Emanuela Berton

PERMANENT ATRIAL FIBRILLATION AFFECTS EXERCISE CAPACITY IN CHRONIC HEART FAILURE PATIENTS.

AIMS The influence of permanent atrial fibrillation on exercise tolerance and cardio-respiratory function during exercise in heart failure (HF) is unknown. METHODS AND RESULTS We retrospectively compared the results of 942 cardiopulmonary exercise tests, performed consecutively at seven Italian laboratories, in HF patients with atrial fibrillation (n = 180) and sinus rhythm (n = 762). By multivariable logistic regression analysis, peak VO(2) (OR 0.376, 95% CI 0.240-0.588, P < 0.0001), O(2)pulse (VO(2)/heart rate, HR) (OR 0.236, 95% CI 0.152-0.366, P < 0.0001), VCO(2) (OR 3.97, 95% CI 2.163-7.287, P < 0.0001), and ventilation (OR 1.38, 95% CI 1.045-1.821, P = 0.0231) were independently associated with atrial fibrillation. Anaerobic threshold (AT) was identified in 132 of 180 (73%) atrial fibrillation and in 649 of 762 (85%) sinus rhythm patients (P = 0.0002). By multivariable logistic regression analysis, only peak VO(2) (OR 0.214, 95% CI 0.155-0.296, P < 0.0001) was independently associated with unidentified AT. At AT, atrial fibrillation HF patients had higher HR (P < 0.0001) and higher VO(2) (P < 0.001) compared with sinus rhythm HF patients. Among AT variables, by multivariable logistic regression analysis, only HR was an independent predictor of atrial fibrillation. CONCLUSION In HF patients with permanent atrial fibrillation, exercise performance is reduced as reflected by reduced peak VO(2). The finding of unidentified AT is associated with a poor performance. In atrial fibrillation patients, VO(2) is higher at AT whereas lower at peak. This last observation raises uncertainties about the use of AT data to define performance and prognosis of HF patients with atrial fibrillation.

The resurgence of rheumatic fever in a developed country area: the role of echocardiography

OBJECTIVES The annual incidence of ARF ranges from 5 to 51/100, 000 population worldwide in the 5- to 15-year age group. In the past, there was a decline in the incidence of ARF; however, focal outbreaks have been reported. This study evaluated the incidence of ARF in 2007-08 in a region of a developed country compared with the previous decade. METHODS A retrospective review of all admission records for ARF in Trieste between January 2007 and December 2008 was undertaken. The diagnosis of ARF was established by the Jones criteria according to the 1992 revision. RESULTS Between January 2007 and December 2008: 13 cases of ARF were recorded, 11 females and 2 males. The estimated incidence was 23 and 27/100, 000 population new cases each year, respectively, in the 5- to 15-year age group. Migratory polyarthritis occurred in 6/13, chorea in 7/13 and clinical carditis in 5/13 cases. Five out of 13 patients had only echocardiographic abnormalities, with no clinical cardiac manifestations. Another two patients did not fulfil diagnostic criteria for ARF, presenting with only three minor criteria, but they revealed silent carditis at echocardiography evaluation. During the follow-up, in one case the carditis receded and in the other it significantly improved. CONCLUSIONS Our experience underlines that ARF has not yet disappeared in industrialized countries. We observed a high incidence of chorea, always associated with mild carditis. Echocardiographic assessment should be routinely performed in all patients with suspected ARF in order to identify those subclinical cases of valvulitis that would otherwise pass undiagnosed without receiving proper prophylaxis.

