Left Ventricular End-diastolic Stiffness Research Articles

IMPACT OF SINGLE-PILL COMBINATION OF VALSARTAN/AMLODIPINE ON LEFT VENTRICULAR HYPERTROPHY AND MYOCARDIAL STIFFNESS IN THE MIDDLE-AGED HYPERTENSIVE PATIENTS

Objective: to investigate effects of single-pill combination (SPC) of valsartan/amlodipine (V/A) on left ventricular (LV) and left atrial (LA) myocardial stiffness (MS) parameters and LV mass index (LVMI) in the middle-aged patients with stage II grade 1–2 essential arterial hypertension (EAH) without concomitant cardiovascular diseases. Design and method: Retrospective, cohort, open-label study. According to the medical records data a group of naïve patients 40–65 years old with stage II grade 1–2 EAH (n = 38, mean age 49.7 ± 7.0 years) was retrospectively formed. All the patients were treated with V/A SPC and all of them had achieved target office blood pressure (BP) <140/90 mmHg. In all included patients clinical and echocardiographic data (acquired using Vivid 7 Dimension system, GE) were available at baseline and on 12th week after reaching the target BP. LVMI, diastolic interventricular septum thickness (IVS) and diastolic LV posterior wall thickness (PWT) were used as a measures of LV hypertrophy. LV end-diastolic stiffness, LV end-systolic elastance (ESE), LV diastolic elastance, LA stiffness index, LA expansion index and tissue Doppler-derived LA strain were calculated as MS parameters. 2-D speckle tracking echocardiography data were acquired for determination of LV myocardial global longitudinal peak strain (LV GLPS). Results: at the end of follow-up LV ESE significantly (p < 0.001) decreased from 4.01 ± 1.12 to 3.46 ± 0.88 mmHg/ml. In the subgroup of patients with initially abnormal LV GLPS (less than 19.7%) this parameter significantly (p = 0.005) increased in absolute value from −16.14 ± 2.21 to −17.30 ± 2.13% (+8,45 ± 13.35%). All LV hypertrophy markers significantly decreased (p < 0.001 for all) – LVMI from 113.40 ± 22.24 to 103.52 ± 21.30 g/m2 (−8.58 ± 7.57%), IVS from 1.30 ± 0.20 to 1.23 ± 0.19 cm (−5.38 ± 5.29%) and PWT from 1.03 ± 0.11 to 0.95 ± 0.11 cm (−7.82 ± 9.29%). After the treatment with V/A SPC the number of patients with LV hypertrophy significantly (p = 0.039) reduced from 65.8% to 39.5%. Conclusions: in naïve 40–65 years old patients with stage II grade 1–2 EAH antihypertensive therapy with V/A SPC provides effective BP control, improves LV MS parameters and reduced LV hypertrophy.

