Vasomotor reactivity evaluation in cardiac rehabilitation.

Endothelial dysfunction is a generalized phenomenon detectable at various levels in the vasculature, and is evident very early in the atherosclerotic process. These peculiarities have stimulated the introduction of new non-invasive techniques dedicated to evaluate the vasomotor response of arteries or districts in favourable position in the body (forearm, hand) that may reflect the response of inner arteries otherwise requiring invasive procedures (i.e. coronary arteries). Moreover, these techniques can be theoretically used to detect abnormalities of vasomotor response before a clinical adverse event may occur in subjects prone to vascular accidents with risk factors for atherosclerosis. Of physical stimuli inducing e-NOS activation and subsequent nitric oxide synthesis, the shear stress produced by pulsatile blood flow is the most important. This property is actually used in clinical practice to study the flow-mediated vasodilation (FMD) of the brachial artery. Any condition that reduces the ability of endothelial cells to produce nitric oxide causes endothelial dysfunction, which is directly reflected into a depressed FMD. There is evidence that brachial artery flow-mediated dilation is improved after local as well as systemic exercise, suggesting that the improvement in endothelial function is generalized and documentable in different arterial districts with similar results. Aerobic exercise induces e-NOS expression and improves the endothelial-dependent relaxation in normal as well as cardiac patients. The endothelium-independent vasorelaxation is generally unchanged after chronic conditioning, but this result is not evident in all studies. The improved endothelial vasoreactivity is correlated with enhanced functional capacity after moderate aerobic exercise, suggesting an important pathophysiological role of oxygen transport in exercise tolerance. These beneficial effects has been described in patients with stable heart failure in II and III NYHA functional class and in patients with coronary artery disease with programs different for frequency, duration and intensity. The evaluation of vasomotor reactivity gives promising results in explaining the effects of medications and exercise training. The demonstration that flow-mediated dilation may quantify endothelial dysfunction in subjects with a variety of conditions can be used in clinical practice not only to assess the effects of interventions, but also to provide a preliminary screening in apparently healthy subjects who have an underlying silent coronary artery disease. In cardiac rehabilitation, there are promising results from FMD evaluation in selecting patients who take major benefits in terms of functional capacity and endothelium-dependent vasodilation.

Comparison of steerable continuous-wave versus pulsed-wave Doppler ultrasonography to renal artery angiography in diagnosing renal artery stenosis.

Pulsed-wave Doppler ultrasonography is widely used to noninvasively diagnose renal artery stenosis. The use of steerable continuous-wave Doppler has never been tested. We compared pulsed and steerable continuous-wave Doppler ultrasonography, demonstrating that although both methods are highly sensitive for severe stenoses, continuous-wave Doppler shows a better sensitivity for mild to moderate stenoses.

Amlodipine in ischaemic left ventricular dysfunction with mild to moderate heart failure.

