Left ventricular fibrosis as a main determinant of filling pressures and left atrial function in advanced heart failure.

AIMS: Advanced heart failure (AdHF) is characterized by variable degrees of left ventricular (LV) dysfunction, myocardial fibrosis, and raised filling pressures which lead to left atrial (LA) dilatation and cavity dysfunction. This study investigated the relationship between LA peak atrial longitudinal strain (PALS), assessed by speckle-tracking echocardiography (STE), and invasive measures of LV filling pressures and fibrosis in a group of AdHF patients undergoing heart transplantation (HTX). METHODS AND RESULTS: We consecutively enrolled patients with AdHF who underwent HTX at our Department. Demographic and basic echocardiographic data were registered, then invasive intracardiac pressures were obtained from right heart catheterization, and STE was also performed. After HTX, biopsy specimens from explanted hearts were collected to quantify the degree of LV myocardial fibrosis. Sixty-four patients were included in the study (mean age 62.5 ± 11 years, 42% female). The mean LV ejection fraction (LVEF) was 26.7 ± 6.1%, global PALS was 9.65 ± 4.5%, and mean pulmonary capillary wedge pressure (PCWP) was 18.8 ± 4.8 mmHg. Seventy-three % of patients proved to have severe LV fibrosis. Global PALS was inversely correlated with PCWP (R = -0.83; P < 0.0001) and with LV fibrosis severity (R = -0.78; P < 0.0001) but did not correlate with LVEF (R = 0.15; P = 0.2). Among echocardiographic indices of LV filling pressures, global PALS proved the strongest [area under the curve 0.955 (95% confidence interval 0.87-0.99)] predictor of raised (>18 mmHg) PCWP. CONCLUSION: In patients with AdHF, reduced global PALS strongly correlated with the invasively assessed LV filling pressure and degree of LV fibrosis. Such relationship could be used as non-invasive indicator for optimum patient stratification for therapeutic strategies.

The Impact of Mental Stress on Cardiovascular Health-Part II.

Endothelial dysfunction is one of the earliest manifestations of atherosclerosis, contributing to its development and progression. Mental stress induces endothelial dysfunction through increased activity of the sympathetic nervous system, release of corticotropin-releasing hormone from the hypothalamus, inhibition of nitric oxide (NO) synthesis by cortisol, and increased levels of pro-inflammatory cytokines. Mental-stress-induced increased output of the sympathetic nervous system and concomitant withdrawal of the parasympathetic inflammatory reflex results in systemic inflammation and activation of a neural-hematopoietic-arterial axis. This includes the brainstem and subcortical regions network, bone marrow activation, release of leukocytes into the circulation and their migration to the arterial wall and atherosclerotic plaques. Low-grade, sterile inflammation is involved in all steps of atherogenesis, from coronary plaque formation to destabilisation and rupture. Increased sympathetic tone may cause arterial smooth-muscle-cell proliferation, resulting in vascular hypertrophy, thus contributing to the development of hypertension. Emotional events also cause instability of cardiac repolarisation due to brain lateralised imbalance of cardiac autonomic nervous stimulation, which may lead to asymmetric repolarisation and arrhythmia. Acute emotional stress can also provoke severe catecholamine release, leading to direct myocyte injury due to calcium overload, known as myocytolysis, coronary microvascular vasoconstriction, and an increase in left ventricular afterload. These changes can trigger a heart failure syndrome mimicking acute myocardial infarction, characterised by transient left ventricular dysfunction and apical ballooning, known as stress (Takotsubo) cardiomyopathy. Women are more prone than men to develop mental-stress-induced myocardial ischemia (MSIMI), probably reflecting gender differences in brain activation patterns during mental stress. Although guidelines on CV prevention recognise psychosocial factors as risk modifiers to improve risk prediction and decision making, the evidence that their assessment and treatment will prevent CAD needs further evaluation.

Detection of myocardial fibrosis by speckle-tracking echocardiography: from prediction to clinical applications.

