Phenotype/Genotype Relationship in Left Ventricular Noncompaction: Ion Channel Gene Mutations Are Associated With Preserved Left Ventricular Systolic Function and Biventricular Noncompaction: Phenotype/Genotype of Noncompaction.

BACKGROUND: Few data exist concerning genotype-phenotype relationships in left ventricular noncompaction (LVNC). METHODS AND RESULTS: From a multicenter French Registry, we report the genetic and clinical spectrum of 95 patients with LVNC, and their genotype-phenotype relationship. Among the 95 LVNC, 45 had at least 1 mutation, including 14 cases of mutation in ion channel genes. In a complementary analysis including 16 additional patients with ion channel gene mutations, for a total of 30 patients with ion channel gene mutation, we found that those patients had higher median LV ejection fraction (60% vs 40%; P < .001) and more biventricular noncompaction (53.1% vs 18.5%; P < .001) than the 81 other patients with LVNC. Among them, both the 19 patients with an HCN4 mutation and the 11 patients with an RYR2 mutation presented with a higher LV ejection fraction and more frequent biventricular noncompaction than the 81 patients with LVNC but with no mutation in the ion channel gene, but only patients with HCN4 mutation presented with a lower heart rate. CONCLUSIONS: Ion channel gene mutations should be searched systematically in patients with LVNC associated with either bradycardia or biventricular noncompaction, particularly when LV systolic function is preserved. Identifying causative mutations is of utmost importance for genetic counselling of at-risk relatives of patients affected by LVNC.

Prognosis of Adults With Isolated Left Ventricular Non-Compaction: Results of a Prospective Multicentric Study.

Background: Whether left ventricular non-compaction (LVNC) bears a different prognosis than dilated cardiomyopathy (DCM) is still a matter of debate. Methods: From a multicenter French prospective registry, we compared the outcomes of 98 patients with LVNC and 65 with DCM. The primary endpoint combined cardiovascular death, heart transplantation, and hospitalization for cardiovascular events. The two groups presented similar outcomes but different left ventricular ejection fractions (LVEF) (43.3% in LVNC vs. 35.95% in DCM, p = 0.001). For this reason, a subgroup analysis was performed comparing only patients with LVEF ≤ 45%, including 56 with LVNC and 49 with DCM. Results: Among patients with LVEF≤ 45%, at 5-year follow-up, the primary endpoint occurred in 33 (58.9%) among 56 patients with LVNC and 18 (36.7%) among 49 patients with DCM (p = 0.02). Hospitalization for heart failure (18 [32.14%] vs. 5 [10.20%], p = 0.035) and heart transplantation were more frequent in the LVNC than in the DCM group. The incidences of rhythmic complications (24 [42.85%] vs. 12 [24.48%], p = 0.17), embolic events, and cardiovascular death were similar between LVNC and DCM cases. Among the 42 patients with LVNC and LVEF > 45%, the primary endpoints occurred in only 4 (9.52%) patients, including 2 hospitalizations for heart failure and 3 rhythmic complications, but no embolic events. Conclusion: In this prospective cohort, patients with LVNC who have left ventricular dysfunction present a poorer prognosis than DCM patients. Heart failure events were especially more frequent, but embolic events were not. Patients with LVNC and preserved ejection fraction present very few events in 5 years.

Right ventricular longitudinal strain: a tool for diagnosis and prognosis in light-chain amyloidosis.

OBJECTIVES: Light-chain (AL) amyloidosis can lead to an infiltrative cardiomyopathy with increased wall thickness (IWT) of very poor prognosis. Our primary aim was to analyse the right ventricle (RV) in patients with IWT to discriminate AL amyloidosis from IWT due to hypertrophic cardiomyopathy (HCM) or to arterial hypertension (HTN). Our secondary aim was to assess if RV dysfunction predicts overall mortality in cardiac AL amyloidosis. METHODS: We retrospectively and consecutively compared clinical, biological and echocardiographic data of 315 patients with IWT: 105 biopsy-proven AL amyloidosis patients, 105 patients with HCM and 105 patients with HTN. The prognostic value of these parameters was analysed in the AL amyloidosis group. RESULTS: Free-wall right ventricular longitudinal strain (FWRVLS) worse than -21.2% discriminates AL amyloidosis [area under the curve (AUC) = 0.744)] from patients with IWT due to other aetiologies. In AL amyloidosis, FWRVLS is the strongest echocardiographic prognostic marker with AUC =0.722 and -16.5% as the optimal cut-off value, beyond which overall mortality increases significantly. It is also the only independent echocardiographic predictor of overall mortality (HR =1.113; 95%CI 1.029-1.204; p = .007), even when adjusted to the Mayo stage and global left ventricular longitudinal strain. CONCLUSIONS: FWRVLS should be considered in the diagnostic and prognostic workup in light-chain amyloidosis.

