Different characteristics of cardiac biomarkers to decide and predict the culprit lesions in patients with suspicious acute coronary syndrome.

This multicenter prospective study was conducted to assess high-sensitivity troponin T (hs-TnT) and other biomarkers to decide and predict culprit lesions indicated for emergency percutaneous coronary intervention (PCI) in patients with suspicious acute coronary syndrome (ACS). We have reported Hs-TnT is the most sensitive biomarker for earlier diagnosis and decision making in patients with suspected ACS. In this study, we had conducted subanalysis investigating the usefulness for prediction of ACS culprit lesion. The patients with suspicious ACS and initially negative whole-blood rapid troponin T test, who underwent coronary angiogram (CAG), were enrolled (n = 74). Hs-TnT, quantitative assay for conventional troponin T (c-TnT), creatine kinase MB isozyme (CK-MB), and heart-type fatty acid-binding protein (H-FABP) were simultaneously measured. ACS culprit lesion was described as total occlusion, subtotal occlusion, and/or angiographical unstable lesion such as thrombosis, ulceration or irregularity. The CAG revealed that 49 cases had ACS lesions to be indicated for emergency PCI. The areas under the ROC curves and ROC-optimized cut-off of hs-TnT, c-TnT, CK-MB, and H-FABP were 0.75, 0.67, 0.68, and 0.75, respectively, and 18, 11, 2.0, and 4.6 ng/ml, respectively. In patients with total occlusion and 90-99 % of diameter stenosis (TIMI 2 or 3), hs-TnT could predict emergency PCI with significantly higher sensitivity compared with H-FABP (hs-TnT >14 ng/ml; 71 %, and H-FABP >6.2 ng/dl; 51 %, p = 0.021) and other biomarkers. Meanwhile, H-FABP displayed significant correlations with number of diseased vessels and presence of thrombotic lesion. The present study first revealed different characteristics of correlation between the angiographic culprit lesions and each cardiac biomarker. For prediction of ACS lesions requiring emergency PCI, hs-TnT had the highest sensitivity with satisfied analytical precision.

High-sensitivity cardiac troponin T for earlier diagnosis of acute myocardial infarction in patients with initially negative troponin T test--comparison between cardiac markers.

BACKGROUND AND PURPOSE: An early diagnosis is essential for therapeutic decision and risk stratification in patients with suspected acute myocardial infarction (AMI). We analyzed and compared the diagnostic value of high-sensitivity troponin T (hs-TnT) and other cardiac markers in patients with an initially negative troponin T test at presentation. METHODS AND SUBJECTS: The present study was a prospective, multicenter study including five participating emergency cardiovascular tertiary centers in Japan. From November 2009 through January 2011, patients with suspected AMI at the emergency room with an initial troponin T (c-TnT) test <100 ng/L were enrolled. RESULTS: A total of 85 patients were prospectively assigned from five participating emergency cardiovascular tertiary centers in Japan. The median time from the onset of chest pain to the T0 sampling was 165 min [IQR 120-180]. The final diagnoses according to the recent universal definition and other standard cut-off values were AMI in 47, unstable angina in 12, and non AMI in 38 patients. The overall ROC-AUC value of hs-TnT, c-TnT, creatine kinase MB, and heart-type fatty acid-binding protein were 0.810, 0.716, 0.782, and 0.880, respectively. The diagnostic sensitivity and negative predictive value of hs-TnT were both 100% for the patients admitted more than 120 min from the onset, however the specificity was limited for the whole time-windows (71%). The absolute value change of the hs-TnT from T0 to T3 sampling 3h later improved the ROC-AUC up to 0.972 and the specificity was 92% at 22 ng/L (ROC-optimized cut-off) and 100% at 105 ng/L (rule-in cut-off). CONCLUSIONS: The hs-TnT displayed 100% sensitivity and negative predictive value for the patients admitted more than 120 min from the onset, however the specificity was limited. The absolute change from T0 to T3 (22 ng/L) improved the total diagnostic performance.

Selective site pacing from the right ventricular mid-septum. Follow-up of lead performance and procedure technique.