BLOOD PRESSURE VARIABILITY AND MYOCARDIAL STIFFNESS IN THE MIDDLE-AGED NAÏVE HYPERTENSIVE PATIENTS

Objective: to assess left ventricular (LV) and left atrial (LA) echocardiographic myocardial stiffness parameters in the middle-aged patients with stage II grade 1–2 essential arterial hypertension (EAH) without concomitant cardiovascular diseases in relation to short-term blood pressure variability (BPV). Design and method: Retrospective, controlled study. According to medical records data a group of naïve patients 40–65 years old with stage II grade 1–2 EAH (n = 100, 47.0% men, mean age 51.9 ± 6.5 years) and a group of healthy controls (n = 86, 32.6% men, mean age 48.8 ± 5.8 years) was retrospectively formed. In all included participants clinical, echocardiographic data (acquired using Vivid 7 Dimension system, GE) and ambulatory blood pressure monitoring [ABPM] (BPLab, BP2005–01.04.00.2540, Petr Telegin, Russia) parameters were available. LV end-diastolic stiffness, LV end-systolic elastance, LV diastolic elastance, LA stiffness index (LASI), LA expansion index and tissue Doppler-derived LA strain were calculated as myocardial stiffness parameters. 2-D speckle tracking echocardiography data were used for determination of LV myocardial global longitudinal peak strain (LV GLPS). BPV was estimated as standard deviation based on ABPM reports. Hypertensive patients were divided into 2 subgroups according to median value of day-time systolic BPV (dtSBPV) – 15 mmHg and into 2 subgroups according to median value of night-time systolic BPV (ntSBPV) – 14 mmHg (subgroups of «high» and «normal» dtSBPV and ntSBPV), and study parameters analyzed separately in these subgroups compared to the control group. Results: in hypertensive patients with «high» dtSBPV (n = 59) LV GLPS (−17.5 ± 3.0%) was significantly (p = 0.002) lower in absolute value and LASI (0.17 ± 0.09) was significantly (p = 0.015) higher compared to the controls (respectively, −19.5 ± 2.6% and 0.12 ± 0.06). No significant differences in myocardial stiffness parameters were obtained compared to the controls in hypertensive patients with «normal» dtSBPV and both «normal» and «high» ntSBPV. Conclusions: the present study reveals that higher dtSPBV predispose to increased LV myocardial stiffness in untreated middle-aged patients with stage II grade 1–2 EAH without concomitant cardiovascular diseases in comparison with sex- and age-matched healthy individuals with normal blood pressure.

A13994 Blood pressure variability and hypertensive target organ damage

Objectives: to investigate an impact of blood pressure variability (BPV) on heart and brain hypertensive damage in the middle-aged untreated patients with grade 1–2 essential arterial hypertension (EAH) without concomitant cardiovascular diseases. Methods: we examined 60 naive hypertensive patients (HP) with EAH and 44 sex- and age-matched healthy individuals. Comprehensive transthoracic echocardiography (Vivid 7 Dimension, GE) with 2D speckle tracking analysis and ambulatory blood pressure monitoring were performed in all participants. BPV was estimated as standard deviation. 41 HP underwent brain magnetic resonance imaging (MAGNETOM Skyra 3.0T, Siemens AG). Fazekas scale was used to quantify the amount of white matter hyperintensities (WMH). Results: nighttime systolic BPV (sBPV) and nighttime diastolic BPV (dBPV) were significantly (p < 0,001 for all) higher in HP (12,1 ± 0,1 vs. 9,3 ± 0,4 mmHg in controls and 9,8 ± 0,4 vs. 6,9 ± 0,3 mmHg in controls, respectively). Correlation analyses in HP revealed significant association of nighttime sBPV with left ventricular (LV) end-systolic elastance (r = −0,375; p < 0,01) and LV end-diastolic stiffness (r = −0,429; p < 0,01). Daytime dBPV significantly correlated with LV diastolic elastance (r = 0,265; p < 0,05), nighttime dBPV - with left atrial expansion index (r = −0,282; p < 0,05). WMH (Fazekas 1 and 2) were found in 53,7% HP patients. In HP with WMH 24 hours sBPV (19,7 ± 3,9 mmHg) and daytime sBPV (18,0 ± 4,5 mmHg) were significantly (p < 0,05 for all) higher compared to same parameters in HP without WMH (17,2 ± 3,3 and 15,7 ± 3,1 mmHg, respectively). Conclusion: middle-aged untreated patients with grade 1–2 uncomplicated EAH are different from the sex- and age-matched healthy individuals by higher nighttime BPV. BPV associated with heart and brain hypertensive organ damage.

