Radiofrequency ablation for benign thyroid nodules.

Benign thyroid nodules are an extremely common occurrence. Radiofrequency ablation (RFA) is gaining ground as an effective technique for their treatment, in case they become symptomatic. Here we review what are the current indications to RFA, its outcomes in terms of efficacy, tolerability, and cost, and also how it compares to the other conventional and experimental treatment modalities for benign thyroid nodules. Moreover, we will also address the issue of treating with this technique patients with cardiac pacemakers (PM) or implantable cardioverter-defibrillators (ICD), as it is a rather frequent occurrence that has never been addressed in detail in the literature.

Relation between the plasma levels of LDL-cholesterol and the expression of the early marker of inflammation long pentraxin PTX3 and the stress response gene p66ShcA in pacemaker-implanted patients.

Our goal was to set up a pilot study to explore the possible relation between the expression of p66((ShcA)) and PTX3, two emerging regulators of stress response and inflammation processes, respectively, and the circulating levels of LDL-cholesterol (LDL), a factor implicated in the development of inflammation and oxidative-stress associated diseases such as atherosclerosis. p66((ShcA)) and PTX3 mRNA contents were determined locally, in subcutaneous adipose specimens of non-diabetic pacemaker-implanted patients, and systemically in the circulating white blood cells (WBC) obtained from the same patients. The mean of the circulating LDL levels (125 mg/dl) was chosen as a threshold to identify two groups here considered to have high (>125 mg/dl) and low (<125 mg/dl) LDL plasma levels. Our data show that PTX3 and p66((ShcA)) mRNA levels are significantly more elevated in WBCs and in adipose tissue samples of patients with high levels of LDL compared to those with low levels. Additionally, a multiple regression analysis indicates that among LDL, TG, HDL, total cholesterol, CRP, creatinine and glucose levels, the only variable significantly affecting p66((ShcA)) and PTX3 mRNA expressions either in adipose tissue or in WBCs is represented by the circulating amount of LDL. In conclusion, our results suggest a potential link between the level of LDL and the expression of two genes involved in inflammation/oxidative stress pathways, i.e., p66((ShcA)) and PTX3, thus contributing to further understand the mechanism through which LDL may mediate the pathogenesis of inflammation and oxidative-stress associated diseases such as atherosclerosis.

Indications for dual-chamber cardioverter defibrillators at implant and at 1 year follow-up: a retrospective analysis in the single-chamber defibrillator era.

AIM: This retrospective four-centre study assessed the current indications for dual-chamber implantable cardioverter defibrillators (ICDs) at implant and during a medium-term follow-up period in a group of patients treated by single-chamber ICD in the pre dual-chamber ICD era. METHODS AND RESULTS: The study population consisted of 153 consecutive patients (127 males, mean age 58 +/- 6 years) treated by single-chamber ICD for ventricular tachycardia and/or ventricular fibrillation. Definite indications for having a dual-chamber ICD included the presence of sinus node dysfunction and of second- or third-degree atrioventricular (AV) block, while possible indications were represented by paroxysmal atrial fibrillation or flutter and first-degree AV block. At implant, dual-chamber ICD would appear definitely indicated in 10.5% of cases, and possibly indicated in an additional 17.5% of cases. During 12 +/- 10 months follow-up, such percentages remained stable (11 and 19.5%, respectively). Inappropriate ICD intervention was documented in five of 13 patients (38%), with episodes of paroxysmal atrial fibrillation or flutter. CONCLUSION: In this non-selected study population, a dual-chamber ICD would have potentially benefited approximately 30% of the patients. During medium-term follow-up, there was no progression towards increasing dual-chamber ICD indications. The 15% cumulative incidence of paroxysmal atrial tachyarrhythmias justifies the activation of dedicated detection algorithms.

Incidence and predictors of sudden cardiac death during long-term follow-up in patients with dilated cardiomyopathy on optimal medical therapy.

