Left Ventricular Ischemia Research Articles

Acute Severe Functional Mitral Regurgitation After Non-Mitral Valve Cardiac Surgery—Left Ventricular Dyssynchrony as a Potential Mechanism

Functional mitral regurgitation (MR) describes valve leakage in the absence of disease or damage to the mitral leaflets or subvalvular apparatus. Significant, new functional MR after cardiopulmonary bypass (CPB) may result from a number of intraoperative processes, including left ventricular (LV) ischemia and enlargement, left atrial enlargement secondary to increased filling pressure, and systolic anterior motion of the mitral valve after mitral repair. Assessment of new MR after CPB is important because it may direct hemodynamic maneuvers or prompt reinitiation of CPB if surgical intervention is deemed necessary. Described extensively in the electrophysiology literature but underreported as a cause of MR after CPB, LV dyssynchrony represents another possible mechanism of functional MR, in which resynchronization of conduction via pacing maneuvers may prove beneficial. Herein, a series of 4 patients in whom new MR was found after non-mitral valve cardiac surgery in the setting of normal LV systolic function is presented, and LV dyssynchrony is proposed as a major contributing factor. The findings suggested that the concomitant observation of new or worsened functional MR, together with normal global and regional LV systolic function, should lead the clinician to consider ventricular dyssynchrony as a possible cause. Attempts to improve or alter ventricular conduction should be considered before contemplating a return to CPB for mitral valve intervention.

Effects of trimetazidine on ventricular remodeling in coronary artery disease patients with left ventricular hypertrophy: the rationale and design of a randomized controlled trial

BackgroundTrimetazidine is a metabolic anti-ischemic agent, which increases the tolerance of cardiomyocytes to ischemia. However, few studies have explored the effect of trimetazidine on ventricular remodeling in coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) with left ventricular hypertrophy (LVH).MethodsIt is a randomized, placebo-controlled trial, and we propose to recruit one hundred and twenty-four CAD patients undergoing PCI with LVH during a 12-month period. They will be randomized to receive either trimetazidine (35 mg twice a day) or placebo in the following 12 months after PCI. Blood tests, echocardiography, symptom of angina and major adverse cardiovascular events (MACEs) will be collected at follow-up visit at 3 and 12 months. The primary end point will be the left ventricular remodeling measured by left ventricular mass index (LVMI) at 3- and 12-month follow-up compared with the baseline. The secondary end points will be the symptom of angina assessed by Seattle Angina Questionnaire, myocardial ischemia measured by 6-min walk test and exercise electrocardiography test, as well as MACEs (defined as a composite of death, myocardial infarction, stroke, recurrent angina, re-hospitalization, change of viable myocardium).DiscussionThis study aims to demonstrate the effect of trimetazidine on left ventricular remodeling and myocardial ischemia in CAD patients undergoing PCI with LVH. Trimetazidine treatment is likely to improve the left ventricular remodeling, symptoms of angina and myocardial ischemia. It might also reduce the risk of MACEs in CAD patients undergoing PCI with LVH.Trial registrationhttp://www.chictr.org.cn, Chinese Clinical Trial Registry (ChiCTR1800017876). Registered on 19 Aug 2018.

Incremental prognostic value of echocardiography of left ventricular remodeling and diastolic function in STICH trial

AimsWe sought to determine which echocardiographic markers of left ventricular (LV) remodeling and diastolic dysfunction can contribute as incremental and independent prognostic information in addition to current clinical risk markers of ischemic LV systolic dysfunction in the Surgical Treatment for Ischemic Heart Failure (STICH) trial.Methods and resultsThe cohort consisted of 1511 of 2136 patients in STICH for whom baseline transmitral Doppler (E/A ratio) could be measured by an echocardiographic core laboratory blinded to treatment and outcomes, and prognostic value of echocardiographic variables was determined by a Cox regression model. E/A ratio was the most significant predictor of mortality amongst diastolic variables with lowest mortality for E/A closest 0.8, although mortality was consistently low for E/A 0.6 to 1.0. Mortality increased for E/A < 0.6 and > 1.0 up to approximately 2.3, beyond which there was no further increase in risk. Larger LV end-systolic volume index (LVESVI) and E/A < 0.6 and > 1.0 had incremental negative effects on mortality when added to a clinical multivariable model, where creatinine, LVESVI, age, and E/A ratio accounted for 74% of the prognostic information for predicting risk. LVESVI and E/A ratio were stronger predictors of prognosis than New York Heart Association functional class, anemia, diabetes, history of atrial fibrillation, and stroke.ConclusionsEchocardiographic markers of advanced LV remodeling and diastolic dysfunction added incremental prognostic value to current clinical risk markers. LVESVI and E/A ratio outperformed other markers and should be considered as standard in assessing risks in ischemic heart failure. E/A closest to 0.8 was the most optimal filling pattern.

