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).

Age-changes in right ventricular function-pulmonary circulation coupling: from pediatric to adult stage in 1899 healthy subjects. The RIGHT Heart International NETwork (RIGHT-NET).

The present study analyzes age-specific changes in RV function and RV-PA coupling in a large cohort of apparently healthy subjects with a wide age-range, to identify reference values and to study the influence of clinical and echocardiographic cofactors. 1899 Consecutive healthy subjects underwent a standardized transthoracic echocardiographic examination. Tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (SPAP) were measured. Ventriculo-arterial coupling was then inferred from the TAPSE/SPAP ratio. A quantile regression analysis was used to estimate quantiles 0.05, 0.10, 0.50 (median), 0.90, and 0.95 of TAPSE, SPAP and TAPSE/SPAP. The association between age and each of these values was determined. The mean age of the group was 45.2 ± 18.5 years (range 1 to 102 years), 971 were males. SPAP increased with age, whereas TAPSE and TAPSE/SPAP ratio decreased. Upon multivariate modeling, the most significant positive associations for TAPSE were body surface area (BSA) driven by the pediatric group, stroke volume (SV), E/A and negatively heart rate and E/e' ratio. SPAP was positively associated with increasing age, SV, E/A, E/e' and negatively with BSA. TAPSE/SPAP ratio was negatively associated with age, female sex, and E/e' and positively with BSA. A preserved relationship between TAPSE and SPAP was found across the different age groups. TAPSE, SPAP and TAPSE/SPAP demonstrate important trends and associations with advancing age, impaired diastolic function, affected by female sex and BSA However the relationship between TAPSE and SPAP is relatively well preserved across the age spectrum.

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.

An efficient algorithm based on electrograms characteristics to identify ventricular tachycardia isthmus entrance in post-infarct patients.

AIMS: Our study assesses the value of electrograms (EGMs) characteristics to identify a ventricular tachycardia (VT) isthmus entrance in patients with post-infarct VT. Post-infarct VTs are mostly due to a re-entrant circuit. A pacemapping (PM) approach is able to localize the VT isthmus during sinus rhythm. Limited data are available about the role of local EGMs in defining VT isthmus location. METHODS AND RESULTS: Twenty consecutive patients (70% male) referred for post-infarct VT catheter ablation were included in the present study. The VT isthmus was defined according to the PM method. At each recording site, 10 characteristics of the local EGM were assessed to predict the location of the VT isthmus entrance. In total, 924 EGMs were acquired, of which 127 were located in the VT isthmus entrance. Logistic regression analysis showed that bipolar voltage, number of EGM positive peaks, and sQRS interval were independently associated with VT isthmus entrance location. The ROC curve best fitted the model at the cut-off 0.1641 (sensitivity 72%, specificity 75.2%, positive predictive value 31.3%, negative predictive value 94.4%, area under the curve 0.78, P < 0.001). Based upon these results, we developed an algorithm implemented in an automatic calculator to determine the likelihood that an EGM is located at a VT isthmus entrance. CONCLUSION: Our study suggests that three EGM characteristics: bipolar voltage, number of positive peaks, and sQRS interval can successfully identify a VT isthmus entrance in post-infarct patients.

Catheter Treatment of Ventricular Tachycardia: A Reference-Less Pace-Mapping Method to Identify Ablation Targets.

OBJECTIVE: A novel method is developed to identify ablation targets for the catheter treatment of ventricular tachycardia (VT). METHODS: The method is based on pace-mapping, which is a validated technique to determine the catheter ablation targets. Conventionally, it consists of stimulating the heart ventricle from various sites and comparing the resulting activation pathways to that of a clinical VT by the analysis of surface electrocardiograms (ECG). In this paper, a novel pace-mapping method is presented, which does not require a reference ECG recording of the VT. A three-dimensional correlation gradient map is reconstructed by semiautomatic analysis of ECG morphological changes within the network of pace-mapping sites. In these maps, abnormal points are identified by high correlation gradient values (i.e., corresponding to slow propagation of the electric influx, as in the core of the reentrant VT circuit). The relation between the conventional and reference-less method is described theoretically and evaluated in a retrospective study including 24 VT ablation procedures. RESULTS: The "reference-less" method was able to identify normal points with a high accuracy (negative predictive value: NPV = 97%), and to detect more abnormal points, as predicted by the theory. Correlation gradients computed by the proposed method were significantly higher in ablation zones than in other zones of the ventricle (p < 10-12), indicating excellent prediction of the ablation targets. SIGNIFICANCE: The reference-less method might either be used in complement of the conventional method or to treat patients in whom VT cannot be induced during the intervention.

