Gut microbiota have been attracting increased attention in many fields of medicine recently. We can perform a comprehensive analysis of gut microbiota using next-generation sequencing techniques together with bioinformatics technology, which expands our knowledge of a large ecosystem consisting of a host and gut microbiota. We summarize some reports about the correlations between gut microbiota and metabolic disorders, particularly atherosclerosis, and discuss future directions for the diagnostic or therapeutic potential of gut microbiota. To take simple examples, we demonstrated that the order Lactobacillales was significantly increased; while the phylum Bacteroidetes was significantly decreased in coronary artery disease (CAD) patients compared with controls or healthy volunteers. The characteristics of gut microbiota in type 2 diabetes and dyslipidemia have been reported. However, these studies have limitations, and the biological significance of gut microbiota and the causal relationships are still controversial. We hope the reports listed in this review article might lead to the development of a novel therapy to prevent CAD via modulating gut microbiota or their metabolites.
Heart failure is a leading cause of cardiovascular mortality in industrialized countries. During development and deterioration of heart failure, cardiomyocytes undergo maladaptive hypertrophy, and changes in the cellular phenotype are accompanied by reinduction of the fetal gene program. Gene expression in cardiomyocytes is regulated by various nuclear transcription factors, co-activators, and co-repressors. The zinc finger protein GATA4 is one such transcription factor involved in the regulation of cardiomyocyte hypertrophy. In response to hypertrophic stimuli such as those involving the sympathetic nervous and renin-angiotensin systems, changes in protein interaction and/or post-translational modifications of GATA4 cause hypertrophic gene transcription in cardiomyocytes. In this article, we focus on cardiac nuclear signaling molecules, especially GATA4, that are promising as potential targets for heart failure therapy.
This study aimed to investigate whether a single session of neuromuscular electrical stimulation (NMES) can enhance vascular endothelial function and peripheral blood circulation in patients with acute myocardial infarction (AMI). Thirty-four male patients with AMI were alternately assigned to 2 groups, and received NMES with muscle contraction (NMES group, n = 17) or without muscle contraction (control group, n = 17) after admission. NMES was performed for quadriceps and gastrocnemius muscles of both legs for 30 minutes. We measured systolic blood pressure as a parameter of cardiovascular responses and the low-frequency component of blood pressure variability as an index of sympathetic activity. Reactive hyperemia peripheral arterial tonometry (RH-PAT) index and transcutaneous oxygen pressure in foot (Foot-tcPO2) were also measured as parameters of vascular endothelial function and peripheral blood circulation, respectively. All patients completed the study without severe adverse events. Systolic blood pressure and the low-frequency component increased significantly during the NMES session in both groups (P < 0.01 and P < 0.05, respectively). However, elevation from systolic blood pressure at rest was < 10 mmHg in both groups. In the NMES group, the RH-PAT index and Foot-tcPO2 increased significantly after NMES (P < 0.05 and P < 0.001, respectively). No significant changes were observed in these parameters throughout the session in the control group. In conclusion, a single session of NMES with muscle contraction enhanced vascular endothelial function, leading to improvement in peripheral blood circulation without inducing excessive cardiovascular and autonomic responses in patients with AMI (UMIN000014196).
There is still much debate about revascularization strategies in aged patients with unprotected left main coronary artery (UPLM) lesions. This study compared the outcomes of percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) in this population.
A total of 126 patients older than 60 years of age with LM lesions who underwent revascularization in our hospital from January 2012 to December 2013 were followed up for an average of 15.2 months. The cumulative incidence of major adverse cardiac and cerebral events (MACCE) was estimated by Kaplan-Meier plots. During follow-up, the CABG group had higher proportions of cardiac death, stroke, and worsening of heart failure while the PCI group had a higher proportion of recurrence of angina (P = 0.04). The MACCE incidence was lower in the PCI group than that in the CABG group (28.9% versus 35.6%, P = 0.04). Multivariate regression identified left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate (eGFR) as predictors of PCI, while age, LVEF, EuroScore, and diabetes were the predictors of CABG. PCI maintained its superiority over CABG after adjustment for risk factors (Hazard ratio: 0.28, P = 0.004). The CABG group included a higher proportion of severe hemorrhagic complications than the PCI group (P = 0.04).
