Heart rate variability and functional severity of congestive heart failure secondary to coronary artery disease.

To investigate the behaviour of heart rate variability (HRV) with the advancing severity of heart failure (CHF) we studied 20 normal subjects and 80 coronary artery disease (CAD) patients in sinus rhythm. CAD patients were selected consecutively in order to form four equal groups of 20 subjects with different degrees of CHF according to the New York Heart Association (NYHA) functional classification. In each subject a 24 h ECG Holter tape was recorded and subsequently analysed to obtain measures of heart rate and HRV. We used several measures of HR and both spectral and non-spectral measures of HRV. Among these we employed the width of the R-R interval distribution over 24 h at three different heights (TV, 10%Var, 50%Var). The CAD group showed significantly lower HRV counts and smaller spectral components than controls. However, these differences were due to the presence of CHF rather than to CAD. Indeed, a progressive and significant increase in heart rate and a contemporary decrease in HRV was observed with the advancing severity of CHF. Class IV patients had the smallest HR variation; the spectral composition in this group was barely detectable. The decrease in time domain measures of HRV followed the increase in NYHA Class in a progressive and regular pattern, while the low frequency and high frequency spectral power showed the largest reduction from NYHA Class I to NYHA Class II patients. No significant change was demonstrated in NYHA Class I patients as compared to Controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart rate variability during the acute phase of myocardial infarction.

BACKGROUND: After acute myocardial infarction (AMI), several abnormalities of the autonomic control to the heart have been described. Heart rate (HR) variability has been used to explore the neural control to the heart. A low HR variability count measured 7-13 days after AMI is significantly related to a poor outcome. Little information is available on HR variability early after AMI and its relation to clinical and hemodynamic data. METHODS AND RESULTS: We studied 54 consecutive patients (42 men and 12 women; mean age, 60.4 +/- 11 years) with evidence of AMI by collecting the 24-hour HR SD from Holter tapes recorded on day 2 or 3. We also measured HR variability in 15 patients with unstable angina and in 35 age-matched normal subjects. HR variability was lower in AMI than in unstable angina patients (57.6 +/- 21.3 versus 92 +/- 19 msec; p less than 0.001) and controls (105 +/- 12 msec; p less than 0.001). Also, HR variability was greater in non-Q-wave than in Q-wave AMI (p less than 0.0001) and in recombinant tissue-type plasminogen activator-treated patients with respect to the rest of the group (p less than 0.02). No difference was found for infarct site. HR variability was significantly related to mean 24-hour HR, peak creatine kinase-MB, and left ventricular ejection fraction (all p less than 0.0001). Patients belonging to Killip class greater than I or who required the use of diuretics or digitalis had lower counts (p less than 0.004, p less than 0.001, and p less than 0.024, respectively). Six patients died within 20 days after admission to the hospital. In these patients, HR variability was lower than in survivors (31.2 +/- 12 versus 60.9 +/- 20 msec; p less than 0.001), and a value less than 50 msec was significantly associated with mortality (p less than 0.025). CONCLUSIONS: HR variability during the early phase of AMI is decreased and is significantly related to clinical and hemodynamic indexes of severity. The causes for the observed changes in HR variability during AMI may be reduced vagal and/or increased sympathetic outflow to the heart. It is suggested that early measurements of HR variability during AMI may offer important clinical information and contribute to the early risk stratification of patients.

Evaluation of mitral stenosis by cine magnetic resonance imaging.

To evaluate the ability of cine magnetic resonance imaging (cine MRI) in the assessment of mitral stenosis (MS), we studied 20 patients (14 women and 6 men, mean age 60.6 +/- 8.5 years) with rheumatic mitral valve stenosis by using an 0.5 T magnet. Cine MRI showed several signs of MS. Mitral leaflet thickening, reduced diastolic opening, and abnormal valve motion toward the left ventricular outflow tract were all common features. MS was also characterized by an abnormal diastolic transmitral signal from blood. Both left atrial and left ventricular dimensions were similar to those obtained at two-dimensional echocardiography (2-DE) (r = 0.89 and r = 0.86, respectively; p less than 0.001). A significant relationship was also found between the maximum mitral leaflet separation measured by cine MRI in diastole and the mitral valve area as calculated using the pressure half-time method and continuous wave Doppler (r = 0.81; p less than 0.001). These data indicate the improved ability of MRI to detect and assess MS and also suggest that this technique may contribute to the noninvasive assessment of MS.

