Prevalence and determinants of left ventricular diastolic dysfunction in obese subjects and the role of left ventricular global longitudinal strain and mass normalized to height.

BACKGROUND: Left ventricular (LV) diastolic dysfunction (DD) is a frequent finding in obesity and may predispose to the development of heart failure (HF). However, no data are available on the prevalence of DD after the introduction of the 2016 Recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging. METHODS AND RESULTS: To assess the impact of the new Recommendations on the prevalence of DD and on their clinical and echocardiographic correlates in obesity, a prospective study was performed in 588 subjects with an ejection fraction (EF) ≥50% and no history of HF either obese (n = 402; mean age: 47 ± 12 years; women 71%; body mass index [BMI]: 44 ± 8 kg/m2 ), overweight (n = 86; BMI: 28 ± 1 kg/m2 ), or with a normal weight (n = 100; BMI: 22 ± 2 kg/m2 ). All subjects underwent an echocardiographic and Doppler study, including the assessment of global longitudinal strain (GLS). DD occurred in 19% of obese patients, 12% of overweight subjects, and 2% of normal weight subjects. We used multivariable logistic analysis to assess the risk of DD. In patients with BMI ≥30 kg/m2 , LV mass normalized to height (2.7) (OR: 1.04, P = .0028), and GLS (OR: 0.85, P = .0032) were associated with an increased risk of DD followed by EF (OR: 0.91, P = .045), diabetes (OR: 1.91, P = .065), and systolic blood pressure (OR: 1.02, P = .076). CONCLUSION: These results show that DD is highly prevalent among obese subjects and impairment of longitudinal systolic mechanics, as reflected by GLS reduction, and LV mass normalized to height are major independent predictors of DD in this patients' population.

Reversal of Ticagrelor-Induced Arrhythmias and Cheyne-Stokes Respiration With Aminophylline Infusion.

Dyspnea and bradyarrhythmias are frequent adverse effects (AEs) of ticagrelor. AEs commonly occur within the first week of therapy, are dose related and usually mild, but sometimes they may cause drug discontinuation. Currently, the exact mechanisms of ticagrelor-related AEs have not been definitively explained. In addition to the prevalent theory of adenosine overload, other reasonable mechanism like a direct central stimulation hypothesis was suggested. We present a case of incessant Cheyne-Stokes respiration associated with heart rate instability in patient with congestive heart failure and non-ST-segment elevation myocardial infarction, supporting the use of aminophylline as a potential reversal agent of ticagrelor-related AEs.

Left ventricular stiffness predicts outcome in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.

OBJECTIVES: Assessment of the prognostic role of left ventricular stiffness (LVS) in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). METHODS: We performed a complete two-dimensional transthoracic echocardiographic study before and after TAVI in patients with severe AS at high surgical risk. In order to assess LVS, we measured LV end-diastolic pressure (EDP) invasively during TAVI and LV end-diastolic volume (EDV) by means of echocardiography. We defined LVS as the EDV indexed by body surface area at an EDP of 20 mm Hg (EDVI20 ). Our aim was to assess the impact of LVS on one-year all-cause mortality after TAVI. RESULTS: One hundred sixty-six patients undergoing TAVI (64% female; mean age 82.7 ± 5.1 years) were enrolled. Seven patients died within the first 30 days after TAVI and 21 within 1 year. Overall follow-up duration was 580 ± 478 days. At multivariate analysis, independent predictors of 1-year all-cause mortality were moderate-to-severe paravalvular leak (PVL; HR 4.7, 95% confidence interval [CI] 1.9-11, P=.0003), female gender (HR 3.5, 95% CI 1.0-12, P=.045), and EDVI20 (HR 0.94, 95% CI 0.90-0.98, P=.015). In particular, patients with higher LVS (EDVI20 ≤48 mL/m2 ) had a 1-year mortality of 26.9% vs 7.4% in patients with lower LVS (EDVI20 >48 mL/m2 ; HR 4.2, 95% CI 1.6-10.6, P=.0007). Patients with higher LVS who developed moderate-to-severe PVL had the worst outcome (incremental chi-square test, P=.014). CONCLUSION: In patients with AS, an increased LVS has a negative prognostic impact. Development of significant PVL in patients with higher LVS had an incremental adverse effect.

Micro-RNA-21 (biomarker) and global longitudinal strain (functional marker) in detection of myocardial fibrotic burden in severe aortic valve stenosis: a pilot study.

