A rare case of cardiac myxoma with light bulb-like cystic morphology: a case report.

Background: Cystic myxomas are quite rare. Moreover, few reports have evaluated the causes that constituted them. Case summary: A 73-year-old Asian man presented for pre-operative examination of osteoarthritis, and transthoracic echocardiography (TTE) revealed an incidental intracardiac mass. Therefore, he was referred to our department for further evaluation. He had no specific symptoms or family history related to tumours and heart failure. The TTE showed a 32 × 24 mm spherical mass adherent to the left atrial septum. The upper part of the mass was cystic in formation and hypoechoic inside and resembled a light bulb. Transoesophageal echocardiography showed the feeding arteries flowing from the bottom into the cystic part. In addition, two jet strips drained from the cystic part in the direction of the mitral valve. Coronary angiography revealed the feeding arteries, which consisted mainly of the right coronary artery conus branch and the left circumflex branch, and the blood flowed into the saccular area from the feeding arteries and excreted towards the mitral valve. Surgical resection was performed due to the mobility, and the histopathology confirmed a cystic myxoma. Discussion: We described the unique anatomical formation of a cystic myxoma, which consisted of an exquisite balance between the tumour-feeding arteries and the draining outlet vessels.

SERCA2a Agonist Effects on Cardiac Performance During Exercise in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Impaired ventricular relaxation influences left ventricular pressures during exercise in heart failure with preserved ejection fraction (HFpEF). Sarco/endoplasmic reticulum calcium-adenosine triphosphatase (SERCA2a) facilitates myocardial relaxation by increasing calcium reuptake and is impaired in HFpEF. OBJECTIVES: This study sought to investigate the effects of istaroxime, a SERCA2 agonist, on lusitropic and hemodynamic function during exercise in patients with HFpEF and control subjects. METHODS: Eleven control subjects (7 male, 4 female) and 15 patients with HFpEF (8 male, 7 female) performed upright cycle exercise with right-sided heart catheterization. Participants received istaroxime (0.5 µg/kg/min) or saline placebo (single-blind, crossover design). Cardiac output, pulmonary capillary wedge pressure (PCWP), and diastolic function were measured at rest and during submaximal exercise. In an exploratory analysis (Hedge's g), 7 patients with HFpEF received higher-dose istaroxime (1.0 µg/kg/min). End-systolic elastance (Ees) was calculated by dividing systolic blood pressure (SBP) × 0.9 by end-systolic volume (ESV) (on 3-dimensional echocardiography). RESULTS: Patients with HFpEF had higher PCWP (25 ± 10 mm Hg vs 12 ± 5 mm Hg; P < 0.001) and lower tissue Doppler velocities during exercise. Istaroxime (0.5 µg/kg/min) had no effect on resting or exercise measures in patients with HFpEF or control subjects. Control subjects had a larger increase in Ees (Δ 1.55 ± 0.99 mm Hg/mL vs Δ 0.86 ± 1.31 mm Hg/mL; P = 0.03), driven by lower ESV. Comparing placebo and istaroxime 1.0 µg/kg/min during exercise, PCWP during the 1.0 µg/kg/min istaroxime dose was slightly lower (Δ 2.2 mm Hg; Hedge's g = 0.30). There were no effects on diastolic function, but there were increases in SBP and s', suggesting a mild inotropic effect. CONCLUSIONS: Low-dose istaroxime had no effect on cardiac filling pressure or parameters of relaxation in patients with HFpEF during exercise. Higher doses of istaroxime may have been more effective in reducing exercise PCWP in patients with HFpEF. (Hemodynamic Response to Exercise in HFpEF Patients After Upregulation of SERCA2a; NCT02772068).

Both New-Onset and Pre-Existing Hypertension Indicate Favorable Clinical Outcomes in Patients Treated With Anti-Vascular Endothelial Growth Factor Therapy.

