Myocardial Contractile Reserve Research Articles

Cine viability magnetic resonance imaging of the heart without increased scan time

Cardiac magnetic resonance imaging (MRI) provides information about myocardial morphology, function, and viability from cine, tagged, and late gadolinium enhancement (LGE) images, respectively. While the cine and tagged images are acquired in a time-resolved fashion, the LGE images are acquired at a single timeframe. The purpose of this work is to develop a method for generating cine LGE images without additional scan time. The motion field is extracted from the tagged images, and is then used to guide the deformation of the infarcted region from the acquired LGE image at the acquired timeframe to any other timeframe. Major techniques for motion estimation, including harmonic phase (HARP) and optical flow analysis, are tested in this work for motion estimation. The proposed method is tested on numerical phantom and images from four human subjects. The generated cine LGE images showed both viability and wall motion information in the same set of images without additional scan time or image misregistration problems. The band-pass optical flow analysis resulted in the most accurate motion estimation compared to other methods, especially HARP, which fails to track points at the myocardial boundary. Infarct transmurality from the generated images showed good agreement with myocardial strain, and wall thickening showed good agreement with that measured from conventional cine images. In conclusion, the developed technique allows for generating cine LGE images that enable simultaneous display of wall motion and viability information. The generated images could be useful for estimating myocardial contractility reserve and for treatment prognosis.

Left Bundle Branch Block Negatively Affects Coronary Flow Velocity Reserve and Myocardial Contractile Reserve in Nonischemic Dilated Cardiomyopathy

Coronary flow velocity reserve (CFVR) of the left anterior descending coronary artery (LAD) and myocardial contractile reserve are often impaired in nonischemic dilated cardiomyopathy (DCM). Whether they are affected by the presence of left bundle branch block (LBBB) remains unaddressed. The aim of the study was to investigate how LBBB influences CFVR of the LAD and myocardial contractile reserve in patients with DCM. One hundred eighty-one patients with DCM (116 men; mean age, 63±12years) underwent high-dose dipyridamole (0.84mg/kg over 6min) stress echocardiography with CFVR evaluation of the LAD by Doppler. All patients had ejection fractions<40% (mean, 31±8%) and angiographically normal or near normal coronary arteries. CFVR was defined as the ratio between hyperemic peak and basal peak diastolic coronary flow velocities. CFVR>2.0 was considered normal. Inotropic reserve was defined as rest-stress variation in wall motion score index≥0.20. This was a prospective analysis of an unselected sample consecutively enrolled and retrospectively selected. The study group was separated on the basis of presence (n=122) or absence (n=59) of LBBB. Patients with LBBB were older (64±11 vs 59±12 years, P=.004) and had reduced resting ejection fractions (30±9% vs 33±7%, P=.02), CFVR of the LAD (1.96±0.41 vs 2.23±0.73, P=.001), and myocardial contractile reserve (variation in wall motion score index, -0.18±0.17 vs -0.33±0.28; P<.001). On multivariate logistic regression analysis, resting ejection fraction (hazard ratio [HR], 1.15; 95% CI, 1.03-1.29; P=.01), smoking habit (HR, 2.63; 95% CI, 1.23-5.62; P=.01), and LBBB (HR, 2.29; 95% CI, 1.05-5.04; P=.04) were independently associated with reduced CFVR, while restrictive transmitral pattern (HR, 2.56; 95% CI, 1.18-5.55; P=.02), end-diastolic volume (HR, 0.98; 95% CI, 0.67-0.99; P=.02), and LBBB (HR, 2.20; 95% CI, 1.11-4.34; P=.02) independently predicted reduced myocardial contractile reserve. CFVR during vasodilator stress echocardiography is a suitable tool for assessing microvascular dysfunction in routine clinical practice. Patients with DCM and LBBB show more severe forms of microvascular dysfunction, which is related to worse left ventricular function and lack of contractile reserve. Therapeutic interventions to restore microvascular function may improve left ventricular function parameters in patients with DCM.

