Objectives. The long term efficacy and safety of a third-generation implantable cardioverter-defibrillator implanted with thoracotomy and nonthoracotomy lead systems was evaluated in a multicenter international study.Background. The clinical impact of transvenous leads for nonthoracotomy implantation and pacing for bradyarrhythmias and tachyarrhythmias in implantable cardioverter defibrillator systems is not well defined.Methods. The safety of the implantation procedure and clinical outcome of 1,221 patients with symptomatic and life-threatening ventricular tachyarrhythmias who underwent implantation of a third generation cardioverter defibrillator using either a thoracotomy approach with epicardial leads (616 patients) or a nonthoracotomy approach with endocardial leads (605 patients) in a nonrandomized manner was analyzed. The implantable cardioverter defibrillator system permitted pacing, cardioversion, defibrillation, arrhythmia event memory and noninvasive tachycardia induction.Results. Successful implantation of an endocardial lead system was achieved in 605 (88.2%) of 686 patients and an epicardial system in 614 (99.7%) of 616 (p < 0.05). Perioperative 30 day mortality rate was 0.8% (1.8% including crossovers) in endocardial implant recipients compared with 4.2% (p < 0.001) in epicardial implant recipients(3.6% without crossovers, p < 0.05, respectively). Implantation mortality risk was significantly lower for nonthoracotomy systems irrespective of left ventricular ejection fraction or New York Heart Association functional class. Pacing therapies prevented need for cardioversion or defibrillation shocks in 89% of all ventricular tachycardia episodes and were comparably effective for both lead systems. Total survival rate at 2 years was significantly higher in endocardial (87.6%) than epicardial (81.9%) lead recipients (p < 0.001). Elimination of perioperative mortality from the analysis demonstrated comparable survival in both groups (p > 0.2).Conclusions. Third-generation cardioverter defibrillators with monophasic waveforms can be successfully implanted with epicardial (99.7%) and endocardial (88.2%) lead systems. We conclude that endocardial leads should be the implant technique of first choice. Improved patient management and tolerance for device therapy is achieved with the addition of antitachycardia pacemaker capability in these systems.

Between 1982 and 1988, we observed 312 patients who were affected by syncope or presyncope and whose spontaneous symptoms could be reproduced by means of carotid sinus massage (CSH); no other definite cause of syncope could be identified. The clinical outcome during a 2- to 8-year follow-up period (mean 44 ± 24 months) was assessed in 262 of them (mean age, 71 ± 11 years; 183 men) and was compared with that of a group of 55 patients who were affected by unexplained syncope (control patients) who were matched 4:1 for age and sex with CSH patients. CSH patients had an overall mortality rate of 7.3 per 100 person-years (cardiovascular, 66%; sudden death, 9%); overall predicted cumulative survival rates at 1, 3, 5, and 7 years were 92%, 80%, 66%, and 53%. Survival was similar in control patients: mortality rate was 5.8 per 100 person-years (cardiovascular, 82%; sudden death, 18%); cumulative survival rates at 1, 3, 5, and 7 years were 85%, 80%, 73%, and 69%. Standardized mortality rate of the general population with similar age and sex distribution, as calculated by means of Italian Istituto Centrale di Statistica death-rate data (1987 edition) was 8 per 100 person-years. Of 13 clinical variables, age, sex, abnormal electrocardiogram, and heart failure (but not CSH type or related arrhythmias) were independently linked to mortality in CSH patients (Cox model). In the vasodepressor form of CSH, patients were younger than those with other forms of CSH and the percentage of women was higher. In conclusion, the long-term outcome for CSH patients is similar to that observed in patients with unexplained syncope and in the general population; outcome is independent of CSH type.

