Low-dose Dobutamine Stress Research Articles

Diagnostic value of low dose dobutamine stress echocardiography in paradoxical low flow low gradient aortic stenosis

Abstract Background In aortic stenosis with low-gradient scenarios distinguishing between fixed and pseudo-severe stenosis becomes challenging. Low-dose dobutamine stress echocardiography (DSE) is recommended for classical low-flow low- gradient stenosis with reduced ejection fraction. Doubts of DSE's utility in paradoxical low-flow low-gradient (PLFLG) stenosis when ejection fraction is preserved are partially reasoned by proposed inefficiency in generating a contractile reserve 1. Guidelines advocate an integrated approach, combining various clinical and imaging aspects 2. Purpose This study aimed to investigate usefulness of DSE in PLFLG stenosis, identifying specific features to predict the possibility of generating significant stroke volume augmentation and distinguishing fixed aortic stenosis. Methods We identified patients with aortic stenosis who underwent DSE and multi-modality imaging at our centre between 2020 and 2023. Among them, those with PLFLG situations were used for detailed analysis. Multiple linear regression analysis was performed to identify parameters predictive of significant contractile reserve, defined as 20% stroke volume increase from baseline. For patients demonstrating contractile reserve we assessed predefined parameters by receiver operating characteristics (ROC) analysis to predict fixed stenosis defined as final aortic valve area < 1cm² and valve area change <0.2cm² or final mean pressure gradient >40mmHg. For predictive value of Agatston score we conducted post-hoc analysis. Results Among 256 DSE cases, 67 were conducted for PLFLG stenosis. Patients were 82 years of median age and mostly female (63%). Symptoms included dyspnea in 90% and angina in 40% of cases. Baseline echo showed median aortic valve area (indexed to body surface area) of 0.8cm² (0.44cm²/m²) with mean pressure gradient of 20mmHg. Contractile reserve was inducible in 70% of patients, of which 74% showed criteria of fixed stenosis. Higher left ventricular end-diastolic diameter (LVESD) and lower baseline systolic flow-rate were predictive for contractile reserve (p<0.05). Among patients with contractile reserve ROC for baseline mean pressure gradient, acceleration time (median 0.08s; range 0.04-0.11s) and acceleration time to ejection time index (0.28; range: 0.148-0.458) revealed good prediction of fixed stenosis in DSE meanwhile Agatston calcium score (median 1076; range: 301-8821) did not (figure 1). No correlation was found between Agatston score probability of severe stenosis and aortic valve pressure gradient behavior with increased stroke volume (figure 2). Conclusion DSE proves to be a useful a method in the differentiation between fixed and pseudo-severe stenosis in PLFLG situation. Our findings question the predictive value of Agatston score for aortic valve behavior with increase of stroke volume and warrant further investigations regarding value of acceleration time and acceleration time to ejection time index in those patients.Receiver operating characteristicsPost-hoc analysis of Agatston score

Combined low-dose dobutamine and exercise stress echocardiography: a new hybrid protocol to detect inducible ischaemia.

Myocardial response to stress echocardiography may be elicited physiologically, through exercise, or pharmacologically, often with dobutamine. Both have advantages but also limitations due to reduced exercise capacity or side-effects to stressor agent/lack of closeness to true pathophysiology of ischaemic cascade. We have combined low-dose dobutamine and exercise, creating a 'hybrid' protocol to utilize the advantages of both techniques and limit the drawbacks. The aim of the study was to evaluate its safety and feasibility. In the hybrid protocol, low-dose dobutamine infusion (up to 10 µg/kg/min) is enhanced by supine bicycle exercise at 3-min increments of workload of 25 W to achieve target heart rate (THR). We analysed safety and outcome data for all the patients who underwent this protocol from 2017 to 2022. Out of 835, 727 (87.1%) patients referred for evaluation of ischaemia underwent the hybrid protocol. The median age was 61 years old and 61% (442/727) were men. The median exercise time was 11 (9-13.5) min with a median maximum workload of 100 W (75-125). Out of 727, 670 (92.2%) achieved THR. Atropine was not used. Out of 727, 192 (26.4%) of studies were positive for ischaemia. Out of 122, 102 (83.6%) with positive stress who underwent invasive angiography had significant coronary disease. The incidence of complications was low: 1/727-severe arrhythmia, 5/727 (0.7%) developed a vasovagal episode, and 14/727 (1.9%) had a hypertensive response to exercise. Our findings suggest that this protocol is safe, feasible, and has a high success rate in achieving THR.

Multiaxial pressure-strain analysis of regional myocardial work in the setting of graded coronary stenoses and dobutamine stress.

