Unmasking the prevalence of amyloid cardiomyopathy in the real world: results from Phase 2 of the AC-TIVE study, an Italian nationwide survey.

AIM: To investigate the prevalence of amyloid cardiomyopathy (AC) and the diagnostic accuracy of echocardiographic red flags of AC among consecutive adult patients undergoing transthoracic echocardiogram for reason other than AC in 13 Italian institutions. METHODS AND RESULTS: This is an Italian prospective multicentre study, involving a clinical and instrumental work-up to assess AC prevalence among patients ≥55 years old with an echocardiogram suggestive of AC (i.e. at least one echocardiographic red flag of AC in hypertrophic, non-dilated left ventricles with preserved ejection fraction). The study was registered at ClinicalTrials.gov (NCT04738266). Overall, 381 patients with an echocardiogram suggestive of AC were identified among a cohort of 5315 screened subjects, and 217 patients completed the investigations. A final diagnosis of AC was made in 62 patients with an estimated prevalence of 29% (95% confidence interval 23%-35%). Transthyretin-related AC (ATTR-AC) was diagnosed in 51 and light chain-related AC (AL-AC) in 11 patients. Either apical sparing or a combination of ≥2 other echocardiographic red flags, excluding interatrial septum thickness, provided a diagnostic accuracy >70%. CONCLUSION: In a cohort of consecutive adults with echocardiographic findings suggestive of AC and preserved left ventricular ejection fraction, the prevalence of AC (either ATTR or AL) was 29%. Easily available echocardiographic red flags, when combined together, demonstrated good diagnostic accuracy.

Functional Tricuspid Regurgitation and Atrial Fibrillation: Which Comes First, the Chicken or the Egg?

Pathophysiology of "atriogenic" functional tricuspid regurgitation in patients with persistent atrial fibrillation.

Do the remodeling effects of sacubitril/valsartan treatment depend upon heart failure duration?

AIMS: The angiotensin receptor and neprilysin inhibitor (ARNI) sacubitril/valsartan (LCZ696) is recommended for the treatment of patients with heart failure in New York Heart Association (NYHA) class II-III and left ventricular ejection fraction (LVEF) 35% or less. We examined the effects of sacubitril/valsartan on cardiac remodeling and their correlation with heart failure duration in patients enrolled in our heart failure clinic from March 2017 to December 2019. METHODS: Echocardiographic and clinical/laboratory data were collected at baseline and at 6-month and 12-month follow-up visits in 69 patients (age 67 ±â€Š12 years, disease duration 8.4 ±â€Š5.8 years, 93% men). RESULTS: At both time points, mean NYHA class, NT-proBNP level, LVEF, LV end-systolic volume, and estimated systolic pulmonary pressure significantly (P < 0.05) improved versus baseline, as did the proportion of patients with diastolic dysfunction grade 3 or functional mitral regurgitation grade 3-4. In the subgroup with mean disease duration less than 8.5 years (n = 40), there was a significant improvement in all variables at both time points; in this group, a recovery of right ventricular function was also seen at the 12-month follow-up. On the contrary, patients with heart failure duration of at least 8.5 years (n = 29) showed only a slight improvement in LVEF and mitral regurgitation at 12 months. There were no significant changes in renal function and/or potassium levels in all patients. CONCLUSION: In patients with a relatively short disease duration, sacubitril/valsartan was associated with a strong favorable remodeling of the left ventricle and improvement in pulmonary circulation.

MASked-unconTrolled hypERtension management based on office BP or on ambulatory blood pressure measurement (MASTER) Study: a randomised controlled trial protocol.