In terms of efficacy and safety, PCI had an advantage over CABG in aged patients with UPLM lesions. Thus, PCI was a reasonable alternative to CABG for this population.
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent risk factor for plaque rupture and atherothrombotic events. However, the associations between serum Lp-PLA2 level and thrombus burden in ST-segment elevation myocardial infarction (STEMI) patients remain unknown.
We consecutively enrolled 351 STEMI patients who underwent primary percutaneous coronary intervention (pPCI). Patients were assigned to a high thrombus burden (HTB) group (n = 230) and a low thrombus burden (LTB) group (n = 121). Baseline data were recorded during hospital admission. Plasma Lp-PLA2 concentration, coronary angiography results, and in-hospital mortality were measured. Plasma Lp-PLA2 level had a high correlation with thrombus burden score (TBS) before pPCI and it was found to be a significant independent predictor of HTB in STEMI patients (P < 0.05). Moreover, TBS, corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC), and plasma Lp-PLA2 level after pPCI in patients with HTB were significantly higher than those in patients with LTB (P < 0.05). Meanwhile, TIMI flow grade (TFG) and TIMI myocardial perfusion grade (TMPG) of HTB patients were markedly lower than those of LTB patients (P < 0.05). Additionally, correlations of plasma Lp-PLA2 level before pPCI with TFG before pPCI and TBS, cTFC, and TMPG after pPCI were modest (P < 0.05). However, the associations of plasma Lp-PLA2 level after pPCI with TFG, TBS, cTFC and TMPG were low (P < 0.05).
These results demonstrated that the plasma Lp-PLA2 level before pPCI is an independent predictor of HTB in STEMI patients, resulting in modestly predicting blood flow and myocardial perfusion of the culprit artery.
Compared to acute myocardial infarction (AMI) with single vessel disease (SVD) or double vessel disease (DVD), AMI with triple vessel disease (TVD) is associated with higher mortality. The aim of this study was to identify the determinants of in-hospital death in AMI with TVD. We identified AMI patients with TVD in our tertiary medical center between January 2009 and December 2014. Baseline patient characteristics including laboratory data, echocardiograms, and coronary angiograms were collected from our hospital records. We divided our study population into a survivor group and non-survivor group. Multivariate stepwise logistic regression analysis was performed to identify the determinants of in-hospital death. A total of 138 AMI patients with TVD were identified and included as the final study population. Fifteen patients died during the hospitalization (mortality rate, 10.9%). Mean systolic blood pressure (134 ± 27 mmHg) was significantly greater in the survivor group compared with the non-survivor group (114 ± 31 mmHg) (P = 0.02). The prevalence of shock on admission was significantly less in the survivor group (15.4%) than in the non-survivor group (66.7%) (P < 0.001). Multivariate stepwise logistic regression analysis revealed that shock status on admission (OR 11.50, 95% CI 3.21-41.14, P < 0.001), the left anterior descending artery (LAD) as the infarct related artery (IRA) (OR 3.83, 95% CI 1.04-14.09, P = 0.04), and serum albumin on admission (OR 0.26, 95% CI 0.08-0.84, P = 0.02) were significantly associated with in-hospital death. In conclusion, shock status on admission, the LAD as the IRA, and a low serum albumin level were the determinants of in-hospital death in AMI patients with TVD.
