Tomoaki Nakata

Cardiac death prediction and impaired cardiac sympathetic innervation assessed by MIBG in patients with failing and nonfailing hearts.

BackgroundAlthough cardiac sympathetic nerve dysfunction is related to poor clinical outcome, a critical sympathetic dysfunction level for predicting cardiac death is still unclear. The current study was designed to investigate which indices derived from metaiodobenzylguanidine (MIBG) imaging have prognostic value compared with clinical and cardiac function variables, and to determine the threshold of cardiac MIBG activity for identifying patients likely to suffer cardiac death in both failing and nonfailing hearts.Methods and ResultsMyocardial I-123-MIBG activity was quantified as a heart-to-mediastinum ratio in 414 consecutive patients, 173 (42%) of whom had symptomatic heart failure. After cardiac function measurements, patients were followed up with an end-point of cardiac or noncardiac death. During a mean follow-up period of 22 months, 37 cardiac deaths occurred: 23 resulted from heart failure, 9 were sudden cardiac deaths, and 5 were fatal myocardial infarctions. Multivariate analysis using the Wald χ2 and the Cox proportional hazard model revealed that late heart-to-mediastinum ratio, the use of nitrates, early heart-to-mediastinum ratio, and left ventricular ejection fraction were independent predictors of cardiac death; late heart-to-mediastinum ratio, New York Heart Association (NYHA) class, the presence of previousmyocardial infarction, and age were independent predictors of heart failure and sudden cardiac death. Late heart-to-mediastinum ratio was the most powerful predictor of overall cardiac death among the variables. The Kaplan-Meier analysis showed that a late heart-to-mediastinum ratio of 1.74 or less, age greater than 60 years, the presence of myocardial infarction, and NYHA functional class 3 or 4 strongly indicated poor clinical outcomes. Furthermore, the more powerful incremental prognostic values were obtained by using MIBG imaging in combination with conventional clinical variables.ConclusionsImpaired cardiac sympathetic innervation assessed by MIBG activity has the greatest potential for predicting cardiac death and may be useful for identifying a threshold level for selecting patients at risk for death by heart failure, sudden cardiac death, and fatal myocardial infarction.

Predicting the Need for an Implantable Cardioverter Defibrillator Using Cardiac Metaiodobenzylguanidine Activity Together with Plasma Natriuretic Peptide Concentration or Left Ventricular Function

Despite widespread use of implantable cardioverter defibrillators (ICDs), their cost and the fact that only a certain group of patients fully benefits from the devices require appropriate risk stratification of patients. This study investigated whether altered cardiac autonomic function is associated with the occurrence of ICD discharge or lethal cardiac events. Methods: Fifty-four ICD-treated patients were prospectively followed after assessment of cardiac metaiodobenzylguanidine (MIBG) activity, quantified as the heart-to-mediastinum ratio (HMR), plasma concentration of brain natriuretic peptide (BNP), and left ventricular ejection fraction (LVEF). Patients were divided into 2 groups based on the presence (group A, n = 21) or absence (group B, n = 33) of appropriate ICD discharge during a 15-mo period. Results: Group A had a significantly lower level of MIBG activity and a higher plasma BNP level than did group B. Univariate analysis revealed BNP level, any medication, and late HMR to be significant predictors, and multivariate analysis showed late HMR to be an independent predictor. An HMR of less than 1.95 with a plasma BNP level of more than 187 pg/mL or an LVEF of less than 50% had significantly increased power to predict ICD shock: positive predictive values, 82% (HMR + BNP) and 58% (HMR + LVEF); negative predictive values, 73% (HMR + BNP) and 77% (HMR + LVEF); sensitivities, 45% (HMR + BNP) and 67% (HMR + LVEF); and specificities, 94% (HMR + BNP) and 70% (HMR + LVEF). Conclusion: When combined with plasma BNP concentration or cardiac function, cardiac MIBG activity is closely related to lethal cardiac events and can be used to identify patients who would benefit most from an ICD.

Human Heart-Type Fatty Acid-Binding Protein as an Early Diagnostic and Prognostic Marker in Acute Coronary Syndrome

Although heart-type fatty acid-binding protein (H-FABP) can be a marker of sarcolemmal injury due to acute myocardial ischemia, the diagnostic or prognostic value is not established in patients with acute chest pain. This multicenter prospective study aimed to determine the diagnostic and prognostic values of H-FABP in 133 patients presenting to an emergency room with suspected acute coronary syndrome (ACS) by comparing with those of conventional biomarkers. H-FABP and myoglobin had greater positive results than did creatine kinase-MB or troponin T. Receiver operating characteristics analysis revealed that H-FABP was the most reliable for detection of ACS and that H-FABP had the greatest sensitivities for identification of patients requiring emergency hospitalization, coronary angiography, and interventional therapy within 7 days among the biomarkers. Thus, H-FABP can be an early diagnostic and prognostic biochemical marker, particularly within the first 6 h from the onset of chest symptoms, in patients with chest pain at an emergency department.

