This study aimed to evaluate the characteristics and prognosis of patients with vasospastic angina (VSA) diagnosed by a provocation test with a secondary prevention implantable cardioverter defibrillator (ICD), compared with patients with organic coronary stenosis. We retrospectively evaluated 309 consecutive patients who received an ICD implantation between January 2010 and March 2018 in our institutions. Of these patients, 206 were implanted with an ICD for secondary prevention. In these 206 patients, 40 with VSA and 72 with organic coronary stenosis were evaluated. Patients with VSA were characterized by younger age (56.1 ± 13.1 versus 69.2 ± 9.5 years, respectively), and a lower prevalence of diabetes (15.0% versus 40.3%, respectively) and heart failure (2.5% versus 26.4%, respectively) than patients with organic coronary stenosis (P < 0.001). Using the Kaplan-Meier analysis, with the VSA group as the reference, the incidence of appropriate ICD shock was similar between the two groups (hazard ratio, 0.85; 95% confidence interval, 0.341-2.109; P = 0.722). The incidence of ventricular fibrillation was significantly higher in the VSA group (hazard ratio, 0.22; 95% confidence interval, 0.057-0.814; P = 0.024), whereas the incidence of major adverse cardiac events, including cardiac death, nonfatal myocardial infarction, hospitalization for unstable angina pectoris, and heart failure, was significantly higher in the organic coronary stenosis group (hazard ratio, 13.1; 95% confidence interval, 1.756-98.17; P = 0.012). In conclusion, patients with VSA with an ICD implanted for secondary prevention have a higher risk of ventricular fibrillation and lower risk of major adverse cardiac events than patients with organic coronary stenosis.

Arterial stiffness contributes to the development of cardiovascular disease (CVD). However, the relationship between the arterial stiffness and exercise tolerance in CVD patients with preserved ejection fraction (pEF) and those with reduced EF (rEF) is unclear. We enrolled 358 patients who participated in cardiac rehabilitation and underwent cardiopulmonary exercise testing at Juntendo University Hospital. After excluding 195 patients who had undergone open heart surgery and 20 patients with mid-range EF, the patients were divided into pEF (n = 99) and rEF (n = 44) groups. Arterial stiffness was assessed using arterial velocity pulse index (AVI) and arterial pressure volume index (API) at rest. The patients in the pEF group were significantly older and had a higher prevalence of coronary artery disease than the rEF group. The pEF group had significantly lower AVI levels and higher API levels than the rEF group. In the pEF group, the peak oxygen uptake (peak VO₂) and the anaerobic threshold was significantly higher than those in the rEF group. The peak VO₂ was significantly and negatively correlated with AVI and API in the pEF group (All, P < 0.05), but not in the rEF group. Multivariate linear regression analyses demonstrated that AVI was independently associated with peak VO₂ (β = −0.34, P < 0.05) in the pEF group. In conclusion, AVI may be a useful factor for assessing exercise tolerance, particularly in CVD patients with pEF.

The effect of a history of cancer on the prognosis of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) is poorly understood.

From the Osaka Acute Coronary Insufficiency Study (OACIS) registry in Osaka, Japan, we enrolled the case data of a total of 3499 patients with AMI treated with PCI between 1998 and 2014, of whom 462 had a cancer history (cancer group, 13.2%) and 3037 did not (non-cancer group, 86.8%). All of the cases were followed for up to five years from discharge.

The Kaplan-Meier curve and multivariate analysis using Cox proportional hazards models revealed that all-cause mortality was significantly higher in the cancer group than in the non-cancer group (adjusted hazard ratio [HR], 2.43; P < 0.001). Deaths from cardiac, cancer, and other causes were treated as competing events, and competing analysis using the cumulative incidence function (CIF) and Fine-Gray model revealed that mortality due to cancer was higher in the cancer group than in the non-cancer group, whereas cardiac mortality was similar between the two groups. The incidences of cardiovascular events, including stroke, recurrent infarction, and heart failure requiring readmission, were also similar between the two groups, although the Kaplan-Meier analysis and univariate Cox proportional hazards model revealed that the incidence of stroke was higher in the cancer group than in the non-cancer group.

A history of cancer increased all-cause and cancer mortality among patients with AMI treated with PCI, although it was not associated with cardiovascular events.

Whether reduced-dose prasugrel has a better efficacy or safety than standard-dose clopidogrel remains unknown in patients undergoing percutaneous coronary intervention (PCI).

A systematic search of PubMed, EMBASE, Google Scholar, and Cochrane Library from database inception to May 1, 2020 was performed to compare the clinical outcomes in patients with acute coronary syndrome or stable coronary artery disease undergoing PCI between those treated with reduced-dose prasugrel and clopidogrel. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using the fixed-effect or random-effect model if significant heterogeneity was observed. The primary efficacy endpoint was major adverse cardiovascular events (MACE), including cardiovascular (CV) death, myocardial infarction (MI), or ischemic stroke. The primary safety endpoint was all bleeding events.

Overall, seven studies with 32,951 patients with PCI were included in the analysis. Reduced-dose prasugrel was associated with a lower risk of MACE than clopidogrel (OR 0.80, 95% CI 0.67-0.97). Except for MI (OR 0.74, 95% CI 0.56-0.98), the secondary efficacy endpoints of CV death, ischemic stroke, all-cause death, and stent thrombosis were similar. For the primary safety endpoint of all bleeding events, there was no significant difference between reduced-dose prasugrel and clopidogrel (OR 1.31, 95% CI 0.87-1.98), but the risk of minor bleeding was significantly higher in reduced-dose prasugrel (OR 1.73, 95% CI 1.25-2.41).

