Abnormal Left Ventricular Relaxation Research Articles

Association of body adiposity with left ventricular concentric remodeling and diastolic dysfunction

AbstractBackgroundObesity is a significant risk factor for heart failure with preserved ejection fraction (HFpEF). In this study, we explore the relationships between body mass index (BMI) and adipose tissue compartments such as visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and epicardial adipose tissue (EAT), with respect to left ventricular (LV) structure and function in subjects with preserved LV systolic function.MethodsBetween January and December 2020, this retrospective study included 749 participants who exhibited preserved LV systolic function and underwent transthoracic echocardiography along with abdominal computed tomography. LV structural and functional variables as well as EAT, VAT, and SAT thickness were evaluated using echocardiography and computed tomography.ResultsSAT decreased, while VAT and EAT progressively increased with age. There were significant correlations between BMI and various adipose tissues, with the strongest correlation observed with SAT (r = .491, p < .001) compared to VAT (r = .371, p < .001) or EAT (r = .135, p < .001). However, EAT demonstrated the most substantial association with decreased LV end‐diastolic dimension, LV end‐systolic dimension, and septal mitral annular velocity and increased relative wall thickness (all p < .05), while VAT and SAT did not show significant associations with LV remodeling and functional parameters after adjusting for clinical variables.ConclusionEAT is the most critical adipose tissue influencing LV geometric and functional changes, compared with VAT or SAT. Thick EAT is associated small LV chamber size, concentric remodeling, and relaxation abnormalities.

Diastolic function in chronic kidney disease.

Chronic kidney disease (CKD) is characterized by clustered age-independent concentric left ventricular (LV) geometry, geometry-independent systolic dysfunction and age and heart rate-independent diastolic dysfunction. Concentric LV geometry is always associated with echocardiographic markers of abnormal LV relaxation and increased myocardial stiffness, two hallmarks of diastolic dysfunction. Non-haemodynamic mechanisms such as metabolic and electrolyte abnormalities, activation of biological pathways and chronic exposure to cytokine cascade and the myocardial macrophage system also impact myocardial structure and impair the architecture of the myocardial scaffold, producing and increasing reactive fibrosis and altering myocardial distensibility. This review addresses the pathophysiology of diastole in CKD and its relations with cardiac mechanics, haemodynamic loading, structural conditions, non-haemodynamic factors and metabolic characteristics. The three mechanisms of diastole will be examined: elastic recoil, active relaxation and passive distensibility and filling. Based on current evidence, we briefly provide methods for quantification of diastolic function and discuss whether diastolic dysfunction represents a distinct characteristic in CKD or a proxy of the severity of the cardiovascular condition, with the potential to be predicted by the general cardiovascular phenotype. Finally, the review discusses assessment of diastolic function in the context of CKD, with special emphasis on end-stage kidney disease, to indicate whether and when in-depth measurements might be helpful for clinical decision making in this context.

Abstract 15848: Prognostic Value of Left Ventricular Diastolic Function in Patients With Hypertrophic Cardiomyopathy

Background: Diastolic dysfunction (DD) is frequently present in patients with hypertrophic cardiomyopathy (HCM) due to abnormal left ventricular (LV) relaxation, wall hypertrophy, increased LV filling pressures and myocardial disarray and fibrosis, even though ejection fraction (EF) remains preserved until late stages. Our aim was to investigate in a large cohort whether contemporary markers of DD and increased filling pressures are associated with outcomes in these patients. Methods: We screened consecutive patients with HCM who had transthoracic echocardiography and no significant valvular heart disease. The associations of septal/lateral e’ velocity, E/e’, left atrial volume index (LAVi), and tricuspid regurgitant velocity (TR) with all-cause mortality were tested. A diastolic score (DS) was also calculated (1 point for each abnormality in e’, E/e’, TR, LAVi). Results: 1,496 patients with HCM were studied (mean age 52±15 yrs; 61% men; LV EF 69±7%; Table). Diastolic abnormalities were highly prevalent in these patients ( Table ). In the subset without septal reduction therapy (SRT; n=900), at a median followup of 9 years (IQR 7-11 yrs; n=78 deaths), increased E/e’ and DS were strongly associated with mortality (log-rank P <.0001 for both; Figure ). However, E/e’ did not remain significant in multivariable models after adjustment for known cardiac risk factors or other significant confounders ( Table ). In contrast, DS >2 remained independently associated with ~2-fold higher mortality risk (adjusted HR 1.91 [1.14-3.20, P =.01]; n=693; Table). In patients who underwent SRT (n=596), these associations showed the same trend but attenuated. Conclusion: In HCM patients who did not require SRT, the severity of DD was associated with mortality, independent of cardiac pump function or known cardiac risk factors. The composite score was more powerful than E/e’. Further studies are needed to fully understand the impact of DD in these patients with and without SRT.

