Interleukin-2 chronotherapy for metastatic renal cell carcinoma: Results of a phase I-II study.

BACKGROUND: Interleukin-2 (IL-2) was the cornerstone treatment for metastatic renal cell carcinoma (RCC) until the advent of tyrosine kinase inhibitors, but it still has therapeutic value. As a single bolus of IL-2 causes toxicity, there is interest in administration regimens with better tolerability and efficacy. Chronotherapy is the administration of therapy according to the circadian rhythm's influence on the immune and hormonal systems. This phase I-II trial evaluated the safety of IL-2 chronotherapy in metastatic RCC patients and determined the maximum tolerated dose. The secondary objective was to identify prognostic factors for survival. METHODS: Three chronomodulation schedules (5:00-13:00, 13:00-21:00, and 21:00-5:00) were tested. Each schedule was an 8-h IL-2 infusion, with a Gaussian distribution of drug concentration peaking at 4 h. To identify the maximum tolerated dose, the dose for different patients was escalated from 2 MIU/m2 (level I) to 18.6 MIU/m2 (level VI). RESULTS: Thirty patients were enrolled and completed treatment. Two patients were treated at 5:00-13:00, 15 at 13:00-21:00, and 13 at 21:00-5:00. Nine cases of grade 3 toxicity occurred in 7 patients at the highest dose (18.6 MIU/m2); no grade 4 toxicity occurred. The maximum tolerated dose was 14.0 MUI/m2. Patients were followed for a median of 16 months (range, 2-107). One patient was lost to follow-up, 3 patients were alive at last contact, and 26 patients died. Six patients achieved long-term survival (≥48 months). There was one complete response, four partial responses, 11 cases of stable disease and 14 of progressive disease. The response rate was 16% (5/30) and disease-control rate was 53% (16/30). Median progression-free survival was 4.5 months, and median overall survival was 14.5 months. Kaplan-Meier analyses revealed significant associations between overall survival and ECOG performance score (0 vs. 1-2), MSKCC score (0-2 vs. ≥ 3), IMDC risk score (0-2 vs. ≥ 3), IL-2 dose level (IV-VI vs. I-III), and prolactin (increase vs. no increase), and but not for chronotherapy schedule. CONCLUSION: IL-2 chronotherapy appears to be safe, moderately toxic and active in metastatic RCC. It may represent a new modality of IL-2 administration for these patients.

'Hot phase' non-dilated left ventricular cardiomyopathy with atypical onset and recurrence: a case report.

Non-dilated left ventricular cardiomyopathy (NDLVC) is a newly categorized cardiomyopathy phenotype includingseveral aetiologies with a linking characteristic represented by the normal left ventricular volume. Inflammatory heart disease (InHD) is a heterogeneous process with variegate clinical manifestations, sometimes in overlap with NDLVC. A 26-year-old woman was admitted forcomplete heart block (CHB) and persistently raised troponin. Echocardiography and coronary angiography were normal. Extensive oedema and late gadolinium enhancement was found at cardiac magnetic resonance. Endomyocardial biopsy showed no signs of active myocarditis. Steroid therapy was started with restoration of atrioventricular conduction but subsequently the patient experienced a mild recurrence with a new troponin relapse. Genetic test was negative for mutations related with the clinical scenario. In this case of NDLVC with InHD the precise diagnostic work-up, including genetic test, was crucial for diagnostic, prognostic andtherapeutic purposes. Multimodality approach is crucial to detect and treat possible recurrences.

Impact of associated significant aortic regurgitation on left ventricular remodeling and hemodynamic impairment in severe aortic valve stenosis.

OBJECTIVES: The left ventricular (LV) response to combined pressure and volume overload [aortic stenosis (AS) and aortic regurgitation (AR)] versus pressure overload (isolated AS)has not been systematically studied. We aimed to assess LV remodeling, functional and hemodynamic consequences inpatients with mixed aortic valve disease versus patients with isolated AS. METHODS: We enrolled 181 patients (67 ± 9 years,109 men) with severe AS (aortic valve area indexed to body surface area <0.6 cm 2 /m 2 ) who underwent preoperative cardiac catheterization and a complete echocardiogram. Pulmonary capillary wedge pressure (PCWP), LV end-diastolic pressure (LVEDP) and pulmonary artery pressure (PAP) were measured. RESULTS: One hundred and ten patients (group A)had isolated severe AS (AR 0­1) and 71 patients (group B)had mixed aortic valve disease (severe AS plus AR 2­3). Patients in group B were younger and in a higher New York Heart Association class (p < 0.01). Severity of AS was similar in both groups. Patients in group B had a higher indexed LV mass, a lower LV ejection fraction, and higher PCWP, LVED Pand PAP (all p ≤ 0.01). CONCLUSIONS: Patients with severe AS and significant AR are more symptomatic than patients with isolated severe AS. The increased burden due to the combined lesion induces pronounced LV remodeling and more severe hemodynamic consequences.

