Decline In Left Ventricular Function Research Articles

Global longitudinal strain: is it a superior assessment method for left ventricular function in patients with chronic mitral regurgitation undergoing mitral valve replacement?

Left ventricular ejection fraction may remain normal or even higher despite significant impairment of contractility in cases of mitral regurgitation. The aim of this study is to evaluate the changes in left ventricular function after mitral valve replacement and to study the role of global longitudinal strain in detecting early left ventricular dysfunction using speckle tracking. Study involved 31 patients who underwent mitral valve replacement for mitral regurgitation. Patient's preoperative and postoperative echocardiography (conventional parameters and global longitudinal strain) and other parameters like functional status, radiological findings, and electrocardiogram were recorded to evaluate left ventricular function. All patients presented in advanced stage with New York heart association class III (67.7%) and IV (32.3%). There was significant decline in left ventricular ejection fraction (with the mean value from 64.58 to 40.13%) and global longitudinal strain (- 15.57 ± 4.98to - 8.97) in the immediate postoperative period (~ 7days). However, there was a rise in both left ventricular ejection fraction (mean 52.48%) and in global longitudinal strain (mean - 14.44 ± 3.67) at 3months. Left ventricular and atrial size decreased significantly immediately after surgery, which further declined at 3months. We also found that patients who attained a left ventricular ejection fraction of > 50% in postoperative period had better left ventricular ejection fraction and global longitudinal strain preoperatively. In addition, they had smaller cardiac size and milder pulmonary hypertension comparatively. Mitral valve replacement in mitral regurgitation results in decline in left ventricular function immediately after surgery. In patients with chronic mitral regurgitation, left ventricular ejection fraction is fallacious and global longitudinal strain can be an important tool to assess left ventricular ejection fraction.

Adjuvant Trastuzumab Therapy: Can We Balance Efficacy and Safety?

Trastuzumab is an effective treatment for HER2-positive breast cancer. Current guidelines recommend withholding trastuzumab in patients experiencing a significant asymptomatic decline in left ventricular function. In this commentary, we discuss the survival benefits afforded by trastuzumab juxtaposed against the risk of trastuzumab-mediated cardiotoxicity. It is not known whether the net benefit of continuing trastuzumab in the setting of mild cardiotoxicity outweighs the associated risks. We describe a potential approach undertaken by our group, and others, and call for a randomized trial.

İzole sol ventrikül noncompaction olan hastalarda miyokard dokusunun analizi

Aim: Videodensitometric myocardial texture analysis (VMTA) has been widely used to investigate left ventricular (LV) dysfunction in various cardiac disorders. Patients with isolated left ventricular noncompaction (IVNC) experience an undulating decline in LV function. The aim of this study was to assess the value of VMTA for evaluating deterioration of LV function in this patient group.Material and Methods: Twenty-two patients with IVNC (10 asymptomatic [preserved LV function], 12 symptomatic [LV dysfunction]) and 12 healthy controls were evaluated. Videodensitometry was used to record background-corrected mean gray levels (BC-MGL) for 2 regions of the mid-basal LV wall (the interventricular septum [IVS] and the posterior wall [PW]) at end-systole and end-diastole. The cyclic variation (CV) index for each region was calculated according to the formula, CV index % = ([BC-MGLend-diastole – BC-MGLend-systole] ÷ BC-MGLend-diastole) × 100. Results: The mean IVS-CV index in the symptomatic IVNC group (12.3 ± 4.9%) was significantly lower than the corresponding findings in the asymptomatic IVNC group (32.3 ± 14.8%, p < 0.05) and control group (36.6 ± 12.1%, p < 0.001). The mean PW-CV index in the symptomatic group (15.1 ± 5.5%) was also significantly lower than the corresponding values in the asymptomatic (27.0 ± 10.4%, p < 0.05) and control groups (28.8 ± 10.9%, p < 0.001). Conclusion: VMTA is a practical, useful adjunct to conventional echocardiography for assessing LV myocardium in patients with IVNC. Detection of reduced CV index values might predict the early stages of LV deterioration in this group.

