Michihiro Yoshimura

Possible increase in insulin resistance and concealed glucose-coupled potassium-lowering mechanisms during acute coronary syndrome documented by covariance structure analysis

Objective Although glucose-insulin-potassium (GIK) therapy ought to be beneficial for ischemic heart disease in general, variable outcomes in many clinical trials of GIK in acute coronary syndrome (ACS) had a controversial impact. This study was designed to examine whether “insulin resistance” is involved in ACS and to clarify other potential intrinsic compensatory mechanisms for GIK tolerance through highly statistical procedure. Methods and results We compared the degree of insulin resistance during ACS attack and remission phase after treatment in individual patients (n = 104). During ACS, homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly increased (P<0.001), while serum potassium levels were transiently decreased (degree of which was indicated by ΔK) (P<0.001). This finding provides a renewed paradox, as ΔK, a surrogate marker of intrinsic GIK cascade activation, probably reflects the validated glucose metabolism during ischemic attack. Indeed, multiple regression analysis revealed that plasma glucose level during ACS was positively correlated with ΔK (P = 0.026), whereas HOMA-IR had no impact on ΔK. This positive correlation between ΔK and glucose was confirmed by covariance structure analysis with a strong impact (β: 0.398, P = 0.015). Intriguingly, a higher incidence of myocardial infarction relative to unstable angina pectoris, as well as a longer hospitalization period were observed in patients with larger ΔK, indicating that ΔK also reflects disease severity of ACS. Conclusions Insulin resistance most likely increases during ACS; however, ΔK was positively correlated with plasma glucose level, which overwhelmed insulin resistance condition. The present study with covariance structure analysis suggests that there are potential endogenous glucose-coupled potassium lowering mechanisms, other than insulin, regulating glucose metabolism during ACS.

Incidence and Factors Associated With the Occurrence of Pulmonary Vein Narrowing After Cryoballoon Ablation

Background— In contrast with traditional radiofrequency ablation, little is known about the influence of cryoballoon ablation on the morphology of pulmonary veins (PVs). We evaluated the influence of cryoballoon ablation on the PV dimension (PVD) and investigated the factors associated with a reduction of the PVD. Methods and Results— Seventy-four patients who underwent cryoballoon ablation for paroxysmal atrial fibrillation were included in the present study. All subjects underwent contrast-enhanced computed tomography both before and at 3 months after the procedure. The PVD (cross-sectional area) was measured using a 3-dimensional electroanatomical mapping system. Each PV was evaluated according to the PVD reduction rate (&Dgr;PVD), which was calculated as follows: (1−post-PVD/pre-PVD)×100 (%). Ninety-two percent of the PVs (271/296) were successfully isolated only by cryoballoon ablation; the remaining 8% of the PVs required touch-up ablation and were excluded from the analysis. Mild (25%–50%), moderate (50%–75%), and severe (≥75%) &Dgr;PVD values were observed in 87, 14, and 3 PVs, respectively, including 1 case with severe left superior PV stenosis (&Dgr;PVD: 94%) in a patient who required PV angioplasty. In multivariable analysis, a larger PV ostium and lower minimum freezing temperature during cryoballoon ablation were independently associated with PV narrowing (odds ratio, 1.773; P=0.01; and odds ratio, 1.137; P<0.001, respectively). Conclusions— A reduction of the PVD was often observed after cryoballoon ablation for atrial fibrillation. A larger PV ostium and lower minimum freezing temperature during cryoballoon ablation were associated with an increased risk of PVD reduction.

Associations between Left Ventricular Cavity Size and Cardiac Function and Overload Determined by Natriuretic Peptide Levels and a Covariance Structure Analysis

The effects of left ventricular (LV) cavity size on cardiac function and overload have not yet been fully elucidated. We performed a covariance structure analysis and drew theoretical path models to clarify the effects of hemodynamic parameters on the stroke volume index (SVI) as a marker of cardiac function and on the plasma B-type natriuretic peptide (BNP) level as a marker of cardiac overload. We simultaneously measured various hemodynamic parameters and the BNP levels during cardiac catheterization in 1,715 inpatients of our institution. The current path models tested the validity of the Frank-Starling law in patients with heart failure using the SVI, the LV end-systolic volume index (LVESVI) and the LV end-diastolic volume index (LVEDVI). Using the BNP levels, the path models clearly demonstrated that LVESVI substantially augmented cardiac overload, whereas LVEDVI palliated this parameter. These volume indices exerted opposite effects on cardiac function and overload. These results advance the understanding of the relationships between LV cavity size and both cardiac function and overload and indicate the increasing importance of LV diastolic volume in heart failure and the utility of LVESVI as an important marker of cardiac remodeling for further relevant studies.

