Simona Sarzi Braga

Prediction of late arrhythmic events after acute myocardial infarction from combined use of noninvasive prognostic variables and inducibility of sustained monomorphic ventricular tachycardia.

A combined use of noninvasive techniques and electrophysiologic study in the prediction of arrhythmic events was prospectively evaluated in 303 surviving patients of acute myocardial infarction (AMI). The most powerful combination of noninvasive prognostic variables in identifying patients suitable for invasive strategies was also assessed. Patients who had > or = 2 variables among left ventricular ejection fraction < 0.4, ventricular late potentials and repetitive ventricular premature complexes (VPCs) were considered eligible for programmed ventricular stimulation. After 15 +/- 7 months of follow-up, 19 patients (6%) had an arrhythmic event. Left ventricular dyskinesia (p < 0.00001) and ejection fraction < 0.4 (p < 0.000001), late potentials (p < 0.001), filtered QRS duration > or = 106 ms (p < 0.00001), VPCs/hour > 6 (p < 0.05), paired VPCs (p < 0.01), > or = 2 runs of unsustained ventricular tachycardia (VT) per monitoring (p < 0.001), heart rate variability index < or = 29 (p < 0.00001) and mean RR interval < or = 750 ms (p < 0.01) were found to be significant univariate predictors of events. At multivariate analysis, only low left ventricular ejection fraction, prolonged filtered QRS duration, reduced heart rate variability index and detection of > or = 2 runs of unsustained VT per monitoring had an independent relation to late arrhythmic events. Of 67 eligible patients, 47 (70%) consented to undergo programmed stimulation. A positive electrophysiologic study was found to be the strongest independent predictor of events among patients preselected by noninvasive techniques. With a good sensitivity (81%), a combined use of noninvasive tests and electrophysiologic study selected a group of post-AMI patients at sufficiently high risk (event rate 65%) to be considered candidates for interventional therapy. The combination of > or = 2 variables among left ventricular ejection fraction < 0.4, filtered QRS duration > or = 106 ms and > or = 2 runs of unsustained VT was superior to the other ones in identifying high-risk subjects (positive and negative predictive values for arrhythmic events of 44 and 99%, respectively). On the basis of the data, this scheme appears to be the most appropriate for selecting patients suitable for electrophysiologic testing and invasive strategies after AMI.

Atrial fibrillation in heart failure patients: Prevalence in daily practice and effect on the severity of symptoms. Data from the ALPHA study registry

Estimates of the prevalence of atrial fibrillation (AF) in heart failure (HF) originate from patients enrolled in clinical trials.

Influence of transdermal scopolamine on cardiac sympathovagal interaction after acute myocardial infarction

In 41 survivors of acute myocardial infarction (AMI) a prospective study was performed in 2 sequential phases. In phase 1, the role of baroreflex sensitivity and heart rate variability as predictors of inducible and spontaneous sustained ventricular tachyarrhythmias was evaluated. In phase 2, the effects of transdermal scopolamine on baroreflex sensitivity, spectral and nonspectral measures of heart rate variability were investigated. At a mean follow-up of 10 +/- 3 months after AMI, 5 of 41 patients (12%) developed a late arrhythmic event. Of these, all (100%) had inducibility of sustained monomorphic ventricular tachycardia at programmed stimulation compared with 3 of 36 patients (8%) without events (p < 0.0001). At multivariate analysis, baroreflex sensitivity had the strongest relation to both inducibility of sustained monomorphic ventricular tachycardia (p < 0.0001) and occurrence of arrhythmic events (p < 0.0001). Of 41 patients, 28 (68%) consented to undergo phase 2 of the investigation. Baroreflex sensitivity significantly (p < 0.00001) increased after transdermal scopolamine as well as heart rate variability indexes. Of these, the mean of SDs of normal RR intervals for 5-minute segments (p < 0.0001) and the total power (p < 0.0001) had the most significant improvement after scopolamine. The present investigation confirms that assessment of autonomic function is an essential part of arrhythmic risk evaluation after AMI. Transdermal scopolamine, administered to survivors of a recent AMI, reverses the autonomic indexes that independently predict arrhythmic event occurrence. On the basis of these data, transdermal scopolamine could be a potential useful tool in the prophylaxis of life-threatening ventricular arrhythmias after AMI.

