Five year prognosis of an Italian cohort of juvenile acute myocardial infarction patients.

AIM: The aim of this study was to describe the five-year prognosis of an Italian cohort of patients following acute myocardial infarction (AMI) occurred at age ≤ 45 years and to investigate the potential role of risk predictors for future cardiovascular events (CVE). METHODS: The study enrolled 112 consecutive patients aged ≤ 45 years admitted to our Coronary Care Unit between March 1995 and January 2007 because of AMI. Clinical characteristics, extent of coronary vessel disease by angiogram and cardiovascular risk factors (including diet, physical activity, alcohol and coffee consumption) were registered. RESULTS: Complete follow-up data was available for 104 (93%) patients with a duration of follow-up of 5.3 (2.9-7.6) years. Twenty-four (23%) patients presented with a new CVE: 16 (15%) angina pectoris, 6 (6%) recurrent AMI, one heart failure and one cardiac death. One in every five patients presented left ventricle systolic function below 50%. Multivariate analysis (Cox proportional regression model) proved physical activity as an independent predictor of new CVE occurrence (P=0.014). Patients who practised moderate aerobic physical activity for at least two hours per week following AMI had significantly higher event-free survival compared with inactive controls (P=0.029). CONCLUSION: Five-year prognosis of juvenile AMI is poor, with one in every five patients presenting a new CVE. Based on the present cohort of patients physical activity following first event plays a relevant prognostic role, supporting the need of careful lifestyle counselling.

Short and long-term outcomes of percutaneous revascularization in patients with prior coronary artery bypass graft.

AIM: Patients with prior coronary artery bypass grafting (CABG) represent a sizable portion of those undergoing percutaneous coronary intervention (PCI): in many instances, it is unclear whether performing PCI on the bypass graft or in the native coronary vessels can offer the best risk-benefit balance. METHODS: We included patients with prior CABG undergoing PCI at our center between July 2002 and June 2004 and we distinguished them in three groups. Those in whom PCI was performed on stenotic saphenous vein graft (SVG group), those in whom PCI was performed on native vessels despite the presence of potentially treatable SVG disease (optional native group), and those in whom PCI had to be performed mandatorily in the native vessels because of chronic SVG occlusions or disease in non-bypassed segments (mandatory native group). The primary end-point was long-term rate of major adverse clinical events (MACE, i.e. death, myocardial infarction, or target vessel revascularization). RESULTS: We identified 109 patients: 28 were in the SVG group, 25 in the optional native group, and 56 in the mandatory native group. Early major adverse cardiac events (MACE) occurred with similar frequency in the three groups (respectively, 9.1%, 0% and 5.7%, P=0.35). After more than three years of follow-up, MACE occurred in 39.3% vs. 28 and 39.4% (P=0.59), death occurred in 27.2 vs. 24.0% vs. 13.5% (P=0.30), and TVR in 27.3% vs. 8.0% vs. 28.8% (P=0.14). CONCLUSION: In selected patients, PCI of native coronary vessels despite the presence of apparently treatable SVG lesions can be envisioned.

Impact of multivessel coronary disease on long-term outcome after percutaneous recanalization of coronary chronic total occlusions.

AIM: Percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) is common even with concomitant multivessel disease. We aimed to investigate the impact of multivessel disease on long-term outcome after PCI for CTO. METHODS: We collected baseline, procedural and follow-up data on patients undergoing successful PCI with stenting for CTO. We divided our population into three groups: patients with 1 vessel disease (1VD), those with 2-vessel disease (2VD) and subjects with 3-vessel disease (3VD). The primary end-point was the occurrence of major adverse cardiac events (MACE), i.e. death, myocardial infarction or target vessel revascularization. RESULTS: A total of 111 patients were included: 24 (21%) in group 1VD, 28 (25%) in group 2VD, and 59 (53%) in group 3VD. Clinical follow-up was available in 109 (98%) of them after a median of 27 months (range 6-68), yielding MACE rates of 1 (4%) in group 1VD, 5 (18%) in group 2VD, and 17 (29%) in group 3VD, respectively (P=0.03). No statistically significant difference was found comparing the 3 groups for the individual rates of death, myocardial infarction or target vessel revascularization (all P>0.05). No case of definite or probable stent thrombosis was adjudicated, despite use of DES in 99 (89%) patients. CONCLUSION: Patients with diffuse coronary disease undergoing PCI for a CTO fare a significantly worse prognosis. Nonetheless, despite liberal use of DES, stent thrombosis is rare in this setting, without differences according to the initial severity of disease, thus supporting the long-term safety of DES, even if used in this "off-label" context.

