Diastolic Functional Reserve Index Research Articles

Early reduction in cardiorespiratory fitness and diastolic reserve following radiation therapy for lung cancer

BackgroundContemporary radiotherapy for the treatment of lung cancer is effective in targeting tumor tissue while limiting heart exposure, yet cardiac toxicity still occurs, often becoming clinically apparent years later. Cardiorespiratory fitness (CRF) is an independent predictor of cardiovascular, cancer-related, and overall mortality and may serve as a sensitive measure of subclinical cardiac toxicity following anti-cancer treatments. Prior work has demonstrated a significant relationship between reduced CRF and impaired left-ventricular (LV) diastolic reserve in cancer survivors following thoracic radiotherapy. The purpose of this study was to assess early longitudinal changes in CRF and cardiac function in patients with lung cancer following radiotherapy.MethodsTen patients (69 [61–76] years, 70% female) with lung cancer without known cardiovascular disease scheduled to receive radiotherapy involving a clinically-relevant heart dose (≥ 5 Gy to > 10% of heart volume) were evaluated prior to and following treatment. Changes in CRF (peak oxygen consumption [VO2peak], oxygen uptake efficiency slope [OUES]), cardiac function (LV ejection fraction [LVEF], rest and exercise diastolic function [diastolic functional reserve index (DFRI)]), cardiac biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity C-reactive protein [hsCRP]), and health-related quality of life (HRQOL; Functional Assessment of Cancer Therapy-General-7 [FACT-G7]) were measured.ResultsThe VO2peak was reduced at baseline (1.245 [0.882–1.605] L·min− 1; 70 [62–86] %-predicted) and significantly declined (1.095 [0.810–1.448] L·min− 1, P = 0.047; 62 [56–76] %-predicted, P = 0.005) at 6.0 [3.0–6.0] months post-radiotherapy. Similarly, a significant decline in the OUES was observed (1.63 [1.27–1.88] to 1.57 [1.12–1.75], P = 0.032). Systolic cardiac function was normal at baseline and did not change following radiotherapy (LVEF; 62 [56–65]% to 66 [57–68]%, P = 0.475). The DFRI significantly declined following radiotherapy (34.9 [22.7–41.6] vs. 12.8 [3.1–35.9]). The hsCRP increased significantly from 4.4 [1.4–5.8] to 6.1 [3.7–20.7] g/L, P = 0.047 with a trend towards higher levels of NT-proBNP (65 [49–125] to 121 [88–191] pg/mL, P = 0.110). Health-related quality of life significantly decreased (FACT-G7; 21.5 [18.8–25] to 15.5 [11.5–20]; P = 0.021) post-radiotherapy.ConclusionsPatients with lung cancer receiving radiotherapy with a clinically-significant heart dose experience reductions in CRF (VO2peak, OUES) as early as six months following treatment with concurrent reductions in diastolic reserve (DFRI), HRQOL, and increases in cardiac biomarkers (NT-proBNP, hsCRP).

Determinants of Cardiorespiratory Fitness Following Thoracic Radiotherapy in Lung or Breast Cancer Survivors

We measured peak oxygen consumption (VO2) in previous recipients of thoracic radiotherapy and assessed the determinants of cardiorespiratory fitness with an emphasis on cardiac and pulmonary function. Cancer survivors who have received thoracic radiotherapy with incidental cardiac involvement often experience impaired cardiorespiratory fitness, as measured by reduced peak VO2, a marker of impaired cardiovascular reserve. We enrolled 25 subjects 1.8 (0.1 to 8.2) years following completion of thoracic radiotherapy with significant heart exposure (at least 10% of heart volume receiving at least 5 Gray). All subjects underwent cardiopulmonary exercise testing, Doppler echocardiography, and circulating biomarkers assessment. The cohort included 16 Caucasians (64%), 15 women (60%) with a median age of 63 (59 to 66) years. The peak VO2 was 16.8 (13.5 to 21.9) ml·kg-1·min-1 or moderately reduced at 62% (50% to 93%) of predicted. The mean cardiac radiation dose was 5.4 (3.7 to 14.7) Gray, and it significantly correlated inversely with peak VO2 (R = -0.445, p = 0.02). Multivariate regression analysis revealed the diastolic functional reserve index and the N-terminal pro-brain natriuretic peptide (NTproBNP) serum levels were independent predictors of peak VO2 (ß = +0.813, p <0.01 and ß = -0.414, p = 0.04, respectively). In conclusion, patients who had received thoracic radiation display a dose-dependent relation between the cardiac radiation dose received and the impairment in peak VO2, the reduction in diastolic functional reserve index, and elevation of NTproBNP.

