Metabolomics Fingerprint Predicts Risk of Death in Dilated Cardiomyopathy and Heart Failure.

Background: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Metabolomics may help refine risk assessment and potentially guide HF management, but dedicated studies are few. This study aims at stratifying the long-term risk of death in a cohort of patients affected by HF due to dilated cardiomyopathy (DCM) using serum metabolomics via nuclear magnetic resonance (NMR) spectroscopy. Methods: A cohort of 106 patients with HF due to DCM, diagnosed and monitored between 1982 and 2011, were consecutively enrolled between 2010 and 2012, and a serum sample was collected from each participant. Each patient underwent half-yearly clinical assessments, and survival status at the last follow-up visit in 2019 was recorded. The NMR serum metabolomic profiles were retrospectively analyzed to evaluate the patient's risk of death. Overall, 26 patients died during the 8-years of the study. Results: The metabolomic fingerprint at enrollment was powerful in discriminating patients who died (HR 5.71, p = 0.00002), even when adjusted for potential covariates. The outcome prediction of metabolomics surpassed that of N-terminal pro b-type natriuretic peptide (NT-proBNP) (HR 2.97, p = 0.005). Metabolomic fingerprinting was able to sub-stratify the risk of death in patients with both preserved/mid-range and reduced ejection fraction [hazard ratio (HR) 3.46, p = 0.03; HR 6.01, p = 0.004, respectively]. Metabolomics and left ventricular ejection fraction (LVEF), combined in a score, proved to be synergistic in predicting survival (HR 8.09, p = 0.0000004). Conclusions: Metabolomic analysis via NMR enables fast and reproducible characterization of the serum metabolic fingerprint associated with poor prognosis in the HF setting. Our data suggest the importance of integrating several risk parameters to early identify HF patients at high-risk of poor outcomes.

Pathophysiology and Treatment of Hypertrophic Cardiomyopathy: New Perspectives.

PURPOSE OF REVIEW: We provide a state of the art of therapeutic options in hypertrophic cardiomyopathy (HCM), focusing on recent advances in our understanding of the pathophysiology of sarcomeric disease. RECENT FINDINGS: A wealth of novel information regarding the molecular mechanisms associated with the clinical phenotype and natural history of HCM have been developed over the last two decades. Such advances have only recently led to a number of controlled randomized studies, often limited in size and fortune. Recently, however, the allosteric inhibitors of cardiac myosin adenosine triphosphatase, countering the main pathophysiological abnormality associated with HCM-causing mutations, i.e. hypercontractility, have opened new management perspectives. Mavacamten is the first drug specifically developed for HCM used in a successful phase 3 trial, with the promise to reach symptomatic obstructive patients in the near future. In addition, the fine characterization of cardiomyocyte electrophysiological remodelling has recently highlighted relevant therapeutic targets. Current therapies for HCM focus on late disease manifestations without addressing the intrinsic pathological mechanisms. However, novel evidence-based approaches have opened the way for agents targeting HCM molecular substrates. The impact of these targeted interventions will hopefully alter the natural history of the disease in the near future.

Structure and Function of Stony Coral Intraskeletal Polysaccharides.

Polysaccharides represent a main weight fraction of the intraskeletal organic matrix of corals, but their structure, as well as their function in the calcification process, has been poorly investigated. This communication shows by a combination of techniques (nuclear magnetic resonance, Fourier transform infrared, and monosaccharide composition) that their key component is a 1→3 ß-d glucuronic acid polymer and evidences its influence in vitro in the calcification process.

Comparison of long-term outcome in anthracycline-related versus idiopathic dilated cardiomyopathy: a single centre experience.

