Central diabetes insipidus and heart: effect of acute arginine vasopressin deficiency and replacement treatment with desmopressin on cardiac performance.

Besides its effects on water balance, arginine vasopressin (AVP) increases peripheral vascular resistance and decreases cardiac output, mainly by decreasing heart rate. The current study was designed to evaluate cardiac performance in patients with central diabetes insipidus (CDI), focusing on the acute effects of desmopressin replacement withdrawal and its subsequent reinstatement in patients with CDI. Twelve patients with CDI and 12 sex- and age-matched healthy subjects entered the study. All patients were receiving treatment with intranasal desmopressin at standard doses. All patients and controls were assessed for water balance, by measuring plasma osmolality and total body water, anterior pituitary function, heart rate, systolic and diastolic blood pressure. Left ventricular (LV), end-diastolic and end-systolic diameters (LVEDD, LVESD) and volumes (LVEDV, LVESD), end-diastolic and end-systolic interventricular septum thickness (EDIVST, ESIVST) and posterior wall thickness (LVEDPWT, LVESPWT), and mass (LVM) were measured by echocardiography. Moreover, LV systolic function was assessed by measuring the ejection fraction (EF), the fractional shortening (FS), the Suga index, the stroke volume and the cardiac output, while LV diastolic function was assessed by measuring early (M1) and late (M2) maximal transmitral blood flow velocities, the ratio between M1 and M2, the mitral deceleration time (MDT) and the isovolumetric relaxation time. All parameters were assessed in the patient group 24 h after discontinuing treatment with nasal desmopressin (baseline study) and 1 week after re-starting replacement treatment, while in the control group before (baseline study) and after 1-week of a nasally administered placebo. At baseline, compared to controls, patients with CDI had increased plasma osmolality (P < 0.01), plasma ACTH (P < 0.01), serum (P < 0.01) and urinary cortisol (P < 0.01) levels, and heart rate (P < 0.05), and decreased total body water (P < 0.05). Systolic and diastolic blood pressure and the other anterior pituitary hormones were similar in patients and controls. At echo-cardiography, EDIVST (P < 0.05), ESIVST (P < 0.01), LVEDPWT (P < 0.05) and LVESPWT (P < 0.01), EF (P < 0.01), Suga index (P < 0.05), FS (P < 0.05), M2 (P < 0.01) and IRT (P < 0.05) were significantly higher while LVESD (P < 0.01), LVESV (P < 0.01), LVEDD (P < 0.05), LVEDV (P < 0.05), M1 (P < 0.05), and M1/M2 (P < 0.01) were significantly lower in patients than in controls. LVM, stroke volume and cardiac output, were similar in patients and controls. In the patient group, after 1 week of replacement treatment with desmopressin, all echocardiographic parameters were normalized, except IVT, LVPWT and the diastolic parameters that were still abnormal compared to controls. No difference was found in any of the parameters in the control group one week after placebo administration. Patients with central diabetes insipidus have increased heart rate and left ventricular contractility, and impaired diastolic function. The altered heart rate and left ventricular contractility, reversible after desmopressin replacement, is likely to be due to stimulation of sympathetic nervous activity, induced by the hypovolemia associated with arginine vasopressin deficiency. Conversely, the impairment of diastolic function, persistent after desmopressin replacement, probably relates to a stable impairment of the left ventricular compliance.

[The incremental prognostic value of the scintigraphic indices of myocardial hypoperfusion in patients with a maximal stress test]. / Valore prognostico incrementale degli indici scintigrafici di ipoperfusione miocardica in pazienti con prova da sforzo massimale.

The additional prognostic value of thallium imaging in patients who are capable of performing a maximal, symptom-limited electrocardiographic stress test is still uncertain. Thus, we evaluated the incremental prognostic value of exercise thallium-201 indexes of myocardial hypoperfusion in 296 patients with suspected or known coronary artery disease who performed a maximal ECG stress test. At 2 year follow-up 20 hard events (16 cardiac deaths and 4 non fatal myocardial infarctions) and 44 soft events (myocardial revascularization procedures) occurred. Considering total events, thallium imaging provided significant additional prognostic information to clinical and exercise stress test data in all patients (p < 0.001) and in patients with previous myocardial infarction (p < 0.001); in patients without previous infarction, whichever the end-point considered, thallium imaging did not add incremental prognostic value. When only hard events were considered, thallium variables added further information only in patients with previous myocardial infarction (p < 0.05). The results of this study demonstrate that scintigraphic indexes of myocardial hypoperfusion obtained by qualitative planar thallium imaging give incremental prognostic information in patients with previous myocardial infarction but not in the subset of patients without previous infarction.

