Microscopic fractional anisotropy outperforms multiple sclerosis lesion assessment and clinical outcome associations over standard fractional anisotropy tensor.

We aimed to compare the ability of diffusion tensor imaging and multi-compartment spherical mean technique to detect focal tissue damage and in distinguishing between different connectivity patterns associated with varying clinical outcomes in multiple sclerosis (MS). Seventy-six people diagnosed with MS were scanned using a SIEMENS Prisma Fit 3T magnetic resonance imaging (MRI), employing both conventional (T1w and fluid-attenuated inversion recovery) and advanced diffusion MRI sequences from which fractional anisotropy (FA) and microscopic FA (µFA) maps were generated. Using automated fiber quantification (AFQ), we assessed diffusion profiles across multiple white matter (WM) pathways to measure the sensitivity of anisotropy diffusion metrics in detecting localized tissue damage. In parallel, we analyzed structural brain connectivity in a specific patient cohort to fully grasp its relationships with cognitive and physical clinical outcomes. This evaluation comprehensively considered different patient categories, including cognitively preserved (CP), mild cognitive deficits (MCD), and cognitively impaired (CI) for cognitive assessment, as well as groups distinguished by physical impact: those with mild disability (Expanded Disability Status Scale [EDSS] <=3) and those with moderate-severe disability (EDSS >3). In our initial objective, we employed Ridge regression to forecast the presence of focal MS lesions, comparing the performance of µFA and FA. µFA exhibited a stronger association with tissue damage and a higher predictive precision for focal MS lesions across the tracts, achieving an R-squared value of .57, significantly outperforming the R-squared value of .24 for FA (p-value <.001). In structural connectivity, µFA exhibited more pronounced differences than FA in response to alteration in both cognitive and physical clinical scores in terms of effect size and number of connections. Regarding cognitive groups, FA differences between CP and MCD groups were limited to 0.5% of connections, mainly around the thalamus, while µFA revealed changes in 2.5% of connections. In the CP and CI group comparison, which have noticeable cognitive differences, the disparity was 5.6% for FA values and 32.5% for µFA. Similarly, µFA outperformed FA in detecting WM changes between the MCD and CI groups, with 5% versus 0.3% of connections, respectively. When analyzing structural connectivity between physical disability groups, µFA still demonstrated superior performance over FA, disclosing a 2.1% difference in connectivity between regions closely associated with physical disability in MS. In contrast, FA spotted a few regions, comprising only 0.6% of total connections. In summary, µFA emerged as a more effective tool than FA in predicting MS lesions and identifying structural changes across patients with different degrees of cognitive and global disability, offering deeper insights into the complexities of MS-related impairments.

Diffusion tensor imaging metrics associated with future disability in multiple sclerosis.

The relationship between brain diffusion microstructural changes and disability in multiple sclerosis (MS) remains poorly understood. We aimed to explore the predictive value of microstructural properties in white (WM) and grey matter (GM), and identify areas associated with mid-term disability in MS patients. We studied 185 patients (71% female; 86% RRMS) with the Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), and Symbol Digit Modalities Test (SDMT) at two time-points. We used Lasso regression to analyse the predictive value of baseline WM fractional anisotropy and GM mean diffusivity, and to identify areas related to each outcome at 4.1 years follow-up. Motor performance was associated with WM (T25FW: RMSE = 0.524, R2 = 0.304; 9HPT dominant hand: RMSE = 0.662, R2 = 0.062; 9HPT non-dominant hand: RMSE = 0.649, R2 = 0.139), and SDMT with GM diffusion metrics (RMSE = 0.772, R2 = 0.186). Cingulum, longitudinal fasciculus, optic radiation, forceps minor and frontal aslant were the WM tracts most closely linked to motor dysfunction, and temporal and frontal cortex were relevant for cognition. Regional specificity related to clinical outcomes provide valuable information that can be used to develop more accurate predictive models that could improve therapeutic strategies.

Impact of graft size and resuspension level of the commissures on aortic insufficiency after reimplantation of the aortic valve.

BACKGROUND: In addition to the size of the graft, the resuspension of the commissures has been described as important for valve function in valve-sparing aortic root replacement procedures. This study describes the influence of a stepwise reduction of the fixation level of the commissures within the graft as well as a stepwise reduction of graft size on valve insufficiency. METHOD: Porcine aortic valves were reimplanted into a tubular graft and the height of the commissures was reduced in a stepwise manner. In a second series of experiments, the diameter of the grafts was reduced by 30 % and 50 %. RESULTS: A reduction of the commissure heights by 10 % and 20 % caused a significant increase in reflux water. Using the criteria of homograft preparation, a 10 %, but not a 20 %, reduction was tolerated. The coaptation level of the valve became increasingly lower, indicating a higher risk for late valve incompetence. A reduction of the prosthesis diameter by 30 % and 50 % did not result in insufficiency of the valve but it lowered the coaptation level. CONCLUSION: Resuspension of the commissures within the graft has a more important impact on early failure rates than the choice of graft size.