OBJECTIVE: In this study, we evaluated the effectiveness of amlodipine in patients with severe ischaemic left ventricular dysfunction (LVD) and mild to moderate heart failure, but not current angina, assessing the effects of the drug on symptoms, left ventricular function and exercise capacity. PATIENTS AND METHODS: We studied 36 patients with ischaemic LVD (radionuclide ejection fraction <40%, left ventricular end-diastolic dimension >60mm) and mild to moderate heart failure (NYHA class II or III) without angina treated with ACE inhibitors (36 of 36), digitalis (34 of 36) and diuretics (30 of 36). Among the 36 recruited patients, 33 fulfilled the study protocol, including 2 weeks of run-in (standard therapy), 8 weeks of treatment (standard therapy + amlodipine 5mg once daily) and 2 weeks of washout (standard therapy). Symptoms graded on a 10-point scale (heart failure score; a higher score representing improvement in symptoms), radionuclide left ventricular ejection fraction (rLVEF), echocardiographic left ventricular end-diastolic dimension (LVEDD), peak aerobic capacity (VO(2max)), exercise time (ET) and total work load (TWL) were measured after run-in, treatment and washout periods. All patients underwent coronary angiography and (201)Thallium (Tl) myocardial scintigraphy. RESULTS: With respect to baseline and washout, after amlodipine treatment the HF score improved (6.6 +/- 1.3 after amlodipine vs 5.9 +/- 1 at baseline and 5.9 +/- 1.1 at washout; p < 0.02), rLVEF increased (33.12 +/- 9.02% vs 29.74 +/- 7.72% and 30.02 +/- 7.39%, respectively; p < 0.001), and VO(2max) (14.35 +/- 4.05 ml/kg/min vs 12.68 +/- 3.21 ml/kg/min and 12.62 +/- 3.59 ml/kg/min, respectively; p < 0.003), ET (440 +/- 169 sec vs 395 +/- 158 sec and 402 +/- 162 sec, respectively; p < 0.02) and TWL (2183.2 +/- 439 kpm vs 1615.5 +/- 427 kpm and 1708.8 +/- 437 kpm, respectively; p < 0.01) were also increased. The increase in VO(2max) was related to systolic blood pressure at rest and at the peak of exercise, and to the presence of viable and/or ischaemic myocardium at (201)Tl myocardial scintigraphy. CONCLUSION: Amlodipine, in addition to standard therapy (including in all cases an ACE inhibitor), reduced symptoms and improved exercise capacity and ventricular function in patients with mild to moderate heart failure due to myocardial ischaemia. Thus, amlodipine is useful in patients with ischaemic LVD and heart failure without angina. The improvement in exercise capacity was greater in patients with scintigraphic evidence of viable and/or ischaemic myocardium and higher blood pressure. However, our study presented some limitations (i.e. an open study with few patients), and only generated a hypothesis that could lead to a wider, multicentre, cooperative trial. Treatment of patients with chronic ischaemic left ventricular dysfunction (LVD) with heart failure symptoms but without angina is a difficult clinical problem. Despite the fact that surgical myocardial revascularisation may improve survival, most patients are not good candidates for surgery. Thus, 'polypharmacy' remains the principal option for these individuals. ACE inhibitors have become a cornerstone in the treatment of all forms of LVD, and have been demonstrated to improve functional class and survival. Nitrates, digitalis and diuretics are also commonly used for their effects on symptoms. Despite there being no evidence that calcium antagonists are useful for the treatment of heart failure or impaired ventricular function after myocardial infarction, these drugs are still prescribed to many patients with ischaemic LVD. However, it is possible that the concomitant administration of ACE inhibitors could reduce the reflex neurohumoral activity caused by some calcium antagonists, while preserving some of the beneficial properties of these agents. Among other calcium antagonists, amlodipine does not adversely affect the clinical status of patients. Some studies have shown that it reduces symptoms, improves exercise tolerance and does not result in neurohormonal stimulation. Moreover, amlodipine appears to have a mortality benefit in patients with dilated cardiomyopathy but not in patients with underlying coronary disease where it appears to have a 'neutral' effect. Thus, it is not clear whether amlodipine is useful in patients with ischaemic LVD, particularly in patients with silent coronary artery disease. In this study, we evaluated the effectiveness of amlodipine, in addition to standard therapy, in patients with ischaemic LVD and mild to moderate heart failure, assessing the effects of the drug on symptoms, LV function and exercise capacity.

Plasma beta-endorphin response to exercise in patients with congestive heart failure.

