Accuracy of global and regional longitudinal strain at peak of dobutamine stress echocardiography to detect significant coronary artery disease.

Dobutamine stress echocardiography (DSE) is sensitive but subjective diagnostic tool to detect inducible ischemia. Nowadays, speckle tracking allows an objective quantification of regional wall function. We aimed to investigate the feasibility and accuracy of global (GLS) and regional longitudinal strain (RLS) during DSE to detect significant coronary stenosis (SCS). We conducted a prospective observational multicenter study including patients undergoing DSE for suspected SCS. 50 patients with positive DSE underwent coronary angiography. Besides visual regional wall motion score index (WMSI), GLS and RLS were determined at rest and at peak stress by Automated Function Imaging. DSE GLS feasibility was 96%. Among 35 patients with SCS, 12 patients were affected by multivessel disease, 18 had stenosis of left anterior descending artery (LAD), 18 of left circumflex (LCX) and 15 of right coronary artery (RCA). At peak stress, both GLS reduction (p = 0.037) and WMSI worsening (p = 0.04) showed significant agreement with coronary angiography for detecting SCS. When single lesion was considered, peak stress GLS and LAD RLS were lower in the obstructed LAD regions than in normo-perfused territories (17.4 ± 5.5 vs. 20.5 ± 4.4%, p = 0.03; 17.1 ± 7.6 vs. 21.6 ± 5.5%, p < 0.02, respectively). Furthermore, the addition of RLS to regional WMSI was able to improve accuracy in LAD SCS prediction (AUC 0.68, p = 0.037). Conversely, in presence of LCX or RCA SCS, LS was less accurate than WMSI at peak stress. In conclusion, DSE strain analysis is feasible and may improve prediction of LAD SCS, whereas regional WMSI assessment performs better in presence of SCS of LCX and RCA.

The Effect of Dobutamine Stress Testing on Vortex Formation Time in Patients Evaluated for Ischemia.

Vortex formation time (VFT) is a dimensionless index used to quantify duration of vortex ring formation during diastole. We sought to investigate the effect of pharmaceutical stress on VFT in patients evaluated for ischemia. For this purpose, a standard dobutamine stress echo (DSE) protocol was performed in 50 consecutive patients, and VFT was calculated at rest and at peak. VFT was calculated from echocardiography measurements using a previously developed mathematical equation. VFTi was calculated as the percentage of change of VFTpeak, compared with VFTrest. Mean VFTrest was 2.46 (0.73) and mean VFTpeak 1.67 (0.57) with mean VFTi - 30.0% (19.8). In 14 (28%) patients, an ischemic response (DSE+) was documented. VFTi was significantly lower in DSE+ patients a finding which remained significant in the multivariate analysis after adjusting for age, sex, hypertension, diabetes, history of coronary artery disease, and relative increase of heart rate during stress. Graphical Abstract.

Feasibility and functional correlates of left atrial volume changes during stress echocardiography in chronic coronary syndromes.

An enlarged left atrial volume index (LAVI) at rest mirrors increased LA pressure and/or impairment of LA function. A cardiovascular stress may acutely modify left atrial volume (LAV) within minutes. Aim of this study was to assess the feasibility and functional correlates of LAV-stress echocardiography (SE) Out of 514 subjects referred to 10 quality-controlled labs, LAV-SE was completed in 490 (359 male, age 67 ± 12 years) with suspected or known chronic coronary syndromes (n = 462) or asymptomatic controls (n = 28). The utilized stress was exercise in 177, vasodilator in 167, dobutamine in 146. LAV was measured with the biplane disk summation method. SE was performed with the ABCDE protocol. The intra-observer and inter-observer LAV variability were 5% and 8%, respectively. ∆-LAVI changes (stress-rest) were negatively correlated with resting LAVI (r = - 0.271, p < 0.001) and heart rate reserve (r = -.239, p < 0.001). LAV-dilators were defined as those with stress-rest increase ≥ 6.8 ml/m2, a cutoff derived from a calculated reference change value above the biological, analytical and observer variability of LAVI. LAV dilation occurred in 56 patients (11%), more frequently with exercise (16%) and dipyridamole (13%) compared to dobutamine (4%, p < 0.01). At multivariable logistic regression analysis, B-lines ≥ 2 (OR: 2.586, 95% CI = 1.1293-5.169, p = 0.007) and abnormal contractile reserve (OR: 2.207, 95% CI = 1.111-4.386, p = 0.024) were associated with LAV dilation. In conclusion, LAV-SE is feasible with high success rate and low variability in patients with chronic coronary syndromes. LAV dilation is more likely with reduced left ventricular contractile reserve and pulmonary congestion.

