Myocardial Scar and Mortality in Severe Aortic Stenosis.

BACKGROUND: Aortic valve replacement (AVR) for aortic stenosis is timed primarily on the development of symptoms, but late surgery can result in irreversible myocardial dysfunction and additional risk. The aim of this study was to determine whether the presence of focal myocardial scar preoperatively was associated with long-term mortality. METHODS: In a longitudinal observational outcome study, survival analysis was performed in patients with severe aortic stenosis listed for valve intervention at 6 UK cardiothoracic centers. Patients underwent preprocedural echocardiography (for valve severity assessment) and cardiovascular magnetic resonance for ventricular volumes, function and scar quantification between January 2003 and May 2015. Myocardial scar was categorized into 3 patterns (none, infarct, or noninfarct patterns) and quantified with the full width at half-maximum method as percentage of the left ventricle. All-cause mortality and cardiovascular mortality were tracked for a minimum of 2 years. RESULTS: Six hundred seventy-four patients with severe aortic stenosis (age, 75±14 years; 63% male; aortic valve area, 0.38±0.14 cm2/m2; mean gradient, 46±18 mm Hg; left ventricular ejection fraction, 61.0±16.7%) were included. Scar was present in 51% (18% infarct pattern, 33% noninfarct). Management was surgical AVR (n=399) or transcatheter AVR (n=275). During follow-up (median, 3.6 years), 145 patients (21.5%) died (52 after surgical AVR, 93 after transcatheter AVR). In multivariable analysis, the factors independently associated with all-cause mortality were age (hazard ratio [HR], 1.50; 95% CI, 1.11-2.04; P=0.009, scaled by epochs of 10 years), Society of Thoracic Surgeons score (HR, 1.12; 95% CI, 1.03-1.22; P=0.007), and scar presence (HR, 2.39; 95% CI, 1.40-4.05; P=0.001). Scar independently predicted all-cause (26.4% versus 12.9%; P<0.001) and cardiovascular (15.0% versus 4.8%; P<0.001) mortality, regardless of intervention (transcatheter AVR, P=0.002; surgical AVR, P=0.026 [all-cause mortality]). Every 1% increase in left ventricular myocardial scar burden was associated with 11% higher all-cause mortality hazard (HR, 1.11; 95% CI, 1.05-1.17; P<0.001) and 8% higher cardiovascular mortality hazard (HR, 1.08; 95% CI, 1.01-1.17; P<0.001). CONCLUSIONS: In patients with severe aortic stenosis, late gadolinium enhancement on cardiovascular magnetic resonance was independently associated with mortality; its presence was associated with a 2-fold higher late mortality.

Magnetic resonance imaging of the time course of hyperpolarized 129Xe gas exchange in the human lungs and heart.

PURPOSE: To perform magnetic resonance imaging (MRI), human lung imaging, and quantification of the gas-transfer dynamics of hyperpolarized xenon-129 (HPX) from the alveoli into the blood plasma. MATERIALS AND METHODS: HPX MRI with iterative decomposition of water and fat with echo asymmetry and least-square estimation (IDEAL) approach were used with multi-interleaved spiral k-space sampling to obtain HPX gas and dissolved phase images. IDEAL time-series images were then obtained from ten subjects including six normal subjects and four patients with pulmonary emphysema to test the feasibility of the proposed technique for capturing xenon-129 gas-transfer dynamics (XGTD). The dynamics of xenon gas diffusion over the entire lung was also investigated by measuring the signal intensity variations between three regions of interest, including the left and right lungs and the heart using Welch's t test. RESULTS: The technique enabled the acquisition of HPX gas and dissolved phase compartment images in a single breath-hold interval of 8 s. The y-intersect of the XGTD curves were also found to be statistically lower in the patients with lung emphysema than in the healthy group (p < 0.05). CONCLUSION: This time-series IDEAL technique enables the visualization and quantification of inhaled xenon from the alveoli to the left ventricle with a clinical gradient strength magnet during a single breath-hold, in healthy and diseased lungs. KEY POINTS: • The proposed hyperpolarized xenon-129 gas and dissolved magnetic resonance imaging technique can provide regional and temporal measurements of xenon-129 gas-transfer dynamics. • Quantitative measurement of xenon-129 gas-transfer dynamics from the alveolar to the heart was demonstrated in normal subjects and pulmonary emphysema. • Comparison of gas-transfer dynamics in normal subjects and pulmonary emphysema showed that the proposed technique appears sensitive to changes affecting the alveoli, pulmonary interstitium, and capillaries.