We present a detailed analysis of regional myocardial blood flow and work to better understand the effects of coronary stenoses and low-dose dobutamine stress. Our analysis is based on a unique open-chest model in anesthetized canines that features invasive hemodynamic monitoring, microsphere-based blood flow analysis, and an extensive three-dimensional (3-D) sonomicrometer array that provides multiaxial deformational assessments in the ischemic, border, and remote vascular territories. We use this model to construct regional pressure-strain loops for each territory and quantify the loop subcomponent areas that reflect myocardial work contributing to the ejection of blood and wasted work that does not. We demonstrate that reductions in coronary blood flow markedly alter the shapes and temporal relationships of pressure-strain loops, as well as the magnitudes of their total and subcomponent areas. Specifically, we show that moderate stenoses in the mid-left anterior descending coronary artery decrease regional midventricle myocardial work indices and substantially increase indices of wasted work. In the midventricle, these effects are most pronounced along the radial and longitudinal axes, with more modest effects along the circumferential axis. We further demonstrate that low-dose dobutamine can help to restore or even improve function, but often at the cost of increased wasted work. This detailed, multiaxial analysis provides unique insight into the physiology and mechanics of the heart in the presence of ischemia and low-dose dobutamine, with potential implications in many areas, including the detection and characterization of ischemic heart disease and the use of inotropic support for low cardiac output.NEW & NOTEWORTHY Our unique experimental model assesses cardiac pressure-strain relationships along multiple axes in multiple regions. We demonstrate that moderate coronary stenoses decrease regional myocardial work and increase wasted work and that low-dose dobutamine can help to restore myocardial function, but often with further increases in wasted work. Our findings highlight the significant directional variation of cardiac mechanics and demonstrate potential advantages of pressure-strain analyses over traditional, purely deformational measures, especially in characterizing physiological changes related to dobutamine.

P357 DOES CARDIAC AMYLOIDOSIS EVER HIDE A SEVERE AORTIC STENOSIS A CASE REPORT

Abstract Case presentation: A 89-year-old man, with an history of paroxysmal atrial fibrillation and chronic renal disease, was admitted to our ER for acute decompensated heart failure. He reported dyspnea on minimal exertion and worsening peripheral edema. He had a history of heart failure and a severe aortic stenosis first diagnosed in 2020 with an echocardiogram demonstrating a left ventricular ejection fraction (LVEF) of 30% and a low-flow low-gradient aortic stenosis (AVA=0,6 cmq, mean pressure gradient=21 mmHg). Besides, in 2019, he underwent a 99m Tc MDP scintigraphy for a prostatic nodule which showed important myocardial uptake of the bone tracer highly suggestive of cardiac amyloidosis. Urinary light chain assessment and determination of immunoglobulin light chain levels were negative for AL amyloidosis. The electrocardiogram showed: sinus rhythm, low voltage in the frontal leads and complete left bundle branch block with secondary repolarization abnormalities. The patient underwent transthoracic echocardiography for staging the severity of the aortic valve stenosis, which revealed borderline results: the aortic valve area was 0.5 cmq with a transaortic mean pressure gradient of 20 mmHg (EF 25%, with GLS of −5%). Low-dose dobutamine stress echocardiography was performed. At rest conditions, there was global hypokinesia with an ejection fraction of 24%. Aortic valve mean pressure was 19 mmHg referring to a calculated aortic valve opening area of 0,78 cmq. Under peak dobutamine stress (30 mcg/kg/min), LVEF increased to 36%. On the basis of these diagnostic findings, aortic stenosis was classified as pseudo-severe due to systolic dysfunction of the left ventricle with preserved contractile reserve. Besides, aortic calcium score of 574 confirmed that the aortic stenosis was non severe. Conclusions This case results exemplary of the fact that amyloidosis does not always hide a severe stenosis. Actually the echo with dobutamine indicates a non-valvular reason for heart-failure and no indication for valve replacement.The discharge suggestions consists of clinical/ echo follow ups and TTR stabilizers. Anyway, Tafamidis is not recommended because of the age and the patient short life expectancy. The implantation of CCM which, during the action potential platea delivers non-excitatory electrical currents and enhances systolic function in patients with heart failure, is proposed to obtain an improvement of symptoms.

Value of Speckle Tracking Echocardiography Combined with Stress Echocardiography in Predicting Surgical Outcome of Severe Aortic Regurgitation with Markedly Reduced Left Ventricular Function.

