Dobutamine-induced Takotsubo syndrome in a paediatric heart transplant patient.

Takotsubo syndrome is a potentially reversible cause of acute systolic dysfunction. Takotsubo syndrome is rare in children, with no reported dobutamine-induced cases to date. We present a 14-year-old male with prior history of heart transplantation, who developed Takotsubo syndrome during dobutamine stress echocardiography. We highlight the importance of its early recognition to ensure supportive measures with avoidance of inotropic medications.

Predictors of exercise-induced pulmonary hypertension in patients with connective tissue disease.

Screening and early detection of pulmonary arterial hypertension (PAH) in connective tissue disease (CTD) are currently recommended for early treatment. Exercise-induced pulmonary hypertension (EIPH) is thought to be a potential risk of developing resting pulmonary hypertension. However, accurate diagnosis of EIPH is needed hemodynamics by right heart catheterization during exercise. Therefore, we compared various parameters of EIPH group with non-EIPH group in patients with CTD. This study aimed to investigate noninvasive predictors of EIPH. A total of 162 consecutive patients with CTD who received screening of PAH was studied. Thirty-four patients with suspected PAH received right heart catheterization (RHC) at rest. Twenty-four patients without PAH underwent RHC during exercise, and they were divided into the EIPH group (n = 7) and the non-EIPH group (n = 17). Exercise tolerance such as 6-min walk distance and peak VO2/kg in the EIPH group was lower than that in the non-EIPH group. For hemodynamics, pulmonary artery pressure, right atrial pressure, and vascular resistance in the EIPH group were significantly higher than those in the non-EIPH group. In echocardiography, RV Tei index in the EIPH group was significantly higher than that in the non-EIPH group (EIPH vs non-EIPH = 0.42 [0.41, 0.47] vs 0.25 [0.20, 0.32], P = 0.007). The receiver operating characteristics curve showed a cutoff value of RV Tei index (0.41) with a sensitivity of 0.857 and specificity of 0.882. In conclusion, RV Tei index might be a feasible predictor of EIPH in patients with CTD.

Outcomes of anatomical versus functional testing for coronary artery disease.

BACKGROUND: Many patients have symptoms suggestive of coronary artery disease (CAD) and are often evaluated with the use of diagnostic testing, although there are limited data from randomized trials to guide care. METHODS: We randomly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography (CTA) or to functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography). The composite primary end point was death, myocardial infarction, hospitalization for unstable angina, or major procedural complication. Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure. RESULTS: The mean age of the patients was 60.8±8.3 years, 52.7% were women, and 87.7% had chest pain or dyspnea on exertion. The mean pretest likelihood of obstructive CAD was 53.3±21.4%. Over a median follow-up period of 25 months, a primary end-point event occurred in 164 of 4996 patients in the CTA group (3.3%) and in 151 of 5007 (3.0%) in the functional-testing group (adjusted hazard ratio, 1.04; 95% confidence interval, 0.83 to 1.29; P=0.75). CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing (3.4% vs. 4.3%, P=0.02), although more patients in the CTA group underwent catheterization within 90 days after randomization (12.2% vs. 8.1%). The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group (10.0 mSv vs. 11.3 mSv), but 32.6% of the patients in the functional-testing group had no exposure, so the overall exposure was higher in the CTA group (mean, 12.0 mSv vs. 10.1 mSv; P<0.001). CONCLUSIONS: In symptomatic patients with suspected CAD who required noninvasive testing, a strategy of initial CTA, as compared with functional testing, did not improve clinical outcomes over a median follow-up of 2 years. (Funded by the National Heart, Lung, and Blood Institute; PROMISE ClinicalTrials.gov number, NCT01174550.).

Myocardial bridging is associated with exercise-induced ventricular arrhythmia and increases in QT dispersion.

