Dobutamine Stress Echo Research Articles

A randomized, double-blind, placebo-controlled, mechanistic trial on the safety, tolerability and pharmacodynamics of ninerafaxstat in patients with angina and chronic coronary syndrome

Abstract Background/Introduction Symptoms of angina resulting from reversible myocardial ischemia in chronic coronary syndromes have a negative impact on quality of life. Metabolic alterations are a key feature of ischemia, including reduced ATP generation by mitochondrial oxidative phosphorylation, NAD+ depletion, anaerobic glycolysis, proton & lactate accumulation leading to contractile dysfunction. Ninerafaxstat is a novel cardiac mitotrope that shifts metabolism from fatty acids towards glucose utilization, optimizing myocardial energy production during ischemia. Purpose We aimed to investigate the safety, tolerability, impact on myocardial glucose utilization and preliminary anti-ischemic efficacy of ninerafaxstat administered for 8 weeks to patients with symptomatic chronic stable angina who were on anti-anginal therapy and had evidence of myocardial stress hypoperfusion using 15O-H2O PET imaging. Methods IMPROVE-Ischemia was an international, randomized, double-blind, placebo-controlled mechanistic trial comparing ninerafaxstat vs. placebo in patients with symptomatic chronic coronary syndrome. The primary endpoint was the safety and tolerability of ninerafaxstat. Key efficacy evaluations were undertaken at baseline and end-of-treatment (Week 8) including imaging core laboratory assessments of 15O-H2O PET perfusion rest and stress imaging to quantify absolute myocardial blood flow (MBF), dobutamine stress echo with contrast for evaluation of LV contractile response during demand stress using the wall motion score index (WMSI) and, in a subgroup of subjects, 18F-FDG-PET imaging of myocardial glucose metabolism. Results The study randomized 58 subjects (mean age 68.6±7.1 years) with symptomatic stable angina and inducible hypoperfusion from 4 sites across 3 countries (Denmark, Finland, Sweden). 22% had type 2 diabetes and 50% had undergone percutaneous and/or surgical coronary revascularization. The majority (68%) were on ≥2 (up to 4) regular anti-anginals. Ninerafaxstat was well tolerated without impact on systemic hemodynamics. At Week 8, ninerafaxstat significantly increased myocardial glucose utilization and, in those with dobutamine-induced deterioration in wall motion at baseline assessment (n=25, pre-specified subgroup), resulted in a ~50% improvement in mean and peak stress WMSI, without altering rest or hyperemic stress MBF (Table 1). Conclusion(s) Treatment with ninerafaxstat was well-tolerated and showed a neutral hemodynamic profile. Ninerafaxstat significantly increased myocardial glucose utilization consistent with its mechanism of action and improved myocardial contractile response to dobutamine stress in subjects with baseline stress inducible deterioration of wall motion. These findings support a direct, metabolically-mediated, anti-ischemic effect of ninerafaxstat on top of existing anti-anginal agents, supporting its further development in cardiac pathologies characterised by ischemia.

Management of anterior ST-elevation myocardial infarction presenting more than 48 hours from symptom onset without reperfusion therapy in the cardiac care unit

ST-elevation myocardial infarction is a form of acute coronary syndrome that is the leading cause of death worldwide. Treatment with reperfusion therapy in the form of primary percutaneous intervention is the main treatment to reduce morbidity and mortality. However, reperfusion therapy is not recommended for patients presenting with symptoms onset of more than 48 hours. A 62-year-old male patient was diagnosed with anterior STEMI with symptoms onset of more than 48 hours based on complaints of anginal chest pain and shortness of breath. ST-segment elevation in V1-V4 and pathological Q in V1-V3 on ECG and increased hs-Troponin I was reported. The patient was not treated with reperfusion therapy based on treatment recommendations. The patient was given vasodilators, beta-blockers, statins, heparinization, and comorbid infection control in the cardiac care ward. Clinical improvement was obtained, and the patient was discharged after seven days of hospitalization and then was planned for Dobutamine Stress Echo during the follow-up visit. Conservative management and viability testing are the main options for patient management in STEMI with symptom onset of more than 48 hours without any complaints of chest pain, stable hemodynamics, and no life-threatening arrhythmia.

Abstract 14082: Evans Syndrome Post Transcatheter Aortic Valve Replacement: A Rare Presentation

