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Although anti-cancer therapy-induced cardiotoxicity is known, until now it lacks a reliable risk predictive model of the subsequent cardiotoxicity in breast cancer patients receiving anthracycline therapy. An artificial intelligence (AI) with a machine learning approach has yet to be applied in cardio-oncology. Herein, we aimed to establish a predictive model for differentiating patients at a high risk of developing cardiotoxicity, including cancer therapy-related cardiac dysfunction (CTRCD) and symptomatic heart failure with reduced ejection fraction. This prospective single-center study enrolled patients with newly diagnosed breast cancer who were preparing for anthracycline therapy from 2014 to 2018. We randomized the patients into a 70%/30% split group for ML model training and testing. We used 15 variables, including clinical, chemotherapy, and echocardiographic parameters, to construct a random forest model to predict CTRCD and heart failure with a reduced ejection fraction (HFrEF) during the 3-year follow-up period (median, 30 months). Comparisons of the predictive accuracies among the random forest, logistic regression, support-vector clustering (SVC), LightGBM, K-nearest neighbor (KNN), and multilayer perceptron (MLP) models were also performed. Notably, predicting CTRCD using the MLP model showed the best accuracy compared with the logistic regression, random forest, SVC, LightGBM, and KNN models. The areas under the curves (AUC) of MLP achieved 0.66 with the sensitivity and specificity as 0.86 and 0.53, respectively. Notably, among the features, the use of trastuzumab, hypertension, and anthracycline dose were the major determinants for the development of CTRCD in the logistic regression. Similarly, MLP, logistic regression, and SVM also showed higher AUCs for predicting the development of HFrEF. We also validated the AI prediction model with an additional set of patients developing HFrEF, and MLP presented an AUC of 0.81. Collectively, an AI prediction model is promising for facilitating physicians to predict CTRCD and HFrEF in breast cancer patients receiving anthracycline therapy. Further studies are warranted to evaluate its impact in clinical practice.

Doxorubicin (Dox), an effective therapy in different types of cancer, is known to exhibit cardiotoxic effects. Despite previous studies indicating the benefits of dapagliflozin (DAPA) in patients experiencing heart failure, it remains uncertain whether DAPA exerts a protective effect on Dox-induced cardiac dysfunction. Signal transducer and activator of transcription 3 (STAT3) participates in various mechanisms of cardioprotection. Herein, we aimed to investigate the effects of DAPA on Dox-induced cardiotoxicity and the role of STAT3. Sprague-Dawley rats were pretreated with oral DAPA for 6 weeks followed by Dox for 4 weeks. Sequential echocardiography was applied to assess cardiac function. For in vitro analysis, cardiomyocytes were treated with 10 μM DAPA and subsequently exposed to 1 μM Dox. The expression of reactive oxygen species- and apoptosis-related proteins was measured. Using STAT3 siRNA, we further examined the effects of STAT3 effect on DAPA-associated protection against Dox-induced apoptosis. In rats treated with Dox, DAPA significantly reduced cardiac fibrosis and improved cardiac function and hemodynamics. Additionally, DAPA effectively inhibited Dox-induced apoptosis and reactive oxygen species (ROS) in cardiomyocytes. Mechanistically, we showed that DAPA decreased cardiac expression of Bax and cleaved caspase 3 but increased Bcl-2 expression. DAPA also significantly rescued Dox-suppressed STAT3 expression. Conversely, knocking down STAT3 in cardiomyocytes reversed the DAPA-related protective effects on Dox-induced cell apoptosis and ROS. Collectively, our findings indicate that DAPA could be useful for preventing Dox-induced cardiotoxicity by restoring STAT3.

Androgen deprivation therapy (ADT) includes bilateral orchiectomy or long-acting gonadotropin-releasing hormone (GnRH) agonists/antagonists. It remains controversial with respect to ADT associated cardiovascular outcomes. Hereby, we compared the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with prostate cancer receiving either surgical castration or GnRH therapies.Using the Taiwan Cancer Registry and Taiwan's National Health Insurance Research Database, we identified 8,413 patients receiving GnRH therapies compared with 694 receiving surgical castration from 2008 to 2017. The median followup duration was 3 years.The crude incidences of 3-year mortality and MACCEs were 19.90% vs 26.51% and 8.23% vs 8.65% in patients receiving GnRH therapies or surgical castration, respectively. After adjusting for age, cancer stage and comorbidities, despite no significant differences in MACCEs between groups there was a slight increase in the incidence of acute myocardial infarction (AMI) in patients receiving surgical castration compared with those receiving GnRH therapies. The mortality adjusted hazard ratios of MACCEs and AMI among patients receiving surgical castration were 1.11- and 1.8-fold higher than those receiving GnRH therapies. Notably, in subgroup analysis regarding cancer stage, patients with cancer stage IV showed the most significantly increasing risk of AMI in those receiving surgical castration compared with GnRH therapies.Collectively, we indicated an increased risk of AMI in patients with prostate cancer, especially in patients receiving surgical castration rather than those receiving GnRH therapies. Our findings highlight concerns regarding the cardiac safety of surgical castration compared with GnRH therapies.

