Vittorio Grassi

QT dispersion and heart rate variability abnormalities in Alzheimer's disease and in mild cognitive impairment.

Objectives: To investigate the effect of cardiovascular changes (i.e., QT interval, QT dispersion (QTD), heart rate variability (HRV), and other cardiovascular measures) in subjects with Alzheimers disease (AD) and mild cognitive impairment (MCI).

Energy cost of exercise in multiple sclerosis patients with low degree of disability

In 10 patients (five females) suffering from multiple sclerosis with mild degree of disability, (EDSS ranging from 0 to 2) and in 10 age and sex matched control subjects we investigated lung function, respiratory muscles strength and cardiorespiratory response to incremental exercise in order to assess the metabolic cost of exercise. In the absence of any impairment of lung volumes and flows and in-and expiratory maximal mouth pressures, at peak of exercise oxygen consumption (VO2max=1886 ± 145 ml/min) and workload (Wmax = 137 ± 9.8 watts) were slightly diminished in patients, as compared with controls (VO2max = 2246 ± 196 ml/min and Wmax = 164 ± 14.7 watts). These findings were associated with an increased heart rate (HR) and reduced oxygen pulse (VO2/HR) at the same workloads. During the whole exercise, however, the slope of the linear relationship between VO2 and work exhibited by the patients, amounting to 9.9 ± 0.6 ml/min/watt, was similar to that of the controls (10.9 ± 0.42 ml/min/watt). Incidentally, both at rest and during exercise, the patients showed a significantly greater minute ventilation (due to a faster respiratory rate, associated with an augmented dead space (P<0.05). We conclude that an increase of metabolic cost of exercise does not occur in multiple sclerosis patients with mild disability, suggesting a lack or a low degree of spasticity and/or ataxia elicited by the effort Thus, their exertional capacity appears to be limited mainly by a poor training. The tachypnea observed in these patients at rest and during exercise was unexpected and the reason for adopting such a pattern of breathing is unclear.

Ambroxol for the Prevention of Chronic Bronchitis Exacerbations: Long-Term Multicenter Trial

In a 6-month, double-blind multicenter trial conducted over the winter, the effects of daily administration of ambroxol retard (75 mg) were compared with those of placebo in preventing exacerbations and improving symptoms and clinical signs in chronic bronchitis patients. The trial was completed by 110 patients in the ambroxol group and by 104 in the placebo group. Initially, there were no significant differences between the groups. By the end of the 2nd month of treatment, 67.2% of the ambroxol group had had no exacerbations compared to 50.4% in the placebo group. At the end of the 6-month trial, 45.5% of the treatment group had had no exacerbations, compared to only 14.4% of the control group. These differences were statistically significant. Patients in the treatment group lost significantly fewer days through illness (442) and had fewer days when they needed antibiotic therapy (371) compared to the placebo group patients (837 and 781). Ambroxol also produced statistically significant symptomatic improvement, measured as difficulty in expectoration, coughing, presence of dyspnea and the auscultatory signs as compared to controls. Since ambroxol was well tolerated and compliance was good, it appears like a drug of choice for pharmacological prophylaxis of chronic bronchitis.

Snoring and risk of cardiovascular disease

In order to evaluate the possible role played by snoring as a risk factor for cardiovascular disease, we studied 400 patients aged 30-80 years, divided into 4 groups matched for age, sex and body mass index. The first group consisted of 100 patients who snored, having risk factors (hypertension, diabetes, obesity, smoking, high serum cholesterol level) for cardiovascular disease. The second group consisted of 100 non-snoring patients with risk factors. The third and fourth groups were formed by 100 snoring and 100 non-snoring patients without risk factors. We investigated the morbidity and the mortality from cardiovascular disease over a period of five years (1982-1987). An increase in morbidity and mortality was found for snorers with risk factors (36 and 17 respectively) compared to non-snorers with risk factors (10 and 4, P less than 0.001), and also to both snorers and non-snorers without risk factors (7 and 3, P less than 0.001; 3 and 1, P less than 0.001 respectively). No difference was noted between snorers and non-snorers without risk factors. A higher morbidity and mortality for cardiovascular disease was found in snorers with risk factors as compared with non-snorers having risk factors. Furthermore, the morbidity and mortality in patients without risk factors was found to be lower compared with that found in snorers with risk factors. In conclusion, snoring worsened the prognosis of patients with risk factors for cardiovascular disease, but did not represent an independent or predictive risk factor in itself.