Description of Case: Evans Syndrome is a rare hematologic condition. Here we present a patient who developed Evans Syndrome post TAVR. A 63-year-old male with history of HFrEF and aortic stenosis presented with 2-week history of worsening shortness of breath and bilateral lower extremity swelling. He was found to be in cardiogenic shock. TTE showed (LFLG) aortic stenosis (AS). Due to concomitant cardiogenic shock and tachyarrhythmias, we were unable to perform dobutamine stress echo. A cardiac CT was performed which revealed an aortic valve calcium score of 2761 (Figure 1). The diagnosis of severe AS was confirmed, and patient underwent TAVR. Postprocedural TTE showed significant improvement in EF. Patient’s complete blood count on admission was remarkable for Hgb of 12.5 g/dL and PLT of 148 k/mm 3 . Both Hgb and PLT began to drop significantly following TAVR. We ruled out vascular access site bleeding, mechanical complication from paravalvular leak, nutritional deficiencies, disseminated intravascular coagulation, heparin-induced thrombocytopenia, thrombotic thrombocytopenic purpura, myelodysplastic syndrome, HIV, hepatitis C. Autoimmune hemolytic anemia was identified given elevated lactate dehydrogenase, low haptoglobin, and positive IgG direct antiglobulin test. We started steroids and treat the case as Evans syndrome. PLT count improved from 67 to 117 k/mm 3 within 2 days of steroids initiation. The bone marrow biopsy was deferred to outpatient follow up given the response to steroids. Patient was discharged on oral prednisone. Three-month follow up showed Hgb and PLT with normal limits. Discussion: Anemia and thrombocytopenia are common complications post TAVR. Both anemia and thrombocytopenia are suggested to be excellent markers for clinical outcomes, morbidity and mortality after TAVR. It is crucial to keep a broad differential for post TAVR anemia and thrombocytopenia. Less common causes should be evaluated and addressed to improve prognosis.

Investigating the impact of non-gated thoracic CT prior to CTCA to reduce layered testing

To determine the proportion of computed tomography (CT) coronary angiography (CTCA) referrals with coronary artery calcification (CAC) evident on previous non-cardiac CT imaging and how this impacted the diagnostic yield for CTCA, the requirement for additional diagnostic testing, and the associated costs to confirm or refute obstructive coronary artery disease (CAD). A retrospective review of CTCA examinations was undertaken between 01/05/2018 and 31/05/2020 in which the examinations were cross referenced for previous non-gated thoracic CT at Royal United Hospitals Bath. Major epicardial vessel CAC on baseline CT was re-evaluated by published semi-quantitative methods, giving a per-patient CAC score (mild=1-3, moderate=4-6, severe >6). Subsequent incomplete CTCA diagnostic yield, further testing, and cost implications were examined. Of the 2140 CTCA examinations identified, 13% (280/2140) had a preceding non-gated thoracic CT (53% female, age 63±11 years). The incomplete diagnostic rate increased with CAC grade, mild 32%, (RR 12; 95% CI 4-40), moderate 64% (RR 25; 95% CI 8-80), severe 75%, (RR 29; 95% CI 9-94). Additional diagnostic testing occurred in 4% for the mild CAC category, and 14% and 42% for moderate and severe, respectively. When severe CAC was identified on a non-gated thoracic CT a cost saving of £171/patient (dobutamine stress echo [DSE]) and £61/patient (myocardial perfusion scintigraphy [MPS]) was established with a direct to functional testing pathway. In patients referred for CTCA where severe CAC was identified on a preceding non-gated thoracic CT a direct to functional testing altered management in 42% of cases and was cost-effective.

Efficacy of Dobutamine Stress Echo to Detect Coronary Disease Post-Cardiac Transplant

Efficacy of Dobutamine Stress Echo to Detect Coronary Disease Post-Cardiac Transplant

Inflammation and coronary flow reserve in chronic stable coronary artery disease: Evidence for a long standing interplay

Abstract Funding Acknowledgements Type of funding sources: None. Background Low grade inflammation is involved in pathogenesis of ischemia and outcome in coronary artery disease (CAD). Dobutamine stress echo (DSE) and coronary flow reserve (CFR) are both related with incident CAD and respective outcome as well. Purpose To evaluate the potential relationship between inflammation, evaluated by high-sensitivity C-reactive protein as surrogate, and DSE outcome/left anterior descending artery (LAD) CFR in stable chronic CAD. Methods We studied 132 consecutive pts (age 58±12years, 18 females, 33 diabetics) with stable CAD, by DSE with concomitant evaluation of LAD CFR. A cut off 3 mg/dL was used to define high and low CRP groups (CRPH/30pts, CRPL/92pts). CRP distribution was positive skewed (median 1.7mg/l) and CRP was then normalized by log transformation (CRP 0.72±0.9, logCRP 3.2±3.3). Sixty-three out of 132 pts had a follow up DSE with a concomitant reevaluation of CFR at 98±74 months. Absolute and % changes of CFR were estimated. Results CRPH and CRPL groups had similar baseline: CFR (CRPH: 2.3±0.6, CRPL: 2.4±0.6mg/dl), creatinine (1.0±0.2 vs 1.1±0.4mg/dl), HbA1c (5.4±1.0 vs 5.6±1.3%) and LDL (109±46 vs 102±35mg/dl). CRPH and CRPL groups had also similar hemodynamic burden at DSE and incidence of positive DSE. dCFR and %dCFR were lower in CRPL (0.20±0.70 vs 0.69±0.92, p = 0.02 and 0.13±0.33 vs 0.46±0.67 p = 0.01). Further clustering based on optimal CAD treatment achieved at baseline (guidelines defined optimal resting heart rate and LDL) did not change the findings. CFR was inversely related with logCRP (figure 1: r=-0.21, p = 0.04) and creatinine (r=-0.18 p = 0.05). Moreover, during follow up the improvement in CFR (%dCFR) was related with baseline logCRP (figure 2: r=0.30 p = 0.03). In stepwise logistic regression analysis for prediction of a CFR>2, including categorical classification of CRP (>3), diabetes, LDL (>80), Lpa(>50) and resting heart rate, then only CRP>3 classification was finally selected (exp(B)=0.38, p = 0.01). Conclusion Inflammation activity evaluated by CRP in stable CAD is related with the estimated LAD CFR irrespectively from the DSE outcome, both at baseline evaluation as well as dynamically during a long term follow up. The relationship is independent from LDL, Lpa levels and diabetic substrate, thus implying a strong pathophysiological interplay.