INTRODUCTION: Masked uncontrolled hypertension (MUCH) carries an increased risk of cardiovascular (CV) complications and can be identified through combined use of office (O) and ambulatory (A) blood pressure (BP) monitoring (M) in treated patients. However, it is still debated whether the information carried by ABPM should be considered for MUCH management. Aim of the MASked-unconTrolled hypERtension management based on OBP or on ambulatory blood pressure measurement (MASTER) Study is to assess the impact on outcome of MUCH management based on OBPM or ABPM. METHODS AND ANALYSIS: MASTER is a 4-year prospective, randomised, open-label, blinded-endpoint investigation. A total of 1240 treated hypertensive patients from about 40 secondary care clinical centres worldwide will be included -upon confirming presence of MUCH (repeated on treatment OBP <140/90 mm Hg, and at least one of the following: daytime ABP ≥135/85 mm Hg; night-time ABP ≥120/70 mm Hg; 24 hour ABP ≥130/80 mm Hg), and will be randomised to a management strategy based on OBPM (group 1) or on ABPM (group 2). Patients in group 1 will have OBP measured at 0, 3, 6, 12, 18, 24, 30, 36, 42 and 48 months and taken as a guide for treatment; ABPM will be performed at randomisation and at 12, 24, 36 and 48 months but will not be used to take treatment decisions. Patients randomised to group 2 will have ABPM performed at randomisation and all scheduled visits as a guide to antihypertensive treatment. The effects of MUCH management strategy based on ABPM or on OBPM on CV and renal intermediate outcomes (changing left ventricular mass and microalbuminuria, coprimary outcomes) at 1 year and on CV events at 4 years and on changes in BP-related variables will be assessed. ETHICS AND DISSEMINATION: MASTER study protocol has received approval by the ethical review board of Istituto Auxologico Italiano. The procedures set out in this protocol are in accordance with principles of Declaration of Helsinki and Good Clinical Practice guidelines. Results will be published in accordance with the CONSORT statement in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT02804074; Pre-results.

Pulmonary hypertension due to a stiff left atrium: Speckle tracking equivalents of large V-waves.

Heart failure with preserved ejection fraction (HFpEF) is a widely heterogeneous clinical condition. Left ventricular diastolic dysfunction is the leading etiology of HFpEF, but there might be patients presenting with a predominant disease of the left atrium (LA). We report a case of HFpEF secondary to a stiff LA, in which we corroborated invasive hemodynamic assessment with LA strain analysis. Pathognomonic, tall V-waves were observed in the wedge position in the absence of mitral regurgitation and with a near-normal QRS-gated, pre-V-wave pressure, indicating that left ventricular diastolic dysfunction was not a major issue in this case. These hemodynamic findings were mirrored by very low LA strain values, compatible with a stiff and noncompliant chamber.

Impact of obstructive sleep apnea on cardiac organ damage in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Both obstructive sleep apnea (OSA) and cardiac organ damage have a crucial role in acute ischemic stroke. Our aim is to explore the relationship between OSA and cardiac organ damage in acute stroke patients. METHODS: A total of 130 consecutive patients with acute ischemic stroke were enrolled. Patients underwent full multichannel 24-h polysomnography for evaluation of OSA and echocardiography to evaluate left ventricle (LV) mass index (LV mass/BSA, LV mass/height), thickness of interventricular septum (IVS) and posterior wall (LVPW), LV ejection fraction and left atrium enlargement. Information on occurrence of arterial hypertension and its treatment before stroke was obtained from patients' history. RESULTS: 61.9% (70) of patients, mostly men (67.1%), with acute stroke had OSA (AHI > 10). Patients with acute stroke and OSA showed a significant increase (P < 0.05) of LV mass index, IVS and LVPW thickness and a significant left atrial enlargement as compared with patients without OSA. LV ejection fraction was not significantly different in stroke patients with and without OSA and was within normal limits. No relationship was found among cardiac alterations, occurrence of OSA and history of hypertension. CONCLUSION: Acute stroke patients with OSA had higher LV mass and showed greater left atrial enlargement than patients without OSA. This study confirms the high prevalence of OSA in stroke patients, suggesting also an association between OSA and cardiac target organ damage. Our finding of structural LV abnormalities in acute stroke patients with OSA suggests a potential role of OSA as contributing factor in determining both cerebrovascular and cardiac damage, even in absence of clear link with a history of blood pressure elevation.