Predicting outcomes of surgical aortic valve replacement (AVR) in patients with chronic severe aortic regurgitation (AR) and markedly reduced left ventricular (LV) function remains a challenge. This study aimed to explore the preoperative echocardiographic index that could predict the recovery of LV systolic function after surgery in patients with chronic severe AR and reduced left ventricular ejection fraction (LVEF). The study group consisted of 50 patients diagnosed with chronic severe AR ( 6 months) and significantly reduced LVEF (18~35%, average 26.2 5.3%). Low-dose dobutamine stress echocardiography (DSE) was performed before surgery. Only patients with an absolute increase in LVEF 8% during DSE were referred for surgical AVR. During following up (over six months to one year after surgery), the patients were divided into two groups by postoperative LVEF ( or 40%). DSE- and speckle tracking echocardiography (STE)-derived LV functional parameters were compared between groups to identify predictors of post-operative improvement in LVEF. A total of 38 patients underwent AVR. One patient died before discharge. Post-surgical LV size and LVEF improved markedly after surgery in all patients (n = 37). Pre-surgical LV end-systolic diameter, baseline global longitudinal strain (GLS) and peak GLS were better in the group with LVEF 40% (n = 18; p 0.05, t test). Baseline GLS and peak GLS correlated moderately with post-surgery LVEF (R = -0.581, p 0.001; R = -0.596, p 0.001; respectively). Logistic regression analysis demonstrated baseline GLS and peak GLS were the independent predictors of post-surgery improvement of LVEF. Peak GLS had the highest prediction value (area under the curve = 0.895, sensitivity and specificity: 89.5% and 77.8%, respectively), with a cutoff value of -9.4%. This study shows that STE combined with DSE can provide sensitive quantitative indices for predicting improvement of LV systolic function after AVR in patients with chronic severe AR and significantly decreased LVEF.

Dobutamine stress echocardiography during transcatheter edge-to-edge mitral valve repair predicts residual mitral regurgitation.

The current study sought to determine whether low-dose dobutamine stress echocardiography (DSE) during transcatheter edge-to-edge mitral valve repair (TMVR) can predict residual mitral regurgitation (MR) at discharge. In most patients, TMVR can successfully reduce MR from severe to mild or moderate. However, general anesthesia during the intervention affects hemodynamics and MR assessment. At discharge transthoracic echocardiogram residual MR (>moderate) is present in 10%-30% of patients which is associated with worse clinical outcome. In consecutive patients the severity of MR was determined at baseline, immediately after TMVR clip implantation and subsequently during low-dose DSE (both under general anesthesia) and at discharge. A total of 39 patients were included (mean age 76.1 ± 8.1 years, 39% male, 56% functional MR, 41% left ventricular ejection fraction < 45%). An increase of MR during DSE was seen in 11 patients, of whom 6 (55%) showed >moderate MR at discharge. None of the 28 patients without an increase of MR during DSE showed >moderate MR at discharge. The diagnostic performance of the test could be established at a sensitivity of 100% and a specificity of 85% in unselected patients. DSE during TMVR is a useful tool to predict residual MR at discharge. It could support procedural decision making, including implantation of additional clips and thus potentially improve clinical outcome.

Влияние миокардиального станнинга на динамику показателей митральной регургитации и ремоделирования после перенесенного инфаркта миокарда

Aim. To study the dynamics of mitral regurgitation depending on the results of low dose dobutaminestress-echocardiography with effectiveness of myocardial reperfusion and in patients after MI with STsegment elevation.Material and methods. The study included 302 patients with STeMI. All patients underwent myocardialreperfusion. Depending on the effectiveness of reperfusion, the patients were divided into 3 groups: group1 – 196 (65%) patients with successful reperfusion; group 2 – 76 (25%) patients with partial reperfusion,group 3 – 30 (10%) patients with no reperfusion. The indicators of systolic function, LV remodeling, mitralregurgitation at rest, under pharmacological load and after a month were studied. To determine the zoneof viable myocardium, stress echocardiography with low doses of dobutamine was used.Results. Indicators characterizing the severity of MR had a negative trend in patients of group 3, who showedan increase in ERO, PISA and vena contracta width. But in patients of the 1st and 2nd groups with the presence of myocardial stunning, an unreliable decrease in these indicators of the degree of MR was noted. Identification of viable zones by low-dose dobutamine stress echocardiography in areas of LV dysfunction preventsthe progression of MR and serious intracardiac hemodynamic disturbances and will also be reversible.Conclusion. The main mechanism in the progression of MR in patients after AMI is LV myocardial dysfunction with further LV remodeling accompanied by dilatation and spherification of its cavity. The presenceof a viable myocardium in the zone of dysfunction can prevent the progression of MR, and even lead toa decrease in its degree with adequate revascularization. Patients with MR, with a lack of viability in thearea of myocardial dysfunction, are candidates for the development of severe MI.

Coronary Wave Intensity Analysis as an Invasive and Vessel-Specific Index of Myocardial Viability.

