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Since increased heart rate (HR) is associated with higher mortality in several cardiac disorders, HR is considered not only a physiological indicator but also a prognostic and biological marker. In heart failure (HF), it represents a therapeutic target in chronic phase. The use or up-titration of beta-blockers, a milestone in HF with reduced left ventricular ejection fraction (LVEF) treatment, is at times limited by patients' hemodynamic profile or intolerance. Ivabradine, a HR-lowering drug inhibiting the f-current in pacemaker cells, has been shown to improve outcome in patients with chronic HF, in sinus rhythm with increased HR beyond beta-blocker therapy. The rationale for this review is to update the role of HR as a prognostic biomarker and a potential therapeutic target in other scenarios than chronic HF; namely, in patients with coexisting atrial fibrillation (AF), in HF with preserved LVEF (HFpEF), in acute HF, and in patients discharged after an episode of acute HF. Preliminary studies and case reports that evaluated the use of ivabradine in the setting of acute HF will be summarized. Recent results of HR reduction in the setting of HFpEF with ivabradine will be presented. Finally, data from large registries and trials that evaluated the prognostic impact of HR in patients with acute HF and sinus rhythm or AF will be reviewed, showing that only patients in sinus rhythm may benefit from HR reduction., (Copyright © 2017. Published by Elsevier B.V.)

Heart rate (HR) is not only a physical sign but also a biomarker. High HR in several cardiac disorders is associated with increased mortality. In heart failure (HF), HR represents an important therapeutic target, both in the acute and chronic phase. Beta-blockers are a milestone of recommended treatments in HF patients with reduced ejection fraction. However, hemodynamic profile or intolerance may limit the use or the optimization of beta-blocker treatment, both during hospitalization and outpatient follow-up. More recently, ivabradine has become available, a drug that lowers HR by blocking the I(f) current in the pacemaker cells at the sinoatrial node level. In the SHIFT trial, ivabradine was shown to improve the outcome of patients with chronic HF, in sinus rhythm, with HR >70 b/min while on beta-blockers. Preliminary data have shown that this drug has a good safety profile and lowers effectively HR even during hospitalization due to worsening HF. However, further studies are warranted to understand if an earlier administration of ivabradine can lead to a better prognosis beyond symptom control and improved hemodynamics. In patients with atrial fibrillation and HF, the target is the restoration of sinus rhythm, alternatively rate control should be pursued with beta-blockers, amiodarone or digitalis, even if there is no clear evidence of an association between ventricular rate response in patients with atrial fibrillation at discharge after an HF hospitalization and major cardiovascular events. In this review, the studies that point to a role of HR both as a biomarker and a therapeutic target in patients with acute and chronic HF are described. In addition, the proportions of patients who do not reach target HR values at discharge after an acute decompensated HF episode or in the chronic phase are evaluated based on the Italian registries.

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

Objective: To assess the prognostic role of B-type natriuretic peptide (BNP) measured at baseline and after 6 months in advanced heart failure patients, candidates for heart transplantation., Methods: Ninety-nine patients with BNP evaluation (mean age 50.8 years, 85% men) were admitted in the heart transplantation waiting list; 39% were in New York Heart Association functional class IV; with hemodynamic patterns of severe heart failure, the cause was ischemic in 45% and idiopathic in 44%. In order to identify more severe patients, BNP values and changes at 6 months were dichotomized according to their upper tertile (>1100 and >or=70 pg/ml, respectively)., Results: Median baseline BNP was 719 pg/ml. After a median of 45 months, 40 events were observed (three cardiac assist device implants, 16 urgent heart transplantations, 13 sudden deaths and eight deaths from heart failure). The event rate was 10.0 and 32.3 per 100 person-years in patients with low and high BNP, respectively. In a bivariable Cox regression, BNP at entry in the list and change in BNP at 6 months were independent predictors of events, with hazard ratios of 4.10 (95% confidence interval 2.14-7.88, P<0.001) and 4.55 (95% confidence interval 2.36-8.80, P<0.001), respectively. Furthermore, the risk increased from neither BNP/BNP change, to one of them and to both of them present., Conclusion: Both high baseline and further increase in BNP levels during midterm follow-up are strong predictors of events in patients with advanced heart failure awaiting heart transplantation.