Pacing from the right ventricular (RV) apex is associated with adverse effects such as heart failure and atrial fibrillation. We attempted pacing from the RV mid-septum, which is theoretically a more physiological pacing site. A total of 172 consecutive patients with indications for permanent pacemaker implantation were studied. A screw-in lead and a curved stylet were used for lead positioning on the RV mid-septum. Pacemaker indices were evaluated at implantation and one year later. As an electrocardiographic parameter, QRS duration was measured in lead II. These data were compared to those of 66 patients subjected to conventional RV apical pacing. Lead placement was successful in all patients of RV mid-septal pacing. There were no technical problems during or after the procedure. The cumulative percentage of ventricular pacing at one year postimplantation was 85 ± 24 % in the SSP group. Sensing, pacing threshold, and lead impedance in the SSP group remained clinically stable over one year. When these measurements were compared between the SSP and AP groups, the pacing threshold and the lead impedance at one year postimplantation in the SSP group were higher (P < 0.05) and lower (P < 0.01), respectively, than those of the AP group. The mean QRS duration was markedly shorter (123 ± 16 versus 150 ± 18 msec, P < 0.0001). Selective site pacing from the RV mid-septum is feasible and results in less conduction delay compared to conventional RV apical pacing, and its procedure seems to be more physiological in permanent pacemaker implantation.

Heart rate turbulence can predict cardiac mortality following myocardial infarction in patients with diabetes mellitus.

BACKGROUND: Previous studies have described the clinical utility of heart rate turbulence (HRT) as an autonomic predictor in risk-stratifying patients after myocardial infarction (MI). Some reports showed that diabetes mellitus (DM) affects the prognostic value of autonomic markers. We assessed the utility of HRT as a risk marker in post-MI patients with DM and without DM. METHODS: We prospectively enrolled 231 consecutive DM patients and 300 non-DM patients after acute MI. HRT was measured using an algorithm based on 24-hour Holter electrocardiograms (ECGs), assessing 2 parameters: turbulence onset (TO) and turbulence slope (TS). HRT was considered positive when both TO ≥0% and TS ≤2.5 ms/R-R interval were met. The endpoint was defined as cardiac mortality. RESULTS: Of patients with DM, 9 patients (4%) were not utilized for HRT assessment because of frequent ventricular contractions or presence of atrial fibrillation. Forty-two of 222 patients (19%) were HRT positive. During follow-up of 876 ± 424 days, 26 patients (22%) reached the endpoint. Several factors including left ventricular ejection fraction (LVEF), renal dysfunction, documentation of nonsustained ventricular tachycardia (VT), and a HRT-positive outcome had significant association with the endpoint. Multivariate analysis determined that renal dysfunction and a positive HRT outcome had significant value with a hazard ratio (HR) of 4.7 (95%CI, 1.9-11.5; P = 0.0008) and 3.5 (95%CI, 1.4-8.8; P = 0.007), respectively. In non-DM patients, only a positive HRT outcome had significant value. CONCLUSIONS: This study reveals that HRT detected by 24-hour Holter ECG can predict cardiac mortality in post-MI patients whether DM is present or not.

Cardiac swinging calcified amorphous tumors in end-stage renal failure patients.

We recently encountered 2 patients with mobile cardiac calcified amorphous tumors who were successfully treated by surgery. Both patients had mitral annular calcification and were on hemodialysis. These tumors showed swinging motion on echocardiography and they grew rapidly. Intraoperatively, the tumors were found to be fragile and they easily detached from their origin. The histologic findings were thrombus with angiogenesis, fibrin, and calcium deposition. This rapid-growing mobile tumor in end-stage renal failure patients is speculated to increase the risk of embolic events and should be included as a special entity of cardiac amorphous tumors.

Circadian variation in out-of-hospital cardiac arrests due to cardiac cause in a Japanese patient population.

BACKGROUND: It has been reported that cardiovascular events occur more frequently in the morning than in the evening. The purpose of the present study was to assess the characteristics of out-of-hospital cardiac arrests due to cardiac cause in a 24-h period in Japanese patients. METHODS AND RESULTS: Of 2,199 consecutive patients with cardiopulmonary resuscitation outside hospital, 1,293 cardiogenic patients were enrolled. The incidence of cardiac arrests was assessed as hourly data (ie, circadian variation), and investigated for differences in age, gender, and the location at onset. Cardiac arrests had an apparent circadian rhythm that was characterized by 2 long zeniths in the morning and evening. The peak was at 17:00-18:00 hours. Younger patients had more cardiac arrests in the morning than in the evening. In contrast, older patients had more events in the evening than in the morning. The circadian rhythm did not differ in gender. Regarding location, the patient's residence was the most common place for cardiac arrest. In the residence, the bathroom was associated with the evening zenith of circadian variation. CONCLUSIONS: Out-of-hospital cardiac arrests due to cardiac cause in Japanese patients have an apparent circadian variation with 2 long zeniths, with an evening predominance in older patients. Aging affects the evening zenith, in that elderly patients > or =80 years old have a zenith associated with bath time in the evening.

Effects of landiolol, an ultra-short-acting beta1-selective blocker, on electrical storm refractory to class III antiarrhythmic drugs.

