Effects on survival of loop diuretic dosing in ambulatory patients with chronic heart failure using a propensity score analysis.

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.

Elevated levels of asymmetric dimethylarginine in chronic heart failure: a pathophysiologic link between oxygen radical load and impaired vasodilator capacity and the therapeutic effect of allopurinol.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide-dependent vasodilation. In 113 patients with chronic heart failure (CHF) and 26 controls, ADMA level was studied in relation to peripheral blood flow and vasodilator capacity. Further, the effects of allopurinol on concentrations of reactive oxygen species (ROS) and ADMA and peripheral vasodilator capacity were tested in a double-blind design. ADMA level was found to be elevated in CHF patients as compared with controls and increased in parallel with New York Heart Association (NYHA) class and exercise capacity (all P < 0.0001). The level of ADMA predicted resting blood flow (P < 0.05) and postischemic vasodilator capacity (P < 0.001). Sixty eight patients died during the follow-up period. The level of ADMA predicted survival after multivariable adjustment (P = 0.04). Allopurinol reduced uric acid (UA) concentration (P < 0.001) and decreased ROS concentration (allantoin, P < 0.01). Allopurinol lowered ADMA concentration (P = 0.02); postischemic vasodilation as well as endothelium-dependent vasodilation (both P < 0.05) improved. ADMA may be a pathophysiologic factor that is modulated by ROS accumulation and contributes to impaired vascular regulation in CHF.

ESPEN Guidelines on Enteral Nutrition: Cardiology and pulmonology.

These guidelines are intended to give evidence-based recommendations for the use of enteral nutrition (EN) in patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD). They were developed by an interdisciplinary expert group in accordance with officially accepted standards and are based on all relevant publications since 1985. They have been discussed and accepted in a consensus conference. EN by means of oral nutritional supplements (ONS) or tube feeding (TF) enables nutritional intake to be maintained or increased when normal oral intake is inadequate. No data are yet available concerning the effects of EN on cachexia in CHF patients. However, EN is recommended to stop or reverse weight loss on the basis of physiological plausibility. In COPD patients, EN in combination with exercise and anabolic pharmacotherapy has the potential to improve nutritional status and function. Frequent small amounts of ONS are preferred in order to avoid postprandial dyspnoea and satiety as well as to improve compliance.

Amino-terminal propeptide of type III procollagen is associated with restrictive mitral filling pattern in patients with dilated cardiomyopathy: a possible link between diastolic dysfunction and prognosis.

OBJECTIVE: To analyse the relation between restrictive mitral pattern, amino-terminal propeptide of type III procollagen (PIIINP), and prognosis in patients with dilated cardiomyopathy. DESIGN: Prospective cohort study of 106 patients with dilated cardiomyopathy. SETTING: Tertiary care centre. MAIN OUTCOME MEASURES: PIIINP concentration, echocardiographic variables, oxygen consumption, hospitalisation for heart failure, and cardiac mortality were evaluated in patients grouped by the presence of non-restrictive (group 1), reversible (group 2), and irreversible restrictive mitral pattern (group 3). RESULTS: Groups differed regarding left ventricular ejection fraction (group 1, mean (SD) 36 (6)%, group 2, 29 (8)%, group 3, 25 (6)%; p = 0.0001), left atrial ejection fraction (group 1, 0.47 (0.1)%, group 2, 0.43 (0.2)%, group 3, 0.26 (0.1)%; p < 0.0001), and PIIINP (p = 0.001). Multivariate analysis showed that PIIINP was related to mitral pattern (odds ratio 0.8, 95% confidence interval 0.23 to 1.4, p = 0.006) independently of left atrial and ventricular ejection fractions. After 21 months, survival was 88% and 34% (p = 0.0001) in patients with non-restrictive and irreversible restrictive mitral patterns, respectively. CONCLUSION: In patients with dilated cardiomyopathy, restrictive mitral pattern is associated with higher PIIINP and worse prognosis.

Leptin, insulin sensitivity and growth hormone binding protein in chronic heart failure with and without cardiac cachexia.