Left Ventricular Myocardial Mechanics in Cirrhosis: A Speckle Tracking Echocardiographic Study.

Cirrhosis is commonly associated with impaired left ventricular (LV) myocardial contractile reserve to stress and diastolic dysfunction. The aim of this study was to assess LV systolic performance at rest, using both "standard" echocardiographic indices and novel deformation-rotational parameters, in order to elucidate the pathophysiologic basis of cardiac dysfunction in cirrhosis. Seventy-seven men with cirrhosis (mean age 54.4 ± 9.7) of variable Child-Pugh class (A, B, C) and 20 healthy control subjects were prospectively evaluated by standard as well as speckle tracking echocardiography. Left ventricular ejection fraction (LVEF) was significantly higher in patients with cirrhosis compared to controls (64.6 ± 5.7% in controls vs. 71 ± 9.5%, 71.2 ± 7.1%, and 73 ± 7% in Child-Pugh classes A, B, and C, respectively, P = 0.002). Interestingly, LV systolic function augmentation was not associated with changes in LV longitudinal deformation (LV strain -19 ± 1.9% in controls vs. -20.1 ± 5.3% in class A vs. -21.3 ± 2.6% in class B vs. -21 ± 3.4% in class C, P = NS), but a statistically significant increase in LV apical systolic rotation and accordingly in LV twist was observed (LV twist 13.0 ± 3° in controls vs. 14.9 ± 5° in class A vs. 16.5 ± 2.8° in class B vs. 18.2 ± 2.9° in class C, P < 0.0005). Despite the increase in LV rotation, time to both basal and apical peak systolic rotation was significantly delayed in patients compared to healthy controls (P = 0.015 and P = 0.017 accordingly). Increased EF in cirrhosis could be attributed to increased LV torsion. Despite the "improved" rotation values at rest, there is a significant time delay in succeeding peak systolic rotation, hampering also the consequent untwisting-diastolic period.

Opportunities Provided by Stress Echocardiography and Stress Speckle tracking for the Evaluation of Myocardial Reserve Among Patients With Heart Defects

Heart failure risk factors research as well as studies of myocardial dysfunction to identify subclinical heart disease are important problems that can be solved with stress echocardiography and new methods of myocardial function analysis. Key factors defining the prognosis of patients with valvular diseases are heart remodeling and myocardial contractility. Heart remodeling types have been studied in detail by the present time. Elucidation of capability of stress echocardiography to detect asymptomatic dysfunction and assess prognosis of the results of surgery is continuing. Most important technological achievements of the last ten years gave us the opportunity to quantitatively assess myocardial function and movement. Tissue Doppler and Speckle Tracking enabled us to find alternative to invasive methods way to determination of parameters of global and regional myocardial function. Nowadays the first research results on the use of Speckle Tracking to estimate the contractile reserve are appearing. A high prognostic significance of global longitudinal deformation has been revealed. The aim of this article is to summarize available data on assessment of severity of valvular heart disease and the state of myocardial contractile reserve using stress echocardiography, Tissue Doppler and Speckle tracking data.

Low-Flow Aortic Stenosis and Reduced Ejection Fraction: New Insights.

Low-Flow Aortic Stenosis and Reduced Ejection Fraction: New Insights.