Myocardial fibrosis (MF) represents the underlying pathologic condition of many cardiac disease, leading to cardiac dysfunction and heart failure (HF). Biopsy studies have shown the presence of MF in patients with decompensating HF despite apparently normal cardiac function. In fact, basic indices of left ventricular (LV) function, such as LV ejection fraction (EF), fail to recognize subtle LV dysfunction caused by MF. Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) is currently recognized as the gold standard imaging investigation for the detection of focal and diffuse cardiac chambers MF; however, its use is limited by its availability and the use of contrast agents, while echocardiography remains the first level cardiac imaging technique due to its low cost, portability and high accessibility. Advanced echocardiographic techniques, above all speckle-tracking echocardiography (STE), have demonstrated reliability for early detection of structural myocardial abnormalities and for the prediction of prognosis in acute and chronic HF. Myocardial strain of both ventricles and also left atrium has been shown to correlate with the degree of MF, providing useful prognostic information in several diseases, such as HF, cardiomyopathies and valvular heart disease. This paper aims to provide an overview of the pathophysiology of MF and the clinical application of STE for the prediction of left and right heart chambers MF in HF patients.

Left atrial strain by speckle tracking predicts atrial fibrosis in patients undergoing heart transplantation.

AIMS: In patients with heart failure (HF), chronically raised left ventricular (LV) filling pressures lead to progressive left atrial (LA) dysfunction and fibrosis. We aimed to assess the correlation of LA reservoir strain (peak atrial longitudinal strain, PALS) by speckle tracking echocardiography (STE) and LA fibrosis assessed by myocardial biopsy in patients undergoing heart transplantation (HTx). METHODS AND RESULTS: Forty-eight patients with advanced HF [mean age 51.2 ± 8.1 years, 29% females; LV ejection fraction ≤25% and New York Heart Association (NYHA) class III-IV] referred for HTx were enrolled and underwent pre-operative echocardiographic evaluation, right heart catheterization, and cardiopulmonary exercise testing. Exclusion criteria were non-sinus rhythm, mechanical ventilation, severe mitral/tricuspid regurgitation, or other valvular disease and poor acoustic window. After HTx, LA bioptic samples were collected and analysed to determine the extent of myocardial fibrosis (%). LA fibrosis showed correlation with PALS (R = -0.88, P < 0.0001), VO2max (R = -0.68, P < 0.0001), NYHA class (R = 0.66, P < 0.0001), LA stiffness (R = 0.58, P = 0.0002), and E/e' (R = 0.44, P = 0.005), while poorly correlated with E/A ratio (R = 0.23, P = 0.21). PALS had a good correlation with NYHA class (R = -0.64, P < 0.0001), PAoP (R = -0.61, P = 0.03) and VO2max (R = 0.57, P = 0.0001). Multivariate regression analysis identified PALS (beta = -0.91, P < 0.001) and LA Volume (beta = -0.19, P = 0.03) as predictors of LA Fibrosis, while E/e' was not a significant predictor (beta = 0.15, P = 0.08). CONCLUSION: Emerging as a possible index of myocardial fibrosis in patients with advanced HF, PALS could help to optimize the management and the selection of those patients with irreversible LA structural damage for advanced therapeutic strategies.

Myocardial Work Does Not Have Additional Diagnostic Value in the Assessment of ATTR Cardiac Amyloidosis.

