Kazuo Munakata

Characteristics and possible mechanism of ventricular arrhythmia dependent on the dispersion of action potential durations.

The arrhythmogenic role of increased dispersion of repolarization (dispersion) was studied in 23 open-chest dogs using six simultaneously recorded monophasic action potentials (MAPs) from the ventricular surface and programmed ventricular premature stimulation (VPS). Increased dispersion was induced by generalized hypothermia (29°C) and regional warm blood (38430C) perfusion through a coronary artery branch. Hypothermia and regional warm blood perfusion increased maximum dispersion from 13 ± 10 to 111 ± 16 msec (p < 0.001), predominantly because of the increased MAP duration difference (10 ± 15 vs 97 ± 16 msec, p < 0.001). The maximal difference between activation times was not significantly changed, but the QRS duration increased from 47 ± 6 to 52 ± 7 msec (p < 0.01). Ventricular arrhythmia did not occur spontaneously but was induced by a single VPS in all 23 dogs during hypothermia and regional warm blood perfusion when dispersion reached a critical magnitude. The critical magnitude of dispersion required to induce ventricular arrhythmia was documented in 16 dogs by stepwise increments or decrements of dispersion. In four dogs, an increase in atrial pacing rate of 24 beats/mm prevented induction of ventricular arrhythmia by decreasing dispersion from a critical magnitude of 103 ± 5 msec to a nonarrhythmogenic value of 86 ± 9 msec (p < 0.05). In six dogs, we compared the stimulation sitedependent effects of VPS applied in the region with short and long MAPs. In all dogs, ventricular arrhythmia was inducible only by VPS from the region with a short MAP. Premature impulses from this region propagated more slowly than those from the region with a long MAP. Our results show that the large dispersion of repolarization facilitates the development of a conduction delay necessary to induce sustained arrhythmia by an early premature stimulus applied at the site with a short MAP.

Global and regional evaluation of systolic and diastolic left ventricular temporal parameters using a novel program for ECG-gated myocardial perfusion SPECT--validation by comparison with gated equilibrium radionuclide angiography and speckle-tracking radial strain from echocardiography.

BACKGROUND A newly developed program, named cardioGRAF, enabled the evaluation of left ventricular (LV) systolic and diastolic temporal parameters for the estimation of heart failure using ECG-gated myocardial perfusion SPECT (GMPS). OBJECTIVE The feasibility of those global (g-) and regional (r-) parameters was validated to compare with gated equilibrium radionuclide angiography (ERNA) and speckle-tracking radial strain (STS) from echocardiography. METHODS Thirty-three patients were studied using GMPS and ERNA (n=11) or GMPS and STS (n=22). The following g- or r-parameters obtained by cardioGRAF and ERNA or STS were compared: time to end systole (TES), time from end systole to peak filling rate (TPF1), time from 0 to peak filling rate (TPF2), time to peak radial strain (TPS), time from peak strain to peak negative strain rate (TP-SR1), and time from 0 to peak negative strain rate (TP-SR2). RESULTS All g-parameters were successfully obtained by cardioGRAF and ERNA. The results demonstrated good correlations (g-TES: r = 0.79, p < 0.005; g-TPF1: r = 0.75, p < 0.02; TPF2: r = 0.83, p < 0.005). The differences were 11.9 +/- 31.8 ms in g-TES, 19.9 +/- 65.4 ms in g-TPF1, and 37.7 +/- 67.4 ms in g-TPF2. All r-parameters were successfully obtained by cardioGRAF. Eight patients and 12 segments were excluded because of the inadequate quality of routine echocardiography for STS analysis. However, r-parameters obtained by cardioGRAF were significantly correlated with those of STS (r-TES and r-TPS: r = 0.61, p = 1 x 10(-8); r-TPF1 and r-TP-SR1: r = 0.69, p = 3 x 10(-11); r-TPF2 and r-TP-SR2: r = 0.76, p = 2 x 10(-15)). The differences were 22.1 +/- 38.2 ms between r-TES and r-TPS, 7.0 +/- 123.4 ms between r-TPF1 and r-TP-SR1, and 38.1 +/- 111.5 ms between r-TPF2 and r-TP-SR2. CONCLUSION The feasibility of evaluating systolic and diastolic temporal parameters by a new program was validated. This program has the potential to evaluate both diastolic and systolic heterogeneous wall motions which express dyssynchrony in heart failure.Background: A newly developed program, named cardioGRAF, enabled the evaluation of left ventricular (LV) systolic and diastolic temporal parameters for the estimation of heart failure using ECG-gated myocardial perfusion SPECT (GMPS).Objective: The feasibility of those global (g-) and regional (r-) parameters was validated to compare with gated equilibrium radionuclide angiography (ERNA) and speckle-tracking radial strain (STS) from echocardiography.Methods: Thirty-three patients were studied using GMPS and ERNA (n=11) or GMPS and STS (n=22). The following g- or r-parameters obtained by cardioGRAF and ERNA or STS were compared: time to en systole (TES), time from end systole to peak filling rate (TPF1), time from 0 to peak filling rate (TPF2), time to peak radial strain (TPS), time from peak strain to peak negative strain rate (TP-SR1), and time from 0 to peak negative strain rate (TP-SR2).Results: All g-parameters were successfully obtained by cardioGRAF and ERNA. The results demonstrated good correlations (g-TES: r=0.79, p<0.005; g-TPF1: r=0.75, p<0.02; TPF2: r=0.83, p<0.005). The differences were 11.9±31.8 ms in g-TES, 19.9±65.4 ms in g-TPF1, and 37.7±67.4 ms in g-TPF2. All r-parameters were successfully obtained by cardioGRAF. Eight patients and 12 segments were excluded because of the inadequate quality of routine echocardiography for STS analysis. However, r-parameters obtained by cardioGRAF were significantly correlated with those of STS (r-TES and r-TPS: r=0.61, p=1×10−8; r-TPF1 and r-TP-SR1: r=0.69, p=3×10−11; r-TPF2 and r-TP-SR2: r=0.76, p=2×10−15). The differences were 21.1±38.2 ms between r-TES and r-TPS, 7.0±123.4 ms between r-TPF1 and r-TP-SR1, and 38.1±111.5 ms between r-TPF2 and r-TP-SR2.Conclusion: The feasibility of evaluating systolic and diastolic temporal parameters by a new program was validated. This program has the potential to evaluate both diastolic and systolic heterogeneous wall motions which express dyssynchrony in heart failure.

