Assessing the Validity of Echocardiographic Criteria for Left Ventricular Diastolic Dysfunction in Patients with Pulmonary Hypertension

Cardiology ◽  
2020 ◽  
Vol 145 (11) ◽  
pp. 703-709
Author(s):  
John David Allison ◽  
Carl Zehner ◽  
Xiaoming Jia ◽  
Ihab Rafic Hamzeh ◽  
Mahboob Alam ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Heart Catheterization ◽  
Mitral Inflow ◽  
Mitral Annular Velocity ◽  
Lv Diastolic Dysfunction ◽  
Lv Diastolic Function

<b><i>Background:</i></b> In patients with pulmonary hypertension (PHT), the assessment of left ventricular (LV) diastolic function by echocardiography may not be reliable. PHT can affect Doppler parameters of LV diastolic function such as mitral inflow velocities and mitral annular velocities. The current guidelines for the assessment of LV diastolic function do not recommend specific adjustments for patients with PHT. <b><i>Methods:</i></b> We analyzed 36 patients from the PHT clinic that had an echocardiogram and right heart catheterization performed within 6 months of each other. Early mitral inflow velocity (E), lateral mitral annular velocity (lateral e’), septal mitral annular velocity (septal e’), tricuspid free wall annular velocity (RV e’) were measured and compared to the invasively measured intracardiac pressures including pulmonary capillary wedge pressure (PCWP), mean pulmonary artery pressure, and right ventricular end-diastolic pressure. <b><i>Results:</i></b> Among patients with PHT, the specificity of the septal e’ for LV diastolic dysfunction was 0.19, and the positive predictive value was 0.13 (lower than the lateral e’ or E/average e’). By receiver-operating characteristic curve analysis, the area under the curve (AUC) of lateral and septal e’ was just 0.64 (<i>p</i> = 0.9) and 0.53 (<i>p</i> = 0.6), respectively, while the AUC of average E/e’ was 0.94 (<i>p</i> &#x3c; 0.001). The septal e’ was paradoxically lower at 6.5 ± 1.9 cm/s for normal PCWP compared to 6.9 ± 1.7 cm/s for elevated PCWP (<i>p</i> = 0.04). 81 versus 40% (<i>p</i> = 0.017) of patients with normal versus elevated PCWP had an abnormal septal e’ &#x3c;7 cm/s. By linear regression, there was no correlation between the Doppler parameters of LV diastolic function and the PCWP. <b><i>Conclusion:</i></b> Our study suggests E/average e’ may be the only reliable tissue Doppler parameter of LV diastolic dysfunction in patients with PHT, and that septal e’ is paradoxically decreased in patients with PHT and normal left-sided filling pressures.

Abstract 10878: Validation of Non-invasive Measures of Diastolic Function in Children: A Simultaneous Echocardiography and Conductance Catheterization Study

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Shahryar M Chowdhury ◽  
Ryan J Butts ◽  
Anthony M Hlavacek ◽  
Carolyn L Taylor ◽  
Varsha M Bandisode ◽  
...  
Keyword(s):  
Diastolic Function ◽  
Diastolic Pressure ◽  
Ductus Arteriosus ◽  
Left Ventricular ◽  
Balloon Occlusion ◽  
Heart Catheterization ◽  
Active Relaxation ◽  
Non Invasive ◽  
Stiffness Constant ◽  
Lv Diastolic Function

Introduction: The accuracy of echocardiography in evaluating left ventricular (LV) diastolic function has not been validated in children. The objective of this study was to compare echocardiographic and gold-standard measures of LV diastolic function in children. Methods: Patients undergoing routine left heart catheterization were prospectively enrolled. Pressure-volume loops (PVL) were obtained via conductance catheters. The end-diastolic pressure-volume relationship was obtained via balloon occlusion of the vena cavae. PVL measures of diastolic function were divided into early active relaxation (the isovolumic relaxation time constant, tau), and ventricular stiffness (the chamber stiffness constant, β). End-diastolic pressure (EDP) was also recorded. Echocardiographic measures of diastolic function were derived from spectral Doppler, tissue Doppler, and 2D speckle-tracking. The relationships between PVL and echocardiographic measures were determined using Spearman’s correlation. Results: Of 24 patients, 18 patients were s/p heart transplant, 5 patients had a small patent ductus arteriosus or coronary fistula. Mean age was 9.1 ± 5.6 years. The median τ was 24.9 ms (IQR 22.8 - 28.4 ms), median β was 0.094 (IQR 0.035 - 0.154), and median EDP was 9 mmHg (IQR 8 - 13 mmHg). Statistically significant correlations between invasive and echocardiographic measures of diastolic function are reported in the Table. No echocardiographic measures correlated with β. Conclusion: Early diastolic echocardiographic measures correlate with tau and may accurately represent early active relaxation in children. Modest associations exist between echocardiographic measures and EDP. The use of these non-invasive measures in accurately assessing LV diastolic function appears promising in children. However, no echocardiographic measures correlate with chamber stiffness. The development of such measures merits further study.