In patients undergoing PCI, a lower risk of MACE was found in patients receiving reduced-dose prasugrel than in those with clopidogrel, but a higher risk of minor bleeding events was noted.

Radial access is recommended for primary percutaneous coronary intervention (PCI), because it has fewer bleeding complications than trans-femoral PCI. However, even if trans-radial PCI is chosen, patients with ST-elevation myocardial infarction (STEMI) presenting with anemia on admission might have poor clinical outcomes. The aim of this retrospective study was to investigate whether anemia on admission was associated with mid-term clinical outcomes in patients who underwent trans-radial primary PCI. The primary endpoint was a composite of all-cause death, recurrent acute myocardial infarction, and readmission for heart failure. A total of 288 consecutive patients with STEMI who underwent trans-radial primary PCI were divided into an anemia group (n = 79) and a non-anemia group (n = 209). The median follow-up duration was 301 days. The anemia group was significantly older than the non-anemia group (77.3 ± 11.9 versus 64.4 ± 12.7 years, respectively; P < 0.001). There were significantly more females in the anemia group than in the non-anemia group (36.7% versus 14.4%, respectively; P < 0.001). Kaplan-Meier analysis revealed that the composite outcome-free survival was significantly worse in the anemia group than in the non-anemia group (P < 0.001). Multivariate Cox hazard model analysis revealed that hemoglobin levels on admission were significantly associated with the composite outcome (per 1 g/dL increase: hazard ratio 0.76, 95% confidence interval 0.66-0.88, P < 0.001) after controlling for confounding factors. In conclusion, baseline anemia was significantly associated with poor clinical outcomes. Patients with STEMI presenting with anemia should be managed carefully, even if trans-radial primary PCI is chosen.

Drug-eluting stent (DES) is well known to be effective in severely calcified lesion after rotational atherectomy (ROTA). However, there are still some situations when stents should be avoided and plain old balloon angioplasty (POBA) should be the preferred option. The present study aims to explore whether POBA is comparably effective to DES in large and calcified coronary pretreated by ROTA in clinical outcomes.

Consecutive patients treated for severely calcified lesions in the large (≥ 3 mm) coronary using ROTA + DES or ROTA + POBA were retrospectively analyzed. The major adverse cardiac events (MACE), including all-cause/cardiac death and target lesion revascularization (TLR) at 1 year and 2 years posttreatment, were compared between groups using the Cox regression analysis to identify independent predictors of TLR and MACE.

The analysis included 285 cases in the ROTA + DES group and 47 cases in the ROTA + POBA group, without relevant differences in clinical baseline characteristics. Of note, lesion length was greater in the ROTA + DES group (37.2 versus 19.3 mm, P < 0.001); the ROTA + DES group had a higher rate of chronic total occlusion (CTO) lesions, with 8.4%, and the ROTA + POBA group had none. The inhospital/30-day mortality rate (5.3%, ROTA + DES; 6.4%, ROTA + POBA) and the 12- and 24-month all-cause/cardiac mortality rate (9.3%, ROTA + DES; 7.7%, ROTA + POBA) were not significantly different between the two groups. TLR rates were not significantly different between the two groups at 12 (4.6%, ROTA + DES; 4.3%, ROTA + POBA) and 24 (5.3%, ROTA + DES; 6.4%, ROTA + POBA) months.

Outcomes were comparable for ROTA + DES and ROTA + POBA in severely calcified large coronary artery intervention with respect to midterm death or TLR rate, especially for short lesion of < 20 mm.

The COVID-19 pandemic severely disrupted cardiovascular care during the spring of 2020 in Europe. Our study analyzed the clinical profile, COVID-19 impact, and 30-day prognosis of invasively managed patients with acute coronary syndrome (ACS) compared to a historical cohort.

All invasively managed ACS patients from March 1st to April 30th, 2020 were compared to a cohort from the same timeframe of 2019 (n = 316). COVID-19 confirmed cases were defined by a positive SARS-CoV-2 polymerase chain reaction (PCR) test (CoV+). The primary outcome was all-cause 30-day mortality and multivariable predictors of this outcome.

A 40.4% reduction in ACS patients was noted (198 cases in 2019 to 118 in 2020), and 11% of 2020 ACS patients were CoV+. Baseline characteristics were similar between groups. There were significantly more in-hospital patients with ACS (15.3% versus 6.1%, P = 0.007), and fewer patients were found to have a culprit lesion (58.5% versus 74.2%, P = 0.004) in 2020 compared to 2019. Thirty-day mortality in 2020 (7%) was not different from that in 2019 (4.2%), P = 0.294, but it was significantly higher in CoV+ patients (23.1%) compared to that in negative SARS-CoV-2 PCR test (CoV−) patients (5%), P = 0.047, in the 2020 group. In the multivariate analysis, CoV+ was an independent mortality predictor (OR = 9.8, 95% CI = 1.48-64.78), along with the left ventricular ejection fraction (LVEF) (OR = 0.91, 95% CI = 0.86-0.97), P = 0.0006.

This study found increased 30-day mortality of invasively managed CoV+ ACS patients compared to that of CoV− patients during the 2020 COVID-19 spring outbreak. In the multivariable analysis, a SARS-CoV-2 positive test was independently associated with 30-day mortality. Further investigations of the underlying physiopathological relations between COVID-19 and ACS are warranted.