A brief period of intensive cardiac rehabilitation improves global longitudinal strain and diastolic function after a first uncomplicated myocardial infarction.

Objectives In patients with abnormal left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI), cardiac rehabilitation with physical training prevents cardiac remodelling. To define the role of rehabilitation in the recovery of ventricular function in less severe cases, we studied its effects on more refined indexes of left ventricular function in uncomplicated, low-risk patients. Methods and results Fifty-five patients underwent percutaneous coronary revascularization after uncomplicated first AMI. Thirty-four started cardiac rehabilitation with counselling and physical training; 21 patients did not train, followed a counselling program and were taken as controls. Echocardiography was performed at baseline, after rehabilitation or counselling program and at six months follow-up. We measured: global strain (GS%) with speckle tracking analysis, E/e' by tissue Doppler imaging (TDI), left ventricular elastance (KLV) from the deceleration time (DT), LVEF, systolic and diastolic volumes, wall motion score index (WMSI). At baseline, groups had similar GS%, KLV, LVEF, DT, E/e', systolic and diastolic volumes, WMSI. Rehabilitation increased peak VO2 by 18% (P < 0.05) and improved GS%, KLV, LVEF, E/e' and WMSI (P < 0.02) that were unchanged in controls. The improvement persisted at six months. Conclusions After a first uncomplicated AMI, abnormalities of left systolic and diastolic ventricular function may be present persisting over time despite a normal LVEF, which are fully reverted by cardiac rehabilitation.

Effects of hypobaric hypoxia exposure at high altitude on left ventricular twist in healthy subjects: data from HIGHCARE study on Mount Everest.

AIMS: Previous studies investigating the effect of hypoxia on left ventricle focused on its global function, an approach that may not detect a selective dysfunction of subendocardial layers that are most sensitive to an inadequate oxygen supply. In the HIGHCARE study, aimed at exploring the effects of high altitude hypoxia on multiple biological variables and their modulation by an angiotensin receptor blocker, we addressed the effects of hypobaric hypoxia on both systolic and diastolic left ventricular geometry and function, focusing on echocardiographic assessment of left ventricle twist to indirectly examine subendocardial left ventricular systolic function. METHODS AND RESULTS: In 39 healthy subjects, physiological and echocardiographic variables, including left ventricular twist and a simplified torsion-to-shortening ratio (sTSR), were recorded at sea level, at 3400 m, and at 5400 m altitude (Mount Everest base camp). Both left ventricular twist and sTSR were greater at 5400 m than at sea level (12.6° vs. 9.6° and 0.285 vs. 0.202, P < 0.05 for both), were linearly related to the reduction in arterial oxygen partial pressure (P < 0.01 for both), and were associated with significant changes in LV dimensions and contractility. No effects of angiotensin receptor blockade were observed on these variables throughout the study. CONCLUSION: Our study, for the first time, demonstrates an increase in left ventricular twist at high altitude in healthy subjects exposed to high altitude hypoxia, suggesting the occurrence of subendocardial systolic dysfunction in such condition.

Lung ultrasound and transthoracic impedance for noninvasive evaluation of pulmonary congestion in heart failure.