OBJECTIVE: To determine whether the net release of beta-endorphin during exercise, similar to that of norepinephrine, is related to functional disability in patients with congestive heart failure. BACKGROUND: Plasma beta-endorphin and norepinephrine levels are elevated at rest in patients with heart failure, reflecting a functional disability. The net release of beta-endorphin during exercise in patients with heart failure is unknown. METHODS: We measured plasma beta-endorphin and norepinephrine levels (respectively: radioimmune and radioenzymatic assay) at rest and during graded exercise testing in 28 patients with congestive heart failure (Weber's class A, 10; B, 9; and C, 9) and in 9 normal subjects. RESULTS: At rest, plasma beta-endorphin levels were higher in patients in classes B and C than in normal subjects (p < 0.05 and < 0.01, respectively). At peak exercise, patients in different functional classes and normal subjects reached similar beta-endorphin levels. However, the net release of beta-endorphin during exercise was lower in patients in classes B and C than in those in class A and normal subjects (p < 0.01 for both). At rest, plasma norepinephrine levels were significantly higher in patients than in normal subjects (p < 0.01). At peak exercise, norepinephrine levels were significantly lower in class C patients than in normal subjects (p < 0.05), and tended to be lower in patients in classes A and B (p = NS). The net release of norepinephrine during exercise was lower in patients than in normal subjects (p < 0.01). In patients, releases of both beta-endorphin and norepinephrine during exercise were related to peak oxygen consumption and duration of exercise, but not to resting left ventricular ejection fraction. CONCLUSIONS: In patients with congestive heart failure, the net release of plasma beta-endorphin during exercise is decreased, like norepinephrine, and reflects a functional disability.

[Doppler flow-velocity analysis of the renal arteries in left ventricular dysfunction]. / Analisi della curva di flusso-velocità doppler delle arterie renali nella disfunzione ventricolare sinistra.

AIM OF THE STUDY: Chronic heart failure leads to renal hypoperfusion. Clinical methods for monitoring renal artery flow have several limitations. We analyzed the renal artery flow-velocity in patients with left ventricular dysfunction and normal controls by pulsed-wave (PW) color-guided Doppler technique. The relation between PW Doppler quantitative indexes and left ventricular ejection fraction (LVEF), creatinine clearance, and age, was also assessed. METHODS: We studied 53 patients with left ventricular dysfunction (LVEF by 2D echo < or = 40%) and no systemic hypertension, diabetes, parenchymal nephropathy, serum creatinine levels > 150 mmol/l, nor renal artery stenosis. Five patients were excluded for suboptimal renal artery PW Doppler recordings. Thus, the study group was constituted of 48 patients (mean age: 64 +/- 13 years). Twenty-eight normal subjects (mean age: 61 +/- 9 years) were the control group. By PW Doppler we measured the maximum (Vmax), the minimum (Vmin) and the mean (Vmean) velocities of both renal arteries. The resistivity index (RI), obtained from the formula (Vmax-Vmin)/ Vmax, and the pulsatility index (PI), obtained from the formula (Vmax-Vmin)/Vmed were calculated. Creatinine clearance was determined in each patient. RESULTS: RI and PI were greater in patients with left ventricular dysfunction than in normal controls. In normal controls, RI and PI were related to age (r: 0.63, p < 0.001; and r: 0.45, p < 0.05) and creatinine clearance (r: -0.44 and -0.40, respectively; both: p < 0.05), not to LVEF. In patients with left ventricular dysfunction, RI and PI were related to LVEF (r: -0.67 and -0.59; both: p < 0.001), other than to age (r: 0.57 and 0.55; both: p < 0.001) and creatinine clearance (r: -0.59, p < 0.001, and r = -0.46, p < 0.01, respectively). In this group, however, there was no sharp separation of RI and PI between patients with different degree of left ventricular dysfunction (LVEF < or = 30% and > 30%). CONCLUSIONS: In patients with left ventricular dysfunction, by renal artery PW Doppler analysis it is possible to detect noninvasively a reduction in regional flow-velocity and an increase in Doppler-derived vascular resistance indexes. These Doppler changes mainly depend on severity of left ventricular dysfunction and less on age of patients.

Regional wall motion analysis by dobutamine stess echocardiography to distinguish between ischemic and nonischemic dilated cardiomyopathy.