A Pooled Analysis of Multicenter Cohort Studies of 123I-mIBG Imaging of Sympathetic Innervation for Assessment of Long-Term Prognosis in Heart Failure

OBJECTIVES The study objectives were to create a cardiac metaiodobenzylguanidine (mIBG) database using multiple prospective cohort studies and to determine the quantitative iodine-123-labeled mIBG indices for identifying patients with chronic heart failure (HF) at greatest and lowest risk of lethal events. BACKGROUND Although the prognostic value of cardiac mIBG imaging in patients with HF has been shown, clinical use of this procedure has been limited. It is required to define universally accepted quantitative thresholds for high and low risk that could be used as an aid to therapeutic decision-making using a large cohort database. METHODS Six prospective HF cohort studies were updated, and the individual datasets were combined for the present patient-level analysis. The database consisted of 1,322 patients with HF followed up for a mean interval of 78 months. Heart-to-mediastinum ratio (HMR) and washout rate of cardiac mIBG activity were the primary cardiac innervation markers. The primary outcome analyzed was all-cause death. RESULTS Lethal events were observed in 326 patients, and the population mortality rate was 5.6%, 11.3%, and 19.7% at 1, 2, and 5 years, respectively. Multivariate Cox proportional hazard model analysis for all-cause mortality identified age (p < 0.0001), New York Heart Association (NYHA) functional class (p < 0.0001), late HMR of cardiac mIBG activity (p < 0.0001), and left ventricular ejection fraction (LVEF) (p = 0.0029) as significant independent predictors. Analysis of the 512-patient subpopulation with B-type natriuretic peptide (BNP) results showed BNP (p < 0.0001), greater NYHA functional class (p = 0.0002), and late HMR (p = 0.0011) as significant predictors, but LVEF was not. The receiver-operating characteristic-determined threshold of HMR (1.68) identified patients at significantly increased risk in any LVEF category. Survival rates decreased progressively with decreasing HMR, with 5-year all-cause mortality rates >7% annually for HMR <1.25, and <2% annually for HMR ≥1.95. Addition of HMR to clinical information resulted in a significant net reclassification improvement of 0.175 (p < 0.0001). CONCLUSIONS Pooled analyses of independent cohort studies confirmed the long-term prognostic value of cardiac mIBG uptake in patients with HF independently of other markers, such as NYHA functional class, BNP, and LVEF, and demonstrated that categoric assessments could be used to define meaningful thresholds for lethal event risk.

Postischemic functional recovery and BMIPP uptake after primary percutaneous transluminal coronary angioplasty in acute myocardial infarction

To correlate asynergic wall motion after primary percutaneous transluminal coronary angioplasty with myocardial perfusion and fatty acid metabolism, quantitative tomographies using thallium and radioiodinated 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) were performed during the acute and recovery stages in 56 consecutive patients with acute myocardial infarction, of whom 32 underwent primary percutaneous transluminal coronary angioplasty (group A) and 24 were conservatively treated (group B); 44 patients (79%) had 1-vessel disease. Reduced myocardial uptakes of thallium and BMIPP and regional wall motion were quantified with a bulls eye technique and a centerline method using contrast left ventriculography, respectively. BMIPP activity was significantly lower than that of thallium at an acute stage in both groups. Abnormal BMIPP activities and the difference in thallium and BMIPP abnormalities (perfusion metabolism mismatch) at an acute stage decreased significantly during follow-up in group A (111 +/- 13 to 99 +/- 12 and 30 +/- 10 to 15 +/- 10, respectively), and not in group B (129 +/- 31 vs 118 +/- 29 and 29 +/- 13 vs 30 +/- 10, respectively). Improvement in regional wall motion abnormality correlated closely with the improved uptakes of thallium and BMIPP (y = 0.64x + 26.4, r = 0.56, p < 0.05; y = 1.1x + 11.1, r = 0.81, p < 0.001; respectively). The mismatched uptake of both tracers at an acute stage was significantly related to recovery from asynergic wall motion during follow-up in group A (y = 0.45x + 13.9, r = 0.65, p < 0.005). In conclusion, despite restored myocardial perfusion by primary coronary angioplasty, BMIPP uptake is impaired in salvaged myocardium at an acute stage of infarction. However, the degree and improvement of perfusion metabolism mismatch in acute myocardial infarction may reflect subsequent recovery from postischemic wall motion abnormality in metabolically impaired but viable myocardium after coronary reperfusion.