Comprehensive assessment of physical fitness in patients with depression

We measured peak oxygen consumption (VO2) in previous recipients of thoracic radiotherapy and assessed the determinants of cardiorespiratory fitness with an emphasis on cardiac and pulmonary function. Cancer survivors who have received thoracic radiotherapy with incidental cardiac involvement often experience impaired cardiorespiratory fitness, as measured by reduced peak VO2, a marker of impaired cardiovascular reserve. We enrolled 25 subjects 1.8 (0.1 to 8.2) years following completion of thoracic radiotherapy with significant heart exposure (at least 10% of heart volume receiving at least 5 Gray). All subjects underwent cardiopulmonary exercise testing, Doppler echocardiography, and circulating biomarkers assessment. The cohort included 16 Caucasians (64%), 15 women (60%) with a median age of 63 (59 to 66) years. The peak VO2 was 16.8 (13.5 to 21.9) ml·kg−1·min−1 or moderately reduced at 62% (50% to 93%) of predicted. The mean cardiac radiation dose was 5.4 (3.7 to 14.7) Gray, and it significantly correlated inversely with peak VO2 (R = −0.445, p = 0.02). Multivariate regression analysis revealed the diastolic functional reserve index and the N-terminal pro-brain natriuretic peptide (NTproBNP) serum levels were independent predictors of peak VO2 (ß = +0.813, p <0.01 and ß = −0.414, p = 0.04, respectively). In conclusion, patients who had received thoracic radiation display a dose-dependent relation between the cardiac radiation dose received and the impairment in peak VO2, the reduction in diastolic functional reserve index, and elevation of NTproBNP.

Left and Right Ventricular Systolic and Diastolic Functional Reserves Are Impaired in Anthracycline-Treated Long-Term Survivors of Childhood Cancers

The aim of this study was to test the hypothesis that left ventricular (LV) and right ventricular (RV) functional reserves are altered in anthracycline-treated long-term survivors of childhood cancers. One hundred three survivors (55% men) aged 25.0±5.8years at 15.2±5.8years after chemotherapy and 61 healthy control subjects (52% men) were studied. Tissue Doppler-derived mitral and tricuspid systolic (s) and early diastolic (e) velocities and LV myocardial acceleration during isovolumic contraction (IVA) were determined at rest and during bicycle exercise. The slope of the LV force-frequency relationship was derived from changes in IVA with heart rate during exercise (ΔIVA/Δ[heart rate]). LV and RV functional reserves were further assessed by the systolic functional reserve index (Δs×[1-1/s at baseline]) and diastolic functional reserve index (Δe×[1-1/e at baseline]). At baseline, mitral annular tissue Doppler indices were similar between survivors and control subjects (P>.05 for all), while tricuspid s and e velocities were significantly lower in survivors (P<.05 for both). The force-frequency relationship slope (P<.001), LV systolic functional reserve index (P<.001), and RV systolic functional reserve index (P=.001) were significantly lower in survivors than control subjects. For diastolic functional reserve, LV but not RV diastolic functional reserve index was significantly lower in survivors (P<.001). Multivariate analysis revealed survivor status (β=-0.39, P<.001) and baseline LV IVA (β=0.15, P<.044) as significant determinants of the LV force-frequency relationship. LV and RV functional reserves during exercise are impaired in anthracycline-treated long-term survivors of childhood cancer.

Relationship of biomarkers of extracellular matrix with myocardial function in Type 2 diabetes mellitus.

