The Utility of Low-Dose-Dobutamine Stress Echocardiography in Patients with Heart Failure with Reduced Ejection Fraction: An Update.

Despite significant advancements in medical therapy, heart failure with reduced ejection fraction (HFrEF) continues to be a significant cause of death and disability. Reversible ischaemic left ventricular dysfunction due to viable myocardium is one such contributing factor. In these cases, coronary revascularization has shown promise in improving left ventricular function and prognosis. For patients with HFrEF and wide QRS, cardiac resynchronization therapy (CRT) is an effective option to address electromechanical dyssynchrony. However, approximately 30% of patients do not respond positively to CRT, highlighting the need to refine candidate selection for this treatment. In some patients with reduced HFrEF, there is a condition known as classical low-flow, low-gradient aortic stenosis (AS) that may be observed. This condition is characterized by a low transaortic flow, which leads to reductions in both the transaortic mean gradient and aortic valve area. Decision-making regarding revascularization, CRT, and pharmacological treatment play a crucial role in managing HFrEF. Cardiac imaging can be valuable in guiding decision-making processes and assessing the prognosis of patients with HFrEF. Among the imaging modalities, dobutamine stress echocardiography has come a long way in establishing itself as a feasible, safe, effective, relatively cheap non-invasive technique. The aim of this review is to explore the current literature on the utility of low-dose stress echocardiography in diagnosing and prognosticating patients with HFrEF.

Complications of exercise and pharmacologic stress echocardiography.

Stress echocardiography is a diagnostic cardiovascular exam that is commonly utilized for multiple indications, including but not limited to the assessment of obstructive coronary artery disease, valvular disease, obstructive hypertrophic cardiomyopathy, and diastolic function. Stress echocardiography can be performed via both exercise and pharmacologic modalities. Exercise stress is performed with either treadmill or bicycle-based exercise. Pharmacologic stress is performed via either dobutamine or vasodilator-mediated (i.e., dipyridamole, adenosine) stress testing. Each of these modalities is associated with a low overall prevalence of major, life-threatening adverse outcomes, though adverse events are most common with dobutamine stress echocardiography. In light of the recent COVID-19 pandemic, the risk of infectious complications to both the patient and stress personnel cannot be negated; however, when certain precautions are taken, the risk of infectious complications appears minimal. In this article, we review each of the stress echocardiographic modalities, examine major potential adverse outcomes and contraindications, assess the risks of stress testing in the setting of a global pandemic, and examine the utilization and safety of stress testing in special patient populations (i.e., language barriers, pediatric patients, pregnancy).

Acute myocardial infarction after a negative Dobutamine stress echocardiogram in a patient with end-stage liver disease.

Dobutamine stress echocardiogram (DSE) is generally a safe and reliable test for detection of myocardial ischaemia. We report the case of a 43-year-old male with end-stage liver disease (ESLD), who underwent DSE as part of workup for liver transplantation. Although the patient had an uneventful negative DSE, within 45 minutes he developed inferior ST-segment elevation myocardial infarction (STEMI). His coronary angiography showed severe 2-vessel coronary artery disease, which was treated with percutaneous coronary intervention (PCI) with implantation of drug-eluting stents (DES). Acute coronary syndrome (ACS) after a normal DSE has previously been reported in the literature. We describe one such case, with added complexity of managing an ACS in a patient with high bleeding risk. Our case is unique in reporting a STEMI after a negative DSE in a liver transplant recipient. Increased physician awareness of potential complications of DSE is essential to allow timely recognition and management.

Stress Echocardiogram in Asymptomatic Severe Aortic Stenosis.

Aortic stenosis (AS) is one of the most common adult valve diseases. Therefore, current guidelines recommend prompt aortic valve intervention once symptoms occur. However, AS is predominantly a disease of the elderly, and these people may be underreporting their symptoms, have other comorbidities, or have a low level of exertion at the baseline or they might make a subconscious adjustment of their activities. Hence, stress testing can be a vital and objective tool to uncover their symptoms and prognosticate.

Use of Computed Tomography Coronary Calcium Score for Coronary Artery Disease Risk Stratification During Liver Transplant Evaluation.

