Effect of hypertension on the optimal anthracycline cumulative dose for developing left ventricular dysfunction in patients with malignant lymphoma.

The most serious adverse effect of anthracycline chemotherapy is progressive dose-dependent left ventricular (LV) dysfunction, and a total cumulative doxorubicin dose ≥ 240 mg/m2 has been classified as putting patients at high risk for developing cardiac dysfunction. Hypertension is the single most important risk factor for heart failure and chemotherapy-induced LV dysfunction, but the effect of hypertension on the total cumulative doxorubicin dose to prevent the development of LV dysfunction in patients scheduled for anthracycline chemotherapy remains uncertain. The aim of this study was to investigate the effect of hypertension on the optimal total cumulative anthracycline dose to prevent the development of LV dysfunction in patients with malignant lymphoma. We retrospectively studied 92 patients with malignant lymphoma and preserved LV ejection fraction (LVEF) who underwent anthracycline chemotherapy. Echocardiography was performed before and 2 months after anthracycline chemotherapy. LV hypertrophy (LVH) was defined as concentric hypertrophy, and LV dysfunction after chemotherapy as a relative decrease in LVEF ≥ 5%. The cutoff value of the total cumulative doxorubicin dose for the development of LV dysfunction was lower for hypertensive patients (n = 23) than for non-hypertensive patients (n = 69) (259.3 mg/m2 vs. 358.9 mg/m2). Importantly, the cutoff value of the total cumulative doxorubicin dose to prevent the development of LV dysfunction in hypertensive patients with LVH was even lower at 40.1 mg/m2. A lower cumulative anthracycline dose can cause LV dysfunction in hypertensive patients with malignant lymphoma, especially when complicated by LVH. Our findings can thus be expected to have clinical implications for better management of such patients.

Characteristics of non-valvular atrial fibrillation with left atrial appendage thrombus who are undergoing appropriate oral anticoagulation therapy.

We investigated the characteristics of patients with non-valvular atrial fibrillation (NVAF) and left atrial (LA) appendage (LAA) thrombus who had been given appropriate oral anticoagulation therapy. We studied 737 NVAF patients who were scheduled for catheter ablation or electrical cardioversion. All patients received appropriate oral anticoagulation therapy for at least 3 weeks prior to echocardiography in accordance with the guidelines. Whether LAA thrombus was present or absent on transesophageal echocardiography (TEE) was determined by at least three senior echocardiologists. LAA thrombi were observed in 22 patients (3.0%). Multivariate logistic regression analysis showed that LAA flow and LA volume index were both independent predictors of LAA thrombus formation; however, LAA flow (≤ 18 cm/s) was indicated as a more powerful predictor. Moreover, the prevalence of LAA thrombus formation in patients with NVAF without LA enlargement (LA volume index ≤ 34 mL/m2) was extremely rare (0.4%). LAA thrombus formation in patients with a mildly dilated LA volume index of 34-49.9 mL/m2 and paroxysmal AF was also extremely rare (0.0%). LAA flow is strongly associated with LAA thrombus formation, even in NVAF patients treated with appropriate oral anticoagulation therapy. Augmented oral anticoagulation therapy or transcatheter or surgical LAA closure should be considered for such patients, especially for those with an LAA flow < 18 cm/s. Furthermore, TEE for evaluating LAA thrombus before catheter ablation or electrical cardioversion may be unnecessary for NVAF patients who are undergoing appropriate oral anticoagulation therapy, depending on LA size.

Easy-to-use preload stress echocardiography by using combined dynamic postural stress can identify high-risk patients with heart failure with reduced ejection fraction.

AIMS: Haemodynamic assessment during stress testing is not commonly performed in patients with heart failure with reduced ejection fraction (HFrEF) because of its invasiveness, lower feasibility, and safety concerns. This study aimed to assess the haemodynamic characteristics of patients with HFrEF in response to non-invasive preload stress during dynamic postural alterations achieved by combining both semi-sitting position and passive leg-lifting and to evaluate whether combined postural stress could be used for risk stratification in these patients. METHODS AND RESULTS: For this study, 101 patients with HFrEF and 35 age-matched and sex-matched healthy controls were prospectively recruited. After all standard echocardiographic measurements were obtained in the left decubitus position, all subjects underwent postural stress testing, which consisted of changing from semi-sitting position to passive leg-lifting. During a median follow-up period of 12.2 months, 21 (21%) patients developed adverse cardiovascular events. In patients without adverse cardiovascular events, the stroke volume index (SVi) significantly changed from 28 ± 8 to 35 ± 10 mL/m2 (P < 0.001) during combined postural stress. By contrast, ΔSVi during combined dynamic postural stress was significantly smaller in patients with cardiovascular events than in those without events (ΔSVi 3.4 ± 4.0 vs. 6.4 ± 3.8 mL/m2 , P = 0.002), which indicated severely diseased heart operated on a relatively flat portion of the Frank-Starling curve. In a multivariate Cox proportional hazard analysis, ΔSVi (hazard ratio 0.81, P = 0.02) was an independent predictor of future adverse cardiovascular events. CONCLUSIONS: The combined assessment of dynamic postural stress is a non-invasive, simple, quick, and easy-to-use clinical tool for assessing preload reserve and risk stratification in HFrEF patients.

"Accelerated aging" of the heart as heart failure with preserved ejection fraction-analysis using leg-positive pressure stress echocardiography.

