An 18-year-old male who had a past medical history of an intracardiac total cavopulmonary connection (TCPC) operation was referred to our hospital for radiofrequency catheter ablation (RFCA) of supraventricular tachycardia (SVT). Two types of SVTs were induced, and 3-dimensional (3D) maps were created using an ultra-high-density 3-dimensional mapping system (Rhythmia). The earliest atrial activation site (EAAS) of SVT1 was at the superior part of the conduit, and the EAAS of SVT2 was at the inferior part of the single atrium (SA). The SVTs were terminated by energy deliveries to the EAAS from the conduit in SVT1 and from inside the single atrium in SVT2. Detailed maps of the SVTs were important to understand the mechanisms of the SVTs. The Rhythmia system was useful for the detailed mapping of complex arrhythmias. The use of Rhythmia in patients after a TCPC is difficult, because puncturing the TCPC conduit and proceeding and manipulating the Orion catheter via a narrow puncture hole are difficult. We were the first to succeed in ablating two atrial tachycardias (ATs) originating from the inside and outside of the conduit after a TCPC operation by using an ultra-high-density 3-dimensional mapping system.
The effect of restoring sinus rhythm by pulmonary vein isolation (PVI) on the quality of life (QOL) of patients with persistent atrial fibrillation (PerAF) has not been adequately investigated. This study was performed to compare the changes in QOL after extended PVI between patients with PerAF and paroxysmal AF (PAF).
Patients with PAF (n = 38) and PerAF (n = 22) who underwent their first PVI and developed no AF recurrence 6 months after PVI were enrolled. QOL surveys were performed at baseline and 6 months post-ablation using Short Form-36 surveys.
The mental component summary score (MCS) (53.4 ± 10.2 to 56.5 ± 7.1, P = 0.019) and physical component summary score (PCS) (46.1 ± 10.6 to 48.5 ± 8.3, P = 0.015) improved after PVI in the PAF group. The PCS, but not the MCS, improved after PVI in the PerAF group (45.8 ± 7.9 to 51.5 ± 6.2, P < 0.001). Changes in the PCS were greater in the PerAF group than in the PAF group (8.6 ± 6.9 versus 2.8 ± 5.2, P = 0.009). Multivariate regression analysis demonstrated that a low baseline MCS and the type of AF (PAF) were independent predictors of an increased MCS and that a low baseline PCS and the type of AF (PerAF) were independent predictors of an increased PCS.
The changes in QOL differed between PAF and PerAF after PVI. Although most patients with PerAF were asymptomatic before PVI, their improvement in physical QOL was greater than that in patients with PAF. Such beneficial effects on physical QOL are likely expected in patients with PerAF with a low PCS before PVI.
Transcatheter aortic valve implantation (TAVI) has been recognized as a standard therapy for severe aortic valve stenosis. However, since some patients who receive TAVI have poor outcomes, the predictors of clinical outcomes after TAVI are important. The aim of this study was to investigate the association between appetite and long-term clinical outcomes.
We screened consecutive cases who received TAVI at our medical center between July 2014 and October 2018. A total of 139 patients who received transfemoral TAVI were included as the final study population. They were divided into a good appetite group (n = 105) and a less appetite group (n = 34) according to their dietary intake rate (> 90%: good appetite group, ≤ 90%: less appetite group). We defined the intake rate as the average for breakfast, lunch, and dinner on the day just before discharge. We defined two-year major adverse cardiovascular and cerebrovascular events (MACCE) as a composite of cardiovascular death, myocardial infarction, any coronary revascularization, history of hospitalization due to heart failure, and disabling acute cerebral infarction. Kaplan-Meier analyses and multivariate Cox regression analysis were performed.
The median duration of the follow-up period was 372 (189-720) days. Kaplan-Meier curves showed that the less appetite group got MACCE more frequently (event free rate of the less appetite group: 76.5% versus the good appetite group: 94.3%, Log Rank P = 0.01). In multivariate Cox regression analysis, having less appetite was a significant predictor of two-year MACCE (HR 5.26, 95%CI 1.66-16.71, P < 0.01).
