Arterial baroreflex modulation of heart rate in patients early after heart transplantation: lack of parasympathetic reinnervation.

BACKGROUND: Orthotopic heart transplantation results in cardiac denervation. The presence of cardiac parasympathetic reinnervation in humans has been widely debated based on the application of differing indirect measures of autonomic control. However no attempt has been made to analyse the reflex heart rate response to baroreceptor stimulation whose occurrence is generally considered a reliable marker of the ability to activate cardiac vagal reflexes. This study tested the hypothesis that the presence of donor heart RR interval lengthening following phenylephrine induced blood pressure increase would be an index of parasympathetic reinnervation. METHODS: Baroreflex sensitivity (BRS) was assessed in 30 patients (mean age 51+/-12 years) 1-24 months after heart transplantation carried out by the standard Lower-Shumway technique. In 6 patients the recipient atrium rate response (P-P interval) to baroreceptor stimulation by phenylephrine was also simultaneously determined by transesophageal recording. RESULTS: None of the 30 patients showed prolongation of RR intervals in the donor heart. The average BRS value was -0.28+/-0.54 ms/mmHg (range -1.3-0.7 ms/mm Hg). In the 6 patients in whom BRS was obtained at both the recipient atrium (P-P) and donor heart (R-R) the changes were 7.6+/-5.7 ms/mm Hg and -0.38+/-0.58 ms/mm Hg respectively (p = 0.02), thus confirming that the absent RR interval lengthening in the donor heart is the consequence of efferent vagal fiber interruption. CONCLUSIONS: The absence of any RR interval prolongation following phenylephrine induced baroreceptor stimulation demonstrates that vagal efferent reinnervation of the donor heart does not occur up to 24 months in patients operated via the standard Lower-Shumway procedure. It is also suggested that analysis of baroreceptor reflexes is a more specific method in the examination of cardiac parasympathetic reinnervation.

The bicaval anastomosis technique for orthotopic heart transplantation yields better atrial function than the standard technique: an echocardiographic automatic boundary detection study.

BACKGROUND: Atrial function is an important determinant of cardiac performance. In patients who undergo operation by standard heart transplantation atrial enlargement, distortion of geometry and asynchronous contraction resulting from the donor/recipient atrial connections may affect atrial function. The bicaval anastomosis technique should be free from these limitations. METHODS: We used the echocardiographic automatic boundary detection technique to obtain on-line time/volume curves of right and left atria from patients who had undergone bicaval (n = 22) or standard (n = 27) heart transplantation and from 15 control subjects. Maximal, middiastolic, preatrial contraction, and minimal volumes of both atria were measured. Reservoir volume (defined as the difference between maximal and middiastolic atrial volumes); pump volume (defined as the difference between preatrial contraction and minimal atrial volumes); and conduit volume (defined as the difference between left ventricular stroke volume and the sum of reservoir and pump volumes) were derived for both atria. Atrial emptying fraction was calculated as the difference between maximal and minimal volumes divided by the maximal volume and expressed in percent and pump fraction as the pump volume divided by the sum of reservoir and pump volumes. Tricuspid and mitral regurgitation, evaluated by color-flow Doppler scanning, were considered significant when they were greater than grade 1. Atrial ejection force was calculated from mitral and tricuspid flow velocities at atrial contraction. RESULTS: In patients who had bicaval heart transplantation, both atria were smaller than in patients who underwent standard heart transplantation. With the bicaval technique right and left atrial emptying (right 45% +/- 9% vs 36% +/- 10%, p < .05; left 51% +/- 8% vs 39% +/- 8%, p < .001) and pump fractions (right 57% +/- 17% vs 19% +/- 13%, p < .001; left 45% +/- 28% vs 22% +/- 12%, p < .01) were greater than with the standard technique and similar to those in control subjects. Right atrial ejection force was significantly greater in bicaval (10.0 +/- 5.6 kdyne) than in standard heart transplantation (4.5 +/- 2.2 kdyne, p < .0001). Significant tricuspid or mitral regurgitation was rarely found in bicaval heart transplant recipients (3 and 1 of the 22 patients, respectively), although they were much more frequent after standard heart transplantation (13 and 8 of the 27 patients, respectively). CONCLUSIONS: Heart transplantation performed with the bicaval anastomosis technique determines smaller atrial volumes, yields better right and left atrial function and fewer atrioventricular valve regurgitation than the standard technique.