The antianginal efficacy of metoprolol OROS has been investigated in comparison with that of atenolol in a multicenter double-blind cross-over trial carried out in patients with stable effort angina. OROS (ORally OSmotic) is a new semi-permeable delivery system with very slow osmotic release of the active drug, which is maintained at virtually constant plasma levels throughout the 24 hours. At the end of a 2-week run-in period, 53 patients with chronic coronary artery disease and documented ischemia during bicycleergometric exercise test were given, on double-blind condition, metoprolol OROS 21/285 and atenolol 100 mg in random order for 4 weeks each. On the last day of each cross-over period, patients underwent a bicycleergometric exercise test 24 hours after the last drug intake. The mean number of anginal attacks (2.54 during the 2-week run-in period) decreased under both metoprolol OROS (1.29 and 1.13 after 2 and 4 weeks of treatment, respectively) and atenolol (1.29 and 0.73 after 2 and 4 weeks of treatment, respectively), with no difference between the two beta-blockers. The same behaviour was observed as regards the nitroglycerin tablets consumption. The exercise test variables (i.e. duration of exercise, maximum workload and peak exercise values of systolic and diastolic blood pressure, heart rate and ST-segment depression) did not differ between the two treatments and did not show a time-effect. The percentage of patients reporting adverse effects was low with both treatments. Two patients were withdrawn from the study during atenolol (gastralgia and heartburn, respectively), and one during metoprolol OROS (gastralgia).(ABSTRACT TRUNCATED AT 250 WORDS)

A new method for selection of the pacing mode in 60 consecutive patients with severe cardie‐inhibitory or mixed carotid sinus syndrome was prospectively validated. ODD pacing was preferred for 26 patients with: (1) the cardioinhibitory form and who had symptomatic pacemaker effect; (2) mixed type I form, (cardioinhibitory and vasodepressor) with symptomatic pacemaker effect, ventriculoatrial conduction or orthostatic hypotension; (3) mixed type II; or (4) severe bradycardia. VVI pacing was seiected in the remaining 34 patients without these symptoms. During a 32 ± 10 month follow‐up period syncope and severe dizziness persisted in five patients in the VVI group (15%) and in three patients in the ODD group (12%). Symptomatic relief occurred in 87% (52/60) of patients. Minor symptoms persisted in 47% of the VVI group and 42% of the DDD group. No patient developed cardiac insufficiency or intolerance to pacing. During a 2‐month duration a single‐blind, randomized, cross‐over study compared VVI and DDD pacing, 69% of the patients programmed from DDD to VVI suffered more frequent, severe, and intolerable symptoms. (1) Thirty four of 60 patients (57% of the entire group) in whom VVI pacing was satisfactory were identified prior to pacemaker implant. In the remainder, VVI pacing was contraindicated as it produced frequent side effects. (2) The preimplant predictive value that VVI pacing would be successful was 85% for those eventually receiving VVI pacemakers and the preimplant predictive value that VVI pacing would fail was 69% for those who underwent DDD implant.

It is generally accepted that a positive response to carotid sinus massage (CSM) or head-up tilt (HUT) in patients affected by syncope suggests a reflex cause of the syncope. To study the role of the autonomic nervous system in causing syncope in the sick sinus syndrome (SSS), CSM and HUT were performed in 35 consecutive patients (20 men, mean age 70 +/- 9 years) with syncope and SSS. Results were compared with those in 35 patients affected by syncope that, despite careful cardiovascular and neurologic examination, were of uncertain origin (21 men; mean age 68 +/- 9 years) and with those of 35 subjects without syncope (20 men; mean age 69 +/- 10). All patients underwent CSM in the supine and standing positions for 10 seconds and HUT to 60 degrees for 60 minutes. In the patients with SSS, the full reproduction of spontaneous symptoms by CSM occurred in 21 (60%) and by HUT, in 19 (54%). At least 1 test was positive in 28 patients (80%): cardioinhibitory or mixed responses in 69%, vasodepressor responses in 11%. The percentages of positive tests in the patients with syncope of uncertain origin were similar to or slightly less than those of patients with SSS (CSM 63%, HUT 26%, overall 74%) with cardioinhibitory or mixed responses in 54% and vasodepressor in 20% (p less than 0.05). In control subjects, syncope was induced by CSM in 1 (3%) and by HUT in 2 (6%); overall positivity was 9%. In conclusion, in most patients affected by syncope and SSS, an abnormal neural reflex probably plays a major role in causing syncope.(ABSTRACT TRUNCATED AT 250 WORDS)