The clinical significance of the incorporation of tissue Doppler imaging into low-dose Dobutamine stress echocardiography in patients with aortic stenosis prior to Transcatheter aortic valve implantation.

BACKGROUND: Low-dose dobutamine stress echocardiography (DSE) is indicated in patients with low flow (stroke volume index [SVi] < 35 ml/m2) low gradient (mean pressure gradient < 40 mmHg) and left ventricular ejection fraction (LVEF) < 50% aortic stenosis (AS) to assess LV contractile reserve (> 20% increase in SVi) and severity grade of AS. Severe AS is defined by a mean pressure gradient of 40 mmHg occurring at any time during the test when aortic valve area remains < 1.0 cm2. CASE PRESENTATION: This case report highlights the utility of mitral annular systolic velocity (S') by tissue Doppler imaging and peak LV outflow tract (LVOT) velocity as markers of LV intrinsic contractile function during DSE in a patient with low flow low gradient AS and reduced EF prior to transcatheter aortic valve implantation (TAVI). CONCLUSIONS: Mitral annular S' and peak LVOT velocities are reliable markers of LV intrinsic contractile function and should be incorporated into routine low-dose DSE.

Long-term prognosis and predictors of outcomes after negative stress echocardiography.

Negative stress echocardiography (NSE) is associated with low cardiovascular morbidity and overall mortality. We aimed to determine the clinical and echocardiographic predictors of overall and cardiovascular outcomes following NSE. Patients who underwent SE between 2013 and 2017 were reviewed. Patients with a history of solid organ transplant or being evaluated for transplant, history of end-stage renal or liver disease, and positive SE were excluded. NSE results were divided into negative diagnostic if patient reached target heart rate (THR) and had no wall motion abnormality (WMA) at rest or stress; negative non-diagnostic if patient had no WMA but did not reach THR or if image quality was non-diagnostic; and abnormal non-ischemic if patient had a resting WMA not worsened at stress along with a personal history of coronary artery disease (CAD). New CAD lesion at 1 year was defined as ≥ 50% stenosis on cardiac catheterization. Of 4119 patients with SE, 2575 were included. All-cause mortality rate was 1.1%/year and CAD rate was 3.1%/year. Predictors of all-cause mortality were age, male gender, history of smoking and being selected for dobutamine SE. Predictors of a new CAD lesion at 1 year were male gender, diabetes, personal history of CAD and abnormal non-ischemic SE. We identified clinical and echocardiographic characteristics in a subset of NSE patients who are at higher risk for subsequent adverse events. These characteristics should be accounted for during the clinical interpretation of SE, and patients found at increased risk for morbidity and mortality warrant continued follow-up.

Role of adjuvant carotid ultrasound in women undergoing stress echocardiography for the assessment of suspected coronary artery disease.