The clinical outcomes of patients with non-ST-segment elevation myocardial infarction (NSTEMI) were comparable or even worse than those with ST-segment elevation myocardial infarction (STEMI). Although successful percutaneous coronary intervention (PCI) to the culprit lesions of NSTEMI would improve the clinical outcomes, some PCI require long fluoroscopy time, reflecting the difficulty of PCI. This study aims to find clinical factors associated with long fluoroscopy time in PCI to the culprit lesion of NSTEMI. We included 374 patients and divided those into the conventional fluoroscopy time (n = 302) and long fluoroscopy time (n = 72) groups according to the quintiles of fluoroscopy time. Clinical and angiographic parameters were compared between the two groups. Calcification and tortuosity were significantly more severe in the long fluoroscopy time group than in the conventional fluoroscopy time group. The prevalence of previous coronary artery bypass grafting (CABG) and bifurcation lesions was significantly greater in the long fluoroscopy time group than in the conventional fluoroscopy time group. In the multivariate stepwise logistic regression analysis, previous CABG (odds ratio [OR], 3.368; 95% confidence interval [CI], 1.407-8.064; P = 0.006), bifurcation lesion (OR, 2.407; 95% CI, 1.285-4.506; P = 0.006), excessive tortuosity (versus mild to moderate tortuosity; OR, 4.095; 95% CI, 1.159-14.476; P = 0.029), and moderate to severe calcification (versus none to mild; OR, 5.792; 95% CI, 3.254-10.310; P < 0.001) were significantly associated with long fluoroscopy time. In conclusion, previous CABG, bifurcation, excessive tortuosity, and moderate to severe calcification were associated with long fluoroscopy time. Our study provided a reference for PCI operators to identify the difficulties in PCI to the culprit lesion of NSTEMI.

Atrial fibrillation (AF) is the most common cardiac arrhythmia; it has been known to increase the risk of stroke and heart failure. The association between air pollutants and AF has remained to be controversial. Thus, in this study, we sought to undertake a systematic review and meta-analysis in order to assess the short- and long-term effects of ambient air pollution on AF.

We searched PubMed, Web of Science, Embase, and Ovid for all related studies up to October 2019. We used the random-effects model to estimate the excess risk percentage (ER%) and confidence intervals (CI) for particulate matter with diameter ≤ 2.5 (PM_2.5) and ≤ 10 μm (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), ozone (O₃), and carbon monoxide (CO). Results were further analyzed by subgroups according to location, age, outcome, and gender.

In total, 18 studies were included in our meta-analysis: 5 evaluated for long-term effects, 12 for short-term effects, and 1 for both long- and short-term effects. For the short term, ER per 10 μg/m³ increase of pollutants was 1.8% (0%-3.7%) for PM_2.5 and 1.1% (−0.2%-2.4%) for PM₁₀; per 10 parts per billion (ppb) increment of gaseous pollutions was 3.2% (0.6%-5.8%) for NO₂, 2.9% (0.3%-5.7%) for SO₂, 0.5% (−3.4%-4.7%) for O₃, and 2.0% (−1.3%-5.4%) for CO per 1000 ppb change. The subgroup analysis showed the short-term effect was significantly different by region, gender, outcome, and age. Meanwhile, in the long term, except for O₃, a statistically significant association was noted between AF incidence and all pollutants.

Our meta-analysis suggests that short-term exposure to part of pollutants (PM_2.5, SO₂, and NO₂) increases AF attack. Further, long-term exposure to air pollution can significantly contribute to the incidence of AF in a healthy population.

Radiofrequency and cryoballoon applications around the pulmonary veins (PVs) could provoke a vagal reflex (VR) by modulating the intrinsic cardiac autonomic nervous system (ICANS).

This study aimed to investigate the incidence, timing, and clinical impact of a VR provoked by a laser balloon application for a PV isolation (PVI).

A total of 92 consecutive paroxysmal atrial fibrillation (PAF) patients underwent a laser balloon PVI of PAF. Acute changes in the heart rate and blood pressure were recorded. The heart rate variability (HRV) was tested by Holter ECGs before and at three months following the ablation. Three hundred forty-five out of 363 PVs were successfully isolated (97%) with laser balloon applications. A VR such as sinus bradycardia (26.1%), transient sinus arrest (9.8%), transient atrioventricular block (1.1%), or a blood pressure reduction (8.7%) was observed during the laser balloon applications for the PVI. The follow-up ended at 12 months. The HRV attenuation was comparable before and at three months after the ablation procedure between that with and without a VR (P = 0.14). The PAF recurrence rate was also comparable between the two groups (P = 0.882).

The laser balloon PVI often provoked a VR, however, the modulation of the ICANS was temporary and for up to three months as measured by the HRV changes after the ablation, and the freedom from any atrial fibrillation recurrence was comparable regardless of the occurrence of a VR.

Atrial fibrillation (AF) is a common complication of acute myocardial infarction (AMI). Although previous studies have investigated mortality rates and the incidences of adverse events associated with new-onset AF (NOAF) in patients with AMI, the effects of emergency percutaneous coronary intervention (PCI) on the incidence of NOAF in patients with AMI remain unclear. The purpose of this study was to investigate the relationship of clinical characteristics, medical history, and the coronary flow disturbance phenomenon (TIMI < 3) following emergency PCI with NOAF in patients with AMI. Between 2012 and 2016, 731 patients with AMI underwent PCI at our facility. Among these, 52 had a history of chronic/paroxysmal AF before admission and were excluded. The remaining 679 patients (mean age 66.4 years, 532 males) were analyzed in this retrospective observational study.