Lp(a) and evolution of left anterior descending velocity reserve in stable coronary artery disease: Is there anything beyond dobutamine stress echo outcome?

Abstract Funding Acknowledgements Type of funding sources: None. Background Elevated Lp(a) is related with premature and accelerated atherosclerosis, thus confering increased risk for incident chronic coronary disease (CAD) and adverse outcome. Dobutamine stress echo (DSE) and coronary flow reserve (CFR) are both related with incident CAD and outcome as well. Purpose Aim of the study was to evaluate the potential relationship between Lp(a) and DSE outcome/left anterior descending (LAD) based CFR in chronic CAD. Methods 132 consecutive pts (age 59±11years, 18 females, 33 diabetics) with stable CAD were studied by DSE with a concomitant evaluation of LAD CFR. Lp(a) distribution was positive skewed (median 18.6 mg/dL) and it was then normalized by log transformation (logLpa: 2.9±1.1). High and low Lpa groups (LpaH/LpaL: 30/92) were defined using the conventional cut off 50 mg/dL. Sixty-eight/132 pts had a follow up DSE with concomitant revaluation of CFR at 98±74 months. Absolute and % changes (%d) of LAD CFR were estimated. Results LpaH and LpaL groups had similar baseline: CFR (2.4±0.5 vs 2.4±0.6), %dCFR (0.33±0.7 vs 0.35±0.8), creatinine (0.98±0.18 vs 1.0±0.26), HbA1c (5.3±0.9 vs 5.3±1.0) and high sensitivity C reactive protein (2.8±2.7 vs 2.6±2.8mg/L). LpaH had lower baseline LDL (93±31 vs 111±50 p = 0.04). LpaH and LpaL groups had also similar hemodynamic burden at DSE and incidence of positive DSE. LpaH nondiabetics had a trend for more nonLAD distribution of ischemia (odds ratio=1.8, p = 0.07) with a greater incidence of previous revascularization (odds ratio=2.3, p = 0.03). Further clustering based on optimal CAD treatment achieved at baseline (guidelines achieved optimal resting heart rate and LDL) did not change the findings. However, improvement in %d LAD CFR during follow up was inversely related with logLpa (figure: R2=0.09 p = 0.05). A similar trend for %d LAD CFR and logLpa was evident for a follow up period shorter than 100 months. Conclusion In chronic CAD, high Lpa levels in the absence of diabetes are related with greater incidence of DSE ischemia. Despite similar CFR baseline values between conventionally defined high and low Lpa groups, the evolution of LADCFR during long term follow up is affected consistently on time by the baseline logLpa. These findings support a potential role of Lpa on ischemic burden and microvascular function in the time domain of CAD.

Dynamic left atrial strain by dobutamine: Evidence for relationship with both left ventricular strain and atrioventricular volumetrics

Abstract Funding Acknowledgements Type of funding sources: None. Background Left atrial strain (LASR) by speckle-tracking echocardiography allows the assessment of LA function in each phase of the cardiac cycle. However, its determinants and its relation with left ventricular (LV) function have not yet been fully described. Moreover, a potential effect of the LV cavities volumes has been recently proposed. Purpose Purpose of the study was to assess the effect of LV functional indices to LASR in combination with LA and LV volumes both at rest (R) and during dobutamine stress echo (D). Methods We studied 58 consecutive patients (age 59/12, male/female 37/19) who underwent D without evidence of ischemia. Using 2-D speckle tracking in apical views, both LA and LV strain analysis was performed at R and D. The following parameters were estimated: LA volumes (max/min), LA emptying function (max-min/max), LA strain (SR: overall, reservoir, conduit, active), LV volumes (systole: LVSvol, diastole: LVDvol) stroke volume (SV), LV ejection fraction (LVEF), LV longitudinal strain (LVSR) and LA/LV max volume ratio (LA/LVvol). Results At R, among LA indices, LAtotalSR only was related to LVSR (r=0.31, p = 0.02). However, at D, LAcondSR, LAactive SR, LAtotalSR were related to LVSR (r=-0.25/0.36/0.3 respectively, all p<0.001). At R, LAEF, LAactiveSR and LAtotalSR were related with La/LVvol (r=-0.40/-0.40/0.45 respectively, all p<0.002). At D, LAEF, LAreservoirSR, LAactiveSR and LAtotalSR were related with La/LVvol (r=-0.39/-0.31/-0.31/-0.42 respectively, all p<0.001). For the determination of LAactiveSR at R, using stepwise multiple regression analysis including LVEF LVSR LVsv, LVDvol, La/LVvol, the greater contribution was provided by La/LVvol (initial R=0.41), with small improvement by LVSR (final R=0.50, p<0.001). In contrast, at D, the greater contribution for LAactiveSR was provided by LVSR (initial R=0.36) with some improvement by La/LVvol (final R=0.47 p<0.001). For the determination of LAtotalSR at R, the greatest contribution was provided by LA/LVvol (initial R=0.45) with improvement by LVSR (R=0.57) and finally by LVDvol (final R=0.64, p<0.001). For LAtotalSR at D, the greatest contribution was provided also by LA/LVvol (initial R=0.43) with further improvement by LVSR (final R=0.54, p<0.001). Conclusions LA strain indices are determined partially by LV strain both at rest and mainly during inotropic stimulation. However, they are further and beyond LV strain modulated by the ratio of LV and LA volumes, which play a key role for the overall LA strain both at R and during D. The LA active component is less dependent on volumes, and it is coherent to LV strain during inotropic modulation. Nonetheless, dynamic LA strain is of interest since it integrates LV/LA function, thus providing new insights for clinical application.