Coronary angiography and viability testing are the cornerstones of diagnosing and managing ischemic cardiomyopathy. At present, no single test serves both needs. Coronary wave intensity analysis interrogates both contractility and microvascular physiology of the subtended myocardium and therefore has the potential to fulfil the goal of completely assessing coronary physiology and myocardial viability in a single procedure. We hypothesized that coronary wave intensity analysis measured during coronary angiography would predict viability with a similar accuracy to late-gadolinium-enhanced cardiac magnetic resonance imaging. Patients with a left ventricular ejection fraction ≤40% and extensive coronary disease were enrolled. Coronary wave intensity analysis was assessed during cardiac catheterization at rest, during adenosine-induced hyperemia, and during low-dose dobutamine stress using a dual pressure-Doppler sensing coronary guidewire. Scar burden was assessed with cardiac magnetic resonance imaging. Regional left ventricular function was assessed at baseline and 6-month follow-up after optimization of medical-therapy±revascularization, using transthoracic echocardiography. The primary outcome was myocardial viability, determined by the retrospective observation of functional recovery. Forty participants underwent baseline physiology, cardiac magnetic resonance imaging, and echocardiography, and 30 had echocardiography at 6 months; 21/42 territories were viable on follow-up echocardiography. Resting backward compression wave energy was significantly greater in viable than in nonviable territories (-5240±3772 versus -1873±1605 W m-2 s-1, P<0.001), and had comparable accuracy to cardiac magnetic resonance imaging for predicting viability (area under the curve 0.812 versus 0.757, P=0.649); a threshold of -2500 W m-2 s-1 had 86% sensitivity and 76% specificity. Backward compression wave energy has accuracy similar to that of late-gadolinium-enhanced cardiac magnetic resonance imaging in the prediction of viability. Coronary wave intensity analysis has the potential to streamline the management of ischemic cardiomyopathy, in a manner analogous to the effect of fractional flow reserve on the management of stable angina.

Speckle-tracking echocardiography for predicting improvement of myocardial contractile function after revascularization: a meta-analysis of prospective trials

Some studies have indicated that the use of 2D-Speckle tracking echocardiography (2DSTE) aids in predicting recovery of myocardial contractile function after revascularization in patients with chronic ischemic left ventricular (LV) dysfunction or acute myocardial infarction (MI). The purpose of this meta-analysis was to evaluate the diagnostic accuracy of 2DSTE strain in the detection of myocardial viability at rest and during low-dose dobutamine (LDD) stress. A systematic review for all prospective trials using 2DSTE to assess myocardial viability until January 2019 was done. Using a standard approach of meta-analysis for diagnostic tests. Overall, nine studies including 525 patients with either chronic ischemic heart disease or acute MI fulfilled the inclusion criteria. Seven studies used longitudinal strain (LS) at rest, nine studies used circumferential strain (CS) at rest, four studies used LS during LDD stress, and four studies used CS during LDD stress. LS and CS during LDD stress showed equally high sensitivity (81.5% and 81.5% respectively) and specificity (81.3% and 81.4% respectively) for detecting reversible dysfunction. At rest, LS and CS showed equally lower sensitivity (67.1%, p < 0.0001 vs. LDD stress and 68.7%, p < 0.0001, vs. LDD stress, respectively) and specificity (64%, p < 0.0001 vs. LDD stress and 65.7%, p = 0.0008 vs. LDD stress, respectively) as compared with LDD stress. LS and CS by 2DSTE during LDD stress accurately identify reversible ischemic myocardial dysfunction in patients with chronic ischemic LV dysfunction or after MI. The use of LDD stress can be recommended over resting strain measures in this setting.

Coronary wave energy to predict functional recovery in patients with ischemic left ventricular dysfunction

Abstract Background Invasive coronary angiography and non-invasive viability testing are the cornerstones of diagnosing and managing ischemic left ventricular dysfunction. At present there is no single test which serves both needs but, if developed, could revolutionise investigation of this condition. Coronary wave intensity analysis (cWIA) interrogates both contractility and microvascular physiology of the subtended myocardium [1,2] and therefore has the potential to fulfil this goal. Objectives We hypothesized that cWIA measured during coronary angiography would predict functional recovery with a similar accuracy to late gadolinium enhanced cardiac magnetic resonance imaging (LGE-CMR). Methods Patients with a left ventricular ejection fraction ≤40% and extensive coronary disease were enrolled. cWIA, fractional flow reserve and microvascular resistance were assessed with a simultaneous coronary Doppler and pressure-sensing guidewire during cardiac catheterization at rest, during hyperaemia and during low-dose dobutamine stress. Viability was assessed using LGE-CMR. Regional left ventricular function was assessed at baseline and 6-month follow up after optimization of medical therapy +/− revascularization, using transthoracic echocardiography. The primary outcome was regional functional recovery. Results Forty participants underwent baseline physiology, LGE-CMR and thirty had echocardiography at baseline and 6 months; 21/42 territories demonstrated functional recovery. Resting backward compression wave energy was significantly greater in recovering than non-recovering territories (−5240±3772 vs. −1873±1605 W m–2 s–1, p=0.099, Figure 1), and had comparable diagnostic accuracy to CMR (area under the curve 0.812 vs. 0.757, p=0.649, Figure 2); a threshold of −2500 W mm–2 s–1 had 86% sensitivity and 76% specificity at predicting recovery. Backward expansion wave energy did not predict recovery. FFR was numerically higher in recovering territories (0.81±0.17 vs. 0.71±0.16, p=0.058), whilst hyperaemic microvascular resistance did not differentiate recovering from non-recovering territories (1.97±0.73 vs. 2.29±1.00, p=0.287). The likelihood of functional recovery was similar in revascularised and non-revascularised territories (15/29 vs. 6/13 respectively, p=0.739). Low-dose dobutamine stress increased the energy of all waves, but did not improve the accuracy of cWIA in predicting recovery. In a regression model, resting backward compression wave energy and optimization of medical therapy predicted functional recovery; fractional flow reserve and hyperemic microvascular resistance did not. Conclusions Backward compression wave energy has similar accuracy to LGE-CMR in the prediction of functional recovery. cWIA has the potential to revolutionise the management of ischaemic left ventricular dysfunction, in a manner analogous to the effect of fractional flow reserve on the management of stable angina. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The British Heart Foundation Clinical Research Training Fellowship

