Tadaaki Kamitani

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.

Abnormal myocardial uptake and clearance of 123I-labeled metaiodobenzylguanidine in patients with chronic renal failure and autonomic dysfunction.

BackgroundPatients with chronic renal failure were evaluated with 123I-labeled metaiodo-benzylguanidine (MIBG) myocardial scintigraphy to investigate the relationship between abnormal findings on MIBG scintigrams and autonomic dysfunction.Methods and ResultsEleven control subjects and 20 patients with chronic renal failure (CRF) (serum creatinine level >8 mg/dl) were evaluated by MIBG myocardial scintigraphy and power spectral analysis (PSA) of the R-R fluctuations of the electrocardiogram. Subjects with CRF were divided into two groups: without (CRF1; nine patients) or with (CRF2; 11 patients) autonomic neuropathy. From MIBG images, the heart/mediastinum mean count rate, defect score, which was scored visually, and clearance rate were calculated. Percent low-frequency power and high-frequency power were obtained from PSA. MIBG scintigrams showed decreased heart/mediastinum mean count rate, a high defect score in both initial and delayed images, and rapid clearance rate in the CRF2 group. PSA showed an abnormally low percent low-frequency power and high-frequency power in the CRF2 group. In addition, there was a weak but significant inverse correlation between percent low-frequency power and defect score.ConclusionAlterations in MIBG scintigrams are seen in patients with autonomic dysfunction in CRF and may be useful for evaluating cardiac sympathetic dysfunction in those patients.

Enhanced vagal modulation and exercise induced ischaemia of the inferoposterior myocardium

Objective: To determine whether the Bezold-Jarisch reflex or enhancement of vagal nerves, which are preferentially distributed in the inferoposterior myocardium, results from exercise induced ischaemia in this region. Methods: On the basis of exercise myocardial scintigraphy and coronary angiography, 145 patients were classified as follows: group I, 34 patients with inferoposterior ischaemia; group A, 32 with anterior ischaemia; and control, 79 without ischaemia. The relation between ischaemic areas and ECG leads with ST segment changes and vagal modulation assessed by heart rate variability (HRV) (high frequency (HF) component (0.15–0.40 Hz) and coefficient of HF component variance (CCVHF), which is the square root of HF divided by mean RR interval) were assessed. Results: The rate of ST segment depression in any lead did not differ between group I and group A. HF and CCVHF were similar before exercise but higher in group I than in group A and the control group after exercise (mean (SEM) HF: 94 (17) ms2, 41 (7) ms2, and 45 (6) ms2, respectively, p  =  0.021; CCVHF: 1.18 (0.09)%, 0.81 (0.07)%, and 0.89 (0.05)%, p  = 0.0053). Furthermore, the percentage change in CCVHF before and after exercise was higher in group I than in group A or controls (mean (SEM) 22 (10)%, −24 (4)%, and −21 (3)%, p < 0.0001). The optimal cut off for diagnosis of inferoposterior ischaemia was −5% with a sensitivity of 74%, specificity 75%, and accuracy 75%. Conclusions: Vagal modulation as assessed by HRV analysis was enhanced in association with exercise induced inferoposterior ischaemia. Exercise ECG testing combined with HRV analysis would increase accuracy in the diagnosis of ischaemic areas in selected patients with angina pectoris.

Diagnostic performance of ultrasonic tissue characterization for subendocardial ischaemia in patients with hypertrophic cardiomyopathy

AIMS Hypertrophic cardiomyopathy (HCM) patients often develop left--ventricular subendocardial ischaemia, a cause of chest symptoms, despite normal epicardial coronary arteries. The aim of this study was to examine whether ultrasonic tissue characterization or late gadolinium enhancement on cardiac magnetic resonance imaging can detect subendocardial ischaemia in patients with HCM. METHODS AND RESULTS Subendocardial ischaemia was quantified on exercise Tc-99m tetrofosmin myocardial scintigraphy in 29 non-obstructive HCM patients with asymmetric septal hypertrophy. Ultrasonic tissue characterization using cyclic variation of integrated backscatter (CV-IB) and late gadolinium enhancement on cardiac magnetic resonance imaging were analysed separately in the right halves and the left halves of the ventricular septum in relation to subendocardial ischaemia. Subendocardial ischaemia was identified in 17 (59%) patients. The ratio of CV-IB in the right-to-left halves of the ventricular septum was significantly higher in patients with subendocardial ischaemia (1.19 ± 0.10) than those without (0.84 ± 0.10, P = 0.04). The optimal cutoff for the detection of subendocardial ischaemia was the ratio of CV-IB >1.0, with a sensitivity of 80%, specificity of 71%, and accuracy of 76%. On the other hand, late gadolinium enhancement was not associated with subendocardial ischaemia in our cohort. CONCLUSION Ultrasonic tissue characterization using CV-IB separately in the right and left halves of the ventricular septum, but not late gadolinium enhancement on magnetic resonance imaging, provided useful information in detecting subendocardial ischaemia in patients with HCM. Ultrasonic tissue characterization may be useful in selecting patients who will benefit from medications to relieve chest symptoms.