Dilated Cardiomyopathy in Pregnancy: Outcomes From an Australian Tertiary Centre for Maternal Medicine and Review of the Current Literature

Peripartum cardiomyopathy is associated with significant risks of decline in left ventricular function and adverse maternal and fetal outcome in subsequent pregnancy. The risks of pregnancy in women with dilated cardiomyopathy are unclear. We aimed to assess the outcome of pregnancy in women with dilated cardiomyopathy seen at our institution and to review the literature on this subject. A retrospective audit of the outcomes of 14 pregnancies to 12 women with dilated cardiomyopathy. There were no cardiac events and no woman had a decline in left ventricular function during pregnancy. There was a high rate of prematurity and adverse fetal outcome related to this, including four neonatal deaths. Maternal outcomes in this small series were satisfactory though only three women had moderate-severe left ventricular dysfunction at baseline. There was a high rate of premature delivery and adverse neonatal outcome.

P1518Left ventricular strain as a sensitive predictor for the decline of left ventricular function in patients with chronic right ventricular pacing

P1518Left ventricular strain as a sensitive predictor for the decline of left ventricular function in patients with chronic right ventricular pacing

Carbonic anhydrase inhibitors reduce cardiac dysfunction after sustained coronary artery ligation in rats.

Two potent carbonic anhydrase (CA) inhibitors with widely differing membrane permeability, poorly diffusible benzolamide (BZ), and highly diffusible ethoxzolamide (ETZ) were assessed to determine whether they can reduce cardiac dysfunction in rats subjected to coronary artery ligation (CAL)-induced myocardial infarction. Rats with evidence of heart failure (HF) at 32 weeks following a permanent left anterior coronary artery occlusion were treated with placebo, BZ, or ETZ (4 mg kgday-1) for 4 weeks at which time left ventricular function and structure were evaluated. Lung weight/body weight (LW/BW) ratio increased in CAL rats by 17±1% vs. control, suggesting pulmonary edema. There was a trend for BZ and ETZ to ameliorate the increase in LW/BW by almost 50% (9±5% and 9±8%, respectively, versus CAL) (P=.16, NS). Echocardiographic assessment showed decreased left ventricular midwall shortening in HF rats, 21±1% vs. control 32±1%, which was improved by BZ to 29±1% and ETZ to 27±1%, and reduced endocardial shortening in HF rats 38±3% vs. control 62±1%, partially restored by BZ and ETZ to ~50%. Expression of the hypoxia-inducible membrane-associated CAIX isoform increased by ~60% in HF rat hearts, and this effect was blocked by ETZ. We conclude that CAL-induced myocardial interstitial fibrosis and associated decline in left ventricular function were diminished with BZ or ETZ treatment. The reductions in cardiac remodeling in HF with both ETZ and BZ CA inhibitors suggest that inhibition of a membrane-bound CA appears to be the critical site for this protection.

Sex-related differences in intrinsic myocardial properties influence cardiac function in middle-aged rats during infarction-induced left ventricular remodeling.

