Applicability and performance of heart failure prognostic scores in dilated cardiomyopathy: the real-world experience of an Italian referral center for cardiomyopathies.

BACKGROUND: The performance of heart failure (HF) risk models is validated in the general population with HF but in specific aetiological settings, and specifically in dilated cardiomyopathy (DCM), has scarcely been explored. We tested eight of the main prognostic scores used in HF in a large real-world population of patients with DCM. METHODS: We included 784 consecutive DCM patients enrolled, both inpatients and outpatients, enrolled between January 2000 and December 2017. The risk of 1 and/or 3-year all-cause mortality/heart transplantation/durable left ventricular assist device (LVAD) implantation (D/HTx/LVAD) was estimated in our cohort according to the following risk scores SHFM, 3-CHF, CHARM, MAGGIC, GISSI-HF, MECKI, Barcelona Bio-HF, Krakow score and their accuracy calculated through the receiver operator characteristic (ROC) curve analysis. RESULTS: During a median follow-up of 5.8 years (Interquartile Range 3.2-7.6 years), 191 patients (20%) died or underwent HTx/LVAD (158 deaths, 30 heart transplantations, and 3 LVAD implantations). The high missing rate allowed to calculated only four prognostic models (MAGGIC, CHARM, 3-CHF and SHFM). All the scores overestimated the rate of D/HTx/LVAD. The prognostic accuracy was suboptimal for MAGGIC (AUC 0.754) and CHARM (AUC 0.720) scores and only modest for 3-CHF (AUC 0.677) and SHFM (AUC 0.667). CONCLUSIONS: Main prognostic scores for the risk stratification of HF are only partially applicable to real-world patients with DCM. MAGGIC and CHARM scores showed the best accuracy, despite the overestimation of risk. Our findings corroborate the need of specific risk scores for the prognostic stratification of DCM. CLINICAL PERSPECTIVE: What is new? The present study is the largest analysis in literature which investigate how the main existing heart failure prognostic risk scores performed in a real-world of dilated cardiomyopathy population, both in- and outpatients. What are the clinical implications? DCM is a stand-alone model of heart failure, where the performance of multiple heart failure prognostic scores for the risk stratification is quite limited. The need for contemporary, dedicated prognostic scores in this disease is increasingly evident.

Strain analysis reveals subtle systolic dysfunction in confirmed and suspected myocarditis with normal LVEF. A cardiac magnetic resonance study.

AIMS: Lake Louise Criteria (LLC) are time-dependent and some acute myocarditis (AM) with preserved left ventricular ejection fraction (LVEF) could be missed, due to the limited accessibility of Cardiac Magnetic Resonance (CMR). We aimed to assess the potential value of cardiac strain measured by feature tracking (FT) imaging in this population. METHODS AND RESULTS: Eighty-three patients with clinically suspected AM and normal LVEF were divided into 39 "confirmed AM" (positive LLC) and 44 "suspected AM" (negative LLC). An age and gender-matched sample of 42 normal subjects underwent CMR. In all groups, FT-derived biventricular strains and STE- global longitudinal strain (GLS) were assessed, being regularly measurable. Strain values < 5th percentile of the control group were considered abnormal. "Suspected" and "confirmed" AM were similar, except for medium time of CMR evaluation (5.2 vs 1 months from presentation, respectively; p = 0.004). Compared to healthy controls, both "suspected" and "confirmed" AM showed significantly impaired strain values. LV-global circumferential strain (GCS), right ventricular GCS and LV-GLS were abnormal in 15.4% and 15.9%, 20.5% and 15.9%, 7.7% and 9.1% in "confirmed" and "suspected" AM, respectively. STE analysis confirmed the results on LV-GLS, however a weak correlation emerged between STE and CMR-FT LV-GLS (p = 0.08). CONCLUSIONS: Compared to STE, CMR-FT analysis provided a more comprehensive and complementary biventricular strain evaluation that resulted similar in "confirmed" and "suspected" AM with normal LVEF. Conversely, mostly biventricular GCS was significantly reduced in up to 20% of patients, compared to healthy controls.