Right Ventricular and Pulmonary Computed Tomography Assessments in Paradoxical Low-Flow Low-Gradient Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement.

Background: Patients with paradoxical low-flow low-gradient aortic stenosis (pLFLG-AS) have high mortality and high degree of TAVR futility. Computed tomography (CT) enables accurate simultaneous right ventricular (RV) and parenchymal lung disease evaluation which may provide useful objective markers of AS severity, concomitant pulmonary comorbidities, and transcatheter aortic valve replacement (TAVR) improvement. However, the prevalence of RV dysfunction and its association with pulmonary disease in pLFLG-AS is unknown. The study objective was to test the hypothesis that pLFLG-AS patients undergoing TAVR have decreased RV function without significant parenchymal lung disease. Methods: Between August 2016 and March 2020, 194 consecutive AS patients completed high-resolution computed tomography (CT) imaging for TAVR evaluation. Subjects were stratified based on echocardiographic criteria as the study group, pLFLG (n=27), and two consecutive control groups: classic severe, normal-flow, high-gradient (n=27) and normal-flow, low-gradient (NFLG) (n=27) AS. Blinded biventricular function and lung parenchymal disease assessments were obtained by high-resolution CT imaging. Results: Patient demographics were similar between groups. pLFLG-AS had lower RV ejection fraction (49±10%) compared to both classic severe (58±7%, p<0.001) and NFLG AS (55±65%, p=0.02). There were no significant differences on lung emphysema (p=0.19), air fraction (p=0.58), and pulmonary disease presence (p=0.94) and severity (p=0.67) between groups. Conclusion: pLFLG-AS patients have lower RV ejection fraction, than classic severe and normal-flow low-gradient AS patients in the absence of significant parenchymal lung disease on CT imaging. These findings support the direct importance of RV function in the pathophysiology of aortic valve disease.

Association of Myocardial Fibrosis and Stroke Volume by Cardiovascular Magnetic Resonance in Patients With Severe Aortic Stenosis With Outcome After Valve Replacement: The British Society of Cardiovascular Magnetic Resonance AS700 Study.

Importance: Low-flow severe aortic stenosis (AS) has higher mortality than severe AS with normal flow. The conventional definition of low-flow AS is an indexed stroke volume (SVi) by echocardiography less than 35 mL/m2. Cardiovascular magnetic resonance (CMR) is the reference standard for quantifying left ventricular volumes and function from which SVi by CMR can be derived. Objective: To determine the association of left ventricular SVi by CMR with myocardial remodeling and survival among patients with severe AS after valve replacement. Design, Setting, and Participants: This multicenter longitudinal cohort study was conducted between January 2003 and May 2015 across 6 UK cardiothoracic centers. Patients with severe AS listed for either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) were included. Patients underwent preprocedural echocardiography and CMR. Patients were stratified by echocardiography-derived aortic valve mean and/or peak gradient and SVi by CMR into 4 AS endotypes: low-flow, low-gradient AS; low-flow, high-gradient AS; normal-flow, low-gradient AS; and normal-flow, high-gradient AS. Patients were observed for a median of 3.6 years. Data were analyzed from September to November 2021. Exposures: SAVR or TAVR. Main Outcomes and Measures: All-cause and cardiovascular (CV) mortality after aortic valve intervention. Results: Of 674 included patients, 425 (63.1%) were male, and the median (IQR) age was 75 (66-80) years. The median (IQR) aortic valve area index was 0.4 (0.3-0.4) cm2/m2. Patients with low-flow AS endotypes (low gradient and high gradient) had lower left ventricular ejection fraction, mass, and wall thickness and increased all-cause and CV mortality than patients with normal-flow AS (all-cause mortality: hazard ratio [HR], 2.08; 95% CI, 1.37-3.14; P < .001; CV mortality: HR, 3.06; 95% CI, 1.79-5.25; P < .001). CV mortality was independently associated with lower SVi (HR, 1.64; 95% CI, 1.08-2.50; P = .04), age (HR, 2.54; 95% CI, 1.29-5.01; P = .001), and higher quantity of late gadolinium enhancement (HR, 2.93; 95% CI, 1.68-5.09; P < .001). CV mortality hazard increased more rapidly in those with an SVI less than 45 mL/m2. SVi by CMR was independently associated with age, atrial fibrillation, focal scar (by late gadolinium enhancement), and parameters of cardiac remodeling (left ventricular mass and left atrial volume). Conclusions and Relevance: In this cohort study, SVi by CMR was associated with CV mortality after aortic valve replacement, independent of age, focal scar, and ejection fraction. The unique capability of CMR to quantify myocardial scar, combined with other prognostically important imaging biomarkers, such as SVi by CMR, may enable comprehensive stratification of postoperative risk in patients with severe symptomatic AS.