Background: End-stage liver disease (ESLD) is not considered a risk factor for atherosclerotic cardiovascular disease (ASCVD). However, lifestyle characteristics commonly associated with increased ASCVD risk are highly prevalent in ESLD. Emerging literature shows a high burden of asymptomatic coronary artery disease (CAD) in patients with ESLD and a high ASCVD risk in liver transplantation (LT) recipients. Coronary artery calcium score (CAC) is a noninvasive test providing reliable CAD risk stratification. We implemented an LT evaluation protocol with CAC playing a central role in triaging and determining the need for further CAD assessment. Here, we inform our results from this early experience. Methods: Patients with ESLD referred for LT evaluation were prospectively studied. We compared accuracy of CAC against that of CAD risk factors/scores, troponin I, dobutamine stress echocardiogram (DSE), and single-photon emission computed tomography (SPECT) to detect coronary stenosis ≥70 (CAD ≥ 70) per left heart catheterization (LHC). Thirty-day post-LT cardiac outcomes were also analyzed. Results: One hundred twenty-four of 148 (84%) patients underwent CAC, 106 (72%) DSE/SPECT, and 50 (34%) LHC. CAC ≥ 400 was found in 35 (28%), 100 to 399 in 17 (14%), and <100 in 72 (58%). LHC identified CAD ≥ 70% in 8 of 29 (28%), 2 of 9 (22%), and 0 of 4, respectively. Two acute coronary syndromes occurred after LT in a patient with CAC 811 (CAD < 70%), and one with CAC 347 (CAD ≥ 70%). No patients with CAC < 100 presented with acute coronary syndrome after LT. When using CAD ≥ 70% as primary endpoint of LT evaluation, CAC ≥ 346 was the only test showing predictive usefulness (negative predictive value 100%). Conclusions: CAC is a promising tool to guide CAD risk stratification and need for LHC during LT evaluation. Patients with a CAC < 100 can safely undergo LT without the need for LHC or cardiac stress testing, whereas a CAC < 346 accurately rules out significant CAD stenosis (≥70%) on LHC, outperforming other CAD risk-stratification strategies.

Segurança do Agente de Contraste SF6 (SonoVueⓇ) no Ecocardiograma sob Estresse Farmacológico / Safety of SF6(SonoVue®) Contrast Agent on Pharmacological Stress Echocardiogram

Resumo Fundamento Em 2007, a Food and Drug Administration (FDA) determinou revisões sobre segurança dos agentes de contraste ecocardiográfico (ACE) disponíveis no mercado após relatos de mortes. Ao longo desses anos, diversos estudos comprovaram a segurança dos ACE, porém com poucos estudos relacionados ao SonoVue®. Objetivos Avaliar a segurança do SonoVue® durante o ecocardiograma sob estresse farmacológico (EEF) por meio da análise da incidência de reações alérgicas e da comparação entre os grupos quanto ao surgimento de arritmia, efeitos colaterais menores e eventos adversos. Métodos Estudo observacional, prospectivo, no qual 2.346 pacientes foram submetidos ao EEF e divididos em dois grupos: grupo 1 com ACE (n=1.099) e grupo 2 sem ACE (n=1.247). Os pacientes foram avaliados durante o EEF - 24 horas e 30 dias. Foi definido p significativo quando <0,05. Resultados O grupo 1 apresentou efeitos colaterais mais leves, como cefaleia (5/0,5% vs. 19/1,5%, p=0,012) e hipertensão reativa (3/0,3% vs . 19/1,5%, p=0,002), menos arritmias como extrassístoles ventriculares (180/16,4% vs . 247/19,8%, p=0,032) e taquicardia paroxística supraventricular (2/0,2% vs . 15/1,2%, p=0,003), assim como nenhum evento adverso como infarto agudo do miocárdio (IAM) e óbito. No grupo 2, um paciente apresentou IAM <24h (1/01%) e dois óbitos <30 dias (2/0,1%). Urticária relacionada ao SonoVue® foi observada em 3 (0,3%) pacientes sem reação anafilática. Conclusão SonoVue® demonstrou segurança durante o EEF, não sendo observados morte, IAM ou reação anafilática. Observou-se menor incidência de efeitos colaterais mais leves e arritmias no grupo que utilizou o ACE, assim como baixa incidência de reações alérgicas leves.

