Diastolic heart failure: Standard Doppler approach and beyond

Evidence of normal systolic left ventricular function has been reported in vp to 30-40% of patients with clinical signs of congestive heart failure, suggesting that diastolic dysfunction is an important predictor of prognosis and mortality. Doppler echocardiography as a noninvasive diagnostic procedure is able to provide immediate and relevant information on functional and structural changes underlying the clinical syndrome of heart failure. Four distinct early filling/late diastole (E/A) ratio patterns (normal, delayed relaxation, pseudonormal, restrictive) can be discerned if viewed within the context of other available clinical information. These patterns evolve from one to another in a single individual, with changes in disease evolution, treatment, and loading condition. They represent a continuum from normal to severe diastolic dysfunction, showing progressively increasing left ventricular (LV) chamber stiffness and subsequently decreasing deceleration time. The combination of Doppler restrictive filling pattern and decreased deceleration time provides important information that helps to differentiate gradations of diastolic dysfunction and has been found to be a potent predictor of prognosis and mortality in various cardiac conditions. When clinical and transthoracic data alone are not sufficient in guiding therapy of congestive heart failure, transesophageal echocardiography can be used to assess most Doppler flows, especially pulmonary venous and left atrial (LA) appendage flows. The use of the multiplane transducer in multiple intermediate scan planes further improves the possibility of optimizing the Doppler incident angle and obtaining the best Doppler recordings of the left upper or right upper pulmonary venous flow. Whereas LV diastolic dysfunction is common in patients with congestive heart failure and appears to be an important predictor of prognosis, little information is available about right ventricular (RV) diastolic dysfunction, The role of RV function in congestive heart failure has probably been underestimated and it is possible that RV diastolic dysfunction assessment is equally important in the follow-up of heart failure patients. Recently, 2 novel echocardiographic technologies for the assessment of ventricular wall dynamics have been developed-color kinesis and tissue Doppler imaging. Both techniques have recently been shown to provide global as well as regional information on LV contraction and filling. Complementary use of both techniques may allow a more complete noninvasive assessment of global and regional systo-diastolic LV function, (C) 1998 by Excerpta Medico, Inc

Transthoracic and transesophageal echocardiography in the hemodynamic assessment of patients with congestive heart failure

All methods for estimating the severity of heart failure, such as clinical and radiographic examination, measures of ventricular performance, and exercise capacity, when used independently, have major limitations. Echocardiography can be used, not only to assess left-ventricular ejection fraction but also other determinants of prognosis (i.e., left-ventricular size and shape, estimation of left atrial and pulmonary artery pressures, right side involvement). The availability of continuous-wave Doppler has permitted us to evaluate pulmonary artery systolic pressure from tricuspid regurgitation, and this contributes to additional powerful data. In long-standing heart failure, pulmonary artery wedge pressure is a predictor of survival, and aggressive therapy to reduce wedge pressure improves survival. Noninvasive estimation of left-atrial pressure and left-ventricular filling pressure have been attempted by continuous-wave Doppler echocardiography in patients with heart failure and mitral regurgitation and by tissue Doppler imaging at the mitral annulus level. A significant relation has been reported between profiles of pulmonary venous flow and left-atrial pressure, but pulmonary venous flow indexes can be better assessed by transesophageal echocardiography (TEE) in terms of detection rate. It has recently been recognized that TEE can provide valuable information on intracardiac hemodynamics and ventricular function. Two-dimensional evaluation of ventricular function and pulsed- and continuous-wave Doppler recordings from the pulmonary artery, pulmonary vein, and mitral inflow are combined to provide these data, which are both qualitative and quantitative, and permit estimation of ventricular ejection fraction, left-atrial pressure, and cardiac output. It would be important to be able to stratify patients with congestive heart failure according to groups with the highest risk for early death because heart transplantation or aggressive medical treatment could be specifically applied to this population. Serial echocardiographic evaluations of the classic variables of systolic left-ventricular function as well as Doppler transmitral flow may be useful in monitoring the progression of the disease and the effects of medical treatment. The degree of pulmonary hypertension is independently associated with the restrictive left-ventricular diastolic filling pattern and with the degree of functional mitral regurgitation. Future studies on the impact of these hemodynamic variables on the outcome of patients with left-ventricular dysfunction are desirable