BACKGROUND: A myocardial bridge (MB) has been associated with ventricular arrhythmia and sudden death during exercise. QT dispersion (QTd) is a measure of abnormal repolarization and may predict ventricular arrhythmia. We investigated the frequency of ventricular arrhythmias during exercise and the QTd at rest and after exercise, in patients with an MB compared to a normal cohort. METHODS: We studied the rest and stress ECG tracings of patients with an MB suspected by focal septal buckling on exercise echocardiography (EE) (Echo-MB group, N = 510), those with an MB confirmed by another examination (MB group, N = 110), and healthy controls (Control group, N = 198). RESULTS: The frequency of exercise-induced premature ventricular contractions (PVCs) was significantly higher in the Echo-MB and MB groups compared with the Control group (both p < .001). In all, 25 patients (4.9%) in the Echo-MB group, seven patients (6.4%) in the MB group and no patients in the Control group had exercise-induced non-sustained ventricular tachycardia (NSVT). There was no difference in the baseline QTd between the groups. In the Echo-MB and MB groups, QTd postexercise increased significantly when compared with baseline (both p < .001). Patients with NSVT had a higher frequency of male gender and an even greater increase in QTd with exercise compared with the non-NSVT group. DISCUSSION: There is an increased frequency of exercise-induced PVCs and NSVT in patients with MBs. Exercise significantly increases QTd in MB patients, with an even greater increase in QTd in MB patients with NSVT. Exercise in MB patients results in ventricular arrhythmias and abnormalities in repolarization.

Persistent but reversible advanced atrio-ventricular block in a heart transplant man induced by dobutamine stress echocardiography.

Dobutamine when used for stress echocardiography (DSE), it rarely causes transient atrio-ventricular (AV) block. We report a heart transplant patient with high cardiovascular risk who developed symptomatic advanced AV block during DSE which persisted after termination of dobutamine administration, necessitating pacemaker implantation. To our knowledge, this is the first published case of persistent high grade AV block in a heart transplant patient induced by DSE.

Safety profile and utility of treadmill exercise in patients with high-gradient hypertrophic cardiomyopathy.

BACKGROUND: Exercise echocardiography in the evaluation of hypertrophic cardiomyopathy (HCM) provides valuable information for risk stratification, selection of optimal treatment, and prognostication. However, HCM patients with left ventricular outflow tract gradients ≥30mm Hg are often excluded from exercise testing because of safety considerations. We examined the safety and utility of exercise testing in patients with high-gradient HCM. METHODS: We evaluated clinical characteristics, hemodynamics, and imaging variables in 499 consecutive patients with HCM who performed 959 exercise tests. Patients were divided based on peak left ventricular outflow tract gradients using a 30-mm Hg threshold into the following: obstructive (n=152), labile-obstructive (n=178), and nonobstructive (n=169) groups. RESULTS: There were no deaths during exercise testing. We noted 20 complications (2.1% of tests) including 3 serious ventricular arrhythmias (0.3% of tests). There was no difference in complication rate between groups. Patients with obstructive HCM had a higher frequency of abnormal blood pressure response (obstructive: 53% vs labile: obstructive: 41% and nonobstructive: 37%; P=.008). Obstructive patients also displayed a lower work capacity (obstructive: 8.4±3.4 vs labile obstructive: 10.9±4.2 and nonobstructive: 10.2±4.0, metabolic equivalent; P<.001). Exercise testing provided incremental information regarding sudden cardiac death risk in 19% of patients with high-gradient HCM, and we found a poor correlation between patient-reported functional class and work capacity. CONCLUSION: Our results suggest that exercise testing in HCM is safe, and serious adverse events are rare. Although numbers are limited, exercise testing in high-gradient HCM appears to confer no significant additional safety hazard in our selected cohort and could potentially provide valuable information.

Global longitudinal strain from resting echocardiogram is associated with long-term adverse cardiac outcomes in patients with suspected coronary artery disease.