Gonadotropin-releasing hormone (GnRH) therapy has been known to increase risks of major adverse cardiovascular and cerebrovascular events (MACCEs). Herein, we aim to estimate whether regular use of aspirin attenuates risks of MACCEs in prostate cancer patients receiving GnRHs. Using Taiwanese National Health Insurance Research Database (NHIRD), we identified 7719 patients diagnosed with prostate cancer who were either aspirin-naïve, received irregular or regular aspirin from 2008 to 2015. Through a multivariable logistic regression model, we investigated the impact of aspirin on MACCEs. Compared with nonusers and irregular users, most patients receiving regular aspirin were older and had more comorbidities. The crude incidence of one-year MACCEs was lowest in aspirin nonusers but highest in irregular users of aspirin compared with regular users of aspirin (2.65% vs. 4.41% vs. 2.85%, p=0.0099). After adjusting for age, cancer stage and comorbidities, irregular aspirin users had a higher risk of one-year MACCEs (adjusted OR: 1.33; 95% CI: 0.93-1.90, p=0.1139) than aspirin nonusers, but conversely, there was a trend of reducing the risk of MACCEs among those who received regular aspirin (adjusted OR: 0.79; 95% CI: 0.44-1.42, p=0.4256). In the subgroup analysis, there were age- and cancer stage-independent higher risks of MACCEs in patients who took aspirin irregularly compared to those in patients who did not take aspirin. The risks were attenuated in patients receiving regular aspirin. Collectively, regular use of aspirin presented a trend of reducing risks of MACCEs in prostate cancer patients receiving GnRHs. However, irregular use of aspirin diminished the benefits.

Mitral regurgitation (MR), the disruption of the mitral valve, contributes to heart failure (HF). Under conditions of volume overload, excess mineralocorticoids promote cardiac fibrosis. The mineralocorticoid receptor antagonist spironolactone is a potassium-sparing diuretic and a guideline-recommended therapy for HF, but whether it can ameliorate degenerative MR remains unknown. Herein, we investigate the efficacy of spironolactone in improving cardiac remodeling in MR-induced HF compared with that of a loop diuretic, furosemide. Using a novel and mini-invasive technique, we established a rat model of MR. We treated the rats with spironolactone or furosemide for twelve weeks. The levels of cardiac fibrosis, apoptosis, and stress-associated proteins were then measured. In parallel, we compared the cardiac remodeling of 165 patients with degenerative MR receiving either spironolactone or furosemide. Echocardiography was performed at baseline and at six months. In MR rats treated with spironolactone, left ventricular function—especially when strained—and the pressure volume relationship significantly improved compared to those of rats treated with furosemide. Spironolactone treatment demonstrated significant attenuation of cardiac fibrosis and apoptosis in left ventricular tissue compared to furosemide. Further, spironolactone suppressed the expression of apoptosis-, NADPH oxidase 4 (NOX4)- and inducible nitric oxide synthase (iNOS)-associated proteins. Similarly, compared with MR patients receiving furosemide those prescribed spironolactone demonstrated a trend toward reduction in MR severity and showed improvement in left ventricular function. Collectively, MR-induced cardiovascular dysfunction, including fibrosis and apoptosis, was effectively attenuated by spironolactone treatment. Our findings suggest a potential therapeutic option for degenerative MR-induced HF.

How renal function influences post-acute myocardial infarction (AMI) cardiac remodeling and outcomes remains unclear. This study evaluated the impact of levels of renal impairment on drug therapy, echocardiographic parameters, and outcomes in patients with AMI undergoing percutaneous coronary intervention (PCI). A total of 611 patients diagnosed with AMI underwent successful PCI, and two echocardiographic examinations were performed within 1 year after AMI. Patients were categorized according to Group 1: severely impaired estimated glomerular filtration rate (eGFR)

Aortic stenosis (AS) is the most prevalent valvular disease in the elderly population and the prevalence of atrial fibrillation (AF) increases in the elderly population. Transcatheter aortic valve replacement (TAVR) becomes an important treatment for patients with AS at high surgical risk. This metanalysis aimed to compare the efficacy and safety of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) in patients with AF undergoing TAVR. We searched the different databases for articles published before January 31, 2022. In total, 7 studies including 25,255 patients were analyzed. Data on demographics, comorbidities, CHA2DS2-VASc score, Society of Thoracic Surgeons (STS) score, and incidences of all-cause mortality, major bleeding, intracranial hemorrhage (ICH), stroke, and thromboembolic events were obtained and analyzed. The VKA group had a lower CHA2DS2-VASc score (3.2 ± 1.2 vs 3.3 ± 1.2; P