Repeat adverse events long after percutaneous coronary revascularization in diabetics.

AIM: Diabetics with coronary artery disease face a high risk of adverse events following coronary revascularization. However, recurrence rates of after the first revascularization have never been appraised. The aim of this study was to evaluate recurrent events in diabetics undergoing percutaneous coronary intervention (PCI) in the current era. METHODS: Authors collected baseline and outcome data of consecutive type-2 diabetics treated with PCI (July 2002-December 2005) . End-points of interest were the long-term rates of major adverse cardiac events (MACE: cardiac death, myocardial infarction [MI], percutaneous target vessel revascularization [TVR-PCI], or coronary artery bypass grafting [CABG]), non-TVR PCI, and stent thrombosis. RESULTS: A total of 429 diabetics were included, 191 (44%) insulin-dependent, with drug-eluting stents implanted in 232 (54%). After a median of 38 months, events were as follows: MACE in 167 (38.9%) subjects, cardiac death in 38 (8.8%), MI in 42 (9.8%), TVR-PCI in 130 (30.3%), CABG in 11 (2.6%), non-TVR-PCI in 52 (12.1%), and definite stent thrombosis in 9 (2.1%). Among the 129 patients undergoing TVR-PCI as first event, as many as 28 (21.7%) underwent a second TVR-PCI, 7 (5.4%) underwent a third TVR-PCI, and a further 2 (1.5%) underwent a fourth TVR-PCI, whereas CABG was performed in 2 (1.5%) and non-TVR-PCI in 4 (3.1%). CONCLUSIONS: This work, originally reporting on the risk of recurrent repeat revascularization events among diabetics treated with PCI, showed that adverse events occur frequently in these patients, but can be managed in most cases safely and successfully by means of repeat PCI only.

Biventricular pacing concomitant to on-pump heart surgery: a case series.

AIM: The aim of this paper was to report the authors' experience on biventricular epicardial pacing (BEP) as first-choice procedure concomitant to on-pump heart surgery for other definite indications. METHODS: BEP was performed in 13 consecutive patients with stage IV heart failure (HF) undergoing on-pump cardiac surgery for other definite indications. All patients were treated with optimized pharmacologic therapy, and showed complete left bundle branch block and reduced (<30%) left ventricular ejection fraction. RESULTS: In all patients, effective BEP was achieved. All patients were discharged alive; functional, ECG and echocardiographic parameters showed significant improvement, better observed at 4-month interval. However, a high mortality rate was noticed during follow up (about 70% at 6 months) with a significant number of sudden cardiac deaths. The absence of functional improvement in the mid-term period (4-month control) related to a poor prognosis. CONCLUSIONS: Epicardial lead placement during cardiac surgery of severe HF patients is safe and effective. A clear evaluation of the effect of BEP alone is precluded because of the interference of the concomitant indications for cardiac surgery and the absence of randomization. The high rate of sudden death noticed in this study raises the important question of whether implantation of a defibrillator would be warranted in such population.

Analysis of recurrent revascularization events following percutaneous coronary intervention of diabetic patients.

AIM: Greater incidence of recurrent events following percutaneous coronary intervention (PCI) has been described among patients with diabetes mellitus (DM). A clear actual picture of these events can hitherto be considered as lacking. Aim of this study was to describe frequency and peculiarity of recurrent cardiovascular events following PCI in a group of high risk DM patients and to compare the impact of repeat PCI and/or surgical revascularizations on the need of further coronary interventions in a long-term follow-up. METHODS: 254 consecutive DM patients undergoing PCI for known coronary artery disease (CAD) were followed by outpatient visits for 39+/-9 months. The registered endpoints were target vessel PCI (TVR PCI), target vessel surgical revascularizations (TVR CABG), non target vessel percutaneous revascularization interventions (NON TVR PCI), and no repeat revascularizations. RESULTS: 74 (35%) of the DM patients undergoing an index PCI required further revascularization and 10 (17%) patients needed more than one repeat TVR procedure. Second TVR revascularisation procedures occurred similarly following first PCI (15%) or surgical revascularisation (17%) driven by coronary lesions located in epicardial vessels treated during the index PCI. Patients undergoing TVR surgical revascularisation disclosed a higher probability of incurring in a second PCI driven by coronary lesions located in epicardial vessels not previously treated (P=0.003) compared to those approached by PCI. CONCLUSIONS: The present study reports on a seemingly superior coronary protection of PCI compared to surgical revascularization in preventing disease progression upon the native coronary arteries. These results need confirmation in larger population samples.