BACKGROUND: In spite of a total mortality reduction in recent years, sudden cardiac death (SD) remains a major problem in patients with idiopathic dilated cardiomyopathy (IDC) and its occurrence is often unpredictable. Furthermore, the risk of SD may change during follow-up because of the natural history of the disease and the effects of therapeutic interventions. In our study, we evaluated the modifications of the risk of SD during follow-up in a cohort of patients with IDC and analyzed the variables predicting SD not only at enrolment but also at the last examination during optimal medical treatment. METHODS: Since 1978, 343 consecutive patients with IDC were enrolled in the Heart Muscle Disease Registry of Trieste (Italy) and submitted to complete invasive and non-invasive study. Patients were re-evaluated usually at intervals of 12 months. RESULTS: After a mean of 68+/-45 months, 125 events (death, heart transplantation or aborted SD) had occurred. The cumulative risk after 5 years was 30%, while after 10 years it almost doubled (54%). During the first 3 months after enrolment, the incidence of SD was high (3%). A plateau, lasting about 3.5 years, followed. A slow but progressive rise in the risk of mortality then occurred (6% at 5 years, 18% at 10 years). No variables evaluated at enrolment were associated with SD at multivariate analysis. On the other hand, the end-diastolic left ventricular diameter (> or = 38 mm/m2) and ejection fraction (< or = 0.30) were predictive of SD if evaluated within 1 year before the event. Beta-blocker treatment was associated with a non-significant reduction of risk. CONCLUSIONS: In patients with IDC the incidence of SD progressively increased during long-term follow-up, especially in those with persistent severe left ventricular dilation and dysfunction who were not on beta-blocker treatment. Serial clinical evaluation may help to select patients at higher risk for SD.

Persistence of restrictive left ventricular filling pattern in dilated cardiomyopathy: an ominous prognostic sign.

OBJECTIVES: We sought to assess the prognostic implications of the evolution of restrictive left ventricular filling pattern (RFP) in dilated cardiomyopathy (DCM). BACKGROUND: Previous work has demonstrated that a RFP in DCM is associated with a poor prognosis. Few data are available on the prognostic implications of the evolution of this pattern. METHODS: The evolution of left ventricular filling was studied by Doppler echocardiography in 110 patients with DCM. According to the left ventricular filling pattern at presentation and after 3 months of treatment, the patients were classified into three groups: Group 1A (n = 24) had persistent restrictive filling; Group 1B (n = 29) had reversible restrictive filling; and Group 2 (n = 57) had nonrestrictive filling. RESULTS: During follow-up (41 +/- 20 months), mortality plus heart transplantations was significantly higher in Group 1A than in Groups 1B and 2 (p < 0.0001). On multivariate analysis, the model incorporating E wave deceleration time at 3 months was more powerful at predicting mortality with respect to this variable at baseline (p = 0.0039). Clinical improvement at 1 and 2 years was significantly more frequent in Groups 1B and 2 than in Group 1A (p < 0.0001 at 2 years). CONCLUSIONS: In patients with DCM, the persistence of restrictive filling at 3 months is associated with a high mortality and transplantation rate. The patients with reversible restrictive filling have a high probability of improvement and excellent survival. Doppler echocardiographic reevaluation of these patients after 3 months of therapy gives additional prognostic information with respect to the initial study.

Predictive value of heart rate in dilated cardiomyopathy treated with metoprolol.

UNLABELLED: Predictive factors of a favourable response to beta-blocker therapy are still unknown and the role of heart rate remains controversial. AIM: To investigate the relation between heart rate and the response to chronic metoprolol treatment in patients with dilated cardiomyopathy (DCM). METHODS: Ninety-eight consecutive patients with DCM, left ventricular ejection fraction (LVEF) < or = 0.40 and blood pressure < or = 140/90 mmHg were treated with metoprolol, associated with digitalis, diuretics and ACE-inhibitors. After 24 +/- 6 months, 48 patients (49%) were classified as "improved" on the basis of a clinical/instrumental score. RESULTS: Rest, mean 24-hour and maximal exercise heart rate were all significantly and directly related to the probability of improvement, but heart rate at rest, supine and in upright position, showed the highest predictive power. The relationship between heart rate and improvement with metoprolol appeared to be non-linear, with an increasing probability in patients with higher heart rate, but with a fall of the slope in cases with extreme tachycardia. By dividing our study population on the basis of the most important clinical variables, this complex relation was evident only in patients at a more advanced stage of the disease. CONCLUSION: Our analysis confirms the strict relationship between heart rate and improvement with chronic metoprolol therapy in patients with DCM. This relation seems to be non-linear and is influenced by the severity of the disease.

