The role of non-invasive imaging modalities in cardiac allograft vasculopathy: an updated focus on current evidences.

Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse form of vasculopathy affecting almost 50% of patients after 10 years from heart transplant and represents the most common cause of long-term cardiovascular mortality among heart transplant recipients. The gold standard diagnostic technique is still invasive coronary angiography, which however holds potential for complications, especially contrast-related kidney injury and procedure-related vascular lesions. Non-invasive and contrast-sparing imaging techniques have been advocated and investigated over the past decades, in order to identify those that could replace coronary angiography or at least reach comparable accuracy in CAV detection. In addition, they could help the clinician in defining optimal timing for invasive testing. This review attempts to examine the currently available non-invasive imaging techniques that may be used in the follow-up of heart transplant patients, spanning from echocardiography to nuclear imaging, cardiac magnetic resonance and cardiac computed tomography angiography, weighting their advantages and disadvantages.

Cardiac amyloidosis characterization by kinetic model fitting on [18F]florbetaben PET images.

OBJECTIVE: To evaluate the feasibility of kinetic modeling-based approaches from [18F]-Flobetaben dynamic PET images as a non-invasive diagnostic method for cardiac amyloidosis (CA) and to identify the two AL- and ATTR-subtypes. METHODS AND RESULTS: Twenty-one patients with diagnoses of CA (11 patients with AL-subtype and 10 patients with ATTR-subtype of CA) and 15 Control patients with no-CA conditions underwent PET/CT imaging after [18F]Florbetaben bolus injection. A two-tissue-compartment (2TC) kinetic model was fitted to time-activity curves (TAC) obtained from left ventricle wall and left atrium cavity ROIs to estimate kinetic micro- and macro-parameters. Combinations of kinetic parameters were evaluated with the purpose of distinguishing Control subjects and CA patients, and to correctly label the last ones as AL- or ATTR-subtype. Resulting sensitivity, specificity, and accuracy for Control subjects were: 0.87, 0.9, 0.89; as far as CA patients, the sensitivity, specificity, and accuracy were respectively 0.9, 1, and 0.97 for AL-CA patients and 0.9, 0.92, 0.97 for ATTR-CA patients. CONCLUSION: Pharmacokinetic analysis based on a 2TC model allows cardiac amyloidosis characterization from dynamic [18F]Florbetaben PET images. Estimated model parameters allows to not only distinguish between Control subjects and patients, but also between AL- and ATTR-amyloid patients.

Post-acute cardiac complications following SARS-CoV-2 infection in partial lipodystrophy due to LMNA gene p.R349W mutation.

PURPOSE: SARS-CoV-2 infection may cause varying degrees of cardiac injury and the presence of underlying cardiovascular morbidities contributes to the frequency and severity of occurrence of this complication. Lipodystrophy syndromes are frequently characterized by severe metabolic derangements that represent relevant cardiovascular risk factors. Besides causing lipodystrophy, mutations in the lamin A/C (LMNA) gene can lead to a wide spectrum of tissue-specific disorders including cardiac involvement. METHODS AND RESULTS: We herein examine the case of two patients affected by atypical progeroid syndrome and partial lipodystrophy due to a heterozygous missense LMNA mutation c.1045 C > T (p.R349W) who presented initially with mild COVID-19 and developed severe cardiovascular complications within few weeks of SARS-CoV-2 infection. Before being infected with SARS-CoV-2, our patients had cardiovascular morbidities (mild mitral regurgitation in one patient, ischemic heart disease with bifascicular block in the other patient) in adjunct to cardiovascular risk factors, but the SARS-CoV-2 infection contributed to quickly and significantly decompensate their balance. CONCLUSION: These findings warn that patients affected by LMNA p.R349W mutation and likely other LMNA mutations associated with cardiovascular morbidity should be considered at extremely elevated risk of post-acute cardiological manifestations and should therefore undergo a vigilant follow-up after SARS-CoV-2 infection. Both patients developed COVID-19 before the specific vaccination was available to them and this unfortunate situation should remark the importance of vaccination coverage against SARS-CoV-2 infection for all patients affected by lipodystrophy, especially those with underlying comorbidities.