Assessing anthracycline‐treated childhood cancer survivors with advanced stress echocardiography

Surveillance for anthracycline cardiotoxicity in cancer survivors typically utilizes resting M-mode and two-dimensional echocardiography, which are insensitive to detection of subtle myocardial changes. We examined childhood cancer survivors treated with anthracyclines during exercise using various echocardiography techniques to investigate if these tools can better detect subclinical cardiac dysfunction. We recruited asymptomatic survivors at least five years post treatment. Echocardiography was performed at rest and at termination of exercise utilizing tissue Doppler techniques and strain rate imaging. Eighty participants were characterized by cardiotoxicity risk status (high [12], moderate [23], low [24], no risk [21]) as defined by the Children's Oncology Group Long Term Follow-Up Guidelines v3.0. The high-risk group had a higher resting heart rate than controls (100 vs. 88 bpm [P for trend = 0.049]). Peak aerobic capacity in all groups was similar. Compared to controls at rest, the high-risk group had evidence of diastolic dysfunction with lower E/A ratios (1.4 vs. 2.0, P = 0.008) and higher septal early diastolic velocities (E/E') of 11.7 versus 9.9 (P = 0.165). With exercise, this difference resolved and myocardial contractile reserve was preserved. Asymptomatic, pediatric cancer survivors at high-risk for anthracycline cardiotoxicity have some evidence of diastolic filling abnormalities at rest. With exercise, they augment their systolic and diastolic function to achieve normal maximal aerobic capacity suggesting they are able to compensate for mild cardiac dysfunction in the early years after exposure. Additionally, findings suggest that routine exercise echocardiography may not be a useful surveillance tool to assess anthracycline cardiotoxicity.

Regional myocardial contractile reserve assessed by strain echocardiography and the response to cardiac resynchronization therapy

Overall response rate to cardiac resynchronization therapy (CRT) is still not optimal. The aim of the study was to evaluate the influence of the regional myocardial contractile reserve during dobutamine infusion in the area of left ventricular (LV) electrode on the response rate and reverse remodeling LV in patients receiving CRT. Biventricular pacemaker was implanted in 41 consecutive patients (33 men, mean age 62 ± 10 years) with LV ejection fraction (LVEF) ≤ 35%, New York Heart Association class III and QRS duration ≥ 120 ms. Myocardial contractile reserve was assessed by LV strain during dobutamine infusion (20 μg/kg/min) using speckle tracking echocardiography. Patients were classified as responders if an increase in LVEF ≥ 5% or decrease in end-systolic volume ≥ 15% was observed after 6 months of CRT. Twenty-four patients were responders and 17 were non-responders. During dobutamine infusion at a rate of 20 μg/kg/min, responders showed significant increase in regional deformation (Δ strain) when compared to non-responders (2.14 ± 2.9 vs. - 0.94 ± 1.74, p = 0.042). Patients with increased deformation in the LV lead area during dobutamine stimulation were more likely to be responders to CRT compared to patients without increased deformation in this area (81% vs. 20%, p = 0.0002). They exhibited significant increase in LVEF (8.8% ± 10.3% vs. 0.3% ± 6.4%, p = 0.01). LV electrode localization in viable myocardium was a good predictor of response to CRT (AUC 0.852, p < 0.0001). Regional contractile reserve assessed by strain rate echocardiography during dobutamine infusion predicts the response to CRT.

Usage of echocardiography with physical loads for diagnosis of myocardial contractile reserve of the left ventricle in athletes.

The work purpose was studying of myocardial contractile reserve of the left ventricle and cardiohemodynamics infringements character under the influence of physical loads in athletes with functional insufficiency of mitral valve according to stress-echocardiography. We examined 72 athletes the aged 9 to 40 years with functional mitral valve insufficiency and normal systolic function of the heart at rest by echo ECG data. Possibility of stress echocardiography with physical loads usage to diagnose decrease of myocardial contractile reserve of the heart left ventricle was proved. It was found that increase in hemodynamic load during physical exercise leads to the disruption of adaptation and manifestation of systolic dysfunction in athletes with I and II degrees of mitral valve regurgitation. This should be considered when constructing training-competitive loads among athletes in terms of prevention of acute physical overloading.

