Massimo Pozzoli

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.

Predictors of primary atrial fibrillation and concomitant clinical and hemodynamic changes in patients with chronic heart failure: A prospective study in 344 patients with baseline sinus rhythm

OBJECTIVES This study investigated the incidence, predisposing factors and significance of the onset of atrial fibrillation (AF) in patients with chronic congestive heart failure (CHF). BACKGROUND The association between CHF and AF is well documented, but the factors that predispose to the onset of the arrhythmia and its impact remain controversial. Methods. We prospectively followed up 344 patients with CHF and sinus rhythm (SR). Over a period of 19 +/- 12 months (mean +/- SD), 28 patients developed atrial fibrillation (AF), which became chronic in 18. RESULTS At baseline, no differences were found in any clinical and hemodynamic variables between patients who developed chronic AF and those who did not. Reversible AF occurring during follow-up and lower mitral flow velocity at atrial contraction as detected at the last evaluation in SR were independent predictors of the subsequent development of chronic AF. When AF occurred, New York Heart Association functional class worsened (from 2.4 +/- 0.5 to 2.9 +/- 0.6, p = 0.0001), peak exercise oxygen consumption declined (from 16 +/- 5 to 11 +/- 5 ml/kg per min, p = 0.002), cardiac index decreased (from 2.2 +/- 0.4 to 1.8 +/- 0.4, p = 0.0008), and mitral and tricuspid regurgitation increased (from grade 1.8 +/- 1.1 to grade 2.4 +/- 1.4, p = 0.0001 and from grade 1.0 +/- 1.2 to grade 1.8 +/- 1.2, p = 0.001, respectively). Systemic thromboembolism occurred in 3 of the 18 patients with AF. Nine of 18 patients died after AF, and the occurrence of AF was a predictor of major cardiac events. CONCLUSIONS In patients with CHF, reversible AF and reduction of left atrial contribution to left ventricular filling predict the subsequent development of chronic AF. The onset of AF is associated with clinical and hemodynamic deterioration and may predispose to systemic thromboembolism and poorer prognosis.

Loading manipulations improve the prognostic value of Doppler evaluation of mitral flow in patients with chronic heart failure

BACKGROUND Mitral flow velocity patterns (MFVPs) evaluated by Doppler echocardiography are strong predictors of survival in various cardiac diseases. However, MFVPs may change over time according to loading conditions. We performed this prospective study to assess whether changes in MFVP induced by loading manipulations provided additional prognostic information in 173 patients with chronic heart failure. METHODS AND RESULTS Simultaneous Doppler echocardiographic and right-sided hemodynamic recordings were obtained at baseline in all patients, during nitroprusside infusion in the 98 patients who had a baseline restrictive (early-to-late flow velocity ratio > 1 and deceleration time < or = 130 ms) MFVP, and during passive leg lifting in the 75 patients who had a baseline nonrestrictive MFVP. Patients were categorized, according to changes in MFVP, into four groups: 61 patients with an irreversible restrictive, 37 with a reversible restrictive, 48 patients with a stable nonrestrictive, and 27 patients with an unstable nonrestrictive MFVP. Fifty patients experienced major cardiac events. Cox analysis revealed that MFVP was a strong predictor of events and that the response to loading manipulations improved its prognostic value. Patients with an irreversible restrictive MFVP had a higher event rate (51%) than patients with a reversible restrictive MFVP (19%). Among patients with a baseline nonrestrictive MFVP, those with a stable nonrestrictive MFVP had the lowest event rate (6%), whereas the event rate was 33% in patients with an unstable nonrestrictive MFVP. CONCLUSIONS In patients with chronic heart failure, MFVPs provide independent prognostic information. Their prognostic value can be further increased by assessment of the changes induced in them by loading manipulations.