Effects of converting enzyme inhibition on baroreflex sensitivity in patients with myocardial infarction.

BACKGROUND: Baroreflex sensitivity provides useful prognostic information in patients after acute myocardial infarction. However, no data are available about the effects of converting enzyme inhibition on this variable. OBJECTIVES: The aim of the study was to evaluate the effects of angiotensin-converting enzyme inhibition on baroreflex sensitivity in patients after uncomplicated myocardial infarction. METHODS: Twenty-five patients after uncomplicated myocardial infarction underwent baroreflex sensitivity evaluation 72 to 96 h after symptom onset and after 4 days of captopril therapy. Twenty additional patients with the same characteristics were evaluated at the same time intervals before and after placebo administration to identify spontaneous baroreflex sensitivity variations. Baroreflex sensitivity was assessed by calculating the regression line relating phenylephrine-induced increases in systolic blood pressure to the attendant changes in the RR interval. RESULTS: The mean baroreflex sensitivity value increased after captopril administration from 6.5 +/- 4.2 to 11.8 +/- 6.1 ms/mm Hg (p less than 0.01) and in individual analyses increased by greater than 2 ms/mm Hg in 68% of patients. Mean plasma renin activity increased after captopril from 3.7 +/- 2.4 to 8.5 +/- 4.9 ng/ml per h (p less than 0.005). No difference was detectable in baroreflex sensitivity and plasma renin activity values according to the site of necrosis. In the control group, baroreflex sensitivity and plasma renin activity remained unchanged between the two studies. CONCLUSIONS: This study demonstrates that in patients with uncomplicated myocardial infarction, captopril significantly improves the chronotropic response to baroreceptor stimulation.

Effects of captopril treatment on left ventricular remodeling and function after anterior myocardial infarction: comparison with digitalis.

The effects of captopril and digoxin treatment on left ventricular remodeling and function after anterior myocardial infarction were evaluated in a randomized unblinded trial. Fifty-two patients with a first transmural anterior myocardial infarction and a radionuclide left ventricular ejection fraction less than 40% were randomly assigned to treatment with captopril (Group A) or digoxin (Group B). The two groups had similar baseline hemodynamic, coronary angiographic, echocardiographic and radionuclide angiographic variables. Among the 40 patients (20 in each group) who were followed up for 1 year, echocardiographic end-diastolic and end-systolic volumes were unmodified in Group A and global wall motion index was improved (p less than 0.01); in Group B, end-diastolic and end-systolic volumes increased (p less than 0.001 for both) and global wall motion index was unchanged. Rest radionuclide ejection fraction increased significantly in both groups (p less than 0.001, Group A; p less than 0.005, Group B). A comparison of the changes in the considered variables between the two groups after 1 year of treatment showed a difference in end-diastolic (p less than 0.005) end-systolic volumes (p less than 0.001) and global wall motion index (p less than 0.005) without differences in radionuclide ejection fraction, which improved to a similar degree in both groups. The results of this study suggest that captopril therapy, started 7 to 10 days after symptom onset in patients with anterior myocardial infarction and an ejection fraction less than 40%, improves both left ventricular remodeling and function and prevents left ventricular enlargement and in these patients performs better than digitalis.

[Influence of age on the short- and medium-term prognosis in patients with acute myocardial infarct]. / Influenza dell'età sulla prognosi a breve e medio termine nei pazienti con infarto acuto del miocardio.