scholarly journals Peripartum Cardiomyopathy Presenting with Predominant Left Ventricular Diastolic Dysfunction: Efficacy of Bromocriptine

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Piercarlo Ballo ◽  
Irene Betti ◽  
Giuseppe Mangialavori ◽  
Leandro Chiodi ◽  
Gherardo Rapisardi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Peripartum Cardiomyopathy ◽  
Lv Function ◽  
Lv Diastolic Dysfunction ◽  
Lv Diastolic Function

Management of patients with peripartum cardiomyopathy (PPCM) is still a major clinical problem, as only half of them or slightly more show complete recovery of left ventricular (LV) function despite conventional evidence-based treatment for heart failure. Recent observations suggested that bromocriptine might favor recovery of LV systolic function in patients with PPCM. However, no evidence exists regarding its effect on LV diastolic dysfunction, which is commonly observed in these patients. Tissue Doppler (TD) is an echocardiographic technique that provides unique information on LV diastolic performance. We report the case of a 37-year-old white woman with heart failure (NYHA class II), moderate LV systolic dysfunction (ejection fraction 35%), and severe LV diastolic dysfunction secondary to PPCM, who showed no improvement after 2 weeks of treatment with ramipril, bisoprolol, and furosemide. At 6-week followup after addition of bromocriptine, despite persistence of LV systolic dysfunction, normalization of LV diastolic function was shown by TD, together with improvement in functional status (NYHA I). At 18-month followup, the improvement in LV diastolic function was maintained, and normalization of systolic function was observed. This paper might support the clinical utility of bromocriptine in patients with PPCM by suggesting a potential benefit on LV diastolic dysfunction.

scholarly journals One-Year Change in the H2FPEF Score After Catheter Ablation of Atrial Fibrillation in Patients With a Normal Left Ventricular Systolic Function

2021 ◽  
Vol 8 ◽  
Author(s):  
Min Kim ◽  
Hee Tae Yu ◽  
Tae-Hoon Kim ◽  
Jae-Sun Uhm ◽  
Boyoung Joung ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Systolic Function ◽  
Left Ventricular ◽  
One Year ◽  
Lv Diastolic Dysfunction ◽  
Fat Volume ◽  
Lv Diastolic Function

Background: It is unclear whether atrial fibrillation (AF) catheter ablation (AFCA) improves the left ventricular (LV) diastolic function. We evaluated the 1-year change in the H2FPEF score, which reflects the degree of LV diastolic function, after AFCA among patients with a normal LV systolic function.Methods and Results: We included 1,471 patients (30.7% female, median age 60 years, paroxysmal-type AF 68.6%) who had available H2FPEF scores at baseline and at 1-year after AFCA to evaluate the 1-year change in the H2FPEF score (ΔH2FPEF score[1−yr]) after AFCA. Baseline high H2FPEF scores (≥6) were independently associated with the female sex, left atrium (LA) diameter, LV mass index, pericardial fat volume, and a low estimated glomerular filtration rate. One year after AFCA, decreased ΔH2FPEF scores[1−yr] were associated with baseline H2FPEF scores of ≥6 [OR, 4.19 (95% CI, 2.88–6.11), p &lt; 0.001], no diabetes [OR, 0.60 (95% CI, 0.37–0.98), p = 0.04], and lower pericardial fat volume [OR, 0.99 (95% CI, 0.99–1.00), p = 0.003]. Increased ΔH2FPEF scores[1−yr] were associated with a baseline H2FPEF score of &lt;6 [OR, 3.54 (95% CI, 2.08–6.04), p &lt; 0.001] and sustained AF after a recurrence within 1 year [SustainAF[1−yr]; OR, 1.89 (95% CI, 1.01–3.54), p = 0.048]. Throughout a 56-month median follow-up, an increased ΔH2FPEF score[1−yr] resulted in a poorer rhythm outcome of AFCA (at 1 year, log-rank p = 0.003; long-term, log-rank p = 0.010).Conclusions: AFCA appears to improve LV diastolic dysfunction. However, SustainAF[1−yr] may contribute to worsening LV diastolic dysfunction, and it was shown by increased ΔH2FPEF scores[1−yr], which was independently associated with higher risk of AF recurrence rate after AFCA.Clinical Trial Registration:ClinicalTrials.gov Identifier: NCT02138695.

