Piero Zardini

Determinants and Prognostic Value of Left Atrial Volume in Patients With Dilated Cardiomyopathy

OBJECTIVES We aimed to investigate the determinants of left atrial (LA) volume and its prognostic value in patients with dilated cardiomyopathy (DCM). BACKGROUND Enlargement of the LA is a marker of mortality in the general population. Patients with DCM are characterized by a wide range of LA sizes, but the clinical role of this observation has been played down. METHODS A complete echocardiographic Doppler examination was performed in 337 patients (age 60 +/- 13 years; 84% male) with the diagnosis of DCM. Left atrial maximal volume (LA(max)) was measured at left ventricular (LV) end systole (four-chamber view; area-length method). Left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV) and ejection fraction (EF) were also measured. Mitral regurgitation (MR) was graded using a 5-point scale. Mitral E-wave (E) and A-wave (A) velocities, as well as their ratio (E/A), were measured off-line. RESULTS Determinants of LA(max) were: atrial fibrillation (r = 0.34, p < 0.0001), LVEDV (r = 0.46, p < 0.0001), EF (r = 0.40, p < 0.0001), MR (r = 0.39, p < 0.0001), and E/A ratio (r = 0.36, p < 0.0001). During follow-up (41 +/- 29 months), 77 patients died and 12 underwent heart transplantation. Univariate Cox analysis showed that LA(max) (hazard ratio [HR] 1.01, 95% confidence interval [CI] 1.007-1.013, p < 0.0001), LVESV (HR 1.003, CI 1.001-1.005, p = 0.0003), E/A ratio (HR 1.6, CI 1.3-2.005, p < 0.0001), and MR (HR 1.21, CI 1.03-1.44, p = 0.02) were related to the outcome. On bivariate Cox analysis, LA(max) predicted the prognosis independently of each determinant. Patients with a larger LA volume (LA(max)/m(2) >68.5 ml/m(2)) had a risk ratio of 3.8 compared with those with a smaller LA volume. CONCLUSIONS In patients with DCM, LA volume is associated with LV remodeling, diastolic dysfunction, and the degree of MR. The maximal volume of the LA has an independent and incremental prognostic value, compared with all its determinants.

Increasing degrees of left ventricular filling impairment modulate left atrial function in humans

We sought to investigate the changes in atrial reservoir, pump, and conduit functions that are associated with increasing degrees of left ventricular filling impairment. In 13 patients with an impaired relaxation type of filling and in 15 with restrictive patterns, the left atrial volume curve was constructed combining Doppler and 2-dimensional echocardiography. Nine normal subjects served as controls. Left atrial reservoir (defined as [maximum - minimum atrial volume] minus the amount of blood flow reversal in the pulmonary veins with atrial contraction), pump (defined by the volume of blood that enters the ventricle with atrial contraction), and conduit functions (defined as left ventricular filling volume - [left atrial reservoir plus pump volume]) were computed and each expressed as a percentage of ventricular filling volume. The atrial reservoir function was higher in the impaired relaxation group than in normal subjects (49+/-8% vs 38+/-8%, p <0.01) but markedly lower in the restrictive group (27+/-8%, p <0.05). The reverse was true for conduit function, exaggerated in restrictive group (54+/-12% vs 36+/-11% in normal subjects, p <0.01) but minimized in patients with an impaired relaxation type of filling (14+/-9%, p <0.001). The atrial pump contributed 19+/-6% of ventricular filling volume in restrictives, 26+/-3% in normals (p <0.01), and 38+/-4% (p <0.001) in the impaired relaxation group. We conclude that increased atrial response to early-stage left ventricular filling impairment is characterized by augmented reservoir and pump functions, according to a Starling mechanism, which becomes hardly effective at end-stage ventricular dysfunction when the limits of the atrial preload reserve are reached. At this stage, conduit in the atrium takes precedence.