Cardiogenic shock and acute kidney injury: the rule rather than the exception.

Cardiogenic shock (CS) is a life-threatening condition of poor end-organ perfusion, caused by any cardiovascular disease resulting in a severe depression of cardiac output. Despite recent advances in replacement therapies, the outcome of CS is still poor, and its management depends more on empirical decisions rather than on evidence-based strategies. By its side, acute kidney injury (AKI) is a frequent complication of CS, resulting in the onset of a cardiorenal syndrome. The combination of CS with AKI depicts a worse clinical scenario and holds a worse prognosis. Many factors can lead to acute renal impairment in the setting of CS, either for natural disease progression or for iatrogenic causes. This review aims at collecting the current evidence-based acknowledgments in epidemiology, pathophysiology, clinical features, diagnosis, and management of CS with AKI. We also attempted to highlight the major gaps in evidence as well as to point out possible strategies to improve the outcome.

Measurement of myocardial amyloid deposition in systemic amyloidosis: insights from cardiovascular magnetic resonance imaging.

BACKGROUND: Cardiac involvement in systemic amyloidosis is caused by the extracellular deposition of misfolded proteins, mainly immunoglobulin light chains (AL) or transthyretin (ATTR), and may be detected by cardiovascular magnetic resonance (CMR). The aim of this study was to measure myocardial extracellular volume (ECV) in amyloid patients with a novel T1 mapping CMR technique and to determine the correlation between ECV and disease severity. METHODS: Thirty-six patients with biopsy-proven systemic amyloidosis (mean age 70 ± 9 years, 31 men, 30 with AL and six with ATTR amyloidosis) and seven patients with possible amyloidosis (mean age 64 ± 10 years, six men) underwent comprehensive clinical and CMR assessment, with ECV estimation from pre- and postcontrast T1 mapping. Thirty healthy subjects (mean age 39 ± 17 years, 21 men) served as the control group. RESULTS: Amyloid patients presented with left ventricular (LV) concentric hypertrophy with impaired biventricular systolic function. Cardiac ECV was higher in amyloid patients (definite amyloidosis, 0.43 ± 0.12; possible amyloidosis, 0.34 ± 0.11) than in control subjects (0.26 ± 0.04, P < 0.05); even in amyloid patients without late gadolinium enhancement (0.35 ± 0.10), ECV was significantly higher than in the control group (P < 0.01). A cut-off value of myocardial ECV >0.316, corresponding to the 95th percentile in normal subjects, showed a sensitivity of 79% and specificity of 97% for discriminating amyloid patients from control subjects (area under the curve of 0.884). Myocardial ECV was significantly correlated with LV ejection fraction (R(2)  = 0.16), LV mean wall thickness (R(2)  = 0.41), LV diastolic function (R(2)  = 0.21), right ventricular ejection fraction (R(2)  = 0.13), N-terminal fragment of the pro-brain natriuretic peptides (R(2)  = 0.23) and cardiac troponin (R(2)  = 0.33). CONCLUSION: Myocardial ECV was increased in amyloid patients and correlated with disease severity. Thus, measurement of myocardial ECV represents a potential noninvasive index of amyloid burden for use in early diagnosis and disease monitoring.

Similar patterns of myocardial metabolism and perfusion in patients with type 2 diabetes and heart disease of ischaemic and non-ischaemic origin.