Left ventricular diastolic abnormalities in vegetarians compared with non-vegetarians.

Vegetarians have less hypertension, diabetes mellitus and obesity, hence possibly lower risk of congestive heart failure (HF). We studied associations between vegetarian diets and echocardiographic markers of stage B HF. In a cross-sectional study, dietary pattern was ascertained by a validated FFQ. Echocardiograms were interpreted using standardised criteria. Participants were free-living subjects in Southern California who were older Adventist Health Study-2 cohort members. After exclusions, 133 subjects aged >60 years were enrolled. Their mean age was 72·7 (sd 8·7) years, 48·1 % were female, 32 % were African American and 71 % were vegetarian. Non-vegetarians had higher body weight (80·3 (sd 15·17) kg v. 71·3 (sd 16·2), P < 0·005), body surface area (1·92 (sd 0·24) m2v. 1·81 (sd 0·22) m2, P = 0·01) and prevalence of hypertension (63 % v. 47 %, P = 0·10). Adjusting for age, sex, race and physical activity, it is found that vegetarians had greater echocardiographic mitral annular e' velocity (a measure of left ventricular (LV) relaxation) 7·44 v. 6·48 (non-vegetarian) cm/s (P = 0·011) and a yet greater contrast when vegans (7·66 cm/s, P = 0·011) were the group of interest. The ratio mid-to-late-diastolic mitral flow velocity (E/A) was also higher in vegans compared with non-vegetarians (1·02 and 0·84, respectively, P = 0·008). Mediation analyses suggested these associations may be partly related to higher blood pressures and BMI in the non-vegetarians. We conclude that vegetarians, especially vegans, appear to have better LV relaxation and fewer diastolic abnormalities than others. As dietary exposure is modifiable, one may speculate pending further investigation about the potential for reduction of stage B HF and later mortality.

MO158: The Association of Left Ventricular Diastolic Dysfunction and Heart Failure in Patients with Chronic Kidney Disease

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) has been linked with an increased risk of cardiovascular events, especially in dialysis population. According to literature data, in the patients with CKD heart function disturbances are twice as common as in the general population [1]. Bearing in the mind that left ventricular hypertrophy (and abnormal left ventricular relaxation) is considered to be one of the most important parameters for the occurrence of cardiovascular disease in CKD [2], the aim of our study was to evaluate the association of left ventricular diastolic dysfunction with heart failure in CKD patients. METHOD The research was conducted as a prospective observational study which included 30 patients with CKD, stage III and IV according KDIGO [3], and left ventricular diastolic dysfunction, and 30 control subjects who also had left ventricular diastolic dysfunction but without CKD. Pulse-wave (PW) Doppler echocardiography in the apical four-chamber view and tissue Doppler imaging were performed to assess left ventricular function [4]. The measurements of mitral inflow by PW Doppler covered early (E-wave) and late (A-wave) diastolic feeling velocities, peak early diastolic velocity at the septal (e′septal) and lateral (e′lateral) mitral annular sites, and E/A ratio. RESULTS A comparison of left ventricular function parameters between two groups of study participants indicated that left ventricular ejection fraction (0.57 ± 0.05% versus 0.61 ± 0.03%) was statistically reduced in CKD patients compared to control subjects (P &amp;lt; .001). Contrary, left ventricular mass index (119.8 ± 27.0 g/m2 versus 100.8 ± 20.4 g/m2P = .003) and interventricular septum thickness (11.8 ± 1.4 mm versus 10.8 ± 1.5 mm, P = .012) were significantly higher in the patients with CKD. There were no significant differences in values of left ventricular end-diastolic (53.7 ± 4.6 mm versus 54.2 ± 3.5 mm, P = .636) and left ventricular end-systolic (34.7 ± 4.5 mm versus 35.7 ± 2.3 mm, P = .265) dimension between CKD patients and controls. The mitral inflow imaging pointed to more pronounced left ventricular diastolic dysfunction in CKD patients than in the subjects without CKD: e′septal (P = .009) and e′lateral (P &amp;lt; .001) velocity. E/A ratio showed no markedly deviation between two study groups (P = .787). On the other hand, when we analysed the frequency of heart failure, it was noted that newly developed episodes of cardiac decompensation were more frequent in patients with CKD than in the control group (Chi square = 6.667, P = .010). Regression analysis confirmed the predictive significance of left ventricular echosonographic characteristics on the occurrence of heart failure in patients with CKD (OR 1.56, 95% CI 1.11‒2.18, P = .011 for left ventricular mass index; OR 1.68, 95% CI 1.01‒2.80, P = .048 for e′). CONCLUSION Heart failure is more common in patients with CKD than in patients with normal kidney function. There is a positive relationship between the presence of left ventricular diastolic dysfunction and the occurrence of heart failure in patients with CKD.

