Applications of Three-Dimensional Printing in the Management of Complex Aortic Diseases.

The use of three-dimensional (3D) printing is gaining considerable success in many medical fields, including surgery; however, the spread of this innovation in cardiac and vascular surgery is still limited. This article reports our pilot experience with this technology, applied as an additional tool for 20 patients treated for complex vascular or cardiac surgical diseases. We have analyzed the feasibility of a "3D printing and aortic diseases project," which helps to obtain a more complete approach to these conditions. 3D models have been used as a resource to improve preoperative planning and simulation, both for open and endovascular procedures; furthermore, real 3D aortic models were used to develop doctor-patients communication, allowing better knowledge and awareness of their disease and of the planned surgical procedure. A 3D printing project seems feasible and applicable as an adjunctive tool in the diagnostic-therapeutic path of complex aortic diseases, with the need for future studies to verify the results.

Sex-Related Differences in Long-Term Outcomes After Early-Onset Myocardial Infarction.

Importance: There is growing awareness of sex-related differences in cardiovascular risk profiles, but less is known about whether these extend to pre-menopausal females experiencing an early-onset myocardial infarction (MI), who may benefit from the protective effects of estrogen exposure. Methods: A nationwide study involving 125 Italian Coronary Care Units recruited 2,000 patients between 1998 and 2002 hospitalized for a type I myocardial infarction before the age of 45 years (male, n = 1,778 (88.9%). Patients were followed up for a median of 19.9 years (IQR 18.1-22.6). The primary composite endpoint was the occurrence of cardiovascular death, non-fatal myocardial re-infarction or non-fatal stroke, and the secondary endpoint of hospitalization for revascularisation by means of a percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Results: ST-elevation MI was the most frequent presentation among both men and women (85.1 vs. 87.4%, p = ns), but the men had a greater baseline coronary atherosclerotic burden (median Duke Coronary Artery Disease Index: 48 vs. 23; median Syntax score 9 vs. 7; both p < 0.001). The primary composite endpoint occurred less frequently among women (25.7% vs. 37.0%; adjusted hazard ratio: 0.69, 95% CI 0.52-0.91; p = 0.01) despite being less likely to receive treatment with most secondary prevention medications during follow up. Conclusions: There are significant sex-related differences in baseline risk factors and outcomes among patients with early-onset MI: women present with a lower atherosclerotic disease burden and, although they are less frequently prescribed secondary prevention measures, experience better long-term outcomes. Trial Registration: 4272/98 Ospedale Niguarda, Ca' Granda 03/09/1998.

Sacubitril/Valsartan to Treat Heart Failure in a Patient with Relapsing Hairy Cell Leukaemia: Case Report.

Experience with angiotensin-receptor neprilysin inhibitors (ARNI) in oncologic patients with heart failure (HF) is limited. We report a case of ARNI started as first-choice therapy in a patient with relapsing hairy cell leukaemia (HCL) and HF with depressed left ventricular ejection fraction (LVEF). A middle-aged male, previously treated with rituximab for HCL, was scheduled for cardiologic screening before starting a new antineoplastic therapy for cancer relapse. The patient had symptomatic HF with reduced LVEF and high NT-proBNP levels. In this patient, early ARNI treatment was well tolerated and produced a rapid and durable improvement of symptoms, LVEF and NT-proBNP levels. Consequently, the oncologic team could start an experimental treatment with obinutuzumab, with complete HCL remission. In conclusion, in this patient with HCL and HF, ARNI therapy was safe and effective, contributing to undelayed cancer treatment.

Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis: Multicenter Lombardy Registry.