Changes in myocardial cytoskeletal intermediate filaments and myocyte contractile dysfunction in dilated cardiomyopathy: an in vivo study in humans.

AIM: To investigate in vivo the intermediate cytoskeletal filaments desmin and vimentin in myocardial tissues from patients with dilated cardiomyopathy, and to determine whether alterations in these proteins are associated with impaired contractility. METHODS: Endomyocardial biopsies were performed in 12 patients with dilated cardiomyopathy and in 12 controls (six women with breast cancer before anthracycline chemotherapy and six male donors for heart transplantation). Biopsy specimens were analysed by light microscopy and immunochemistry (desmin, vimentin). Myocyte contractile protein function was evaluated by the actin-myosin in vitro motility assay. Left ventricular ejection fraction was assessed by echocardiography and radionuclide ventriculography. RESULTS: Patients with dilated cardiomyopathy had a greater cardiomyocyte diameter than controls (p < 0.01). The increase in cell size was associated with a reduction in contractile function, as assessed by actin-myosin motility (r = -0.643; p < 0.01). Quantitative immunochemistry showed increased desmin and vimentin contents (p < 0.01), and the desmin distribution was disturbed in cardiomyopathy. There was a linear relation between desmin distribution and actin-myosin sliding in vitro (r = 0.853; p < 0.01) and an inverse correlation between desmin content and ejection fraction (r = -0.773; p < 0.02). Negative correlations were also found between myocardial vimentin content and the actin-myosin sliding rate (r = -0.74; p < 0.02) and left ventricular ejection fraction (r = -0.68; p < 0.01). CONCLUSIONS: Compared with normal individuals, the myocardial tissue of patients with dilated cardiomyopathy shows alterations of cytoskeletal intermediate filament distribution and content associated with reduced myocyte contraction.

Improved outcome of pulmonary aspergillosis in heart transplant recipients with early diagnosis and itraconazole treatment.

Pulmonary aspergillosis is a severe complication in heart transplant recipients. The drug of choice for this infection is amphotericin B, but its use is limited because of its side effects. We observed six cases of pulmonary aspergillosis in a group of 200 patients who had received heart transplants from January 1988 to January 1999. Predisposing factors such as previous rejection, neutropenia and/or cytomegalovirus reactivation were present in all patients. The clinical presentation was characterized by fever and a non-productive cough. X-rays showed monolateral or diffuse infiltrate with or without nodular lesions. The median interval between symptoms and diagnosis was 5 d (range 4-7). Diagnosis was made by culturing trans-tracheal aspirate samples. Aspergillus fumigatus was isolated in 3 patients and A. niger in the other 3. All patients were treated with itraconazole at 200-400 mg/day for 20-60 d and all recovered. One patient treated with the lowest dosage for the shortest term had a recurrence after 1 month and needed a second 30-day course of itraconazole at a higher dosage. No significant side effects were registered. Itraconazole is effective in the therapy of pulmonary aspergillosis, particularly when an early diagnosis is made.

[Pathology of heart transplantation.(Morphological study of 1246 endomyocardial biopsies from 167 transplanted hearts). Causes of early, intermediate, and late deaths]. / Patologia del trapianto cardiaco. (Studio morfologico di 1246 biopsie endomiocardiche (BEM) da 167 trapianti cardiaci). Cause di mortalità precoce, intermedia e tardiva.