AIMS: Cardiac dysfunction is a severe complication of anthracycline-containing anticancer therapy. The outcome of anthracycline-induced cardiomyopathy (AICM) compared with other non-ischaemic causes of heart failure (HF), such as idiopathic dilated cardiomyopathy (IDCM), is unresolved. The aim of this study was to compare the survival of AICM patients with an IDCM cohort followed at our centre from 1990 to 2016. METHODS AND RESULTS: We included 67 patients (67% female, 50 ± 15 years) with AICM, defined as onset of otherwise unexplained left ventricular ejection fraction (LVEF) ≤50% following anthracycline therapy, and 488 IDCM patients (28% female, 55 ± 12 years). Patients were followed with constantly optimized HF therapy, for 7.6 ± 5.5 and 8.1 ± 5.5 years, respectively. In both cohorts, 25% of patients reached the combined endpoint of death/heart transplantation. Overall survival rates at 5 and 10 years were similar (AICM: 86% and 61%, IDCM: 88% and 75%; P = 0.61), and so was cardiovascular survival (AICM: 91% and 76%, IDCM: 91% and 80%; P = 0.373), also after 1:1 propensity matching (P = 0.27) and adjusting for age, LVEF and left ventricular size. A trend toward higher all-cause mortality was present in AICM patients [hazard ratio (HR) 1.67, 95% confidence interval (CI) 0.95-2.92, P = 0.076]. No differences were observed between AICM and IDCM with regard to pharmacological HF therapy, but AICM patients were less likely to receive devices (13% vs. 41.8% in IDCM, P < 0.001). CONCLUSION: Cardiovascular mortality in patients with AICM did not differ from that of a matched IDCM cohort, despite cancer-related morbidity and less prevalent use of devices. These data suggest that patients with AICM should be treated with appropriate guideline-directed medical therapies similar to other non-ischaemic dilated cardiomyopathies.

Impact of Genotype on the Occurrence of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy.

Genes associated with hypertrophic cardiomyopathy (HC) are not uniformly expressed in the atrial myocardium. Whether this may impact susceptibility to atrial fibrillation (AF) is unresolved. To analyze the prevalence and clinical correlates of AF in relation to genotype in a large HC cohort, prevalence and clinical profile of AF were assessed in 237 patients with HC, followed for 14 ± 10 years. Patients were divided into 3 genetic subgroups: (1) MYBPC3 (58%), (2) MYH7 (28%), and (3) "other genotypes" (14%; comprising TNNT2, TNNI3, TPM1, MYL2, complex genotypes, Z-line, and E-C coupling genes). Left atrial size was similar in the 3 subsets. AF occurred in 74 patients with HC (31%), with no difference among groups (31% in MYBPC3, 37% in MYH7 and 18% in other genotypes, p = 0.15), paroxysmal/persistent AF (12%, 18%, and 12%, respectively; p = 0.53), paroxysmal/persistent evolved to permanent (12%, 12%, and 3%, p = 0.36) or permanent AF (7%, 7%, and 3%, p = 0.82). Age at AF onset was younger in the group with other genotypes (37 ± 10 years) compared to the first 2 groups (53 ± 14 and 51 ± 17, respectively; p = 0.05) because of early onset associated with complex genotypes and a specific JPH2 mutation associated with abnormal intracellular calcium handling. At multivariate analysis, independent predictors of AF were atrial diameter (p ≤0.05) and age at diagnosis (p = 0.09), but not genetic subtype (p = 0.35). In conclusion, in patients with HC, genetic testing cannot be used in clinical decision making with regard to management strategies for AF. Genotype is not predictive of onset or severity of AF, which appears rather driven by hemodynamic determinants of atrial dilatation. Exceptions are represented by rare genes suggesting specific molecular pathways for AF in genetic cardiomyopathies.

Prognostic role of N-terminal pro-brain natriuretic peptide in asymptomatic hypertensive and diabetic patients in primary care: impact of age and gender : Results from the PROBE-HF study.

