[Natriuretic peptides in heart failure]. / Peptidi natriuretici come guida alla prognosi e terapia nello scompenso cardiaco.

The recent discovery of cardiac endocrine function, together with the development of accurate and feasible assay methods for cardiac natriuretic hormone evaluation, i.e. for B-type natriuretic peptide (BNP) and inactive peptide NT-proBNP have confirmed their pathophysiological and clinical significance for cardiovascular disease assessment. Concerning heart failure, their value is for diagnostic screening in selected/unselected populations, for differential diagnosis of dyspnea and for prognostic stratification, and as a guide for follow-up and treatment of patients. Recent Italian recommendations pointed out that BNP/NT-proBNP has a role in ruling-out the diagnosis of heart failure in patients with dubious signs/symptoms: plasma BNP/NT-proBNP concentrations help in the clinical evaluation of chronic heart failure patients when risk stratification is needed, whereas the routine BNP/NT-proBNP assay is still not recommended to guide therapeutic decision-making.

Relationships between cardiac pain and objective markers of transient myocardial ischemia.

Cardiac pain is a key symptom for diagnosis of myocardial ischemia in man, even if a minority of transient myocardial ischemic episodes are painful. A multiparametric monitoring approach - associating non-invasive and invasive monitoring techniques during transient myocardial ischemia with and without pain - allows to achieve a clinical diagnosis and obtain information about the pathophysiology of the anginal syndrome.

Clinical characteristics of anginal pain in man.

The clinical recognition of the cardiac origin of chest pain or discomfort on the basis of the description made by the patient, is often difficult. Nevertheless, considering the importance of the correct diagnosis of such syndrome, much work has been done in this field. In this report we will comment data from the literature and from our own, on the quality, duration, irradiation and on the precipitating or relieving factors that are more frequently associated with anginal pain.

Transient myocardial ischemia and cardiac pain. Importance of duration of ischemia, heart rate behaviour and circadian distribution.

In 40 drug-free patients 2052 episodes of transient myocardial ischemia (28% painful) were recorded by 24-h ambulatory ECG. Pain was more frequently associated with longer duration of ischemia and greater ST segment shift and with the presence of ventricular arrhythmias within the ischemic episode. Heart rate always showed a growing trend during the ischemic episode. Circadian distribution of painless ischemic episodes showed a maximum peak at 2 a.m. while the most painful attacks occurred early in the morning (6 a.m.).

The contribution of ventricular tachyarrhythmias to the genesis of cardiac pain during transient myocardial ischaemia in patients with variant angina.

The 24-h ambulatory electrocardiograms of 15 patients with both variant angina and ischaemia-related arrhythmias were analyzed to correlate cardiac pain with the following variables: site, type, duration and magnitude of ECG changes, presence and type of arrhythmias and time of occurrence of ischaemic attacks during the 24-h. Apart from sublingual nitrate therapy, Holter monitoring was performed in the Coronary Care Unit (CCU), in the drug-free state in all patients. During a total of 79 days of monitoring, patients had 1385 ischaemic episodes, of which only 30% were painful. The site of ischaemia did not predict the occurrence of pain. Pain was more frequently associated with ST-segment elevation, longer ischaemic duration, increased time to peak ECG change, and greater ST-segment shift and arrhythmias. When the 259 attacks in association with ventricular arrhythmias were compared to the arrhythmia-free episodes, they were more frequently painful for the same duration and magnitude of ECG ischaemic changes. Furthermore, the complexity of arrhythmias increased the probability of cardiac pain. Most ischaemic episodes occurred at night and a decrease in the frequency of painful episodes (apart from those associated with arrhythmias) was apparent. Thus, in addition to electrocardiographic severity and duration of ischaemia, the presence of ventricular arrhythmias and the time of occurrence seem to influence pain perception during ischaemia.

Improvement of walking distance in patients with intermittent claudication by chronic local therapy with isosorbide dinitrate ointment.