Heart-centered positioning and tailored beam-shaping filtration for reduced radiation dose in coronary artery calcium imaging: A Multi-Ethnic Study of Atherosclerosis (MESA) Study.

PURPOSE: Cardiac computed tomography has a clear clinical role in the evaluation of coronary artery disease and assessment of coronary artery calcium (CAC) but the use of ionizing radiation limits the clinical use. Beam-shaping "bow-tie" filters determine the radiation dose and the effective scan field-of-view diameter (SFOV) by delivering higher X-ray fluence to a region centered at the isocenter. A method for positioning the heart near the isocenter could enable reduced SFOV imaging and reduce dose in cardiac scans. However, a predictive approach to center the heart, the extent to which heart centering can reduce the SFOV, and the associated dose reductions have not been assessed. The purpose of this study is to build a heart-centered patient positioning model, to test whether it reduces the SFOV required for accurate CAC scoring, and to quantify the associated reduction in radiation dose. METHODS: The location of 38,184 calcium lesions (3151 studies) in the Multi-Ethnic Study of Atherosclerosis was utilized to build a predictive heart-centered positioning model and compare the impact of SFOV on CAC scoring accuracy in heart-centered and conventional body-centered scanning. Then, the positioning model was applied retrospectively to an independent, contemporary cohort of 118 individuals (81 with CAC > 0) at our institution to validate the model's ability to maintain CAC accuracy while reducing the SFOV. In these patients, the reduction in dose associated with a reduced SFOV beam-shaping filter was quantified. RESULTS: Heart centering reduced the SFOV diameter 25.7% relative to body centering while maintaining high CAC scoring accuracy (0.82% risk reclassification rate). In our validation cohort, imaging at this reduced SFOV with heart-centered positioning and tailored beam-shaping filtration led to a 26.9% median dose reduction (25-75th percentile: 21.6%-29.8%) without any calcium risk reclassification. CONCLUSIONS: Heart-centered patient positioning enables a significant radiation dose reduction while maintaining CAC accuracy.

Automated cardiac volume assessment and cardiac long- and short-axis imaging plane prediction from electrocardiogram-gated computed tomography volumes enabled by deep learning.

AIMS: To develop an automated method for bloodpool segmentation and imaging plane re-slicing of cardiac computed tomography (CT) via deep learning (DL) for clinical use in coronary artery disease (CAD) wall motion assessment and reproducible longitudinal imaging. METHODS AND RESULTS: One hundred patients who underwent clinically indicated cardiac CT scans with manually segmented left ventricle (LV) and left atrial (LA) chambers were used for training. For each patient, long-axis (LAX) and short-axis planes were manually defined by an imaging expert. A DL model was trained to predict bloodpool segmentations and imaging planes. Deep learning bloodpool segmentations showed close agreement with manual LV [median Dice: 0.91, Hausdorff distance (HD): 6.18 mm] and LA (Dice: 0.93, HD: 7.35 mm) segmentations and a strong correlation with manual ejection fraction (Pearson r: 0.95 LV, 0.92 LA). Predicted planes had low median location (6.96 mm) and angular orientation (7.96 ° ) errors which were comparable to inter-reader differences (P > 0.71). 84-97% of DL-prescribed LAX planes correctly intersected American Heart Association segments, which was comparable (P > 0.05) to manual slicing. In a test cohort of 144 patients, we evaluated the ability of the DL approach to provide diagnostic imaging planes. Visual scoring by two blinded experts determined ≥94% of DL-predicted planes to be diagnostically adequate. Further, DL-enabled visualization of LV wall motion abnormalities due to CAD and provided reproducible planes upon repeat imaging. CONCLUSION: A volumetric, DL approach provides multiple chamber segmentations and can re-slice the imaging volume along standardized cardiac imaging planes for reproducible wall motion abnormality and functional assessment.

Assessment of Ventilatory Heterogeneity in Chronic Obstructive Pulmonary Disease Using the Inspired Sinewave Test.