Aims: Right ventricular (RV) dysfunction is a marker of poor prognosis in heart failure (HF) patients. It is still unclear whether RV function might influence response to cardiac resynchronization therapy (CRT)., Methods: Forty-four consecutive patients with HF, large QRS, and either intraventricular or interventricular dyssynchrony underwent echocardiographic evaluation before, 1 month after, and 6 months after CRT. Response to CRT was considered in case of significant LV reverse remodeling, defined as the occurrence of LV end-systolic volume (LVESV) reduction > or =15% at 6 months., Results: All echocardiographic indexes of baseline RV function and dimensions were significantly more impaired in nonresponders versus responders to CRT: tricuspid annular plane systolic excursion (TAPSE 15 +/- 4 mm vs 20 +/- 5 mm, P = 0.001), RV systolic pulmonary artery pressure (RVSP 39 +/- 14 mmHg vs 27 +/- 8 mmHg, P = 0.02), RV end-diastolic area (RVEDA 23 +/- 6 cm(2) vs 16 +/- 3 cm(2) P < 0.001), RV end-systolic area (RVESA 16 +/- 6 cm(2) vs 8 +/- 2 cm(2), P = 0.001), and RV fractional area change (30 +/- 12% vs 48 +/- 8%, P < 0.001). All the indexes of RV function significantly correlated with the percentage of LVESV reduction after CRT. Severe RV dysfunction was defined as TAPSE < or =14 mm and the population was stratified into two groups based on baseline TAPSE < or = or > 14 mm. As compared to those with high TAPSE (n = 30), patients with low TAPSE (n = 14) were less likely to show LV reverse remodeling after CRT (76% vs 14%, P < 0.001)., Conclusions: Our study suggests that RV function significantly affects response to CRT. Poor LV reverse remodeling occurs after CRT in patients with HF having severe RV dysfunction at baseline.

Background: Heart failure patients with implantable defibrillators (ICD) frequently visit the clinic for routine device monitoring. Moreover, in the case of clinical events, such as ICD shocks or alert notifications for changes in cardiac status or safety issues, they often visit the emergency department or the clinic for an unscheduled visit. These planned and unplanned visits place a great burden on healthcare providers. Internet-based remote device interrogation systems, which give physicians remote access to patients' data, are being proposed in order to reduce routine and interim visits and to detect and notify alert conditions earlier., Methods: The EVOLVO study is a prospective, randomized, parallel, unblinded, multicenter clinical trial designed to compare remote ICD management with the current standard of care, in order to assess its ability to treat and triage patients more effectively. Two-hundred patients implanted with wireless-transmission-enabled ICD will be enrolled and randomized to receive either the Medtronic CareLink monitor for remote transmission or the conventional method of in-person evaluations. The purpose of this manuscript is to describe the design of the trial. The results, which are to be presented separately, will characterize healthcare utilizations as a result of ICD follow-up by means of remote monitoring instead of conventional in-person evaluations., Trial Registration: ClinicalTrials.gov: NCT00873899.

Background: Experimentally, vagal stimulation (VS) is protective in chronic heart failure (HF). In man, VS is used in refractory epilepsy but has never been used in cardiovascular diseases. Increased sympathetic and reduced vagal activity predict increased mortality in HF., Aims: This pilot study assessed feasibility and safety and tested possible efficacy of chronic VS in HF patients., Methods: We studied 8 patients (mean age 54 years). CardioFit (BioControl Medical), a VS implantable system delivering pulses synchronous with heart beats through a multiple contact bipolar cuff electrode, was used. VS was started 2-4 weeks after implant, slowly raising intensity; patients were followed 1, 3 and 6 months thereafter., Results: All procedures were successful: as sole surgical side effect, one patient had transient hoarseness. VS was well tolerated, with only mild side effects (cough and sensation of electrical stimulation). There was a significant improvement in NYHA class, Minnesota quality of life (from 52+/-14 to 31+/-18, p < 0.001), left ventricular end-systolic volume (from 208+/-71 to 190+/-83 ml, p = 0.03), and a favourable trend toward reduction in end-diastolic volume., Conclusions: This novel approach to the treatment of patients with HF is feasible, and appears safe and tolerable. The preliminary efficacy results appear promising. These findings suggest the opportunity to proceed with a larger multicentre study.