BACKGROUND: The association between natriuretic peptides and clinical outcome in asymptomatic hypertensive and diabetic patients with no clinical evidence of heart failure (HF) is still unclear. We assessed the prognostic value of NT-pro BNP, and its interactions with age and gender, in a cohort of asymptomatic, stage A/B HF hypertensive and diabetic patients enrolled in primary care. METHODS: NT-proBNP was measured in 1012 asymptomatic subjects with systemic hypertension and/or type-2 diabetes (age 66.6 ± 7.8 years, 48 % males) with no clinical evidence of HF. Patients were prospectively followed over 49.8 ± 6.7 months for the development of cardiac death, HF hospitalization, and nonfatal myocardial infarction. RESULTS: Patients with NT-proBNP above the 80th age- and gender-specific percentile showed a threefold risk of events as compared to those with NT-proBNP under this cut-off [hazard ratio 3.2 (2.6-8.3), p < 0.0001]. In multivariable analysis, NT-proBNP added independent and incremental prognostic information to a predictive model including established risk factors (p < 0.0001). After stratification by age, increased NT-proBNP predicted outcome among patients in the second and third age tertiles, but not among those in the first tertile. Increased NT-proBNP was associated with a 3.6-fold risk in women and a 2.9-fold risk in men. Addition of the gender-NT-proBNP interaction to prognostic models further improved prediction of events (p = 0.014). CONCLUSIONS: NT-proBNP measurement adds independent and incremental information for the prediction of clinical outcome in asymptomatic, stage A-B HF hypertensive and diabetic patients taken from primary care. This prognostic value might be further evident in the elderly and among women.

Clinical Spectrum, Therapeutic Options, and Outcome of Advanced Heart Failure in Hypertrophic Cardiomyopathy.

BACKGROUND: The clinical course of patients with hypertrophic cardiomyopathy and advanced heart failure (HF) subtended by progressive left ventricular dysfunction has received limited attention. Our aim was to assess the outcome of HF and impact of treatment options including the implantable cardioverter-defibrillator and heart transplantation (HT) in patients with hypertrophic cardiomyopathy evaluated at 2 Italian referral centers >3 decades. METHODS AND RESULTS: All-cause mortality and a combined end point including death, HT, or appropriate implantable cardioverter-defibrillator shock were assessed in 71 consecutive patients with HF not related to outflow obstruction (7% of the entire hypertrophic cardiomyopathy cohort) followed up for 6.1±6.9 years after development of New York Heart Association class III to IV symptoms. At enrollment, left ventricular ejection fraction was <50% in 55 patients and >50% in 16; all had restrictive left ventricular filling. During follow-up, 35 patients died (49%%; 5-year rate, 49%) and 53 met the combined end point (75%; 5-year rate, 62%). Most events occurred in the 3 years after HF onset (17% per year compared with only 3% per year subsequently). Appropriate implantable cardioverter-defibrillator shocks occurred in 11 of 34 implanted patients. Of 37 patients evaluated for HT, 14 were transplanted, 10 listed, and 13 excluded; 2 early post-HT deaths occurred in patients with elevated pulmonary vascular resistance. Eleven of the 14 HT patients were alive at 10±8 years. CONCLUSIONS: In hypertrophic cardiomyopathy, advanced HF not associated with outflow obstruction portends a severely unfavorable prognosis, particularly in the first 3 years after onset of symptoms, despite frequently preserved systolic function in about one quarter of the patients. Outcome of HT is favorable but requires early consideration, as the window of opportunity may be short.

Chagas disease as a cause of heart failure and ventricular arrhythmias in patients long removed from endemic areas: an emerging problem in Europe.

Chagas disease is a parasitic disease caused by the protozoan Trypanosoma cruzi. In endemic areas (South and Central America), Chagas disease represents a relevant public health issue, and is the most frequent cause of cardiomyopathy. In nonendemic areas, such as Europe, Chagas disease represents an emerging problem following the establishment of sizeable communities from Brazil and Bolivia. Chagas cardiomyopathy represents the most frequent and serious complication of chronic Chagas disease, affecting about 20-30% of patients, potentially leading to heart failure, arrhythmias, thromboembolism, stroke and sudden death. Because late complications of Chagas disease may develop several years or even decades after the acute infection, it may be extremely challenging to reach the correct diagnosis in patients long removed from the countries of origin. We report two examples of Chagas cardiomyopathy in South American women permanently residing in Italy for more than 20 years, presenting with cardiac manifestations ranging from left ventricular dysfunction and heart failure to isolated ventricular arrhythmias. The present review emphasizes that Chagas disease should be considered as a potential diagnosis in patients from endemic areas presenting with 'idiopathic' cardiac manifestations, even when long removed from their country of origin, with potential implications for treatment and control of Chagas disease transmission.