From January 1988 through October 1997, 167 cardiac transplants were performed. 1246 endomyocardial biopsies (EMBs) from 138 cardiac allograft recipients were investigated and graded according to the Working Formulation (WF) criteria. The specimens were inadequate in 44 EMBs (3.5%), while 598 (48%) showed no rejection. The grade of rejection was: mild (grade 1A and 1B) in 531 EMBs (42.6%), mild/moderate (grade 2) in 38 (3.1%), and moderate (grade 3A and 3B) in 35 (2.8%). The indications for transplantation were: dilated cardiomyopathy (46.1%); ischemic disease (37.1%); valvular disease (12%); hypertrophic cardiomyopathy (1.8%); myocarditis (1.2%); congenital cardiopathy (0.6%), restrictive cardiomyopathy (0.6%) and chronic rejection (0.6%). The most reliable histologic feature of acute rejection was the myocyte necrosis or damage in presence of pironinophilic mononuclear cell infiltrate, so our protocol requires multifocal or diffuse myocyte damage (rejection grade 3A and 3B) to perform an additional treatment, which was required in 35 cases (2.8%). An intermediate grade mild/moderate 2, was introduced from the WF to classify the EMBs in which the myocyte necrosis was scant or not clear; this grade in our series generally resolves without any additional treatment; in order to monitor the rejection another EMB was performed 5 days after in these patients. The EMBs showed also the following lesions other than acute rejection: Quilty A (79 patients; 57.25%), Quilty B (24 pts; 17.39%), early ischemic necrosis (43 pts; 31.15%) and late ischemic necrosis (5 pz; 3.62%). Quilty B and late ischemic necrosis were correlated with acute rejection (grade 2), furthermore the patients with graft vascular disease showed 3 or more episodes of acute rejection. These findings confirm the relationship between acute and chronic rejection. Furthermore, a relationship between chronic rejection (4 pts) and infection from hepatitis C (antibodies positive 3 pts/4) and cytomegalovirus (antibodies positive 4 pts/4) was found in our series. In the follow-up period (117 months), a 30.72% death rate was recorded; the main causes of death were: early failure of the transplanted heart (30 pts) in 4 of them associated with pulmonary hypertension, infections (6 pts), sudden death (4 pts), graft's vasculopathy (4 pts), acute pancreatitis (1 pts) pulmonary embolism (1 pts), lung (1 pts) and ovary (1 pts) carcinoma, acute rejection (1 pts), others (2 pts). In the early period (< 1 month), the most frequent cause of death was the early failure of the transplanted heart, while in the late period (> 1 year) the chronic rejection following by sudden death and tumours. The actuarial survival curve drops to 83.13% after the first post-operative month, abates to 75.30 at the end of the first year, and progressively decreases to 70.48% at the end of the fifth follow-up year. The mortality rate was 38.7% in pts transplanted for ischemic disease and 24.7% for dilated cardiomyopathy. Cardioplegia seems to play an important role in the success of the heart transplant.

Bioelectrical impedance analysis before and after Novacor implantation.

In this study Bioelectrical Impedance Analysis was performed in 5 patients with end stage heart failure in whom a left ventricular assist device (Novacor) was successfully implanted. Whole body measurements of bioelectrical indices resistance and reactance were taken before surgery and 3, 7, 12, and 15 days after it. After surgery there was a significant decrease in reactance, indicating a shift of body fluids from intra- to extra-cellular space.

Heart transplantation in patients with diuretic resistant heart failure.

Advanced heart failure is becoming an increasing cause of mortality and morbidity in a large number of patients. Heart transplantation is the treatment of choice for many selected patients in this group. According to the clinical status at the time of transplant, patients may have a different outcome related to the early survival, while the late results are similar and not affected by the patient's initial clinical status. All surviving patients showed recovery of kidney function as soon the cardiac output was restored to normal values. High urine output was present in a large number of patients in the early postoperative period. However, in severely ill patients with cardiac index <2.5 l/min/m2, diuretic resistance and mortality were higher.

Body impedance studies in end-stage heart failure.

This study adds another category of patients to those amenable to body impedance analysis (BIA). BIA measurements were obtained for the first time in 23 male patients with end-stage heart failure who were waiting for heart transplantation, and the data were compared with those obtained in 69 healthy controls matched for age, sex, height and weight. The data indicate that in end-stage heart failure there is an increased reactance (p<0.01) and an altered intracellular water/extracellular water ratio (p<0.03) due to the increased intracellular water (p<0.01) and decreased extracellular water (p<0.01).

Renal reserve is normal in patients with dilative cardiomyopathy waiting for heart transplantation.

Renal reserve was explored by means of an oral protein load (2 g/kg body weight) under the form of cooked red meat in a group of 9 patients with end-stage heart failure (ESHF), class III of the New York Heart Association receiving loop diuretics and angiotensin-converting enzyme (ACE) inhibitors, and in a group of 18 healthy controls (HC) matched for age, gender, and height under an identical dietary regimen providing 40 cal/kg per day, 1 g/kg body weight of protein per day, Na 120 mmol/day, and K 50 mmol/day. Baseline glomerular filtration rate averaged 109.5+/-9.89 ml/min x 1.73 m2 in HC and 71.9+/-8.8 ml/min x 1.73 m2 in ESHF. Renal plasma flow averaged 540+/-27 ml/min x 1.73 m2 in HC and 235+/-47 ml/min x 1.73 m2 in ESHF. The filtration fraction was significantly higher in ESHF (p<0.01). Renal reserve averaged 26.03+/-3.28 ml/min x 1.73 m2 in HC and 27.2+/-7.12 ml/min x 1.73 m2 (not significant). Renal reserve averaged 123.9+/-2.9% in HC and 137.3+/-6.68% in ESHF (not significant). The filtration capacity was significantly higher in HC (p<0.001). The data point to a normalcy of renal reserve in ESHF which may depend on the chronic use of ACE inhibitors.