New-onset AF was observed in 45 patients (6.6%). In univariate analysis, the hazard ratios (HRs) for patient age (HR 1.04, 95%CI 1.02-1.07), Killip II-IV (HR 2.34, 95%CI 1.29-4.23), elevated D-dimer level (> 1.0 μg/mL; HR 3.32; 95%CI 1.77-6.23), and coronary flow disturbance phenomenon (HR 5.61; 95%CI 2.88-10.9) were significantly higher in the NOAF group. In multivariate analysis, an elevated D-dimer level (> 1.0 μg/mL; HR 2.44; 95%CI 1.17-5.11) and coronary flow disturbance phenomenon (HR 4.61; 95%CI 2.29-9.27) were found to be independent risk factors for NOAF. An elevated D-dimer level at admission and the presence of coronary flow disturbance phenomenon after PCI were risk factors for NOAF following emergency PCI in patients with AMI.

This study aims to evaluate the incidence of ischemic stroke or transient ischemic attack (TIA) based on CHA₂DS₂-VASc scores in non-AF Chinese patients with sinus rhythm.

We used health check-up data of 101,510 participants from the Kailuan Cohort Study. Participants' risk levels were defined by their CHA₂DS₂-VASc scores (range 0-3): Men with scores of 0, 1, or ≥ 2 and women with scores of 1, 2, or ≥ 3 were considered at low, intermediate, or high risk, respectively. Cox proportional hazards model was used to assess the association between the CHA₂DS₂-VASc-determined risk and the incidence of ischemic stroke/TIA.

The mean 7.5 year follow-up examination revealed 2968 ischemic strokes/TIA events. The incidence rates for ischemic stroke/TIA events in men and women were 3.8% and 1.5%, respectively. The incidence of ischemic stroke/TIA increased with elevated predicted risks based on CHA₂DS₂-VASc scores in men: 2.2% for low-risk, 4.1% for intermediate-risk, and 7.8% for high-risk groups (P < 0.001 for trend). The incidences of ischemic stroke/TIA also increased with elevated predicted risks in women: 0.8% for low-risk, 2.1% for intermediate-risk, and 5.0% for high-risk groups (P < 0.001 for trend). Compared with low-risk group, the crude hazard ratio (95% confidence interval) of ischemic stroke/TIA for men in moderate- and high-risk groups were 1.96 (1.79-2.14; P < 0.001) and 4.18 (3.81-4.57; P < 0.001). Similar findings were observed in women.

Risks of ischemic stroke/TIA events was high, particularly among those with high CHA₂DS₂-VASc scores.

Second-generation cryoballoon (CB) ablation is effective in achieving pulmonary vein (PV) isolation (PVI) in atrial fibrillation (AF) patients. The "crosstalk" (CST) phenomenon has been reported to reduce unnecessary applications during CB ablation. Nevertheless, it is unclear under what conditions the CST phenomenon occurs.

To seek the predictors of the CST phenomenon during CB-guided PVI, CST phenomenon in achieving ipsilateral superior PVI during inferior PV ablation was analyzed in AF patients who underwent de novo ablation using CB. CB occlusion status and nadir balloon temperature (NT) were compared in these patients, and all ablated superior PVs were categorized into three groups according to the necessity of the touch up ablation and effectiveness of the phenomenon.

Of 1082 superior PVs, 16, 40, and 1026 were classified into the CST success, CST failure, and control groups (unnecessary CST), respectively. The proportion of superior PVs ablated with complete occlusion using the CB was significantly higher in the CST success group than in the other two groups. The proportion of superior PVs ablated with NT ≤ −46°C was higher in the CST success group than in the CST failure group. The CST phenomenon was always observed if CB ablation of the superior PVs was performed with both complete occlusion and NT ≤ −46°C and was almost always ineffective if it did not meet these two criteria (sensitivity, 100%; specificity, 93%).

Successful CST ablation was highly predicted if complete PV occlusion and NT ≤ −46°C during CB ablation of the superior PVs were achieved.

The reasons of residual left ventricular outflow tract (LVOT) obstruction following alcohol septal ablation (ASA) remain unclear, and outcomes of myectomy following failed ASA remain underreported.

Thirteen symptomatic patients (10 women, a median age of 60.0 years) who underwent septal myectomy following failed ASA were reviewed. The patients were followed up for a median of 6 months. The clinical characteristics and outcomes of these patients were analyzed and were compared with those of 178 patients who underwent isolated myectomy without previous ASA at our institution during the same period.

In the first ASA procedure, the median number of septal perforator arteries injected was 1.0 with the median value of peak creatine kinase following ablation of 978.5 U/L.Uncontrollable extent and location of infarcted myocardium caused by ablation and mitral subvalvular anomalies were found in four (30.8%) and seven (53.8%) patients, respectively. No operative or follow-up deaths occurred. The median maximum LVOT gradients fell from preoperative 112.0 to 8.5 mmHg at follow-up (P < 0.001). Compared with controls, patients with failed ASA had a higher proportion of mitral subvalvular anomalies (53.8% versus 13.5%, P = 0.001) and developed a higher incidence of complete atrioventricular block following myectomy (15.4% versus 1.7%, P = 0.038).