BACKGROUND: In patients with heart failure, many indexes are available for noninvasive identification of pulmonary congestion: E/E' at echocardiography; plasma levels of brain natriuretic peptide (BNP) (pg/ml); number of B-lines at lung ultrasound; and transthoracic conductance [thoracic fluid content (TFC)TT = 1/Ω] at impedance cardiography (ICG). METHODS: We obtained 75 measures from 50 patients (72 ±â€Š10 years, NYHA 2.4 ±â€Š0.7, ejection fraction 31 ±â€Š7%), 25 of them studied before and after intravenous diuretics, in whom we assessed the following: E/e' from Doppler echocardiogram; BNP plasma levels; presence and number of B-lines at lung ultrasound; and TFCTT from ICG. We determined the relationship among these indexes and their change with treatment, and compared B-lines and TFC for the diagnosis of pulmonary congestion. Finally, we considered the timing and the personnel required for performing and interpreting each test. RESULTS: A mutual relationship was observed between all the variables. After clinical improvement, changes in each variable were of similar direction and magnitude. Congestion (estimated by chest radiograph) was present in 59% of the patients: TFC value and B-line number had the best sensitivity and specificity for its detection. BNP determination and ICG assessment were performed by a nurse (15 min), and echocardiography and lung ultrasound were performed by a cardiologist (15 min). CONCLUSION: The correlation between all indexes and their consensual change after improvement of the clinical status suggests that they all detect pulmonary congestion, and that using at least two indexes improves sensitivity and specificity. The choice among the methods may be determined by the patient characteristics or by the clinical setting.

Clinical and psychological telemonitoring and telecare of high risk heart failure patients.

We conducted a trial of telemonitoring and telecare for patients with chronic heart failure leaving hospital after being treated for clinical instability. Eighty patients were randomized before hospital discharge to a usual care group (n=40: follow-up at the outpatient clinic) or to an integrated management group (n=40: patients learned to use a handheld PDA and kept in touch daily with the monitoring centre). At enrolment, the groups were similar for all clinical variables. At one-year follow-up, integrated management patients showed better adherence, reduced anxiety and depression, and lower NYHA class and plasma levels of BNP with respect to the usual care patients (e.g. NYHA class 2.1 vs 2.4, P<0.02). Mortality and hospital re-admissions for congestive heart failure were also reduced in integrated management patients (P<0.05). Integrated management was more expensive than usual care, although the cost of adverse events was 42% lower. In heart failure patients at high risk of relapse, the regular acquisition of simple clinical information and the possibility for the patient to contact the clinical staff improved drug titration, produced better psychological status and quality of life, and reduced hospitalizations for heart failure.

Prognostic value of noninvasive hemodynamic evaluation of the acute effect of levosimendan in advanced heart failure.

AIMS: Optimization of inotropic treatment in worsening heart failure sometimes requires invasive hemodynamic assessment in selected patients. Impedance cardiography (ICG) may be useful for a noninvasive hemodynamic evaluation. METHODS: ICG was performed in 40 patients (69 ± 8 years; left ventricular ejection fraction 27.5 ± 5.6%; New York Heart Association 3.18 ± 0.34; Interagency Registry for Mechanically Assisted Circulatory Support 5.48 ± 0.96, before and after infusion of Levosimendan (0.1­0.2 µg/kg per min for up to 24 h). Echocardiogram, ICG [measuring cardiac index (CI), total peripheral resistances (TPRs) and thoracic fluid content (TFC)] and plasma levels of brain natriuretic peptide (BNP) were obtained; in nine patients, right heart catheterization was also carried out. RESULTS: When right catheterization and ICG were performed simultaneously, a significant relationship was observed between values of CI and TPR, and between TFC and pulmonary wedge pressure. ICG detected the Levosimendan-induced recovery of the hemodynamic status, associated with improved systolic and diastolic function and reduction in BNP levels. One-year mortality was 4.4%. At multivariate analysis, independent predictors of mortality were: no improvement in the severity of mitral regurgitation, a persistent restrictive filling pattern (E/E' > 15), a reduction of BNP levels below 30% and a change below 10% in CI, TPR and TFC. When combined, absence of hemodynamic improvement at ICG could predict 1-year mortality with better sensitivity (86%) and specificity (85%) than the combination of echocardiographic and BNP criteria only (sensitivity 80% and specificity 36%). CONCLUSION: Noninvasive hemodynamic evaluation of heart failure patients during infusion of inodilator drugs is reliable and may help in their prognostic stratification.

Transthoracic bioimpedance and brain natriuretic peptide assessment for prognostic stratification of outpatients with chronic systolic heart failure.