Left Ventricular Strain Normalizes After Balloon Aortic Valvuloplasty in Infants with Congenital Aortic Stenosis.

Severe aortic stenosis (AS) causes left ventricular (LV) afterload and subendocardial ischemia. Despite this, most infants with AS have normal LV ejection fraction (EF). Strain analysis using two-dimensional speckle tracking echocardiography (2DSTE) may identify more sensitive markers of systolic dysfunction. We sought to show changes in LV strain after balloon aortic valvuloplasty (BAV) in infants with AS. Twenty-seven infants ≤ 1year of age with AS who underwent BAV from 2007 to 2017 were included. Echocardiograms before/after BAV were retrospectively analyzed with 2DSTE. Median age was 29days (interquartile range 3-52) and LV EF was 64 ± 10%. Global longitudinal strain (GLS) significantly improved post-BAV (- 17 ± 5 vs. - 20 ± 4%, p = 0.001) with no difference in global circumferential strain. Peak longitudinal strain was abnormal at the inferoseptal base and mid-ventricle (- 15 ± 6 and - 17 ± 5 = 7%, respectively) and significantly improved in the basal and mid-anterolateral segments (- 17 ± 5 vs. - 21 ± 5%, p < 0.01; - 17 ± 6% vs. - 20 ± 5%, p = 0.01, respectively). Five (20%) patients underwent reintervention, and had significantly higher peak-to-peak pre and post-BAV AS gradients (86 ± 14 vs. 61 ± 20mmHg, p = 0.02; 33 ± 17 vs. 21 ± 10mmHg, p = 0.04, respectively). In conclusion, longitudinal strain is abnormal in infants with AS and improves to previously published normal values after BAV.

Competency-Based Medical Education: Do the Cardiac Imaging Training Guidelines Have it Right?

ObjectivesThis study sought to: 1) determine if the current training volume guidelines are reasonable for attaining competence for interpreting myocardial perfusion imaging (MPI); and if not, 2) identify potential thresholds for training volumes and competence. BackgroundThere is a growing desire to adopt competency-based medical education (CBME). As such, the implementation of CBME will require new and novel methods of defining, measuring, and assessing clinical competence. The potential use of CBME in cardiac imaging has not been well studied. MethodsConsecutive MPI studies were interpreted independently by trainees, and expert readers reviewed the same studies. Studies were quantified using summed scores and % left ventricular (LV) ischemia and the kappa agreement between trainee and expert were measured every 50 cases. Agreement for all MPI and abnormal MPI cases was calculated. ResultsA total of 24 trainees interpreted 9,668 MPI studies over 37 months. Agreement between trainees and expert readers increased with MPI case volumes but at different rates. The threshold for competence was set at 2 SDs below expert interobserver agreement. The average trainee surpassed this threshold for both summed stress score and %LV ischemia after 800 studies and after 400 abnormal MPI studies. Trainees learned at different rates and surpassed the competence threshold after different case volumes. ConclusionsThe use of CBME within nuclear cardiology appears to be feasible. Our results suggest that current guidelines may be insufficient to ensure competence and would support the need to increase the MPI case volumes. The use of CBME principles would suggest that trainees may achieve competence at different rates and our results suggest a shift in focus from volume-based learning toward target agreement thresholds.

Final Analysis of a Phase 1b Study of Daratumumab in Combination with Carfilzomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma (RRMM)

Final Analysis of a Phase 1b Study of Daratumumab in Combination with Carfilzomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma (RRMM)

Effect of ulinastatin on myocardial ischemia-reperfusion injury through JNK and P38 MAPK signaling pathways.