BACKGROUND: Occasionally it is difficult to inhibit electrical storm (ES) with standard pharmacological treatment. In the present study the effect of landiolol, an ultra-short-acting beta(1)-selective blocker, on ES refractory to class III antiarrhythmic drugs was evaluated. METHODS AND RESULTS: The study group comprised 42 consecutive patients who developed ES for which intravenous class III antiarrhythmic drugs, such as amiodarone and nifekalant, were ineffective. Landiolol was administered intravenously with an initial dose of 2.5 microg x kg(-1) x min(-1), which was doubled if it was ineffective, up to a maximum dose of 80 microg x kg(-1) x min(-1). Landiolol inhibited ES in 33 patients (79%) at a mean dose of 7.5+/-12.2 microg x kg(-1) x min(-1). All patients in whom landiolol was ineffective died of arrhythmia. Of the 33 patients in whom landiolol was effective, 25 survived and were discharged (60% of all patients). Landiolol significantly decreased heart rate (P<0.0001), but did not affect blood pressure. Landiolol was not discontinued for adverse effects in any of the responders. Age, APACHE II score, and pH of arterial blood gas differed significantly between the responders and nonresponders. CONCLUSIONS: Landiolol is useful as a life-saving drug for class III antiarrhythmic drug-resistant ES. The main mechanism of ES refractory to class III antiarrhythmic drugs could be abnormal automaticity but not reentry.

Circadian variation of late potentials in idiopathic ventricular fibrillation associated with J waves: insights into alternative pathophysiology and risk stratification.

BACKGROUND: The presence of J waves on ECGs is related to idiopathic ventricular fibrillation (VF). OBJECTIVE: The purpose of this study was to investigate the pathophysiology of J waves by assessing risk markers that reflect electrophysiologic abnormalities. METHODS: The study enrolled 22 idiopathic VF patients (17 men and 5 women; mean age 36 +/- 13 years). Patients were divided into two groups according to the presence or absence of J waves. The following risk stratifiers were assessed: late potentials (LPs; depolarization abnormality marker) for 24 hours using a newly developed signal-averaging system, and T-wave alternans and QT dispersion (repolarization abnormality markers). Frequency-domain heart rate variability (HRV), which reflects autonomic modulation, also was assessed. The results were compared to those of 30 control subjects with J waves and 30 with no J wave, matched for age and gender to the idiopathic VF patients. RESULTS: J waves were present in 7 (32%) idiopathic VF patients. The incidence of LP in the idiopathic VF J-wave group was higher than in the idiopathic VF non-J-wave group (86% vs 27%, P = .02). In contrast, repolarization abnormality markers did not differ between the two groups. In the idiopathic VF J-wave group, dynamic changes in LP parameters (fQRS, RMS(40), LAS(40)) were observed and were pronounced at nighttime; this was not the case in the idiopathic VF non-J-wave group and the control J-wave group. High-frequency components (vagal tone index) on frequency-domain HRV analysis were associated with J waves in idiopathic VF patients (P < .05). CONCLUSION: Idiopathic VF patients with J waves had a high incidence of LP showing circadian variation with night ascendancy. J waves may be more closely associated with depolarization abnormality and autonomic modulation than with repolarization abnormality.

Effects of intravenous nifekalant as a lifesaving drug for severe ventricular tachyarrhythmias complicating acute coronary syndrome.

BACKGROUND: Intravenous amiodarone (AMD) has been used for the treatment of ventricular tachycardia/fibrillation (VT/VF) in emergency care medicine. However, AMD acts slowly and is occasionally accompanied by hypotension and bradycardia. The antiarrhythmic effect of intravenous nifekalant (NIF) was assessed in patients with VT/VF complicating acute coronary syndrome (ACS) according to our study protocol. METHODS AND RESULTS: Among a series of 1,143 ACS patients, 41 patients who suffered sustained VT/VF were enrolled; 19 failed to respond to a preceding lidocaine (LID) injection. NIF was given first as an intravenous bolus injection (0.2 mg/kg) and then as a continuous intravenous infusion at a relatively low dose level (0.2 mg x kg(-1) x h(-1)). Sustained VT/VF was successfully inhibited by NIF in 34 patients (83%). In subgroup analysis, NIF achieved VT/VF inhibition in 79% of patients who received preceding LID and in 86% of patients who received direct NIF. There were no significant changes in systolic blood pressure or heart rate following NIF therapy. A corrected QT interval was significantly prolonged (P<0.01), whereas torsade de pointes developed in only 1 patient (2%). CONCLUSIONS: An intravenous bolus injection and subsequent continuous infusion of NIF at a relatively low dosage were effective in treating severe ventricular tachyarrhythmias complicating ACS, reducing the potential risk of proarrhythmia.