Isosorbide dinitrate ointment (100 mg tid) was directly applied to 30 male patients with stable, documented intermittent claudication on the areas where ischemic pain was experienced. The symptom-free distance walked (DWA) and the maximum distance reached (MDR) basally, after one, three, six, and twelve months were evaluated by means of treadmill stress tests (TSTs) (angle 0 degree-velocity constant/patient). After the basal TST, patients were randomly divided into two groups: placebo group and therapy group (double blind), and a further TST was administered one month later. DWA results were 74 +/- 8 m vs 297 +/- 83 m and MDR results were 163 +/- 22 m vs 506 +/- 86 m in the therapy group (basal vs one month TST: p less than .01) and 94 +/- 24 m vs 96 +/- 15 m and 232 +/- 53 m vs 183 +/- 26 m in the placebo group, respectively (basal vs one month TST: NS). Being confident that a significant placebo effect was absent, the authors opened the trial and treated all patients, repeating further TSTs at three, six, and twelve months. The following results were obtained: DWA was 84 +/- 13 m, 316 +/- 63 m, 374 +/- 55 m, and 452 +/- 61 m; and MDR was 197 +/- 29 m, 431 +/- 59 m, 514 +/- 57 m, and 547 +/- 59 m, respectively, in basal conditions and after three, six, and twelve months of treatment (p less than .01 for all the values for both DWA and MDR vs basal values).(ABSTRACT TRUNCATED AT 250 WORDS)

[Technical ambulatory ECG innovations in performance evaluation]. / Novità tecniche in ECG dinamica nella valutazione delle prestazioni.

Evaluating the performances of the instrumentation for Ambulatory ECG (AECG) analysis is a need largely recognized by both manufacturers and users. The most generally accepted method is the beat-by-beat comparison with annotated data bases, representing the different ECG abnormalities. Available data bases are aimed at arrhythmias detection evaluation, while it is recognized that the AECG ST-T changes detection has a great relevance in the analysis of ischemic heart disease. A concerted action of the European Community on Ambulatory Monitoring has been approved for achieving a comprehensive reference standard for assessing the quality of AECG instrumentation. The European project has been concentrated on the problem of ST-T analysis. An annotated data base is being developed with the contribution of european experts. A pilot study has been performed for establishing the criteria related to the development and annotation; particularly the definition of significant ST-T changes has been established. The data base will include 2-hour double channel AECG records, which contain at least one ST-T episode. Each record is annotated beat by beat according to the established scheme, identifying arrhythmic beats, rhythm changes, ST-T changes and noisy segments. A coordinating center has been established for interacting with the participating groups and for performing the operations related to the generation and management of the data base. For the time being 14 Groups of 8 Countries are participating to the annotation of the data base. A minimum number of 100 records is planned within June 1988.

[Ambulatory electrocardiography in patients with angina pectoris]. / L'elettrocardiografia dinamica nel paziente anginoso.

In the diagnosis of ischemic heart disease, long-term ECG recording has several distinct advantages. It allows one to relate patient symptoms to cardiac disturbances and to detect asymptomatic events, reveals the possible ischemic genesis of arrhythmias, and it is the most suitable method to assess the acute and chronic effectiveness of treatment and the evolution of the disease. In spite of these advantages, Holter monitoring has several limitations: the analysis of a single lead, is responsible in most systems for the low sensitivity in detecting ischemia occurring in unexplored regions; the period of 24-48 hours may not be sufficient for screening patients due to the unpredictable spontaneous variability of the disease; a common standard of analysis is still lacking even if the European Communities concerted action in Ambulatory Monitoring could represent the solution to this problem. Nevertheless the role of Holter monitoring appears essential in the ambulatory screening of patients with suspected ischemia for a better characterization of patients with ascertained myocardial ischemia, and for the evaluation of treatment and of the evolution of the disease.

Findings from long-term electrocardiographic monitoring of patients with variant angina in a coronary care unit.