The aim of this study was to investigate the effect of ulinastatin (UTI) on myocardial ischemia-reperfusion injury (MIRI) through the c-Jun N-terminal kinase (JNK) signaling pathway and p38 mitogen-activated protein kinase (MAPK) signaling pathway. Healthy adult male Sprague-Dawley (SD) rats were randomly divided into 5 groups, including the sham group (n=10), MIRI group (model group, n=10), UTI group (n=10), UTI + JNK inhibitor SP600125 (UTI+SP600125 group, n=10) and UTI + p38 MAPK inhibitor SB203580 (UTI+SB203580 group, n=10). Hemodynamics, myocardial infarction and the messenger ribonucleic acid (mRNA) expressions of p38 MAPK, JNK, superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) were compared among groups. The protein levels of p38 MAPK and JNK in serum were detected via Western blotting. Furthermore, the correlations of serum p38 MAPK and JNK with TNF-α were analyzed. In the UTI group, the left ventricular systolic pressure (LVSP), the left ventricular end-diastolic pressure (LVEDP) and maximal rate of increase of the left ventricular pressure (+dp/dtmax) were significantly higher than those of the model group. However, the maximal rate of the decrease of the left ventricular pressure (-dp/dtmax), infarction area and ischemia area were significantly smaller than those of the model group. LVSP, LVEDP and +dp/dtmax in UTI+SP600125 group and UTI+SB203580 group were markedly higher than those of the UTI group. Meanwhile, the mRNA expressions of p38 MAPK and JNK in the UTI group were significantly lower than those of the model group. However, the mRNA expression levels of p38 MAPK and JNK in UTI+SP600125 group and UTI+SB203580 group were remarkably higher than the UTI group. Besides, the UTI group showed a markedly higher level of SOD and significantly lower levels of MDA, NO, TNF-α, IL-6 and hs-CRP than the model group. Furthermore, UTI+SP600125 group and UTI+SB203580 group showed significantly higher levels of MDA, NO, TNF-α, IL-6 and hs-CRP than the UTI group. The protein levels p38 MAPK and JNK were remarkably lower in the UTI group than those of the model group. However, they were remarkably higher in UTI+SP600125 group and UTI+SB203580 group than the UTI group. In addition, both p38 MAPK and JNK proteins were positively correlated with TNF-α (r=0.983 and 0.892, p=0.043 and p=0.033). UTI may inhibit MIRI caused by p38 MAPK signaling pathway and JNK signaling pathway by down-regulating TNF-α expression, thereby protecting and improving MIR.

5201Intra-cardiac thrombus in patients undergoing ventricular tachycardia ablation. a computed tomographic scan study

Abstract Background Embolic event is one of the complications of VT ablation. This may be due to the presence of intra-cardiac thrombus before ablation. However, there is no clear consensus on how to rule out thrombus before the procedure. Objective We sought to examine the prevalence and risk factors of intra-cardiac thrombus with cardiac computed tomographic (CT) scan in patients undergoing scar-related VT ablation. Methods In absence of contra-indication, all patients undergoing scar-related VT ablation at our institution underwent contrast-enhanced cardiac CT within one week before ablation. 324 consecutive patients (292 male, 59±16 yo) have been included in this study. The etiology was ischemic cardiomyopathy (CMP) (n=191), arrhythmogenic right ventricular CMP (ARVC) (n=37), congenital CMP (n=11) or other CMP (n=85). LVEF was &lt;40% in 154 patients (48%). Results Intra-cardiac thrombus was diagnosed in 29 (9%) patients: in the left atrium (n=8), in the right atrium (n=1), in the left ventricle (n=15), in the right ventricle (n=3), in right and left atrium (n=1), and in left atrium and right ventricle (n=1). Moreover in 2, a bilateral pulmonary embolism was identified. The population with thrombus was older (65±12 vs 58±16 years, p=0,005), with more permanent atrial fibrillation (AF) (28% vs 8%; p=0.005). Patients with left ventricular (LV) aneurysm were at higher risk of thrombus 50% vs 3% (p&lt;0.001). The average CHADSVASC score was similar for both groups (2,5 vs 2,1; p=0.179). After matching for age and sex, only ischemic CMP and LV aneurysm were risk factors for thrombus. Because of arrhythmic storm, ablation was performed by epicardial approach only, in 5 patients with intra-ventricular thrombus and by retroaortic approach only, in 2 patients with LAA thrombus. No embolic event occurred during these procedures. Conclusion CT scans help eliminating intra-cardiac thrombus before VT ablation procedure. A high proportion of thrombus (9%) was identified. Whereas LV thrombus should systematically be ruled out before scar related VT ablation, in patients with AF, a LAA thrombus should also be eliminated as well as RV thrombus in patients with ARVC. Acknowledgement/Funding ANR-10-IAHU-04