Comparison of Diagnostic Value Between STE+LDDSE and CMR-FT for Evaluating Coronary Microvascular Obstruction in Post-PCI Patients for STEMI.

BackgroundCoronary microvascular obstruction (CMVO) is closely associated with poor prognosis of ST-segment elevation myocardial infarction (STEMI) patients. However, data showing the comparison between cardiac magnetic resonance feature tracking (CMR-FT) and speckle tracking echocardiography (STE) combined with low-dose dobutamine stress echocardiography (LDDSE) in evaluating CMVO was scarcely available. We aimed to explore and compare the predictive value between CMR-FT and STE+LDDSE in detecting CMVO.MethodsSixty-one STEMI patients were executed cardiac magnetic resonance and echocardiography within the first 5–7 days after primary percutaneous coronary intervention (PCI). The myocardial strain analysis was performed in STE, STE+LDDSE, and CMR-FT, and strain parameters included radial strain (RS), circumferential strain (CS), and longitudinal strain (LS). ROC curves were performed to predict infarcted myocardium segments with CMVO.ResultsFinally, 324 infarcted myocardium segments were analyzed, including 100 infarcted segments with CMVO and 224 segments without CMVO by the gold standard assessment of late gadolinium-enhancement cardiac magnetic resonance imaging (LGE-CMR). The results showed that CS was generally superior to RS and LS in identifying CMVO. CS in CMR-FT facilitated the detection of CMVO, with a sensitivity, specificity, and accuracy of 78.00%, 81.25%, and 80.25%, respectively. The sensitivity, specificity, and accuracy of CS in STE combined with LDDSE were better than STE alone (76.00% vs 60.00%, 79.91% vs 64.29%, and 78.70% vs 62.96%, P < 0.05). In addition, CMR-FT is not superior to STE+LDDSE for detection of CMVO (P > 0.05).ConclusionLow-dose dobutamine can improve the clinical value of STE for evaluating CMVO in STEMI patients. Compared with CMR-FT, STE+LDDSE might be a better choice for STEMI patients because of its safety, convenience, and low-cost.

The evaluation of coronary microvascular obstruction in patients with STEMI by cardiac magnetic resonance T2-STIR image and layer-specific analysis of 2-dimensional speckle tracking echocardiography combined with low-dose dobutamine stress echocardiography.

This study was designed to assess coronary microvascular obstruction (MVO) in patients with acute ST-segment elevation myocardial infarction (STEMI) by cardiac magnetic resonance T2-weighted short tau inversion recovery (T2-STIR) image and layer-specific analysis of 2-dimensional speckle tracking echocardiography combined with low-dose dobutamine stress echocardiography (LDDSE-LS2D-STE). 32 patients were enrolled to perform cardiac magnetic resonance and echocardiography 5-7days after primary percutaneous coronary intervention. Infarcted myocardium was categorized into MVO+ group and MVO- group by late gadolinium enhancement as gold standard. At T2-weighted image, the area of hyper-intense region and hypo-intense core inside were marked as A1, A2 and A2/A1 > 0 represented MVO. Strain parameters were composed of longitudinal strain (LS), circumferential strain and radial strain at rest and dobutamine stress. There were 94 MVO+ segments, 136 MVO- segments according to gold standard. 96 segments had hypo-intense core at T2-STIR image. The sensitivity and specificity of T2-STIR in detecting MVO were 91.49 and 92.65%. Endocardial LS was superior to other parameters, and stress endocardial LS was higher than that of resting endocardial LS (sensitivity: 77.11% vs 72.29%, specificity: 93.28% vs 83.19%, AUC: 0.87 vs 0.82, P < 0.05). The combination of T2-STIR and stress endocardial LS in parallel test could improve sensitivity significantly (98.05% vs 91.49%). T2-STIR has higher diagnostic value in detecting MVO with some limitations. However, LDDSE-LS2D-STE with cost-effective and handling may be a good alternative to T2-STIR. It provides additional and reliable diagnostic tools to identify MVO in STEMI patients after reperfusion.