[Changes in the wall motion of left ventricle in dipyridamole-induced ischemic cardiopathy studied by nuclear magnetic resonance. A comparison with myocardial scintigraphy with 99mTc MIBI]. / Alterazioni della motilità parietale del ventricolo sinistro nella cardiopatia ischemica indotte da dipiridamolo studiate con risonanza magnetica nucleare. Confronto con la scintigrafia miocardica mediante 99mTc MIBI.

To investigate whether magnetic resonance imaging (NMR) can detect alterations in LV contractility during myocardial ischemia, ten patients aged 32-72 with coronary artery disease underwent ECG gated NMR performed at 0.5 Tesla after intravenous infusion of high dose dipyridamole (DP) (0.7 mg/Kg) over 5 minutes. LV contraction in planes similar to echo short axis projection was imaged under condition, 3' and 15-20' after infusion of DP by fast multiphasic imaging (FMI), multiple angulated cine-NMR sequence with a temporal resolution of 50 m/sec. Entity and size of perfusion defects after DP were determined by Tc 99m MIBI myocardial scintigraphy. In all patients changes in LV contractility appeared at NMR in the same site of perfusion impairments revealed with MIBI. In 8 patients the alterations lasted even more than 20' after the first NMR scan. NMR provides the opportunity of performing long-lasting assessment of ventricular wall contractility and enables to exactly localize the site and extension of kinetic changes as well as their time of onset and time duration.

Effect of heparin, aspirin, or alteplase in reduction of myocardial ischaemia in refractory unstable angina.

399 out of 474 inpatients with unstable angina were monitored for 48 h and 97 of these were found to be refractory to conventional antianginal treatments and entered a randomised double-blind study. With the initial protocol heparin infusion or bolus were compared with aspirin; with a modified protocol, heparin infusion, the best of these three treatments, was compared with alteplase. Patients were monitored for 3 days after starting treatment and then observed clinically for 4 more days. On the first days of treatment heparin infusion significantly decreased the frequency of angina (by 84-94%), episodes of silent ischaemia (by 71-77%), and the overall duration of ischaemia (by 81-86%). Heparin bolus and aspirin were not effective. Alteplase caused small (non-significant) reductions on the first day only. Only minor bleeding complications occurred.

[Nuclear magnetic resonance in congenital cardiopathies in adults]. / La risonanza magnetica nucleare nelle cardiopatie congenite dell'adulto.

Magnetic resonance imaging is a newly developed diagnostic technique recently used for the study of the cardiovascular system. One of the most promising fields of application for magnetic resonance is the study of congenital heart diseases. Since it offers high contrast and resolution tomographic images of the heart, this technique appears particularly suitable for the anatomic assessment of cardiovascular malformations. In order to evaluate the potential of magnetic resonance imaging in the evaluation of congenital heart diseases, we reviewed 21 cases of cardiac malformations (age: 9-81, mean: 48 +/- 23). Two dimensional echo-cardiography was performed on all of them. Out of the 21 patients, 13 were imaged to confirm previous diagnoses based on echocardiographic (8) or angiographic (5) data. Four more patients underwent a cardiac angiography after the magnetic resonance study. The remaining eight patients were imaged due to a poor echocardiographic examination (4) and for other reasons (4). Eight patients had an atrial septal defect, 1 had a patent foramen ovale, 2 had a ventricular septal defect, 1 had a corrected transposition of the great vessels, 2 had an aortic coarctation, 2 had a developmental venous abnormality, 5 had different congenital diseases of the aorta or of the pulmonary valve or artery. Image quality was optimal in 18 out of the 21 patients studied (85.7%). In the remaining 3 subjects image quality enabled a diagnosis. In all patients magnetic resonance imaging correctly depicted the cardiac malformation and in some cases furnished data on the severity of the disease. In 9 cases (4 atrial septal defects, 2 developmental venous abnormalities, 2 aortic aneurysms, 1 right pulmonary artery atresia) magnetic resonance imaging provided the diagnosis. These data indicate that magnetic resonance imaging may represent an important non-invasive diagnostic tool capable of offering valuable information on adult patients with suspected congenital heart disease. It is also possible to foresee that this technique will play an outstanding role as a non invasive alternative imaging technique whenever echocardiography cannot be performed is not satisfactory. Furthermore, magnetic resonance imaging should be considered a major diagnostic technique to be used for the anatomic study of the heart prior to resorting to angiography.

Increase in number of myocardial ischemic episodes following nifedipine administration in two patients. Detection of silent episodes by Holter monitoring and role of heart rate.

