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133Xenon ventilation scan as a functional assessment in bronchiectasis.

BACKGROUND: Mucus impaction in the airways impairs ventilation and exercise tolerance in patients with bronchiectasis. Parameters for evaluating the ventilatory dynamic change have been limited by variable cofactors. We developed a tool to evaluate the changes directly on images of a ventilation scan. MATERIALS AND METHODS: We used a 133Xenon ventilation washout scan to assess the time of half clearance (T1/2) of the regions of interest (ROIs) corrected by that of a control area (CA) as T1/2ROI/CA. We then compared the ventilation washout scan with high-resolution computer tomography (HRCT) scoring to assess the severity of bronchiectasis, as well as conducting 6-minute walking tests or spirometry for the evaluation of the clinical response to a 3-day course of chest physiotherapy. Nine patients with bronchiectasis and mucus hypersecretion were enrolled in this study. RESULTS: The functional impairments by mucus impaction or air trapping were well documented in the ventilation washout scan, which not only provided an anatomical image but also dynamic profiles. The ratios of T1/2ROI/CA were significantly correlated to the corresponding scoring of HRCT (3.45 +/- 0.85 vs 7.50 +/- 1.51, r2 = 0.61, p = 0.023, n = 8). The improvement in T1/2ROI/CA (from 3.45 +/- 0.85 to 2.60 +/- 0.59, p = 0.022, n = 9) was paralleled by an increase in the 6-minute walking test (from 310.4 +/- 43.2 m to 352.4 +/- 45.1 m, p = 0.028, n = 7). CONCLUSION: The 133Xenon scan may be used to evaluate the heterogeneity of ventilation abnormalities and the efficacy of clinical therapy directly in patients with bronchiectasis.

Bronchiectasis↗

Effect of exercise training on skeletal muscle fibre characteristics in men with chronic heart failure. Correlation between skeletal muscle alterations, cytokines and exercise capacity.

BACKGROUND: In patients with congestive heart failure (CHF) there is a shift from aerobic type I muscle fibres to less aerobic type II fibres. Exercise training has been shown to have beneficial effects on exercise performance, peripheral pathology and the neurohumoral profile in stable patients with CHF. This study evaluated the effect of a 3 month exercise training program on skeletal muscle characteristics and the correlation of these to cytokines and exercise capacity in CHF patients. METHODS: Skeletal muscle biopsies for enzyme-histochemical analysis were performed in 15 CHF patients in New York Heart Association classes II-III, with a mean ejection fraction of 33+/-5% before and after a 12 week training period. The patients were trained for 30 min, five times a week at 80% of the peak heart rate achieved at baseline ergometer cycle test. Fifteen healthy men were used as controls. Plasma samples were examined by enzyme immunoassays for levels of pro-inflammatory cytokines. RESULTS: (a) At baseline we found muscle atrophy in five of the patients. The percent area of type I fibres (40.7+/-12.0 vs. 56.4+/-11.0%, P<0.05) and the thickness of type IIA (56.10+/-7.8 vs. 71.6+/-11.9 microm, P<0.001) and B-fibres (49.0+/-8.9 vs. 63.9+/-10.6 microm, P<0.001) were reduced, whereas the percent area of type IIA fibres (52.1+/-13.3 vs. 36.4+/-9.9%, P<0.05) was increased in heart failure patients compared to healthy controls. There was a modest correlation between fibre thickness and the level of interleukin 6 (r=-0.657, P=0.008). (b) After exercise training there was a reduction in muscle area examined by light-microscopy, measured as a percentage of field (-2.7, P=0.003) with an concomitant increase in interstitium. This reduction correlated to the increase in the 6-min walk test (r=-0.558, P=0.031). The thickness of type IIB fibres increased (+5.6 microm, P=0.068) and the area of type I fibres decreased (-6.1%, P=0.062). CONCLUSIONS: Patients with CHF have a relatively increased area of type IIA fibres and a relatively decreased area of type I fibres compared to healthy individuals. The thickness of type IIA and type IIB fibres is decreased compared to normal individuals. A modest negative correlation between the level of interleukin 6 and fibre thickness at baseline, suggests that inflammatory cytokines may be involved in the pathogenesis of the CHF related myopathy. A significant correlation between the reduction of muscle area, with increased interstitum, and the increase in the 6-min walk test may indicate that the improvement is due to increased capillary density permitting better flow reserve to exercising muscles.

