Predictors for all-cause mortality in men after transcatheter aortic valve replacement: A report from the LAPLACE-TAVI registry.

Background: Information regarding the outcomes of transcatheter aortic valve replacement (TAVR) in men is limited. This study aimed to investigate short- to mid-term outcomes and prognostic predictors in this population. Method and Results: The data of 519 men were analyzed from 1,693 consecutive patients with symptomatic severe aortic stenosis who underwent TAVR at six hospitals between April 2010 and July 2020. The primary endpoint was all-cause mortality at 30 days after TAVR. The mean age and Society of Thoracic Surgeons (STS) score were 83.7 ± 5.9 years and 6.3 ± 4.7%, respectively. Overall, 23.5% of patients consumed alcohol with a frequency of > 1 drinks/week, and 12.1% consumed alcohol with a frequency of > 8 drinks/week, while 66.1% were former smokers and 4.2% were current smokers. Mortality at 30 days was 0.8%. During the median follow-up period of 448 days, the estimated survival rates at 1 year post-TAVR was 90.7 ± 1.4%. In multivariate analysis, the serum albumin level [hazard ratio (HR): 2.20, 95% confidence interval (CI):1.36-3.62, p = 0.001], atrial fibrillation (HR: 1.79, 95% CI: 1.13-2.82, p = 0.012), and STS score (HR: 1.33, 95% CI: 1.06-1.67, p = 0.015) were independently associated with all-cause mortality following TAVR. Adjusted hazard ratios of current smoking, heavy drinking, and presence of cancer were 1.05 (95% CI: 0.36-2.98),1.37 (95% CI: 0.75-2.48), and 1.13 (95% CI: 0.75-2.48), respectively. Conclusion: Our study demonstrated that serum albumin levels, atrial fibrillation, and STS score were independently associated with all-cause mortality following TAVR in men.

Glycoprotein nonmetastatic melanoma protein B regulates lysosomal integrity and lifespan of senescent cells.

Accumulation of senescent cells in various tissues has been reported to have a pathological role in age-associated diseases. Elimination of senescent cells (senolysis) was recently reported to reversibly improve pathological aging phenotypes without increasing rates of cancer. We previously identified glycoprotein nonmetastatic melanoma protein B (GPNMB) as a seno-antigen specifically expressed by senescent human vascular endothelial cells and demonstrated that vaccination against Gpnmb eliminated Gpnmb-positive senescent cells, leading to an improvement of age-associated pathologies in mice. The aim of this study was to elucidate whether GPNMB plays a role in senescent cells. We examined the potential role of GPNMB in senescent cells by testing the effects of GPNMB depletion and overexpression in vitro and in vivo. Depletion of GPNMB from human vascular endothelial cells shortened their replicative lifespan and increased the expression of negative cell cycle regulators. Conversely, GPNMB overexpression protected these cells against stress-induced premature senescence. Depletion of Gpnmb led to impairment of vascular function and enhanced atherogenesis in mice, whereas overexpression attenuated dietary vascular dysfunction and atherogenesis. GPNMB was upregulated by lysosomal stress associated with cellular senescence and was a crucial protective factor in maintaining lysosomal integrity. GPNMB is a seno-antigen that acts as a survival factor in senescent cells, suggesting that targeting seno-antigens such as GPNMB may be a novel strategy for senolytic treatments.

Long-Term Outcomes in Patients with Not-Retrieval Inferior Vena Cava Filter Under Anticoagulation.

Since permanent inferior vena cava (IVC) filters increase deep vein thrombosis (DVT), filter retrieval should be performed as possible. Despite the guideline recommendation, IVC filters are not always retrieved in clinical practice. To date, many patients with not-retrieval IVC filters have been prescribed anticoagulant therapy, but the long-term prognosis, including venous thromboembolism (VTE) and bleeding events, remains unknown. In this study, 195 patients who underwent IVC filter implantation between 2006 and 2017 at 3 institutions in Niigata City have been investigated about their deaths, VTE recurrence, and bleeding events. After peaking 2009, the number of IVC filter implantation gradually decreased. During observational period, there were 158 patients with not-retrieval IVC filters (the overall retrieval rate of 19.0%). The not-retrieval group included significantly older and more patients with cancer compared to the retrieval group. Anticoagulation therapy was continued in 88% of the not-retrieval group. During a mean follow-up of 5.0 years, 6 symptomatic DVT events associated with inadequate control of anticoagulation and 13 bleeding events were observed. A total of 52 patients died and only the presence of cancer was prognostic risk factor. Although long-term anticoagulation therapy may be associated with bleeding events, there were few recurrent VTE under optimal anticoagulation. It is anticipated that even if the IVC filter cannot be retrieved, appropriate anticoagulation is useful for prevention of DVT recurrence despite the risk of bleeding.