Isotropic Reconstruction of MR Images Using 3D Patch-Based Self-Similarity Learning.

Isotropic three-dimensional (3D) acquisition is a challenging task in magnetic resonance imaging (MRI). Particularly in cardiac MRI, due to hardware and time limitations, current 3D acquisitions are limited by low-resolution, especially in the through-plane direction, leading to poor image quality in that dimension. To overcome this problem, super-resolution (SR) techniques have been proposed to reconstruct a single isotropic 3D volume from multiple anisotropic acquisitions. Previously, local regularization techniques such as total variation have been applied to limit noise amplification while preserving sharp edges and small features in the images. In this paper, inspired by the recent progress in patch-based reconstruction, we propose a novel isotropic 3D reconstruction scheme that integrates non-local and self-similarity information from 3D patch neighborhoods. By grouping 3D patches with similar structures, we enforce the natural sparsity of MR images, which can be expressed by a low-rank structure, leading to robust image reconstruction with high signal-to-noise ratio efficiency. An Augmented Lagrangian formulation of the problem is proposed to efficiently decompose the optimization into a low-rank volume denoising and a SR reconstruction. Experimental results in simulations, brain imaging and clinical cardiac MRI, demonstrate that the proposed joint SR and self-similarity learning framework outperforms current state-of-the-art methods. The proposed reconstruction of isotropic 3D volumes may be particularly useful for cardiac applications, such as myocardial infarction scar assessment by late gadolinium enhancement MRI.

Pulmonary Circulation on the Crossroads Between the Left and Right Heart in Systemic Sclerosis: A Clinical Challenge for Cardiologists and Rheumatologists.

Involvement of the right heart-pulmonary circulation system in systemic sclerosis is a typical feature, with critical prognostic implications. Pulmonary hypertension may occur in association with interstitial lung disease or as a result of an isolated pulmonary vascular disease that may affect both the precapillary arterioles and the postcapillary venules, as well as a consequence of left heart involvement. These apparently different phenotypes often underlie a significant pathophysiologic overlap, which makes the diagnosis and management of these patients highly complex and uncertain.

The Right Heart-Pulmonary Circulation Unit and Left Heart Valve Disease.

Valvular heart disease (VHD) is frequently accompanied by pulmonary hypertension (PH). In asymptomatic patients, PH is rare, although the exact prevalence is unknown and mainly stems from the severity of the VHD and the presence of diastolic dysfunction. PH can also be depicted during exercise echocardiography. PH either at rest or during exercise is also a powerful determinant of outcome and is independently associated with reduced survival, regardless of the severity of the underlying valvular pathology. Therefore, because PH is a marker of poor prognosis, assessment of PH in VHD is crucial for risk stratification and management of patients with VHD.

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.

Can MRI detect pulmonary hypertension in a population pre-selected by echocardiography?

Background The place of magnetic resonance imaging (MRI) in the assessment of pulmonary hypertension (PH) remains controversial. Several studies proposed to use MRI to assess pulmonary pressure but the level of proof is low. Purpose To evaluate the diagnostic power of cardiac MRI within a non-selected population of patients suspected of PH after an echocardiography. Material and Methods Fifty-six consecutive patients, suspected of PH after an echocardiography, were assessed with right heart catheterization and cardiac MRI (including a high temporal resolution pulmonary flow curve). We extracted from the MRI data the main parameters proposed by all precedent studies available in the literature. We looked for multivariate linear relations between those parameters and the mean pulmonary arterial pressure (mPAP), and eventually assessed with a logit regression the ability of those parameters to diagnose PH in our population. Results The multivariate model retained only two parameters: the right ventricle ejection fraction and the pulmonary trunk minimum area. The prediction of mPAP (r2 = 0.5) yielded limits of agreement of 15 mmHg. However, the prediction of PH within the population was feasible and the method yielded a specificity of 80% for a sensitivity of 100%. Conclusion The performance of MRI to assess mPAP is too low to be used as a replacement for right heart catheterization but MRI could be used as second line examination after echocardiography to avoid right heart catheterization for normal patients.