Age limits for heart transplantation: medical aspects.

OBJECTIVE: To contribute to the analysis of the medical issue of aging as a selection criteria for heart transplantation (HT) METHODS: Elderly candidates (52 subjects, aged > or = 60) were compared with younger patients (64 candidates, aged 50-55) in: clinical pattern (sex, etiology, duration of disease); laboratory and instrumental data (multiple organ function, hemodynamics, maximal and submaximal exercise capacity, nutritional status); follow-up (death, transplantation, status I, decompensation, complications) of at least 6 months. RESULTS: When compared with younger candidates, over 60 patients did not differ in clinical pattern, in all instrumental data, in end-organ function, in transplantation rate, in fatal and non-fatal cardiac events. In both groups the medical management was similarly complex. CONCLUSION: In regard to the medical issue, no reasons emerged to exclude older patients suitable from HT.

Interaction between exercise training and ejection fraction in predicting prognosis after a first myocardial infarction.

BACKGROUND: Although recent meta-analysis trials have shown that exercise training may improve survival after myocardial infarction, the mechanism of this beneficial effect is still unknown. The purpose of this study was to detect possible interactions between exercise training and predictors of prognosis after a first myocardial infarction. METHODS AND RESULTS: Patients with uneventful clinical courses after a first myocardial infarction were randomly assigned to a 4-week training period (125 patients, group 1) or to a control group (131 patients, group 2). Before randomization, all patients underwent a symptom-limited exercise test (28 +/- 2 days after myocardial infarction), 24-hour Holter monitoring, and coronary arteriography (31 +/- 3 days after the acute episode). After a mean follow-up period of 34.5 months, 18 patients had cardiac deaths (5 in group 1 and 13 in group 2). Multivariate analysis by Cox regression model showed that ejection fraction was the only independent prognostic indicator (P = .03). Evidence existed of an interaction between ejection fraction and exercise training, showing an effect of physical training on survival that depended on the patient's ejection fraction. Among patients with ejection fractions < 41%, the relative risk for an untrained patient was 8.63 times higher than for a trained patient (P = .04), whereas for ejection fractions > 40%, the estimated risks for trained and untrained patients were similar. CONCLUSIONS: These data show that exercise training may prolong survival in post-myocardial infarction patients with depressed left ventricular function. A randomized trial in such patients seems warranted.

The effects of physical training in post-myocardial infarction patients with exercise-induced silent ischaemia.

To assess the clinical significance of monitoring during physical training in post-myocardial infarction (MI) patients with asymptomatic exercise-induced ischaemia, we studied 232 patients who were survivors of first recent acute MI and consecutively admitted to the same CCU, who underwent an exercise test (ET) and coronary angiography within two months of the acute event. We selected the 97 patients with multivessel disease. Among them, 60 showed a negative ET and no angina; 37 showed a positive ET with significant ST segment depression, 32 of them had no angina. The 37 patients with positive ET repeated the stress test within a week. In eight of them, the two ETs differed because ischaemia was induced once with and once without precipitation of angina, while the workload (WL) and double product (DP) at the ischaemic threshold of 0.1 mV ST segment depression were not different. During a four-week training period, seven of the asymptomatic patients complained of effort angina and three of angina at rest. To assess training effects, we selected 60 non-consecutive patients with asymptomatic (38) and symptomatic (22) exercise-induced ischaemia. All the symptomatic and 25 asymptomatic patients followed a four-week physical training programme based on the ischaemic threshold. The remaining 13 asymptomatic patients did not undergo physical training. The pre-training period ergometric patterns were comparable between painful and pain-free patients. Training resulted in a similar increase in the WL at the ischaemic threshold (+45% in asymptomatic and +47% in symptomatic patients, both P less than 0.05), without any difference in the DP threshold.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical significance of mitral regurgitation in patients with recent myocardial infarction.