BACKGROUND: Reduced LV longitudinal strain (GLS) and increased relative apical sparing (RELAPS) and increased wall thickness have been proposed as features for transthyretin cardiac amyloidosis (ATTR-CA). Myocardial work (MW) has recently been shown as useful afterload independent disease marker, hence we aimed to investigate its use in differentiating ATTR-CA from heart failure with increased septal thickness but no cardiac amyloidosis (CA) (HFnCA). METHODS: This study included patients with HF and increased septal thickness ≥ 14 mm. We included 59 patients with hereditary (ATTRv) and 27 wild type transthyretin amyloidosis (ATTRwt) described as ATTR-CA based on DPD scintigraphy. We also enrolled 30 non-amyloidosis heart failure patients with negative DPD scintigraphy, as a control group. Myocardial work (MW) was used to assess the index (GWI), constructive (GCW) and wasted (GWW) work. Relative wall thickness (RWT) and relative apical sparing (RELAPS) were tested as conventional measures. RESULTS: The RWT and RELAPS were higher in ATTR-CA (p < 0.001) and predicted ATTR-CA (RWT; AUC = 0.84, p < 0.001) and RELAPS (AUC = 0.81, p < 0.001). MW; GWI (p = 0.04), GCW (p = 0.03), GWW (p = 0.001) were all lower in ATTR-CA compared with HFnCA but only GWW predicted ATTR-CA, (AUC = 0.75, p < 0.001). Binary logistic univariate regression analysis showed RWT (p = 0.003, ß = 16.2) and RELAPS (p = 0.003, ß = 2.3) to be associated with ATTR-CA but not MW. GWI and GCW correlated with NT-proBNP (p < 0.05) and Troponin (p < 0.01), but not RWT or RELAPS. CONCLUSION: Myocardial work had lower accuracy, compared to RWT or RELAPS, in identifying ATTR-CA but was better related to biomarkers. Thus, MW assessment is unlikely to have additional value in improving the diagnosis of heart failure due to ATTR-CA.

Aortic Valve Stenosis and Cardiac Amyloidosis: A Misleading Association.

The association between aortic stenosis (AS) and cardiac amyloidosis (CA) is more frequent than expected. Albeit rare, CA, particularly the transthyretin (ATTR) form, is commonly found in elderly people. ATTR-CA is also the most prevalent form in patients with AS. These conditions share pathophysiological, clinical and imaging findings, making the diagnostic process very challenging. To date, a multiparametric evaluation is suggested in order to detect patients with both AS and CA and choose the best therapeutic option. Given the accuracy of modern non-invasive techniques (i.e., bone scintigraphy), early diagnosis of CA is possible. Flow-charts with the main CA findings which may help clinicians in the diagnostic process have been proposed. The prognostic impact of the combination of AS and CA is not fully known; however, new available specific treatments of ATTR-CA have changed the natural history of the disease and have some impact on the decision-making process for the management of AS. Hence the relevance of detecting these two conditions when simultaneously present. The specific features helping the detection of AS-CA association are discussed in this review, focusing on the shared pathophysiological characteristics and the common clinical and imaging hallmarks.

Computed Histological Quantification of Atherosclerotic Plaque Microcalcifications.

Inflammation has a central role in atherosclerotic plaque formation and rupture. Intense macrophage inflammatory activity results in microcalcifications which are strongly associated with plaque vulnerability. Microcalcifications with specific critical size between 5 and 65 µ, located in the fibrous cap producing local mechanical stress on the plaque surface and may directly contribute to plaque rupture. Hence, accurate assessment of microcalcifications size and dimension has significant clinical importance. Current invasive and noninvasive plaque imaging has limited spatial resolution which limits accurate definition of microcalcifications in the atherosclerotic plaques. We describe a new imaging technique with high spatial resolution, based on confocal microscopic analysis, using a dedicated software which allows automatic characterization of microcalcifications and quantitative assessment of their extent and localization.

Left atrial structure and function predictors of recurrent fibrillation after catheter ablation: a systematic review and meta-analysis.

BACKGROUND: Catheter ablation (CA) has become a conventional treatment for atrial fibrillation (AF), but remains with high recurrence rate. The aim of this meta-analysis was to determine left atrial (LA) structure and function indices that predict recurrence of AF. METHODS: We systematically searched PubMed-Medline, EMBASE, Scopus, Google Scholar and the Cochrane Central Registry, up to September 2017 in order to select clinical trials and observational studies which reported echocardiographic predictors of AF recurrence after CA. Eighty-five articles with a total of 16 126 patients were finally included. RESULTS: The pooled analysis showed that after a follow-up period of 21 ± 12 months, patients with AF recurrence had larger LA diameter with weighted mean difference (WMD: 2·99 ([95% CI 2·50-3·47], P<0·001), larger LA volume index (LAVI) maximal and LAVI minimal (P<0·0001 for both), larger LA area (P<0·0001), lower LA strain (P<0·0001) and lower LA total emptying fraction (LA EF) (P<0·0001) compared with those without AF recurrence. The most powerful LA predictors (in accuracy order) of AF recurrence were as follows: LA strain <19% (OR: 3·1[95% CI, -1.3-10·4], P<0·0001), followed by LA diameter ≥50 mm (OR: 2·75, [95% CI 1·66-4·56,] P<0·0001), and LAVmax >150 ml (OR: 2·25, [95% CI, 1.1-5·6], P = 0·0002). CONCLUSIONS: Based on this meta-analysis results, a dilated left atrium with diameter more than 50 mm and volume above 150 ml or myocardial strain below 19% reflect an unstable LA that is unlikely to hold sinus rhythm after catheter ablation for atrial fibrillation.

