Collagen triple helix repeat-containing protein 1 is a novel biomarker of right ventricular involvement in pulmonary hypertension.

BACKGROUND: Pulmonary hypertension leads to right ventricular failure, which is a major determinant of prognosis. Circulating biomarkers for right ventricular function are poorly explored in pulmonary hypertension. This study aimed to clarify the significance of collagen triple helix repeat-containing protein 1 (CTHRC1) as a biomarker of right ventricular failure in pulmonary hypertension. METHODS: A monocrotaline-induced pulmonary hypertension rat model was used to evaluate right ventricular CTHRC1 expression and its relationship with fibrosis. Next, human plasma CTHRC1 levels were measured in controls (n = 20), pulmonary arterial hypertension (n = 46), and chronic thromboembolic pulmonary hypertension (CTEPH) patients (n = 64) before the first and after the final balloon pulmonary angioplasty. RESULTS: CTHRC1 expression was higher in the right ventricles of rats with monocrotaline-induced pulmonary hypertension than in those of controls. CTHRC1 was co-localized with vimentin and associated with fibrosis in the right ventricles. Plasma CTHRC1 levels were higher in human pulmonary arterial hypertension (P = 0.006) and CTEPH patients (P = 0.011) than in controls. Plasma CTHRC levels were correlated with B-type natriuretic peptide (R = 0.355, P < 0.001), tricuspid lateral annular peak systolic velocity (R = -0.213, P = 0.029), and right ventricular fractional area change (R = -0.225, P = 0.017). Finally, plasma CTHRC1 levels were decreased after the final balloon pulmonary angioplasty (P < 0.001) in CTEPH. CONCLUSIONS: CTHRC1 can be a circulating biomarker associated with right ventricular function and fibrosis in pulmonary hypertension and might reflect the therapeutic efficacy of balloon pulmonary angioplasty in CTEPH.

Heart Failure Post-Myocardial Infarction Promotes Mammary Tumor Growth Through the NGF-TRKA Pathway.

Background: Epidemiological investigations suggest that patients with heart failure have a higher incidence of cancer; however, the causal role of cardiac disease on cancer progression remains unclear. Objectives: This study aimed to investigate the impact and underlying mechanisms of myocardial infarction (MI)-induced heart failure on tumor cell growth. Methods: We generated a syngeneic mouse model by implanting mammary tumor-derived 4T1 cells into BALB/c mice with MI resulting from ligation of the left anterior descending artery. Results: Mice with MI exhibited increased tumor volume, tumor weight, and Ki67-positive proliferative cells in the tumor tissue compared with the sham-operated mice. Furthermore, RNA sequencing analysis in the tumor tissue revealed significant enrichment of pathways related to tumor progression, particularly the PI3K-AKT pathway in the MI mice. Upregulation of tropomyosin receptor kinase A (TRKA) phosphorylation, an upstream regulator of PI3K-AKT signaling, was observed in the tumor tissue of the MI mice. We also observed elevated levels of circulating nerve growth factor (NGF), a ligand of TRKA, and increased NGF expressions in the myocardium after MI. In in vitro experiments, NGF stimulation led to increased cell proliferation, as well as phosphorylation of TRKA and AKT. Notably, inhibition of TRKA by small interfering RNA or the chemical inhibitor GW441756 effectively blocked these effects. Administration of GW441756 resulted in the suppression of tumor volume and cell proliferation in the MI mice. Conclusions: Our study demonstrates that MI promotes mammary tumor growth through the NGF-TRKA pathway. Consequently, inhibiting TRKA could represent a therapeutic strategy for breast cancer patients concurrently experiencing heart failure after MI.

Prognostic significance of left atrial strain combined with left ventricular strain using cardiac magnetic resonance feature tracking in patients with heart failure with preserved ejection fraction.