Aged↗

Intravenous iloprost for treatment failure of aerosolised iloprost in pulmonary arterial hypertension.

Treatment with aerosolised iloprost, a prostacyclin analogue, has beneficial effects in patients with pulmonary arterial hypertension (PAH). It is unclear if patients, whose clinical condition deteriorates under treatment with aerosolised iloprost, benefit from switching to continuous intravenous iloprost. The current authors report on 16 patients with severe PAH who received continuous intravenous iloprost after primary or secondary failure of treatment with aerosolised iloprost. Determinants of efficacy were survival, New York Heart Association (NYHA) class, and walking distance in the 6-min walk test. Of 93 patients with PAH treated with aerosolised iloprost, 16 required switching to intravenous iloprost for clinical deterioration. These patients had severe right heart failure with a cardiac index of 1.6+/-0.2 L x min(-1) x m(-2) and a mixed-venous oxygen saturation of 52+/-6%. Five of these patients showed no improvement and eventually died. Three patients had further deterioration in NYHA class and exercise capacity; two of them underwent lung transplantation; the third patient is still alive. Eight patients showed marked clinical improvement; one underwent lung transplantation and the others are currently alive and stable. In the latter group of patients, the walking distance in the 6-min walk test increased from 205+/-94 to 329+/-59 m. It was not possible to identify clinical or haemodynamic factors that would predict whether switching from inhaled to intravenous iloprost would have a beneficial effect. In patients with pulmonary arterial hypertension who deteriorated while being treated with aerosolised iloprost, switching to continuous intravenous iloprost caused substantial improvement in exercise capacity in eight of 16 patients but could not prevent progression of pulmonary hypertension in the remaining eight patients. Since it was impossible to predict the individual effects of this approach, intravenous prostaglandin treatment should be considered in pulmonary arterial hypertension patients who deteriorate while receiving iloprost aerosol.

Administration, Inhalation↗

Selective pulmonary vasodilators for severe pulmonary hypertension: comparison between endpoints.

UNLABELLED: The therapeutic approach to severe pulmonary arterial hypertension (PAH), whether primary or secondary to connective tissue disorders, thromboembolic phenomena or congenital heart disease with Eisenmenger syndrome, has evolved in recent years following the introduction of selective pulmonary vasodilators, including prostacyclin analogs and endothelin receptor antagonists. AIM: To correlate three different endpoints (6-minute walk test, Tei index and peak tricuspid regurgitation velocity by Doppler echocardiographic study) during follow-up of PAH patients under selective vasodilator therapy. METHODS: Eleven patients (9 female, age 42 +/- 18 years) with severe PAH (> or = 65 mmHg), 64% with Eisenmenger syndrome, in NYHA class > or = II, were assessed during a follow-up of 11 +/- 8 months. Eight patients were already under therapy with iloprost or bosentan. RESULTS: There was no correlation between the three endpoints before and after therapy as assessed by Pearson's correlation coefficient. There was, however, an improvement in all of them after selective vasodilatory therapy. CONCLUSION: Therapeutic response can be accurately measured by the traditional endpoint (6-minute walk test) or by echocardiographic endpoints. However, the lack of correlation between them excludes their use as alternatives in patient follow-up.

Adult↗

Comparative effects of ventricular resynchronization therapy in heart failure patients with or without coronary artery disease.