Quantitative assessment of cibenzoline administration for vagally mediated paroxysmal atrial fibrillation using frequency-domain heart rate variability analysis.

BACKGROUND: Cibenzoline (CBZ), a class I antiarrhythmic drug, has been widely used to maintain sinus rhythm in patients with paroxysmal atrial fibrillation (P-AF). This agent has an anticholinergic action and will become the drug of first choice for vagally mediated P-AF. We assessed its efficacy quantitatively by analyzing the frequency-domain heart rate variability (FD-HRV) of the Holter electrocardiogram (ECG) in patients with vagal P-AF. METHODS: We enrolled 65 consecutive patients with vagal P-AF, but 31 patients were excluded because of the occurrence of significant arrhythmias during the 24-h Holter recordings. Accordingly, CBZ was administered to the remaining 34 patients. After administration, a Holter ECG recording was made again. High frequency (HF) components, i.e., vagal tone index, on the FD-HRV analysis from 00:00 h to 06:00 h were used for assessment. In 14 patients, the treatment was changed to disopyramide (DSP) and the same analyses were performed. RESULTS: In two patients, the FD-HRV analysis was not utilized after administration. Finally, 32 patients were available for evaluation. CBZ was considered effective for vagal P-AF in 24 patients (75%). After administration, the HF component levels decreased (1589+/-795 ms(2) vs. 850+/-524 ms(2), p<0.0001). Comparison of the pre-administration HF component levels between the CBZ-responsive group and the CBZ-non-responsive group showed higher levels in the CBZ-responsive group (1766+/-758 ms(2) vs. 1058+/-690 ms(2), p=0.026). Although no significant difference in the reduction of the HF component levels was found between CBZ and DSP, DSP had anticholinergic side effects in two patients (14%). CONCLUSIONS: In vagal P-AF patients, larger HF components on the FD-HRV analysis could be a hallmark of the antiarrhythmic action of CBZ. The reduction in the HF component levels after drug administration is useful for a quantitative assessment of anticholinergic action.

Time-domain T-wave alternans measured from Holter electrocardiograms predicts cardiac mortality in patients with left ventricular dysfunction: a prospective study.

BACKGROUND: Time-domain T-wave alternans (TWA) is useful for identifying patients at risk for serious events after myocardial infarction. OBJECTIVE: The purpose of this study was to prospectively evaluate the utility of time-domain TWA measured from Holter ECGs in predicting cardiac mortality in patients with left ventricular (LV) dysfunction. METHODS: Two hundred ninety-five consecutive patients with LV dysfunction were enrolled in the study. Patients were divided into two groups: the ischemic group (n = 195) and the nonischemic group (n = 100). Time-domain TWA was assessed using the modified moving average method from routine 24-hour Holter ECGs recorded during daily activity. The maximal time-domain TWA voltage at heart rate or=65 microV. The primary end-point was defined as cardiac mortality. RESULTS: Mean maximal time-domain TWA voltage was 54 +/- 16 microV. During follow-up of 390 +/- 212 days, 27 patients (17 in the ischemic group and 10 in the nonischemic group) died of cardiac causes. Fifty-three patients (18%) were time-domain TWA positive and 242 (82%) were time-domain TWA negative. Univariate Cox proportional hazards analyses revealed that older age, New York Heart Association functional class III or IV, diabetes, renal dysfunction, nonsustained ventricular tachycardia, and time-domain TWA were associated with cardiac mortality. In multivariate analysis, time-domain TWA had the most significant value (hazard ratio = 17.1, P <.0001). This index also was significant in both subgroups (ischemic group: hazard ratio = 19.0, P <.0001; nonischemic group: hazard ratio = 12.3, P = .002). CONCLUSION: Time-domain TWA measured from 24-hour Holter ECGs predicts cardiac mortality in patients with ischemic and nonischemic LV dysfunction.

Heart rate turbulence as a predictor of cardiac mortality and arrhythmic events in patients with dilated cardiomyopathy: a prospective study.