Low institutional or operator experience with ablation, uncontrollable extent and location of infarcted myocardium caused by ablation, and mitral subvalvular anomalies may be reasons for failed ASA. Surgical myectomy for the treatment of residual LVOT obstruction after unsuccessful ASA may be associated with favorable results.

It is unclear whether patients with hypertension are more likely to be infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population and whether there is a difference in the severity of coronavirus disease (COVID-19) pneumonia in patients who have taken ACEI/ARB drugs compared with those who have not.

This observational study included data from all patients with clinically confirmed COVID-19 admitted to Hankou Hospital, Wuhan, China, between January 5 and March 8, 2020. Data were extracted from clinical and laboratory records. Follow-up was cut off on March 8, 2020.

A total of 274 patients, 75 with hypertension and 199 without hypertension, were included in the analysis. Compared with patients without hypertension, patients with hypertension were older and were more likely to have preexisting comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease. Moreover, patients with hypertension tended to have higher positive rate for SARS-CoV-2 PCR detection. Multivariate logistic regression analysis showed that age (P = 0.005) and gender (P = 0.019) were independent risk factors associated with the severity of pneumonia in patients on admission, whereas ACEI/ARB treatment (P = 0.184) was not.

Patients with COVID-19 with hypertension were significantly older and were more likely to have underlying comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease. ACEI/ARB drugs did not influence the severity of pneumonia in patients with SARS-CoV-2. In future studies, a larger sample size and multi-center clinical data would be needed to support these conclusions.

Cardiovascular event rates of patients with a dipper blood pressure (BP) and dipper heart rate (HR) pattern are lower than those of patients with nondipper BP and HR patterns. However, how the pacemaker mode affects the diurnal BP and HR patterns remains unclear.

We enrolled nine patients (average age 74.4 ± 6.6 years, 4 males and 5 females) with sick sinus syndrome who required atrial pacing. We investigated sequential 6-month pacing regimens (DDD mode at 60 bpm and sleep rate mode). We set the lower rate of sleep rate mode as follows: 60 bpm during the daytime and 50 bpm during the nighttime. The order of pacing mode was randomized, with crossover design. Ambulatory BP monitoring was performed at baseline, 6 months, and 12 months, BP category was classified into four groups (extreme dipper, dipper, nondipper, and riser pattern), and HR was classified into dipper and nondipper patterns.

Nighttime HR during the sleep rate mode was significantly lower than that at DDD (57.1 ± 6.2 versus 63.5 ± 3.8 bpm, P = 0.001). The dipper HR pattern was increased in the sleep rate mode compared with those at baseline or DDD mode (versus baseline: 89% versus 44%, P = 0.035; versus DDD: 89% versus 22%, P = 0.004). The dipper BP pattern significantly increased in the sleep rate mode compared with the baseline (56% versus 11%, P = 0.035), but the difference between the sleep rate mode and DDD mode was statistically marginal (56% versus 22%, P = 0.081).

The pacemaker settings in the sleep rate mode increased the dipper HR and BP patterns in pacemaker-dependent patients with sick sinus syndrome.

Myocardial infarction (MI) is the most prevalent disease with severe mortality, and hypoxia-induced cardiac injury and cardiomyocyte apoptosis are the significant and harmful consequences of this disease. The cross talk between hypoxia signaling and glycolysis energy flux plays a critical role in modulating MI-related heart disorder. However, the underlying mechanism remains unclear. Here, we aimed to explore the effect of a key glycolytic enzyme of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 (PFKFB2) on cardiac dysfunction and apoptosis in response to hypoxia. Our data demonstrated that the mRNA and protein expression of PFKFB2 were significantly elevated in the MI mice. The MI treatment promoted the activation of PFKFB2 in vivo, as presented by the remarkably increased phosphorylation levels of PFKFB2. PFKFB2 depletion enhanced MI-induced cardiac dysfunction and cardiomyocyte apoptosis in the MI mouse model. Moreover, hypoxia treatment dramatically upregulated the expression and activation of PFKFB2 in a time-dependent manner in cardiomyocytes. Hypoxia-stimulated PFKFB2 relieved hypoxia-induced cardiomyocyte apoptosis in vitro. PFKFB2 activated the fructose-2, 6-bisphosphate (Fru-2, 6-p2) /PFK/anaerobic adenosine triphosphate (ATP) glycolysis energy flux in response to hypoxia in cardiomyocytes. Mechanically, hypoxia-activated PFKFB2 by stimulating the hypoxia-inducible factor 1 (HIF-1) /ATK signaling. Thus, we conclude that HIF-1/AKT axis-activated PFKFB2 alleviates cardiac dysfunction and cardiomyocyte apoptosis in response to hypoxia. Our finding presents a new insight into the mechanism by which HIF-1/AKT/PFKFB2 signaling modulates MI-related heart disorder under the hypoxia condition, providing potential therapeutic targets and strategy for hypoxia-related myocardial injury.

Dilated cardiomyopathy (DCM) is a common cause of heart failure. TTN, which encodes titin protein, is a representative causative gene of DCM, and is presented mainly as a truncation variant. However, TTN truncation variants are also found in healthy individuals, and it is therefore important to evaluate the pathogenicity of each variant. In this study, we analyzed 67 cardiomyopathy-associated genes in a male Japanese patient who was hospitalized for recurrent severe heart failure and identified a novel truncation variant, TTN Ser17456Arg fs*14. This TTN truncation variant was located in the A-band region. Moreover, the patient's mother with heart failure harbored the same variant, whereas the father and brother without heart failure did not harbor the variant. To examine the functional changes associated with the truncation variant, H9c2 cells were subjected to genome editing to generate cells with a homologous truncation variant. The cells were differentiated using all-trans-retinoic acid, and the mRNA expression of skeletal actin and cardiac actin were found to be increased and decreased, respectively, consistent with known changes in patients with DCM or heart failure. In contrast, another cell with the titin truncation variant used as a control showed no changes in heart failure-related genes. In summary, we found a novel TTN truncation variant in familial DCM patients and confirmed its functional changes using a relatively simple cell model. The novel truncation variant was identified as a pathogenic and disease-causing mutation.