Imaging the right heart pulmonary circulation unit: Insights from advanced ultrasound techniques.

The right heart pulmonary circulation unit (RH-PCU) is a key determinant of prognosis in several cardiorespiratory diseases. Although right heart catheterization is considered the gold standard for pulmonary hemodynamic assessment, a comprehensive cardiovascular ultrasound approach is an essential step in the diagnostic-prognostic clinical pathway of patients with suspect or overt pulmonary hypertension. The exponential development of advanced ultrasound techniques (strain, 3-dimensional echocardiography and lung ultrasound) has led to new insights into the evaluation of RH-PCU structure and function, overcoming some limitations of standard Doppler echocardiography. In the near future, exercise Doppler echocardiography may become a useful technique for detecting a latent stage of pulmonary hypertension and for evaluating right ventricular contractile reserve.

Hypereosinophilic cardiac disease.

Hypereosinophilia may be due to several aetiologies. Cardiac complications are not uncommon, whatever the causes. Clinical presentations of hypereosinophilic cardiac diseases may vary widely from asymptomatic form to fatal necrotic myocarditis or irreversible restrictive cardiomyopathy. As a major cause of morbidity and mortality, diagnosis of cardiac involvement is crucial. Until recently the diagnosis was exclusively based on cardiac biopsy. Nowadays, multimodal cardiac imaging, including echocardiography and cardiac magnetic resonance imaging, is the cornerstone of the diagnosis. Cardiac magnetic resonance imaging has emerged as a very useful tool for the diagnosis allowing precise tissue characterization. It has even been proposed as a surrogate to cardiac biopsy. It should be systematically performed in case of hypereosinophilia. Early and appropriate treatment is crucial to avoid the evolution toward irreversible cardiac lesions. These treatments are symptomatic but should also be adapted to the underlying diseases.

Bilateral vs unilateral internal mammary revascularization in patients with left ventricular dysfunction.

AIM: To investigate the survival benefit of bilateral internal mammary artery (BIMA) grafts in patients with left ventricular dysfunction. METHODS: Between 1996 and 2009, we performed elective, isolated, primary, multiple cardiac arterial bypass grafting in 430 consecutive patients with left ventricular ejection fraction ≤ 40%. The early and long-term results were compared between 167 patients undergoing BIMA grafting and 263 patients using left internal mammary artery (LIMA)-saphenous venous grafting (SVG). RESULTS: The mean age of the overall population was 60.1 ± 15 years. In-hospital mortality was not different between the two groups (7.8% vs 10.3%, P = 0.49). Early postoperative morbidity included myocardial infarction (4.2% vs 3.8%, P = 0.80), stroke (1.2% vs 3.8%, P = 0.14), and mediastinitis (5.3% vs 2.3%, P = 0.11). At 8-year follow-up, Kaplan-Meier-estimated survival (74.2% vs 58.9%, P = 0.02) and Kaplan-Meier-estimated event-free survival (all cause deaths, myocardial infarction, stroke, target vessel revascularization, heart failure) (61.7% and 41.1%, P < 0.01) were significantly higher in the BIMA group compared with the LIMA-SVG group in univariate analysis. The propensity score matching analysis confirmed that BIMA grafting is a safe revascularization procedure but there was no long term survival (P = 0.40) and event-free survival (P = 0.13) in comparison with LIMA-SVG use. CONCLUSION: Our longitudinal analysis suggests that BIMA grafting can be performed with acceptable perioperative mortality in patients with left ventricular dysfunction.

Exercise Testing and Stress Imaging in Mitral Valve Disease.