Simultaneous assessment of Tc-99m-sestamibi and I-123-BMIPP myocardial distribution in patients with myocardial infarction: evaluation of left ventricular function with ECG-gated myocardial SPECT.

Abstract123I-labeled 15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid (BMIPP) is a branched-chain free fatty acid that is used to evaluate various cardiac diseases. The aim of the present study was to investigate the relationship between myocardial perfusion (99mTc-sestamibi) and BMIPP uptake, and to correlate perfusion and metabolic alterations with regional left ventricular dysfunction in patients with myocardial infarction (MI). ECG-gated dual-isotope myocardial SPECT was performed on 130 patients with MI with sestamibi (555 MBq) and BMIPP (148 MBq). The patients were classified into 3 groups according to PTCA therapy and the interval between the onset of infarction and RI injection (OR time). Group A (n-56) included patients whose OR time was less than one month and who had undergone successful PTCA, Group B (n=36) had OR times of less than one month and had conservative medical therapy, and Group C (n=38) had OR times of over one month. The severity scores of the dual-isotope images were calculated from the defect scores in 9 segments. From the ECG-gated SPECT data with sestamibi, the left ventricular ejection fraction (LVEF; %) and regional wall motion were determined automatically using the QGS programTM. LVEF obtained from gated SPECT correlated well with the severity scores for sestamibi and BMIPP (r=−0.68 and −0.76, respectively). The Δ severity scores (BMIPP scores — sestamibi scores) of Group A were significantly higher than those of the other two groups (3.6±3.0 vs. 1.5±1.7 and 1.0±1.4, p<0.001). The rate of dysfunctional segments with normal sestamibi distribution was significantly higher in Group A than in Group C (20.7% vs. 6.7%, p<0.001). ECG-gated dual-isotope SPECT is useful since myocardial perfusion, fatty acid metabolism and left ventricular function can be analyzed during a single examination, so that this procedure has the potential to provide comprehensive information when evaluating patients with ischemic heart disease.

Quantification of left ventricular regional functions using ECG-gated myocardial perfusion SPECT —validation of left ventricular systolic functions—

