Left atrial function: bridge to central and hormonal determinants of exercise capacity in patients with chronic heart failure.

UNLABELLED: The stroke volume response to exercise is a critical determinant in meeting peripheral metabolic demands in patients with chronic hear failure. The Left atrium, by its position, is important in coupling right and left ventricles, to left preload reserve and to modulate sympathetic activity. We performed this study to investigate the relationship between exercise capacity and diastolic and systolic left atrium function in patients with chronic heart failure. METHODS: We considered 128 consecutive patients with severe chronic heart failure (EF < 35%) due to ischemic or idiopathic dilated cardiomyopathy. Cardiac output, right atrial pressure, pulmonary artery pressures and mean pulmonary wedge pressure (A, X, V, Y wedge pressures) were determined during right cardiac catheterization. By Echocardiography evaluation, we measured atrial pressures and volume during early and late left atrial systolic filling and we calculated left atrial chamber stiffness by this equation P = A*eKV1. (P = left atrial pressure; A = elastic constant (mmHg*ml); e = the base of the natural logarithm; V1 = left atrial volume (ml); K = left atrial chamber stiffness constant (ml-1) = ln (V/X)/(maximal--minimal left atrial volumes)). All patients performed cardiopulmonary exercise test with modified Noughton protocol. Plasma norepinephrine and Atrial natriuretic factor levels were determined. RESULTS: Maximal and minimal left atrial volumes were inversely related to oxygen consumption (r = -.44, p < .001; r = -.61, p < .001). At rest, no differences were found in plasma norepinephrine concentrations (309 +/- 152 pg/ml vs 309 +/- 394 pg/ml; p = ns) and systemic vascular resistance (1706 +/- 435 vs 1771 +/- 524 dynes/cm sec-5; p = ns) in patients with large or normal left atrial volumes. During exercise the chronotropic response increased less in patients with large atrial volumes (56 +/- 13 vs 45 +/- 14; p = .001). The left atrial chamber stiffness constant was inversely related to peak oxygen consumption and exercise time. Patients with different chamber stiffness showed statistical difference in peak VO2 (16 +/- 4 vs 11 +/- 3 ml/kg/min; p = .0001). Left atrial ejection fraction was directly related to peak oxygen consumption (r = 0.55), but the most strongly correlation was with atrial filling fraction (r = .67). CONCLUSIONS: This study demonstrates a strong relationship between left atrial function and exercise capacity in patients with chronic heart failure.

Echo-Doppler mitral flow monitoring: an operative tool to evaluate day-to-day tolerance to and effectiveness of beta-adrenergic blocking agent therapy in patients with chronic heart failure.

OBJECTIVES: The goals of this study were: 1) to assess the predictive value of baseline mitral flow pattern (MFP) and its changes after loading manipulations as regards tolerance to and effectiveness of beta-adrenergic blocking agent treatment in patients with chronic heart failure (CHF); and 2) to analyze the prognostic implications of chronic MFP modifications after beta-blocker treatment. BACKGROUND: In patients with CHF, carvedilol therapy induces clinical and hemodynamic improvements. Individual management, clinical effectiveness and prognostic implications, however, remain unclear. The MFP changes induced by loading manipulations provide independent prognostic information. METHODS: Echo-Doppler was performed at baseline and after loading manipulations in 116 consecutive patients with CHF (left ventricular ejection fraction: 25 +/- 7%); 54 patients with a baseline restrictive MFP were given nitroprusside infusion; 62 patients with a baseline nonrestrictive MFP performed passive leg lifting. According to changes in MFP, we identified four groups: 17 with irreversible restrictive MFP (Irr-rMFP), 37 with reversible restrictive MFP (Rev-rMFP), 12 with unstable nonrestrictive MFP (Un-nrMFP) and 50 with stable nonrestrictive MFP (Sta-nrMFP). Carvedilol therapy (44 +/- 27 mg) was administered blind to results of loading maneuvers. After six months, MFP was reassessed and patients reclassified according to chronic MFP changes. During follow-up, tolerance to and effectiveness of treatment and major cardiac events (death, readmission and urgent transplantation) were considered. RESULTS: Changes of MFP after loading manipulations were more accurate than baseline MFP in predicting both tolerance to (p < 0.01) and effectiveness of (p < 0.05) carvedilol. After 26 +/- 14 months of follow-up, cardiac events had occurred in 23/102 patients (23%). The event rate in patients with chronic Irr-rMFP or Un-nrMFP was markedly higher than it was in those with Rev-rMFP or Sta-nrMFP. CONCLUSIONS: In our patients, tolerance to and effectiveness of carvedilol was predicted better by echo-Doppler MFP changes after loading manipulations than by baseline MFP. Chronic changes of MFP after therapy are strong predictors of major cardiac events.