OBJECTIVE: Regulation of growth hormone (GH) receptor expression and hence tissue GH sensitivity may be important for the conflicting results found in treatment studies with recombinant growth hormone in chronic heart failure (CHF). Growth hormone-binding protein (GHBP) corresponds to the extracellular domain of the GH receptor and is closely related to measures of body composition and, specifically, to size of visceral fat tissue. Leptin, the adipocyte specific (ob) gene product, has been proposed as the signal linking adipose tissue and GHBP/GH-receptor expression. CHF has recently been shown to be a hyperleptinaemic and insulin-resistant state regardless of aetiology. This study aimed to examine the influence of leptin on GHBP in CHF patients with and without cardiac cachexia compared with healthy control subjects. METHODS: We studied 47 male patients with CHF (mean age 61+/-2 years, New York Heart Association (NYHA)-class 2.7+/-0.1, left ventricular ejection fraction (LVEF) 28+/-2%, peak oxygen consumption 16.8+/-0.9 ml/kg/min) and 21 male healthy controls of similar age. Of the CHF patients, 19 were cachectic (cCHF; non-oedematous weight loss >7.5% over at least 6 months) and 28 non-cachectic (ncCHF; similar for age and LVEF). Insulin sensitivity was assessed by an intravenous glucose tolerance test using the minimal model approach. RESULTS: Compared with healthy controls, patients had elevated levels of leptin (7.6+/-0.7 vs 4.8+/-0.7 ng/ml, P<0.05), insulin (76.2+/-8.9 vs 41.4+/-6.0 pmol/l, P<0.01), and reduced insulin sensitivity (2.43+/-0.2 vs 3.48+/-0.3 min(-1).microU.ml(-1).10(4), P<0.005) but similar GHBP levels (901+/-73 vs 903+/-95 pmol/l). Leptin levels were increased in ncCHF (9.11+/-1.0 ng/ml, P=0.001) but were not different from normal in cCHF (5.32+/-0.7 ng/ml, P>0.5). After correction for total body fat mass, both ncCHF and cCHF were hyperleptinaemic (41.8+/-3.8 and 37.9+/-0.38 vs 24.4+/-2.1 ng/ml/100 g, ANOVA P=0.001). In both patients and controls there was a direct correlation between leptin levels and GHBP (r=0.70 and r=0.71 respectively, both P<0.0001). This relationship was stronger than between GHBP and several parameters of body composition (body mass index (BMI), total and regional body fat mass or % body fat) and held true when sub-groups were tested individually (ncCHF r=0.62, P<0.001; cCHF r=0.79, P<0.0001). In multivariate regression analysis in all CHF patients, serum leptin levels emerged as the strongest predictor of GHBP, independent of age, BMI, total and regional fat mass or % body fat, fasting insulin level and insulin sensitivity. CONCLUSION: Fat mass corrected leptin levels are elevated in CHF patients with and without cachexia. Reduced total fat mass may account for lower leptin levels in cachectic CHF patients compared with non cachectic patients. Leptin strongly predicts GHBP levels in CHF regardless of its hyperleptinaemic state or severely altered body composition as in cardiac cachexia. Leptin could be the signalling link between adipose tissue and GHBP/GH receptor expression in CHF.

Prognostic implications of evaluation of contractile reserve in akinetic and hypokinetic segments during low dose dobutamine echocardiography in patients with acute myocardial infarction.

BACKGROUND: Previous studies have reported the prognostic value of myocardial viability (MV) detected using low-dose dobutamine echocardiography (DbE). However, viability was frequently evaluated as improvement in regional wall motion score index, which includes increased function in hypokinetic segments, in which viable myocardium is necessarily present. It is not known whether an evaluation focusing on akinetic segments, in which the possible presence of viable myocardium is unknown, might have more prognostic value. The aim of this study was to compare the prognostic value of the improvement of myocardial function during dobutamine infusion in akinetic and hypokinetic regions in patients with acute myocardial infarction (AMI). METHODS: 191 patients with uncomplicated AMI and at least one akinetic segment were retrospectively selected from those consecutively examined at our echo-laboratory to evaluate MV using DbE. Myocardial viability was evaluated both as an increment in RWMSI (Delta RWMSI), which takes into consideration improvement in both akinetic and hypokinetic regions, and as an improvement of function in akinetic (Delta akinetic) and hypokinetic (Delta hypokinetic), segments considered separately. Follow-up evaluation was performed at 30+/-13 months. RESULTS: On the basis of the Delta RWMSI, 94/191 patients were judged to have myocardial viability, whereas considering myocardial viability in akinetic segments only, 72/191 patients showed viability. At follow-up 18 patients had died (six viable considering Delta RWMSI; three viable considering Delta akinetic). The presence of a previous AMI, the site of AMI, RWMSI and the number of akinetic segments, and Delta RWMSI and Delta akinetic were related to mortality at univariate Cox analysis. At multivariate stepwise Cox regression analysis Delta akinetic, but not Delta hypokinetic proved to be significantly related to mortality. The Kaplan-Meier survival curves were no different in patients with or without viable myocardium evaluated as Delta RWMSI, while they were significantly different considering patients with or without viability in akinetic segments (P=0.04). CONCLUSION: In conclusion our study confirms the prognostic importance of the evaluation of myocardial viability in infarcted patients. However, it points out that it is the presence of viability in akinetic segments that affects long-term survival in these patients. This supports the hypothesis that other mechanisms, above and beyond the effect on regional wall motion, are involved in the beneficial effects of myocardial viability.