Prognostic impact of significant mitral regurgitation in patients with severe low flow, low gradient aortic stenosis undergoing transcatheter aortic valve replacement

Abstract Funding Acknowledgements Type of funding sources: None. Aim The aim of this study was to determine the prevalence and prognostic implications of MR severity in patients with LFLG-AS undergoing TAVR, and to evaluate whether the improvement of MR after procedure could influence 1-year outcome. Methods All consecutive patients with severe LFLG-AS undergoing TAVR in two high-volume Italian centres from 2017 to 2022 were prospectively included. LFLG-AS was defined as indexed aortic valve area (AVAì) ≤0.6 cm2/m2; mean gradient <40 mmHg and stroke volume index <36 ml/m2. LFLG-AS was classified as classical if LVEF was <50%, and paradoxical if LVEF was >50%. Dobutamine stress-echo was systematically performed in patients with LVEF<50% in order or exclude pseudo-severe AS. The study population was divided into two groups according to the baseline MR severity: ≤2+ (moderate or less than moderate) and >2+ (moderately-severe or severe) and reassessed after TAVR. The primary outcome was the composite of all-cause death and hospitalization for HF up to 1 year. The secondary outcomes were the single components of the primary outcome. Results The study included 268 patients [81±6 years; 53% females]; of them, 57 (21.3%) patients showed MR>2+ at hospital admission. Patients with MR>2+ showed a significantly higher NYHA class at admission (p = 0.001); higher EuroSCORE II (p<0.001); lower LVEF at baseline (p = 0.003); higher RV dysfunction (p = 0.003) compared with those with MR≤2+. Death was reported in 2 (0.7%) patients, vascular complications in 8 (3%), and permanent pacemaker implantation in 23 (8.5%). The primary outcome was reported in 55 (20.5%) patients; all-cause death was reported in 29 (10.8%) patients, and HF hospitalization in 34 (12.7%). At one year, patients with MR>2+ showed a significantly higher percentage of the primary outcome (p <0.001) and of all-cause mortality (p<0.001), which was related to cardiovascular cause in the majority of cases, and of HF rehospitalization (p<0.001). The survival free from the primary and secondary outcome was significantly lower in patients with MR>2+ compared with those with MR≤2+ (Log-Rank <0.001; Figure 1). The absence of MR improvement after TAVR was associated with higher percentage of the primary outcome (p = 0.020), all-cause death (p = 0.044), and HF rehospitalization (p = 0.030) at one year. The one-year survival free from the primary and secondary outcome was significantly higher in patients with MR improvement than in those without (Log-Rank = 0.009; Figure 2). Conclusion MR>2+ was reported in about 20% of patients with LFLG-AS undergoing TAVR, portend a worse clinical outcome up to one year. TAVR may improve MR severity, resulting in a potential outcome benefit after discharge. Our study suggests that both, the presence and the persistence of moderately-severe or severe MR, are of utmost importance for patient prognostic stratification, and should be carefully and systematically assessed in the very high-risk clinical scenario of LFLG-AS undergoing TAVR.