BACKGROUND: Hypertension is a frequent adverse event caused by vascular endothelial growth factor signaling pathway (VSP) inhibitors. However, the impact of hypertension on clinical outcomes during VSP inhibitor therapy remains controversial.Methods and Results: We reviewed 3,460 cancer patients treated with VSP inhibitors from the LIFE Study database, comprising Japanese claims data between 2016 and 2020. Patients were stratified into 3 groups based on the timing of hypertension onset: (1) new-onset hypertension (n=569; hypertension developing after VSP inhibitor administration); (2) pre-existing hypertension (n=1,790); and (3) no hypertension (n=1,101). Time to treatment failure (TTF) was used as the primary endpoint as a surrogate for clinical outcomes. The median (interquartile range) TTF in the new-onset and pre-existing hypertension groups was 301 (133-567) and 170 (72-358) days, respectively, compared with 146 (70-309) days in the non-hypertensive group (P<0.001 among all groups). In an adjusted Cox proportional hazard model, new-onset (hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.50-0.68; P<0.001) and pre-existing (HR 0.85; 95% CI 0.73-0.98; P=0.026) hypertension were independent factors for prolonged TTF. The TTF of new-onset hypertension was longer than that of pre-existing hypertension (HR 0.68; 95% CI 0.62-0.76; P<0.001). CONCLUSIONS: This study highlighted that new-onset hypertension induced by VSP inhibitors was an independent factor for favorable clinical outcomes. Pre-existing hypertension before VSP inhibitor initiation was also a significant factor.

IMPROVE bleeding score predicts major bleeding in advanced gastrointestinal cancer patients with venous thromboembolism.

BACKGROUND: The incidence of venous thromboembolism has been reported as 20% in cancer patients. Anticoagulation therapy is the standard treatment for venous thromboembolism. On the other hand, bleeding should be carefully managed, because advanced cancer, particularly gastrointestinal cancer, carries a high risk of bleeding. However, the optimal management for cancer-associated thromboembolism remains to be clarified. METHODS: We retrospectively examined patients with advanced gastrointestinal cancer, including gastric cancer and colorectal cancer, who were treated with chemotherapy between 2014 and 2018 for the incidence and characteristics of venous thromboembolism and bleeding. RESULTS: In total, 194 patients (120 men, 74 women) were enrolled in this study. The underlying pathology was gastric cancer in 74 cases and colorectal cancer in 120 cases. Of the 194 patients, 40 patients (20.6%) were diagnosed with venous thromboembolism and 10 patients (5.2%) were diagnosed with concomitant pulmonary thromboembolism. Conversely, bleeding was observed in 29 patients (15%). The location of bleeding was the primary tumor in 17 cases, metastatic tumor in 9 and hemorrhagic gastric ulcer in 3. Within the venous thromboembolism group (n = 40), bleeding was observed in 10 patients (25%). Multivariate analysis showed that International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) bleeding score ≥7 correlated significantly with major bleeding (P = 0.01). In patients with a low risk of bleeding, major bleeding was observed in only three patients. CONCLUSIONS: IMPROVE bleeding score may predict the risk for bleeding in gastrointestinal cancer patients with venous thromboembolism. Selecting patients with a low risk of bleeding using with IMPROVE bleeding score is expected to contribute to the safer management of anticoagulation therapy for cancer-associated thromboembolism.

Case Report: Bronchogenic Cyst in the Right Atrium of a Young Woman.

A 31-year-old woman was referred to our hospital for evaluation of a cardiac mass in the right atrium. Cardiac magnetic resonance imaging indicated a cystic mass filled with fluid accumulation in the right atrium. The mass was identified as a cardiac cyst and was surgically removed. Pathological examination revealed an extremely rare bronchogenic cyst. Bronchogenic cysts are benign congenital abnormalities of primitive foregut origins that form in the mediastinum during embryonic development. There is unusual clinical dilemmas surrounding the treatment plan for cardiac surgery or biopsy of cardiac masses, especially in patients with rare cardiac cysts. The anatomical location of the cyst can be related to various clinical symptoms and complications. In cases of indeterminate cardiac cysts, direct cyst removal without prior biopsy is of utmost importance.

Early-onset cardiac dysfunction following allogeneic haematopoietic stem cell transplantation.