Coronary microvascular dysfunction is an early feature of cardiac involvement in patients with Anderson-Fabry disease.

AIMS: Male patients with Anderson-Fabry disease (AFD) often exhibit cardiac involvement, characterized by LV hypertrophy (LVH), associated with severe coronary microvascular dysfunction (CMD). Whether CMD is present in patients without LVH, particularly when female, remains unresolved. The aim of the study was to investigate the presence of CMD by positron emission tomography (PET) in AFD patients of both genders, with and without evidence of LVH. METHODS AND RESULTS: We assessed myocardial blood flow following dipyridamole infusion (Dip-MBF) with 13N-labelled ammonia by PET in 30 AFD patients (age 51 ± 13 years; 18 females) and in 24 healthy controls. LVH was defined as echocardiographic maximal LV wall thickness ≥13 mm. LVH was present in 67% of patients (n = 20; 10 males and 10 females). Dip-MBF was reduced in all patients compared with controls (1.8 ± 0.5 and 3.2 ± 0.5 mL/min/g, respectively, P < 0.001). For both genders, flow impairment was most severe in patients with LVH (1.4 ± 0.5 mL/min/g in males and 1.9 ± 0.5 mL/min/g in females), but was also evident in those without LVH (1.8 ± 0.3 mL/min/g in males and 2.1 ± 0.4 mL/min/g in females; overall P = 0.064 vs. patients with LVH). Analysis of variance (ANOVA) for the 17 LV segments showed marked regional heterogeneity of MBF in AFD (F = 4.46, P < 0.01), with prevalent hypoperfusion of the apical region. Conversely, controls showed homogeneous LV perfusion (F = 1.25, P = 0.23). CONCLUSIONS: Coronary microvascular function is markedly impaired in AFD patients irrespective of LVH and gender. CMD may represent the only sign of cardiac involvement in AFD patients, with potentially important implications for clinical management.

Prognostic value of N-terminal pro-brain natriuretic Peptide in outpatients with hypertrophic cardiomyopathy.

In hypertrophic cardiomyopathy, the plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) correlate with functional capacity. However, their prognostic relevance remains unresolved. We followed up 183 stable outpatients with hypertrophic cardiomyopathy (age 50 ± 17 years, 64% men) for 3.9 ± 2.8 years after NT-proBNP measurement. The primary end point included cardiovascular death, heart transplantation, resuscitated cardiac arrest, and appropriate implantable cardioverter-defibrillator intervention. The secondary end point (SE) included heart failure-related death or hospitalization, progression to end-stage disease, and stroke. The median NT-proBNP level was 615 pg/ml (intertertile range 310 to 1,025). The incidence of the primary end point in the lower, middle, and upper tertiles was 0%, 1.3%, and 2.1% annually, respectively (overall p = 0.01). On multivariate analysis, the only independent predictors of the primary end point were NT-proBNP (hazard ratio for log-transformed values 5.8, 95% confidence interval 1.07 to 31.6; p = 0.04) and a restrictive left ventricular filling pattern (hazard ratio 5.19, 95% confidence interval 1.3 to 21.9; p = 0.02). The NT-proBNP cutoff value of 810 pg/ml had the best sensitivity for the primary end point (88%), but the specificity was low (61%). The incidence of the SE in the lower, middle, and upper NT-proBNP tertiles was 4.6%, 12.0%, and 11.2% annually, respectively (overall p = 0.001). An NT-proBNP level of <310 pg/ml was associated with a 75% reduction in the rate of SE compared with a level of ≥310 pg/ml (hazard ratio 0.25, 95% confidence interval 0.11 to 0.57; p = 0.001), independent of age, left ventricular outflow tract obstruction, or atrial fibrillation. In conclusion, in stable outpatients with hypertrophic cardiomyopathy, plasma NT-proBNP proved a powerful independent predictor of death and heart failure-related events. Although the positive predictive accuracy of an elevated NT-proBNP level was modest, low values reflected true clinical stability, suggesting the possibility of avoiding or postponing aggressive treatment options.