Long-term, dose-dependent effects of spironolactone on left ventricular function and exercise tolerance in patients with chronic heart failure

OBJECTIVES This study was designed to assess the effects of spironolactone (SP) on left ventricular (LV) function and exercise tolerance in patients with chronic heart failure (CHF). BACKGROUND In severe heart failure (HF), SP improves survival, but the underlying mechanisms are not clear. METHODS We randomized 106 outpatients with HF to SP (12.5 to 50 mg/day) (group 1) or control (group 2). Complete echocardiography and cardiopulmonary exercise testing were performed at baseline and 12 months after randomization. RESULTS Left ventricular end-systolic volume at baseline and at follow-up was 188 +/- 94 ml and 171 +/- 97 ml in group 1 and 173 +/- 71 ml and 168 +/- 79 ml in group 2 (treatment group-by-time interaction, p = 0.03). Left ventricular ejection fraction at baseline and at follow-up was 33 +/- 7% and 36 +/- 9% in group 1 and 34 +/- 7% and 34 +/- 9% in group 2 (treatment group-by-time interaction, p = 0.02). At baseline, 9 patients in group 1 and 3 patients in group 2 had a restrictive mitral filling pattern, a marker of severe diastolic dysfunction; at follow-up, 3 patients in group 1 and no patient in group 2 improved their pattern. No patient in group 1 and 4 patients in group 2 worsened their pattern (chi-square, p = 0.02). Peak oxygen consumption increased significantly in patients treated with 50 mg of SP and decreased in group 2 (17.7 +/- 5.2 vs. 18.5 +/- 5.9 and 19.1 +/- 5.6 vs. 17.9 +/- 5.3, respectively; analysis of variance, p = 0.01). CONCLUSIONS Spironolactone improves LV volumes and function; furthermore, it improves exercise tolerance at the highest administered dose. Our data might explain the mortality reduction during aldosterone antagonism in patients with HF.

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.

Aortic Distensibility Independently Affects Exercise Tolerance in Patients With Dilated Cardiomyopathy

Background—Peak exercise oxygen consumption (&OV0312;o2) is crucial for the prognostic stratification of patients with congestive heart failure, but its hemodynamic determinants are still not completely understood. Aortic wall elasticity modulates left ventricular function and coronary blood flow. Whether an increased aortic pulse-wave velocity (PWV), a known marker of arterial stiffness, may predict peak &OV0312;o2 in patients with dilated cardiomyopathy (DCM) has to be clarified. Methods and Results—A total of 78 patients with clinical diagnosis of DCM (aged 62±11 years; female 29%; mean ejection fraction 34±9%) were selected. All patients underwent a complete echocardiographic-Doppler evaluation. Aortic PWV was measured by Doppler ultrasonography immediately before the exercise. A bicycle exercise test with expiratory gas exchange monitoring was performed to determine &OV0312;o2. Plasma concentration of the amino-terminal propeptide of type III procollagen (PIIINP), a marker of extracellular matrix turnover, was determined. Mean PWV was 5.7±2.2 m/s, and &OV0312;o2 was 16.5±4.5 mL · kg−1 · min−1. The hemodynamic variables correlated with &OV0312;o2 were PWV (r =−0.39, P =0.0007) and stroke volume (r =0.38, P =0.002). In a multivariate analysis, PWV (P =0.04) and stroke volume (P =0.05) were independently correlated with &OV0312;o2, accounting for 34% of its variance. PIIINP levels correlated with PWV (r =0.35, P =0.002) and a more restrictive diastolic filling pattern (r =0.40, P =0.02). Conclusions—Increased aortic stiffness measured by PWV is an independent predictor of peak &OV0312;o2 and could partially explain exercise intolerance in patients with DCM.

Prognostic value of detection of myocardial viability using low-dose dobutamine echocardiography in infarcted patients