Effect of thrombolysis on heart rate variability and life-threatening ventricular arrhythmias in survivors of acute myocardial infarction.

OBJECTIVES The aim of the present study was to determine the influence of early thrombolysis on ventricular tachyarrhythmias (clinical and inducible) and heart rate variability in survivors of myocardial infarction at high risk for life-threatening ventricular arrhythmias. BACKGROUND A greater electrical heart stability may be important in improving survival in patients treated with thrombolysis. Few data are available about the influence of fibrinolysis on postinfarction arrhythmic events and other prognostic variables, such as inducible ventricular tachycardia and heart rate variability. METHODS The study group comprised 51 consecutive patients who underwent electrophysiologic study within 30 days of infarction, owing to the presence of two or more of the following criteria: left ventricular ejection fraction < 40%, late potentials and repetitive ventricular ectopic beats. Thirty patients underwent thrombolysis within 6 h of the onset of symptoms (Group A), and 21 received conventional treatment (Group B). Inducibility of sustained monomorphic ventricular tachycardia was tested in both groups, and the standard deviation of all normal RR intervals during 24-h Holter monitoring was calculated. All patients were prospectively evaluated for occurrence of arrhythmic events. RESULTS The two groups were similar with regard to left ventricular ejection fraction (mean +/- 1 SD 38 +/- 6% [Group A] vs. 36 +/- 8% [Group B]). Ventricular tachycardia was induced in 6 (20%) of 30 Group A patients versus 14 (67%) of 21 Group B patients (p = 0.002). The standard deviation of normal RR intervals was higher in Group A than in Group B (113 +/- 36 vs. 90 +/- 39 ms, p = 0.05). In patients with anterior infarction, the standard deviation of normal RR intervals was higher in 19 patients with thrombolysis than in 16 patients with conventional treatment (118 +/- 41 vs. 74 +/- 24 ms, p = 0.0002). During a mean follow-up period of 23 +/- 11 months, 4 (13%) of 30 Group A patients had an arrhythmic event versus 9 (43%) of 21 Group B patients (p = 0.04). CONCLUSIONS After myocardial infarction, in high risk patients, thrombolysis significantly reduced the occurrence of arrhythmic events independently of left ventricular function. This effect may be related to both an improvement in electrical heart stability, as elucidated by electrophysiologic study, and a favorable action on the cardiac sympathovagal balance.

T wave alternans is a predictor of death in patients with congestive heart failure

Few data are available about the prognostic role of T wave alternans in patients with congestive heart failure. To assess the ability of T wave alternans, used alone or in combination with other risk markers, to predict cardiac death in decompensated patients, we enrolled 46 patients, mean age 59+/-9, males 89%, ischemic etiology 61%, NYHA class III 35%, left ventricular ejection fraction 29+/-7%. After 1.6 years follow-up, seven patients died from cardiac death (16%), non-sudden in six (86%) and sudden in one (14%). T wave alternans was positive in 24 (52%), negative in 13 (28%), indeterminate in nine patients (20%). T wave alternans was positive in all patients with events (100%) but only in 16 of 37 patients without (41%) (P=0.02). Other predictors of cardiac death were O(2) consumption at the peak of exercise (P=0.03), standard deviation of all NN intervals (P=0.05) and Wedge pressure (P=0.03). When receiver operator characteristics curves were calculated, the highest area (0.73) was found for O(2) consumption at the peak of exercise considering the single variables and for O(2) consumption at the peak of exercise plus T wave alternans (0.79) for combination of them; the comparison of the two receiver operator characteristics curves did not reach statistical difference (P=0.5). In conclusion, this is the first study reporting that T wave alternans can predict cardiac death, with a marginal additional prognostic power when used in combination with measurement of O(2) consumption at the peak of exercise.