Elderly patients with acute myocardial infarction (AMI) have a higher subsequent mortality than younger ones, yet the reasons for this adverse prognosis are poorly understood. We compared the clinical course and the prognosis of 163 patients aged 40 to 69 years with 112 patients older than 70 years. During hospitalization period 15.9% of younger and 37.5% of older patients died; at 1 year follow-up the cardiac mortality rate was 8.7% in younger and 12.9% in older patients. In elderly patients a greater prevalence of female gender, diabetes mellitus, anterior myocardial infarction, atrial fibrillation and a greater incidence of heart failure and shock were observed. Multivariate stepwise analysis identified shock and heart rate greater than or equal to 90 bpm at the time of admission as the most important prognostic variables for in-hospital mortality in both groups; heart failure (Killip class II and III) was significant in younger patients, while non Q wave myocardial infarction correlated with a better prognosis in elderly. In elderly patients who survived AMI, predischarge Holter monitoring showed higher frequency and complexity of ventricular arrhythmias, and radionuclide angiography lower left ventricular ejection fraction (E.F.) values. In these patients no difference was found in E.F. values despite myocardial infarction sites. At 1 year follow-up E.F. less than 40% and ventricular arrhythmias (3-4 Moss grading system) were significantly related to prognosis in younger patients, while E.F. less than 40% and clinical signs of heart failure in elderly. Therefore, low E.F. and heart failure account for a worse prognosis in elderly patients, while ventricular arrhythmias in younger ones. The results of this study support aggressive management even in elderly patients following AMI to preserve left ventricular function. In elderly patients a large use of antiarrhythmic drugs is not recommended because of low prognostic value of ventricular arrhythmias.

Prevalence and prognostic significance of silent myocardial ischaemia detected by exercise test and continuous ECG monitoring after acute myocardial infarction.

The incidence and prognostic significance of silent myocardial ischaemia in 165 patients who survived a first acute myocardial infarction were assessed by means of maximal exercise stress test and 24 h continuous ECG monitoring performed before discharge. During the 1 year follow-up period 10 cardiac deaths occurred; moreover seven patients suffered a fatal myocardial re-infarction and 14 developed unstable angina. Cardiac death occurred in five of 40 patients (12.5%) with ST segment depression on stress test by in only three of 117 (2.6%) without ST segment changes (P less than 0.01). One-hundred-and-three of 117 patients (88.0%) without angina or ST segment depression on stress testing survived 1 year without cardiac events, compared with 24 of 40 patients (60.0%) with ST segment depression whether or not associated with angina (P less than 0.001). Cardiac death occurred in five of 25 patients (20.0%) with ST segment depression on continuous ECG monitoring, compared with five of 140 (3.6%) without (P less than 0.01). One-hundred-and-seventeen out of 140 patients (83.6%) without angina or ST segment depression survived 1 year follow-up without cardiac events, compared with 13 of 25 (52.0%) with ST segment depression with or without angina (P less than 0.01). Classifying patients in a 2 x 5 contingency table according to the occurrence of ST segment depression on exercise testing and/or ECG ambulatory monitoring, the Yates corrected chi-square test showed a significant pattern when cardiac deaths and cardiac events were considered together (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[The clinical characterization and prognostic significance of episodes of transient myocardial ischemia in patients with a recent myocardial infarct]. / Caratterizzazione clinica e significato prognostico degli episodi di ischemia miocardica transitoria in pazienti con recente infarto del miocardio.

The incidence and prognostic significance of silent myocardial ischemia were assessed in 175 patients who survived a first acute myocardial infarction (AMI). This was done by means of a 24-hour continuous ECG monitoring which was performed before discharge. Twenty-six out of 175 patients (14.8%) showed one episode or more of S-T segment depression; 19 of these reported no pain at all while the other 7 reported both painful and painless episodes. A total of 65 ischemic episodes were registered; of these 53 (81.5%) were painless and 12 (18.5%) were painful. No difference in the duration of ischemic episodes or in heart rate at the onset of S-T segment depression was detected for painless or painful episodes. The S-T segment depression episodes showed a peak in the morning but were higher in the afternoon and this circadian pattern was statistically significant both with regard to duration (p less than 0.05) and to the number of episodes (p less than 0.05). Cardiac death occurred in 5 of the 26 patients (19.2%) with S-T segment depression during continuous ECG monitoring, and in 5 of the 149 (3.4%) without S-T segment depression (p less than 0.01). In patients with ischemia duration greater than 60 min/24 hours, the mortality rate was higher (p less than 0.05). No cardiac events (unstable angina, non-fatal re-infarction, balloon angioplasty and/or coronary by-pass) occurred in 117 out of 149 patients (78.5%) without ST-segment depression, while these events were observed in 13 out of the 26 patients (50%) with ischemic episodes during Holter monitoring (p less than 0.01). Sensitivity and specificity of S-T segment depression was respectively 29.3 and 89.5% for cardiac death and cardiac events considered together.(ABSTRACT TRUNCATED AT 250 WORDS)

[Nisoldipine in the therapy of stable exercise angina: evaluation of its efficacy in ergometric tests compared with propranolol]. / La nisoldipina nella terapia dell'angina stabile da sforzo: valutazione dell'efficacia mediante prove ergometriche e confronto con il propranololo.