The metabolic exercise test data combined with Cardiac And Kidney Indexes (MECKI) score and prognosis in heart failure. A validation study

BACKGROUND The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a prognostic model to identify heart failure (HF) patients at risk for cardiovascular mortality (CVM) and urgent heart transplantation (uHT) based on 6 routine clinical parameters: hemoglobin, sodium, kidney function by the Modification of Diet in Renal Disease (MDRD) equation, left ventricle ejection fraction (LVEF), percentage of predicted peak oxygen consumption (VO2) and VE/VCO2 slope. OBJECTIVES MECKI score must be generalizable to be considered useful: therefore, its performance was validated in a new sequence of HF patients. METHODS Both the development (MECKI-D) and the validation (MECKI-V) cohorts were composed of consecutive HF patients with LVEF <40% able to perform a symptom-limited cardiopulmonary exercise testing. The CVM or uHT rates were analyzed at one, two and three years in both cohorts: all patients with a censoring time shorter than the scheduled follow-up were excluded, while those with events occurring after 1, 2 and 3 years were considered as censored. RESULTS MECKI-D and MECKI-V consisted of 2009 and 992 patients, respectively. MECKI-V patients had a higher LVEF, higher peak VO2 and lower VE/VCO2 slope, higher prescription of beta-blockers and device therapy: after the 3-year follow-up, CVM or uHT occurred in 206 (18%) MECKI-D and 44 (13%) MECKI-V patients (p<0.000), respectively. MECKI-V AUC values at one, two and three years were 0.81 ± 0.04, 0.76 ± 0.04, and 0.80 ± 0.03, respectively, not significantly different from MECKI-D. CONCLUSIONS MECKI score preserves its predictive ability in a HF population at a lower risk.

Renal Function and Peak Exercise Oxygen Consumption in Chronic Heart Failure With Reduced Left Ventricular Ejection Fraction

BACKGROUND Chronic kidney disease is associated with sympathetic activation and muscle abnormalities, which may contribute to decreased exercise capacity. We investigated the correlation of renal function with peak exercise oxygen consumption (V̇O2) in heart failure (HF) patients. METHODS AND RESULTS: We recruited 2,938 systolic HF patients who underwent clinical, laboratory, echocardiographic and cardiopulmonary exercise testing. The patients were stratified according to estimated glomerular filtration rate (eGFR). Mean follow-up was 3.7 years. The primary outcome was a composite of cardiovascular death and urgent heart transplantation at 3 years. On multivariable regression, eGFR was predictor of peakV̇O2(P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, B-type natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakV̇O2<12 ml·kg(-1)·min(-1)was 1.75 (95% confidence interval (CI): 1.06-2.91; P=0.0292) in patients with eGFR ≥60, 1.77 (0.87-3.61; P=0.1141) in those with eGFR of 45-59, and 2.72 (1.01-7.37; P=0.0489) in those with eGFR <45 ml·min(-1)·1.73 m(-2). The area under the receiver-operating characteristic curve for peakV̇O2<12 ml·kg(-1)·min(-1)was 0.63 (95% CI: 0.54-0.71), 0.67 (0.56-0.78), and 0.57 (0.47-0.69), respectively. Testing for interaction was not significant. CONCLUSIONS Renal dysfunction is correlated with peakV̇O2. A peakV̇O2cutoff of 12 ml·kg(-1)·min(-1)offers limited prognostic information in HF patients with more severely impaired renal function.

Prognostic value of cardiopulmonary exercise testing in Idiopathic Dilated Cardiomyopathy

BACKGROUND Although cardiopulmonary exercise testing (CPET) is considered as an important tool in risk stratification of patients with heart failure (HF), prognostic data in the specific setting of Idiopathic Dilated Cardiomyopathy (iDCM) are still undetermined. The aim of the study was to test the prognostic value of CPET in a large cohort of iDCM patients. METHODS AND RESULTS We analyzed 381 iDCM patients who consecutively performed CPET. The study end-point was a composite of cardiovascular death/urgent heart transplantation (CVD/HTx). In the overall population the average values of peak oxygen consumption (peak VO2/kg) and percent-predicted peak VO2 (peak VO2%) were 17.1±5.1ml/kg/min and 59±15%, respectively. Mean VE/VCO2 slope was 29.8±6.1. During a median follow-up of 47months (interquartile range 23-84), 83 patients experienced CVD/HTx. Peak VO2% (Area Under the Curve [AUC] 0.74; 95% CI 0.71-0.85, p<0.001) and VE/VCO2 slope (AUC 0.78; 95% CI 0.74-0.84, p<0.001) were more accurate in predicting CVD/HTx compared to peak VO2/kg (AUC 0.60; 95% CI 0.54-0.68, p=0.003) (p<0.001 for both comparisons). The most accurate threshold values for outcome prediction in our iDCM cohort were <60% for peak VO2% and >29 for VE/VCO2 slope. At multivariable analysis peak VO2% and VE/VCO2 slope were the strongest predictors of CVD/HTx, either as continuous and categorical variables, whereas peak VO2/kg was not independently related with prognosis. CONCLUSION In a large population of iDCM patients peak VO2% and VE/VCO2 slope emerged as the strongest prognostic CPET variables. Prospective studies will be necessary to confirm these data.

