Ventricular Diastolic Relaxation Research Articles

Percutaneous Coronary Intervention in a Saphenous Vein Graft Failure: A Case Report

Abstract: Recent published data from the Society of Thoracic Surgery (STS) national database displayed that among patients aged >65 years old who survived following an initial coronary artery bypass graft (CABG) operation, rates of repeat revascularization at 1, 5, 10, and 18 years were 2%, 8%, 16%, and 25%, respectively. The most preferred mode of revascularization was percutaneous coronary intervention (PCI). While remain the most frequently used conduits beside left internal mammary artery (LIMA), saphenous vein grafts (SVGs) have high failure rates. Percutaneous coronary intervention in SVGs is associated with an increased risk of distal coronary embolization, commonly resulting in periprocedural MI. We reported a 79-year-old male patient admitted due to progressive symptoms of chronic coronary syndrome. The patient had a history of hypertension and a CABG surgery in 2012. Electrocardiogram showed ischemia and old myocardial infarction (OMI) in inferior leads as well as poor R wave progression in the precordial leads. Transthoracic echocardiogram displayed a normal ejection fraction but impaired left ventricular (LV) diastolic relaxation. Diagnostic coronary angiography revealed a 70% tubular stenosis in proximal part of SVG supplying posterior descending artery, patent LIMA graft to left anterior descending artery, and complex lesion on native vessel (chronic total occlusion in mid right coronary artery). Implantation of drug eluting stent in SVG-posterior descending artery was performed. Direct-stenting PCI technique using undersized-stent was done to prevent any complications. In conclusion, despite the high risk of complications, vein graft intervention was successfully performed without any complications. Since the high rates of in-stent restenosis following PCI in SVGs, long-term dual antiplatelet therapy should be commenced in this patient. Keywords: saphenous vein graft; vein graft intervention; percutaneous coronary intervention

Anesthetic management for renal transplant in patients with grade III diastolic dysfunction: case reports

BackgroundLeft ventricular diastolic dysfunction is frequently noticed in patients with multiple co-morbidities. Echocardiography is used to determine the presence of diastolic dysfunction and to grade its severity. In left ventricular diastolic dysfunction, the ventricular diastolic distensibility, filling, or relaxation is abnormal; however, the left ventricular ejection fraction may be normal or decreased.Case presentationWe present anesthetic management of two patients with diastolic dysfunction grade III for renal transplant. During declamping in renal transplant, high central venous pressures are required for adequate perfusion of the transplanted kidney. In the operation theater standard monitors including NIBP, SpO2 and five lead ECG were attached. An arterial line (radial) and central line (right internal jugular) were established for IBP and CVP monitoring. Infusions of furosemide and dopamine were started. Nitrogycerine and milrinone infusions were prepared but were not required intraoperatively. Both the patients were extubated at the end of surgery.ConclusionsIncreased incidence of major adverse cardiovascular events has been reported in surgical patients having grade III diastolic dysfunction. Hemodynamic instability and fluid overload in this set of patients are known to generate pulmonary edema.

Pressure‐based beat‐to‐beat right ventricular ejection fraction and Tau from continuous measured ventricular pressures in COVID‐19 ARDS patients

We evaluated pressure-based right ventricular ejection fraction (RVEF) and diastolic isovolumetric relaxation time constant (Tau) from continuously (up to 30 days) invasive measured right ventricular pressures in mechanically ventilated patients with severe COVID-19 acute respiratory distress syndrome(ARDS). We retrospectively calculated beat-to-beat ejection fraction from right ventricular pressures and dp/dt maximum and minimum in 39 patients treated between October 1st, 2020 and June 30th, 2021. After performing a stepwise logistic regression with survival as a dependent variable, we divided the patients into survivors and nonsurvivors based on their 60-day mortality. Independent outcome variables were the values of RVEF and Tau over time after insertion of the right ventricular probe along with right ventricular systolic and diastolic pressures (RVSP) and the estimated pulmonary artery diastolic pressure (ePAD).RVEF increased significantly over time in the survivors (estimate: 0.354; 95% confidence interval,CI: 0.18-0.53; p < 0.001) but remained unchanged in the nonsurvivors. Tau increased significantly in the nonsurvivors (estimate: 0.001; 95% CI: 0.0004-0.0018; p < 0.002) but not in the survivors. On the last measurement day,RVSP and ePAD were significantly lower while RVEF was significantly higher in the survivors compared to the nonsurvivors. In COVID-19 ARDS patient's, calculation of beat-to-beat RVEF and Tau from continuously invasive measured right ventricular pressures seems to unravel contrary trends in RVEF with an increase in the surviving and a decrease in the nonsurviving patients. Tau remained unchanged in the surviving but increased in the nonsurviving patients over time.