[Bundle-branch reentry ventricular tachycardia induced by sinus beat]. / Tachicardia ventricolare da rientro branca a branca indotta da battito sinusale.

A spontaneous episode of bundle branch reentry ventricular tachycardia was recorded in a 50 year old man few weeks after operation for a severe aortic valve regurgitation. After surgery, the patient developed recurrent syncope and showed a bradycardia-dependent left bundle branch block and a HV interval of 70 ms. A bundle branch reentry ventricular tachycardia with left bundle branch block morphology, easily induced during premature ventricular stimulation, occurred spontaneously after the longest sinus cycle of a sequence conducted to the ventricles with a left bundle branch block morphology of the QRS complexes. During left bundle branch block an incomplete and concealed anterograde conduction along the left bundle branch was supposed to be present and its disappearance was considered the trigger mechanism of the spontaneous ventricular tachycardia. The negative results obtained with the signal-averaged ECG in our case support the concept that intramyocardial delay is not essential for this type of ventricular tachycardia.

Metoprolol in dilated cardiomyopathy: is it possible to identify factors predictive of improvement? The Heart Muscle Disease Study Group.

BACKGROUND: Some controlled clinical trials showed a beneficial effect of beta-blockers on symptoms, exercise tolerance, and left ventricular function in dilated cardiomyopathy. The purpose of this study was to investigate if there are clinical variables at baseline that could predict a favorable response to long-term metoprolol therapy. METHODS AND RESULTS: Since November 1987, 94 consecutive patients with dilated cardiomyopathy and left ventricular ejection fraction less than 0.40 were treated with metoprolol (mean final dosage, 136 +/- 32 mg) associated with tailored medical therapy with digitalis, diuretics, and angiotensin-converting enzyme inhibitors. Eighty-four surviving patients had a complete 2-year noninvasive follow-up period. Ten patients died or were transplanted before the final assessment. Improvement was defined according to a clinical score based on left ventricular ejection fraction (increase > or = 10 U), left ventricular end-diastolic diameter (decrease > or = 10%), regression of restrictive filling pattern, New York Heart Association functional class, exercise tolerance (increase > or = 2 minutes), and cardiothoracic ratio (decrease > or = 10%). According to these criteria, 48 patients (51.1%) were classified as improved. Multivariate analysis identified a group of patients with a history of mild hypertension (blood pressure between 140/90 and 170/100 mmHg) and significantly higher probability of improvement with longterm metoprolol (odds ratio [OR], 2.22; 95% confidence interval, 1.25-3.94; P = .007). Among the 71 patients with normal blood pressure (< 140/90 mmHg), heart rate in upright position (100 vs 75 beats/min: OR, 2; 95% confidence interval, 1.38-4.94; P = .003), left ventricular ejection fraction 0.20-0.33 versus less than 0.20 (OR, 4.72; 95% confidence interval, 1.06-21.04; P = .042), and New York Heart Association class I-II versus III-IV (OR, 2.74; 95% confidence interval, 0.97-7.75; P = .05) were significantly associated with a positive response to metoprolol. At baseline, both supine and upright heart rate were significantly higher in patients who improved, but heart rate in the upright position was the most significant predictor of improvement in patients with normal blood pressure at multivariate analysis. CONCLUSIONS: According to the authors' logit model, patients with a history of mild hypertension or with a higher resting heart rate, associated with controlled symptoms of heart failure (New York Heart Association class I-II) or moderate to severe left ventricular ejection fraction (range, 0.20-0.33) showed a remarkable probability of long-term (2-year) improvement on metoprolol.