We previously determined that residual left ventricular (LV) myocardium of middle‐aged rats had sex‐related differences in regional tissue properties 4 weeks after a large myocardial infarction (MI). However, the impact of such differences on cardiac performance remained unclear. Therefore, our current study aimed to elucidate whether sex‐related changes in MI‐induced myocardial remodeling can influence cardiac function. A similar‐sized MI was induced in 12‐month‐old male (M‐MI) and female (F‐MI) Sprague–Dawley rats by ligation of the left coronary artery. The cardiac function was monitored for 2 months after MI and then various LV parameters were compared between sexes. We found that although two sex groups had a similar pattern of MI‐induced decline in LV function, F‐MI rats had greater cardiac performance compared to M‐MI rats, considering the higher values of EF (39.9 ± 3.4% vs. 26.7 ± 7.7%, P < 0.05), SW index (40.4 ± 2.1 mmHg • mL/kg vs. 20.2 ± 3.3 mmHg • mL/kg, P < 0.001), and CI (139.2 ± 7.9 mL/min/kg vs. 74.9 ± 14.7 mL/min/kg, P < 0.01). The poorer pumping capacity in M‐MI hearts was associated with markedly reduced LV compliance and prolonged relaxation. On the tissue level, F‐MI rats revealed a higher, than in M‐MI rats, density of cardiac myocytes in the LV free wall (2383.8 ± 242.6 cells/mm2 vs. 1785.7 ± 55.9 cells/mm2, P < 0.05). The latter finding correlated with a lower density of apoptotic cardiac myocytes in residual LV myocardium of F‐MI rats (0.18 ± 0.08 cells/mm2 vs. 0.91 ± 0.30 cells/mm2 in males, P < 0.01). Thus, our data suggested that F‐MI rats had markedly attenuated decline in cardiac performance compared to males due to ability of female rats to better retain functionally favorable intrinsic myocardial properties.

Changes in Ventricular Function After Vigorous Aerobic Exercise Training in Women with Pulmonary Arterial Hypertension

PURPOSE: To determine if 10 weeks of vigorous aerobic exercise training (AET) worsens left ventricular diastolic and systolic function in a group of women with pulmonary arterial hypertension (PAH). METHODS: 18 women with PAH (age 56.2 ± 8.8 years, BMI 28.8 ± 7.3 kg/m2) underwent 10 weeks of vigorous AET at 70-80% heart rate reserve. Indices of cardiac function were measured during a graded exercise test (GXT) to peak exhaustion using bioelectrical impedance cardiography (ZCG) before and after the AET. A small subset (N=7) participated in a 10-week waiting period prior to beginning the AET and performed an additional GXT with ZCG before that period. A cohort of sedentary women serving as healthy controls (N=19) also performed a GXT with ZCG and were used for comparison. RESULTS: Left ventricular ejection fraction (EF; 48 ± 9.2 vs. 61.5 ± 13.3 %, p=0.034) and the systemic vascular resistance index (SVRI; 2,258 ± 419.1 vs. 2,939 ± 962.4 dyn·s/cm5·m2, p=0.008) were significantly lower in the baseline PAH group vs. healthy groups respectively at supine rest. At peak exercise, heart rate (HR) was lower in the PAH group vs. healthy control group (140 ± 13.3 vs. 170 ± 13.8 bpm, p<0.001) and SVRI higher in the PAH group (828 ± 141.1 vs. 824 ± 300.9 dyn·s/cm5·m2, p=0.050) when controlling for age and HR. After AET, the PAH group did not have a significant decline in left ventricular function, but rather a decrease in SVRI (828 ± 141.1 vs. 766 ± 139.6 dyn·s/cm5·m2, p=0.020) at peak exercise. The subset of subjects with PAH who participated in the 10-week waiting period had a significant decline in the early diastolic left ventricular filling ratio (EDFR; 95.9±19.4 vs. 76.2±18.9%, p=0.043) prior to AET. The EDFR remained unchanged after the AET training period in all subjects. CONCLUSIONS: Vigorous AET does not appear to be associated with significant declines in either left ventricular systolic or diastolic function in women with PAH. AET may be beneficial for reducing afterload and may be protective against decline in left ventricular diastolic function occurring over time. Funding Source: NIH/IRP 1 Z01 CL060068-02 CC.

Coronary Microembolization with Normal Epicardial Coronary Arteries and No Visible Infarcts on Nitrobluetetrazolium Chloride-Stained Specimens: Evaluation with Cardiac Magnetic Resonance Imaging in a Swine Model.