scholarly journals Safety, Feasibility, and Impact of Enalapril on Cardiorespiratory Physiology and Health in Preterm Infants with Systemic Hypertension and Left Ventricular Diastolic Dysfunction

2021 ◽  
Vol 10 (19) ◽  
pp. 4519
Author(s):  
Amy H. Stanford ◽  
Melanie Reyes ◽  
Danielle R. Rios ◽  
Regan E. Giesinger ◽  
Jennifer G. Jetton ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Preterm Infants ◽  
Cardiovascular Health ◽  
Case Series ◽  
Left Ventricular ◽  
Systemic Hypertension ◽  
Lv Diastolic Dysfunction ◽  
Lv Diastolic Function

Neonatal hypertension has been increasingly recognized in premature infants with bronchopulmonary dysplasia (BPD); of note, a sub-population of these infants may have impaired left ventricular (LV) diastolic function, warranting timely treatment to minimize long term repercussions. In this case series, enalapril, an angiotensin-converting enzyme (ACE) inhibitor, was started in neonates with systemic hypertension and echocardiography signs of LV diastolic dysfunction. A total of 11 patients were included with birth weight of 785 ± 239 grams and gestational age of 25.3 (24, 26.1) weeks. Blood pressure improvement was noticed within 2 weeks of treatment. Improvement in LV diastolic function indices were observed with a reduction in Isovolumic Relaxation Time (IVRT) from 63.1 ± 7.2 to 50.9 ± 7.4 msec and improvement in the left atrium size indexed to aorta (LA:Ao) from1.73 (1.43, 1.88) to 1.23 (1.07, 1.29). Neonatal systemic hypertension is often underappreciated in ex-preterm infants and may be associated with important maladaptive cardiac changes with long term implications. It is biologically plausible that identifying and treating LV diastolic dysfunction in neonates with systemic hypertension may have a positive modulator effect on cardiovascular health in childhood and beyond.

Abstract 4511: Left Ventricular Diastolic Dysfunction Occurs Following Percutaneous ASD Closure: An Effect of Ventricular-Arterial Compliance Mismatch?

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Paul White ◽  
Stephen Hoole ◽  
Rajesh Kharbanda ◽  
Evelyn Lee ◽  
Leonard Shapiro
Keyword(s):  
Diastolic Dysfunction ◽  
Pulmonary Edema ◽  
Diastolic Function ◽  
Diastolic Pressure ◽  
Arterial Compliance ◽  
Left Ventricular ◽  
General Anaesthetic ◽  
Arterial Elastance ◽  
Asd Closure ◽  
Lv Diastolic Function

Percutaneous ASD closure can result in hemodynamic compromise and pulmonary edema immediately after closure, particularly in older adults. We hypothesized that the percutaneous Amplatzer® septal occluder (ASO) device would influence LV diastolic function. Eighteen adult patients (6 male, 41±20 years) undergoing elective ASO device implantation for secundum ASD closure (Qp:Qs >1.5) under general anaesthetic had LV (18 patients) and RV (11 patients) conductance catheter assessment. Load dependent (time constant of diastolic relaxation (Tau)) and independent (end-diastolic pressure volume relationship (EDPVR), effective arterial elastance (Ea) and ventricular-arterial (V-A) coupling (Ees/Ea)) indices were measured before and after closure. Following closure of the ASD with an ASO device (8 –34mm), LV Tau increased (msec: 47.7(8.2) vs. 51.4(9.6), p<0.05) and there was a trend to increased LV EDPVR (1.1 (0.7) vs. 1.4 (1.1), p=0.19). The Ea increased significantly (mmHg/ml: 8.6 (5.8) vs. 10.8 (6.3), p=0.01) and V-A coupling deteriorated (Ees/Ea 0.61 (0.59) vs. 0.37 (0.18), p=0.09). RV hemodynamics remained constant. Percutaneous ASD closure causes an immediate deterioration in LV diastolic function, as a result of altered V-A coupling due to an increase in Ea. This could explain why patients develop pulmonary edema after ASD closure. Correcting Ea offers a potential therapeutic target to prevent diastolic dysfunction following ASO implantation.