PURPOSE: Measuring myocardial strain using two-dimensional speckle tracking echocardiography has emerged as a new tool to identify subclinical ventricular dysfunction. Abnormal strain has been shown to have superior sensitivity compared with dobutamine stress echocardiography for viability assessment; however, there is a paucity of data regarding the prediction of long-term major adverse cardiac events. We compared the prognostic ability of both global longitudinal strain (GLS) from resting echocardiograms to regional wall motion score index (WMSI) from stress echocardiograms in their ability to predict long-term major adverse cardiac events. METHODS: Patients referred for stress echocardiography, who also underwent coronary angiography within 3 months of stress echo (n=122), were enrolled. Patients with reduced ejection fractions (<40%) were excluded. Patients were followed for a median of 3.4 years for major adverse cardiac events, readmissions and repeat cardiac testing. RESULTS: Patients with abnormal GLS (GLS <16.8%) from the resting echocardiogram obtained as part of the exercise echocardiogram experienced a significantly shorter time to major adverse cardiac events (p=0.026), first cardiovascular hospitalization and repeat cardiac testing (p=0.0011) compared to those with normal GLS. Abnormal GLS appears to be a better predictor than abnormal WMSI in predicting major adverse cardiac events (p=0.174) and time to first cardiovascular hospitalization or repeat cardiac testing (p=0.0093). CONCLUSION: GLS may be a better predictor of long-term major adverse cardiac events, readmissions and repeat cardiac testing than WMSI in patients undergoing stress echocardiography.

Vulnerability to sympathetic stress does not persist in takotsubo stress cardiomyopathy.

OBJECTIVE: Our objective was to investigate whether dobutamine stress echocardiography (DSE) could induce abnormal cardiac function in takotsubo stress cardiomyopathy (TSC) patients in a stable condition after the acute attack. METHODS AND RESULTS: This was a case-control study and a substudy of the Stockholm Myocardial Infarction With Normal Coronaries (SMINC) study. Twenty-two patients with a previous episode of TSC and 22 sex- and age-matched control subjects were recruited from the SMINC study and investigated with the use of DSE. All TSC patients had a previous normal cardiovascular magnetic resonance investigation. Tissue Doppler imaging-derived time phases of the cardiac cycle were recorded to calculate myocardial performance index (MPI) to assess ventricular function. Compared with control subjects at rest, TSC patients had a slightly but significantly higher left ventricular MPI (LV-MPI; 0.53 vs 0.59; P = .01) and as a trend higher right ventricular MPI (0.38 vs 0.47; P = .08), although during DSE these variables did not differ significantly. CONCLUSION: We found no difference in standard diastolic parameters between TSC and control subjects, but a significant higher value in LV-MPI in the TSC group at rest. However, no such difference could be demonstrated during DSE between the groups, indicating that vulnerability to sympathetic stimulation does not persist in TSC patients.

The risk of adverse events associated with atropine administration during dobutamine stress echocardiography in cardiac transplant patients: a 28-year single-center experience.

BACKGROUND: Although dobutamine stress echocardiography (DSE) is performed in heart transplant patients, the safety profile of atropine administration in DSE in this setting is unclear. METHODS AND RESULTS: We identified heart transplant patients who received atropine during DSE from January 1984 to August 2011 at our institution and compared them with a propensity-scored matched control group of heart transplant patients who underwent DSE without atropine. Adverse events were defined as significant arrhythmias (sinus arrest, Mobitz type II heart block, complete heart block, ventricular tachycardia, or ventricular fibrillation), hypotension requiring hospitalization, syncope or presyncope, myocardial infarction, and death. Forty-five heart transplant patients (median age 62 years, 82% male) received 0.2-1 mg atropine during DSE. Of these, 1 patient (2.2%) developed temporary complete heart block. No adverse events were identified in the control group of 154 patients who received dobutamine without atropine. CONCLUSIONS: Our findings suggest that complete heart block can occur infrequently with the administration of atropine in heart transplant patients undergoing DSE. Therefore, patients should be appropriately monitored for these adverse events during and after DSE.

The role of optical coherence tomography in clarifying the mechanisms for dobutamine stress echocardiography-induced takotsubo cardiomyopathy.