Close linkage between serum uric acid and cardiac dysfunction in patients with ischemic heart disease according to covariance structure analysis

High serum uric acid (UA) level has been assumed to be a risk factor for left ventricular (LV) dysfunction; however, the precise relationship between these conditions has not been fully examined because many confounding factors are associated with UA level. We herein examined the precise relationship by proposing structural equation models. The study population consisted of 1432 cases with ischemic heart disease who underwent cardiac catheterization. Multiple regression analyses and covariance structure analyses were performed to elucidate the cause-and-effect relationship between UA level and LV ejection fraction (LVEF). A path model exploring the factors contributing to LVEF showed that high UA was a significant cause of reduced LVEF (Pu2009=u20090.004), independent of other significant factors. The degree of atherosclerosis, as estimated by the number of diseased coronary vessels, was significantly affected by high UA (Pu2009=u20090.005); and the number of diseased coronary vessels subsequently led to reduced LVEF (Pu2009<u20090.001). Another path model exploring the factors contributing to UA level showed that LVEF was a significant cause of high UA (Pu2009=u20090.001), while other risk factors were also independent contributing factors. This study clearly demonstrated that there was a close link between high UA and LV dysfunction, which was represented by possible cause-and-effect relationship.

Manifold implications of obesity in ischemic heart disease among Japanese patients according to covariance structure analysis: Low reactivity of B-type natriuretic peptide as an intervening risk factor

Background/Objectives Obesity is believed to be one of the major risk factors for cardiovascular disease in Western countries. However, the effects of obesity should be continuously examined in the Japanese population because the average bodily habitus differs among countries. In this study, we collectively examined the significance of obesity and obesity-triggered risk factors including the low reactivity of B-type natriuretic peptide (BNP), for ischemic heart disease (IHD) in Japanese patients. Methods and results The study patients consisted of 1252 subjects (IHD: n = 970; non-IHD: n = 282). Multiple logistic regression analysis revealed that dyslipidemia, hypertension, diabetes, and the low reactivity of BNP were significant risk factors for IHD, but body mass index (BMI) was not. A theoretical path model was proposed by positioning BMI at the top of the hierarchical model. Exploratory factor analysis revealed that BMI did not play a causative role in IHD (P = NS). BMI was causatively linked to other risk factors (P<0.001 for hypertension; P<0.001 for dyslipidemia; P<0.001 for HbA1c; P<0.001 for LogBNP), and these factors played a causative role in IHD (P<0.001 for hypertension; P<0.001 for dyslipidemia; P<0.001 for HbA1c; P<0.001 for LogBNP). The intrinsic power of the low reactivity of BNP induced by high BMI on the promotion of IHD was fairly potent. Conclusion This study demonstrated that obesity per se is not a strong risk factor for IHD in Japanese patients. However, several important risk factors triggered by obesity exhibited a causative role for IHD. The low reactivity of BNP is a substantial risk factor for IHD.