Eleven patients with frequent episodes of variant angina underwent 24-hour electrocardiographic monitoring in a coronary care unit for a total of 70 days to assess circadian variation in ischemic episodes and its correlation with circadian heart rate (HR) rhythm. In each patient a series of 4 to 13 consecutive days, in the absence of therapy, with 8 or more ischemic episodes per day were analyzed. Harmonic regression models were fitted to the hourly number of ischemic episodes and the hourly values of HR. Out of 54 days, with 8 or more episodes per day for a total of 1,357 episodes, a circadian rhythm was observed for 34 days (64%), in at least 1 day in all patients and during the entire period of observation in only 3. Its presence was independent of the number of episodes; the peak of periodic functions occurred at 2.9 +/- 2.7 AM. A cadian rhythm for HR was observed in 61 of the 70 days (87%), consistently in 7 patients; the nadir occurred at 2.4 +/- 1.5 AM; simultaneous cycling in HR and transient ischemia was found on 32 days. The intrapatient difference between the peak and the nadir of the ischemic and the HR function was, on average, 2.6 +/- 3.3 hours. Thus, a circadian rhythm of ischemic episodes was present in all patients although it was not consistently present; simultaneous occurrence of circadian variation in ischemic episodes and HR was observed only in 60% of the days with a sufficiently high number of attacks and when this occurred, a significant phase shift was observed; occasional loss of HR cycling was observed in some patients, without an apparent cause.

Detection of spontaneous episodes in post-infarction angina. Comparison between CCU and Holter monitoring.

The objects of this study are: to evaluate the incidence of early post-infarction angina in patients who developed transmural infarction (Q-AMI) or sub-endocardial infarction (no Q-AMI) during hospitalization; to compare data obtained from patients monitored in Coronary Care Unit (CCU) with those obtained from Holter monitoring. The 107 patients under study (55 with Q-AMI and 52 with no Q-AMI) presented the acute event on average 7.4 and 5.1 days after admittance in the CCU, respectively. A history of angina was present in all except 1 patient with Q-AMI and in all with no Q-AMI. After AMI the angina disappeared in 22 of the patients with Q-AMI and in 31 with no Q-AMI, while it continued in 33 and 21 of these patients, respectively. Twenty-one patients underwent ECG recording according to the Holter technique while in CCU, for an average of 4.4 days before and 5.2 days after the onset of AMI. The comparative analysis of the results obtained from the CCU and from Holter monitoring shows that the CCU greatly underestimates the number of ischaemic episodes, even when pain is present (4.5 episodes per patient per day before AMI and 2 after, versus 13.7 and 6.8 with Holter monitoring). The number of ventricular arrhythmias also seemed lower when analysing data from CCU monitoring. These data demonstrate the importance of Holter monitoring, even in patients admitted to a CCU, for a precise evaluation of the ischaemic and arrhythmic phenomena.

Electrocardiographic monitoring: temporal versus spatial information and data processing.

In the diagnosis of ischemic heart disease, long-term electrocardiographic recording has several distinct advantages. It allows one to relate patient symptoms to cardiac disturbances and to detect asymptomatic events, furnishes the whole spectrum of electrocardiographic alterations accompanying ischemic attacks, reveals the possible ischemic genesis of dysrhythmias, and is the most suitable method to assess the acute and chronic effectiveness of treatment and the evolution of the disease. In addition to its valuable application in the screening and follow-up of ambulatory patients, its use in the Coronary Care Unit is of great interest, being in this context much more sensitive than visual electrocardiographic monitoring. In spite of these advantages, Holter monitoring has several limitations: the recording and replay systems are below recommended standards; the analysis of a single lead is responsible in most systems for the low sensitivity in detecting ischemia occurring in unexplored regions; the period of 24-48 hours, usually adopted for Holter monitoring, may not be sufficient for screening patients with suspected myocardial ischemia due to the unpredictable spontaneous variability of the disease; a common standard of analysis is still lacking and a reliable computerized analysis is needed to manage data overflow. In conclusion, although further research and technical developments are desired to improve reliability and data processing, the role of Holter monitoring appears essential in the ambulatory screening of patients with suspected ischemia for a better characterization of patients with ascertained myocardial ischemia, and for the evaluation of treatment and of the evolution of the disease.