scholarly journals Impact of Left Ventricular Diastolic Dysfunction and Biomarkers on Pulmonary Hypertension in Patients with Severe Aortic Stenosis

Medicina ◽  
2018 ◽  
Vol 54 (4) ◽  
pp. 63
Author(s):  
Birutė Gumauskienė ◽  
Aušra Krivickienė ◽  
Regina Jonkaitienė ◽  
Jolanta Vaškelytė ◽  
Adakrius Siudikas ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Severe Aortic Stenosis ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Ventricular Diastolic Dysfunction ◽  
Lv Diastolic Dysfunction

Background: Severe aortic stenosis (AS) complicated by pulmonary hypertension (PH) is associated with poor outcomes after surgical aortic valve replacement (AVR). There is still scarce information about predictors of secondary PH in this group of patients. Objectives: The aim of this study was to investigate the prognostic impact of biomarkers together with conventional Doppler echocardiographic parameters of left ventricular diastolic function on elevated pulmonary systolic pressure (PSP) in severe AS patients before surgical AVR. Methods: Sixty patients with severe isolated AS (aortic valve area <1 cm2) underwent echocardiography, N-terminal pro B-type natriuretic peptide (NT-proBNP) and growth differentiation factor-15 (GDF-15) measurements before AVR. PSP, left ventricular ejection fraction (LV EF), parameters of LV diastolic function (E/E’ ratio, mitral valve deceleration time (MV DT) and left atrial (LA) volume) were evaluated. PH was defined as an estimated PSP ≥ 45 mmHg. Results: Of the 60 patients, 21.7% with severe isolated AS had PH with PSP ≥ 45 mmHg (58.5 ± 11.2 mmHg). LV EF did not differ between groups and was not related to an elevated PSP (50 ± 8 vs. 49 ± 8%, p = 0.58). Parameters of LV diastolic dysfunction (E/E’ ratio > 14 (OR 6.00; 95% CI, 1.41–25.48; p = 0.009), MV DT ≤ 177.5 ms (OR 9.31; 95% CI, 2.06–41.14; p = 0.001), LA volume > 100 mL (OR 9.70; 95% CI, 1.92–49.03; p = 0.002)) and biomarkers (NT-proBNP > 4060 ng/L (OR 12.54; 95% CI, 2.80–55.99; p < 0.001) and GDF-15 > 3393 pg/mL (OR 18.33; 95% CI, 2.39–140.39; p = 0.001)) were significantly associated with elevated PSP in severe AS. Conclusions: Left ventricular diastolic dysfunction and elevated biomarkers levels could predict the development of pulmonary hypertension in patients with severe aortic stenosis. Elevation of biomarkers paired with worsening of LV diastolic dysfunction could help to stratify patients for earlier surgical treatment before the development of pulmonary hypertension.

scholarly journals HDL-C to hsCRP ratio is associated with left ventricular diastolic function in absence of significant coronary atherosclerosis

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Lufan Sun ◽  
Xiaorui Liu ◽  
Wenna Li ◽  
Dalin Jia
Keyword(s):  
Regression Analysis ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Coronary Atherosclerosis ◽  
Protective Factor ◽  
Density Lipoprotein ◽  
Left Ventricular Diastolic Function ◽  
Left Ventricular ◽  
Lv Diastolic Dysfunction ◽  
Lv Diastolic Function