Aim: We sought to verify which changes in right ventricular pressures occur before acute heart failure (HF) in patients with advanced systolic left ventricular (LV) dysfunction. In patients with chronic HF, continuous hemodynamic monitoring by implantable devices may detect increases in pulmonary pressures before the onset of symptoms., Methods: A device which allowed monitoring of right ventricular systolic (RVSP) and diastolic pressure (RVDP) and an estimate of pulmonary artery diastolic pressure (ePAD) was implanted in 10 patients with advanced LV systolic dysfunction and frequent cardiovascular hospitalizations [mean age 56.8 years; New York Heart Association (NYHA) classes IIIb-IV; LV ejection fraction at echocardiography 21 +/- 2%]., Results: During a follow-up period of 15 +/- 12 months, 18 hospitalizations due to acute HF were recorded; 10 episodes were characterized by symptoms due to low-cardiac output (LCO) and eight episodes were characterized by symptoms due to pulmonary congestion. RVSP and ePAD increased before six hospitalizations and decreased before three episodes; RVDP increased before 10 hospitalizations and decreased before one. The extent of RVDP increase was 16 +/- 24% before pulmonary congestion episodes and 29 +/- 32% before LCO episodes., Conclusion: An increase in RVDP was the most frequent hemodynamic change detected by the implantable hemodynamic monitor before hospitalizations due to acute HF in patients having advanced systolic LV dysfunction.

Background: The management of patients with chronic heart failure turns to new diagnostic and therapeutic approaches, focusing on an integrated network among general practitioners and cardiologists., Methods: In order to improve heart failure patient care, we developed a pilot study to assess the feasibility of a homecare program including visits performed by hospital cardiologists on request of general practitioners., Results: This pilot study confirmed the feasibility of the collaborative project among general practitioners and cardiologists and the suitability of home visits performed on request. In 80/96 visits (85%) the cardiologist confirmed that home visit could be shared. Preliminary epidemiological data showed an elderly population (mean age 82 years) with prevalence of females (60%); hypertension in 46%, diabetes in 27%, and infrequent access to outpatient visits., Conclusions: This integrated management showed good results in terms of an improvement of cooperation among general practitioners and cardiologists, and allowed to verify a very high level of diagnostic accuracy of general practitioners.

Background: Heart rate (HR) reduction may be useful in treatment of patients with heart failure (HF). There are no data on the haemodynamic effects of ivabradine (a selective I(f) current inhibitor) in advanced HF patients., Aims: To assess the haemodynamic effects of ivabradine in patients with advanced HF and markedly depressed left ventricular (LV) function., Methods and Results: Ten NYHA class III patients (50+/-12 years, LV ejection fraction 21+/-7%) underwent 24-h haemodynamic monitoring. Ivabradine 0.1 mg/kg was infused over 90', followed by 0.05-0.075 mg/kg in the subsequent 90'. Baseline HR was 93+/-8 bpm, cardiac index (CI) 2.2+/-0.6 l/min*m2; LV stroke volume 44+/-11 ml and systolic work 39+/-13 g. Ivabradine significantly reduced HR, by a maximum of 27% (to 68+/-9 bpm) at 4 h, without decreasing CI. Ivabradine increased stroke volume and LV systolic work by a maximum of 51% (to 66+/-17 ml) and 53% (to 58+/-20 g) at 4 h. No serious adverse events occurred., Conclusion: In patients with advanced HF and markedly depressed LV function, the acute administration of ivabradine is well tolerated, effectively reduces HR, markedly increases stroke volume and preserves cardiac output. Ivabradine appears a promising approach for the treatment of patients with moderate and advanced heart failure.

Background: Elevated plasma levels of cytokines have been associated with an increased risk of congestive heart failure (CHF) even in people without history of myocardial infarction. Here we have tested the hypothesis that effective removal of pro-inflammatory cytokines in patients with advanced CHF unresponsive to diuretic treatment is associated with diuresis restoration and with a significant reduction of B-type natriuretic peptide (BNP) circulating levels., Methods: We prospectively enrolled 10 patients with decompensated CHF (NYHA classes III-IV). Five patients unresponsive to diuretic treatment underwent a short course of intermittent haemodiafiltration (iHDF), whereas five patients responsive to diuretics were treated with intravenous boluses of furosemide. Renal function was similar between the two groups., Results: Excess body fluids were removed in both groups always resulting in a reduction of pulmonary congestion and peripheral oedema. NYHA class improved in all patients, but one treated by intravenous boluses of furosemide. Only patients treated with iHDF showed a significant reduction of circulating interleukin-8 and monocyte chemoattractant protein-1. After the end of iHDF treatment, patients showed consistent restoration of diuretic responsiveness to significantly lower doses of oral furosemide up to one month of follow-up. Plasma levels of BNP before treatment were significantly higher in the iHDF group, lowering significantly in both groups after treatment., Conclusions: Our results suggest that HDF is an effective treatment for patients with advanced CHF when cytokines have to be cleared and diuretic responsiveness needs to be restored. In our experience, iHDF is a cost-effective option when compared with continuous ultrafiltration methods because it can be performed in a routine dialysis unit without adjunctive costs for machinery or personnel training.