Vasopressin Antagonism in Heart Failure

Treatment of chronic heart failure (HF) is based on interference with the renin-angiotensin-aldosterone system and the adrenergic nervous system. Diuretics are used in volume-expanded patients. Insights from clinical trials and registries establish the need to consider correcting both cardiac loading conditions and nonload-related biological factors if HF therapy is to be optimized. Arginine vasopressin (AVP) represents a potentially attractive target for therapy in both acute and chronic HF. Excessive AVP secretion could contribute to both systolic and diastolic wall stress via V1a- and V2-mediated effects on the peripheral vasculature and on water retention. Arginine vasopressin also may directly and adversely affect myocardial function due to the effect of V1a activation on myocardial contractility and cell growth. Last, AVP may contribute to hyponatremia, a powerful predictor of poor outcome in HF. The development of effective nonpeptide antagonists to both the V1a and V2 receptors for AVP now allows for testing the hypotheses that interfering with AVP-mediated signaling could be beneficial in HF. This review summarizes the theoretical rationale for further development of such therapy, reviews the status of current compounds under development, and suggests key issues that need to be addressed as these agents undergo further clinical testing

Pathophysiology of Heart Failure

Heart failure occurs when the heart is unable to maintain a cardiac output sufficient to satisfy the oxygen requirements of the body despite adequate blood volume and hemoglobin content. Regardless of the initial cause of heart failure and in spite of compensatory mechanisms, patients often follow a course of worsening heart failure that is characterized by a low cardiac output, high filling pressures, and increased peripheral vascular resistance. In addition to persistence of the initiating event, cardiac deterioration may be caused or aggravated by a variety of factors including depletion of cardiac norepinephrine stores, down-regulation of myocardial beta-adrenergic receptors, microvascular spasm with resultant further cellular necrosis, and subendocardial ischemia perpetuating myocardial failure

Chronic exposure to ivabradine reduces readmissions in the vulnerable phase after hospitalization for worsening systolic heart failure: a post-hoc analysis of SHIFT

Aims: During the post-discharge phase following a heart failure hospitalization (HFH), patients are at high risk of early readmission despite standard of care therapy. We examined the impact of chronic exposure to ivabradine on early readmissions in patients hospitalized for heart failure during the course of the SHIFT study (Systolic Heart Failure treatment with the If inhibitor ivabradine Trial). Methods and results: A total of 1186 of the 6505 randomized patients experienced at least one HFH during the study, and had a more severe profile than those without HFH. Of these 1186 patients, 334 patients (28%) were rehospitalized within 3 months for any reason, mostly for cardiovascular causes (86%), including HFH (61%). Ivabradine was associated with fewer all-cause hospitalizations at 1 month [incidence rate ratio (IRR) 0.70, 95% confidence interval (CI) 0.50–1.00, P < 0.05], 2 months (IRR 0.75, 95% CI 0.58–0.98, P = 0.03), and 3 months (IRR 0.79, 95% CI 0.63–0.99, P = 0.04). A trend for a reduction in cardiovascular and HF hospitalizations was also observed in ivabradine-treated patients. Conclusion: We demonstrate in this post-hoc analysis that chronic exposure to ivabradine reduces the incidence of all-cause hospitalizations during the vulnerable phase after a HFH. Further studies are needed to investigate if in-hospital or early post-discharge initiation of ivabradine could be useful to improve early outcomes in patients hospitalized for HF

Geographic variation in heart failure trials: time for scepticism?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107539/1/ejhf112.pd

Abnormal liver function tests in acute heart failure: relationship with clinical characteristics and outcome in the PROTECT study

Aims: Episodes of acute heart failure (AHF) unfavourably affect multiple organs, which may have an adverse impact on the outcomes. We investigated the prevalence and clinical consequences of abnormal liver function tests (LFTs) in AHF patients enrolled in the PROTECT study. Methods and results: The LFTs comprised serial assessment of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and albumin at baseline and during follow-up (daily until discharge, on days 7 and 14). The prevalence of abnormal LFTs (above upper limit of normal for AST and ALT or below lower limit of normal for albumin) was: at baseline AST 20%, ALT 12%, albumin 40%; and at day 14: AST 15%, ALT 9%, albumin 26%. Abnormal LFTs at baseline were associated with a higher risk of in-hospital death with odds ratios [95% confidence interval (CI)] of 3.5 (1.7–7.3) for AST, 3.9 (1.8–8.4) for ALT, and 2.8 (1.3–5.9) for albumin (all P < 0.01). Abnormal baseline and discharge LFTs had an unfavourable impact on 180-day mortality with hazard ratios (95% CI) for baseline AST, ALT, and albumin of 1.3 (1.0–1.7), 1.1 (1.0–1.2), 1.4 (1.1–1.8), respectively, and 1.5 (1.1–2.0), 1.5 (1.0–2.2), and 1.6 (1.2–2.1), for discharge AST, ALT, albumin, respectively (all P < 0.05). Analysis of LFTs trajectories (calculated as changes in LFTs over time) revealed that increasing AST and ALT on day 3 as well as decreasing albumin on day 4 were independent prognosticators of 180-day outcome (all P < 0.05). Conclusions: Abnormal LFTs are frequent in AHF at baseline and during hospital stay and predict worse outcomes. Whether this association is causal and what are the underlying mechanisms involved require further study