The diabetic heart utilizes ketone bodies as an energy source

BACKGROUNDnDiabetic heart is characterized by failure of insulin to increase glucose uptake and increasingly relies on free fatty acids (FFAs) as a source of fuel in animal models. However, it is not well known how cardiac energy metabolism is altered in diabetic hearts in humans. We examined cardiac fuel metabolism in the diabetics as compared to non-diabetics who underwent cardiac catheterization for heart diseases.nnnMATERIAL AND METHODSnThe study subjects comprised 81 patients (male 55, female 26, average age 63.0±10.0years) who underwent the cardiac catheterization for heart diseases. Thirty-six patients were diagnosed as diabetics (diabetic group) and 45 as non-diabetics (non-diabetic group). Blood samplings were done in both the aortic root (Ao) and coronary sinus (CS) simultaneously and the plasma levels of FFAs, glucose, lactate, pyruvate, total ketone bodies and β-hydroxybutyrate were measured and compared between the two groups.nnnRESULTSnThe myocardial uptake of glucose, lactate and pyruvate were decreased, whereas those of total ketone bodies, β-hydroxybutyrate and acetoacetate were increased in the diabetics as compared to the non-diabetics. However, the myocardial uptakes of FFAs were not significantly increased in the diabetics as compared to the non-diabetics.nnnCONCLUSIONSnCardiac uptakes of carbohydrate (glucose, lactate and pyruvate) were decreased, whereas those of total ketone bodies and β-hydroxybutyrate were increased in the diabetics as compared to the non-diabetics in humans. Ketone bodies therefore are utilized as an energy source partially replacing glucose in the human diabetic heart.

Conflicting relationship between age-dependent disorders, valvular heart disease and coronary artery disease by covariance structure analysis: Possible contribution of natriuretic peptide

Background It is conceivable that contemporary valvular heart disease (VHD) is affected largely by an age-dependent atherosclerotic process, which is similar to that observed in coronary artery disease (CAD). However, a comorbid condition of VHD and CAD has not been precisely examined. The first objective of this study was to examine a possible comorbid condition. Provided that there is no comorbidity, the second objective was to search for the possible reasons by using conventional risk factors and plasma B-type natriuretic peptide (BNP) because BNP has a potentiality to suppress atherosclerotic development. Methods The study population consisted of 3,457 patients consecutively admitted to our institution. The possible comorbid condition of VHD and CAD and the factors that influence the comorbidity were examined by covariance structure analysis and multivariate analysis. Results The distribution of the patients with VHD and those with CAD in the histograms showed that the incidence of VHD and the severity of CAD rose with seniority in appearance. The real statistical analysis was planned by covariance structure analysis. The current path model revealed that aging was associated with VHD and CAD severity (P < 0.001 for each); however, as a notable result, there was an inverse association regarding the comorbid condition between VHD and CAD (Correlation coefficient [β]: -0.121, P < 0.001). As the second objective, to clarify the factors leading to this inverse association, the contribution of conventional risk factors, such as age, gender, hypertension, smoking, diabetes, obesity and dyslipidemia, to VHD and CAD were examined by multivariate analysis. However, these factors did not exert an opposing effect on VHD and CAD, and the inverse association defied explanation. Since different pathological mechanisms may contribute to the formation of VHD and CAD, a differentially proposed path model using plasma BNP revealed that an increase in plasma BNP being drawn by VHD suppressed the progression of CAD (β: -0.465, P < 0.001). Conclusions The incidence of VHD and CAD showed a significant conflicting relationship. This result supported the likely presence of unknown diverse mechanisms on top of the common cascade of atherosclerosis. Among them, the continuous elevation of plasma BNP due to VHD might be one of the explicable factors suppressing the progression of CAD.

Propensity-Score Matched Comparison of Midterm Angiographic Outcomes of Sirolimus- Versus Everolimus- and Biolimus-Eluting Stents for De Novo Coronary Stenosis

We conducted propensity-score matched comparisons of midterm angiographic outcomes of sirolimus (SES) versus either everolimus- (EES) or biolimus- (BES) eluting stents after placements for coronary stenosis in a daily practice environment since previous randomized trials did not demonstrate the superiority of EES and BES over SES in terms of midterm angiographic outcomes.The present study was a non-randomized, retrospective, and lesion-based study, recruiting angiographically followed-up lesions within 550 days after successful and elective SES (n = 1793), EES (n = 1303), or BES (n = 324) placement for de novo native coronary stenosis during the period from August 2004 to January 2014 at 6 institutes. The endpoint, as an angiographic surrogate marker of clinical efficacy, was the distribution of in-stent follow-up percent diameter stenosis (%DS) which comprised the percentages of 1) follow-up %DS < 20 and 2) follow-up %DS > 50. Propensityscore matched analyses were conducted to adjust 21 baselines.In 1215 baseline adjusted lesions, the endpoints in the EES group [1) 74.1%, and 2) 4.6%] were significantly different from those in the SES group [57.9%; P < 0.001, 7.2%; P = 0.006, respectively). In 307 baseline adjusted lesions, the endpoints in the BES group [1) 80.5%, 2) 2.0%] were significantly different from those in the SES group [59.3%; P < 0.001, 2) 8.1%; P = 0.001, respectively].The present study is the first to confirm the superiority of midterm angiographic outcomes after the placement of EES and BES over SES for de novo coronary stenosis in a clinical setting.

