Daniela Girfoglio

Does Information on Systolic and Diastolic Function Improve Prediction of a Cardiovascular Event by Left Ventricular Hypertrophy in Arterial Hypertension

Left ventricular (LV) mass (LVM) is the most important information requested in hypertensive patients referred for echocardiography. However, LV function also predicts cardiovascular (CV) risk independent of LVM. There is no evidence that addition of LV function significantly improves model prediction of CV risk compared with LVM alone. Thus, composite fatal and nonfatal CV or cerebrovascular events were evaluated in 5380 hypertensive outpatients (2336 women, 298 diabetics, and 1315 obese subjects) without prevalent CV disease (follow-up: 3.5±2.8 years). We compared 5 risk models using Cox regression and adjusting for age and sex: (1) LV mass normalized for height in meters2.7 (LVMi); (2) LVMi, concentric LV geometry, by relative wall thickness (>0.43), ejection fraction, and transmitral diastolic pattern (by thirtiles of mitral deceleration index); (3) LVMi, LV geometry, midwall shortening, and mitral deceleration index thirtiles; (4) as No. 2 with the addition of left atrial dilatation (>23 mm); and (5) as No. 3 with the addition of left atrial dilatation. Individual hazard functions were compared using receiving operating characteristic curves and z statistics. Areas under the curves increased from 0.60 in the model with the sole LVMi to 0.62 in the others (all P values for differences were not significant). The additional information on systolic and diastolic function decreased the contribution (Wald statistics) of LVMi in the Cox model without improving the model ability to predict CV risk. We conclude that risk models with inclusion of information on LV geometry and systolic and diastolic function, in addition to LVMi, do not improve the prediction of CV events but rather redistribute the impact of individual predictors within the risk variance.

Lack of Reduction of Left Ventricular Mass in Treated Hypertension: The Strong Heart Study

Background Hypertensive left ventricular mass (LVM) is expected to decrease during antihypertensive therapy, based on results of clinical trials. Methods and Results We assessed 4‐year change of echocardiographic LVM in 851 hypertensive free‐living participants of the Strong Heart Study (57% women, 81% treated). Variations of 5% or more of the initial systolic blood pressure (SBP) and LVM were categorized for analysis. At baseline, 23% of men and 36% of women exhibited LV hypertrophy (LVH, P<0.0001). At the follow‐up, 3% of men and 10% of women had regression of LVH (P<0.0001 between genders); 14% of men and 15% of women, free of baseline LVH, developed LVH. There was an increase in LVM over time, more in men than in women (P<0.001). Participants whose LVM did not decrease had similar baseline SBP and diastolic BP, but higher body mass index (BMI), waist/hip ratio, heart rate (all P<0.008), and urinary albumin/creatinine excretion (P<0.001) than those whose LVM decreased. After adjusting for field center, initial LVM index, target BP, and kinship degree, lack of decrease in LVM was predicted by higher baseline BMI and urinary albumin/creatinine excretion, independently of classes of antihypertensive medications, and significant effects of older age, male gender, and percentage increase in BP over time. Similar findings were obtained in the subpopulation (n=526) with normal BP at follow‐up. Conclusions In a free‐living population, higher BMI is associated with less reduction of hypertensive LVH; lack of reduction of LVM is independent of BP control and of types of antihypertensive treatment, but is associated with renal damage.

Cardiovascular Biomarkers, Cardiac Dysfunction, and Outcomes in Patients With Type 2 Diabetes: A Prospective, Multicenter Study

Although diabetes is a major risk factor for ischemic heart disease or heart failure (HF), and despite the fact that echocardiography has revealed a high prevalence of left ventricular (LV) diastolic and systolic dysfunctions and hypertrophy (1–3), routine screening for cardiovascular disease using echocardiography in asymptomatic patients with type 2 diabetes is not recommended by current guidelines (4). The availability of laboratory markers of cardiovascular risk would substantially contribute to the early and simple screening of patients at increased risk of HF, allowing them to be better targeted with appropriate pharmacological therapies (5). As part of the LV Dysfunction in Diabetes (DYDA) study, we assessed the relations between different laboratory markers, including centrally assayed glycated hemoglobin (HbA1c), N-terminal probrain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP), …