In conclusion, among the patients who received transfemoral TAVI, appetite status just before discharge was significantly associated with long-term outcome.
Therapy-resistant ventricular arrhythmias can occur during accidental advanced hypothermic conditions. On the other hand, hypothermic therapy using mild cooling has been successfully accomplished with infrequent ventricular arrhythmia events.
To further clarify the therapeutic-resistant arrhythmogenic substrate which develops in hypothermic conditions, an experimental study was performed using a perfusion wedge preparation model of porcine ventricle, and electrophysiological characteristics, inducibility of ventricular arrhythmias, and effects of therapeutic interventions were assessed at 3 target temperatures (37, 32 and 28°C).
As the myocardial temperature decreased, myocardial contractions and the number of spontaneous beats deceased. Depolarization (QRS width, stimulus-QRS interval) and repolarization (QT interval, ERP) parameters progressively increased, and dispersion of the ventricular repolarization increased. At 28°C, VF tended to be inducible more frequently (1/11 at 37°C, 1/11 at 32°C, and 5/11 hearts at 28°C), and some VFs at 28°C required greater defibrillation energy to resume basic rhythm.
An advanced but not a mild hypothermic condition had an enhanced arrhythmogenic potential in our model. In the advanced hypothermic condition, VF with relatively prolonged F-F intervals and a greater defibrillation energy were occasionally inducible based on the arrhythmogenic substrate characterized as slowed conduction and prolonged repolarization of the ventricle.
Myocardial infarction (MI) occurs when the heart muscle is severely damaged due to a decrease in blood flow from the coronary arteries. During recovery from an MI, cardiac fibroblasts become activated and produce extracellular matrices, contributing to the wound healing process in the damaged heart. Inappropriate activation of the fibroblasts leads to excessive fibrosis in the heart. However, the molecular pathways by which cardiac fibroblasts are activated have not yet been fully elucidated.
Here we show that serum deprivation, which recapitulates the cellular microenvironment of the MI area, strikingly induces collagen production in C3H/10T1/2 cells. Based on transcriptomic and pharmacological studies, we found that cell cycle perturbation is directly linked to collagen production in fibroblasts. Importantly, collagen synthesis is increased independently of the transcriptional levels of type I collagen genes. These results reveal a novel mode of fibroblast activation in the ischemic area, which will allow us to gain insights into the molecular mechanisms underlying cardiac fibrosis and establish a basis for anti-fibrotic therapy.
Severe ventricular arrhythmias such as high-grade atrioventricular block and ventricular tachycardia may cause lethal conditions or sudden death in patients with cardiac sarcoidosis (CS). Physicians should examine patients carefully for these conditions and treat them appropriately. As arrhythmias are being better diagnosed and treated, physicians are increasingly aware of atrial arrhythmias, which have not been focused upon as CS-related conditions, in patients with CS. This article reports a case of atrial flutter in sarcoidosis, and discusses literature findings on atrial arrhythmias and atrial involvement of CS. It is highly likely that atrial arrhythmia and supraventricular conduction disorder associated with or caused by CS are more common than previously thought. Physicians should pay careful attention for these conditions in the diagnosis and treatment of CS.
The evaluation of baroreflex sensitivity (BRS), which maintains systemic circulatory homeostasis, is an established tool to assess cardiovascular autonomic neuropathy in type 2 diabetes mellitus (T2DM). As BRS plays an important function in blood pressure regulation, reduced BRS leads to an increase in blood pressure variability, which further leads to reduced BRS. This sequence of events becomes a vicious cycle. The major risk factors for reduced BRS are T2DM and essential hypertension, but many other risk factors have been reported to influence BRS. In recent years, reports have indicated that glycemic variability (GV), such as short- and long-term GV that are considered important risk factors for macrovascular and microvascular complications, is involved in reductions in BRS independently of blood glucose levels. In this review, we discuss reduced BRS in T2DM, its features, and the potential for its reversal.
