Prevalence of atrial thrombi in patients with atrial fibrillation/flutter and subtherapeutic anticoagulation prior to cardioversion.

AIMS: Thromboembolism may complicate electrical cardioversion (ECV) of atrial fibrillation/flutter (AF). The use of 3 weeks of warfarin before ECV results in a substantial reduction of thromboembolic complications. Nevertheless, in patients scheduled for ECV subtherapeutic INR levels are common. We sought to assess the prevalence and the predictors of atrial thrombi in patients affected with sustained AF in whom subtherapeutic INR values were detected in the 3 weeks preceding scheduled ECV. METHODS AND RESULTS: Forty-one patients with persistent AF and > or =3 weeks warfarin anticoagulation who exhibited subtherapeutic INR values in the last 3 weeks underwent a transoesophageal echocardiogram (TOE) before a scheduled ECV. A left atrial appendage (LAA) thrombus was diagnosed on TOE in four patients (9.8%). Patients with thrombus had lower INR values (1.45+/-0.09 vs 1.72+/-0.20; p=0.0068), lower LAA emptying velocities (13.75+/-4.5 vs 25.86+/-12.4 cm/s; p=0.0313) and higher prevalence of atrial smoke (100 vs 37.8%,p=0.03). CONCLUSIONS: Subtherapeutic levels of anticoagulation before elective ECV of AF may expose patients to post-ECV thromboembolic sequelae, especially in patients with lowest INR values. Current recommendations of a full course of therapeutic anticoagulation before ECV of persistent AF should be firmly observed.

Reproducibility of asystole during head-up tilt testing in patients with neurally mediated syncope.

Tilt induced prolonged asystole has been considered to identify a distinct subgroup of patients with neurally mediated syncope and management including permanent pacemaker implantation has been suggested. To evaluate the reproducibility of asystolic response during head-up tilt testing (HUT), 33 patients with neurally mediated syncope and asystolic response (> or = 3 seconds) during HUT prospectively underwent two consecutive tests 13 +/- 15 days apart. On repeat tilt testing asystole was reproduced in 12 patients (36%), while 8 patients still had a positive HUT, but without asystole. Remarkably, 13 patients (40%) had a negative repeat HUT. Among 12 patients with asystole on both HUTs there was no significant difference in duration of asystole (14 371 +/- 11 430 ms vs 13 707 +/- 10 470 ms, P = ns) and time to syncope (36 +/- 20 min vs 37 +/- 20 min, P = ns) during initial and repeat HUTs. In conclusion, asystole during tilt testing does not seem to be a reproducible response.

Isolated noncompaction of the ventricular myocardium. A study in an adult male and literature review.

Noncompaction of the ventricular myocardium is a rare congenital disorder characterized by the presence of numerous prominent trabeculations and deep intertrabecular recesses which communicate with the left ventricular cavity. The disease uniformly affects the left ventricle, sometimes also affecting the right ventricle. Noncompaction of the ventricular myocardium is believed to be a disorder of endomyocardial embryogenesis. Familial occurrence has been observed. It may be accompanied by depressed ventricular function, cardiac arrhythmia and systemic embolism. Although noncompaction of the ventricular myocardium is a congenital myocardial disorder, the onset of symptoms is frequently delayed until adulthood. We describe a case of noncompaction of the ventricular myocardium in a 33-year-old male with the typical echocardiographic and cardiac magnetic resonance imaging features of this disease.

Comparison of diagnostic accuracy of sublingual nitroglycerin test and low-dose isoproterenol test in patients with unexplained syncope.