The safety and efficacy of a new dihydropyridine calcium antagonist, nisoldipine, were studied in comparison with propranolol, in patients with stable angina. Following 2 weeks of wash-out of the current therapy and 1 week of placebo, 26 patients underwent two cycloergometer tests, before and 2 hours after placebo administration. Subsequently, 10 mg of nisoldipine twice daily or 40 mg of propranolol three times daily were administered over a 4 week period, in a randomized single-blind fashion. Cycloergometer tests were performed after 2 and 4 weeks, before and two hours after drug administration. Two patients, one out of the nisoldipine group and one out of the propranolol, were considered drop outs. Statistical analysis of the results was performed using two-way variance analysis. With both drugs, time to 1 mm exercise induced ST-segment depression (p less than 0.01), time to angina (p less than 0.01), and exercise tolerance (p less than 0.01) improved furthermore, ST-segment and heart rate recovery time decreased (p less than 0.01). Rate-pressure product values at ischemic threshold and at peak exercise remained unchanged with nisoldipine, while significant reductions were observed with propranolol (p less than 0.01). Maximum ST-segment depression was reduced (p less than 0.01) with both drugs and a further improvement was observed two hours after drug administration (p less than 0.05). At submaximum work-load, rate pressure product values and ST-segment depression were improved with both drugs (p less than 0.01); this improvement was more evident two hours after drug administration. No significant side effects were observed with either drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Phase analysis of radionuclide angiography in acute myocardial infarction.

Standard deviation of the histogram of left ventricular phase distribution (SDP-LV) obtained by radionuclide angiography (RNA) was studied in 75 acute myocardial infarction (AMI) patients, 37 with anterior or anteroseptal (Group A) and 38 with inferior, inferolateral or posterior necrosis (Group I). In order to evaluate sensitivity, specificity and accuracy of SDP-LV compared to ejection fraction (EF) and peak filling rate (PFR), 16 controls and 29 patients with coronary artery disease with normal kinesis proved by angiography were studied. Patients were also compared according to normal or abnormal EF and PFR. Sensitivity of PFR was better than those of EF and PFR (86.6% vs 38.7% and 70.6%, respectively). Specificity of SDP-LV was 89.6%, better than that of PFR (58.6%), but just less than that of EF (93.1%). The accuracy of SDP-LV turned out to be better than those of EF and PFR (87.5% vs 53.8% and 67.3%, respectively). Ejection fraction correlated with SDP-LV in the total study population (r = -0.54, P less than 0.001), and in Groups A (r = -0.44, P less than 0.01) and I (r = -0.43, P less than 0.05); SDP-LV correlated with PFR in the total population (r = -0.35, P less than 0.05), but not in Group A or I. Mean SDP-LV was higher in Group A than I and in patients with lower EF; no difference was found among patients with different PFR values.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial hypertrophy and left ventricular diastolic function in hypertensive patients: an echo Doppler evaluation.

The presence and the characteristics of left ventricular diastolic dysfunction in mild to moderate systemic hypertension were evaluated in 13 normotensive subjects (Group I), in 12 hypertensive subjects without (Group II) and 28 with (Group III) LV hypertrophy who underwent two-dimensional Doppler echocardiographic study. Among Group III patients, a subset (n = 12) with a dilated left ventricle was identified. Diastolic filling parameters were impaired in Group III patients while, in Group II, they were intermediate between Groups I and III. In all Group III patients normalized peak filling rate (nPFR) correlated directly with mean velocity of circumferential fibre shortening (mVCF) (r = 0.55; P less than 0.001) and inversely with left ventricular mass index (LVM) (r = -0.60; P less than 0.001), left ventricular end-diastolic diameter (LVIDd) (r = -0.63; P less than 0.001), LV peak systolic stress (LVWST) (r = -0.64; P less than 0.01). A separate analysis showed that these correlations were also present in patients without left ventricular dilation; in the subset with left ventricular dilation nPFR correlated only with LVWST (r = -0.73; P less than 0.01), but not with LVM, mVCF, LVIDd. Thus, left ventricular hypertrophy is one of the major determinants of diastolic dysfunction in hypertensives; other factors influence nPFR values in hypertensive patients when the left ventricle dilates.