AIMS/HYPOTHESIS: Type 2 diabetes and insulin resistance are often associated with the co-occurrence of coronary atherosclerosis and cardiac dysfunction. The aim of this study was to define the independent relationships between left ventricular dysfunction or ischaemia and patterns of myocardial perfusion and metabolism in type 2 diabetes. METHODS: Twenty-four type 2 diabetic patients--12 with coronary artery disease (CAD) and preserved left ventricular function and 12 with non-ischaemic heart failure (HF)--were enrolled in a cross-sectional study. Positron emission tomography (PET) was used to assess myocardial blood flow (MBF) at rest, after pharmacological stress and under euglycaemic hyperinsulinaemia. Insulin-mediated myocardial glucose disposal was determined with 2-deoxy-2-[(18)F]fluoroglucose PET. RESULTS: There was no difference in myocardial glucose uptake (MGU) between the healthy myocardium of CAD patients and the dysfunctional myocardium of HF patients. MGU was strongly influenced by levels of systemic insulin resistance in both groups (CAD, r = 0.85, p = 0.005; HF, r = 0.77, p = 0.01). In HF patients, there was an inverse association between MGU and the coronary flow reserve (r = -0.434, p = 0.0115). A similar relationship was observed in non-ischaemic segments of CAD patients. Hyperinsulinaemia increased MBF to a similar extent in the non-ischaemic myocardial of CAD and HF patients. CONCLUSIONS/INTERPRETATION: In type 2 diabetes, similar metabolic and perfusion patterns can be detected in the non-ischaemic regions of CAD patients with normal cardiac function and in the dysfunctional non-ischaemic myocardium of HF patients. This suggests that insulin resistance, rather than diagnosis of ischaemia or left ventricular dysfunction, affects the metabolism and perfusion features of patients with type 2 diabetes.

Death occurred due to undiagnosed systemic amyloidosis: a case report.

Abstract: Amyloidosis is a disorder related to errors in protein folding. We present a clinical case of systemic amyloidosis manifesting as hypotension, tachycardia, pain, weight loss, asthenia, anorexia, dysphagia, and mood deflection in a 49-year-old-year-old woman with a previous clinical history of articular and muscular pain, correlated to suspected seronegative arthritis. The blood test revealed kidney insufficiency, an electrocardiogram identified low voltages of the peripheral leads and T waves anomalies. A serum protein electrophoresis revealed the presence of high levels of monoclonal kappa free chains. The woman started to have a sense of suffocation, and after one week she was found dead in her bed. After the autopsy, the results of Congo red staining of the myocardium were characteristic of amyloid. According to the autoptic and the histological examination, death occurred due to acute cardiac and respiratory arrest secondary to amyloid cardiomyopathy in a patient with undiagnosed systemic amyloidosis.

C-type natriuretic peptide and its relation to non-invasive indices of left ventricular function in patients with chronic heart failure.

C-type natriuretic peptide (CNP) significantly increases in chronic heart failure (CHF) patients as a function of clinical severity. Aim of this study was to evaluate in CHF patients the relationship between circulating CNP concentrations and echo-Doppler conventional indices of left ventricular (LV) function as well as less load independent parameters as dP/dt. LV ejection fraction (EF), left ventricular end-diastolic dimension (LVEDD) and LV dP/dt were evaluated together with plasma CNP levels in 38 patients with CHF and in 63 controls. CNP levels resulted significantly higher in CHF patients than in controls (7.19+/-0.59 pg/ml vs. 2.52+/-0.12 pg/ml, p<0.0001). A significant correlation between dP/dt and CNP levels (r=-0.61, p<0.0001) was observed. A good correlation with EF (r=-0.55, p<0.001) and a less significant relation with LVEDD (r=0.316, p<0.05) were also reported. When patients were divided according to dP/dt values a very significant difference in CNP levels was observed: Group I (<600, n=25) vs. Group II (>600, n=13): 8.46+/-0.69 and 4.75+/-0.75 pg/ml, respectively, p<0.001. This is the first study that reports a correlation between CNP and dP/dt in CHF patients, thus suggesting a possible role on cardiac contractility.

Prognostic value of pulmonary blood volume by first-pass contrast-enhanced CMR in heart failure outpatients: the PROVE-HF study.