Clinical utility of N-terminal pro-B-type natriuretic peptide for risk stratification of patients with acute decompensated heart failure. Derivation and validation of the ADHF/NT-proBNP risk score

BACKGROUND NT-proBNP has been associated with prognosis in acute decompensated heart failure (ADHF). Whether NT-proBNP provides additional prognostic information beyond that obtained from standard clinical variables is uncertain. We sought to assess whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) determination improves risk reclassification of patients with ADHF and to develop and validate a point-based NT-proBNP risk score. METHODS This study included 824 patients with ADHF (453 in the derivation cohort, 371 in the validation cohort). We compared two multivariable models predicting 1-year all-cause mortality, including clinical variables and clinical variables plus NT-proBNP. We calculated the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI). Then, we developed and externally validated the NT-proBNP risk score. RESULTS One-year mortalities for the derivation and validation cohorts were 28.3% and 23.4%, respectively. Multivariable predictors of mortality included chronic obstructive pulmonary disease, estimated glomerular filtration rate, sodium, hemoglobin, left ventricular ejection fraction, and moderate to severe tricuspid regurgitation. Adding NT-proBNP to the clinical variables only model significantly improved the NRI (0.129; p=0.0027) and the IDI (0.037; p=0.0005). In the derivation cohort, the NT-proBNP risk score had a C index of 0.839 (95% CI: 0.798-0.880) and the Hosmer-Lemeshow statistic was 1.23 (p=0.542), indicating good calibration. In the validation cohort, the risk score had a C index of 0.768 (95% CI: 0.711-0.817); the Hosmer-Lemeshow statistic was 2.76 (p=0.251), after recalibration. CONCLUSIONS The NT-proBNP risk score provides clinicians with a contemporary, accurate, easy-to-use, and validated predictive tool. Further validation in other datasets is advisable.

The European Association of Preventive Cardiology Exercise Prescription in Everyday Practice and Rehabilitative Training (EXPERT) tool: A digital training and decision support system for optimized exercise prescription in cardiovascular disease. Concept, definitions and construction methodology

Background Exercise rehabilitation is highly recommended by current guidelines on prevention of cardiovascular disease, but its implementation is still poor. Many clinicians experience difficulties in prescribing exercise in the presence of different concomitant cardiovascular diseases and risk factors within the same patient. It was aimed to develop a digital training and decision support system for exercise prescription in cardiovascular disease patients in clinical practice: the European Association of Preventive Cardiology Exercise Prescription in Everyday Practice and Rehabilitative Training (EXPERT) tool. Methods EXPERT working group members were requested to define (a) diagnostic criteria for specific cardiovascular diseases, cardiovascular disease risk factors, and other chronic non-cardiovascular conditions, (b) primary goals of exercise intervention, (c) disease-specific prescription of exercise training (intensity, frequency, volume, type, session and programme duration), and (d) exercise training safety advices. The impact of exercise tolerance, common cardiovascular medications and adverse events during exercise testing were further taken into account for optimized exercise prescription. Results Exercise training recommendations and safety advices were formulated for 10 cardiovascular diseases, five cardiovascular disease risk factors (type 1 and 2 diabetes, obesity, hypertension, hypercholesterolaemia), and three common chronic non-cardiovascular conditions (lung and renal failure and sarcopaenia), but also accounted for baseline exercise tolerance, common cardiovascular medications and occurrence of adverse events during exercise testing. An algorithm, supported by an interactive tool, was constructed based on these data. This training and decision support system automatically provides an exercise prescription according to the variables provided. Conclusion This digital training and decision support system may contribute in overcoming barriers in exercise implementation in common cardiovascular diseases.

Proportion of patients needing an implantable cardioverter defibrillator on the basis of current guidelines: impact on healthcare resources in Italy and the USA. Data from the ALPHA study registry

AIMS Implantable cardioverter defibrillators (ICD) improve survival in selected patients with left ventricular dysfunction or heart failure (HF). The objective is to estimate the number of ICD candidates and to assess the potential impact on public health expenditure in Italy and the USA. METHODS AND RESULTS Data from 3513 consecutive patients (ALPHA study registry) were screened. A model based on international guidelines inclusion criteria and epidemiological data was used to estimate the number of eligible patients. A comparison with current ICD implant rate was done to estimate the necessary incremental rate to treat eligible patients within 5 years. Up to 54% of HF patients are estimated to be eligible for ICD implantation. An implantation policy based on guidelines would significantly increase the ICD number to 2671 implants per million inhabitants in Italy and to 4261 in the USA. An annual increment of prophylactic ICD implants of 20% in the USA and 68% in Italy would be necessary to treat all indicated patients in a 5-year timeframe. CONCLUSION Implantable cardioverter defibrillator implantation policy based on current evidence may have significant impact on public health expenditure. Effective risk stratification may be useful in order to maximize benefit of ICD therapy and its cost-effectiveness in primary prevention.