Nicorandil attenuates ventricular dysfunction and organ injury after cardiopulmonary bypass

BackgroundNicorandil, an adenosine triphosphate-sensitive potassium channel agonist and nitric oxide donor, is a coronary vasodilator used to treat ischemia-induced chest pain, but it's potential cardioprotective benefits during open heart surgery have not been thoroughly investigated. The study objective was to assess the impact of nicorandil on postoperative ventricular dysfunction and end-organ injury in an established experimental model of open-heart surgery with cardiopulmonary bypass (CPB) and cardioplegic arrest. We hypothesized that nicorandil would attenuate myocardial ischemia-reperfusion (IR) injury, preserve ventricular function, and reduce end-organ injury. MethodsRabbits were cannulated for CPB, followed by 60 min of aortic cross-clamp (ACC) with cold cardioplegic arrest, and 120 min of recovery after ACC removal. Nicorandil (or normal saline vehicle) was given intravenously 5 min before ACC and continued throughout the recovery period. Left ventricular developed pressure (LVDP), systolic contractility (LV + dP/dt), and diastolic relaxation (LV -dP/dt) were continuously recorded, and blood and tissue samples were collected for measurement of oxidant stress (OS), inflammation, apoptosis, and organ injury. ResultsNicorandil significantly attenuated IR-induced LV dysfunction compared to saline control (R-120: LV + dP/dt: 1596 ± 397 vs. 514 ± 269 mmHg/s, p = 0.010; LV -dP/dt: −1524 ± 432 vs. -432 ± 243 mmHg/s, p < 0.001; LVDP: 55 ± 11 vs. 22 ± 5 mmHg, p = 0.046). Furthermore, nicorandil inhibited IR-induced increases in OS, inflammation, apoptosis, and organ injury. ConclusionsNicorandil exhibits myocardial protection by attenuation of IR-induced LV dysfunction associated with OS, inflammation, apoptosis, and organ injury. Nicorandil should be explored further as a potential therapeutic strategy for limiting global IR injury during open-heart surgery in humans.

Platelet-rich plasma exhibits anti-inflammatory effect and attenuates cardiomyocyte damage by reducing NF-κB and enhancing VEGF expression in isoproterenol induced cardiotoxicity model.

The present study investigated the cardioprotective effects of activated platelet-rich plasma (PRP) on high dose isoproterenol (ISO) induced cardiotoxicity. ISO was injected at a dose of 85 mg/kg/day, s.c. for 2 days. Cardiac function parameters including dp/dt max/min, left ventricular end diastolic pressure (LVEDP), relaxation constant (tau) and electrocardiogram (ECG) changes, anti-oxidant and membrane bound enzymes assays, pro-inflammatory cytokine levels, collagen content, immunohistochemical staining/gene expression of vascular endothelial growth factor (VEGF), cTnI (cardiac troponin I), NF-κB (nuclear factor kappa B), Smad-2/3, TGF-β (transforming growth factor), collagen-1/3 proteins were evaluated. PRP and platelet-poor plasma (PPP) were injected intramyocardially (200 μl in each ventricle region) 3 h after first dose of ISO under anesthesia. ISO injection induced cardiac dysfunction, hypertrophy, fibrosis, necrosis due to decline in anti-oxidant capacity, enhanced NF-κB and reduced cTnI immunostaining. However, the PRP injection attenuated these cardiac pathological changes by exerting anti-inflammatory properties and promoting cardiomyocyte repair.