Preclinical Systolic Dysfunction in Patients with Stage 3 Chronic Kidney Disease

AbstractIntroduction: Chronic kidney disease (CKD) is associated with increased cardiovascular risk and mortality. We evaluated whether stage 3 (s3)-CKD is associated with abnormalities of the cardiovascular system. Methods: Thirty-nine asymptomatic s3-CKD patients, free of prevalent cardiovascular disease, were compared with 44 control subjects with comparable prevalence of hypertension (66% vs 69% in s3-CKD). In addition to standard echocardiographic parameters, we computed non-invasive effective arterial elastance (EAE, in mmHg/mL/beat), systolic left ventricular elastance (LVe, in mmHg/mL) and myocardial mechanic efficiency (MME, in mL/sec), using previously reported formulas. Results: s3-CKD and controls were comparable for age, sex, lipid profile and prevalence of diabetes mellitus and smoking habit. Left ventricular (LV) mass, geometry and stroke work were similar in the two groups, with both ejection fraction and midwall shortening (mS) significantly reduced in the CKD group (both p < 0.001). Within the s3-CKD group, 36% had clear-cut depressed mS. EAE and peripheral resistance were higher in s3-CKD than in controls (both p < 0.005), and MME was reduced in CKD (p < 0.005), an impairment even clearer after controlling for LV mass, and increasing with increasing values of LV mass (p < 0.001). In addition, at a given level of peripheral resistance, LV geometry was less concentric in s3-CKD than in controls (p < 0.05). Conclusions: s3-CKD asymptomatic patients show a peculiar cardiovascular phenotype, characterized by impaired mechano-energetic efficiency and reduced midwall mechanics, in the presence of inadequately compensating LV concentric remodelling. Whether these characteristics might result in higher cardiovascular risk in s3-CKD should be investigated.

DEPRESSED CARDIAC MECHANICS IN HYPERTENSIVE PATIENTS WITH MODERATE CHRONIC RENAL INSUFFICIENCY: A SPECKLE-STRAIN STUDY: PP.9.346

Background: Systolic dysfunction in hypertension (HTN) and chronic kidney disease (CKD) is related to left ventricular (LV) hypertrophy. However, it has been suggested that in CKD interstitial collagen deposition is higher than in HTN, possibly further impairing systolic function. Accordingly, the aim of the present study was to compare echocardiographic speckle tracking strain (ϵ) in hypertensive patients with or without CKD. Methods: Standard Doppler echocardiography was obtained in 11 hypertensive patients with moderate CKD (stage III, GFR = 36 ± 12 mL/min/1.73 m2) and 22 age matched HTN (mean age 58 ± 14yrs) with normal renal function. Patients with significant valvular disease and/or reduced ejection fraction were excluded. Traditional assessment of LV systolic function included ejection fraction, and fractional and midwall shortening. Speckle tracking ϵ was evaluated in all three planes (circumferential, longitudinal, and radial). Results: CKD patients showed similar body mass index, systolic and diastolic blood pressure as compared to HTN (P = NS). LV mass index was similar in the HTN (49 g/m2.7) and the CKD group (50 g/m2.7) as well as relative wall thickness (0.48 vs 0.50; all p = NS). Traditional indices of systolic function were unable to discriminate between the two groups. In contrast, analysis of ϵ demonstrated a significant reduction in both circumferential and longitudinal ϵ in the CKD group (Figure). Figure 1. No caption available. Conclusions: Despite similar LV geometry and traditional systolic function indices, analysis of ϵ demonstrates impairment of cardiac mechanics in CKD, possibly caused by the presence of more severe myocardial fibrosis. Analysis of cardiac mechanics by speckle tracking echocardiography might be more sensitive in the assessment of CV risk in hypertensive CKD patients.