Aims: Pulmonary blood volume (PBV) is a novel clinical application of cardiovascular magnetic resonance (CMR) imaging for the quantitative grading of haemodynamic congestion. In this study, we aimed to assess the prognostic value of PBV in a cohort of outpatients with chronic heart failure (HF). Methods and results: One hundred and twelve consecutive patients (91 men, 67 ± 12 years) and 53 age- and sex-matched healthy controls underwent echocardiography and contrast-enhanced CMR. PBV was calculated as the product of stroke volume and the number of cardiac cycles for an intravenous bolus of gadolinium contrast to pass through the pulmonary circulation determined by first-pass perfusion imaging. Compared with healthy controls, HF outpatients showed significantly higher PBV index (PBVI, 308 ± 92 vs. 373 ± 175, mL/m2, P = 0.012) and pulmonary transit time (6.8 ± 1.8 vs. 9.5 ± 4 s, P ≤0.001). During a median follow-up of 26 ± 17 months, 27 patients (24%) reached the composite end point of cardiovascular death, HF hospitalization, or sustained ventricular arrhythmias/appropriate implantable cardioverter-defibrillator intervention. Using a cut-off point of PBVI >492 mL/m2, corresponding to two standard deviations above the mean of healthy controls, event-free survival was significantly lower in patients with higher PBVI (P < 0.001). At multivariable-adjusted Cox regression analysis, PBVI was an independent predictor of the composite cardiovascular end point (per 10% increase hazard ratio 1.31, 95% confidence interval: 1.02-1.69, P = 0.03). Conclusions: PBVI is a novel application of perfusion CMR potentially useful to quantitatively determine haemodynamic congestion as a surrogate marker of left ventricular diastolic dysfunction. PBVI might prove to be helpful in stratifying the prognosis of asymptomatic or mildly symptomatic patients with left ventricular dysfunction.

[Natriuretic peptides in heart failure]. / Peptidi natriuretici come guida alla prognosi e terapia nello scompenso cardiaco.

The recent discovery of cardiac endocrine function, together with the development of accurate and feasible assay methods for cardiac natriuretic hormone evaluation, i.e. for B-type natriuretic peptide (BNP) and inactive peptide NT-proBNP have confirmed their pathophysiological and clinical significance for cardiovascular disease assessment. Concerning heart failure, their value is for diagnostic screening in selected/unselected populations, for differential diagnosis of dyspnea and for prognostic stratification, and as a guide for follow-up and treatment of patients. Recent Italian recommendations pointed out that BNP/NT-proBNP has a role in ruling-out the diagnosis of heart failure in patients with dubious signs/symptoms: plasma BNP/NT-proBNP concentrations help in the clinical evaluation of chronic heart failure patients when risk stratification is needed, whereas the routine BNP/NT-proBNP assay is still not recommended to guide therapeutic decision-making.

Hyperinsulinemia and autonomic nervous system dysfunction in obesity: effects of weight loss.

BACKGROUND: Because hyperinsulinemia acutely stimulates adrenergic activity, it has been postulated that chronic hyperinsulinemia may lead to enhanced sympathetic tone and cardiovascular risk. METHODS AND RESULTS: In 21 obese (body mass index, 35+/-1 kg/m(2)) and 17 lean subjects, we measured resting cardiac output (by 2-dimensional echocardiography), plasma concentrations and timed (diurnal versus nocturnal) urinary excretion of catecholamines, and 24-hour heart rate variability (by spectral analysis of ECG). In the obese versus lean subjects, cardiac output was increased by 22% (P:<0.03), and the nocturnal drop in urinary norepinephrine output was blunted (P:=0.01). Spectral power in the low-frequency range was depressed throughout 24 hours (P:<0.04). During the afternoon and early night, ie, the postprandial phase, high-frequency power was lower, heart rate was higher; and the ratio of low to high frequency, an index of sympathovagal balance, was increased in direct proportion to the degree of hyperinsulinemia independent of body mass index (partial r=0.43, P:=0.01). In 9 obese subjects who lost 10% to 18% of their body weight, cardiac output decreased and low-frequency power returned toward normal (P:<0.05). CONCLUSIONS: In free-living subjects with uncomplicated obesity, chronic hyperinsulinemia is associated with a high-output, low-resistance hemodynamic state, persistent baroreflex downregulation, and episodic (postprandial) sympathetic dominance. Reversal of these changes by weight loss suggests a causal role for insulin.

Improved exercise capacity with acute aminophylline administration in patients with syndrome X.