Takotsubo cardiomyopathy is a clinical disorder characterized by a transient dilatation and akynesis or dyskinesis of the left ventricular (LV) apex, mimicking an anterior wall acute myocardial infarction in the absence of significant coronary artery disease (CAD). It typically occurs during an episode of severe emotional or physical stress. Recent reports suggested the potential of dobutamine stress echocardiography (DSE) in inducing the aforementioned syndrome. The transient dysfunction of the LV does not fit any known coronary distribution. Furthermore, there is no obstructive CAD demonstrated at angiography to account for the observed dysfunction. Consequently, the pathophysiology of this syndrome is still undetermined. Here, we report a case of DSE-induced Takotsubo cardiomyopathy in which high-resolution intracoronary imaging was utilized to exclude possible vessel alterations to help provide potential mechanistic explanations for the development of this condition.

The safety profile of perflutren microsphere contrast echocardiography during rest and stress imaging: results from an Australian multicentre cohort.

BACKGROUND: Contrast enhanced echocardiography (CEE) is utilised when sub-optimal image quality results in non-diagnostic echocardiograms. However, there have been numerous safety notices issued by regulatory authorities regarding rare but potentially serious adverse reactions (AR). This multi-centre, retrospective analysis was performed to assess the short-term safety of CEE in a broad range of indications. METHODS: All CEE performed over 58 months at three institutions were assessed for AR within 30 min. RESULTS: A total of 5956 CEE were performed in 5576 patients. A total of 4903 were stress CEE and 1053 resting CCE. Bolus administration in 5719, infusion in 237 cases; 89.9% of CCE were outpatients. Commonest CEE indication was functional stress testing (82.3%). There were 16 AR related to CEE (0.27%). All AR were mild, transient and all patients made a full recovery. No cases of serious anaphylaxis or death within 30 min of contrast administration. Comparing those with and without an AR, there were no significant differences in age, gender, BMI, LVEF, patient location, exam type or RVSP. There was a slightly increased likelihood of an AR during infusion versus bolus dosing (p = 0.02). CONCLUSION: CEE is a safe investigation in a broad range of indications and clinical scenarios. AR are very rare, mild and transient.

Exercise Stress Echocardiography of the Right Ventricle and Pulmonary Circulation.

BACKGROUND: Exercise echocardiography is used for assessment of pulmonary circulation and right ventricular function, but limits of normal and disease-specific changes remain insufficiently established. OBJECTIVES: The objective of this study was to explore the physiological vs pathologic response of the right ventricle and pulmonary circulation to exercise. METHODS: A total of 2,228 subjects were enrolled: 375 healthy controls, 40 athletes, 516 patients with cardiovascular risk factors, 17 with pulmonary arterial hypertension, 872 with connective tissue diseases without overt pulmonary hypertension, 113 with left-sided heart disease, 30 with lung disease, and 265 with chronic exposure to high altitude. All subjects underwent resting and exercise echocardiography on a semirecumbent cycle ergometer. All-cause mortality was recorded at follow-up. RESULTS: The 5th and 95th percentile of the mean pulmonary artery pressure-cardiac output relationships were 0.2 to 3.5 mm Hg.min/L in healthy subjects without cardiovascular risk factors, and were increased in all patient categories and in high altitude residents. The 5th and 95th percentile of the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio at rest were 0.7 to 2.0 mm/mm Hg at rest and 0.5 to 1.5 mm/mm Hg at peak exercise, and were decreased at rest and exercise in all disease categories and in high-altitude residents. An increased all-cause mortality was predicted by a resting tricuspid annular plane systolic excursion to systolic pulmonary artery pressure <0.7 mm/mm Hg and mean pulmonary artery pressure-cardiac output >5 mm Hg.min/L. CONCLUSIONS: Exercise echocardiography of the pulmonary circulation and the right ventricle discloses prognostically relevant differences between healthy subjects, athletes, high-altitude residents, and patients with various cardio-respiratory conditions. (Right Heart International NETwork During Exercise in Different Clinical Conditions; NCT03041337).