Left Ventricular Diastolic Dysfunction in Chronic Thromboembolic Pulmonary Hypertension

<h3>Purpose</h3> Impairment of left ventricular (LV) relaxation is associated with increased mortality after surgical treatment of pulmonary hypertension (PH). We sought to describe the pathophysiology of LV diastolic dysfunction in a porcine model of chronic thromboembolic pulmonary hypertension (CTEPH). The reversibility of LV diastolic dysfunction was investigated in patients with CTEPH after pulmonary endarterectomy (PEA). <h3>Methods</h3> CTEPH was induced in 2-month-old Large White piglets (PH group, n=6) by ligation of the left pulmonary artery (PA) followed by weekly embolization of right lower lobe for 5 weeks using a strong tissue glue (N-acetyl cyanoacrylate). These animals were compared to sham-operated animals (controls, n=6). LV diastolic function was assessed using echocardiography and conductance catheter measurements. LV fibrosis was investigated at 6 weeks using red Sirius staining of myocardial tissues. Echocardiographic measurements for LV diastolic function were retrospectively analyzed in 102 patients, before and after PEA. <h3>Results</h3> Mean PA pressure was higher at 6 weeks in PH animals compared to controls (28.5 [28.0; 34.2] vs. 14.0 [12.5; 14.0] mmHg, p<0.01). Increased end-diastolic LV pressure was observed in PH group (21.9 [18.1; 22.7] vs. 12.2 [11.7; 13.8] mmHg, p=0.013), along with a marked decrease in the curve-fitting constant (c) and the maximum rate of LV filling (dV/dt_max), respectively by 49% (p=0.03) and 74% (p=0.014). Stiffness constant ß was strongly correlated with Doppler imaging index E/A (r=-0.94, p=0.015). Mean LV fibrosis score was significantly higher in PH group at 6 weeks (5.11±0.89% vs. 3.29±1.14%, p<0.01). Pre-operative impairment of LV filling pattern was remarkable in patients with CTEPH (E/A = 0.81±0.32; E/E'=6.42±2.84), and significantly improved at 7 days post PEA (+30%, p<0.001). At 6 months, E/A ratio was significantly higher (0.91 [0.75; 1.20] vs. 0.76 [0.66; 0.94], p=0.05) but remained abnormal, despite significant decrease in mean pulmonary vascular resistance (7.3 ±3.1WU vs. 3.8±1.5WU, p<0.001). <h3>Conclusion</h3> Impaired myocardial stiffness was associated with LV fibrosis in our piglet model of CTEPH. Mild LV diastolic dysfunction was observed at 6 months in patient with CTEPH despite significant decrease in RV pressure overload after PEA. Myocardial fibrosis may be responsible for persistent abnormal LV relaxation.

Different Pathophysiology and Outcomes of Heart Failure With Preserved Ejection Fraction Stratified by K-Means Clustering.