Improving survival rates of patients with idiopathic dilated cardiomyopathy in Tuscany over 3 decades: impact of evidence-based management.

BACKGROUND: Contemporary therapeutic options have led to substantial improvement in survival of patients with heart failure. However, limited evidence is available specifically on idiopathic dilated cardiomyopathy. We thus examined changes in prognosis of a large idiopathic dilated cardiomyopathy cohort systematically followed during the past 30 years. METHODS AND RESULTS: From 1977 to 2011, 603 consecutive patients (age, 53±12 years; 73% men; left ventricular ejection fraction, 32±10%) fulfilling World Health Organization criteria for idiopathic dilated cardiomyopathy, including negative coronary angiography, were followed up for 8.8±6.3 years. Patients were subdivided in 4 enrollment periods on the basis of heart failure treatment eras: (1) 1977-1984 (n=66); (2) 1985-1990 (n=102); (3) 1991-2000 (n=197); (4) 2001-2011 (n=238). Rates of patients receiving angiotensin-converting enzyme inhibitors/angiotensin receptors blockers, ß-blockers, and devices at final evaluation increased from 56%, 12%, 8% (period 1) to 97%, 86%, 17% (period 4), respectively (P<0.05). There was a trend toward enrollment of older patients with less severe left ventricular dilatation and dysfunction during the years. During follow-up, 271 patients (45%) reached a combined end point including death (heart failure related, n=142; sudden death, n=71; and noncardiac, n=22) or cardiac transplant (n=36). A more recent enrollment period represented the most powerful independent predictor of favorable outcome {period 2 versus 1 (hazard ratio [HR], 0.64; P=0.04), period 3 versus 1 (HR, 0.35; P<0.001), period 4 versus 1 (HR, 0.14; P<001)}. Each period was associated with a 42% risk reduction versus the previous one (HR, 0.58; 95% confidence interval, 0.50-0.67; P<0.001), reflecting marked decreases in heart failure-related mortality and sudden death (period 4 versus 1: HR, 0.10; P<001 and HR, 0.13; P<0.0001, respectively). CONCLUSIONS: Evidence-based treatment has led to dramatic improvement in the prognosis of idiopathic dilated cardiomyopathy during the past 3 decades. The benefits of controlled randomized trials can be replicated in the real world, emphasizing the importance of tailored follow-up and long-term continuity of care.

Body mass index, gender, and clinical outcome among hypertensive and diabetic patients with stage A/B heart failure.

OBJECTIVE: The existence of an "obesity paradox" in asymptomatic patients with preclinical heart failure (HF) has not been investigated. The prognostic value of BMI in a cohort of hypertensive and diabetic patients with stage A/B HF enrolled in the PROBE-HF study was explored. DESIGN AND METHODS: BMI was measured in 1003 asymptomatic subjects (age 66.4 ± 7.8 years, 48% males) with hypertension and/or type 2 diabetes and no clinical evidence of HF. Predefined endpoints were all-cause mortality and a composite of death and hospitalization for cardiac causes. RESULTS: During a follow-up of 38.5 ± 4.1 months, 33 deaths were observed. Mortality in the normal BMI group (1.6 deaths per 100 patient-years) did not differ to that in the overweight group (1.1 per 100 patient-years, p = 0.31), but was higher than that in the obese group (0.4 per 100 patient-years, p = 0.0089). In multivariable analysis, obesity (hazard ratio [HR] 0.27 [0.09-0.85], p = 0.025) but not overweight (HR 0.68 [0.32-1.45], p = 0.32) was associated with lower risk of death. Obesity was also independently associated with reduced risk of the composite endpoint (HR 0.54 [0.28-0.99], p = 0.047). CONCLUSION: In asymptomatic hypertensive and diabetic patients with preclinical HF, obesity is associated with better survival and reduced risk of events.