Effect of hydroxymethylglutaryl coenzyme-a reductase inhibitors on the long-term progression of rheumatic mitral valve disease.

BACKGROUND: At present, no medical therapy is known to affect the progression of rheumatic mitral stenosis (MS). We sought to assess the effect of statin treatment on long-term progression of MS in a large population. METHODS AND RESULTS: From our 20-year database, we identified all patients with rheumatic MS with > or =2 echocardiographies > or =1 year apart. Exclusion criteria were previous intervention on the mitral valve, more than moderate aortic regurgitation, or symptoms at first examination. The study sample included 315 patients (mean age, 61+/-12 years; 224 women); 35 patients (11.1%) were treated with statins, and 280 (88.9%) were not. Mean follow-up period was 6.1+/-4.0 years (range, 1 to 20). The rate of decrease in mitral valve area was significantly lower in the statin group compared with the untreated group (0.027+/-0.056 versus 0.067+/-0.082 cm(2)/y; P=0.005). The annualized change in mean transmitral gradient was lower in statin-treated patients (0.20+/-0.59 versus 0.58+/-0.96 mm Hg/y; P=0.023). The prevalence of fast MS progression (annual change in mitral valve area >0.08 cm(2)) was significantly lower in the statin group (P=0.008). An increase in systolic pulmonary artery pressure of >10 mm Hg was found in 17% of patients in the statin group versus 40% of untreated patients (P=0.045). CONCLUSIONS: Our study shows a significantly slower progression of rheumatic MS in patients treated with statins. These findings could have an important impact in the early medical therapy of patients with rheumatic heart disease.

CME: long-term outcome in asymptomatic patients with severe aortic regurgitation, normal left ventricular ejection fraction, and severe left ventricular dilatation.

BACKGROUND: Although the guidelines consider severe left ventricular (LV) dilatation a class IIaC indication for surgery in asymptomatic patients with severe aortic regurgitation (AR) and normal LV function, the optimal management remains controversial. We aimed to assess the LV enlargement, hypertrophy and function, and the outcomes in these patients by the presence of severe LV dilatation at baseline. METHODS: From our 20-year database, we identified all asymptomatic patients with severe AR and LV ejection fraction (EF) >50% and ≥2 echocardiograms ≥1 year apart. LV end-diastolic diameter >70 mm or LV end-systolic diameter >50 mm or LV end-systolic diameter index >25 mm/m(2) defined severe LV dilatation. A composite end point included onset of symptoms or LV dysfunction. RESULTS: Eighty-four patients (52 ± 18 years, 61 men) were enrolled and followed-up for 7.1 ± 5.1 years. Two groups were defined: 22 patients with and 62 patients without severe LV dilatation at baseline. The progression of LV dilatation and hypertrophy, and the LVEF at last exam were similar in both groups. Twelve of 22 and 34 of 62 patients (P = 0.59) reached the end point. Vasodilators did not modify the progression of LV enlargement/hypertrophy. Ten of 22 and 25 of 62 patients (P = 0.45) underwent surgery and had similar postoperative LV diameters, mass, EF. CONCLUSIONS: The progression of LV enlargement/hypertrophy and outcomes in asymptomatic patients with severe AR, normal LV function, and severe LV dilatation or the postoperative LV parameters were not influenced by the severe LV dilatation, suggesting that a close follow-up could delay surgery in this population.

Isolated left atrial cryoablation of atrial fibrillation in conventional mitral valve surgery.