Abstract Background In 2007, the United States Food and Drug Administration mandated safety reviews of commercially available echocardiographic contrast agents (ECA), following reports of death. During the past years, different studies have proven the safety of ECA, but there have been few studies on SonoVue®. Objectives To evaluate the safety of SonoVue® during pharmacological stress echocardiography (PSE), by analyzing the incidence of allergic reactions and comparing groups regarding the appearance of arrhythmia, minor side effects and adverse events. Methods In this observational, prospective study, 2346 patients underwent PSE, and they were divided into the following 2 groups: group 1 with ECA (n = 1099) and group 2 without ECA (n = 1247). Patients were evaluated during PSE, at 24 hours, and at 30 days. Statistical significance was defined as p < 0.05. Results Group 1 had fewer minor side effects, such as headache (5/0.5% versus 19/1.5%, p = 0.012) and less reactive hypertension (3/0.3% versus 19/1.5%, p = 0.002); fewer arrhythmias, such as ventricular extrasystoles (180/16.4% versus 247/19.8%, p = 0.032) and paroxysmal supraventricular tachycardia (2/0.2% versus 15/1.2%, p = 0.003); and no adverse events, such as acute myocardial infarction (AMI) or death. In group 2, 1 patient had AMI in < 24 hours (1/01%), and there were 2 deaths in < 30 days (2/0.1%). SonoVue®-related urticaria was seen in 3 (0.3%) patients, without anaphylactic reaction. Conclusion SonoVue® demonstrated safety during PSE. No cases of death, AMI, or anaphylactic reaction were observed. There was a lower incidence of minor side effects and arrhythmias in the group that received ECA, as well as a low incidence of mild allergic reactions.

Rate pressure product, age predicted maximum heart rate or heart rate reserve. Which one better predicts cardiovascular events following exercise stress echocardiography?

BACKGROUND: Age-predicted maximum heart rate (APMHR) has been demonstrated to be a poor predictor of future cardiovascular (CV) events and is yet to be validated as a termination point during exercise testing. In contrast, maximum rate pressure product (MRPP) is recognized as a strong predictor of CV outcome with superior CV event prediction over APMHR. Heart rate reserve (HRR) has been shown to be a powerful predictor of CV mortality during exercise testing, however thus far, this is not confirmed for non-fatal CV events. The aim of this study was to compare APMHR, MRPP and HRR as predictors of CV events following otherwise negative exercise treadmill testing. METHODS: After exclusions, 1080 patients being investigated for coronary artery disease performed an exercise stress echocardiogram (ESE) to volitional fatigue on a motorised treadmill. Blood pressure was measured manually, and ultrasound images performed as per current American Society of Echocardiography guidelines. Rate pressure product and HRR were calculated throughout the test and maximum values were identified. Patients were followed for 5.3±2.6 mean years. RESULTS: From receiver operating characteristic analysis, cut points were established for APMHR (94.6%) (AUC 0.687), MRPP (25085) (AUC 0.729) and HRR% (95.9) (AUC 0.688). MRPP outperformed both APMHR and HRR% for the prediction of future CV events. Furthermore, on Cox proportional hazard analysis MRPP was the strongest uni- and multivariate predictor (p<0.0001) with APMHR and HRR% failing to reach any statistical significance. CONCLUSIONS: The current study demonstrates the substantial prognostic power of MRPP over both APMHR and HRR% to predict CV events following an otherwise negative ESE for myocardial ischemia.

Reversed Apico-Basal Myocardial Relaxation Sequence During Exercise in Long QT Syndrome Mutations Carriers With History of Previous Cardiac Events.

BACKGROUND: Recent echocardiography studies in inherited long QT syndrome (LQTS) have shown left ventricular (LV) myocardial relaxation disturbances to follow markedly prolonged and dispersed mechanical contraction. AIM: We used speckle-tracking echocardiography to assess disturbances in LV myocardial relaxation sequence during exercise and their relationship to symptoms. METHODS: Forty seven LQTS patients (45 ± 15 years, 25 female and 20 symptomatic, LVEF: 65 ± 6%) and 35 controls underwent exercise echocardiogram using Bruce protocol. ECG and echo parameters were recorded at rest, peak exercise (p.e.) and recovery. RESULTS: Between patients and controls there were no differences in age, gender, HR or LVEF. At p.e, patients had longer time to LV longitudinal ESR (tESR) at all three LV segments; basal (p < 0.0001), mid- cavity (p = 0.03) and apical (p = 0.03) whereas at rest such difference was noted only at base (p = 0.0007). Patients showed reversed apico-basal relaxation sequence (ΔtESRbase-apex) with early relaxation onset occurring later at base than at apex, both at rest (49 ± 43 vs. -29 ± 19 ms, p < 0.0001) and at p.e. (46 ± 38 vs. -40 ± 22 ms, p < 0.0001), particularly in symptomatic patients (69 ± 44 vs. 32 ± 26, p < 0.0007). ΔtESRbase-apex correlated with longer QTc interval, lower ESR and attenuated LV stroke volume. CONCLUSION: LQTS patients show reversed longitudinal relaxation sequence, which worsens with exercise, particularly in those with previous cardiac events.