[New evidences on the use of aldosterone receptor antagonists in left ventricular dysfunction: from myocardial infarction to heart failure]. / Nuove evidenze sull'impiego degli antialdosteronici nella disfunzione ventricolare sinistra: spironolattone ed eplerenone. Dal postinfarto allo scompenso cardiaco.

Heart failure and myocardial infarction result in considerable consumption of healthcare resources. Therefore, there is interest in the availability of drug therapies that can favorably modify their prognosis in the post-acute phase, reducing mortality and rehospitalization rates. Aldosterone antagonists represent a class of drugs which offer advantages in these settings, in addition to those obtained with beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, even though attention should be drawn to their potential adverse effects. In particular, eplerenone exhibits a better safety profile than spironolactone. Since it has very little affinity for glucocorticoid, androgen and progesterone receptors, eplerenone has less antiandrogenic and progestagenic effects, resulting in a lower incidence of gynecomastia. The EPHESUS study showed that eplerenone can reduce mortality in the short and long term and the rate of new hospitalizations after a myocardial infarction complicated by heart failure. In addition, in the EMPHASIS-HF study eplerenone reduced cardiovascular mortality and hospitalizations after mild heart failure (NYHA class IIa). Despite these important results, which confirmed those obtained with spironolactone in severe heart failure in the RALES study, aldosterone antagonists are still underutilized. In particular, eplerenone is not yet available in Italy, although it is recommended by the latest European Society of Cardiology guidelines.

[Continuity of care in heart failure: pilot study of the Tuscany region]. / Continuità assistenziale nello scompenso cardiaco: studio pilota della regione Toscana.

BACKGROUND: Heart failure (HF) is one of the leading causes of hospitalization and medical expenditure, especially in elderly patients. Cooperation between specialists and general practitioners may improve outcomes. A 1-year hospital-territory disease management program was designed in collaboration with the Tuscany Region and the Ministry of Health involving specialists, general practitioners and nurses to investigate the impact of our model on healthcare organization and hospitalization rates in patients with HF. METHODS: The program used a web-based clinical report form, and monitoring of patients from specialists and nurses was coordinated by the general practitioners. We enrolled 106 patients (78.3% male, mean age 74.6 years), with a mean left ventricular ejection fraction 49% and mean Charlson index 2.2. RESULTS: A statistically significant reduction was observed in the number of hospitalizations and emergency calls compared with the previous year. HF severity did not substantially changed in 69.8% of patients, whereas it improved in 17.0% and worsened in 13.2% (NYHA class). CONCLUSIONS: Our preliminary data suggest that cooperation between hospitals and medical systems in the territory by means of a web-based clinical report may result in better management of healthcare interventions in the territory with subsequent reduction of hospitalizations. An extension of this model is now ongoing for collecting data from different areas, both within and outside Tuscany.

[Prevalence and subtypes of systemic hypertension in an unselected patient population with severe obesity undergoing bariatric surgery]. / Prevalenza e tipologie di ipertensione arteriosa in una popolazione di pazienti non selezionati affetti da obesità morbigena in previsione di intervento di chirurgia bariatrica.