BACKGROUND: In patients with chronic heart failure, physical evaluation and clinical judgment may be inadequate for prognostic stratification. HYPOTHESIS: Information obtained with simple bedside tests would be helpful in patient management. METHODS: We report on 142 outpatients with systolic heart failure seen at our heart failure unit from 2007 to 2010 (ages 69.4 ± 8.9 years; ejection fraction [EF] 30.6 ± 6.1%; 43% with implanted defibrillators and/or resynchronization devices). At their first visit, we assessed levels of brain natriuretic peptide (BNP) (pg/mL), evaluated transthoracic conductance (TFC) (1/kΩ) by transthoracic bioimpedance, and performed echocardiography. RESULTS: Four-year mortality was 21.2%. At multivariate analysis, surviving and deceased subjects did not differ regarding New York Heart Association, age, gender, heart failure etiology, or EF at index visit. Patients who died had higher BNP and TFC (BNP = 884 ± 119 pg/mL vs 334 ± 110 pg/mL; TFC = 50 ± 8/kΩ vs 37 ± 7/kΩ, both P < 0.001]. Patients with BNP < 450 pg/mL and TFC < 40/kΩ had a 2.1% 4-year mortality, compared to 46.5% mortality of patients having BNP ≥ 450 pg/mL and TFC ≥ 40/kΩ. BNP ≥ 450 pg/mL and TFC ≥ 40/kΩ showed high sensitivity (91%) and specificity (88%)in identifying patients who died at follow-up. CONCLUSIONS: The combined use of BNP and impedance cardiography during the first assessment of a patient in a heart failure unit identified those carrying a worse medium-term prognosis. This approach could help the subsequent management of patients, allowing better clinical and therapeutic strategies.

Intermittent levosimendan infusions in advanced heart failure: favourable effects on left ventricular function, neurohormonal balance, and one-year survival.

The role of repeated infusions of Levosimendan (LEVO) in patients with chronic advanced heart failure is still unclear. Thirty-three patients with chronic heart failure presenting clinical deterioration were randomized 2:1 to receive monthly infusions of LEVO (n = 22) or Furosemide (Controls, n = 11). At the first drug's administration, noninvasive hemodynamic evaluation was performed; before and after each infusion, we assessed NYHA class, systolic and diastolic function, functional mitral regurgitation, and brain natriuretic peptide (BNP) levels. Noninvasive hemodynamic in the LEVO group showed vasodilation and decrease in thoracic conductance (index of pulmonary congestion), whereas in Controls, only a reduced thoracic conductance was observed. In the LEVO group, systolic and diastolic function, ventricular volumes, severity of mitral regurgitation, and BNP levels improved over time from baseline and persisted 4 weeks after the last infusion (P < 0.01). In Controls, no change developed over time in cardiac function and BNP levels. In LEVO-treated patients, 1-year mortality tended to be lower than in those treated with Furosemide. In conclusion, serial LEVO infusions in advanced heart failure improved ventricular performance and favorably modulated neurohormonal activation. Multicenter randomized studies are warranted to test the effect of LEVO on long-term outcome.

Transthoracic impedance accurately estimates pulmonary wedge pressure in patients with decompensated chronic heart failure.

Routine cardiac catheterization to assess pulmonary capillary wedge pressure (PCWP) is not recommended in heart failure (HF), and various noninvasive tools have been proposed. The authors evaluated the reliability of echocardiography, brain natriuretic peptide (BNP), and thoracic electrical bioimpedance (TEB) in predicting PCWP in 29 patients (72±4 years, New York Heart Association class 3.5±0.9, ejection fraction 28%±6%) who underwent hemodynamic evaluation for worsening HF. Echocardiography was performed immediately before the hemodynamic study. During clinical stability, PCWP, plasma BNP, and TEB were simultaneously assessed. Among TEB variables, thoracic conductance (thoracic fluid content [TFC]=1/kΩ) was used. PCWP was related with E/E' obtained with mitral Doppler and mitral annulus tissue Doppler imaging echocardiography ( R=0.55, P<.005), with BNP levels (R=0.43, P<.01) and TFC values (R=0.69, P<.001). For detection of PCWP ≥15 mm Hg, TFC ≥35/kΩ had high specificity (97%) and sensitivity (86%) and negative (92%) and positive (97%) predictive value, while E/E' and BNP levels had poorer specificity. After infusion of the inodilator levosimendan, changes in TFC and PCWP were of the same order of magnitude and mutually related. In worsening HF, TEB could help avoid right heart catheterization, since it may estimate PCWP better than BNP or echocardiography. Moreover, TFC could be used for noninvasive assessment of drugs' effect.