Chronic infusion of dobutamine and nitroprusside in patients with end-stage heart failure awaiting heart transplantation: safety and clinical outcome.

BACKGROUND: in patients with severe heart failure additional therapeutic support with intravenous inotropic or vasodilator drugs is frequently employed in an attempt to obtain hemodynamic and clinical control. No data comparing the use and efficacy of chronic intravenous inotropic and vasodilator therapy in patients with advanced heart failure are available. AIMS: we evaluated, in a group of patients with advanced heart failure undergoing chronic infusion with dobutamine or nitroprusside, in addition to optimized oral therapy, (1) the safety of chronic infusion, (2) the efficacy of both drugs in managing unloading therapy and (3) clinical outcome of the two therapeutic strategies. METHODS: one hundred and thirteen patients receiving optimized oral therapy, in functional class III/IV with symptoms and signs of refractory heart failure and requiring additional pharmacological support with either intravenous dobutamine or nitroprusside were evaluated. Clinical and therapeutic management and clinical outcome of the two groups were considered. RESULTS: dobutamine was administered for 12 h/day for 20+/-23 days at a dosage of 7+/-3 microg/kg/min to 43 patients. The mean dose of nitroprusside was 0.76+/-0.99 microg/kg/min. The mean duration of use of this drug, administered as a 12-h/day infusion was 22+/-38 days. Nitroprusside infusion allowed greater doses of short-term ACE-inhibitors to be used compared to pre-infusion (ACE-inhibitor dose: 55+/-30 mg/day vs. 127+/-30 mg/day P<0.0001) and during dobutamine infusion (ACE-inhibitor dose: 85+/-47 mg/day vs. 127+/-30 mg/day P<0.002). Nitroprusside unlike dobutamine significantly improved the NYHA functional class. Of the 113 patients, 109 (97%) had a cardiac event during a mean follow-up of 337+/-264 days. Forty-four patients required hospitalization for worsening congestive heart failure, 45/113 (39%) patients died during the follow-up and 27/113 (24%) patients had a heart transplant in status one. Hospitalization, because of worsening heart failure was less frequent in the nitroprusside than in the dobutamine subgroup [29/51 (57%) vs. 19/22 (86%) P<0.02]. The overall mortality was 28% (20/70) in the nitroprusside group and 58% (25/43) in the dobutamine group (odds ratio 0.33 CI 0.16 to 0.73 P<0.006). In the group treated with nitroprusside, heart transplantation in status one was performed in 16/33 patients (48%), while in the dobutamine group this was done in 11/14 patients (78%) (odds ratio 0.25 CI 0.06-1.02 P<0.06). There was a significant reduction in the combined end-point of mortality/heart transplantation in status one in patients treated with nitroprusside compared to those treated with dobutamine (36/70 (51%) vs. 36/43 (84%) - (odds ratio 0.34 CI 0.14-0.80 P<0.01). The incidence of adverse events in the patients treated with nitroprusside was similar to that in those treated with dobutamine (20% vs. 17% P=ns). CONCLUSIONS: for patients awaiting heart transplantation chronic intermittent nitroprusside infusions are more effective and safer than dobutamine in relieving symptoms, facilitating unloading therapy management and improving survival. Whether chronic intermittent infusion of nitroprusside could represent a feasible medical strategy in out-patients with severe heart failure remains to be investigated.

[Rehabilitation day-hospital of the heart failure unit: structure and functions]. / Day-hospital riabilitativo nell'Unità per lo Scompenso Cardiaco: strutturazione e funzione.

Chronic heart failure has emerged as an important public health problem. The consequent increase in the sanitary services has induced an increased consumption of financial resources and conditioned the need to investigate new sanitary models that guarantee, by integrating the inpatient and outpatient health care delivery, the continuity of health assistance. Cardiac rehabilitation in the context of a day-hospital Heart Failure Unit allows for the organization of a rehabilitation program including various health approaches aimed at guaranteeing a multidisciplinary program and the relief continuity. This article describes the experience developed in the Heart Failure Unit of Montescano.

Six-minute walking performance in patients with moderate-to-severe heart failure; is it a useful indicator in clinical practice?