OBJECTIVE: Due to the low prevalence of obstructive coronary artery disease (CAD) in women, stress testing has a relatively low predictive value for this. Additionally, conventional cardiovascular risk scores underestimate risk in women. This study sought to evaluate the role of atherosclerosis assessment using carotid ultrasound (CU) in women attending for stress echocardiography (SE). METHODS: This was a prospective study in which consecutive women with recent-onset suspected angina, who were referred for clinically indicated SE, underwent CU. RESULTS: 415 women (mean age 61±10 years, 29% diabetes mellitus, mean body mass index 28) attending for SE underwent CU. 47 women (11%) had inducible wall motion abnormalities, and carotid disease (CD) was present in 46% (carotid plaque in 41%, carotid intima-media thickness >75th percentile in 15%). Women with CD were older (65 vs 58 years, p<0.001), and more likely to have diabetes (41% vs 21%, p=0.001), hypertension (67% vs 36%, p<0.01) and a higher pretest probability of CAD (59% vs 41%, p<0.001). 40% of women classified as low Framingham risk were found to have evidence of CD.The positive predictive value of SE for flow-limiting CAD was 51%, but with the presence of carotid plaque, this was 71% (p<0.01). Carotid plaque (p=0.004) and ischaemia (p=0.01) were the only independent predictors of >70% angiographic stenosis. In women with ischaemia on SE and no carotid plaque, the negative predictive value for flow-limiting disease was 88%.During a follow-up of 1058±234 days, there were 15 events (defined as all-cause mortality, non-fatal myocardial infarction, heart failure admissions and late coronary revascularisation). Age (HR 1.07 (1.00-1.15), p=0.04), carotid plaque burden (HR 1.65 (1.36-2.00), p<0.001) and ischaemic burden (HR 1.41 (1.18-1.68), p<0.001) were associated with outcome. There was a stepwise increase in events/year from 0.3% when there were no ischaemia and atherosclerosis, 1.1% when there was atherosclerosis and no ischaemia, 2.2% when there was ischaemia and no atherosclerosis and 10% when there were both ischaemia and atherosclerosis (p<0.001). CONCLUSION: CU significantly improves the accuracy of SE alone for identifying flow-limiting disease on coronary angiography, and improves risk stratification in women attending for SE, as well identifying a subset of women who may benefit from primary preventative measures.

Head-to-head comparison of prognostic accuracy in patients undergoing noncardiac surgery of dobutamine stress echocardiography versus computed tomography coronary angiography (PANDA trial): A prospective observational study.

BACKGROUND: Dobutamine stress echocardiography (DSE) and coronary computed tomography angiography (CTA) can provide perioperative prognostic information in risk stratification of patients undergoing noncardiac surgery. This study directly compared the prognostic value of DSE and CTA in patients undergoing noncardiac surgery. METHODS: Between 2014 and 2016, 215 patients with more than one clinical risk factor for perioperative cardiovascular (CV) events were enrolled prospectively. They received both DSE and CTA before noncardiac surgery. Perioperative clinical risk was classified according to the revised cardiac risk index (RCRI), DSE results were categorized as abnormal (inducible ischemia and/or nonviable infarction) or not. CTA results were assessed using the severity of stenosis, with significant stenosis being ≥50% of the luminal diameter). After the exclusion, a total of 206 patients remained. Perioperative CV events were defined as CV death, non-fatal myocardial infarction (MI), myocardial injury, pulmonary edema, non-fatal stroke, and systemic embolism within 30 days after surgery. RESULTS: Twenty-four patients (12%) had perioperative cardiac events (1 cardiac death, 10 non-fatal MI, 8 myocardial injury, 11 pulmonary edema, 1 non-fatal stroke, and 1 pulmonary embolism). Following adjustment for baseline RCRI score, abnormal result on DSE (OR, 6.08, 95% CI, 2.41 to 15.31, P < 0.001), significant CAD on CTA (OR, 18.79; 95% CI, 5.24 to 67.42, P < 0.001), and high CACS (OR, 4.19; 95% CI, 1.39 to 12.60, P = 0.011) remained significant predictors of perioperative CV events. CONCLUSIONS: DSE and CTA are independent predictive factors of events in patients undergoing noncardiac surgery. Among them, assessment of significant CAD using CTA might show a higher prognostic value compared with DSE before noncardiac surgery. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02250963.

Nebivolol attenuates the anticonvulsant action of carbamazepine and phenobarbital against the maximal electroshock-induced seizures in mice.