MYOCARDIAL STIFFNESS AND LEFT VENTRICULAR HYPERTROPHY IN THE MIDDLE-AGED HYPERTENSIVE PATIENTS

Objective: to investigate left ventricular (LV) and left atrial (LA) stiffness parameters in middle-aged patients with grade 1–2 essentiial arterial hypertension (EAH) without concomitant cardiovascular diseases according to the presence of LV hypertrophy (LVH). Design and method: Case-control study. We examined 127 naive patients with uncomplicated grade 1–2 EAH and divided them into two groups according to the LV mass index (LVMI). The first one is included 96 hypertensive patients (HP) with LVH (mean LVMI 125,8 ± 2,1 g/m2, mean age 52,6 ± 0,7 years; mean office blood pressure (BP) 151,9 ± 1,5/93,8 ± 1,1 mm Hg). The second group consisted of 31 patients without LVH (mean LVMI 89,7 ± 2,1 g/m2, mean age 51,3 ± 1,0 years; mean office BP 138,7 ± 2,1/83,5 ± 1,9 mm Hg). 44 healthy individuals (mean age 51,5 ± 1,0 years; mean office BP 120,1 ± 2,0/80,5 ± 1,0 mm Hg) represented the control group. All the patients underwent 24-hours ambulatory BP monitoring. Comprehensive transthoracic echocardiography using Vivid 7 Dimension system (GE) was also performed. LV end-diastolic stiffness, LV end-systolic elastance, LV diastolic elastance, LA stiffness index, LA expansion index and tissue Doppler-derived (TDD) LA strain were calculated. 2-D speckle tracking echocardiography data were acquired for determination of LV myocardial global longitudinal peak strain (LV GLPS). Results: TDD LA strain was significantly higher in HP without LVH (60,01 ± 4,77%) compared to HP with LVH (49,77 ± 1,49%; p < 0,05). LV GLPS was significantly lower in absolute value in HP with LVH (−16,9 ± 0,3%) and HP without LVH (−17,5 ± 0,6%) compared to controls (−19,9 ± 0,4%; p < 0,001 and p < 0,01, respectively). No significant differences between studied groups were obtained in other myocardial stiffness parameters. LV GLPS showed a weak but significant associations with office diastolic BP (r = 0,354; p < 0,01), 24 h systolic BP (r = 0,291; p < 0,05), 24 h pulse pressure (r = 0,296; p < 0,05), and average night-time systolic and diastolic BP (r = 0,343; p < 0,01 and r = 0,262; p < 0,05, respectively). Conclusions: the present study reveals that disturbances in myocardial stiffness parameters occur early, before the development of echocardiographic signs of LHV. They are earlier markers of target organ damage even in middle-aged untreated patients with grade 1–2 uncomplicated EAH.

MYOCARDIAL STIFFNESS IN THE MIDDLE-AGED HYPERTENSIVE PATIENTS IN THE PRESENCE OF OVERWEIGHT OR OBESITY

Objective: to evaluate left ventricular (LV) and left atrial (LA) stiffness parameters in middle-aged patients with arterial hypertension grade 1–2 without concomitant cardiovascular diseases in terms of the presence of overweight or obesity. Design and method: Case-control study. We examined 127 naive patients with uncomplicated essential arterial hypertension grade 1–2 and divided them into three groups in accordance with body mass index (BMI) values. The first one is included 19 patients with normal weight - mean BMI 23,2 ± 0,2 kg/m2, mean age 50,6 ± 1,0 years; 7 men; mean office blood pressure 142,1 ± 3,6/ 83,2 ± 2,5 mm Hg). The second group consisted of 52 patients with overweight - mean BMI 28,0 ± 0,2 kg/m2, mean age 53,1 ± 1,0 years; 26 men; mean office blood pressure 147,9 ± 2,0/ 90,9 ± 1,5 mm Hg). And the third group is included 56 patients with obesity - mean BMI 34,2 ± 0,4 kg/m2, mean age 52,0 ± 0,8 years; 33 men; mean office blood pressure 151,7 ± 2,0/ 94,4 ± 1,5 mm Hg). Comprehensive transthoracic echocardiography using Vivid 7 Dimension system (GE) were performed. LV end-diastolic stiffness, LV end-systolic elastance (ESE), LV diastolic elastance, LA stiffness index, LA expansion index and tissue Doppler-derived LA strain were calculated. 2-D speckle tracking echocardiography data were acquired for determination of LV myocardial global longitudinal peak strain (LV GLPS). Results: LV GLPS was significantly (p < 0,001) lower in absolute value in patients with obesity (−15,6 ± 0,4%) compared with overweight group (−18,0 ± 0,4%) and the patients with normal weight (−18,5 ± 0,5%). LV ESE was significantly lower in patients with obesity (3,75 ± 0,13 mm Hg/ml) compared with overweight persons (4,34 ± 0,16 mm Hg/ml; p < 0,05) and the patients with normal weight (4,81 ± 0,26 mm Hg/ml; p < 0,001). No significant differences between studied groups were obtained in other myocardial stiffness parameters. Conclusions: The present study reveals that obesity leads to increased LV myocardial stiffness in untreated middle-aged patients with uncomplicated arterial hypertension grade 1–2 in comparison with sex-, age- and hypertension history-matched patients with overweight or normal BMI.

