equivocal coronary stenosis and its interventional resolution.

Electrocardiographic score as a predictor of mortality after subarachnoid hemorrhage.

Electrocardiographic (ECG) changes are often associated with subarachnoid hemorrhage (SAH), but it is not well known whether these have prognostic value. The present study retrospectively investigated 122 consecutive patients with SAH caused by ruptured aneurysms. The patients were classified based on the in-hospital outcome into 80 survivors and 42 nonsurvivors. In nonsurvivors, abnormalities often observed on the 12-lead ECG on arrival at hospital were abnormal Q wave, ST depression, and T wave inversion. The ECG score was defined as the total number of leads that had any of these 3 ECG abnormalities. Univariate analysis revealed a strong correlation of in-hospital death with the ECG score, the neurological status estimated by the grading of Hunt and Kosnik, age, and QTc interval. In age- and sex-adjusted multiple logistic regression analysis, the ECG score was the most powerful risk stratifier (ECG score > or = 6 vs ECG score < 6; p=0.0026, odds ratio 14.39, 95% confidence interval 2.54-81.71). The ECG score, a new and simple method of semi-quantification, was a powerful risk predictor in the present patients with SAH.

Echocardiographically documented acute aortic insufficiency induced by Amplatz left guide catheter.

This paper examines a case of sudden systolic pressure fall, tachycardia, low pulse pressure, and high pulmonary artery wedge pressure due to acute aortic insufficiency which was induced by an Amplatz left (AL-1) guide catheter used for better guide support during percutaneous transluminal coronary angioplasty of the right coronary artery. AL guide catheters can cause acute aortic insufficiency, of which practitioners should be aware when sudden hemodynamic collapse occurs.