Background: Stratified medicine may enable the development of effective treatments for particular groups of patients with heart failure with preserved ejection fraction (HFpEF); however, the heterogeneity of this syndrome makes it difficult to group patients together by common disease features. The aim of the present study was to find new subgroups of HFpEF using machine learning.Methods: K-means clustering was used to stratify patients with HFpEF. We retrospectively enrolled 350 outpatients with HFpEF. Their clinical characteristics, blood sample test results and hemodynamic parameters assessed by echocardiography, electrocardiography and jugular venous pulse, and clinical outcomes were applied to k-means clustering. The optimal k was detected using Hartigan's rule.Results: HFpEF was stratified into four groups. The characteristic feature in group 1 was left ventricular relaxation abnormality. Compared with group 1, patients in groups 2, 3, and 4 had a high mean mitral E/e′ ratio. The estimated glomerular filtration rate was lower in group 2 than in group 3 (median 51 ml/min/1.73 m2 vs. 63 ml/min/1.73 m2 p < 0.05). The prevalence of less-distensible right ventricle and atrial fibrillation was higher, and the deceleration time of mitral inflow was shorter in group 3 than in group 2 (93 vs. 22% p < 0.05, 95 vs. 1% p < 0.05, and median 167 vs. 223 ms p < 0.05, respectively). Group 4 was characterized by older age (median 85 years) and had a high systolic pulmonary arterial pressure (median 37 mmHg), less-distensible right ventricle (89%) and renal dysfunction (median 54 ml/min/1.73 m2). Compared with group 1, group 4 exhibited the highest risk of the cardiac events (hazard ratio [HR]: 19; 95% confidence interval [CI] 8.9–41); group 2 and 3 demonstrated similar rates of cardiac events (group 2 HR: 5.1; 95% CI 2.2–12; group 3 HR: 3.7; 95%CI, 1.3–10). The event-free rates were the lowest in group 4 (p for trend < 0.001).Conclusions: K-means clustering divided HFpEF into 4 groups. Older patients with HFpEF may suffer from complication of RV afterload mismatch and renal dysfunction. Our study may be useful for stratified medicine for HFpEF.

Key factors of diastolic dysfunction and abnormal left ventricular relaxation in diabetic rats.

To study the diastolic functions using color Doppler M-mode (CDMM) for noninvasive analysis of the intraventricular pressure difference (IVPD) in diabetic rats. Two equal groups of rats were included: control and streptozotocin-induced DM (n = 15). The cardiac functions were examined monthly using conventional echocardiography and CDMM with a specific MATLAB software. Echocardiography was performed under 2% isoflurane mask inhalation. Five months thereafter, all rats were killed for macroscopic and microscopic examinations of the cardiac fibrosis. DM rats showed higher systolic blood pressure and diastolic dysfunction, i.e., decreases in several parameters such as E, E/A, TDIs, and IVPDs, compared to the controls. Moreover, obvious cardiac fibrosis was seen in perivascular and interstitial tissues, but there were no notable differences in terms of gross lesions. Because of the noninvasive nature of CDMM, IVPD and other conventional echocardiographic parameters can be used as reliable indicators generally for evaluating cardiac function and particularly the change in intraventricular pressure.

14 Myocardial dysfunction in ANCA vasculitis measured by two-dimensional speckle tracking echocardiography

Aim Myocardial involvement in patients with systemic vasculitis portends a poorer prognosis. We sought to determine the extent of myocardial dysfunction in Granulomatosis with polyangitis and Churg Strauss disease using speckle tracking and strain imaging. Methods 20 patients and 22 controls with no prior cardiac history were recruited from December 2015 to April 2016. Baseline demographics recorded included age, sex, cardiovascular risk factors, time since diagnosis, immunosuppressive therapy and vasculitis damage index score (VDI). We performed transthoracic echocardiography using Vivid 7 GE machine along with twelve lead electrocardiograms (ECG) and biochemical analysis at the study visit. A single blinded operator utilising Echo Pac 11 software performed offline analysis of strain and speckle tracking measurements. Results Mean age of the vasculitis group was 56 ± 10 years with 50% being male, while mean age of controls was 53 ± 9 years with 55% male. There were no significant differences between groups in age, incidence of hypertension (p = 0.3) or diabetes (p = 0.6). Radial strain was significantly reduced in the vasculitis cohort (P = 0.05). The vasculitis cohort also showed a non-significant reduction in longitudinal strain and abnormal diastology as reflected in a reduction in tissue Doppler E’ velocities, decreased transmittal E/A ratio and increased E/E’ ratio when compared to controls (Table 1). There were negative correlations between increasing VDI score and reduction in mitral inflow velocities r = −0.5 (p = 0.02), number of clinical relapses and tissue Doppler E’ r = −0.6 (p = 0.009) and length of cyclophosphamide use with tissue Doppler E’ r = −0.5 (p = 0.02). Conclusion This is one of the largest studies investigating myocardial dysfunction in ANCA positive vasculitis. Patients demonstrated a reduction in radial strain and evidence of abnormal left ventricular relaxation. This may be indicative of underlying cardiac involvement.