High tumour necrosis factor-alpha levels are associated with exercise intolerance and neurohormonal activation in chronic heart failure patients.

Immune activation plays an important role in the progression of chronic heart failure (CHF). We sought to investigate whether different degrees of tumor necrosis factor-alpha (TNF-alpha) activation are associated with exercise intolerance, neurohormonal activation and alterations in muscle mass and function in patients with CHF without cardiac cachexia. Patients were divided into quartiles according to their TNF levels (first quartile: 0.98-4.90 pg/ml, second quartile: 5.00-6.60 pg/ml; third quartile 6.80-9.00 pg/ml; fourth quartile 9.80-32.00 pg/ml). Patients underwent cardiopulmonary exercise testing, quadriceps muscle strength test, quadriceps fatigue test, and assessment of thigh muscle and fat cross-sectional area (CSA) by computerized tomography scanning. Patients in the highest TNF quartile had the lowest peak oxygen consumption [13.1 (+/-4.1) ml/kg/min vs 18.1 (+/-5.3), 18.8 (+/-4.8) and 18.7 (+/-5.6) ml/kg/min, P<0.01] the greatest relation of ventilation and dioxide production (VE/VCO(2)) slope (P<0.05) and the most elevated catecholamine levels (P<0.05) compared to patients in the first three quartiles. Patients with the lowest TNF levels had preserved thigh muscle size and quadriceps strength. Strength/muscle CSA was similar in the four groups. Muscle strength during fatigue testing was significantly lower in the fourth quartile (P=0.01) compared with the other three groups. In CHF patients only the highest levels of TNF are associated with poor functional status and neurohormonal activation. This group of patients may represent the appropriate target population for TNF antagonism.

Mitral regurgitation and left ventricular diastolic dysfunction similarly affect mitral and pulmonary vein flow Doppler parameters: the advantage of end-diastolic markers.

Enhanced early mitral flow and reduced systolic pulmonary vein flow may be caused both by increased left ventricular pressure as the result of diastolic dysfunction and by increased transmitral flow as the result of mitral regurgitation. Nevertheless, Doppler parameters are widely used to predict left ventricular filling pressure. We aimed to analyze the interference of mitral regurgitation with Doppler parameters usually used to estimate left ventricular filling pressure and to identify markers independent of mitral regurgitation, which could reliably estimate increased left ventricular filling pressure. Eighty-four patients (age, 62 +/- 9 years; 82% men) had a complete echocardiographic Doppler examination. Transmitral E- and A-wave velocity, E deceleration time and A duration, pulmonary vein systolic and diastolic velocities, and reversal flow duration and maximal and minimal left atrial volumes were measured. The difference between the duration of pulmonary vein and mitral A waves was calculated (A'-A). Mitral regurgitant volume was quantitatively assessed by echocardiography. Left ventricular end-diastolic pressure was measured invasively. Patients had a wide range of left ventricular ejection fraction (14% to 70%), mitral regurgitant volume (0 to 94 mL), and left ventricular end-diastolic pressure (3 to 37 mm Hg). E velocity, E/A, pulmonary vein systolic and diastolic, and systo-diastolic ratios were significantly and independently correlated with both left ventricular end-diastolic pressure and mitral regurgitant volume. A'-A showed a strong correlation with left ventricular end-diastolic pressure (r = 0.70; P <.0001), but the relation with mitral regurgitant volume was not significant (r = 0.19; P =.08). Mitral regurgitation affects the majority of Doppler parameters widely used to predict filling pressure but does not influence Ad'-Ad, which proved to be the strongest predictor of left ventricular end-diastolic pressure.

Chronic heart failure in the very elderly: clinical status, survival, and prognostic factors in 188 patients more than 70 years old.