Early Recovery of Left Ventricular Function After Revascularization in Acute Coronary Syndrome.

The aim of this study was to assess the accuracy of echocardiographic techniques in detecting the early recovery of left ventricular (LV) function after revascularization in acute coronary syndrome (ACS). In 80 consecutive patients with ACS (age 55.7 ± 9.4 years, 77% male, 15% with CCS Angina III), an echocardiographic examination of left ventricle regional wall motion abnormalities (LV RWMA), peak systolic strain rate (PSSR), peak systolic strain (PSS) and end systolic strain (ESS) was performed before and after percutaneous intervention (PCI). Of the 80 patients, one vessel stenosis (>70%) was present in 53 (66%), two vessel disease in 12 (15%) and multivessel disease in 15 patients (19%). In total, 51% of patients had hypertension, 40% diabetes and 23% dyslipidemia. After PCI, regional PSS, ESS and PSSR of their segments subtended by the culprit vessel improved; left anterior descending-LAD, circumflex-LCx and right coronary-RCA (p<0.05 for all) as well as global S and SR (p < 0.05 for all). In univariate analysis, hypertension (HTN) (ß = -0.294 (-0.313-0.047), p = 0.009, smoking ß = -0.244 (-0.289-0.015) =0.03, WMA ß = -0.317 (-0.284-0.014), p = 0.004 and the number of diseased vessels ß = -0.256 (-0.188- 0.054) p=0.03 were predictors of delta global SR. In multivariate analysis, only HTN ß = 0.263 (0.005-3.159) and the number of diseased vessels ß =0.263 (0.005 - 3.159), p=0.04) predicted delta global SR. In ACS, the echocardiographic regional myocardial deformation is accurate in detecting early recovery of LV myocardial function after culprit lesion revascularization. Also, the findings of this study support the current practice regarding the crucial importance of proximal epicardial vessel PCI treatment on LV function compared to more distal lesions.

ACUTE HF score, a multiparametric prognostic tool for acute heart failure: A real-life study.

BACKGROUND: Acute heart failure (AHF) is the first cause of hospitalization for over-65 individuals, associated with high mortality and readmission rate. The aim of this study was to assess the prognostic value of a multiparametric score combining clinical, biochemical and echocardiographic indexes in AHF for clinical practice. METHODS: 830 patients hospitalized for AHF were enrolled. Exclusion criteria were: active neoplasms; previous heart transplantation or left ventricular assist device implantation. Different variables were analyzed: etiology of AHF, clinical and biochemical data, lung congestion on chest-X ray, echocardiographic parameters and administered therapy. The endpoints were: all-cause mortality at 30 days, 6 months and 5 years and the duration of hospitalization. RESULTS: 771 patients met eligibility criteria. Using the univariate and multivariate analysis the indexes with the best correlation with outcome were discretized and used to create the ACUTE HF score, computed as: 1.4*[serum creatinine>2 mg/dl] + 0.8*[ejection fraction<30] + 0.7*[age > 76] + 0.7*[prior hospitalization for AHF] + 0.9*[prior stroke/transient ischemic attack] + 0.5*[more than moderate mitral regurgitation] + 0.8*[use of non-invasive ventilation] and used to divide patients into 3 groups according to the risk of 6-months mortality. With the receiver operating curves and Kaplan-Meier analysis, this score proved to have a high predictive power for mortality at 30 days, 6 months and 5 years from hospitalization, and for event-free survival rates, providing a risk stratification capability superior to that of single variables. CONCLUSIONS: The ACUTE HF score could be a complete and useful tool for assessing prognosis of AHF patients. It could represent a step in the long standardization pathway of prognostic protocols for AHF.