Effects of Amlodipine/Lisinopril Fixed-Dose Combination on Severity of Left Ventricular Hypertrophy and Parameters of Myocardial Stiffness in Patients With Hypertension

To assess effects of 12 weeks treatment with the amlodipine/lisinopril fixed-dose combination (ALFDC) on the left ventricular (LV) mass index (LVMI), parameters of LV and left atrial stiffness. At phase 1 of the study we examined 44 healthy subjects (21 men, 23 women, mean age 51.5+/-1.0 years) and 60 untreated patients (31 men, 29 women, mean age 53.6+/-0.8 years) with stage II grade 1-2hypertension. Myocardial stiffness parameters, LVMI were calculated using data of transthoracic echocardiography. 2-D speckle tracking echocardiography was used for determination of LV myocardial global longitudinal peak strain (GLPS). All participants underwent ambulatory blood pressure (BP) monitoring, and office BP measurement. At phase 2 a subgroup of 30 untreated patients (16 men, 14 women; mean age 52.7+/-1.11years) received ALFDC in a start dose of 5 mg/10 mg titrated every 14 days to achieve BP<140/90 mm Hg. Therapy in selected doses was continued for 12 weeks thereafter. In hypertensive patients LV GLPS was significantly lower while LA stiffness index higher compared with controls (17.08+/-0.38 vs. 19.91+/-0.41%, p<0.001, and 0.20+/-0.01 vs. 0.16+/-0.01, p<0.01, respectively). There were no significant differences in the LA tissue Doppler derived strain, LV end-systolic elastance, LA expansion index between hypertensive and control groups. After ALFDC therapy BP was significantly (p<0.001) reduced: systolic (S)BP from 154.4+/-2.7 to 130.6+/-1.2, diastolic (D)BP from 96.5+/-1.3 to 83.0+/-0.5 mm Hg. After therapy LV GLPS, LA expansion index, LV diastolic elastance significantly increased (from 17.10+/-0.57 to 18.29+/-0.35%, p<0.01; from 1.47+/-0.08 to 1.68+/-0.08, p<0.001; from 9.25+/-0.99 [10-2] to 10.88+/-1.0 8 [10-2], p<0.05, respectively) while LVMI, LV end-diastolic stiffness, and LA stiffness index significantly (p<0.001) decreased (from 129.4+/-4.5 to 111.8+/-3.3 g/m2, from 0.16+/-0.01 to 0.12+/-0.01 mm Hg/ml, from 0.21+/-0.02 to 0.15+/-0.01, respectively). Change in the LA tissue Doppler derived strain correlated with the change in dynamics of nighttime SBP (r=-0.410, p<0.05). There was direct relationship between change in LV diastolic elastance and nighttime DBP (r=0.424; p<0.05); and an inverse correlation between changes in LV end-diastolic stiffness and dynamics of the daytime SBP and DBP (r=-0.404; p<0.05 and r=-0.364; p<0.05, respectively). Change of LVMI after ALFDC treatment correlated with dynamics of 24-hour, daytime SBP, and daytime pulse pressure (r=0.382, p<0.05, r=0.478, p<0.01, and r=0.364, p<0.05, respectively). In untreated patients with stage II, 1-2 degree hypertension 12-week therapy with ALFDC allowed to achieve target BP levels, reduced severity of LV hypertrophy and improved stiffness parameters of the myocardium.