Notched QRS for the Assessment of Myocardial Fibrosis in Hypertrophic Cardiomyopathy

BACKGROUND Patients with hypertrophic cardiomyopathy (HCM) sometimes develop myocardial fibrosis in association with adverse cardiovascular events. Electrocardiography (ECG) could provide helpful information on myocardial fibrosis in HCM, as in coronary artery disease. METHODS AND RESULTS A total of 60 patients with HCM without bundle branch block underwent cardiac magnetic resonance imaging (CMR). The extent or location of late gadolinium enhancement (LGE) was examined in relation to 12-lead ECG. A notch on QRS was defined as at least 2 consecutive spikes in the same polarity with a reversal of direction ≥90° and the initial negative deflection ≥0.05 mV. LGE was associated with notched QRS, leftward QRS axis, and prolonged QRS duration, but not with any other findings such as abnormal Q waves, R-wave amplitude, or ST-T changes. Notched QRS was most useful in determining the presence or absence of myocardial fibrosis, with a sensitivity of 70% and a specificity of 81% using a cut-off of the number of leads with notched QRS ≥2. The number of notched QRS leads was positively correlated with LGE volume (P<0.01) and the lead distribution of notched QRS was informative about the location of LGE. CONCLUSIONS A notch on QRS was useful in estimating myocardial fibrosis as assessed on CMR LGE in HCM patients without bundle branch block.

Holter Monitoring and Long-Term Prognosis in Hypertrophic Cardiomyopathy

Objectives: Limited data are available regarding Holter monitoring for cardiovascular events except for ventricular tachycardia as a risk marker for sudden death in hypertrophic cardiomyopathy (HCM). We aimed to examine Holter findings in relation to the long-term prognosis in patients with HCM. Methods: Ambulatory Holter monitoring was performed in 106 HCM patients with sinus rhythm. All were prospectively followed for the composite endpoint of sudden death, cardiovascular death, and hospitalization for heart failure or stroke associated with atrial fibrillation. Results: Cardiovascular events occurred in 19 patients during a mean follow-up of 10.1 years. Neither arrhythmia information nor autonomic information as assessed by heart rate variability and turbulence significantly differed between HCM patients with and without cardiovascular events. Average heart rates were lower in HCM patients with cardiovascular events (64.7 ± 11.2 beats/min) than in those without (73.7 ± 10.2 beats/min, p = 0.001). Multivariate Cox proportional hazards regression analysis after adjustment for baseline characteristics showed that lower average heart rate remained an independent predictor of cardiovascular events (HR: 0.47 per 10 increase; 95% CI: 0.25–0.87; p = 0.016). Conclusion: Average heart rate on Holter monitoring predicted long-term prognosis in our cohort. Further multicenter studies are needed to confirm our results.

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.

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.

Mitral Valve Prolapse Revisited.

A 75-year-old man was admitted with abrupt onset of dyspnea during sleep. On examination, his blood pressure was 222/165 mm Hg, pulse was 160 bpm, and oxygen saturation was 75% while breathing ambient air. Heart sounds were difficult to assess because of coarse crackles and his moaning. There was no edema in the extremities. An ECG showed sinus tachycardia with a QRS duration of 111 milliseconds, and a chest radiograph showed pulmonary edema without cardiomegaly. A presumed diagnosis of acute heart failure was made, and isosorbide dinitrate was administered intravenously with supplemental oxygen via a face mask. Cardiac auscultation after stabilization of vital signs showed a holosystolic murmur at the apex and an early systolic click at the left sternal border. Mitral regurgitation resulting from mitral valve prolapse (MVP) was most likely but was not confirmed by transthoracic echocardiography because of a lack of definitive evidence (Figure 1). Of note, another extra sound during early diastole was heard best at the third left sternal border. Figure 1. Apical 2-chamber views of the left ventricle (LV) on transthoracic echocardiography show insufficient coaptation of the mitral leaflets ( A , arrow) and …

Right bundle branch block and ventricular septal fibrosis in patients with hypertrophic cardiomyopathy

BACKGROUND Right bundle branch block (RBBB) is associated with ventricular septal fibrosis in patients with hypertrophic cardiomyopathy (HCM) after alcohol septal ablation, but little data are available in HCM patients without a history of septal ablation. METHODS Magnetic resonance late gadolinium enhancement (LGE) was performed in 59 HCM patients with no history of alcohol septal ablation. The location and extent of LGE were examined in relation to electrocardiographic features including RBBB. RESULTS LGE volume was higher in 7 HCM patients with RBBB (7.3±7.4g/cm) than in patients without RBBB (2.9±7.4g/cm, p=0.016). LGE volume was positively correlated to QRS duration of RBBB (correlation coefficient=0.93, p=0.023). The diagnostic value of RBBB was highly specific for the detection of LGE in the ventricular septum, with sensitivity 21% and specificity 94%. CONCLUSIONS The presence of RBBB may be a simple marker for detecting ventricular septal fibrosis in HCM patients who had no history of alcohol septal ablation. Further studies are necessary to confirm our findings.