Right ventricular involvement in transthyretin amyloidosis.

BACKGROUND: The extent of right ventricular (RV) involvement in transthyretin amyloidosis (ATTR) is unknown. OBJECTIVES: This study sought to establish the degree of RV involvement in ATTR amyloidosis, and compare findings with RV involvement in hypertrophic cardiomyopathy (HCM). METHODS: Forty-two patients with ATTR amyloidosis and echocardiographic evidence of cardiac amyloidosis (cardiac ATTR), 19 ATTR patients with normal left ventricular (LV) wall thickness (non-cardiac ATTR), 25 patients with diagnosed HCM and 30 healthy controls were included in this study. Echocardiographic measurements for conventional parameters, as well as RV global and segmental strain, were recorded. RESULTS: When comparing RV structure and function between cardiac ATTR amyloidosis and HCM patients, only segmental strain differed between the two groups. In cardiac ATTR amyloidosis, we found an RV apex-to-base strain gradient with highest deformation in the apex. This pattern was reversed in patients with HCM. CONCLUSIONS: RV involvement is common in cardiac ATTR patients. The present study also detected an RV apical sparing pattern in patients with ATTR cardiomyopathy, similar to what has previously been described for the left ventricle in these patients. This pattern was not seen in HCM patients. Further studies are needed to assess the clinical importance of these findings.

Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis.

BACKGROUND: Cardiac amyloidosis (CA) is a myocardial disease and commonly under-diagnosed condition. In CA patients, atrial fibrillation might occur in the absence of left atrial (LA) enlargement. OBJECTIVES: The aim of this study is to assess LA size and function, and its relationship with atrial arrhythmia in patients with hereditary transthyretin amyloidosis (ATTR). METHODS: Forty-six patients with confirmed ATTR amyloidosis on abdominal biopsy were studied. Assessment with 2D echocardiography and 2D strain showed 31 patients had increased LV wall thickness (LVWT) (septal thickness >12 mm), and 15 had normal LVWT. In addition to conventional measurements, LV and LA global longitudinal strain (GLS%) and strain rate (SR) were obtained. Western blot analysis was done to assess fibril type. ATTR patients with increased LVWT were compared with 23 patients with hypertrophic cardiomyopathy (HCM) and 31 healthy controls. ATTR amyloidosis patients also underwent 24 hour Holter monitoring to determine the presence of atrial arrhythmia. RESULTS: Atrial deformation during atrial systole was reduced in ATTR amyloidosis patients with increased LVWT independent of LA size and in contrast to HCM. Twenty of the ATTR amyloidosis patients (54%) had ECG evidence of significant atrial arrhythmic events. LA strain rate, during atrial systole, was the only independent predictor of atrial arrhythmia (ß = 3.28, p = .012). CONCLUSION: In ATTR cardiomyopathy with increased LVWT, LA myocardial function is abnormal, irrespective of atrial cavity size. Reduced LA myocardial SR during atrial systole, irrespective of cavity volume, E/e' and LV deformation, is also a strong predictor for atrial arrhythmic events.

Quality of life questionnaire predicts poor exercise capacity only in HFpEF and not in HFrEF.