BACKGROUND: Due to co-occurrence of seizures and cardiovascular disorders, nebivolol, a widely used selective ß1-blocker with vasodilatory properties, may be co-administered with antiepileptic drugs. Therefore, we wanted to assess interactions between nebivolol and four conventional antiepileptic drugs: carbamazepine, valproate, phenytoin and phenobarbital in the screening model of tonic-clonic convulsions. METHODS: Seizure experiments were conducted in the electroconvulsive threshold and maximal electroshock tests in mice. The chimney test served as a method of assessing motor coordination, whereas long-term memory was evaluated in the computerized step-through passive-avoidance task. To exclude or confirm pharmacokinetic interactions, we measured brain concentrations of antiepileptic drugs using the fluorescence polarization immunoassay. RESULTS: It was shown that nebivolol applied at doses 0.5-15 mg/kg did not raise the threshold for electroconvulsions. However, nebivolol at the dose of 15 mg/kg reduced the anti-electroshock properties of carbamazepine. The effect of valproate, phenytoin, and phenobarbital remained unchanged by combination with the ß-blocker. Nebivolol significantly decreased the brain concentration of valproate, but did not affect concentrations of remaining antiepileptic drugs. Therefore, contribution of pharmacokinetic interactions to the final effect of the nebivolol/carbamazepine combination seems not probable. Nebivolol alone and in combinations with antiepileptic drugs did not impair motor performance in mice. Nebivolol alone did not affect long-term memory of animals, and did not potentiate memory impairment induced by valproate and carbamazepine. CONCLUSIONS: This study indicates that nebivolol attenuated effectiveness of some antiepileptic drugs. In case the results are confirmed in clinical settings, this ß-blocker should be used with caution in epileptic patients.

Myocardial Energetics in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The role of coronary microvascular disease and its impact on functional and energetic reserve in heart failure with preserved ejection fraction (HFpEF) remains unclear. We hypothesized that in response to submaximal pharmacologic stress (dobutamine), patients with HFpEF have impairment in left ventricular (LV) myocardial mechanical (external work [EW]), energetic (myocardial O2 consumption [MVO2]), and myocardial blood flow (MBF) reserve. We further assessed whether coupling of MBF to EW is impaired in HFpEF and associated with compensatory increases or pathological decreases in myocardial O2 extraction. Lastly, we assessed whether coupling of MVO2 to EW (mechanical efficiency) was impaired in HFpEF. METHODS AND RESULTS: In prospectively enrolled patients with HFpEF (n=19) and age/sex-matched healthy controls (n=19), we performed 11C-acetate positron emission tomography assessing MVO2 and MBF at rest and during dobutamine infusion. EW was calculated as stroke volume (echo)×end-systolic pressure×heart rate. At rest, compared with controls, patients with HFpEF had higher LV EW, MVO2, and MBF. With dobutamine, LV EW, MVO2, and MBF increased in both HFpEF and controls; however, the magnitude of increases was significantly smaller in HFpEF. In both groups, MBF increased in relation to EW, but in HFpEF, the slope of the relationship was significantly smaller than in controls. Myocardial O2 extraction was increased in HFpEF. Mechanical efficiency was similar in HFpEF and controls. In a post hoc analysis, HFpEF patients with LV hypertrophy (n=10) had significant reductions in LV mechanical efficiency relative to controls. CONCLUSIONS: In HFpEF during submaximal dobutamine stress, there is myocardial mechanical-, energetic- and flow-reserve dysfunction with impaired coupling of blood flow to demand and slight increases in myocardial O2 extraction. These findings provide evidence that coronary microvascular dysfunction is present in HFpEF, limits O2 supply relative to demand, and is associated with reserve dysfunction.

Stress increases intracardiac 4D flow cardiovascular magnetic resonance -derived energetics and vorticity and relates to VO2max in Fontan patients.

BACKGROUND: We hypothesize that dobutamine-induced stress impacts intracardiac hemodynamic parameters and that this may be linked to decreased exercise capacity in Fontan patients. Therefore, the purpose of this study was to assess the effect of pharmacologic stress on intraventricular kinetic energy (KE), viscous energy loss (EL) and vorticity from four-dimensional (4D) Flow cardiovascular magnetic resonance (CMR) imaging in Fontan patients and to study the association between stress response and exercise capacity. METHODS: Ten Fontan patients underwent whole-heart 4D flow CMR before and during 7.5 µg/kg/min dobutamine infusion and cardiopulmonary exercise testing (CPET) on the same day. Average ventricular KE, EL and vorticity were computed over systole, diastole and the total cardiac cycle (vorticity_volavg cycle, KEavg cycle, ELavg cycle). The relation to maximum oxygen uptake (VO2 max) from CPET was tested by Pearson's correlation or Spearman's rank correlation in case of non-normality of the data. RESULTS: Dobutamine stress caused a significant 88 ± 52% increase in KE (KEavg cycle: 1.8 ± 0.5 vs 3.3 ± 0.9 mJ, P < 0.001), a significant 108 ± 49% increase in EL (ELavg cycle: 0.9 ± 0.4 vs 1.9 ± 0.9 mW, P < 0.001) and a significant 27 ± 19% increase in vorticity (vorticity_volavg cycle: 3441 ± 899 vs 4394 ± 1322 mL/s, P = 0.002). All rest-stress differences (%) were negatively correlated to VO2 max (KEavg cycle: r = - 0.83, P = 0.003; ELavg cycle: r = - 0.80, P = 0.006; vorticity_volavg cycle: r = - 0.64, P = 0.047). CONCLUSIONS: 4D flow CMR-derived intraventricular kinetic energy, viscous energy loss and vorticity in Fontan patients increase during pharmacologic stress and show a negative correlation with exercise capacity measured by VO2 max.

