Additive prognostic value of cardiopulmonary exercise testing in elderly patients with heart failure.

To date, the role of CPET (cardiopulmonary exercise testing) for risk stratification in elderly patients with HF (heart failure) with depressed or preserved ventricular function has not been evaluated. In the present study, we analysed whether CPET is useful in predicting outcome in this population. A total of 220 NYHA (New York Heart Association) class I-III patients with HF > or =70 years of age [median age, 75 years; 23% had NYHA class III; and 59% had preserved ventricular systolic function (left ventricular ejection fraction > or =40%)] performed maximal CPET (peak expiratory exchange ratio >1.00). Median peak oxygen uptake was 11.9 ml.kg(-1) of body weight.min(-1), median VE/VCO(2) slope (slope of the minute ventilation/carbon dioxide production ratio) was 33.2 and 45% had an EVR (enhanced ventilatory response) to exercise (VE/VCO(2) slope > or =34). During 19 months of follow-up, 94 patients (43%) met the combined end point of death and hospital admission for worsening HF, arrhythmias or acute coronary syndromes. By Cox multivariable analysis, a creatinine clearance of <50 ml/min {HR (hazard ratio), 1.657 [95% CI (confidence interval), 1.055-2.602]} and EVR [HR, 1.965 (95% CI, 1.195-3.231)] were the best predictors of outcome, while ventricular function had no influence on prognosis. In conclusion, in elderly patients with HF, a steeper VE/VCO(2) slope provides additional information for risk stratification across the spectrum of ventricular function and identifies a high-risk population, commonly not considered in exercise testing guidelines.

Long-term cognitive and behavioural follow-up in three patients with eye closure-triggered paroxysmal activity.

PURPOSE: To study clinical, EEG, neuropsychological and behavioural evolution of three patients presenting with epileptic activity triggered by eye closure (EC) over a mean 10-year follow-up period. METHODS: All patients were studied at the time of the first observation (T0) and after a long follow-up period (T1). At both T0 and T1, each patient underwent: 1) traditional and specific activation techniques during prolonged video-EEG monitoring to detect possible inducing factors; 2) neuropsychological evaluations during video-EEG monitoring either with eyes closed or eyes open to detect any transient cognitive impairment (TCI); 3) detailed neuropsychological assessment without simultaneous EEG recording, to detect any stable cognitive impairment (SCI). RESULTS: EEG recordings showed transient, generalized paroxysms in one case and a continuous epileptic activity triggered by eye closure in the other two cases, at both T0 and T1. In all patients, no particular epileptiform discharge-induced factors were identified except for eye blinking (spontaneous, voluntary or induced by corneal reflex). The results of neuropsychological assessment while eyes were closed as compared to performances with eyes open, showed no significant differences at T0 or at T1 in two cases, thus possibly indicating the absence of TCI. Wechsler Intelligence Scales showed a decrease in performance at T1 in the two patients with eye closure-induced, continuous epileptiform activity. Detailed neuropsychological assessment without EEG recordings demonstrated an impairment of facial recognition ability in all three patients at T1. CONCLUSIONS: The lack of any differences between the results of neuropsychological tests performed with eyes open and eyes closed in two patients might suggest that not all eye-closure-triggered paroxysms are associated with TCI. On the other hand, our data highlight that EC-triggered, EEG epileptic discharges can produce long-lasting neuropsychological and behavioural effects, and also indicate that EEG discharges recurring over time might exert a disruptive effect on cognitive functions. Our three patients showed extreme variability across the neuropsychological tasks except for a facial recognition deficit that was evident in all cases, thus suggesting a possible dysfunction of temporo-occipital brain structures and/or of the fusiform face area as recently demonstrated by combined fMRI/EEG studies in patients with fixation-off sensitivity.

Multiparametric risk stratification in patients with mild to moderate chronic heart failure.