Cancer patients with diabetes have an increasing risk of Dox-induced cardiotoxicity. Despite previous studies reporting benefits of dapagliflozin on the cardiovascular system, it remains unknown whether dapagliflozin has a cardioprotective effect in cancer patients with diabetes. We aimed to investigate the potential of dapagliflozin for preventing doxorubicin (Dox)-induced cardiotoxicity. Using Taiwan National Health Insurance Database, the incidence of heart failure of cancer patients with or without diabetes was investigated. Streptozotocin (STZ)-induced diabetic rats were pretreated with oral dapagliflozin for 6 weeks followed by Dox for 4 weeks via intraperitoneal injection. Sequential echocardiography was applied to assess cardiac function. For in vitro analysis, cardiomyocytes cultured in high glucose were treated with dapagliflozin at 10 μM and subsequently exposed to Dox at 1 μM. Apoptosis and endoplasmic reticulum (ER) stress-related protein expression were measured. Among the studied patients, those with diabetes had a higher risk of major adverse cardiovascular events including the development of heart failure. In diabetic rats, dapagliflozin reduced cardiac fibrosis and significantly improved cardiac function. Dapagliflozin effectively inhibited Dox-induced apoptosis and reactive oxygen species in cardiomyocytes under high glucose. Mechanistically, we showed that dapagliflozin decreased the cardiac expression of Bax and cleaved caspase 3 but increased Bcl-2. Dapagliflozin also significantly reduced ER stress-associated proteins including GRP78, PERK, eIF-2α, ATF-4, and CHOP. Our study revealed for the first time that dapagliflozin mitigated Dox-induced cardiomyocyte apoptosis in diabetes. These results indicate that dapagliflozin could be useful for preventing cardiotoxicity in diabetic cancer patients receiving Dox treatment.

Dapagliflozin (DAPA), a sodium–glucose cotransporter 2 inhibitor, is approved for treatments of patients with diabetes. The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial disclosed DAPA’s benefits in symptomatic heart failure, but the underlying mechanism remains largely unknown. In this longitudinal and prospective study, we investigated changes of left ventricular functions including speckle tracking in patients with diabetes who were free from symptomatic heart failure post–DAPA treatment. Using a rat model with streptozotocin-induced diabetes, we measured the effects of DAPA on myocardial function. In patients with diabetes, following 6 months of DAPA treatment, despite no significant changes in left ventricular ejection fraction, the diastolic function and longitudinal strain improved. Likewise, compared with control, the diabetic rat heart developed pronounced fibrosis and a decline in strain and overall hemodynamics, all of which were mitigated by DAPA treatment. In contrast, despite insulin exerting a glucose-lowering effect, it failed to improve myocardial function and fibrosis. In our in vitro study, under high glucose cardiomyocytes showed significant activations of apoptosis, reactive oxygen species, and endoplasmic reticulum (ER) stress–associated proteins, which were attenuated by the coincubation of DAPA. Mechanistically, DAPA suppressed ER stress, reduced myocardial fibrosis, and improved overall function. The results can lead to further improvement in management of left ventricular function in patients with diabetes.

Although androgen deprivation therapy (ADT) has been proposed to be associated with a higher risk of venous thromboembolisms (VTEs), whether gonadotropin-releasing hormones (GnRHs), such as both agonists and antagonists, are also associated with VTEs remain unclear. Using the Taiwan Cancer Registry (TCR) linked with the National Health Insurance Research Database, we identified patients diagnosed with prostate cancer from 2008 to 2015. Patients who received GnRH were 1:1 propensity score matched with non-GnRH users by age and cancer stage at diagnosis and clinical stage. Cox regression analysis was applied to estimate the incidences of VTEs with death as a competing event at the 5-year follow-up. The VTE incidence among GnRH users was 1.13% compared with 0.98% among non-users. After adjusting with potential confounding factors, the risk of VTEs showed borderline statistical significance among GnRH users and non-users. Notably, in the subgroup analysis among patients receiving GnRH therapy, those younger than 70 years old or at an earlier stage (stage I/II) were at a higher risk of VTEs. Different from previous studies, our findings highlighted critical concerns regarding the cardiac safety of GnRH therapies in prostate cancer patients at a relatively younger age or at an earlier stage.