Despite the widespread use of head-up tilt testing as a means for diagnosing vasovagal syncope, standardization of test methodology remains a controversial issue. The aim of this study was to compare the diagnostic value of head-up tilt testing potentiated with sublingual nitroglycerin with that of head-up tilt testing potentiated with low-dose isoproterenol. For this purpose, 71 patients with unexplained syncope (mean age 43 years) and 30 asymptomatic controls were studied. All underwent the sublingual nitroglycerin and low-dose isoproterenol tests on separate days in a randomized fashion. The protocol of the 2 tests was similar and consisted of 2 phases. Initially, subjects were tilted at 60 degrees for 20 minutes without medication; then, if syncope did not occur, patients and controls received sublingual nitroglycerin (300 microg) or low-dose intravenous isoproterenol (mean infusion rate 1.3 +/- 0.5 microg/min) and continued to be tilted at 60 degrees for a further 20 minutes. During the sublingual nitroglycerin test, a positive response (syncope associated with sudden hypotension and bradycardia) occurred in 35 patients (49%), a negative response in 36 (51%), and drug intolerance in none (0%). During the low-dose isoproterenol test, these percentages were 41%, 59%, and 6%, respectively. A concordant response was observed in 53 cases (75%). Among controls, 3 subjects (10%) had a positive response to the sublingual nitroglycerin test and 4 (13%) to the low-dose isoproterenol test. It is concluded that sublingual nitroglycerin and low-dose isoproterenol are equivalent tests for evaluating patients with unexplained syncope. The sublingual nitroglycerin test, however, is simpler, better tolerated, and safer than the low-dose isoproterenol test and, thus, more suitable for routine clinical use.

[The tilt test enhanced with oral nitroglycerin in patients with unexplained syncope: the Italian Protocol. The Working Group on Syncope of the Associazione Italiana di Aritmologia e Cardiostimolazione--the Arrhythmia Area of the Associazione Nazionale Medici Cardiologi Ospedalieri]. / Tilt test potenziato con nitroglicerina orale nei pazienti con sincope inspiegata: "Il Protocollo Italiano". Gruppo di Lavoro sulla Sincope AIAC--Area Aritmie ANMCO.

The head-up tilt testing potentiated with oral nitroglycerin, devised by an Italian group, is a simple, safe and powerful, but still not a standardized, diagnostic tool. In fact, owing to its rapid diffusion, the original protocol received, often arbitrarily, subsequent modifications. Thus a task force of experienced cardiologists defined the best methodology for the test on strictly evidence-based criteria. Particular attention was reserved to some controversial topics, such as the tilting angle, the duration of the passive and pharmacological stages of the test, the type and dosage of the drug utilized. We hope that the enclosed protocol, named by us as "The Italian Protocol", will be accepted as the standard methodology of the head-up tilt testing potentiated with oral nitrates.

'The Italian Protocol': a simplified head-up tilt testing potentiated with oral nitroglycerin to assess patients with unexplained syncope.

Head-up tilt testing potentiated by sublingual nitroglycerin (NTG), advocated by an Italian group, is a simple and safe but still not a standardized, diagnostic tool for the investigation of syncope. In fact, owing to its rapid spread, the original protocol received, often arbitrarily, many subsequent modifications. We now define the best methodology of the test on strictly evidence-based criteria as: stabilization phase of 5 min in the supine position; passive phase of 20 min at a tilt angle of 60 degrees; provocation phase of further 15 min after 400 micrograms NTG sublingual spray. Test interruption is made when the protocol is completed in the absence of symptoms, or there is occurrence of syncope, or occurrence of progressive (> 5 min) orthostatic hypotension. We intend that this protocol, named by us as 'The Italian Protocol', will be accepted as the standard methodology of the tilt test potentiated by sublingual nitrates.

Early cardioversion of atrial fibrillation and atrial flutter guided by transoesophageal echocardiography: a single centre 8.5-year experience.