To verify the role of abnormal neural mechanisms in unexplained syncopes, we evaluated the results of carotid sinus massage (CSM), eyeball compression (EBC), and head-up tilt test (HUT) in the basal state (B) and during isoproterenol infusion (ISO) in: (1) 100 consecutive patients affected by syncope which, despite careful cardiovascular and neurologic examination, was of uncertain origin (age 60 +/- 18 years; 54 men) and (2) 25 healthy subjects matched 4:1 with the patients of the previous group. All the patients underwent CSM and EBC in the supine and standing position for 10 seconds and HUT at 60 degrees for 60 minutes; if HUT-B was negative (68 cases), it was repeated during ISO (1 to 5 micrograms/min) infusion. In the patients with uncertain syncope, spontaneous symptoms were fully reproduced in 49%, 16%, 32%, and 16% of cases respectively by means of CSM, EBC, HUT, and HUT-ISO; overall positivity for at least one test was observed in 79% of cases. The results of CSM, EBC, or HUT-ISO were linked to age, sex, and underlying heart disease. In the healthy subjects, syncope was induced by CSM, EBC, HUT, and HUT-ISO in one case each; overall positivity was 16%. In conclusion, neural reflex induction tests reproduced spontaneous symptoms in most patients affected by uncertain syncope, while they evoked normal responses in most healthy subjects. Therefore on the basis of results of induction tests, the diagnosis of neurally mediated syncope can be ascribed to most patients affected by syncope of uncertain origin.

The real incidence of pacemaker implants for carotid sinus syndrome (CSS) and the relation between CSS and sick sinus syndrome (SSS) is not precisely known. Patients who needed pacing therapy because of atrial bradyarrhythmias were investigated by means of carotid sinus massage, dynamic ECG, and invasive electrophysiological sinus node evaluation. Of 298 consecutive patients receiving a pacemaker implant, 36 (12%) had a severe cardioinhibitory carotid sinus reflex with reproducible spontaneous symptoms (CSS), 33 (11%) had sinus bradycardia less than 50 beats/min or an abnormal electrophysiological evaluation (SSS) and 24 (8%) had both (CSS + SSS). The annual incidence was 40, 37, and 26, respectively, implants per year/million of inhabitants (total incidence 325). Patients affected by CSS, if compared with those affected by SSS, showed: a higher prevalence of syncope (97% vs 42%); more syncopal episodes per patient (2.9 +/- 2 vs 1.8 +/- 0.9); a lower prevalence of associated cardiac diseases (53% vs 100%); cardiac enlargement (36% vs 88%); heart failure (6% vs 36%) and paroxysmal atrial fibrillation (0% vs 42%); and a more frequent indication for VVI pacing (75% vs 3%). In patients with CSS + SSS, intermediate characteristics were present. In conclusion, CSS is as frequent an indication to cardiac pacing as SSS; clinical differences justify a distinction between them, even if they are associated in 26% of cases.

UNLABELLED:At present, patients affected by carotid sinus syndrome and, more general by speaking, by vasovagal syncopes, are being considered more and more for pacemaker implant. However, neither the real incidence of the carotid sinus syndrome or its relation with the sick sinus syndrome with which it is often associated or even confused is precisely known. Of a total of 298 consecutive pacemaker implants, 36 (12%) were executed for carotid sinus syndrome, 33 (11%) for sick sinus syndrome and 24 (8%) for both. The annual incidence was respectively of 40, 37 and 26 implants per year/million of inhabitants. Patients affected by carotid sinus syndrome, when compared with those affected by sick sinus syndrome, showed: a higher prevalence of syncopes (97 vs 42%) more syncopal episodes per patient (2.9 +/- 2 vs 1.8 +/- 0.9), a lower prevalence of associated cardiac diseases (53 vs 100%), cardiac enlargement (36 vs 88%), heart failure (6 vs 36%) and paroxysmal atrial fibrillation (0 vs 97%), a more frequent indication to VVI pacing (75 vs 3%). Generally, when both syndromes were present, the patients showed intermediate characteristics.IN CONCLUSION:carotid sinus syndrome is a frequent indication of cardiac pacing as sick sinus syndrome; even if an association is present in about one third of patients, a distinction between carotid sinus syndrome and sick sinus syndrome is justified by theoretical and practical considerations.