Temporal trends in baseline characteristics and peri-procedural complications of percutaneous drug-eluting stent implantation for unprotected left main disease: a single high-volume center experience.

AIM: Percutaneous drug-eluting stent (DES) implantation is commonly used in patients with unprotected left main (ULM) disease. As this procedure has been performed routinely in Turin Center since 2002, this article aimed to summarize a five year-experience in DES implantation in the ULM. METHODS: Baseline, procedural and in-hospital outcome data of all patients with ULM undergoing percutaneous coronary intervention (PCI) with DES between July 2002 and October 2006 at Turin Center have been collected. Patients were randomized into four groups: A (patients treated between July 2002 and December 2003), B (treated in 2004), C (treated in 2005) and D (treated in 2006). The baseline surgical risk features was to be compared with the European System for Cardiac Operative Risk Evaluation, disease location in the ULM, and in-hospital major adverse cerebro-cardiovascular events (MACCE), defined as death, myocardial infarction, repeat percutaneous revascularization, coronary artery bypass grafting, stroke, or stent thrombosis. RESULTS: Out of a total of 4 432 coronary interventional procedures 198 patients treated with DES in the ULM were identified. There was a significant increase in the number of patients treated (P=0.00095), but no difference in EuroSCORE across groups (P=0.14). Conversely, there was a significant temporal trend in the incidence of bifurcational ULM being treated with DES (P=0.03). Intriguingly, despite this increase in adverse lesion characteristics, no significant increase was found in the rate of in-hospital MACCE (P=0.93). CONCLUSION: In this single-center study, the number of patients being treated with DES for ULM disease has risen across the years, although keeping a similar surgical risk profile. Distal ULM involvement is no longer considered an absolute contraindication to PCI, as testified by the increasing frequency of such lesion among patients undergoing DES implantation at this Institution, with remarkably low rates of adverse events.

Is dobutamine stress echocardiography predictive of middle and late term outcomes in mitral stenosis patients?

AIM: In mitral stenosis (MS) patients with a poor symptom-echocardiography correlation, dobutamine stress echocardiography (DSE) still does not have a confirmed utility and predictive value. Our aim is to evaluate usefulness of DSE in assessing 2 and 5 years clinical outcomes. METHODS: Forty-four consecutive patients with known MS were submitted, between April 1998 and July 1999, to basal and DSE. Patients were divided in 2 groups: group A if during DSE was reached a mean mitral gradient (MG) = or > 15 mmHg and/or a pulmonary arterial pressure (PAP) = or > 60 mmHg, and group B if MG and/or PAP were respectively lower than 15 and 60 mmHg. Endpoints considered were death, hospitalization for acute pulmonary edema, complications associated with mitral valve disease and mitral valve interventions (percutaneous or surgical). Mean follow-up was 73.6+/-16.6 months. RESULTS: Mean age was 55.2+/-10.5 years; 83.7% were women; NYHA class was I-II-III respectively in 18.6%, 58.1% and 23.3% of the patients; mean mitral valve area was 1.39+/-0.26 cm2; mean MG 8.05+/-2.54 mmHg; PAP 39.3+/-7.9 mmHg. Twenty-five patients met criteria for group A and 18 for group B. The event-free interval (27.9+/-32.1 months in group A vs 53.5+/-25.8 months in group B; P=0.008) and the 2 years event-free survival (40% for group A vs 88.9% for group B; P=0.002) showed significantly different patterns between the 2 groups. The 5 years survival analysis did not reach significance. CONCLUSION: DSE seems to detect MS patients that will have rapid evolution of their valvular disease within 24 months.

The Myocardial Performance Index detects chronic cardiac allograft dysfunction sooner than other methods.