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

Clinical trials investigating traditional inotropic agents in patients with heart failure demonstrated an increased mortality rate (odds ratio 1.50; IC=0.51-3.92), high incidence of discontinuation of infusion therapy (odds ratio 0.46; IC=0.083-2.29) due to major side effects and, most of all, a limited clinical benefit (odds ratio 0.75; IC=1.42-0.08). On this background a new class of inotropic drugs, the calcium-sensitisers, have been developed. The safety and efficacy of levosimendan (Simdax) has been recently demonstrated in trials (LIDO e RUSSLAN) in patients with heart failure due to ischemic and not ischemic disease. Twenty-six patients with decompensated heart failure of different etiology have been treated with 24 hour infusion of levosimendan. In this experience the levosimendan improved the clinical status and the left ventricular ejection fraction.

Aims: The study aimed at evaluating the prevalence of interventricular and intraventricular contractile dyssynchrony in heart failure patients with either normal or prolonged QRS duration., Methods and Results: Echocardiography and tissue Doppler imaging (TDI) were performed in 158 consecutive patients with advanced left ventricular dysfunction (LVEF<35%); 61 patients had a normal QRS duration (Group 1), 21 patients had left bundle branch block with a QRS duration between 120 and 150 ms (Group 2) and 76 patients had a QRS duration #10878;150 ms (Group 3). Interventricular dyssynchrony (defined by the presence of an interventricular mechanical delay greater than 40 ms) was found in 12.5%, 52.4% and 72% of patients in Group 1, 2 and 3, respectively (p < 0.001). Intraventricular dyssynchrony (defined by the presence of one or more differences greater than 50 ms among regional pre-ejection periods) was observed in 29.5%, 57.1% and 71% of patients in Group 1, 2 and 3, respectively (p < 0.001). No relationship was found between interventricular and intraventricular dyssynchrony., Conclusions: A substantial proportion of heart failure patients with a slightly prolonged QRS or even with normal conduction may exhibit ventricular dyssynchrony. Both standard echocardiography and TDI are necessary to describe the entire spectrum of mechanical abnormalities due to dyssynchrony.

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

Decompensated heart failure is associated with high rates of morbidity and mortality and it is responsible for numerous hospitalizations. The current approach to acute exacerbations is based on diuretics, vasodilators and inotropes. Compared with the impressive development of new therapeutic agents designed for other cardiovascular diseases, little progress has been observed in developing new drugs for the treatment of decompensated heart failure. Moreover, a series of controlled clinical trials failed to show a better outcome or a reduction in morbidity during treatment with inotropes, even though promising results were recently observed in controlled clinical trials with new classes of drugs, such as calcium sensitizers and nesiritide; these agents will probably modify the treatment options of decompensated heart failure in the coming years.

Objectives: This study was designed to assess whether testing of potential reversibility of pulmonary hypertension (PHT) may be a useful means of defining the short-term prognosis of patients with advanced heart failure and elevated pulmonary artery pressure. In such patients, the reversibility of PHT after acute vasodilator administration is associated with a low early mortality rate after heart transplantation. However, its short-term prognostic value has not yet been determined., Methods and Results: Between 1994 and 1998, 76 patients with advanced heart failure and PHT underwent right heart cathetherization. The hemodynamic measurements, including thermodilution-derived right ventricular ejection fraction, were repeated after an intravenous bolus of nitroglycerin (NTG). During a median follow-up period of 8.2 months (25% and 75% centiles, 3.3 and 18.9 months), 47 patients had a cardiac event (death or urgent heart transplantation). With Cox survival analysis, a multivariate model that included the New York Heart Association class and the hemodynamic variables obtained after NTG administration allowed a better assessement of the short-term prognosis of the patients than a model including the baseline variables. The evaluation of right ventricular function during the acute NTG-induced pulmonary vasodilation was of critical importance in obtaining such a refinement in the prognostic stratification., Conclusions: The prognostic evaluation of patients with advanced heart failure and PHT should include the assessment of the changes of right ventricular ejection fraction after acute afterload reduction.