The study evaluated the relationship of extracellular matrix and renin angiotensin system with myocardial dysfunction in Type 2 diabetes mellitus. All patients underwent resting and exercise echocardiography, including conventional parameters, E/E' ratio, global longitudinal strain and diastolic function reserve index. Plasma matrix metalloproteinase-1, TIMP-1, amino-terminal propeptide of type I and type III procollagen and renin angiotensin system activity were measured. As patients with diastolic dysfunction had a higher plasma level of TIMP-1 and propeptide of type III procollagen than those with no diastolic dysfunction. After multivariate adjustment, TIMP-1 associated with E/E' (both at rest and stress) and diastolic function reserve index. TIMP-1 is independently associated with myocardial diastolic dysfunction in patients with Type 2 diabetes mellitus.

Impaired myocardial relaxation with exercise determines peak aerobic exercise capacity in heart failure with preserved ejection fraction.

BackgroundHeart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by impaired exercise capacity due to shortness of breath and/or fatigue. Assessment of diastolic dysfunction at rest and with exercise may provide insight into the pathophysiology of exercise intolerance in HFpEF.AimsTo measure echocardio‐Doppler‐derived parameters of diastolic function as they relate to various indices of aerobic exercise capacity in HFpEF.MethodsWe selected 16 subjects with clinically stable HFpEF, no evidence of volume overload, but impaired functional capacity by cardiopulmonary exercise testing [peak oxygen consumption (VO2)]. We measured the transmitral E and A flow velocities, E/A ratio, and E deceleration time (DT) and tissue Doppler E′ velocity. We also indexed the E′ to the DT, as additional measure of impaired relaxation (E′DT), and calculated the diastolic functional reserve index (DFRI), as the product of E′ at rest and change in E′ with exercise.ResultsE′ velocity, at rest and peak exercise, as well as the DFRI positively correlated with peak VO2, whereas DT, E′DT, and E/E′ with exercise inversely correlated with peak VO2. Of note, the E′DT at rest also significantly predicted E′ velocity at peak exercise (R = +0.81, P < 0.001). Exercise E′ was the only independent predictor of peak VO2 at multivariable analysis (R = +0.67, P = 0.005).ConclusionsThe E′ velocity at peak exercise is a strong and independent predictor of aerobic exercise capacity as measured by peak VO2 in patients with HFpEF, providing the link between abnormal myocardial relaxation with exercise and impaired aerobic exercise capacity in HFpEF.

Altered myocardial response in patients with diabetic retinopathy: an exercise echocardiography study.

BackgroundType 2 diabetes mellitus (T2DM) complicated by retinopathy is associated with altered left ventricular (LV) structure and resting myocardial dysfunction unlike T2DM without retinopathy. The myocardial response to stress has not been compared in patients with and without diabetic retinopathy. The aim of this retrospective study was to determine the relationship between retinopathy and myocardial function in patients with T2DM at rest and during exercise echocardiography.Methods134 patients with T2DM and no evidence of underlying coronary artery disease were recruited. All patients underwent retinal photography to screen for diabetic retinopathy, and resting and exercise echocardiography. Resting echocardiography was analyzed by conventional echocardiographic parameters and speckle tracking derived global longitudinal strain (GLS). Exercise echocardiography parameters included diastolic function reserve index (DFRI) and stress GLS.ResultsThe mean age of participants was 60 years and 49 % were male. Diabetic retinopathy was identified in 43 patients (32 %). Resting echocardiography revealed that those with diabetic retinopathy had a higher prevalence of impaired diastolic function, higher E/E′ ratio (LV filling pressures) and impaired resting GLS compared with those without. Exercise echocardiography revealed that those with diabetic retinopathy also had more impaired DFRI and stress GLS. Multivariable analysis showed that the presence of diabetic retinopathy was independently associated with high resting E/E′, diastolic dysfunction grade, impaired resting GLS, low DFRI and impaired stress GLS.ConclusionsIn conclusion, the presence of diabetic retinopathy was independently associated with impaired resting myocardial function (diastolic and systolic function) and myocardial function during stress (evaluated by DFRI and stress GLS).Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-015-0281-5) contains supplementary material, which is available to authorized users.