Milrinone Acts as a Vasodilator But Not an Inotrope in Children After Cardiac Surgery-Insights From Wave Intensity Analysis.

Milrinone is an inodilator widely used in the postoperative management of children undergoing cardiac surgery. The literature supporting its inotropic effect is sparse. We sought to study the effect of milrinone on the vasculature and its effects on the ventricular function using wave intensity analysis. We also intended to evaluate the feasibility of using wave intensity analysis by the bedside. prospective single-center observational study. PICU of a tertiary children's hospital. Children (< 18 yr) admitted to PICU following cardiac surgery who required to be commenced on a milrinone infusion. Echocardiography and Doppler ultrasound assessments for wave intensity analysis were performed prior to commencing milrinone and 4-6 hours after milrinone infusion. Wave intensity analysis was successfully performed and analyzed in 15 of 16 patients (94%). We identified three waves-a forward compression wave, backward compression wave, and forward decompression wave. The waves were described with their cumulative intensity and wave-related pressure change. There was a 26% reduction in backward compression wave cumulative intensity following the introduction of milrinone. Other variables (backward compression wave cumulative intensity/forward compression wave cumulative intensity ratio, backward compression wave wave-related pressure change, backward compression wave wave-related pressure change/forward compression wave wave-related pressure change ratio) consistent with vasodilation also decreased after milrinone. It also decreased the vascular wavespeed by 7.1% and increased the distensibility of the vessels by 14.6%. However, it did not increase forward compression wave cumulative intensity, a variable indicating the systolic force generated by the ventricle. Forward decompression wave cumulative intensity indicating ventricular early diastolic relaxation also did not change. In a cohort of children recovering in PICU after having undergone cardiac surgery, we found that milrinone acted as a vasodilator but did not demonstrate an improvement in the contractility or an improved relaxation of the left ventricle as assessed by wave intensity analysis. We were able to demonstrate the feasibility and utility of wave intensity analysis to further understand ventriculo-vascular interactions in an intensive care setting.

Deep phenotyping of cardiac function in heart transplant patients using cardiovascular system models.

Right heart catheterization data from clinical records of heart transplant patients are used to identify patient-specific models of the cardiovascular system. These patient-specific cardiovascular models represent a snapshot of cardiovascular function at a given post-transplant recovery time point. This approach is used to describe cardiac function in 10 heart transplant patients, five of which had multiple right heart catheterizations allowing an assessment of cardiac function over time. These patient-specific models are used to predict cardiovascular function in the form of right and left ventricular pressure-volume loops and ventricular power, an important metric in the clinical assessment of cardiac function. Outcomes for the longitudinally tracked patients show that our approach was able to identify the one patient from the group of five that exhibited post-transplant cardiovascular complications. Heart transplant patients are followed with periodic right heart catheterizations (RHCs) to identify post-transplant complications and guide treatment. Post-transplant positive outcomes are associated with a steady reduction of right ventricular and pulmonary arterial pressures, toward normal levels of right-side pressure (about 20mmHg) measured by RHC. This study shows that more information about patient progression is obtained by combining standard RHC measures with mechanistic computational cardiovascular system models. The purpose of this study is twofold: to understand how cardiovascular system models can be used to represent a patient's cardiovascular state, and to use these models to track post-transplant recovery and outcome. To obtain reliable parameter estimates comparable within and across datasets, we use sensitivity analysis, parameter subset selection, and optimization to determine patient-specific mechanistic parameters that can be reliably extracted from the RHC data. Patient-specific models are identified for 10 patients from their first post-transplant RHC, and longitudinal analysis is carried out for five patients. Results of the sensitivity analysis and subset selection show that we can reliably estimate seven non-measurable quantities; namely, ventricular diastolic relaxation, systemic resistance, pulmonary venous elastance, pulmonary resistance, pulmonary arterial elastance, pulmonary valve resistance and systemic arterial elastance. Changes in parameters and predicted cardiovascular function post-transplant are used to evaluate the cardiovascular state during recovery of five patients. Of these five patients, only one showed inconsistent trends during recovery in ventricular pressure-volume relationships and power output. At the four-year post-transplant time point this patient exhibited biventricular failure along with graft dysfunction while the remaining four exhibited no cardiovascular complications.