A 70-year-old man with dyspnea was admitted to our department and received standard therapy for recurrent heart failure. He was diagnosed with polycystic kidney disease (PKD) in his thirties and received hemodialysis for 4 years before undergoing renal transplantation at age 45. Although his left ventricular ejection fraction (LVEF) was preserved in his 50s, LVEF decreased progressively from 61% to 24%, while left ventricular diastolic dimension (LVDd) increased from 54 mm to 65 mm between 63 and 69 years of age. Right ventricular endomyocardial biopsy demonstrated myocardial disarray and interstitial fibrosis. Genetic analysis identified a heterozygous frameshift mutation in PKD1, which encodes polycystin-1, a major causative gene of PKD. We detected PKD1 protein expression in myocardial tissue by immunostaining. Recent epidemiological studies and animal models have clarified the pathological correlation between ventricular contractile dysfunction and PKD1 function. Here, we present a case of old-age onset progressive cardiac contractile dysfunction with a PKD1 gene mutation.
The progression of renal dysfunction reduces serum albumin and deteriorates the binding capacity of protein-bound uremic toxins. We evaluated the prognostic implications of serum indoxyl sulfate (IS) and albumin levels in patients with cardiovascular disease.
We prospectively enrolled 351 consecutive patients undergoing percutaneous revascularization for coronary artery disease or peripheral artery disease. The primary endpoint was all-cause mortality. Patients were assigned to four groups according to the median levels of serum IS (0.1 mg/dL) and albumin (3.9 g/dL).
During the median follow-up time of 575 days, 16 patients died. The IS level was significantly higher in nonsurvivors (0.33 versus 0.85 mg/dL, P < 0.05). On the Kaplan-Meier curve, the high IS/low albumin group presented the highest mortality rate (log-rank test, P < 0.01). Cox proportional hazard analysis revealed that high IS/low albumin (hazard ratio (HR): 5.33; 95% confidence interval (CI): 1.71-16.5; P < 0.01), diastolic pressure (HR: 0.94; 95% CI: 0.91-0.98; P < 0.01), prior stroke (HR: 4.54; 95% CI: 1.33-15.4; P = 0.01), and left ventricular ejection fraction (LVEF) (HR: 0.92; 95% CI: 0.88-0.96; P < 0.001) were associated with increased mortality. Furthermore, the combination of IS and albumin levels significantly conferred an additive value to LVEF for predicting mortality (C-statistic: 0.69 versus 0.80; P < 0.001; net reclassification improvement: 0.83; P < 0.001; integrated discrimination improvement: 0.02; P = 0.02).
A lower albumin level adds potentiating effects on IS as a prognostic factor for cardiovascular disease.
Pitsini Mongkhonsiri, Terdthai Tong-un, James Michael Wyss, Sanya Roysommuti
Sudden unexplained nocturnal death syndrome (SUNDS) is prominent among northeast Thai men. This study tests the hypothesis that Thai men with positive family history of SUNDS display abnormal diurnal, autonomic nervous system responses to stress. Healthy northeast Thai men (20-49 years old) lived in the same rural area were divided into two groups based on their positive (PF) or negative family (NF1) history of SUNDS. A second control included Thai men with an NF history of SUNDS from a non-endemic area (NF2). All data were collected at 4:00-6:00 AM (nighttime) and 4:00-6:00 PM (daytime). All three groups displayed nighttime decreases in mean arterial pressure, heart rate, and blood glucose. Furthermore, all subjects displayed similar glucose tolerance and electrolyte balance. The tachycardic responses to a four-minute step test were similar among groups in the daytime, but the nighttime responses were significantly blunted in the PF group compared to either control group (about 20 bpm less). Tachycardic responses to a cold pressor test tended to decrease more during the nighttime in the PF compared to NF1 and NF2 groups, but the difference was not significant. Arterial pressure responses to the exercise were similar among the three groups during the nighttime, whereas in the NF2, daytime mean arterial pressures increased more than those in the other groups. The present data suggest that Thai men with a PF history of SUNDS display blunted sympathetic nervous system responses to stress during the nighttime, a potential factor that may trigger cardiac arrhythmias and contribute to SUNDS.