In this prospective study, we evaluated pacing therapy in 60 consecutive patients affected by syncopes or pre-syncopes and cardioinhibitory or mixed carotid sinus hypersensitivity. We preferred DDD/DVI pacing for the 26 patients who had: 1) the cardioinhibitory form and presence of symptomatic pacemaker effect, or 2) the mixed type I form and presence of symptomatic pacemaker effect, ventriculo-atrial conduction, or orthostatic hypotension, or 3) the mixed type II form, or 4) the presence of severe sinus bradycardia. We preferred VVI mode in the other 34 patients. Syncope or pre-syncope persisted in one patient of the VVI group after the pacemaker implant and in one patient of the DDD/DVI group. Therefore, we obtained the suppression of severe symptoms in 97% of cases (58/60 pts). Yet minor symptoms persisted in 35% and 38% of patients of the two groups, respectively. No patient developed clinical signs of cardiac insufficiency or intolerance to pacing therapy. Besides, in DDD/DVI patients, we performed a single-blind, randomized, cross-over study for a comparison between the DDD/DVI and VVI mode: each patient was paced for two months using each mode and for each period symptoms were analyzed. The VVI period, compared to the DDD/DVI, resulted in a significantly higher incidence of symptoms: syncope 8% vs. 0%; pre-syncope 31% vs 0%; minor symptoms 58% vs. 31%; cardiac failure 19% vs. 0%. So the DDD/DVI mode was preferred by 69% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty uremic patients submitted to three different dialytic procedures (6 patients to acetate dialysis, 8 patients to bicarbonate dialysis, 6 patients to hemofiltration) were monitored in respect to the hemodynamic parameters recorded with a thermistor Swan-Ganz catheter. During acetate dialysis there was an increment of cardiac index (CI) up to positive values (+4.8%), while resistance index (RI) decreased progressively until it reached -16.5%. During bicarbonate dialysis CI, after an initial fall, remained constant and RI increased (+8.6%). During hemofiltration CI decreased constantly throughout the entire procedure while RI increased until +12.9%. We concluded that during diffusive transport the buffer used plays an important role in determining hemodynamic responses to fluid removal; during convective transport vascular resistance increases in spite of acetate.

Cardioinhibitory carotid sinus hypersensitivity is present in about one third of patients affected by sinus dysfunction. Aim of the study was to evaluate whether carotid sinus hypersensitivity is related to a well defined (intrinsic or extrinsic) sinus node damage. Fifty-four patients with ecg signs of sinus dysfunction underwent an electrophysiological study and carotid sinus massage. Spontaneous heart rate and corrected sinus node recovery time were measured in basal condition, after adrenergic blockade (propranolol 0.2 mg/Kg i.v.) and after autonomic blockade (propranolol 0.2 mg/Kg i.v. plus atropine 0.04 mg/Kg i.v.). The association between sinus dysfunction and cardioinhibitory carotid sinus hypersensitivity was found in 18/54 pt. (16 men, 2 women; mean age +/- 1 SD 63.6 +/- 14.5 years). The remaining 36 patients (19 men, 17 women; mean age +/- 1 SD 65.8 +/- 9.8 years), affected by sinus dysfunction alone, were used as controls. No electrophysiological differences between the two groups were found; particularly, an abnormal intrinsic heart rate (according to Jose values) or an abnormal intrinsic corrected sinus node recovery time (greater than 385 msec.) were present in 83% of the patients in both groups. Among sinus dysfunction clinical features, heart rate, presence of spontaneous syncope, sino-atrial block or sinus arrest and organic heart disease were similar in the two groups while the percentage of patients with spontaneous atrial tachyarrhythmias (bradi-tachy syndrome) was significantly smaller (11% vs 44%; p less than 0.01) in carotid sinus hypersensitivity group. In conclusion, in sinus dysfunction patients, the presence of carotid sinus hypersensitivity cannot be used as a criterion to differentiate a subgroup with peculiar clinical and electrophysiological sinus node characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemical data and clinical tolerance were evaluated in eight uremic patients treated by Biofiltration (BF) for 5-20 months. In four patients hemodynamic parameters were monitored with a Swan-Ganz catheter during a session of BF. BF provides long-term biochemical safety and improved tolerance to fluid removal.