Prognostic Impact of BNP Variations in Patients Admitted for Acute Decompensated Heart Failure with In-Hospital Worsening Renal Function.

BACKGROUND: The significance of worsening renal function (WRF) in patients admitted for acute decompensated heart failure (ADHF) is still controversial. We hypothesised that changes in brain natriuretic peptide (BNP) might identify patients with optimal diuretic responsiveness resulting in transient WRF, not negatively affecting the prognosis. Our aim was to verify if in-hospital trends of BNP might be helpful in the stratification of patients with WRF after treatment for ADHF. METHODS: 122 consecutive patients admitted for ADHF were enrolled. Brain natriuretic peptide and eGFR were evaluated at admission and discharge. A 20% relative decrease in eGFR defined WRF, whereas a BNP reduction ≥40% was considered significant. The primary combined endpoint was death/urgent heart transplantation and re-hospitalisation for ADHF. RESULTS: Worsening renal function occurred in 23% of patients without differences in outcome between patients with and without WRF (43% vs. 45%, p=0.597). A significant reduction in BNP levels over the hospitalisation occurred in 59% of the overall population and in 71% of patients with WRF. At a median follow-up of 13.0 (IQR 6-36) months, WRF patients with ≥40% BNP reduction had a lower rate of death/urgent heart transplantation/re-hospitalisation compared to WRF patients without BNP reduction (30% and 75%, respectively; p=0.007). Favourable BNP trend was the strongest variable in predicting the outcome in WRF patients (HR 0.222, 95% CI 0.066-0.753, p=0.016). CONCLUSIONS: Worsening renal function does not affect the prognosis of ADHF and, when associated with a significant BNP reduction, identifies patients with adequate decongestion at discharge and favourable outcome.

Hospitalization rate as a proxy for the quality of life evaluation: the case of dilated cardiomiopathy.

RATIONALE, AIMS AND OBJECTIVES: Some objective indicators like symptoms, toxicity, performance status, rate of hospitalization or re-employment have been already employed in scientific literature as proxies of Quality of Life assessment, and, in spite of the intrinsic limitations of such a measurement, they represent a valuable source of information in all the situations where a formal assessment is impossible, due to budget, time or human resources constrains. We concentrate here on some models for the analysis of frequency of hospitalization data and we discuss an application to the Hearth Muscle Disease Study Group data. METHODS: A sample of 235 patients with dilated cardiomyopathy (DCM) prospectively treated at the Department of Cardiology (Trieste, Italy) have been observed during a period of 18 years, from 1978 to 1992 and data regarding hospitalization history were collected. The hospitalization process depends on the time since the last event, and usually is a function of a set of explanatory variables, such as the current state of the patient, treatments he has been receiving and the severity of disease. We propose here a semi-Markov representation of the hospitalization process, and we analyze data regarding DCM, implementing Exponential, Weibull, and Cox models; in Cox models we take care also of the stratification according to the duration or to the levels of the state factor. RESULTS: The probability of experiencing a second hospitalization within one year after the first one is estimated about 0.50, and within two years about 0.30. After this point the probability remains constant at a 0.10 level. The same pattern is observed for the second hospitalization, while things are getting worse after the third hospitalization, when the probability of not having a subsequent hospitalization is about 0.10 within one year. Betablockers have a strong influence in enlarging the time interval spent between an hospitalization and the other. CONCLUSIONS: The hospitalization process can be viewed only as a rough approximation of the good standing of the patient. However, for diseases like DCM can be reasonable, because of the relatively fast increment in the worsening conditions of the patients and the consequently high chances of observing new hospitalizations up to the absorbing state (the death). Moreover a very detailed modeling of the process leads to extract as much information as possible from the data.

Adding sufentanil to levobupivacaine or ropivacaine intrathecal anaesthesia affects the minimum local anaesthetic dose required.