BACKGROUND: Chronic heart failure (CHF) is a frequent disease with a dismal prognosis, but little is known about survival in the very elderly. There are no data on the prognostic value of cardiopulmonary exercise testing in this population. We aimed to assess exercise capacity, survival, and prognostic parameters in elderly patients with CHF. METHODS: We evaluated 188 patients with CHF >70 years old (mean 77 +/- 4 years, range 70-94 years) seen at our heart failure clinic between March 1992 and June 1998. A cardiopulmonary exercise test was performed in 102 patients (peak VO2 15.3 +/- 4.7, VE/VCO2 slope 39.6 +/- 15.01). All patients were followed up for at least 12 months. The prognostic end point of the study was all-cause mortality. RESULTS: At the end of follow-up (16 +/- 10 mo, range 12-41 mo), 67 patients (35.6%) had died (1-year mortality rate 26% [95% confidence interval 20-32]). In univariate analysis New York Heart Association class (NYHA) (relative risk [RR] = 2.56, P <.0001), VE/VCO2 (RR = 1.041, P <.0001), peak VO2 (RR = 0.87, P =.0007), and fractional shortening (RR = 0.95, P <.0001) predicted mortality. Peak VO2 predicted mortality independently of age, NYHA class, and left ventricular ejection fraction. A subgroup of 12 patients with dynamic left ventricular outflow tract obstruction during stress had an excellent outcome, with a 100% survival at the end of follow-up (mean 16 +/- 7 mo, range 12-39 mo). CONCLUSIONS: The prognosis in elderly patients with CHF is poor. Valid exercise testing results can be obtained in more than 50% of elderly patients with CHF. NYHA class and peak VO2 are the strongest prognostic factors in this population.

Failure of aldosterone suppression despite angiotensin-converting enzyme (ACE) inhibitor administration in chronic heart failure is associated with ACE DD genotype.

OBJECTIVES: The objective of this study was to assess whether the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism influences the adequacy of the neurohormonal response to ACE inhibitors in patients with chronic heart failure (CHF). BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathophysiology of CHF, and aldosterone levels closely relate to outcome in patients with CHF. Angiotensin-converting enzyme inhibitors suppress the RAAS, but a significant proportion of patients exhibit elevated serum levels of aldosterone despite long-term administration of apparently adequate doses of these agents. METHODS: We prospectively studied 132 patients with CHF (ejection fraction <45%) receiving long-term therapy with ACE inhibitors for over six months. Patients taking aldosterone antagonists were excluded from the study. "Aldosterone escape" was defined as being present when plasma aldosterone levels were above the normal range in our laboratory (>42 nmol/L). Patients were then divided into two subgroups according to the presence (group 1) or absence (group 2) of aldosterone escape. Genotype analysis for the ACE I/D polymorphism was performed by polymerase chain reaction. RESULTS: The prevalence of aldosterone escape in our patients was 10% (13/132). The two groups of patients did not differ regarding the dose of ACE inhibitor, diuretics and their renal function. There was a statistically significant different distribution of genotypes between the two groups, with a higher proportion of DD genotype in group 1 compared with group 2 (62% vs. 24%, p = 0.005). CONCLUSIONS: Patients with CHF with aldosterone escape have a higher prevalence of DD genotype compared with patients with aldosterone within the normal limits. Angiotensin-converting enzyme gene polymorphism contributes to the modulation and adequacy of the neurohormonal response to long-term ACE-inhibitor administration in CHF.

Skeletal muscle mass independently predicts peak oxygen consumption and ventilatory response during exercise in noncachectic patients with chronic heart failure.

OBJECTIVES: We sought to assess whether skeletal muscle mass might be a predictor of peak oxygen consumption (Vo2) and relation of the ventilation to carbon dioxide production (VE/VCo2) slope in patients with chronic heart failure (CHF) independent of clinical conditions, neurohormonal activation and resting hemodynamics. BACKGROUND: A variety of abnormalities characterize skeletal muscle and contribute to exercise intolerance in patients with CHF. Skeletal muscle mass is a determinant of peak Vo2 both in healthy patients and in patients with CHF, but there are no reports on the independent predictive value of this parameter, which can be measured with great accuracy by whole-body dual energy X-ray absorptiometry (DEXA). The influence of skeletal muscle mass on VE/VCo2 slope is not known either. METHODS: We prospectively evaluated 120 consecutive noncachectic patients with CHF. Every patient underwent a cardiopulmonary exercise test, an echo-Doppler examination and an evaluation of neurohormonal activation and body composition as assessed by DEXA. RESULTS: At the univariate analysis, New York Heart Association (NYHA) class (p < 0.0001), age (p < 0.0001), male gender (p < 0.0001) and plasma renin (p < 0.0001) significantly related with peak Vo2. There was a significant correlation between lean mass and absolute peak Vo2 (r = 0.70, p < 0.0001) and VE/VCo2 slope (r = -0.27; p < 0.01). At the multivariate analysis, lean mass predicted peak Vo2 and VE/VCo2 slope independently of NYHA functional class, age, gender, neurohormonal activation and resting hemodynamics. CONCLUSIONS: Skeletal muscle mass is an independent predictor of peak Vo2 and VE/VCo2 slope in stable noncachectic patients with CHF. Future studies will determine whether an increase in skeletal muscle mass in the individual patient might result in an improvement in parameters of exercise capacity.

