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).

Feasibility of semi-recumbent bicycle exercise Doppler echocardiography for the evaluation of the right heart and pulmonary circulation unit in different clinical conditions: the RIGHT heart international NETwork (RIGHT-NET).

Exercise Doppler echocardiography (EDE) is a well-validated tool in ischemic and valvular heart diseases. However, its use in the assessment of the right heart and pulmonary circulation unit (RH-PCU) is limited. The aim of this study is to assess the semi-recumbent bicycle EDE feasibility for the evaluation of RH-PCU in a large multi-center population, from healthy individuals and elite athletes to patients with overt or at risk of developing pulmonary hypertension (PH). From January 2019 to July 2019, 954 subjects [mean age 54.2 ± 16.4 years, range 16-96, 430 women] underwent standardized semi-recumbent bicycle EDE with an incremental workload of 25 watts every 2 min, were prospectively enrolled among 7 centers participating to the RIGHT Heart International NETwork (RIGHT-NET). EDE parameters of right heart structure, function and pressures were obtained according to current recommendations. Right ventricular (RV) function at peak exercise was feasible in 903/940 (96%) by tricuspid annular plane systolic excursion (TAPSE), 667/751 (89%) by tissue Doppler-derived tricuspid lateral annular systolic velocity (S') and 445/672 (66.2%) by right ventricular fractional area change (RVFAC). RV-right atrial pressure gradient [RV-RA gradient = 4 × tricuspid regurgitation velocity2 (TRV)] was feasible in 894/954 patients (93.7%) at rest and in 816/954 (85.5%) at peak exercise. The feasibility rate in estimating pulmonary artery pressure improved to more than 95%, if both TRV and/or right ventricular outflow tract acceleration time (RVOT AcT) were considered. In high specialized echocardiography laboratories semi-recumbent bicycle EDE is a feasible tool for the assessment of the RH-PCU pressure and function.

A multicentric quality-control study of exercise Doppler echocardiography of the right heart and the pulmonary circulation. The RIGHT Heart International NETwork (RIGHT-NET).

PURPOSE: This study was a quality-control study of resting and exercise Doppler echocardiography (EDE) variables measured by 19 echocardiography laboratories with proven experience participating in the RIGHT Heart International NETwork. METHODS: All participating investigators reported the requested variables from ten randomly selected exercise stress tests. Intraclass correlation coefficients (ICC) were calculated to evaluate the inter-observer agreement with the core laboratory. Inter-observer variability of resting and peak exercise tricuspid regurgitation velocity (TRV), right ventricular outflow tract acceleration time (RVOT Act), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler tricuspid lateral annular systolic velocity (S'), right ventricular fractional area change (RV FAC), left ventricular outflow tract velocity time integral (LVOT VTI), mitral inflow pulsed wave Doppler velocity (E), diastolic mitral annular velocity by TDI (e') and left ventricular ejection fraction (LVEF) were measured. RESULTS: The accuracy of 19 investigators for all variables ranged from 99.7 to 100%. ICC was > 0.90 for all observers. Inter-observer variability for resting and exercise variables was for TRV = 3.8 to 2.4%, E = 5.7 to 8.3%, e' = 6 to 6.5%, RVOT Act = 9.7 to 12, LVOT VTI = 7.4 to 9.6%, S' = 2.9 to 2.9% and TAPSE = 5.3 to 8%. Moderate inter-observer variability was found for resting and peak exercise RV FAC (15 to 16%). LVEF revealed lower resting and peak exercise variability of 7.6 and 9%. CONCLUSIONS: When performed in expert centers EDE is a reproducible tool for the assessment of the right heart and the pulmonary circulation.

The Right Heart International Network (RIGHT-NET): Rationale, Objectives, Methodology, and Clinical Implications.

The Right Heart International Network is a multicenter international study aiming to prospectively collect exercise Doppler echocardiography tests of the right heart pulmonary circulation unit (RHPCU) in large cohorts of healthy subjects, elite athletes, and individuals at risk of or with overt pulmonary hypertension. It is going to provide standardization of exercise stress echocardiography of RHPCU and explore the full physiopathologic response.

Stressing the Cardiopulmonary Vascular System: The Role of Echocardiography.