Revascularization can improve ventricular function in patients with viable myocardium, but whether and how the presence of viable myocardium affects prognosis of infarcted patients is still far from clear. Thus, 202 patients (173 men, 59 +/- 9 years old) with a previous or recent myocardial infarction (MI) and regional asynergies underwent low-dose dobutamine echocardiography (5-15 microg/kg per min) to assess myocardial viability and were followed for a period of 16 +/- 11 months after revascularization (89 patients) or medical therapy (113 patients). Four groups of patients were defined: (1) patients with viability, revascularized (n = 64); (2) patients with viability, treated medically (n = 52); (3) patients without viability, revascularized (n = 25); and (4) patients without viability, treated medically (n = 61). Of these patients, 45 (23%) patients suffered 57 cardiac events: 18 cardiac deaths (9%), 7 MIs, 12 unstable angina, 9 heart failures, and 11 new revascularization procedures. Patients with viability, revascularized, experienced a slightly lower event rate (22%) compared with patients with viability, treated medically, patients without viability, treated medically and patients without viability, revascularized (29%, 31%, and 36%, respectively; p = not significant [NS]). The frequency of events was then evaluated in those 108 patients with an ejection fraction < or =33%, in whom 14 cardiac deaths occurred: the incidence of cardiac death was slightly lower in patients with viability, revascularized (3/37, 8%) than in the patients with viability, treated medically (4/26, 15%), patients without viability, revascularized (2/11, 18%), or patients without viability, treated medically (5/34, 15%) (p = NS). Nonfatal cardiac events were significantly fewer (p <0.05) in patients with viability, revascularized (8%) and in patients without viability, treated medically (6%) than in patients with viability, treated medically and patients without viability, revascularized (27%). In infarcted patients with severe left ventricular dysfunction, the presence of viable myocardium, if left unrevascularized, leads to further events. On the contrary, in the absence of myocardial viability, revascularization could lead to a worse prognosis than medical therapy.

Is vasopressin superior to adrenaline or placebo in the management of cardiac arrest? A meta-analysis.

Vasopressin is currently recommended in the management of patients with cardiac arrest, but its efficacy is still incompletely established. We systematically reviewed randomized trials comparing vasopressin to control treatment in the management of cardiac arrest in humans and animals. Two human and 33 animal studies were retrieved. At pooled analysis vasopressin appeared equivalent to adrenaline (epinephrine) in the management of human cardiac arrest (N=240), with, respectively 63 (78/124) vs 59% (68/116) ROSC (P=0.43), and 16 (20/124) vs 14% (16/116) survival to hospital discharge (P=0.52). In animal trials (N=669) vasopressin appeared instead significantly superior to both placebo (ROSC, respectively 93 [98/105] vs 19% [14/72], P<0.001) or adrenaline (ROSC, respectively 84 [225/268] vs 52% [117/224], P<0.001). In conclusion, vasopressin is superior to both placebo or adrenaline in animal models of cardiopulmonary resuscitation. Evidence in humans is still limited and confidence intervals estimates too wide to reliably confirm or disprove results obtained in experimental animal settings.

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.

Ventricular remodeling and infarct expansion.

Infarct expansion, defined as an alteration in the ventricular topography due to thinning and lengthening of the infarcted segment, develops within the first few hours of the acute symptoms, mostly in patients with a large, transmural, anterior myocardial infarction. Shape changes, peculiar to risk region location and due to disparity in regional ventricular architecture, could be posited as the first step in the process of infarct expansion, with various cellular mechanisms contributing to subsequent continued early and late ventricular dilation. Because the increase in left ventricular volume is expected to be linearly dependent on the extent of the infarction, limiting infarct size, by thrombolysis, would proportionally reduce enlargement of the cavity. The effect of thrombolysis on left ventricular volume, however, seems not to be completely accounted for by the lessening effect of reperfusion on infarct size, because data suggest a restraining effect of reperfusion on the process of ventricular dilation in addition to the lessening effect on infarct size. If this turns out to be true, then the achievement of a patent vessel even beyond the time period when that patency may be expected to salvage myocardium would be further justified. Theoretical predictions substantiate the potential effectiveness in restraining ventricular dilation of stiffening of the necrotic region alone, independently of myocardial salvage in infarcted patients. The process of progressive ventricular dilation involves not only a primary alteration in function of the infarcted region, but also a time-dependent secondary change in the noninfarcted tissue itself, finalized to restore stroke volume despite a persistently depressed ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of left atrial size in predicting postoperative symptomatic improvement in patients with aortic stenosis

Although surgery is highly effective for symptomatic relief in patients with aortic stenosis, symptoms of congestive heart failure may be still present postoperatively. This group of patients with aortic stenosis is characterized by a wide range of left atrial size, which can predict postoperative symptomatic improvement.