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.

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.

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.

Web Health Monitoring Survey: A New Approach to Enhance the Effectiveness of Telemedicine Systems.

BACKGROUND: Aging of the European population and interest in a healthy population in western countries have contributed to an increase in the number of health surveys, where the role of survey design, data collection, and data analysis methodology is clear and recognized by the whole scientific community. Survey methodology has had to couple with the challenges deriving from data collection through information and communications technology (ICT). Telemedicine systems have not used patients as a source of information, often limiting them to collecting only biometric data. A more effective telemonitoring system would be able to collect objective and subjective data (biometric parameters and symptoms reported by the patients themselves), and to control the quality of subjective data collected: this goal be achieved only by using and merging competencies from both survey methodology and health research. OBJECTIVE: The objective of our study was to propose new metrics to control the quality of data, along with the well-known indicators of survey methodology. Web questionnaires administered daily to a group of patients for an extended length of time are a Web health monitoring survey (WHMS) in a telemedicine system. METHODS: We calculated indicators based on paradata collected during a WHMS study involving 12 patients, who signed in to the website daily for 2 months. RESULTS: The patients' involvement was very high: the patients' response rate ranged between 1.00 and 0.82, with an outlier of 0.65. Item nonresponse rate was very low, ranging between 0.0% and 7.4%. We propose adherence to the chosen time to connect to the website as a measure of involvement and cooperation by the patients: the difference from the median time ranged between 11 and 24 minutes, demonstrating very good cooperation and involvement from all patients. To measure habituation to the questionnaire, we also compared nonresponse rates to the items between the first and the second month of the study, and found no significant difference. We computed the time to complete the questionnaire both as a measure of possible burden for patient, and to detect the risk of automatic responses. Neither of these hypothesis was confirmed, and differences in time to completion seemed to depend on health conditions. Focus groups with patients confirmed their appreciation for this "new" active role in a telemonitoring system. CONCLUSIONS: The main and innovative aspect of our proposal is the use of a Web questionnaire to virtually recreate a checkup visit, integrating subjective (patient's information) with objective data (biometric information). Our results, although preliminary and if need of further study, appear promising in proposing more effective telemedicine systems. Survey methodology could have an effective role in this growing field of research and applications.

Is the digital divide an obstacle to e-health? An analysis of the situation in Europe and in Italy.

INTRODUCTION: The digital divide affecting elderly patients may compromise the diffusion of telemedicine systems for this age segment. It might be that the difficulties in the passage from trials to the effective distribution of telemedicine systems are also due to the awareness of a personal digital divide in the target population. MATERIALS AND METHODS: The analysis aims to estimate the number of people over the age of 50 years with potential cardiovascular problems able to access the Web. It made use of data from several sources (the Survey of Health, Ageing and Retirement in Europe and the Istituto Nazionale di Statistica Multiscopo Survey). Furthermore, with regard to Italy, the estimates obtained from official data were compared with those obtained in a survey investigating heart failure patients in Tuscany. RESULTS: In 2011, the percentage of people suffering from cardiovascular diseases and with Web access was 24% in Europe, with significant differences by country (ranging from 53% in Switzerland to below 20% in Italy, Spain, and Portugal). In Italy, however, the proportion of people with Web access increased from 2007 to 2011, and the survey in Tuscany showed that elderly people with limited information and communications technology skills overcame challenges and learned how to connect to the Web because they started to appreciate new technologies. CONCLUSIONS: The opportunity to use the Internet to monitor patients with chronic disease can serve as a challenge to reduce the digital divide gap and, furthermore, to increase their social and technological inclusion.

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.

The informative contribution of the "virtual medical visit" in a new heart failure telemedicine integrated system.