BACKGROUND: There is controversy about the outcome of patients with acute myocarditis (AM), and data are lacking on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management, and long-term outcome of patients with AM based on a retrospective multicenter registry from 19 Italian hospitals. METHODS: A total of 684 patients with suspected AM and recent onset of symptoms (<30 days) were screened between May 2001 and February 2017. Patients >70 years of age and those >50 years of age without coronary angiography were excluded. The final study population comprised 443 patients (median age, 34 years; 19.4% female) with AM diagnosed by either endomyocardial biopsy or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance. RESULTS: At presentation, 118 patients (26.6%) had left ventricular ejection fraction <50%, sustained ventricular arrhythmias, or a low cardiac output syndrome, whereas 325 (73.4%) had no such complications. Endomyocardial biopsy was performed in 56 of 443 (12.6%), and a baseline cardiac magnetic resonance was performed in 415 of 443 (93.7%). Cardiac mortality plus heart transplantation rates at 1 and 5 years were 3.0% and 4.1%. Cardiac mortality plus heart transplantation rates were 11.3% and 14.7% in patients with complicated presentation and 0% in uncomplicated cases (log-rank P<0.0001). Major AM-related cardiac events after the acute phase (postdischarge death and heart transplantation, sustained ventricular arrhythmias treated with electric shock or ablation, symptomatic heart failure needing device implantation) occurred in 2.8% at the 5-year follow-up, with a higher incidence in patients with complicated forms (10.8% versus 0% in uncomplicated AM; log-rank P<0.0001). ß-Adrenoceptor blockers were the most frequently used medications both in complicated (61.9%) and in uncomplicated forms (53.8%; P=0.18). After a median time of 196 days, 200 patients had follow-up cardiac magnetic resonance, and 8 of 55 (14.5%) with complications at presentation had left ventricular ejection fraction <50% compared with 1 of 145 (0.7%) of those with uncomplicated presentation. CONCLUSIONS: In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction <50%, ventricular arrhythmias, or low cardiac output syndrome at presentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent left ventricular systolic dysfunction.

[New oral anticoagulants (NOAC) in nephrology]. / I nuovi Anti-Coagulanti Orali (NOAC): cosa deve sapere un Nefrologo.

The new or direct oral anticoagulants [new oral anticoagulants (NOAC) or direct oral anticoagulants (DOAC)] were launched in the Italian market in 2013. Although these compounds share common pharmacological indications with vitamin K antagonists (warfarin or acenocumarol), they have different mechanisms of action, do not require a constant anticoagulant monitoring but are more efficacious and safer than vitamin K antagonists. The use of these molecules (Dabigatran, Apixaban, Rivaroxaban, Betrixaban, Edoxaban) is constantly rising in daily practice. However, while available data suggest that NOAC/DOAC use is safe, dosage should be adjusted based on renal or liver function. It should be acknowledged that commonly available blood tests [Prothrombin Time (PT) and partial thromboplastin time (PTT)] are not indicated to monitor the anticoagulant activity of these compounds. With the exception of dabigatran, we currently lack of an antidote to reverse the anticoagulant effect of NOAC/DOAC. We herein review available evidence on NOAC/DOAC pharmacokinetic, risk factors for bleeding, interventions to reverse the anticoagulant activity in case of hemorrhages or need of urgent surgery and/or NOAC/DOAC overdose or side effects.

Levels of circulating pro-angiogenic cells predict cardiovascular outcomes in patients with chronic heart failure.

BACKGROUND: Circulating pro-angiogenic cells (PACs) contribute to vascular and myocardial regeneration. A low level of PACs is associated with worse outcome in patients with coronary heart disease. However, little is known about PACs in heart failure (HF). METHODS AND RESULTS: Blood was sampled at baseline in 111 patients with HF, 67 from 5 Italian Centers and 44 from Frankfurt, Germany. In cultured mononuclear cells from peripheral blood, PACs were counted as double-stained by tetramethylindocarbocyanine-labeled acetylated LDL and fluorescein-5-isothiocyanate-labeled lectin. Mean age of the patients was 62 years, 12 were females, 66 had ischemic etiology, 26 were in New York Heart Association Class >II. Cutoffs for PACs were assessed by receiver operating characteristic curves, to identify the optimal cutoffs for PAC level in predicting outcomes. Mean level of PACs was 35+/-29 (mean+/-SD) cells/mm(2), 2- to 3-fold lower than in age-matched healthy volunteers, but unrelated to severity of HF, age, or sex. Over 2.5 years, 12 cardiovascular deaths and 47 first hospitalizations for cardiovascular reasons were recorded. After adjustment for demographic and clinical variables, elevated creatinine and natriuretic peptides, and PACs

Long-term outcome and risk stratification in dilated cardiolaminopathies.