ObjectiveWe have developed a program to quantify regional left ventricular (LV) function and wall motion synchrony using ECG-gated myocardial perfusion SPECT (MPS). This preliminary study was undertaken to validate the use of this program for estimating regional LV systolic function.MethodsPatients were subjected to MPS by99mTc-sestamibi at rest. The study included 20 patients who were confirmed to have a low probability of coronary artery disease (LPG; low probability group), 19 heart disease patients who were examined by MPS and equilibrium radionuclide angiography (ERNA) (ERG; ERNA group), and 24 patients who were examined by MPS and 2-dimensional echocardiography (2DE) (2DEG; 2DE group). The values of the ejection fraction (EF) and peak ejection rate (PER) were estimated. The global functions evaluated by this program were compared with those obtained by ERNA in the ERG. For regional assessment, the reference values of the functional indices were obtained for 17 LV segments in LPG. The Z score, (reference average value of the segment — patient’s value of the segment)/reference standard deviation of the segment, was used for the evaluation of regional functions; a score equal to or greater than 2 was defined as abnormal. Semiquantitative visual interpretation of 2DE was used as the standard to assess wall motion. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these criteria and the relationship between 2DE grading and Z scoring were validated in 2DEG.ResultsThe values of the global EF and PER evaluated by this program correlated with those determined by ERNA (r = 0.76 and 0.58, respectively; p < 0.005 and 0.01, respectively). The sensitivities of regional EF and PER for segmental wall motion abnormalities were 86.7% and 68.7%, respectively; their specificities were 86.7% and 95.5%, respectively; their PPVs were 64.3% and 79.2%, respectively; and their NPVs were 96.0% and 91.7%, respectively. The Z scores of these indices significantly correlated with the scores determined by 2DE (rs = 0.70 and 0.68, respectively; p < 10-10).ConclusionThe potential of this program to quantify the regional systolic function was validated.

Increased accumulation of acidic fibroblast growth factor in left ventricular myocytes of patients with idiopathic cardiomyopathy

To clarify the pathophysiologic role of fibroblast growth factors in idiopathic cardiomyopathy, we evaluated endomyocardial biopsy specimens obtained from 24 patients (nine with hypertrophic cardiomyopathy [HCM], 12 with dilated cardiomyopathy [DCM], and three with hypertensive hypertrophy) and six controls. All the specimens were stained for acidic fibroblast growth factor (aFGF) and basic FGF (bFGF) with immunohistochemistry. In situ hybridization was carried out for detection of aFGF mRNA. The average diameter of the myocytes, the percent area of interstitial fibrosis, and capillary vessel density were assessed in each biopsy specimen with morphometric methods. Positive staining of aFGF was observed in the myocytes of the biopsy specimens taken from 15 of 21 (71%) patients with cardiomyopathy (six of nine HCM, nine of 12 DCM) and all hypertensive hypertrophy patients but in none of the controls (p < 0.01). The average diameter of the myocytes was significantly larger in the patients with positive aFGF staining than in those with negative staining (23.1 +/- 1.5 versus 18.3 +/- 1.2 microm, p < 0.05). The percent area of fibrosis and the density of capillaries did not differ between the two groups. Intense expression of aFGF mRNA was observed in the myocytes from the patients with positive aFGF protein. In conclusion, the expression of FGF was significantly increased in myocytes obtained from the left ventricle of patients with cardiomyopathy. Acidic FGF may contribute to the hypertrophy of myocytes as the repair response to myocardial injury in patients with idiopathic cardiomyopathy.

Efficacy of High-Throughput Leukocytapheresis for Rheumatoid Arthritis With a Reduced Response to Infliximab

Infliximab (INF), a tumor necrosis factor‐alpha (TNF‐α) inhibitor, is an effective drug for patients with rheumatoid arthritis (RA). However, some patients receive no clinical benefit, or the agents gradually lose their effect. Five sessions of high‐throughput leukocytapheresis (LCAP) were given at a frequency of once a week using a Cellsorba CS‐180S to four patients with a reduced response to INF. The clinical response to LCAP was evaluated using the 28‐joint disease activity score with C‐reactive protein (DAS28‐CRP) and with the erythrocyte sedimentation rate (DAS28‐ESR). DAS28‐CRP decreased significantly from 5.8 ± 0.6 before LCAP to 3.9 ± 0.7 (P = 0.0182) at 1–2 weeks after completion of five sessions of LCAP, and DAS28‐ESR decreased significantly from 6.4 ± 0.6 to 4.6 ± 0.5 (P = 0.0267). Moreover, all patients had a moderate response according to the European League Against Rheumatism (EULAR) response criteria. The effect of LCAP continued for at least 6 months after its completion in all patients, with no changes in any of their concomitant drugs, and the effect was maintained for at least 1 year in three of the four patients. These results indicate that LCAP is a useful treatment for RA patients with a reduced response to INF.

Usefulness of rosuvastatin to prevent periprocedural myocardial injury in patients undergoing elective coronary intervention.