This study aimed to improve and further explore a ventricular septal defect (VSD) canine model on the basis of the transcatheter puncture method and to evaluate its application and teaching value.

In order to lessen the complications of VSD closure, it is necessary to improve the currently available treatment devices using appropriate animal models.

In this study, we used 16 healthy adult canines as our models. After anesthesia, the VSD puncture was performed, followed by balloon dilatation of the perforation. VSD was confirmed by angiography. The venous-artery orbit was established, and the VSD was then closed once the catheter and occluder were across the defect.

Of the experimental canines, 14 of the 16 canines were successfully modeled, giving a success rate of 87.5%. The canines underwent an immediate creation of a venous-artery orbit for teaching practice and were implanted with an occluder during the procedure. After 4 weeks, 13 canines survived. As per our findings, most VSD types established by the puncture were perimembranous (10 of 13, 77%).

The current model has a high success rate. The model can not only avoid the risk of infection and hemodynamic disorders associated with an open thoracotomy, but can also be effectively used in evaluating the impact of occluders. It can also directly measure the parameters of the devices during the procedure, thus having a very high experimental and teaching value.

Coronary artery disease (CAD) is one of the heavy health burdens worldwide. Aberrant proliferation of vascular smooth muscle cells (VSMCs) contributes to the occurrence and development of CAD. This study aimed at exploring differentially expressed microRNAs (miRNAs) and their regulatory mechanisms in the development of CAD.

The miRNA expression profile of GSE28858 was obtained from the Gene Expression Omnibus database. Differentially expressed miRNAs (DEmiRNAs) between CAD and healthy control samples were analyzed using limma package in R. Target genes of DEmiRNAs were predicted, and a miRNA-target gene network was constructed. The relationship between miR-665 and transforming growth factor beta receptor 1 (TGFBR1) was selected for further analysis. The interaction between miR-665 and TGFBR1 was confirmed by dual luciferase reporter assay. Effects of miR-665 on cell viability and apoptosis of VSMCs were evaluated by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Besides, western blot assays for BCL2L11 and caspase 3 were also conducted.

A total of 38 upregulated miRNAs and 28 downregulated miRNAs were identified. The expression level of miR-665 was significantly downregulated in patients with CAD. TGFBR1 was proved to be a target gene of miR-665. Besides, ectopic expression of miR-665 obviously inhibited VSMC growth and promoted VSMC apoptosis. TGFBR1 overexpression in VSMCs transfected with miR-665 mimic could restore the effect of miR-665 on the proliferation and apoptosis of VSMCs.

MiR-665 might participate in the proliferation and apoptosis of VSMCs by targeting TGFBR1.

Extracellular vesicles (EV) that are derived from endothelial progenitor cells (EPC) have been determined to be a novel therapy for acute myocardial infarction, with a promise for immediate "off-the-shelf" delivery. Early experience suggests delivery of EVs from allogeneic sources is safe. Yet, clinical translation of this therapy requires assurances of both EV stability following cryopreservation and absence of an adverse immunologic response to EVs from allogeneic donors. Thus, more bioactivity studies on allogeneic EVs after cold storage are necessary to establish quality standards for its widespread clinical use. Thus, in this study, we aimed to demonstrate the safety and efficacy in delivering cryopreserved EVs in allogeneic recipients as a therapy for acute myocardial infarction.

In this present study, we have analyzed the cardioprotective effects of allogeneic EPC-derived EVs after storage at −80°C for 2 months, using a shear-thinning gel (STG) as an in vivo delivery vehicle. EV size, proteome, and nucleic acid cargo were observed to remain steady through extended cryopreservation via nanoparticle tracking analysis, mass spectrometry, and nanodrop analysis, respectively. Fresh and previously frozen EVs in STG were delivered intramyocardially in a rat model of myocardial infarction (MI), with both showing improvements in contractility, angiogenesis, and scar thickness in comparison to phosphate-buffered saline (PBS) and STG controls at 4 weeks post-MI. Pathologic analyses and flow cytometry revealed minimal inflammatory and immune upregulation upon exposure of tissue to EVs pooled from allogeneic donor cells.

Allogeneic EPC-EVs have been known to elicit minimal immune activity and retain therapeutic efficacy after at least 2 months of cryopreservation in a post-MI model.