AIM: Many noninvasive techniques have been proposed for the early detection of chronic heart graft dysfunction. Diastolic dysfunction may precede systolic dysfunction, and often is prominent; therefore, the aim of the study was to investigate the clinical and prognostic value of a Doppler-derived index of both systolic and diastolic function in heart transplanted patients (Myocardial Performance Index, MPI). METHODS: The MPI was measured in 63 consecutive patients (mean age 55 years, 49 men and 14 women) in sinus rhythm with an orthotopic heart transplantation for at least 1 year (mean 5.3 years) and in 63 age and sex-matched controls. A complete clinical examination was performed at the time of enrollment and was repeated after 3 months. RESULTS: At 3 months, 11 patients (17.5%) presented events (heart failure, hospitalisation or cardiac death). Patients were divided into 2 groups: Group A (52 patients) without events in the follow-up and Group B (11 patients) with events. The values of MPI in Group B (0.55+/-0.19) were significantly higher than values in Group A (0.34+/-0.18, P=0.001). Whereas the values of the index did not differ significantly between Group A and control group (0.34+/-0.18 vs 0.33+/-0.10, P=NS). In the univariate analysis, the population of heart transplanted patients was dichotomised in subgroups by a cut-off MPI of 0.47 and a cut-off ejection fraction (EF) of 50%. Nine patients (41%) with MPI=or>0.47 presented events, while only 2 patients (5%) with MPI<0.47 had any event (P<0.001; c2 12.9). Six patients (85%) with EF<50% had events, while only 5 patients (9%) with EF=or>50% had an event (P<0.001; c2 14). In the multivariate analysis only MPI (chi squared=22.6, P=0.018) and EF (chi squared=20.8, P=0.025) were significant independent predictors of heart failure or cardiac death. By looking at Kaplan-Meyer curves, MPI seems to be better than EF in the earlier detection of graft dysfunction. CONCLUSION: MPI, as a combined systolic and diastolic index, may detect graft dysfunction earlier than EF.

Amiodarone and desethylamiodarone distribution in the atrium and adipose tissue of patients undergoing short- and long-term treatment with amiodarone.

The time to onset of action of amiodarone is often long in patients treated for arrhythmias; one reason might be a slow entry of the drug into the target organ, the heart. Amiodarone and desethylamiodarone, its active metabolite, were measured in the plasma, atrial tissue and pericardial fat of patients undergoing cardiac surgery. Two groups were studied: patients treated with amiodarone for less than 28 days (short-term group) and those treated for 28 days or more (long-term group). Plasma levels of amiodarone in the two groups were not different, whereas levels of desethylamiodarone were significantly higher in the long-term group. Average concentrations of amiodarone in the atrium were higher with longer treatment periods (30.2 +/- 5.6 versus 13.2 +/- 2.5 micrograms/g wet weight of tissue); the same was true for desethylamiodarone (40.3 +/- 7.7 versus 15.7 +/- 3.7 micrograms/g). Amiodarone concentrations in fat were also significantly higher in the long-term than in the short-term group. Atrium/plasma concentration ratios of desethylamiodarone were higher than those of amiodarone, whereas fat plasma concentration ratios of desethylamiodarone were lower. In conclusion, the equilibration of amiodarone and desethylamiodarone concentrations between myocardium and plasma appears to occur slowly in patients undergoing long-term treatment with amiodarone.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term follow-up of right ventricular monomorphic extrasystoles.

OBJECTIVES: The purpose of this study was to verify in a long-term follow-up whether frequent monomorphic right ventricle extrasystoles may progress to arrhythmogenic right ventricular dysplasia (ARVD). BACKGROUND: Frequent monomorphic right ventricle extrasystoles are generally considered benign. However, in patients with this pattern, cardiac magnetic resonance (MR) has recently shown anatomical and functional abnormalities of the right ventricle. METHODS: Sixty-one patients who had been classified by noninvasive examinations as having frequent idiopathic right ventricle ectopy were contacted after 15 +/- 2 years (12 to 20) and submitted to clinical examination, electrocardiogram (ECG), Holter monitoring, stress test, signal averaged ECG, echocardiography and, in 11 patients, cardiac MR. The primary end point was to ascertain the presence of cases of sudden death or progression to ARVD. RESULTS: At the end of the follow-up, 55 patients were alive; six died, none of sudden death; eight stated to be well but refused further examinations. The 47 patients examined had normal ECG; in 24 patients (51%), extrasystoles were no longer present at Holter monitoring; late potentials were present in up to 15% of the patients; the right ventricle was normal at echocardiography. In 8 of 11 patients (73%), cardiac MR showed focal fatty replacement and other abnormalities of the right ventricle. CONCLUSIONS: In this long-term follow-up study, no patient died of sudden death nor developed ARVD; two-thirds of the patients were asymptomatic, and, in half of the patients, ectopy had disappeared. Focal fatty replacement in the right ventricle was present in most.