The cardiopulmonary vascular system represents a key determinant of prognosis in several cardiorespiratory diseases. Although right heart catheterization is considered the gold standard for assessing pulmonary hemodynamics, a comprehensive noninvasive evaluation including left and right ventricular reserve and function and cardiopulmonary interactions remains highly attractive. Stress echocardiography is crucial in the evaluation of many cardiac conditions, typically coronary artery disease but also heart failure and valvular heart disease. In stress echocardiographic applications beyond coronary artery disease, the assessment of the cardiopulmonary vascular system is a cornerstone. The possibility of coupling the left and right ventricles with the pulmonary circuit during stress can provide significant insight into cardiopulmonary physiology in healthy and diseased subjects, can support the diagnosis of the etiology of pulmonary hypertension and other conditions, and can offer valuable prognostic information. In this state-of-the-art document, the topic of stress echocardiography applied to the cardiopulmonary vascular system is thoroughly addressed, from pathophysiology to different stress modalities and echocardiographic parameters, from clinical applications to limitations and future directions.

Impact of ejection fraction on infectious, renal, and respiratory morbidity for patients undergoing noncardiac surgery.

OBJECTIVE: We sought to determine if decreased left ventricular systolic function was associated with an increased risk of postoperative infectious, respiratory, or renal complications in patients undergoing noncardiac surgery. DESIGN: Retrospective cohort study. SETTING: Single tertiary-care, university-based medical center. PATIENTS: We studied individuals who participated in the American College of Surgeons National Quality Improvement Program and had a preoperative echocardiogram conducted at our institution. INTERVENTIONS: None. MEASUREMENTS: The incidences of postoperative respiratory (need for postoperative mechanical ventilation or unplanned intubation), renal (acute renal failure or renal insufficiency), and infectious (pneumonia, urinary tract infection, sepsis, or wound infection) complications were analyzed. MAIN RESULTS: Postoperative infections (n=175, 10%) represented the most common postoperative complication seen in the study population of 1692 individuals. Respiratory complications occurred in 77 (5%) and renal complications occurred in 29 (2%) participants. The time between the echocardiogram and surgery ranged from 7 months (interquartile range [IQR] 1.8-15.7) for those with severely reduced left ventricular ejection fraction (LVEF) to 24 months (IQR 2.5-38.6) for those with a normal LVEF (P=.038). Univariate analysis demonstrated a relationship between decreased preoperative LVEF and infectious and renal complications, but not respiratory complications. After adjusting for preoperative characteristics, decreased preoperative LVEF was associated with infectious (odds ratio, 1.33; 95% confidence interval, 1.03-1.68; P=.0265) and renal (odds ratio, 1.69; 95% confidence interval, 1.12-2.48; P=.0142) complications. CONCLUSIONS: Decreased preoperative LVEF is associated with postoperative infections and renal complications.

Echocardiography in liver transplant candidates.

Involvement of the cardiovascular system in patients with end-stage liver disease (ESLD) is well recognized and may be seen in several scenarios in adult liver transplantation (LT) candidates. The hemodynamic effects of ESLD may result in apparent heart disease, or in some instances may mask cardiac disease. Alternatively, cardiac disease can occasionally be the underlying etiology of ESLD. LT imposes significant hemodynamic stresses, with cardiovascular complications accounting for considerable perioperative mortality and morbidity. Pre-operative assessment of the cardiac status of LT candidates is thus critically important for risk stratification and management. Cardiac imaging plays an integral role in the assessment of LT candidates. In this review, we discuss the role of cardiac imaging, including transthoracic echocardiography with Doppler and contrast enhancement, noninvasive functional assessment for routine pre-operative assessment of coronary artery disease, and transesophageal echocardiography in select cases to aid in intra-operative fluid management and monitoring in LT candidates.

Pilot study of cardiac magnetic resonance imaging for detection of embolic source after ischemic stroke.

BACKGROUND: Transesophageal echocardiography (TEE) is the standard for evaluating cardioembolic sources of stroke, although many strokes remain cryptogenic after TEE. Cardiac magnetic resonance (CMR) imaging may have advantages over TEE. We performed a prospective pilot study comparing CMR to TEE after stroke to assist in planning future definitive studies. METHODS: Individuals with nonlacunar stroke within 90 days of undergoing clinical TEE were prospectively identified and underwent a 1.5 Tesla research CMR scan. Exclusion criteria included >50% relevant cervical vessel stenosis and inability to undergo nonsedated CMR. A descriptive comparison of cardioembolic source (intracardiac thrombus/mass, aortic atheroma ≥ 4 mm, or patent foramen ovale [PFO]) by study type was performed. RESULTS: Twenty patients underwent CMR and TEE a median of 6 days apart. The median age was 51 years (interquartile range [IQR] 40, 63.5), 40% had hypertension, 15% had diabetes, 25% had a previous stroke/transient ischemic attack, 5% had atrial fibrillation, and none had coronary disease or heart failure. No patient had intracardiac thrombus or mass detected on either study. Aortic atheroma ≥ 4 mm thick was identified by TEE in 1 patient. CMR identified aortic atheroma as <4 mm in this patient (3 mm on CMR compared with 5 mm on TEE). PFO was identified in 6 of 20 patients on TEE; CMR found only 1 of these. CONCLUSIONS: In this pilot study, TEE identified more potential cardioembolic sources than CMR imaging. Future studies comparing TEE and CMR after stroke should focus on older subjects at higher risk for cardiac disease to determine whether TEE, CMR, or both can best elucidate potential cardioembolic sources.