We aimed to evaluate the prognostic value of left ventricular global longitudinal strain (LVGLS) and left atrial strain (LAS) obtained from magnetic resonance imaging (MRI) feature tracking in patients with heart failure with preserved ejection fraction (HFpEF). We retrospectively enrolled consecutive patients with HFpEF admitted to our hospital who underwent cardiac MRI. LVGLS and LAS were obtained from cine MRI by feature tracking. The end point was defined as a composite of all-cause death, myocardial infarction, and hospitalization due to decompensated HF. One-hundred patients with HFpEF were enrolled. Mean LVGLS and LAS were - 13.7 ± 3.7% and 22.5 ± 11.6%, respectively. During follow-up of 4.4 ± 1.9 years, 24 events occurred. Multivariate Cox proportional hazards model analysis demonstrated LAS was independently associated with adverse cardiac events. Kaplan-Meier curve analysis revealed that the patients with both LVGLS and LAS worse than the median (LVGLS ≥ - 12.2% and LAS ≤ 13.8%) had a significantly lower event-free rate compared to those with preserved strain (Log-rank P < 0.001). Simultaneous assessment of LVGLS and LAS using MRI was useful for risk stratification in the patients with HFpEF.

Predictive Value of Aortic Valve Calcium Volume Measured by Computed Tomography for Paravalvular Leakage After Transcatheter Aortic Valve Implantation.

Paravalvular leakage (PVL) is a complication of transcatheter aortic valve implantation (TAVI) for aortic stenosis, leading to an adverse prognosis. We investigated whether aortic valve calcium volume (Ca-Vol) measured by preoperative cardiac computed tomography had a predictive value for PVL after TAVI using a third-generation self-expandable valve.We retrospectively analyzed 59 consecutive patients who underwent TAVI using a third-generation self-expandable valve. We measured Ca-Vol in the aortic valve and each cusp (non-coronary cusp [NCC], right-coronary cusp [RCC], and left-coronary cusp [LCC]). We divided the patients into 2 groups: a PVL group (32.2%) and a non-PVL group (67.8%). Total Ca-Vol was significantly higher in the PVL group than in the non-PVL group (P < 0.001). Ca-Vol in each cusp was also significantly higher in the PVL group ([NCC] P < 0.001, [RCC] P = 0.001, [LCC] P < 0.001). Univariate logistic regression analysis for PVL indicated that the total and per-cusp Ca-Vols were predictors for PVL (total, odds ratio [OR] 4.0, P < 0.001; NCC, OR 12.5, P = 0.002; RCC, OR 16.0, P = 0.008; LCC, OR 44.5, P < 0.001).Receiver operating characteristic curve analysis of Ca-Vol for predicting PVL revealed the optimal cut-off values of Ca-Vol were 2.4 cm3 for the total, 0.74 cm3 for NCC, 0.73 cm3 for RCC, and 0.56 cm3 for LCC (area under the curve, 0.85, 0.79, 0.76, and 0.83, respectively).Preoperative total, NCC, RCC, and LCC calcium volumes were significant predictors for PVL after TAVI using third-generation self-expandable valves.

Calcium-Phosphorus Product Is Associated with Adverse Prognosis in Hospitalized Patients with Heart Failure and Chronic Kidney Disease.

It has been reported that high levels of calcium-phosphorus (Ca-P) product are an indicator of coronary calcification and mortality risk in patients undergoing chronic hemodialysis. In the present study, we aimed to evaluate the significance of Ca-P product to predict the prognosis of patients with heart failure (HF) and chronic kidney disease (CKD). We conducted a prospective observational study of 793 patients with decompensated HF and CKD, and measured the value of Ca-P product. The cut-off value was obtained from the survival classification and regression tree (CART) analysis to predict post-discharge all-cause mortality and/or worsening HF, and the patients were divided into 2 groups: a high group (Ca-P product > 28, n = 594) and a low group (Ca-P product ≤ 28, n = 199). We compared the patient baseline characteristics and post-discharge prognosis between the 2 groups. The age as well as the prevalence of male sex, ischemic etiology, and anemia were significantly higher in the low group than in the high group. In contrast, there was no difference in echocardiographic parameters between the 2 groups. In the Kaplan-Meier analysis (mean follow-up 1089 days), all-cause mortality and/or worsening HF event rates were higher in the low group than in the high group (log-rank P = 0.001). In the multivariable Cox proportional hazard analysis, lower Ca-P product was found to be an independent predictor of all-cause mortality and/or worsening HF (hazard ratio 0.981, P = 0.031). Lower Ca-P product predicts adverse prognosis in patients with HF and CKD.

Geriatric Nutritional Risk Index predicts bleeding event in patients with heart failure.