AIMS: Myocardial fibrosis (MF) is a deleterious consequence of aortic valve stenosis (AVS). Global longitudinal strain (GLS) is a novel left ventricular (LV) functional parameter potentially useful to non-invasively estimate MF. MicroRNAs (miRNAs) are non-coding small ribonucleic acids (RNA) modulating genes function, mainly through RNA degradation. miRNA-21 is a biomarker associated with MF in pressure overload. The aim of the present study was to find an integrated algorithm for detection of MF using a combined approach with both bio- and functional markers. METHODS: Thirty-six patients (75.2 ± 8 y.o.; 63 % Female) with severe AVS and preserved LV ejection fraction (EF), candidate to surgical aortic valve replacement (sAVR) were enrolled. Clinical, bio-humoral evaluation (including plasmatic miRNA-21 collected using specific tubes, PAXgene, for stabilization of peripheral RNA) and a complete echocardiographic study, including GLS and septal strain, were performed before sAVR. Twenty-eight of those patients underwent sAVR and, in 23 of them, an inter-ventricular septum biopsy was performed. Tissues were fixed in formalin and embedded in paraffin. Sections were stained with Hematoxylin and Eosin for histological evaluation and with histochemical Masson trichrome for collagen fibers. The different components were calculated and expressed as micrometers(2). To evaluate tissue miRNA components, sections 2-µm thick were cut using a microtome blade for each slide. Regression analysis was performed to test association between dependent variable and various predictors included in the model. RESULTS: Despite a preserved EF (66 ± 11 %), patients presented altered myocardial deformation parameters (GLS -14,02 ± 3.8 %; septal longitudinal strain, SSL -9.63 ± 2.9 %; septal longitudinal strain rate, SL-Sr -0.58 ± 0.17 1/s; Septal Longitudinal early-diastolic strain rate, SL-SrE 0.62 ± 0.32 1/s). The extent of MF showed an inverse association with both GLS and septal longitudinal deformation indices (GLS: R(2) = 0.30; p = 0.02; SSL: R(2) = 0.36; p = 0.01; SL-Sr: R(2) = 0.39; p < 0.001; SL-SrE: R(2) = 0.35; p = 0.001). miRNA-21 was mainly expressed in fibrous tissue (p < 0.0001). A significant association between MF and plasmatic miRNA-21, alone and weighted for measures of structural (LVMi R(2) = 0.50; p = 0.0005) and functional (SSL R(2) = 0.35; p = 0.006) remodeling, was found. CONCLUSIONS: In AVS, MF is associated with alterations of regional and global strain. Plasmatic miRNA-21 is directly related to MF and associated with LV structural and functional impairment.

Incremental Value of Pocket-Sized Echocardiography in Addition to Physical Examination during Inpatient Cardiology Evaluation: A Multicenter Italian Study (SIEC).

BACKGROUND: We prospectively assessed the incremental value of a pocket-sized echocardiography (PSE) device during cardiology consultations, in addition to physical examination, ECG reading, and chest x-ray. METHODS: A total of 443 consecutive patients (53% men), referred for bedside consultations, underwent physical examination, ECG, and CXR, followed by PSE examination. The physician completed a detailed questionnaire (clinical and echocardiographic data, scanning time, abnormal results). Receiver operating characteristic (ROC) curve analysis was generated to test the predictive discrimination value of the different methods. The incremental value of PSE examination compared to clinical visit alone or combined with ECG results was expressed as a global chi-square value. RESULTS: The PSE examination did not influence the definitive diagnosis in only 23.5% of cases, while 25.3% of the diagnoses were confirmed and verified by PSE. The clinical diagnosis was enriched by PSE in 21.9% of cases, and the diagnosis was changed in 26.2%. The area under curve (AUC) of physical examination + ECG results (sensitivity: 80%; specificity: 67%) was significantly higher than physical examination alone (sensitivity: 75%; specificity: 62%) (P < 0.0002), and the AUC of PSE results (sensitivity: 88%; specificity: 86%) was significantly higher than physical examination + ECG results (P < 0.0001). The PSE results, combined with clinical and ECG results, had a significant incremental diagnostic value during cardiology consultation when compared to the clinical visit alone or with ECG results (P < 0.0001). CONCLUSIONS: PSE had an incremental diagnostic value during bedside cardiology consultation, increasing the number of appropriate diagnoses and reducing the routine use of echocardiography.

Investigating the water availability hypothesis of pot binding: small pots and infrequent irrigation confound the effects of drought stress in potato (Solanum tuberosum L.).