Role of the heart surgeon in the emergency treatment of diuretic resistant edema in grades III-IV heart failure.

Acute or chronic valvular diseases, acute myocardial infarction and its complications, dilated cardiomyopathies, all may became the cause of heart failure leading to different degrees of cardiogenic edema. Today cardiac failure is treated from its the early stage by medical and/or surgical therapy. Thereafter, in a small population of patients, heart failure may became unresponsive to any kind of standard medical treatment. Conventional surgical procedures are often inadequate and carry a high risk of perioperative mortality. This study analyzes the outcome of 139 patients with end-stage cardiomyopathy who underwent heart transplantation between January 1988 and October 1996. We found that patients transplanted while on severe decompensation are at a higher perioperative mortality due to irreversible multi-organ failure. The study also suggests that the implantation of a left ventricle assist device as a bridge to transplantation is a promising maneuver for the most severe patients.

[Infective endocarditis today; heart surgery in its treatment: how and when]. / L'endocardite infettiva oggi; la cardiochirurgia nella terapia: come e quando.

The authors report the experience of 161 surgical cases operated between 1980 and 1992 because of valve endocarditis. Two hundred and two surgical procedures were performed. Patients were divided into two groups: Group I (EN) considered 117 patients with endocarditis on the native valve; Group II (EP) included 64 patients with prosthetic endocarditis. In 23 patients the prosthesis was implanted for previous endocarditis on the native valve (EP1); in 41 patients the prosthesis was implanted for other valve diseases (EP2). Each group was described according to sex, age, site of endocarditis, previous cardiac diseases, socio-economical level, hemodynamic and infective conditions at surgery, etiology of endocarditis, surgical indication, pathology report, surgical procedure and results. The results were evaluated considering surgical mortality, late mortality and recurrence of endocarditis. The main risk factors were correlated to overall survival and recurrency. Hospital mortality was 7.6% in EN, 13% in EP1, 36.5% in EP2; endocarditis recurrency was 20.3% in EN, 65% in EP1, 19.2% in EP2. Sixteen patients with prosthetic endocarditis were submitted to a second reoperation with 50% mortality; 4 patients to a third reoperation with 50% mortality; 1 patient to a fourth reoperation with no mortality. Actuarial overall survival was 40.3% at 12 years in Group EN, 33.3% at 12 years in Group EP1, 73.4% at 12 years in Group EP2. Finally the Authors report the experience of 12 stentless grafts (autologous, homologous and eterologous) implanted between March 1991 and July 1994 in patients with valve or prosthetic endocarditis with no recurrency at 42 months of follow-up.

Early experience with the Jyros bileaflet valve in the mitral position: high incidence of valve thrombosis.

The Jyros valve is a new bileaflet valve with the unusual feature that the hinge is expected to rotate continuously inside the housing. Nine isolated Jyros mitral prostheses were implanted from July to October 1993. All patients survived the surgical procedure and during the follow up underwent transthoracic (TTE) and transesophageal echocardiograms (TEE) for the evaluation of hinge rotation. Neither TTE nor TEE were able to show hinge rotation in any patient at any time. Five patients had prosthetic thrombosis. In the successfully treated with thrombolysis. In the remaining patient thrombolysis was contraindicated. Eight patients are alive; one died of gastro-intestinal bleeding a few months after discharge. The absence of hinge rotation may be the triggering mechanism of valve thrombosis although no explanted prostheses were available for examination. Further studies are necessary to understand the mechanism of valve thrombosis with the Jyros bileaflet prosthesis.

Non-inflammatory aortic root disease and floppy aortic valve as cause of isolated regurgitation: a clinico-morphologic study.