[Stratification of the thromboembolic risk in patients with non-rheumatic atrial fibrillation: assessment of left atrial dysfunction]. / La stratificazione del rischio tromboembolico nei pazienti con fibrillazione atriale non reumatica: il contributo della disfunzione auricolare sinistra.

BACKGROUND: Patients with non rheumatic atrial fibrillation (NRAF) have an increased risk for thromboembolic complications. Recent evidence suggests that left atrial appendage function (contraction, filling dynamics) may provide clues to the thrombogenic potential of this structure. The aim of this study was to identify left atrial spontaneous echocontrast and thrombus between patients with NRAF and their relationship with left atrial appendage function. METHODS: Transthoracic (TTE) and biplane or multiplane transesophageal echocardiography (TEE) were performed in 143 patients with chronic NRAF enrolled in the Trieste Area Study on non rheumatic Atrial Fibrillation (TASAF), an ongoing prospective community study with a follow-up period of 2 years. The maximal and minimal areas of the left atrial appendage were measured during three cardiac cycles and the peak emptying and filling velocities profile were obtained by pulsed wave Doppler at the orifice of the left atrial appendage. The left atrium and appendage were inspected for thrombus and spontaneous echocontrast. RESULTS: Left atrial appendage thrombus was present in 37 patients (26%) and spontaneous echocontrast in 60 patients (42%), 45% of patients with spontaneous echocontrast had thrombus. Univariate analysis identified positive correlation of thrombus with duration of atrial fibrillation (p = 0.05), hypertension (p = 0.01), left atrial area (p = 0.005), mitral annular calcification (p = 0.01), left ventricular dysfunction (p = 0.03) and a non significant correlation with the mitral valve prolapse (p = 0.08) in the TTE. The presence of mitral regurgitation did not demonstrate a protective effect (p = 0.73) against thrombosis. The variables of left atrial appendage function identifying a subgroup of patients with increased risk of thrombus formation were: shortening fraction of the area in the horizontal and vertical sections (p = 0.0001 and p = 0.002 respectively), the peak filling and emptying velocity in horizontal (p = 0.0001 equal for both) and vertical sections (p = 0.0001 equal for both). In summary these patients have a larger left atrial maximal area (p = 0.004) and a lower flow velocity profile (p < 0.00001) and more intense spontaneous echocontrast (p < 0.00001) than the others. Spontaneous echocontrast was correlated with left ventricular dysfunction (p = 0.008), left atrial area (p = 0.02) and there was a non-significant correlation with mitral annular calcification (p = 0.09) and lower left ventricular shortening fraction (p = 0.06). Transesophageal echocardiography variables have identified the subgroup of patients with an increased risk of echocontrast formation. This was positively associated with a low flow velocity profile (p = 0.0001), a left atrial appendage low shortening fraction in horizontal section (p = 0.001) and in vertical section (p = 0.05) and a low peak filling velocity in horizontal section (p = 0.003) and in vertical section (p = 0.004) and a low peak emptying velocity in horizontal section (p = 0.003) and in vertical section (p = 0.001). Prophylactic therapy with anticoagulant or antiplatelet agents has little benefits in our experience. CONCLUSIONS: Spontaneous echocontrast and low flow profile velocity (low peak emptying and filling velocity) and increased area of left atrial appendage were strongly associated with left atrial and/or appendage thrombus in patients with NRAF. The assessment of left atrial appendage function by TEE is an important component of the comprehensive evaluation of potentially increased risk of thrombus formation.

Nonpredictive value of fibrosis in dilated cardiomyopathy treated with metoprolol.