BACKGROUND: Recent trends of surgery for atrial fibrillation (AF) are towards more safe and effective energy sources, as well as to simplified sets of atrial lesions. METHODS: One hundred eighteen (mean age, 67.4 ± 9.2 years) selected patients with paroxysmal/persistent AF and mitral valve (MV) disease underwent cryoablation of AF combined with conventional (not via mini-thoracotomy) MV surgery; the lesion set was limited to only the left atrium. Multivariable analyses identified predictors of cardiac rhythm at hospital discharge and follow-up. RESULTS: There were 7 (5.9%) hospital deaths; 33 (28%) patients were discharged on AF. Higher values of preoperative left atrial volume index (odds ratio [OR] = 1.07, 95% confidence interval [95%CI]: 1.01-1.13) and mixed etiology of MV disease (OR = 4.19, 95%CI: 1.23-14.2) were predictors of hospital discharge on AF. Seventy-four (66.7%) patients were on stable sinus rhythm at follow-up (median period, 6.6 years); the 1, 5, and 10-year nonparametric estimates of adjusted freedom from AF were 98.1%, 89.2% and 45.6%, respectively. Higher values of preoperative systolic pulmonary artery pressure (hazard ratio [HR] = HR = 1.04, 95%CI: 1.01-1.08) and AF at hospital discharge (HR = 4.14, 95%CI: 1.50-11.4) were predictors of AF at follow-up. CONCLUSIONS: During conventional MV surgery, a cryo-lesion set limited to only the left atrium may give good, immediate and long-term results. Left atrial dilation and mixed etiology of MV disease were predictors of hospital discharge on AF. Preoperative pulmonary hypertension and AF at discharge combined with an increased risk of AF at follow-up.

Echo-tracking assessment of carotid artery stiffness in patients with aortic valve stenosis.

BACKGROUND: There is little information about mechanical properties of large arteries in patients (pts) with aortic stenosis (AS). METHODS: Nineteen patients with AS (aortic valve area: 0.88 +/- 0.29 cm(2)) and 24 control subjects without AS but with a similar distribution of risk factors were recruited. beta index, pressure-strain elastic modulus (Ep), arterial compliance (AC), augmentation index (AIx), and local pulse-wave velocity (PWV) were obtained at the level of right common carotid artery (CCA) by a real time echo-tracking system. Time to dominant peak of carotid diameter change waveform, corrected for heart rate (tDPc), and maximum rate of rise of carotid diameter (dD/dt) were measured. Systemic arterial compliance (SAC) was also calculated. Parameters of AS severity (mean gradient, valve area, stroke work loss [SWL]) were determined. RESULTS: tDPc was higher in patients with AS than in controls (7.9 +/- 0.6 vs. 6.6 +/- 0.7, P < 0.0001) while dD/dt was lower (5.3 +/- 3.6 mm/s vs. 7.8 +/- 2.8 mm/s, P = 0.01). AIx was significantly higher in AS group (32.5 +/- 13.6% vs. 20.6 +/- 12.2%, P = 0.005) and had a linear correlation both with tDPc (r = 0.63, P < 0.0001) and with dD/dt (r =-0.38, P = 0.01). There was a significant correlation between carotid AC and SAC (r = 0.49, P = 0.03), but only carotid AC was related to SWL (r = 0.51, P = 0.02), while SAC was not (P = 0.26). CONCLUSIONS: AIx was the only parameter of arterial rigidity found to be higher in patients with AS than in controls. Carotid AC showed a significant correlation with SAC and it seemed to be more closely related to AS severity than to SAC.

Stage-related effect of statin treatment on the progression of aortic valve sclerosis and stenosis.

It has been suggested that statins could slow the progression of aortic stenosis (AS), but this hypothesis is still debated and has not been validated in large series of patients by long-term follow-up studies. Moreover, information about the role of statins in patients with different degrees of severity of AS is scarce. From our 1988 to 2007 echocardiographic database, we retrospectively identified all asymptomatic patients with aortic valve sclerosis (abnormal irregular thickening of the aortic valve with a peak aortic velocity [Vmax] > or =1.5 and <2 m/s), mild AS (Vmax > or =2 and <3 m/s), and moderate AS (Vmax > or =3 and <4 m/s), age > or =50 years, and with > or =2 echocardiographic studies > or =2 years apart. Exclusion criteria were moderate/severe aortic regurgitation, bicuspid aortic valve, rheumatic valve disease, and ejection fraction <40%. The final study population consisted of 1,046 patients (mean age 70 +/- 8 years, 587 men); 309 were treated with statins. Mean follow-up duration was 5.6 +/- 3.2 years (range 2 to 19). Progression of AS was slower in patients receiving statins compared with untreated patients in aortic sclerosis (0.04 +/- 0.09 vs 0.07 +/- 0.10 m/s/year, p = 0.01) and mild AS (0.09 +/- 0.15 vs 0.15 +/- 0.15 m/s/year, p = 0.001), but not in moderate AS (0.21 +/- 0.18 vs 0.22 +/- 0.15 m/s/year, p = 0.70). In multivariate analysis only statin therapy, initial Vmax, and dialysis were independently related to progression of aortic valve disease. In conclusion, in a large series of patients with long-term follow-up, statins were effective in slowing the progression of aortic valve disease in aortic sclerosis and mild AS, but not in moderate AS. These results suggest that statin therapy should be taken into consideration in the early stages of this common disease.