BACKGROUND: There is marked variability in the symptoms and outcomes of patients with chronic obstructive pulmonary disease (COPD) which are poorly predicted by spirometry/FEV1%pred. Furthermore, as spirometry requires the performance of potentially distressing respiratory manoeuvres which are to some extent user-effort dependent, there is need for non-invasive and simple-to-perform techniques to identify subtypes of COPD which are more closely related to clinically relevant outcomes. MATERIALS AND METHODS: The inspired sinewave test (IST) sinusoidally modulates the inspired concentration of a tracer gas (N2O) over successive tidal breaths. A single-compartment tidal-ventilation lung model processes the amplitude/phase of the expired N2O sinewave and estimates cardiopulmonary variables including: effective lung volume and indices of ventilatory heterogeneity (VH; ELV180/FRCpleth and ELV180/ELVpred). 83 COPD patients and 53 healthy controls performed the IST test, standard pulmonary function tests (Spirometry, body plethysmography and the single breath test of carbon monoxide uptake), and symptom severity questionnaires (COPD assessment test, CAT; mMRC dyspnoea-scale, mMRC-DS; Cough+Mucus score; C+M score). RESULTS: ELV180/FRCpleth and ELV180/ELVpred were significantly lower in patients with COPD vs healthy participants (0.34±0.11 vs 0.68±0.14 and 0.7±0.27 vs 0.98±0.15, respectively; P<0.05). Multivariable regression analysis demonstrated that ELV180/FRCpleth was a stronger and independent predictor of CAT, mMRC-DS and C+M score vs FEV1%pred. ELV180/ELVpred was a stronger and independent and better predictor of C+M score vs FEV1%pred. Phenotyping patients, based upon ELV180/ELVpred and FRC%pred, uncovered significant symptomatic differences between groups. CONCLUSION: The IST indices of VH were superior and independent predictors of symptom severity vs FEV1%pred and has potential as a non-invasive and simple-to-perform method to stratify patients into subgroups related to clinically relevant features of COPD.

Markers of Myocardial Damage Predict Mortality in Patients With Aortic Stenosis.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined. OBJECTIVES: Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality. METHODS: Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years' follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome. RESULTS: There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m2) and small (LVEDVi ≤55 mL/m2) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort. CONCLUSIONS: Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR.

Extracellular Myocardial Volume in Patients With Aortic Stenosis.

BACKGROUND: Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis. OBJECTIVES: This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes. METHODS: Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery-based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters. RESULTS: Four-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p < 0.05 for all), the latter 2 associations being independent of all other clinical variables (p = 0.035 and p < 0.001). After a median of 3.8 years (IQR: 2.8 to 4.6 years) of follow-up, 52 patients had died, 14 from adjudicated cardiovascular causes. A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6, and 52.7 deaths per 1,000 patient-years; log-rank test; p = 0.009). Not only was ECV% associated with cardiovascular mortality (p = 0.003), but it was also independently associated with all-cause mortality following adjustment for age, sex, ejection fraction, and late gadolinium enhancement (hazard ratio per percent increase in ECV%: 1.10; 95% confidence interval [1.02 to 1.19]; p = 0.013). CONCLUSIONS: In patients with severe aortic stenosis scheduled for aortic valve intervention, an increased ECV% is a measure of left ventricular decompensation and a powerful independent predictor of mortality.

Sex differences in left ventricular remodelling, myocardial fibrosis and mortality after aortic valve replacement.

OBJECTIVES: To investigate sex differences in left ventricular remodelling and outcome in patients undergoing surgical or transcatheter aortic valve replacement (SAVR/TAVR). METHODS: In this multicentre, observational, outcome study with imaging core-lab analysis, patients with severe aortic stenosis (AS) listed for intervention at one of six UK centres were prospectively recruited and underwent cardiovascular magnetic resonance imaging. The primary endpoint was all-cause mortality and secondary endpoint was cardiovascular mortality. RESULTS: 674 patients (425 men, 249 women, age 75±14 years) were included: 399 SAVR, 275 TAVR. Women were older, had higher surgical risk scores and underwent TAVR more frequently (53% vs 33.6%, p<0.001). More men had bicuspid aortic valves (BAVs) (26.7% vs 14.9%, p<0.001) and demonstrated more advanced remodelling than women. During a median follow-up of 3.6 years, 145 (21.5%) patients died, with no significant sex difference in all-cause mortality (23.3% vs 20.5%, p=0.114), but higher cardiovascular mortality in women (13.7% vs 8.5%, p=0.012). There were no significant sex-related differences in outcome in the SAVR or TAVR subgroups, or after excluding those with BAV. Factors independently associated with all-cause mortality were age, left ventricular ejection fraction (LVEF), BAV (better) and myocardial fibrosis detected with late gadolinium enhancement (LGE) in men, and age, LVEF and LGE in women. Age and LGE were independently associated with cardiovascular mortality in both sexes. CONCLUSIONS: Men demonstrate more advanced remodelling in response to a similar severity of AS. The higher cardiovascular mortality observed in women following AVR is accounted for by women having less BAV and higher risk scores resulting in more TAVR. LGE is associated with a worse prognosis in both sexes.