Young and aging hearts undergo different remodeling post pressure overload, but the regulator that determines responses to pressure overload at different ages remains unknown. With an angiotensin II (Ang II)-induced hypertensive model, miR-21 knockout mice (miR-21sup-/-/sup) were observed regarding the effects of miR-21 on hypertension-induced cardiac remodeling in young (12 week-old) and old (50 week-old) mice. Although the aged heart represented a more significant hypertrophy and was associated with a higher expression of miR-21, Ang II-induced cardiac hypertrophy was attenuated in miR-21sup-/-/supmice. Upon results of cardiac-specific arrays in miR-21-overexpressing cardiomyocytes, we found a significant downregulation of S100a8. In bothiin vitro/iandiin vivo/imodels, miR-21/S100a8/NF-κB/NFAT pathway was observed to be associated with pressure overload-induced hypertrophic remodeling in aged hearts. To further investigate whether circulating miR-21 could be a biomarker reflecting the aged associated cardiac remodeling, we prospectively collected clinical and echocardiographic information of patients at young (lt;65 y/o) and old ages (≥65 y/o) with and without hypertension. Among 108 patients, aged subjects presented with a significantly higher expression of circulating miR-21, which was positively correlated with left ventricular wall thickness. Collectively, miR-21 was associated with a prominently hypertrophic response in aged hearts under pressure overload. Further studies should focus on therapeutic potentials of miR-21.

With an increasing prevalence, peripheral arterial disease (PAD), cause by atherosclerosis is a new threat to public health beyond coronary artery disease and involves aberrant vascular endothelial cell proliferation and angiogenesis. The degree of vascular remodeling is influenced by the processes described. MicroRNA-21 (miR-21) has been found to play a critical role in cellular functions, including angiogenesis. Nevertheless, the effect of miR-21 on endothelial cells in response to hypoxia is largely unknown. Using wild-type C57BL/6J and miR-21–/– mice, we compared the capability of angiogenesis in response to hindlimb hypoxic/ischemia. In an in vitro study, we further studied whether overexpression of miR-21 mitigates hypoxia-induced apoptosis and impaired angiogenesis. Also, we prospectively collected the sera of patients with limb ischemia and followed the clinical information, including major adverse limb events (MALEs). Using laser Doppler perfusion imaging and CD31 staining, compared with miR-21–/– mice, wild-type mice expressed a significantly higher capability of angiogenesis and less apoptosis following 28 days of hindlimb hypoxic/ischemic surgery. In our in vitro study, after 24 h of hypoxia, proliferation, migration, and tube formation were significantly impaired in cells treated with the miR-21 inhibitor but rescued by the miR-21 mimic. Mechanistically, by suppressing PTEN/PI3K/AKT, miR-21 promoted angiogenesis and suppressed apoptosis in endothelial cells post hypoxia. In patients with limb ischemia, the high expression of circulating miR-21 was associated with less subsequent MALE. Collectively, miR-21 could be a biomarker associated with the endogenous ability of angiogenesis and reflect subsequent MALE in patients. Additionally, abolishing miR-21 impairs angiogenesis and promotes apoptosis post limb ischemia. Further studies are required to elucidate the clinical applications of miR-21.

BACKGROUND: Despite the increasing prevalence of therapies utilizing immune checkpoint inhibitors (ICIs), the associated cardiovascular complications have been poorly reported. Given the fatality of ICI-related complications, especially myocarditis, optimal risk stratification to predict major adverse cardio- and cerebrovascular events (MACCEs) in patients receiving ICIs is mandatory. METHODS: We collected clinical data from patients receiving ICIs, and the primary outcomes were MACCEs, including myocarditis, heart failure, and ischemic stroke. Other systemic immune responses relating to ICIs were also recorded. The median follow-up duration was 3 years. RESULTS: Among 580 patients, the incidence of MACCEs was 3.9%. Older patients, male patients, and patients with lung cancer, liver cirrhosis, or diabetes had higher risks of MACCEs. There was no significant difference between the use of PD-1/PD-L1 inhibitors or CTLA inhibitors in terms of developing cardiovascular toxicities. The development of ICI-related MACCEs was associated with worse survival. Notably, after re-review by specialists, three patients eventually diagnosed with ICI-related myocarditis had not previously been identified. Only one was treated with pulse steroids, and none survived. The most common concomitant extracardiac immune-related adverse events were myositis/dermatitis, endocrine toxicity and hepatitis. CONCLUSIONS: Collectively, ICIs may lead to severe cardiovascular toxicities and require more attention. Early identification, proper diagnosis, and prompt treatment are pivotal for improving survival.