BACKGROUND: We carried out this prospective, randomized, double-blind study in order to evaluate whether the intrathecal addition of sufentanil 3.3 mcg affects both the minimum local anaesthetic dose (MLAD) of spinal levobupivacaine and ropivacaine for a caesarean section and enhances the spinal block characteristics. METHODS: One hundred and eighty women were randomly allocated into four groups: levobupivacaine (Group L), levobupivacaine plus sufentanil (Group L+S), ropivacaine (Group R) and ropivacaine plus sufentanil (Group R+S). Each received 3 ml of the study solution intrathecally as part of a combined spinal/epidural technique. The initial dose was 12 mg for Groups L and L+S, and 15 mg for Groups R and R+S. The test solution was required to achieve a visual analogue pain score (VAPS) of 30 mm or less to be considered effective at skin incision, uterine incision, birth, peritoneal closure and at the conclusion of surgery. Effective or ineffective responses determined a 0.5 mg decrease or increase of the same drug, respectively, for the next patient in the same group, using an up-down sequential allocation. RESULTS: Using the Dixon and Massey formula, the MLAD was 10.65 mg [confidence interval (CI) 95%: 10.14-11.56] in Group L, 4.73 mg (CI 95%: 4.39-5.07) in Group L+S, 14.12 mg (CI 95%: 13.50-14.60) in Group R and 6.44 mg (CI 95%: 5.86-7.02) in Group R+S. CONCLUSIONS: The addition of sufentanil reduced the MLAD of both the local anaesthetics. It did not affect their potency ratio significantly and resulted in enhanced spinal anaesthesia.

'Free' copper in serum of Alzheimer's disease patients correlates with markers of liver function.

Non-ceruloplasmin bound copper ('free') seems slightly elevated in Alzheimer's disease (AD) patients. To test the hypothesis of a correlation between 'free' copper and liver function in AD. We evaluated 51 AD patients and 53 controls through typical tests for chronic liver disease (AST, ALT, gamma-GT, Albumin, prothrombin time - PT-, bilirubins), along with copper, ceruloplasmin, iron, cholesterol in the serum and apolipoprotein E epsilon4 (APOE4) genotype. Absolute serum copper and 'free' copper were higher, albumin was lower and PT longer in AD patients than in controls. 'Free' copper correlated negatively with markers of liver function, in that albumin and albumin/PT ratio (r = -0.43, p = 0.004), and positively with direct bilirubin. Copper and 'free' copper were higher in the APOE4 carriers. These results suggest that abnormalities in copper metabolism might have an effect on liver function in AD.

Ictal clinical and scalp-EEG findings differentiating temporal lobe epilepsies from temporal 'plus' epilepsies.

Temporal 'plus' epilepsies are characterized by seizures involving a complex epileptogenic network including the temporal lobe and the closed neighboured structures such as the orbito-frontal cortex, the insula, the frontal and parietal operculum and the temporo-parieto-occipital junction. Temporal 'plus' epilepsies are currently identified by means of intracerebral electrodes but whether their diagnosis can be suspected non-invasively has not been evaluated yet. The aim of this retrospective study was to address this issue in 80 consecutive patients who were thought to suffer from non-lesional temporal lobe seizures which finally proved, on the basis of stereotactic intracerebral EEG (SEEG) recordings, to be 'purely' temporal (TL group, n = 58) or temporal 'plus' (T+ group, n = 22). Our results showed that the two groups of patients were difficult to differentiate on the basis of general clinical features or MRI data. Even the presence of hippocampal sclerosis did not distinguish the two groups. Conversely, both ictal clinical symptoms and scalp-EEG findings significantly differentiated TL from T+ patients. Patients with TL epilepsies more frequently presented an ability to warn at seizure onset (P = 0.003), an abdominal aura (P = 0.05), gestural automatisms (P = 0.04) and a post-ictal amnesia (P = 0.02). Patients suffering from T+ epilepsies more frequently had gustatory hallucinations (P = 0.02), rotatory vertigo (P = 0.02) and auditory illusions (P = 0.02) at seizure onset; they exhibited more frequently contraversive manifestations of the eyes and/or head (P = 0.001), piloerection (P = 0.03) and ipsilateral tonic motor signs (P = 0.05), and they were more often dysphoric in the post-ictal phase (P = 0.0001). Cluster analysis mainly indicated that some associations of symptoms were relevant for differentiating TL cases from T+ cases. Interictal EEG of T+ patients more frequently exhibited bilateral or precentral abnormalities, while ictal EEG more frequently pointed over the anterior frontal, temporo-parietal and precentral regions. Neither TL interictal spikes, nor TL ictal EEG onset, allowed us definitely to rule out the possibility of T+ epilepsies. Our findings may be useful for identifying, among patients suffering from 'atypical' non-lesional TL epilepsies, those who should undergo invasive recordings before surgery.

Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF [beta]-amyloid, and h-tau.

OBJECTIVE: To assess whether serum copper in Alzheimer disease (AD) correlates with cognitive scores, beta-amyloid, and other CSF markers of neurodegeneration. METHODS: The authors studied copper, ceruloplasmin, total peroxide, and antioxidants levels (TRAP) in serum; beta-amyloid in plasma; and copper, beta-amyloid, h-tau, and P-tau in the CSF of 28 patients with AD and 25 healthy controls, in relation to clinical status. RESULTS: Serum copper (p < 0.0001), peroxides (p = 0.002), a copper fraction unexplained by ceruloplasmin (p < 0.0001), and CSF h-tau (p = 0.001) were increased in AD, whereas serum TRAP (p = 0.03) and CSF beta-amyloid were decreased (p < 0.0001). Plasma beta-amyloid increased with age in healthy controls (r = 0.6; p = 0.05). CSF markers of AD correlated with serum copper variables. CSF copper was partially dependent on the serum copper fraction unexplained by ceruloplasmin (t = 2.2, p = 0.04). CSF beta-amyloid seemed to be related to serum copper (r = -0.46; p = 0.002). Mini-Mental Status Examination scores correlated positively with beta-amyloid (r = 0.46, p = 0.002) and inversely with copper unexplained by ceruloplasmin (r = -0.45, p = 0.003). CONCLUSIONS: The authors' results confirm the existence of changes in copper component distribution, particularly the copper fraction unexplained by ceruloplasmin and support the hypothesis of a beta-amyloid and copper connection in Alzheimer disease.

Minimum local anaesthetic dose (MLAD) of intrathecal levobupivacaine and ropivacaine for Caesarean section.

We determined the minimum local anaesthetic dose (MLAD) of spinal levobupivacaine and ropivacaine for Caesarean section. Ninety women were randomly allocated to two groups and received 3 ml of study solution by a combined spinal/epidural technique. The initial dose was 12 mg for levobupivacaine and 17 mg for ropivacaine groups. To be considered effective, a test solution had to achieve a visual analogue pain score (VAPS) of 30 mm or less at skin incision, uterine incision, birth, peritoneal closure, and at the end of surgery. Effective or ineffective responses determined, respectively, a 0.3 mg decrease or increase of the same drug for the next patient in the same group, using up-down sequential allocation. The MLAD of levobupivacaine was 10.58 mg (CI 95%: 10.08-11.09) and the MLAD of ropivacaine 14.22 mg (CI 95%: 13.67-14.77), using the Dixon and Massey formula. The potency ratio between spinal levobupivacaine and spinal ropivacaine was 1.34.

High volume of subarachnoid levobupivacaine decreases drug requirement in first stage labor analgesia.