The relationship between ventricular-vascular uncoupling during exercise and impaired left ventricular longitudinal functional reserve in hypertensive patients

Uncoupling between heart and vessel may be accompanied by left ventricular (LV) dysfunction during exercise. We investigated the association between ventricular-vascular uncoupling during exercise and impaired LV longitudinal functional reserve in hypertensive subjects. Supine bicycle exercise echocardiography (25-watt, 3-minute increments) was performed in 216 hypertensive patients (106 male; mean age, 58 ± 9 years). Arterial elastance (Ea), end-systolic ventricular elastance (Ees), and ventricular-vascular interaction (VVI) index (Ea/Ees) were calculated at rest and at each stage of exercise. The patients were divided into three groups according to the tertile value of VVI ratio. The VVI ratio was defined as the ratio of VVI index at 50 W exercise over VVI index at rest; normal VVI response (n = 72); borderline VVI response (n = 72); and abnormal VVI response (n = 72). There were no significant differences in conventional echo parameters, mitral inflow velocities, mitral annular early diastolic (E’) velocity, and mitral annular systolic velocity (S’) at rest among the three groups. However, E’ velocities and S’ velocities at 25 W and 50 W were significantly lower in patients with abnormal VVI response compared with those in the other groups (P = .010 at 25 W, P = .008 at 50 W in E’ velocity; P = .022 at 25 W, P = .043 at 50 W in S’ velocity). Longitudinal diastolic functional reserve index from rest to 50 W was significantly lower in patients with abnormal VVI response compared with the other groups. Ventricular-vascular uncoupling during exercise was related to impaired LV longitudinal functional reserve in hypertensive patients.

Usefulness of At Rest and Exercise Hemodynamics to Detect Subclinical Myocardial Disease in Type 2 Diabetes Mellitus

Patients with type 2 diabetes mellitus (T2DM) might have subclinical myocardial dysfunction identified at rest or unmasked during exercise. We examined the correlates of the myocardial exercise response in patients with T2DM. Myocardial dysfunction was sought during at rest and exercise echocardiography in 167 healthy patients with T2DM (97 men, 55 ± 10 years). Myocardial ischemia was excluded using stress echocardiography. Standard echocardiography and color tissue Doppler imaging measures (early diastolic tissue velocity [Em], strain, and strain rate) were acquired at baseline and peak stress. The calibrated integrated backscatter was calculated from the at rest parasternal long-axis view. The longitudinal diastolic functional reserve index after exercise was defined as ΔEm [1 - (1/Em(base))]. The clinical, anthropometric, and metabolic data were collected at rest and stress. Subclinical myocardial dysfunction at baseline (n = 24) was independently associated with weight (odds ratio [OR] 1.02, p = 0.04) and hemoglobin A1c (OR 1.36, p = 0.03). This group displayed an impaired exercise response that was independently associated with a reduced exercise capacity (OR 0.84, p = 0.034) and longitudinal diastolic functional reserve index (OR 0.69, p = 0.001). Inducible myocardial dysfunction (stress Em <-9.9 cm/s) was identified after exercise in 70 of the remaining 143 subjects. This finding was associated with calibrated integrated backscatter (OR 1.08, p = 0.04) and lower peak heart rate (OR 0.97, p = 0.002) but not metabolic control. The intensity of the metabolic derangement in patients with T2DM was associated with subclinical at rest myocardial dysfunction, but not with the myocardial exercise response. In conclusion, the association of an abnormal stress response with nonmetabolic factors, including backscatter and blunted peak heart rate, suggests potential roles for myocardial fibrosis and cardiac autonomic neuropathy in patients with nonischemic diabetic heart disease.

Passive Leg-Raise Is Helpful to Identify Impaired Diastolic Functional Reserve During Exercise in Patients With Abnormal Myocardial Relaxation

The aim of this study was to demonstrate the usefulness of leg raise in identifying lower diastolic functional reserve to exercise. One hundred fifty-four patients with abnormal left ventricular relaxation on Doppler mitral inflow with preserved left ventricular ejection fractions were enrolled. After resting evaluations, Doppler echocardiographic measurements were repeated during passive leg raise and graded supine bicycle exercise. Patients were divided into 3 groups according to resting E/e' ratio and its response to leg raise: group IA (persistent E/e' < 15 [n = 112]), group IB (change to E/e' > or = 15 after leg raise [n = 19]), and group II (persistent E/e' > or = 15 [n = 23]). Group II had lower S', e', and diastolic reserve index values during exercise compared with group IA but not with group IB. Group IB had higher E/e' ratios during exercise and lower diastolic functional reserve index values accompanied by lower exercise capacity compared with group IA. Passive leg raise might be helpful in identifying a subgroup with lower diastolic functional reserve and lower exercise capacity among patients with abnormal relaxation.