Acquired Systemic-to-pulmonary Venous Shunt or Persistent Left Superior Vena Cava? A Rare Right-to-left Shunt Case-based Discussion.

Cardiac shunts are often described in congenital or pediatric populations, but systemic-to-pulmonary venous shunts in adult patients are reported in literature in isolated case reports. We present the case of a 70-year-old female with a left superior vena cava (SVC) draining into the left atrium by the left superior pulmonary vein, with a complete right-to-left shunt of the superior venous circulation caused by a former catheter thrombosis in the right SVC. Diagnosis was suspected after a contrast echocardiography showing an exclusive perfusion of left heart after intravenous injection and confirmed by helical computed tomography with three-dimensional reconstruction. After medico-surgical discussion, a first-line conservative treatment with oxygen therapy was chosen, due to the stability of symptoms and high predicted risk of perioperative mortality. The particularities of this case are that we cannot determine if the origin of this shunt is a latent persistent left SVC becoming symptomatic after the SVC obstruction or an abnormal collateral pathway due to the thrombosis and the unusual indirect communication through a pulmonary vein.

Quantitative regional analysis of left atrial function by Doppler tissue imaging-derived parameters discriminates patients with posterior and anterior myocardial infarction.

BACKGROUND: Doppler tissue imaging can now be used for the assessment of left atrial (LA) function. LA function was evaluated by this technique in a group of patients hospitalized for acute myocardial infarction and in a control population. METHODS: Patients were all prospectively imaged with a scanner. To study the LA, a region of interest was located in the proximal part of the lateral and septal LA walls. Doppler tissue imaging, tissue tracking, strain, and delays were recorded. RESULTS: In all, 12 patients with posterior (age 54 +/- 9 years) and 13 with anterior (age 64 +/- 16 years) acute myocardial infarction, along with 16 control patients (age 54 +/- 9 years), were analyzed. Early diastolic septal velocity was found to be the best parameter for discriminating among the 3 groups. Peak strain was also relevant and did not correlate with left ventricular function. CONCLUSIONS: LA is accessible to Doppler tissue imaging analysis. Strain can quantify LA function relatively independently of left ventricular function, and may provide new insights on LA function.

Tissue Doppler echocardiographic quantification. Comparison to coronary angiography results in Acute Coronary Syndrome patients.

BACKGROUND: Multiples indices have been described using tissue Doppler imaging (DTI) capabilities. The aim of this study was to assess the capability of one or several regional DTI parameters in separating control from ischemic myocardium. METHODS: Twenty-eight patients with acute myocardial infarction were imaged within 24-hour following an emergent coronary angioplasty. Seventeen controls without any coronary artery or myocardial disease were also explored. Global and regional left ventricular functions were assessed. High frame rate color DTI cineloop recordings were made in apical 4 and 2-chamber for subsequent analysis. Peak velocity during isovolumic contraction time (IVC), ejection time, isovolumic relaxation (IVR) and filling time were measured at the mitral annulus and the basal, mid and apical segments of each of the walls studied as well as peak systolic displacement and peak of strain. RESULTS: DTI-analysis enabled us to discriminate between the 3 populations (controls, inferior and anterior AMI). Even in non-ischemic segments, velocities and displacements were reduced in the 2 AMI populations. Peak systolic displacement was the best parameter to discriminate controls from AMI groups (wall by wall, p was systematically < 0.01). The combination IVC + and IVR< 1 discriminated ischemic from non-ischemic segments with 82% sensitivity and 85% specificity. CONCLUSION: DTI-analysis appears to be valuable in ischemic heart disease assessment. Its clinical impact remains to be established. However this simple index might really help in intensive care unit routine practice.

Does exercise have deleterious consequences for the lungs of patients with chronic heart failure?