Heterogeneity of clinical presentation in Tako-Tsubo syndromes: the prevalence of normal segmental wall motion and normal ECG pattern.

AIM: The aim of this study is to report the heterogeneity of clinical presentation in Tako-Tsubo syndrome (TTS), including a significant prevalence of normal ECG and echocardiographic patterns in a series of consecutive patients from a single center. METHODS AND RESULTS: From our database we selected a total of 168 cases of TTS. A total of 140 of these (Group A); 14 men (10%), mean age 60.3 years, range 39-87; 126 women (90%), mean age 66.1 years, range 43-93; matched the following reported criteria: typical stenocardic pain immediately following an emotional acute stress, or acute medical or surgical event within the preceding 12 h; acute rise and fall of troponin release; absence of significant coronary disease at coronary angiography. ECG findings at presentation ranged from T wave abnormalities (41 cases, 29.3%) to ST elevation (52 cases, 37.1%) and ST depression (11 cases, 7.9%), whereas in 36 cases (25.7%) the ECG was normal. Echocardiography at presentation showed akinesia of the total apical or medium-apical segments in 74 patients (53%), whereas it showed akinesia of left ventricular wall segments in other locations in 30 patients (21%) and even normal regional wall motion and thickening in 36 patients (26%). We described also a series of 13 female patients (mean age 70.2 years; age range 45-85 years) (Group B) who did not complain of chest pain at presentation, but showed a classical Tako-Tsubo evolution of wall motion abnormalities at echocardiography. Finally we selected 15 female patients (mean age 69.3 years; age range 49-89 years) (Group C) who formally did not report acute stress immediately preceding their presentation to the hospital for chest pain. They showed a classical Tako-Tsubo evolution of wall motion abnormalities at echocardiography and only one case of normal ECG pattern at presentation. CONCLUSION: In this series of acute TTS, a wide variability of ECG and echocardiographic patterns are observed, ranging from ST elevation with coexisting segmental wall motion abnormalities of the typical TTS to a clinical presentation characterized by normal ECG and normal segmental wall motion pattern.

Clinical and echocardiographic predictors of long-term outcome of a large cohort of patients with bicuspid aortic valve.

BACKGROUND AND OBJECTIVES: Bicuspid aortic valve (BAV) disease is the most common congenital cardiac malformation. The aim of the present article is to determine clinical and echocardiographic prognostic factors and provide a predictive model of outcome of a large cohort of patients with BAV. METHODS: We retrospectively enrolled 337 patients consecutively assessed for echocardiography at our Cardiology Department from 1993 to 2014. We considered aortic valve replacement, aortic surgery and cardiovascular death as a clinical combined end-point. Predictors of outcome were determined by Cox regression. RESULTS: Mean age was 29.2 ±â€Š19.8 years, median 27.1 years. A total of 38.4% patients presented a history of hypertension. Mean duration of follow-up was 8.4 ±â€Š6.1 years, range 0-21 years. A total of 73 patients underwent aortic valve replacement and/or aortic surgery during follow-up. Age at surgery was 45.2 ±â€Š15.6 years. Seven patients died because of cardiovascular causes. At multivariate analysis, baseline clinical predictors were history of hypertension [hazard ratio (HR) 2.289, 95% confidence interval (CI) 1.350-3.881, P = 0.002], larger ascending aortic diameter (HR 2.537, 95% CI 1.888-3.410, P < 0.001), moderate-to-severe aortic regurgitation (HR 2.266, 95% CI 1.402-3.661, P = 0.001) and moderate-to-severe aortic stenosis (HR 2.807, 95% CI 1.476-5.338, P = 0.002). A predictive model was created by integrating these four independent covariates. It allows the calculation of calculate a risk score for each patient, which helps better tailor appropriate treatment in BAV patients. CONCLUSION: At enrolment, history of hypertension, a wider aortic diameter, moderate-to-severe aortic regurgitation and aortic stenosis were independently correlated to combined end-point. Long-term follow-up showed low cardiovascular mortality (2.1%) and a high prevalence of cardiac surgery (21.6%).