Diastolic function in acute myocardial infarction: a radionuclide study.

We studied left ventricular diastolic function by equilibrium gated radionuclide angiography in patients as follows: 75 with acute myocardial infarction (AMI), 35 with anterior or anteroseptal necrosis (Group A) and 40 with inferior, inferolateral, or posterior necrosis (Group I). The ejection fraction (EF) was lower in Group A than Group I (41.9 +/- 2.5 vs. 57.1 +/- 2.0%, p less than 0.001), as was peak diastolic filling rate normalized to end diastolic volume (PDFR-EDV/sec) (1.9 +/- 0.1 vs. 2.4 +/- 0.1 EDV/sec, p less than 0.05). PDFR normalized to stroke volume was similar in both groups. An excellent linear correlation was found between EF and PDFR-EDV/sec in the total study population. Isovolumic relaxation period (IRP) was beyond our upper normal value of 94 msec in 64% of patients and it was shorter in Group A than I (95.8 +/- 12.7 vs. 147.0 +/- 13.6 msec, p less than 0.05). The presence of shorter IRP in Group A than in I is probably a result of an earlier mitral valve opening as a consequence of higher left atrial pressure.

[Different modalities of classification and prognostic significance of ventricular arrhythmias after acute myocardial infarct. Prospective study]. / Differenti modalitá di classificazione e significato prognostico delle aritmie ventricolari dopo infarto acuto del miocardio. Studio prospettivo.

In our study we compared the prognostic significance of clinical variables, laboratory results and different classification models of ventricular ectopic beats recorded by means of a pre-discharge 24 hour ambulatory electrocardiographic monitoring, in 210 survivors of acute myocardial infarction. In addition a full multivariate analysis of the factors affecting survival time was carried out using Cox's proportional hazards (multiple) regression model. Multivariate stepwise discriminant analysis identified hypertension, congestive heart failure assessed by Killip class, and the grading system for ventricular arrhythmias as the most important prognostic variables. When Moss grading system for ventricular arrhythmias was used, the relative risk was a superior as heavy Moss grading system (Moss 2 vs Moss 1 and Moss 3-4 vs Moss 1, relative risk = 1.2 and 3.6 total death, respectively). Furthermore, the hazard ratio of Moss grading system was higher utilizing as comparison patients without ventricular ectopic beats (relative risk = 1.7 for Moss 2 and 5.3 for Moss 3-4) than patients with ventricular ectopic beats less than one/hour (relative risk = 1.2 for Moss 2 and 3.7 for Moss 3-4). Thus, in survivors of acute myocardial infarction, a rational and useful ventricular ectopic beats categorization includes both frequency and the presence or absence of malignant characteristics.

[Prognostic evaluation of patients surviving acute myocardial infarct: univariate and multivariate analysis]. / Valutazione prognostica dei pazienti sopravvissuti ad infarto acuto del miocardio: analisi uni e multivariata.

The relationship between 31 variables and survival after acute myocardial infarction was evaluated in 432 patients discharged from our Coronary Care Unit from 1975 to 1984. The patients were followed for 1 to 105 months and either univariate and multivariate analysis were performed. For end-point death the significant variables (p less than 0.05) selected by the univariate analysis were: age, diabetes, smoke, heart rate at recovery, supraventricular arrhythmias, cardiac failure and complex ventricular arrhythmias either during recovery, either after discharge and finally spontaneous angina after hospital discharge. Meanwhile, for the end-point cardiac death age, smoke and supraventricular arrhythmias were not yet significant while arterial pressure at recovery and effort angina after hospital discharge were. Multivariate analysis identified cardiac failure during recovery, diabetes, complex ventricular arrhythmias before and spontaneous angina after discharge as independent variables contributing to total mortality: effort angina was a further significant one relatively to cardiac death. Thus, our study points out the importance of multivariate survival analysis when evaluating the relationship between survival after discharge for the effect of other prognostic factors. Moreover, providing identification of high risk cohorts permits appropriate interventions designed to lessen risk.