Exercise Induced Worsening of Mechanical Heterogeneity and Diastolic Impairment in Long QT Syndrome.

BACKGROUND: Electromechanical heterogeneities due to marked dispersion of ventricular repolarisation and mechanical function have been associated with symptoms in long QT syndrome (LQTS) patients; Aim: To examine the exercise response of longitudinal LV systolic and diastolic myocardial function and synchronicity in LQTS patients and its relationship with symptoms; Methods: Forty seven (age 45 ± 15 yrs, 25 female, 20 symptomatic) LQTS patients and 35 healthy individuals underwent an exercise test (Bruce protocol). ECG and echo parameters were recorded at rest, peak exercise (p.e.), and recovery; Results: LQTS patients had prolonged and markedly dispersed myocardial contraction, delayed early relaxation phase, and significantly decreased filling time at all exercise phases. Unlike controls, these electromechanical disturbances deteriorated further with exercise, during which additional decrease of the LV diastolic myocardial function and attenuated LV stroke volume were noted. Such abnormal responses to exercise were seen to a greater degree in symptomatic patients and in the LQT1 subgroup and improved with B-blocker therapy. Worsening myocardial contraction dispersion at p.e. was the strongest discriminator for previous clinical events, and its discriminating power excelled further by adding early relaxation delay; Conclusions: Electromechanical disturbances were shown to worsen during exercise in LQTS patients and were more pronounced in those with previous arrhythmic events.

From Other Journals: A Review of Recent Articles in Pediatric Cardiology.

In this review, we provide a brief description of recently published articles addressing topics relevant to pediatric cardiologists. Our aim is to provide a summary of the latest articles published recently in other journals in our field. The articles address (1) cardiac resynchronization in children with symptomatic ventricular dysfunction and dyssynchrony which seems to result in higher transplant-free survival, (2) outcomes of aortic leaflet reconstruction including Ozaki procedure to repair aortic valve disease in adolescents, (3) meta-analysis for risk factors of ventricular tachycardia and death after repaired tetralogy of Fallot which reiterates the known risk factors and showed that the severity of pulmonary regurgitation is not in itself associated with outcomes although the ventricular response to regurgitation (dilation and dysfunction) is, (4) preschool promotion of healthy life style did not associate with sustained effect when evaluated later in childhood although repeated intervention seems to have a dose-related effect to promote healthy life style, (5) the lack of beneficial effects of angiotensin-converting enzyme inhibitors in the interstage period, and (6) a new phenomenon of acute heart failure and multisystem inflammatory syndrome in children temporarily related to the COVID-19 pandemic.

From Other Journals: A Review of Recent Articles in Pediatric Cardiology.

In this review, we provide a brief description of recently published articles addressing topics relevant to pediatric cardiologists. Our hope is to provide a summary of the latest articles published recently in other journals in our field. The articles address the following: (1) transcatheter closure of sinus venous atrial septal defect which is feasible in adults with careful planning, (2) exercise echocardiography in children with hypertrophic cardiomyopathy which was found to be very helpful to identify low-risk patients when there is no gradient at rest or during exercise, (3) features of Fontan patients with normal exercise capacity who typically report more active life style and have less complications during the post-Fontan admissions, (4) the natural history of Anderson-Tawil syndrome which is characterized by high incidence of life-threatening arrhythmogenic events especially when there is history of syncope, ventricular tachycardia, or the use of amiodarone, (5) pulmonary artery banding in complete atrioventricular septal defects which were found to be a safe alternative to early complete repair and served as a bridge to biventricular repair with variable effect on common atrioventricular valve regurgitation and (6) tricuspid valve interventions (TVI) in patients undergoing pulmonary valve replacement (PVR) which further reduce tricuspid regurgitation beyond what is expected in PVR alone without increasing early complications or hospital length of stay.