Hypertension (HT) is known to be the most prevalent risk factor for paroxysmal atrial fibrillation (PAF), however, its mechanisms have not been fully clarified. Our aim was to investigate the differences in left atrial (LA) function between healthy subjects, and hypertensive patients without PAF (HT-PAF(-)) and with PAF (HT-PAF(+)) using 3-dimensional (3D) speckle tracking imaging (STI). A total of 144 subjects were enrolled: 44 HT-PAF(+) (27 males; mean age 69 ± 10 years), 50 HT-PAF(-) (31 males; mean age 63 ± 11 years), and 50 controls (31 males; mean age 51 ± 14 years). All subjects were in sinus rhythm during the examination. LA volume, LA emptying fraction (LAEF), and LA wall strain were analyzed by 3D area tracking imaging. The maximal value of the global strain curve was defined as the peak global strain. The standard deviation of the time from the R-wave on the electrocardiogram to peak positive values of the segmental strain curves corrected by the R-R’ interval in 6 mid LA segments (TP-SD) was calculated to assess LA dyssynchrony. LAEF and peak global strain were lower in HT-PAF(+) than in HT-PAF(-) (P < 0.01) and in the control (P < 0.01). Moreover, TP-SD was higher in HT-PAF(+) than in HT-PAF(-) (P < 0.05) and in the control (P < 0.01). Multivariate analysis revealed LA volume index, peak global strain, and TP-SD were independent determinants of HT-PAF(+). The presence of PAF is associated with diminished LA compliance and advanced mechanical dyssynchrony, as well as LA geometric deformation.
Direct oral anticoagulants (DOACs) have been shown to be safe and effective for the prevention of stroke in nonvalvular atrial fibrillation (NVAF) patients, however, experience with peri-AF ablation management of DOACs is scarce. This study aimed to investigate the safety and feasibility of periprocedural anticoagulation therapy with rivaroxaban in Japanese patients undergoing paroxysmal non-valvular AF (NVAF) ablation using radiofrequency energy.
This study was a multicenter, prospective pilot study. In paroxysmal NVAF patients, rivaroxaban (15 mg or 10 mg once-daily) was started at least 4 weeks prior to AF ablation, discontinued on the day of the procedure, resumed within 24 hours after ablation, and continued at least 3 months afterwards. During the interruption of rivaroxaban, bridging anticoagulation therapy with unfractionated heparin was given. Follow-up of the patients continued for 3 months.
A total of consecutive 74 patients (mean age, 62 ± 9 years, 58 [78.4%] male) were enrolled. The mean follow-up period was 108 ± 79 days. Their mean CHADS2 score and CHA2DS2-VASc score were 1.2 ± 1.0 and 0.6 ± 0.7, respectively. Their mean HAS-BLED score was 1.0 ± 0.8. Neither major bleeding nor thromboembolic events, except in a case with bleeding from gastric cancer (1.4%), were observed in the periprocedural period of the AF ablation.
The present multicenter study demonstrated the safety and feasibility of periprocedural anticoagulation therapy with rivaroxaban in Japanese patients undergoing catheter ablation of paroxysmal NVAF.
Carvedilol has established its evidence to improve prognosis and facilitate left ventricular reverse remodeling (LVRR) in heart failure patients with reduced left ventricular ejection fraction (LVEF), and many studies have supported its dose-dependency. However, there are few studies demonstrating the effect of high dose carvedilol in Japan. We enrolled 23 patients with idiopathic non-ischemic cardiomyopathy, in whom LVEF remained 45% or less despite 20 mg/ day of carvedilol therapy for > 3 months. After high dose (40 mg/day) carvedilol therapy for > 3 months, LVEF improved (+9.1%, P = 0.002), and LV end-diastolic diameter (LVDd) and LV end-systolic diameter (LVDs) reduced (-4.6 and -6.9 mm, respectively, P < 0.05) compared with the baseline data. Finally, 17 patients achieved LVRR after the high dose, when LVRR was defined as 1) those with final EF > 45%, and 2) those with final EF < 45% but who attained increases in LVEF > 10%, or LVEF > 5% with a decrease in LV end-diastolic dimension index (LVDDI) > 5%. Baseline predictors for LVRR after high dose carvedilol were the change rates of log B-type natriuretic peptide (BNP), LVDd, and LVDs from the time of pre-carvedilol introduction to enrollment (P < 0.05, respectively). In conclusion, high dose carvedilol triggered additional LVRR in patients with idiopathic non-ischemic cardiomyopathy and the change rates of log BNP, LVDd, and LVDs at 20 mg carvedilol may be predictors for the additional LVRR at high dose.