UNLABELLED: In patients with advanced heart failure, intraventricular conduction delay (IVCD) and left ventricular systolic dysfunction (LVSD), multisite cardiac pacing can be proposed as an additive treatment. The aim of this study was to assess the clinical effectiveness of atrioventricular pacing according to the etiology of LVSD, by comparing the outcome of patients with and without coronary artery disease. Between August 1997 and November 1998, 103 patients were included in the InSync trial and received a biventricular pacemaker and a specifically designed left ventricular pacing lead. Baseline evaluation (12 lead ECG, New York Heart Association Class, quality of life (QOL) and distance walked during the 6 min walk test) was repeated in survival patients at 1, 3, 6 and 12 months after pacemaker implantation. Patients were split in two groups, ischemic (N = 48) and non-ischemic (N = 55), according the result of a recent coronary angiography, the existence of coronary angioplasty or coronary artery bypass or the history of a prior myocardial infarction. RESULTS: The mortality rate was similar in the two groups with a mean 12 months actuarial survival rate of 78%. Nevertheless, the delay between the death and the pacemaker implantation was significantly higher in the non-ischemic group. A significant reduction in QRS duration and a significant improvement in NYHA class (-1.5). QOL score (-50%) and 6 min walking test (+18%) were observed similarly in the two groups. CONCLUSION: This study shows that biventricular pacing improves significantly functional status of patients with LVSD, IVCD and advanced heart failure, regardless the etiology of the cardiomyopathy, ischemic or not, without over-mortality in ischemic patients.

Aged↗

Bilateral lung transplantation for cystic fibrosis. The Toronto Lung Transplant Group.

Between March 1988 and March 1991, 17 patients underwent bilateral lung transplantation for end-stage lung disease caused by cystic fibrosis. There were 11 male and six female patients. Ages ranged from 19 to 41 years (mean age 28 years). Preoperative mean arterial oxygen tension with the patient breathing room air was 54 +/- 6 mm Hg; forced vital capacity, 1.8 +/- 0.7 L; forced expiratory volume in 1 second, 0.9 +/- 0.3 L; and 6-minute walk test, 506 +/- 44 m. Immunosuppression consisted of cyclosporine, azathioprine, and prednisone. Induction immunosuppression was obtained with Minnesota antilymphocyte globulin. All patients received perioperative antibiotics according to sputum cultures and sensitivities. There were six operative deaths, four of which resulted from bacterial infection. Two patients required a second transplantation, one receiving a single lung and one undergoing bilateral lung replacement. Significant functional improvement was observed in all survivors. At 3 months follow-up, mean arterial oxygen tension on room air was 95 +/- 6 mm Hg (p less than 0.01); forced vital capacity, 3 +/- 0.8 L (p less than 0.01); forced expiratory volume in 1 second, 2.6 +/- 0.9 L (p less than 0.01); and 6-minute walk test, 678 +/- 47 m (p less than 0.01). The actuarial survival rate was 66% at 3 months and 58% at 6, 12, and 24 months. The most frequent cause of morbidity and mortality was acute pneumonia resulting from Pseudomonas cepacia. For patients with respiratory failure caused by cystic fibrosis, bilateral lung transplantation is an effective treatment option associated with significant functional improvement.

Adult↗

Vasoresponsiveness of sarcoidosis-associated pulmonary hypertension.

OBJECTIVE: To assess short-term and long-term responses to treatment with pulmonary vasodilators in patients with sarcoidosis-related pulmonary hypertension. METHODS: A prospective, observational study was performed on eight patients with moderate-to-severe sarcoidosis-related pulmonary hypertension. Patients underwent a short-term vasodilator trial, using inhaled nitric oxide (iNO), IV epoprostenol, and/or oral calcium-channel blockers. A favorable short-term response was considered a > or = 20% decrease in pulmonary vascular resistance (PVR). Five patients received long-term treatment with iNO (with one patient receiving epoprostenol in addition) and underwent follow-up hemodynamic and/or 6-min walk testing. Two patients received long-term treatment with calcium-channel blockers. RESULTS: Baseline (+/- SE) mean pulmonary artery pressure (mPAP) was 55 +/- 4 mm Hg and PVR was 896 +/- 200 dyne.s.cm(-5). A favorable short-term response was seen in seven of eight patients receiving iNO, four of six patients receiving epoprostenol, and two of five patients receiving calcium-channel blockers. With iNO, PVR decreased 31 +/- 5% (p = 0.006) and mPAP decreased 18 +/- 4% (p = 0.003); with epoprostenol, PVR decreased 25 +/- 6% (p = 0.016) and mPAP decreased 6 +/- 2% (p = not significant). Decreased systemic vascular resistance was the only significant response to treatment with calcium-channel blockers. Follow-up 6-min walk test results improved in all five patients receiving long-term treatment with iNO. Follow-up hemodynamic responses in three patients showed preserved vasoresponsiveness. These three patients subsequently died, as did the two patients receiving calcium-channel blockers. The two remaining patients continue to receive iNO. CONCLUSION: In the short term, pulmonary hypertension in patients with sarcoidosis is responsive to treatment with pulmonary vasodilators; these patients may benefit from long-term iNO therapy.