The effect of atropine used in dobutamine stress echocardiography on pupil diameter.

BACKGROUND: The use of atropine during dobutamine stress echocardiography (DSE) is contraindicated in persons with narrow angle glaucoma though there is limited evidence that low doses of intravenous atropine do not cause pupillary dilation. OBJECTIVE: The aim of this study is to investigate whether atropine when administered in persons without glaucoma during dobutamine stress echocardiography causes pupillary dilation. METHODS AND RESULTS: Out of 144 patients without a history of glaucoma referred for DSE for clinical indications, 105 patients received intravenous atropine doses ranging from 0.1 mg to 1.25 mg (most patients received 0.25-0.75 mg). Pupil diameter of both eyes was measured under the same light conditions before and after the DSE using a CP-30 Optical Digital PD Ruler. For the total of 210 examined eyes pupil diameter remained unaltered after each DSE test (3.65 ± 0.799 mm before vs 3.63 ± 0.766 mm after, p = .737). Similarly, pupil diameter remained unchanged when left and right eyes were assessed separately (right eye: 3.770 ± 0.812 before vs 3.752 ± 0.745 mm after, p = .821 and left eye: 3.521 ± 0.770 before vs 3.499 ± 0.770 mm after, p = .806). Diameter of right and left pupil were also unaltered after grouping patients by sex and iris pigmentation. Age, weight, atropine dose and propranolol dose were not correlated with changes in pupil diameter. CONCLUSION: Intravenous atropine in usual doses administered in DSE does not cause mydriasis in adults without glaucoma. Future studies need to confirm our findings and expand the investigation regarding safety of atropine use during DSE in patients with narrow angle glaucoma.

Recent advances in stress echocardiography.

PURPOSE OF REVIEW: This article reviews the recent advances in stress echocardiography, with particular attention to articles published in 2010 and 2011. It summarizes the developments in the diagnostic and prognostic capabilities of stress echocardiography, discusses new data regarding the safety of stress echocardiography, and highlights emerging roles for stress echocardiography in the areas of left ventricular assist devices, cardiac transplantation, strain-rate echocardiography, and myocardial perfusion imaging. RECENT FINDINGS: Stress echocardiography represents a well validated tool in the diagnosis and assessment of patients with known or suspected coronary artery disease. Recently, data have emerged supporting the prognostic capabilities of stress echocardiography in patients with various levels of systolic dysfunction, diastolic abnormalities, and valvular heart disease. New studies continue to document the safety of stress echocardiography, particularly with regard to arrhythmias, neuropsychiatric symptoms, dosing of dobutamine, and intravenous contrast. Studies are now suggesting that stress echocardiography may play novel roles in the evaluation of patients with left ventricular assist devices or potential donors for cardiac transplantation. Technologic developments in myocardial contrast perfusion imaging, three-dimensional imaging, and strain-rate echocardiography will continue to advance the field. SUMMARY: Stress echocardiography represents a dynamic, versatile, and well validated tool for the noninvasive assessment of patients with a wide spectrum of cardiovascular diseases.

Takotsubo (apical ballooning) syndrome in the recovery period following dobutamine stress echocardiography: a first report.

We report a case of Takotsubo syndrome occurring in the recovery phase after a dobutamine stress echocardiogram. Takotsubo syndrome is a widely acknowledged cause of reversible left ventricular systolic dysfunction. It has garnered much attention from the cardiological community since its presentation frequently mimics that of ST-segment elevation myocardial infarction. The exact aetiology remains incompletely defined, although stress is recognized frequently as a precipitating factor. In recent years it has emerged that stress testing, as part of a patient's investigative assessment, can also induce Takotsubo's syndrome. All prior reports of dobutamine-induced Takotsubo's syndrome have described apical ballooning at peak stress. We describe the case of an 85-year-old lady who developed apical ballooning in the recovery period after a dobutamine stress echocardiogram, despite having normal left ventricular wall motion at rest and at peak stress. We believe this to be the first such case reported in the literature. Dobutamine stress testing can precipitate Takotsubo's syndrome not just at peak stress but also during the recovery period. All those performing dobutamine stress tests should be aware of this rare but potentially important complication.