Changes in lung function in patients with chronic heart failure (CHF), usually reported at rest, may be exacerbated during exercise and induce post-exercise effects. We investigated the hypothesis that post-exercise induced changes in lung function in CHF patients are due to the consequences of left atrial overload. Twenty-one CHF patients and six healthy subjects (Ctrl) participated in this study. Transfer lung capacity for carbon monoxide (T(LCO)) and maximal expiratory flows (V (max)) were measured before a maximal exercise test and 1h, 2h and 20h afterwards. CHF patients were divided in two groups according to their ventilatory response to the maximal exercise test (V(E) vs. V(CO(2)) relationship slopes above or below 34, i.e., CHF>34 and CHF<34). Compared with the Ctrl group, in CHF groups resting T(LCO) and V(max) were lower. After exercise, further changes in T(LCO) and V(max) were observed in CHF>34. T(LCO) per unit volume (K(CO)) was increased 1h post-exercise while maximal expiratory flow between 25 and 75% of forced vital capacity was decreased 2h and 20h post-exercise. We observed a negative correlation between the delta T(LCO) 1h post-exercise from rest and the delta T(LCO) 2h post-exercise from rest. The decreases in pulmonary V(max) we observed well after exercise following increases in K(CO) in patients with high ventilatory response to exercise (CHF>34) might indicate bronchial congestion resulting from increased left atrial pressure during exercise. We propose that endurance training should be prescribed cautiously for these patients.

Resting echocardiographic assessments of left atrial function and filling pressure interest in the understanding of exercise capacity in patients with chronic congestive heart failure.

OBJECTIVE: Doppler echocardiography is well recognized as the primary noninvasive imaging technique to assess global and regional cardiac function. Cardiopulmonary exercise testing has become a powerful tool to predict outcome in chronic heart failure (CHF). We looked for cardiac determinants, using resting echocardiographic parameters, of exercise tolerance in patients with CHF. METHODS: Transthoracic echocardiography and standardized cardiopulmonary exercise testing were performed in 75 patients (59 +/- 11 years) with CHF, New York Heart Association functional class II to III. Systolic and diastolic function, filling pressures, and left ventricular, right ventricular, and left atrial (LA) regional function were assessed using Doppler tissue velocities and strain values. RESULTS: Maximal workload (86 +/- 41 W) and peak oxygen (14.6 +/- 3.1 mL/min/kg) correlated with left ventricular filling pressure estimates (E/Ea and E/Vp) but also with end-diastolic pulsed Doppler tissue velocity at the mitral annulus (Aa), LA volume, and regional LA function assessed by strain analysis. In multivariate analysis, maximum workload and peak oxygen were shown to correlate with right ventricular peak strain, although Aa and E/Ea were the best predictors of exercise capacity. CONCLUSION: Capacity to exercise in patients with CHF is understandable by resting echocardiography. Filling pressures, and LA and right ventricular functions, are its cardiac best determinants. Adding Aa peak velocity in resting echocardiographic evaluation of patients with CHF is found useful.

Echocardiographic right ventricular strain analysis in chronic heart failure.

OBJECTIVE: We sought to compare the additive value of right ventricular (RV) function assessed by longitudinal systolic strain (epsilon% - ROI: 9.2 at 10.8 mm) with cardiopulmonary exercise testing (CPET) or brain natriuretic peptide (BNP) in patients with heart failure (HF). METHOD: We studied 19-patients (age = 56 +/- 8 years) in New York Heart Association HF class III-IV, who underwent standard and tissue Doppler echocardiography, CPET and BNP measurements on the same day. RV function was assessed by systolic strain (epsilon, %, ROI: 9.2-10.8 mm) in the mid-segment. Clinical outcomes were examined at 6 months. RESULTS: epsilon (-19.9+/-6.8%) was correlated with BNP (R = 0.52, P = 0.02), slope VE/VCO(2) (R = -0.65, P = 0.003), peak VO(2) (R = 0.46, P = 0.04) and the maximal workload (Watts) developed during CPET (R = 0.54, P=0.02). During follow-up, 1-patient died, 1-underwent heart transplantation, and 4 were re-hospitalized for worsening HF. Patients with major adverse cardiac events (MACE) had a significantly higher mean BNP concentration (852.8 ng/mL +/- 1114.3 vs. 201.4+ /- 293.8, P = 0.03), higher VE/VCO(2) (41.3 +/- 3.6 vs. 35.0 +/- 4.8 P < 0.001) and lower epsilon (-13.9 +/- 4.9 vs. -22.2+ /- 5.8, P < 0.001) than patients who remained MACE-free. By multivariate analysis, ST was the only predictor of MACE. CONCLUSION: In HF-patients presenting, RV-function assessed by systolic epsilon was reliable, easily measurable and a stronger prognosticator than CPET or BNP.