OBJECTIVES: The aim of this study was to analyze the long-term follow-up of dilated cardiolaminopathies. BACKGROUND: Lamin A/C (LMNA) gene mutations cause a variety of phenotypes. In the cardiology setting, patients diagnosed with idiopathic dilated cardiomyopathy (DCM) plus atrioventricular block (AVB) constitute the majority of reported cases. METHODS: Longitudinal retrospective observational studies were conducted with 27 consecutive families in which LMNA gene defects were identified in the probands, all sharing the DCM phenotype. RESULTS: Of the 164 family members, 94 had LMNA gene mutations. Sixty of 94 (64%) were phenotypically affected whereas 34 were only genotypically affected, including 5 with pre-clinical signs. Of the 60 patients, 40 had DCM with AVB, 12 had DCM with ventricular tachycardia/fibrillation, 6 had DCM with AVB and Emery-Dreifuss muscular dystrophy type 2 (EDMD2), and 2 had AVB plus EDMD2. During a median of 57 months (interquartile range 36 to 107 months), we observed 49 events in 43 DCM patients (6 had a later event, excluded from the analysis). The events were related to heart failure (15 heart transplants, 1 death from end-stage heart failure) and ventricular arrhythmias (15 sudden cardiac deaths and 12 appropriate implantable cardioverter-defibrillator interventions). By multivariable analysis, New York Heart Association functional class III to IV and highly dynamic competitive sports for >or=10 years were independent predictors of total events. By a bivariable Cox model, splice site mutations and competitive sport predicted sudden cardiac death. CONCLUSIONS: Dilated cardiomyopathies caused by LMNA gene defects are highly penetrant, adult onset, malignant diseases characterized by a high rate of heart failure and life-threatening arrhythmias, predicted by New York Heart Association functional class, competitive sport activity, and type of mutation.

Importance of the echocardiographic evaluation of right ventricular function in patients with AL amyloidosis.

BACKGROUND: Patients with AL amyloidosis often present with signs of congestive heart failure. AIM: This study was prospectively designed to assess the significance of RV dysfunction in AL amyloidosis. METHODS AND RESULTS: Seventy-four patients with biopsy proven AL amyloidosis underwent a thorough echocardiographic evaluation. A tricuspid annular plane systolic excursion (TAPSE)<17 mm was taken as marker of RV dysfunction. Plasma NT-proBNP determinations were performed in all cases. RV function was normal in 60 patients and reduced in 14 patients. Patients with RV dysfunction had thicker left ventricular (LV) walls (p<0.01), lower LV end-diastolic volumes (p<0.01), lower LV ejection fraction (p<0.01) and more frequently a restrictive LV filling pattern (p<0.01). RV dimensions and RV free wall thickness were not significantly different in the two groups. A thick interventricular septum and a reduced TAPSE were associated with high NT-proBNP levels (both p<0.01). Seven patients died during a median follow-up period of 19 months; TAPSE<17 mm was the only echocardiographic parameter associated with poor survival. CONCLUSION: In patients with AL amyloidosis, RV dysfunction is associated with more severe involvement of the left ventricle, higher plasma levels of NT-proBNP and with poor prognosis.

Getting old with a new heart: impact of age on depression and quality of life in long-term heart transplant recipients.

BACKGROUND: Limited research has been done on depression and quality of life in long-term survival after heart transplantation. The aim of the present study was to investigate the role of age on depression and quality of life in a sample of long-term heart transplant recipients. METHODS: We investigated 137 consecutive patients recruited in a single center who were still alive at more than 10 years after transplantation. Quality of life and depression were rated with the Medical Outcome Study Short Form (SF-36) and the Beck Depression Inventory (BDI), respectively. Sociodemographic, clinical, affective, and quality of life data for long-term survival patients stratified by current age younger than 70 years (young) and 70 years or older (old) were compared using Fisher's exact tests and Student's t-tests. RESULTS: The SF-36 Mental Component Summary did not significantly differ between the young subjects (48.75 +/- 10.2) compared with old (48.47 +/- 10.1; p = 0.897). By contrast, the SF-36 Physical Component Summary was higher in younger subjects (46.88 +/- 10.2 vs 40.81 +/- 10.6, p = 0.008). According to BDI, 37.4% of the young group and 13.3% of the old group scored above the selected threshold of 10 (p = 0.014). CONCLUSIONS: In the light of our findings, older age does not seem to negatively affect the mental component of quality of life in the long term after heart transplantation, but it does on the physical component, as expected. On the other hand, it may be even associated with a lower prevalence of depressive symptoms more than 10 years after surgery. Hence, age per se does not represent a major limiting factor when considering candidates for this procedure, at least with regard to the issue of psychologic distress.