To maximise the throughput of novel, high-throughput phenotyping platforms, many researchers have utilised smaller pot sizes to increase the number of biological replicates that can be grown in spatially limited controlled environments. This may confound plant development through a process known as "pot binding", particularly in larger species including potato (Solanum tuberosum), and under water-restricted conditions. We aimed to investigate the water availability hypothesis of pot binding, which predicts that small pots have insufficient water holding capacities to prevent drought stress between irrigation periods, in potato. Two cultivars of potato were grown in small (5 L) and large (20 L) pots, were kept under polytunnel conditions, and were subjected to three irrigation frequencies: every other day, daily, and twice daily. Plants were phenotyped with two Phenospex PlantEye F500s and canopy and tuber fresh mass and dry matter were measured. Increasing irrigation frequency from every other day to daily was associated with a significant increase in fresh tuber yield, but only in large pots. This suggests a similar level of drought stress occurred between these treatments in the small pots, supporting the water availability hypothesis of pot binding. Further increasing irrigation frequency to twice daily was still not sufficient to increase yields in small pots but it caused an insignificant increase in yield in the larger pots, suggesting some pot binding may be occurring in large pots under daily irrigation. Canopy temperatures were significantly higher under each irrigation frequency in the small pots compared to large pots, which strongly supports the water availability hypothesis as higher canopy temperatures are a reliable indicator of drought stress in potato. Digital phenotyping was found to be less accurate for larger plants, probably due to a higher degree of self-shading. The research demonstrates the need to define the optimum pot size and irrigation protocols required to completely prevent pot binding and ensure drought treatments are not inadvertently applied to control plants.

Advantages of real time three-dimensional echocardiography in the assessment of right ventricular volumes and function in patients with pulmonary hypertension compared with conventional two-dimensional echocardiography.

BACKGROUND: In recent years, right ventricular (RV) function has acquired greater relevance as a clinical and prognostic marker in many physiopathological conditions. The study aims to point out the value of real time three-dimensional echocardiography (RT3DE) and tissue Doppler imaging (TDI) in the evaluation of patients affected by pulmonary hypertension (PH), compared with conventional two-dimensional (2D) echocardiography. METHODS: We enrolled 44 subjects affected by PH who underwent 2D and Doppler echocardiography, RT 3D Echocardiography and TDI evaluation of the RV, and a healthy control group. PH itself can induce severe functional and structural abnormalities of the RV, such as RV hypertrophy, RV dilation, and RV systolic and diastolic dysfunction. RESULTS: In this study, RV FAC, and TAPSE showed marked alterations in patients with PH compared to the control group (C): (RVFAC: [PH] 0.29 ± 0.07 vs. [C] 0.49 ± 0.05%, P < 0.0001; TAPSE: [PH] 15.3 ± 3.2 vs. [C] 21.1 ± 2.6 mm, P > 0.0001). The 3D RV end-diastolic volume was significantly higher in PH than in C (PH) (138.7 ± 25.3 vs. [C] 82.8 ± 12.5 mL, P < 0.0001] as well as 3D RV end-systolic volume (PH) (97.6 ± 21.5 vs. [C] 39.3 ± 9.5 mL, P < 0.0001). The 3D RV ejection fraction (EF) was significantly lower in the pulmonary hypertension group than in healthy subjects (31.8 ± 6.8 vs. [C] 52.5 ± 4.7%, P < 0.0001). CONCLUSIONS: In patients with PH, evaluation of the RV diastolic and systolic volume and EF by RT3DE has shown a higher discriminating power in comparison, respectively, with 2DRV diastolic area and the relative fractional area changes.

Predicting the transition to and progression of heart failure with preserved ejection fraction: a weighted risk score using bio-humoural, cardiopulmonary, and echocardiographic stress testing.