Transcatheter coil embolization for large pulmonary arteriovenous fistulae through an artificial tricuspid ball valve.

Pulmonary arteriovenous fistulae (PAFs) occur congenitally or are acquired. A PAF can cause hypoxemia, sudden death from rupture, abscess formation, and embolism. Treatment for PAF is transcatheter embolization or surgery. Transcatheter embolization is the first choice of treatment; however, this treatment is impossible to perform if a patient has had tricuspid or pulmonary valve replacement. In this paper, we describe a case of PAFs complicated with tricuspid valve replacement with a ball valve (which had been performed 40 years earlier) that was treated with transcatheter embolization. .

Conservative treatment with an intra-aortic balloon pump to treat acute myocardial infarction due to spontaneous coronary artery dissection.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome. Treatment for SCAD includes conservative approaches, percutaneous coronary intervention (PCI), and coronary artery bypass graft surgery. Although the success rate of PCI is low, conservative treatment often leads to a good clinical course. Three patients with SCAD who were conservatively treated with intra-aortic balloon pumping without coronary intervention are presented. All three patients continue to do well. .

Relationship Between Heart Rate at Discharge and Long-Term Outcomes of Surgically Treated Patients With Type A Acute Aortic Dissections.

BACKGROUND: Resting heart rate (HR) at discharge is an important predictor of mortality after acute myocardial infarction. However, in patients with Stanford type A acute aortic dissections (TA-AADs), the relationship between HR and long-term outcomes is unclear. Therefore, this relationship was investigated in the present study.Methods and Results:Surgically treated consecutive patients with TA-AAD (n=721) were retrospectively categorized according to HR quartiles, recorded within 24 h before discharge (<70, 70-77, 78-83, and ≥84 beats/min). The study endpoints included aortic aneurysm-related deaths, sudden deaths, aortic surgeries, and hospitalizations for recurrence of acute aortic dissections. The mean (±SD) patient age was 65.8±13.0 years. During a median observation period of 5.8 years (interquartile range 3.9-8.5 years), 17.2% of patients (n=124) experienced late aortic events. Late aortic surgery was performed in 14.0% of patients. After adjusting for potential confounders, including ß-blocker use, HR at discharge remained an independent predictor of long-term aortic outcomes. Patients with discharge HR ≥84 beats/min had a higher risk (hazard ratio 1.86; 95% confidence interval 1.06-3.25; P=0.029) of long-term aortic events than those with HR <70 beats/min; the cumulative survival rates were similar among the groups (log-rank, P=0.905). CONCLUSIONS: In surgically treated patients with TA-AAD, HR at discharge independently predicted long-term aortic outcomes. Consequently, HR in patients with TA-AAD should be optimized before discharge, particularly if the HR is ≥84 beats/min.

Cardiac mitofusin-1 is reduced in non-responding patients with idiopathic dilated cardiomyopathy.

Prognosis of severe heart failure remains poor. Urgent new therapies are required. Some heart failure patients do not respond to established multidisciplinary treatment and are classified as "non-responders". The outcome is especially poor for non-responders, and underlying mechanisms are largely unknown. Mitofusin-1 (Mfn1), a mitochondrial fusion protein, is significantly reduced in non-responding patients. This study aimed to elucidate the role of Mfn1 in the failing heart. Twenty-two idiopathic dilated cardiomyopathy (IDCM) patients who underwent endomyocardial biopsy of intraventricular septum were included. Of the 22 patients, 8 were non-responders (left ventricular (LV) ejection fraction (LVEF) of < 10% improvement at late phase follow-up). Electron microscopy (EM), quantitative PCR, and immunofluorescence studies were performed to explore the biological processes and molecules involved in failure to respond. Studies in cardiac specific Mfn1 knockout mice (c-Mfn1 KO), and in vitro studies with neonatal rat ventricular myocytes (NRVMs) were also conducted. A significant reduction in mitochondrial size in cardiomyocytes, and Mfn1, was observed in non-responders. A LV pressure overload with thoracic aortic constriction (TAC) c-Mfn1 KO mouse model was generated. Systolic function was reduced in c-Mfn1 KO mice, while mitochondria alteration in TAC c-Mfn1 KO mice increased. In vitro studies in NRVMs indicated negative regulation of Mfn1 by the ß-AR/cAMP/PKA/miR-140-5p pathway resulting in significant reduction in mitochondrial respiration of NRVMs. The level of miR140-5p was increased in cardiac tissues of non-responders. Mfn1 is a biomarker of heart failure in non-responders. Therapies targeting mitochondrial dynamics and homeostasis are next generation therapy for non-responding heart failure patients.

Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice.

Elimination of senescent cells (senolysis) was recently reported to improve normal and pathological changes associated with aging in mice1,2. However, most senolytic agents inhibit antiapoptotic pathways3, raising the possibility of off-target effects in normal tissues. Identification of alternative senolytic approaches is therefore warranted. Here we identify glycoprotein nonmetastatic melanoma protein B (GPNMB) as a molecular target for senolytic therapy. Analysis of transcriptome data from senescent vascular endothelial cells revealed that GPNMB was a molecule with a transmembrane domain that was enriched in senescent cells (seno-antigen). GPNMB expression was upregulated in vascular endothelial cells and/or leukocytes of patients and mice with atherosclerosis. Genetic ablation of Gpnmb-positive cells attenuated senescence in adipose tissue and improved systemic metabolic abnormalities in mice fed a high-fat diet, and reduced atherosclerotic burden in apolipoprotein E knockout mice on a high-fat diet. We then immunized mice against Gpnmb and found a reduction in Gpnmb-positive cells. Senolytic vaccination also improved normal and pathological phenotypes associated with aging, and extended the male lifespan of progeroid mice. Our results suggest that vaccination targeting seno-antigens could be a potential strategy for new senolytic therapies.

Long-Term Prognosis of Patients Who Underwent Percutaneous Transvenous Mitral Commissurotomy for Mitral Stenosis.

The long-term prognosis for up to 20 years of patients who have undergone percutaneous transvenous mitral commissurotomy (PTMC) for mitral stenosis (MS) is unknown.We examined 77 of 93 patients (83%) with MS and who underwent PTMC from 1989 to 2002 at our institute, as well as the occurrence of either one of the following clinical endpoints until September 1, 2018: all-cause death or repeat intervention for the mitral valve.The mean follow-up duration was 20.5 ± 7.3 years. The mean age was 51 ± 11 years. Overall, the 20-year survival rate was 71% ± 5%; without any intervention, the 20-year survival rate was 40% ± 6%. In patients who achieved good immediate results (i.e., mitral valve area (MVA) of ≥ 1.5 cm2 without mitral regurgitation (MR) of > 2/4 after PTMC), the 20-year survival rate was 80% ± 6%; without any intervention, the 20-year survival rate was 54% ± 7%.In our 20-year observational study, patients who have undergone PTMC for MS had favorable prognosis, especially in those who achieved good immediate results. In those who had poor immediate results, careful follow-up is needed because they might have more clinical event and any intervention for the mitral valve.

Pulmonary Artery Sarcoma Diagnosed Using an Endovascular Catheter Forceps Biopsy.

We herein report a case of pulmonary artery sarcoma (PAS) in a 64-year-old woman. She was admitted to our hospital because of massive genital bleeding from endometrial cancer. Contrast-enhanced computed tomography (CT) revealed a left pulmonary artery mass and deep vein thrombosis. She underwent anticoagulant therapy for one year. However, the mass lesion gradually expanded. 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT showed a positive uptake of FDG by the mass. An endovascular catheter biopsy was performed for the differentiation of endometrial cancer metastasis or primary sarcoma. The biopsy specimen tissue comprised spindle-shaped cells. Thus, the patient was diagnosed with PAS.

Adult ALCAPA: from histological picture to clinical features.

BACKGROUND: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital coronary anomaly that results in high mortality if left untreated. Our aim was to extend our knowledge of the histological, angiographic, and clinical characteristics of ALCAPA in order to deepen our understanding of this rare entity. CASE PRESENTATION: We were involved in the assessment, treatment, and pathological evaluation of two adult ALCAPA patients who were rescued from ventricular fibrillation and then surgically treated to establish a dual coronary artery system. Histological studies indicated various chronic ischemic changes in the myocardium, patchy fibrosis, and severely thickened arteriolar walls in both ventricles. The first patient is alive and well 11.5 years after surgical correction without any implantable cardioverter defibrillator (ICD) activations. The second patient required re-do surgery 9 months after the initial operation but subsequently died. Histologically, chronic ischemic alteration of the myocardium and thickened arteriolar walls persisted even after surgical correction, and coronary angiography (CAG) showed an extremely slow flow phenomenon even after surgical correction in both patients. The average postoperative opacification rate in the first case was 7.36 + 1.12 (n = 2) in the RCA, 3.81 + 0.51 (n = 3) in the left anterior descending (LAD) artery, and 4.08 + 0.27 (n = 4) in the left circumflex (LCx) artery. The slow flow phenomenon may represent persistent high arteriolar resistance in both ventricles. CONCLUSIONS: Seldom reported or new findings in adult ALCAPA were identified in two cases. More frequent diagnosis of adult ALCAPA can be expected because of the widespread availability of resuscitation and more advanced diagnostic modalities. Accumulation of pathological and clinical findings and confirmation of the long-term follow-up results after treatment may contribute to expanding our knowledge of this rare entity and establishing optimal treatment.