AIMS: The 6-min walk test has been incorporated into studies on the efficacy of new therapies and into prognostic stratification for chronic heart failure patients. Firm conclusions on the usefulness of the test in clinical practice are still lacking. The aim of this study was to investigate (1) the correlation between walk test performance and standard indices of cardiac function and exercise capacity, and (2) the prognostic value of the walk test with respect to peak VO2 and NYHA class. METHODS AND RESULTS: Three hundred and fifteen chronic heart failure patients (age: 53+/-9 years, NYHA class: II (182), III (133)) underwent a functional evaluation and a 6-min walk test. Of these, 270 were followed-up for a minimum of 6 months (mean 387+/-177 days). Walked distance was 396+/-92 m. There was no significant correlation between distance walked and central haemodynamic data. Functional capacity, as measured by ergometry, correlated moderately with distance walked (duration: r=0.48, peak VO2: r=0.59, anaerobic threshold: r=0.54; all P<0.001). During follow-up, 46 patients died from cardiovascular causes and 12 were urgently transplanted. Either of these events were considered end points of the study. Survival analysis was performed from a continuous walk test and peak VO2 measurements or after categorization of (a) quartile segmentation, (b) cut-off points from the literature and (c) thresholds from receiver operating characteristic curves. At univariate survival analysis (Cox regression), the association of the walk test with survival was of significance (P=0.03, continuous variable), or borderline significance (0.05< or =P< or =0.1, after categorization). Peak VO2 was always significant, independent of the scale used (0.005< or =P< or =0.03). The strongest association was found for NYHA class (P<0.001), which showed the highest sensitivity and specificity for the prediction of the event (0.64 and 0.65, respectively). When walk test performance, continuous or categorized, was entered into a multivariate model with NYHA class or peak VO2, it lost any significant association with survival (P>0.76 in all models with NYHA class and P>0.27 in all models with peak VO2). CONCLUSION: In moderate-to-severe chronic heart failure patients, the 6-min walk test is not related to cardiac function and only moderately related to exercise capacity. Walking performance does not provide prognostic information which can complement or substitute for that provided by peak VO2 or NYHA class. Hence the test is of limited usefulness as a decisional indicator in clinical practice.

Non-invasive estimation of right atrial pressure by combined Doppler echocardiographic measurements of the inferior vena cava in patients with congestive heart failure.

BACKGROUND: In patients with congestive heart failure, evaluation of right atrial pressure (RAP) provides useful therapeutic, functional and prognostic information. The aim of this study was to investigate whether a combination of inferior vena cava variables measured by Doppler echocardiography could provide a reliable non-invasive estimate of RAP. METHODS: One hundred consecutive patients with severe congestive heart failure (ejection fraction 24 +/- 6%) due to dilated cardiomyopathy were evaluated by simultaneous Doppler echocardiography and hemodynamic studies. RAP, end-expiratory (IVCDmax) and end-inspiratory (IVCDmin) diameters of the inferior vena cava, its collapse index [CIIVC = (IVCDmax - IVCDmin/IVCDmax)*100] and systolic fraction of forward inferior vena cava flow were measured and correlated by both single and multilinear regression analysis. The accuracy of generated equations was tested in a separate testing group of 61 patients at baseline and a subgroup of 20 patients after loading manipulations, prospectively studied in the same methodological setting. RESULTS: All Doppler echocardiographic variables were correlated with RAP. The IVCDmin showed the strongest correlation (r = 0.84, p < 0.0001). Stepwise regression analysis identified two equations for predicting RAP: 1) RAP = (6.4*IVCDmin + 0.04*CIIVC - 2) (r = 0.82, p < 0.0001, SEE 1.7 mmHg) in all patients, and 2) RAP = (4.9*IVCDmin + 0.01*CIIVC - 0.2) (r = 0.92, p < 0.0001, SEE 1.2 mmHg) in patients without tricuspid regurgitation. In the testing group estimated and measured RAP was strongly correlated at baseline (r = 0.95, SEE 1.3 mmHg, p < 0.00001) and after loading manipulations (r = 0.96, SEE 1.2 mmHg, p < 0.00001). The agreement between invasive and non-invasive measurements of RAP in identifying patients with normal (< or = 5 mmHg), moderately increased (< 5 RAP < 10 mmHg) and markedly increased (> or = 10 mmHg) RAP was 81 or 93% using equation 1 or 2, respectively. CONCLUSIONS: Our results provide evidence that in patients with congestive heart failure indices derived from Doppler measurements of the inferior vena cava can be used to produce an accurate, strong and non-invasive estimate of RAP. This is another example of the usefulness of Doppler echocardiography in evaluating hemodynamic profile and its changes in patients with congestive heart failure. Echocardiographic assessment of the inferior vena cava should be included in the evaluation of patients with congestive heart failure.