AIMS: We aimed to elucidate the association between malnutrition and the occurrence of bleeding events in patients with heart failure. METHODS AND RESULTS: We evaluated the nutritional status of patients with heart failure [n = 2044, median (inter-quartile range) age 69.0 (59.0-78.0) years, 1209 (59.1%) males] using the Geriatric Nutritional Risk Index (GNRI). The primary endpoint was a composite of bleeding events such as haemorrhagic stroke or gastrointestinal bleeding. According to the survival classification and regression tree analysis, the accurate cut-off point of GNRI for predicting the primary endpoint was 106.2. We divided the patients into two groups based on GNRI levels: high GNRI group (GNRI ≥ 106.2, n = 606, 29.6%) and low GNRI group (GNRI < 106.2, n = 1438, 70.4%). We compared the patients' characteristics and prognosis between the two groups. The low GNRI group was older [72.0 (63.0-79.0) vs. 63.0 (53.0-73.0) years, P < 0.001] and had a lower prevalence of male sex (56.9% vs. 64.5%, P = 0.001). There were no differences in the use of antiplatelet agents and anticoagulants between the two groups. Levels of B-type natriuretic peptide were higher [321.1 (123.3-667.4) vs. 111.6 (42.6-235.4) pg/mL, P < 0.001] and levels of haemoglobin were lower [12.4 (10.8-13.7) vs. 14.2 (12.9-15.4) g/dL, P < 0.001] in the low GNRI group. The Kaplan-Meier analysis demonstrated that bleeding event rates were higher in the low GNRI group (log-rank P < 0.001). The multivariable Cox proportional hazard analysis revealed that low GNRI (hazard ratio 1.952, 95% confidence interval 1.002-3.805, P = 0.049) was associated with bleeding events. CONCLUSIONS: Heart failure patients with poor nutritional status, determined by GNRI under 106.2, experienced high bleeding event rates. Comprehensive management is required to avoid bleeding event in those populations.

Targeting N-Myristoylation Through NMT2 Prevents Cardiac Hypertrophy and Heart Failure.

Protein diversity can increase via N-myristoylation, adding myristic acid to an N-terminal glycine residue. In a murine model of pressure overload, knockdown of cardiac N-myristoyltransferase 2 (NMT2) by adeno-associated virus 9 exacerbated cardiac dysfunction, remodeling, and failure. Click chemistry-based quantitative chemical proteomics identified substrate proteins of N-myristoylation in cardiac myocytes. N-myristoylation of MARCKS regulated angiotensin II-induced cardiac pathological hypertrophy by preventing activations of Ca2+/calmodulin-dependent protein kinase II and histone deacetylase 4 and histone acetylation. Gene transfer of NMT2 to the heart reduced cardiac dysfunction and failure, suggesting targeting N-myristoylation through NMT2 could be a potential therapeutic approach for preventing cardiac remodeling and heart failure.

Characteristics of right pulmonary vein with an epicardial connection needing additional carina ablation for isolation.

Background: This study thought to elucidate the anatomical features that can predict an epicardial connection (EC) between the right pulmonary vein (RPV) and right atrium. Methods: We retrospectively analyzed 251 consecutive patients undergoing initial radiofrequency pulmonary vein isolation. We defined EC as present when RPV could not be isolated with circumferential ablation and additional ablation for the conduction gap if needed, and RPV isolation could be achieved by ablation for the earliest activation site >10 mm inside the initial ablation line. Using computed tomography data, we evaluated the RPV bifurcation angle, and the area occupation ratio of the carina region to the RPV antrum (ARC) for predicting EC. In subjects with EC undergoing RPV activation mapping after circumferential ablation, the correlation between conduction delay and bipolar/unipolar potential voltage in the carina region was investigated. Results: There were ECs in 45 out of 251 patients (17.9%). The RPV bifurcation angle (47.7° vs. 38.8°, p < .001) and ARC (37.2% vs. 29.7%, p < .001) were significantly greater in the EC (+) group. Multivariate logistic regression analysis revealed that RPV bifurcation angle (odds ratio [OR]: 1.994, p = .002) and ARC (OR: 3.490, p = .013) were independent predictors of EC. In nine patients with EC undergoing carina region mapping, the unipolar potential voltage was correlated with conduction delay in RPV with EC (R = -0.401, p < .001). Conclusion: Anatomical features suggesting a wider RPV carina region could predict the presence of EC, and potential with high voltage could be helpful for detecting EC connection sites.

