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Background: The relation between systolic pulmonary pressure (sPAP) and left atrium in patients with heart failure (HF) is unclear. Diastolic dysfunction, expressed as restrictive mitral filling pattern (RMP), and functional mitral regurgitation (FMR) are associated with both LA enlargement and increased sPAP. We aimed to evaluate whether atrial dilation might modulate the consequences of RMP and FMR on the pulmonary circulation of patients with HF with reduced ejection fraction (HFrEF)., Methods: 1256 HFrEF patients were retrospectively recruited in four Italian centers. Left ventricular (LVD) and atrial (LAD) diameters were measure by m-mode, and EF were measured. RMP was defined as E-wave deceleration time lower than 140 ms. FMR was quantitatively measured. sPAP was evaluated based on maximal tricuspid regurgitant velocity and estimated right atrial pressure., Results: Final study population was formed by 1005 patients because of unavailability of sPAP in 252 patients. Mean EF was 33 ± 3, 35% had RMP, 67% had mild, and 26% moderate-to-severe FMR. 69% of patients had increased sPAP. A significant association was observed between sPAP and EF, RMP, FMR, and LAD (p < 0.0001 for all). At multivariate analysis, LAD was positively associated with sPAP (p < 0.0001) independently of EF, RMP, and FMR. Analogously, LAD (p < 0.05) was associated with more severe symptoms and worse prognosis after adjustment for LV function and FMR., Conclusion: LA dilation was positively associated with sPAP independently of EF, RMP, and FMR. This highlights that LA size should be considered a marker of the severity of the disease.

Background: B-lines evaluated by lung ultrasound (LUS) are the sonographic sign of pulmonary congestion, a major predictor of morbidity and mortality in patients with heart failure (HF). Our aim was to assess the prognostic value of B-lines at discharge to predict rehospitalization at 6 months in patients with acute HF (AHF)., Methods: A prospective cohort of 100 patients admitted to a Cardiology Department for dyspnea and/or clinical suspicion of AHF were enrolled (mean age 70 ± 11 years). B-lines were evaluated at admission and before discharge. Subjects were followed-up for 6-months after discharge., Results: Mean B-lines at admission was 48 ± 48 with a statistically significant reduction before discharge (20 ± 23, p < .0001). During follow-up, 14 patients were rehospitalized for decompensated HF. The 6-month event-free survival was highest in patients with less B-lines (≤ 15) and lowest in patients with more B-lines (> 15) (log rank χ(2) 20.5, p < .0001). On multivariable analysis, B-lines > 15 before discharge (hazard ratio [HR] 11.74; 95 % confidence interval [CI] 1.30-106.16) was an independent predictor of events at 6 months., Conclusions: Persistent pulmonary congestion before discharge evaluated by ultrasound strongly predicts rehospitalization for HF at 6-months. Absence or a mild degree of B-lines identify a subgroup at extremely low risk to be readmitted for HF decompensation.

Objective: To ascertain whether increasing doses of orally administered furosemide are associated with impaired survival in outpatients with chronic heart failure (CHF) and left ventricular (LV) systolic dysfunction., Methods: Transthoracic echo-Doppler examination was carried out at baseline in 813 consecutive CHF outpatients with LV ejection fraction ≤ 45%. The total daily dose of furosemide was assessed for each patient. Chronic kidney disease (CKD) was defined by a glomerular filtration rate < 60 ml/min/1.73 m(2). The end-point was all-cause mortality. To control the prognostic effect of furosemide for the propensity of using high doses of the drug, the Cox model was stratified by the propensity score, itself computed from a multivariable logistic model. Mean follow up was 44 months., Results: After stratification for the propensity score, the risk of death increased linearly across quartiles of furosemide dose (HR 1.38, 95% CI 1.14-1.68, p < 0.001). A daily dose of 50 mg was identified as the best threshold value to predict a high risk of death within 3 years with an area under the ROC curve of 0.68 (95% CI 0.64-0.72). Increasing doses of furosemide were associated with an increased risk of death regardless of LV filling pattern, CKD and background therapy with ACE-inhibitors or beta-blockers., Conclusions: In outpatients with CHF, after stratification for the propensity score, the risk of death increased linearly across quartiles of furosemide daily dose. A threshold furosemide dose of 50 mg was related with the worse outcome., (© 2013 John Wiley & Sons Ltd.)

Background: The Doppler echocardiographic restrictive mitral filling pattern (RFP) is an important prognostic indicator in patients with heart failure (HF), but the interaction between RFP, left ventricular ejection fraction (LVEF) and filling pattern remains uncertain., Aims: To determine whether the RFP is predictive of mortality independently of LVEF in patients with HF., Methods: Online databases were searched to identify studies assessing the relationship between prognosis and LV filling pattern in patients with HF. Individual patient data from 18 studies (3540 patients) were extracted and collated at the MeRGE Coordinating Centre (The University of Auckland)., Results: Overall, RFP was associated with higher all-cause mortality than the non-restrictive filling pattern: hazard ratio 2.42 (95% CI 2.06, 2.83). In multivariable analysis the RFP, LVEF, NYHA class and age were independent predictors of mortality. The prevalence of the RFP was inversely related to LVEF but remained a predictor of mortality even in those patients with preserved LVEF., Conclusions: The restrictive mitral filling pattern is a powerful predictor of mortality, independent of LVEF and age, in patients with HF. Doppler-derived LV filling patterns are an accessible marker from echocardiography that can readily be incorporated in risk stratification of all patients with HF.