The efficacy of the adenosine receptor blocker aminophylline on exercise capacity in patients with effort ischemia and documented coronary artery disease has been previously documented. In this study the effect of aminophylline on effort electrocardiographic (ECG) alterations and chest pain was tested in eight patients with syndrome X (anginal chest pain on effort, ischemic ECG changes during exercise, positive dipyridamole test, normal epicardial coronary arteries on angiography and absence of coronary spasm after ergonovine). After double-blind, randomized intravenous infusion of aminophylline (6 mg/kg body weight over 15 min) or placebo (20 ml of saline solution over 15 min), the eight patients with syndrome X underwent an upright bicycle exercise stress test on 2 consecutive days. After aminophylline, there was an increase in effort tolerance (aminophylline 7.7 +/- 1.2 min of exercise versus placebo 5.6 +/- 0.9, p less than 0.01) paralleled by an increase of the rate-pressure product (mm Hg x beats/min x 1/100) at 0.1 mV of ST segment depression or at peak exercise (aminophylline 278 +/- 55 versus placebo 230 +/- 24, p less than 0.05). Aminophylline provoked the abolition of ECG signs of ischemia in all eight patients. Thus, at a dosage that should effectively inhibit adenosine receptors, aminophylline infusion exerts a beneficial effect on exercise-induced chest pain and ischemia-like ECG changes in syndrome X. This effect occurs possibly through the prevention of myocardial flow maldistribution elicited by inappropriate adenosine release during effort in the presence of increased coronary resistance at the level of small intramural coronary arteries. This study, however, does not document the ischemic nature of effort-induced pain and ECG alterations in syndrome X.

Design and optimization of lipid-modified poly(amidoamine) dendrimer coated iron oxide nanoparticles as probes for biomedical applications.

Superparamagnetic iron oxide nanoparticles with a wide size range (2.6-14.1 nm) were synthesized and coated with the amphiphilic poly(amidoamine) PAMAM-C12 dendrimer. The resulting well dispersed and stable water suspensions were fully characterized in order to explore their possible use in biomedical applications. The structural and magnetic properties of the nanoparticles were preserved during the coating and were related to their relaxometric behaviour. The Nuclear Magnetic Resonance Dispersion (NMRD) profiles were found to be in accordance with the Roch model. The biocompatibility was assessed by means of cell viability tests and Transmission Electron Microscopy (TEM) analysis. The nanoparticles' capability of being detected via Magnetic Resonance Imaging (MRI) was investigated by means of clinical MRI scanners both in water and agar gel phantoms, and in a mouse model.

Autonomic and hemodynamic responses to insulin in lean and obese humans.

To study the acute effects of insulin on autonomic control of cardiac function, we performed spectral analysis of heart rate variability and measured cardiac dynamics (by two-dimensional echocardiography) in 18 obese (BMI = 35 +/- 1 kg.m-2) and 14 lean (BMI = 24 +/- 1 kg.m-2) subjects in the basal state and in response to physiological hyperinsulinemia (1 mU.min-1.kg-1 insulin clamp). In the lean group, insulin promptly (within 20 min) and consistently depressed spectral powers, both in the low-frequency and high-frequency range. These changes were twice as large as accounted for by the concomitant changes in heart rate (68 +/- 2 to 70 +/- 2 beats/min). At the end of the 2-h clamp, stroke volume (67 +/- 4 to 76 +/- 9 ml.min-1) and cardiac output (4.45 +/- 0.21 to 5.06 +/- 0.55 l.min-1) rose, whereas peripheral vascular resistance fell. The low-to-high frequency ratio increased from 1.7 +/- 0.2 to 2.3 +/- 0.3 (P < 0.01), indicating sympathetic shift of autonomic balance. In the obese group, all basal spectral powers were significantly lower (by 40% on average) than in the lean group, and were further reduced by insulin administration. The low-to-high frequency ratio was higher than in controls at baseline (2.4 +/- 0.4, P < 0.03), and failed to increase after insulin (2.2 +/- 0.3, P = ns). Furthermore, obesity was associated with higher resting stroke volume (89 +/- 5 vs. 67 +/- 4 ml.min-1, P < 0.01) and cardiac output (6.01 +/- 0.31 vs. 4.45 +/- 0.21 l.min-1, P = 0.001) but lower peripheral vascular resistance (15.1 +/- 0.8 vs. 19.2 +/- 1.1 mmHg.min.L-1, P = 0.002), whereas mean arterial blood pressure was similar to control (90 +/- 2 vs. 86 +/- 2 mmHg, P = not significant). We conclude that physiological hyperinsulinemia causes acute desensitization of sinus node activity to both sympathetic and para-sympathetic stimuli, sympathetic shift of autonomic balance, and a high-output, low-resistance hemodynamic state. In the obese, these changes are already present in the basal state, and may therefore be linked with chronic hyperinsulinemia.