To distinguish between ischemic and nonischemic dilated cardiomyopathy (DCM), we studied 43 patients with left ventricular dysfunction (15 ischemic and 28 nonischemic detected by coronary angiography) by dobutamine stress echocardiography. At rest, there were more normal segments (p<0.001) and a trend toward more akinetic segments (p, not significant) per ischemic than per nonischemic DCM patient. However, either at rest or with low-dose dobutamine, individual data largely overlapped. At peak dose, in ischemic DCM, regional contraction worsened in many normal or dys-synergic regions at rest (in the latter case after improvement with low-dose dobutamine); in contrast, in nonischemic DCM, further mild improvement was observed in a variable number of left ventricular areas. Thus with peak-dose dobutamine, more akinetic and less normal segments were present per ischemic than per nonischemic DCM patient (both, p<0.001). A value of six or more akinetic segments was 80% sensitive and 96% specific for ischemic DCM. Our data show that analysis of regional contraction by dobutamine stress echocardiography can distinguish between ischemic and nonischemic DCM.

[Plasma levels of basal beta-endorphin and after effort in patients with severe left ventricular dysfunction and heart failure]. / Livelli plasmatici di beta-endorfina basali e dopo sforzo in pazienti con disfunzione ventricolare sinistra severa e scompenso cardiaco.

BACKGROUNDS: Purpose of the study was to evaluate beta-endorphin plasma levels at rest and after exercise, and the beta-endorphin release, in relation to exercise capacity, in patients with severe left ventricular dysfunction and heart failure. METHODS: Beta-endorphin plasma levels were assayed by radio-immunoassay before and after cardiopulmonary exercise testing in 28 heart failure patients with radionuclide ejection fraction < 35%, left ventricular end-dyastolic dimension > 60 mm and heart failure, and in 9 age-matched normal subjects. According to Weber's classification, 10 patients were in class A, 9 in class B, and 9 in class C. RESULTS: Beta-endorphin plasma levels at rest were respectively 3.52 +/- 2.31 pmol/L in patients, and 1.77 +/- 0.84 pmol/L (p < 0.05) in normals. In patients, baseline beta-endorphin correlated to VO2max (r = -0.76), peak rate-pressure product (r = -0.60) and exercise time (r = -0.56), then progressively increasing from class A to C. After exercise, beta-endorphin plasma levels increased respectively to 6.42 +/- 3.44 pmol/L (p < 0.001 vs baseline) in patients, and to 5.46 +/- 2.14 pmol/L (p < 0.001 vs baseline and NS vs patients) in normals. In patients, the release during exercise of beta-endorphin (exercise - baseline/baseline x 100) correlated to VO2max (r = 0.82), peak rate-pressure product (r = 0.64) and exercise time (r = 0.55), then progressively decreasing from class A to C. At multivariate analysis beta-endorphin release showed the greater correlation to exercise capacity parameters. CONCLUSIONS: In heart failure patients, beta-endorphin plasma levels are elevated at rest and its release during exercise is reduced in relation to functional impairment.

Considerations of brain death on a SPECT cerebral perfusion study.

Brain death imaging is often a diagnostic challenge. Cerebral angioscintigraphy is extensively used for this analysis, but this test does not allow the perfusion evaluation of the posterior fossa. The authors report a case in which a SPECT study showed persistence of blood flow in infratentorial structures with total absence of cerebral (supratentorial) perfusion. This finding excluded the diagnosis of brain death.

[Recurrent cardiac echinococcosis: a report of a case with multiple intrapericardial cysts]. / Echinococcosi cardiaca recidivante: descrizione di un caso con cisti multiple intrapericardiche.

A case of an isolated recurrent cardiac hydatidosis with multiple intrapericardial cysts is presented. The patient, who underwent 2 previous surgical resection of intramyocardial and pericardial hydatid cysts, presented with atypical chest pain. The ECG and the perfusion scintigraphy with 201-thallium showed a previous lateral myocardial infarction. The diagnosis of recurrent cardiac hydatidosis was made by two-dimensional echocardiography and computed tomography and was confirmed by clinical and biochemical findings.

Systolic ejection murmurs in the elderly: aortic valve and carotid arteries echo-Doppler findings.