Transmural myocardial ischaemia complicating recovery after dobutamine-atropine stress echocardiography in patients with non-significant coronary artery disease: insights from invasive assessment of coronary physiology.

In the proposed selection of cases, traditional imaging is integrated with contemporary diagnostic tools available in the cath-lab to navigate the potential mechanisms underlying a very rare complication occurring in the recovery phase of dobutamine-atropine stress echocardiography. The data, collected in a time frame of nearly 15 years, provide interesting elements to possibly evolve from speculative considerations to plausible confirmation of the candidate pathophysiological mechanism mediating the occurrence of transmural myocardial ischaemia after beta-blockers administration.

Acute ST segment elevation during exercise stress echocardiography due to severe pulmonary hypertension.

A 51-year-old female undergoing an outpatient stress echocardiogram to evaluate atypical chest pain developed acute ST elevation in the anterior precordial leads on electrocardiogram following exercise. Echocardiography revealed a severe rise in pulmonary artery systolic pressure (PASP) with marked right ventricular (RV) enlargement and interventricular septum flattening. Subsequently, cardiac catherization confirmed an exercise-induced elevation in PASP and diagnosed pulmonary arterial hypertension without evidence of coronary artery disease. This case suggests that an acute elevation in pulmonary artery pressure with RV dilation may be a potential cause of acute ST elevation during stress testing.

Severe chest pain during stress dobutamine echocardiogram in patient with patent epicardial coronary arteries.

Dobutamine induced ST-segment elevation in the absence of obstructive coronary artery disease is a rare condition. We report a case of a 37-year-old man, a smoker, who developed severe chest pain associated with transient ST-segment elevation in anterolateral leads and significant segmental wall motion abnormalities during dobutamine stress echocardiography that was immediately relieved by sublingual nitrates without evidence of acute myocardial infarction. Coronary angiogram showed patent epicardial coronary arteries.

Early atropine-dobutamine echocardiography in diabetic patients.

OBJECTIVE: We sought to explore the efficacy and safety of the early atropine-dobutamine stress echocardiography (EA-DSE) protocol in comparison with the conventional atropine-dobutamine stress echocardiography (CA-DSE) protocol, in diabetic patients undergoing dobutamine stress echocardiography (DSE) for suspected coronary artery disease (CAD). METHODS AND RESULTS: We enrolled 100 consecutive diabetic patients referred to our stress echocardiography labs for suspected CAD. Patients were randomly assigned to undergo either of the following two DSE protocols: CA-DSE (group 1; 50 patients) or EA-DSE (group 2; 50 patients) where atropine was started at a dobutamine infusion rate of 20 microg/kg/min, up to a maximum dose of 2.0 mg. Patients were monitored for adverse drug reactions. Test duration was calculated. All patients underwent coronary angiography. The mean age of the whole study population was 54.9 +/- 2.8 y, 56 (56%) being males. Patients in group 1 had a longer test duration (29.7 +/- 3.4 versus 14.7 +/- 1.3 minutes, respectively, P < 0.05). At peak stress, group 1 had a significantly lower heart rate, significantly higher systolic and diastolic blood pressure, and rate-pressure product (P < 0.05 for all). Group 1 patients had a higher incidence of arrhythmias, exaggerated blood pressure response, and hypotension as compared with group 2. The EA-DSE protocol had a similar diagnostic accuracy in comparison with the CA-DSE protocol (90% versus 92% respectively). CONCLUSIONS: In diabetic patients with suspected CAD undergoing DSE, adopting the EA-DSE protocol offers shorter test duration, fewer adverse effects, and a diagnostic accuracy similar to that of the CA-DSE.