Clementina Dugo

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.

ECG-derived spatial QRS-T angle is associated with ICD implantation, mortality and heart failure admissions in patients with LV systolic dysfunction

Background Increased spatial QRS-T angle has been shown to predict appropriate implantable cardioverter defibrilIator (ICD) therapy in patients with left ventricular systolic dysfunction (LVSD). We performed a retrospective cohort study in patients with left ventricular ejection fraction (LVEF) 31–40% to assess the relationship between the spatial QRS-T angle and other advanced ECG (A-ECG) as well as echocardiographic metadata, with all-cause mortality or ICD implantation for secondary prevention. Methods 534 patients ≤75 years of age with LVEF 31–40% were identified through an echocardiography reporting database. Digital 12-lead ECGs were retrospectively matched to 295 of these patients, for whom echocardiographic and A-ECG metadata were then generated. Data mining was applied to discover novel ECG and echocardiographic markers of risk. Machine learning was used to develop a model to predict possible outcomes. Results 49 patients (17%) had events, defined as either mortality (n = 16) or ICD implantation for secondary prevention (n = 33). 72 parameters (58 A-ECG, 14 echocardiographic) were univariately different (p<0.05) in those with vs. without events. After adjustment for multiplicity, 24 A-ECG parameters and 3 echocardiographic parameters remained different (p<2x10-3). These included the posterior-to-leftward QRS loop ratio from the derived vectorcardiographic horizontal plane (previously associated with pulmonary artery pressure, p = 2x10-6); spatial mean QRS-T angle (134 vs. 112°, p = 1.6x10-4); various repolarisation vectors; and a previously described 5-parameter A-ECG score for LVSD (p = 4x10-6) that also correlated with echocardiographic global longitudinal strain (R2 = - 0.51, P < 0.0001). A spatial QRS-T angle >110° had an adjusted HR of 3.4 (95% CI 1.6 to 7.4) for secondary ICD implantation or all-cause death and adjusted HR of 4.1 (95% CI 1.2 to 13.9) for future heart failure admission. There was a loss of complexity between A-ECG and echocardiographic variables with an increasing degree of disease. Conclusion Spatial QRS-T angle >110° was strongly associated with arrhythmic events and all-cause death. Deep analysis of global ECG and echocardiographic metadata revealed underlying relationships, which otherwise would not have been appreciated. Delivered at scale such techniques may prove useful in clinical decision making in the future.

Association between plasma ceramides and inducible myocardial ischemia in patients with established or suspected coronary artery disease undergoing myocardial perfusion scintigraphy

BACKGROUND Recent studies have suggested that specific plasma ceramides are independently associated with major adverse cardiovascular events in patients with coronary artery disease (CAD), but it is currently unknown whether plasma ceramide levels are associated with stress-induced reversible myocardial ischemia. METHODS We measured six previously identified high-risk plasma ceramide molecules [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1)] in 167 consecutive patients with established or suspected CAD who underwent either exercise or dypiridamole myocardial perfusion scintigraphy (MPS) for various clinical indications. Plasma ceramide levels were measured by a targeted liquid chromatography-tandem mass spectrometry assay both at baseline and after MPS. RESULTS Seventy-eight patients had inducible myocardial ischemia on stress MPS. Women had significantly higher circulating levels of basal and post-stress Cer(d18:1/16:0) and Cer(d18:1/18:0) compared to men, whereas all other plasma ceramides did not differ between the sexes. Of the six measured plasma ceramides, basal Cer(d18:1/24:1) showed the strongest association with the presence of stress-induced myocardial perfusion defects in univariate analysis (unadjusted-odds ratio 1.48 per 1-SD increment, 95% confidence interval 1.08-2.04). Notably, after adjustment for age, sex, smoking, dyslipidemia, hypertension, diabetes, prior history of CAD, left ventricular ejection fraction, and type of stress testing (exercise vs. dypiridamole), all measured ceramides, except for plasma Cer(d18:1/24:0), were independently associated with the presence of inducible myocardial ischemia. CONCLUSIONS Distinct plasma ceramides are positive and independent predictors of stress-induced myocardial perfusion defects in patients with established or suspected CAD referred for clinically indicated MPS. Further research is needed to examine whether distinct plasma ceramides could be a useful therapeutic target for treatment and management of CAD.

Diagnostic Utility of High Sensitivity Troponins for Echocardiographic Markers of Structural Heart Disease

The conventional use of high-sensitivity troponins (hs-troponins) is for diagnosing myocardial infarction however they also have a role in chronic disease management. This pilot study assessed the relationship of hs-troponins with echocardiographic markers of left ventricular hypertrophy (LVH) and structural heart disease (SHD). Patients undergoing computer gomography (CT) coronary angiogram for low-intermediate risk chest pain and healthy volunteers were recruited. Hs-troponins Singulex I, Abbott I and Roche T and N-terminal pro-brain natriuretic peptide (NT-proBNP) were evaluated in relation to SHD parameters including left ventricular hypertrophy (LVHEcho) and left atrial enlargement (LAEEcho) on echocardiography. 78 subjects who underwent echocardiography were included in this study. C-statistics (95% confidence interval) of the four biomarkers for predicting LVHEcho were 0.84 (0.72–0.92), 0.84 (0.73–0.92), 0.75 (0.63–0.85) and 0.62 (0.49–0.74); for LAEEcho 0.74 (0.6–0.85), 0.78 (0.66–0.88), 0.55 (0.42–0.67) and 0.68 (0.62–0.85); and composite SHD 0.79 (0.66–0.88), 0.87 (0.75–0.94), 0.62 (0.49–0.73) and 0.74 (0.62–0.84) respectively. Optimal cut points for SHD were >1.2 ng/L, >1.6 ng/L, >8 ng/L and >18 pmol/L respectively. These results advocate the potential role of hs-troponins as screening tools for structural heart disease with theranostic implications.

Relation of elevated serum uric acid levels to first-degree heart block and other cardiac conduction defects in hospitalized patients with type 2 diabetes

AIMS Several studies have reported that moderately elevated serum uric acid levels are associated with an increased risk of tachyarrhythmias (mainly atrial fibrillation) in patients with and without type 2 diabetes mellitus (T2DM). It is currently unknown whether an association also exists between elevated serum uric acid levels and cardiac conduction defects in patients with T2DM. METHODS We retrospectively analyzed a hospital-based sample of 967 patients with T2DM discharged from our Division of Endocrinology over the years 2007-2014. Standard electrocardiograms were performed on all patients and were interpreted by expert cardiologists. RESULTS Overall, 267 (27.6%) patients had some type of conduction defects on electrocardiograms (defined as at least one block among first-degree atrio-ventricular block, second-degree block, third-degree block, left bundle branch block, right bundle branch block, left anterior hemi-block or left posterior hemi-block). Patients in the 3rd serum uric acid tertile had a higher prevalence of any cardiac conduction defects than those belonging to 2nd or 1st tertile, respectively (35.8% vs. 25.0% vs. 22.6%; p<0.0001). Elevated serum uric acid levels were associated with a nearly twofold increased risk of cardiac conduction defects after adjustment for age, sex, hemoglobin A1c, diabetes duration, metabolic syndrome, chronic kidney disease, chronic obstructive pulmonary disease, ischemic heart disease, valvular heart disease and medication use (adjusted-odds ratio 1.84, 95% confidence intervals 1.2-2.9; p=0.009). CONCLUSIONS Moderately elevated serum uric acid levels are associated with an increased prevalence of any cardiac conduction defects in hospitalized patients with T2DM, independent of multiple risk factors and potential confounding variables.