Perivascular adipose tissue (PVAT) secretes large amounts of inflammatory mediators and plays a certain role in atherosclerosis formation from the exterior of the vessel. In the present study, we examined the expression level of inflammation-related mediators using adipose tissue samples harvested from patients with and without coronary artery disease (CAD). The subjects were 23 patients who underwent elective coronary bypass surgery (CAD group) and 17 patients who underwent elective mitral valve surgery (non-CAD group) between January 2017 and March 2018. The adipose tissue was harvested from three sites: the ascending aorta (AO), subcutaneous fat (SC), and pericoronary artery (CO) for the measurement of the expression levels of interleukin (IL) -1β, IL-6, IL-10, tumor necrosis factor (TNF) -α, interferon (INF) -γ, and arginase (Arg) -1. In both the non-CAD and CAD groups, the expression levels of all mediators, except Agr-1, which showed a tendency to have higher levels in the SC than in the AO and CO, tended to upregulate in the AO than in the SC and CO. The CAD group had higher values of almost all mediators, except Arg-1. Most importantly, the expression levels of IL-1β, IL-6, and IL-10 in the coronary artery were significantly higher in the CAD group. The expression levels of inflammatory mediators in the pericoronary adipose tissue were significantly higher in the CAD than in the non-CAD group. The adipose tissue appears to influence atherosclerosis formation from the exterior of the coronary artery.

Endothelial injury and inflammation have been found to be essential in the pathogenesis of coronary artery disease (CAD). Circulating exosomes are of great value as novel biomarkers for CAD. However, the role of circulating exosomes in the pathogenesis of CAD remains unclear. Thus, in this study, we aimed to examine whether circulating exosomes from CAD are involved in the endothelial injury and inflammation. The serum-derived exosomes were isolated from CAD and controls using an ExoQuick reagent, and these were then quantified by measuring the protein levels using BCA methods. The uptake of exosomes by human umbilical vein endothelial cells (HUVECs) was observed by laser scanning microscope and analyzed via flow cytometry. Then, HUVECs were treated with vehicle, exosomes from CAD (CAD-exo), and controls (ctrl-exo) in the absence and presence of vascular endothelial growth factor (VEGF). Cell viability, migration, and angiogenesis were evaluated using CCK-8 assay, scratch assay, and tube formation assay. Inflammatory factors including IL-1β, IL-6, TNF-α, ICAM-1, and VCAM-1 levels were detected via qPCR. As per our findings, no significant differences were noted in uptake of ctrl-exo and CAD-exo by HUVECs. CAD-exo suppressed cell viability in a dose-dependent manner. Compared with ctrl-exo, CAD-exo-treated HUVECs significantly suppressed migration and angiogenesis. However, CAD-exo had a stronger inhibitory effect on VEGF-induced migration and angiogenesis compared with ctrl-exo. Moreover, IL-1β, TNF-α, and ICAM-1 were determined to be significantly upregulated in HUVECs treated with CAD-exo, but IL-6 and VCAM-1 expressions were not affected. Overall, our results suggest that CAD-exo are involved in endothelial injury and inflammation, which may, in turn, cause endothelial dysfunction and potentially promote the development of CAD.

Exercise preconditioning (EP) provides protective effects for acute cardiovascular stress; however, its mechanisms need to be further investigated. Autophagy is a degradation pathway essential for myocardium health. Therefore, we investigated whether intermittent myocardial ischemia-hypoxia affected Beclin1 and whether the changes in autophagy levels contribute to EP-induced early myocardial protective effects. Rats were trained on a treadmill using an EP model (four cycles of 10 minutes of running/10 minutes of rest). Exhaustive exercise (EE) was performed to induce myocardial injury. Cardiac troponin I (cTnI) and ischemia-hypoxia staining were used to evaluate myocardial injury and protection. Double-labeled immunofluorescence staining and western blot analysis were employed to examine related markers. EP attenuated the myocardial ischemic-hypoxic injury induced by EE. Compared with the control (C) group, the dissociations of Beclin1/Bcl-2 ratio and Beclin1 expression were both higher in all other groups. Compared with the C group, PI3KC3 and the LC3-II/LC3-I ratio were higher in all other groups, whereas LC3-II was higher in the EE and EEP + EE groups. p62 was higher in the EE group than in the C group but lower in the EEP + EE group than in the EE group. We concluded that EP increases Beclin1 via intermittent myocardial ischemia-hypoxia and induces autophagy, which exerts early myocardial protective effects and reduces the myocardial ischemic-hypoxic injury induced by exhaustive exercise.

The retrograde approach has significantly improved the success rates in complex coronary total occlusion (CTO) lesions. It has also become the predominant and important strategy in CTO recanalization. However, unsuccessful crossing of the collateral channels is the strongest predictor of retrograde failure, and adverse collateral channel morphology, including large channel entry angle, could reduce the success rate of collateral channel crossing. Reverse wire technique (RWT) was specifically developed for bifurcation lesions with an extremely angulated side branch, and nowadays, this can be achieved by the support of a dual-lumen catheter (DLC). We report a novel method named "simplified dual-lumen catheter-facilitated RWT" to facilitate markedly angulated collateral channel entry in retrograde CTO intervention. This new technique is simplified by making the reverse bend with the support of a DLC in the aorta instead of outside the guiding catheter, which is feasible, effective, and safe for markedly angulated collateral channel entry in retrograde CTO percutaneous coronary intervention (PCI).

A method to manage ST-segment elevated myocardial infarction (STEMI) caused by very late stent thrombosis (VLST) has yet to be established. In this case series, we present several cases of STEMI caused by VLST, which were successfully revascularized using a perfusion balloon. Since the perfusion balloon (Ryusei: Kaneka Medix Corporation, Osaka, Japan) has the unique advantage of maintaining blood flow during balloon inflation, we can keep dilating the target lesion for more than several minutes. Extended inflation might work to prevent acute recoil, and to achieve optimal expansion without an additional stent. Our case series may provide a reasonable option for the treatment of VLST.