The effect of empagliflozin on contractile reserve in heart failure: Prespecified sub-study of a randomized, double-blind, and placebo-controlled trial

Sodium-glucose co-transporter-2 inhibitors improve cardiac structure but most studies suggest no change in left ventricular (LV) systolic function at rest. Whether sodium-glucose co-transporter-2 inhibitors improve LV contractile reserve is unknown. We investigated the effect of empagliflozin on LV contractile reserve in patients with heart failure (HF) and reduced ejection fraction. Prespecified sub-study of the Empire HF trial, a double-blind, placebo-controlled, and randomized trial. Patients with LV ejection fraction (LVEF) ≤ 40% on guideline-directed HF therapy were randomized (1:1) to empagliflozin 10 mg or placebo for 12 weeks. The treatment effect on contractile reserve was assessed by low dose dobutamine stress echocardiography. In total, 120 patients were included. The mean age was 68 (SD 10) years, 83% were male, and the mean LVEF was 38 (SD 10) %. Respectively 60 (100%) and 59 (98%) patients in the empagliflozin and placebo groups completed stress echocardiography. No statistically significant effect of empagliflozin was observed for the contractile reserve assessed by LV-GLS (adjusted mean absolute change, empagliflozin vs placebo, 0.7% [95% confidence interval {CI} -0.5 to 2.0, P=.25]) or LVEF (adjusted mean absolute change, empagliflozin vs placebo, 2.2% [95% CI -1.4 to 5.8, P=.22]) from baseline to 12 weeks. LV-GLS contractile reserve was associated with accelerometer-measured daily activity level (coefficient -24 accelerometer counts [95% CI -46 to -1.8, P=.03]). Empagliflozin for 12 weeks added to guideline-directed HF therapy did not improve LV contractile reserve in patients with HF and reduced ejection fraction.

Associations between blood biomarkers, cardiac function and adverse outcome in a young tetralogy of Fallot cohort

BackgroundTo determine the potential prognostic value and clinical correlations of blood biomarkers in a cohort of patients with Tetralogy of Fallot (TOF). MethodsIn the setting of multicenter prospective research studies TOF patients underwent blood sampling, cardiopulmonary exercise testing and low-dose dobutamine stress cardiac magnetic resonance (CMR) imaging. In the blood sample NT-proBNP, GDF-15, Galectin-3, ST-2, DLK-1, FABP4, IGFBP-1, IGFBP-7, MMP-2, and vWF were assessed. During subsequent follow-up, patients were evaluated for reaching the study endpoint (cardiac death, arrhythmia-related hospitalization or cardioversion/ablation, VO2 max ≤65% of predicted). Regression analysis was used to explore the correlation between blood biomarkers (corrected for age and gender) and other clinical parameters. The potential predictive value of blood biomarkers and events were assessed with Kaplan-Meier analysis and Cox proportional hazard analysis. ResultsWe included 137 Fallot patients, median age 19.2 (interquartile range: 14.6–25.7) years, median age at TOF-repair 0.9 (0.5–1.9) years. After a median follow-up of 8.7 (6.3–10.7) years, 20 (14.6%) patients reached the composite endpoint. In a multivariable cox-regression analysis corrected for age at study baseline, elevated IGFBP-7 and MMP-2 levels were associated with the composite endpoint. We also noted a correlation between DLK-1 and relative change in right ventricular end systolic volume during dobutamine stress CMR (β = −0.27, p = 0.010), a correlation between FABP4 and Max VO2 (β = −0.41, p ≤0.001 and between MMP-2 and tricuspid valve E/A ratio (β = −0.15, p = 0.037). ConclusionsIGFBP-7, MMP-2 and DLK-1 levels are related to cardiac function and long-term outcome in TOF patients.

Utility of dobutamine stress echocardiography in aortic valve regurgitation and reduced left ventricular function.

Predictors for post-operative reverse remodeling in patients with severe aortic regurgitation (AR) and reduced left ventricular ejection fraction (LVEF) are unknown. We performed low-dose dobutamine stress echocardiography (DSE) in patients with severe AR and reduced LVEF to evaluate the relationship between contractile reserve (CR) and reverse remodeling after surgery. In 31 patients with chronic severe AR and reduced LVEF (LVEF<50%), we performed pre-operative DSE, assessed CR, and examined whether changes in preoperative DSE were associated with improvement of post-operative LVEF after aortic valve surgery. The pre-operative echocardiographic findings were as follows: left ventricular (LV) end-diastolic dimension: 67 ± 10mm, LV end-systolic dimension: 52 ± 13mm, and LVEF: 42 ± 8%. All patients underwent aortic valve surgery. Patients with pre-operative LVEF of ≥45% exhibited a significant increase in LVEF; however, patients with pre-operative LVEF of <45% showed no significant change. When we examined the results of DSE performed in patients with pre-operative LVEF of <45%, ΔLVEF of ≥6% (with CR) during DSE was related to an improvement in post-operative LVEF; ΔLVEF of ≥6% during DSE predicted an improvement in post-operative LVEF, with sensitivity 100%; specificity 78%; and area under curve (AUC) .92. DSE might be a helpful tool for predicting post-operative reverse remodeling in patients with severe AR and moderately reduced LVEF.