ObjectiveTo assess magnetic resonance imaging (MRI) features of coronary microembolization in a swine model induced by small-sized microemboli, which may cause microinfarcts invisible to the naked eye.Materials and MethodsEleven pigs underwent intracoronary injection of small-sized microspheres (42 µm) and catheter coronary angiography was obtained before and after microembolization. Cardiac MRI and measurement of cardiac troponin T (cTnT) were performed at baseline, 6 hours, and 1 week after microembolization. Postmortem evaluation was performed after completion of the imaging studies.ResultsCoronary angiography pre- and post-microembolization revealed normal epicardial coronary arteries. Systolic wall thickening of the microembolized regions decreased significantly from 42.6 ± 2.0% at baseline to 20.3 ± 2.3% at 6 hours and 31.5 ± 2.1% at 1 week after coronary microembolization (p < 0.001 for both). First-pass perfusion defect was visualized at 6 hours but the extent was largely decreased at 1 week. Delayed contrast enhancement MRI (DE-MRI) demonstrated hyperenhancement within the target area at 6 hours but not at 1 week. The microinfarcts on gross specimen stained with nitrobluetetrazolium chloride were invisible to the naked eye and only detectable microscopically. Increased cTnT was observed at 6 hours and 1 week after microembolization.ConclusionCoronary microembolization induced by a certain load of small-sized microemboli may result in microinfarcts invisible to the naked eye with normal epicardial coronary arteries. MRI features of myocardial impairment secondary to such microembolization include the decline in left ventricular function and myocardial perfusion at cine and first-pass perfusion imaging, and transient hyperenhancement at DE-MRI.

Persistent Recovery of Normal Left Ventricular Function and Dimension in Idiopathic Dilated Cardiomyopathy During Long‐Term Follow‐up: Does Real Healing Exist?

BackgroundAn important number of patients with idiopathic dilated cardiomyopathy have dramatically improved left ventricular function with optimal treatment; however, little is known about the evolution and long‐term outcome of this subgroup, which shows apparent healing. This study assesses whether real healing actually exists in dilated cardiomyopathy .Methods and ResultsPersistent apparent healing was evaluated among 408 patients with dilated cardiomyopathy receiving tailored medical treatment and followed over the very long‐term. Persistent apparent healing was defined as left ventricular ejection fraction ≥50% and indexed left ventricular end‐diastolic diameter ≤33 mm/m2 at both mid‐term (19±4 months) and long‐term (103±9 months) follow‐up. At mid‐term, 63 of 408 patients (15%) were apparently healed; 38 (60%; 9% of the whole population) showed persistent apparent healing at long‐term evaluation. No predictors of persistent apparent healing were found. Patients with persistent apparent healing showed better heart transplant–free survival at very long‐term follow‐up (95% versus 71%; P=0.014) compared with nonpersistently normalized patients. Nevertheless, in the very long term, 37% of this subgroup experienced deterioration of left ventricular systolic function, and 5% died or had heart transplantation.ConclusionsPersistent long‐term apparent healing was evident in a remarkable proportion of dilated cardiomyopathy patients receiving optimal medical treatment and was associated with stable normalization of main clinical and laboratory features. This condition can be characterized by a decline of left ventricular function over the very long term, highlighting the relevance of serial and individualized follow‐up in all patients with dilated cardiomyopathy, especially considering the absence of predictors for long‐term apparent healing.

Advantages of Strain Echocardiography in Assessment of Myocardial Function in Severe Sepsis