Exercise echocardiography and technetium-99m MIBI single-photon emission computed tomography in the detection of coronary artery disease

To compare the relative diagnostic value of exercise echocardiography with perfusion technetium-99m metoxyisobutylisonitrile single-photon emission computed tomography (SPECT) in detecting coronary artery disease (CAD), 75 patients with suspected CAD but a normal electrocardiogram (ECG) at rest were included in a prospective correlative study. Both the exercise echocardiograms and SPECT studies were performed in conjunction with the same symptom-limited bicycle exercise test. The development of either a new wall motion abnormality or a reversible perfusion defect after exercise, or both, were regarded as a positive test for the exercise echocardiographic and SPECT studies, respectively. The results of these 2 diagnostic tests were compared with coronary arteriography. Exercise echocardiography identified 35 (71%) and SPECT 41 (84%, p = 0.13) of the 49 patients with significant CAD (defined as greater than 50% diameter stenosis). Twenty-five of the 26 patients (96%) without significant coronary stenosis had negative exercise echocardiographic results and 23 of 26 (88%) had negative SPECT results. Exercise-induced new wall motion abnormalities showed a good correlation with reversible perfusion defects, and the results of the 2 methods were concordant in 65 of 75 patients (agreement = 88%, kappa = 0.75 +/- 0.14). Both the diagnostic accuracy of exercise echocardiography and SPECT were significantly higher than the exercise ECG (81 vs 64%, p less than 0.02 and 88 vs 64%, p less than 0.005). The sensitivity and specificity for detecting individual diseased vessels were 60 and 95% for exercise echocardiography and 67 and 94% for SPECT.(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler echocardiography reliably predicts pulmonary artery wedge pressure in patients with chronic heart failure with and without mitral regurgitation

OBJECTIVES This study was performed to assess whether the combination of multiple echocardiographic and Doppler variables can provide a reliable estimation of pulmonary artery wedge pressure in patients with chronic heart failure. BACKGROUND In patients with chronic heart failure a high pulmonary artery wedge pressure is associated with poor prognosis, more severe symptoms and low exercise tolerance. Several Doppler echocardiographic indexes have been shown to be related to pulmonary artery wedge pressure, but the dispersion of data has generally not allowed a quantitative assessment of this important variable. METHODS Simultaneous Doppler echocardiographic examinations and right heart catheterizations were performed in 231 patients with chronic heart failure due to dilated cardiomyopathy. Mitral and pulmonary venous flow velocity variables, left atrial volumes, mitral regurgitation jet area and left ventricular ejection fraction were correlated with pulmonary artery wedge pressure by both single and multilinear regression analysis. The reliability of the obtained multilinear equations was then tested in a separate group of 60 patients. RESULTS By univariate analysis, the deceleration rate of early diastolic mitral flow and the systolic fraction of pulmonary venous flow showed the strongest correlations (r=0.78 and =-0.76, respectively). Stepwise regression analysis led to two multilinear equations for predicting pulmonary artery wedge pressure in the whole population: the first included only two-dimensional echocardiographic and mitral flow velocity variables (r=0.84) and the second also included pulmonary venous flow variables (r=0.87). The highest correlation was obtained (r=0.89) by a third equation in the 73 patients without significant mitral regurgitation. Correlation coefficients between estimated and measured pulmonary artery wedge pressure were 0.91 (SEE=2.7 mm Hg) and 0.97 (SEE=1.8 mm Hg) when the first and the second equation, respectively, were applied to the testing group. CONCLUSIONS These results indicate that, in patients with chronic heart failure due to dilated cardiomyopathy, pulmonary artery wedge pressure can be reliably estimated even when mitral regurgitation is present by combining Doppler echocardiographic variables of mitral and pulmonary venous flow.