BACKGROUND: Few studies have described the clinical usefulness of heart rate turbulence (HRT), an autonomic predictor of mortality, in stratifying patients with dilated cardiomyopathy (DCM) at risk of cardiac mortality and arrhythmic events. We prospectively assessed the utility of HRT for risk stratification in patients with ischemic or nonischemic DCM. METHODS: We enrolled 375 consecutive patients with DCM including ischemic (n = 241) and nonischemic causes (n = 134). HRT was measured using an algorithm based on routine 24-hour Holter electrocardiograms, assessing 2 parameters: turbulence onset (TO) and turbulence slope (TS). HRT was considered positive when both TO was > or = 0% and TS was < or = 2.5 ms/R-R interval. The primary endpoint was defined as cardiac mortality and the secondary endpoint as occurrence of hemodynamically stable sustained ventricular tachyarrhythmias. RESULTS: Of patients enrolled, 83 patients (22.1%) were not utilized for HRT assessment because there were too few ventricular premature beats, or for other reasons. Eighty-one of 292 patients (27.7%) were HRT-positive. During follow-up of 445 +/- 216 days, 30 patients (10.3%) reached the primary endpoint and 17 patients, the secondary endpoint. The hazard ratio (HR) of patients with an HRT-positive outcome was 6.4 (95%CI, 3.0-14.1; P < 0.0001) for the primary endpoint and 5.1 (95%CI, 2.8-9.3; P < 0.0001) for combined endpoints. On subanalysis, HRT positivity was significantly associated in both the ischemic and nonischemic DCM patients with both the primary endpoint (HR = 4.9, P = 0.0006 and HR = 12.3, P = 0.002, respectively) and with combined endpoints. CONCLUSIONS: HRT is a powerful risk stratification marker for cardiac mortality and arrhythmic events in patients with DCM whether ischemia is present or not.

Antiarrhythmic effect of bisoprolol, a highly selective beta1-blocker, in patients with paroxysmal atrial fibrillation.

In the treatment of arrhythmia, beta-blockers are mainly used to regulate the heart rate. However, beta-blockers are also known as drugs with an antiarrhythmic effect due to the suppression of sympathetic activity. We evaluated the antiarrhythmic effects of a highly selective beta(1)-blocker, bisoprolol, in patients with diurnal paroxysmal atrial fibrillation (P-AF). A total of 136 patients with symptomatic diurnal P-AF were enrolled. Patients were divided into a diurnal-specific P-AF group and a diurnal & nocturnal P-AF group, as well as into a bisoprolol single use group and a combined use group with an antiarrhythmic drug. The effects of bisoprolol were evaluated in 3 categories: subjective symptom improvement, quality of life (QOL) improvement, and elimination of P-AF episode in Holter electrocardiograms (ECGs). For patients with effective treatment, a long-term effect up to 24 months was evaluated. Five patients (3.7%) discontinued bisoprolol due to side effects. Following administration of bisoprolol, 109 patients (80%) experienced subjective symptom improvement, 103 patients (76%) experienced QOL improvement, and elimination of P-AF episodes in ECGs was observed in 84 patients (62%). The elimination rate of P-AF episodes in ECGs was higher in the diurnal P-AF group than in the diurnal & nocturnal P-AF group (P=0.042). There was no significant difference between the bisoprolol single use group and the combined use group. A long-term suppressive effect by bisoprolol was observed in 70 of 83 patients (84%). The results demonstrate that bisoprolol has an antiarrhythmic effect against sympathetic diurnal P-AF, improving subjective symptoms and QOL and eliminating P-AF episodes in ECGs.

The full stomach test as a novel diagnostic technique for identifying patients at risk of Brugada syndrome.

INTRODUCTION: Autonomic modulation, particularly high vagal tone, plays an important role in the occurrence of ventricular tachyarrhythmias in the Brugada syndrome. Food intake modulates vagal activity. We assessed the usefulness of a novel diagnostic technique, the "full stomach test," for identifying a high-risk group in patients with a Brugada-type electrocardiogram (ECG). METHODS AND RESULTS: In 35 patients with a Brugada-type ECG, we assessed 12-lead ECGs before and after a large meal, a pilsicainide pharmacological test, spontaneous ST-segment change, late potentials by signal-averaged ECG, microvolt T-wave alternans, and four other ECG parameters. These patients were divided into two groups (i.e., high-risk group [n = 17] and indeterminate risk group [n = 18]). The full stomach test was defined as positive when augmentation of characteristic ECG abnormalities was observed after meals. Thirteen patients had a prior history of life-threatening events such as aborted sudden death and syncope, with a total of 30 episodes. These episodes had a circadian pattern, at night and after meals. The full stomach test was positive in 17 of the study patients (49%). A positive test outcome was characterized by a higher incidence of a history of life-threatening events than a negative test outcome (P = 0.015, odds ratio = 7.1). In comparison between the two groups, the incidence (82%) of positive outcomes in the high-risk group was significantly higher than that (17%) in the indeterminate risk group (P = 0.0002). CONCLUSIONS: Characteristic ECG changes diagnostic of Brugada syndrome are augmented by a large meal. These data are associated with a history of life-threatening events in Brugada syndrome.