Lack of correlation between the antiarrhythmic effect of L-propionylcarnitine on reoxygenation-induced arrhythmias and its electrophysiological properties.

1. The antiarrhythmic effect of L-propionylcarnitine (L-PC) was evaluated in the guinea-pig isolated heart; arrhythmias were induced with hypoxia followed by reoxygenation and by digitalis intoxication. 2. L-PC 1 microM, was found to be the minimal but effective antiarrhythmic concentration against reoxygenation-induced ventricular fibrillation. No antiarrhythmic effect was observed against digitalis-induced arrhythmias. D-Propionylcarnitine, L-carnitine and propionic acid did not exert antiarrhythmic effects. 3. During hypoxia and reoxygenation L-PC consistently prevented the rise of the diastolic left ventricular pressure, and significantly reduced the release of the cardiac enzymes creatine kinase (CK) and lactic dehydrogenase (LDH). 4. The electrophysiological effects of L-PC were then studied on either normal sheep cardiac Purkinje fibres or those manifesting oscillatory after potentials induced by barium or strophanthidin. 5. L-PC (1 and 10 microM) did not significantly modify action potential characteristics and contractility of normal Purkinje fibres, or the amplitude of OAP induced by strophanthidin or barium. 6. It is concluded that the antiarrhythmic action of L-PC on reoxygenation-induced arrhythmias is not correlated with its direct electrophysiological effects studied on normoxic preparations.

Cardiac aging, calcium overload, and arrhythmias.

The effect of aging was tested on experimental ventricular arrhythmias in isolated heart preparations from normal Wistar rats (NWR), Wistar Kyoto rats (WKY), and spontaneously hypertensive rats (SHR). Delayed afterdepolarizations and triggered activity induced by high-calcium perfusion (16 mM) in isolated papillary muscles were more frequent in the 24-month-old than in 6-month-old NWR. Reperfusion-VA were more severe in 14-month-old SHR than in WKY. The authors have previously shown that: (1) reperfusion- and reoxygenation-induced VA, in the isolated Langendorff perfused heart, were significantly more severe and frequent in 24-month-old than in 6-month-old NWR; (2) no age-related difference in the incidence of programmed electrical stimulation (PES, train of stimuli + 1 or 2 extrastimuli)-induced VA was observed in isolated NWR hearts during control perfusion, after coronary artery ligation or during hypoxia; (3) on the contrary, the incidence of PES-induced VA was significantly higher in isolated hearts from 14-month-old SHR than from 3-month-old SHR, and 3-month-old and 14-month-old WKY. It was concluded that "physiological" aging is associated with a higher propensity to calcium-related VA, while "pathological" aging characterized by hypertension of long duration increases the incidence of PES-induced VA, probably caused by myocardial fibrosis, which could facilitate reentry.

A simple method of recognizing geriatric patients at risk for death and disability.

OBJECTIVE: To identify prognostic indicators for geriatric patients discharged from an acute care hospital. DESIGN: Prospective observational study. SETTING: Base line assessment at discharge from an acute care hospital; reassessment after 1 year at home. PATIENTS: One hundred-seventy-eight consecutive patients over 70 years of age (mean age +/- SD = 75.6 +/- 13.1 years, range 70-95 years, 52% males); 56% were dependent in one or more Activities of Daily Living, 21% had abnormal Mini Mental State Scores. MAIN OUTCOME MEASURES: mortality, increasing physical dependence, health care utilization. RESULTS: Mortality was directly related to a low ADL score at hospital discharges (Odds Ratio = 3.31, Confidence Limits = 1.91-5.75), neoplastic disease (OR = 3.59, CL = 2.01-6.43), cardiovascular disease (OR = 2.47, CL = 1.40-4.36), and drug use, expressed as the total number of individual preparations prescribed at discharge (OR = 1.72, CL = 1.05-2.83). Low ADL score, cardiovascular and neoplastic disease were also predictive of increasing physical dependency. The use of health care services, quantified by an appropriately designed score, did not correlate with any of the baseline variables, with the implication that the use of the health care services was not proportional to the need for care. CONCLUSIONS: Elderly subjects at major risk of death and disability can be easily identified at discharge by a simple assessment of their medical and functional state.