Left Atrial Appendage Dysfunction: A Cause of Thrombosis? Evidence by Transesophageal Echocardiography-Doppler Studies

The blood flow velocity patterns within the left atrial appendage were studied by transesophageal color flow imaging and pulsed Doppler in 84 patients. At the time of the study, 57 of the patients were in sinus rhythm, 25 were in atrial fibrillation, and two were in atrial flutter. The relationships between atrial rhythm, blood flow pattern and the presence/absence of spontaneous echocardiographic contrast or thrombus within the appendage were investigated. Transesophageal echocardiography allowed recording of blood flow velocities in 81 of the 84 patients studied. In 51 of the 55 patients in sinus rhythm the pulsed Doppler study showed a biphasic blood flow pattern, whereas a multiphasic pattern was found in the two patients with atrial flutter and in 14 patients with atrial fibrillation. In four patients with sinus rhythm and 10 patients with atrial fibrillation, no significant blood flow velocity could be detected. Thrombus or spontaneous echocardiographic contrast were found within the left atrial appendage in 20 patients, and in all these patients blood flow was either absent or significantly reduced. Our findings indicate that an absent or low blood flow velocity within the left atrial appendage represents a predisposing factor for thrombosis. Isolated left atrial appendage dysfunction has been documented in four patients during sinus rhythm, which may lead to thrombosis. This observation may offer an explanation for cardioembolic events that occur occasionally in patients without apparent heart disease and sinus rhythm.

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.

Mitral flow velocity changes after 6 months of optimized therapy provide important hemodynamic and prognostic information in patients with chronic heart failure

Transmitral flow velocity patterns evaluated by Doppler echocardiography provide important hemodynamic and prognostic information in various cardiac conditions. However, these patterns may change over time, and so far the hemodynamic and prognostic significance of these changes has not been established. Accordingly, we performed this study to determine the hemodynamic and prognostic value of changes in transmitral flow velocity patterns after 6 months of optimized medical treatment in patients with chronic heart failure due to ischemic or nonischemic dilated cardiomyopathy. Ninety-eight consecutive patients with chronic heart failure underwent a clinical examination, a cardiopulmonary exercise test, and simultaneous Doppler echocardiographic and hemodynamic studies at baseline and after 6 months, patients were followed up for 12 +/- 7 months. Cardiac death and heart transplantation while patients were in critical condition were considered events. A restrictive pattern was defined by an early-to-late peak diastolic velocity ratio > 1 and an early diastolic deceleration time < or = 130 msec. Patients were grouped according to their mitral flow pattern at baseline and its changes after chronic optimized therapy. No significant changes in clinical, ergometric, and hemodynamic variables were found after 6 months in the 49 patients who had a persistent restrictive transmitral flow pattern or the 24 patients who had a persistent nonrestrictive transmitral flow pattern. In the 19 patients who had a restrictive pattern at baseline that reverted into a nonrestrictive pattern, this change was accompanied by a highly significant reduction in pulmonary wedge pressure (from 25 +/- 7 mm Hg to 11 +/- 3 mm Hg) and by an increase in exercise capacity, whereas in the 6 patients who had a nonrestrictive pattern that became restrictive, hemodynamic features markedly deteriorated. Seventeen of the 21 events occurred in the 49 patients (event rate 35%) with a persistent restrictive pattern, whereas the event rate was much lower in the 19 patients with a reversible restrictive pattern (5%) and in the 24 patients with a persistent nonrestrictive pattern (4%). Two (33%) of the 6 patients in whom a restrictive pattern developed had events. Cox analysis revealed that a restrictive transmitral flow pattern (p = 0.0068) and peak rate of oxygen consumption (p = 0.0056) detected at the late examination were significantly related to cardiac events. These results show that in patients with chronic heart failure, changes in transmitral flow patterns after chronic optimized therapy are correlated with changes in pulmonary wedge pressure, are accompanied by changes in functional capacity, and provide relevant independent prognostic information.

Doppler evaluations of left ventricular diastolic filling and pulmonary wedge pressure provide similar prognostic information in patients with systolic dysfunction after myocardial infarction.