B-cell posttransplant lymphoproliferative disorders in heart and/or lungs recipients: clinical and molecular-histogenetic study of 17 cases from a single institution.

BACKGROUND: Posttransplantation lymphoproliferative disorders (PTLDs) are heterogeneous lymphoid proliferations representing a major complication of solid organ transplant. This study details the clinicopathological and molecular features of 17 B-cell PTLDs observed in a single center series of 988 heart and/or lung transplant recipients. METHODS: Cases were classified according to World Health Organization lymphoma classification and tested for Epstein-Barr Virus (EBV), clonality, histogenetic phenotypic (CD10, Bcl-6, MUM1, CD138), and genotypic (immunoglobulin and BCL-6 genes somatic hypermutation) markers. RESULTS: This series of 17 PTLDs included: two B-cell monoclonal polymorphic PTLDs and 15 B-cell monomorphic PTLDs (13 diffuse large B-cell lymphomas [DLBCL] and 2 Burkitt lymphomas [BL]). EBV was detected in 9/17 cases. A monoclonal immunoglobulin variable (IGV) genes rearrangement was documented in 17/17 cases; IGV somatic hypermutation was found in 88% of cases, indicating a prevalent origin from germinal center (GC)-experienced B cells. Using immunophenotypic markers, three histogenetic profiles were identified: a) CD10/bcl-6/MUM1/CD138, mimicking GC B-cells; b) CD10-/bcl-6+/MUM1+/CD138-, reminiscent of B-cells at the latest phases of GC reaction; and c) CD10-/bcl-6-/MUM1+/CD138+/-, consistent with preterminally differentiated B-cells. CONCLUSIONS: Correlation between morphology, histogenesis, and EBV status demonstrated a high degree of homogeneity in the two GC-related groups, mostly including EBV-negative cases with BL and DLBCL-centroblastic features; the third group, consisting of post GC EBV-positive cases, was histologically less homogeneous, as it included polymorphic PTLDs and DLBCL with immunoblastic and anaplastic features. The EBV-negative cases with GC histogenetic phenotype showed a slightly better outcome; however, such less aggressive prognostic trend was not confirmed by statistical analysis.

Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects.

BACKGROUND: Primary desminopathies are caused by desmin gene [DES (MIM*125660)] mutations. The clinical spectrum includes pure myopathies, cardiomuscular diseases and cardiomyopathies. Patients with restrictive cardiomyopathy (RCM) plus atrioventricular block (AVB) due to DES defects are frequently unrecognized unless desmin accumulation is specifically investigated in endomyocardial biopsy (EMB) by ultrastructural study. AIMS: To describe a cardiological phenotype characterized by RCM plus AVB due to desmin accumulation caused by DES defects. METHODS AND RESULTS: Desmin accumulation was diagnosed by means of ultrastructural and immunocytochemical studies of EMB in four unrelated probands with RCM and AVB. Candidate genes [DES and alphaB-crystallin (CRYAB)] were screened using sequence analysis. Four DES gene mutations were identified: three new (R16C, T453I and a 10 bp deletion at the exon-intron boundary of exon 3 disrupting the donor splice site) and one known (R406W). The disease was autosomal dominant in two families, recessive in one and associated with a de novo mutation in one. The mutations cosegregated with phenotype in all patients. CRYAB gene screening was negative. CONCLUSIONS: A cardiac phenotype characterized by RCM and AVB caused by desmin accumulation is associated with DES mutations. Although the mutations affected different domains, the cardiac phenotype was identical.

Two simple echo-Doppler measurements can accurately identify pulmonary hypertension in the large majority of patients with chronic heart failure.