Out of 34 consecutive patients with angina and treated with nifedipine, two subjects (5.8 percent) showed a significant increase of transient myocardial ischemic episodes during the period of treatment, as assessed by continuous Holter ECG monitoring. In both these patients, a large proportion of ischemic episodes happened to be asymptomatic. A relationship between nifedipine intake, heart rate increase, and number of ischemic episodes was observed. This occasional aggravation of myocardial ischemia could be related to an increase in myocardial oxygen demand medicated through a drug-induced reflex tachycardia.

[Demonstration of an acute myocardial infarction by nuclear magnetic resonance: comparison with 2-dimensional echocardiography in localization of the necrotic area]. / Dimostrazione dell'infarto miocardico acuto mediante risonanza magnetica nucleare: confronto con la ecocardiografia bidimensionale nella localizzazione dell'area necrotica.

In order to evaluate the ability of magnetic resonance imaging (MRI) to detect acute myocardial infarction (AMI) in man, we studied 15 normal volunteers and 22 patients with a recent AMI (13.5 +/- 7.7 days, range 4-28). To establish the ability of MRI in localizing the site of infarction we also performed a comparison between the segments of the left ventricle showing evidence of AMI by MRI and those presenting wall motion abnormalities by 2-dimensional echocardiography. By using strict criteria and 2 imaging planes MRI proved to be a reliable technique for the detection of AMI. MRI correctly identified AMI in 20 out of 22 subjects (90.9%). The site of AMI appeared as an area of increased signal intensity on spin echo images, particularly evident on late echoes: 15 patients had MRI findings compatible with transmural AMI and 5 patients with non-transmural AMI. The site of AMI as detected by MRI closely correlated with that indicated by 2-dimensional echocardiography, thus showing that MRI is a reliable tool for AMI localization. We also observed that the number of left ventricular segments judged as infarcted by MRI was significantly higher than that showing wall motion abnormalities. As MRI correctly identified the presence of 2 subendocardial lesions, not detected by echocardiography, it is suggested that MRI may be superior to echocardiography in detecting non-transmural lesions and the lateral extension of a transmural infarct. Our data show that MRI is a reliable tool for the detection and location of recent AMI in man. In particular MRI can locate AMI with a precision similar to that offered by 2-dimensional echocardiography.

Decrease in frequency of anginal episodes by control of thrombin generation with low-dose heparin: a controlled cross-over randomized study.

Increased thrombin generation is frequently associated with an increase in anginal activity. A cross-over, single-blind, completely randomized study was planned in order to evaluate whether the control of thrombin generation affected the increase in anginal activity. After discharge from the hospital, 24 patients (18 men and 6 women, aged 40 to 69 years) suffering from spontaneous angina were followed up to 12 months and were alternatively treated during two consecutive 6-month periods with calcium heparin, 12,500 IU by the subcutaneous route, or with placebo by the intramuscular route, in addition to the usual antianginal medications. Thrombin generation and clinical activity of angina were assessed every 15 days by measuring fibrinopeptide A (FPA) plasma levels and by grading in three classes (symptomless, mildly symptomatic, and severely symptomatic) the anginal activity on the basis of the number and the time concentration of the ischemic attacks and ECG changes. Low-dose heparin treatment significantly reduced both the FPA plasma level (from 4.1 +/- 3.7 to 2.3 +/- 1.8 ng/ml, p less than 0.001) and the clinical activity of angina. During heparin treatment, the frequency of the observations in the severely and mildly symptomatic classes decreased, respectively, by 53% and by 30%, whereas that in the symptomless class increased by 23% (p less than 0.001) in comparison with the period on placebo. Present results indicate that the control of thrombin generation obtained by low-dose heparin treatment favorably affects the degree of anginal activity in patients with spontaneous angina.

Magnetic resonance imaging of blood flow in thoracic vessels of patients with impaired left ventricular function.

In order to test the ability of magnetic resonance (MR) in the detection of pathologic flow conditions in man, we imaged 10 normal volunteers and 10 patients with congestive heart failure (CHF) with ECG-gated MR. We used a single spin-echo sequence on a transverse plane through the main vessels of the upper chest. The analysis of the variation of the mean signal intensity vs time from the ascending aorta (AA), descending aorta (DA), and pulmonary artery (PA) of the ten normal volunteers on the TE = 30 ms images, showed a common pattern characterized by an end-diastolic intraluminal signal not present in other moments of the cardiac cycle. On the contrary, in patients with CHF, we did not observe the systolic disappearance of the intraluminal MR signal. The main difference between CHF patients and control subjects was found in the DA where an abnormally high signal intensity was present for the whole cardiac cycle. The MR imaging can offer blood flow information underlying the behavior of intraluminal signal intensity and could provide functional information in patients with heart failure.