Abstract 10098: Assessment of a Rate Pressure Product Target During Stress Echocardiograms in Patients With Advanced Cirrhosis

Introduction: Dobutamine and exercise stress echo are routinely performed on patients with advanced cirrhosis though have low sensitivity in this patient population, even when target heart rate is achieved. This is in part due to their unique cardiovascular physiology which is frequently marked by reduced peripheral vascular resistance with low blood pressure, impaired chronotropic response to stress, hyperdynamic left ventricular systolic function and elevated cardiac output. In the general population, achieving a rate pressure product (RPP), defined as peak systolic blood pressure multiplied by peak heart rate, > 25,000 is typically considered a high level of stress and is an adequate workload to detect ischemia, however this has not been validated in patients with advanced cirrhosis. We aimed to assess the impact of achieving a RPP > 25,000 on the ability of stress echo to detect obstructive coronary artery disease (CAD) in patients with advanced cirrhosis. Methods: We performed a case-control study on patients with advanced cirrhosis where 88 had and 97 did not have CAD based on invasive coronary angiography. A total of 159 patients (85.9%, 77 with CAD and 82 without) had dobutamine and 26 (14.1%, 11 with CAD and 15 without) had exercise as their stress modality. Continuous variables were compared by means of Wilcoxon Rank Sum test. Categorical variables were expressed as numbers and percentages and compared by means of chi-square and Fisher exact tests. Results: The average maximum RPP was 19,999 ± 4,969.4 with 32 patients (17.3%) achieving a RPP > 25,000 (14 with and 18 without CAD, P = 0.63). The average percent of maximum predicted HR (MPHR) achieved was 86.7 ± 9.2% with 136 patients (73.5%) achieving > 85% of MPHR. Achieving a maximum RPP > 25,000 (OR 0.83, 95% CI 0.39 - 1.79, P = 0.63) or a MPHR > 85% (OR 1.04, 95% CI 0.54 - 1.99, P = 0.92) did not improve the ability of stress echo to detect obstructive CAD. Conclusions: Achieving a maximum RPP > 25,000 did not improve the ability of stress echo to detect obstructive CAD in patients with advanced cirrhosis.

Abstract 14497: Predictors of Hypertensive Response During Stress Echocardiography

Introduction: Hypertensive response during stress echocardiography has been predominately studied in a healthy population without many comorbidities, unlike the patients for which these tests are indicated. We performed a retrospective study identifying clinical predictors of hypertensive response to both exercise (EXE) and dobutamine (DSE) stress echo. Methods: Retrospective analysis was performed on all patients who underwent stress echo from January 1, 2015 to February 28, 2017 in a tertiary care academic center. Patient demographics, comorbidities, medications and stress echo parameters were evaluated. Patients were characterized based on stress echo completed as EXE or DSE. The primary outcome was hypertensive response. Results: 4670 patients were enrolled: 1238 in the DSE group and 3432 in the EXE group. On multivariable analysis, only resting SBP remained a significant predictor of hypertensive response during DSE (odds ratio (OR) per 20mmHg 3.21, CI 1.57-6.59, p =.001) with an AUC of 0.76. On multivariable analysis, obesity (OR 2.27, CI 1.08-4.8, p =.03), diabetes (OR 3.24, CI 1.22-8.6, p =.02), resting SBP (OR 4.44, CI 2.35-8.38, p <.001), and black race (v. white, OR 4.53, CI 1.62-12.67, p =.004) remained significant predictors of hypertensive response during EXE, with an AUC of 0.82. Conclusions: Elevated resting systolic blood pressure is a strong predictor of hypertensive response in both groups. Controlling resting blood pressure prior to stress testing reduces non-diagnostic test results and improves safety.

Abstract 12772: Transcatheter Aortic Valve Replacement Improves Functional and Quality Of Life Outcomes in Patients With Low Gradient Aortic Stenosis

Introduction: Aortic stenosis (AS) is the most common valvular disease, and severe disease can significantly impact morbidity. Less data exists examining the functional and quality of life (QOL) effects of transcatheter aortic valve replacement (TAVR) in patients with severe low-gradient AS in both low-flow and normal-flow states. Hypothesis: Patients with symptomatic, severe, low-gradient AS would have improvements in functional and QOL outcomes at 30-days and 1-year following TAVR procedures. Methods: A single center, retrospective study examined symptomatic, severe, low-gradient AS variants. These had an aortic valve area of ≤1.0 cm 2 , mean transvalvular gradient <40 mmHg, and peak aortic valve velocity of <4 m/s. Classical low-flow low-gradient (CLFLG) AS was defined as a left ventricular ejection fraction (LVEF) <50%. CLFLG group underwent dobutamine stress echo to assess AS severity (Stage D2). Paradoxical low-flow low-gradient (PLFLG) AS was defined as LVEF ≥50% and a stroke volume index (SVi) ≤35mL/m 2 (Stage D3). Normal-flow low-gradient (NFLG) AS was defined as LVEF ≥50% and SVi >35mL/m 2 (Stage D4). The primary outcome was change in New York Heart Association (NYHA) classification and a 12-item Kansas City Cardiomyopathy Questionnaire overall score (KCCQ-OS) at 30-days and 1-year following TAVR. Results: A total of 191 patients were included for analysis: 46 CLFLG, 83 PLFLG, and 62 NFLG AS. At baseline, 130 (68%) had NYHA class III or IV symptoms. Mean baseline KCCQ-OS for all groups was 38±23 (Figure 1). The mean KCCQ-OS at 30-days and 1 year were 62±22 and 68±20. There were no significant differences in KCCQ-OS between the groups at 30-days and 1-year. Following TAVR, 92% and 88% of the cohort had NYHA class I or II symptoms at 30-days and 1 year. Conclusions: Patients with symptomatic, severe low-gradient AS had significant and sustained improvements in their functional and QOL metrics at 30-days and 1-year following TAVR procedures regardless of flow-state.