Effects of Lung Volume Reduction Surgery on Left Ventricular Diastolic Filling and Dimensions in Patients With Severe Emphysema

Data on the influence of lung volume reduction surgery (LVRS) on cardiac function and hemodynamics are scarce and controversial. Previous studies have focused mainly on right ventricular function and pulmonary hemodynamics. Here, we evaluated the effects of LVRS on left ventricular (LV) end-diastolic filling pattern, dimensions, stiffness, and performance, as well as pulmonary and systemic hemodynamics. A prospective, open, controlled study. Patients with severe emphysema undergoing LVRS (10 patients). Patients scheduled for pulmonary lobectomy due to carcinoma (ie, the lobectomy group) served as control subjects (10 patients). LV dimensions and mitral flow velocities were measured by transesophageal, two-dimensional, Doppler echocardiography, and central hemodynamics were measured by a pulmonary artery thermodilution catheter. Measurements were performed during anesthesia in the supine position, before and after surgery, without and with passive leg elevation. Baseline cardiac index (CI) [- 21%], stroke volume index (SVI) [- 31%], stroke work index (SWI) [- 26%], and LV end-diastolic area index (EDAI) [- 15%] were significantly (p < 0.001) lower, whereas LV end-diastolic stiffness (LVEDS) did not differ in the LVRS group compared to the lobectomy group. The time from peak early diastolic filling to zero flow (E-dec time) [58%] and the deceleration slope of early diastolic filling (E-dec slope) [45%] were significantly higher (p < 0.01), whereas peak early diastolic filling velocity (E-max) [- 31%; p < 0.01] and the proportion of E-max vs peak late diastolic filling velocity (A-max) [ie, the E/A ratio] (- 27%; p < 0.001) were significantly lower compared to the lobectomy group. LVRS significantly increased CI (40%; p < 0.001), SVI (34%; p < 0.001), SWI (58%; p < 0.001), LV EDAI (18%; p < 0.001), E-max (44%; p < 0.01), A-max (15%; p < 0.05) and E/A ratio (28%; p < 0.01), decreased E-dec time (- 31%; p < 0.05) and E-dec slope (- 98%; p < 0.01), and had no effect on LVEDS. In the lobectomy group, surgery affected none of these variables. LV function is impaired in patients with severe emphysema due to small end-diastolic dimensions. LVRS increases LV end-diastolic dimensions and filling, and improves LV function.

Peroxynitrite, the breakdown product of nitric oxide, is beneficial in blood cardioplegia but injurious in crystalloid cardioplegia.

Peroxynitrite (ONOO(-)) has been implicated as a primary mediator in the deleterious effects of nitric oxide (NO) in crystalloid solutions, possibly due to a lack of detoxification mechanisms, leading to the formation of.OH. In contrast, ONOO(-) may exert cardioprotective effects in blood environments secondary to detoxification and the subsequent formation of NO-donating nitrosothiols. This dichotomy in physiological effects of ONOO(-) may exist between crystalloid and blood cardioplegia (BCP) environments. In the present study, we tested the hypothesis that ONOO(-) is cardiotoxic in crystalloid cardioplegia but cardioprotective in BCP in ischemically injured hearts. In anesthetized dogs on cardiopulmonary bypass, global 37 degrees C ischemia was imposed for 30 minutes, followed by 60 minutes of intermittent 4 degrees C hyperkalemic crystalloid (Plegisol) or BCP with (+) or without (-) 5 micromol/L authentic ONOO(-). After 2 hours of reperfusion, left ventricular (LV) function (end-systolic pressure-volume relations, in percent of baseline) was 56+/-3% in Plegisol-, which was further reduced in Plegisol+ to 40+/-4%.* In contrast, postischemic systolic function was better in BCP+ groups than in BCP- groups (96+/-2%* versus 82+/-2%, respectively). Differences in functional recovery could not be attributed to differences in hemodynamics. LV end-diastolic stiffness was significantly increased with the addition of ONOO(-) in both Plegisol (298+/-26% versus 466+/-30%*) and BCP (201+/-22% versus 267+/-13%*) groups. Consistent with increased LV chamber stiffness, myocardial edema was increased in BCP+ compared with BCP- (78.9+/-0.3% versus 76.4+/-0.3%*) and in Plegisol+ compared with Plegisol- (81.1+/-0.3% versus 79.6+/-0.4%*). Creatine kinase activity was significantly increased in Plegisol+ (48+/-6) compared with that in Plegisol- (31+/-6) but was unchanged in BCP- (14+/-2) relative to BCP+ (18+/-1). Nitrotyrosine (ng/mg protein) accumulation in LV myocardial biopsy samples confirmed myocardial exposure to ONOO(-) or its metabolites (Plegisol- 1.2+/-0.1, Plegisol+ 3.31+/-0.3*, BCP- 1.4+/-0.2, BCP+ 2.9+/-0.2*). We conclude that (1) the postcardioplegic cardiodynamic effects of ONOO(-) depend on its environment and (2) ONOO(-) in crystalloid solution impairs postcardioplegia systolic and diastolic functional recovery, whereas (3) ONOO(-) in BCP increases functional recovery. This environment-dependent dichotomy in the effect of ONOO(-) may affect the benefits of NO-related adjuncts to crystalloid or BCP solutions (*P<0.05 versus group without ONOO(-)). :II-384-II-391.)