Frequency, prognosis and predictors of improvement of systolic left ventricular function in patients with 'classical' clinical diagnosis of idiopathic dilated cardiomyopathy.

In patients with dilated cardiomyopathy (DCM) of different aetiologies, a variable frequency of improvement in the left ventricular (LV) systolic function has been reported, while in patients with a 'classic' idiopathic DCM, the frequency of improvement is still under debate, and clinical and haemodynamic predictors of recovery of the LV function are needed. The aim of the present study was to determine the frequency of improvement in the LV systolic function in idiopathic DCM and to identify predictors of reversibility of the impaired LV contractility. A sample of 98 consecutive patients with idiopathic DCM was retrospectively evaluated. Echocardiographic and Doppler measurements were directly taken from the routine echo-report. LV systolic function was assessed semiquantitatively using a score index (SFSI). According to the improvement in the LV systolic function, the patients were divided into group 1 patients with improvement, and group 2 patients without improvement. During a follow-up of at least 12 months, 19 patients (19%) showed an improvement, with a significant increase in the mean SFSI; all these group 1 patients survived without heart transplant; in group 2, 18 patients (23%) died and 3 (4%) received a heart transplant. Patients in group 1 had a significantly shorter duration of symptoms (P=0.0045), a younger age (P=0.006), a shorter DtE (P=0.04), a lower SFSI (P<0.01), a worse NYHA class (P<0.001) and more frequently had a history of hypertension (P<0.0001). The same variables were significant predictors of improvement at the univariate analysis. At the multivariate logistic regression analysis, a shorter duration of symptoms (P=0.02), a history of hypertension (P=0.003), and a worse NYHA class (P=0.01) were independent predictors of improvement. A relatively large percentage of patients with an idiopathic DCM will have a marked improvement in the LV systolic function. This is more likely to happen in the presence of a short duration of symptoms and a history of hypertension. After an improvement, the prognosis is excellent.

Relationship between mitral regurgitation and myocardial viability after acute myocardial infarction: their impact on prognosis.

Mitral regurgitation (MR) after acute myocardial infarction (AMI) is an important prognostic factor. Although its mechanisms are still debated, ventricular remodeling probably plays an important role. Because myocardial viability (MV) in the infarct zone reduces infarct expansion and ventricular remodeling, it is also possible that its presence counteracts the development of mitral regurgitation in infarcted patients. To evaluate this issue 191 patients with uncomplicated AMI, wall motion abnormalities (akinesis) and semiquantitative evaluation of MR were retrospectively selected from those consecutively examined at our echo-laboratory to evaluate MV using low-dose dobutamine echocardiography (DbE). Follow-up evaluation was performed at 30+/-13 months. Seventy-nine patients had no MR; 86 patients had grade 1 MR, 11 patients had grade 2 MR, nine patients had grade 3 MR, and six patients had grade 4 MR. Patients with significant MR (>grade 1) were older (63+/-7 vs. 59+/-10 years, P=0.03), had lower reduction of RWMSI (DeltaRWMSI) during DbE (0.08+/-0.11 vs. 0.22+/-0.28, P=0.01), more stenotic vessels at coronary angiography (2.35+/-0.93 vs. 1.67+/-1.12, P=0.01), and more frequently had anterior-inferior AMI (P<0.0001); they also had a non-significant tendency to higher RWMSI (2.04+/-0.38 vs. 1.92+/-0.28, P=0.06). In a multivariate regression analysis, DeltaRWMSI proved to be significantly related to the grade of MR (P=0.02). Eighteen patients died during follow-up. Death was more frequent in patients with MR (10/165 vs. 8/26, P=0.0003). At multivariate stepwise Cox regression analysis both the extent of ventricular dysfunction and the presence of MR were significantly related to mortality (P<0.0001 and P=0.01, respectively); DeltaRWMSI showed a non-significant tendency to influence mortality (P=0.09). When MR was excluded from the multivariate analysis, DeltaRWMSI remained significantly related to mortality (P=0.05). In conclusion our study suggests that the presence of MV in infarcted patients influences the development of MR. This reduction of MR may be one of the mechanisms by which MV affects mortality after AMI and should be considered in all studies that evaluate MV after myocardial infarction.