Noninvasive evaluation of coronary velocity reserve: need for correction of the sympathetic tone

Abstract Introduction Noninvasively Doppler estimated coronary velocity (as a surrogate of flow) reserve (CVR) by adenosine is a useful parameter for risk stratification in chronic coronary syndromes (CAD). However, baseline velocity fluctuation due to sympathetic drive, as in mental stress, may affect the evaluation of the actual CVR. Aim Aim of the study was to assess the effect of b blocker administration following adenosine infusion in the coronary velocity and thus the consequences in the estimated CVR. Patients and methods Sixty (females 8) patients (pts) with stable CAD (mean/SD: age 64/10, ejection fraction % 55/8) were studied before the performance of a dobutamine stress echo. Distal left anterior descending (LAD) velocity was estimated at rest (CVrest), at maximal adenosine infusion (140γ/kg/min: CVaden) and following esmolol infusion 3–5 min later (CVbbl). CVR was estimated using as baseline velocity either CVrest (CVRrest) or CVbbl (CVRbbl). Respective changes of heart rate (HR) and systolic blood pressure (SBP) were also estimated. Results CVbbl was smaller than CVrest (23/7 vs 29/13, p<0.0.01). Thus, CVRbbl was greater than CVRrest (3/0.9 vs 2.7/0.6, p<0.001) with an absolute difference (dCVR) of 0.46/0.84, a % difference (%dCVR) of 23/34%, with a modest linear relationship (R2=0.08, p=0.02 figure). The %dCVR was also linearly related to CVRrest (R2=0.13, p=0.003 figure) and it was independent from age, HR/BP changes and the dobutamine stress echo outcome. Differences between CVRbbl and CVRrest were greater in females (females/males: dCVR 1.2/0.9 vs 0.36/0.8, %dCVR 0.67/0.56 vs 0.36/0.26, both p<0.001). Conclusions Noninvasively estimated CVR is affected by the baseline sympathetic tone, irrespectively from the age in stable CAD. A gender effect is evident, reiterating the microvascular susceptibility in females. Thus, potential mental stress background must be considered, and b-blockade subsequently might be applied during CVR evaluation to overcome any sympathetic effect. Funding Acknowledgement Type of funding sources: None.

Atrial and Ventricular Arrhythmia Prevalence During Dobutamine Stress Echo in Hypertensive Patients Before Non-Cardiac Surgery

Atrial and Ventricular Arrhythmia Prevalence During Dobutamine Stress Echo in Hypertensive Patients Before Non-Cardiac Surgery

Comparison of Coronary Artery Calcium Scoring with Dobutamine Stress Echo for Detection of Coronary Artery Disease Before Liver Transplantation.

BackgroundDobutamine stress echocardiography (DSE) is commonly used for cardiovascular assessment before orthotopic liver transplantation (OLT). The coronary artery calcium score (CACS) is a useful screening tool for coronary artery disease (CAD). We aimed to compare the sensitivity and specificity of DSE and CACS for CAD in OLT candidates.Material/MethodsA total of 265 of the 1589 patients who underwent OLT at our center between 2008 and 2019 had preoperative coronary angiography (CAG). Of these, 173 had DSE and 133 had a CT scan suitable for CACS calculation within 1 year of OLT. Patients with a nondiagnostic DSE were excluded (n=100). Two reviewers evaluated CACS on CT scans. The sensitivity/specificity of DSE and CACS for detection of angiographically significant CAD were calculated for patients with both tests (n=36).A separate analysis compared the sensitivity/specificity of a diagnostic DSE (n=73) and CACS (n=133) against CAG for all patients with either test.ResultsSensitivity and specificity were 57.1% and 89.7%, respectively, for DSE, compared with 71.4% and 62.1% for CACS at ≥100 Agatston score. For the analysis of all patients with either test, the sensitivity/specificity of DSE for detection of CAD and CACS were 30.8% and 85.0% and 80.0% and 62.8%, respectively. On ROC analysis, CACS was a satisfactory predictor of obstructive CAD (AUC, 0.76±0.06, 95% CI, 0.66–0.87; P<0.001).ConclusionsCACS may be an important tool for cardiovascular assessment in patients undergoing OLT. DSE was nondiagnostic in a large percentage of OLT candidates, limiting its use in this population.

Diagnostic Accuracy of Dobutamine Stress Echocardiography for Detection of Cardiac Allograft Vasculopathy in Orthotopic Heart Transplant Patients.