Assessment and impact of diastolic function by echocardiography in elderly patients.

Doppler echocardiography is the gold standard for assessment of diastolic dysfunction, which is increasingly recognised as a cause of heart failure, especially in the elderly. Using a combination of Doppler echocardiography techniques, it is possible to identify grades of diastolic dysfunction, estimate left ventricular filling pressures and establish the chronicity of diastolic dysfunction. These physiologically-derived measures have been widely validated against invasive measurements of left heart pressures and have been shown to be prognostically valuable in a wide range of clinical settings. This review explores the mechanisms, and approaches to the assessment of diastolic dysfunction in the elderly. The challenge for clinicians is to identify pathophysiological changes from those associated with normal ageing. When used in combination, and taking age into account, Doppler echocardiographic parameters are helpful in the assessment of dyspnoea in older patients and provide prognostic insights.

Bias associated with left ventricular quantification by multimodality imaging: a systematic review and meta-analysis.

PURPOSE: Cardiac MR (CMR) is the gold standard for left ventricular (LV) quantification. However, two-dimensional echocardiography (2DE) is the most common approach, and both three-dimensional echocardiography (3DE) and multidetector CT (MDCT) are increasingly available. The clinical significance and interchangeability of these modalities remains under-investigated. Therefore, we undertook a systemic review to evaluate the accuracy and absolute bias in LV quantification of all the commonly available non-invasive imaging modalities (2DE, CE-2DE, 3DE, MDCT) compared to cardiac MR (CMR). METHODS: Studies were included that reported LV echocardiographic (2DE, CE-2DE, 3DE) and/or MDCT measurements compared to CMR. Only modern CMR (SSFP sequences) was considered. Studies involving small sample size (<10 patients) and unusual cardiac geometry (ie, congenital heart diseases) were excluded. We evaluated LV end-diastolic volume (LVEDV), end-systolic volume (LVESV) and ejection fraction (LVEF). RESULTS: 1604 articles were initially considered: 65 studies were included (total of 4032 scans (echo, CT, MRI) performed in 2888 patients). Compared to CMR, significant biased underestimation of LV volumes with 2DE was seen (LVEDV-33.30 mL, LVESV -16.20 mL, p<0.0001). This difference was reduced but remained significant with CE-2DE (LVEDV -18.05, p<0.0001) and 3DE (LVEDV -14.41, p<0.001), while MDCT values were similar to CMR (LVEDV -1.20, p=0.43; LVESV -0.13, p=0.91). However, excellent agreement for echocardiographic LVEF evaluation (2DE LVEF 0.78-1.01%, p=0.37) was observed, especially with 3DE (LVEF 0.14%, p=0.88). CONCLUSIONS: Comparing imaging modalities to CMR as reference standard, 3DE had the highest accuracy in LVEF estimation: 2DE and 3DE-derived LV volumes were significantly underestimated. Newer generation CT showed excellent accuracy for LV volumes.

The prognostic impact of diastolic dysfunction in patients with chronic heart failure and post-acute myocardial infarction: Can age-stratified E/A ratio alone predict survival?

OBJECTIVE: To determine the prognostic implications of diastolic filling grades and identify whether age-stratified E/A ratio alone can identify patients at high risk of death post-AMI and HF. We hypothesized that in response to ageing and pathology, a normal E/A (>1) could be considered abnormal in patients post-AMI older than 65years, and that in patients with symptomatic HF, a normal E/A always represents advanced diastolic dysfunction. METHODS AND RESULTS: This is a sub-analysis of the Meta-analysis Research Group in Echocardiography (MeRGE) which combined individual patient data from 30 prospective studies and demonstrated that restrictive filling was an important and independent predictor of all-cause mortality. This sub-analysis is restricted to those studies in which continuous E/A data were available (20 studies) and includes a total of 3082 AMI and 2321 HF patients. Patients were classified at the time of echocardiography into four filling patterns: normal, abnormal relaxation, pseudonormal, and restrictive filling. Post-AMI patients were divided into four groups on the basis of age and E/A, while patients with HF were classified into three groups, based on only E/A. Mortality across groups was compared using Kaplan-Meier survival analysis and Cox proportional hazards. In multivariable analyses in the AMI patients, age-stratified E/A was an independent predictor of outcome (HR 1.43 (95% CI: 1.31-1.56)), and in the HF cohort, E/A was confirmed as an independent predictor of mortality (HR 1.12 (95% CI 1.09-1.16)) alongside age and ejection fraction. CONCLUSIONS: Age-stratified E/A is an independent predictor of mortality after AMI and in HF patients, regardless of left ventricular ejection fraction, age and gender. E/A ratio could be a first step echocardiographic risk stratification, which could precede and indicate the need for more advanced diagnostic and prognostic considerations in high-risk AMI and HF patients.