ß-adrenergic modulation of discrimination learning and memory in the auditory cortex.

Despite vast literature on catecholaminergic neuromodulation of auditory cortex functioning in general, knowledge about its role for long-term memory formation is scarce. Our previous pharmacological studies on cortex-dependent frequency-modulated tone-sweep discrimination learning of Mongolian gerbils showed that auditory-cortical D1/5 -dopamine receptor activity facilitates memory consolidation and anterograde memory formation. Considering overlapping functions of D1/5 -dopamine receptors and ß-adrenoceptors, we hypothesised a role of ß-adrenergic signalling in the auditory cortex for sweep discrimination learning and memory. Supporting this hypothesis, the ß1/2 -adrenoceptor antagonist propranolol bilaterally applied to the gerbil auditory cortex after task acquisition prevented the discrimination increment that was normally monitored 1 day later. The increment in the total number of hurdle crossings performed in response to the sweeps per se was normal. Propranolol infusion after the seventh training session suppressed the previously established sweep discrimination. The suppressive effect required antagonist injection in a narrow post-session time window. When applied to the auditory cortex 1 day before initial conditioning, ß1 -adrenoceptor-antagonising and ß1 -adrenoceptor-stimulating agents retarded and facilitated, respectively, sweep discrimination learning, whereas ß2 -selective drugs were ineffective. In contrast, single-sweep detection learning was normal after propranolol infusion. By immunohistochemistry, ß1 - and ß2 -adrenoceptors were identified on the neuropil and somata of pyramidal and non-pyramidal neurons of the gerbil auditory cortex. The present findings suggest that ß-adrenergic signalling in the auditory cortex has task-related importance for discrimination learning of complex sounds: as previously shown for D1/5 -dopamine receptor signalling, ß-adrenoceptor activity supports long-term memory consolidation and reconsolidation; additionally, tonic input through ß1 -adrenoceptors may control mechanisms permissive for memory acquisition.

Echocardiographic assessment at rest and during stress in patients with intermittent claudication.

Objective. Skeletal muscle perfusion during walking relies on complex interactions between cardiac activity and vascular control mechanisms, why cardiac dysfunction may contribute to intermittent claudication (IC) symptoms. The study aims were to describe cardiac function at rest and during stress in consecutive IC patients, to explore the relations between cardiac function parameters and treadmill performance, and to test the hypothesis that clinically silent myocardial ischemia during stress may contribute to IC limb symptomatology. Design. Patients with mild to severe IC (n = 111, mean age 67 y, 52% females, mean treadmill distance 195 m) underwent standard echocardiography, dobutamine stress echocardiography (SE) and treadmill testing. The patient cohort was separated in two groups based on treadmill performance (HIGH and LOW performance). Results. Ten patients (9%) had regional wall motion abnormalities of which three had left ventricular ejection fraction <50% at standard echocardiography. A majority had lower than expected systolic- and diastolic ventricular volumes. LOW performers had smaller diastolic left ventricular volumes and lower global peak systolic velocity during dobutamine stress. No patient demonstrated significant cardiac dysfunction during dobutamine provocation that was not also evident at standard echocardiography. Conclusions. Most IC patients were without signs of ischemic heart disease or cardiac failure. The majority had small left ventricular volumes. The hypothesis that clinically silent myocardial ischemia impairing left ventricular function during stress may contribute to IC limb symptomatology was not supported.

Effective dose of dobutamine in augmenting free flap blood flow during reconstructive surgery of the lower extremity.