Impact of integrated home care services on hospital use.

OBJECTIVE: To examine the effect of a home care program based on comprehensive geriatric assessment and case management on hospital use and costs among frail older individuals. DESIGN: Quasi-experimental study with a 6-month follow-up. SETTING: Vittorio Veneto, a town in northern Italy. PARTICIPANTS: One hundred fifteen frail older people who applied for integrated home care services. INTERVENTION: Each patient was assessed with the Minimum Data Set for Home Care, and, subsequently, a case manager and a multidisciplinary team delivered social and health care services as indicated. MAIN OUTCOME MEASURES: We determined the hospital admissions and days spent in the hospital for all subjects during the first 6 months after the implementation of the home care program and compared them with the rate of hospitalization that the same patients had experienced in the 6 months preceding the implementation of the program. RESULTS: After the implementation of the integrated home care program, there was a significant reduction in the number of hospitalizations compared with pre-implementation (56% vs 46%, respectively; P < .001), associated with a reduction in the number of hospital days, both at the individual patient level (28+/-23 days vs 18+/-15 days, respectively; P < .01) and for each admission (16+/-12 days vs 12+/-8 days, respectively; P < .01). This resulted in a 29% cost reduction with an estimated savings of $1260 per patient. CONCLUSIONS: The implementation of an integrated home care program based on the use of a comprehensive geriatric assessment instrument guided by a case manager has a significant impact on hospitalization and is cost-effective.

Nutritional assessment: a primary component of multidimensional geriatric assessment in the acute care setting.

OBJECTIVE: To test the prognostic role of nutritional variables as a component of geriatric multidimensional assessment and to study the effect of hospitalization on nutritional status. DESIGN: Validation cohort study: multidimensional assessment on admission and at discharge and a weekly nutritional assessment. SETTING: General Medicine and Geriatrics wards in an acute-care university hospital. PATIENTS: A consecutive sample of 302 patients aged 79 +/- 6 years, range 70-96 years. MAIN OUTCOME MEASURES: Mortality, longstay (> 29 days), loss of lean body mass as expressed by a negative change in mid-arm muscle circumference (MAMC). RESULTS: Incidence of mortality, longstay, and decreased MAMC was 6.9%, 24.8%, and 64.2%, respectively. According to logistic regression analysis, mortality was independently predicted by preadmission dependency in at least one Activity of Daily Living (odds ratio = 2.08, confidence limits = 1.19-3.65), clinical diagnosis of malnutrition (OR = 1.89, CL = 1.11-3.21), serum albumin < 3.5 g/dL (OR = 1.82, CL = 1.06-3.14). This predictive model allowed us to recognize 75% of the patients at risk of death by targeting 23% of the population. Longstay was independently predicted by stroke (OR = 1.54, CL = 1.01-2.35), clinical diagnosis of malnutrition (OR = 1.41, CL = 1.04-1.93), and more than five comorbid diseases (OR = 1.39, CL = 1.01-1.94). Dependency in at least one ADL was the only independent predictor of decreased MAMC (OR = 1.71, CL = 1.27-2.30). CONCLUSIONS: Nutrition variables are a cardinal component of multidimensional assessment in the acute-care setting. Nutritional status deteriorates during the hospital stay, mostly in physically dependent patients.

Trends in antihypertensive drugs in the elderly: the decline of thiazides.