INTRODUCTION: Telemedicine systems consist of collection, transmission, and analysis of biometric data essentially based on instrumental measures. Our goal was to evaluate if information collected from patients has an incremental informative value in automatically rating the patient's health status. MATERIALS AND METHODS: We present preliminary results of a new telemedicine system (ASCOLTA) obtained by observation of 12 heart failure patients (New York Heart Association Class IIb-III). Instrumental data (electrocardiogram, oxygen saturation level, and respiration rate) were wirelessly collected daily together with clinical data (weight, heart rate, and blood pressure values) and patients' information obtained through a Web-based questionnaire, simulating a virtual medical visit. Health status was independently judged by two blinded cardiologists and by the patient's cardiologist on the basis of 348 daily clinical reports. Random forest classification analysis was applied to 240 complete clinical report variables in order to estimate the judged health status. RESULTS: The use of "patient's information" led to a better predictive ability in comparison with using only physiological parameters assessed by instruments. The complete set of variables (Patient+Instrumental) achieved 84% concordance, compared with 72% for the instrumental-only variables and 69% for the patient-only variables. The receiver operator characteristics curves graphically confirmed the described results. CONCLUSIONS: Patients have an active role in home monitoring, and their information appears relevant for a new telemedicine approach integrating subjective and objective vital signs. Combining patient information with instrumental parameters, it is possible to achieve a more correct automatic classification of health status of heart failure patients.

Somatic overgrowth predisposes to seizures in autism spectrum disorders.

BACKGROUND: Comorbidity of Autism Spectrum Disorders with seizures or abnormal EEG (Autism-Epilepsy Phenotype) suggests shared pathomechanisms, and might be a starting point to identify distinct populations within the clinical complexity of the autistic spectrum. In this study, we tried to assess whether distinct subgroups, having distinctive clinical hallmarks, emerge from this comorbid condition. METHODS: Two-hundred and six individuals with idiopathic Autism Spectrum Disorders were subgrouped into three experimental classes depending on the presence of seizures and EEG abnormalities. Neurobehavioral, electroclinical and auxological parameters were investigated to identify differences among groups and features which increase the risk of seizures. Our statistical analyses used ANOVA, post-hoc multiple comparisons, and the Chi-squared test to analyze continuous and categorical variables. A correspondence analysis was also used to decompose significant Chi-squared and reduce variables dimensions. RESULTS: The high percentage of children with seizures (28.2% of our whole cohort) and EEG abnormalities (64.1%) confirmed that the prevalence of epilepsy in Autism Spectrum Disorders exceeds that of the general population. Seizures were associated with severe intellectual disability, and not with autism severity. Interestingly, tall stature (without macrocephaly) was significantly associated with EEG abnormalities or later onset seizures. However, isolated macrocephaly was equally distributed among groups or associated with early onset seizures when accompanied by tall stature. CONCLUSIONS: Tall stature seems to be a phenotypic "biomarker" of susceptibility to EEG abnormalities or late epilepsy in Autism Spectrum Disorders and, when concurring with macrocephaly, predisposes to early onset seizures. Growth pattern might act as an endophenotypic marker in Autism-Epilepsy comorbidity, delineating distinct pathophysiological subtypes and addressing personalized diagnostic work-up and therapeutic approaches.

Measuring the effectiveness of homeopathic care through objective and shared indicators.

OBJECTIVE: To test a methodology to evaluate, at population level, the effectiveness of homeopathic treatment through standard objective public health indicators. METHODS AND SETTINGS: Indicators of hospitalization and drug use were obtained from the Health Statistical Documentation System of Tuscany for two homeopathic centers in the Local Health Authority of Pisa, Italy. We compared homeopathic users with the general population in the same area and by comparing patients before and after homeopathic treatment. RESULTS: The homeopathic patients used less drugs than the reference population, this effect was more evident for patients with repeated homeopathic consultations. A significant decrease in drug use was found on comparing the same patients before and after homeopathic treatment. Hospitalization indicators tended to favour patients who had received homeopathic treatment but were not always statistically significant. CONCLUSIONS: This paper demonstrates a new methodological approach to assess the effectiveness of a therapeutic modality, without ad-hoc clinical trials. This methodology can be used by public health institutions in which non-conventional medicines are integrated into the public health care system.

Carotid intima-media thickness in asymptomatic patients with arterial hypertension without clinical cardiovascular disease: relation with left ventricular geometry and mass and coexisting risk factors.

We analyzed in NYHA I hypertensives the interactions between Carotid Intima-Media Thickness (IMT), Hypertension and Cardiovascular (CV) risk factors and relationships between IMT, CV risk factors and left ventricular (LV) geometric remodelling. 198 asymptomatic, never treated, essential hypertensives (age: 58.2 +/- 13) and 67 (age-gender matched) healthy subjects, were studied. Complete clinical examination, 2D Doppler echocardiography and vascular echography were performed in all study subjects. Major values of IMT are present in concentric LVH. Distribution of IMT among risk factors groups shows an higher IMT respect to increasing number of risk factors (P < 0.001). Significant correlation are present between pulse pressure and IMT (P < 0.006; r = 0.19) and IMT and LVM (P < 0.0001; r = 0.35). Altered patterns of LV geometry and carotid structural changes occur in many patients with essential hypertension. LVH or carotid remodeling are greater in elderly, in patients with higher systolic BP and with associated CV risk factors.