Progression of aortic valve sclerosis and aortic valve stenosis: what is the role of statin treatment?

BACKGROUND: It has recently been suggested that statins could slow the progression of aortic stenosis, but this hypothesis has not been validated in large series. Moreover, there is little information about the role of statin treatment in patients with aortic valve sclerosis. METHODS: From our database 1988--2002, we retrospectively identified 1136 consecutive patients with aortic valve sclerosis (peak aortic velocity [Vmax] > 1.5 and < 2 m/s), or mild to moderate aortic stenosis (Vmax 2.0-3.9 m/s) and with > or = 2 echocardiographic studies > or = 6 months apart; 121 (11 %) were treated with statins. As a control group we randomly selected 121 age-gender-matched patients not treated with statins, with similar initial Vmax. RESULTS: The mean follow-up duration was 54+/-34 months in the statin group, and 50+/-33 months in controls (p = 0.35). There were no differences between statin-treated patients and controls with respect to age, gender, and prevalence of hypertension. More patients in the statin group had documented hypercholesterolemia, diabetes, or had proven coronary artery disease. Overall, the rate of change of Vmax was not different between statin-treated patients and controls (0.13+/-0.24 vs 0.14+/-0.19 m/s/year, p = 0.72). However, in the subgroup of patients with aortic valve sclerosis (n = 52, 26 statin-treated, 26 controls), the rate of change of Vmax was significantly lower in statin-treated patients (0.04+/-0.04 vs 0.08+/-0.06 m/s/year, p = 0.007). CONCLUSIONS: The results of our retrospective study show that statins could be beneficial in retarding the progression of valvular aortic sclerosis to aortic stenosis. This suggests that statins retard the progression of aortic valve lesion in its early stage, a finding that may have important implications in the management of this very common disease.

Left ventricular shape and mass impact torsional dynamics in asymptomatic patients with chronic aortic regurgitation and normal left ventricular ejection fraction.

Chronic aortic regurgitation (AR) is associated with a unique pattern of left ventricular (LV) volume and pressure overload, leading to LV remodelling. LV torsional motion, a key component of LV performance, can be altered in this setting. We aimed to assess the impact of LV remodelling on LV torsional dynamics parameters using speckle-tracking echocardiography (STE) in asymptomatic AR patients. We prospectively enrolled 60 patients with chronic AR and LVEF > 50% and 55 healthy controls. LV rotation, twisting and untwisting were assessed using STE. Patients with AR had higher LV diameters, volumes and mass, a more spherical LV shape than controls, but similar LVEF. In AR patients we found reduced peak LV apical rotation and decreased (2.1 ± 0.8 vs 2.9 ± 0.9°/cm, p < 0.001) and delayed (time to peak LV twist: 0.94 ± 0.12 vs 0.99 ± 0.09, p = 0.004) peak LV torsion. Also, peak LV untwisting velocity was decreased (-123.5 ± 41.5 vs -152.3 ± 55.0°/s, p = 0.002) due to lower peak LV apical diastolic rotation rate. LV shape influenced LV torsional dynamics, a more spherical LV displaying reduced peak LV apical rotation and diastolic rotation rate and decreased LV twist. A more hypertrophied LV had a lower peak LV torsion, peak LV apical diastolic rotation rate and peak LV untwisting velocity. LV apical rotation and torsion are decreased and LV twist is delayed in patients with chronic AR and normal LVEF, detecting early subclinical LV dysfunction before LVEF declines. Also, LV untwisting is reduced in these patients. LV remodelling impairs LV torsional dynamics parameters in this setting.

Effect of statins on the progression of bioprosthetic aortic valve degeneration.

To date, there is no proved medical therapy able to significantly reduce the degenerative process of biologic prosthetic aortic valves. It has recently been suggested that statins may reduce the progression of native aortic valve stenosis. We examined the effect of statin treatment on bioprosthetic aortic valve degeneration and found a beneficial effect of statins in slowing bioprosthetic degeneration.

Left atrium remodeling after acute myocardial infarction (results of the GISSI-3 Echo Substudy).

To evaluate the existence, timing, and determinants of post-infarction left atrial remodeling, we studied a subgroup of 514 patients from the Third Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico Echo Substudy who underwent 4 serial 2-dimensional echocardiograms up to 6 months after acute myocardial infarction. This study is the first to demonstrate, in a large series of patients, the existence of early and late left atrial remodeling after low-risk acute myocardial infarction and the relation of left atrial remodeling to left ventricular remodeling.