AIMS: Risk stratification of heart failure (HF) patients with preserved ejection fraction (HFpEF) can promote a more personalized treatment. We tested the prognostic value of a multi-parametric evaluation, including biomarkers, cardiopulmonary exercise testing-exercise stress echocardiography (CPET-ESE), and lung ultrasound, in HFpEF patients and subjects at risk of developing HF (HF Stages A and B). BACKGROUND: Risk stratification of heart failure (HF) patients with preserved ejection fraction (HFpEF) can promote a more personalized treatment. DESIGN: We tested the prognostic value of a multi-parametric evaluation, including biomarkers, cardiopulmonary exercise testing-exercise stress echocardiography (CPET-ESE), and lung ultrasound, in HFpEF patients and subjects at risk of developing HF (HF Stages A and B). METHODS AND RESULTS: We performed a resting clinical/bio-humoural evaluation and a symptom-limited CPET-ESE in 274 patients (45 Stage A, 68 Stage B, and 161 Stage C-HFpEF) and 30 age- and sex-matched healthy controls. During a median follow-up of 18.5 months, we reported 71 HF hospitalizations and 10 cardiovascular deaths. Cox proportional-hazards regression identified five independent predictors and each was assigned a number of points proportional to its regression coefficient: stress-rest ΔB-lines >10 (3 points), peak oxygen consumption <16 mL/kg/min (2 points), minute ventilation/carbon dioxide production slope ≥36 (2 points), peak systolic pulmonary artery pressure ≥50 mmHg (1 point) and resting N-terminal pro-brain natriuretic peptide (NT-proBNP) >900 pg/mL (1 point). The event-free survival probability for low risk (<3 points), intermediate risk (3-6 points), and high risk (>6 points) were 93%, 52%, and 20%, respectively. The area under the curve (AUC) for the scoring system to predict events was 0.92 (95% CI 0.88-0.96), with an accuracy significantly higher than the individual components of the score (all P < 0.01 vs. individual AUCs). CONCLUSION: A weighted risk score including NT-proBNP, markers of cardiopulmonary dysfunction and indices of exercise-induced pulmonary congestion identifies HFpEF patients at increased risk for adverse events and Stage A and B subjects more likely to progress towards more advanced HF stages.

Cardiac Reserve and Exercise Capacity: Insights from Combined Cardiopulmonary and Exercise Echocardiography Stress Testing.

BACKGROUND: Cardiopulmonary exercise testing (CPET) represents the gold standard to estimate peak oxygen consumption (VO2) noninvasively. To improve the analysis of the mechanisms behind effort intolerance, we examined whether exercise stress echocardiography measurements relate to directly measured peak VO2 during exercise in a large cohort of patients within the heart failure (HF) spectrum. METHODS: We performed a symptom-limited graded ramp bicycle CPET exercise stress echocardiography in 30 healthy controls and 357 patients: 113 at risk of developing HF (American College of Cardiology/American Heart Association stage A-B) and 244 in HF stage C with preserved (HFpEF, n = 101) or reduced ejection fraction (HFrEF, n = 143). RESULTS: Peak VO2 significantly decreased from controls (23, 21.7-29.7 mL/kg/minute; median, interquartile range) to stage A-B (18, 15.4-20.7 mL/kg/minute) and stage C (HFpEF: 13.6, 11.8-16.8 mL/kg/minute; HFrEF: 14.2, 10.7-17.5 mL/kg/minute). A regression model to predict peak VO2 revealed that peak left ventricular (LV) systolic annulus tissue velocity (S'), peak tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (right ventricle-pulmonary artery coupling), and low-load left atrial (LA) reservoir strain/E/e' (LA compliance) were independent predictors, in addition to peak heart rate, stroke volume, and workload (adjusted R2 = 0.76, P < .0001). The model was successfully tested in subjects with atrial fibrillation (n = 49) and with (n = 224) and without (n = 163) beta-blockers (all P < .01). Peak S' showed the highest accuracy in predicting peak VO2 < 10 mL/kg/minute (cut point ≤ 7.5 cm/sec, area under the curve = 0.92, P < .0001) and peak VO2 > 20 mL/kg/minute (cut point > 12.5 cm/sec, area under the curve = 0.84, P < .0001) in comparison with the other cardiac variables of the model (P < .05). CONCLUSIONS: Peak VO2 is directly related to measures of LV systolic function, LA compliance, and right ventricle-pulmonary artery coupling, in addition to heart rate and stroke volume and independently of workload, age, and sex. The evaluation of cardiac mechanics may provide more insights into the causes of effort intolerance in subjects from HF stages A-C.

Persistent congestion, renal dysfunction and inflammatory cytokines in acute heart failure: a prognosis study.

