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, β1adrenergic receptor (AR) Arg389Gly, β2AR Arg16Gly, and β2AR 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); β1AR389 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 β1AR Arg389Gly polymorphisms are independent predictors of reverse remodeling and systolic function recovery in CHF patients under optimal treatment

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

Novel assessment of cardiorespiratory interactions in aortic stenosis

The outcome in aortic stenosis (AS) depends on the correct timing of aortic valve replacement. Currently, this is based on symptoms and cardiac response to pressure overload. In patients with multiple medical conditions, uncertainty exists concerning their symptomatic onset and in distinguishing cardiac from respiratory causes of breathlessness. An accurate assessment of lung disease and optimal tools to discriminate between cardiac and respiratory dyspnoea are needed in AS, in whom decompensation may confound respiratory assessment, and conversely, chronic obstructive pulmonary disease (COPD) is a major reason for delay or avoidance of surgery. Advanced imaging allows the assessment of cardiac and respiratory co-morbidities, potentially reducing the misinterpretation of symptoms, and, therefore, may enable more appropriate treatment in cardiopulmonary disease. The thesis explores the importance of lung disease in AS and the limitations of standard respiratory assessment in decompensated cardiac disease. Secondly, novel ways of discriminating between respiratory and cardiac effects in AS are assessed. Lastly, the importance of the right ventricular response to pressure overload is evaluated. In summary, this thesis demonstrates the role of cardiorespiratory assessment in cardiac disease, including novel morpho-functional imaging evaluation of the cardiopulmonary interactions in AS. Patients with advanced lung disease who would not improve after valve replacement may in the future avoid a high-risk futile intervention. On the contrary, those with a hyperdynamic right ventricle and apparent respiratory dysfunction determined by cardiac disease might avoid cardiac under-treatment.</p

Novel assessment of cardiorespiratory interactions in aortic stenosis

The outcome in aortic stenosis (AS) depends on the correct timing of aortic valve replacement. Currently, this is based on symptoms and cardiac response to pressure overload. In patients with multiple medical conditions, uncertainty exists concerning their symptomatic onset and in distinguishing cardiac from respiratory causes of breathlessness. An accurate assessment of lung disease and optimal tools to discriminate between cardiac and respiratory dyspnoea are needed in AS, in whom decompensation may confound respiratory assessment, and conversely, chronic obstructive pulmonary disease (COPD) is a major reason for delay or avoidance of surgery. Advanced imaging allows the assessment of cardiac and respiratory co-morbidities, potentially reducing the misinterpretation of symptoms, and, therefore, may enable more appropriate treatment in cardiopulmonary disease. The thesis explores the importance of lung disease in AS and the limitations of standard respiratory assessment in decompensated cardiac disease. Secondly, novel ways of discriminating between respiratory and cardiac effects in AS are assessed. Lastly, the importance of the right ventricular response to pressure overload is evaluated. In summary, this thesis demonstrates the role of cardiorespiratory assessment in cardiac disease, including novel morpho-functional imaging evaluation of the cardiopulmonary interactions in AS. Patients with advanced lung disease who would not improve after valve replacement may in the future avoid a high-risk futile intervention. On the contrary, those with a hyperdynamic right ventricle and apparent respiratory dysfunction determined by cardiac disease might avoid cardiac under-treatment.</p

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

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

PurposeCardiac 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.MethodsThe 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&nbsp;&gt;&nbsp;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.ResultsHeart 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.ConclusionsHeart-centered patient positioning enables a significant radiation dose reduction while maintaining CAC accuracy

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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, β1adrenergic receptor (AR) Arg389Gly, β2AR Arg16Gly, and β2AR 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); β1AR389 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 &lt; .05 for all). Conclusions. ACE I/D and β1AR Arg389Gly polymorphisms are independent predictors of reverse remodeling and systolic function recovery in CHF patients under optimal treatment