BACKGROUND: The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is the most widely used measure of quality of life (QoL) in HF patients. This prospective study aimed to assess the relationship between QoL and exercise capacity in HF patients. METHODS: The study subjects were 118 consecutive patients with chronic HF (62 ± 10 years, 57 females, in NYHA I-III). Patients answered a MLHFQ questionnaire in the same day of complete clinical, biochemical and echocardiographic assessment. They also underwent a 5 min walk test (6-MWT), in the same day, which grouped them into; Group I: ≤ 300 m and Group II: >300 m. In addition, left ventricular (LV) ejection fraction (EF), divided them into: Group A, with preserved EF (HFpEF) and Group B with reduced EF (HFrEF). RESULTS: The mean MLHFQ total scale score was 48 (±17). The total scale, and the physical and emotional functional MLHFQ scores did not differ between HFpEF and HFpEF. Group I patients were older (p = 0.003), had higher NYHA functional class (p = 0.002), faster baseline heart rate (p = 0.006), higher prevalence of smoking (p = 0.015), higher global, physical and emotional MLHFQ scores (p < 0.001, for all), larger left atrial (LA) diameter (p = 0.001), shorter LV filling time (p = 0.027), higher E/e' ratio (0.02), shorter isovolumic relaxation time (p = 0.028), lower septal a' (p = 0.019) and s' (p = 0.023), compared to Group II. Independent predictors of 6-MWT distance for the group as a whole were increased MLHFQ total score (p = 0.005), older age (p = 0.035), and diabetes (p = 0.045), in HFpEF were total MLHFQ (p = 0.007) and diabetes (p = 0.045) but in HFrEF were only LA enlargement (p = 0.005) and age (p = 0.013. A total MLHFQ score of 48.5 had a sensitivity of 67% and specificity of 63% (AUC on ROC analysis of 72%) for limited exercise performance in HF patients. CONCLUSIONS: Quality of life, assessment by MLHFQ, is the best correlate of exercise capacity measured by 6-MWT, particularly in HFpEF patients. Despite worse ejection fraction in HFrEF, signs of raised LA pressure independently determine exercise capacity in these patients.

The effect of statins on valve function and calcification in aortic stenosis: A meta-analysis.

BACKGROUND: Aortic calcification has been shown to share the same risk factors as atherosclerosis which suggested a potential benefit from statins therapy. In view of the existing conflicting results, we aimed to provide objective evidence on the effect of statins in aortic stenosis (AS). METHODS AND RESULTS: A meta-analysis of eligible studies that used statins in AS was performed. Fourteen studies were identified, 5 randomized controlled trials (RCTs) and 9 observational studies. In the 14 studies as a whole, no significant differences were found in all cause mortality (OR = 0.98, p = 0.91), cardiovascular mortality (OR = 0.80, P = 0.23) or the need for valve replacement (OR = 0.93, p = 0.45) between the statins and the control groups. LDL-cholesterol dropped in the statins groups in both <24 months and ≥ 24 months follow-up (p < 0.001 for both) but not in controls (p = 0.35 and p = 0.33, respectively). In the <24 months statins group, the annual increase in peak aortic velocity and peak gradient was less (p < 0.0001 and p = 0.004, respectively), but the mean gradient, valve area and calcification score were not different from controls. In the ≥ 24 months statins group, none of the above parameters was different from controls. CONCLUSIONS: Despite the consistent beneficial effect of statins on LDL-cholesterol levels, the available evidence showed no effect on aortic valve structure, function or calcification and no benefit for clinical outcomes.

Atherosclerotic Calcification Detection: A Comparative Study of Carotid Ultrasound and Cone Beam CT.

BACKGROUND AND AIM: Arterial calcification is often detected on ultrasound examination but its diagnostic accuracy is not well validated. The aim of this study was to determine the accuracy of carotid ultrasound B mode findings in detecting atherosclerotic calcification quantified by cone beam computed tomography (CBCT). METHODS: We analyzed 94 carotid arteries, from 88 patients (mean age 70 ± 7 years, 33% females), who underwent pre-endarterectomy ultrasound examination. Plaques with high echogenic nodules and posterior shadowing were considered calcified. After surgery, the excised plaques were examined using CBCT, from which the calcification volume (mm3) was calculated. In cases with multiple calcifications the largest calcification nodule volume was used to represent the plaque. Carotid artery calcification by the two imaging techniques was compared using conventional correlations. RESULTS: Carotid ultrasound was highly accurate in detecting the presence of calcification; with a sensitivity of 88.2%. Based on the quartile ranges of calcification volumes measured by CBCT we have divided plaque calcification into four groups: <8; 8-35; 36-70 and >70 mm3. Calcification volumes ≥8 were accurately detectable by ultrasound with a sensitivity of 96%. Of the 21 plaques with <8 mm3 calcification volume; only 13 were detected by ultrasound; resulting in a sensitivity of 62%. There was no difference in the volume of calcification between symptomatic and asymptomatic patients. CONCLUSION: Carotid ultrasound is highly accurate in detecting the presence of calcified atherosclerotic lesions of volume ≥8 mm3; but less accurate in detecting smaller volume calcified plaques. Further development of ultrasound techniques should allow better detection of early arterial calcification.