Time course and determinants of left ventricular function recovery after primary angioplasty in patients with acute myocardial infarction.

OBJECTIVES: We sought to evaluate the importance of time in relation to treatment, time course and determinants of recovery of left ventricular (LV) function in patients with acute myocardial infarction (AMI) undergoing primary percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Myocardial salvage has been shown to be dependent on the time elapsed from the onset of AMI to reperfusion. METHODS: Left ventricular function was evaluated at hospital admission, after angioplasty, at 24 h and 6 months by both echocardiography and angiography and at 1, 7, 30, 90 and 180 days by echocardiography in 101 consecutive patients. RESULTS: Patients were allocated to three groups according to interval between symptom onset and angioplasty: <2 h (group A), 2 to 4 h (group B) and >4 h (group C). Patients in groups A and B showed a progressive improvement of LV function between day 7 and day 90, which became statistically significant at day 30 (p < 0.01). No LV function changes were noted in group C patients. Thrombolysis In Myocardial Infarction (TIMI) flow grade <3 at 24 h was not associated with any significant change in LV volume and function during the six-month follow-up period. Restenosis, when associated with TIMI flow grade 3 in the infarct-related vessel, did not influence LV function. Flow grade <3 of the infarct-related artery was not associated with any improvement of cardiac events independently from the time to treatment at the initial procedure. CONCLUSIONS: Patients undergoing primary PTCA for AMI have a good recovery of LV function if TIMI flow grade 3 is restored within 4 h. Coronary angioplasty limits further remodeling of the LV in patients treated after 4 h.

Different patterns of atrial activation in idiopathic atrial fibrillation: simultaneous multisite atrial mapping in patients with paroxysmal and chronic atrial fibrillation.

OBJECTIVES: We aimed to evaluate: 1) the behavior of electrical activity simultaneously in different atrial regions during atrial fibrillation (AF); 2) the difference of atrial activation between paroxysmal and chronic AF; 3) the atrial refractoriness dispersion; and 4) the correlation between the effective refractory periods (ERPs) and the FF intervals. BACKGROUND: Little data exist on the electrophysiologic characteristics of the different atrial regions in patients with AF. A more detailed knowledge of the electrical activity during AF may provide further insights to improve treatment of AF. METHODS: Right and left atria were extensively mapped in 30 patients with idiopathic AF (18 paroxysmal and 12 chronic). In different atrial locations, we analyzed 1) the FF interval duration; and 2) the grade of organization and, in case of organized electrical activity, the direction of atrial activation. Furthermore, in patients with paroxysmal AF, we determined the atrial ERP, evaluated the ERP dispersion and assessed the presence of a correlation between the ERPs and the FF intervals. RESULTS: In patients with chronic AF, we observed a shortening of the FF intervals and a greater prevalence of disorganized activity in all the atrial sites examined. In patients with paroxysmal AF, a significant dispersion of refractoriness was observed. The right lateral wall showed longer FF intervals and more organized atrial activity and, unexpectedly, the shortest mean ERPs. In contrast, the septal area showed shorter FF intervals, greater disorganization and the longest mean ERPs. CONCLUSIONS: Electrical activity during AF showed a significant spatial inhomogeneity, which was more evident in patients with paroxysmal AF. The mean FF intervals did not correlate with the mean ERPs.

Clinical and therapeutic implications of chronic left ventricular dysfunction in coronary artery disease.