Alpha-1-Antitrypsin Deficiency-Associated Cervical Artery Dissection: Report of Three Cases

The pathogenesis of cervical artery dissection is poorly understood. Deficiency of the elastase inhibitor alpha-1-antitrypsin may represent a predisposing condition. Biochemical and genetic analyses in a series of 12 consecutive patients with spontaneous dissection of the neck vessels showed 3 cases associated to alpha-1-antitrypsin deficiency, in combination with transient precipitating factors. A disequilibrium between proteolytic enzymes and protease inhibitors may contribute to the pathogenesis of cervical artery dissection leading to structural abnormalities of the extracellular matrix and increasing the susceptibility of the vessel wall to additional short-lived trigger mechanisms.

Cardiovascular Effects of a Single Slow Release Lanreotide Injection in Patients with Acromegaly and Left Ventricular Hypertrophy

In our study we assessed the effects of a single i.m. injection of slow-release Lanreotide (30 mg) (SR-L), a new long-acting somatostain analog, on circulating GH levels, baseline cardiac function (M-mode, 2D guided, doppler-echocardiographic study) and cardiopulmonary response to exercise (cycloergometric test, performed using a computer drived, electrically braked cycle ergometer), tested at baseline, after 7 and 14 days from the injection in 10 acromegalic patients (5 M, 5 F, mean age 57.7 ± 3.1 yrs, body mass index (BMI) 27 ± 0.8 kg/m2, blood pressure 141 ± 6.5/82 ± 3 mmHg). SR-L administration decreased GH levels in acromegalic patients (mean±SEM) from 16.1 ± 6.9 to 10.8 ± 5.1 µg/L (p = 0.045) after 7 days and to 11.9 ± 5 µg/L (p = 0.078) after 14 days from the injection. Moreover, we observed a significant (p<0.05) decrease in systolic blood pressure and heart rate at the 7th (135 ± 6.1 vs 141 ± 6.5 mmHg, and 68 ± 2.1 vs 74 ± 2.1 bpm) and 14th (137 ± 6.2 vs 141 ± 6.5 mmHg, and 72 ± 2 vs 74 ± 2.1 bpm) day of the study with respect to the baseline values. After SR-L administration we also found an increase in ejection fraction (69 ± 2 vs 63 ± 2.3% at 7th day, p = 0.006; 65 ± 2.3 vs 63 ± 2.3% at the 14th day, p = 0.027) and shortening fraction (40.8 ± 1.8 vs 36.6 ± 1.9% at 7th day, p = 0.005; 38.7 ± 1.8 vs 36.6 ± 1.9% at the 14th day, p = 0.045). The positive acute cardiac response to SR-L injection was also demonstrated by the increase in A/E velocity ratios at 7th (1.14 ± 0.1 vs 0.98 ± 0.07, p = 0.016) and 14th (1.04 ± 0.08 vs 0.98 ± 0.07, p = 0.008) day of the study. After SR-L injection, exercise capacity and VO2 at anaerobic thresold were also increased with respect to the baseline test: 61.1 ± 8.2 vs 38.9 ± 6.8 watts (p = 0.002) and 1012.4 ± 71.5 vs 915.3 ± 77.8 mL/min (p = 0.033) after 7 days, and 61.4 ± 7.2 vs 38.9 ± 6.8 watts (p = 0.002) and 1010.1 ± 62.5 vs 915.3 ± 77.8 mL/min (p = 0.010) after 14 days from the injection. In conclusion, these results suggest that in acromegalic patients: (1) SR-L causes a rapid improvement in baseline cardiac function and in cardiopulmonary performance during exercise in acromegaly; (2) the endocrine (decrease in GH levels) and echocardiographic responses to SR-L are maximal after 7 days from the injection, whereas the effect of SR-L on the exercise performance are longer lasting.

Carbapenems in the Treatment of Severe Community-Acquired Pneumonia in Hospitalized Elderly Patients: A Comparative Study Against Standard Therapy

Abstract In this open, prospective, study were enrolled 204 hospitalized elderly patients with severe (88 males, 116 females, age range 70-94). Patients were randomized to receive one of the following antibiotic treatment regimens: meropenem 500 mg i.v. t.i.d. (52); imipenem/cilastatin 500 mg i.v. t.i.d. (51), clarithromycin 500 mg + ceftriaxone 1 g i.v. b.i.d. (52), clarithromycin 500 mg + amikacin 250 mg i.v. b.i.d. (49). In 99 cases causative germs were isolated (24 meropenem, 26 imipenem, 23 clarithromycin + ceftriaxone, 26 ceftriaxone + amikacin). A satisfactory clinical, bacteriological response was achieved respectively in 86.5% 77% in meropenem; 86.3% 71% in imipenem/cilastatin; 69% 61% in ceftriaxone + clarithromycin and in 85.7% 77% in clarithromycin + amikacin. The mean total cost for each patient was 1,560; 1,620; 1,760 and 1,792 in meropenem, imipenem/cilastatin, clarithromycin + ceftriaxone and clarithromycin + amikacin respectively. This study shows that treatment with either meropenem or imipenem is as efficacious as conventional therapy in the treatment of community acquired pneumonia (CAP), and that meropenem is the most cost-effective.