Challenges for 'diastology': contributions from Japanese researchers.

Diastology is a study to treat diastole of the heart. Transmitral flow and pulmonary venous flow velocities recorded by pulsed Doppler echocardiography provide more important information about left ventricular (LV) diastolic dysfunction [left atrial (LA)-LV coupling] than cardiac catheterization in clinical practice; however, these waveforms are influenced by loading conditions, particularly preload. The early diastolic mitral annular and LV wall motion indices measured by tissue Doppler echocardiography can evaluate LV relaxation abnormality and filling pressure by being relatively preload independent. In addition, the role of concomitant systolic longitudinal dysfunction is well characterized in asymptomatic patients and in patients with heart failure and preserved ejection fraction. Two-dimensional speckle tracking echocardiography is an angle-independent method, and has the potential to evaluate the contraction and relaxation abnormalities in the longitudinal, circumferential, and radial directions of the LV myocardium as well as LV torsion/untwisting and, moreover, deformation of the LA myocardium and large arterial wall. As a result, this new technique can facilitate the early detection of impaired LA-LV-arterial coupling in patients before occurrence of overt heart failure symptoms.

Effect of non-alcoholic fatty liver disease on left ventricular diastolic function and geometry in the Korean general population.

Previous studies showed that non-alcoholic fatty liver disease (NALFD) could be related to subclinical left ventricular (LV) diastolic dysfunction and remodeling. However, this association is still equivocal in the general population. Thus, this study was carried out to examine whether NAFLD is associated with the risk for LV diastolic dysfunction and remodeling. A cross-sectional study was carried out for 20 821 Korean men and women who received a health checkup including echocardiography from 2011 to 2012. The study population was divided into three groups of normal, mild and moderate-to-severe NAFLD detected by ultrasonography. Using multivariable logistic regression analysis, the odd ratios of abnormal LV relaxation and remodeling were analyzed according to the degree of NAFLD. Additionally, adjusted mean values of LV diastolic functional and structural parameters were evaluated in the three groups. Compared with the normal group, the mild and moderate-to-severe NAFLD groups had higher odd ratios for abnormal LV relaxation (mild group 1.29, 95% confidence interval 1.15-1.46; moderate-to-severe group 1.95, 95% confidence interval 1.61-2.35) and increased relative wall thickness (>0.42; mild group 1.26, 95% confidence interval 1.05-1.52; moderate-to-severe group 1.46, 95% confidence interval 1.08-1.95). Analyzing adjusted mean values of LV parameters also showed the significant association between the degree of NAFLD and impaired LV diastolic function and concentric LV remodeling. The risk for LV diastolic dysfunction and remodeling proportionally increased according to the degree of NAFLD. NAFLD is significantly associated with LV functional and structural alteration.

Abnormal left ventricular relaxation and symptoms of heart failure

The purpose of our study was to assess the echocardiographic and angiographic parameters in patients with symptomatic heart failure (HF) and mild diastolic dysfunction (grade I). It remains uncertain why some patients with mild diastolic dysfunction exhibit HF symptoms and others are asymptomatic. The study enrolled 80 hospitalized patients with impaired left ventricular (LV) relaxation. Patients were divided into two groups; one group had chronic functional class II to III dyspnea and the other group had no symptoms of HF. After admission, echocardiography and coronary angiography were performed for all patients and LV systolic and diastolic parameters were compared between the two groups. More patients in the asymptomatic group were hypertensive (p-value: 0.012). However, coronary artery disease was more prevalent in symptomatic patients (p-value: 0.022). The LV ejection fraction (EF) was significantly lower in symptomatic patients [median 54.33%, 95% confidence interval (53.76-54.87%) in asymptomatic patients and median 49.43, 95% confidence interval (47.23-50.91%) in symptomatic patients, p-value<0.001]. Furthermore, the systolic LV internal dimension was significantly larger in this group (p-value: 0.037). The results of logistic regression identified that only the absolute level of the LVEF was the negative determinant of the occurrence of HF in patients with impaired LV relaxation. Our study showed that LV systolic performance has an important role in occurrence of HF symptoms in patients with grade I diastolic dysfunction.