In patients with myocardial ischemia, left ventricular dysfunction (LV) may arise from irreversible damage (cell death), myocardial stunning (postischemic dysfunction), or myocardial hibernation (persistent myocardial dysfunction at rest due to underperfusion). Chronic LV dysfunction usually refers to hibernating myocardium. However, stunning might also become chronic, producing persistent myocardial dysfunction. Clinical studies have demonstrated that many patients with coronary artery disease have subsequent recurring ischemic (symptomatic or silent) episodes at short intervals in the same area and that each episode may be followed by myocardial stunning. In these patients the myocardium may not recover fully between episodes and function may remain reversibly depressed for long periods or may even be clinically depressed. The recognition of both stunning and hibernation is very important clinically and therapeutically, since chronic LV dysfunction may have a negative effect on mortality and morbidity in patients with coronary artery disease. Moreover, both clinical states are potentially correctable. Pharmacologic intervention with beta blockers, angiotensin-converting enzyme inhibitors, or calcium antagonists might improve or protect hibernating myocardium. The acute hemodynamic effects of the dihydropyridine calcium antagonist nisoldipine have been investigated in patients with chronic LV dysfunction probably arising from hibernating myocardium. Nisoldipine was found to improve both left ventricular systolic and diastolic function without activating the adrenergic system. The improvement in systolic function may be due to a redistribution of coronary blood flow and to a slight reduction in afterload induced by nisoldipine. On the other hand, nisoldipine may improve diastolic function in these patients by an intrinsic mechanism, Reducing intracellular calcium overload or balancing intracellular calcium homeostasis in the ischemic areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac ultrastructure in primary restrictive cardiomyopathy.

A five-year clinical follow-up and the results of myocardial biopsies are described in a patient with primary restrictive cardiomyopathy. Histologic examination of a right ventricular endomyocardial biopsy taken early in the course of the illness was not contributory. Histologic examination of a left ventricular endomyocardial biopsy five years later showed hypertrophy and disarray of myocytes, thickening of the endocardium, and interstitial fibrosis. Connective tissue was compact and regularly oriented in the endocardium, but tangled and irregularly oriented in the interstitium. It is concluded that the irregular network of collagen fibrils and elastic fibers limits diastolic relaxation and prevents ventricular dilatation; that the coexisting hypertrophy results from an attempt to maintain normal pump function; and that the myocyte disarray is a consequence of abnormal mechanical forces generated under conditions of severe fibrosis.

GH-independent cardiotropic activities of hexarelin in patients with severe left ventricular dysfunction due to dilated and ischemic cardiomyopathy.

AIM: To investigate acute cardiotropic activities of hexarelin in patients with severe left ventricular dysfunction due to ischemic (iCMP) and dilated cardiomyopathy (dCMP). METHODS AND RESULTS: We studied the effect of intravenous hexarelin administration on growth hormone (GH) levels and left ventricular ejection fraction (LVEF) evaluated by radionuclide angiography in eight patients with dCMP (age 53.0+/-2.8, LVEF 16.7+/-2.1%) and five patients with iCMP (age 52.0+/-2.8 years, LVEF 22.6+/-2.1). Results were compared with a group of seven normal subjects (age 37.4+/-3.4 years, LVEF 64.0+/-1.5%) and seven patients with severe growth-hormone deficiency (GHD; age 42.0+/-4.4 years, LVEF 50.0+/-1.9%) previously studied with the same methodology. In dCMP and iCMP patients hexarelin induced a similar significant (P<0.05) increase in GH levels. In iCMP patients hexarelin induced a LVEF increase (peak LVEF 26.2+/-2.5%, P<0.05) as observed in normals and GHD, while in dCMP LVEF was unchanged (peak LVEF 17.7+/-1.7, P=NS). In all groups other hemodynamic parameters were unchanged. CONCLUSIONS: Acute hexarelin administration increases LVEF in iCMP patients (as in normals and GHD) but not in dCMP patients in spite of a similar GH releasing effect and basal LVEF. A possible explanation of the positive inotropic effect of hexarelin in iCMP could be a direct stimulation on viable myocardium or myocardial contractile reserve.

Distribution of amiodarone and desethylamiodarone in a patient with acute myocardial infarction after intravenous administration.

The autopsy tissues concentration of amiodarone and desethylamiodarone of a man with acute myocardial infarction treated acutely with intravenous amiodarone is reported. Our data indicate that amiodarone is quickly distributed into all highly perfused tissues after intravenous administration with a high amiodarone/desethylamiodarone ratio. We also report here the autopsy case of a woman who died after 30 days of oral therapy with amiodarone. The increase in heart/plasma ratio of amiodarone and desethylamiodarone concentrations and the decrease in amiodarone/desethylamiodarone ratio after one month of therapy could explain the latency in the antiarrhythmic action of the drug.