Normoxic re-oxygenation ameliorates end-organ injury after cardiopulmonary bypass

BackgroundIn a rabbit model of cardiopulmonary bypass (CPB) and cardioplegic arrest, we previously showed that hyperoxic myocardial reperfusion was associated with increased left ventricular (LV) systolic dysfunction and myocardial injury compared with normoxic reperfusion. The aim of this study was to evaluate in our experimental model the impact of post-CPB reperfusion conditions on other organs potentially vulnerable to ischemic injury such as the brain and kidney.MethodsAfter 60 min of CPB, aortic cross-clamp, and cold cardioplegic arrest, rabbits were reperfused under hyperoxic or normoxic conditions for 120 min. Left ventricular systolic contractility (LV + dP/dt) and diastolic relaxation (LV –dP/dt) were continuously recorded, and end-organ injury was assessed by measuring circulating biomarkers specific for kidney (cystatin C and creatinine) and brain injury [S100B and neuron specific enolase (NSE)]. At completion of the protocol, kidney and brain tissues were harvested for measuring oxidant stress (OS), inflammation and apoptosis.ResultsFollowing aortic cross-clamp removal, rabbits exposed to normoxic reperfusion demonstrated preserved LV systolic and diastolic function compared with hyperoxic reperfusion (LV + dP/dt: 70 ± 14% of pre-CPB vs. 36 ± 21%, p = 0.018; LV -dP/dt: 72 ± 36% of pre-CPB vs. 33 ± 20%, p = 0.023). Similarly, CPB increased plasma creatinine, S100B and NSE that were significantly attenuated by normoxic reperfusion compared with hyperoxic reperfusion (creatinine: 4.0 ± 0.5 vs. 7.1 ± 0.8 mg/dL, p = 0.004; S100B: 4.0 ± 0.8 vs. 6.7 ± 1.0 ng/mL, p = 0.047; NSE: 57.7 ± 6.8 vs. 101.3 ± 16.1 pg/mL, p = 0.040). Furthermore, both kidney and brain tissues showed increased mRNA expression and activation of pathways for OS, inflammation, and apoptosis, that were reduced under normoxic compared with hyperoxic conditions.ConclusionsNormoxic reperfusion ameliorates cardiac, renal and neural injury compared with hyperoxic reperfusion in an in vivo animal model of CPB and cardioplegic arrest. This protective effect of normoxic reperfusion may be due to a reduction in signaling pathways for OS, inflammation, and apoptosis.

Evolution of Echocardiographic Measures of Cardiac Disease From CKD to ESRD and Risk of All-Cause Mortality: Findings From the CRIC Study

Abnormal cardiac structure and function are common in chronic kidney disease (CKD) and end-stage renal disease (ESRD) and linked with mortality and heart failure. We examined changes in echocardiographic measures during the transition from CKD to ESRD and their associations with post-ESRD mortality. Prospective study. We studied 417 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) who had research echocardiograms during CKD and ESRD. We measured change in left ventricular mass index, left ventricular ejection fraction (LVEF), diastolic relaxation (normal, mildly abnormal, and moderately/severely abnormal), left ventricular end-systolic (LVESV), end-diastolic (LVEDV) volume, and left atrial volume from CKD to ESRD. All-cause mortality after dialysis therapy initiation. Cox proportional hazard models were used to test the association of change in each echocardiographic measure with postdialysis mortality. Over a mean of 2.9 years between pre-and postdialysis echocardiograms, there was worsening of mean LVEF (52.5% to 48.6%; P<0.001) and LVESV (18.6 to 20.2mL/m2.7; P<0.001). During this time, there was improvement in left ventricular mass index (60.4 to 58.4g/m2.7; P=0.005) and diastolic relaxation (11.11% to 4.94% with moderately/severely abnormal; P=0.02). Changes in left atrial volume (4.09 to 4.15mL/m2; P=0.08) or LVEDV (38.6 to 38.4mL/m2.7; P=0.8) were not significant. Worsening from CKD to ESRD of LVEF (adjusted HR for every 1% decline in LVEF, 1.03; 95% CI, 1.00-1.06) and LVESV (adjusted HR for every 1mL/m2.7 increase, 1.04; 95% CI, 1.02-1.07) were independently associated with greater risk for postdialysis mortality. Some missing or technically inadequate echocardiograms. In a longitudinal study of patients with CKD who subsequently initiated dialysis therapy, LVEF and LVESV worsened and were significantly associated with greater risk for postdialysis mortality. There may be opportunities for intervention during this transition period to improve outcomes.