Does in-patient ECG monitoring have an impact on medical care in chronic heart failure patients?

BACKGROUND: Heart failure patients' management in non-intensive care units might be improved by telemetry monitoring. However, telemetry adds the cost and evidence of this effectiveness is not available. AIM: To evaluate the utility of the ECG monitoring in chronic heart failure patients admitted to a non-intensive care unit. METHODS: A prospective analysis of the utility of telemetry in 711 patients admitted to a Heart Failure Unit from March 1996 to September 1997. RESULTS: One hundred and ninety-nine patients underwent telemetry; 108 telemetry findings were recorded, in 35% of NYHA class II, in 46% in NYHA class III-IV and 43% in unstable patients. Reasons for telemetry were: known arrhythmia (n=82), electrolytes disturbances (n=20), atrial fibrillation (n=12), symptoms (n=48), i.v. dobutamine (n=13), drugs control (n=16), devices control (n=8). Crossing reasons for telemetry and detected events we had, respectively, 63, 11, 2, 17, 5, 6, and 0 telemetry findings. Treatment was guided by telemetry results in only 33 cases (respectively in 18, 0, 4, 5, 5, 1, and 0 cases). Physicians perceived telemetry as unhelpful in 30% of cases; as helpful in 70%. The percentage of inutility, usefulness with and without related medical intervention were similar between stable and unstable patients (30, 18, 51% and 31, 15, 54%, respectively). CONCLUSION: In a heart failure unit ECG monitoring is mostly used in severe and unstable patients. However, medical decisions are rarely guided by the telemetry findings. The usefulness of telemetry might be underestimated because one of the uncounted results might be the avoidance of inappropriate intervention.

Invasive and non-invasive determinants of pulmonary hypertension in patients with chronic heart failure.

BACKGROUND: In patients with chronic heart failure, pulmonary hypertension is an important predictive marker of adverse outcome. Its invasive and non-invasive determinants have not been evaluated. OBJECTIVE: This study was performed to evaluate hemodynamic determinants of pulmonary hypertension in chronic heart failure and to compare the predictive value of Doppler indices with that of invasively measured hemodynamic indices. METHODS: Right heart catheterization and transthoracic echo-Doppler were simultaneously performed in 259 consecutive patients with chronic heart failure (ejection fraction 24% +/- 7%) who were in sinus rhythm and receiving optimized medical therapy. Systolic pulmonary artery pressure (sPAP), cardiac index, transpulmonary gradient pressure, and pulmonary wedge pressure (PWP) were measured invasively. Left atrial and ventricular systolic and diastolic volumes, the ratio of maximal early to late diastolic filling velocities (E/A ratio), deceleration time (DT) and atrial filling fraction (AFF) of transmitral flow, systolic fraction of forward pulmonary venous flow (SFpvf), and mitral regurgitation were quantified by echo-Doppler. RESULTS: Patients with pulmonary hypertension had greater left atrial systolic and diastolic dysfunction, more left ventricular diastolic abnormalities, and greater hemodynamic impairment. The correlations between systolic left ventricular indices, mitral regurgitation, and sPAP were generally poor. Among invasive and non-invasive measurements, PWP (r = 0.89, p < 0.0001) and SFpvf (r = -0.68, p < 0.0001) showed the strongest correlation with sPAP. When we compared all patients with those without mitral regurgitation, the correlations between E/A ratio (r = 0.56 vs r = 0. 74, p < 0.002), SFpvf (r = -0.68 vs r = -0.84, p < 0.03), and systolic pulmonary artery pressure were significantly stronger. Multivariate analysis revealed that PWP was the strongest invasive independent predictor of systolic pulmonary artery pressure in patients with (R(2) = 0.87, p < 0.0001) and without (R(2) = 0.90, p < 0.0001) mitral regurgitation. A PWP > or= 18 mm Hg (odds ratio [95% CL], 142 (41-570) was strongly associated with systolic pulmonary hypertension. Among non-invasive variables DT, SFpvf, and AFF were identified as independent predictors of sPAP in patients with (R(2) = 0.56, p < 0.0001) and without (R(2) = 0.78, p < 0.0001) mitral regurgitation. A DT < 130 (odds ratio [95% CL], 3.5 (1.3-8.5), SFfvp < 40% (odds ratio [95% CL], 333 (41-1,007), and AFF < 30% (odds ratio [95% CL], 2 (1.3-7) most strongly predicted systolic pulmonary hypertension. CONCLUSIONS: The results of this study indicate that in patients with chronic heart failure, venous pulmonary congestion is an important determinant of systolic pulmonary artery hypertension. Hemodynamic and Doppler determinants showed similar predictive power in identifying systolic pulmonary artery hypertension.