BackgroundMitral regurgitation (MR) is a major contributor for heart failure (HF) and atrial fibrillation. Despite the advancement of MR surgeries, an effective medical therapy to mitigate MR progression is lacking. Sodium glucose cotransporter 2 inhibitors, a new class of antidiabetic drugs, has shown measurable benefits in reduction of HF hospitalization and cardiovascular mortality but the mechanism is unclear. We hypothesized that dapagliflozin (DAPA), a sodium glucose cotransporter 2 inhibitor, can improve cardiac hemodynamics in MR‐induced HF.Methods and ResultsUsing a novel, mini‐invasive technique, we established a MR model in rats, in which MR induced left heart dilatation and functional decline. Half of the rats were randomized to be administered with DAPA at 10 mg/kg per day for 6 weeks. After evaluation of electrocardiography and echocardiography, hemodynamic studies were performed, followed by postmortem tissue analyses. Results showed that DAPA partially rescued MR‐induced impairment including partial restoration of left ventricular ejection fraction and end‐systolic pressure volume relationship. Despite no significant changes in electrocardiography at rest, rats treated with DAPA exhibited lower inducibility and decreased duration of pacing‐induced atrial fibrillation. DAPA also significantly attenuated cardiac fibrosis, cardiac expression of apoptosis, and endoplasmic reticulum stress‐associated proteins.ConclusionsDAPA was able to suppress cardiac fibrosis and endoplasmic reticulum stress and improve hemodynamics in an MR‐induced HF rat model. The demonstrated DAPA effect on the heart and its association with key molecular contributors in eliciting its cardio‐protective function, provides a plausible point of DAPA as a potential strategy for MR‐induced HF.

Cancer patients with diabetes have an increasing risk of Dox-induced cardiotoxicity. Despite previous studies reporting benefits of dapagliflozin on the cardiovascular system, it remains unknown whether dapagliflozin has a cardioprotective effect in cancer patients with diabetes. We aimed to investigate the potential of dapagliflozin for preventing doxorubicin (Dox)-induced cardiotoxicity. Using Taiwan National Health Insurance Database, the incidence of heart failure of cancer patients with or without diabetes was investigated. Streptozotocin (STZ)-induced diabetic rats were pretreated with oral dapagliflozin for 6 weeks followed by Dox for 4 weeks via intraperitoneal injection. Sequential echocardiography was applied to assess cardiac function. For in vitro analysis, cardiomyocytes cultured in high glucose were treated with dapagliflozin at 10 μM and subsequently exposed to Dox at 1 μM. Apoptosis and endoplasmic reticulum (ER) stress-related protein expression were measured. Among the studied patients, those with diabetes had a higher risk of major adverse cardiovascular events including the development of heart failure. In diabetic rats, dapagliflozin reduced cardiac fibrosis and significantly improved cardiac function. Dapagliflozin effectively inhibited Dox-induced apoptosis and reactive oxygen species in cardiomyocytes under high glucose. Mechanistically, we showed that dapagliflozin decreased the cardiac expression of Bax and cleaved caspase 3 but increased Bcl-2. Dapagliflozin also significantly reduced ER stress-associated proteins including GRP78, PERK, eIF-2α, ATF-4, and CHOP. Our study revealed for the first time that dapagliflozin mitigated Dox-induced cardiomyocyte apoptosis in diabetes. These results indicate that dapagliflozin could be useful for preventing cardiotoxicity in diabetic cancer patients receiving Dox treatment.

Background: Cancer patients with diabetes have an increasing risk of Dox-induced cardiotoxicity. Despite previous studies reporting benefits of dapagliflozin on the cardiovascular system, it remains unknown whether dapagliflozin has a cardioprotective effect in cancer patients with diabetes receiving Dox therapy. The purpose of this study was to investigate the potential of dapagliflozin for preventing doxorubicin (Dox)-induced cardiotoxicity.Methods: Using Taiwan National Health Insurance Database, the incidence of heart failure of cancer patients with or without diabetes was investigated. Streptozotocin (STZ)-induced diabetic rats were pretreated with oral dapagliflozin (10 mg/kg/day) for 6 weeks followed by Dox (5 mg/kg/week) for 4 weeks via intraperitoneal injection. Sequential echocardiography was applied to assess cardiac function. For in vitro analysis, cardiomyocytes cultured in high glucose (30 mM) were treated with dapagliflozin at 10 M and subsequently exposed to Dox at 1 M. Apoptosis and endoplasmic reticulum (ER) stress-related protein expression were measured by immunohistochemistry and Western blotting.Results: Among the studied patients, those with diabetes had a higher risk of major adverse cardiovascular events including the development of heart failure. In diabetic rats, dapagliflozin reduced cardiac fibrosis and significantly improved cardiac function. Dapagliflozin effectively inhibited Dox-induced apoptosis and reactive oxygen species in cardiomyocytes under high glucose. Mechanistically, we showed that dapagliflozin decreased the cardiac expression of Bax and cleaved caspase 3 but increased Bcl-2. Dapagliflozin also significantly reduced ER stress-associated proteins including GRP78, PERK, eIF-2, ATF-4, and CHOP. Conclusions: Our study revealed for the first time that dapagliflozin mitigated Dox-induced cardiomyocyte apoptosis in diabetes via inhibiting ER stress. These results indicate that dapagliflozin could be useful for preventing cardiotoxicity in diabetic cancer patients receiving Dox treatment.