Global Myocardial Contractile Reserve Assessed by High‐Dose Dobutamine Stress Echocardiography Predicts Response to the Cardiac Resynchronization Therapy

Myocardial contractile reserve (CR) is a strong prognostic factor in patients with heart failure. The presence of significant myocardial fibrosis can lead to a reduced response to cardiac resynchronization therapy (CRT). We assumed that myocardial CR assessed by high-dose dobutamine stress echocardiography (DSE) would predict response to CRT. Fifty-two consecutive symptomatic patients with heart failure (New York Heart Association [NYHA] class III), with depressed ejection fraction (EF) of the left ventricle (26.3 ± 6.9%) and dyssynchronous contractions (QRS duration 149.8 ± 23.8 msec) underwent DSE before CRT implantation. The difference in EF at rest and at peak (40 μg/kg per minute) DSE indicated global CR. Responders to CRT were defined by a decrease in left ventricular end-systolic volume of ≥15% and/or an increase in EF of ≥5% after 6 months of CRT. During high-dose dobutamine infusion, responders (28 patients, 54%) showed a greater increase in EF compared with nonresponders (Δ 11 ± 7% vs. Δ 2 ± 9%, P = 0.007). CR correlated moderately with an improvement in EF after 6 months of CRT (r = 0.50, P = 0.0009). Furthermore, responders showed significant improvement in clinical status, evaluated by a reduction in NYHA functional class (-0.8 ± 0.6 vs. 0.1 ± 0.4, P = 0.02), compared with nonresponders. A 7% exercise-induced increase in EF yielded sensitivity of 79% and specificity of 87% in predicting the response to CRT after 6 months. Myocardial CR assessed by high-dose DSE can play a potentially important role in identifying responders to CRT.

Prediction of surgical prognosis with dobutamine stress echocardiogram in patients with ischemic cardiomyopathy

Objectives: Dobutamine stress echocardiography (DSE) was performed prospectively at our institute since 2006. The DSE was used to assess the myocardial viability and contractile reserve in patients with ischemic cardiomyopathy (left ventricular ejection fraction [LVEF]? 30%). We aim to evaluate the role of DSE and surgical prognosis in assessment of myocardial viability in patients with ischemia cardiomyopathy.

Interleukin-1β Blockade Improves Left Ventricular Systolic/Diastolic Function and Restores Contractility Reserve in Severe Ischemic Cardiomyopathy in the Mouse

Interleukin-1β (IL-1β) modulates the inflammatory response during acute myocardial infarction (AMI) and progression to ischemic cardiomyopathy. We investigated whether blockade of IL-1β after the onset of the cardiac dysfunction prevented left ventricular (LV) adverse remodeling in a mouse model of anterior nonreperfused AMI. Infarct size and LV systolic function were assessed by echocardiography 7 days after coronary artery ligation. Mice with large infarct size and LV ejection fraction (LVEF) <40% were randomly assigned to treatment with a monoclonal antibody directed toward IL-1β antibody (10 mg/kg IL-1β-AB) or with a cyclosporine directed antibody (10 mg/kg control-AB). Echocardiogram was repeated after 10 weeks, followed by assessment of contractile reserve using isoproterenol challenge and LV catheterization. After 10 weeks, control-AB-treated mice showed significantly increased LV end-diastolic diameter (+15%, P < 0.001) and decreased LVEF (-18%, P = 0.050). IL-1β-AB had no significant effect on LV end-diastolic diameter (+10%, P = 0.25 vs. control-AB) but significantly prevented LVEF reduction (+7%, P = 0.031 vs. control-AB), enlargement of the right ventricle (P = 0.024), impairment in myocardial performance index (P = 0.028) and contractile reserve (P = 0.008), and increased LV end-diastolic pressure (P = 0.030). IL-1β blockade using a monoclonal antibody in mice with severe LV dysfunction after AMI prevents further deterioration in LV systolic and diastolic function and restores contractile reserve.