Incidence of chronic heart failure with preserved left ventricular ejection fraction in patients with hypertension and isolated mild diastolic dysfunction

Heart failure (HF) with preserved ejection fraction (HFPEF) is still a challenge in clinical practice. The prognosis of patients with HFPEF is similar to or only slightly better than that of patients with HF with reduced ejection fraction (HFREF). Impaired relaxation is the mildest form of diastolic dysfunction, which should not be accompanied by symptoms of HFPEF. The aim of the study was to assess the incidence of chronic HFPEF in patients with hypertension and isolated mild diastolic dysfunction. It was a cross-sectional study including 210 patients (mean age, 56.11 ±6.24 years; women, 58%) with isolated abnormalities of left ventricular relaxation and arterial hypertension. In addition, we identified patients with type 2 diabetes to compare the incidence of HFPEF between patients with and without diabetes. HFPEF was diagnosed when clinical symptoms of HF were present simultaneously with echocardiographic markers of elevated left ventricular diastolic pressure, pulmonary congestion on chest X-ray, or elevated serum brain natriuretic peptide (BNP) levels. HFPEF was diagnosed in 42% of the patients with impaired relaxation. An elevated left atrial volume index (>34 ml/m²) was observed in 38% of the patients; E/e' ratio exceeding 8, in 37%; elevated BNP levels, in 39%; and pulmonary congestion on chest X-ray, in 41%. Independent predictors of HFPEF were age, systolic blood pressure of 140 mmHg or higher, type 2 diabetes, coronary artery disease, and an estimated glomerular filtration rate of less than 60 ml/min/1.73 m². In diabetic patients, a positive correlation was found between an insulin dose (>80 units/day) and BNP levels. Patients with isolated relaxation abnormalities constitute a clinically heterogeneous group because some of these individuals present with symptoms of HFPEF and a simultaneous increase in BNP levels. Therefore, the question of whether diastolic dysfunction is mild should be readdressed, and it should be emphasized that these patients have a serious prognosis with the risk of HF. In diabetic patients, a positive correlation between high insulin doses and BNP levels requires further research.

Left Ventricular Diastolic Function Assessment Using Time Differences Between Mitral Annular Velocities and Transmitral Inflow Velocities in Patients with Heart Failure

Evaluation of left ventricular (LV) diastolic function is important in clinical echocardiography. The relationship between mitral annular velocities and transmitral inflow velocities provide additional information about LV filling and diastolic function. This study evaluates the relationships of time intervals between peaks E of mitral inflow velocities and E' of mitral annular velocities, and peaks A and A' in patients with heart failure (HF). Eighty patients with HF and 50 age- and gender-matched normal healthy subjects were prospectively recruited and underwent full echocardiograms. The following time intervals were measured: (1) from the onset of R-wave on the ECG to the peak of E-wave on the transmitral flow (TMF) (R-pE); (2) from R to peak of E'-wave on the LV lateral wall of tissue Doppler imaging (TDI) (R-pE'); (3) from onset of P-wave to peak of A-wave on the TMF (P-pA); and (4) from onset of P-wave to peak of A'-wave (P-pA') of TDI. Early-diastolic temporal discordance (EDTD) and late-diastolic temporal discordance (LDTD) were calculated as the difference between the time intervals (R-E) and (R-E'), (P-pA) and (P-p A'). EDTD significantly decreased in patients with HF compared with normal subjects (18.0±54.1ms vs. 28.0±33.5ms, P<0.05). There was also a significant decrease in LDTD in HF patients compared with normal subjects (19.6±23.5ms vs. 34.8±20.6; P<0.05). EDTD and LDTD decreased in patients with heart failure, and they may be useful tools in identifying abnormal LV relaxation and left atrial contraction for LV diastolic function.

Early detection of abnormal left ventricular relaxation in acute myocardial ischemia with a quadratic model

AimsThe time constant of left ventricular (LV) relaxation derived from a monoexponential model is widely used as an index of LV relaxation rate, although this model does not reflect the non-uniformity of ventricular relaxation. This study investigates whether the relaxation curve can be better fitted with a “quadratic” model than with the “conventional” monoexponential model and if changes in the LV relaxation waveform due to acute myocardial ischemia could be better detected with the quadratic model. Methods and resultsIsovolumic relaxation was assessed with quadratic and conventional models during acute myocardial ischemia performed in 6 anesthetized pigs. Mathematical development indicates that one parameter (Tq) of the quadratic model reflects the rate of LV relaxation, while the second parameter (K) modifies the shape of the relaxation curve. Analysis of experimental data obtained in anesthetized pigs showed that the shape of LV relaxation consistently deviates from the conventional monoexponential decay. During the early phase of acute myocardial ischemia, the rate and non-uniformity of LV relaxation, assessed with the quadratic function, were significantly enhanced. Tq increased by 16% (p<0.001) and K increased by 12% (p<0.001) within 30 and 60min, respectively, after left anterior descending (LAD) coronary artery occlusion. However, no significant changes were observed with the conventional monoexponential decay within 60min of ischemia. ConclusionsThe quadratic model better fits LV isovolumic relaxation than the monoexponential model and can detect early changes in relaxation due to acute myocardial ischemia that are not detectable with conventional methods.