Previous studies have demonstrated that in patients with various types of cardiac diseases and left ventricular dysfunction, left ventricular filling patterns assessed by Doppler of mitral flow are correlated to ventricular filling pressure, the prognostic value of which is well known. The current study was carried out to determine the prognostic importance of a noninvasive evaluation of left ventricular filling by Doppler of mitral flow in patients with systolic dysfunction after myocardial infarction and to compare its value with that of pulmonary wedge pressure. One hundred seven patients with a left ventricular ejection fraction < 40% were studied 3 to 12 weeks after myocardial infarction. All patients underwent a complete clinical examination, a standard two-dimensional and Doppler echocardiographic examination, and right-sided heart catheterization at rest and during a cardiopulmonary bicycle exercise test. Early and late diastolic peak flow velocities, their ratio, and the deceleration time of early diastolic velocity were measured from pulsed-wave Doppler of mitral flow. Follow-up data were obtained for 101 patients. During a mean period of 25 (median 21, range 12 to 60) months cardiac events (death, heart transplantation, or heart failure requiring hospitalization) occurred in 43 (42%) patients. Patients with cardiac events during follow-up were in a worse functional class and had a more impaired exercise capacity and higher capillary pulmonary wedge pressure at baseline examination. Among Doppler echocardiographic variables, in patients with cardiac events a greater early to late diastolic peak velocity ratio of mitral flow (1.9 +/- 0.9 pl/min vs 1.2 +/- 0.8 pl/min, p < 0.001) and a shorter early diastolic deceleration time (112 +/- 35 vs 145 +/- 42 msec, p < 0.001) were found. Cox analysis revealed that the combination of early to late diastolic peak flow velocity ratio of mitral flow and New York Heart Association functional class were the strongest noninvasive independent predictors of cardiac events. One-year event-free probability of survival was 90% in patients with an early to late diastolic peak velocity ratio < or = 1 (all but 1 in New York Heart Association functional class I or II) but was significantly less in patients with an early to late diastolic peak velocity ratio > 1 (64% in functional class I or II and 36% functional class III). Similar results were obtained when mean pulmonary wedge pressure was considered instead of the ratio between peak flow velocities of mitral flow.(ABSTRACT TRUNCATED AT 400 WORDS)

In-hospital and 1-year outcomes of acute heart failure patients according to presentation (de novo vs. worsening) and ejection fraction. Results from IN-HF Outcome Registry

BACKGROUND To investigate the outcomes of hospitalized patients with both de-novo and worsening heart failure (HF) with preserved left ventricular ejection fraction (LVEF) (HFpEF) (LVEF ≥ 50%), compared to those with reduced LVEF (HFrEF). METHODS AND RESULTS We studied 1669 patients (22.6% HFpEF) hospitalized for acute HF in the prospective multi-center nationwide Italian Network on Heart Failure (IN-HF) Outcome Registry. In all patients LVEF was assessed during hospitalization. De-novo HF presentations constituted 49.6% of HFpEF and 43.1% of HFrEF hospitalizations. All-cause mortality during hospitalization was lower in HFpEF than HFrEF (2.9% vs 6.5%, p=0.01), but this mortality difference was not significant at 1 year (19.6% vs 24.4%, p=0.06), even after adjusting for clinical covariates. Similarly, there were no differences in 1-year mortality between HFpEF and HFrEF when compared by cause of death (cardiovascular vs non-cardiovascular) or mode of presentation (worsening HF vs de novo). Rehospitalization rates (all-cause, non-cardiovascular, cardiovascular, HF-related) at 90 days and 1 year were also similar. Mode of presentation influenced rehospitalizations in HFpEF, where those presenting with worsening HFpEF had higher all-cause (36.8% vs 21.6%, p=0.001), cardiovascular (28.1% vs 14.9%, p=0.002), and HF-related (21.1% vs 7.7%, p=0.0003) rehospitalization rates at 1 year compared to those with de novo presentations. CONCLUSIONS Outcomes at 1 year following hospitalization for HFpEF are as poor as that of HFrEF. A prior history of HF decompensation or hospitalization identifies patients with HFpEF at particularly high risk of recurrent events. These findings may have implications for clinical practice, quality and process improvements and trial design.