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.

Comparison of ESC and NICE guidelines for patients with suspected coronary artery disease: evaluation of the pre-test probability risk scores in clinical practice.

The European Society of Cardiology (ESC) and UK National Institute for Health and Care Excellence (NICE) have recently published guidelines for investigating patients with suspected coronary artery disease (CAD). Both provide a risk score (RS) to assess the pre-test probability for CAD to guide clinicians to undertake the most effective investigation. The aim of the study was to establish whether there is a difference between the two RS models. We retrospectively reviewed records of 479 patients who presented to a UK district general hospital with chest pain between August 2011 and April 2013. The RS was calculated using ESC and NICE guidelines and compared. From the 479 patients, 277 (58%) were male and the mean age was 60 years. The mean RS was greater using NICE guidelines compared with ESC (66.3 vs 47.9%, 18.4% difference; p<0.0001). The difference in mean RS was smaller in patients with typical chest pain (13.0%). When we divided the cohort based on NICE criteria into 'high'- and 'low'-risk groups, the difference in the mean RS was 24.3% in the 'high'-risk group (p<0.001) compared with 2.8% in the 'low'-risk group. The UK NICE risk score model overestimates risk compared with the ESC model.

Chest pain on exertion after the Takeuchi repair of anomalous origin of the left coronary artery: right ventricular ischemia due to severe pulmonary outflow tract obstruction.

Right ventricular (RV) outflow obstruction (in the form of valvar or supravalvular pulmonary stenosis) is a well-known complication of the Takeuchi procedure. We describe a 13-year-old male with exertional chest pain, pulmonary stenosis, RV hypertrophy, and consequent RV ischemia, which was confirmed using stress echocardiography and single-photon emission tomography.

Low flow low gradient aortic stenosis: clinical pathways.

Aortic stenosis patients with severe LV dysfunction and low cardiac output present with relatively low transvalvular gradients. It is difficult to distinguish them from aortic sclerosis and LV dysfunction with low cardiac output. The former condition is severe AS with LV dysfunction and latter is primarily a contractile dysfunction. Dobutamine stress echocardiogram is key to diagnosis. AS with LV dysfunction associated with preserved contractile reserve benefit from valve replacement and those without contractile reserve needs critical evaluation on a case to case basis. Patients of AS with LV dysfunction with associated coronary artery disease need coronary angiograms to decide regarding need for valve replacement with bypass surgery. A subset of AS patients have low flow, low mean gradients with preserved ejection fraction in whom one must evaluate global hemodynamic load to assess ventriculo-arterial impedence. In this review an approach to the clinical pathways for assessment of low flow, low gradient aortic stenosis has been discussed.

Exercise stress echocardiography in patients with aortic stenosis: impact of baseline diastolic dysfunction and functional capacity on mortality and aortic valve replacement.

BACKGROUND: Patients with aortic stenosis (AS) often undergo exercise echocardiography. Diastolic dysfunction (DD) is frequently associated with AS but little is known about its impact on functional capacity (FC). We sought to determine the relationship between DD and FC and their impact on mortality and need for aortic valve replacement (AVR) in patients with AS. METHODS AND RESULTS: Data was analyzed for consecutive patients with any degree of AS undergoing exercise stress echocardiography between 2000 and 2010 at our institution. The primary endpoint was a composite of death or need for AVR. We identified 1,267 patients [mean age 67±11 years, ejection fraction (56±7)%, mean aortic valve gradient 19±12 mmHg, mean maximal metabolic equivalents (METs) achieved 8±2.6]. The proportion with normal, stage 1, and ≥ stage 2 diastology was 195 (15%), 928 (73%), 144 (12%). A total of 475 (37.5%) patients had a primary outcome with 164 deaths (mean follow up 5.6±4.1 years) and 341 AVR (mean follow up 2.4±2.6 years). Predictors of FC were age, gender, body mass index, Bruce protocol, heart rate recovery (HRR), ejection fraction, mean aortic valve gradient, and diabetes but not baseline DD. Baseline DD [HR 1.82, 95% CI (1.17, 2.82), P=0.008] and FC [HR 0.93, 95% CI (0.88, 0.98), P=0.003] were independent predictors of death or AVR. CONCLUSIONS: For patients with AS undergoing exercise echocardiography, baseline DD was not predictive of FC. However, both baseline DD and FC were independent predictors of death or need for AVR.