OBJECTIVE: Heart failure following allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a serious complication that requires early detection; however, the clinical implications of early-onset cancer therapy-related cardiac dysfunction (CTRCD) following allo-HSCT remain unclear. We investigated the determinants and prognostic impact of early-onset CTRCD in allo-HSCT recipients. METHODS: The records of 136 patients with haematological malignancies who underwent allo-HSCT at our institute were retrospectively reviewed. Early-onset CTRCD was defined as a decrease in left ventricular ejection fraction (LVEF) of ≥10% and an LVEF of ≤53% within 100 days after HSCT. RESULTS: Early-onset CTRCD was diagnosed in 23 out of 136 included patients (17%), and the median duration from HSCT to CTRCD diagnosis was 24 (9-35) days. Patients were followed up for 347 (132-1268) days. In multivariate logistic regression analysis, cumulative doxorubicin dosage (each 10 mg/m2) and severity of acute graft-versus-host disease (GVHD/grade) were independent indicators of early-onset CTRCD (OR (95% CI) 1.04 (1.00 to 1.07); p=0.032; OR (95% CI) 1.87 (1.19 to 2.95), p=0.004, respectively). The overall and primary disease death rates were significantly higher in allo-HSCT recipients with early-onset CTRCD than in those without early-onset CTRCD (HR (95% CI) 1.98 (1.11 to 3.52), p=0.016; HR (95% CI) 2.96 (1.40 to 6.29), p=0.005, respectively), independent of primary disease type, remission status and transplantation type. CONCLUSIONS: Severe acute GVHD and higher cumulative anthracycline are two significant determinants of early-onset CTRCD. Early-onset CTRCD following allo-HSCT regulates survival in patients with haematological malignancies.

1 Year HIIT and Omega-3 Fatty Acids to Improve Cardiometabolic Risk in Stage-A Heart Failure.

OBJECTIVES: This study aims to determine whether 1 year of high-intensity interval training (HIIT) and omega-3 fatty acid (n-3 FA) supplementation would improve fitness, cardiovascular structure/function, and body composition in obese middle-aged adults at high-risk of heart failure (HF) (stage A). BACKGROUND: It is unclear if intensive lifestyle interventions begun in stage A HF can improve key cardiovascular and metabolic risk factors. METHODS: High-risk obese adults (n = 80; age 40 to 55 years; N-terminal pro-B-type natriuretic peptide >40 pg/mL or high-sensitivity cardiac troponin T >0.6 pg/mL; visceral fat >2 kg) were randomized to 1 year of HIIT exercise or attention control, with n-3 FA (1.6 g/daily omega-3-acid ethyl esters) or placebo supplementation (olive oil 1.6 g daily). Outcome variables were exercise capacity quantified as peak oxygen uptake (V.O2), left ventricular (LV) mass, LV volume, myocardial triglyceride content (magnetic resonance spectroscopy), arterial stiffness/function (central pulsed-wave velocity; augmentation index), and body composition (dual x-ray absorptiometry scan). RESULTS: Fifty-six volunteers completed the intervention. There was no detectible effect of HIIT on visceral fat or myocardial triglyceride content despite a reduction in total adiposity (Δ: -2.63 kg, 95% CI: -4.08 to -0.46, P = 0.018). HIIT improved exercise capacity by ∼24% (ΔV.O2: 4.46 mL/kg per minute, 95% CI: 3.18 to 5.56; P < 0.0001), increased LV mass (Δ: 9.40 g, 95% CI: 4.36 to 14.44; P < 0.001), and volume (Δ: 12.33 mL, 95 % CI: 5.61 to 19.05; P < 0.001) and reduced augmentation index (Δ: -4.81%, 95% CI: -8.63 to -0.98; P = 0.009). There was no independent or interaction effect of n-3 FA on any outcome. CONCLUSIONS: One-year HIIT improved exercise capacity, cardiovascular structure/function, and adiposity in stage A HF with no independent or additive effect of n-3 FA administration. (Improving Metabolic Health in Patients With Diastolic Dysfunction [MTG]; NCT03448185).

Effect of renin-angiotensin system inhibitors in patients with cancer treated with anti-VEGF therapy.

BACKGROUND: Cancer treatment with vascular endothelial growth factor signalling pathway (VSP) inhibitors frequently causes hypertension. Although previous reports suggested that the antihypertensive drug renin-angiotensin system inhibitor (RASI) may have a positive synergistic effect with VSP inhibitors, the actual impact on clinical outcomes is unknown. OBJECTIVES: The study aims to clarify whether RASIs exhibit clinical benefits for patients with cancer with hypertension. METHOD: From the Longevity Improvement and Fair Evidence Study database, comprising Japanese claims data between 2016 and 2020, we reviewed 2380 patients treated with VSP inhibitors who received antihypertensive treatment during cancer therapy. The patients were classified into two groups: with-RASI (n=883) and without-RASI (n=1497). In addition, 1803 of these patients treated for hypertension with RASI-only (n=707) or calcium channel blocker-only (n=1096) were also reviewed. The time-to-treatment failure (TTF), the interval from initiation of chemotherapy to its discontinuation, was applied as the primary endpoint. RESULTS: The median TTFs were 167 (60-382) days in the with-RASI group and 161 (63-377) days in the without-RASI group (p=0.587). All models, including Cox proportional hazard models and multiple propensity score models, did not reveal the superiority of with-RASI treatment. In the propensity score matching model, the HR for treatment with-RASI compared with that for without-RASI was 0.96 (95% CI 0.86 to 1.06, p=0.386). In addition, the TTFs of RASI-only were not superior to calcium channel blocker-only (p=0.584). CONCLUSIONS: RASIs for hypertension do not benefit clinical outcomes during cancer therapy with VSP inhibitors. In addition, RASIs and calcium channel blockers have comparable clinical efficacy as first-line antihypertensive.