Echocardiographic Detection of Early Myocardial Calcification in Acute Neonatal Myocarditis Due to Coxsackie Virus Type B

We read with interest the case of the neonate with a myocardial infarction, in whom an acute enteroviral myocarditis (EM) was suspected. The patient subsequently died of heart failure at the age of 9 months [2]. We describe a similar patient but with a positive outcome. An 8-day-old, full-term neonate was admitted with polypnea, jaundice, and feeding difficulties. The neonate’s cardiorespiratory conditions suddenly deteriorated, requiring intubation and circulatory support by inotropes, fluids, and diuretics. Mother and sister had concomitant fever, which suggested a possible viral infection. Electrocardiography (ECG) showed inferior and lateral necrosis, ST elevation in leads I-V5–V6, and low QRS voltages (Fig. 1a). Echocardiography showed very poor left ventricle (LV) function, severe hypokinesia of the posteroinferior segments, and mild mitral, tricuspid, and aortic regurgitations (Supplementary materials 1 and 2). Myocardial necrosis markers were significantly elevated, with a troponin peak level of 3.3 ng/ml. Blood culture results were positive for enterovirus infection. After 2 days, the patient was resuscitated with DC shock for ventricular fibrillation. Catecholamines were stopped, whereas captopril and carvedilol were titrated and continued. Persistent ventricular and atrial tachyarrhythmias required long-term antiarrhythmic therapy with amiodarone. The echocardiographic evolution was peculiar. Left ventricle function recovered very slowly. Thinned, akinetic segments with hyperlucent areas were evident for many weeks in the lateral and inferior wall and in the posteromedial papillary muscle, suggesting patchy myocardium fibrosis or scar evolution (Fig. 1c and Supplementary material 3). During the follow-up period, the child was asymptomatic. Anomalies of coronary arteries were ruled out by angiography. All drugs were progressively discontinued. At this writing, the patient is 29 months old. No fibrosis or hyperlucency are detectable at echocardiography, and LV function is normal (Supplementary material 4). Narrow Q waves still are present on ECG in I, aVL, and V6 as markers of previous necrosis (Fig. 1b–d). Our case confirms that EM in the neonate may occur as a myocardial infarction [3] with a positive ECG, a troponine curve, and echocardiographic imaging. Myocardial lesions can evolve in fibrosis or scar [1]. In the acute phase, serious ventricular and atrial arrhythmias can occur [5]. Our patient recovered completely, probably because the extent of the myocardium lesions in the acute phase was limited. In the era of widespread preand postnatal imaging, viral myocarditis can be considered one of the most frequent causes of neonatal cardiac collapse [4]. In patients with viral myocarditis, early diagnosis, intensive monitoring, and aggressive treatment of heart failure and arrhythmias, including angiotensin-converting enzyme (ACE)-inhibitors and beta-blockers as soon as possible, can be life saving. Electronic supplementary material The online version of this article (doi:10.1007/s00246-011-0080-z) contains supplementary material, which is available to authorized users.

564 Patients affected by heart failure with peak oxygen consumption between 10-18 ml/kg/min: cardiopulmonary test offers additional parameters for a better prognostic stratification?