UNLABELLED: Two-dimensional echographic and color Doppler studies of the heart and carotid arteries (CA) were performed in 45 patients greater than sixty-five years old without aortic stenosis, 23 with (Group 1) and 22 without (group 2) precordial ejection systolic murmur (SM). Aortic cusps thickening was found in 11 Group 1 (48%) and 2 Group 2 (9%) patients (p less than 0.001). Aortic root and aortic arch size were similar in the two groups. Maximum aortic flow velocity was significantly greater in Group 1 (200 60 cm/sec) than in Group 2 (120 20 cm/sec) (p less than 0.001). Left ventricular outflow systolic maximum velocity was similar in the two groups. A bilateral neck murmur was heard in 10/23 Group 1 patients (43%); in this group, patients with cervical SM had a greater maximum aortic flow velocity than those without cervical SM (230 + 60 cm/sec vs 172 + 32 cm/sec, p less than 0.001). In Group 1, 3 patients had a cervical SM louder on one neck side; only in these 3 patients were ipsilateral obstructive CA plaques found. A unilateral neck SM was heard in 4/22 Group 2 patients (18%); in these 4, ipsilateral obstructive CA were found. CONCLUSIONS: (1) in the elderly, precordial ejection SM is related to mild increase in maximum aortic flow velocity and thickening of aortic cusps; (2) in patients with precordial SM radiated to both neck sides, maximum aortic flow velocity tends to be more markedly increased; (3) in patients with precordial SM, a cervical SM louder on one neck side should suggest coexistent ipsilateral CA stenosis.

[Diagnosis of recent posterolateral myocardial infarction: an electrocardiographic, echocardiographic and scintigraphic study]. / Diagnosi di infarto posterolaterale recente: studio elettrocardiografico, ecocardiografico e scintigrafico.

ECG and 2D echocardiography were studied in 64 patients with previous myocardial infarction and evidence of posterolateral fixed defect at 201 TI scintigraphy. The defect was isolated posterolateral in 47 patients (group 1), and posterolateral + inferoapical in 17 (group 2). Thirty subjects with no history of myocardial infarction and no 201 TI defects constituted the control group. We calculated sensitivity, specificity and predictive value of ECG and 2D echocardiography (pertinent wall motion abnormality) in the recognition of posterolateral infarction. ECG data were also analyzed using multivariate analysis. Among the ECG criteria, a positive T wave in V1 proved to be 100% sensitive and 76% specific both in group 1 and in group 2. At multivariate analysis, a 2-variable model (positive T wave inV1 + R/S ratio greater than or equal to 1 in V1-V2) had a sensitivity of 95 and 100% in group 1 and 2, respectively; the specificity was 80%. A 3-variable model (+ R wave duration in V1-V2 greater than or equal to 0.04 sec) proved to be less sensitive (70 and 88% in group 1 and 2, respectively), with a specificity of 97%. A pertinent dyssynergy at 2D echocardiography was 70% sensitive for posterolateral myocardial infarction in group 1, but only 29% in group 2, with a specificity of 100%. These results indicate: 1) standard ECG is more sensitive but less specific than 2D echocardiography in the recognition of previous postolateral myocardial infarction; 2) the recognition of posterolateral involvement can be frequently missed by 2D echocardiography in patients with associated inferior myocardial infarction.

[Increase of plasma levels of beta-endorphin during maximum bicycle ergometry effort in sedentary and trained subjects]. / Incremento dei livelli plasmatici di beta-endorfina durante sforzo massimale al cicloergometro in sedentari ed allenati.

Plasmatic levels of beta-endorphin during maximal graded bicycle stress test were measured by RIA on extracted plasma in 10 well-trained (A group) and in 8 untrained subjects (C group). Blood samples were obtained at rest, at peak work load and at the third, 10th and 90th min of recovery. For every stress test the following were evaluated: exercise time, maximum work load, total work load, maximum double product and mean K (an index of velocity of heart rate recovery during the first three minutes after the exercise). Both groups A and C showed a significant rise in beta-endorphin activity at the third minute of recovery; the increase was significantly greater in trained rather than in sedentary subjects (p less than 0.01). Beta-endorphin release was closely related to mean K; no relationship was found between exercise time, maximum work load, total work load, maximum double product and beta-endorphin rise. Our data shows that a release of beta-endorphin occurs during the initial phase of recovery after a maximal stress test; beta-endorphin rise is greater in trained subjects and correlates with the speed of heart rate recovery, but has no relationship with the duration and the grade of the effort. Whether beta-endorphin increase plays a role in the rapid decrease of adrenergic tone which occurs after exercise or represents a secondary phenomenon remains to be determined.