Additional value of pulmonary vein parameters in defining pseudonormalization of mitral inflow pattern.

BACKGROUND: An echocardiographic assessment of left ventricular (LV) diastolic dysfunction is still challenging when identifying a pseudonormal mitral pattern (PSE) in an unselected population. The present study analyzed and compared the accuracy of various parameters in correctly identifying a PSE pattern in patients with a broad range of ejection fraction (EF) and degree of mitral regurgitation. METHODS: Eighty-two patients with E/A > or = 1 and an invasive determination of left ventricular end-diastolic pressure (LVEDP) were enrolled in the study. Mitral E wave (E(max)) and A (A(max)) velocities, E (DTe) and A (DTa) deceleration times, pulmonary vein systolic and diastolic velocities, and time velocity integrals were measured. The different duration between mitral and pulmonary vein A wave (A'-A) also was calculated. E(max) and E/A during Valsalva maneuver were measured and expressed as percentage compared with baseline. LV end-diastolic (LVD), end-systolic (LVS), and EF were measured from the apical four-chambers view (area-length method). Left atrial end-systolic (LA(max)) and end-diastolic (LA(min)) were measured from the apical four- and two-chambers views (area-length method). Left atrial filling volume (LA(fill)) was the difference between LA(max) and LA(min). Mitral regurgitant volume was estimated by the following equation: MR(vol) = 6.18 + (1.01 * LA(fill)) - (0.783 * PVs %). RESULTS: Thirty-two patients (age: 55 +/- 21 years; 75% male) had LVEDP < or = 18 mmHg and were classified as normal mitral pattern (Group 1). Fifty patients (age: 57 +/- 22 years; 76% male) had LVEDP > 18 mmHg, and were classified accordingly as having PSE (Group 2). At logistic univariate analysis, DTa (0.005), LV EF (0.01), A'-A (< 0.0001) and % E/A (0.03) were the more powerful predictors of PSE. A'-A had the highest global accuracy in identifying PSE in patients with reduced (90%) and normal (88%) LV EF. CONCLUSION: A'-A has the highest accuracy in identifying PSE in an unselected population. This parameters should be implemented in routine echocardiography since it allows additional information about LV diastolic function assessment.

Left atrial overload can be used to estimate mitral regurgitant volume.

This study was conducted to assess the accuracy of the estimated mitral regurgitant volume using both the left atrial filling volume and the systolic component of pulmonary vein flow expressed as the percent of its total. Since mitral regurgitation fills the left atrial chamber, the variation in atrial volume during ventricular systole has been proposed as a means to evaluate the severity of regurgitation. Although the correlation with invasive grading of mitral regurgitation is good, there is an unacceptable overlap among grades caused by the absence of information concerning pulmonary vein flow, which enters the left atrium while regurgitation occurs. The Doppler regurgitant volume, or Dp-RVol (mitral stroke volume minus aortic stroke volume) was quantified in 74 patients with any degree and etiology of mitral regurgitation. Atrial volumes were measured from the four-chamber apical view (biplane area-length method). The systolic time-velocity integral of pulmonary vein flow was expressed as the percent of the total (PVs%) (systolic-diastolic) time-velocity integral. These parameters were subjected to multivariate analysis and a regression equation was obtained. The equation was subsequently applied to a group of 31 patients without mitral regurgitation, as evaluated by color Doppler or continuous-wave Doppler and to the overall population (105 patients) in order to estimate the mitral regurgitant volume. In 74 patients with mitral regurgitation, the Doppler regurgitant volume was univariately correlated with the left atrial filling volume (r= 0.74; p<0.0001) and the systolic pulmonary vein velocity integral expressed as the percent of the total (r=0.67; p<0.0001). In multiple regression analysis, the combination of atrial filling and the pulmonary vein velocity integral provided the more accurate estimation of the regurgitant volume (R2=0.84; standard error of the estimate [SEE], 13.9 mL; p<0.0001; Dp-RVol equals 7.84+[1.08*left atrial filling volume] 2 [0.839*PVs%]). In 31 patients with no mitral regurgitation detected by color Doppler or continuous wave Doppler the estimated regurgitant volume was 4.3±6.6 mL. In the overall population the estimated regurgitant volume and the Doppler regurgitant volume correlated well with each other (R2=0.85; SEE, 11.5 mL; p<0.0001). The equation was 100% sensitive and 98% specific in detecting a regurgitant volume higher than 55 mL. The combination of the atrial filling volume and the systolic pulmonary vein time-velocity integral expressed as the percent of the total allows reliable estimation of the regurgitant volume in patients with mitral regurgitation. (c)2001 CHF, Inc.