Metabolic Activity in Central Neural Structures of Patients With Myocardial Injury.

BackgroundIncreasing evidence suggests a psychosomatic link between neural systems and the heart. In light of the growing burden of ischemic cardiovascular disease across the globe, a better understanding of heart‐brain interactions and their implications for cardiovascular treatment strategies is needed. Thus, we sought to investigate the interaction between myocardial injury and metabolic alterations in central neural areas in patients with suspected or known coronary artery disease.Methods and ResultsThe association between resting metabolic activity in distinct neural structures and cardiac function was analyzed in 302 patients (aged 66.8±10.2 years; 70.9% men) undergoing fluor‐18‐deoxyglucose positron emission tomography and 99mTc‐tetrofosmin single‐photon emission computed tomography myocardial perfusion imaging. There was evidence for reduction of callosal, caudate, and brainstem fluor‐18‐deoxyglucose uptake in patients with impaired left ventricular ejection fraction (<55% versus ≥55%: P=0.047, P=0.022, and P=0.013, respectively) and/or in the presence of myocardial ischemia (versus normal perfusion: P=0.010, P=0.013, and P=0.016, respectively). In a sex‐stratified analysis, these differences were observed in men, but not in women. A first‐order interaction term consisting of sex and impaired left ventricular ejection fraction or myocardial ischemia was identified as predictor of metabolic activity in these neural regions (left ventricular ejection fraction: P=0.015 for brainstem; myocardial ischemia: P=0.004, P=0.018, and P=0.003 for callosal, caudate, or brainstem metabolism, respectively).ConclusionsMyocardial dysfunction and injury are associated with reduced resting metabolic activity of central neural structures, including the corpus callosum, the caudate nucleus, and the brainstem. These associations differ in women and men, suggesting sex differences in the pathophysiological interplay of the nervous and cardiovascular systems.

The relationship between R wave peak time and left ventricular mass index in patients with end-stage renal disease on hemodialysis.

Cardiovascular complications have been reported to be the main cause of mortality in patients with end-stage renal disease (ESRD). Although left ventricular hypertrophy is the most common clinical presentation of cardiac remodeling, cardiovascular complications may also include disturbances of the heart conduction system. The R wave peak time (RWPT) has been previously associated with left ventricular hypertrophy and myocardial ischemia. In this study, we aimed to investigate the relationship between RWPT and echocardiographic parameters in patients with ESRD. This study enrolled 66 patients (29 females, age 57.2 ± 12.8years) with ESRD, and 72 controls (37 females, age 55.3 ± 10.1years) with similar risk factors. All patients underwent electrocardiography and transthoracic echocardiography. The RWPT was defined as the interval between the onset of the QRS complex and the peak of the R or R' wave. There was no significant difference in terms of clinical and demographic parameters between ESRD patients and controls. Left ventricular ejection fraction was similar between the groups. However, left atrial diameter, interventricular septal thickness, posterior wall thickness, left ventricular mass (LVM) and left ventricular mass index (LVMI) were significantly higher in patients with ESRD. Among electrocardiographic parameters, P wave and QRS complex durations and RWPT were significantly higher in patients with ESRD. Prolonged RWPT, increased LVM and LVMI were identified as associates of ESRD. Furthermore, RWPT correlated well with LVM and LVMI. The present study demonstrated that RWPT prolonged significantly in patients with ESRD. Furthermore, prolonged RWPT has been associated with increased LVM and LVMI.