[Release of beta-endorphin and beta-lipotropin during submaximal exertion in sedentary and active subjects. Endogenous opiate peptides during exertion in sedentary and active subjects]. / Rilascio di beta-endorfina e beta-lipotropina durante sforzo sottomassimale in sedentari ed allenati. Peptidi oppiacei endogeni durante sforzo in sedentari ed allenati.

Some recent studies suggest that changes in the endogenous opioid peptides (POE) secretion during stress may be involved in various hemodynamic, respiratory and hormonal responses to exercise. To evaluate the relationship between fitness and POE release, 10 mixed-type exercise trained athletes (A) and 10 sedentary normal controls (C) were examined by bicycle stress testing; maximum oxygen uptake (VO2max) and peak work load (PWL) were greater in A than C (VO2max = 61.8 +/- 5.2 vs 40.2 +/- 6.1 ml/kg; PWL = 1525 +/- 229 vs 915 +/- 305 kgm.both p less than 0.01). After 24 hours A and C underwent rectangular bicycle stress testing (two 20' steps at 60% and 80% VO2max). Total plasmatic beta-endorphin (BEP) and its precursor beta-lipotropin (BLPH) were dosed by radioimmunoassay at rest, at 60% VO2max, at 80% VO2max and after complete recovery. Physical exercise caused a transient rise of BEP + BLPH plasma levels in both A and C. In A the increase was greater and occurred earlier than in C. The POE release under submaximal exercise showed a close correlation with oxygen uptake and therefore with fitness. This relation appeared in A at both low and high effort levels, whereas in C it was more strict at higher effort level. There results suggest that POE system play an important role in the adaptive mechanisms in sport practice.

[The FG syndrome (McK 30545). Description of 2 cases with subaortic stenosis]. / La "FG syndrome" (McK *30545). Descrizione di due casi con stenosi sottoaortica.

This paper reports on two brothers affected by FG syndrome (a rare X-linked syndrome with multiple congenital anomalies and mental retardation) and subvalvular aortic stenosis of the discrete type. This is a previously unrecognized association. The FG syndrome was firstly described by Opitz and Kaveggia in 1974. Nearly 20 cases have been reported: congenital heart diseases previously reported are atrial septal defect, ventricular septal defect and hypoplastic left heart. The clinical appearance of the two cases we have observed was that of mental retardation and typical features including abnormal facies (dolicocephaly, frontal prominence, poorly modeled auricles, micrognathia, prominent lower lip and lack of expression), anteriorly displaced anal opening, clinodactyly, great broad toes. A chromosome study showed a normal 46 XY constitution. Discrete subvalvular aortic stenosis was diagnosed by typical physical and echocardiographic findings.

Digoxin serum concentration measurement in patients with suspected digitalis-induced arrhythmias.

The serum digoxin concentration (SDC) was measured in 100 consecutive patients with suspected digitalis-induced arrhythmias. In 24 (toxic group) of these subjects arrhythmias disappeared after glycoside withdrawal. The mean (+/- SD) SDC was 2.88 +/- 1.89 ng/ml in the toxic group and 1.00 +/- 0.61 in the nontoxic group (p less than 0.0001). With respect to digitoxicity, the SDC showed a predictive accuracy rate of 88%, a specificity rate of 89%, and a sensitivity rate of 62%. Since our results were obtained from symptomatic patients, we observed a better predictive accuracy rate than other authors, who studied symptomatic and asymptomatic subjects. The high percentage of false-negatives makes it impossible to consider the SDC by itself a diagnostic test for digitoxicity. However, the SDC is a useful test since all other parameters are less sensitive and/or less rapid indicators of probable digitalis intoxication.