AIMS: Chronic kidney dysfunction (CKD) and persistent congestion influence heart failure prognosis, but little is known about the role of inflammation in this association. We assessed the relationship between inflammatory biomarkers, persistent congestion and CKD and their prognostic implications in patients with acute heart failure. METHODS: We enrolled 97 hospitalised patients (mean age: 66 ±â€Š12 years, ejection fraction: 30 ±â€Š8%) with acute heart failure. Before discharge, congestion was assessed using a heart failure scoring system on the basis of Framingham criteria. Circulating levels of high-sensitivity C-reactive protein, TGF-ß-1, IL-1, IL-6, IL-10, TNF-α, soluble tumour necrosis factor receptor type 1 and 2 were measured. Patients were divided into four groups according to the presence of CKD (estimated glomerular filtration rate <60 ml/min/1.73 m) and congestion (Framingham heart failure score ≥2). The primary end point was the combination of death and rehospitalisation for acute heart failure. RESULTS: During a median follow-up of 32 months, 37 patients died and 14 were rehospitalised for acute heart failure. Patients with CKD and congestion had significantly higher TNF-α (P = 0.037), soluble tumour necrosis factor receptor type 1 (P = 0.0042) and soluble tumour necrosis factor receptor type 2 (P = 0.001), lower TGF-ß-1 (P = 0.02) levels, and the worst outcome (P < 0.0001). Congestion (P = 0.01) and CKD (P = 0.02) were independent predictors of the end-point together with N-terminal prohormone of brain natriuretic peptide (P = 0.002) and TNF-α (P = 0.004). TNF-α attenuated the direct relation between CKD, congestion and outcome, explaining 40% of the difference in the outcome. CONCLUSION: In patients hospitalised with acute heart failure, the prognostic impact of persistent congestion and CKD is associated with increased cytokine levels, which may also interfere with the outcome.

Interactive role of diastolic dysfunction and ventricular remodeling in asymptomatic subjects at increased risk of heart failure.

Diastolic dysfunction (DD) and left ventricular remodeling (LVR) characterize patients at risk for heart failure (HF). To assess the prognostic impact of different diastolic function algorithms and a complex LVR classification (CRC) in asymptomatic subjects with preserved ejection fraction (EF) at risk for HF. We analyzed 1923 asymptomatic patients (male 43%; age 57, 33-76 years) with at least one cardiovascular risk factor and preserved (> 50%) EF. We used three algorithms for LV diastolic function assessment (Paulus et al. in Eur Heart J 28(20):2539-2550, 2007; Nagueh et al. in J Am Soc Echocardiogr 22(2):107-133, 2009, Eur Heart J Cardiovasc Imaging 17(12):1321-1360, 2016), and two algorithms for LVR (classic and CRC). We considered a composite end-point: cardiac death and hospitalization for HF. The highest presence of DD was diagnosed by Nagueh 2009 (211, 11%), while the prevalence according to Nagueh 2016 (63 patients, 3.2%) turned out to be the lowest (p < 0.001 vs the other algorithms). According to CRC, 780 (48.6%) patients had normal or physiologic hypertrophy, 298 (15.5%) concentric remodeling, 85 (4.4%) eccentric remodeling, 294 (15.3%) concentric hypertrophy, 39 (2%) mixed hypertrophy, 80 (4.1%) dilated hypertrophy, 73 (3.7%) eccentric hypertrophy and 294 (15.3%) were unclassifiable. After 39-month follow-up (261 events, 13.6%), Cox-regression (adjusted for age, gender, history of stable ischemic heart disease, classic remodeling classification) identified CRC (p = 0.01) and Nagueh 2016 (p < 0.001) as independent predictors of end-point. The coexistence of an adverse LVR by CRC and DD by Nagueh 2016 was associated with the worst prognosis. A concurrent structural (CRC) and functional (Nagueh Op. Cit) analysis improves prognostic stratification in asymptomatic subjects at risk for HF with preserved EF.

Prognostic Value of a Tissue Doppler Index of Systodiastolic Function in Patients with Asymptomatic Heart Failure.

INTRODUCTION: Doppler echocardiography with early diastolic transmitral velocity (E)/early mitral annular diastolic velocity (E') ratio has been proposed as the best predictor for evaluating left ventricle (LV) filling pressure. A dimensionless index E/(E' × S') ratio (S' = systolic mitral annulus velocity) resulted in readily, reproducible, and reliable predictor of LV filling pressure. We assessed the prognostic impact of E/E' × S') in patients with asymptomatic heart failure (HF). MATERIALS AND METHODS: We calculated E/(E' × S') in 337 patients (179 male, 53%; age 54.7 ± 13.7 years) using the average of septal and lateral mitral annular velocities. We considered a composite endpoint as follows: all-cause death, acute myocardial infarction, stroke, and HF exacerbation. RESULTS: Baseline ejection fraction resulted 60.2 ± 11.8%; E/E' × S') was 1.45 ± 0.8, with S' 7.4 ± 2.4 cm/s and E/E' 9.5 ± 5.4. After a 22-month median follow-up, there were 42 events: 5 deaths (12%), 3 acute myocardial infarctions (7%), 1 stroke (2%), and 33 HF hospitalizations (79%). In patients reaching the composite endpoint, E/(E' × S') resulted 2.07 ± 1.1 versus 1.3 ± 0.7 in event-free population (P < 0.001). In a Cox-regression analysis, adjusted for confounding clinical factors and conventional echo parameters, E/(E' × S') (P < 0.001), age (P < 0.001), and male gender (P = 0.03) resulted independent predictors of the composite endpoint. CONCLUSIONS: E/(E' × S') was an independent predictor for the future cardiac events in asymptomatic HF.