Early impairment of coronary flow reserve and increase in minimum coronary resistance in borderline hypertensive patients.

OBJECTIVE: To evaluate relations between coronary flow velocity and myocardial oxygen demand at rest, as well as coronary vasodilator capacity and flow reserve, in asymptomatic subjects with borderline hypertension as compared to normotensive controls and patients with sustained high blood pressure (HBP) and without left ventricular hypertrophy (LVH). SUBJECTS AND METHODS: Forty-two asymptomatic males were studied: 13 healthy normotensive volunteers; 12 subjects with borderline HBP and 17 asymptomatic subjects with sustained systemic hypertension. Coronary flow velocity in left anterior descending artery and coronary flow reserve were assessed by transesophageal echo-doppler at baseline and during intravenous adenosine infusion. Left ventricular mass, peak systolic wall stress (PSWS; Pa), and midwall fractional shortening (MFS; %) were obtained from M-mode images of the left ventricle in transthoracic long-axis view and in transesophageal transgastric view. RESULTS: Coronary flow velocity at baseline was not significantly different in the three groups, despite significantly higher rate-pressure product (RPP) in the hypertensive groups as compared with controls. Only in control subjects, was resting coronary flow velocity significantly correlated with RPP (y = 4279 + 200x, r = + 0.58, P < 0.05) and PSWS (y = 17.2 + 5.1 x, r = + 0.62, P < 0.05). Coronary reserve was 3.5 +/- 0.65 in controls and significantly lower (P < 0.05) in borderline hypertensive (2.87 +/- 0.46) and in sustained hypertensive subjects (2.66 +/- 0.56). Minimum coronary resistance was significantly increased in both hypertensive groups (1.30 +/- 0.29 and 1.39 +/- 0.48 mmHg/s per cm) as compared to normotensive controls (0.93 +/- 0.20 mmHg/s per cm, P < 0.01). CONCLUSIONS: In asymptomatic subjects with borderline hypertension and without LVH, a significant reduction in coronary flow reserve is already detectable and appears almost entirely related to an impaired coronary vasodilator capacity rather than to an increased myocardial oxygen demand.

Findings from long-term electrocardiographic monitoring of patients with variant angina in a coronary care unit.

Eleven patients with frequent episodes of variant angina underwent 24-hour electrocardiographic monitoring in a coronary care unit for a total of 70 days to assess circadian variation in ischemic episodes and its correlation with circadian heart rate (HR) rhythm. In each patient a series of 4 to 13 consecutive days, in the absence of therapy, with 8 or more ischemic episodes per day were analyzed. Harmonic regression models were fitted to the hourly number of ischemic episodes and the hourly values of HR. Out of 54 days, with 8 or more episodes per day for a total of 1,357 episodes, a circadian rhythm was observed for 34 days (64%), in at least 1 day in all patients and during the entire period of observation in only 3. Its presence was independent of the number of episodes; the peak of periodic functions occurred at 2.9 +/- 2.7 AM. A cadian rhythm for HR was observed in 61 of the 70 days (87%), consistently in 7 patients; the nadir occurred at 2.4 +/- 1.5 AM; simultaneous cycling in HR and transient ischemia was found on 32 days. The intrapatient difference between the peak and the nadir of the ischemic and the HR function was, on average, 2.6 +/- 3.3 hours. Thus, a circadian rhythm of ischemic episodes was present in all patients although it was not consistently present; simultaneous occurrence of circadian variation in ischemic episodes and HR was observed only in 60% of the days with a sufficiently high number of attacks and when this occurred, a significant phase shift was observed; occasional loss of HR cycling was observed in some patients, without an apparent cause.

Consensus statement concerning cardiotoxicity occurring during haematopoietic stem cell transplantation in the treatment of autoimmune diseases, with special reference to systemic sclerosis and multiple sclerosis.