Impact of radiofrequency ablation of frequent post-infarction premature ventricular complexes on left ventricular ejection fraction.

BACKGROUND: Frequent idiopathic premature ventricular complexes (PVC) are associated with a reversible form of cardiomyopathy. The effect of frequent PVCs on left ventricular function has not been evaluated in post-infarction patients. OBJECTIVE: This study sought to evaluate the value of post-infarction PVC ablation and possible determinants of a reversible cardiomyopathy. METHODS: Thirty consecutive patients (24 men, age 61 +/- 12, left ventricular ejection fraction [LVEF] 0.36 +/- 0.12) with remote myocardial infarction referred for implantable cardioverter-defibrillator (ICD) implantation for primary prevention of sudden death or for management of symptomatic ventricular tachycardia or PVCs were evaluated. Fifteen patients with a high PVC burden (>or=5% of all QRS complexes on 24-h Holter monitor) underwent mapping and ablation of PVCs before ICD implantation. The remaining 15 patients served as a control group. LVEF was assessed by echocardiography, and scar burden was assessed by cardiac magnetic resonance imaging with delayed enhancement (DE-MRI) in both groups. RESULTS: PVC ablation was successful in 15 of 15 patients and reduced the mean PVC burden from 22 +/- 12% to 2.6 +/- 5.0% (P <.001). After the procedure, LVEF increased significantly from 0.38 +/- 0.11 to 0.51 +/- 0.09 in the PVC ablation group (P = .0001). In the control group, LVEF remained unchanged within the same time frame (0.34 +/- 0.14 vs. 0.33 +/- 0.15; P = .6). Patients with frequent PVCs had a significantly smaller scar burden by DE-MRI compared with control patients. Five of the patients with frequent PVCs underwent ICD implantation. CONCLUSION: Post-infarction patients with frequent PVCs may have a reversible form of cardiomyopathy. DE-MRI may identify patients in whom the LVEF may improve after ablation of frequent PVCs.

Stress echocardiography from 1979 to present.

Stress echocardiography was initially developed in 1979 and has seen substantial success in the evaluation of patients with known or suspected coronary artery disease. It has proven applicable to clinical questions of diagnosis, prognosis and follow-up. It has been heavily dependent on technologic advancements, initially digital capturing for side-by-side visualization and, more recently, developments in detailed methods of evaluating myocardial mechanics and contrast echocardiography for perfusion.

Evans blue staining of cardiomyocytes induced by myocardial contrast echocardiography in rats: evidence for necrosis instead of apoptosis.

High mechanical index (MI) echocardiography with contrast agent has been shown to induce Evans blue staining of cardiomyocytes, seen 1 d after exposure, in addition to contraction band necrosis, seen immediately after exposure. This research examined the roles of necrosis vs. apoptosis in these bioeffects. Myocardial contrast echocardiography at high MI with 1:4 electrocardiogram triggering was performed in anesthetized rats at 1.5 MHz. Histologically observable cell injury was accumulated by infusing a high dose of 50 microL/kg ultrasound contrast media via tail vein for 5 min at the start of 10 min of scanning. Evans blue dye or propidium iodide was injected as an indicator of cardiomyocyte plasma membrane integrity. Histologic sections were stained using the terminal dUTP nick-end labeling (TUNEL) method for labeling nuclei with DNA degradation (e.g., apoptosis). Evans blue fluorescent cells were counted on frozen sections or on hematoxylin-stained and TUNEL-labeled paraffin sections. In addition, transmission electron microscopy was used to assess potential apoptotic nuclei. Hypercontraction and propidium iodide staining were observed immediately after imaging exposure. Although TUNEL-positive cells were evident after 4 h, these also had indications of contraction band necrosis, and features of apoptosis were not confirmed by electron microscopy. Inflammatory cell infiltration was evident after 24 h. A second, more subtle injury was recognized by Evans blue staining, with minimal inflammatory cell infiltration at the morphologically intact stained cells after 24 h. Apoptosis was not detected by the TUNEL method in the cardiomyocytes stained with Evans blue at 24 h. However, Evans blue-stained cell numbers declined after 48 h, with continued inflammatory cell infiltration. The initial insult for Evans blue-stained cardiomyocytes apparently induced partial permeability of the plasma membrane, which led to gradual degeneration (but not apoptosis) and necrosis after 24 to 48 h.