AIMS: To analyse the safety and impact on maintenance of sinus rhythm of transoesophageal echocardiographically guided early cardioversion associated with short-term anticoagulation in a large series of patients with atrial fibrillation and atrial flutter. METHODS AND RESULTS: Patients who were candidates for cardioversion were eligible for inclusion if they had atrial fibrillation or atrial flutter lasting longer than 2 days or of unknown duration. Patients received short-term anticoagulation with warfarin or heparin and underwent transthoracic echocardiography followed by transoesophageal echocardiography. Early cardioversion was performed if no thrombus was seen on the transoesophageal study. Warfarin was maintained for 1 month after cardioversion. In patients with atrial thrombi, cardioversion was deferred and prolonged anticoagulation was prescribed. The study population included 183 patients. One hundred and sixty nine patients without atrial thrombi underwent early cardioversion. Fourteen patients with atrial thrombi (7.6%) underwent a second transoesophageal echocardiogram after a median of 4 weeks of oral warfarin, and cardioversion was performed if clot regression was documented. No patient in our study population had a clinical thromboembolic event at 1 month follow-up (95% C.I. 0-0.016). The immediate success rate of cardioversion was better among patients with atrial fibrillation < 4 weeks duration compared with patients with atrial fibrillation of longer or of unknown duration: 96.6% vs 85%, respectively (P = 0.014). At 1 month follow-up, the percentage of arrhythmia relapses in patients with initially successful cardioversion was similar in the two groups (29% vs 26%, P = ns); thus the initial better outcome in patients with recent-onset arrhythmia was not lost. CONCLUSION: Transoesophageal echocardiography-guided early cardioversion in concert with short-term anticoagulation is safe. This approach permits abbreviation of the overall duration of atrial fibrillation and has a better impact on the maintenance of sinus rhythm for patients in whom the duration of atrial fibrillation is < 4 weeks.

Reproducibility of head-up tilt testing potentiated with sublingual nitroglycerin in patients with unexplained syncope.

Head-up tilt testing (HUTT) potentiated with sublingual nitroglycerin has gained acceptance as means of diagnosing neurally mediated syncope. To evaluate the reproducibility of HUTT potentiated with sublingual nitroglycerin, 48 patients with unexplained syncope prospectively underwent 2 consecutive tests 1 to 28 days apart. The initial test ended in syncope in 34 patients (71%). In 9 patients (19%) the test was positive during the drug-free phase, whereas 25 patients (52%) had syncope after nitroglycerin administration. Of these 34 patients with an initial positive test result, 27 (79%) had a reproducible outcome on repeat testing. Of 12 patients (25%) with an initial negative test result, 10 (83%) had a reproducible outcome on repeat testing. Of 2 patients (4%) with a first test ending in exaggerated response, both had a negative repeat test response. The overall reproducibility of sublingual nitroglycerin tilt-table testing was 77%. In a group of 23 patients with both positive tests, 19 (83%) had the same response modality (2 vasodepressor, 4 cardioinhibitory, 13 mixed response). In the same group of patients, individual trough heart rates correlated well with each other between tests. Finally, in the 27 patients with both positive tests, intrapatient time of onset of symptoms did not significantly correlate between tests. Thus, in patients with syncope of unknown origin, HUTT potentiated with sublingual nitroglycerin provides an adequate reproducibility when repeated on different days.

Atrial thrombosis in cardiac amyloidosis: diagnostic contribution of transesophageal echocardiography.

Few cases of atrial thrombosis detected by transesophageal echocardiography (TEE) in cardiac amyloidosis have been reported recently. We present the cases of 3 consecutive patients affected by AL-type cardiac amyloidosis, symptomatic for heart failure and in sinus rhythm. All patients had a cardiac restrictive pattern at Doppler examination. TEE showed left atrial thrombus in 2 patients and biatrial thrombi in 1 patient; conventional transthoracic echocardiography detected only 1 left atrial thrombus. Our experience confirms the association between cardiac amyloidosis and atrial thrombosis, even in sinus rhythm. TEE should be considered to assess thromboembolic risk in all cases of cardiac amyloidosis with severe diastolic dysfunction.

Atrial thrombi resolution after prolonged anticoagulation in patients with atrial fibrillation.