Role of growth hormone in chronic heart failure: therapeutic implications.

Chronic heart failure is a multi-etiological cardiovascular disorder with high prevalence and poor prognosis. Medical treatment of dilated cardiomyopathy is aimed at alleviating heart failure symptoms. Diuretics, angiotensin-converting enzyme (ACE) inhibitors and very recently, beta-blockers have been shown to have favorable effects on symptoms, exercise capacity and mortality. Growth hormone (GH) and insulin-like growth factor (IGF)-1 are involved in several physiological processes such as the control of muscle mass and function, body composition and regulation of nutrient metabolism. The role of GH and IGF-1 as modulators of myocardial structure and function is well established. Receptors for both GH and IGF-1 are expressed by cardiac myocytes; therefore, GH may act directly on the heart or via the induction of local or systemic IGF-1, while IGF-1 may act by endocrine, paracrine or autocrine mechanisms. Patients with acromegaly have an increased propensity to develop ventricular hypertrophy and cardiovascular diseases; impaired cardiac efficiency can also be observed in patients with GH deficiency. Animal models of pressure and volume overload have demonstrated up-regulation of cardiac IGF-1 production and expression of GH and IGF-1 receptors, implying that the local regulation of these factors is influenced by hemodynamic changes. Moreover, experimental studies suggest that GH and IGF-1 have stimulatory effects on myocardial contractility, possibly mediated by changes in intracellular calcium handling. Heart failure is due to ventricular dilation with inadequate wall thickening that leads to impaired cardiac performance; therefore, based on previous evidence we would expect beneficial effects from the use of GH in these patients. Several papers have highlighted the positive influence of GH in the regulation of heart development and performance. In patients with GH deficiency, GH administration dramatically improves cardiac function. In small open studies, acute and chronic GH treatment has demonstrated beneficial effects in patients with heart failure due to ischemic or idiopathic cardiomyopathy. Recently, two randomized, placebo-controlled studies did not show any significant GH-mediated improvement in cardiac performance in patients with dilated cardiomyopathy, despite significant increases in IGF-1. Acquired GH resistance might be an important feature of severe heart failure and explain the diverse responses to GH therapy observed in different patients. Whether GH treatment will finally find a place in the treatment of heart failure, and with which modalities, remains to be established.

Role of growth hormone in chronic heart failure. Therapeutic implications.

Congestive heart failure is a multiple aetiology, high prevalence, poor prognosis cardiovascular disorder. Medical treatment of dilated cardiomyopathy is aimed at alleviating the symptoms of heart failure. Diuretics, ACE inhibitors and very recently, beta-blockers have been shown to have favourable effects on symptoms, exercise capacity and mortality. Growth hormone (GH) and insulin-like growth factor (IGF)-1 are involved in several physiological processes such as the control of muscle mass and function, body composition and regulation of nutrient metabolism. The roles of GH and IGF-1 as modulators of myocardial structure and function are well established. Receptors for both GH and IGF-1 are expressed by cardiac myocytes; therefore, GH may act directly on the heart or via the induction of local or systemic IGF-1, whereas IGF-1 may act by endocrine, paracrine or autocrine mechanisms. Patients with acromegaly have an increased propensity to develop ventricular hypertrophy and cardiovascular diseases and, in addition, an impaired cardiac efficiency is observed in patients with GH deficiency. Animal models of pressure and volume overload have demonstrated up-regulation of cardiac IGF-1 production and expression of GH and IGF-1 receptors, implying that the local regulation of these factors is influenced by haemodynamic changes. Moreover, experimental studies suggest that GH and IGF-1 have stimulatory effects on myocardial contractility, possibly mediated by changes in intracellular calcium handling. Heart failure is caused by ventricular dilatation with abnormal wall thickening, which leads to impaired cardiac performance; therefore, based on the evidence available for GH we would expect beneficial effects from the use of GH in these patients. Several papers highlight the positive influence of GH in the regulation of heart development and performance. In patients with GH deficiency, GH administration dramatically improves cardiac function. In small nonblind studies, both short and long term GH treatment have demonstrated beneficial effects in patients with heart failure secondary to ischaemic or idiophatic cardiomyopathy. Recently, two randomised, placebo-controlled studies, did not show significant GH-mediated improvement in cardiac performance in patients with dilated cardiomyopathy, despite significant increases in IGF-1. Acquired GH resistance, might be an important feature of severe heart failure and explain the different responses to GH therapy seen in different patients. Whether GH treatment will finally find a place, and with which modalities, in the treatment of heart failure remains to be established.