Prognostic role of transesophageal echocardiography in acute type A aortic dissection.

BACKGROUND: Acute type A aortic dissection (AAD) remains a highly lethal entity for which emergent surgical correction is standard care. Prior studies have identified specific clinical findings as being predictive of outcome. The prognostic significance of specific findings on imaging studies is less well described. We sought to identify the prognostic value of transesophageal echocardiography (TEE) in medically and surgically treated patients with AAD. METHODS: We studied 522 AAD patients enrolled over 6 years in the International Registry of Acute Aortic Dissection who underwent TEE. Multivariate analysis identified independent associations of inhospital mortality, first using clinical variables (model 1), after which TEE data were added to build a final model (model 2). RESULTS: Inhospital mortality was 28.7%. Transesophageal echocardiographic evidences of pericardial effusion (P = .04), tamponade (P < .01), periaortic hematoma (P = .02), and patent false lumen (P = .08) were more frequent in nonsurvivors. Dilated ascending aorta (P = .03), dissection localized to the ascending aorta (P = .02), and thrombosed false lumen (P = .08) were less common in nonsurvivors. Model 1 identified age > or = 70 years, any pulse deficit, renal failure, and hypotension/shock as independent predictors of death. Model 2 identified dissection flap confined to ascending aorta (odds ratio 0.2, 95% CI 0.1-0.6) and complete thrombosis of false lumen (odds ratio 0.15, 95% CI 0.03-0.86) as protective. In the medically treated group, mortality was 31% for subjects with a partially or completely thrombosed false lumen versus 66% in the presence of a patent false lumen. CONCLUSIONS: Transesophageal echocardiography provides prognostic information in AAD beyond that provided by clinical risk variables.

Metoprolol reverses left ventricular remodeling in patients with asymptomatic systolic dysfunction: the REversal of VEntricular Remodeling with Toprol-XL (REVERT) trial.

BACKGROUND: There are no randomized, controlled trial data to support the benefit of beta-blockers in patients with asymptomatic left ventricular systolic dysfunction. We investigated whether beta-blocker therapy ameliorates left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction. METHOD AND RESULTS: Patients with left ventricular ejection fraction <40%, mild left ventricular dilation, and no symptoms of heart failure (New York Heart Association class I) were randomly assigned to receive extended-release metoprolol succinate (Toprol-XL, AstraZeneca) 200 mg or 50 mg or placebo for 12 months. Echocardiographic assessments of left ventricular end-systolic volume, end-diastolic volume, mass, and ejection fraction were performed at baseline and at 6 and 12 months. The 149 patients randomized to the 3 treatment groups (200 mg, n=48; 50 mg, n=48; and placebo, n=53) were similar with regard to all baseline characteristics including age (mean, 66 years), gender (74% male), plasma brain natriuretic peptide (79 pg/mL), left ventricular end-diastolic volume index (110 mL/m2), and left ventricular ejection fraction (27%). At 12 months in the 200-mg group, there was a 14+/-3 mL/m2 decrease (least square mean+/-SE) in end-systolic volume index and a 6+/-1% increase in left ventricular ejection fraction (P<0.05 versus baseline and placebo for both). The decrease in end-diastolic volume index (14+/-3) was different from that seen at baseline (P<0.05) but not with placebo. In the 50-mg group, end-systolic and end-diastolic volume indexes decreased relative to baseline but were not different from what was seen with placebo, whereas ejection fraction increased by 4+/-1% (P<0.05 versus baseline and placebo). CONCLUSION: Beta-blocker therapy can ameliorate left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction.

Microvascular permeabilization and cardiomyocyte injury provoked by myocardial contrast echocardiography in a canine model.