Cardiovascular failure is an important feature of severe sepsis and mortality in sepsis. The aim of our study was to explore myocardial dysfunction in severe sepsis. Prospective experimental study. Operating room at Intervention Centre, Oslo University Hospital. Eight Norwegian Landrace pigs. The pigs were anesthetized, a medial sternotomy performed and miniature sensors for wall-thickness measurements attached to the epicardium and invasive pressure monitoring established, and an infusion of Escherichia coli started. Hemodynamic response was monitored and myocardial strain assessed by echocardiography. Left ventricular myocardial function was significantly reduced assessed by longitudinal myocardial strain (-17.2% ± 2.8% to -12.3% ± 3.2%, p = 0.04), despite a reduced afterload as expressed by the left ventricular end-systolic meridional wall stress (35 ± 13 to 18 ± 8 kdyn/cm, p = 0.04). Left ventricular ejection fraction remained unaltered (48% ± 7% to 49% ± 5%, p = 0.4) as did cardiac output (6.3 ± 1.3 to 5.9 ± 3 L/min, p = 0.7). The decline in left ventricular function was further supported by significant reductions in the index of regional work by pressure-wall thickness loop area (121 ± 45 to 73 ± 37 mm × mm Hg, p = 0.005). Left ventricular myocardial wall thickness increased in both end diastole (11.5 ± 2.7 to 13.7 ± 2.4 mm, p = 0.03) and end systole (16.1 ± 2.9 to 18.5 ± 1.8 mm, p = 0.03), implying edema of the left ventricular myocardial wall. Right ventricular myocardial function by strain was reduced (-24.2% ± 4.1% to -16.9% ± 5.7%, p = 0.02). High right ventricular pressures caused septal shift as demonstrated by the end-diastolic transseptal pressure gradient (4.1 ± 3.3 to -2.2 ± 5.8 mm Hg, p = 0.01). The present study demonstrates myocardial dysfunction in severe sepsis. Strain echocardiography reveals myocardial dysfunction before significant changes in ejection fraction and cardiac output and could prove to be a useful tool in clinical evaluation of septic patients.

The contribution of cardiac mechanics to isolated increases in peripheral blood flow (1073.4)

The human heart responds to whole‐body increases in cardiovascular demand by enhancing heart rate (HR) and intrinsic cardiac muscle function. However, it is not known if enhanced left ventricular (LV) muscle function ('LV mechanics') also contributes to localized increases in peripheral blood flow and, if so, whether enhanced peripheral blood flow per se or other arterial hemodynamic signals are the mechanism for acutely adjusting LV mechanics. We performed cardiac and vascular ultrasonography in eight healthy individuals (4 women) during 1) Baseline, 2) Bilateral arm heating (BAH), and 3) BAH with partial brachial artery occlusion (BAH+OCC) at mean arterial pressure (MAP, 85±15 mmHg). BAH markedly increased skin temperatures (32.71±0.69 to 39.21±0.60 deg. C, p&lt;0.0001) while rectal core temperature was unaltered (p=0.54). Brachial artery blood flow measured in the left arm increased almost threefold with BAH (98±46 to 266±96 mL/min, P&lt;0.0001) and returned to baseline levels with BAH+OCC. Arterial wave reflection, as assessed by applanation tonometry, had a tendency to increase with BAH and remained elevated with BAH+OCC (p=0.07). Increased cardiac output (p=0.02) was entirely explained by increased HR of 3‐4 bpm (P=0.002). In contrast, LV mechanics ‐ evaluated by systolic longitudinal strain and diastolic untwisting velocity ‐ did not change with BAH but they declined significantly with BAH+OCC (both p&lt;0.05), which was accompanied by a rise in MAP (P&lt;0.0001).In conclusion, the heart contributes to isolated increases in peripheral blood flow by enhancing HR but not its intrinsic LV muscle mechanics. Because LV output was maintained during the period of enhanced blood flow demand and increased afterload (=BAH+OCC), reduced systolic and diastolic LV mechanics during this condition may reflect an intrinsic protection of LV myofibers from pressure stress rather than a decline in LV function.