BACKGROUND: The assessment of pulmonary hypertension in patients with heart failure is of great clinical importance not only for diagnostic purposes but also for prognostication. The present study was undertaken on a consecutive basis with a group of patients with chronic heart failure. Patients were evaluated for their suitability for heart transplantation: (1) to explore the diagnostic accuracy of several echo Doppler parameters of pulmonary hemodynamics in predicting the presence of elevated pulmonary artery pressure (defined as pulmonary artery systolic pressure > or =35 mmHg and mean pulmonary artery pressure >20 mmHg); (2) to assess the diagnostic ability of the same parameters to identify patients with elevated pulmonary vascular resistance; and (3) to evaluate the influence of right ventricular function and degree of tricuspid regurgitation in modifying diagnostic accuracy. METHODS: Echo Doppler examination and right heart catheterization were performed consecutively within 24 hours in 86 patients. The optimal cut-off value for a series of echo Doppler parameters capable of identifying patients with pulmonary hypertension was obtained by dividing the entire sample into 2 groups; the optimal threshold (highest sensitivity and specificity) of the echo and Doppler parameters used to classify patients with and without pulmonary hypertension was determined in 67% of cases by means of the receiver operating characteristic (ROC) curve: this was the testing sample. The proportion of cases classified correctly according to the selected cut-off was computed. The remaining 33% of cases represented the validation sample: sensitivity, specificity and predictive values (and their 95% confidence intervals [CIs]) for identifying pulmonary hypertension were calculated from the proposed cut-offs in this second sample. Finally, the overall performance of the echo Doppler parameters was assessed over the whole sample by considering the extent of the area under the ROC curve (A-ROC) and its 95% CI, for the dichotomic measurement. RESULTS: On right heart catheterization, a pulmonary artery systolic (PAPs) pressure > or =35 mmHg plus a mean pressure (mean PAP) >20 mmHg was documented in 49 of 86 cases (57%), for whom mean values were 56 +/- 17 and 38 +/- 11 mmHg, respectively. The proportion of cases identified correctly as having pulmonary hypertension was highest for PAPs (88%) and mean PAP (85%) in addition to acceleration time of pulmonary artery systolic flow (ACT) (79%) and pulmonary artery diastolic pressure obtained utilizing the early phase of the tricuspid regurgitation spectral flow (PAPd/TR) (75%). PAPd/TR performed better in the validating sample in terms of diagnostic ability, with high sensitivity and specificity (100% and 60%) and positive and negative predictive values (PPV 80%, NPV 100%). PAPs, mean PAP, ACT and PAPd/TR confirmed their prevailing diagnostic ability (A-ROC from 0.74 to 0.86) in identifying pulmonary hypertension with fair to high feasibility (67% to 91%) and an odds ratio (OR) indicative of strong association. ACT and PAPd/TR, the 2 parameters with the highest feasibility, allowed us to identify 46 of 49 (94%) hypertensive cases. The same parameters did not perform well in identifying patients with increased vascular resistance, with A-ROC ranging from 0.55 to 0.69. Heterogeneity of effect, due to right ventricular function or tricuspid regurgitation degree, could not be demonstrated in the ability of the echo Doppler measurements to identify pulmonary hypertension. CONCLUSIONS: ACT, PAPd/TR, PAPs and mean PAP have been shown to accurately classify patients with chronic heart failure with or without pulmonary hypertension. In particular, ACT and PAPd/TR alone allowed reliable and accurate definition of pulmonary hypertension in 94% of patients, regardless of right ventricular function or degree of tricuspid regurgitation. Non-invasive pulmonary pressure assessment by the referred method might be useful in the evaluation of heart transplant candidates.

EBV positive primary cutaneous CD30+ large T-cell lymphoma in a heart transplanted patient: case report.

Most post-transplant lymphoproliferative disorders (PTLDs) are of B-cell origin, whereas T-cell lymphomas rarely occur. We detail the clinicopathological features of the first case of Epstein-Barr virus (EBV)-associated primary cutaneous CD30+ anaplastic large cell lymphoma (ALCL) in the setting of heart transplant. A 71-year-old patient, 111 months after transplant, presented with multiple cutaneous lesions on the left thigh; histological and immunohistochemical examinations led to diagnosis of T-cell CD30+ ALCL. In situ hybridization demonstrated the presence of EBV-positive tumour cells. The patient received radiotherapy, but he relapsed at the same cutaneous site with loco-regional nodal spread. Chemotherapy was administered resulting in complete remission; four years later the patient is alive and well. Our findings indicate that primary cutaneous EBV+ CD30+ ALCLs should be included within the T-cell PTLDs spectrum; further studies are required to confirm whether they may be also considered, in transplantation settings, a distinct lymphoma subset with relatively favourable outcome.