PM429 Early LV Dysfunction in Stage 3 Chronic Kidney Disease (CKD) Assessed by Stress Based Ventricular Contractility Index

Introduction: Ischemic heart disease is the most important cause of cardiac morbidity and death. Early detection of cardiac deterioration is imperative. To reach a large population safe, easy accessible and reliable non-invasive investigation methods are required. Objectives: Speckle-tracking echocardiography is a new technique founded on pure 2D gray scale ultrasound acquisition and provides non-doppler, angle-independent and objective quantification of myocardial deformation and of left ventricular systolic and diastolic dynamics. Left ventricular dysfunction is a sensitive predictor of cardiovascular atherosclerotic diseases. Methods:We investigated 969 male, self-supporting and ambulant patients, divided in 495 healthy subjects (HS) with documented normal coronary arteries and in 474 coronary patients (CP), treated with multiple stent implantation or bypass surgery. Both groups were divided in three age groups: 40-59y, 60-79y and 80-99y. We measured by speckle-tracking echocardiography the “global longitudinal peak systolic strain average” (GLPSSavg) of the left ventricle, divided in 24 segments, and also the “average peak longitudinal strain of the 5 myocardial segments with the lowest strain values” (Avg5LSS). The more negative the strain value, the better the myocardial contractile reserve. Measurement of sum maximal diameter left atrium plus maximal diameter left ventricle in cm (LALV). Results: For all age groups significant decrease (p1⁄40,000) of GLPSSavg in CP compared with HS but quasi unchanged results with aging. Also statistically significant decrease (p1⁄40,000) of Avg5LSS for all age groups in CP compared with HS but with a tendency to a progressive decrease of Avg5LSS with aging. LALV is in all age groups statistically significantly larger (p1⁄40,000) in CP compared with HS. Progressive increase of LALV with aging. (Table 1)

PM427 Non-Invasive Contribution To The Diagnosis Of Ischemic Heart Disease Using Speckle-Tracking Echocardiography Of The Left Ventricle

Introduction: Ischemic heart disease is the most important cause of cardiac morbidity and death. Early detection of cardiac deterioration is imperative. To reach a large population safe, easy accessible and reliable non-invasive investigation methods are required. Objectives: Speckle-tracking echocardiography is a new technique founded on pure 2D gray scale ultrasound acquisition and provides non-doppler, angle-independent and objective quantification of myocardial deformation and of left ventricular systolic and diastolic dynamics. Left ventricular dysfunction is a sensitive predictor of cardiovascular atherosclerotic diseases. Methods:We investigated 969 male, self-supporting and ambulant patients, divided in 495 healthy subjects (HS) with documented normal coronary arteries and in 474 coronary patients (CP), treated with multiple stent implantation or bypass surgery. Both groups were divided in three age groups: 40-59y, 60-79y and 80-99y. We measured by speckle-tracking echocardiography the “global longitudinal peak systolic strain average” (GLPSSavg) of the left ventricle, divided in 24 segments, and also the “average peak longitudinal strain of the 5 myocardial segments with the lowest strain values” (Avg5LSS). The more negative the strain value, the better the myocardial contractile reserve. Measurement of sum maximal diameter left atrium plus maximal diameter left ventricle in cm (LALV). Results: For all age groups significant decrease (p1⁄40,000) of GLPSSavg in CP compared with HS but quasi unchanged results with aging. Also statistically significant decrease (p1⁄40,000) of Avg5LSS for all age groups in CP compared with HS but with a tendency to a progressive decrease of Avg5LSS with aging. LALV is in all age groups statistically significantly larger (p1⁄40,000) in CP compared with HS. Progressive increase of LALV with aging. (Table 1)

PM428 Accuracy and reproducibility of completely automated 3-dimensional left ventricular ejection fraction quantification