Heart failure (HF) with mid-range ejection fraction (HFmrEF) is defined as HF with a left ventricular (LV) ejection fraction (LVEF) of 41-49%. However, the change in LV function and the subsequent prognosis in these patients remain unclear. We aimed to investigate whether LV global longitudinal strain (LV GLS) could differentiate the changes in LVEF and predict the clinical outcomes in patients with HFmrEF.According to the changes in LVEF on follow-up echocardiography, 273 outpatients with HFmrEF were divided into 3 groups: HFwEF (HF with worse EF:40%), HFsEF (HF with similar EF: 40-49%), and HFrecEF (HF with recovered EF:50%). Further, the LV GLS at diagnosis was evaluated.The average follow-up duration was 31 months. Among patients with HFmrEF, the more impaired the LV GLS at baseline, the higher probability of HFwEF development. In comparison with patients with HFwEF and HFsEF, those with HFrecEF had a lower risk of hospitalization for HF. At a cut-off value of -11%, LV GLS differentiated the subsequent risk of cardiovascular death in patients with HFmrEF. In Cox regression, patients with LV GLS-11% had a high risk of cardiovascular death.In patients with HFmrEF, LV GLS is associated with LVEF changes and subsequent cardiovascular death. Patients with HFrecEF had a lower risk of hospitalization for HF.

Supplemental material, sj-pdf-2-pul-10.1177_2045894020943858 for Right ventricular reserve post mitral valve repair is associated with heart failure hospitalization by Wei-Ting Chang, Nan-Chun Wu, Jhih-Yuan Shih, Chih-Hsin Hsu, Zhih-Cherng Chen and Bor-Chih Cheng in Pulmonary Circulation

Supplemental material, sj-pdf-2-pul-10.1177_2045894020943858 for Right ventricular reserve post mitral valve repair is associated with heart failure hospitalization by Wei-Ting Chang, Nan-Chun Wu, Jhih-Yuan Shih, Chih-Hsin Hsu, Zhih-Cherng Chen and Bor-Chih Cheng in Pulmonary Circulation

Transcatheter heart valve-in-valve implantation in failed surgical bioprosthetic valves has shown promising outcomes, prompting the stepwise expansion of their applications in different clinical scenarios. Recently, there is increased interest in valve-in-valve techniques for the treatment of patients with complex congenital heart disease. Herein, we report a case of successful transapical transcatheter atrioventricular valve-in-valve implantation in a patient with Fontan circulation and dextrocardia. The patient was previously treated with total cavopulmonary connection and atrioventricular valve replacement with recurrent prosthesis dysfunction.

// Kun-Ling Tsai 1,* , Ching-Hsia Hung 1,2,* , Shih-Hung Chan 3 , Jhih-Yuan Shih 4 , Yung-Hsin Cheng 5 , Yi-Ju Tsai 1 , Huei-Chen Lin 2,6 and Pei-Ming Chu 7 1 Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan 2 Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan 3 Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan 4 Department of Internal Medicine, Chi-Mei Hospital, Tainan, Taiwan 5 Department of Education and Research, Taipei City Hospital, Taipei, Taiwan 6 Department of Physical Therapy, Shu-Zen Junior College Of Medicine And Management, Taiwan 7 Department of Anatomy, School of Medicine, China Medical University, Taichung, Taiwan * These authors have contributions equally to this work Correspondence to: Pei-Ming Chu, email: // Keywords : atherosclerosis, ROS, endothelial cells, lectin-like oxidized LDL receptor 1, baicalein, Gerotarget Received : July 06, 2016 Accepted : October 13, 2016 Published : October 20, 2016 Abstract Atherosclerosis is considered to be a form of chronic inflammation and a disorder of lipid metabolism. Oxidative transformations in the lipid and apolipoprotein B (Apo B) constituent of low density lipoprotein drive the initial step in atherogenesis due to macrophage scavenger receptors identify oxidized LDL (oxLDL) but non-oxidized LDL. The human vascular endothelial cells fact a critical role in vasodilation, provides a nonadhesive surface for circulation, reduces vascular smooth muscle proliferation, inflammation, thrombus formation and platelet aggregation. Assembly of oxLDL contribute to stimulation of endothelial cells with up-regulation of adhesion molecules, increase oxidative stress to the vascular endothelium and inhibition of NO-mediated vasodilation. When adhesion molecules are over-expressed on the surface of endothelial cells under oxLDL stimulation, it will recruit monocytes to the arterial wall. Then adherent monocytes will migrate into the subendothelial space and subsequently differentiate into macrophages. In the subendothelial space, oxLDL will be taken up by macrophages, thereby causing the substantial cholesterol accumulation and the foam cells production.