Low-dose dobutamine stress gated blood pool SPECT assessment of left ventricular contractile reserve in ischemic cardiomyopathy: a feasibility study.

The purpose of the present study was to evaluate the feasibility of gated blood pool single-photon emission computed tomography (GBPS) with low-dose dobutamine (LDD) stress test, performed on a single-photon emission computed tomography (SPECT) camera equipped with cadmium-zinc-telluride (CZT) solid-state detectors, in assessing of left ventricle (LV) contractile reserve in patients with ischemic cardiomyopathy (ICM). A total of 52 patients (age 59 ± 7.2years, 47 men and 5 women) with ICM and a control group of 10 patients without obstructive coronary artery lesion underwent GBPS and transthoracic echocardiography (TTE) at rest and during LDD stress test (5, 10, 15µg/kg/min). The duration of each GBPS step was 5min. Stress-induced changes in LV ejection fraction (ΔLVEF), peak ejection rate, LV volumes, and mechanical dyssynchrony (phase histogram standard deviation, phase histogram bandwidth and entropy) obtained with GBPS were estimated. All GBPS indices except end-diastolic volume showed significant dynamics during stress test in both groups. The majority of parameters in ICM patients showed significant changes at a dobutamine dose of 10µg/kg/min as compared to the rest study. Seventeen percent of ICM patients, but none from the control group, showed a decrease in LVEF during stress, accompanied by a significant increase in entropy. The intra- and inter-observer reproducibility was excellent for both rest and stress studies. There was a moderate correlation (r = 0.5, p = 0.01) between GBPS and TTE, with a mean difference value of - 1.7 (95% confidence interval - 9.8; 6.4; p = 0.06) in ΔLVEF. Low-dose dobutamine stress GBPS performed with high-efficiency CZT-SPECT cameras can be performed for evaluating stress-induced changes in LV contractility and dyssynchrony with lower acquisition time. A dobutamine dose of 10µg/kg/min can potentially suffice to detect stress-induced changes in patients with ICM during GBPS. ClinicalTrials.gov identifier: NCT04508608 (August 7, 2020).

Safety of low-dose dobutamine stress test in coronary slow flow phenomenon

Purpose: To investigate the feasibility and safety of a low-dose dobutamine stress test in coronary slow flow phenomenon (CSFP) patients.Methods: One hundred and forty-two CSFP patients, and forty-four patients without CSFP or significant epicardial coronary stenosis who served as the control group, were retrospectively reviewed. All patients were infused intravenously with dobutamine at an initial infusion rate of 5 μg/kg/min which was then increased at 8-min intervals to 10, 15, and 20 μg/kg/min. Symptoms and echocardiography were monitored simultaneously.Results: Patient tolerance decreased as the doses of dobutamine increased. No termination of the test occurred without dobutamine or at the infusion rate of 5 μg/kg/min. Nonetheless, when the infusion rates were adjusted to 15 and 20 μg/kg/min, the incident of side effects reached up to 30.9 %, and a few patients experienced ST-segment depression in precordial electrocardiographic leads. There were no induced arrhythmias without dobutamine, while the incidence of arrhythmias was highest at the infusion rate of 20 μg/kg/min. Malignant arrhythmias such as ventricular fibrillation and sustained ventricular tachycardia, were not detected. No significant differences were showed in echocardiogram result for left ventricular ejection fraction (LVEF) between CSFP and control group (63.7±7.9 in the CSFP group, versus 64.3±7.2 in the control group; p = 0.63).Conclusion: A low-dose dobutamine stress test is safe and feasible in CSFP patients.

Abstract 13062: The Effect of Empagliflozin on Contractile Reserve in Heart Failure: Prespecified Sub-Study of a Randomized, Double-Blind, and Placebo-Controlled Trial

Introduction: Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve cardiac structure but most studies suggest no change in left ventricular (LV) systolic function at rest. Whether SGLT2 inhibitors improve LV contractile reserve is unknown. We investigated the effect of empagliflozin on LV contractile reserve in patients with heart failure (HF) and reduced ejection fraction (HFrEF). Methods: Prespecified sub-study of the Empire HF trial, a double-blind, placebo-controlled, and randomized trial. Patients with LV ejection fraction (LVEF) ≤40% on guideline-directed HF therapy were randomized (1:1) to empagliflozin 10 mg or placebo for 12 weeks. The treatment effect on contractile reserve was assessed by low dose dobutamine stress echocardiography. Results: In total, 120 patients were included. The mean age was 68 (SD 10) years, 83% were male, and the mean LVEF was 38 (SD 10) %. Respectively 60 (100%) and 59 (98%) patients in the empagliflozin and placebo groups completed stress echocardiography. No statistically significant effect of empagliflozin was observed for the contractile reserve assessed by LV-GLS [adjusted mean absolute change, empagliflozin versus placebo, 0.7% (95% CI -0.5 to 2.0, P=0.25)] or LVEF [adjusted mean absolute change, empagliflozin versus placebo, 2.2% (95% CI -1.4 to 5.8, P=0.22)] from baseline to 12 weeks. LV-GLS contractile reserve was associated with accelerometer-measured daily activity level [coefficient, -24 accelerometer counts (95% CI -46 to -1.8, P=0.03)] as opposed to LVEF contractile reserve [coefficient, -2.9 accelerometer counts (95% CI -10 to 4.5, P=0.43)]. Conclusions: Empagliflozin for 12 weeks added to guideline-directed HF therapy did not improve LV contractile reserve in patients with HFrEF. Registration: NCT03198585. https://www.clinicaltrials.gov/ct2/show/NCT03198585?term=Empire+HF&amp;draw=2&amp;rank=1