Dietary nitrate supplementation does not influence thermoregulatory or cardiovascular strain in older individuals during severe ambient heat stress.

NEW FINDINGS: What is the central question of this study? Does dietary nitrate supplementation with beetroot juice attenuate thermoregulatory and cardiovascular strain in older adults during severe heat stress? What is the main finding and its importance? A 7-day nitrate supplementation regimen lowered resting mean arterial pressure in thermoneutral conditions. During heat stress, core and mean skin temperatures, vasodilatory responses, sweat loss, heart rate and left ventricular function were unchanged, and mean arterial pressure was only transiently reduced, post-supplementation. These data suggest nitrate supplementation with beetroot juice does not mitigate thermoregulatory or cardiovascular strain in heat-stressed older individuals. ABSTRACT: This study tested the hypothesis that dietary nitrate supplementation with concentrated beetroot juice attenuates thermoregulatory and cardiovascular strain in older individuals during environmental heat stress. Nine healthy older individuals (six females, three males; aged 67 ± 5 years) were exposed to 42.5 ± 0.1°C and 34.0 ± 0.5% relative humidity conditions for 120 min before (CON) and after 7 days of dietary nitrate supplementation with concentrated beetroot juice (BRJ; 280 ml, ∼16.8 mmol of nitrate daily). Core and skin temperatures, body mass changes (indicative of whole-body sweat loss), skin blood flow and cutaneous vascular conductance, forearm blood flow and vascular conductance, heart rate, arterial blood pressures and indices of cardiac function were measured. The 7-day beetroot juice regimen increased plasma nitrate/nitrite levels from 27.4 ± 15.2 to 477.0 ± 102.5 µmol l-1 (P < 0.01) and lowered resting mean arterial pressure from 90 ± 7 to 83 ± 10 mmHg at baseline under thermoneutral conditions (P = 0.02). However, during subsequent heat stress, no differences in core and skin temperatures, skin blood flow and vascular conductance, forearm blood flow and vascular conductance, whole-body sweat loss, heart rate, and echocardiographic indices of systolic function and diastolic filling were evident following nitrate supplementation (all P > 0.05). Mean arterial pressure was lower in BRJ vs. CON during heat stress (treatment-by-time interaction: P = 0.02). Overall, these findings suggest that dietary nitrate supplementation with concentrated beetroot juice does not attenuate thermoregulatory or cardiovascular strain in older individuals exposed to severe ambient heat stress.

Impact of Treatment with Direct Acting Antiviral Drugs on Glycemic Control in Patients with Hepatitis C and Diabetes Mellitus.

AIM: To assess the effect of treating chronic hepatitis C virus (HCV) infection with direct acting antiviral drugs (DAAs) on glycemic control in patients with concomitant diabetes mellitus (DM). METHODS: We performed a retrospective case-control study in a viral hepatitis ambulatory clinic in Shreveport, Louisiana, during the period 11/01/2014 to 12/31/2017. All the clinic patient ages 18 years and above with treatment-naïve/biopsy-proven chronic hepatitis C and DM (hemoglobin A1C level ≥ 6.5%) who were eligible for treatment were included in the study. Of 118 such patients, 59 were treated with oral DAAs for 8-12 weeks with the goal of achieving a sustained virologic response (SVR). A control group of 59 patients did not receive treatment for their hepatitis C and was followed in the clinic. Patients in the control group did not receive treatment either due to insurance issues or refusal of hepatitis C treatment. RESULTS: Fifty-five of the 59 patients treated with DAAs (93%) achieved a SVR. Six months after treatment completion, their mean ± SEM HbA1C level had decreased by 1.1 ± 0.03% (P < 0.0001). Four of the 59 patients treated with DAAs did not achieve a SVR. Their mean HbA1C 6 months after treatment completion had increased by 0.8 ± 0.2%. Furthermore, there was no improvement in HbA1C levels over time in the untreated group (mean HbA1C increase, 0.2 ± 0.05%; P < 0.0001 vs. the treatment group, which had a mean HbA1C decrease of 0.9 ± 0.2%). CONCLUSION: This controlled study demonstrated that treatment of chronic hepatitis C with DAAs results in statistically significant and meaningful reductions in hemoglobin A1C levels in patients with coexisting diabetic mellitus if a SVR is achieved.