Early contribution of arterial wave reflection to left ventricular relaxation abnormalities in a community-dwelling population of normotensive and untreated hypertensive men and women

We examined the contribution of arterial wave reflection to early abnormalities in left ventricular relaxation, whether this association was modified by gender or hypertension, and the role of reflected wave timing and amplitude. We studied a cohort of normotensive and untreated essential hypertensive Taiwanese participants (675 men, 601 women, mean age 52 years). Doppler flow and applanation tonometry were performed to assess carotid-femoral pulse wave velocity (PWV) and augmentation index (AI). Diastolic parameters including transmitral E/A, E-deceleration time, and left atrial diameter were measured by echocardiography. In multivariate models predicting E/A, women were more likely to have lower E/A than men (β −0.08, p<.001). AI was significantly associated with lower E/A in both men (β −0.09, p=0.005) and women (β −0.12, p<.001) independent of PWV. Inclusion of AI in the overall model reduced the gender difference in E/A by 61% and rendered it non-significant. There was a significant interaction between AI and hypertension (p=0.02). The inverse association between AI and E/A was significant only in normotensive men and women, and only for the amplitude but not timing of the reflected wave. In conclusion, the contribution of wave reflection to left ventricular diastolic dysfunction was independent of arterial stiffness, more pronounced in normotensive individuals, and explained a significant portion of the gender difference in diastolic function.

Extent and severity of coronary artery disease by coronary CT angiography is associated with elevated left ventricular diastolic pressures and worsening diastolic function

BackgroundPatients with flow-limiting coronary stenoses exhibit elevated left ventricular end-diastolic pressure (LVEDP) and abnormal left ventricular (LV) relaxation. ObjectiveWe investigated the relationship of extent and severity of coronary artery disease (CAD) by coronary CT angiography (CTA) to LVEDP and measures of LV diastolic dysfunction. MethodsWe identified consecutive patients undergoing coronary CTA and transthoracic echocardiography who were assessed for diastolic function. CAD was evaluated on a per-patient, per-vessel, and per-segment basis for intraluminal diameter stenosis by using an 18-segment model (0 = none, 1 = 1%–49%, 2 = 50%–69%, and 3 = 70%–100%) and summed over segments to obtain overall coronary plaque burden (segment stenosis score [SSS]; maximum = 54). Transthoracic echocardiography evaluated mitral inflow E wave-to-A wave ratio, tissue Doppler early mitral annual tissue velocity axial excursion, stage of diastolic dysfunction, and LV dimensions and estimated LVEDP from the ratio of mitral inflow velocity to early mitral annular (medial) tissue velocity. ResultsFour hundred seventy-eight patients (57% women; mean age, 57.9 ± 14.6 years; 24.9% prior CAD) comprised the study population. Increasing per-patient maximal coronary stenosis, number of vessels with obstructive stenosis, and SSS were associated with increased LVEDP. The prevalence of advanced diastolic dysfunction increased with greater number of obstructive vessels. In multivariable analyses, SSS was associated with increased LVEDP (0.8 mm Hg per tertile increase in SSS, 0.5–1.1; P < .001); reduced E′ axial excursion (−0.3; 95% confidence interval [CI], −0.5 to −0.1; P = .001), increased LV mass index (1.6 g/m2 per tertile increase in SSS; P = .04), and increased relative wall thickness (0.005; 95% CI, 0.004–0.009; P = .03), with consistent relationships persisting even among persons with per-patient maximal stenosis <50% and LV ejection fraction ≥55%. ConclusionsExtent and severity of obstructive as well as nonobstructive CAD by coronary CTA are associated with increased LVEDP and measures of diastolic dysfunction.