Therapy with ß-adrenergic blocking agents has been advocated as a potential useful approach in heart failure. Recent studies suggest that histologic parameters may be helpful in assessing the effectiveness of ß-blocker treatment in dilated cardiomyopathy (DCM). In order to predict the response to ß-blockers in DCM, fibrous tissue was evaluated at endomyocardial biopsy (EMB) in 45 patients (pts) with a mean left ventricular ejection fraction of 0.28 ± 0.07, who were successively long-term treated with metoprolol (M) (mean dosage 138 ±26 mg/die). EMB was performed from left (n = 32) or right (n = 13) ventricle by means of a King's bioptome or the Cordis adaptation of this instrument. Quantification of fibrous tissue was performed at 9 × magnification and with a computerized morphometric system. Qualitative evaluation at light microscopy distinguished four types of fibrosis: pericellular, perivascular, focal, and endocardial. Volume fraction of fibrous tissue ranged from 1.3 to 35.5% (mean 12.1 ± 9.3%) and was not significantly correlated with any clinical variable considered. After 24 ± 12 months of treatment, 25 pts were considered improved (group A), whereas the remaining 20 pts were considered not improved (group B), according to criteria based on ejection fraction, left ventricular end-diastolic diameter, filling pattern at Doppler-Echocardiography, cardiothoracic ratio, NYHA functional class, and exercise duration at ergometric test. Volume fraction of fibrous tissue did not differ significantly between the two groups (group A = 12.1 ± 9.1%; group B = 11.3 ± 9.6%;p = NS). Dominant pericellular type of fibrosis was equally distributed between the two groups (group A = 9 25 pts, 36%; group B = 10 20 pts, 50%), whereas a perivascular and/or focal replacement fibrosis was more frequent in group A (group A = 10 20 pts, 50%; group B = 2 20 pts, 10%; p = .05, OR 5.55 at univariate analysis). At multivariate analysis mean aortic blood pressure was the only variable discriminating the two groups; the type of fibrosis, although not statistically significant, maintained a high value of odds-ratio (5.23). In conclusion, extent of total fibrosis assessed by EMB may range widely in patients with DCM, is not correlated with the most important clinical variables, and is not predictive of long-term response to ß-blocker treatment. Otherwise, prevalent perivascular and/or focal replacement fibrosis could be associated with a higher probability of improvement after long-term ß-blocker treatment.

[Safety and tolerability of beta-blockers in severe cardiac decompensation from dilated cardiomyopathy]. / Tollerabilità ed effetti dei betabloccanti nello scompenso cardiaco severo da cardiomiopatia dilatativa.

BACKGROUND: Several reports from controlled and uncontrolled studies, mainly in the setting of heart failure due to dilated cardiomyopathy (DCM), indicate that chronic betablockade may improve hemodynamics and clinical function. There are few reports on the effects of betablockers in patients with severe heart failure. METHODS: Thirty-five patients (27 M; 8 F; mean age 44.3 +/- 16.7 years; range 14-66 years) with DCM, advanced functional (NYHA III-IV) and severe left ventricular dysfunction (LVEF < or = 25%) underwent a test dosage with metoprolol (5 mg b.i.d.). Five patients (14%) did not tolerate the drug; 30 were chronically treated with metoprolol (mean dosage 127 +/- mg/die). No differences in baseline characteristics were observed between tolerant and not tolerant patients, except for the E-deceleration time (103 +/- 42 ms vs 84 +/- 17 ms; p<0.05). Seven alive patients did not reach a minimum follow up of 18 months. Nineteen patients (54.3%) had a follow up of at least 18 months. They were classified as ¿improved¿ (11 pts; and ¿not improved¿ (8 pts; 42%) on the basis of a score, which included left ventricular ejection fraction (> or = 0.10), left ventricular end diastolic diameter (> or = 10%), regression of restrictive filling pattern, NYHA functional class (> or = 1), cardio-thoracic ratio (> or = 10%) and exercise time (> or = 2 min). No differences were observed at baseline between ¿improved¿ and ¿not improved¿ patients, with exception for a history of slight hypertension (p<0.01), congestive heart failure score (p<0.04) and right ventricular function (p<0.05). RESULTS: An overall improvement of all the main clinical-instrumental parameters were observed in the 19 long term treated patients. At the end of follow up 16 long term treated patients were in NYHA class > or = 2 and in 9 LVEF was > or = 40%. During follow up, among the 30 patients who tolerated the drug, 1 pt died suddenly after 12 months of betablocker therapy and 5 pts were transplanted. No major events occurred among ¿improved¿ patients, after 24 +/- 6 months of follow-up. The actuarial survival curve of our study population shows that survival at 1, 2, 3 and 4 years was respectively 87%, 75%, 67% and 66%. These results confirm previous trials evidence that a progressively increasing dose of beta-blockers confers functional benefit in DCM with severe heart failure.