Predictive Value of Cardiac Magnetic Resonance Feature Tracking after Acute Myocardial Infarction: A Comparison with Dobutamine Stress Echocardiography.

In acute ST-segment elevation myocardial infarction (STEMI) late gadolinium enhancement (LGE) may underestimate segmental functional recovery. We evaluated the predictive value of cardiac magnetic resonance (CMR) feature-tracking (FT) for functional recovery and whether it incremented the value of LGE compared to low-dose dobutamine stress echocardiography (LDDSE) and speckle-tracking echocardiography (STE). Eighty patients underwent LDDSE and CMR within 5–7 days after STEMI and segmental functional recovery was defined as improvement in wall-motion at 6-months CMR. Optimal conventional and FT parameters were analyzed and then also applied to an external validation cohort of 222 STEMI patients. Circumferential strain (CS) was the strongest CMR-FT predictor and addition to LGE increased the overall accuracy to 74% and was especially relevant in segments with 50–74% LGE (AUC 0.60 vs. 0.75, p = 0.001). LDDSE increased the overall accuracy to 71%, and in the 50–74% LGE subgroup improved the AUC from 0.60 to 0.69 (p = 0.039). LGE + CS showed similar value as LGE + LDDSE. In the validation cohort, CS was also the strongest CMR-FT predictor of recovery and addition of CS to LGE improved overall accuracy to 73% although this difference was not significant (AUC 0.69, p = 0.44). Conclusion: CS is the strongest CMR-FT predictor of segmental functional recovery after STEMI. Its incremental value to LGE is comparable to that of LDDSE whilst avoiding an inotropic stress agent. CS is especially relevant in segments with 50–74% LGE where accuracy is lower and further testing is frequently required to clarify the potential for recovery.

Clinical Value of Stress Transaortic Flow Rate During Dobutamine Echocardiography in Reduced Left Ventricular Ejection Fraction, Low-Gradient Aortic Stenosis: A Multicenter Study.

Low rest transaortic flow rate (FR) has been shown previously to predict mortality in low-gradient aortic stenosis. However limited prognostic data exists on stress FR during low-dose dobutamine stress echocardiography. We aimed to assess the value of stress FR for the detection of aortic valve stenosis (AS) severity and the prediction of mortality. This is a multicenter cohort study of patients with reduced left ventricular ejection fraction and low-gradient aortic stenosis (aortic valve area <1 cm2 and mean gradient <40 mm Hg) who underwent low-dose dobutamine stress echocardiography to identify the AS severity and presence of flow reserve. The outcome assessed was all-cause mortality. Of the 287 patients (mean age, 75±10 years; males, 71%; left ventricular ejection fraction, 31±10%) over a mean follow-up of 24±30 months there were 127 (44.3%) deaths and 147 (51.2%) patients underwent aortic valve intervention. Higher stress FR was independently associated with reduced risk of mortality (hazard ratio, 0.97 [95% CI, 0.94-0.99]; P=0.01) after adjusting for age, chronic kidney disease, heart failure symptoms, aortic valve intervention, and rest left ventricular ejection fraction. The minimum cutoff for prediction of mortality was stress FR 210 mL/s. Following adjustment to the same important clinical and echocardiographic parameters, among the three criteria of AS severity during stress, ie, the guideline definition of aortic valve area <1cm2 and aortic valve mean gradient ≥40 mm Hg, or aortic valve mean gradient ≥40 mm Hg, or the novel definition of aortic valve area <1 cm2 at stress FR ≥210 mL/s, only the latter was independently associated with mortality (hazard ratio, 1.72 [95% CI, 1.05-2.82]; P=0.03). Furthermore aortic valve area <1cm2 at stress FR ≥210 mL/s was the only severe aortic stenosis criterion that was associated with improved outcome following aortic valve intervention (P<0.001). Guideline-defined stroke volume flow reserve did not predict mortality. Stress FR during low-dose dobutamine stress echocardiography was useful for the detection of both AS severity and flow reserve and was associated with improved prediction of outcome following aortic valve intervention.