The aim of the present study was to investigate whether percutaneous coronary intervention-related periprocedural myocardial infarction (MI) can be suppressed more significantly with high- compared with low-dose rosuvastatin. A total of 232 patients scheduled to undergo elective percutaneous coronary intervention within 5 to 7 days were assigned to groups that would receive either 2.5 or 20 mg/day of rosuvastatin (n = 116 each). The incidence of periprocedural MI did not significantly differ between the high and low-dose groups (8.7% vs 18.7%, p = 0.052). In patients who were not taking statins at the time of enrollment, high-dose rosuvastatin significantly suppressed periprocedural MI compared with the low dose (10.5% vs 30.0%, p = 0.037). The difference was not significant in patients who were already taking statins (high vs low dose 7.6% vs 10.6%, p = 0.582). In conclusion, the incidence of percutaneous coronary intervention-related periprocedural MI was reduced more effectively by high-dose than by low-dose rosuvastatin in statin-naive patients. However, low-dose rosuvastatin is sufficient for patients who are already taking statins.

Rapid data acquisition protocol in ECG-gated myocardial perfusion SPECT with Tc-99m-tetrofosmin

Into 25 patients with heart disorders,99mTc-tetrofosmin 555–740 MBq was injected intravenously at rest. After 40 minutes, ECG-gated myocardial perfusion SPECT was performed with a two detector gamma camera VERTEX (ADAC), setting up two detectors to form a 90-degree angle. Sixteen frames per R-R interval were acquired during a 180° rotation from the RAO 45° to the LPO 45°. A pair of data sets with standard (SDA) and rapid data acquisition (RDA) protocols was collected. In an SDA protocol, SPECT imaging was performed for 50 sec per step in 5° angular steps (total acquisition time; 15 minutes). An RDA protocol was conducted with 12 sec per step, 6° angular steps (acquisition time, 3 minutes). LVEF (%) and LVEDVml quantitated automatically with a QGS program showed excellent correlations between two protocols with correlation coefficients of 0.980 (p < 0.01) and 0.983 (p < 0.01), respectively. Subsequently visual assessment of regional wall motion based on a four-point grading system was carried out with a 3-D cine LV display. High complete agreement was gained with 158 (90.3%) out of total 175 segments, so that assessment of the global and regional LV function with the RDA protocol demonstrated high reliability and feasibility.

Relationship between left ventricular function and wall motion synchrony in heart failure assessed by ECG-gated myocardial perfusion SPECT

ObjectiveTo confirm the relationship between left ventricular (LV) function and wall motion synchrony, and to identify the difference of synchrony between an ischemic heart disease (IHD) patient group and other heart disease (OHD) patient group among classified groups in heart failure, systolic, and diastolic parameters were compared using electrocardiograph-gated single-photon emission computed tomography.Methods and resultsTwenty IHD and 30 OHD patient groups, comprised New York Heart Association functional class I–III (IHD1-3 and OHD1-3), and 15 controls were examined. The LV functions (ejection fraction, EF; peak-filling rate, PFR) and synchrony, which was estimated from the time lag between the earliest and latest regional systolic or diastolic temporal parameters (maximum difference of regional time to end-systole, MD-TES, or maximum difference of regional time to peak filling, MD-TPF), were compared. The LV function correlated with its synchrony in IHD and OHD (EF vs. MD-TES: r = −0.86, P = 1.3 × 10−6 in IHD and r = −0.69, P = 2.8 × 10−5 in OHD. PFR versus MD-TPF: r = −0.67, P < 0.002 in IHD and r = −0.63, P < 0.0002 in OHD). Dyssynchronous normal EF was observed in three IHD (15%) and six OHD (20%). Dyssynchronous normal PFR was observed in six IHD (30%) and six OHD (20%). MD-TES was significantly smaller in control group (CG) than in IHD3 and OHD3 (P < 0.005), and in IHD1 than in IHD3 and OHD3 (P < 0.05). MD-TPF was significantly smaller in CG than in IHD2, IHD3, and OHD3 (P < 0.05). However, there was no significant difference between LV synchrony in IHD and OHD, or among LV synchrony of the same functional classes between these two groups.ConclusionsThis study confirms that LV function is correlated with wall motion synchrony. No statistically significant difference was confirmed in wall motion synchrony between IHD and OHD. However, dyssynchrony appears in the patients without apparent global LV dysfunction. This feature may facilitate identification of synchronous disorder in HF patients with preserved global LV function. It is expected that detection of such a disorder may lead to the initiation of appropriate treatments for early stage HF and prevent its progression.

Baroreflex mechanisms and response to exercise in patients with heart disease

Past reports showed that the baroreflex continuously regulates hemodynamics during exercise. However, it is still clinically unclear. If baroreflex mechanism is able to influence actually exercise cardiovascular control, baroreflex sympathetic and/or parasympathetic function relates to response to exercise. Therefore, we examined the relationship of heat rate changes to both blood pressure increment and decrement with tolerance and chronotropic response to peak exercise in patients with heart disease.