LEFT VENTRICULAR MASS IS A PREDICTOR OF FOLLOW-UP UNCONTROLLED BLOOD PRESSURE IN HYPERTENSIVE PATIENTS: 4B.04

Background: Left ventricular (LV) hypertrophy (LVH) is considered as a target organ response to chronic arterial hypertension and is used to stratify cardiovascular (CV) risk. LV mass (LVM) is also increased in subjects developing subsequent hypertension. Whether initial LVM also influences effective therapeutic control of blood pressure (BP) is unknown. Methods: We estimated risk of suboptimal BP control in relation to baseline LVM index (LVMi) in 4693 hypertensive outpatients from the Campaniasalute Network, with at least 1 yr follow-up (mean 4 ± 3yrs) and without prevalent CV disease (age 53 ± 11 yrs, 43% women, 5% diabetic). BP was defined uncontrolled when systolic BP> = 140mmHg or/and diastolic BP>=90mmHg (or BP>=130 or/and 80 mmHg in diabetic patients) at the last available outpatient visit. Results: Poor BP control was detected in 2240 patients (48%), despite treatment with 2 or more antihypertensive drugs. Patients with uncontrolled BP were older, more often obese (28% versus 21%) and diabetic (9% versus 1.6%), with a longer duration of hypertension and higher baseline BP, heart rate, LVMi, and prevalence of LVH (36% versus 26%, all p < 0.0001), with no difference in sex distribution. Of 1440 patients with baseline LVH, 803 (or 56%) had uncontrolled BP at follow-up, compared to 44% of those without LVH (p < 0.0001). In multivariate analyses, odds of uncontrolled BP increased significantly with higher baseline systolic BP, heart rate, BMI, duration of hypertension, diabetes (all p < 0.0001) and greater baseline LVMi (OR = 1.10/10 g/m2.7, 1.04–1.20, p = 0.002) independent of age, gender and number of medications. When specific classes of medications were added to the previous model, only use of anti-Renin-Angiotensin System reduced the risk of uncontrolled BP (OR = 0.83, 0.71–0.95, p = 0.01), with no impact for other classes of drugs (diuretics, β-blockers, Ca++-channel blockers and α-blockers). Conclusions: We conclude that in a large population of treated hypertensive patients, higher baseline left ventricular mass is significantly associated with risk of uncontrolled BP independently of age, gender, body max index, diabetes and antihypertensive therapy.

ATRIAL STRAIN BY 2D SPECKLE TRACKING OUTPERFORMS ATRIAL VOLUME IN IDENTIFYING HYPERTENSIVE PATIENTS WITH DIASTOLIC DYSFUNCTION: PP.8.336

Background: Left atrial (LA) dilation is considered a marker of diastolic dysfunction (DD). However LA size is affected by loading conditions (e.g. overweight, physical excercise, mild mitral regurgitation), and dilation might also be found in individuals with normal LV diastolic function. LA deformation by 2D Speckle Strain Imaging (2DSI) is a novel method to analyze LA diastolic function, which might improve the ability of identifying DD in hypertensives (HTN). Methods: 39 HTN with grade 1–2 DD (76 ± 14yrs; 72%females) and 66 healthy volunteers (NLS; 44 ± 16yrs; 55%females) underwent standard echocardiography with complete evaluation of diastolic function and LA 2DSI. LA volume was calculated by the area-length method. Gender-specific ASE recommended partition values were used to define LA dilation. Receiver operating curves were used to compare the accuracy of LA volume and LA2DSI in differentiating HTN with DD from NLS. Results: HTN were older and more often women as compared to NLS (both p < 0.05). In analysis of covariance, adjusting for covariates, HTN showed reduced LA 2DSI (23.8 ± 8.2% vs 43.0 ± 11.1%) and higher LA volume (58 ± 27 mL vs 41 ± 14 mL), resulting in a higher prevalence of LA dilation (38% vs 12%; all p < 0.01). Comparison of ROC suggested a significantly better performance of LA 2DSI, as compared to LA volume, in differentiating HTN with DD from NLS (AUC = 0.89 vs 0.68; p = 0.001). In details, an LA 2DSI partition value of 26% demonstrated 75% specificity and 76% sensitivity in identifying HTN with DD. Figure 1. No caption available. Conclusion: Reduced LA diastolic function by 2DSI is often found in HTN patients and is associated with increased LA volume. Presence of LA 2DSI < 26% is significantly more accurate than presence of LA dilation in differentiating HTN with DD from normal controls. Further studies are needed to verify the prognostic superiority of LA 2DSI.