Association between Left Ventricular Postsystolic Shortening and Diastolic Relaxation in Asymptomatic Patients with Systemic Hypertension.

Few data have existed on myocardial postsystolic shortening (PSS) accounting for left ventricular (LV) diastolic dysfunction in systemic hypertension. We examined this relationship, along with clinical and other cardiac parameters, in asymptomatic patients with hypertension. We analyzed 104 patients on pharmacological treatment for hypertension who had no signs or symptoms of heart failure for conventional and speckle tracking echocardiography. The sum of the postsystolic index for multiple LV segments (total PSI) and global longitudinal strain (GLS) was computed and used as measures for global PSS and myocardial systolic function, respectively. The tissue Doppler e' and the speckle tracking-derived global strain rate during early diastole (e'sr) were obtained as indicators of LV relaxation. The circumferential end-systolic stress was also determined noninvasively and substituted for a measure of myocardial afterload. Main variables that correlated with the e' and e'sr were shown to be age, LV mass index, left atrial volume index, GLS, and the total PSI. Multivariate analysis including gender, circumferential end-systolic stress, and the use of calcium channel blockers as possible covariates revealed that age (β=-0.29, P=0.002), total PSI (β=-0.26, P=0.008), and LV mass index (β=-0.25, P=0.017) were significant independent determinants of e' and that age (β=-0.34, P<0.001) and GLS (β=-0.28, P=0.006) were of e'sr. Our findings indicate that while depending on the degree of GLS, PSS may affect diastolic relaxation in patients with asymptomatic, but treated, hypertensive patients.

Characterization of regional left ventricular function in nonhuman primates using magnetic resonance imaging biomarkers: a test-retest repeatability and inter-subject variability study.

Pre-clinical animal models are important to study the fundamental biological and functional mechanisms involved in the longitudinal evolution of heart failure (HF). Particularly, large animal models, like nonhuman primates (NHPs), that possess greater physiological, biochemical, and phylogenetic similarity to humans are gaining interest. To assess the translatability of these models into human diseases, imaging biomarkers play a significant role in non-invasive phenotyping, prediction of downstream remodeling, and evaluation of novel experimental therapeutics. This paper sheds insight into NHP cardiac function through the quantification of magnetic resonance (MR) imaging biomarkers that comprehensively characterize the spatiotemporal dynamics of left ventricular (LV) systolic pumping and LV diastolic relaxation. MR tagging and phase contrast (PC) imaging were used to quantify NHP cardiac strain and flow. Temporal inter-relationships between rotational mechanics, myocardial strain and LV chamber flow are presented, and functional biomarkers are evaluated through test-retest repeatability and inter subject variability analyses. The temporal trends observed in strain and flow was similar to published data in humans. Our results indicate a dominant dimension based pumping during early systole, followed by a torsion dominant pumping action during late systole. Early diastole is characterized by close to 65% of untwist, the remainder of which likely contributes to efficient filling during atrial kick. Our data reveal that moderate to good intra-subject repeatability was observed for peak strain, strain-rates, E/circumferential strain-rate (CSR) ratio, E/longitudinal strain-rate (LSR) ratio, and deceleration time. The inter-subject variability was high for strain dyssynchrony, diastolic strain-rates, peak torsion and peak untwist rate. We have successfully characterized cardiac function in NHPs using MR imaging. Peak strain, average systolic strain-rate, diastolic E/CSR and E/LSR ratios, and deceleration time were identified as robust biomarkers that could potentially be applied to future pre-clinical drug studies.