Exercise Contractile Reserve for Predicting Mortality in Non-Ischemic Ventricular Dysfunction

Objectives: A preserved contractile reserve is a marker of favorable outcome in different cardiac diseases. In some studies, using drugs, an increase in left ventricular (LV) systolic function was associated to better prognosis in patients with dilated cardiomyopathy. We aimed to assess whether a positive contractile reserve (CR) to physical exercise is a marker of good outcome in patients with LV systolic dysfunction not related to coronary artery disease (CAD). Design: From our exercise echocardiography database we extracted patients with LV systolic dysfunction (LVEF ≤45), negative coronary angiography, and absence of a history of CAD. A positive CR was considered when peak LVEF was higher that resting LVEF. The endpoint was overall mortality. Results and Conclusions: Among the 225 patients included, 105 had a positive CR and 120 a negative CR. Resting LV function was similar in patients with positive and negative CR (LVEF 35±8 vs. 34±9; wall motion score index 1.81±0.34 vs. 1.80±0.29; both p=NS). During a follow up of 6.2+4.7 years (25-75th percentiles 2.2-9.5), there were 71 deaths. Ten-year mortality rates were 34% for patients with CR and 67% for patients without CR (p=0.003). After multivariate adjustment that included clinical variables, medications, resting LV function, and exercise testing variables the only predictors of death were age (hazard ratio (HR) 1.07, 95% Confidence Interval (CI) 1.04-1.10, p&lt;0.001), and absence of CR (HR 1.80, 95% CI 1.09-2.98, p=0.02). In conclusion, in patients with non- ischemic LV dysfunction, a positive CR to physical exercise is a marker of better outcome.

An integrated model of materno-foetal cardiac dysfunction in severe pre-eclampsia.

Maternal cardiovascular deterioration in severe pre-eclampsia is due to a combination of factors in the setting of severe trophoblastic ischaemia and the outpouring of maternal cathecolamines, leading to increased left ventricular afterload and increasing ventricular volumes, resulting in increased left ventricular stroke work and demand myocardial ischaemia. This is the substrate for ventricular arrhythmias. Foetal cardiac dysfunction is most likely on the basis of the increased afterload, consequent upon widespread vasoconstriction, due to angiogenic imbalances. In this integrated model, chronic trophoblastic ischaemia is the central role player by releasing vasoactive substances that induce haemodynamic alterations in the maternofoetal complex, augmented and modified by 'latent' maternal cardiovascular dysfunction and increased maternal cathecolamine secretion on the one hand, and altered foetal signalling mechanisms on the other, all three components of the materno-placental-foetal complex being in constant interaction with each other. This unified hypothesis may explain the development of both maternal and foetal morbidity and/or mortality on a unitary basis in severe, complicated preeclampsia.

Infused cardioplegia index: A new tool to improve myocardial protection. A cohort study

BackgroundStrategies for cardio-protection are essential in coronary artery bypass graft surgery. The authors explored the relationship between cardioplegia volume, left ventricular mass index and ischemia time by means of the infused cardioplegia index and its relationship with post-operative low cardiac output syndrome. DesignAll patients undergoing coronary artery bypass graft surgery between January 2013 and December 2015 were included. Low cardiac output syndrome was defined according to criteria of the SEMICYUC's consensus document. The perioperative factors associated with low cardiac output syndrome were estimated, and using a ROC curve, the optimum cut-off point for the infused cardioplegia index to predict the absence of low cardiac output syndrome was calculated. ResultsOf 360 patients included, 116 (32%) developed low cardiac output syndrome. The independent risk predictors were: New York Heart Association Functional Classification (OR 1.8 [95% CI=1.18–2.55]), left ventricle ejection fraction (OR 0.95 (95% CI=0.93–0.98]), ICI (OR 0.99 [95% CI=0.991–0.996]) and retrograde cardioplegia (OR 1.2 [95% CI=1.03–1.50]). The infused cardioplegia index showed an area under the ROC curve of 0.77 (0.70–0.83; p<.001) for the absence of postoperative low cardiac output syndrome using the optimum cut-off point of 23.6ml·min−1 (100g/m2 of LV). ConclusionsThe infused cardioplegia index presents an inverse relationship with the development of post-operative low cardiac output syndrome. This index could form part of new strategies aimed at optimizing cardio-protection. The total volume of intermittent cardioplegia, especially that of maintenance, should probably be individualized, adjusting for ischemia time and left ventricle mass index.