Role of Cytokine Hemoadsorption in Cardiopulmonary Bypass-Induced Ventricular Dysfunction in a Porcine Model

Little is known about the effect of cardiopulmonary bypass alone on cardiac function; in an attempt to illuminate this relationship and test a possible mechanism, we used Cytosorb™, a device capable of removing virtually all types of circulating cytokines to test the hypothesis that hemoadsorption of cytokines during bypass attenuates bypass-induced acute organ dysfunction. Twelve Yorkshire pigs (50–65 kg) were instrumented with a left ventricular conductance catheter. Baseline mechanics and cytokine expression (tumor necrosis factor [TNF], interleukin-6 [IL-6], and interleukin-10) were measured before and hourly after 1 hour of normothermic cardiopulmonary bypass. Animals underwent bypass without (cardiopulmonary bypass [CPB], n = 6) or with (CPB+HA, n = 6) the Cytosorb™ device. Data were compared with “historical” controls (n = 6) that were similarly instrumented but underwent observation instead of bypass. Five hours after separation from bypass (or observation), animals were euthanized. Myocardial water content was determined postmortem. Neither TNF nor IL-6 was significantly elevated in either experimental group versus controls at any time point. Preload recruitable stroke work and dP/dtmax were significantly depressed immediately after separation from bypass in both CPB+HA and CPB and remained depressed for the duration of the experiment. Although Tau remained unchanged, dP/dTmin was significantly diminished in both bypass groups at all time points after separation from bypass. Cytokine hemoadsorption had no effect on any measurable index of function. Differences in postmortem data were not evident between groups. One hour of normothermic CPB results in a significant and sustained decline in left ventricular function that appears unrelated to changes in cytokine expression. Because we did not appreciate a significant change in cytokine concentrations postbypass, the capacity of cytokine hemoadsorption to attenuate CPB-induced ventricular dysfunction could not be assessed.

Evaluating the metabolic approach to treatment of diabetic coronary patients

Diabetic patients with coronary artery disease have an altered myocardial metabolism of glucose and free fatty acids (FFA) and accelerated and diffuse atherogenesis with involvement of peripheral coronary segments that causes chronic hypoperfusion and hibernation. Therefore, in coronary diabetic patients the ischaemic metabolic changes that occur as a consequence of the mismatch between blood supply and cardiac metabolic requirements are heightened by the diabetic metabolic alterations.Important metabolic alterations in diabetic patients are the decreased utilization of glucose and the increase in muscular and myocardial FFA uptake and oxidation. These metabolic changes are responsible for the increased susceptibility of the diabetic heart to myocardial ischaemia and to a greater decrease of myocardial performance for a given amount of ischaemia compared to non diabetic hearts.A therapeutic approach aimed at an improvement of cardiac metabolism through manipulations of the utilization of metabolic substrates should result in an improvement of myocardial ischaemia and of left ventricular function. The inhibition of FFA oxidation improves cardiac metabolism at rest, increases the cardiac resistance to ischaemia and therefore reduces the decline of left ventricular function due to chronic hypoperfusion and repetitive episodes of myocardial ischaemia in patients with and without diabetes.Modulation of myocardial FFA metabolism should be the key target for metabolic interventions in diabetic patients with coronary artery disease.

Worsening Left Ventricular Apical Peak Strain Early After Right Ventricular Pacing

We aimed to determine the effect of short-term right ventricle pacing (RV) on left ventricle (LV) mechanics using speckle tracking analysis. Conventional echocardiography and two-dimensional strain imaging was studied in 38 patients, mean age 81.6 ± 7.0, that had undergone pacemaker placement and were greater than 90% ventricularly paced. Mean duration of 24 months of RV pacing resulted in a significant decline in: LV apical diastolic rotational velocities (−59.0 ± −38.9 °/s to −28.0 ± −11.5 °/s, p 0.02), peak strain in the LV apical septal wall (−15.6 ± 8.5 to −13.5 ± 7.6, p 0.02), peak strain in LV apical lateral wall (−13.4 ± 8.9 to −11.4 ± 7.3, p 0.02). Thus, with only 24 months of RV pacing, there was a significant decline in peak strain of the LV apex and in apical diastolic rotational velocity that could account for eventual decline in left ventricular function.