BACKGROUND: Cardioversion of atrial fibrillation in nonanticoagulated patients may be associated with clinical thromboembolism. Prolonged anticoagulation with warfarin before cardioversion of atrial fibrillation produces a marked reduction of cardioversion-related thromboembolism. The benefit of anticoagulant therapy is generally believed to be due to atrial thrombi organization. PATIENTS AND METHODS: Transesophageal echocardiography (TEE) is highly accurate for diagnosis of atrial thrombi and gives the possibility to serially evaluate the effects of anticoagulant therapy. One hundred twenty-three patients with atrial fibrillation lasting longer than 2 days underwent TEE before cardioversion. An atrial thrombus was identified in 11 patients (9%), and was always confined to the left atrial appendage. TEE was repeated after a median of 4 weeks of oral warfarin. Atrial thrombus had completely resolved in 9 of 11 patients (81.8%; 95% CI, 48.2 to 97.7%); in two patients, clot was still present. No patient had clinical thromboembolism between the two TEE studies. CONCLUSIONS: In the population of our study, a prolonged course of warfarin therapy was associated with resolution of atrial thrombi in the majority of patients. According to these data, the mechanism of thromboembolism reduction with 4 weeks of anticoagulation before cardioversion in patients with atrial fibrillation seems to be related mainly to thrombus lysis rather than organization. Due to the possibility of thrombus persistence even after prolonged anticoagulation, follow-up with TEE before cardioversion is necessary to document thrombus resolution.

Head-up tilt testing potentiated with oral nitroglycerin: a randomized trial of the contribution of a drug-free phase and a nitroglycerin phase in the diagnosis of neurally mediated syncope.

BACKGROUND: Since the pharmacological challenge with nitroglycerin (NTG) follows the initial drug-free phase in current tilt testing protocols, the effects of nitroglycerin alone and the appropriate duration of the basal phase are unknown. METHODS: To optimize the test, a randomized intra-patient comparison of two protocols was undertaken: a conventional nitroglycerin test (cHUT) consisting of passive upright posture at 60 degrees for 45 min followed, if negative, by sublingual NTG 0.4 mg spray, with the test continued for 20 min; and, accelerated nitroglycerin test (aHUT) consisting of passive upright posture at 60 degrees for 5 min--to rule out orthostatic hypotension--followed by sublingual NTG 0.4 mg spray, with the test continued for 20 min. Eighty-four consecutive patients (33 males; mean age 55+/-22) with unexplained syncope underwent both cHUT and aHUT in a randomized sequence with a 24-72 h interval between them. Additionally, 25 age-matched control subjects underwent aHUT. RESULTS: In the drug-free phase, cHUT was positive in 15/84 patients (18%) and aHUT in 1/84 patients (1%). After NTG, cHUT and aHUT showed the same positivity rate of 33% (28/84 patients). The overall positivity rate was therefore higher with cHUT than with aHUT (51% vs 35%, P=0.04). Times to syncope were 29+/-12 min, (range 2-44) for cHUT drug-free phase, 5+/-2 min (range 2-9) for cHUT NTG phase, and 5+/-2 min (range 2-9) for aHUT. Only one (4%) of the control subjects had a positive response to aHUT. CONCLUSIONS: The contribution of NTG to the diagnosis is independent of the presence of an unmedicated phase. The appropriate duration of the NTG phase is 10 min. aHUT has good specificity, but a positivity rate lower than cHUT; thus a drug-free phase is necessary to increase the sensitivity of the test.

Effects of long-term vasodilator therapy in patients with carotid sinus hypersensitivity.