Success of surgical free flap transfer depends on achieving and maintaining adequate perfusion across the microvascular anastomosis. The purpose of this prospective study was to determine the optimal infusion rate of dobutamine to augment duplex ultrasound measured blood flow to the tissue flap during surgery.Twenty-one patients undergoing general anesthesia for lower limb reconstructive surgery were recruited. The optimal dobutamine dose was evaluated using the modified Dixon's up-and-down method, starting at 6 µg·kg·min, and then titrated in increments of 1 µg·kg·min.The optimal dose of dobutamine for improving blood flow to the tissue flap was 3.50 ±â€Š0.57 µg·kg·min in 50% of patients. The 95% effective dose of dobutamine calculated by probit analysis was 4.46 µg·kg·min (95% confidence interval: 3.99-7.00 µg·kg·min).The results of our study suggest that a dobutamine infusion rate less than 5 µg·kg·minprovides significant improvement of blood flow to the tissue flap, while minimizing cardiovascular side effects.

The value of a simplified approach to end-systolic volume measurement for assessment of left ventricular contractile reserve during stress-echocardiography.

The peak stress/rest ratio of left ventricular (LV) elastance, or LV force, is a load-independent index of left ventricular contractile reserve (LVCR) with stress echo (SE). To assess the accuracy of LVCR calculated during SE with approaches of different complexity. Two-hundred-forty patients were referred to SE for known or suspected coronary artery disease or heart failure and, of those, 200 patients, age 61 ± 15, 99 females, with interpretable volumetric SE were enrolled. All readers had passed the upstream quality control reading for regional wall motion abnormality (RWMA) and end-systolic volume (ESV) measurement. The employed stress was dipyridamole (0.84 mg, 6 min) in 86 (43%) and dobutamine (up to 40 mcg/kg/min) in 114 (57%) patients. All underwent SE with evaluation of RWMA and simultaneous LVCR assessment with stress/rest ratio of LV force (systolic blood pressure by cuff sphygmomanometer/ESV). ESV was calculated in each patient by two of three methods: biplane Simpson rule (S, in 100 patients), single plane area-length (AL, apical four-chamber area and length, in 100 patients), and Teichholz rule (T, from parasternal long axis and/or short axis view, in 200 patients). RMWA were observed in 54 patients. Success rate for ESV measurement was 76% (100/131) for S, 92% (100/109) for AL, and 100% (240/240) for T. There were 100 paired measurements (rest and stress) with S versus T, and 100 with AL versus T. The analysis time was the shortest for T (33 ± 8 s at rest, 34 ± 7 s at stress), intermediate for AL (70 ± 22 s at rest 67 ± 21 s at stress), and the longest for S (136 ± 24 at rest 129 ± 27 s at stress, p < 0.05 vs. T and AL). ESV absolute values were moderately correlated: T versus S (r rest = 0.746, p < 0.01, n = 100; r stress = 0.794, p < 0.01, n = 100); T vs. AL (r = 0.603 p < 0.01, n = 100, at rest and r = 0.820 p < 0.01 n = 100 at peak stress). LVCR values were tightly correlated independently of the method employed: T versus S (r = 0.899, p < 0.01, n = 100), and T versus AL (r = 0.845, p < 0.01, n = 100). LVCR can be accurately determined with all three methods used to extract the raw values of ESV necessary to generate the calculation of Force. Although S is known to be more precise in determining absolute ESV values, the relative (rest-stress) changes can be assessed, with comparable accuracy, with simpler and more feasible T and AL methods, characterized by higher success rate, shorter imaging and analysis time.

Diagnostic Performance of Dobutamine Stress Echocardiography in End-Stage Liver Disease.