Cardiac dysfunction in exacerbations of chronic obstructive pulmonary disease is often not detected by electrocardiogram and chest radiographs.

Cardiac dysfunction is common in exacerbations of chronic obstructive pulmonary disease (COPD), even in patients without clinically suspected cardiac disorders. To investigate associations between electrocardiogram (ECG) and chest radiograph abnormalities and biochemical evidence of cardiac dysfunction (N-terminal pro-B-type natriuretic peptide and troponin T) in patients hospitalised with exacerbations of COPD at Waikato Hospital. Independent examiners, blinded to NT-proBNP and troponin T levels, assessed ECG for tachycardia, atrial fibrillation, ventricular hypertrophy and ischaemic changes in 389 patients and chest radiographs for signs of heart failure in 350 patients. Associations between electrocardiographic and radiographic abnormalities with at least moderate interrater agreement and cardiac biomarkers were analysed. High NT-proBNP values (>220 pmol/L) were associated with atrial fibrillation (22 vs 6%), right ventricular hypertrophy (24 vs 15%), left ventricular hypertrophy (15 vs 4%), ischaemia (59 vs 33%) and cardiomegaly (42 vs 20%). High troponin T values (>0.03ug/L or high-sensitivity >50 ng/L) were associated with tachycardia (65 vs 41%), right ventricular hypertrophy (26 vs 15%) and ischaemia (60 vs 36%). None of the electrocardiographic or radiographic abnormalities was sensitive or specific for cardiac biomarker abnormalities. Ischaemia on ECG was the best indicator for raised NT-proBNP (sensitivity 59%, specificity 67%). Tachycardia and ischaemia were the best indicators of raised troponin T (sensitivity 65 and 60%, specificity 59 and 64% respectively). ECG and chest radiograph abnormalities have poor sensitivity and specificity for diagnosing acute cardiac dysfunction in exacerbations of COPD. Cardiac biomarkers provide additional diagnostic information about acute cardiac dysfunction in exacerbations of COPD.

Evaluation of patients with myocardial infarction undergoing percutaneous coronary intervention (PCI) using low dose dobutamine stress echocardiography

Coronary artery disease (CAD) is a spectrum of heart diseases which has the highest mortality in the world. Systolic left ventricular (LV) function is an important predictor of outcome, and its precise assessment remains of great importance for the choice of treatment in populations with myocardial infarction (MI). This study was aimed to assess the function and viability of ischemic myocardium of LV before and after the percutaneous coronary intervention (PCI) by using 2dimentional (2D) STE with LDDSE and to know the usefulness of low dose dobutamine (LDD) test in detecting the viable ischemic LV area. The results of the current study revealed there was a significant decrease (improvement) in GLS before dobutamine from (-10.49±3.4) to (-12.87±3.44) after dobutamine. Then there was a significant increase (deterioration) in GLS from (-12.87±3.44) after giving 5 mg/kg/min dobutamine to (-11.56±3.29) after giving 10 mg/kg/min dobutamine (P value &lt; 0.001). While there were no significant differences in GLS after low dose dobutamine (-12.87±3.44) with the same parameters 3-6 months after PCI (-13.48±3.7). Left anterior descending artery (LAD) is the most common affected artery in our study. The study concluded that GLS provides a sensitive measure of LV function and appears reduced despite preserved LVEF also GLS can detect the viability of ischemic myocardium of LV with using LDD test which then assessed by PCI.

A case report: unmasking a singular culprit for cardiogenic shock: looking beyond the coronary tree.

