Effects of Synchronizing Foot Strike and Cardiac Phase on Exercise Hemodynamics in Patients With Cardiac Resynchronization Therapy: A Within-Subjects Pilot Study to Fine-Tune Cardio-Locomotor Coupling for Heart Failure.

BACKGROUND: Despite advances in medical and cardiac resynchronization therapy (CRT), individuals with chronic congestive heart failure (CHF) have persistent symptoms, including exercise intolerance. Optimizing cardio-locomotor coupling may increase stroke volume and skeletal muscle perfusion as previously shown in healthy runners. Therefore, we tested the hypothesis that exercise stroke volume and cardiac output would be higher during fixed-paced walking when steps were synchronized with the diastolic compared with systolic portion of the cardiac cycle in patients with CHF and CRT. METHODS: Ten participants (58±17 years of age; 40% female) with CHF and previously implanted CRT pacemakers completed 5-minute bouts of walking on a treadmill (range, 1.5-3 mph). Participants were randomly assigned to first walking to an auditory tone to synchronize their foot strike to either the systolic (0% or 100±15% of the R-R interval) or diastolic phase (45±15% of the R-R interval) of their cardiac cycle and underwent assessments of oxygen uptake (V̇o2; indirect calorimetry) and cardiac output (acetylene rebreathing). Data were compared through paired-samples t tests. RESULTS: V̇o2 was similar between conditions (diastolic 1.02±0.44 versus systolic 1.05±0.42 L/min; P=0.299). Compared with systolic walking, stroke volume (diastolic 80±28 versus systolic 74±26 mL; P=0.003) and cardiac output (8.3±3.5 versus 7.9±3.4 L/min; P=0.004) were higher during diastolic walking; heart rate (paced) was not different between conditions. Mean arterial pressure was significantly lower during diastolic walking (85±12 versus 98±20 mm Hg; P=0.007). CONCLUSIONS: In patients with CHF who have received CRT, diastolic stepping increases stroke volume and oxygen delivery and decreases afterload. We speculate that, if added to pacemakers, this cardio-locomotor coupling technology may maximize CRT efficiency and increase exercise participation and quality of life in patients with CHF.

Randomized Controlled Trial of Moderate- and High-Intensity Exercise Training in Patients With Hypertrophic Cardiomyopathy: Effects on Fitness and Cardiovascular Response to Exercise.

Background Moderate intensity exercise training (MIT) is safe and effective for patients with hypertrophic cardiomyopathy, yet the efficacy of high intensity training (HIT) remains unknown. This study aimed to compare the efficacy of HIT compared with MIT in patients with hypertrophic cardiomyopathy. Methods and Results Patients with hypertrophic cardiomyopathy were randomized to either 5 months of MIT, or 1 month of MIT followed by 4 months of progressive HIT. Peak oxygen uptake (V˙O2; Douglas bags), cardiac output (acetylene rebreathing), and arteriovenous oxygen difference (Fick equation) were measured before and after training. Left ventricular outflow gradient and volumes were measured by echocardiography. Fifteen patients completed training (MIT, n=8, age 52±7 years; HIT, n=7, age 42±8 years). Both HIT and MIT improved peak V˙O2 by 1.3 mL/kg per min (P=0.009). HIT (+1.5 mL/kg per min) had a slightly greater effect than MIT (+1.1 mL/kg per min) but with no statistical difference (group×exercise P=0.628). A greater augmentation of arteriovenous oxygen difference occurred with exercise (Δ1.6 mL/100 mL P=0.005). HIT increased left ventricular end-diastolic volume (+17 mL, group×exercise P=0.015) compared with MIT. No serious arrhythmias or adverse cardiac events occurred. Conclusions This randomized trial of exercise training in patients with hypertrophic cardiomyopathy demonstrated that both HIT and MIT improved fitness without clear superiority of either. Although the study was underpowered for safety outcomes, no serious adverse events occurred. Exercise training resulted in salutary peripheral and cardiac adaptations. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03335332.

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).

Evaluation of coronary flow is useful in patients with left coronary cusp thrombus formation after left ventricular assist device implantation.

Left ventricular assist device (LVAD) is essential for patients with severe heart failure, but there is a risk of thrombus formation on the aortic root and cusps, leading to coronary artery occlusion. Even with the narrowing of the echo-window due to LVAD, careful observation of coronary flow by transthoracic echocardiography can evaluate the patency of coronary flow non-invasively and immediately.

Cardiac remodeling in well-healed burn survivors after 6 months of unsupervised progressive exercise training.