Administration, Inhalation↗

Minimally invasive coronary artery bypass grafting without cardiopulmonary bypass.

UNLABELLED: To determine the feasibility and the effectiveness of minimally invasive direct coronary artery bypass without cardiopulmonary bypass (MICABG) in patients with left anterior descending (LAD) coronary artery disease, we evaluated 90 consecutive patients who underwent MICABG at the University Hospital of Groningen. PATIENTS: Between January 1995 and December 1996, 50 patients (mean age 60 +/- 10.3 years) with documented myocardial ischemia and isolated stenosis of the LAD were selected for MICABG. Patients with any associated cardiac disease or with acute or evolving myocardial infarction were excluded. METHODS: A small left antero-lateral thoracotomy in the 5th intercostal space was made in all patients, anastomosing the left internal mammary artery (LIMA) to the LAD. A short-term (3 days) postoperative rehabilitation programme was used. Emotional stress (STAY-DY-1 score), wound pain (VAS: visual analogue score) and O2-saturation after a 6 min walking test were measured during hospitalisation and at the first follow-up examination (2.5 week after discharge). RESULTS: Mean operative time was 92 +/- 25 min (range 60-170). We recorded 1 (1.1%) in-hospital death and three cases (3.3%) of perioperative myocardial infarction. In two cases the MICABG was converted to the midline sternotomy. One patient underwent urgent reoperation on postoperative day 1 via midline sternotomy. Mean hospital stay was 4.4 +/- 2 days. Emotional stress was significantly reduced during and after hospitalisation, compared with the admission day. Wound pain was mild (3.5/10 VAS) on postoperative day 1 and reduced significantly during hospitalisation and at first follow-up examination. O2-saturation after a 6 min walking test had significantly improved at the first follow-up examination. CONCLUSION: These results indicate that MICABG is feasible and effective in patients with LAD stenosis and leads to a fast psycho-physical recovery.

Cardiopulmonary Bypass↗

Intermittent 6-month low-dose dobutamine infusion in severe heart failure: DICE multicenter trial.

BACKGROUND: Patients with end-stage heart failure are often refractory to maximal oral therapy, and they have high mortality rates, poor quality of life, and frequent hospitalizations with elevated health care costs. Intermittent dobutamine therapy has been suggested as an additional option in this clinical setting. METHODS AND RESULTS: Thirty-eight patients clinically stable for at least 48 hours with standard treatment, New York Heart Association (NYHA) functional class III or IV, cardiac index </=2.2 L/min/m(2), and left ventricular ejection fraction </=30% were randomly assigned to ambulatory intermittent dobutamine or optimal standard treatment. Dobutamine was infused at 2.5 microgram/kg/min with a portable pump 48 hours/week for 6 months. The primary study end point was the reduction of hospitalizations for worsening of congestive heart failure (CHF); changes in NYHA functional class, 6-minute walking test, and mortality rates were secondary end points. During the 6-month follow-up, all patients in dobutamine and control groups underwent weekly clinical visits with serum sodium and potassium measurement. Baseline characteristics were age 65 +/- 2 years, NYHA class III/IV 17/21, ejection fraction 22% +/- 1%, and cardiac index 1.89 +/- 0.1 L/min/m(2), without differences between treatment groups. Hospitalizations for all causes over a 6-month period were 17 and 11 in control and dobutamine groups; 11 of 17 and 7 of 11 were for worsening CHF. Four control patients but none in the dobutamine group had 2 or more hospitalizations for worsening of CHF. There were no significant differences in NYHA functional class and in 6-minute walking test. Three patients in the control group died and 5 in the dobutamine group died. Two patients in the dobutamine group underwent heart transplantation. Protocol was discontinued in the dobutamine group for severe ventricular arrhythmias (1 patient), infusion system failure (1 patient), and consent withdrawal (1 patient). In 3 patients in the dobutamine group, drug dose was increased to 5 microgram/kg/min because of CHF. CONCLUSIONS: Six-month intermittent low-dose dobutamine administration was well tolerated by patients with severe CHF; it did not improve the functional status and did not significantly increase the mortality rate as found with higher dobutamine doses in other studies. Hospitalizations for all causes and for worsening of CHF tended to be fewer in the dobutamine group.