Heart failure with preserved ejection fraction.

Progressive aging of the population and prolongation of life expectancy have led to the rising prevalence of heart failure (HF). Despite the improvements in medical therapy, the mortality rate of this condition has remained unacceptably high, becoming the primary cause of death in the elderly population. Almost half of patients with signs and symptoms of HF are found to have a nearly normal ejection fraction, which delineates a distinct clinical syndrome, known as HF with preserved ejection fraction (HF-PEF). While early research focused on the importance of diastolic dysfunction, more recent studies reported the pathophysiological complexity of the disease with multiple cardiovascular abnormalities contributing to its development and progression. HF-PEF is a challenging major health problem with yet no solution as there is no evidence-based treatment which improves clinical outcomes. This review summarizes the state of current knowledge on diagnosis, prognosis and treatment of HF-PEF, with particular insights on the pathological characteristics in the elderly population.

Identification of high-risk chronic heart failure patients in clinical practice: role of changes in left ventricular function.

BACKGROUND: Left ventricular (LV) dysfunction and remodeling are key pathophysiological features underlying disease progression in chronic heart failure (CHF). HYPOTHESIS: To describe the course of LV dysfunction and identify predictors and prognostic impact of changes in LV volumes and function in stable CHF patients under optimal therapy. METHODS: There were 318 consecutive CHF outpatients who underwent a repeated echocardiographic evaluation at baseline and at 1 year and subsequently followed-up for at least 12 months. The end point of the study was all-cause mortality. RESULTS: Mean LV ejection fraction (LVEF) was 33 ± 7% at baseline and 36 ± 9% at follow-up. Twenty-four percent of patients had an improvement of LVEF >5 absolute points (group 1); 58% remained stable (group 2), 17% worsened at >5 absolute points (group 3). Age, New York Heart Association class, diuretic dose, renal function, and baseline LVEF were independent predictors of LVEF improvement at 1 year. At the Cox analysis, patients in group 3 had a 4-fold higher risk of death when compared with group 1 (hazard ratio: 3.99, 95% confidence interval: 1.6-9.9, P = 0.002), independently of age, etiology, and symptoms severity. CONCLUSIONS: In stable CHF outpatients, LV function improves in 24% of cases; a modest decrease in LV systolic function is associated with a significantly higher risk of all-cause mortality, independent of other markers of disease severity.

Progression of Left Ventricular Dysfunction and Remodelling under Optimal Medical Therapy in CHF Patients: Role of Individual Genetic Background.

Background. Neurohormonal systems play an important role in chronic heart failure (CHF). Due to interindividual heterogeneity in the benefits of therapy, it may be hypothesized that polymorphisms of neurohormonal systems may affect left ventricular (LV) remodelling and systolic function. We aimed to assess whether genetic background of maximally treated CHF patients predicts variations in LV systolic function and volumes. Methods and Results. We prospectively studied 131 CHF outpatients on optimal treatment for at least six months. Echocardiographic evaluations were performed at baseline and after 12 months. Genotype analysis for ACE I/D, ß1adrenergic receptor (AR) Arg389Gly, ß2AR Arg16Gly, and ß2AR Gln27Glu polymorphisms was performed. No differences in baseline characteristics were detected among subgroups. ACE II was a significant predictor of improvement of LV end-diastolic and end-systolic volume (P = .003 and P = .002, respectively) but not of LV ejection fraction (LVEF); ß1AR389 GlyGly was related to improvement of LVEF (P = .02) and LV end-systolic volume (P = .01). The predictive value of polymorphisms remained after adjustment for other clinically significant predictors (P < .05 for all). Conclusions. ACE I/D and ß1AR Arg389Gly polymorphisms are independent predictors of reverse remodeling and systolic function recovery in CHF patients under optimal treatment.