[Isosorbide dinitrate ointment in the long-term treatment of intermittent claudication]. / Isosorbide dinitrato in pasta nel trattamento a lungo termine della claudicatio intermittens.

We evaluated the long-term therapy with Isosorbide Dinitrate Ointment (ISDN-O): 300 mg daily on the painful leg area in 20 male patients (pts) affected by Intermittent Claudication. The efficacy of the treatment was assessed on the basis of the subjective evaluation of pain threshold (daily diary) and objectively by repeated treadmill stress tests performed by each patient at a constant speed, selected according to the severity of symptoms, and by the evaluation of changes both of the distance walked without symptoms (DWS) and of the maximal distance reached (MDR). The maximal duration of the test was 15 minutes independently from the speed. The reproducibility of treadmill tests and the acute effect of isosorbide dinitrate ointment administration were preliminarly evaluated in 2 groups of 5 patients each. The distance walked without symptoms and maximal distance reached in two control stress tests performed in two successive days were: distance walked without symptoms 37 +/- 29 vs 36 +/- 22 m (NS) and maximal distance reached 97 +/- 40 vs 98 +/- 37 m (NS). During the control period and 1 hour after the drug administration distance walked without symptoms was 34 +/- 31 vs 43 +/- 50 m (NS) and maximal distance reached 89 +/- 53 vs 97 +/- 57, (NS) respectively. In a group of 5 patients the effect of one month administration of placebo was evaluated: distance walked without symptoms was m 68 +/- 29 and m 104 +/- 62 and maximal distance reached was m 156 +/- 103 and m 188 +/- 97 basally and after 1 month of placebo (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Unreliability of conventional visual electrocardiographic monitoring for detection of transient ST segment changes in a coronary care unit.

Visual monitoring at the central station of coronary care units (CCUs) may not adequately assess the presence and frequency of transient asymptomatic ST segment changes in patients with unstable angina. We have performed continuous 24-h electrocardiographic recordings over a total period of 50 days in 10 patients admitted to our CCU with frequent attacks of angina at rest. Over the corresponding period, at the central monitoring station (6 beds), the nursing-staff detected only 31 transient ischaemic episodes (27 with ST elevation, 4 with depression, 9 of which were asymptomatic). By contrast the retrospective analogue analysis of tapes identified 213 ischaemic episodes: 143 with ST elevation (greater than or equal to 0.2 mV) and 70 with ST depression (greater than or equal to 0.2 mV); usual CCU monitoring failed to report changes during 13 episodes (8 with ST elevation, 5 with depression) accompanied by anginal pain. When the tapes were played back in real time on a CCU monitoring scope, a cardiologist (who had the option of interrupting the play-back whenever tired) recognized 48% of the episodes when presented in groups of 4 and randomly positioned on the screen together with 2 other electrocardiographic tracings not related to the study; he recognized 92% of the episodes when only one ECG was presented on the screen. Thus conventional visual monitoring in a CCU considerably underestimates the incidence of transient ischaemic ST segment changes, some of which were accompanied by pain. This low rate of detection is the result of the presentation on the central monitoring station of several ECGs and of fatigue.

Intravenous dl-carnitine fails to increase the double-product during atrial pacing in patients with effort angina. A double-blind randomized study.

Infusions of DL-carnitine are reported to improve the tolerance to atrial pacing of patients with angina pectoris. In the present study, six patients with angina of effort and triple vessel disease received two placebo and two carnitine infusions administered in a double-blind randomized fashion. Carnitine did not affect either the double product (heart rate X systolic blood pressure) at maximal pacing (ST depression: 2.3 +/- 0.2 mm, +/- SEM) or the tolerated pacing time. Intravenous carnitine, in the dose given, is of no therapeutic benefit in myocardial ischemia precipitated by tachycardia. It could be effective when free fatty acids are elevated as during catecholamine stimulation.