AIM: Using the statistic method of sequential allocation, we realized a prospective double-blind study in order to establish the minimum local anesthetic concentration (MLAC) of large intrathecal volume of levobupivacaine, during the first stage labour analgesia in spontaneous and induced laboring women. METHODS: Seventy-five nulliparous, at term, with cervical dilatation <5 cm parturients requesting combined spinal/epidural analgesia, were enrolled. The starting concentration was chosen according to recent literature. Total volume of study solution was 10 ml and efficacy was assessed with a visual analogue pain scale at the height of the uterine contraction. RESULTS: We established that MLAC of levobupivacaine, in 10 ml intrathecal volume, during the first stage of spontaneous and induced labour was 0.0134% and 0.0195%, respectively. No complications occurred during the study and the only side effect was shivering, which is common even in other anesthetic techniques. We produced a very selective sensitive block. Neither sympathetic nor motor block occurred. CONCLUSIONS: Low intrathecally concentration of local anesthetic allows the anesthetist to reduce the total amount of drug and improves not only the differential blockade between motor and sensitive but also between sympathetic and sensitive fibers.

Fetal subcutaneous tissue thickness (SCTT) in healthy and gestational diabetic pregnancies.

OBJECTIVE: To determine reference values of fetal subcutaneous tissue thickness (SCTT) throughout gestation in a healthy population and to compare them with those from a population of pregnant women with gestational diabetes under standard therapy. METHODS: Three hundred and three women recruited from a high-risk pregnancy clinic were classified as being healthy (n = 218) or as having gestational diabetes (n = 85) on the basis of a negative or positive oral glucose tolerance test, respectively. They were enrolled into the cross-sectional study at 20 weeks' gestation. Ultrasound examinations were performed approximately every 3 weeks until delivery at term. The mid-arm fat mass and lean mass (MAFM, MALM), the mid-thigh fat mass and lean mass (MTFM, MTLM), the abdominal fat mass (AFM) and the subscapular fat mass (SSFM) were evaluated. Time-specific reference ranges were constructed from the 218 healthy women and a conventional Student's t-test was performed to compare SCTT values between the two study groups throughout gestation. RESULTS: Normal ranges, including 5th, 50th and 95th centiles of the distribution, were generated for each SCTT parameter obtained in each of the two groups of women. Significant differences were found between the two study groups at 37-40 weeks' gestation for MTFM, at 20-22 and 26-28 weeks for MTLM, at 31-34 and 35-37 weeks for MAFM, at 26-28 and 38-40 weeks for SSFM, and at 39-40 weeks for AFM, the mean residual values always being greater in gestational diabetic women than they were in the group of healthy pregnant women. CONCLUSIONS: We provide gestational age-specific reference values for fetal SCTT. Fetal fat mass values, particularly in late gestation, are greater in women with gestational diabetes compared with healthy women. The reference values may have a role in assessing the influence of maternal metabolic control on fetal state.

Evaluation of links in heroin seizures.

The evaluation of a link between two heroin seizures using a descriptive method is presented. It is based on the measure of the angles between two chromatograms assimilated to vectors, and interpreted using a continuous approach based on the likelihood ratio of Bayes' theorem. A complete evaluation model thus avoids the drawbacks of decision thresholds used until now to establish a link. Validation is obtained through tests and simulation methods.

Post-traumatic superior sagittal sinus thrombosis. Case report and analysis of the international literature.

The objective of this study is to focus attention on cerebral venous sinus thrombosis (CVST), a rather infrequent disease, especially when following closed head injury. Consequently we started from the clinical case report, concerning a patient admitted to our polyvalent ICU in the Hospital of Avezzano (AQ), Italy. The patient was a 15-year-old girl, that developed superior sagittal sinus (SSS) thrombosis following closed head injury (pedestrian run down by a car): owing to slow and progressive onset of deep coma with severe intracranial hypertension, emergency decompressive craniectomy was performed. The result was satisfying: patient conditions progressively improved, with return to consciousness, to good mobility and to good mental status. At present, 1 year after trauma, only mild disability is left over (right hand prehensile strength loss, and slightly moving gait). In conclusion, considering the literature data (intracerebral haematoma and deep coma are poor outcome predictors) and clinical evolution, we decided an aggressive surgical approach to save the patient's life, with satisfying results.