Perturbations in fatty acid metabolism and apoptosis are manifested in calcific coronary artery disease: An exploratory lipidomic study.

BACKGROUND: Controversy exists concerning the beneficial or harmful effects of the presence of ectopic calcification in the coronary arteries. Additionally, further elucidation of the exact pathophysiological mechanism is needed. In this study, we sought to identify metabolic markers of vascular calcification that could assist in understanding the disease, monitoring its progress and generating hypotheses describing its pathophysiology. METHODS: Untargeted lipid profiling and complementary modeling strategies were employed to compare serum samples from patients with different levels of calcific coronary artery disease (CCAD) based on their calcium score (CS). Subsequently, patients were divided into three groups: no calcification (NC; CS=0; n=26), mild calcification (MC; CS:1-250; n=27) and severe (SC; CS>250; n=17). RESULTS: Phosphatidylcholine levels were found to be significantly altered in the disease states (p=0.001-0.04). Specifically, 18-carbon fatty acyl chain (FAC) phosphatidylcholines were detected in lower levels in the SC group, while 20:4 FAC lipid species were detected in higher concentrations. A statistical trend was observed with phosphatidylcholine lipids in the MC group, showing the same tendency as with the SC group. We also observed several sphingomyelin signals present at lower intensities in SC when compared with NC or MC groups (p=0.000001-0.01). CONCLUSIONS: This is the first lipid profiling study reported in CCAD. Our data demonstrate dysregulations of phosphatidylcholine lipid species, which suggest perturbations in fatty acid elongation/desaturation. The altered levels of the 18-carbon and 20:4 FAC lipids may be indicative of disturbed inflammation homeostasis. The marked sphingomyelin dysregulation in SC is consistent with profound apoptosis as a potential mechanism of CCAD.

RV Longitudinal Deformation Correlates With Myocardial Fibrosis in Patients With End-Stage Heart Failure.

OBJECTIVES: This study was performed to determine the accuracy of right ventricular (RV) longitudinal strain (LS) in predicting myocardial fibrosis in patients with severe heart failure (HF) undergoing heart transplantation. BACKGROUND: RVLS plays a key role in the evaluation of its systolic performance and clinical outcome in patients with refractory HF. METHODS: We studied 27 patients with severe systolic HF (ejection fraction ≤25% and New York Heart Association functional class III to IV, despite full medical therapy and cardiac resynchronization therapy) using echocardiography before heart transplantation. RV free wall LS, right atrial LS, sphericity index (SI), and tricuspid annular plane systolic excursion (TAPSE) were all measured. Upon removal of the heart, from the myocardial histologic analysis, the ratio of the fibrotic to the total sample area determined the extent of fibrosis (%). RESULTS: RV myocardial fibrosis correlated with RV free wall LS (r = 0.80; p < 0.0001), SI (r = 0.42; p = 0.01) and VO2 max (r = -0.41; p = 0.03), with a poor correlation with TAPSE (r = -0.34; p = 0.05) and right atrial LS (r = -0.37; p = 0.03). Stepwise multivariate analysis showed that RV free wall LS (ß = 0.701, p < 0.0001) was independently associated with RV fibrosis (overall model R(2) = 0.64, p < 0.0001). RV free wall LS was the main determinant of myocardial fibrosis. In the subgroup of patients with severe RV fibrosis, RV free wall LS had the highest diagnostic accuracy for detecting severe myocardial fibrosis (area under the curve = 0.87; 95% confidence interval: 0.80 to 0.94). CONCLUSIONS: In late-stage HF patients, the right ventricle is enlarged, with reduced systolic function due to significant myocardial fibrosis. RV free wall myocardial deformation is the most accurate functional measure that correlates with the extent of RV myocardial fibrosis and functional capacity.

Left ventricular response to pressure afterload in children: aortic stenosis and coarctation: a systematic review of the current evidence.