A clinico-morphologic study was performed on 1120 patients who underwent aortic valve replacement at the Department of Medical and Surgical Cardiology, 2nd University Medical School of Naples, Naples, Italy, from January 1981 through December 1991. In 69 cases the aortic valve was incompetent due to a non-inflammatory aortic root disease such as myxomatous infiltration of the cusps and or aortic root dilatation. Among these patients males were prevalent (male/female ratio = 2.2). The mean age was 37 +/- 7.5 years. A floppy mitral valve was diagnosed in 16 cases while in one a left atrial myxoma was found. The patients were divided into 3 groups: Group 1-29 patients with aortic root dilatation and normal cusps; Group 2-25 patients with aortic root dilatation and myxomatous infiltration of aortic cusps (floppy aortic valve); and Group 3-15 patients with floppy aortic valve and undilated aortic root. At the gross examination the cusps of the patients in Groups 2 and 3 were redundant, thin, soft and gelatinous. The histology showed myxomatous infiltration with disruption of the fibrous layer. In patients with aortic root dilatation the histology of the aortic root fragments showed a cystic medial necrosis. Deep correlation was found between the root dilatation and the grade of aortic wall cystic medial necrosis. Cusp's diastasis was the cause of aortic regurgitation in patients with aortic root dilatation, while cusp prolapse caused aortic incompetence in presence of the floppy aortic valve and undilated aortic root.(ABSTRACT TRUNCATED AT 250 WORDS)

Long term results of surgery for prosthetic valve endocarditis.

Operative mortality, recurrence and late survival were analyzed in 64 patients operated for prosthetic valve endocarditis (PVE) between 1980-1992: age, sex, drug addiction, early vs. late PVE, micro-organism, sepsis at the time of surgery, indication for surgery, prosthesis type and site were assessed as potential risk factors. PVE developed after replacement for native valve endocarditis in 23 cases (Group A) and after replacement for other valvular disease in 41 patients (Group B). The overall operative mortality was 28.1% (18/64); 16 operative survivors underwent a second reoperation with eight operative deaths (50%), four of them a third procedure with two operative deaths (50%), and one patient had a successful fourth intervention. Female sex (p = 0.015) and sepsis at the time of surgery (p = 0.013), were found statistically significant independent predictors of operative mortality. Age (p:0.002), mechanical valves (p:0.05) and mitral position (p:0.03) were significant predictors of PVE recurrence. None of the risk factors considered were significant for late survival. Twelve-year actuarial survival for all patients was 52.11 +/- 10%; it was 33.3 +/- 13% for Group A and 73.4 +/- 14% for Group B (p:0.04). Patients with mechanical valves and bioprostheses had an actuarial survival of 39.5 +/- 15% and 48.5 +/- 14% respectively with no significant difference. PVE is still a challenging complication of heart valve replacement; patients with PVE after native valve endocarditis have a very poor outcome. Prompt prosthetic replacement is recommended whenever the antibiotic treatment is unsuccessful and/or the hemodynamic status deteriorates.

Surgical pathology of the aortic valve: gross and histological findings in 1120 excised valves.

From January 1981 through December 1991, 1120 consecutive aortic valves were surgically explanted and their gross anatomy and histology studied at our university. Rheumatic disease (65%), dystrophic calcific valvular disease (23%), noninflammatory disease of the aortic root and/or floppy aortic valve (6.3%), and endocarditis (5.4%) were the causes of valve dysfunction. Among the total population the male sex predominated. The male to female ratio was 2.4 in the group with dystrophic calcific valvular disease and 1.6 in the group with bacterial endocarditis. The mean age was 37 ± 7.5 years in the group with non-inflammatory disease of the aortic root and/or aortic cusps. In the group with dystrophic calcific valvular disease, the mean age was 62 ± 6.3 years. Among the 1120 patients, 717 (64.03%) underwent surgery for aortic stenotic-incompetence, 250 (22.25%) for isolated aortic stenosis, and 153 (13.72%) for isolated aortic incompetence. In 449 cases (40.13%) a mitral pathology was associated. Chronic rheumatic aortic disease usually caused stenotic insufficiency (92.8%). Dystrophic calcific aortic disease caused pure stenosis in 84.8% of the cases. Among these, 46 patients (18.4%) had a congenitally bicuspidal aortic valve. Pure aortic incompetence was caused by noninflammatory aortic root and/or cusp disease in 44% of patients, infective endocarditis in 40%, and rheumatic disease in 16%. Patients with noninflammatory aortic root and/or cusp disease were divided into three groups: 29 patients with aortic root dilatation and normal cusps, 25 patients with aortic root dilatation and mixomatous infiltration of aortic cusps (floppy aortic valve), and 15 patients with floppy aortic valve and normal aortic root. Aortic incompetence was caused by cusp retraction caused by chronic rheumatic disease, cusp perforation or tears caused by infective endocarditis, and cusp prolapse for floppy aortic valve. Cusp diastasis has been the cause of aortic incompetence in patients with dilated aortic root. In patient with floppy aortic valve caused by the fibrous lamina disarray, the cusps prolapsed toward the left ventricle, causing valve regurgitation.