Perioperative immunosuppressive therapy and coronary ostial angioplasty for unstable angina with Takayasu arteritis.

A young female patient with Takayasu arteritis presented with unstable angina due to bilateral coronary artery involvement. Steroid pulse therapy and subsequent prednisolone administration were started, but early coronary artery bypass grafting was required because of the multiple angina attacks at rest, with a prednisolone dose of 22.5 mg (0.45 mg/kg/day). Since the left internal thoracic artery which was grafted to the left anterior descending artery resulted in graft failure a few days after the surgery, the immunosuppressive therapy was intensified with the addition of tocilizumab and methotrexate. After controlling the disease activity, coronary ostial angioplasty using external iliac artery grafts was successfully performed, with a prednisolone dose of 15 mg (0.3 mg/kg/day). Ten months after the operation, the patient has been free from chest pain. The present case demonstrated the importance of adequate preoperative immunosuppressive therapy, even when early surgical intervention is required. Learning objective: There are no established treatment regimens for immunosuppressive management in cases of Takayasu arteritis (TAK) requiring immediate surgical intervention. Even when early surgery is required, it is important to reduce disease activity with appropriate preoperative immunosuppressive therapy using steroids in addition to biological agents, such as tocilizumab. Coronary ostial angioplasty is the effective surgical revascularization technique for TAK with coronary artery involvement.

A Case of Giant Goiter Associated with Airway Stenosis Caused by Long-Term Intravenous Epoprostenol Therapy for Idiopathic Pulmonary Arterial Hypertension.

Idiopathic pulmonary arterial hypertension is a progressive and life-threatening disease with pulmonary vasculature remodeling, leading to right-sided heart failure. Epoprostenol (prostaglandin I2) is highly recommended for patients with severe pulmonary arterial hypertension (PAH) categorized by the World Health Organization as functional class III or IV. It has been reported that prostaglandin I2 analogs can cause thyroid gland swelling and abnormal thyroid function. A 34-year-old woman was diagnosed with idiopathic pulmonary arterial hypertension and started receiving continuous intravenous epoprostenol. Three years after starting epoprostenol, she began complaining of neck swelling and was diagnosed with Graves' disease. The patient's thyroid function was controlled by thiamazole and levothyroxine; nevertheless, her thyroid gland enlargement worsened as the epoprostenol dose was titrated. After 20 years, she developed respiratory failure with a giant goiter leading to airway stenosis, and she passed away. The pathological autopsy confirmed a massive goiter associated with hyperthyroidism and airway stenosis. We experienced a case of idiopathic pulmonary hypertension with a giant goiter and airway stenosis after long-term intravenous epoprostenol therapy.

Acute coronary syndrome with severe coronary calcification in a patient with pseudo-pseudohypoparathyroidism.

A 40-year-old female with a history of steroid therapy for juvenile rheumatoid arthritis was brought to our hospital because of chest pain. A diagnosis of non-ST elevation myocardial infarction was made, and emergency coronary angiography revealed stenotic lesions with severe calcification in the left anterior descending artery and the right coronary artery. Percutaneous coronary intervention with rotational atherectomy followed by a drug-coated balloon was performed to the lesion in the left anterior descending artery. The patient had characteristic physical findings including short stature, a round face, and 'knuckle-dimple sign'. Whole-body computed tomography showed many ectopic calcifications, indicating Albright's hereditary osteodystrophy. Ellsworth-Howard test revealed that urinary cyclic adenosine monophosphate response was positive, thus a diagnosis of pseudo-pseudohypoparathyroidism (PPHP) was made. Here, we describe a rare case of PPHP complicated by acute coronary syndrome with severely calcified coronary arteries. Learning objective: Pseudo-pseudohypoparathyroidism (PPHP) presents with several characteristic physical findings and ectopic calcifications. Since PPHP involves coronary artery calcification as in the present case, it may be considered as a cause of coronary artery disease.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension:its history and development, and regional medical cooperation in Fukushima.