ObjectiveCardiac allograft vasculopathy is one of the leading causes of late graft failure and subsequent death in orthotopic heart transplant. Although invasive coronary angiography is the gold standard modality for detection of cardiac allograft vasculopathy, dobutamine stress echocardiography has been recently frequently used as an alternative. Our aim was to evaluate the diagnostic performance of dobutamine stress echocardiography for detection of cardiac allograft vasculopathy in transplant patients.MethodsA retrospective analysis was conducted using a total of 150 dobutamine stress echocardiographic exams that were performed on 99 patients in our institution, with paired coronary angiogram and no acute rejection, within a median of 538 [interquartile range 371–816] days. Sensitivity and specificity of dobutamine echocardiography to detect allograft vasculopathy was evaluated. Allograft vasculopathy was defined as Grade 1 or higher based on ISHLT criteria. A positive dobutamine stress echo result was defined by new or worsening wall motion abnormality.ResultsMedian age of the population at transplant was 34 [interquartile range 22–46] years; 76 (77%) patients were male. Allograft vasculopathy was present in 31 (20.6%) out of 150 coronary angiograms. Only 7 (4.6%) of that number were positive on dobutamine stress echocardiography. Sensitivity and specificity for allograft vasculopathy detection was 3% and 94%, respectively. Out of 7 false positive dobutamine stress echocardiograms, two were in patients with myocardial bridging. Two patients with mild acute rejection had both negative dobutamine stress echo.ConclusionsOverall, positivity of dobutamine stress echocardiography in patients after heart transplant is low. It has high specificity, but very low sensitivity for detection of cardiac allograft vasculopathy. Dobutamine stress echocardiography should only be cautiously used as an alternative to coronary angiography.

Blunted heart rate reserve with dobutamine stress echocardiography predicts outcome in diabetes and/or chronic kidney disease

Abstract Background A blunted heart rate reserve (HRR) during dobutamine stress echo (DSE) is an index of the altered cardiac sympathetic reserve, which is frequently present in diabetes mellitus (DM) or chronic kidney disease (CKD). Aim To assess the prognostic value of HRR during DSE. Methods We recruited 280 patients (mean age 62.9±13.1 years; 128 (45.7%) male; 28.2% on beta-blockers at the time of testing) who underwent DSE for known or suspected coronary artery disease and/or heart failure and were followed-up. Four subsets were identified: Group 1 (111 pts without DM or CKD); group 2 (37 with DM without CKD); group 3 (90 with CKD with or without DM); and group 4 (42 with CKD on dialysis). HRR was calculated by EKG as the peak/rest HR ratio. Results Ischemia was identified in 34/280 (12.1%) pts. During a median follow-up time of 40.3±30.5 months, 120 events occurred: 46 deaths, 15 non-fatal myocardial infarctions, 23 hospital admissions for acute decompensated heart failure, and 36 myocardial revascularizations. Multivariable comparison of HRR among the 4 groups using post hoc test showed a blunted HRR in group 3 (1.66±0.32) and 4 (1.65±0.27) when compared with group 1 (HRR 1.85±0.35), p&amp;lt;0.01. Group 2 (1.73±0.28) was not different from any group (p=ns). Groups 3 and 4 were not different between them (p=ns). A post hoc Tukey test for HRR separated in tercils, 1st: HRR &amp;lt;1.59, 2nd: 1.59 &amp;lt; HRR &amp;lt;1.86 and 3rd: HRR &amp;gt;1.86 (p&amp;lt;0.000). Kaplan-Meier curves showed blunted HRR as an independent predictor of event-free survival in the overall group - 1st: 66.08±5.9 months, 95% CI 54.3–77.7; 2nd: 69.52±6.5, 95% CI 56.6–82.3; 3rd: 90.05±5.3, 95% CI 79.5–100.5. See Figure. HRR was comparable in patients with and without inducible ischemia and off or on beta-blockers. Conclusion A blunted HRR during DSE is frequent in patients with DM and CKD, independent of inducible ischemia and use of beta-blockers, and is a useful non-imaging predictor of adverse events. Funding Acknowledgement Type of funding sources: None.

Blunted heart rate reserve during dobutamine stress echocardiography is a predictor of outcome in diabetes and/or chronic kidney disease

Abstract Funding Acknowledgements Type of funding sources: None. Background A blunted heart rate reserve (HRR) during dobutamine stress echo (DSE) is an index of altered cardiac sympathetic reserve, which is frequently present in diabetes mellitus (DM) or chronic kidney disease (CKD). Aim To assess the prognostic value of HRR during DSE. Methods We recruited 280 patients (pts) (mean age 62.9 ± 13.1 years); 128 (45.7%) male; 28.2% on beta-blockers at the time of testing) who underwent DSE for known or suspected coronary artery disease and/or heart failure and were followed-up. Four subsets were identified: Group 1 (111 pts without DM or CKD); group 2 (37 with DM without CKD); group 3 (90 with CKD with or without DM); and group 4 (42 with CKD on dialysis). HRR was calculated by EKG as the peak/rest HR ratio. Results Ischemia was identified in 34/280 (12.1%) pts. During a median follow-up time of 40.3 ± 30.5 months, 120 events occurred: 46 deaths, 15 non-fatal myocardial infarctions, 23 hospital admissions for acute decompensated heart failure, and 36 myocardial revascularizations. Multivariable comparison of HRR among the 4 groups using post hoc test showed a blunted HRR in group 3 (1.66 ± 0.32) and 4 (1.65 ± 0.27) when compared with group 1 (HRR 1.85 ± 0.35), p &amp;lt; 0.01. Group 2 (1.73 ± 0.28) was not different from any group (p = ns). Groups 3 and 4 were not different between them (p = ns). A post hoc Tukey test for HRR separated in tercils, 1st: HRR &amp;lt; 1.59, 2nd: 1.59 &amp;lt; HRR &amp;lt; 1.86 and 3rd: HRR &amp;gt; 1.86 (p &amp;lt; 0.000). Kaplan-Meier curves showed blunted HRR as an independent predictor of event-free survival in the overall group - 1st: 66.08 ± 5.9 months, 95% CI 54.3-77.7; 2nd: 69.52 ± 6.5, 95% CI 56.6-82.3; 3rd: 90.05 ± 5.3, 95% CI 79.5-100.5. See Figure. HRR was comparable in patients with and without inducible ischemia and off or on beta-blockers. Conclusion A blunted HRR during DSE is frequent in patients with DM and CKD, independent of inducible ischemia and use of beta-blockers, and is a useful non-imaging predictor of adverse events. Abstract Figure. HR ratio and event-free survival curves