Peroxynitrite, the Breakdown Product of Nitric Oxide, Is Beneficial in Blood Cardioplegia but Injurious in Crystalloid Cardioplegia

Background —Peroxynitrite (ONOO − ) has been implicated as a primary mediator in the deleterious effects of nitric oxide (NO) in crystalloid solutions, possibly due to a lack of detoxification mechanisms, leading to the formation of ·OH. In contrast, ONOO − may exert cardioprotective effects in blood environments secondary to detoxification and the subsequent formation of NO-donating nitrosothiols. This dichotomy in physiological effects of ONOO − may exist between crystalloid and blood cardioplegia (BCP) environments. In the present study, we tested the hypothesis that ONOO − is cardiotoxic in crystalloid cardioplegia but cardioprotective in BCP in ischemically injured hearts. Methods and Results —In anesthetized dogs on cardiopulmonary bypass, global 37°C ischemia was imposed for 30 minutes, followed by 60 minutes of intermittent 4°C hyperkalemic crystalloid (Plegisol) or BCP with (+) or without (−) 5 μmol/L authentic ONOO − . After 2 hours of reperfusion, left ventricular (LV) function (end-systolic pressure-volume relations, in percent of baseline) was 56±3% in Plegisol−, which was further reduced in Plegisol+ to 40±4%.* In contrast, postischemic systolic function was better in BCP+ groups than in BCP− groups (96±2%* versus 82±2%, respectively). Differences in functional recovery could not be attributed to differences in hemodynamics. LV end-diastolic stiffness was significantly increased with the addition of ONOO − in both Plegisol (298±26% versus 466±30%*) and BCP (201±22% versus 267±13%*) groups. Consistent with increased LV chamber stiffness, myocardial edema was increased in BCP+ compared with BCP− (78.9±0.3% versus 76.4±0.3%*) and in Plegisol+ compared with Plegisol− (81.1±0.3% versus 79.6±0.4%*). Creatine kinase activity was significantly increased in Plegisol+ (48±6) compared with that in Plegisol− (31±6) but was unchanged in BCP− (14±2) relative to BCP+ (18±1). Nitrotyrosine (ng/mg protein) accumulation in LV myocardial biopsy samples confirmed myocardial exposure to ONOO − or its metabolites (Plegisol− 1.2±0.1, Plegisol+ 3.31±0.3*, BCP− 1.4±0.2, BCP+ 2.9±0.2*). Conclusions —We conclude that (1) the postcardioplegic cardiodynamic effects of ONOO − depend on its environment and (2) ONOO − in crystalloid solution impairs postcardioplegia systolic and diastolic functional recovery, whereas (3) ONOO − in BCP increases functional recovery. This environment-dependent dichotomy in the effect of ONOO − may affect the benefits of NO-related adjuncts to crystalloid or BCP solutions (* P &lt;0.05 versus group without ONOO − ). :II-384–II-391.)