Chronic thromboembolic pulmonary hypertension (CTEPH) is designated as an intractable disease by the Ministry of Health, Labour and Welfare of Japan, and has an extremely poor prognosis if untreated. Surgical pulmonary endarterectomy is the curative treatment for cases in which the organized thrombi are located in the central part of the pulmonary artery, but there had been no effective treatment for cases in which the thrombi are located in the peripheral part of the pulmonary artery. Recently, balloon pulmonary angioplasty (BPA), a transcatheter procedure to dilate stenotic or occluded lesions in the peripheral pulmonary artery, has been rapidly developed. Although BPA was once a globally abandoned procedure due to hemorrhagic complications, Japanese experts have improved the technique, and its safety and efficacy have been enhanced. As a result, BPA is now being reevaluated worldwide. This review describes the history and development of BPA in the treatment of CTEPH, as well as the status of this treatment in Fukushima Prefecture.

Impaired Repopulating Ability of Uhrf2-/- Hematopoietic Progenitor Cells in Mice.

UHRF proteins catalyze the ubiquitination of target proteins and are involved in regulating gene expression. Some studies reported a reduced expression of UHRF2 in acute leukemia cells, but the role of UHRF2 in hematopoiesis remains unknown. Here, we generated Uhrf2-/- mice to clarify the role of UHRF2 deletion in hematopoiesis. Compared to Uhrf2+/+ mice, Uhrf2-/- mice showed no differences in complete blood counts, as well as bone marrow (BM) findings and spleen weights. Proportions of cells in progenitor fractions in BM were comparable between Uhrf2+/+ mice and Uhrf2-/- mice. However, in competitive repopulation assays with BM transplants (BMT), the proportions of Uhrf2-/- cells were decreased relative to Uhrf2+/+ cells in all lineages. After the second BMT, Uhrf2-/- neutrophils were few, while 20-30% of Uhrf2-/- T cells and B cells were still detected. RNA sequencing showed downregulation of some genes associated with stem-cell function in Uhrf2-/- hematopoietic stem/progenitor cells (HSPCs). Interestingly, trimethylated histone H3 lysine 9 was increased in Uhrf2-/- HSPCs in a cleavage under targets and tagmentation assay. While UHRF2 deletion did not cause hematologic malignancy or confer a growth advantage of HSPCs, our results suggest that UHRF2 may play a role in the regulation of hematopoiesis.

The Prognostic Implications of Living Alone on Long-Term Mortality in Patients with Chronic Coronary Syndrome after Percutaneous Coronary Intervention.

Living alone is associated with increased cardiac events and mortality in patients with acute myocardial infarction. However, the prognostic impact of living alone with chronic coronary syndrome (CCS) still remains unclear. In the present study, we examined the relationship between living alone and long-term mortality in patients with CCS who underwent percutaneous coronary intervention (PCI).Consecutive 830 patients with CCS who underwent PCI were enrolled and divided into 2 groups according to whether or not they were living alone at the time of admission (living alone group and non-living alone group). We compared the clinical characteristics between the 2 groups and followed up cardiac mortality. The living alone group was younger compared with the non-living alone group (67.5 versus 70.7 years old, P = 0.017). The prevalence of comorbidities, including coronary risk factors, atrial fibrillation, heart failure, stroke, peripheral artery disease, coronary lesion characteristics, laboratory data, and left ventricular ejection fraction, were comparable between the 2 groups. During the follow-up period (median 1,622 days), 52 cardiac deaths occurred. In the Kaplan-Meier analysis, cardiac mortality was significantly higher in the living alone group than in the non-living alone group (24% versus 11%, P = 0.008). In the multivariable Cox proportional hazard analyses after adjusting for possible confounding factors, living alone was an independent predictor of cardiac mortality (hazard ratio, 2.426, 95% confidence interval 1.225-4.804, P = 0.011).Among CCS patients who underwent PCI, living alone was associated with high long-term cardiac mortality.

Utility of short-time electrocardiogram to assess risk for atrial arrhythmia recurrence: Impact of atrial premature beat occurrence 1 day after pulmonary vein isolation for atrial fibrillation.