Beta-blockade therapy in chronic heart failure: diastolic function and mitral regurgitation improvement by carvedilol.

BACKGROUND: In patients with chronic heart failure, the use of carvedilol therapy induces clinical and hemodynamic improvement. However, although the benefits of this beta-blocker have been established in patients with chronic heart failure, the mechanisms underlying them and the changes in left ventricular systolic function, diastolic function, and mitral regurgitation during long-term therapy remain unclear. OBJECTIVE: To identify the clinical and functional effects of carvedilol, focusing on diastolic function and mitral regurgitation variations. METHODS: Forty-five consecutive patients with chronic heart failure (ejection fraction 24% +/- 7%), 17 with dilated ischemic and 28 with nonischemic cardiomyopathy, were treated with carvedilol (mean dose 44 +/- 30 mg) and matched for clinical (New York Heart Association functional class and heart failure duration) and hemodynamic (cardiac index and pulmonary wedge pressure) characteristics to a control group. Clinical and echocardiographic variables were measured in the 2 groups at baseline and after 6 months and the results compared. RESULTS: After 6 months of treatment with carvedilol, left ventricular ejection fraction had increased from 24% +/- 7% to 29% +/- 9% (P <.0001); this change was caused by a reduction in end-systolic volume index (106 +/- 41 vs 93 +/- 37 mL/m(2); P <. 0001). Deceleration time of early diastolic filling increased (134 +/- 74 vs 196 +/- 63 ms; P <.0001). Seventeen of the 27 patients with demonstrated improvement of left ventricular diastolic filling moved from having a restrictive filling pattern to having a normal or pseudonormal left ventricular filling pattern. In the control group, no significant changes in deceleration time of early diastolic filling were found (139 +/- 74 vs 132 +/- 45 ms; P = not significant). The effective regurgitant orifice area decreased significantly in the carvedilol group but not in the control group. These changes were associated with a significant reduction of the mitral regurgitant stroke volume in the carvedilol group (50 +/- 25 vs 16 +/- 13 mL; P <.0001) but not in the control group (57 +/- 29 vs 47 +/- 24 mL; P = not significant). These changes of mitral regurgitation were closely associated with significant improvement of forward aortic stroke volume (r = -.57, P <.0001). These findings were not observed in patients in the control group. CONCLUSIONS: The results of this study show that long-term carvedilol therapy in patients with chronic heart failure was able to prevent or partially reverse progressive left ventricular dilatation. The effects on left ventricular remodeling were associated with a concomitant recovery of diastolic reserve and a decrease of mitral regurgitation, which have been demonstrated to be powerful prognostic predictors in such patients. Overall these findings provide important insights into the pathophysiologic mechanisms by which carvedilol improves the clinical course of patients with chronic heart failure.

Association between hemodynamic impairment and Cheyne-Stokes respiration and periodic breathing in chronic stable congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Irregular breathing occurs frequently in patients with congestive heart failure (CHF) both during daytime and nighttime. Many factors are involved in the genesis of these breathing abnormalities, but the role of the hemodynamic impairment remains controversial. This study investigated the relation between worsening ventricular function and the frequency of respiratory disorders in patients with mild to severe CHF. One hundred fifty patients with CHF (mean age 53 +/- 8 years, left ventricular (LV) ejection fraction 26 +/- 7, in New York Heart Association [NYHA] classes II to IV, and who underwent stable therapy for > or =2 weeks) were studied. Analysis of instantaneous lung volume signal and arterial oxygen saturation during awake daytime revealed a normal respiratory pattern in 63 patients, whereas 87 had a persistent alteration of breathing, with a typical Cheyne-Stokes respiration (CSR) in 42 and periodic breathing (PB [oscillation of tidal volumes without apnea]) in 45 patients. Patients with PB and CSR showed a more pronounced hemodynamic impairment with a significantly reduced cardiac index, an increased pulmonary arterial wedge pressure, and a longer lung-to-ear circulation time (LECT) compared with patients with normal respiratory patterns. In a logistic regression model that included all of the variables significantly associated with breathing disorders, cardiac index and LECT emerged as the major determinants of CSR. In those patients with LECT > or =30 seconds (upper quartile) and cardiac index < or =1.9 L/min/m2 (lower quartiles), the incidence of CSR was significantly higher (69%) than in patients with lower LECT and higher cardiac index (14%, p <0.001). In conclusion, abnormalities of breathing activity during daytime are significantly associated with a prolonged circulation time and a more severe impairment of systolic and diastolic LV indexes.