To assess the efficacy and tolerability of two doses of chlorthalidone (CHL) and slow-release (SR) metoprolol (MET) given in fixed combination (standard dose: CHL 25 mg and MET 200 mg; lower dose: CHL 12.5 mg and MET 100 mg), a multicenter (5 Centers), double-blind, between-patients study was planned. Seventy-three mild to moderate hypertensive patients, 45 males and 28 females, aged 25-68 years (mean 51.4), at WHO stage I or II, were enrolled into the study. After a 2-week placebo wash-out period, eligible patients were randomly given either of the two drugs for six weeks: 33 were given the standard dose and 40 the lower one. Every 2 weeks, in the morning and 24 h after-dosing lying and standing systolic (SBP), diastolic blood pressure (DBP) and heart rate (HR) were recorded at rest. At the end of the placebo period and at the end of the study 24 h after-dosing a sub-maximal bicycle ergometer exercise test was performed. In comparison with placebo, both doses induced a significance decrease (p less than 0.01) in lying and standing SBP, DBP and HR, as well as in peak-exercise SBP, HR and pressure-rate product. Furthermore, a significant difference (p less than 0.05) of the higher dose versus the lower one was also observed at the end of the study in the above-mentioned parameters except for SBP at rest and at peak exercise and standing HR at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Five patients with lymphoma and Vincristine induced myocardial infarction are described in the medical literature. We report two new cases, in whom an anterior myocardial infarction developed few hours after the second administration of the drug. In the reported cases a strict cause-to-effect relationship between the drug and acute myocardial infarction seems indicated by: the striking temporal coincidence between Vincristine administration and onset of chest pain; the additional myocardial infarctions in patients in whom the treatment was continued after the first event; the nearly constant absence of important coronary risk factors and the young age of the patients, making preexisting coronary atherosclerosis unlikely. The mechanism for the described association is still unknown: the possible causes are discussed.

The normal range and the reproducibility of the cardioinhibitory carotid sinus reflex were studied in 288 apparently healthy subjects of different ages (aged from 17 to 84 yrs., 156 males, 132 females). In each subject we chose the longest RR interval as an activation index of the reflex obtained by carotid sinus massage; its mean value increased slightly with advancing age. In the were 1, 5, 2, 5, 3, 3 sec. respectively, with a 99% confidence limit. No sex difference was found. We studied also a group of 105 patients (aged from 39 to 82 yrs., 67 males, 38 females) with various types of cardiovascular disorders, without a previous history of spontaneous syncope. Abnormal maximum RR values were found in 18 of them (17%). This percentage was significantly higher than in normals (2%). In 11 patients (10%) the carotid sinus stimulation evoked a syncopal attack. It seems therefore that a statistically abnormal carotid sinus hypersensitivity can occur in a substantial number of cardiovascular patients without necessarily leading to spontaneous syncopal attacks. Finally the reproducibility of the cardioinhibitory reflex was tested in 42 patients with maximum RR interval values ranging from normal to extremely abnormal. In each subject a significant correlation (r = 0.79) was found between the maximum RR interval values tested in two occasions at intervals ranging from 1 hour to 3 months; besides a concordance in normal or abnormal result was present in 93% of the cases.

The systolic blood pressure was measured during clinostatism and 15'', 1', 5' after standing in 101 patients with carotid sinus syndrome and in 101 controls matched for age, sex, and prevalence of organic heart disease. In the carotid sinus syndrome group we observed a greater systolic blood pressure reduction from the supine to standing position (20 +/- 19 vs 14 +/- 11 mmHg), a lower orthostatic pressure (111 +/- 23 vs 120 +/- 21 mmHg) and a greater incidence of orthostatic hypotension (defined as a blood pressure reduction greater than or equal to 50 mmHg or greater than or equal to 20 mmHg when orthostatic pressure was lower than 100 mmHg) (35% vs 17%). Twenty-three carotid sinus syndrome patients received a VVI pacemaker for control of their symptoms; after a mean follow-up of 12.2 +/- 7.7 months, unchanged or reduced symptoms persisted in 6 out 9 (67%) patients with previous orthostatic hypotension while only in 1 out of 14 (7%) patients without this feature. In conclusion, orthostatic hypotension is frequently associated with a carotid sinus syndrome and may account for relapses in some patients treated with VVI pacing.

Three patients with 1:1 atrio-ventricular conduction at rest developed fixed 2nd or 3rd degree atrio-ventricular block during exercise testing. In all patients electrophysiologic study documented block distal to the atrioventricular node. The exercise induced block probably occurred because of increased atrial rate and abnormal refractoriness of the His-Purkinje conduction system. These findings suggest that high degree atrioventricular block appearing during exercise reflects conduction disease of the His-Purkinje system rather than of the atrio-ventricular node, even in absence of bundle branch block. These patients should be considered for permanent cardiac pacing.