Severe aortic stenosis and myocardial function: diagnostic and prognostic usefulness of ultrasonic integrated backscatter analysis.

BACKGROUND: The aim of this study was to assess the myocardial reflectivity pattern in severe aortic valve stenosis through the use of integrated backscatter (IBS) analysis. Patients with aortic stenosis (AS) were carefully selected in the Department of Cardiology. METHODS AND RESULTS: Thirty-five subjects (AS: valve orifice < or =1 cm2; 12 female; mean age, 71.8+/-6.2 years) and 25 healthy subjects were studied. All subjects of the study had conventional 2D-Doppler echocardiography and IBS. Backscatter signal was sampled at the septum and posterior wall levels. Patients with AS were divided into 2 groups: 16 patients with initial signs of congestive heart failure and a depressed left ventricular systolic function (DSF) (ejection fraction [EF] range, 35% to 50%) and 19 asymptomatic patients with normal left ventricular systolic function (NSF) (EF >50%). Myocardial echo intensity (pericardium related) was significantly higher at the septum and posterior wall levels in DSF than in NSF and in control subjects. IBS variation, as an expression of variation of the signal, appeared to be significantly lower in AS with DSF than in NSF and in control subjects, at both the septum and posterior wall levels. Patients with DSF underwent aortic valve replacement, and, during surgical intervention, a septal myocardial biopsy was made for evaluation of myocardium/fibrosis ratio. Abnormally increased echo intensity was detected in left ventricular pressure overload by severe aortic stenosis and correlated with increase of myocardial collagen content (operating biopsy). CONCLUSIONS: One year after aortic valve replacement, we observed a significant reduction of left ventricular mass, and, only if pericardial indexed IBS value (reduction of interstitial fibrosis) decreased, it was possible to observe an improvement of EF and of IBS variation.

Incremental value of ultrasonic tissue characterization (backscatter) in the evaluation of left ventricular myocardial structure and mechanics in essential arterial hypertension.

BACKGROUND: Ultrasonic backscatter parameters were analyzed in hypertensive patients and divided into groups according to both severity of left ventricular hypertrophy (LVH) (group A: no LVH [n=52]; B: mild to moderate LVH [n=55]; and C: severe LVH [n=10]) and left ventricular geometry (normal geometry [n=44]; concentric remodeling [n=8]; concentric hypertrophy [n=25]; and eccentric hypertrophy [n=40]). METHODS AND RESULTS: We studied 117 male, essential hypertensive patients and 19 normotensive, age-matched (40+/-5 years), healthy subjects who served as controls. Ambulatory and office blood pressure measurements were taken and 2-dimensional Doppler echocardiography and ultrasonic myocardial integrated backscatter (IBS) were performed. A group from the hypertensive study population (n=16) was observed after a period of pharmacological antihypertensive treatment to determine the behavior of backscatter parameters in relation to eventual regression of left ventricular mass (LVM). The cyclic variation index (CVIs) of the backscatter signal at the septum level was grouped according to each LVM level and was 29.4+/-9.3 (controls), 15+/-11 (group A), 9.5+/-10 (group B), and -1.5+/-8.6 (group C) (P<0.001). CVI septum values grouped according to left ventricular geometry were 15+/-11 (normal geometry), 12+/-7 (concentric remodeling), 7+/-11 (concentric hypertrophy), and 7.8+/-11 (eccentric hypertrophy) (P<0.01). Follow-up data demonstrate a significant reduction of LVM after therapy, as well as a significant increase in CVIs toward normal values. CONCLUSIONS: Hypertensive patients with higher LVM had the worst prognosis; in fact, those patients had the most significant CVI alterations. Regression of LVM subsequent to chronic pharmacological therapy induces a normalization of ultrasonic backscatter parameters. Ultrasonic tissue characterization (backscatter) analysis could allow early identification of patients at risk of developing complications of hypertensive cardiopathy.