[An analysis of the decision process in the pharmacological treatment of a patient with chronic heart failure by means of a therapy management information system: the experience of the Montescano Heart Failure Unit]. / Analisi del processo decisionale del trattamento farmacologico nel paziente con scompenso cardiaco cronico attraverso un sistema informatizzato di gestione della terapia: esperienza dell'Unità per lo Scompenso Cardiaco di Montescano.

A computer-based system integrated into the hospital information system for the pharmacological management of the chronic heart-failure patients admitted to the heart-failure unit of Montescano is presented. The major aims of the system involved monitoring the patients' treatment history and the related therapeutic decision-making. The treatment history of the first 151 consecutive CHF patients admitted after the system implementation is examined. The prescribed drug doses at admission and at discharge are compared, as well as the differences in etiology and NYHA class between patients discharged with or without each drug. Several considerations can be drawn from this analysis. First of all, in heart failure patients the choice of drugs is limited and optimal treatment is a result of individualized dosages. Secondly, time and trials are necessary to obtain optimal treatment. Consequently, continuity of care and in- and out-hospital networks are advisable. Third, a computer-based system offers advantages not only for the pharmacological management itself, but also for improving the quality of care through continuous analysis of the decision-making process.

Reproducibility of the six-minute walking test in patients with chronic congestive heart failure: practical implications.

This study assesses the reproducibility of the 6-minute walking test in patients with chronic heart failure using 2 different measurement protocols. Practical suggestions for the clinical setting are given.

Peak exercise oxygen consumption in chronic heart failure: toward efficient use in the individual patient.

OBJECTIVES: This study sought to 1) assess the short-, medium-and long-term prognostic power of peak oxygen consumption (VO2) in patients with heart failure; 2) verify the consistency of a nonmeasurable anaerobic threshold (AT) as a criterion of nonapplicability of peak VO2; 3) develop simple rules for the efficient use of peak VO2 in individualized prognostic stratification and clinical decision making. BACKGROUND: Peak VO2, when AT is identified, is among the indicators for heart transplant eligibility. However, in clinical practice the application of defined peak VO2 cutoff values to all patients could be inappropriate and misleading. METHODS: Six hundred fifty-three patients consecutively considered for eligibility for heart transplantation were followed up. Outcomes (cardiac death and urgent transplantation) were determined when all survivors had a minimum of 6 months of follow-up. RESULTS: Contraindication to the exercise test identified very high risk patients. The relatively small sample of women did not allow inferences to be drawn. In men, peak VO2 stratified into three levels (< or = 10, 10 to 18 and >18 ml/kg per min) identified groups at high, medium and low risk, respectively. The prognostic power of peak VO2 < or = 10 ml/kg per min was maintained even when the AT was not detected. In patients in New York Heart Association functional class III or IV, peak VO2 did not have prognostic power. In patients in functional class I or II, peak VO2 stratification was prognostically valuable, but less so at 6 than at 12 or 24 months. Age did not influence peak VO2 prognostic stratification. CONCLUSIONS: A contraindication to exercise testing should be considered a priority for listing patients for heart transplantation. Only in less symptomatic male patients does a peak VO2 < or = 10 ml/kg per min identify short-, medium- and long-term high risk groups. A peak VO2 >18 ml/kg per min implies good prognosis with medical therapy.

Restrictive cardiomyopathy, atrioventricular block and mild to subclinical myopathy in patients with desmin-immunoreactive material deposits.