Controversial opinions exist with respect to the relationship between maternal folic acid (FA) supplementation and birth prevalence of congenital heart defects (CHDs).
Eligible articles were retrieved by searching databases, including PubMed, Cochrane library, EMBASE, CNKI, and WanFang up to September 2015. A meta-analysis was performed to evaluate the effects of FA on CHDs. Odds ratios (ORs) and 95% confidence interval (CIs) were merged using STATA 12.0. Meta-regression analysis was used to explore the possible sources of heterogeneity. Subgroup analysis according to the selected sources was also performed. Publication bias was assessed by Egger’s test.
Twenty studies were included in the meta-analysis. The overall analysis showed that FA supplementation was significantly associated with decreased risk of CHDs. The meta-regression analysis showed that geographical area could be an important source of heterogeneity. The subgroup analysis based on the geographical area revealed that FA supplementation during pregnancy was a protective factor against CHDs in Chinese and European patients, but not in American patients. Subgroup analysis according to literature quality also displayed positive associations between FA supplementation and the decreased risk of CHDs of China.
FA supplementation during pregnancy significantly decreases the risk of CHDs in newborns in China and Europe.
Left ventricular (LV) diastolic dysfunction is considered the main cause of heart failure with preserved ejection fraction (HFpEF). There have been few reports on the correlation between LV diastolic dysfunction and arterial stiffness in patients with clinical cardiovascular disease.
This cross-sectional study enrolled 100 patients (67 men, 33 women; mean age, 70 years). All participants were diagnosed with cardiovascular disease. A total of 89 (89%) patients had coronary artery disease or HF. Patients with reduced EF and valvular disease were excluded. Arterial stiffness was assessed by the cardio-ankle vascular index (CAVI), and LV diastolic dysfunction was estimated using echocardiography. The patients were divided into two groups based on the median value of CAVI. In all patients the ratio of early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e’) was significantly higher in the high CAVI group than in the low CAVI group (15.5 ± 6.4 versus 12.5 ± 2.9, P = 0.003). In the HF subgroup, E/e’ was also significantly higher in the high CAVI group than in the low CAVI group (17.2 ± 5.9 versus 13.0 ± 3.1, P = 0.026). In univariate regression analysis, CAVI was significantly associated with E/e’ in all patients (β = 0.28, P = 0.004) and in HF patients (β = 0.4, P = 0.028). Also in multivariate analysis, CAVI remained as an independent predictive factor of E/e’ (β = 0.252, P = 0.037).
A high CAVI was independently associated with LV diastolic dysfunction in patients with clinical cardiovascular disease. These results suggested that arterial stiffness contributed to the development of LV diastolic dysfunction.
Scoring of myocardial infarction (MI) disease extent in cardiac magnetic resonance (CMR) images has been generally presented in terms of area-based infarct size. However, gradual thinning of the infarcted wall and compensatory hypertrophy of the noninfarcted remote wall during left ventricular (LV) remodeling after MI complicate the accuracy of infarct size measurement. In this study, we measured and compared infarct sizes in mice on late gadolinium enhancement (LGE) images using area-, length-, and radial sector-based methods.
MI was induced by permanent ligation of the left coronary artery (n = 6). LGE images were acquired 30 minutes after intravenous injection of Gd-DTPA-BMA. Percentages of infarct size (%Area, %Length, and %Sector) on the LGE images were calculated and compared with histological findings.
Infarct sizes obtained by an area-based approach were smaller than those obtained by other measurements. The area-based approach underestimated infarct size compared with the length-based approach. Most infarct sizes measured by each method demonstrated a similar trend, with maximum values determined by sector-based measurements using a mean + SD threshold. Spearman’s rank correlation coefficients indicated that the 3 measurements were strongly correlated (P < 0.05) to each other. Significant differences and trends were observed between sector-based infarct sizes with different thresholds when 16 or more sectors were used.
In conclusion, our study demonstrated that methods used for the histological calculation of infarct size could be applied to CMR analysis. Moreover, our results showed a similar trend to histological assessment. Sector-based CMR approaches can be useful for infarct size measurement.