Differential predictive factors for cardiovascular events in patients with or without cancer history.

Although attention has been paid to the relationship between malignant diseases and cardiovascular diseases, few data have been reported. Moreover, there have also been few reports in which the preventive factors were examined in patients with or without malignant disease histories requiring percutaneous coronary intervention (PCI).This was a retrospective, single-center, observational study. A total of 1003 post-PCI patients were divided into a malignant group, with current or past malignant disease, and a nonmalignant group. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, revascularization, and admission due to heart failure within 5 years of PCI. Kaplan-Meier analysis showed a significantly higher probability of the primary endpoint in the malignant group (P = .002). Multivariable Cox hazard analyses showed that in patients without a history of malignant, body mass index (BMI) and the presence of dyslipidemia were independent and significant negative predictors of the primary endpoint (BMI: hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.53-0.99, P = .041; prevalence of dyslipidemia: HR 0.72, 95% CI 0.52-0.99, P = .048), and the presence of multi-vessel disease (MVD) and the prevalence of peripheral artery disease (PAD) were independent and significant positive predictors of the primary endpoint (prevalence of MVD: HR 1.68, 95% CI 1.18-2.40, P = .004; prevalence of PAD: HR 1.51, 95% CI 1.03-2.21, P = .034). In patients with histories of malignancy, no significant independent predictive factors were identified.Patients undergoing PCI with malignancy had significantly higher rates of adverse cardiovascular events but might not have the conventional prognostic factors.

The Impending Epidemic of Cardiovascular Diseases in Patients With Cancer in Japan.

Onco-cardiology, a new academic field, aims to improve the quality of life and prognosis of cancer patients and survivors with cardiovascular diseases (CVD). With the aging of the population, an epidemic of cancer with CVD is emerging in developed countries. Cancer and CVD share risk factors, pathophysiology, treatments, and preventive and rehabilitative measures. A multidisciplinary team-based approach is needed to support cancer treatment to maximize its effectiveness and minimize its cardiotoxic potential. Basic and clinical onco-cardiology are already being practiced harmoniously. However, systematization in academia and clinical practice and accumulation of evidence have just started. In this review, we present the epidemiology, common risk factors between cancer and CVD, future epidemic of CVD in patients with cancer, and the necessity for an onco-cardiological approach to managing the burden of CVD in cancer patients and survivors.

Correction to: Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study.

n the original publication, in a title of Table 2.

Future projection of cancer patients with cardiovascular disease in Japan by the year 2039: a pilot study.

BACKGROUND: The number of cancer patients in Japan is estimated to rise to 3.5 million by 2025. The disease burden may be further complicated by comorbidities caused by cardiovascular disease (CVD). Predicting the number of cancer patients with CVD can help anticipate future resource needs. METHODS: We used statistics derived from the Niigata Cancer Center CVD Study (2015) as well as population estimates from the National Cancer Center's Cancer Registry and Statistics survey of 2017 for convenience. We simply multiplied the projected number of cancer patients through the year 2039 by the CVD prevalence in 2015, with patients classified by sex, age, and cancer type to estimate the number of cancer patients with CVD. RESULTS: The total number of Japanese cancer patients with CVD was 253,000 in 2015 and is predicted to increase rapidly by 30,000 in 2020 and peak at 313,000 in 2030-2034. Men will dominate the CVD population at 2.5-fold the number of women. The growth rate of the population with both cancer and CVD will be greater than that of the cancer-only population (1.23 vs 1.18, P < 0.001), and will comprise notably high proportions of patients with prostatic, breast, and uterine cancers (1.80, 1.57, and 1.66, P < 0.001, respectively). CONCLUSION: Future cancer patients will be older and more likely to have CVD. Although men will continue to dominate this population, the increase in the number of women will be pronounced. Cancer care providers should be trained to recognize CVD and provide any necessary interventions concurrently with cancer therapy.