Clinical implications of midventricular obstruction and intravenous propranolol use in transient left ventricular apical ballooning (Tako-tsubo cardiomyopathy)

BACKGROUND Persistent hypotension with dynamic midventricular obstruction (MVO) in patients with transient left ventricular (LV) apical ballooning (Tako-tsubo cardiomyopathy) is an important complication that needs to be treated. PURPOSE The objective of this study is to determine the effects of intravenous propranolol challenge on MVO in transient LV apical ballooning. SUBJECTS AND METHODS Thirty-four patients (12 males, 22 females, mean age 64 +/- 17 years, age range 22-84 years) with LV apical ballooning were enrolled. The hemodynamic and echocardiographic effects of propranolol (0.05 mg/kg, maximum 4 mg) were analyzed in 13 patients. RESULTS (1) Midventricular obstruction was present in 8 (24%) of 34 patients, and the pressure gradient (PG) ranged from 28 to 140 mm Hg. (2) Patients with MVO had similar demographic and clinical characteristics (symptoms, peak creatine kinase, plasma catecholamine levels) as those without MVO; however, in patients with MVO, abnormal Q waves on electrocardiogram and hypotension were more prevalent. (3) In the MVO group, intravenous propranolol changed the PG from 90 +/- 42 to 22 +/- 9 mm Hg, the systolic blood pressure (SBP) from 85 +/- 11 to 116 +/- 20 mm Hg, and the LV ejection fraction (LVEF) from 30% +/- 7% to 43% +/- 4%. (4) In all subjects, the changes in the PG after propranolol injection had a significant linear correlation with the SBP and LVEF changes: deltaSBP = 4.738 + 0.315 x deltaPG (r = 0.689 (P < .001) and deltaLVEF = 2.973 + 0.1321 x deltaPG (r = 0.715, P < .001). CONCLUSION Intravenous propranolol is useful for treating dynamic MVO in patients with transient LV apical ballooning.

Quantitative assessment of left ventricular and left atrial functions by strain rate imaging in diabetic patients with and without hypertension.

Background: Impaired left ventricular (LV) function is shown by strain rate (SR) imaging in patients with diabetes mellitus (DM). Left atrium (LA) function in patients with DM, however, has not been assessed by this method and the effect of hypertension (HT) on LV and LA functions in diabetic patients has not been fully studied. The aim of this study was to quantitatively assess LA function in diabetic patients with and without HT in combination with LV function. Methods: Conventional echocardiographic and SR imaging studies were performed in 55 subjects with normal systolic LV function (LV ejection fraction of 55% or more) and no evidence of coronary artery disease: 17 with DM (DM group), 22 who have both DM and HT (DM+HT group), and 16 age‐matched controls. SR imaging was performed from three apical views, and peak SR was measured at 12 LV segments and 5 LA segments. Mean peak systolic SR (LVs and LAs, respectively), early diastolic SR (LVe and LAe, respectively) and late diastolic SR (LVa and LAa, respectively) were calculated by averaging data in each LV and LA segment. Results: Despite no significant differences in age, LV ejection fraction and E/A ratio among the three groups, systolic blood pressure, LA dimension and LV mass index in the DM+HT group were significantly larger than those in the controls. The DM group had reduced systolic and diastolic LV functions and impaired LA reservoir and conduit functions compared with those in the controls, as shown by lower LVs (P < 0.05), LVe (P < 0.01), LAs (P < 0.01), and LAe (P < 0.05). The DM+HT group had reduced LVs (P < 0.01), LVe (P < 0.01), LAs (P < 0.01) and LAe (P < 0.01) compared with those in the controls. The DM+HT group had significantly lower LVe (P < 0.05) and LAe (P < 0.05) than did the DM group. Conclusions: SR imaging can detect impairment of LA reservoir and conduit functions as well as LV systolic and diastolic dysfunctions in patients with DM, even in the absence of LV hypertrophy and LA dilatation. Coexisting HT augments the impairment of LV diastolic and LA conduit functions in diabetic patients.