The aging process is a significant risk factor for heart failure. The incidence of heart failure with preserved ejection fraction (HFpEF) dramatically increases with age. Although HFpEF occurs along a continuum of aging of the cardiovascular system, the pathophysiology that differentiates overt HFpEF from physiological aging is not fully understood. A total of 102 subjects were prospectively recruited: 25 patients with HFpEF and 77 healthy controls. Controls were stratified into three age-groups: young (n = 27, 20-40 years), middle aged (n = 25, 40-65 years), and elderly (n = 25, > 65 years). All participants underwent preload stress echocardiography using a leg-positive pressure (LPP) maneuver. With an increase in age, progressive concentric left ventricular (LV) remodeling was observed in healthy controls, resulting in the hemodynamic consequences of an age-dependent increase in the E/e' ratio (ANOVA, P < 0.001). During LPP stress, the E/e' ratio significantly increased in the middle-aged and elderly groups (from 8 ± 2 to 9 ± 3, from 10 ± 2 to 12 ± 3, P < 0.05, respectively), and this was more pronounced in patients with HFpEF (from 16 ± 5 to 17 ± 7, P < 0.05). Forward stroke volume (SV) significantly increased in each healthy group during LPP stress (all P < 0.001) but failed to increase in the HFpEF group (from 43 ± 13 to 44 ± 14 mL/m2, P = 0.65). In a multivariate analysis, LV mass index (odds ratio [OR] 1.051, P < 0.05), E/e' ratio (OR 1.480; P < 0.05), and change in SV (OR 0.780; P < 0.05) were independent parameters that differentiated HFpEF from physiological aging. Structural remodeling and impaired preload reserve may both be critical features that characterize the pathophysiology of HFpEF.

Association between clinical risk factors and left ventricular function in patients with breast cancer following chemotherapy.

The sequential or concurrent use of two different types of agents such as anthracyclines and trastuzumab may increase myocardial injury and cancer therapeutics-related cardiac dysfunction (CTRCD), which is often the result of the combined detrimental effect of the two therapies for breast cancer patients. However, the association between clinical risk factors and left ventricular (LV) function in such patients is currently unclear. We studied 86 breast cancer patients with preserved LV ejection fraction (LVEF) and treated with anthracyclines, trastuzumab, or both. Echocardiography was performed before and 16 days after chemotherapy. In accordance with the current position paper, clinical risk factors for CTRCD were defined as: cumulative dose of doxorubicin > 240 mg/m2, age > 65-year-old, body mass index > 30 kg/m2, previous radiation therapy, B-type natriuretic peptide > 100 pg/mL, previous history of cardiovascular disease, atrial fibrillation, hypertension, diabetes, and smoking. The relative decrease in LVEF after chemotherapy for patients with more than four risk factors was significantly greater than that for patients without (- 9.3 ± 10.8% vs. - 2.2 ± 10.2%; p = 0.02). However, this finding did not apply to patients with more than one, two or three risk factors. Patients with more than four risk factors also tended to show a higher prevalence of CTRCD than those without (14.3% vs. 2.8%; p = 0.12). Moreover, the relative decrease in LVEF became greater as the number of risk factors increased. This study found multiple risk factors were associated with LV dysfunction following chemotherapy. Our findings can thus be expected to have clinical implications for better management of patients with breast cancer referred for chemotherapy.

Impact of hypertension on left ventricular function in patients after anthracycline chemotherapy for malignant lymphoma.

BACKGROUND: Hypertension is considered an important risk factors for cancer therapeutics-related cardiac dysfunction (CTRCD) as well as heart failure. However, the impact of hypertension and left ventricular (LV) hypertrophy (LVH), which is associated with hypertension, on LV function in patients treated with anthracycline chemotherapy for malignant lymphoma remains uncertain. METHOD: We studied 92 patients with malignant lymphoma and with preserved LV ejection fraction (LVEF). Echocardiography was performed before and two-month after anthracycline chemotherapy. CTRCD was defined as the presence of an absolute decrease in LVEF ≥10% to a final value <53%. LVH was defined as concentric hypertrophy, which was determined as relative wall thickness ≥ 0.42 and LV mass index >95 g/m2 for females and > 115 g/m2 for males. RESULTS: Relative decrease in LVEF after anthracycline chemotherapy in patients with hypertension (n = 23) was significantly higher than that in patients without hypertension (n = 69) (-5.8% [-9.4, -1.3]) vs. (-1.1% [-4.1, 2.5]); P = .005). Moreover, the prevalence of CTRCD in patients with hypertension tended to be higher than in those without hypertension (17% vs. 5%, p = .09). A sequential logistic model for predicting CTRCD, based on baseline clinical variables including major clinical risk factors, was improved by the addition of the complication of hypertension (P = .049), and further improved by the addition of the presence of LVH (P = .023). CONCLUSIONS: Hypertension, especially when complicated by LVH, was found to be associated with LV dysfunction after anthracycline chemotherapy in patients with malignant lymphoma and preserved LVEF. Watchful observation or early therapeutic intervention may thus be needed for such patients by the addition of the presence of LVH.

Glucocorticoid-sensitive Paroxysmal Atrial Fibrillation, Sick Sinus Syndrome, and Mitral Regurgitation in a Patient with Malignant Rheumatoid Vasculitis.

An 80-year-old woman with rheumatoid arthritis presented with chest pain. Clinical examination revealed new-onset paroxysmal atrial fibrillation with symptomatic sinus pauses and worsening mitral regurgitation, which were both resistant to conventional therapies. Based on her skin lesions, an increase in pleural and pericardial effusion, possible myocardial involvement, and a positive finding for immune complex testing, rheumatoid vasculitis was diagnosed. Subsequent glucocorticoid therapy suppressed systemic inflammation, resulting in structural, functional, and electrical reverse remodeling of the left atrium with complete remission of atrial arrhythmias and also an improvement of mitral regurgitation. This case highlights the importance of evaluating the underlying disease activity in a case of de novo paroxysmal atrial fibrillation associated with systemic autoimmune disease.