Association between time of increased fibrinopeptide A levels in plasma and episodes of spontaneous angina: a controlled prospective study.

Thirty-seven patients affected by spontaneous angina and 15 comparable control subjects were enrolled in a 12-month prospective study to evaluate the relationship between blood clotting activation (assessed by fibrinopeptide A [FPA] plasma concentration) and the occurrence of myocardial ischemic attacks. FPA measurements and clinical examinations in patients were performed every 2 weeks. In control subjects blood sampling was performed every 4 weeks. Data from 28 patients who completed the study and from the 15 control subjects were analyzed. The clinical activity of angina was divided into three classes (asymptomatic, mildly symptomatic, and severely symptomatic) on the basis of the number and time-concentration of the ischemic attacks and ECG changes during the 15 days preceding each clinical examination. In all but one patient, a cyclic pattern of activity of coronary artery disease was observed. During follow-up studies, 624 FPA measurements were performed in patients and 173 in control subjects. Mean values were 4.68 +/- 4.53 and 1.32 +/- 0.60 ng/ml, respectively (p less than 0.001). FPA levels differed markedly in relation to the activity of angina. A relationship between FPA levels and activity of disease (r = 0.54, p less than 0.01) was found in time course. Bolus heparin administration (100 IU/kg) during the active phase of angina sharply but incompletely lowered FPA plasma levels, indicating thrombin formation both intravascularly and extravascularly. Present results indicate that a marked blood clotting activation occurs simultaneously with the outbursts of clinical activity of spontaneous angina.

Twenty-four-hour heart rate behavior in patients with impaired left ventricular function due to coronary heart disease.

We performed a 24-hour Holter monitoring study on 45 patients affected by coronary artery disease (CAD) with different degrees of left ventricular impairment, and on 15 controls, in order to observe heart rate (HR) changes. According to the ejection fraction (EF) determined by cardiac angiography, CAD patients were divided into 3 groups of 15 each: the first with EF greater than 0.5; the second with EF between 0.35 and 0.5 and the third with EF less than 0.35. Spontaneous HR variation during 24 h did not differ among controls and CAD patients with normal EF values. On the contrary, with the reduction of ventricular function, CAD patients showed increasingly higher values of HR only during the night. Patients with markedly reduced EF values showed higher values of HR than controls even during some hours of the day. During the night EF and HR showed a good linear correlation with the highest r value at 5 a.m. (r = 0.7, p less than 0.001). Present data show that a reduction in left ventricular performance results in an altered 24-hour HR pattern with a reduced HR slowing at night proportional to the extent of left ventricular dysfunction.

[Methods for studying the heart with magnetic resonance]. / Metodologia di studio del cuore con risonanza magnetica.

Magnetic resonance imaging is a new completely non-invasive diagnostic technique now available even for heart studies. Due to the long time of this examination the main goal for the application to the cardiovascular diagnosis is to obtain the major number of information in a reasonable time for the patient. On the basis of our initial experience with this technique we propose a method suitable for the morphological, functional and tissular characterization in cardiovascular diagnosis.

[Cardiac imaging with nuclear magnetic resonance. Preliminary experience]. / L'"imaging" cardiaco con la risonanza magnetica nucleare. Esperienze preliminari.

Magnetic Resonance Imaging (MRI) is a new completely noninvasive diagnostic tool available for studying the cardiovascular system. In order to assess its utility in cardiovascular protonic imaging, we studied normal individuals and patients with different heart diseases by means of a 0.5 Tesla superconductive magnet triggered by the ECG. Images were obtained in 38 subjects. By electronically angulating the gradients and by acquiring the images at different phases of the cardiac cycle we obtained several different diagnostic possibilities which can allow both anatomic and functional studies of the heart. On the 21 patients, MRI showed the main features of each disease. Our initial experience with MRI confirms the need for oblique images of the heart in order to obtain planes useful in cardiovascular diagnosis. Among many diagnostic possibilities we tested the ability of MRI in the detection of acute and old myocardial infarction. Although MRI requires extensive application in order to delineate its role in cardiovascular diagnosis it is to be considered an important diagnostic tool and a very interesting investigative method.