MicroRNAs distribution in different phenotypes of Aortic Stenosis.

Aortic valve stenosis (AVS) represents a cluster of different phenotypes, considering gradient and flow pattern. Circulating micro RNAs may reflect specific pathophysiological processes and could be useful biomarkers to identify disease. We assessed 80 patients (81, 76.7-84 years; 46, 57.5%females) with severe AVS. We performed bio-humoral evaluation (including circulating miRNA-1, 21, 29, 133) and 2D-echocardiography. Patients were classified according to ACC/AHA groups (D1-D3) and flow-gradient classification, considering normal/low flow, (NF/LF) and normal/high gradient, (NG/HG). Patients with reduced ejection fractionwere characterized by higher levels of miRNA1 (p = 0.003) and miRNA 133 (p = 0.03). LF condition was associated with higher levels of miRNA1 (p = 0.02) and miRNA21 (p = 0.02). Levels of miRNA21 were increased in patients with reduced Global longitudinal strain (p = 0.03). LF-HG and LF-LG showed higher levels of miRNA1 expression (p = 0.005). At one-year follow-up miRNA21 and miRNA29 levels resulted significant independent predictors of reverse remodeling and systolic function increase, respectively. Different phenotypes of AVS may express differential levels and types of miRNAs, which may retain a pathophysiological role in pro-hypertrophic and pro-fibrotic processes.

Critical Limb Ischemia: A Practical Up-To-Date Review.

Critical limb ischemia (CLI) is the most advanced form of peripheral artery disease. It is associated with significant morbidity and mortality and high management costs. It carries a high risk of amputation and local infection. Moreover, cardiovascular complications remain a major concern. Although it is a well-known entity and new technological and therapeutic advances have been made, this condition remains poorly addressed, with significantly heterogeneous management, especially in nonexperienced centers. This review, from a third-level dedicated inpatient and outpatient cardioangiology structure, aims to provide an updated summary on the topic of CLI of its complexity, encompassing epidemiological, social, economical and, in particular, diagnostic/imaging issues, together with potential therapeutic strategies (medical, endovascular, and surgical), including the evaluation of cardiovascular risk factors, the diagnosis, and treatment together with prognostic stratification.

The integrated value of sST2 and global longitudinal strain in the early stratification of patients with severe aortic valve stenosis: a translational imaging approach.

Aortic valve stenosis (AVS) is associated with significant myocardial fibrosis (MF). Global longitudinal strain (GLS) is a sensible indicator of systolic dysfunction. ST2 is a member of the interleukin (IL)-1 receptor family and a modulator of hypertrophic and fibrotic responses. We aimed at assessing: (a) the association between adverse LV remodeling, LV functional parameters (including GLS) and sST2 level. (b) The association between MF (detected by endo-myocardial biopsy) and sST2 in patients with AVS undergoing surgical valve replacement. Twenty-two patients with severe AVS and preserved EF underwent aortic valve replacement. They performed laboratory analysis, including serum ST2 (sST2), echocardiography and inter-ventricular septum biopsy to assess MF (%). We included ten controls for comparison. Compared to controls, patients showed higher sST2 levels (p < 0.0001). sST2 showed correlation with Age (r = 0.58; p = 0.0004), E/e' average (r = 0.58; p = 0.0007), GLS (r = 0.61; p = 0.0002), LAVi (r = 0.51; p = 0.003), LVMi (r = 0.43; p = 0.01), sPAP (r = 0.36; p = 0.04) and SVi (r = -0.47; p < 0.005). No correlation was found between MF and sST2. At ROC analysis, a sST2 ≥ 284 ng/mL had the best accuracy to discriminate controls from patients with impaired GLS, i.e. GLS ≤ 17% (AUC 0.80; p = 0.003; sensitivity 95%; specificity 83%) and increased E/e' average (AUC 0.87; p = 0.0001; sensitivity 96%; specificity 74%). At multivariate regression analysis GLS resulted the only independent predictor of sST2 levels (R2 = 0.35; p =  0.0004). Patients with severe AVS present elevated sST2 levels. LV GLS resulted the only independent predictor of sST2 levels.

Classification and Prognostic Evaluation of Left Ventricular Remodeling in Patients With Asymptomatic Heart Failure.