Myocardial scar burden is an important prognostic factor after myocardial infarction. This cohort study compared assessment of left ventricle scar burden between pathological Q waves on electrocardiography (ECG), Selvester multiparametric ECG scoring system for scar burden, and global longitudinal strain (GLS) by speckle-tracking echocardiography 6 months after myocardial infarction. The scar burden was defined by late gadolinium enhancement cardiac magnetic resonance as fraction of total left ventricle tissue. ECG measures were presence of pathologic Q waves and Selvester scores. GLS was the average of peak strain from 16 left ventricle segments. In 34 patients aged 58 ± 10 years (mean ± SD), the scar burden was 19% (9, 26) (median [quartiles]) and 79% had scar burden >5%. Patients with scar burden >5% more frequently had pathologic Q waves (63% vs 14%) and had worse Selvester scores (5 [3, 7] vs 0 [0, 1]) and worse GLS (−16.6 ± 2.4% vs −19.9 ± 1.1%). Pathologic Q waves, Selvester scores, ejection fraction, and GLS related to scar burden in univariable analyses. Sensitivity and specificity for detecting scar burden >5% was 63% and 86% (pathologic Q waves), 89% and 86% (Selvester score), 81% and 86% (ejection fraction), 89% and 86% (GLS), and 96% and 71% (combination of Q waves, Selvester score, and GLS). In conclusion, Selvester score and GLS related to scars 6 months after myocardial infarction, and pathologic Q waves were only weakly associated with scar and GLS was associated with scar independently of ECG markers.

As cancer therapies have improved, patient life spans have been extended but quality of life has been threatened by chemotherapy induced cardiotoxicity. Most cardiac complications remain unobserved until specific symptoms develop. Speckle-tracking echocardiography is a sensitive imaging modality in detecting early occult myocardial dysfunction.A total number of 35 patients newly diagnosed with breast cancer and preparing for epirubicin therapy were prospectively recruited. Echocardiography, including speckle-tracking echocardiography, was performed sequentially at baseline (T1), after the first cycle (T2) and after the third cycle (T3) of epirubicin. At each visit, the severity of dyspnea was evaluated by the assessment scale.Compared with the baseline, right ventricular longitudinal strain (RVLS_FW) at T2 significantly declined (-22.49 ± 4.97 vs. -18.48 ± 4.46, p = 0.001), which was also positively associated with the development of dyspnea (RRVLS_FW sensitively predicts dyspnea development in breast cancer patients receiving epirubicin therapy. However, larger scale studies are required to validate its role in long-term patient survival.

Radial artery occlusion (RAO) occurs in 2% to 18% of patients after transradial access (TRA) cardiac catheterization. Using a kaolin-filled pad (QuikClot) reduces compression time during TRA and might reduce RAO. We examined the RAO risk with the kaolin-filled pad after TRA cardiac catheterization. This was a prospective cross-sectional study of 260 patients who underwent TRA cardiac catheterization in a cardiac ward of a Medical Center from 2012 to 2016. Patients were randomly assigned to 1 of 2 groups: the case group (n = 130) was postoperatively treated with a kaolin-filled pad, and the control group (n = 130) was treated with conventional hemostasis. Color duplex ultrasound was used to evaluate the 24-hour and 1-month postoperative radial artery flow velocity, diameter, patency, and RAO risk. RAO risk was not significantly different between the case and control groups after 24 hours (4.6% vs 5.4%, P = .776) or after 1 month (5.4% vs 6.1%, P = .789), regardless of whether it was a first TRA cardiac catheterization (after 24 hours [P = .153] or after 1month [P = .617], respectively) or a repeated TRA cardiac catheterization (after 24 hours [P = .754] or after 1month [P = .753], respectively). Using a kaolin-filled pad after TRA cardiac catheterization did not significantly reduce RAO risk compared with conventional hemostasis.

Changes in the three phases of left atrial (LA) function have not been well studied in hypertension. We studied phasic function of LA by speckle tracking echocardiography (STE) in hypertension. Sixty-one consecutive untreated hypertension patients and 32 sex- and age-matched healthy participants were included. Two-dimensional (2D) images obtained from apical four-chamber and two-chamber views were used for STE analysis of LA. LA peak positive strain (39.8 ± 10.9 vs. 45.3 ± 12.7 %, p = 0.031), peak negative strain (−2.2 ± 1.5 vs. −3.0 ± 1.9 %, p = 0.029), and conduit strain rate (−2.0 ± 0.5 vs. −2.4 ± 0.6 1/s, p = 0.005) were significantly decreased in hypertension. Twenty hypertensive patients (32%) had diastolic dysfunction. Positive strain (34.8 ± 7.2 vs. 42.2 ± 11.6 %, p = 0.012) and conduit strain rate (−1.7 ± 0.4 vs. −2.2 ± 0.5 1/s, p