Impaired Cardiac Sympathetic Innervation and Myocardial Perfusion Are Related to Lethal Arrhythmia: Quantification of Cardiac Tracers in Patients with ICDs

Despite widespread prophylactic use of implantable cardioverter defibrillator (ICD) therapy, sudden cardiac death and refractory arrhythmia events are still important clinical issues to be overcome. We examined whether the impairment of cardiac sympathetic innervation and myocardial perfusion is responsible for lethal arrhythmic events and has prognostic value by comparing conventional clinical indices. Methods: In consecutive ICDs implanted in 60 patients, cardiac uptake of 123I-metaiodobenzylguanidine and 99mTc-tetrofosmin at rest was quantified, and then patients were prospectively followed with endpoints of appropriate ICD shocks or cardiac death. Cardiac metaiodobenzylguanidine activity was quantified as a heart-to-mediastinum ratio (HMR), and impaired tetrofosmin uptake was graded as a summed score (SS) using a computerized technique with a percentage of tracer uptake. Results: During a mean 29-mo interval, ICD shock was documented in 30 patients (50%); 3 cardiac deaths were also observed in this group of patients. Patients with ICD shocks had a significantly smaller HMR and a greater SS than did those without (1.73 ± 0.34 vs. 2.06 ± 0.46, P = 0.003, and 18.0 ± 16.2 vs. 5.7 ± 4.4, P = 0.001, respectively). Kaplan–Meier analysis showed that patients who had both an HMR of 1.90 or less and an SS of 12 or greater had a significantly greater ICD discharge rate than did those who had both an HMR greater than 1.90 and an SS less than 12 (94% vs. 18%, P < 0.005) (log rank, 15.14; P < 0.0005). Multivariate analysis with a Cox model identified the greatest Wald χ2 of 6.454 and a hazard ratio of 3.857 (P = 0.011) when an HMR of 1.9 or less and tetrofosmin SS of 12 or greater were combined. Conclusion: Impairment of cardiac sympathetic innervation and myocardial perfusion is related to lethal arrhythmic events leading to sudden death, and the combined assessment of these can identify patients for whom prophylactic ICD use has the greatest potential.

Cardiac metaiodobenzylguanidine activity can predict the long-term efficacy of angiotensin-converting enzyme inhibitors and/or beta-adrenoceptor blockers in patients with heart failure

PurposeAlthough the benefits of treatment with angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are well known, no method has as yet been established to predict the efficacy of drug therapy. This study tested whether cardiac 123I-metaiodobenzylguanidine (MIBG) activity is of prognostic value and can predict the improvement in heart failure patients resulting from treatment with ACE inhibitors and/or beta-blockers.MethodsFollowing quantification of the heart-to-mediastinum ratio (HMR) of MIBG activity, 88 patients with heart failure who were treated with ACE inhibitors and/or beta-blockers (treated group) and 79 patients with heart failure who were treated conventionally without the aforementioned agents, and who served as controls, were followed up for 43 months with a primary endpoint of cardiac death.ResultsThe treated group had a significantly lower prevalence of cardiac death and a significantly lower mortality at 5 years compared with the control group (15% vs 37% and 21% vs 42%, p<0.05, respectively). Multivariate analysis revealed that significant predictors were HMR, age, nitrate use and ventricular tachycardia for the treated group, and HMR, nitrate use and NYHA class for the control group. The drug treatment significantly reduced mortality from 36% to 12% when HMR was 1.53 or more and from 53% to 37% when HMR was less than 1.53. The reduction in risk of mortality within 5 years in patients without a severe MIBG defect (67%) was twice that in patients with such a defect (32%) (p<0.05).ConclusionThe reduction in mortality risk achieved by using ACE inhibitors and/or beta-blockers is associated with the severity of impairment of cardiac MIBG uptake. Cardiac MIBG activity can consequently be of long-term prognostic value in predicting the effectiveness of such treatment in patients with heart failure.

The Spectrum of Findings in Supra-Aortic Takayasu’s Arteritis as Seen on Spiral CT Angiography and Digital Subtraction Angiography

Takayasu’s arteritis (TA) mainly affects the aorta and its major branches. The lesions are distributed in all elastic arteries that possess vasa vasorum. The frequency of the sites of arterial involvement reflects racial and geographic differences [1–7]. In Japan, stenosis or occlusion of the supra-aortic arch branches is commonly observed and leads to pulseless disease [5–7]. We present the spiral CT angiography (CTA) and intraarterial digital subtraction angiography (IA-DSA) findings of the aortic arch in TA. The spectrum of findings on CTA are stenosis, occlusion, dilatation, arterial wall thickening, and calcification of the aortic arch branches.