OBJECTIVES: This study determined the test performance of dobutamine stress echocardiography (DSE) in end-stage liver disease (ESLD). BACKGROUND: The reported sensitivity of DSE in ESLD has been variable. METHODS: Data from 633 ESLD patients who had coronary angiography within 6 months after DSE was analyzed. RESULTS: The prevalence of coronary arterial disease (CAD) (≥70% stenosis by quantitative angiography) was 12% (74 of 633 patients). DSE sensitivity was 24% (17 of 72 patients), and specificity was 90% (503 of 559 patients). The positive and negative predictive values were 23% (17 of 73 patients) and 90% (503 of 558 patients), respectively. Stratifying the cohort into low-, intermediate-, and high-risk CAD groups yielded sensitivities of 0%, 21%, and 32%, respectively. Independent predictors of an accurate ischemic DSE result included left ventricular internal dimension at end-diastole (LVIDd) >4.8 cm and assigning ischemia based on tardokinesis or lack of low-to-peak dose hyperkinesis (p < 0.05 for all). DSE sensitivity was 38% in LVIDd >4.8 cm versus 13% with LVIDd ≤4.8 cm (p = 0.013). The sensitivity was 67% when tardokinesis or lack of hyperkinesis was considered abnormal versus 15% (p < 0.001) for readings that did not consider tardokinesis or lack of hyperkinesis abnormal. There was a higher frequency of cardiac events in patients with significant CAD who had abnormal (45%) versus normal (18%) DSE (p = 0.01). CONCLUSIONS: The sensitivity of DSE in ESLD was low. DSE sensitivity was higher for those with larger cavity dimension and when tardokinesis or lack of hyperkinesis was considered abnormal. An abnormal DSE in those with significant CAD was associated with worse outcome.

Echocardiography for prediction of 6-month and late response to cardiac resynchronization therapy: implementation of stress echocardiography and comparative assessment along with widely used dyssynchrony indices.

Non-response cardiac resynchronization therapy (CRT) remains an issue, despite the refinement of selection criteria. The purpose of this study was to investigate the role of stress echocardiography along with dyssynchrony parameters for identification of CRT responders or late responders. 106 symptomatic heart failure patients were examined before, 6 months and 2-4 years after CRT implementation. Inotropic contractile reserve (ICR) and inferolateral (IL) wall viability were studied by stress echocardiography. Dyssynchrony was assessed by: (1) Septal to posterior wall motion delay (SPWMD) by m-mode. (2) Septal to lateral wall delay (SLD) by TDI. (3) Interventricular mechanical delay (IVMD) by pulsed wave Doppler for (4) difference in time to peak circumferential strain (TmaxCS) by speckle tracking. (5) Apical rocking (ApR) and septal flash (SF) by visual assessment. At 6 months there were 54 responders, with 12 additional late responders. TmaxCS had the greatest predictive value with an area under curve (AUC) of 0.835, followed by the presence of both ICR and viability of IL wall (AUC 0.799), m-mode (AUC = 0.775) and presence of either ApR or SF (AUC = 0.772). Predictive ability of ApR and of ICR is augmented if late responders are also included. Performance of dyssynchrony parameters is enhanced, in patients with both ICR and IL wall viability. Stress echocardiography and dyssynchrony parameters are simple and reliable predictors of 6-month and late CRT response. A stepwise approach with an initial assessment of ICR and viability and, if positive, further dyssynchrony analysis, could assist decision making.

Can stress echocardiography identify patients who will benefit from percutaneous mitral valve repair?

The aim of the current study was to investigate whether stress echocardiography improves selection of patients who might have clinical benefit from percutaneous mitral valve repair with the MitraClip. In total, 39 patients selected for MitraClip implantation underwent preprocedural low-dose stress (dobutamine or handgrip) echocardiography from which stroke volume, ejection fraction and MR grade were measured. Outcome after MitraClip implantation was determined by New York Heart Association classification and Quality of Life questionnaires. Clinical benefit from MitraClip treatment was defined as survival and NYHA class I-II at 6 months follow-up. In total, 36 patients with a technically successful procedure were included in the analysis (mean age 79 ± 8 years, 47% male, 50% functional MR). Clinical benefit was achieved in 18 patients. All seven patients with MR decreasing during stress remained in NYHA III-IV or died within 6 months, while 62% (18 out of 29) of the patients with stable or increased MR during stress had clinical benefit (p = 0.008). Significant increase in Quality of Life on 4/8 subscales of the RAND Short Form-36 questionnaire was observed: Physical Functioning (p < 0.001), Social Functioning (p < 0.001), Mental Health (p = 0.022) and Vitality (p = 0.026) was seen in patients with an increase in stroke volume during stress echocardiography. Patients with a decreased MR during preprocedural stress echocardiography remained more symptomatic than patients with a stable or increased MR during stress. Stress echocardiography may support patient selection for percutaneous mitral valve repair.