OBJECTIVE Postsystolic shortening is associated with hypertensive heart disease, and the degree of postsystolic shortening can be measured by postsystolic strain index (PSI) of the left ventricle (LV) derived from speckle tracking echocardiography. We studied the association between PSI with delayed diastolic lengthening and diastolic dysfunction in hypertension. METHODS This study recruited 46 patients (mean age 56 ± 13 years, 24 men) with untreated hypertension, and 26 normal individuals (mean age 55 ± 11 years, 9 men) as controls. Hypertension patients were further divided into two groups based on the presence of diastolic dysfunction. PSI was calculated as [(postsystolic peak longitudinal strain - end-systolic strain)/end-systolic strain] × 100%. Timing of left-ventricular diastolic lengthening was determined by measurements of time to onset of early diastolic mitral annulus lengthening by tissue Doppler imaging. RESULTS Total PSI was significantly higher in patients with diastolic dysfunction (252 ± 257 vs. 98 ± 72%, P = 0.002). After multivariate analysis, PSI was independently associated with diastolic dysfunction in hypertension [every 10% increment of PSI, odds ratio (OR) 1.13, 95% confidence interval (CI) 1.01-1.27, P = 0.036]. PSI was independently correlated with serum procollagen type I carboxyterminal propeptide (beta = 0.382, P = 0.028) after multivariable analysis, and time delay from onset of early mitral inflow to onset of early diastolic medial (beta = 0.405, P = 0.004) or lateral (beta = 0.582, P

Background The objective of this study was to investigate myocardial deformation of the left atrium (LA) assessed by two-dimensional speckle tracking echocardiography in patients with permanent atrial fibrillation (AF) and its value for risk stratification for stroke. Methods We recruited 66 consecutive patients with permanent AF who were referred to our echocardiography laboratory for evaluation. These patients were divided into two groups according to the presence of previous stroke or not. Results Peak positive longitudinal strain (LASp) during atrial filling, peak strain rate in the reservoir phase of LA (LASRr), and peak strain rate in the conduit phase (LASRc) were identified from LA strain and strain rate curves. The ratio of peak early filling velocity (E) of mitral inflow to early diastolic annulus velocity (E') of the medial annulus (E/E') was calculated. LASp (10.44% ± 4.2% vs. 15.69% ± 5.1%, P 001), LASRr (1.09 ± 0.27 1/s vs. 1.37 ± 0.32 1/s, P = .001), and LASRc (−1.28 ± 0.38 1/s vs. −1.62 ± 0.43 1/s, P = .002) were significantly lower in patients with AF with stroke than those without stroke. By multivariate analysis controlling for age, LA volume index, and left ventricular ejection fraction, LASp (OR 0.787, 95% CI, 0.639–0.968, P = .023) and LASRr (OR 0.019, 95% CI, 0.001–0.585, P = .023) were independently associated with stroke but not LASRc, E', and E/E' ratio. Conclusion Decreased LASp and LASRr were independently associated with stroke in patients with permanent AF.

Background Impaired left atrial (LA) deformation is noted in patients with severe primary mitral regurgitation (MR), but its prognostic value is unknown. The aim of this study was to investigate the prognostic significance of LA deformation parameters in patients with chronic severe primary MR. Methods A total of 104 patients with asymptomatic chronic severe primary MR (Carpentier type II) and preserved left ventricular systolic function were prospectively recruited. Global peak positive strain of the left atrium (LASp) and strain rate in the LA filling phase (LASRr) as well as strain rate in the LA conduit phase were identified using two-dimensional speckle-tracking echocardiography. Results During a mean follow-up period of 13.2 ± 9.5 months, 22 patients reached a composite end point of death and mitral valve repair or replacement prompted by heart failure development. Among the clinical and echocardiographic parameters, LV end-systolic volume index (19.5 ± 9.5 vs 15.7 ± 6.3 mL/m 2 , P = .028), LASp (22.7 ± 10.4% vs 27.2 ± 9.1%, P = .049), and LASRr (1.97 ± 0.6 vs 2.33 ± 0.6 1/sec, P = .013) varied between the two groups in terms of end points but not age, LA volume index, left ventricular ejection fraction, pulmonary artery systolic pressure, and presence of atrial fibrillation. After multivariate analysis, low LASp (odds ratio, 3.606; 95% CI, 1.294–10.052; P = .014) and low LASRr (odds ratio, 2.857; 95% CI, 1.078–7.572; P = .035) remained powerful outcome indicators. Conclusions In patients with asymptomatic severe primary MR, reduced LASp and LASRr predicted a worse prognosis. These findings may offer additional information to guide early surgery.