Correlation between changes in diastolic dysfunction and health-related quality of life after cardiac rehabilitation program in dilated cardiomyopathy

Chronic heart failure (CHF) is a complex syndrome characterized by progressive decline in left ventricular function, low exercise tolerance and raised mortality and morbidity. Left ventricular diastolic dysfunction plays a major role in CHF and progression of most cardiac diseases. The current recommended goals can theoretically be accomplished via exercise and pharmacological therapy so the aim of the present study was to evaluate the impact of cardiac rehabilitation program on diastolic dysfunction and health related quality of life and to determine the correlation between changes in left ventricular diastolic dysfunction and domains of health-related quality of life (HRQoL). Forty patients with chronic heart failure were diagnosed as having dilated cardiomyopathy (DCM) with systolic and diastolic dysfunction. The patients were equally and randomly divided into training and control groups. Only 30 of them completed the study duration. The training group participated in rehabilitation program in the form of circuit-interval aerobic training adjusted according to 55–80% of heart rate reserve for a period of 7months. Circuit training improved both diastolic and systolic dysfunction in the training group. On the other hand, only a significant correlation was found between improvement in diastolic dysfunction and health related quality of life measured by Kansas City Cardiomyopathy Questionnaire. It was concluded that improvement in diastolic dysfunction as a result of rehabilitation program is one of the important underlying mechanisms responsible for improvement in health-related quality of life in DCM patients.

Ischemic changes on rubidium-82 positron emission tomography imaging are associated with left ventricular functional and volumetric change independent of metabolic properties and echocardiographic functional variables in ischemic cardiomyopathy

Positron emission tomography (PET) imaging allows identification of stress-induced ischemia and myocardial viability in patients with ischemic cardiomyopathy. We assessed the left ventricular (LV) functional response to vasodilator stress in patients with advanced ischemic cardiomyopathy undergoing pharmacologic stress (PET) perfusion and metabolic imaging. Additionally, we aimed to determine if mitral regurgitation (MR), right ventricular (RV) dysfunction and diastolic function influenced the observed LV responses to pharmacologic stress. In 161 patients (81% men; 65 ± 13 years), PET and echocardiography were performed within a week for noninvasive evaluation of myocardial ischemia and viability (scored using 17-segment model), as well as ventricular and valvular function. Patients were stratified based on ischemic defects in any segments versus hibernation/scar defects only. The LV volumes, EF by gating and transient ischemic dilatation (TID) index were generated automatically. Wall thickening (WT) scores were determined visually. The subgroup with reversible/ischemic segments on PET imaging (N = 55) exhibited greater end-systolic (ESV) and end-diastolic volume (EDV) enlargement during stress (13 ± 22 and 16 ± 43 ml increase respectively, vs. 0 ± 18 ml [P < 0.0001] and 2 ± 24 ml [P = 0.01]), a decrease in LVEF during stress (mean -3% vs. +2%), and greater TID indices (mean 1.13 ± 0.18 vs. 1.02 ± 0.12) compared to hibernation/scar only (N = 92). In addition, mean WT scores during stress declined significantly only in the ischemic subgroup (P < 0.0001 for regional LAD, non-LAD and global wall thickening scores). The prevalence and the severity of MR and RV dysfunction did not differ between groups. By univariate analysis, global and LAD territory segmental ischemia, global sum stress score (SSS), TID index, resting EF, ESV enlargement during stress, as well as global WT changes correlated with post-stress LVEF decline. Multivariate predictors included SSS, resting LVEF, and ESV change. Ischemic changes on vasodilator PET imaging are associated with global LV functional decline and volumetric dilatation, presumably due to stunning effect. Severity of RV dysfunction and MR had limited impact on the above changes.