INTRODUCTION: Atrial premature beats (APBs) are the trigger for atrial fibrillation (AF). We sought to investigate the clinical significance of APB occurrence 1 day after pulmonary vein isolation (PVI) for AF using a short-time electrocardiogram. METHODS: A total of 206 patients undergoing PVI for paroxysmal AF were included. Electrocardiogram recording for 100 consecutive beats was performed 1 day after PVI. The patients were divided into two groups: those with reproducible APBs (≥1 beat) during reassessment (APB group, n = 49) or those without (non-APB group, n = 157). Late recurrence was defined as atrial tachyarrhythmia recurrence 3-12 months after PVI. The impact of APB occurrence on outcomes was investigated. RESULTS: Late recurrence occurred in 19 patients (9.2%). The presence of low-voltage areas, left atrial volume, and recurrence rate were higher in the APB group than in the non-APB group. In the APB group, the patients with recurrence had lower prematurity index (PI, coupling interval of APB/previous cycle length) compared to those without. Receiver-operating characteristic analysis revealed PI (<59.3) to be a predictive factor of recurrence (area under the curve: 0.733). The study subjects were then reclassified into three groups according to the absence of APB occurrence (n = 157), presence thereof with PI ≥ 59.3 (n = 33), and presence with PI < 59.3 (n = 16). The multivariate Cox models revealed that APB with PI < 59.3 was an independent predictor for recurrence (hazard ratio, 8.735; p < 0.001). CONCLUSION: A short-time electrocardiogram enables risk assessment for arrhythmia recurrence, and APB with low PI 1 day after PVI is a powerful predictor.

Hepatic Venous Stasis Index Reflects Hepatic Congestion and Predicts Adverse Outcomes in Patients With Heart Failure.

Background It has been reported that the hepatic vein waveforms determined by abdominal ultrasonography can assess hepatic congestion in patients with heart failure (HF). However, the parameter that quantifies hepatic vein waveforms has not been established. We suggest the hepatic venous stasis index (HVSI) as the novel indicator to evaluate hepatic congestion quantitatively. To examine the clinical significance of HVSI in patients with HF, we aimed to clarify the associations of HVSI with the parameters of cardiac function and right heart catheterization, as well as that with prognosis, in patients with HF. Methods and Results We performed abdominal ultrasonography, echocardiography, and right heart catheterization in patients with HF (n=513). The patients were divided into 3 groups based on HVSI as follows: HVSI 0 (HVSI=0, n=253), low HVSI (HVSI 0.01-0.20, n=132), and high HVSI (HVSI>0.20, n=128). We examined the associations of HVSI with parameters of cardiac function and right heart catheterization and followed up for cardiac events defined as cardiac death or worsening HF. There was a significant increase in level of B-type natriuretic peptide, inferior vena cava diameter, and mean right atrial pressure with increasing HVSI. During the follow-up period, cardiac events occurred in 87 patients. In the Kaplan-Meier analysis, cardiac event rate increased across increasing HVSI (log-rank, P=0.002). Conclusions HVSI assessed by abdominal ultrasonography reflects hepatic congestion and right-sided HF and is associated with adverse prognosis in patients with HF.

Prognostic Role of Circulating LTBP-2 in Patients With Dilated Cardiomyopathy: A Novel Biomarker Reflecting Extracellular Matrix LTBP-2 Accumulation.

BACKGROUND: Dilated cardiomyopathy (DCM) is a life-threatening disease related to heart failure. Extracellular matrix proteins have an important role in the pathogenesis of DCM. Latent transforming growth factor beta-binding protein 2 (LTBP-2), a type of extracellular matrix protein, has not been investigated in DCM. METHODS: First, we compared plasma LTBP-2 levels in 131 patients with DCM who underwent endomyocardial biopsy and 44 controls who were matched for age and sex and had no cardiac abnormalities. Next, we performed immunohistochemistry for LTBP-2 on endomyocardial biopsy specimens and followed the DCM patients for ventricular assist device (VAD) implantation, cardiac death, and all-cause death. RESULTS: Patients with DCM had elevated plasma LTBP-2 levels compared with controls (P < 0.001). Plasma LTBP-2 levels were positively correlated with LTBP-2-positive fraction in the myocardium from the biopsy specimen. When patients with DCM were divided into 2 groups according to LTBP-2 levels, Kaplan-Meier analysis demonstrated that patients with high plasma LTBP-2 were associated with increased incidences of cardiac death/VAD and all-cause death/VAD. In addition, patients with high myocardial LTBP-2-positive fractions were associated with increased incidences of these adverse outcomes. Multivariable Cox proportional hazard analysis showed that plasma LTBP-2 and myocardial LTBP-2-positive fraction were independently associated with adverse outcomes. CONCLUSIONS: Circulating LTBP-2 can serve as a biomarker to predict adverse outcomes, reflecting extracellular matrix LTBP-2 accumulation in the myocardium in DCM.