Low-Gradient Aortic Stenosis: Solving the Conundrum Using Multi-Modality Imaging.

Up to 1/3 of patients with both reduced or preserved left ventricular ejection fraction (LVEF), harbor a mean pressure gradient (MPG) < 40 mm Hg (peak velocity (PV) < 4 m/s), suggesting moderate aortic stenosis (AS) and an aortic valve area (AVA) < 1 cm2 suggesting severe AS raising uncertainties regarding AS severity and appropriate management. In patients with reduced LVEF, increased transvalvular flow and stroke volume ≥ 20% (i.e. contractile reserve) during low-dose dobutamine echocardiography enables distinguishing patients with "true-severe AS" (severe AS with secondary LV dysfunction, PV ≥ 4 m/s or MPG > 30-40 mm Hg at peak while AVA remains <1 cm2) from patients with "pseudo-severe AS" (moderate AS with associated LV dysfunction due to ischemic or dilated cardiomyopathy, AVA at peak ≥1 cm2 with a MPG < 30-40 mm Hg). However, interpretation of dobutamine stress echocardiography is often challenging, and absence of contractile reserve is observed in 20 to 30% of patients. Measurement of the degree of calcification (AVC) using computed tomography is an accurate and flow-independent method for the assessment of AS severity. A score > 1250 AU in women and >2000 UA in men strongly suggest severe AS. Combination of dobutamine echocardiography and AVC scoring enables assessment of AS severity with high confidence. The subset of patients with discordant grading and preserved LVEF is heterogenous and encompasses various conditions. A minority harbor a low flow state related to a reduced myocardial performance, an increased arterial afterload or combination of both. A low flow state is an important prognostic factor but does not provide any information regarding AS severity. Similarly to patients with reduced LVEF, assessment of the degree of AVC seems the best method to differentiate patients with pseudo-severe AS from patients with true severe AS. The latter should be referred for an intervention if symptomatic whereas the optimal management of the former subset remains uncertain.

Asymptomatic myocardial ischemia forecasts adverse events in cardiovascular magnetic resonance dobutamine stress testing of high-risk middle-aged and elderly individuals.

BACKGROUND: Current guidelines for assessing the risk of experiencing a hospitalized cardiovascular (CV) event discourage stress testing of asymptomatic individuals; however, these recommendations are based on evidence gathered primarily from those aged < 60 years, and do not address the possibility of unrecognized "silent myocardial ischemia" in middle aged and older adults. METHODS: We performed dobutamine cardiovascular magnetic resonance (CMR) stress testing in 327 consecutively recruited participants aged > 55 years without CV-related symptoms nor known coronary artery disease, but otherwise at increased risk for a future CV event due to pre-existing hypertension or diabetes mellitus for at least 5 years. After adjusting for the demographics and CV risk factors, log-rank test and Cox proportional hazards models determined the additional predictive value of the stress test results for forecasting hospitalized CV events/survival. Either stress-induced LV wall motion abnormalities or perfusion defects were used to indicate myocardial ischemia. RESULTS: Participants averaged 68 ± 8 years in age; 39% men, 75% Caucasian. There were 38 hospitalized CV events or deaths which occurred during a mean follow-up of 58 months. Using Kaplan-Meier analyses, myocardial ischemia identified future CV events/survival (p <  0.001), but this finding was more evident in men (p <  0.001) versus women (p = 0.27). The crude hazard ratio (HR) of myocardial ischemia for CV events/survival was 3.13 (95% CI: 1.64-5.93; p < 0.001). After accounting for baseline demographics, CV risk factors, and left ventricular ejection fraction/mass, myocardial ischemia continued to be associated with CV events/survival [HR: 4.07 (95% CI: 1.95-8.73) p < 0.001]. CONCLUSIONS: Among asymptomatic middle-aged individuals with risk factors for a sentinel CV event, the presence of myocardial ischemia during dobutamine CMR testing forecasted a future hospitalized CV event or death. Further studies are needed in middle aged and older individuals to more accurately characterize the prevalence, significance, and management of asymptomatic myocardial ischemia. TRIAL REGISTRATION: ( ClinicalTrials.gov identifier): NCT00542503 and was retrospectively registered on October 11th, 2007.