Positive end-expiratory pressure aggravates left ventricular diastolic relaxation further in patients with pre-existing relaxation abnormality

BackgroundPositive end-expiratory pressure (PEEP) has been known to adversely influence cardiac output. Even though left ventricular (LV) diastolic function significantly contributes to LV performance, the effects of PEEP on LV diastolic function remains controversial. We, therefore, aimed to examine the effects of PEEP on LV diastolic function by use of pulsed wave Doppler tissue imaging in patients with pre-existing LV relaxation abnormality. MethodsSeventeen patients with peak early diastolic velocity of lateral mitral annulus (E′) <8.5 cm s−1 among patients who underwent coronary artery bypass graft surgery were evaluated. Echocardiographic and haemodynamic variables were measured with 0, 5, and 10 cmH2O of PEEP. E′ and deceleration time (DT) of peak early transmitral filling velocity (E) were used as echocardiographic indicators of LV diastolic function. ResultsMean arterial blood pressure decreased during 10 cmH2O PEEP, compared with that during 0 cmH2O PEEP. E′ showed a gradual and significant decrease with an incremental increase in PEEP (6.9±0.9, 5.8±0.9, and 5.2±1.2 cm s−1 during 0, 5, and 10 cmH2O PEEP, respectively), and DT of E was prolonged during 10 cmH2O PEEP, compared with that during 0 cmH2O PEEP. ConclusionsIncreasing PEEP led to a progressive decline in LV relaxation in patients with pre-existing LV relaxation abnormality.

Prediction of Coronary Artery Stenosis at Rest in Patients With Normal Left Ventricular Wall Motion

Noninvasive detection of coronary artery stenosis usually requires a stress test in patients without left ventricular (LV) regional wall motion abnormalities (RWMA). In contrast, abnormal regional LV relaxation caused by ischemia may persist beyond recovery from transient ischemia. The aim of the present study was to determine whether segmental analysis of abnormal regional LV relaxation using the strain imaging diastolic index (SI-DI) at rest could predict coronary artery stenosis in the three major vessels in patients without LV dysfunction or RWMA. We performed 2D speckle tracking echocardiography and coronary angiography in 85 patients without RWMA with suspected coronary artery disease. Patients with LV dysfunction or acute coronary syndrome were excluded. Echocardiographic images of the LV were obtained in the apical 2-, 3-, and 4-chamber views and divided into 6 segments. In each segment, SI-DI derived from transverse strain imaging was determined. Forty-eight patients had significant coronary artery stenosis (≥ 70%). The optimal cutoff values of SI-DI were 60.5% in the mid anteroseptal segment for detecting left anterior descending artery stenosis (sensitivity, 83.3%; specificity, 81.1%), 60.5% in the basal anterolateral segment for detecting left circumflex artery stenosis (sensitivity, 80.9%; specificity, 90.3%), and 61.5% in the basal inferior segment for detecting right coronary artery stenosis (sensitivity, 74.1%; specificity, 77.8%). A segmental analysis of SI-DI at rest predicted coronary artery stenosis in the three major vessels in patients without RWMA. This noninvasive method may be useful for detecting coronary artery stenosis without a stress test.

Relationship Between Effective Arterial Elastance, Total Vascular Resistance, and Augmentation Index at the Ascending Aorta and Left Ventricular Diastolic Function in Older Women

Heart failure with preserved ejection fraction (HFpEF) is frequently observed in older women. Increased arterial stiffness in this population may be a cause of HFpEF. In 75 patients who underwent cardiac catheterization and who had no significant coronary artery stenosis or left ventricular (LV) wall motion abnormalities, the LV relaxation time constant (Tp) was calculated. The LVEF was obtained from left ventriculography, and plasma brain natriuretic peptide (BNP) level was measured. From the pressure waveforms at the ascending aorta, the augmentation index (AIx) was calculated. Effective arterial elastance (Ea) and total vascular resistance (TVR) were also determined. No significant differences were found between genders for age, heart rate, central blood pressure, or LVEF. Ea, TVR, AIx, and BNP level were significantly greater in women than in men, but only AIx was significantly correlated with Tp (r=0.25, P=0.04) and BNP level (r=0.33, P=0.005). The arterial system is stiffer in women than in men of the same age. Among the parameters of arterial stiffness, only AIx is related to abnormal LV relaxation and increased BNP level. Elevated AIx is a factor that causes LV diastolic dysfunction and may be associated with the development of HFpEF in this gender.