Introduction: Ischemic heart disease is the most important cause of cardiac morbidity and death. Early detection of cardiac deterioration is imperative. To reach a large population safe, easy accessible and reliable non-invasive investigation methods are required. Objectives: Speckle-tracking echocardiography is a new technique founded on pure 2D gray scale ultrasound acquisition and provides non-doppler, angle-independent and objective quantification of myocardial deformation and of left ventricular systolic and diastolic dynamics. Left ventricular dysfunction is a sensitive predictor of cardiovascular atherosclerotic diseases. Methods:We investigated 969 male, self-supporting and ambulant patients, divided in 495 healthy subjects (HS) with documented normal coronary arteries and in 474 coronary patients (CP), treated with multiple stent implantation or bypass surgery. Both groups were divided in three age groups: 40-59y, 60-79y and 80-99y. We measured by speckle-tracking echocardiography the “global longitudinal peak systolic strain average” (GLPSSavg) of the left ventricle, divided in 24 segments, and also the “average peak longitudinal strain of the 5 myocardial segments with the lowest strain values” (Avg5LSS). The more negative the strain value, the better the myocardial contractile reserve. Measurement of sum maximal diameter left atrium plus maximal diameter left ventricle in cm (LALV). Results: For all age groups significant decrease (p1⁄40,000) of GLPSSavg in CP compared with HS but quasi unchanged results with aging. Also statistically significant decrease (p1⁄40,000) of Avg5LSS for all age groups in CP compared with HS but with a tendency to a progressive decrease of Avg5LSS with aging. LALV is in all age groups statistically significantly larger (p1⁄40,000) in CP compared with HS. Progressive increase of LALV with aging. (Table 1)

Relation of Preprocedural Assessment of Myocardial Contractility Reserve on Outcomes of Aortic Stenosis Patients With Impaired Left Ventricular Function Undergoing Transcatheter Aortic Valve Implantation

Transcatheter aortic valve implantation (TAVI) is associated with improved left ventricular (LV) function in patients with aortic stenosis (AS) and LV dysfunction; however, the outcome after TAVI of patients with low left ventricular ejection fraction (LVEF) is unclear. This study aimed to characterize the baseline, procedural, and long-term outcomes of patients with low LVEF undergoing TAVI and to assess the prognostic utility of pre-TAVI balloon aortic valvuloplasty (BAV) and dobutamine stress echocardiography (DSE) to predict TAVI benefits. Consecutive patients with symptomatic severe AS who underwent TAVI from 2007 to 2013 were analyzed. Two groups were compared: normal or near normal LV function (LVEF >45%) and LVEF ≤45% at baseline. In total, 371 patients were analyzed; 272 (73%) had preserved LVEF and 99 (27%) had low LVEF. Patients with low LVEF had higher Society of Thoracic Surgeons score and EuroSCORE. Short- and long-term mortality was similar between groups (1-year rate: 22.2% vs 22.4%, p= 0.79). Of the patients with low LVEF, 24% demonstrated improvement (≥10%) in LVEF at 30days; patients with improvement had lower mortality at 1year than those without (8% vs 27%, p= 0.06). Contractile reserve in DSE did not predict LVEF recovery in patients with low LVEF but did predict lower mortality. LVEF recovery after BAV predicted greater LVEF improvement after TAVI. In conclusion, patients with severe AS and impaired LV function benefit from TAVI and have comparable procedural outcomes compared with patients with preserved LVEF. Both DSE and BAV provide complementary data with regard to recovery of LVEF and mortality, both periprocedural and late after TAVI.

Contractile reserve assessed by dobutamine test identifies super-responders to cardiac resynchronization therapy.