Cardiohemodynamics and Efficiency of Frank - Starling Mechanism in Aging

In adult and old Wistar rats, we studied cardio-hemodynamics and efficiency of Frank − Starling mechanisms. To evaluate systolic and diastolic function of the heart in vivo, the left-ventricular pressure and volume with visualization of the curves during the cardiac cycle were recorded using ultra miniature catheter 2F (Millar Instruments, USA). We have revealed left ventricular diastolic dysfunction and impaired relaxation of the heart in old rats, which is evidenced by the reduction in the maximum rate of left ventricular pressure generation under an increase in both end-diastolic stiffness and active relaxation constant. The results indicate that the efficiency of Frank-Starling mechanism (ΔSV/ΔEDV) decreases in old rats. At the same time, oxygen consumption in old rats increases by 70%, and stroke work of the heart increases 1.7 times. It means that despite the similar stroke volume, the heart of old rats perform more stroke work, with greater oxygen consumption, indicating that the heart of old rats works less effectively.

Improved Loaded In Vitro Motility Assay and Actin Filament Tracking Software Delineates the Effect of Hypertrophic and Dilated Cardiomyopathy Mutations on the Power Output of Cardiac Myosin

Hypertrophic (HCM) and dilated (DCM) cardiomyopathies are important causes of heart failure, arrhythmia, and sudden cardiac death. HCM is the most common heritable cardiovascular disorder, affecting 1 in 500 individuals, and is caused primarily by mutations that alter proteins of the cardiac sarcomere. Sarcomeric protein mutations are an increasingly recognized cause of familial DCM as well. HCM is associated with severe thickening of the left ventricular wall, preserved/increased systolic (contractile) and impaired diastolic (relaxation) function of the heart. DCM hearts have dilated left ventricular chambers and suffer from inadequate systolic activity. More than 300 point mutations in beta-cardiac myosin are associated with HCM or DCM. It is believed that HCM and DCM mutations increase and decrease respectively the power output of cardiac myosin which leads to a cascade of downstream signaling that gradually leads to the disease phenotype. To test this hypothesis it is essential to measure the power output of all HCM/DCM mutants in a high throughput manner. To quantitatively measure the load dependent myosin power output, we first improved the loaded in vitro motility assay (LIMA) by replacing load generating molecule alpha-actinin with alpha-catenin, which was generously provided by James Nelson at Stanford University. For accurate-and-fast data analysis, we developed a software called FAST that runs over parallel CPUs. Our initial results indicate that two HCM mutants (R719W, R403Q) have higher power output than the wildtype cardiac myosin. FAST-LIMA will be an essential tool for screening drugs that revert the effects of HCM/DCM mutations on the power output of beta-cardiac myosin.

Echocardiographic evaluation and comparison of the effects of sevoflurane and desflurane on left ventricular relaxation indices in patients with diastolic dysfunction scheduled for coronary artery bypass grafting surgery

Background Effect of inhalational anesthetics on diastolic function in humans is still controversial, although inhalational anesthetics have been shown to have negative lusitropic action in experimental studies, which were explained by interference of inhalational anesthetics with calcium homeostasis. Aim This prospective randomized study aims to evaluate and compare the effects of sevoflurane and desflurane on left ventricular (LV) diastolic function in patients with impaired LV relaxation due to ischemic heart disease using transesophageal Doppler echocardiography. Patients and methods After approval from the local ethics committee and informed consent, 24 patients scheduled for coronary artery bypass grafting surgery were enrolled in the study. Patients were selected by a preoperative transthoracic echocardiographic diagnosis of impaired relaxation or grade 1 diastolic dysfunction. Anesthetic induction was standardized in both groups. Patients randomly received 1 MAC of sevoflurane ( n = 12) or desflurane ( n = 12) for maintenance of anesthesia. Hemodynamic parameters and transesophageal echocardiography (TEE) derived ventricular diastolic relaxation indices before and after the study drug administration were compared. LV filling pressures were kept within normal range throughout the study period to exclude the effect of the loading conditions on diastolic function. Results The two study drugs significantly reduced the systemic vascular resistance index with a significant increase in the cardiac index. Hemodynamic changes measured by invasive arterial line and pulmonary artery catheter were comparable between the two groups. In terms of LV relaxation indices, the two agents led to a significant improvement in diastolic function. Transmitral and tissue Doppler E/A and Em/Am ratios improved significantly accompanied by a significant decrease in deceleration time and isovolumetric relaxation time. The effect of the two agents on diastolic relaxation parameters was comparable. Conclusion Sevoflurane and desflurane appear to improve LV relaxation. This can be explained by a significant reduction in afterload produced by these vapors. The positive effect of these inhalational agents on LV relaxation can have a beneficial effect on the anesthetic management of patients with diastolic dysfunction.