OBJECTIVES: We present clinical data and heart and skeletal muscle biopsy findings from a series of patients with ultrastructural accumulations of granulofilamentous material identified as desmin. BACKGROUND: Desmin cardiomyopathy is a poorly understood disease characterized by abnormal desmin deposits in cardiac and skeletal muscle. METHODS: Clinical evaluation, endomyocardial and skeletal muscle biopsy, light and electron microscopy and immunohistochemistry were used to establish the presence of desmin cardiomyopathy. RESULTS: Six hundred thirty-one patients with primary cardiomyopathy underwent endomyocardial biopsy (EMB). Ultrastructural accumulations of granulofilamentous material were found in 5 of 12 biopsy samples from patients with idiopathic restrictive cardiomyopathy and demonstrated specific immunoreactivity with anti-desmin antibodies by immunoelectron microscopy. Immunohistochemical findings on light microscopy were nonspecific because of a diffuse intracellular distribution of desmin. All five patients had atrioventricular (AV) block and mild or subclinical myopathy. Granulofilamentous material was present in skeletal muscle biopsy samples in all five patients, and unlike the heart biopsy samples, light microscopic immunohistochemical analysis demonstrated characteristic subsarcolemmal desmin deposits. Two patients were first-degree relatives (mother and son); another son with first-degree AV block but without myopathy or cardiomyopathy demonstrated similar light and ultrastructural findings in skeletal muscle. Electrophoretic studies demonstrated two isoforms of desmin--one of normal and another of lower molecular weight--in cardiac and skeletal muscle of the familial cases. CONCLUSIONS: Desmin cardiomyopathy must be considered in the differential diagnosis of restrictive cardiomyopathy, especially in patients with AV block and myopathy. Diagnosis depends on ultrastructural examination of EMB samples or light microscopic immunohistochemical studies of skeletal muscle biopsy samples. Familial desminopathy may manifest as subclinical disease and may be associated with abnormal isoforms of desmin.

Arterial baroreflex modulation of heart rate in chronic heart failure: clinical and hemodynamic correlates and prognostic implications.

BACKGROUND: In chronic heart failure (CHF), arterial baroreflex regulation of cardiac function is impaired, leading to a reduction in the tonic restraining influence on the sympathetic nervous system. Because baroreflex sensitivity (BRS), as assessed by the phenylephrine technique, significantly contributes to postinfarction risk stratification, the aim of the present study was to evaluate whether in CHF patients a depressed BRS is associated with a worse clinical hemodynamic status and unfavorable outcome. METHODS AND RESULTS: BRS was assessed in 282 CHF patients in sinus rhythm receiving stable medical therapy (age, 52+/-9 years; New York Heart Association [NYHA] class, 2.4+/-0.6; left ventricular ejection fraction [LVEF], 23+/-6%). The BRS of the entire population averaged 3.9+/-4.0 ms/mm Hg (mean+/-SD) and was significantly related to LVEF and hemodynamic parameters (LVEF, P<.005; cardiac index and pulmonary wedge pressure, P<.001 by regression analysis). Patients in NYHA classes III or IV and those with severe mitral regurgitation had markedly depressed vagal reflexes. The association of BRS with survival was described after its categorization in three groups: below the lowest quartile (<1.3 ms/mm Hg), between the lowest quartile and the median (1.3 to 3 ms/mm Hg), and above the median (>3 ms/mm Hg). During a mean follow-up of 15+/-12 months, 78 primary events (cardiac death, nonfatal cardiac arrest, and status 1 priority transplantation) occurred (27.6%). BRS was significantly related to outcome (log rank, 9.1; P<.01), with a relative risk of 2.7 (95% confidence interval, 1.6 to 4.7) for patients with the major derangement in BRS (<1.3 ms/mm Hg). At multivariate analysis, BRS was an independent predictor of death after adjustment for noninvasive known risk factors but not when hemodynamic indexes were also considered. In CHF patients with severe mitral regurgitation, however, BRS remained a strong prognostic marker independent of hemodynamic function. CONCLUSIONS: In moderate to severe CHF, a depressed sensitivity of vagal reflexes parallels the deterioration of clinical and hemodynamic status and is significantly associated with poor survival. Particularly in patients with severe mitral regurgitation the baroreceptor modulation of heart rate provides prognostic information of incremental value to hemodynamic parameters.

Age limits for heart transplantation: medical aspects.

OBJECTIVE: To contribute to the analysis of the medical issue of aging as a selection criteria for heart transplantation (HT) METHODS: Elderly candidates (52 subjects, aged > or = 60) were compared with younger patients (64 candidates, aged 50-55) in: clinical pattern (sex, etiology, duration of disease); laboratory and instrumental data (multiple organ function, hemodynamics, maximal and submaximal exercise capacity, nutritional status); follow-up (death, transplantation, status I, decompensation, complications) of at least 6 months. RESULTS: When compared with younger candidates, over 60 patients did not differ in clinical pattern, in all instrumental data, in end-organ function, in transplantation rate, in fatal and non-fatal cardiac events. In both groups the medical management was similarly complex. CONCLUSION: In regard to the medical issue, no reasons emerged to exclude older patients suitable from HT.

Dobutamine and nitroprusside infusion in patients with severe congestive heart failure: hemodynamic improvement by discordant effects on mitral regurgitation, left atrial function, and ventricular function.