Adult↗

The effect of micronutrient supplementation on quality-of-life and left ventricular function in elderly patients with chronic heart failure.

AIMS: Chronic heart failure (CHF) is a common and leading cause of death in industrialized countries. The potential benefits of micronutrient supplementation in CHF are extensive. Therefore, we examined the influence of long-term multiple micronutrient supplementation on left ventricular (LV) function, levels of pro-inflammatory cytokines, and quality-of-life (QoL) in elderly patients with CHF. METHODS AND RESULTS: Thirty CHF patients [age 75.4 (0.7), mean (SEM), LV ejection fraction (LVEF) < or =35%] were randomized to receive capsules containing a combination of high-dose micronutrients (calcium, magnesium, zinc, copper, selenium, vitamin A, thiamine, riboflavin, vitamin B(6), folate, vitamin B(12), vitamin C, vitamin E, vitamin D, and Coenzyme Q10) or placebo for 9 months in a double-blind fashion. All subjects were on stable optimal medical therapy for at least 3 months before enrolment. At randomization and at study end, tumour necrosis factor-alpha and its soluble receptors TNFR-1 and TNFR-2 were measured and six-minute walk test and QoL were assessed. Cardiac magnetic resonance scanning was performed to evaluate cardiac dimensions and LVEF. Two patients died during follow-up. The remaining patients (14 randomized to placebo and 14 to micronutrients) were well matched for LV function, symptoms, and exercise capacity. At the end of the follow-up period, LV volumes were reduced in the intervention group with no change in the placebo group [-13.1 (17.1)% vs. +3.8 (10.0)%; P<0.05]. LVEF increased by 5.3+/-1.4% in the intervention group and was unchanged in the placebo group (P<0.05). Patients taking micronutrients also had a significant improvement in QoL score between enrolment and study end [+9.5 (1.6)%; P<0.05], whereas those taking placebo had a slight deterioration [-1.1 (0.8)%; P=0.12]. Six-minute walk test and inflammatory cytokine levels remained unchanged in both groups. CONCLUSION: Long-term multiple micronutrient supplementation can improve LV volumes and LVEF and QoL scores in elderly patients with heart failure due to LV systolic dysfunction.

Aged↗

Effects of withdrawal of inhaled steroids in men with severe irreversible airflow obstruction.

Inhaled corticosteroid therapy has proven efficacy for asthmatics, but the benefit for patients with chronic obstructive pulmonary disease (COPD) is less well supported. We hypothesized that withdrawal of inhaled steroids in elderly patients with severe irreversible airway obstruction would not lead to a deterioration in respiratory function. We designed a prospective, double-blind, randomized, placebo-controlled, crossover study to follow spirometry, quality of life questionnaire, six-minute (6-min) walk test, and sputum markers of inflammation during a 6-wk placebo treatment period and a 6-wk treatment period with beclomethasone dipropionate (BDP), 336 microg/d. There were 24 men receiving BDP who entered the study; 15 completed the study. Their mean age was 66.9 +/- 1.9 yr, and mean FEV(1) was 1.61 +/- 0.1 L (47% of predicted). There was a significant decrease in the mean FEV(1 )while using the placebo inhaler (1.70 L versus 1.60 L, baseline versus placebo: 95% CI, 0.002 to 0.195; p < 0.05). There was a decrease in the mean percentage change in FEV(1) for the study subjects during the placebo treatment period as compared with the BDP treatment period (-6.28 versus 5.03%, placebo versus BDP: 95% CI, -23.38 to 0.76; p = 0.06). Six-minute walk test results and sputum analysis for cell count and differential were not significantly different during placebo and BDP treatment periods. Borg scale assessment of dyspnea after exercise was increased while using the placebo inhaler as compared with baseline, and decreased during the BDP treatment period. Chronic Respiratory Disease Questionnaire (CRQ) scores revealed no significant difference between placebo and BDP. This study has demonstrated that in elderly patients with severe irreversible airway obstruction, withdrawal of inhaled corticosteroid therapy leads to a deterioration in ventilatory function and increased exercise-induced dyspnea.