IntroductionIn this study, we sought to determine whether myocardial contractile reserve (CR) assessed by dobutamine stress echocardiography (DSE) can identify patients who experience nearly complete normalization of left ventricular (LV) function after the implantation of a cardiac resynchronization therapy (CRT) pacemaker.Material and methodsThe study group consisted of 55 consecutive patients with non-ischemic dilated cardiomyopathy, LV ejection fraction (LVEF) < 35%, and prolonged QRS complex duration, who were scheduled for CRT pacemaker implantation. The DSE (20 µg/kg/min) was performed in all patients. The CR assessment was based on a change in the wall motion score index (ΔWMSI) and ΔLVEF during DSE. Super-response was defined as an increase in LVEF to > 50% and reduction in left ventricular end-systolic dimension to < 40 mm 12 months following the CRT implantation.ResultsA total of 7 patients (12.7%) were identified as super-responders to CRT. When compared to non-super-responders, these patients had significantly higher values of the dobutamine-induced change in ΔWMSI (1.031 ±0.120 vs. 0.49 ±0.371, p < 0.01), and ΔEF (17.9 ±2.2 vs. 8.8 ±6.2, p < 0.01). Receiver operating characteristic analysis showed that dobutamine-induced changes in ΔWMSI ≥ 0.7 and ≥ 14% for ΔEF are the best discriminators for a super-response. Patients with ΔWMSI ≥ 0.7 and ΔEF ≥ 14% are significantly less often hospitalized (p < 0.01) for worsening of heart failure during 28.5 ±3.0 months of the follow-up.ConclusionsContractile reserve assessed by DSE can identify patients with dilated cardiomyopathy who are likely to experience near normalization of LV function following CRT.

Diagnosis and management of ischemic cardiomyopathy: Role of cardiovascular magnetic resonance imaging

Coronary artery disease (CAD) represents an important cause of mortality. Cardiovascular magnetic resonance (CMR) imaging evolved as an imaging modality that allows the assessment of myocardial function, perfusion, contractile reserve and extent of fibrosis in a single comprehensive exam. This review highlights the role of CMR in the differential diagnosis of acute chest pain by detecting the location of obstructive CAD or necrosis and identifying other conditions like stress cardiomyopathy or myocarditis that can present with acute chest pain. Besides, it underlines the prognostic implication of perfusion abnormalities in the setting of acute chest pain. Furthermore, the review addresses the role of CMR to detect significant CAD in patients with stable CAD. It elucidates the accuracy and clinical utility of CMR with respect to other imaging modalities like single-photon emission computed tomography and positron emission tomography. Besides, the prognostic value of CMR stress testing is discussed. Additionally, it summarizes the available CMR techniques to assess myocardial viability and describes algorithm to identify those patient who might profit from revascularization those who should be treated medically. Finally, future promising imaging techniques that will provide further insights into the fundamental disease processes in ischemic cardiomyopathy are discussed.

Diabetes mellitus activates fetal gene program and intensifies cardiac remodeling and oxidative stress in aged spontaneously hypertensive rats

BackgroundThe combination of systemic arterial hypertension and diabetes mellitus (DM) induces greater cardiac remodeling than either condition alone. However, this association has been poorly addressed in senescent rats. Therefore, this study aimed to analyze the influence of streptozotocin-induced DM on ventricular remodeling and oxidative stress in aged spontaneously hypertensive rats (SHR).MethodsFifty 18 month old male SHR were divided into two groups: control (SHR, n = 25) and diabetic (SHR-DM, n = 25). DM was induced by streptozotocin (40 mg/kg, i.p.). After nine weeks, the rats underwent echocardiography and myocardial functional study in left ventricular (LV) isolated papillary muscle preparations. LV samples were obtained to measure myocyte diameters, interstitial collagen fraction, and hydroxyproline concentration. Gene expression of atrial natriuretic peptide (ANP) and α- and β-myosin heavy chain (MyHC) isoforms was evaluated by RT-PCR. Serum oxidative stress was assessed by measuring lipid hydroperoxide concentration and superoxide dismutase and glutathione peroxidase activities. Statistics: Student’s t test or Mann-Whitney test, p < 0.05.ResultsSHR-DM presented higher blood glucose (487 ± 29 vs. 89.1 ± 21.1 mg/dL) and lower body weight (277 ± 26 vs. 339 ± 38 g). Systolic blood pressure did not differ between groups. Echocardiography showed LV and left atrial dilation, LV diastolic and relative wall thickness decrease, and LV systolic and diastolic function impairment in SHR-DM. Papillary muscle study showed decreased myocardial contractility and contractile reserve in SHR-DM. Myocyte diameters and myocardial interstitial collagen fraction and hydroxyproline concentration did not differ between groups. Increased serum pro-oxidant activity and gene expression of ANP and β/α-MyHC ratio were observed in DM.ConclusionDiabetes mellitus induces cardiac dilation and functional impairment, increases oxidative stress and activates fetal gene program in aged spontaneously hypertensive rats.