BACKGROUND: In patients affected by carotid sinus hypersensitivity, long-term vasodilator therapy might increase the risk of syncopal episodes by reducing systolic blood pressure and venous return to the heart. METHODS AND RESULTS: Thirty-two patients (mean age 73 +/- 9 years; 20 men) who met all the following criteria were included: (1) one or more episodes of syncope occurring during long-term (>6 months) treatment with angiotensin-converting enzyme inhibitors, long-acting nitrates, calcium antagonists, or a combination of these; (2) a positive response to carotid sinus massage, defined as the reproduction of spontaneous syncope in the presence of ventricular asystole > or =3 seconds or a fall in systolic blood pressure > or =50 mm Hg; (3) negative workup for other causes of syncope. The patients were randomly assigned to continue or to discontinue use of vasodilators; carotid sinus massage was repeated 2 weeks after randomization. By the end of the study period, the baseline values of systolic blood pressure were significantly different between the 2 groups of patients both in supine (P=.01) and upright (P=.03) positions. Syncope had been induced by carotid sinus massage in 81% of patients in the "on-vasodilator" group and in 62% of patients in the "off-vasodilator" group (P=.21). The cardioinhibitory reflex was of similar magnitude in the 2 groups, being found in 50% of the patients in each group, with a maximum ventricular pause of 7.1 +/- 2.7 and 6.7 +/- 1.8 seconds, respectively. The percentage decrease of blood pressure did not differ between the 2 groups, even if, in absolute values, the baseline difference of blood pressure roughly persisted for the duration of the test. In consequence of that, the rise of blood pressure to similar values was delayed approximately 30 seconds in the "on-vasodilator" group and took more than 2 minutes to return to baseline values. CONCLUSIONS: In patients affected by carotid sinus hypersensitivity, chronic vasodilator therapy does not have a direct effect on carotid sinus reflexivity, although the delayed recovery of pretest blood pressure values could indirectly potentiate the severity of the clinical manifestations of the syndrome. The persistence of hypotension for a longer time after the end of the massage suggests that vasodilators cause an impairment of compensatory mechanisms.

Effects of chronic vasodilator therapy to enhance susceptibility to vasovagal syncope during upright tilt testing.

To evaluate the effect of chronic vasodilator therapy on susceptibility to vasovagal syncope, 45 patients with syncope and a positive response to tilt testing were randomly assigned to continue or to discontinue vasodilators. The study result demonstrated that chronic vasodilator therapy enhances susceptibility to vasovagal reaction during upright tilt testing.

Risk factors for acute hepatitis B: a case-control study.

Over the period 1989-1991 a case-control study was carried out in the area of Naples comparing 162 subjects with acute hepatitis B and 788 hospitalized control subjects. The results of multivariate analysis showed that surgical intervention (odds ratio 3.8; 95% CI 1.2-11.7), household contact with an hepatitis B surface antigen (HBsAg) positive carrier (odds ratio 2.7; 95% CI 1.1-6.7) and intravenous drug use (odds ratio 13.0; 95% CI 3.2-52.7) were risk factors independently associated with hepatitis B. No association was found with the other risk factors considered, such as blood transfusion, hospitalization, other percutaneous exposures, dental therapy, contact with an icteric case, barber shop shaving and two or more sexual partners. As a significant proportion of the general population undergoes surgical intervention, efficient procedures for sterilization of instruments should be implemented, together with the use of disposable materials, to control the spread of HBV infection in surgical settings.

Gastrointestinal peptide hormones in acute viral hepatitis.

Liver affects the release and clearance of many hormones, but the interactions between gastrointestinal peptides and liver function are obscure. Aim of this study was to evaluate plasma concentrations of gastrointestinal peptides during acute hepatic cytonecrosis and during liver regeneration in man. The study was performed in ten patients with viral hepatitis (8 virus A, 2 virus B) in the acute phase (alanine transaminase = 3073 +/- 739 U/L; mean +/- SEM), and at days 7, 45 and 52 after the initial evaluation, during clinical and biochemical recovery (52nd day, alanine transaminase = 77 +/- 26). Plasma concentrations of the following hormones were evaluated by radioimmunoassay: glucagon, insulin, gastrin, vasoactive intestinal peptide, bombesin, neurotensin, cholecystokinin, secretin and motilin. Only serum bombesin and cholecystokinin were significantly (p < 0.01) increased in the acute phase of hepatitis (bombesin: 138 +/- 21 pg/ml; cholecystokinin: 57 +/- 7 pg/ml); they returned to normal values during convalescence (bombesin: 60 +/- 8; cholecystokinin: 31 +/- 4). During hepatocellular necrosis, plasma concentrations of cholecystokinin and bombesin, which are both cellular growth factors and regulatory signals of food introduction and satiety state, were increased by 83% and 130%, respectively. Increase of these hormones may cause the dyspepsia and lack of appetite that characterizes the initial phase of acute viral hepatitis.