Immune dysfunction is implicated in dilated cardiomyopathy (DCM). Previous studies found that TIM1 polymorphisms were associated with immune dysfunction. However, the associations between TIM1 polymorphisms and DCM have not been investigated. Therefore, we conducted the present study to evaluate whether TIM1 polymorphisms were associated with DCM in the Han Chinese population. A total of 396 DCM patients and 403 healthy controls were enrolled in this case-control study. Two promoter region single nucleotide polymorphisms (SNPs) of TIM1 gene, -416G>C and -1454G>A, were genotyped by PCR-RFLP. The associations between two SNPs genotyped and the overall survival (OS) of DCM patients were evaluated with Kaplan-Meier analysis and Cox regression analysis. Plasma TIM-1 levels were further measured by ELISA. We found that the C allelic frequency of -416G>C and A allelic frequency of -1454G>A were higher in DCM patients than that in controls (P < 0.001). The genotypic frequencies of both SNPs were associated with DCM susceptibility in the codominant, dominant, and overdominant models (P < 0.01). They were also associated with the OS of DCM patients in the dominant, recessive, and overdominant models (P < 0.001). The CC genotype of -416G>C and AA genotype of -1454G>A were associated with the worst prognosis (P < 0.001). In addition, the plasma TIM-1 levels in DCM patients were higher than that in controls (259.0 pg/mL versus 149.8 pg/mL, P = 0.035). The CC genotype of 416G>C and AA genotype of -1454G>A were associated with the highest TIM-1 production (P < 0.01). Overall, our findings suggest that TIM1 polymorphisms are associated with DCM susceptibility and prognosis in this Han Chinese population.
A rapid pacing-induced heart failure model is commonly used in developing dilated cardiomyopathy (DCM). Traditionally, the right ventricular lead was connected with a single chamber pacemaker specific for animals that had a high frequency. However, the pacemaker used in this model is commercially unavailable. We developed a “pacing bigeminal” method using a commercially available dual-chamber (DDD) pacemaker to achieve high-frequency pacing. Twenty beagles were assigned to group A (n = 10) (pacing bigeminal method) and group B (n = 10) (traditional method). Echocardiographic measurements and electrocardiograms were obtained at baseline, at two weeks of pacing, and at 4 weeks of end pacing. LV anterior wall cardiac samples were obtained at 2 weeks of pacing and 4 weeks of end pacing for myocardial microscopic evaluation. Clinical manifestation and exposure time were also observed. After pacing for 10.5 ± 2.3 (714) days, the beagles in group B experienced heart failure, whereas in group A, only 7.9 ± 2.5 (5-12) days (P < 0.05) were needed to reach heart failure. Both methods could induce wide QRS duration, heart rate elevation, and myocardial microscopic changes (P > 0.05). In conclusion, this pacing bigeminal-induced heart failure method is feasible and can induce heart failure faster than the traditional method, which makes it a promising alternative method.
To determine the effect of the xanthine oxidase (XO) inhibitor allopurinol on myocardial energy metabolism in a chronic heart failure rat model after myocardial infarct.
An AMI model was established in 6-week-old rats via the ligation of the anterior descending coronary artery. Thirty-five rats were randomly divided into the following 3 groups: an ALLO group, an AMI group, and a Sham group. Heart failure was successfully diagnosed via echocardiography and blood tests. Xanthine oxidase (XO), malondialdehyde (MDA), PGC-1α, CPT-1, and GLUT4 were monitored in the myocardium.
The TEM results demonstrated that myofilament lysis and mitochondrial swelling were alleviated in the ALLO group compared with the AMI group (without ALLO). The results also demonstrated that cardiac function was significantly improved in the ALLO group compared with the AMI group. Compared with the AMI group, the ALLO group exhibited increased respiratory-chain enzyme activity, as well as increased PGC-1α and CPT-1 mRNA and protein expression, decreased MDA content, and decreased XO and GLUT4 mRNA and protein expression.