OBJECTIVES: The aim of this research was to evaluate the potential for myocardial contrast echocardiography (MCE) to provoke microscale bioeffects in a canine model. BACKGROUND: Myocardial contrast echocardiography induces bioeffects in rat hearts, but translation of such results to larger animal models is uncertain. METHODS: Dogs were anesthetized and prepared for open- (n = 22) or closed- (n = 6) chest MCE. Evans blue dye was injected intravenously as an indicator of microvascular leakage, and propidium iodide was used to stain for irreversibly injured myocytes in frozen sections. The contrast agent (Definity, Bristol-Myers Squibb Medical Imaging Inc., North Billerica, Massachusetts) was diluted in saline and infused intravenously at 2 microl/kg/min. Myocardial contrast echocardiography in a short-axis (open-chest) or modified four-chamber view (closed-chest) with 1:4 end systolic electrocardiogram triggering was performed at 1.5 MHz for 10 min in a single imaging plane. RESULTS: Petechiae and leakage of Evans blue were observed in the ultrasound scan plane within the anterior left ventricle. For 1.2 MPa and 2.2 MPa, open- or closed-chest MCE, Evans blue content in tissue within the scan plane was significantly greater than in tissue outside this plane. Counts of propidium-iodide-stained nuclei for 2.2 MPa open-chest MCE were also significantly greater inside than outside the scan plane. CONCLUSIONS: In a canine model, MCE induces myocardial injury comparable to that seen in the rodent model.

Influence of contrast agent dose and ultrasound exposure on cardiomyocyte injury induced by myocardial contrast echocardiography in rats.

PURPOSE: To detect specific cardiomyocyte injury induced by myocardial contrast material-enhanced echocardiography (ie, myocardial contrast echocardiography) in rats and to ascertain the influences of contrast material dose and ultrasound exposure on this injury. MATERIALS AND METHODS: All animal procedures were approved by the university committee for the use and care of animals. Myocardial contrast echocardiography with 1:4 electrocardiographic (ECG) triggering was performed at 1.5 MHz in 61 anesthetized rats. Evans blue (EB) dye was injected as the vital stain for cardiomyocyte injury. At the start of myocardial contrast echocardiography, which lasted 10 minutes, perflutren lipid microsphere-based contrast material was infused through the tail vein for 5 minutes. Premature heartbeats were counted from the ECG record. The numbers of EB-stained cells counted on sections of heart specimens obtained 24 hours after myocardial contrast echocardiography and then either fresh frozen or embedded in paraffin were determined by using fluorescence microscopy. Results were compared statistically by using t tests and Mann-Whitney rank sum tests. RESULTS: EB-stained cells were concentrated in the anterior region of the myocardium. In the paraffin-embedded specimens, EB-stained cells were often accompanied by but largely separate from areas of inflammatory cell infiltration. At end-systolic triggering with a 50 microL/kg dose of microsphere contrast material, the EB-stained cell count increased with increasing peak rarefactional pressure amplitude, with significantly increased cell counts at 1.6 MPa (P < .02) and 2.0 MPa (P < .005) relative to the cell counts at sham myocardial contrast echocardiography. Premature heartbeats had a similar exposure-response relationship; however, number of premature heartbeats and EB-stained cell count did not appear to be directly related (coefficient of determination r2 = 0.03). The EB-stained cell counts at end-diastolic triggering were not significantly different from those at end-systolic triggering (P > .1). EB-stained cell counts increased with increasing contrast material dose, from 10 to 50 microL/kg, at 2.0 MPa. CONCLUSION: Cardiomyocyte injury was induced by the interaction of ultrasound pulses with contrast agent microbubbles during myocardial contrast echocardiography in rats, and the numbers of injured cells increased with increasing contrast agent dose and ultrasound exposure.

The influence of agent delivery mode on cardiomyocyte injury induced by myocardial contrast echocardiography in rats.

Myocardial contrast echocardiography (MCE) can induce bioeffects in rat hearts by local activation of the contrast agent gas bodies. This study was designed to examine the influence of agent delivery mode on the magnitude of cardiomyocyte injury. A total of 69 hairless rats were anesthetized and mounted vertically in a water bath. Evans blue dye was injected as vital stain for cardiomyocyte injury. Definity contrast agent was diluted in saline and injected via tail vein at 20 or 80 microL/kg in bolus or infusion mode. In 12 rats, 0.57 mg/kg dipyridamole was given to simulate a stress test. MCE in a short axis view with 1:4 or 1:16 ECG triggering was performed at 1.5 MHz for 5 or 20 min. The peak rarefactional pressure amplitude was set to 1.1 or 2.0 MPa. Premature beats were counted from the ECG record. Evans blue fluorescent cells were counted on frozen sections from the center of the scan plane of heart samples obtained 24 h postMCE. Infusion of the contrast agent led to more cardiomyocyte injury than did bolus injection. Dipyridamole stress also increased the effect. Varying the infusion rate or trigger interval was less important than the overall dosage during scanning. Exposure at 1.1 MPa and 80 microL/kg yielded significant cell killing relative to shams. Premature beats generally followed the same trends as cell injury, except that lower infusion rates tended to increase this effect. Contrast agent delivery mode, as well as dose and peak rarefactional pressure amplitude, has a significant influence on the bioeffects potential of MCE.