Inactivation of Myosin Binding Protein C Homolog in Zebrafish as a Model for Human Cardiac Hypertrophy and Diastolic Dysfunction

BackgroundSudden cardiac death due to malignant ventricular arrhythmia is a devastating manifestation of cardiac hypertrophy. Sarcomere protein myosin binding protein C is functionally related to cardiac diastolic function and hypertrophy. Zebrafish is a better model to study human electrophysiology and arrhythmia than rodents because of the electrophysiological characteristics similar to those of humans.Methods and ResultsWe established a zebrafish model of cardiac hypertrophy and diastolic dysfunction by genetic knockdown of myosin binding protein C gene (mybpc3) and investigated the electrophysiological phenotypes in this model. We found expression of zebrafish mybpc3 restrictively in the heart and slow muscle, and mybpc3 gene was evolutionally conservative with sequence homology between zebrafish and human mybpc3 genes. Zebrafish with genetic knockdown of mybpc3 by morpholino showed ventricular hypertrophy with increased myocardial wall thickness and diastolic heart failure, manifesting as decreased ventricular diastolic relaxation velocity, pericardial effusion, and dilatation of the atrium. In terms of electrophysiological phenotypes, mybpc3 knockdown fish had a longer ventricular action potential duration and slower ventricular diastolic calcium reuptake, both of which are typical electrophysiological features in human cardiac hypertrophy and heart failure. Impaired calcium reuptake resulted in increased susceptibility to calcium transient alternans and action potential duration alternans, which have been proved to be central to the genesis of malignant ventricular fibrillation and a sensitive marker of sudden cardiac death.Conclusionsmybpc3 knockdown in zebrafish recapitulated the morphological, mechanical, and electrophysiological phenotypes of human cardiac hypertrophy and diastolic heart failure. Our study also first demonstrated arrhythmogenic cardiac alternans in cardiac hypertrophy.

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.

The Efficacy of Cardiac Findings in Assessing the Outcome in Preterms with Bronchopulmonary Dysplasia

To evaluate if cardiac dysfunctions are important in assessing the outcome in newborns with Bronchopulmonary Dysplasia (BPD), by evaluating cardiac functions with N-terminal prohormone of brain natriüretic peptide (NT-proBNP) levels, M-mode and tissue doppler echocardiography at 6-12 mo of age. Twenty eight patients were retrospectively classified as mild, moderate and severe according to the diagnostic criterias for BPD. All cases were assessed with standard M-mode, tissue doppler echocardiography and NT-proBNP levels. Control group consisted of 28 healthy infants, having similar postnatal ages as patients and were assessed with standard M-mode and tissue doppler echocardiography. The age of patients with BPD was 9.8 ± 2.3 mo and control group was 9.5 ± 2.6 mo. There was no significant difference between the postnatal ages of two groups (p > 0.05). Neither pulmonary hypertension nor pulmonary/tricuspid regurgitation was detected. The M-mode echocardiography measurements did not differ between patients and control group (p > 0.05). Tissue doppler echocardiography, tricuspid valve medial segment early diastolic myocardial relaxation velocity (TME') measurements of patients were found significantly lower, peak transtricuspid filling velocity in the early diastole (TE)/TME' ratios and isovolumetric relaxation time (IVRT) measurements were found significantly higher than control group (p < 0.05). Tricuspid E, TE/TLE' (Tricuspid valve lateral segment early diastolic myocardial relaxation velocity), TE/RVLE'(Right ventricular lateral segment early diastolic myocardial relaxation velocity), TE/TME' levels were also found as significantly abnormal in patients with severe BPD. A significant correlation was found between right ventricular diastolic disfunctions and severity of BPD (p < 0.05). No statistically significant difference was found between NT-proBNP levels, BPD stages and tissue doppler echocardiography measurements (p > 0.05). This is the first study evaluating cardiac findings in patients with BPD by tissue doppler echocardiography and NT-proBNP at the same time. On the basis of cardiac evaluations, tissue doppler echocardiography measurements were found as significant and specific for the early assessment of right ventricular diastolic disfunctions.