BACKGROUND: Obesity plays a pivotal role in the development of systemic hypertension and the two diseases are often related. Severe obesity is getting more and more prevalent in our country. The aim of this study was to evaluate the prevalence of systemic hypertension in an unselected population of obese patients observed in the Regional Referral Center for Surgical Obesity of our hospital. METHODS: 233 consecutive patients (52 male, 181 female, mean age 42 years, mean weight 120 kg, mean body mass index [BMI] 43.7 kg/m2) were screened in order to plan a surgical procedure for severe obesity. Each patient underwent cardiovascular clinical evaluation, ECG and echocardiographic examination, blood pressure ambulatory monitoring, and 24h Holter monitoring. RESULTS: Thirty-five percent of patients were under drug treatment for hypertension or were at least aware of being hypertensive; among the remaining 65% of patients who declared having normal blood pressure, 33% suffered from systemic hypertension, 11% had isolated clinical hypertension, and 14% had masked hypertension. Thus, the global prevalence of systemic hypertension in this population raised to 72.5%. ECG and echocardiographic findings were normal in about 90% of the whole population, whereas 24h Holter monitoring showed minor or major abnormalities in approximately 25% of patients. At a follow-up of at least 18 months, a subgroup of 48 patients showed a decrease in body weight from 129 to 92 kg, BMI from 47 to 33 kg/m 2, blood pressure from 134.4/86.4 to 127.7/81.1 mmHg, and heart rate from 79.7 to 69.4 bpm. CONCLUSIONS: The prevalence of systemic hypertension in an unselected population of severely obese patients is much higher than in the general population. The surgical procedures performed in the Regional Referral Center for Surgical Obesity of our hospital were virtually free from serious adverse events and proved to be effective in reducing not only body weight and BMI but also blood pressure. We believe that ambulatory blood pressure and 24h Holter monitoring are the most relevant examinations to be performed in these patients in the preoperative period.

Effects of ULTRAfiltration vs. DIureticS on clinical, biohumoral and haemodynamic variables in patients with deCOmpensated heart failure: the ULTRADISCO study.

AIMS: To evaluate the clinical, biohumoral, and haemodynamic effects of ultrafiltration vs. intravenous diuretics in patients with decompensated heart failure (HF). Signs and symptoms of volume overload are often present in these patients and standard therapy consists primarily of intravenous diuretics. Increasing evidence suggests that ultrafiltration can be an effective alternative treatment. METHODS AND RESULTS: Thirty patients with decompensated HF were randomly assigned to diuretics or ultrafiltration. Haemodynamic variables, including several novel parameters indicating the overall performance of the cardiovascular system, were continuously assessed with the Pressure Recording Analytical Method before, during, at the end of treatment (EoT) and 36 h after completing treatment. Aldosterone and N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma levels were also measured. Patients treated with ultrafiltration had a more pronounced reduction in signs and symptoms of HF at EoT compared with baseline, and a significant decrease in plasma aldosterone (0.24 ± 0.25 vs. 0.86 ± 1.04 nmol/L; P < 0.001) and NT-proBNP levels (2823 ± 2474 vs. 5063 ± 3811 ng/L; P < 0.001) compared with the diuretic group. The ultrafiltration group showed a significant improvement (% of baseline) in a number of haemodynamic parameters, including stroke volume index (114.0 ± 11.7%; P < 0.001), cardiac index (123.0 ± 20.8%; P < 0.001), cardiac power output (114.0 ± 13.8%; P < 0.001), dP/dt(max) (129.5 ± 19.9%; P < 0.001), and cardiac cycle efficiency (0.24 ± 0.54 vs. -0.14 ± 0.50 units; P < 0.05), and a significant reduction in systemic vascular resistance 36 h after the treatment (88.0 ± 10.9%; P < 0.001), which was not observed in the diuretic group. CONCLUSIONS: In patients with advanced HF, ultrafiltration facilitates a greater clinical improvement compared with diuretic infusion by ameliorating haemodynamics (assessed using a minimally invasive methodology) without a marked increase in aldosterone or NT-proBNP levels.

Rotational mechanics of the left ventricle in AL amyloidosis.

AIMS: The aim of this study was to investigate whether alterations in left ventricular (LV) twisting and untwisting motion could be induced by cardiac involvement in patients with immunoglobulin light-chain (AL) systemic amyloidosis. METHODS AND RESULTS: Forty-five patients with AL amyloidosis and 26 control subjects were evaluated. After standard echocardiographic measurement and two-dimensional (2D) speckle tracking echocardiography, LV rotation at both basal and apical planes, twisting, twisting rate, and longitudinal strain were measured. Tissue Doppler imaging (TDI) derived early diastolic peak velocity at septal mitral annulus (E') was also evaluated. Twenty-six of 45 patients with systemic amyloidosis were classified as having cardiac amyloidosis (CA) if the mean value of the LV wall thickness was ≥ 12 mm or not (NCA) if this value was not reached. In NCA patients, both LV twist and untwisting rate were increased while they were decreased in CA patients making them similar to the control group. Longitudinal strain was reduced only in CA patients. Impaired relaxation as indicated by E' values was progressively reduced in the course of the disease. CONCLUSIONS: Both twisting and untwisting motions are increased in patients with AL systemic amyloidosis with no evidence of cardiac involvement while they are reduced in patients with evident amyloidosis cardiac involvement. This finding suggests that impaired LV relaxation induces a compensatory mechanism in the early phase of the disease, which fails in more advanced stage when both twisting and untwisting rates are reduced. The increase in LV rotational mechanics could be a marker of subclinical cardiac involvement.