The prognostic implications of the presence of mitral regurgitation (MR) in patients with recent myocardial infarction has not been clarified yet. In March 1983, we undertook a prospective study in patients surviving a first episode of acute myocardial infarction. Over a 4-year period, 266 patients entered the study. Left ventriculography documented the presence of MR in 51 patients, while 215 did not have angiographic evidence of MR. The presence of MR was associated with larger infarcts, as shown by greater values of peak CK (P less than 0.05) and by the prevalence of Q-wave vs non-Q-wave infarctions (P less than 0.05). Transient left ventricular failure during hospitalization was more frequent in patients with MR (P less than 0.05), while the occurrence of early post-infarction angina was similar in the two groups of patients. No difference was found in the extent of coronary disease, yet patients with MR had higher values of left ventricular end diastolic pressure (LVEDP) (P less than 0.005) and a lower ejection fraction (EF) (P less than 0.001). Patients with MR had a reduced exercise capacity (P less than 0.005), but signs of myocardial ischaemia were similarly distributed in the two groups. Patients with anterior infarcts and MR had higher left ventricular volumes than patients without MR, while no difference was found between patients with and patients without MR and inferior infarction, suggesting that left ventricular dilatation may play an important role in the pathogenesis of MR in patients with anterior but not in those with inferior infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Variable threshold of exertional ischaemia in patients with positive exercise test at low workload.

In order to determine individual variability of ischaemic threshold on different days, 18 patients with exertional ischaemia at low workload were studied. All patients performed two exercise tests during different days in the morning and three on the same day at 9 am, 2 pm and 5 pm. The test performed in the morning on different days resulted in a significant difference in the mean values of rate pressure product at the ischaemic threshold as a consequence of individual variability observed in 10 patients. In 8 of these patients the differences were greater than 4000 mmHg beats min-1. Two patients showed respectively, 1 and 5 negative exercise tests despite the greater values of rate pressure product reached. Only 3 patients showed circadian variation of the ischaemic threshold; in these 3 patients variations of rate pressure product at the ischaemic threshold were also observed between different days. These data indicate that in patients with exertional ischaemia at low workload the rate pressure product at the ischaemic threshold shows considerable variability between tests performed on different days.

[Left ventricular aneurysm in recent myocardial infarction. Echocardiographic study]. / L'aneurisma ventricolare sinistro nell'infarto miocardico recente. Studio ecocardiografico.

UNLABELLED: Detection of post-infarction left ventricular aneurysm may have important clinical and therapeutic consequences. Differences in selection and in diagnostic criteria account for the wide range of incidence of left ventricular aneurysm in angiographic and autopsy series. To assess the incidence and related pathological features of ventricular aneurysm, 410 consecutive patients were studied by two-dimensional echocardiography 3 to 8 weeks after the onset of an acute myocardial infarction. In 395 patients (96.3%) technically adequate echograms were obtained: 42 patients (10.6%) had evidence of left ventricular aneurysm defined as a well demarcated bulge in diastole and in systole with a thinned, a-diskinetic walls. The incidence rate of left ventricular aneurysm was 17% in 188 anterior myocardial infarctions, 1.9% in 157 inferior ones, 25.9% in 27 anterior plus inferior infarctions; ventricular aneurysms were not found in any of 15 lateral and 8 posterior myocardial infarctions. Aneurysms were apical or apical-anterior in 25 patients (59.5%), apical-septal in 8 (19%), apical-diaphragmatic in 3 (7.1%), apical-septal-diaphragmatic in 3 (7.1%) and postero-basal in 3 (7.1%). Intraaneurysmal thrombi were detected in 24 patients (57.1%). In 12 cases echograms showed pericardial effusion; this was more frequent (28.6%) than in patients without an aneurysm (7.9%; p less than 0.001). Among patients with an aneurysm, heart failure was present in 19 (45.2%), mitral regurgitation in 3 (7.1%), of systemic emboly in 4 (9.5%), severe ventricular arrhythmias in 4 (9.5%) and angina in 5 (11.9%). IN CONCLUSION: left ventricular aneurysm is a frequent early complication of myocardial infarction. Two-dimensional echocardiography provides non-invasive direct information on localization, extent and related pathological features of ventricular aneurysm and thus appears to be a useful screening technique.

Is old age a contraindication to cardiac rehabilitation after acute myocardial infarction?