OPINION STATEMENT: Mitral valve disease represented by mitral stenosis and mitral regurgitation is the second most frequent valvulopathy. Mitral stenosis leads to an increased left atrial pressure whereas mitral regurgitation leads to an increased left atrial pressure associated with a volume overload. Secondary to an upstream transmission of this overpressure, both mitral stenosis and regurgitation lead to pulmonary hypertension and right heart failure. In addition, mitral regurgitation also leads to left ventricular dilatation and dysfunction with left heart failure. Depending on the anatomy of the valvular and subvalvular apparatus, valve repair (percutaneous mitral commissurotomy for mitral stenosis and valvuloplasty for mitral regurgitation) might be possible. If the anatomy is not favorable, valve replacement by mechanical or biological prosthesis is indicated. Most of the intervention indications are based on clinical symptoms and resting transthoracic echocardiography. Outcomes of patients operated based upon resting echo abnormalities might however not be optimal. Therefore early intervention might be beneficial based upon abnormal exercise testing, which has been demonstrated to more sensitive to identify high-risk patients. In this last decade, especially exercise echocardiography has been found to be a crucial tool in the management of patients with mitral valve disease.

Interactions between mitral valve and left ventricle analysed by 2D speckle tracking in patients with mitral valve prolapse: one more piece to the puzzle.

AIMS: Two-dimensional echocardiography often reveals abnormal left ventricle (LV) lateral wall kinetics in patients presenting with mitral valve prolapse (MVP). However, relations between MVP and LV deformation are not clearly established. The aim of this study was to assess and quantify mitral valve chordae, leaflets, and LV myocardial interactions using speckle tracking echocardiography (STE). METHODS AND RESULTS: Using STE-derived longitudinal strain curves, LV peak longitudinal strain (PLS, %), post-systolic index (PSI), and pre-stretch index (PST) were analysed in 100 patients with MVP and normal LV ejection fraction. Global, regional, and segmental values were compared according to mitral regurgitation severity and MVP location. Twenty healthy subjects served as control patients. There was no significant difference among control and MVP group for global and regional PLS (-23.7 ± 3.2 vs. -23.1 ± 2.2). In contrast, patients with MVP had significantly higher values of global PST (3.2 ± 4.1 vs. 1.3 ± 1.2; P = 0.01) and global PSI (3.2 ± 0.4 vs. 1.7 ± 1.1; P = 0.05) compared with controls, located mainly in the lateral wall and basal segments. Both anterior and posterior MVPs were responsible for PSI in basal inferior segments and PST in anterior ones. Mid-wall segmental deformation pattern changes were mainly observed at the level of the segments adjacent to the papillary muscle. CONCLUSION: This study supports the hypothesis that pathological early-systolic shortening and late systolic, post-systolic deformation are attributed to an increased interaction between wall deformation and mitral valve events in patients with MVP. STE is a useful tool in the assessment of interplays between MV leaflets and myocardium and helps to demonstrate changes in temporal pattern of myocardial deformation.

Ventricular Dysfunction in Patients with Acute Coronary Syndrome Undergoing Coronary Surgical Revascularization: Prognostic Impact on Long-Term Outcomes.

BACKGROUND: Patients with non-ST elevation acute coronary syndrome complicated by left ventricular dysfunction (LVEF) are a poor prognosis group. The aim of our study was to assess the short and long term LEVF prognostic value in a cohort of NSTE-ACS patients undergoing surgical revascularization. METHODS: We performed elective and isolated CABG on a cohort of 206 consecutive patients with LVEF≤0.40 complicating acute coronary syndrome. The case cohort was compared with a cohort of controls (LVEF>0.40) randomly selected (2:1) among patients who underwent the procedure during this period. RESULTS: The Kaplan-Meier 5-year estimated survival rates for patients in the low and normal LVEF groups were 70.8% (95% confidence interval CI: 64.2-77.4) and 81.7% (95%CI: 77.8-85.6), respectively. A low LVEF was associated with both a higher all-cause (HR [95%CI] = 1.84[1.18-2.86]) and a higher cardiovascular mortality (HR = 2.07 [1.27-3.38]) during the first 12 months of follow-up. After adjustment for potential confounders, a low LVEF remained associated with a higher cardiovascular mortality only (1.87[1.03-3.38]) during the first 12 months of follow-up. After 12 months of follow-up, a low LVEF was no more associated with all-cause, nor cardiovascular mortality. CONCLUSION: Patients with low LVEF might require more intensive care than patients with normal LVEF during the year after the surgical procedure, but once the first postoperative year over, the initial low LVEF was no more associated with long term mortality.