Patients with asymptomatic heart failure (HF; stage A and B) are characterized by maladaptive left ventricular (LV) remodeling. Classic 4-group classification of remodeling considers only LV mass index and relative wall thickness as variables. Complex remodeling classification (CRC) includes also LV end-diastolic volume index. Main aim was to assess the prognostic impact of CRC in stage A and B HF. A total of 1,750 asymptomatic subjects underwent echocardiographic examination as a screening evaluation in the presence of cardiovascular risk factors. LV dysfunction, both systolic (ejection fraction) and diastolic (transmitral flow velocity pattern), was evaluated, together with LV remodeling. We considered a composite end point: all-cause death, myocardial infarction, coronary revascularizations, cerebrovascular events, and acute pulmonary edema. CRC was suitable for 1,729 patients (men 53.6%; age 58.3 ± 13 years). Two hundred thirty-eight patients presented systolic dysfunction (ejection fraction <50%) and 483 diastolic dysfunction. According to the CRC, 891 patients were normals or presented with physiologic hypertrophy, 273 concentric remodeling, 47 eccentric remodeling, 350 concentric hypertrophy, 29 mixed hypertrophy, 86 dilated hypertrophy, and 53 eccentric hypertrophy. Age and gender distribution was noticed (p <0.001). After a median follow-up of 21 months, Kaplan-Meier analysis showed different survival distribution (p <0.001) of the CRC patterns. In multivariate Cox regression (adjusted for age, gender, history of stable ischemic heart disease, classic remodeling classification, systolic, and diastolic dysfunction), CRC was independent predictor of primary end point (p = 0.044, hazard ratio 1.101, 95% CI 1.003 to 1.21), confirmed in a logistic regression (p <0.03). In conclusion, CRC could help physicians in prognostic stratification of patients in stage A and B HF.

Incremental prognostic value of a complex left ventricular remodeling classification in asymptomatic for heart failure hypertensive patients.

We evaluated the prognostic impact of a complex remodeling classification (CRC) in asymptomatic patients with arterial hypertension (AH). We retrospectively included 749 hypertensive patients (female 325, 43.4% age 62 ± 11.3 years) in Stages A and B of heart failure. CRC was evaluated including indexed left ventricular mass, end-diastolic volume, and relative wall thickness. After 45-month follow-up, we considered a composite endpoint: total mortality, myocardial infarction, myocardial revascularization, cerebrovascular events, and acute pulmonary edema. Blood pressure was controlled in 265 patients (35.4%), 317 (42.3%) were in Grade 1 of AH, 123 (16.4%) in Grade 2, and 44 (5.9%) in Grade 3. Considering CRC, 292 patients (38%) presented normal/physiological hypertrophy, 102 (13.6%) concentric remodeling, 29 (3.9%) eccentric remodeling, 157 (21%) concentric hypertrophy, 11 (1.5%) mixed hypertrophy, 52 (6.9%) dilated hypertrophy, and 36 (4.8%) eccentric hypertrophy. We observed a total of 73 events (9.7%). Kaplan-Meier method demonstrated a significant different survival in CRC-derived classes (P < .001). Cox regression demonstrated CRC as independent predictor (P = .01), after adjusting for age, gender, diabetes mellitus, grade of hypertension, antihypertensive therapy, stable ischemic heart disease, obesity, systolic and diastolic dysfunction, and classic remodeling classification. In asymptomatic patients with AH, CRC is an independent predictor of poor outcome.

Prevalence and Prognostic Impact of Metabolic Syndrome in Asymptomatic (Stage A and B Heart Failure) Patients.

BACKGROUND: Metabolic syndrome (MS) has an increased risk of cardiovascular events. Its relationship with asymptomatic left ventricular dysfunction (LVD) and prognosis has not been completely clarified. OBJECTIVES: To determine, in asymptomatic patients (Stage A, B heart failure, HF), whether MS is associated with left ventricular systolic dysfunction (LVSD) and left ventricular diastolic dysfunction and its predictive role for cardiovascular events. MATERIALS AND METHODS: We included 1920 nonconsecutive patients without symptoms of HF, with at least one cardiovascular risk factor, undergoing echocardiographic evaluation as preventive screening. We subdivided the study population according to the presence (Group 1) or absence (Group 2) of MS. The primary endpoint was a composite of cardiac death, myocardial infarction, coronary artery revascularization, stroke, and acute pulmonary edema. Secondary endpoints were hospitalization for HF and HF progression. RESULTS: Overall prevalence of MS was 13.4% (n = 262, Group 1). In Group 2 (n = 1658), the prevalence of LVSD was 12.2%, while the prevalence of LVSD was 21.8% in Group 1 (relative risk [RR] 2.01; 95% confidence interval 1.4-2.8; P < 0.001). Adjusting for age and gender, MS resulted an independent predictor of LVSD (P < 0.001). After a median follow-up of 22 months, Group 1 patients had a significantly higher incidence of primary events (P < 0.001), including cardiac death (P = 0.04), and secondary events (P < 0.001). Both primary and secondary endpoints were more frequent in patients with LVSD (P < 0.001). In multivariate survival analysis, MS (but not its specific components) and LVSD were independently associated both with primary and secondary events (P ≤ 0.003). Incremental chi-square analysis showed the presence of combined LVD added to MS, and age raised significantly the predictive value of the model for the primary endpoint (Incremental chi-square = 8.6). CONCLUSIONS: In stage A and B HF subjects, the coexistence of MS with functional or structural cardiac abnormalities, detected by echocardiography, showed a significant incremental value in predicting clinical cardiovascular events.