BACKGROUND: Whether brain natriuretic peptide (BNP) combined with cardiopulmonary exercise test (CPx) and echocardiographic findings improves prognostic stratification in mild-to-moderate systolic heart failure (HF) is unclear. METHODS AND RESULTS: A total of 244 consecutive stable outpatients, median age of 71 (62-76) years, with New York Heart Association (NYHA) Class I-III HF and left ventricular ejection fraction (LVEF) < 45% underwent BNP measurement, Doppler echocardiography, and a maximal CPx. Median BNP was 166 (70-403) pg/mL, median LVEF 35% (28%-40%). A restrictive filling pattern (RFP) was present in 44 patients (18%). At CPx, peak oxygen uptake was 12 (9.7, 14.4) mL/kg/min and an enhanced ventilatory response to exercise (EVR, slope of the ventilation to CO2 production ratio, > or = 35) was found in 90 patients (37%) During 18 (9-37) follow-up months, 80 patients died or were admitted for worsening HF (33%). In addition to simple bedside clinical variables (NYHA Class III, creatinine clearance, hemoglobin), BNP levels were predictive of outcome (HR 1.35 [1.12-1.63]). However, both RFP (HR 3.36 [2.09-5.41]) and a steeper minute ventilation-carbon dioxide output slope (HR 1.50 [1.19-1.88]) outperformed BNP as prognostic markers. Patients with both RFP and EVR had a 7.30 (95% CI 4.02-13.25) HR for death or HF-admission versus subjects with neither predictor. CONCLUSIONS: This study highlights the importance of a multiparametric approach for optimal risk stratification in the elderly with mild-to-moderate HF. Patients at high risk should undergo closer follow-up and be carefully evaluated for different therapeutic options, including nonpharmacologic treatment.

Role of electroanatomic mapping in assessing the extent of atrial standstill: diagnostic and therapeutic implications.

Atrial standstill is characterized by failure of atrial excitation, either spontaneous or induced by atrial electric stimulation. We report the case of a 38-year-old man with severe bradycardia and junctional escape rhythm associated with dilative cardiomyopathy. Electroanatomic mapping showed the absence of atrial viability in almost the entire right atrial endocardial surface and excluded the feasibility of atrial pacing.

Prognostic value of brain natriuretic peptide and enhanced ventilatory response to exercise in patients with chronic heart failure.

Whether brain natriuretic peptide (BNP), combined with a cardiopulmonary exercise test (CPx) parameters or echocardiography improves prognostic stratification in mild-to-moderate systolic heart failure (HF) is currently unclear. In 156 consecutive stable outpatients with mild to moderate HF and left ventricular ejection fraction (LVEF) <40%, we assessed the impact of BNP assay, Doppler echocardiography and CPx on survival. Median BNP plasma levels were 207 [90-520] pg/mL. Mean LVEF was 33 +/- 7%. Left bundle branch block (LBBB) was present in 52 patients (33%) and a restrictive filling pattern in 35 (22%). The slope of the relation between minute ventilation and carbon dioxide production (VE/VCO(2) slope) averaged 35 +/- 8; an enhanced ventilatory response (EVR) to exercise (VE/VCO(2) slope >35) was found in 67 patients (43%). During 759 +/- 346 days of follow-up, 24 patients died. By multivariate analysis, the strongest independent predictors of all-cause death among clinical, echocardiographic variables and BNP were LBBB and beta-blocker treatment. When CPx variables were added, the best predictors of mortality were LBBB, beta-blockade and VE/VCO(2) slope. This study highlights the value of a sequential approach, based on clinical, laboratory and functional data to identify high-risk HF patients. BNP assay might constitute a simple alternative tool for patients with an inability or with clinical contraindications to exercise, advanced physical deconditioning and unreliable CPx results. However, whenever feasible, CPx with assessment of EVR is recommended for a more accurate prediction of prognosis.

Restrictive mitral inflow pattern is a strong independent predictor of lack of viable myocardium after a first acute myocardial infarction.

In patients with acute myocardial infarction (AMI) a restrictive mitral inflow pattern successfully predicts clinical outcome. The impact of myocardial viability on the mitral inflow velocities, however, is unknown. One hundred and forty-one patients with a first AMI underwent two-dimensional, Doppler and dobutamine stress echocardiography (DSE). Patients were classified into two groups based on Doppler measurement of left ventricular filling: a restrictive group (18 patients), and a non-restrictive group (123 patients). In the non-restrictive group, myocardial viability at DSE was found in 56 patients, while in the restrictive group only three patients showed contractile reserve (46% vs. 16%, p<0.03). The multivariate logistic regression analysis demonstrated that restrictive mitral inflow pattern was a strong independent predictor of lack of viable myocardium (OR=12.45, p<0.001).

Brain natriuretic peptide plasma level is a reliable indicator of advanced diastolic dysfunction in patients with chronic heart failure.