Masson Tumor in the Left Atrial Appendage Presenting as Cardioembolic Cerebral Infarction.

A 70-year-old woman presented with aphasia caused by acute infarction in the left middle cerebral artery. Cardiac investigation revealed progressively increasing mobile mass in the left atrial appendage over 2 months (from 9 to 15 mm). Decision was made to proceed with mass resection, and pathological evaluation confirmed Masson tumor. (Level of Difficulty: Advanced.).

Serum Brain Natriuretic Peptide Concentration 60 Days After Surgery as a Predictor of Long-Term Prognosis in Patients Implanted With a Left Ventricular Assist Device.

Mechanical circulatory support by a left ventricular assist device (LVAD) is used to bridge patients with advanced heart failure to transplant or as a definitive treatment. We retrospectively sought predictors of long-term outcome in a cohort of 83 patients who had undergone LVAD treatment. We subjected perioperative clinical data of patients to statistical analysis to establish parameters associated with all-cause mortality, and the cutoff values, sensitivity, and specificity of those that had a statistically significant relation with survival. Mean follow-up was 717 days (standard deviation, 334 days; range, 17-1,592 days). Fourteen patients (16.8%) died, but nine (10.8%) were weaned from support. Serum brain natriuretic peptide (BNP) concentration measured 60 days after implantation was significantly associated with all-cause mortality. The optimal BNP cutoff value to predict death during LVAD support was 322 pg/ml, with a sensitivity of 71.4% and specificity of 79.8%. Two-year survival was 92.0% in those with 60 days serum BNP concentration <322 pg/ml compared with 70.5% in those in whom it was ≥322 pg/ml (p = 0.003). The relation between BNP and survival likely reflects recovery of native myocardial function and improvements in global health and should assist clinicians in the on-going management of long-term LVAD therapy.

Left coronary artery occlusion caused by a large thrombus on the left coronary cusp in a patient with a continuous-flow ventricular assist device.

Despite continual improvements in ventricular assist device (VAD) therapy, various clinical issues are emerging. Importantly, various types of thromboembolic complications have been reported to date. Recently, we encountered a rare continuous-flow VAD-related thromboembolic event that resulted in acute myocardial infarction. A 26-year-old female who just underwent HeartMate II(®) VAD implantation suddenly developed widespread anterolateral myocardial infarction on postoperative day 16. Echocardiography and aortography revealed a large thrombus on the left coronary cusp of the aortic valve that almost completely occluded the left coronary ostium. After VAD implantation, her aortic valve did not open, even at relatively low pump speeds; this was thought to be one of the causes for thrombus formation. Continuous suction of blood from the left ventricle and non-pulsatile flow into the ascending aorta resulted in a continuously closed aortic valve and stagnation of blood in the coronary cusp. Furthermore, both small body size (body surface area <1.3 m(2)) and postoperative right ventricular failure may have exacerbated blood stagnation and thrombus formation in this patient. We should have adjusted the anticoagulation and antiplatelet therapy protocols based on the patient's condition. She underwent off-pump coronary artery bypass surgery and remained in clinically stable condition afterwards.

Overcoming the blockade at the upstream of caspase cascade in Fas-resistant HTLV-I-infected T cells by cycloheximide.

In spite of carrying large amount of Fas death receptor on the cell surface, Human T cell lymphotropic virus type-I (HTLV-I)-infected T cell lines are resistant to Fas-mediated cytotoxicity. We investigated the mechanism(s) of HTLV-I-induced Fas resistance. Western blotting and enzymatic activity analyses revealed that the Fas-elicited apoptotic signal in HTLV-I-infected T cells was intervened at the level(s) prior to the activation of caspase-8. Upon stimulation, the clustering of Fas receptors scarcely occurred in HTLV-I-infected cells. Cycloheximide treatment converted the resistant cells to sensitive cells; the presence of short-lived anti-apoptotic molecule(s) that can block the caspase-8 activation within HTLV-I-infected T cells is suggested.