NON INVASIVE EVALUATION OF MYOCARDIAL STIFFNESS IN ARTERIAL HYPERTENSION: PP.22.348

Background: Heart failure with preserved ejection fraction (HFPEF) is frequent in hypertension in the absence of preceding myocardial infarction and is attributed to abnormal myocardial stiffness (MS), altering the physiological pressure/volume relationship. A direct non-invasive measure of MS is still a challenge. Methods: Using standard transthoracic Doppler-echocardiography and tissue-Doppler, we generated a single point LV end-diastolic (ED) pressure (P)/volume (V) ratio as an estimate of MS in 59 normotensive and 64 hypertensive subjects (18–91 yrs). ED-P was calculated as LV pressure before atrial contraction (estimated by E/E’ ratio) + peak atrio-ventricular gradient at the atrial contraction (from peak A velocity). ED-P/V was 0.15 ± 0.05 in normotensive subjects and the value of 0.20 (90th percentile) defined increased MS. We also generated P/V loops for subjects with (n = 33) or without (n = 90) increased ED-P/V, by assuming: 1) P at mitral opening = 5 mmHg; 2) End of isometric contraction corresponding to aortic diastolic P; 3) Peak-systolic P = cuff systolic P occurring at 2/3 of LV empting; 4) End-systolic P estimated as: mean cuff P*0.98 + 11, corresponding to the time of end-systolic V. Results: Subjects with high ED-P/V (n = 33, 82% hypertensive) exhibited higher ejection fraction and relative wall thickness with lower midwall shortening, stroke volume and stroke work (see figure) than those with normal ED-P/V (all p < 0.0001) and similar LV mass. Conclusions: Thus, a CV phenotype at high risk of HFPEF corresponds to a high non-invasively determined single-beat ED-P/V ratio as an estimate of increased myocardial stiffness. This method might identify hypertensive patients at high risk of HFPEF. Figure 1. No caption available.

Preclinical Systolic Dysfunction in Patients With Stage 3 Chronic Renal Disease: Pp.9.376:

Background: Chronic kidney disease (CKD) is associated with increased cardiovascular (CV) risk. Cardiac abnormalities have been studied in severe CKD but not in the most prevalent stage 3 (s3), often under-diagnosed. We evaluated whether s3-CKD is associated with abnormalities of CV system. Methods: 39 asymptomatic patients with s3-CKD (GFR = 45 ± 10 ml/min/1.73m2), free of prevalent CV disease, from the outpatient clinic of the Department of Nephrology, were compared with 44 control subjects with GFR>60 ml/min/1.73m2 (GFR = 84 ± 14 ml/min/1.73m2) and comparable prevalence of hypertension (66% vs 69 in s3-CKD). In addition to standard echocardiographic parameters of left ventricular (LV) geometry and function, we computed non-invasive effective arterial elastance (EAe in mmHg/mL/beat, using an estimate of end-systolic pressure), systolic LV elastance (LVe, in mmHg/mL) and myocardial mechanic efficiency (MME, in mL/sec), using previously reported formulas. Results: s3-CKD and controls were comparable for age, sex, lipid profile, prevalence of diabetes and smoking habit. LV mass, LV geometry and stroke work were similar in the two groups, but both ejection fraction and midwall shortening (mS) were significantly reduced in s3-CKD (both p < 0.001), with 36% s3-CKD with clear-cut depressed mS. EAe and peripheral resistance were higher in s3-CKD than in controls (both p < 0.002), without significant difference in LVe, resulting in an apparently favorable vascular ventricular coupling. However MME was substantially reduced in CKD (p < 0.004). For comparable levels of LV mass, MME was substantially reduced in s3-CKD, compared to controls, with the difference increasing with increasing values of LV mass (p < 0.001 for slope). Similarly, at a given level of peripheral resistance, LV geometry was less concentric in s3-CKD than in controls (p < 0.05). Conclusions: We conclude that s3-CKD asymptomatic patients present with a peculiar CV phenotype, characterized by impaired mechano-energetic efficiency and reduced midwall mechanics, in the absence of compensating LV concentric remodeling, to avoid fall in ejection fraction. How much these characteristics might impact evolution toward more pronounced LV abnormalities in more advanced CKD and incident heart failure should be investigated.