Effects of oral pirenzepine on heart rate variability and baroreceptor reflex sensitivity after acute myocardial infarction

OBJECTIVES Our aims were 1) to assess whether oral pirenzepine could increase indexes of cardiac vagal activity in postinfarction patients, and 2) to compare the effects of this agent with those of transdermal scopolamine. BACKGROUND Depression of vagal tone and reflexes predicts a poor arrhythmic outcome after myocardial infarction. Interventions for shifting the sympathovagal balance toward vagal dominance are now of increased clinical interest. Intravenous pirenzepine increases RR interval variability in normal volunteers, a finding that could have therapeutic implications if confirmed in postinfarction patients after oral administration of the drug. METHODS In a single-blind placebo-controlled crossover trial, short-term RR interval variability and baroreceptor reflex sensitivity were evaluated in 20 patients an average of 19 +/- 6 days after infarction. Analysis was performed during control conditions and during administration of placebo, oral pirenzepine and transdermal scopolamine. RESULTS Compared with placebo, at a dose of 25 mg twice daily, pirenzepine significantly increased all time and frequency domain measures of RR interval variability and augmented baroreceptor reflex sensitivity by 60% (mean +/- 1 SD 10.4 +/- 5.9 vs. 6.5 +/- 3.2 ms/mm Hg, p = 0.0007). Pirenzepine and scopolamine showed a similar vagomimetic effect, but the overall incidence of adverse effects was lower with pirenzepine (1 [5%] of 20 vs. 10 [50%] of 20). CONCLUSIONS In patients with a recent myocardial infarction, oral pirenzepine proved equal to transdermal scopolamine in significantly increasing indexes of cardiac vagal activity. These data suggest that oral pirenzepine may have a therapeutic potential for preventing malignant ventricular arrhythmias after infarction.

The ADHF/NT-proBNP risk score to predict 1-year mortality in hospitalized patients with advanced decompensated heart failure

BACKGROUND The acute decompensated heart failure/N-terminal pro-B-type natriuretic peptide (ADHF/NT-proBNP) score is a validated risk scoring system that predicts mortality in hospitalized heart failure patients with a wide range of left ventricular ejection fractions (LVEFs). We sought to assess discrimination and calibration of the score when applied to patients with advanced decompensated heart failure (AHF). METHODS We studied 445 patients hospitalized for AHF, defined by the presence of severe symptoms of worsening HF at admission, severely depressed LVEF, and the need for intravenous diuretic and/or inotropic drugs. The primary outcome was cumulative (in-hospital and post-discharge) mortality and post-discharge 1-year mortality. Separate analyses were performed for patients aged ≤ 70 years. A Seattle Heart Failure Score (SHFS) was calculated for each patient discharged alive. RESULTS During follow-up, 144 patients (32.4%) died, and 69 (15.5%) underwent heart transplantation (HT) or ventricular assist device (VAD) implantation. After accounting for the competing events (VAD/HT), the ADHF/NT-proBNP scores C-statistic for cumulative mortality was 0.738 in the overall cohort and 0.771 in patients aged ≤ 70 years. The C-statistic for post-discharge mortality was 0.741 and 0.751, respectively. Adding prior (≤6 months) hospitalizations for HF to the score increased the C-statistic for post-discharge mortality to 0.759 in the overall cohort and to 0.774 in patients aged ≤ 70 years. Predicted and observed mortality rates by quartiles of score were highly correlated. The SHFS demonstrated adequate discrimination but underestimated the risk. The ADHF/NT-proBNP risk calculator is available at http://www.fsm.it/fsm/file/NTproBNPscore.zip. CONCLUSIONS Our data suggest that the ADHF/NT-proBNP score may efficiently predict mortality in patients hospitalized with AHF.