Ten years of "extended" life: quality of life among heart transplantation survivors.

BACKGROUND: Long-term quality of life (QOL) outcome in heart transplant recipients still remains uncertain. This study evaluates the health status and QOL of survivors with associated predictors 10 years after heart transplantation. PATIENTS AND METHODS: A total of 276 patients who underwent heart transplantation in the Department of Cardiac Surgery, University of Pavia, between 1985 and 1992 were included in a cross-sectional study. Patients still alive 10 years after transplantation (n=122) were asked to complete the SF36 questionnaire and then received a full clinical examination. All QOL instruments that were used had acceptable reliability and validity. Descriptive statistics, Kaplan-Meier estimate, correlation coefficients, and general linear regression were used to analyze the data. RESULTS: Survival rates 1, 5, and 10 years after transplantation were 87%, 77%, and 57%, respectively, and the average life expectancy was 9.16 years. The mental QOL of patients 10 years after heart transplantation was similar to that among the general population. The physical QOL was worse among patients when compared with the QOL of the general population, with predictors including older age, being married, the presence of complications, and impaired renal function. CONCLUSIONS: Heart transplantation ensures a relatively high QOL even 10 years after surgery. Predictors of a poor QOL were determined, which may help to identify those patients for whom a poor outcome is likely so treatment can be tailored accordingly.

Enoximone echocardiography: a novel test to evaluate left ventricular contractile reserve in patients with heart failure on chronic beta-blocker therapy.

BACKGROUND: It has been suggested that an extensive contractile reserve identified recognised by means of dobutamine stress echocardiography may predict a better prognosis in patients with severe left ventricular dysfunction at rest. However, the clinical use of dobutamine stress echocardiography may be limited in patients with chronic heart failure by the substantial proportion of such patients treated with beta-blockers, since the inotropic response to adrenergic stimulation is known to be attenuated in patients receiving beta-adrenoceptor blockers. Enoximone is a positive inotropic agent that inhibits cyclic adenosine monophosphate-specific phosphosdiesterase. We therefore tested the hypothesis that enoximone may be an alternative to dobutamine in evaluating left ventricular contractile reserve in patients with systolic dysfunction on chronic beta-blocker therapy. METHODS: We studied 26 patients (21 males and five females) with a mean age of 58 PlusMinus; 10 years: 11 were not receiving beta-blockers (noBB group); 15 were receiving carvedilol at a mean dose of 34 mg/day (BB group). Dobutamine was infused at doses of 5 and 10 micrograms/kg/min, and enoximone at a dose of 1.5 mg/kg. RESULTS: The ejection fraction in the noBB group increased by 9% with dobutamine and 8.73% with enoximone (p = 0.86); in the BB group, it increased by 6% with dobutamine and 8.94% with enoximone (p = 0.03). Regional peak systolic velocities were evaluated by means of tissue Doppler imaging in four basal and four medium level segments. In the noBB group, they increased more with dobutamine than with enoximone in three of the eight segments; no significant differences were found in the BB group. Dobutamine induced non-sustained ventricular tachycardia in three patients and supraventricular tachycardia in one, whereas enoximone did not induce any repetitive arrhythmias. CONCLUSIONS: Enoximone might be preferable to low-dose dobutamine for evaluating left ventricular contractile reserve in chronically beta-blocked heart failure patients as it is slightly more potent and has a better safety profile.

Celiac disease in patients with sporadic and inherited cardiomyopathies and in their relatives.

AIMS: To investigate celiac disease (CD) and related co-morbidity in patients with familial and sporadic cardiomyopathy and in their relatives. METHODS AND RESULTS: We screened anti-human-tissue-transglutaminase (IgA and IgG anti-h-tTG) and anti-endomysial antibodies (AEAs) in 238 consecutive adult patients with inherited or sporadic dilated cardiomyopathy (DCM), 418 relatives, and 2000 healthy blood donors. HLADQ2-DQ8 was tested in tTG-positive subjects. The IgA-tTG-positive patients with cardiomyopathy underwent duodenal biopsy. Twenty-six subjects were tTG-positive: five DCM patients (2.1%), two of 28 (7.1%) and three of 390 (0.7%) relatives with and without echocardiographic abnormalities respectively, and 16 controls (0.8%). Twenty-two of 26 subjects were AEA-positive, and 25 HLA-positive. Of the five patients with cardiomyopathy and biopsy-proven CD, four suffered iron-deficiency anaemia. Two CD-positive DCM patients and two tTG-positive relatives were from families with inherited disease in which CD did not co-segregate with DCM. CONCLUSIONS; The higher prevalence of CD in patients with sporadic or inherited DCM, and of tTG-positive serology in relatives with echocardiographic abnormalities, suggests that immune-mediated mechanisms are active in subsets of patients/families. However, gluten intolerance cannot be considered causative since CD seems to be associated but not co-segregated with DCM in familial cases.

Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis.

BACKGROUND: Brain natriuretic peptide (BNP) is a marker of ventricular dysfunction and can be used to assess prognosis in heart failure and after myocardial infarction. Heart involvement is the most important prognostic factor and causes death in almost all patients with light-chain amyloidosis (AL). We investigated the prognostic value of NT-proBNP and its utility in monitoring amyloid heart dysfunction. METHODS AND RESULTS: NT-proBNP was quantified at diagnosis in 152 consecutive patients seen at the coordinating center of the Italian Amyloidosis Study Group (Pavia) from 1999 throughout 2001. Heart involvement was estimated on the basis of clinical signs, electrocardiography, and echocardiography. NT-proBNP concentrations differed in patients with (n=90, 59%) and without (n=62, 41%) heart involvement (median: 507.8 pmol/L versus 22.1 pmol/L, P=10(-7)). The best cutoff for heart involvement was at 152 pmol/L (sensitivity: 93.33%, specificity: 90.16%, accuracy: 92.05%) and distinguished two groups with different survival (P<0.001). The Cox multivariate model including NT-proBNP was better than models including echocardiographic and clinical signs of heart involvement. NT-proBNP appeared to be more sensitive than conventional echocardiographic parameters in detecting clinical improvement or worsening of amyloid cardiomyopathy during follow-up. CONCLUSIONS: NT-proBNP appeared to be the most sensitive index of myocardial dysfunction and the most powerful prognostic determinant in AL amyloidosis. It adds prognostic information for newly diagnosed patients and can be useful in designing therapeutic strategies and monitoring response. NT-proBNP is a sensitive marker of heart toxicity caused by amyloidogenic light chains.

Clinicopathological correlates can predict acute myocarditis in patients with recent-onset heart failure: preliminary data.

BACKGROUND: The aim of this study was to verify whether or not the clinical profile could be helpful in diagnosing myocarditis in patients with recent-onset (< 6 months) heart failure, suspected myocarditis and a biopsy-proven diagnosis. METHODS: From March 1998 to December 2000, 118 patients underwent a complete clinical, hemodynamic, echocardiographic and laboratory examination and a diagnostic endomyocardial biopsy in our Department; among them, 28 patients were admitted with clinically suspected myocarditis; in 9, the diagnosis was confirmed by the histopathologic findings. RESULTS: At the time of presentation, patients with biopsy-proven myocarditis showed early in-hospital admission (median 6 vs 69 days) with fever, a higher sinus rate and a significantly lower systolic blood pressure. Left ventricular dilation was observed in the non-myocarditis group only (left ventricular end-diastolic diameter 65.0 +/- 8.9 vs 52.6 +/- 5.8 mm); right ventricular function, as assessed by evaluation of the tricuspid annulus plane systolic excursion (TAPSE) and the right ventricular ejection fraction (RVEF) were found to be significantly lower in the myocarditis group (TAPSE 14.2 +/- 3.6 vs 20.3 +/- 7.0 mm; RVEF 21.3 +/- 11.1 vs 30.3 +/- 11.5%). Only patients with biopsy-proven myocarditis had an increase in serum creatine kinase and inflammatory markers (erythrocyte sedimentation rate and white blood cell count). Three cases had a clinical presentation of fulminant myocarditis showing marked increases in the serum levels of creatine kinase and inflammatory markers, and severely compromised right ventricular function and cardiac index. CONCLUSIONS: At univariate analysis, an early onset, fever, tachycardia, hypotension, a reduced right ventricular function, increased creatine kinase, erythrocyte sedimentation rate and white blood cell count were predictive of myocarditis. In patients with recent-onset heart failure, the clinical, laboratory and echocardiographic profiles can suggest, but not prove, a diagnosis of myocarditis.