Ventricular Torsion: Research Tool or Novel Clinical Indicator?

Ventricular Torsion: Research Tool or Novel Clinical Indicator?

Reduced diastolic function and left ventricular mass in HIV-negative preadolescent children exposed to antiretroviral therapy in utero

Abnormalities in left ventricular morphology and function have been reported in HIV-negative infants exposed to antiretroviral therapy (ART) in utero that persists throughout preschool age. The objective of this study was to determine if these abnormalities persist, resolve, or worsen during preadolescence. Cross-sectional observation study. Thirty HIV-negative children born to HIV-positive women and exposed to ART in utero (mean age 8 ± 2 years, 37% female, 74% African-American) and 30 HIV-negative children born to HIV-negative women (mean age 8 ± 3 years, 37% female, 76% African-American) underwent two-dimensional Doppler, tissue Doppler, and strain echocardiography to evaluate left ventricular systolic and diastolic function. Weight, body surface area, heart rate and blood pressure were similar between groups. For the ART-exposed group, left ventricular mass index was lower (60 ± 9 vs. 67 ± 12 g/m, P < 0.02) and early diastolic annular velocity was lower (15.0 ± 2.2 vs. 16.3 ± 2.5 cm/s, P < 0.03) compared to controls. Left ventricular systolic function did not differ between groups. Lower maternal third trimester CD4 count was associated with lower early diastolic annular velocity; other non-HIV-related variables including cocaine use and increased maternal age correlated with lower left ventricular mass index. Abnormalities in left ventricular systolic performance previously reported in HIV-negative infants and preschool aged children exposed to ART in utero were not apparent in preadolescent children. Left ventricular diastolic relaxation was reduced compared with controls suggesting residual effects of ART exposure on left ventricular diastolic function. Larger, longitudinal studies are necessary to confirm these observations.

In-treatment stroke volume predicts cardiovascular risk in hypertension

To evaluate whether lower stroke volume during antihypertensive treatment is a predictor of cardiovascular events independent of left ventricular geometric pattern. The association between left ventricular stroke volume and combined cardiovascular death, stroke and myocardial infarction, the prespecified primary study endpoint, was assessed in Cox regression analysis using data from baseline and annual follow-up visits in 855 patients during 4.8 years of randomized losartan-based or atenolol-based treatment in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy. During follow-up, a total of 91 primary endpoints occurred. At baseline, lower left ventricular stroke volume was associated with smaller body size, female sex, lower left ventricular mass and stress-corrected midwall shortening, higher relative wall thickness and total peripheral resistance, more concentric left ventricular geometry and impaired diastolic relaxation (all P < 0.01). Baseline stroke volume did not predict outcome. However, in time-varying multivariable Cox regression analysis, lower in-treatment left ventricular stroke volume indexed for height was associated with higher risk of cardiovascular events {hazard ratio 1.69 per 1 SD (6 ml/m) lower stroke volume [95% confidence interval (CI) 1.35-2.11], P < 0.001} independent of in-treatment left ventricular mass and concentric geometry and in a secondary model also independent of stress-corrected midwall shortening, impaired diastolic relaxation, heart rate, new-onset atrial fibrillation and study treatment [hazard ratio 1.46 per 1 SD (6 ml/m) lower stroke volume (95% CI 1.13-1.88)]. Assessment of in-treatment left ventricular stroke volume may reflect cardiac and vascular remodeling and impairment and, hence, adds information on cardiovascular risk in treated hypertensive patients beyond assessment of left ventricular structure alone. NCT 00338260.