The last decade has seen the publication of different editions of guidelines for the pharmacological treatment of hypertension that were based on the results of large, randomised trials. Since these guidelines were meant to inform practitioners, we analysed the pattern of prescription of antihypertensive agents between 1988 and 1997 among older hospitalised adults. Because of the wealth of data supporting the use of thiazides diuretics, we focused on diuretic prescription, to identify independent predictors of their utilisation. To this end, we used the GIFA database that includes patients admitted to academic medical centres throughout Italy between 1988 and 1997. We studied 5061 patients over 65 years of age selected among a population of 28 411, based on the diagnosis of arterial hypertension at discharge. The use of ACE-inhibitors has been raising steadily through the years, and they are the agents most commonly used since 1996. Calcium channel blockers showed a similar trend and were the top prescribing drug until 1995; afterwards, the documentation of potentially severe side effects has resulted in a nearly 20% reduction of their use. Beta-blockers have remained unpopular throughout the decade. Instead, the prescription of diuretics as a class showed a biphasic trend; an initial decrease with a prolonged steady state and a more recent raise. However, at a separate analysis, it was a evident that a progressive increase of the use of loop diuretics since 1988 has been paralleled by a nearly 50% reduction of thiazides prescriptions. Loop diuretics were more likely to be prescribed to older individuals, those with cardiac heart failure, coronary heart disease and high creatinine level. In contrast, independent predictors of thiazides use were female gender, good functional status, preserved renal function, and absence of cardiovascular comorbidity. In conclusion, despite continued recommendations to use thiazides diuretics for the treatment of hypertension among older individuals, their use has been declining steadily between 1988 and 1997. A possible explanation is that the choice to prescribe a thiazides diuretic is influenced by age, functional status and comorbidity.

Construct validity of the 15-item geriatric depression scale in older medical inpatients.

The construct validity of the 15-item Geriatric Depression Scale (sfGDS) has been assessed in selected populations. The aim of this study was to assess the appropriateness of applying the sfGDS to unselected older inpatients. The main component analysis of sfGDS was performed in 2032 medical inpatients (mean age = 76.3 +/- 8.4). sfGDS did not qualify as a unidimensional test. Three factors explained 47.7% of variance and explored the following dimensions: positive attitude toward life, distressing thoughts/negative judgment about the own condition, and inactivity/reduced self-esteem. The internal homogeneity was poor (Cronbach's alpha = .46). A higher fraction of variance was explained in patients independent in all or dependent in > or = 1 activity of daily living (ADL). In older medical inpatients, sfGDS is not a single construct, which prevents the univocal interpretation of the final score. The higher fraction of explained variance in patients with comparable ADL performance probably reflects the dependency of affective from physical status.

Efficacy of almitrine-raubasine in cognitive disorders of aging: a double-blind, placebo-controlled, clinical and psychometric study.

Early treatment of age-related cognitive impairment can be decisive in enabling elderly patients to remain at home. A double-blind, placebo-controlled trial of almitrine-raubasine was conducted in 40 elderly outpatients (25 women, 15 men; mean age: 73.5 years) with moderate cognitive impairment randomized into two groups, one receiving almitrine and raubasine, the other placebo, two tablets daily for 90 days. They were assessed at T0, T45 and T90 days, using the Toulouse-Pieron test, 8 subtests from the Wechsler Adult Intelligence Scale (WAIS) and the Sandoz Clinical Assessment for Geriatrics (SCAG). End-of-study results were significantly better in the almitrine-raubasine group in all tests: Toulouse-Pieron test (p less than 0.001), WAIS (p less than 0.001), and SCAG (p less than 0.001).

Effects of verapamil on reoxygenation and programmed electrical stimulation-induced ventricular arrhythmias in the isolated heart.

The antiarrhythmic effect of verapamil was tested on spontaneous ventricular arrhythmias during reoxygenation after 15 min of glucose-free hypoxia and on programmed electrical stimulation-(8 stimuli + 1 or 2 extrastimuli) induced ventricular fibrillation in isolated Langendorff perfused guinea pig hearts. Verapamil (1 mg/l) added during hypoxia and reoxygenation significantly reduced, during reoxygenation, the incidence of arrhythmias (46%, N = 13 vs. controls 87%, N = 30; P less than 0.01), of ventricular fibrillation (0%, N = 13 vs. controls 70%, N = 30; P less than 0.001) and of programmed stimulation-induced ventricular fibrillation (0%, N = 10 vs. controls 100%, N = 16). No effect was observed on programmed stimulation-induced ventricular fibrillation during hypoxia (90%, N = 10 vs. controls 100%, N = 10). Verapamil added during reoxygenation reduced the incidence of reoxygenation arrhythmias and ventricular fibrillation (47% and 29%, N = 17, P less than 0.01 and P less than 0.05 vs. controls, respectively) but it had no effect on programmed stimulation-induced ventricular fibrillation (100%, N = 10). It is likely that verapamil exerts its antiarrhythmic effect by preventing cellular calcium overload during hypoxia and reoxygenation.