The role of N-terminal PRO-brain natriuretic peptide and echocardiography for screening asymptomatic left ventricular dysfunction in a population at high risk for heart failure. The PROBE-HF study.

BACKGROUND: Screening for asymptomatic left ventricular dysfunction (ALVD) in subjects at risk for heart failure (HF) can affect clinical management. The aim of the present study is to examine the role of NT-pro BNP in the diagnosis of ALVD in subjects with hypertension and diabetes from primary care. METHODS AND RESULTS: A total of 1012 subjects with hypertension and/or diabetes and no symptoms or signs of HF were assessed by B-type natriuretic peptide (NT-proBNP) assay and echocardiography. Diastolic dysfunction was present in 368/1012 subjects (36.4%): 327 (32.4%) with mild diastolic dysfunction and 41 (4%) with a moderate-to-severe diastolic dysfunction. Systolic dysfunction was present in 11/1012 (1.1%). NT-proBNP levels were 170 +/- 206 and 859 +/- 661 pg/mL, respectively, in diastolic and systolic dysfunction and 92 +/- 169 in normal subjects (P < .0001). Pooling moderate-to-severe diastolic with systolic dysfunction, a total of 52 subjects (5.1 %) were obtained: best cutoff value of NT-proBNP was 125 pg/mL (males <67 years: sensitivity [Sens] 87.5%, specificity [Spec] 92.7%, negative predictive value [NPV] 99.5%, positive predictive value [PPV] 33.3%; females <67 years: Sens 100%, Spec 84.1%, NPV 100%, PPV 33.3%; males >or=67 years: Sens 100%, Spec 77.1%, NPV 100%, PPV 32.5%; females >or=67 years: Sens 100%, Spec 59.9%, NPV 100%, PPV 23%). CONCLUSIONS: The prevalence of ALVD in subjects at risk for HF is 5.1%. Because of its excellent NPV, NT-proBNP can be used by general practitioners to rule out ALVD in hypertensive or diabetic patients.

Tissue Doppler and strain imaging: a new tool for early detection of cardiac amyloidosis.

Using traditional echocardiography, the diagnosis of cardiac amyloidosis (CA) is often only possible in advanced stage when recommended therapies may have adverse effects. The aim of our study was to evaluate whether additional information can be derived from Tissue and strain Doppler imaging (TDI and SDI). Forty patients with systemic amyloidosis and 24 healthy subjects underwent traditional, tissue and strain Doppler echocardiography. Patients were classified having CA if mean wall thickness (mT), was half of the sum septum and posterior wall thickness, was > or =12 mm. The following parameters were evaluated: peak early diastolic velocity (Em) as index of ventricular relaxation, mitral E-wave to Em ratio (E/Em) as index of left ventricular (LV) filling pressure and mean LV strain peak curves (mSt) as global long-axis contraction index. In non cardiac amyloidosis (NCA), both Em and mSt were lower than in age matched controls (p < 0.01, p < 0.05, respectively) and higher than in CA (p < 0.01 and p < 0.01, respectively). Both Em and mSt were related to mT (p < 0.001). A significant (p < 0.01) nonlinear relation was observed between plasma terminal of pro B-natriuretic peptide and mT, Em, E/Em and mSt. TDI and SDI are able to detect amyloid myocardial involvement in such an early stage that cannot be evidenced by using traditional echocardiography.