BackgroundCardiogenic shock remains challenging in its therapy and aetiology.Case summaryA 74-year-old woman admitted for cardiogenic shock requiring mechanical ventilation and high-dose inotropics and vasopressors with an electrocardiogram showing left ventricular (LV) lateral wall ischaemia had diffuse coronary artery disease but TIMI III flow in the coronary tree. An echocardiogram showed a suspicious mass invading the left ventricle and computed tomography scan revealed an advanced lung cancer with LV wall and pulmonary artery invasion as the cardiogenic shock cause.DiscussionWhen managing cardiogenic shock, it is important to consider different and not obvious diagnosis. A high level of clinical suspicion and multimodality imaging assessment was very important in the present case to attain the diagnosis.

Left ventricular hypertrophy contributes to Myocardial Ischemia in Non-obstructive Coronary Artery Disease (the MicroCAD study)

BackgroundThe underlying mechanisms causing myocardial ischemia in non-obstructive coronary artery disease (CAD) are still unclear. We explored whether left ventricular hypertrophy (LVH) was associated with myocardial ischemia in patients with stable angina and non-obstructive CAD. Methods132 patients (mean age 63 ± 8 years, 56% women) with stable angina and non-obstructive CAD diagnosed as <50% stenosis by coronary computed tomography angiography (CCTA) underwent myocardial contrast stress echocardiography. Left ventricular (LV) hypertrophy (LVH) was identified by LV mass index >46.7 g/m2.7 in women and >49.2 g/m2.7 in men. Patients were grouped according to presence or absence of myocardial ischemia by myocardial contrast stress echocardiography. The number of LV segments with ischemia at peak stress was taken as a measure of the extent of myocardial ischemia. ResultsMyocardial ischemia was found in 52% of patients, with on average 5 ± 3 ischemic LV segments per patient. The group with myocardial ischemia had higher prevalence of LVH (23 vs. 10%, p = 0.035), while age, sex and prevalence of hypertension did not differ between groups (all p > 0.05). In multivariable regression analyses, LVH was associated with presence of myocardial ischemia (odds ratio 3.27, 95% confidence interval [1.11–9.60], p = 0.031), and larger extent of myocardial ischemia (β = 0.22, p = 0.012), independent of confounders including age, hypertension, obesity, hypercholesterolemia, calcium score and segment involvement score by CCTA. ConclusionsLVH was independently associated with both presence and extent of myocardial ischemia in patients with stable angina and non-obstructive CAD by CCTA. These results suggest LVH as an independent contributor to myocardial ischemia in non-obstructive CAD.Clinical trial registration number: ClinicalTrials.gov, identifier NCT018535271.

Impact of Mitral Regurgitation Severity and Cause on Effort Tolerance-Integrated Stress Myocardial Perfusion Imaging and Echocardiographic Assessment of Patients With Known or Suspected Coronary Artery Disease Undergoing Exercise Treadmill Testing.

BackgroundMitral regurgitation (MR) has the potential to impede exercise capacity; it is uncertain whether this is because of regurgitation itself or the underlying cause of valvular insufficiency.Methods and ResultsThe population comprised 3267 patients who underwent exercise treadmill myocardial perfusion imaging and transthoracic echocardiography within 6±8 days. MR was present in 28%, including 176 patients (5%) with moderate or greater MR. Left ventricular systolic function significantly decreased and chamber size increased in relation to MR, paralleling increments in stress and rest myocardial perfusion deficits (all P<0.001). Exercise tolerance (metabolic equivalents of task) decreased stepwise in relation to graded MR severity (P<0.05). Workload was significantly lower with mild versus no MR (mean±SD, 9.8±3.0 versus 10.1±3.0; P=0.02); magnitude of workload reduction significantly increased among patients with advanced versus those with mild MR (mean±SD, 8.6±3.0 versus 9.8±3.0; P<0.001). MR‐associated exercise impairment was accompanied by lower heart rate and blood pressure augmentation and greater dyspnea (all P<0.05). Both functional and nonfunctional MR subgroups demonstrated significantly decreased effort tolerance in relation to MR severity (P≤0.01); impairment was greater with functional MR (P=0.04) corresponding to more advanced left ventricular dysfunction and dilation (both P<0.001). Functional MR predicted reduced metabolic equivalent of task–based effort (B=−0.39 [95% CI, −0.62 to −0.17]; P=0.001) independent of MR severity. Among the overall cohort, advanced (moderate or greater) MR was associated with reduced effort tolerance (B=−1.36 [95% CI, −1.80 to −0.93]; P<0.001) and remained significant (P=0.01) after controlling for age, clinical indexes, stress perfusion defects, and left ventricular dysfunction.Conclusions MR impairs exercise tolerance independent of left ventricular ischemia, dysfunction, and clinical indexes. Magnitude of exercise impairment parallels severity of MR.