Value of transesophageal echocardiography in the diagnosis of compressive, atypically located pericardial cysts.

Pericardial cysts are not common and rarely cause symptoms. We report 2 cases of atypically located pericardial cysts with hemodynamic compromise because of the direct compression of the pulmonary veins and the right pulmonary artery. In the first case, transesophageal echocardiography (TEE) disclosed a round cystic mass compressing the posterior wall of the right pulmonary artery, with blood flow reduction in the right lung. Because of the symptoms, the pericardial cyst was drained and the patient had an uneventful 1-year follow-up. In the second case, a large cystic mass compressing the left atrium and the pulmonary vein outflow was clearly shown by TEE in a patient with severe respiratory distress, cyanosis, and low blood pressure. A left ventricular thoracotomy was performed with the drainage of 500 mL serous fluid from the cyst.

Thrombus in the right atrial appendage during pulmonary and paradoxical embolism: a case report.

We report the case of a 56-year-old woman who was admitted because of left pulmonary embolism. An episode of ischemic stroke occurred during hospitalization. Transesophageal echocardiography revealed a right atrial appendage thrombus and a patent foramen ovale with right to left shunting. This suggested paradoxical embolism across a patent foramen ovale as the most reasonable explanation of the ischemic stroke in this patient, in the presence of right cardiac overload secondary to the hemodynamically significant pulmonary embolism. The patient's clinical conditions dramatically improved after anticoagulant therapy.

Spontaneous closure of postinfarction ventricular septal rupture. A case report.

Spontaneous closure of a postinfarction ventricular septal rupture is extremely rare. We present such a case in which the postinfarction ventricular septal rupture closed spontaneously during follow-up. We postulate that the spontaneous closure of the ventricular septal rupture was probably due to thrombosis in the apical and septal aneurysm.

Reliability of new and old Doppler echocardiographic indexes of the severity of aortic stenosis in patients with a low cardiac output.

BACKGROUND: In addition to the conventional "flow-corrected" parameters (continuity equation and aortic valve resistance), new and simpler Doppler echocardiographic indexes of the severity of aortic stenosis have recently been introduced. These measures can be classified as "function-corrected" indexes (fractional shortening-velocity ratio and ejection fraction-velocity ratio) and "pressure-corrected" indexes (percent stroke work loss). Little information however is available about the diagnostic accuracy of each of these parameters in identifying patients with severe aortic stenosis in low-flow states, in which the diagnosis and clinical decision-making are more difficult and challenging. METHODS: We analyzed 161 patients with aortic stenosis (96 males, 65 females, mean age 68 +/- 9 years) and a low cardiac output (thermodilution cardiac index < or = 2.5 l/min/m2). All patients underwent both cardiac catheterization and echocardiography within 48 hours one of the other. The invasive Gorlin valve area was used as gold standard (severe aortic stenosis = Gorlin < or = 0.8 cm2). Echocardiographic indexes were assessed by an investigator who was unaware of the hemodynamic findings. RESULTS: The mean Gorlin aortic valve area was 0.7 +/- 0.3 cm2; cardiac catheterization allowed the identification of 129 patients with severe aortic stenosis and of 32 with mild-to-moderate aortic stenosis. The diagnostic accuracy of the Doppler gradient alone was low (sensitivity 55%). The best linear correlation with the Gorlin value was found using the "function-corrected" ejection fraction-velocity ratio (r = 0.85). Similarly, the best combination of sensitivity and specificity in identifying patients with severe aortic stenosis, as assessed by cardiac catheterization, was observed using the ejection fraction-velocity ratio (sensitivity 87%, specificity 88%). CONCLUSIONS: In patients with aortic stenosis and a low cardiac output, the "function-corrected" ejection fraction-velocity ratio offers the better diagnostic accuracy, as compared with the cardiac catheterization valve area calculation.

[Proarrhythmic effects of propafenone in a woman with hepatopathy: is it always a simple drug in clinical practice?]. / Effetto proaritmico del propafenone in donna con epatopatia: è sempre un farmaco di semplice utilizzo nella pratica clinica?

A 65-year-old woman with a history of alcoholic liver disease and presenting with fever and vomiting was admitted to an internal medicine unit. In view of recent atrial fibrillation with inadequate heart rate control, digoxin and propafenone were included in the therapeutic regimen. After a few days sinus rhythm was restored but suddenly ventricular arrhythmias with the characteristics of a non-responsive electrical storm arose shortly following the appearance of clinical symptoms of drug intoxication.