An Integrated Measure of Left Ventricular Diastolic Function Based on Relative Rates of Mitral E and A Wave Propagation

Background and objectives: The mitral E wave propagation inside the left ventricle is slowed in patients with abnormal left ventricular (LV) relaxation with a prolongation of its transit time to the LV outflow tract (T e). On the contrary, the mitral A wave propagation is faster in those with elevated LV end-diastolic stiffness, resulting in a shortening of its transit time (T a). We hypothesized that the T e/T a ratio may serve an integrated measure of global LV diastolic function. Methods and results: The T e/T a ratio was measured with Doppler echocardiography in 94 subjects: 25 normal subjects, 38 patients with LV hypertrophy (18 with secondary LV hypertrophy and 20 with hypertrophic cardiomyopathy), and 31 patients undergoing left heart catheterization for clinical indications. The T e/T a ratio was 1.98 ± 0.61 in the normal subjects, 3.32 ± 0.93 in patients with secondary LV hypertrophy ( P < .0001 vs normal), and 3.18 ± 1.36 in patients with hypertrophic cardiomyopathy ( P = .0003 vs normal). In the invasive group the T e/T a ratio (range 0.56 to 3.60) correlated significantly with Tau ( r = 0.76, P < .0001), peak negative dP/dt ( r = -0.46, P = .01), the LV late diastolic stiffness index ( r = 0.57, P = .0013), LV pre–A wave pressure ( r = 0.46, P = .0096), LV end-diastolic pressure ( r = 0.58, P = .0007), and the amount of LV pressure rise with atrial systole ( r = 0.52, P = .0032) but not with the heart rate. Tau and LV stiffness were its sole determinants by stepwise multiple regression (R = 0.82). Conclusions: The ratio of mitral E and A wave transit times inside the LV (T e/T a ratio) is closely related to LV relaxation, its late diastolic stiffness, and filling pressures and gives valuable insights into LV diastolic performance. (J Am Soc Echocardiogr 1999;12:811-6.)

Early effects of coronary artery bypass surgery and cold cardioplegic ischemia on left ventricular diastolic function: Evaluation by computer-assisted transesophageal echocardiography

Although left ventricular (LV) systolic function undergoes a temporary decrease after cardiopulmonary bypass (CPB) in patients undergoing coronary artery bypass grafting (CABG), data on the effects of CABG and cardioplegic arrest on LV diastolic function are contradictory. The objective of the present study was to further evaluate the effects of CABG and CPB on LV diastolic function. A prospective study. A multi-institutional investigation at a university hospital. 20 patients on beta-receptor antagonists, scheduled for CABG and with a preoperative ejection fraction over 0.5. Central hemodynamic measurements, transesophageal LV short-axis images, and mitral Doppler flow profiles were obtained before and after volume loading that in turn was performed both before surgical incision and after weaning from CPB. Heart rate, cardiac output, and peak atrial filling velocity increased; systemic vascular resistance decreased; whereas stroke volume, LV area ejection fraction, deceleration rate and slope of early diastolic filling, time-velocity integral of early diastolic filling, and the ratio between early and atrial peak filling velocity were unchanged post-CPB compared with pre-CPB. LV end-diastolic stiffness that was calculated for each patient pre-CPB and post-CPB using the formula: P = B*eS*A), where P is the LV filling pressure and A is the end-diastolic short-axis area, was unchanged post-CPB compared with pre-CPB. Both the active and passive components of LV diastolic function are well maintained shortly after CABG and cardioplegic arrest in patients with a good preoperative systolic LV function.

Exercise-induced cardiac hypertrophy is associated with an increased myocardial compliance.