Role of electrocardiography and echocardiography in prevention and predicting outcome of subjects at increased risk of heart failure.

BACKGROUND: Asymptomatic left ventricular dysfunction (ALVD) is relatively common in both community and high-risk populations. Early pharmacological intervention can improve clinical outcomes in subjects with this condition. OBJECTIVES: This multicentre study consists on electrocardiographic and echocardiographic examination of stage A and B heart failure (HF) asymptomatic subjects with one or more cardiovascular risk factors, to assess the prognostic value of cardiovascular risk factors per se, clinical history, and electrocardiographic and echocardiographic parameters in prediction of progression of HF and/or in development of cardiovascular primary or secondary events. MATERIAL AND METHODS: A total of 2142 asymptomatic subjects (mean age 63 years, 1162 males) performed an electrocardiographic and echocardiographic examination. Electrocardiogram (ECG) pathological signs according to Minnesota code and left ventricular dysfunction both systolic and diastolic by echocardiography were evaluated. There were 2002 subjects who were followed up for 26 ± 11 months, observing their primary and secondary end points. RESULTS: At follow up, the study population presented 111 primary end points (5.2%) and 441 secondary end points (20.6%). ECG criteria of LV hypertrophy and signs of ischaemia or previous myocardial infarction (p < 0.0001) were highly significantly related to primary end points. Both ECG and echocardiography (systolic function) are able at Kaplan-Meier cumulative survival curves to predict primary end points (p < 0.0001). CONCLUSIONS: Presence or absence of left ventricular systolic and /or diastolic dysfunction has an incremental value in comparison to cardiovascular risk factors, clinical history, and ECG findings to predict both the evolution towards a more severe HF stage (stage C) and also the occurrence of cardiovascular events.

Integrated reverse left and right ventricular remodelling after MitraClip implantation in functional mitral regurgitation: an echocardiographic study.

AIMS: The aim of the present study was to investigate the changes of left and right ventricular (RV) dimensions and function after MitraClip implantation in high-risk surgical patients with severe functional mitral regurgitation (MR). METHODS AND RESULTS: Study population included 35 patients with functional MR. All the patients underwent clinical and echocardiographic evaluation at baseline, before discharge and at 6-month follow-up. The mean age was 75 years (63-81), 65.7% (n = 23) was male with a mean logistic EuroSCORE of 20%. Percutaneous mitral valve repair acronym (PMVR) resulted in significantly reduced MR and improved in New York Heart Association functional class. Echocardiography revealed improvement in left ventricular (LV) size and function since discharge with further improvement at 6 months. During the follow-up, a significant improvement in RV function was also observed by the baseline values. At baseline, before discharge and 6 months, respectively, the tricuspid annulus plane systolic excursion (TAPSE) was 16.8 ± 3.9, 18.7 ± 3.4, and 19.3 ± 4.5 mm (P = 0.001); the systolic pulmonary artery pressure (SPAP) was 50.1 ± 6.8, 41.2 ± 6.8, and 38.1 ± 6.8 mmHg (P < 0.0001); and the systolic velocity at the tricuspid annular (RV-Sm) was 8.8 ± 2.9, 10.4 ± 3.5, and 17.7 ± 3.1 cm (P < 0.0001). CONCLUSION: MitraClip implantation induces a significant reverse remodelling of LV, with reduction in both diastolic and systolic LV volumes and an increase in the cardiac index. The concomitant reduction in LV filling pressure, obtained after MitraClip implantation, reflects nearly immediately on the haemodynamics of the right sections. In fact, since discharge, we observed both a reverse remodelling of the right sections, with a significant reduction in SPAP, and a significant increase in longitudinal RV systolic function as shown by the increase in TAPSE and RV-Sm.