Mortality and morbidity in reoperation comparing to first intervention in coronary revascularization.

BACKGROUND: Coronary artery reoperation represents about 20% of coronary artery operations. In this study we compared mortality and morbidity of first intervention and redo operation. EXPERIMENTAL DESIGN: a retrospective study. SETTINGS: patients who underwent coronary artery reoperations in a University Cardiac Surgery Division in 1991-1994. PATIENTS: our clinical survey was composed of two groups: group A included 44 consecutive patients (mean age 60+/-7 years, males/females=41/3) who underwent a coronary artery reoperation in the years 1991-1994 at the University Cardiac Surgery Division of Turin; group B included 344 patients (mean age 58+/-8 years, males/females=289/55) randomly selected among those who underwent a first coronary operation in the above indicated period of time and centre. All patients had angina pectoris refractory to maximal medical therapy. INTERVENTIONS: all patients underwent a coronary artery operation in extracorporeal circulation (ECC), under mild hypothermia (30-32 degrees C), during a single aortic clamp period, with antegrade cold crystalloid cardioplegia (St. Thomas). MEASURES: comparison of clinical preoperative features, risk factors and postoperative mortality and morbidity between the two groups. RESULTS: In reoperated patients we observed a greater mean akinesis score (p<0.001) and severe left ventricular dysfunction presence (p=0.014). Reoperation mortality was 11.4% against first operation mortality of 3.2% (p=0.03). Female gender (p=0.03), intra-aortic balloon counterpulsation need (p=0.002), adrenaline use (p=0.004) and low cardiac output syndrome (p=0.007) were all perioperative risk factors in group A. CONCLUSIONS: Coronary artery reoperation involves a higher mortality and morbidity compared to the first operation, especially related to the reduced left ventricular function which characterises the population that undergoes reoperation.

Plasma levels and urinary excretion of verapamil, norverapamil, N-dealkylverapamil (D617), N-dealkylnorverapamil (D620) following oral administration of a slow-release preparation.

The kinetics of verapamil and of its N-dealkylated metabolites (norverapamil, D617, D620) were studied in six cardiac patients with normal cardiac indexes after 120 mg oral administration of the drug both as conventional preparation and as slow-release preparation. Following a dose of the slow-release preparation, the drug concentration curves were smoother and the mean bioavailability was lower in comparison with the conventional preparation. A patient taking inducing agents (phenobarbital and phenytoin) exhibited a strikingly low bioavailability. Following administration of the conventional preparation, the mean plasma half-lives of verapamil, norverapamil, D617 and D620 were 4.4, 6.6, 8.5, and 15.8 h respectively and the drug concentrations showed a triexponential decay. Urinary excretion data indicate that a saturation phenomenon may occur at level of renal tubular transport and that a competition may be suspected between D620 and the other compounds. It is concluded that various mechanisms, i.e. changes in hepatic and renal clearances, occurrence of a deep compartment, and the properties of the pharmaceutical preparation may affect verapamil kinetics during long-term treatment.

Noninvasive ultrasonic biopsy: evaluation of early arteriosclerotic lesions progression in normal asymptomatic, hyperlipidemic, and diabetic subjects.

Noninvasive ultrasonic biopsy (UB) is a method of detecting early arteriosclerotic changes by high-resolution ultrasound scanning of the carotid and femoral bifurcation. Six UB classes (scoring 0 to 10) have been identified in 2000 asymptomatic subjects and 600 vascular patients followed up for four years. The incidence of silent coronary ischemia (tested by effort test) and the occurrence of symptomatic events in four years are increased in advanced classes and with increasing UB score. The rate of progression (ROP) in four years to the next UB class has been defined in normal subjects (1.4% in class I, 3.1% in II, 10.7% in III, 17.9% in IV, and 79.2% in class V). In a group of 305 asymptomatic hyperlipidemic subjects and in a group of 269 diabetics the ROP (in four years) was significantly higher. Therefore ultrasonic biopsy is useful to identify subjects at risk of coronary ischemia and cardiovascular events and to follow up noninvasively the progression of arteriosclerosis.