Vasospastic ischemic mechanism of frequent asymptomatic transient ST-T changes during continuous electrocardiographic monitoring in selected unstable angina patients.

Asymptomatic episodes of ST segment and/or T wave changes are often reported during Holter monitoring in patients with angina pectoris. However, the interpretation of such changes is debated relative to silent myocardial ischemia. We studied 11 patients admitted to the CCU because of frequent episodes of unstable anginal attacks who had undergone repeated periods of Holter monitoring, characterized by predominantly occurring asymptomatic episodes of ST segment and/or T wave changes associated with less frequent typical anginal attacks. In a total of 89 days of Holter monitoring, the patients evidenced 520 episodes of transient ECG changes including 180 of ST elevation, 73 of ST depression, and 267 of T wave alterations. Only 12% of episodes were symptomatic. Coronary injection during asymptomatic ST-T changes was performed in eight patients. In six it was possible to document spontaneous coronary spasm. In seven patients ergonovine administration induced anginal pain, ST-T changes, and coronary spasm. In all patients the anginal attacks completely disappeared with medical treatment and the asymptomatic episodes were abolished in six and reduced in four. Our findings support the hypothesis that in certain selected unstable anginal patients, transient asymptomatic ECG changes are caused by acute myocardial ischemia.

Myocardial cell damage during attacks of vasospastic angina in the absence of persistent electrocardiographic changes.

We have investigated whether vasospastic anginal attacks might be associated with myocardial cell damage even when permanent ORS or ST-T changes are absent. We obtained serum time-activity curves of creatine kinase MB, of myoglobin, and of alpha hydroxybutyrate dehydrogenase in 15 patients with vasospastic angina admitted to our Coronary Care Unit (CCU). A slight but consistent rise and fall of both myoglobin and creatine kinase MB was observed in 7 patients (4 presented a definitive myocardial uptake of 99mTc pyrophosphate, and I had a faint deposition). A similar pattern was observed for myoglobin alone in 3 patients (1 presented a negative myocardial scan), while no consistent changes were found in the remaining 5 patients (2 presented a faint deposition of 99mTc pyrophosphate). No significant change of alpha hydroxybutyrate dehydrogenase was observed in any of the patients. The coherent rise and fall of the levels of myocardial cytosolic components after prolonged episodes of vasospastic angina suggests that cell damage may occur even in the absence of persistent QRS and ST-T changes.

[Hourly distribution of episodes of angina at rest. Effect of medical treatment]. / Distribuzione oraria degli episodi di angina a riposo. Effetto della terapia medica.

Aim of the study was to evaluate whether frequency of myocardial ischemic attacks at rest (IA) had any identifiable distribution during 24-hour periods. Two ECG leads were continuously recorded by an Oxford 4-24 tape recorder for a total of 148 days in 10 patients admitted to CCU because of frequent spontaneous anginal attacks. During 48 days, in absence of therapy, 682 IA were recorded (2.03 per patient per day). They showed a symmetrical bell-shaped distribution curve in the 24 hour periods with a peak occurring at 5 a.m. and 43% of IA from 0 to 6 a.m. Only 25% of IA was symptomatic with the lowest values (10%) between 2 and 6 a.m. Distribution of IA was independent from their distinctive electrocardiographic feature [ST (71%) or T changes]. During 100 days with therapy [Verapamil and/or Isosorbide dinitrate ointment) a marked reduction of episodes was observed (0.64 per patient per day), while their distribution, the incidence of different electrocardiographic patterns and percentage of symptomatic IA remained unchanged. Attenuated incidence, but inalterated distribution of IA with therapy suggest its possible effect on the threshold response of coronary smooth muscle to vasoconstrictor stimuli rather than its primary effect on pathogenetic factors.