Medical treatment of asymptomatic chronic aortic regurgitation

Chronic aortic regurgitation results in left ventricular (LV) dilation, increased LV work and, eventually, a decline in LV function and heart failure. An important question is whether pharmacological therapy could preserve LV function and delay the need for aortic valve replacement. Vasodilators have a number of theoretical advantages. By lowering blood pressure, they reduce the regurgitant volume and decrease LV afterload. This article summarizes the clinical studies that have evaluated vasodilators in asymptomatic patients with chronic aortic regurgitation. Some studies suggest favorable effects on LV function and clinical outcomes, but results are inconsistent, making it difficult to draw definite conclusions. In general, studies have been too small to reliably evaluate the overall benefits and risks of this treatment, and in several studies there was no significant difference in measured blood pressure by treatment allocation. For these reasons, decisions on whether vasodilators are indicated in individual patients must currently be based on clinical judgment alone.

Coronary microembolization causes long-term detrimental effects on regional left ventricular function

Objectives. To investigate whether coronary microemboli have long-term effects on left ventricular (LV) function in an experimental model. Furthermore, to determine if first-pass perfusion and late gadolinium enhancement (LGE) patterns differs between small- and large-sized microemboli. Design. Six pigs underwent left anterior descending (LAD)-coronary microembolization with small-sized (40–120 μm, n∼250 000) microemboli using a combined x-ray and MRI-system. MR-images before, one hour after and 7–8 weeks after microembolization were obtained. Results were compared to MRI obtained by large-sized (100–300 μm, n∼7200) microemboli. Results. Cine MRI showed an acute drop in ejection fraction (from 49.5 ± 2.6% to 32.5 ± 2.8) that substantially recovered at 7–8 weeks (47.5 ± 3.2%). Regional LV-function assessed as circumferential, longitudinal and radial strain declined in both microinfarcts and remote regions followed by partial recovery at 7–8 weeks. The decline in LV function and the severe perfusion deficit from the small microemboli was similar to the large microemboli at one hour. There was a significant recovery in perfusion at 7–8 weeks in the microinfarcts. LGE demonstrated the microinfarcts at 7–8 weeks but not at one hour and the microinfarcts were confirmed by histopathology. Conclusion. Microembolization causes long-term, regional LV dysfunction and this study confirmed the need of a comprehensive MRI-protocol for the detection of microinfarcts. These findings suggest that even small microemboli (40–120 μm in diameter), which may escape the distal protective devices influence cardiac function.

WNT Signaling in Adult Cardiac Hypertrophy and Remodeling

On pathological stress, the heart reactivates several signaling pathways that traditionally were thought to be operational only in the developing heart. One of these pathways is the WNT signaling pathway. WNT controls heart development but is also modulated during adult heart remodeling. This review summarizes the currently available data regarding WNT signaling during left ventricular (LV) remodeling. Upstream, soluble frizzled-related proteins (sFRPs) block WNT-dependent activation of the canonical WNT pathway. By inhibition of WNT activation, these factors also reduce β-catenin-dependent transcription by altering the ratio of cytoplasmic/nuclear β-catenin. In experimental settings, sFRPs injected into the heart attenuated LV remodeling. sFRPs are secreted from autologous bone marrow-derived mononuclear cells. Disheveled is a signaling intermediate of both the canonical and noncanonical WNT pathway. Similarly to the effect of sFRP, depletion of a disheveled isoform attenuated LV remodeling. In contrast, disheveled activation led to progressive dilated cardiomyopathy. Inhibition of nuclear β-catenin signaling downstream of the canonical WNT pathway significantly reduced postinfarct mortality and functional decline of LV function following chronic left anterior descending coronary artery ligation. WNT signaling also affects mobilization and homing of bone marrow-derived vasculogenic progenitor cells. Finally, heart-specific WNT/β-catenin interaction partners have been identified that will possibly allow targeting this pathway in a tissue-specific manner. In summary, the WNT pathway plays a pivotal role in adult cardiac remodeling and may be suitable for therapeutic interventions. Currently, several molecular and cellular mechanisms whereby WNT inhibition attenuates LV remodeling are proposed. Reactivation of the developmental program to restore functional LV myocardium from resident precursor cells may significantly contribute to this process.