Comprehensive assessment of molecular function, tissue characterization, and hemodynamic performance by non-invasive hybrid imaging: Potential role of cardiac PETMR.

Noninvasive cardiovascular imaging plays a key role in diagnosis and patient management including monitoring treatment efficacy. The usefulness of noninvasive cardiovascular imaging has been extensively studied and shown to have high diagnostic reliability and prognostic significance, while the nondiagnostic results frequently encountered with single imaging modality require complementary or alternative imaging techniques. Hybrid cardiac imaging was initially introduced to integrate anatomical and functional information to enhance the diagnostic performance, and lately employed as a strategy for comprehensive assessment of the underlying pathophysiology of diseases. More recently, the utility of computed tomography has grown in diversity, and emerged from being an exploratory technique allowing functional measurement such as stress dynamic perfusion. Cardiac magnetic resonance imaging (CMR) is widely accepted as a robust tool for evaluation of cardiac function, fibrosis, and edema, yielding high spatial resolution and soft-tissue contrast. However, the use of intravenous contrast materials is typically required for accurate diagnosis with these imaging modalities, despite the associated risk of renal toxicity. Nuclear cardiology, established as a molecular imaging technique, has advantages in visualization of the disease-specific biological process at cellular level using numerous probes without requiring contrast materials. Various imaging modalities should be appropriately used sequentially to assess concomitant disease and the progression over time. Therefore, simultaneous evaluation combining high spatial resolution and disease-specific imaging probe is a useful approach to identify the regional activity and the stage of the disease. Given the recent advance and potential of multiparametric CMR and novel nuclide tracers, hybrid positron emission tomography MR is becoming an ideal tool for disease-specific imaging.

Impact of bleeding event for new cancer diagnosis in patients with antiplatelet therapy after percutaneous coronary intervention.

BACKGROUND: Bleeding is a frequent event in coronary artery disease (CAD) patients treated with antiplatelet therapy after percutaneous coronary intervention (PCI). The impact of bleeding in CAD patients with antiplatelet therapy for cancer diagnosis remains unclear. METHODS AND RESULTS: Consecutive 1565 CAD patients treated with antiplatelet therapy after PCI, without anticoagulation therapy, were enrolled. We aimed to investigate the relationships between bleeding events and the incidence of new cancer diagnosis. Among 1565 patients, 178 (11.3 %) experienced any bleeding events defined as Bleeding Academic Research Consortium (BARC) type 1, 2, 3, or 5 bleeding and 75 (4.7 %) experienced minor bleeding events defined as BARC 1 or 2 bleeding, and 116 (7.4 %) were diagnosed with new cancer during a mean follow-up period of 1528 days. Among 178 patients with any bleeding and 75 patients with minor bleeding events, 20 (11.2 %) and 13 (17.3 %) were subsequently diagnosed with new cancer, respectively. The proportion of new cancer diagnosis was higher in patients with any bleeding and minor bleeding events than in those without bleeding events (3.3 versus 1.6 per 100 person-years, p < 0.001 and 6.2 versus 1.6 per 100 person-years, p < 0.001, respectively). Multivariate Cox proportional hazard analysis revealed that any bleeding and minor bleeding events were associated with higher rate of new cancer diagnosis [hazard ratio (HR) 2.27, p = 0.003 and HR 3.93, p < 0.001, respectively]. Additionally, any gastrointestinal bleeding and minor gastrointestinal bleeding events were associated with higher rate of new gastrointestinal cancer diagnosis (HR 8.67, p < 0.001 and HR 12.74, p < 0.001, respectively). CONCLUSIONS: In CAD patients with antiplatelet therapy after PCI, any bleeding and minor bleeding events were associated with subsequent new cancer diagnosis. Even minor bleeding events may be the first manifestation of underlying cancer during antiplatelet therapy after PCI.