Digitalis in the treatment of heart failure in the elderly. The GIFA study results.

Digitalis glycosides have played an important role in the treatment of patients with heart failure (HF) for more than two centuries. Despite the introduction of new therapeutic strategies in the treatment of HF, and controversies regarding the role of digitalis in HF in sinus rhythm and its effect on mortality, digoxin is one of the most commonly prescribed drugs in the community and in hospital settings, particularly in the elderly. The Italian Group of Pharmacosurveillance in the Elderly (GIFA) monitored 20,047 hospitalized patients in 1988, 1991 and 1993, and found that digoxin was the most frequently prescribed drug in the management of HF. Inappropriate prescriptions of digitalis, defined with standardized criteria, were uncommon, and the mean daily dosage was low. Compared to earlier studies the incidence rate of adverse drug reactions (ADRs) to digoxin, was also low. The reduction in ADRs incidence was probably due to a better understanding of digoxin pharmacokinetics and to a lower daily dosage in the elderly. Nevertheless, digoxin toxicity was significantly more frequent in patients aged >or= 80 years than in those aged < 65 and and 65-79 years. In a multidrug approach to the treatment of chronic HF, digoxin exerts clinical benefits also in patients with sinus rhythm, it is not costly, it is easy to administer, and toxic effects are not common.

Increased propensity of the aged myocardium to develop calcium-related electrophysiological alterations.

The electrico-mechanical effects of calcium overload have been studied in cardiac papillary muscles of young adult and senescent Wistar rats driven at different rates. Action potential duration and contraction duration were found to be more prolonged in senescent than in younger animals during control conditions. Oscillatory afterpotentials and aftercontractions were more frequent in senescent than in younger rats during high calcium perfusion. Triggered activity was induced in senescent fibers but not in younger ones. Resting tension increased more in senescent fibers whereas the peak tension was not different in the two groups. It is concluded that aging is associated with a reduced capacity of the cardiac cells to handle an increased calcium load.

Low atrial tachycardia as primary cause of the heart failure complicating congestive cardiomyopathy.

A 50-years-old man with severe heart failure was diagnosed to have congestive cardiomyopathy and low atrial tachycardia at a fixed rate of 103 bpm. Conventional therapy for heart failure exerted a beneficial effect but complete clinical improvement was achieved only by reducing the rate of low atrial tachycardia with amiodarone. This suggests that in this situation tachycardia itself played a main role in the genesis of hemodynamic derangement.

Health care for older people in Italy: The U.L.I.S.S.E. Project (Un link informatico sui servizi sanitari esistenti per l'anziano - a computerized network on health care services for older people).

OBJECTIVES: The U.L.I.S.S.E. study is aimed at describing older patients who are cared for in hospitals, home care or nursing homes in Italy. DESIGN: The U.L.I.S.S.E. study is an observational multicenter prospective 1-year study. SETTING: Overall, 23 acute geriatric or internal medicine hospital units, 11 home care services and 31 nursing homes participated in the study. MEASUREMENTS: The patient's evaluation was performed using comprehensive geriatric assessment instruments, i.e. the interRAI Minimum Data Set, while data on service characteristics were recorded using ad-hoc designed questionnaires. RESULTS: The older subjects who are in need of acute and long term care in Italy have similar characteristics: their mean age is higher than 80 years, they have a high level of disability in ADL, an important multimorbidity, and are treated with several drugs. The prevalence of cognitive impairment is particularly high in nursing homes, where almost 70% of residents suffer from it and 40% have severe cognitive impairment. On the other hand, there is a shortage of health care services, which are heterogeneous and fragmented. CONCLUSIONS: Health care services for older people in Italy are currently inadequate to manage the complexity of the older patients. An important effort should be undertaken to create a more integrated health care system.