Increased QT dispersion: a negative prognostic finding in chronic obstructive pulmonary disease

ObjectiveChronic obstructive pulmonary disease (COPD) is a highly prevalent syndrome, deeply affecting the cardiovascular system as well as the lungs. We investigated the prognostic role of the QT interval and QT dispersion (QTD) in predicting all-cause, respiratory and cardiovascular mortality in COPD, and the relationship between these electrocardiographic parameters and pulmonary function in a prospective longitudinal study.MethodsWe studied 246 COPD patients without significant comorbidities, with a mild to moderate functional impairment, admitted to the Department of Internal Medicine from January 1995 to December 2001, performing a 5-year mean follow-up (5–116 months) up to August 2004. After clinical stabilisation, an electrocardiogram and functional respiratory tests were obtained, allowing measurement of the QT interval and QTD, forced vital capacity (FVC), forced expiratory volume at 1 s (FEV1), inspiratory capacity, FEV1/FVC ratio, partial oxygen pressure and partial carbon dioxide pressure in arterial blood.ResultsAt the end of the follow-up period, 81 patients were dead, 165 still alive; 36 died because of respiratory causes, 23 because of cardio-cerebrovascular events, 21 because of cancer (mainly lung cancer). A significant high incidence of sudden cardiac death was observed. QTD and QTcD showed a significant relationship with respiratory functional parameters. Maximal QT interval, QTcD and QTD appear to be independent predictors of all-cause, cardiovascular and respiratory mortality (relative risk 1.94, 3.22, 2.88, respectively). Age>65 years, partial oxygen pressure <60 mmHg and inspiratory capacity <80% of the predicted value were the only other independent predictive parameters.ConclusionsMaximal QT interval, QTD and QTcD are independent predictors of mortality. A significant incidence of cardiac sudden death was observed. These findings suggest the need for a global and multidisciplinary risk assessment in COPD patients. Intriguing relationships between the QTD and functional respiratory parameters were also observed.

Increased prevalence of silent myocardial ischaemia and severe ventricular arrhythmias in untreated patients with Alzheimer's disease and mild cognitive impairment without overt coronary artery disease.

OBJECTIVE To assess the prevalence and the characteristics of silent myocardial ischaemia (SMI) and ventricular arrhythmias (VA) in subjects with Alzheimers disease (AD) and mild cognitive impairment (MCI) and their relationships with QT interval dispersion (QTD). METHODS Thirty-three subjects with AD, 39 subjects with MCI, and 29 cognitive healthy control subjects matched for demographic characteristics, hypertensive condition, smoking habits, and laboratory parameters were enrolled. Each subject underwent clinical and cognitive examination, a structural brain imaging study, electrocardiogram (ECG), 24-h ECG recording, 24-h blood pressure monitoring, and echocardiogram. Detection and characterization of QT dispersion, SMI and VA were performed. RESULTS The three groups were comparable regarding demographic and basal cardiovascular characteristics: notwithstanding this, SMI episodes were observed only in AD and MCI patients (19 and 14, respectively). A significantly greater prevalence of repetitive ventricular premature beats was observed in AD (mean 8.56+/-13.1) and in MCI (1.8+/-7.2) vs. control (0.7+/-1.7). The QTD, the ischaemic burden and the number of repetitive ventricular beats revealed to be significantly related. CONCLUSIONS Increased prevalence of SMI and potentially ominous VA were found in AD and, to a lesser extent, in MCI. SMI and repetitive VA were significantly related with QTD. These findings could be related to an increased risk of sudden cardiac death in AD and MCI patients.

Airway hyperresponsiveness in a large group of subjects with α1-antitrypsin deficiency: a cross-sectional controlled study

Abstract.  Malerba M, Radaeli A, Ceriani L, Tantucci C, Grassi V (University of Brescia, Brescia, Italy). Airway hyperresponsiveness in a large group of subjects with α1‐antitrypsin deficiency: a cross‐sectional controlled study. J Intern Med 2003; 253: 351–358.