ALLO improves myocardial energy metabolism in rats with chronic heart failure, which may result from the regulation of PGC-1α in the setting of glycolipid metabolism, enhancing the production of ATP.
A 39-year-old man exhibiting unstable angina was admitted to our hospital, and urgent coronary angiography revealed stenosis of the proximal left anterior descending coronary artery (LAD). A drug eluting stent was implanted at this site, and the patient was discharged uneventfully on the 3rd hospital day. Optical frequency-domain imaging (OFDI) was successful in detecting an intra-plaque hematoma, minor intimal disruption, and thrombus at the culprit lesion in this patient. These observations suggest that this hematoma might be the result of subsequent blood filling into the ruptured plaque through this minor intimal disruption.
A 62-year-old man with a family history of coronary artery disease and a history of smoking, diabetes and dyslipidemia was admitted to our hospital with chest pain from acute myocardial infarction. Emergent coronary angiography was performed with intervention to a mid-right coronary occlusion with drug-eluting stent implantation. Optical coherence tomography (OCT) visualized well-apposed stent struts and no remarkable tissue protrusion, stent underexpansion, malapposition, edge dissection, and hematoma. Immediately after OCT imaging, a coronary angiogram showed a filling defect surrounded by contrast medium at the site of the stented lesion. OCT imaging was performed again and a low backscattering protrusion suggestive of white thrombus in the coronary lumen was clearly visualized in OCT imaging. We performed thrombus aspiration immediately after OCT imaging. Aspirated thrombi were off-white in color. We made a diagnosis of early-onset heparin-induced-thrombocytopenia (HIT) due to thrombus formation within the stent and positive HIT antibodies. OCT in the acute phase of stent thrombosis allowed us to promptly identify the main causative mechanisms of early stent thrombosis.
Advanced heart failure (HF) is sometimes complicated with brain impairment because of a microthrombosis caused by decreased left ventricular contraction or reduced brain circulation. Some patients may recover after left ventricular assist device (LVAD) implantation. However, little is known about the perioperative therapeutic strategy in patients suffering from such complications, particularly from a cardiac rehabilitation viewpoint. We report on a 58-year-old male patient with a previous history of poliomyelitis and a light paralysis in the left upper extremity, who suffered left hemiplegia with no evidence of stroke after hemodynamic deterioration. The combination therapy of perioperative cardiac rehabilitation and LVAD therapy improved his left hemiplegia as well as activities of daily living, and the patient was discharged on foot on postoperative day 72 after briefing the family on LVAD home management. Early initiation of cardiac rehabilitation before LVAD implantation may be a key for the smooth discharge and resocialization of patients suffering from brain impairment complicated with advanced HF.
Although some patients with fulminant myocarditis can be rescued owing to the improvements in mechanical circulatory support therapy, there are few reports providing evidence of cardiac rehabilitation during mechanical circulatory supports, particularly among pediatric patients. We treated two pediatric patients who underwent aggressive cardiac rehabilitation during mechanical support. Five days after the initiation of extracorporeal membrane oxygenation therapy aggressive cardiac rehabilitation was started in a 10-year-old girl with fulminant myocarditis. After explantation of the device, she was discharged on postoperative day 23. A 6-year-old girl with fulminant myocarditis started receiving cardiac rehabilitation two days after the initiation of an extracorporeal left ventricular assist device, despite having hemiplegia due to a recent broad stroke. She achieved an exercise capacity of supported walking for 280 meters after 127 days of cardiac rehabilitation and then went abroad to undergo heart transplantation when she was in the best physical condition possible. Early initiation of cardiac rehabilitation may be safe and effective for successful pediatric mechanical circulatory support therapy; this acts as a bridge to explantation or heart transplantation.
An error appeared in the article titled “Therapeutic Strategy for Heart Failure in Becker Muscular Dystrophy” by Koichi Kimura, Hiroyuki Morita, Akinori Nakamura, Katsu Takenaka, Masao Daimon (Vol. 57, No. 5, 527-529, 2016). The name of the last author on page 527 and the back cover should be “Masao Daimon” and not “Daimon Masao”.