Integrated wall stress: a new methodological approach to assess ventricular workload and myocardial contractile reserve

BackgroundWall stress is a useful concept to understand the progression of ventricular remodeling. We measured cumulative LV wall stress throughout the cardiac cycle over unit time and tested whether this “integrated wall stress (IWS)” would provide a reliable marker of total ventricular workload.Methods and resultsWe applied IWS to mice after experimental myocardial infarction (MI) and sham-operated mice, both at rest and under dobutamine stimulation. Small infarcts were created so as not to cause subsequent overt hemodynamic decompensation. IWS was calculated over one minute through simultaneous measurement of LV internal diameter and wall thickness by echocardiography and LV pressure by LV catheterization. At rest, the MI group showed concentric LV hypertrophy pattern with preserved LV cavity size, LV systolic function, and IWS comparable with the sham group. Dobutamine stimulation induced a dose-dependent increase in IWS in MI mice, but not in sham mice; MI mice mainly increased heart rate, whereas sham mice increased LV systolic and diastolic function. IWS showed good correlation with a product of peak-systolic wall stress and heart rate. We postulate that this increase in IWS in post-MI mice represents limited myocardial contractile reserve.ConclusionWe hereby propose that IWS provides a useful estimate of total ventricular workload in the mouse model and that increased IWS indicates limited LV myocardial contractile reserve.

Dynamic relationship of left-ventricular dyssynchrony and contractile reserve in patients undergoing cardiac resynchronization therapy

Contradicting reports have been published regarding the relation between a dobutamine-induced increase in either cardiac dyssynchrony or left-ventricular ejection fraction (LVEF) and the response to cardiac resynchronization therapy (CRT). Using apical rocking (ApRock) as surrogate dyssynchrony parameter, we investigated the dobutamine stress echocardiography (DSE)-induced changes in left-ventricular (LV) dyssynchrony and LVEF and their potential pathophysiological interdependence. Fifty-eight guideline-selected CRT candidates were prospectively enrolled for low-dose DSE. Dyssynchrony was quantified by the amplitude of ApRock. An LVEF increase during stress of >5% was regarded significant. Scar burden was assessed by magnetic resonance imaging. Mean follow-up after CRT implantation was 41 ± 13 months for the occurrence of cardiac death. ApRock during DSE predicted CRT response (AUC 0.88, 95% CI 0.77-0.99, P < 0.001) and correlated inversely with changes in EF (r = -0.6, P < 0.001). Left-ventricular ejection fraction changes during DSE were not associated with CRT response (P = 0.082). Linear regression analysis revealed an inverse association of LVEF changes during DSE with both, total scar burden (B = -2.67, 95CI -3.77 to -1.56, P < 0.001) and the DSE-induced change in ApRock amplitude (B = -1.23, 95% CI -1.53 to -0.94, P < 0.001). Kaplan-Meier analysis revealed that DSE-induced increase in ApRock, but not LVEF, was associated with improved long-term survival. During low-dose DSE in CRT candidates with baseline dyssynchrony, myocardial contractile reserve predominantly results in more dyssynchrony, but less in an increase in LVEF. Dyssynchrony at baseline and its dobutamine-induced changes are predictive of both response and long-term survival following CRT.