Administration, Inhalation↗

Immediate and long-term hemodynamic and clinical effects of sildenafil in patients with pulmonary arterial hypertension receiving vasodilator therapy.

OBJECTIVE: To determine the immediate and long-term effects of adding sildenafil, a phosphodiesterase-5 inhibitor, to the medical regimen of patients with pulmonary arterial hypertension (PAH). PATIENTS AND METHODS: Thirteen patients with PAH received empirical adjunctive sildenafil treatment at the Mayo Clinic in Rochester, Minn, between November 1, 2000, and August 31, 2001. All received a 25-mg dose of sildenafil, increased by 25 mg at 8-hour intervals, if tolerated, up to 100 mg during hemodynamic monitoring for 24 to 48 hours. Long-term effects on right heart hemodynamics were assessed by noninvasive right ventricular systolic pressure, right ventricular index of myocardial performance, and a 6-minute walk test. RESULTS: Sildenafil significantly increased cardiac output (CO) (P = .04) and decreased pulmonary artery systolic pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and mean arterial pressure (P < or = .01) at peak measurements (obtained 1-2 hours after highest dose). At trough measurements (obtained 8 hours after highest dose), sildenafil significantly decreased pulmonary artery systolic pressure, mean pulmonary artery pressure, and mean arterial pressure (P = .01). Ten patients discharged from the hospital were taking the highest-tolerated dose of sildenafil every 8 hours. The right ventricular systolic pressure and right index of myocardial performance showed no significant improvement at follow-up (117 +/- 70 days), although concomitant treatment with epoprostenol could be tapered in 2 patients. Changes in New York Heart Association classes were inconsistent, and improvements in the 6-minute walk test were not significant. CONCLUSION: Sildenafil has an immediate pulmonary vasodilator effect in patients already receiving vasodilators for PAH. Its long-term effects on right heart function and functional status are equivocal. A large, prospective, well-designed study is needed to determine the effects of sildenafil on PAH, both in untreated and concurrently treated patients.

Adult↗

Efficacy of nebulized flunisolide combined with salbutamol and ipratropium bromide in stable patients with moderate-to-severe chronic obstructive pulmonary disease.

BACKGROUND: The efficacy of nebulized corticosteroids in the prevention of exacerbation of chronic obstructive pulmonary disease (COPD) has been poorly studied. OBJECTIVE: To evaluate the efficacy and tolerability of nebulized flunisolide (1 mg) + salbutamol/ipratropium bromide (1,875/375 microg) b.i.d. in comparison with placebo + salbutamol/ipratropium bromide. METHODS: This was a randomized, parallel-group, double-blind study on 114 patients with COPD of moderate-to-severe degree. The main outcome was the frequency of severe exacerbations over a 6-month period. Before and after treatment, respiratory symptoms, forced expiratory volume in 1 s (FEV(1)), shuttle walking test distance and St. George's Respiratory Questionnaire scores were evaluated. RESULTS: The total number of exacerbations was slightly lower in the flunisolide group compared to the placebo group (19 vs. 34, p = 0.054); the number of patients experiencing at least one exacerbation during the study was also decreased (16 vs. 26, p = 0.059). In particular, type 3 Anthonisens's exacerbations were significantly reduced by flunisolide (p = 0.044). In the placebo group, scores were higher than in the flunisolide group but nonsignificant for dyspnea, cough, sputum amount and purulence. FEV(1) was significantly increased compared to baseline in both groups, and the area under the FEV(1)-time curve during the 6-month period was significantly greater in the flunisolide group (5.2 +/- 10.6 vs. 2.1 +/- 5.0, flunisolide vs. placebo, respectively; p = 0.047). For shuttle walking test distance and scores of the St. George's Respiratory Questionnaire, no significant difference between the baseline evaluation and the end of the study was observed in both groups. CONCLUSIONS: Nebulized flunisolide is a good alternative to other inhaled corticosteroids when added to nebulized salbutamol/ipratropium bromide in the long-term treatment of moderate-to-severe COPD patients.