Autologous haematopoietic stem cell transplantation is now a feasible and effective treatment for selected patients with severe autoimmune diseases. Worldwide, over 650 patients have been transplanted in the context of phase I and II clinical trials. The results are encouraging enough to begin randomised phase III trials. However, as predicted, significant transplant-related morbidity and mortality have been observed. This is primarily due to complications related to either the stage of the disease at transplant or due to infections. The number of deaths related to cardiac toxicity is low. However, caution is required when cyclophosphamide or anthracyclines such as mitoxantrone are used in patients with a possible underlying heart damage, for example, systemic sclerosis patients. In November 2002, a meeting was held in Florence, bringing together a number of experts in various fields, including rheumatology, cardiology, neurology, pharmacology and transplantation medicine. The object of the meeting was to analyse existing data, both published or available, in the European Group for Blood and Marrow Transplantation autoimmune disease database, and to propose a safe approach to such patients. A full cardiological assessment before and during the transplant emerged as the major recommendation.

Assessment of heart involvement.

Cardiac involvement frequently occurs in systemic sclerosis (SSc), contributing to the occurrence of symptoms, namely dyspnoea, fatigue, palpitations, and in some instances to the clinical evolution and prognosis of the disease. A thorough baseline screening of heart functioning and appropriate follow-up monitoring is therefore mandatory in all SSc patients. This consists of various simple, non-invasive ambulatory diagnostic procedures (visit, electrocardiogram, chest X-ray, Doppler-bidimensional echocardiogram), which provide information on the presence of rhythm and conduction disturbances, cardiac morphology and function, as well as on the possible presence of pulmonary hypertension (PH). When needed, added tests may be carried out, including long-term ambulatory electrocardiographic recording, assessment of cardiopulmonary performance by the six-minute walking test or cardiopulmonary stress test, cardiac catheterization (mandatory to confirm and better estimate PH), cardiac magnetic resonance imaging, and nuclear studies of myocardial function and perfusion.

Estimation of the power spectral density in nonstationary cardiovascular time series: assessing the role of the time-frequency representations (TFR).

Spectral analysis of cardiovascular series has been proposed as a noninvasive tool for investigating the autonomic control of the cardiovascular system. The analysis of such series during autonomic tests requires high resolution estimators that are capable to track the transients of the tests. A comparative evaluation has been made among classical (FFT based), autoregressive (both block and sequential mode) and time-frequency representation (TFR) based power spectral estimators. The evaluation has been performed on artificial data that have typical patterns of the nonstationary series. The results documented the superiority of the TFR approach when a sharp time resolution is required. Moreover, the test on a RR-like series has shown that the smoothing operation is effective for rejecting TFR cross-terms when a simple, two-three components series is concerned. Finally, the preliminary application of the selected methods to real RR interval time series obtained during some autonomic tests has shown that the TFR are capable to correctly represent the transient of the series in the joint time-frequency domain.

Electrocardiographic monitoring: temporal versus spatial information and data processing.

In the diagnosis of ischemic heart disease, long-term electrocardiographic recording has several distinct advantages. It allows one to relate patient symptoms to cardiac disturbances and to detect asymptomatic events, furnishes the whole spectrum of electrocardiographic alterations accompanying ischemic attacks, reveals the possible ischemic genesis of dysrhythmias, and is the most suitable method to assess the acute and chronic effectiveness of treatment and the evolution of the disease. In addition to its valuable application in the screening and follow-up of ambulatory patients, its use in the Coronary Care Unit is of great interest, being in this context much more sensitive than visual electrocardiographic monitoring. In spite of these advantages, Holter monitoring has several limitations: the recording and replay systems are below recommended standards; the analysis of a single lead is responsible in most systems for the low sensitivity in detecting ischemia occurring in unexplored regions; the period of 24-48 hours, usually adopted for Holter monitoring, may not be sufficient for screening patients with suspected myocardial ischemia due to the unpredictable spontaneous variability of the disease; a common standard of analysis is still lacking and a reliable computerized analysis is needed to manage data overflow. In conclusion, although further research and technical developments are desired to improve reliability and data processing, the role of Holter monitoring appears essential in the ambulatory screening of patients with suspected ischemia for a better characterization of patients with ascertained myocardial ischemia, and for the evaluation of treatment and of the evolution of the disease.