Congenital aortic stenosis (CAS) and Coarctation of Aorta (CoA) represent two forms of pressure afterload that affect the left ventricle (LV), hence require regular echocardiographic monitoring. Subclinical dysfunction of the LV exists even in asymptomatic patients with preserved left ventricular ejection fraction (EF), implying low sensitivity of EF in predicting optimum time for intervention. In this article we review patterns of LV myocardial deformation before and after correction of CAS and CoA in infants, children and adolescents, showing their important role in monitoring the course of LV dysfunction. A systematic search using PubMed was performed and suitable studies are presented on a narrative form. Normal EF and/or fractional shortening (FS), with subclinical myocardial dysfunction are reported in all studies before intervention. The short-term results, after intervention, were related to the type of procedure, with no improvement or further deterioration related to surgery but immediate improvement after balloon intervention. Long term follow-up showed further improvement but still subnormal function. Thus correction of CAS and CoA before irreversible LV dysfunction is vital, and requires longitudinal studies in order to identify the most accurate parameter for function prognostication. Until then, conventional echocardiographic parameters together with myocardial velocities and deformation parameters should continue to provide follow-up reproducible measures of ventricular function.

Coronary and carotid atherosclerosis: how useful is the imaging?

The recent advancement of imaging modalities has made possible visualization of atherosclerosis disease in all phases of its development. Markers of subclinical atherosclerosis or even the most advanced plaque features are acquired by invasive (IVUS, OCT) and non-invasive imaging modalities (US, MRI, CTA). Determining plaques prone to rupture (vulnerable plaques) might help to identify patients at risk for myocardial infarction or stroke. The most accepted features of plaque vulnerability include: thin cap fibroatheroma, large lipid core, intimal spotty calcification, positive remodeling and intraplaque neovascularizations. Today, research is focusing on finding imaging techniques that are less invasive, less radiation and can detect most of the vulnerable plaque features. While, carotid atherosclerosis can be visualized using noninvasive imaging, such as US, MRI and CT, imaging plaque feature in coronary arteries needs invasive imaging modalities. However, atherosclerosis is a systemic disease with plaque development simultaneously in different arteries and data acquisition in carotid arteries can add useful information for prediction of coronary events.

Simultaneous quantification of myocardial and blood flow velocities based on duplex mode ultrasound imaging.

BACKGROUND: Ultrasound imaging of the heart is a commonly used clinical tool to assess cardiac function. The basis for this analysis is the quantification of cardiac blood flow and myocardial velocities. These are typically measured using different imaging modes and on different cardiac cycles. However, due to beat-to-beat variations such as irregular heart rhythm and transient events, simultaneous acquisition is preferred. There exists specialized ultrasound systems for this purpose; however, it would be beneficial if this could be achieved using conventional ultrasound systems due to their wide availability. The conventional Duplex mode ultrasound allows simultaneous acquisition, however at a highly reduced spatial and temporal resolution. METHODS: The aim of this work was to present and evaluate the performance of a novel method to recover myocardial tissue velocity using conventional Duplex ultrasound imaging, and to demonstrate its feasibility for the assessment of simultaneous blood flow and myocardial velocity in-vivo. The essence of the method was the estimation of the axial phase shift of robust echogenic structures between subsequent image frames. The performance of the method was evaluated on synthetic tissue mimicking B-mode image sequences at different frame rates (20-60 Hz) and tissue velocities (peak velocities 5-15cm/s), using cardiac deformation and displacement characteristics. The performance was also compared to a standard 2-D speckle tracking technique. RESULTS: The method had an overall high performance at frame rates above 25 Hz, with less than 15% error of the peak diastolic velocity, and less than 10 ms peak timing error. The method showed superior performance compared to the 2-D tracking technique at frame rates below 50 Hz. The in-vivo quantification of simultaneous blood flow and myocardial tissue velocities verified the echocardiographic patterns and features of healthy subjects and the specific patient group. CONCLUSIONS: A novel myocardial velocity quantification method was presented and high performance at frame rates above 25 Hz was shown. In-vivo quantification of simultaneous myocardial and blood flow velocities was feasible using the proposed method and conventional Duplex mode imaging. We propose that the methodology is suitable for retrospective as well as prospective studies on the mechanics and hemodynamics of the heart.