Epigenetic Down-Regulation of Sirt 1 via DNA Methylation and Oxidative Stress Signaling Contributes to the Gestational Diabetes Mellitus-Induced Fetal Programming of Heart Ischemia-Sensitive Phenotype in Late Life.

Rationale: The incidence of gestational diabetes mellitus (GDM) is increasing worldwide. However, whether and how GDM exposure induces fetal programming of adult cardiac dysfunctional phenotype, especially the underlying epigenetic molecular mechanisms and theranostics remain unclear. To address this problem, we developed a late GDM rat model.Methods: Pregnant rats were made diabetic on day 12 of gestation by streptozotocin (STZ). Experiments were conducted in 6 weeks old offspring.Results: There were significant increases in ischemia-induced cardiac infarction and gender-dependent left ventricular (LV) dysfunction in male offspring in GDM group as compared to controls. Exposure to GDM enhanced ROS level and caused a global DNA methylation in offspring cardiomyocytes. GDM attenuated cardiac Sirt 1 protein and p-Akt/Akt levels, but enhanced autophagy-related proteins expression (Atg 5 and LC3 II/LC3 I) as compared to controls. Ex-vivo treatment of DNA methylation inhibitor, 5-Aza directly inhibited Dnmt3A and enhanced Sirt 1 protein expression in fetal hearts. Furthermore, treatment with antioxidant, N-acetyl-cysteine (NAC) in offspring reversed GDM-mediated DNA hypermethylation, Sirt1 repression and autophagy-related gene protein overexpression in the hearts, and rescued GDM-induced deterioration in heart ischemic injury and LV dysfunction.Conclusion: Our data indicated that exposure to GDM induced offspring cardiac oxidative stress and DNA hypermethylation, resulting in an epigenetic down-regulation of Sirt1 gene and aberrant development of heart ischemia-sensitive phenotype, which suggests that Sirt 1-mediated signaling is the potential therapeutic target for the heart ischemic disease in offspring.

Left ventricle ejection fraction and strain derived by three-dimensional echocardiography are associated with exercise capacity in the patients with heart failure

Background/Aim. Echocardiography represents the most commonly performed noninvasive cardiac imaging tests for the patients with heart failure (HF). The aim of this study was to assess the relationship between the exercise capacity parameters [peak oxygen consumption (VO2) and the minute ventilation-carbon dioxide production relationship (VE/VCO2)] and the three-dimensional speckle-tracking echocardiography (3D-STE) imaging of left ventricular (LV) function in the HF patients with the reduced LV ejection fraction (LVEF). Methods. This cross-sectional study included 80 patients with diagnosed ischemic LV systolic dysfunction (LVEF &lt; 45%) divided into subgroups based on the proposed values of analyzed cardiopulmonary exercise testing (CPET) variables: VO2 peak ? 15 mL/kg/min, VO2 peak &gt; 15 mL/kg/min, VE/VCO2 slope &lt; 36 and VE/VCO2 slope ? 36. All patients underwent a physical examination, laboratory testing, two-dimensional (2D) and 3DE, and CPET. Results. LVEF, global longitudinal, circumferential, radial and area strains were significantly lower in the subgroups of subjects with a peak VO2 less, or equal to 15 mL O2/kg per min and with a VE/VCO2 slope greater, or equal to 36 compared to the subgroups of subjects with a peak VO2 greater than 15 mL O2/kg per min and with a VE/VCO2 slope less than 36. There was a significantly positive correlation between the peak VO2 values and parameters of 3DE, and a significantly negative correlation between the VE/VCO2 slope values and parameters of 3DE. Conclusion. The results of this study provide further evidence that the LV function can be noninvasively and objectively measured by 3D-STE. A significant correlation between examined parameters suggests that LVEF and strain derived by 3DE are associated with exercise capacity in the patients with HF.