Prediction of new onset of resting pulmonary arterial hypertension in systemic sclerosis.

BACKGROUND: Early detection of pulmonary arterial hypertension (PH) is crucial in systemic scleroderma. However, predictors of new onset of resting PH during follow-up (FUPH) have been poorly explored. AIM: To determine whether nailfold videocapillaroscopy (NVC) grade and exercise echocardiographic variables are predictors of FUPH. METHODS: We prospectively enrolled 40 patients with systemic sclerosis (age 54±13 years; 68% women). All patients underwent graded semisupine exercise echocardiography and NVC. Baseline resting PH and FUPH were defined as systolic pulmonary arterial pressure (sPAP)>35 mmHg, and exercise-induced PH (EIPH) as exercise sPAP>50 mmHg. RESULTS: Seventeen patients developed EIPH (43%). During follow-up (FU) (25±15 months), 11 patients without baseline PH developed FUPH (28%), all from the EIPH group. Patients with FUPH were significantly older (60±14 vs 50±12 years; P=0.04), had higher resting and exercise sPAP (30±4 vs 22±5 and 60±12 vs 40±11 mmHg, respectively; P<0.0001) and a higher exercise E/e' ratio (9.4±0.7 vs 5.8±0.4; P=0.0003) and presented more frequently NVC grade>2 (90% vs 35%; P=0.0009). After adjustment for age, resting sPAP, exercise sPAP and NVC grade>2 were associated with maximal resting sPAP during follow-up and FUPH (P<0.05). Patients with both EIPH and NVC grade>2 had a very high incidence of FUPH (82%), and both variables remained strongly associated with FUPH after adjustment for age (hazard ratio 11.6, 95% confidence interval 2.4-55.3; P=0.002). CONCLUSION: Exercise echocardiography and NVC can identify a subgroup of patients with systemic sclerosis who are at risk of developing FUPH.

Impact of Serial B-Type Natriuretic Peptide Changes for Predicting Outcome in Asymptomatic Patients With Aortic Stenosis.

BACKGROUND: The aim of this study was to determine the impact on the outcome of serial B-type natriuretic peptide (BNP) changes during follow-up in asymptomatic patients with ≥ moderate aortic stenosis (AS) and preserved left ventricular ejection fraction. METHODS: We prospectively screened 69 patients who underwent comprehensive transthoracic echocardiography, BNP level measurement at baseline and after every 6 or 12 months. Annualized BNP changes were calculated as the difference between the last and baseline BNP measurements divided by the duration of follow-up. The primary endpoint was the occurrence of symptoms, aortic valve replacement, or cardiovascular death. RESULTS: During a follow-up of 30 ± 19 months, 43 patients experienced a cardiac event. These patients were significantly older (73 ± 9 vs 65 ± 16 years; P = 0.010), had more often dyslipidemia (79% vs 42%; P = 0.038), more severe AS (peak velocity: 3.9 ± 0.6 vs 3.5 ± 0.6 m/s; P = 0.002), larger indexed left atrial area (10.2 ± 2.5 vs 8.7 ± 1.9 cm(2)/m(2); P = 0.006), and a higher increase in annualized BNP (+90 ± 155 vs +7 ± 49 pg/mL/y; P = 0.010). Patients with higher annualized BNP changes (> 20 pg/mL/y) had a significantly lower cardiac event-free survival (1 year: 63 ± 8% vs 97 ± 3%; 3 years: 31 ± 8% vs 68 ± 8%; P < 0.001). Using the multivariate Cox proportional hazards model, higher annualized BNP changes were significantly associated with increased risk of cardiac events (hazard ratio: 2.73, 95% confidence interval: 1.27-5.86; P = 0.010) after adjustment for age, dyslipidemia, and echocardiographic parameters. CONCLUSIONS: In asymptomatic patients with AS and preserved left ventricular ejection fraction, the use of serial BNP changes may help to anticipate development of class I indication for aortic valve replacement.