Aged↗

Ventricular pacing improves exercise tolerance in patients with chronic heart block.

Exercise capacity was assessed by means of a simple six minute walking test in a group of 18 patients with heart block whose only presenting symptom was breathlessness. None was in overt cardiac failure. Patients were studied before and after implantation of a transvenous, ventricular, demand pacing system (study group). Eight patients with an implanted pacemaker admitted for elective generator replacement were assessed in the same manner (control group). Exercise capacity in the study group was significantly increased within 48 hours of pacing, and this improvement was maintained in most patients during the follow up period of up to 30 months. In contrast, exercise capacity was unaffected by generator replacement in the control group. Simple ventricular pacing produces symptomatic benefit in patients with heart block accompanied by breathlessness. This benefit is apparent within 48 hours of pacing and is maintained; it can be assessed objectively by a six minute walking test.

Aged↗

Safety and efficacy of epoprostenol in patients with severe congestive heart failure. Epoprostenol Multicenter Research Group.

Patients with advanced heart failure often remain severely symptomatic and have a high mortality rate despite currently available therapy. We studied the safety and efficacy of a new approach to the patient with refractory heart failure: continuous intravenous treatment via a portable infusion pump with epoprostenol (prostacyclin), a potent pulmonary and systemic vasodilator. A group of 33 patients with severe heart failure (64% New York Heart Association class IV and 36% class III) and profound ventricular dysfunction (median left ventricular ejection fraction, 0.15)--despite prior treatment with diuretics (100%), digitalis (91%), angiotensin-converting enzyme inhibitors (85%), and dobutamine (30%)--underwent a baseline 6-minute walk test prior to dose titration with epoprostenol during invasive hemodynamic monitoring. Subjects responding during the dose titration were randomized, on an open basis, to receive either continuous epoprostenol infusion via an indwelling central venous catheter plus conventional therapy or conventional therapy alone for 12 weeks. The initial dose-ranging study with epoprostenol produced a significant decline in systemic and pulmonary vascular resistance and a substantial increase in cardiac index despite a fall in pulmonary capillary wedge pressure. Symptoms related to vasodilation were noted within the first week after randomization to epoprostenol in 9 of 16 patients but resolved with adjustment of the infusion and concomitant medications in all but one subject. Dose adjustments during the chronic epoprostenol infusion were infrequent after the first week and complications related to the drug delivery system were rare. The change in distance walked from baseline to the last available 6-minute walk test was significantly greater in patients who received epoprostenol compared with patients assigned to standard therapy (72 +/- 40 vs -39 +/- 32 m, mean +/- SEM; p = 0.033). Our study suggests that long-term intravenous infusion of epoprostenol is feasible in patients with severe heart failure and our hemodynamic and functional results suggest clinical benefit as well. However, until recent results indicating an adverse effect of epoprostenol on survival are fully evaluated, the role of this drug in the treatment of advanced heart failure will remain uncertain.

Aged↗

Training responses of two age groups during treadmill walking.