Relevant hemodynamic information can be obtained by a comprehensive Doppler echocardiographic examination in patients with various cardiac diseases. The assessment of left heart hemodynamics by Doppler echocardiography has been addressed by several investigators. The feasibility and the accuracy of methods for the estimation of left ventricular filling pressure and cardiac output have been validated by comparative right heart catheterization. Studies have shown that Doppler echocardiography can allow the measurement of pulmonary artery pressures from the pressure gradients across the tricuspid and pulmonary valves. The possibility of completely characterizing cardiac hemodynamics noninvasively has recently been documented: in patients with acute myocardial infarction, automated cardiac output measurement along with the assessment of left ventricular filling by Doppler echocardiography may be used for the identification of hemodynamic subsets. Although Doppler echocardiography can provide noninvasive measures of hemodynamic indices, its value has been disputed since the technique is patient-dependent, time-consuming and requires meticulous acquisition and interpretation by skilled operators. The use of contrast agents may improve the accessibility of both right-sided and left-sided Doppler signals, potentially increasing the number of patients to whom the noninvasive hemodynamic assessment could be applied.

In the progression from myocardial hypertrophy to heart failure, abnormalities in the interstitial space of the heart seem to play a critical role. The formation of an extracellular oedema and the alterations in coronary subendocardial perfusion are associated with the development of interstitial fibrosis. Cardiac experimental studies documented the presence of augmented interstitial fluid volume and pressure and a subsequent remodelling of the fibrillar network of the extracellular space of the myocardium during the phases of the cardiovascular response to a sudden overload. Variations of the Starling's forces balance caused by enhanced endothelial permeability or due to an impairment of cardiac lymphatic drainage may contribute to the development of an acute heart failure. During stable hyperfunction, the organization of a chronic oedema should account for interstitial changes in the hypertrophic myocardium. Reactive fibrosis seems to be under hormonal control. The activation of the renin-angiotensin-aldosterone system is responsible for interfascicular and intercellular accumulation of fibrillar collagen within the cardiac interstitium. Perivascular fibrosis in the subendocardium may impair intramyocardial distribution of coronary flow. When an inadequate hypertrophy occurs, because of an elevation in ventricular wall stress, myocardial oxygen consumption rises and this may lead to the exhaustion of coronary blood flow reserve in the subendocardial layers. This underperfusion may be responsible for the development of myocardial ischemia. Coronary hemodynamic changes in the microcirculation as those prompted by interstitial alterations may contribute to the onset of myocyte necrosis and to the formation of restorative fibrosis. The progressive mechanical overload of the spared hypertrophied myocytes could explain the initiation of a positive feedback mechanism which perpetuates endomyocardial perfusion impairment, interstitial oedema and remodelling, finally, causing myocyte deaths and fibrous tissue proliferation. These structural alterations and their pathophysiological counterparts appear to be closely related to the evolution from compensatory hypertrophy to chronic myocardial failure in hypertrophic heart disease.

The effects of the methylxanthine drugs doxofylline, theophylline and bamifylline were investigated on the basis of clinical and gasometric parameters in hypoxic patients with chronic heart failure. A parallel, double-blind, randomized study was conducted in 48 in-patients with NYHA II-IV chronic heart failure with normo- or hypercapnic hypoxaemia. They were divided into three groups and then submitted to a 4-day run-in with placebo. Either doxofylline 800 mg b.i.d., theophylline slow-release 400 mg b.i.d. or bamifylline 1200 mg b.i.d. were administered orally in each group of 16 patients for 10 days. Exercise capacity was estimated through NYHA class modification. Gasometric determinations, including arterial oxygen tension (PaO2), carbon dioxide tension (PaCO2) and oxygen saturation (SaO2), were measured from arterial blood samples at the time of enrollment (T-4), at the onset of xanthine therapy (T0) and at the end of the trial (T9). After 10 days' treatment, the NYHA class was found to be diminished in 50% of the doxofylline group, 50% of the bamifylline group and 44% of the theophylline group. PaO2 showed a > 15% increase in 75% of the doxofylline group, 56% of the theophylline group and 43% of the bamifylline group (responders). In all three groups the responders presented a highly significant enhancement in PaO2 and SaO2 (p < 0.01 T0 vs T9). Doxofylline exhibited the highest percent increase in PaO2 and SaO2 with respect to T0. The effects on cardiac rhythm showed a progressive heart-rate reduction in the doxofylline group, whereas patients receiving theophylline presented an increase rate of beating. In conclusion, the use of methylxanthines in patients with chronic heart failure seems to be particularly effective especially when a significant ventilatory dysfunction is present. Doxofylline appears to be specially useful because of its ability not to interfere with cardiac rhythm.