Comprehensive assessment of the aortic valve in critically ill patients for the non-cardiologist. Part I: Aortic stenosis of the native valve.

Aortic stenosis (AS) causes left ventricular outflow obstruction. Severe AS has major haemodynamic implications in critically ill patients, in whom increased cardiac output and oxygen delivery are often required. Transthoracic echocardiography (TTE) plays akey role in the AS severity grading. In this review, we will give an overview of how to use the simplified Bernoulli equation to convert the echo Doppler measured velocities (cm s-1) to AS peak and mean gra-dient (mm Hg) and how to calculate the aortic valve area (AVA), using the continuity equation, based on the principle of preservation of flow. TTE allows quantification of compensatory left ventricular (LV) hypertrophy, assessment of LV systolic function, and determination of LV diastolic function and LV loading. Subsequently, the obtained results from the TTE study need to be integrated to establish the AS severity grading. The pitfalls of echocardiographic AS severity assessment are explained, and how to deal with inconsistency between AVA and mean gradient. The contribution of transoesophageal echocardiography, low-dose dobutamine stress echo (in case of low-flow low-gradient AS), echocardiography strain imaging, cardiac magnetic resonance imaging, cardiac multidetector computed tomography and the relatively new concept of Flow Pressure Gradient Classification to the work-up for aortic stenosis is discussed. Finally, the treatment of AS is overviewed. Elective aortic valve replacement is indicated in patients with severe symptomatic AS. In the ICU, afterload reduction by vasodilator therapy and treatment of pulmonary and venous congestion by diuretics could be considered.

Abstract 12881: Noninvasive In Vivo Assessment of Cardiac Metabolism in Dobutamine-stressed Ischemic Rat Hearts Using Hyperpolarized 13 C MRI

Introduction and Hypothesis: Conventional metabolic imaging methods such as PET, dobutamine stress echo or late gadolinium enhancement do not directly detect the functional state of the critical organelle in oxidative metabolism, the mitochondrion. Hyperpolarized (HP) 13 C-metabolic imaging has been used to assess mitochondrial function in preclinical models and is an exciting new imaging method for evaluating the ischemic myocardium noninvasively. This study aims to evaluate myocardial response to dobutamine stress in ischemic rat hearts using HP-[1- 13 C]pyruvate. Methods: Metabolism of HP[1- 13 C]pyruvate was investigated in male SD rats in four groups: 1. normal myocardium (NM), 2. ischemic myocardium (IM), 3. NM+dobutamine, 4. IM+dobutamine. The myocardial ischemic model was developed by partial occlusion of the coronary artery as described in earlier studies by others. For dobutamine stress HP-MRS, intra-peritoneal injection of 1.5 mg/kg of dobutamine was administered before positioning the animal in the MRI scanner. 13 C data were acquired 7 days after the surgery in a 4.7 T MRI scanner using a Varian 60 mm dual-tuned 1 H/ 13 C linear volume coil. Anatomical 1 H images were acquired for slice planning and positioning. 13 C intensity maps were generated and displayed as overlays on grayscale 1 H images. In separate experiments, in vivo HP- 13 C-MRS data acquisition was initiated immediately after the pyruvate injection. Results: The HP signals from [1- 13 C]lactate, [1- 13 C]alanine, and 13 C-bicarbonate were detected in real-time 13 C spectra from hearts following injection of HP[1- 13 C]pyruvate. In hearts with partial coronary ligation, the MRS data were acquired from a mixture of ischemic and nonischemic myocardium. A 27% decrease in bicarbonate production was observed in hearts with ischemic myocardium compared to control hearts. After stimulation of NM hearts with dobutamine, less bicarbonate was produced from HP-pyruvate likely due to an increased contribution of other endogenous substrates to acetyl-CoA. Production of bicarbonate was unchanged in IM hearts following adrenergic stimulation. Conclusions: Our results demonstrated that decreased oxidative metabolism of pyruvate as a result of myocardial ischemia and dobutamine stress.