Case control study of risk factors for hepatitis A: Naples 1990-1991. Hepatitis Collaborating Group.

An increased incidence of hepatitis A was observed in Naples from 1990-1991. A hospital-based case-control study was carried out to evaluate the relative importance of various risk factors. A hundred and ninety-eight cases and 238 hospital controls were recruited during the study period. The strongest association was contact with a jaundiced person among children. A correlation was also shown for children and adults with raw shellfish consumption and pre-school nursery attendance or presence in the household of children attending pre-school nurseries. History of travel and intravenous drug use were risk factors for adult subjects. Considering the relative importance of the specific risk factors we found that 38% of the acute hepatitis A cases were attributable to contact with a jaundiced person, 15% to presence in the household of children attending pre-school nurseries and 28% to raw shellfish consumption.

Severe left ventricular dynamic outflow tract gradient secondary to localized septal hypertrophy and concomitant acute ischaemic parietal dyssynergy.

Localized basal septal hypertrophy (LSH) is usually an incidental echocardiographic finding and, as opposed to asymmetric hypertrophic cardiomyopathy (AHC), is of no clinical significance. We report a case of a patient with LSH who developed a severe left ventricular outflow gradient during acute myocardial ischaemia, apical akinesis and compensatory hyperkinesis of basal parietal segments.

Risk factors for acute non-A, non-B hepatitis and their relationship to antibodies for hepatitis C virus: a case-control study.

A case-control study was carried out comparing 333 case subjects with non-A, non-B hepatitis and 1095 hospital control subjects. Of 333 case subjects, 197 (59%) were positive for hepatitis C antibody (anti-HCV). Excluding blood transfusion and intravenous drug use, surgical intervention and dental therapy were strongly associated with anti-HCV-positive cases: in particular, obstetric and gynecology surgical intervention was found to be strongly associated with HCV positivity (odds ratio [OR] = 32; 95% confidence interval [CI] = 7, 147). Raw shellfish consumption was a risk factor for anti-HCV-negative cases (OR = 2.2; 95% CI = 1.0, 5.1), thus suggesting an enterically transmitted virus in sporadic non-A, non-B hepatitis in Italy.

Typhoid fever in the Neapolitan area: a case-control study.

Typhoid fever is endemic in the Neapolitan area, where its yearly incidence rate largely exceeds the corresponding national figure. During the period from January to June, 1990, a matched case-control study was carried out in order to identify risk factors of the disease in this area; 51 subjects (mean age 27.2 years) with typhoid fever were compared with 102 controls matched with respect to age, sex and educational level. Consumption of raw shellfish was reported by 76.5% of the cases, as opposed to 19.6% of the controls (P < 0.01). Subjects who had eaten this food item had a 13.3-fold risk (C.I. 95% = 5.5 - 32.8) of contracting typhoid fever. In contrast, no risk was found to be associated with consumption of cooked shellfish, raw vegetables, ice-cream, non-potable water, or unpasteurized milk. The risk factor identified in this study shows that hazardous dietary habits and inadequate sewage treatment facilities, combined with lack of sanitation in the harvesting and marketing of shellfish, play a major role in the endemicity of typhoid fever in the Neapolitan area.

Vaccine-induced escape mutant of hepatitis B virus.

In southern Italy, 44 contacts of hepatitis B virus carriers, including infants of carrier mothers, became HBsAg positive despite passive and active immunisation according to standard protocols. In 32 of these vaccinees infection was confirmed by the presence of additional markers of viral replication. In 1 infant, serious disease occurred. The virus from this patient is an escape mutant with a different sequence from that of the isolate from the mother. A point mutation from guanosine to adenosine at nucleotide position 587 resulted in an aminoacid substitution from glycine to arginine in the highly antigenic a determinant of HBsAg. This mutation is stable: it is present in an isolate from the child 5 years later. In some of these patients, including this child, the a determinant, to which a large part of the vaccine-induced immunity is directed, has been partly lost. Binding to HBsAg of a monoclonal antibody, previously mapped to the region of the mutation, was reduced in the child relative to that of the mother.