The purpose of the present study was to use a previously developed treadmill walking test to determine training-induced changes within and between two groups of untrained men during a six week training period. One group consisted of seven middle-aged (mean age, 41.3 yr), and the second group consisted of seven young adult (mean age, 19.9 yr), men. Heart rates following training were significantly lower at all work intensities for the middle-aged men (p less than 0.005) whilst for the young adults only the 12.5% and 15% (p less than 0.025) work levels were significantly lower. Blood lactic acid concentrations (p less than 0.005), Respiratory Exchange Ratios (p less than 0.05), Ventilatory Equivalents (p less than 0.005) and mean Two Mile times (p less than 0.005) were all significantly lower after training for the older age group but this was not so for the younger adult group. The oxygen cost of the walking test was lower for four of the workloads of the middle-aged, but only for the final workload (p less than 0.005) for the young adults, after training. The performance test did not disadvantage the middle-aged subjects yet the results demonstrated that the test provided a common means of reflecting the training state of the two groups whether the level of activity took place on the treadmill or on the track.

Adolescent↗

The quantitation of blood flow/metabolism coupling at rest and after exercise in peripheral arterial insufficiency, using PET and 15-0 labeled tracers.

Regional blood flow and oxygen uptake of the lower limbs were studied in 11 patients with arterial insufficiency (10 with severe unilateral, 1 with bilateral intermittent claudication). Regional muscle blood flow (F), oxygen consumption rate (R), and oxygen extraction fraction (E) were evaluated by positron emission tomography (PET) and bolus inhalation of C15O2 and 15O2 by the patient. Tomograms were recorded at the greatest diameter of legs, at rest and ten minutes after a treadmill walk test leading to the development of ischemic pain in the affected leg. In 5 patients, F and E were correlated with the results of occlusive venous strain gauge plethysmography and with the measurements of blood gases in one brachial artery and in the femoral vein of the affected limb. Blood flow values measured at rest and after exercise by PET were poorly correlated with the plethysmographic findings. This may be because PET does not interfere with flow as venous occlusion plethysmography does in low peripheral pressure conditions. The results show that F, R, and E were not significantly different in normal and pathologic legs at rest. The values of F and R were significantly higher in pathologic than in normal lower limbs, ten minutes after exercise, whereas E was not significantly altered by exercise at any side. This suggests that, during the recovery from a walk test, the delayed increase in oxygen uptake is proportional to the delayed hyperemia in the ischemic muscles ("oxygen debt") and probably not linked to a luxury perfusion.

Aged↗

Immediate and chronic effects of AV-delay optimization in patients with cardiac resynchronization therapy.

BACKGROUND: Acute changes of the AV-delay in CRT patients have a significant impact on hemodynamics. However, the chronic functional effects of AV-delay optimization have not been systematically examined despite of their potential role for chronic functional improvement. METHODS: Therefore, in this study we investigated whether optimization of AV-delay in CRT patients as assessed by echocardiographic measurement of the velocity time integral of the left ventricular outflow tract (LVOT-VTI) chronically changes (1) echocardiographic parameters of systolic and diastolic left ventricular function, (2) walking distance in the 6-min walk test, (3) levels of NT-proBNP and (4) quality of life as assessed by a standard questionnaire. 33 patients underwent optimization of AV-delay 31+/-8 weeks after initiation of CRT. Follow up (FU) was conducted 43+/-5 days later. RESULTS: E/Ea, the ratio of peak E-wave of mitral inflow and of TDI of the mitral annulus, significantly decreased immediately post-optimization (11+/-1 vs. 14+/-1 at baseline, p<0.05) and further decreased at FU (8+/-1, p<0.05 vs. immediately post-optimization) indicating improvement of diastolic function, while traditional parameters of diastolic function derived from pulse wave Doppler remained unchanged. There was a slight increase of LV-ejection fraction as assessed by echocardiography acutely after optimization (baseline: 25+/-2%, optimized: 28+/-1%, p<0.05), while LV-ejection fraction at FU did not differ from baseline. 6-min walk test improved from 449+/-17 m (baseline) to 475+/-17 m at FU (p<0.05). During this period NT-proBNP significantly decreased from 3193+/-765 ng/l to 2593+/-675 ng/l (p<0.05). Quality of life was unchanged at FU. CONCLUSION: This study demonstrates for the first time chronic functional improvement due to AV-delay optimization in patients with CRT.

Acute Disease↗