Background: Peak oxygen consumption (VO2) an old-time classic parameter used to stratify HF patients (pts) was recently combined to VE/VCO2 slope, in order to improve heart transplant selection criteria. The lack of prognostic factors is particularly evident in the subgroup of pts with intermediate grade of risk (i.e. with a peak VO2 between 10 and 18 ml/kg/min).We sought to analyse the predictive role of aerobic indexes obtained during Cardiopulmonary Exercise Testing (CPET) in pts affected by idiopathic dilated cardiomyopathy (IDC) with a peak VO2 between 10 and 18 ml/kg/min. Methods:We analyzed 171 IDC pts enrolled in the Trieste Heart Muscle Disease Registry who underwent CPET from 1997 and 2005. Among these, 97 pts had a peak VO2 between 10 and 18 ml/kg/min (mean age 48±10 yrs, males 71%, NYHA class III-IV 20%, left ventricle ejection fraction (LVEF) 0.30±0.11, peak VO2 14±2 ml/kg/min, ACE-inhibitors 93%, beta-blockers 88%). Combined end-point was considered Cardiovascular Death/Major Ventricular Arrhythmias/Cardiovascular Hospitalizations at 1 year. Results: At univariate analysis, pts who satisfied the end point criteria at one-year, in comparison with those who did not, showed a trend towards more advanced functional NYHA class, lower LVEF and lower circulatory power. The only parameter significantly associated to our combined end-point resulted a higher VE/VCO2 slope (34±7 vs 29±4, p=0.003). At multivariate analysis VE/VCO2 slope was selected as an independent predictor of one-year cardiovascular endpoint (for a 2-unit increase: O.R.1.41, 95% I.C. 1.08-1.85, p=0.012) together with LVEF (for a 5point decrease: O.R.1.71, 95% I.C. 1.08-2.71, p=0.025). At ROC curves VE/VCO2 slope had an AUC of 0.694 for our study end-point with a cut-off value of 28. Conclusions: In pts classified at intermediate risk according to peak VO2, VE/VCO2 slope may add prognostic power to identify pts at higher risk of early heart transplant indication.

565 Prognostic role of cardiopulmonary exercise indexes in patients with heart failure receiving beta-blockers

Background: Peak oxygen consumption (VO2) an old-time classic parameter used to stratify HF patients (pts) was recently combined to VE/VCO2 slope, in order to improve heart transplant selection criteria. The lack of prognostic factors is particularly evident in the subgroup of pts with intermediate grade of risk (i.e. with a peak VO2 between 10 and 18 ml/kg/min).We sought to analyse the predictive role of aerobic indexes obtained during Cardiopulmonary Exercise Testing (CPET) in pts affected by idiopathic dilated cardiomyopathy (IDC) with a peak VO2 between 10 and 18 ml/kg/min. Methods:We analyzed 171 IDC pts enrolled in the Trieste Heart Muscle Disease Registry who underwent CPET from 1997 and 2005. Among these, 97 pts had a peak VO2 between 10 and 18 ml/kg/min (mean age 48±10 yrs, males 71%, NYHA class III-IV 20%, left ventricle ejection fraction (LVEF) 0.30±0.11, peak VO2 14±2 ml/kg/min, ACE-inhibitors 93%, beta-blockers 88%). Combined end-point was considered Cardiovascular Death/Major Ventricular Arrhythmias/Cardiovascular Hospitalizations at 1 year. Results: At univariate analysis, pts who satisfied the end point criteria at one-year, in comparison with those who did not, showed a trend towards more advanced functional NYHA class, lower LVEF and lower circulatory power. The only parameter significantly associated to our combined end-point resulted a higher VE/VCO2 slope (34±7 vs 29±4, p=0.003). At multivariate analysis VE/VCO2 slope was selected as an independent predictor of one-year cardiovascular endpoint (for a 2-unit increase: O.R.1.41, 95% I.C. 1.08-1.85, p=0.012) together with LVEF (for a 5point decrease: O.R.1.71, 95% I.C. 1.08-2.71, p=0.025). At ROC curves VE/VCO2 slope had an AUC of 0.694 for our study end-point with a cut-off value of 28. Conclusions: In pts classified at intermediate risk according to peak VO2, VE/VCO2 slope may add prognostic power to identify pts at higher risk of early heart transplant indication.