Neuregulin-4 (Nrg4) is a newly discovered adipokine that is synthesized in many tissues and plays an important role in modulating systemic energy metabolism and in the development of metabolic disorders. However, little is known about the relationship between Nrg4 and coronary artery disease (CAD). In this study, we investigated the association between Nrg4 and the presence and severity of CAD.
We enrolled 73 patients diagnosed by coronary angiography (CAG) as having CAD and 32 controls. The CAD group was divided into two subgroups according to their SYNTAX score. Plasma levels of Nrg4 were measured in all participants and compared among different groups. The relationship between Nrg4 and CAD was analyzed. Receiver operating characteristic (ROC) analysis was conducted to evaluate the usefulness Nrg4 in assessing the presence and severity of CAD.
Nrg4 levels were negatively associated with the SYNTAX score (r = −0.401, P = 0.000). The patients with a higher SYNTAX score had significantly lower Nrg4 levels as compared with the low SYNTAX score subgroup and the controls (P < 0.05). The Nrg4 levels of the low SYNTAX score subgroup were much lower than controls (P < 0.05). Furthermore, an association between Nrg4 and CAD (odds ratio, 0.279; 95% confidence interval, 0.088-0.882) was observed. Nrg4 had 43.8% sensitivity and 96.9% specificity for identifying CAD, and 73.1% sensitivity and 87.3% specificity for identifying patients who had severe coronary artery lesions.
Nrg4 levels were found to be inversely associated with the presence and severity of CAD.
A 77-year-old man was referred to our hospital for angina on effort. Coronary angiography and computed tomography demonstrated a single coronary artery arising from the right sinus of Valsalva. The left circumflex coronary artery (LCx) anomalously deriving near from the ostium of right coronary artery exhibited severe stenosis in the bifurcation of the obtuse marginal branch. Although the bifurcation lesion still remains a therapeutic challenge for guide extension catheter (GEC)-based percutaneous coronary intervention, under the guidance of intravascular ultrasound imaging, we successfully implanted an everolimus-eluting stent at the bifurcated LCx lesion and performed kissing balloon inflation using 0.014- and 0.010-inch systems through GECs.
The aim of this study was to determine the correlation between periodontopathic bacteria and diabetes mellitus (DM) status in cardiovascular disease (CVD) subjects.
DM is associated with the progression of periodontitis. Several epidemiological studies have suggested that periodontitis may be a risk factor for CVD. However, no study has compared the periodontal condition between well-controlled and poorly-controlled DM patients with CVD.
The subjects were well-controlled (n = 73) or poorly-controlled (n = 39) DM patients with CVD. Blood examinations and dental clinical measurements, including number of teeth, probing pocket depth, bleeding on probing (BOP), and clinical attachment level (CAL) were performed. Periodontopathic bacterial existence was evaluated.
Worsened CAL and BOP rate were detected in the uncontrolled DM group compared to the controlled group. We found increased salivary Porphyromonas gingivalis counts in the uncontrolled DM group compared to well-controlled DM subjects.
Specific periodontopathic bacterial infection may affect DM condition in CVD patients.
Fluorine-18 fluorodeoxygluose (18F-FDG) positron emission tomography (PET) is a useful tool for evaluating disease activity in sarcoidosis including cardiac involvement. A 67-year-old patient who developed atrioventricular block requiring permanent pacemaker implantation was diagnosed with cardiac sarcoidosis. The patient did not undergo steroid or immunosuppressive therapy but underwent serial 18F-FDG PET examination, which showed spontaneous reduction in the myocardial FDG uptake, indicating the remission of immune-inflammatory activity. Although the global systolic function remained preserved, thinning of the septal wall emerged during the clinical course of follow-up, which is characteristic for cardiac sarcoidosis.