OBJECTIVES: In patients with severe heart failure additional therapeutic support with intravenous inotropic or vasodilator drugs is frequently used in the attempt to obtain hemodynamic control. The nature and extent to which diastolic filling, atrial function, and mitral regurgitation are modified by these drugs have not been fully explored. The aim of this study was to compare the acute adaptations of the left ventricular performance, left atrial function, and mitral regurgitation that accompanied hemodynamic improvement during intravenous dobutamine and nitroprusside infusions in patients with severe chronic heart failure. METHODS: Forty consecutive patients with severe heart failure were evaluated by simultaneous echo-Doppler and hemodynamic investigations at baseline and during nitroprusside and dobutamine administration. Mitral flow velocity variables, left atrial and ventricular volumes, left atrial reservoir, conduit and pump volumes, and mitral regurgitation jet area were compared by analysis of variance for repeated measurements. RESULTS: Nitroprusside increased cardiac output (2.1 +/- .5 vs 2.6 +/- .5 L/min/m2, p < 0.004), reduced left ventricular filling pressure (25 +/- 6 vs 14 +/- 4 mm Hg, p < 0.0001), and improved left atrial pump volume (19 +/- 3 vs 26 +/- 12 ml, p < 0.02) without variations in left atrial reservoir and conduit volume. The restoration of preload reserve and improvement of the atrial contribution to left ventricular diastolic filling were demonstrated by the Doppler mitral flow pattern, which moved from a restrictive to a normal pattern. Furthermore mitral regurgitation decreased in all patients (9 +/- 4.6 vs 4.6 +/- 3.4 cm2, p < 0.0001). Dobutamine increased cardiac output (2.1 +/- .5 vs 2.8 +/- .6 L/min/m2), but the effects on pulmonary wedge pressure and mitral regurgitation were variable and unpredictable. Left atrial reservoir and conduit volumes increased, whereas left atrial pump volume did not change (19 +/- 13 vs 22 +/- 14 ml, p = NS). Furthermore Doppler mitral flow showed a persistent restrictive pattern. CONCLUSIONS: In patients with advanced congestive heart failure both nitroprusside and dobutamine improve cardiac output, with different adaptations of left ventricular performance and left atrial function. Nitroprusside seems to restore both atrial and ventricular pump function better. Careful echo-Doppler monitoring during drug infusion provides information relevant to the clinical treatment of individual patients.

Sick euthyroid syndrome in patients with moderate-to-severe chronic heart failure.

BACKGROUND: Changes in peripheral thyroid hormone concentration and metabolism can occur in euthyroid patients suffering from severe non-thyroidal illnesses. Recently, sick euthyroid syndrome has been reported in patients suffering from advanced heart failure. AIM: This study was to evaluate prospectively the presence and pathophysiological implications of sick euthyroid syndrome in moderate-to-severe chronic heart failure patients. METHODS: The study population were 199 chronic heart failure patients admitted over a 2-year period to our heart failure unit for assessment of cardiac transplantation. They were closely followed up with clinical and instrumental examinations (including clinical, hormonal, nutritional and cardiac function evaluations). Sick euthyroid syndrome was defined as a serum total triiodothyronine value of less than the lowest normal limit (< 1.23 nmol.l-1) in the presence of a normal serum thyroid stimulating hormone concentration. RESULTS: Sick euthyroid syndrome was found in 36/199 patients (18%). According to the New York Heart Association (NYHA) classification of severity of heart failure, sick euthyroid syndrome patients appear in higher NYHA classes (31% of classes III and IV, vs 7% of class I and II). Such patients also weigh less and are more frequently malnourished. Alterations in cardiac index, ventricular filling pressures, functional impairment, and the liver function parameters, were more significant in sick euthyroid syndrome than in non-sick euthyroid syndrome patients. Serum norepinephrine and atrial natriuretic factor were significantly higher, and insulin significantly lower in the sick euthyroid syndrome group. During follow-up, deaths were significantly more frequent in sick euthyroid syndrome patients (13/27, 48%) than in non-sick euthyroid syndrome (30/141, 21%; P < 0.005). In six sick euthyroid syndrome patients who underwent heart transplantation, mean total triiodothyronine values increased from 0.9 +/- 0.1 before to 1.96 +/- 0.3 nmol.l(-1)post-transplantation (P < 0.05). CONCLUSIONS: In a large and representative population of patients with moderate-to-severe heart failure, sick euthyroid syndrome shows a prevalence of 18%. Its occurrence was related to the degree of functional cardiac impairment, but was not an independent negative prognostic factor. Preliminary results indicate that heart transplantation is associated with reversibility of sick euthyroid syndrome.