Changing mortality in dilated cardiomyopathy. The Heart Muscle Disease Study Group.

OBJECTIVE: To analyse the changes in mortality in dilated cardiomyopathy over the past 15 years and to identify the factors that might have influenced survival. DESIGN: Follow up study of 235 patients (aged 16-70) systematically enrolled on a register from 1 January 1978 to 31 December 1992. SETTING: Hospital department of cardiology. PATIENTS: Three groups corresponding to three periods of 5 years: group 1 (diagnosis between 1 January 1978 and 31 December 1982) 26 patients; group 2 (diagnosis between 1 January 1983 and 31 December 1987) 65 patients; and group 3 (diagnosis between 1 January 1988 and 31 December 1992) 144 patients. MAIN OUTCOME MEASURES: Death or heart transplantation. RESULTS: Two and four year survival was 73.8% and 53.8% in group 1, 87.7% and 72.3% in group 2, and 90.3% and 82.9% in group 3 (P = 0.02). During the 15 years of the study period the number of cases increased progressively and the baseline clinical characteristics changed (that is, patients were younger and less severely affected), partly explaining the improvement in survival. None the less, the three mortality curves tended to diverge progressively and the improvement in survival in the different groups was still significant after stratification for the severity of the disease, suggesting that treatment had a sustained effect. A progressively higher proportion of patients were treated with angiotensin converting enzyme (ACE) inhibitors and more recently with beta blockers. In group 2, after stratification for the severity of heart failure, patients who were treated with ACE inhibitors showed a better survival than patients who were not. Furthermore, analysis of group 3 showed that beta blockers had a significant additive effect with conventional therapy both by intention to treat and actual treatment. Four year survival in patients with mild and moderate to severe heart failure treated with beta blockers, and usually digitalis and ACE inhibitors, was respectively 90% and 87.5%. CONCLUSIONS: The improvement in the survival of patients with dilated cardiomyopathy over the past 15 years may be explained by earlier diagnosis, new treatments, and a change in the clinical characteristics of the patients at enrolment.

[New knowledge on the subject of therapy in cardiac decompensation in the light of large trials]. / Nuove conoscenze in tema di terapia dello scompenso cardiaco alla luce dei grandi trial.

Although an underlying disturbance in cardiac function can be identified in most patients with congestive heart failure, manifestations of the disease are greatly influenced by other factors, particularly neurohumoral and peripheral adaptive responses which occur secondary to impaired cardiac function. Until recently diuretic agents and digoxin formed the basis of conventional treatment of this condition. The majority of clinical trials published since 1980, indicate that digoxin lessens symptoms and reduces morbidity associated with congestive heart failure particularly in patients with more advanced symptoms and ventricular dysfunction. The efficacy of digitalis in congestive heart failure may in part result from sympathoinhibitory properties such as the activation of baroreceptorial mechanisms. At present there is no conclusive evidence that cardiac glycosides improve survival. Several trials clearly indicate that angiotensin converting enzyme inhibitors (enalapril, captopril) can reduce both morbidity and mortality in symptomatic congestive heart failure. Asymptomatic patients like those with severe left ventricular dysfunction and those who are at high risk for left ventricular remodeling after anterior wall myocardial infarction may also benefit from ACE-inhibition therapy. Increasing evidence suggests that beta-adrenergic blockade can produce symptomatic and hemodynamic improvement in heart failure of idiopathic and ischemic aetiology. Appropriately powered randomized controlled trials are required to determine the impact on survival of beta-blockers.