Aerobic exercise is important in the rehabilitation of individuals with prior burn injuries, but no studies have examined whether adult burn survivors demonstrate cardiac remodeling to long-term aerobic exercise training. In this study, we tested the hypothesis that 6 months of progressive exercise training improves cardiac magnetic resonance imaging-based measures of cardiac structure and function in well-healed burn survivors. Secondary analyses explored relations between burn surface area and changes in cardiac structure in the cohort of burn survivors. V̇o2peak assessments and cardiac magnetic resonance imaging were performed at baseline and following 6 months of progressive exercise training from 19 well-healed burn survivors and 10 nonburned control participants. V̇o2peak increased following 6 months of training in both groups (Control: Δ5.5 ± 5.8 mL/kg/min; Burn Survivors: Δ3.2 ± 3.6 mL/kg/min, main effect of training, P < 0.001). Left ventricle (LV) mass (Control: Δ1.7 ± 3.1 g/m2; Burn survivors: Δ1.8 ± 2.7 g/m2), stroke volume (Control: Δ5.8 ± 5.2 mL/m2; Burn Survivors: Δ2.8 ± 4.2 mL/m2), and ejection fraction (Control: Δ2.4 ± 4.0%; Burn Survivors: Δ2.2 ± 4.3%) similarly increased following 6 months of exercise training in both cohorts (main effect of training P < 0.05 for all indexes). LV end-diastolic volume increased in the control group (Δ6.5 ± 4.5 mL/m2) but not in the cohort of burn survivors (Δ1.9 ± 2.7 mL/m2, interaction, P = 0.040). Multiple linear regression analyses revealed that burn surface area had little to no effect on changes in ventricular mass or end-diastolic volumes in response to exercise training. Our findings provide initial evidence of physiological cardiac remodeling, which is not impacted by burn size, in response to exercise training in individuals with well-healed burn injuries.NEW & NOTEWORTHY Aerobic exercise is important in the rehabilitation of individuals with prior burn injuries, but no studies have examined whether adult burn survivors demonstrate cardiac remodeling to long-term aerobic exercise training. In this study, we tested the hypothesis that 6 months of progressive exercise training would improve cardiac magnetic resonance imaging-based measures of cardiac structure and function in well-healed burn survivors. Our findings highlight the ability of exercise training to modify cardiac structure and function in well-healed burn survivors and nonburned sedentary controls alike.

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.

Altered cardiac ß1 responsiveness in hyperthermic older adults.

Compared with younger adults, passive heating induced increases in cardiac output are attenuated by ∼50% in older adults. This attenuated response may be associated with older individuals' inability to maintain stroke volume through ionotropic mechanisms and/or through altered chronotropic mechanisms. The purpose of this study was to identify the interactive effect of age and hyperthermia on cardiac responsiveness to dobutamine-induced cardiac stimulation. Eleven young (26 ± 4 yr) and 8 older (68 ± 5 yr) participants underwent a normothermic and a hyperthermic (baseline core temperature +1.2°C) trial on the same day. In both thermal conditions, after baseline measurements, intravenous dobutamine was administered for 12 min at 5 µg/kg/min, followed by 12 min at 15 µg/kg/min. Primary measurements included echocardiography-based assessments of cardiac function, gastrointestinal and skin temperatures, heart rate, and mean arterial pressure. Heart rate responses to dobutamine were similar between groups in both thermal conditions (P > 0.05). The peak systolic mitral annular velocity (S'), i.e., an index of left ventricular longitudinal systolic function, was similar between groups for both thermal conditions at baseline. While normothermic, the increase in S' between groups was similar with dobutamine administration. However, while hyperthermic, the increase in S' was attenuated in the older participants with dobutamine (P < 0.001). Healthy, older individuals show attenuated inotropic, but maintained chronotropic responsiveness to dobutamine administration during hyperthermia. These data suggest that older individuals have a reduced capacity to increase cardiomyocyte contractility, estimated by changes in S', via ß1-adrenergic mechanisms while hyperthermic.

Limits to submaximal and maximal exercise in patients with hypertrophic cardiomyopathy.

Patients with hypertrophic cardiomyopathy (HCM) often have reduced exercise capacity, and it is unclear whether cardiovascular regulation during exercise is intact in these patients. We aimed to determine the relationship between cardiac output (Q̇c) and oxygen uptake (V̇o2), and stroke volume (SV) reserve in HCM compared with healthy participants and participants with left ventricular hypertrophy (LVH) but not HCM. Sixteen patients with HCM (48 ± 7 yr, 44% female), 16 participants with LVH (49 ± 5 yr, 44% female), and 61 healthy controls (CON: 52 ± 5 yr, 52% female) completed submaximal steady-state treadmill exercise followed by a maximal exercise test. V̇o2, Q̇c, SV, and arteriovenous oxygen difference were measured during rest and exercise, and Q̇c/V̇o2 slopes were constructed, The Q̇c/V̇o2 slope was blunted in HCM compared with CON and LVH [HCM 4.9 ± 0.7 vs. CON 5.5 ± 1.0 (P = 0.027) vs. LVH 6.0 ± 1.0 AU (P = 0.002)] and participants with HCM had a lower SV reserve (HCM 53 ± 33%, controls 83 ± 33%, LVH 82 ± 22%; HCM vs. controls P = 0.002; HCM vs. LVH P = 0.015). Despite a blunted Q̇c/V̇o2 slope, 75% of patients with HCM achieved ≥80% predicted V̇o2max by augmenting a-vo2 difference at maximal exercise (16.0 ± 0.8 mL/100 mL vs. 13.8 ± 2.7 mL/100 mL, P = 0.021). Patients with HCM do not appropriately match Q̇c to metabolic demand, primarily due to inadequate stroke volume augmentation. Despite this central limitation, many patients achieve normal exercise capacities by significantly increasing peripheral oxygen extraction.NEW & NOTEWORTHY Through state-of-the-art hemodynamic and oxygen uptake methodologies, this study found the cardiac output response to increasing metabolic demand is blunted among patients with hypertrophic cardiomyopathy (HCM), primarily due to a reduced stroke volume reserve. Many patients with HCM augment their peripheral oxygen extraction during maximal exercise to achieve normal exercise capacity and overcome ineffective matching of cardiac output. Peripheral adaptations that compensate for cardiac limitations may contribute to the heterogeneity of functional limitations observed within this patient population.