Takotsubo cardiomyopathy is described as a transient reversible cardiomyopathy which typically occurs in older women after emotional or physical stress. This cardiomyopathy is also recognized as a "syndrome" because it develops in conjunction with various diseases. Since the clinical presentation of takotsubo syndrome (TTS) is similar to acute coronary syndrome (ACS), TTS should be distinguished from ischemic heart disease. Although the pathophysiology of TTS has not well been established, a number of its specific features have been suggested. The predictor of mortality in TTS is still unknown. In this review article, we describe a series of treatment decisions in TTS.
The molecular pathophysiology of heart failure, which is one of the leading causes of mortality, is not yet fully understood. Heart failure can be regarded as a systemic syndrome of aging-related phenotypes. Wnt/β-catenin signaling and the p53 pathway, both of which are key regulators of aging, have been demonstrated to play a critical role in the pathogenesis of heart failure. Circulating C1q was identified as a novel activator of Wnt/β-catenin signaling, promoting systemic aging-related phenotypes including sarcopenia and heart failure. On the other hand, p53 induces the apoptosis of cardiomyocytes in the failing heart. In these molecular mechanisms, the cross-talk between cardiomyocytes and non-cardiomyocytes (e,g,. endothelial cells, fibroblasts, smooth muscle cells, macrophages) deserves mentioning. In this review, we summarize recent advances in the understanding of the molecular pathophysiology underlying heart failure, focusing on Wnt/β-catenin signaling and the p53 pathway.
The quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER) are important concepts in cost-effectiveness analysis, which is becoming increasingly important in Japan. QALY is used to estimate quality of life (QOL) and life years, and can be used to compare the efficacies of cancer and cardiovascular treatments. ICER is defined as the difference in cost between treatments divided by the difference in their effects, with a smaller ICER indicating better cost-effectiveness. Here, we present a review of cost-effectiveness analyses in Japan as well other countries. A number of treatments were shown to be cost-effective, e.g., statin for secondary prevention of cardiovascular disease, aspirin for primary prevention of cardiovascular disease, DOAC for high-risk atrial fibrillation, beta blockers, ACE inhibitors, and ARB for heart failure, sildenafil and bosentan for pulmonary hypertension, CABG for multi-vessel coronary disease, ICD for ventricular tachycardia, and CRT for heart failure with low ejection fraction, while others were not cost-effective, e.g., epoprostenol for pulmonary hypertension and LVAD for end-stage heart failure. Further investigations are required regarding some treatments, e.g., PCSK-9 inhibitors for familial hypercholesterolemia, PCI for multi-vessel coronary disease, catheter ablation for atrial fibrillation, and TAVI for severe aortic stenosis. Ethical aspects should be taken into consideration when utilizing the results of cost-effectiveness analysis in medical policy.
The cardiopulmonary exercise test (CPX) is an essential examination for detecting pathophysiological derangement and determining treatment policy because it clarifies not only the changes of hemodynamics but also abnormality in the whole body during exercise where heart disease patients often feel symptoms.
To utilize CPX effectively, we must understand each parameter, such as peak oxygen uptake (peak VO2), peak VO2/HR, and VE/VCO2. In addition, comparison of each parameter, for example, peak VO2 and VE/VCO2, and peak VO2 and peak VO2/HR, is useful to detect the pathophysiological abnormalities.
In this article, I will describe how CPX should be used in clinical settings.
Type 2 diabetes mellitus (T2DM) is a major risk factor of coronary artery diseases (CAD). Clinical outcomes in CAD with T2DM are poor despite improvement in medications and intervention devices. Coronary artery bypass grafting (CABG) is superior to percutaneous coronary intervention (PCI) in treating diabetic patients with multivessel coronary artery diseases (MVD). However, selecting a revascularization strategy should depend not only on the lesion complexity but also on the patient’s background and comorbidities. In addition, comprehensive risk management with medical and non-pharmacological therapies is important, as is confirmation of whether risk managements are appropriately achieved. Recently, novel anti-diabetic drugs have been demonstrated to have effectiveness in reducing cardiovascular events, which was independent of their glucose-lowering effect. Furthermore, non-pharmacological interventions using exercise and diet during the earlier stages of abnormal glucose metabolism might be beneficial in preventing the development or progression of T2DM and reducing the incidence of cardiovascular events.