Fifty male patients older than 65 years of age (mean 66.3) underwent a symptom-limited exercise test on an average of 34 days after acute myocardial infarction. After 4 weeks of supervised rehabilitation training and after one-year follow-up, the patients underwent controlled exercise tests. The ergometric parameters were compared with respective values in 10 healthy males (mean age 66.4, range 65-75). The rehabilitation training induced a substantial improvement in physical capacity (total work from 3149 +/- 1326 to 4791 +/- 1403 kg; P less than 0.001) with a better cardiovascular response: increased maximum oxygen pulse (from 8.97 +/- 2 to 10.7 +/- 2; P less than 0.001), decreased heart rate (from 120.5 +/- 16.1 to 111.3 +/- 14.7 beats min-1; P less than 0.05) and a decreased double product at a 75 W work load (from 22 866 +/- 4005 to 20 472 +/- 3982 beats min-1 mmHg; P less than 0.05). The recovery of physical capacity and cardiovascular tolerance in the physical exercise was nearly complete as compared with healthy subjects of the same age. During the training period one patient died from heart failure. In all the other patients the same improvement was still maintained one-year later. In conclusion, old age does not seem to be per se a contraindication to cardiac rehabilitation. Physiological beneficial effects from cardiac rehabilitation can also be received by patients older than 65 years of age.

Exertional hypotension after myocardial infarction.

A retrospective study was conducted on 488 patients admitted in our rehabilitation center after a recent acute myocardial infarction. Purpose of the study was to assess the incidence and prognostic value of exertional hypotension in these patients. Of 488 patients admitted to the study 33 (6%) were found to have exertional hypotension; 14 patients had an inferior myocardial infarction, 18 patients had an anterior myocardial infarction, 3 patients had a history of previous myocardial infarction. In the follow-up period (28.3 +/- 13.2 months) the worse prognosis (death or pulmonary oedema) was associated with the presence during exercise of hypotension, ST segment elevation in leads were Q waves were present and no ST depression in other leads. In conclusion, recent anterior myocardial infarctions associated with hypotension and ST segment elevation during exercise appear to be at risk for future cardiac events.

[History of pre-existing angina and post-infarct myocardial ischemia (symptomatic and asymptomatic)]. / Storia di angina pregressa ed ischemia miocardica post-infartuale (sintomatica e asintomatica).

353 patients enrolled in a cardiac rehabilitation program underwent a bicycle-ergometric test 28-60 days after an acute myocardial infarction. Twenty-nine patients (8.2%) had a previous history of chronic angina pectoris (more than 6 months before an acute myocardial infarction): 3 of these subjects did not develop myocardial ischemia after infarction; 26 (89.6%) (Group A) had an ischemic response on effort with horizontal or downsloping S-T segment depression of 2 mV. Ninety-four of 324 Patients without history of chronic angina pectoris had an ischemic response at exercise test (Group B) (p less than 0.001). In Group A the association of ischemic electrocardiographic changes and pain during the test was more frequent than in Group B (42.3% vs. 16%) p less than 0.01). During rehabilitation and follow up period (27.2 +/- 14 months) we observed that only 11.5% of Group A Patients remained symptomatic compared to 69.1% Group B Patients (p less than 0.001). In conclusion, a history of chronic pre-infarction angina pectoris appears to be a predictor of symptomatic ischemia after myocardial infarction.

Incidence and prognostic significance of symptomatic and asymptomatic exercise-induced ischemia in patients with recent myocardial infarction.

To determine the incidence and the significance of anginal chest pain during abnormal exercise testing (S-T greater than or equal to 0.1 mV) in patients with recent myocardial infarction we reviewed a series of 353 patients who underwent maximal bicycle exercise stress 4-8 weeks following acute myocardial infarction. Of the 353 patients, 26 had ischemic ECG changes and chest pain (group A); 85 patients had ischemic ECG changes but no chest pain (group B). The two groups differ significantly only in the frequency of a history of typical angina pectoris more than 6 months prior to acute myocardial infarction (group A 42.3% vs. group B 15.2%, p less than 0.01). Typical chest pain is more frequent in anterior versus inferior myocardial infarction (50 vs. 14.4%, p less than 0.001). The patients were followed up for 28.8 +/- 8.7 months with clinical and exercise testing controls. The incidence of exertional angina during the follow-up was significantly more frequent in group A patients than in group B patients (80.7 vs. 24.7%, p less than 0.001). Unstable angina pectoris was more frequent in group A (34.6 vs. 11.8%, p less than 0.01). There was no statistically significant difference in mortality (group A 3.8% vs. group B 5.9%) and cardiac events (group A 3.8% vs. group B 5.9%) between the two groups. Thus, we concluded that the occurrence of anginal pain associated with S-T segment depression during exercise testing does not increase the prognostic risk.