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.

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.

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).

Rheological Abnormalities in Human Erythrocytes Subjected to Oxidative Inflammation.

Erythrocytes are oxygen carriers and exposed to redox cycle in oxygenation and deoxygenation of hemoglobin. This indicates that circulating erythrocytes are vulnerable to the oxidative injury occurring under the imbalance of redox homeostasis. In this review article, two topics are presented concerning the human erythrocytes exposed to the oxidative inflammation including septic and sterile conditions. First, we demonstrate rheological derangement of erythrocytes subjected to acute oxidative injury caused by exogenous generators of reactive oxygen species (ROS). Erythrocyte filterability as whole-cell deformability has been estimated by the gravity-based nickel mesh filtration technique in our laboratory and was dramatically impaired in a time-dependent manner after starting exposure to the ROS generators, that is associated with concurrent progression of membrane protein degradation, phospholipid peroxidation, erythrocyte swelling, methemoglobin formation, and oxidative hemolysis. Second, we introduce an impairment of erythrocyte filterability confirmed quantitatively in diabetes mellitus and hypertension of animal models and patients under treatment. Among the cell geometry, internal viscosity, and membrane property as the three major determinants of erythrocyte deformability, erythrocyte membrane alteration is supposed to be the primary cause of this impairment in these lifestyle-related diseases associated with persistent oxidative inflammation. Excessive ROS trigger the inflammatory responses and reduce the erythrocyte membrane fluidity. Oxidative inflammation increasing erythrocyte membrane rigidity underlies the impaired systemic microcirculation, which is observed in diabetic and/or hypertensive patients. On the other hand, elevated internal viscosity caused by sickle hemoglobin polymerization is a primary cause of impaired erythrocyte filterability in sickle cell disease (SCD). However, oxidative inflammation is also involved in the pathophysiology of SCD. The physiologic level of ROS acts as signaling molecules for adaptation to oxidative environment, but the pathological level of ROS induces suicidal erythrocyte death (eryptosis). These findings provide further insight into the ROS-related pathophysiology of many clinical conditions.

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.

Valvulo-Arterial Impedance and Dimensionless Index for Risk Stratifying Patients With Severe Aortic Stenosis.

The hemodynamic effects of aortic stenosis (AS) consist of increased left ventricular (LV) afterload, reduced myocardial compliance, and increased myocardial workload. The LV in AS patients faces a double load: valvular and arterial loads. As such, the presence of symptoms and occurrence of adverse events in AS should better correlate with calculating the global burden faced by the LV in addition to the transvalvular gradient and aortic valve area (AVA). The valvulo-arterial impedance (Zva) is a useful parameter providing an estimate of the global LV hemodynamic load that results from the summation of the valvular and vascular loads. In addition to calculating the global LV afterload, it is paramount to estimate the stenosis severity accurately. In clinical practice, the management of low-flow low-gradient (LF-LG) severe AS with preserved LV ejection fraction requires careful confirmation of stenosis severity. In addition to the Zva, the dimensionless index (DI) is a very useful parameter to express the size of the effective valvular area as a proportion of the cross-section area of the left ventricular outlet tract velocity-time integral (LVOT-VTI) to that of the aortic valve jet (dimensionless velocity ratio). The DI is calculated by a ratio of the sub-valvular velocity obtained by pulsed-wave Doppler (LVOT-VTI) divided by the maximum velocity obtained by continuous-wave Doppler across the aortic valve (AV-VTI). In contrast to AVA measurement, the DI does not require the calculation of LVOT cross-sectional area, a major cause of erroneous assessment and underestimation of AVA. Hence, among patients with LG severe AS and preserved LV ejection fraction, calculation of DI in routine echocardiographic practice may be useful to identify a subgroup of patients at higher risk of mortality who may derive benefit from aortic valve replacement. This article aims to elucidate the Zva and DI in different clinical situations, correlate with the standard indexes of AS severity, LV geometry, and function, and thus prove to improve risk stratification and clinical decision making in patients with severe AS.