Diastolic dysfunction and abnormal exercise ventilation predict adverse outcome in elderly patients with chronic systolic heart failure.

BACKGROUND: Heart failure is increasing in the elderly and represents a socioeconomic burden requiring the correct management for which risk stratification is mandatory. Among younger patients, echocardiogram and cardiopulmonary exercise test are useful in prognostic stratification. Few studies have analyzed the utility of these tests in elderly patients. METHODS: We report on 90 patients over 70 years old, on whom cardiopulmonary tests and echocardiograms were performed between 1998 and 2006 (67 M, 23 F; 75 ± 3 years; ejection fraction (EF) 30 ± 6%; NYHA 2.1 ± 0.8; 60% ischemic; therapy according to international guidelines). Echocardiographic variables were (1) left ventricular ejection fraction (EF); (2) severity of diastolic dysfunction on multiparametric examination of Doppler and TDI parameters; (3) severity of functional mitral regurgitation. Cardiopulmonary variables were (1) peak VO(2); (2) peak O(2) pulse; (3) peak respiratory quotient (RQ); (4) VE/VCO(2) slope. Endpoint considered was mortality of any cause at three-years follow-up. RESULTS: Mortality was 21%. At univariate analysis, survivors (n = 71) and deceased (n = 19) were similar for age, NYHA class, peakVO(2) and RQ; they differed for EF, severity of mitral regurgitation, severity of diastolic dysfunction, O(2) pulse and VE/VCO(2) slope. At multivariate analysis, only VE/VCO(2) slope and severe diastolic dysfunction (restrictive filling pattern) discriminated between the two groups. In particular, the association of restrictive filling pattern and VE/VCO(2) slope ≥ 45 predicted 3-year mortality with sensitivity of 84% and specificity of 88%. CONCLUSIONS: Echocardiographic and cardiopulmonary data can identify high-risk elderly patients with systolic heart failure, who may need aggressive clinical management.

Clinical relevance of cardiac structure and function abnormalities in patients with Cushing's syndrome before and after cure.

OBJECTIVES: Sustained hypercortisolism impacts cardiac function, and, indeed, cardiac disease is one of the major determinants of mortality in patients with Cushing's syndrome. The aim of this study was to assess the clinical relevance of cardiac structure and function alterations by echocardiography in patients with active Cushing's syndrome and after disease remission. STUDY DESIGN: Seventy-one patients (61 women, 10 men) with Cushing's syndrome and 70 age-, sex- and blood pressure-matched controls were enrolled. Echocardiography was performed in 49 patients with active disease and at several time points after remission in 44 patients (median follow-up 46.4 months), and prevalence of abnormal left ventricular mass measurements and systolic and diastolic functions indices was compared between patients with active disease, after remission and controls. Twenty-two patients were evaluated both before and after remission. RESULTS: Up to 70% of patients with active Cushing's syndrome presented abnormal left ventricular mass parameters; 42% presented concentric hypertrophy and 23% concentric remodelling. Major indices of systolic and diastolic functions, i.e. ejection fraction and E/A ratio, respectively, were normal. Upon remission of hypercortisolism, left ventricular mass parameters ameliorated considerably, although abnormal values were still more frequent than in controls. Both cortisol excess and hypertension contribute to cardiac mass alterations and increase the prevalence of target organ damage. CONCLUSIONS: Cushing's syndrome is associated with an increased risk for abnormalities of cardiac mass, which ameliorates, but does not fully disappear after remission. Systolic and diastolic functions are largely within the normal range in these patients.