Abstract Background High-density lipoprotein cholesterol (HDL-C) is considered as a protective marker of coronary atherosclerotic disease (CAD). It is still not clear if HDL-C is associated with left ventricular (LV) diastolic function in an inflammation-related manner in absence of significant coronary atherosclerosis. Methods 392 patients who complained of chest pain and were suspected of CAD without heart failure were enrolled in this study. Coronary angiography or coronary artery CT scan was performed to detect coronary atherosclerosis. Transthoracic echocardiography was performed to evaluate cardiac function. Plasma level of HDL-C and high-sensitive C-reactive protein (hsCRP) were determined in each subject. Relationship between HDL-C/hsCRP ratio and LV diastolic function in subjects without significant coronary atherosclerosis was investigated. Results 204 subjects without significant coronary plaques were analyzed finally, including 84 males and 120 females whose ages ranged from 30 to 84 years old. When divided into HDL-C/hsCRP quartiles, those in the fourth quartile demonstrated the best diastolic function (E/e’ 10.14 ± 2.87, P = 0.02 ). HDL-C/hsCRP was the most significant factor correlated with E/e’ in univariate regression analysis (r = − 0.232, P < 0.001) and multiple regression analysis adjusted by other factors (standardized β = − 0.258 , P < 0.0005 ). In logistic regression, HDL-C/hsCRP was proved to be a protective factor of LV diastolic dysfunction E/e’ > 14 (OR = 0.649, 95%CI 0.444–0.948,P = 0.025 ). The sensitivity and specificity of using HDL-C/hsCRP < 0.98 to predict LV diastolic dysfunction were 64.3% and 56.2%, respectively. HDL-C/hsCRP ratio presented a reduced trend as increasing rate of CV risk factors. Conclusions HDL-C/hsCRP ratio strongly correlates with LV diastolic function in absence of significant coronary atherosclerosis. Low HDL-C/hsCRP ratio tends to relate with LV diastolic dysfunction.

scholarly journals Tachycardia-induced myocardial ischemia and diastolic dysfunction potentiate secretion of ANP, not BNP, in hypertrophic cardiomyopathy

2006 ◽  
Vol 290 (3) ◽  
pp. H1064-H1070 ◽  
Author(s):  
Shinsuke Kido ◽  
Naoyuki Hasebe ◽  
Yoshinao Ishii ◽  
Kenjiro Kikuchi
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Myocardial Ischemia ◽  
Diastolic Dysfunction ◽  
Diastolic Pressure ◽  
Systolic Function ◽  
Left Ventricular ◽  
Atrial Pacing ◽  
Catheter Tip ◽  
Lv Systolic Function ◽  
Lv Diastolic Dysfunction

The aim of this study was to investigate what factor determines tachycardia-induced secretion of atrial and brain natriuretic peptides (ANP and BNP, respectively) in patients with hypertrophic cardiomyopathy (HCM). HCM patients with normal left ventricular (LV) systolic function and intact coronary artery ( n = 22) underwent rapid atrial pacing test. The cardiac secretion of ANP and BNP and the lactate extraction ratio (LER) were evaluated by using blood samples from the coronary sinus and aorta. LV end-diastolic pressure (LVEDP) and the time constant of LV relaxation of tau were measured by a catheter-tip transducer. These parameters were compared with normal controls ( n = 8). HCM patients were divided into obstructive (HOCM) and nonobstructive (HNCM) groups. The cardiac secretion of ANP was significantly increased by rapid pacing in HOCM from 384 ± 101 to 1,268 ± 334 pg/ml ( P < 0.05); however, it was not significant in control and HNCM groups. In contrast, the cardiac secretion of BNP was fairly constant and rather significantly decreased in HCM ( P < 0.01). The cardiac ANP secretion was significantly correlated with changes in LER ( r = −0.57, P < 0.01) and tau ( r = 0.73, P < 0.001) in HCM patients. Tachycardia potentiates the cardiac secretion of ANP, not BNP, in patients with HCM, particularly when it induces myocardial ischemia and LV diastolic dysfunction.