Left ventricular (LV) chamber and myocardial wall compliance were investigated in rats with exercise-induced cardiac hypertrophy. Voluntary exercise training was performed on running wheels. After 16 wk of exercise training, cardiac performance was measured in anesthetized open-chest ventilated rats. LV end-diastolic performance was calculated from both short-axis external diameter and long-axis segmental length measurements. Exercise-trained rats developed significant LV hypertrophy (1.03 +/- 0.02 g) compared with control rats (0.91 +/- 0.03 g; P < 0.01). The physiological hypertrophy was associated with an increased LV wall thickness-to-internal radius ratio consistent with a concentric geometry. LV end-diastolic stiffness (slope of the linearized LV end-diastolic pressure-strain relationship) was decreased in both the short (P < 0.02) and long (P < 0.02) axis of LV as a result of exercise training. The LV end-diastolic chamber stiffness (slope of the linearized LV end-diastolic pressure-volume relationship) was also decreased in the exercised group (P < 0.05). The decreased chamber stiffness occurred as a consequence of a decrease in the regional myocardial wall elastic stiffness (slope of the linearized LV end-diastolic stress-strain relationship; P < 0.05). Thus an increased LV wall thickness as a result of exercise-induced LV hypertrophy is associated with an enhanced ventricular chamber compliance, which in turn is attributed to a decrease in the diastolic stiffness of the myocardial wall.

Divergent effects of intravenous dobutamine and nitroprusside on left atrial contribution to ventricular filling in dogs with chronic heart failure

The left atrial (LA) contribution to left ventricular (LV) filling is often attenuated in patients with heart failure. It remains uncertain, however, whether therapy with positive inotropic agents or vasodilators improves or further impairs this maladaptation. In the present study, the effects of intravenous dobutamine and nitroprusside on the LA contribution to LV filling was examined in seven dogs with chronic heart failure produced by multiple sequential intracoronary microembolizations. Pulsed Doppler echocardiography was used to measure mitral inflow velocity before and after an intravenous infusion of dobutamine (4 μg/kg/min) and an intravenous infusion of nitroprusside (3 μg/kg/min). The percent LA contribution to LV filling was calculated as the ratio of the time-velocity integral of the LA component of mitral inflow velocity (Ai) to the time-velocity integral of total diastolic inflow velocity (Ti) times 100. Dobutamine increased LV filling pressure, LV end-diastolic wall stress, LV end-diastolic stiffness, and Ei, but had no effect on Ai or the percent LA contribution to filling (14% ± 3% vs 12% ± 2%) ( p < 0.34). In contrast, nitroprusside decreased LV filling pressure, LV end-diastolic wall stress, and end-diastolic stiffness, and increased Ei, Ai, and the percent LA contribution to LV filling (12% ± 2% vs 17% ± 2%) ( p < 0.01). The results indicate that dobutamine and nitroprusside have divergent effects on the LA contribution to LV filling. In dogs with chronic heart failure, dobutamine appears to impair LA contribution to the LV filling by augmenting LA workload, whereas nitroprusside appears to elicit greater LA contribution to LV filling by reducing the LA workload.

Age-related differences in the response to myocardial ischemic stress

Clinical experience indicates that the risk of reparative cardiac operations is increased in the neonatal period relative to that in older infants and children. Age-related differences in the susceptibility to myocardial ischemic dysfunction were evaluated by comparison of left ventricular function and metabolism in neonatal (mean age = 7 days) and weanling (mean age = 96 days) piglets. Six animals in each group supported on cardiopulmonary bypass were subjected to (1) 120 minutes of hypothermic crystalloid cardioplegic arrest (CP-120) and (2) 15 minutes of normothermic ischemic arrest (NA-15) after a 60 minute interval of reperfusion. Left ventricular systolic and diastolic function was measured after each intervention via endocardially implanted ultrasonic dimension crystals in a septolateral minor-axis position. In both groups, systolic dysfunction was evidenced by an increase in the dimension-axis intercept (p = 0.001), but not the slope of the end-systolic pressure-dimension relation. Left ventricular end-diastolic stiffness, expressed as left ventricular end-diastolic pressure versus Lagrangian strain, increased to a similar degree in both groups (p = 0.001). Adenosine triphosphate levels declined significantly (p = 0.001) in both groups in response to the ischemic interventions with no evident intergroup differences. Lactate levels increased significantly during the course of the experiment (p = 0.04); however, the increases were greater (p = 0.009) at all intervals in the neonatal group. This study demonstrates age-related metabolic differences in response to ischemia consistent with a greater dependence on glycolysis in neonatal myocardia. However, the fact that discriminating age-related differences in left ventricular function were not evident suggests that factors other than young age per se account for the increased surgical mortality in the neonatal period.