Echocardiographic determinants of mortality in patients >67 years of age with chronic heart failure.

This study sought to assess the prognostic significance of echocardiographic measurements of left and right ventricular dimensions and function in patients >67 years of age with chronic congestive heart failure (CHF). This is a retrospective follow-up of elderly patients who underwent an echocardiography in the tertiary cardiac center. A total of 185 patients (131 men) aged >/=68 years (mean +/- SD 75 +/- 5) with CHF were enrolled into the study. After undergoing a detailed echocardiographic examination, all patients were followed-up for a median of 20 months (interquartile range 9 to 36). During the follow-up period 54 patients (29%) died. Left ventricular (LV) M-mode isovolumic relaxation time (IVRT), end-diastolic and end-systolic diameters, fractional shortening and mass, transmitral E:A ratio, and left atrial dimension, as well as New York Heart Association class and the age were found by Cox proportional-hazards univariate analyses to predict the outcome in these patients (all p <0.05). In multivariate analyses including these measurements, LV IVRT (p <0.04), age (p <0.03), and New York Heart Association class (p <0.001) were found to be the independent predictors of outcome. In the Kaplan-Meier analysis, patients with LV IVRT >30 ms had a better prognosis at 3 years (cumulative survival 78% [95% confidence interval 65% to 91%]) than those with LV IVRT 67 years of age with CHF. LV M-mode IVRT is among the most important independent predictors of outcome in this population.

Long-term prognostic value of the stenosis of the infarct-related artery and the presence of viable myocardium in akinetic ventricular regions in infarcted patients.

BACKGROUND: Recent studies have reported that adequate perfusion of the infarct-related artery improves survival in patients with myocardial infarction, independently of left ventricular pump function. However, it is not known whether or not this reduction in mortality is independent of myocardial viability within the infarct zone. The aim of this study was to evaluate the prognostic value of the patency of the infarct artery and the presence of myocardial viability in akinetic regions in patients with myocardial infarction. METHODS: Low-dose dobutamine echocardiography was performed in 154 patients with recent or previous myocardial infarction and known coronary anatomy. In each patient three vascular regions were defined. Each akinetic region was considered viable if function improved during dobutamine echocardiography, and irrorated by a not stenotic akinetic area-related artery if the supplying vessel had a stenosis < 75% or had been successfully revascularized within 1 month of dobutamine echocardiography. RESULTS: At follow-up of 34 +/- 14 months, 19 patients died of cardiac death. At univariate Cox analysis end-diastolic and end-systolic volumes, ejection fraction, previous myocardial infarction, regional wall motion score index, and stenosis of the akinetic area-related artery were related to mortality. At multivariate analysis, stenosis of the akinetic area-related artery remained a significant predictor of mortality (p = 0.04), with higher mortality (13/66 vs 6/88, p = 0.02) in patients with a stenotic akinetic area-related artery, without differences in ejection fraction (35 +/- 9 vs 34 +/- 10%). Mortality was lower in patients with myocardial viability if they had a not stenotic akinetic area-related artery (1/43 vs 4/21, p = 0.02), while no difference was found among non-viable patients, with or without stenosis of the akinetic area-related artery (5/45 vs 9/45). CONCLUSIONS: The present study confirms the prognostic role of the patency of the infarct-related artery. However, it suggests that the lower mortality in patients with a patent artery supplying akinetic infarcted regions is related to the presence of myocardial viability in these regions.

Chronic heart failure and cardiac cachexia and links between the endocrine and immune systems.

Body wasting, i.e., cachexia, is seen in a variety of chronic illnesses, including also heart failure. Chronic heart failure (CCHF) is a complex syndrome affecting many body systems. There are a variety of interactions between the endocrine and the immune systems. The abnormalities seen in patients with cachexia in CHF, i.e., in patients with cardiac cachexia, are discussed to illustrate some links between these regulatory systems.The available evidence suggests that cardiac cachexia is a multifactorial neuroendocrine and metabolic disorder with a poor prognosis. Comparing the features of cachectic and non-cachectic CHF patients to those of healthy subjects, it is mainly the cachectic patients who show raised plasma levels of catecholamines, cortisol, aldosterone and tumor necrosis factor-α, and the highest plasma renin activity. Patients with cardiac cachexia may also suffer from anabolic deficiency. The development of a condition of catabolic/anabolic imbalance is suggested as the key abnormality for the development of cardiac cachexia.