[Ergospirometric evaluation of 53 physical exercises used in cardiological rehabilitation]. / Valutazione ergospirometrica di 53 esercizi a corpo libero impiegati nella riabilitazione cardiologica.

Fifty-three calisthenics used in a cardiac rehabilitation program were evaluated in a group of patients who, 30-60 days after myocardial infarction, had undergone a multistage symptom-limited bicycle exercise test without S-T segment modifications or arrhythmias. The following measurements were made oxygen uptake (VO2), oxygen uptake/Kg (VO2/Kg), ventilation/m' (VE), heart rate/m' (HR), systolic blood pressure (sBP) and METS. A good correlation was observed during the physical exercises between HR and VO2 (r = 0.59; p less than 0.001) and between HR and VO2/Kg (r = 0.64; p less than 0.001). Such correlation was similar to that observed during bicycle ergometric test. Lower values were obtained for the correlations between sBP and both VO2 and VO2/Kg, but they were still statistically significant (p less than 0.001). Heart rate and sBP were lower during calisthenics than during bicycle exercise from a VO2 level of 600-800 ml up. It is therefore possible to tailor a safe training program based on calisthenics whose level of energy expenditure is known: HRxsBP reached during such physical exercises will be lower than during bicycle ergometric test, VO2 being equal.

[Hypotensive response to the exercise test after recent myocardial infarct: prognostic implications]. / Risposta ipotensiva alla prova da sforzo dopo infarto miocardico recente: implicazioni prognostiche.

The incidence and the prognostic value of exertional hypotension was studied in 488 consecutive patients admitted to the Montescano Rehabilitation Center after acute myocardial infarction. During a symptom-limited bicycle ergometric test performed 28 to 60 days after acute myocardial infarction 33 patients (6.8%) showed exertional hypotension. These patients were grouped according to effort S-T segment modifications: Group A (n = 13) with S-T segment depression in ECG-leads without Q waves; Group B (n = 11) with S-T segment elevation in leads where Q waves were present; Group C (n = 9) with no exercise S-T changes. Group B patients had a larger infarct size by ECG criteria and a lower maximal work capacity at the functional stress test. The follow-up of the patients after discharge was 28.3 +/- 13.2 months. During rehabilitation and follow-up, 2 patients of Group B died and 5 suffered an acute pulmonary oedema; 3 patients of Group A and 1 of Group B had angina at rest. Group C patients had no complications. Thus, exertional hypotension and S-T elevation appear to be predictive of future cardiac event.

Short-term reproducibility of ergometric parameters in functional stress test after recent myocardial infarction.

In order to assess the short-term reproducibility of the most important ergometric parameters, 108 males (mean age 50.3 +/- 7.8 years) underwent a functional stress test (FST) on average 35 days after myocardial infarction. The exercise test was repeated 3 days later in the same conditions. Patients were fasting and in pharmacological washout. The following parameters were analyzed: total work performed (TWP), VO2, heart rate (HR), systolic blood pressure (SBP), arrhythmias and S-T segment depression and elevation. TWP and VO2 values did not show any significant difference during the two tests under the various workloads. HR and SBP responses proved to be well reproducible in patients with HR and SBP not exceeding the mean values obtained from 222 normal subjects who underwent the same exercise test by more than +/- 1 SD; reproducibility was significantly lower in the other patients, particularly in patients with HR and SBP exceeding normal values by more than +/- 1 SD. Therefore, in this case, further FST are necessary to obtain more reliable parameters to decide on individual pharmacological and exercise prescriptions. Arrhythmias were reproducible up to 67% (p less than 0.01) regardless of Lown's class and the presence of S-T segment depression or elevation. S-T segment depression or elevation was reproducible up to 100%.