Effects of beta-blockade on exercise performance at high altitude: a randomized, placebo-controlled trial comparing the efficacy of nebivolol versus carvedilol in healthy subjects.

AIMS: Exposure to high altitude (HA) hypoxia decreases exercise performance in healthy subjects. Although ß-blockers are known to affect exercise capacity in normoxia, no data are available comparing selective and nonselective ß-adrenergic blockade on exercise performance in healthy subjects acutely exposed to HA hypoxia. We compared the impact of nebivolol and carvedilol on exercise capacity in healthy subjects acutely exposed to HA hypobaric hypoxia. METHODS: In this double-blind, placebo-controlled trial, 27 healthy untrained sea-level (SL) residents (15 males, age 38.3 ± 12.8 years) were randomized to placebo (n = 9), carvedilol 25 mg b.i.d. (n = 9), or nebivolol 5 mg o.d. (n = 9). Primary endpoints were measures of exercise performance evaluated by cardiopulmonary exercise testing at sea level without treatment, and after at least 3 weeks of treatment, both at SL and shortly after arrival at HA (4559 m). RESULTS: HA hypoxia significantly decreased resting and peak oxygen saturation, peak workload, VO(2) , and heart rate (HR) (P < 0.01). Changes from SL (no treatment) differed among treatments: (1) peak VO(2) was better preserved with nebivolol (-22.5%) than with carvedilol (-37.6%) (P < 0.01); (2) peak HR decreased with carvedilol (-43.9 ± 11.9 beats/min) more than with nebivolol (-24.8 ± 13.6 beats/min) (P < 0.05); (3) peak minute ventilation (VE) decreased with carvedilol (-9.3%) and increased with nebivolol (+15.2%) (P= 0.053). Only peak VE changes independently predicted changes in peak VO(2) at multivariate analysis (R= 0.62, P < 0.01). CONCLUSIONS: Exercise performance is better preserved with nebivolol than with carvedilol under acute exposure to HA hypoxia in healthy subjects.

Acute effects of levosimendan on mitral regurgitation and diastolic function in patients with advanced chronic heart failure.

BACKGROUND: We analyzed the inodilator properties of levosimendan in patients with chronic heart failure and severe functional mitral regurgitation. METHODS: We studied 20 patients under optimal treatment and in stable clinical condition (New York Heart Association 3.19 + or - 0.66; 70 + or - 7 years). Levosimendan was infused as a bolus (12 microg/kg in 10 min) followed by a 24-h infusion (0.1-0.2 microg/kg per min). Before and after infusion, Doppler echocardiography, brain natriuretic peptide determination and noninvasive hemodynamic monitoring with bioimpedance cardiography were performed. RESULTS: Levosimendan improved left ventricular ejection fraction (ejection fraction 31 + or - 4 from 27 + or - 4, P < 0.05), decreased brain natriuretic peptide (333 + or - 139 from 629 + or - 63 pg/ml, P < 0.01), reduced mitral valve effective regurgitant orifice area to 27 + or - 5 from 36 + or - 7 mm (P < 0.01) and the velocity of displacement of mitral annulus [ratio between E and E' waves on Doppler and tissue Doppler (E/E') from 22.7 + or - 1.6 to 13.1 + or - 0.6, P < 0.01]. Noninvasive hemodynamic monitoring showed increased acceleration index (a marker of inotropism), and reduced peripheral resistances and thoracic fluid content (P < 0.01). After 4 weeks of washout, some of these effects were still evident. CONCLUSION: In patients with chronic heart failure and functional mitral regurgitation, levosimendan acutely improved systolic and diastolic function, reduced mitral regurgitation and modulated neurohormonal activation, with a tendency for these changes to persist over a short-term follow-up.