In this study, we present a case of a 22-year-old female with a family history of syncope, suffering from recurrent syncope since childhood. She had an obvious prolonged QTc interval of up to 651 ms, a bifid T wave pattern on electrocardiogram, and torsade de pointes, corresponding to a syncope episode. Additionally, her echocardiogram showed left ventricular non-compaction in the apex. After treatment with mexiletine, the QTc interval has been observed to shorten immediately, and the T wave morphology recovered. A similar effect was also observed in her mother and young sister. Administration of propranolol prolonged her QTc interval. Target sequencing of candidate genes revealed a missense mutation in the pore area of the hERG protein, coded by KCNH2. We diagnosed this as a case of type 2 long QT syndrome in which mexiletine could be effective in shortening the QTc interval.

Embolic myocardial infarction (MI) caused by infective endocarditis (IE) is rare, but it is increasingly recognized as an important complication. This complication typically occurs in patients with aortic valve endocarditis during the acute phase of the infection. It is also known to have a high mortality rate; however, the best practice for its management is unclear owing to scarce available data. In addition, most cases of embolic acute MI (AMI) caused by IE are indirectly diagnosed with a combination of angiographic examination such as coronary angiography or cardiac computed tomography. Herein, we report a case of fatal embolic ST-elevation MI (STEMI) caused by mitral valve IE during the healed phase, which was clearly proven by the pathology findings.

A 61-year-old woman suffered chest pain and was admitted to a nearby hospital emergency department. She was diagnosed with acute myocardial infarction probably due to thromboembolism in the left anterior descending coronary artery and aspiration thrombectomy was performed. Afterwards, she developed refractory heart failure with severe global left ventricular dysfunction and was transferred to our hospital. An ¹⁸F-FDG-PET/CT scan revealed abnormal ¹⁸F-FDG uptake in non-infarcted regions of the left ventricle. Non-caseating granulomas were detected by biopsy from a skin eruption. She was diagnosed with cardiac sarcoidosis. In cases of refractory heart failure which cannot be explained only by myocardial infarction, evaluation of other undiagnosed cardiomyopathies is important for optimal management.

We had a 58-year-old man with advanced heart failure and progressive end-organ dysfunction refractory to inotropes. Following detailed discussions, he decided not to receive ventricular assist device therapy considering his comorbidity of schizophrenia. A palliative care team initiated 2.5 mg of morphine together with low-dose anti-heart failure medications, which improved not only his heart failure symptoms but also the congestive heart failure itself. Aggressive commitments of the palliative care team might improve not only patients' quality of life but also advanced heart failure itself.

Recessive mutations in the Myosin regulatory light chain 2 (MYL2) gene are the cause of an infantile-onset myopathy, associated with fatal myocardial disease of variable macromorphology. We here present the first Japanese family affected with recessive MYL2 myopathy. Affected siblings manifested typical features and the proband's autopsy findings were compatible with the diagnosis of noncompaction cardiomyopathy. The rapidly progressive clinical course of this recessive MYL2 cardiomyopathy highlights the crucial role of c-terminal tails in MYL2 protein in maintaining cardiac morphology and function.

While the advancement of perioperative management has expanded Fontan candidacy, not all patients have a successful postoperative course. Our case was a right isomerism patient who could not leave the ICU due to high central venous pressure and low output syndrome. Initial observation of the monitor ECG showed his rhythm to be supraventricular, however, an echocardiogram indicated simultaneous contraction of the atrium and ventricle, implying a junctional rhythm. While neither central venous pressure nor blood pressure improved with temporary pacing, better central venous and pulmonary venous blood flow patterns during pacing unraveled its positive impact. The patient successfully left the ICU after permanent pacing implantation. Hemodynamic study revealed a beneficial impact of atrial pacing in securing cardiac output and ventricular preload, lowering central venous pressure, and shortening blood transit time, which is partly attributed to the optimization of the fenestration function in reservation of the preload. Our case emphasizes the significant advantage of atrial pacing in a failing Fontan patient with junctional rhythm by reducing venous congestion and maximizing the benefit of fenestration.

Primary hemangioma of the mediastinum is extremely rare. Herein, we present a unique case of hemangioma mimicking left atrial mass in the posterior mediastinum. We reviewed the literature and found 17 other hemangiomas in the posterior mediastinum. Herein, we summarize the age, gender, symptoms, diagnostic methods, image diagnosis, size, treatments, histologic features, outcomes, and follow-up of 17 cases. Most of the cases were asymptomatic and were accidentally detected in chest radiographs. Diagnostic methods mainly included chest X-ray, computed tomography (CT), and magnetic resonance imaging (MRI). All patients underwent surgical resection, recovered well, and had no recurrence during follow-up.

In this study, we present the case of a 34-year-old man who was diagnosed with primary cardiac angiosarcoma 1 month after hospital admission. Cardiac angiosarcoma is a relatively rare disease that can be easily misdiagnosed as pneumonia or other diseases. Although surgery is the preferred treatment to prolong survival time, highly malignant tumors with local infiltration and systemic metastasis can lead to poor prognosis.

The errors appeared in the article entitled "Handgrip Strength Is an Independent Predictor of Cardiovascular Outcomes in Diabetes Mellitus" by Yoshinobu Morikawa, Rika Kawakami, Manabu Horii, Yuta Yamamoto, Matahiro Yabuta, and Yoshihiko Saito (Vol. 62, No. 1, 50-56, 2021). The Tables II and III on page 53, and Table IV on page 54 should be replaced by the following tables.