Background: Noninvasive estimation of pulmonary artery systolic and diastolic pressures usually requires the investigation of both tricuspid and pulmonary regurgitant jets and an estimate of right atrial pressure. A new, noninvasive method to obtain pulmonary diastolic pressure (based on the hemodynamic demonstration that right ventricular systolic pressure and pulmonary artery diastolic pressure are equal at the time of pulmonary valve opening) from the analysis of tricuspid regurgitation alone has been described in a small cohort of patients. We sought to verify the accuracy of this method in a large population of patients with heart failure., Methods: An estimate of pulmonary artery diastolic pressure was obtained by transposing the pulmonary opening time (from the onset of the R wave on the electrocardiographic tracing to the beginning of pulmonic forward flow on Doppler examination) onto the tricuspid regurgitant velocity curve and calculating the pulmonary artery diastolic pressure value as the pressure gradient between the right ventricle and right atrium at this time. The study group included 86 consecutive patients (64 men, aged 52 +/- 11 years) with heart failure (New York Heart Association class > or =II, 94%) who were in stable clinical condition with a chiefly idiopathic (57%), ischemic (24%), or other form (13%) of dilated cardiomyopathy. Noninvasive, right-sided pressures were compared with invasive measurements obtained during right heart catheterization performed within 24 hours. The Bland and Altman graphic method was used together with the calculation of the Lin concordance correlation coefficient and its 95% CI to assess the agreement between hemodynamic and echocardiographic measurements., Results: Catheter-derived pulmonary artery systolic pressure ranged from 8 to 119 mm Hg (mean 42 +/- 21 mm Hg), pulmonary artery diastolic pressure from 1 to 59 mm Hg (mean 20 +/- 11 mm Hg), and right atrial pressure from -5 to 20 mm Hg (mean 6 +/- 5 mm Hg). Tricuspid regurgitation was detected in 75 of 86 patients (87%). Pulmonary artery systolic pressure ranged from 13 to 110 mm Hg (mean 44 +/- 21 mm Hg); the pressure gradient between the right ventricle and right atrium at time t of the pulmonary valve opening on the tricuspid regurgitation velocity curve was measurable in 70 of 75 (93%) cases and ranged from 3.5 to 64 mm Hg (mean 22 +/- 11 mm Hg). Good agreement was observed not only for pulmonary artery systolic pressure but also for pulmonary artery diastolic pressure, based on the analysis of the tricuspid regurgitation velocity jet, with a slight difference between measurements (-1.8 and 0.1, respectively), no evident pattern of point scattering, and a high concordance correlation coefficient that was elicited by the virtually total overlapping of lines on the graph. Overall results were not significantly different whether patients with depressed right ventricular function (right ventricular ejection fraction < or =35%), with a tricuspid regurgitation grade > or =2 and atrial fibrillation were included in the analysis., Conclusions: The narrow paired difference for the estimate of pulmonary artery systolic pressure and the even better difference for pulmonary artery diastolic pressure using the tricuspid regurgitation velocity curve analysis indicates that this new method reliably estimates invasive right-sided pressures over a wide range of pressure values in patients with heart failure. The overall good correlation with invasive values indicates that Doppler examination of tricuspid regurgitation alone may provide a simple and comprehensive new method for the noninvasive evaluation of right ventricular and pulmonary hemodynamics in patients with heart failure.

Background: A deleterious effect of complete left bundle-branch block (LBBB) on left ventricular function has been established. Nevertheless, the independent effect of a widened QRS on mortality rate in congestive heart failure (CHF) is still controversial. Therefore, we carried out this analysis to determine whether LBBB is an independent predictor of mortality in CHF., Methods and Results: We analyzed the large Italian Network on CHF Registry of unselected outpatients with CHF of different causes. The registry was established by the Italian Association of Hospital Cardiologists in 1995. Complete 1-year follow-up data were available for 5517 patients. The main underlying cardiac diagnosis was ischemic heart disease in 2512 patients (45.6%), dilated cardiomyopathy in 1988 patients (36.0%), and hypertensive heart disease in 714 patients (12.9%). Other causes were recorded in the remaining 303 cases (5.5%). LBBB was present in 1391 patients (25.2%) and was associated with an increased 1-year mortality rate from any cause (hazard ratio, 1.70; 95% confidence interval, 1.41 to 2.05) and sudden death (hazard ratio, 1.58; 95% confidence interval, 1.21 to 2.06). Multivariate analysis showed that such an increased risk was still significant after adjusting for age, underlying cardiac disease, indicators of CHF severity, and prescription of angiotensin-converting enzyme inhibitors and beta-blockers., Conclusion: LBBB is an unfavorable prognostic marker in patients with CHF. The negative effect is independent of age, CHF severity, and drug prescriptions. These data may support the rationale of randomized trials to verify the effects on mortality rate of ventricular resynchronization with multisite cardiac pacing in patients with CHF and LBBB.

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

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

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