Spiral activation of the superior vena cava: The utility of ultra-high-resolution mapping for caval isolation

BACKGROUNDnLittle is known about the manner in which the superior vena cava (SVC) is activated during sinus rhythm.nnnOBJECTIVEnThe purpose of this study was to assess the manner of caval activation with an ultra-high-density mapping system (Rhythmia, Boston Scientific, Marlborough, MA) and its utility for SVC isolation.nnnMETHODSnForty patients with atrial fibrillation (mean age 55 ± 12 years; paroxysmal atrial fibrillation in 23[58%]) who underwent SVC mapping with Rhythmia were studied. The location of the sinus node (SN), phrenic nerve (PN), and the manner of caval activation during sinus rhythm were analyzed. The SVC was isolated by radiofrequency applications at electrical connections, shown as breakthroughs on the Rhythmia map.nnnRESULTSnThe SN location varied widely (lateral/posterior/anterior 60%/8%/32%), while the PN was mostly located in the lateral segment (lateral/anterior 82%/18%). In 36 patients who underwent SVC isolation, the mean number of breakthroughs was 2.5xa0±xa00.8. The first breakthrough predominantly located in the anterior aspect (anterior/septal/posterior/lateral 78%/14%/5%/3%), and atrial activation was conducted superiorly and clockwise from the SN (referred to as spiral activation) in 32 patients (89%). The mean rotation angle from the SN to the first breakthrough was 79° ± 41°. In addition, 10 patients (25%) showed the SN within the SVC. Although radiofrequency applications were needed at the PN capture site in 11 patients (31%) the SVC was successfully isolated without any complications in all patients.nnnCONCLUSIONnThe SN location showed great heterogeneity; however, atrial activation predominantly showed a clockwise spiral form. This is the first report to use ultra-high-resolution mapping to demonstrate the manner of spiral activation, which is useful for the safe and efficient isolation of the SVC.

Effect of air removal with extracorporeal balloon inflation on incidence of asymptomatic cerebral embolism during cryoballoon ablation of atrial fibrillation

BACKGROUNDnAsymptomatic cerebral embolism (ACE) is sometimes detected after cryoballoon ablation of atrial fibrillation. The removal of air bubbles from the cryoballoon before utilization may reduce the rate of ACE.nnnOBJECTIVEnThis study aims to compare the incidence of ACE between a conventional and a novel balloon massaging method during cryoballoon ablation.nnnMETHODSnOf 175 consecutive patients undergoing initial cryoballoon ablation of paroxysmal atrial fibrillation, 60 (34.3%) patients underwent novel balloon massaging with extracorporeal balloon inflation in saline water (group N) before the cryoballoon was inserted into the body. The remaining 115 (65.7%) patients underwent conventional balloon massaging in saline water while the balloon remained folded (group C). Of those, 86 propensity score-matched patients were included.nnnRESULTSnThe baseline characteristics were similar between the 2xa0groups. In group N, even after balloon massaging in saline water was carefully performed, multiple air bubbles remained on the balloon surface when the cryoballoon was inflated in all cases. Postprocedural cerebral magnetic resonance imaging detected ACE in 14.0% of all patients. The incidence of ACE was significantly lower in group N than in group C (4.7% vs 23.3%; P = .01). According to multivariable analysis, the novel method was the sole factor associated with the presence of ACE (odds ratio 0.161; 95% confidence interval 0.033-0.736; P = .02).nnnCONCLUSIONnPreliminary removal of air bubbles in heparinized saline water with extracorporeal balloon inflation reduced the incidence of ACE. Since conventional balloon massaging failed to remove air bubbles completely, this novel balloon massaging method should be recommended before cryoballoon utilization.