Abstract 13910: Importance of Non-invasive Estimates of Left Ventricular Filling Pressures in Critically Ill Patients

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Abdelrahman M Ahmed ◽  
Brandon Wiley ◽  
Jacob C Jentzer ◽  
Nandan S Anavekar ◽  
Allan S Jaffe
Keyword(s):  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Troponin T ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
Icu Mortality ◽  
Lv Diastolic Function

Introduction: The presence of cardiac dysfunction predicts adverse outcomes in the intensive care unit (ICU). We explored the relationship of cardiac injury and left ventricular (LV) systolic and diastolic dysfunction (LVDD) to outcomes in critically ill patients. Methods: This is a retrospective analysis of adult medical ICU admissions from May, 2018 through October 2019. Patients with elevated high-sensitivity troponin T (hs-cTnT) and an echocardiogram performed within 72 hours of admission were included. Patients were classified as having normal LV diastolic function, isolated LVDD, concomitant LV diastolic and systolic dysfunction (LVDDSD) or indeterminate LV diastolic function based on American Society of Echocardiography 2016 guidelines. LV systolic dysfunction was defined as an ejection fraction (EF) < 50%. Results: Overall, 222 patients were included. LVDD was seen in 123 patients (55.4%). Thirty patients (13.5%) were classified with indeterminate diastolic function and 56 normal diastolic function (25.2%). Of those with LVDD , 59.3% had LVDDSD while isolated LVDD was seen in 40.7%.Patients with LVDDSD had a higher median hs-cTnT at baseline compared to patients with isolated LVDD [102ng/L IQR (50-257) vs. 77 ng/L (33.5-166); p=0.047]. Medial e’ velocity and tricuspid valve systolic regurgitant velocity were often associated with LV systolic dysfunction (p=0.0172 and 0.0013, respectively). LVDDSD was associated with a longer length of stay than patients with isolated LVDD [2.9 (1.6-4.0) vs.1.8 (1.1-3.3); p-value 0.03].Twenty-nine patients died during their ICU stay (13%). Patients with LVDDSD had 9.6-fold higher odds of dying in the ICU than patients with isolated LVDD (p=0.0048). Reduced medial e’ velocity (OR 0.63, CI 0.4-1.0, p=0.0285) and increased E/e’ (OR 1.08, CI 1.01-1.15, p=0.0192) were associated with ICU mortality. The association between LVEF<50% and ICU mortality was less pronounced (OR 0.95, CI 0.01-0.98; p=0.0023). Conclusions: Concomitant LV systolic and diastolic dysfunction and measures of increased cardiac filling pressures are strong predictors of mortality.

scholarly journals Genetic inhibition of calcineurin induces diastolic dysfunction in mice with chronic pressure overload

2009 ◽  
Vol 297 (5) ◽  
pp. H1814-H1819 ◽  
Author(s):  
Ricardo J. Gelpi ◽  
Shumin Gao ◽  
Peiyong Zhai ◽  
Lin Yan ◽  
Chull Hong ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Systolic Function ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Aortic Banding ◽  
Lv Systolic Function ◽  
Calcineurin Inhibition ◽  
Lv Diastolic Function ◽  
Isovolumic Relaxation

Calcineurin is a Ca2+/calmodulin-dependent protein phosphatase that induces myocardial growth in response to several physiological and pathological stimuli. Calcineurin inhibition, induced either via cyclosporine or genetically, can decrease myocardial hypertrophy secondary to pressure overload without affecting left ventricular (LV) systolic function. Since hypertrophy can also affect LV diastolic function, the goal of this study was to examine the effects of chronic pressure overload (2 wk aortic banding) in transgenic (Tg) mice overexpressing Zaki-4β (TgZ), a specific endogenous inhibitor of calcineurin, on LV diastolic function. As expected, in the TgZ mice with calcineurin inhibitor overexpression, aortic banding reduced the degree of LV hypertrophy, as assessed by LV weight-to-body weight ratio (3.5 ± 0.1) compared with that in non-Tg mice (4.6 ± 0.2). LV systolic function remained compensated in both groups with pressure overload. However, the LV end-diastolic stress-to-LV end-diastolic dimension ratio, an index of diastolic stiffness and LV pressure half-time and isovolumic relaxation time, two indexes of isovolumic relaxation, increased significantly more in TgZ mice with aortic banding. Protein levels of phosphorylated phospholamban (PS16), sarco(endo)plasmic reticulum Ca2+-ATPase 2a, phosphorylated ryanodine receptor, and the Na+/Ca2+ exchanger were also reduced significantly ( P < 0.05) in the banded TgZ mice. As expected, genetic calcineurin inhibition inhibited the development of LV hypertrophy with chronic pressure overload but also induced LV diastolic dysfunction, as reflected by both impaired isovolumic relaxation and increased myocardial stiffness. Thus genetic calcineurin inhibition reveals a new mechanism regulating LV diastolic function.

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