The aim of the study was to determine the value of brain natriuretic peptide for the identification of diastolic dysfunction status in congestive heart failure. We studied 204 patients with stable heart failure. Brain natriuretic peptide plasma levels were correlated with echocardiographic parameters of diastolic dysfunction. Diastolic dysfunction was classified as mild (abnormal echocardiographic relaxation pattern) and severe (pseudo-normal or restrictive pattern). A significant correlation between brain natriuretic peptide levels and the other parameters was detected. Brain natriuretic peptide dosage, then, seems to be a reliable tool for the assessment of diastolic dysfunction status in patients with congestive heart failure.

The cardiopulmonary exercise test is safe and reliable in elderly patients with chronic heart failure.

AIM: To assess safety and feasibility of cardiopulmonary exercise test (CPX) in elderly patients with chronic heart failure (CHF) and left ventricular dysfunction. METHODS AND RESULTS: We analysed 395 cardiopulmonary exercise tests (CPXs) performed in 227 clinically stable patients with CHF [mean age 76 years, males 70%, mean New York Heart Association (NYHA) class 2.2 +/- 0.5] and impaired left ventricular function (mean ejection fraction 43 +/- 12%). Ninety-eight out of 395 CPXs (25%) were performed in patients older than 80 years. A standard bicycle exercise ramp protocol was used, with increments of 10 W/min. An expiratory exchange ratio (RER) >or= 1.05 at the peak of CPX was considered as the index of maximal exercise. Average workload was 65 +/- 23 W. No adverse reactions were observed, although one test was stopped for non-sustained ventricular tachycardia. The main reasons for stopping were exhaustion (50%), dyspnoea (30%), maximal predicted heart rate (17%), orthopaedic problems (2.5%) and significant ST segment depression (0.5%). In the overall cohort, 80% of patients achieved an RER >or= 1.05 and, in 56% of them, the RER was >or= 1.15. The anaerobic threshold (AT) was detectable in 80% of CPXs, and mean oxygen consumption (VO2) at AT was 9 +/- 6 ml/kg per min, whereas mean peak VO2 was 11 +/- 3 ml/kg per min. In the cohort of patients aged > 80 years, 71% reached an RER >or= 1.05 and 47% reached an RER >or= 1.15. In these older patients, AT was detectable in 68% of CPXs performed, and the mean peak VO2 was 10 +/- 3 ml/kg per min. CONCLUSIONS: In elderly patients with CHF, the CPX is safe, feasible and able to provide basic information for individual risk assessment. These findings potentially extend the indications of CPX, which is currently applied to selected middle-aged patients with CHF, to the elderly population.

Brain natriuretic peptide is a reliable indicator of ventilatory abnormalities during cardiopulmonary exercise test in heart failure patients.

BACKGROUND: Whether brain natriuretic peptide (BNP), a neurohormone marker of ventricular dysfunction, correlates with an enhanced ventilatory response (EVR) during cardiopulmonary exercise test, a well-known predictor of prognosis, in systolic heart failure (HF) is currently unknown. MATERIAL/METHODS: Resting BNP was measured in 134 consecutive stable outpatients aged 69 +/- 11 years with mild to moderate HF and LV ejection fraction (LVEF) < 40% who performed a maximal exercise test. EVR was assessed as the slope of the relation between minute ventilation and carbon dioxide production (VE/VCO2 slope) > or = 35. RESULTS: LVEF averaged 33 +/- 7%, BNP 350 +/- 396 pg/ml, and the VE/VCO2 slope 36 +/- 8. Fifty-six of 123 patients (45%) had EVR. BNP correlated with VE/VCO2 slope (r = 0.453; p < 0.01). By multivariate logistic regression, plasma BNP was the only independent predictor of EVR (RR: 1.004 per unit increment, 95% CI: 1.002-1.006, p < 0.0001). A BNP > or = 160 pg/ml had 86% sensitivity, 67% specificity, and 76% overall accuracy for the prediction of EVR (chi square: 37.4, RR 12.2, 95% CI: 4.96-30.3, p < 0.0001, AUC 0.815 (95%CI. 0.738-0.892)). CONCLUSIONS: In systolic HF, plasma BNP is related to an enhanced ventilatory response to exercise and offers a simple and reliable alternative to the cardiopulmonary exercise test in patients with inability or contraindications to exercise.