Abstract 4204: Impact of Left Ventricular Diastolic Functional Reserve on Clinical Outcome in Patients with Diabetes Mellitus

Left ventricular (LV) longitudinal diastolic functional reserve, assessed by the change of early diastolic mitral annular velocity (E′) during exercise, is abnormal in patients with diabetes without overt heart disease. However, its impact on clinical outcome has not been explored previously. We hypothesized that LV diastolic reserve could further stratify diastolic dysfunction, and have a prognostic significance in patients with diabetes. Of 1,170 patients who were referred for diastolic stress echocardiography, 227 consecutive patients (mean age 58 years, male 103, mean ejection fraction [EF] 68 %) with diabetes were identified. LV diastolic function reserve index (DFRI) was calculated as E′ base x ΔE′; where ΔE′ is the change of E′ from baseline to exercise. The primary end-point was a composite of all-cause death and re-hospitalization for heart failure. The median follow-up duration was 34 months, and the primary end-point was occurred in 14 (6.1%) of 227 patients. Among the predictors that showed a significance in the univariate Cox analysis, including age, coronary artery disease history, renal insufficiency, LV mass index, LAVI, and EF, LV DFRI was the most independent predictor of adverse outcomes. When patients were classified by the median value of DFRI at 50W of exercise, patients with DFRI &lt; 13.5 showed poorer clinical outcomes compared to those with DFRI ≥ 13.5 (p=0.001). The assessment of LV diastolic functional reserve using exercise Doppler echocardiography is helpful in further stratifying diastolic dysfunction, and provides incremental prognostic information in patients with diabetes without overt heart disease.

Left ventricular diastolic functional reserve during exercise in patients with impaired myocardial relaxation at rest

Background: Patients with similar grade diastolic dysfunction at rest may have a spectrum of alterations in diastolic function during exercise. Objective: To evaluate (a) whether exercise could unmask further diastolic...

Incremental Value of Left Ventricular Diastolic Function Reserve Index for Predicting Exercise Capacity in Patients with Hypertrophic Cardiomyopathy

The changes of left ventricular diastolic function during exercise are heterogeneous in patients with hypertrophic cardiomyopathy (HCM). We sought to investigate whether exertional changes of mitral annular velocities and plasma N-terminal-pro-B-type natriuretic peptide (BNP) concentration are associated with exercise capacity in patients with HCM. After a comprehensive echocardiographic study, 32 patients with HCM performed symptom-limited graded supine bicycle exercise. Echocardiographic Doppler parameters were measured at each stage of exercise. Blood samples were collected at rest and immediately after exercise to determine the concentration of pro-BNP. Resting pro-BNP (r = -0.620, P < .001), E'(base) (r = 0.414, P = .018), and DeltaE'(50W) (change of E' from base to 50 W of exercise) (r = 0.367, P = .039) were significantly correlated with exercise duration. Left ventricular longitudinal diastolic function reserve index, defined as DeltaE' x E'(base), significantly correlated with exercise duration (at 50 W, r = 0.540, P = .001) independent of age, sex, body mass index, and resting pro-BNP level. When combining DeltaE' x E'(50W) (<5.85 cm(2)/s(2)) and resting pro-BNP (>740 mg/dL), the predictive accuracy for exercise capacity could be improved (for <500 seconds, global chi(2) = 5.84 in pro-BNP vs 8.10 in pro-BNP + DeltaE' x E'(50W), P = .023). The assessment of left ventricular longitudinal diastolic function reserve can provide incremental information to pro-BNP for the prediction of exercise capacity in patients with HCM.