Short-term Clinical Effects Research Articles

Short-term endotracheal climate changes and clinical effects of a heat and moisture exchanger with an integrated electrostatic virus and bacterial filter developed for laryngectomized individuals

Conclusion: Both the regularly used heat and moisture exchanger (R-HME) and the HME with both an antimicrobial and hygroscopic element (F-HME) are effective moisture exchangers. The antimicrobial filter of the F-HME acts as a heat exchanger. The external features of the F-HME were experienced as inconvenient, but decreased sputum production was reported as well. Objectives: Recently an HME with an integrated antimicrobial filter has become available for use in laryngectomized patients. The purpose of this study was to assess its short-term endotracheal climate changes and feasibility in daily practice. Methods: Endotracheal temperature and humidity were successfully measured in 13 laryngectomized patients (2652 analysed full breaths), during 10 min rest-breathing with the R-HME, with an F-HME and without HME in a randomized sequence. Additionally, a 3 week prospective clinical feasibility trial was conducted in 17 laryngectomized patients. Results: Both R-HME and F-HME increase endotracheal minimum humidity values (5.8 and 4.7 mgH2O/L, respectively; p < 0.0001). Compared with open stoma breathing, in contrast to the R-HME, the F-HME increases both end-inspiratory and end-expiratory temperature values (1.1°C, and 0.6°C, respectively). After the 3-week clinical feasibility trial, one patient dropped out; 11 patients (11/16 = 69%) disliked the larger design of the F-HME and all patients reported less optimal airtight occlusion. Five patients (5/16 = 31%) reported remarkably decreased sputum production.

Corticosteroid injections, eccentric decline squat training and heavy slow resistance training in patellar tendinopathy

A randomized-controlled single-blind trial was conducted to investigate the clinical, structural and functional effects of peritendinous corticosteroid injections (CORT), eccentric decline squat training (ECC) and heavy slow resistance training (HSR) in patellar tendinopathy. Thirty-nine male patients were randomized to CORT, ECC or HSR for 12 weeks. We assessed function and symptoms (VISA-p questionnaire), tendon pain during activity (VAS), treatment satisfaction, tendon swelling, tendon vascularization, tendon mechanical properties and collagen crosslink properties. Assessments were made at 0 weeks, 12 weeks and at follow-up (half-year). All groups improved in VISA-p and VAS from 0 to 12 weeks (P<0.05). VISA-p and VAS improvements were maintained at follow-up in ECC and HSR but deteriorated in CORT (P<0.05). In CORT and HSR, tendon swelling decreased (-13+/-9% and -12+/-13%, P<0.05) and so did vascularization (-52+/-49% and -45+/-23%, P<0.01) at 12 weeks. Tendon mechanical properties were similar in healthy and injured tendons and were unaffected by treatment. HSR yielded an elevated collagen network turnover. At the half-year follow-up, treatment satisfaction differed between groups, with HSR being most satisfied. Conclusively, CORT has good short-term but poor long-term clinical effects, in patellar tendinopathy. HSR has good short- and long-term clinical effects accompanied by pathology improvement and increased collagen turnover.

"Short term clinical effects of a herbal-based toothpaste: A randomized controlled clinical trial"

"Short term clinical effects of a herbal-based toothpaste: A randomized controlled clinical trial"

Short-Term Clinical and Microbiological Effects of Systemic Ornidazole vs. Metronidazole in the Treatment of Generalized Chronic Periodontitis Patients

Background: The purpose of this study was to evaluate and compare the clinical and microbiological effects of systemic ornidazole (ORN) and metronidazole (MET) in sites with/without scaling and root planning (SRP) in generalized chronic periodontitis patients.Methods: Ramfjord 6 teeth with total of 192 sites in 40 systemically healthy patients suffering from generalized chronic periodontitis with pocket depth ≥ 5mm and no SRP in previous 3 months were included. Patients were randomly placed into three groups (Gp I= SRP + ORN and MET given orally, Gp II= only ORN and MET given orally, Gp III= SRP+ placebo given orally). A total of 120 gingival crevicular fluid samples were collected randomly. The gingival scores (GS), probing depth (PD) scores, bleeding on probing (BOP), counts of spirochetes (SPI), gram positive cocci (GPC), gram positive bacilli (GPB), gram negative cocci (GNC) and gram negative bacilli (GNB) were evaluated at pretreatment (day 0), and post treatments (day 14 and 28 day).Results: Results revealed that SRP alone did bring some reduction in GS, PD and BOP scores but extent of reduction in all three clinical parameters was significantly less as compared to ORN/MET + SRP groups. The ORN and MET both showed similar and comparatively higher improvement in clinical parameters as compared to ORN and MET alone and placebo. Microbiological findings also indicated that ORN and MET also led to similar and comparatively higher gradual decrease in counts of SPI, GNC and minimal decrease in GNB from baseline onwards to the end of study, which was replaced by increase in population of GPC and GPB. The improvement of ORN and MET was found to be similar, clinically and microbiologically.Conclusions: TheORN andMET combined with SRP showed beneficial shifts in bacterial population associated with substantial clinical improvements. Study found both ORN and MET equally effective adjunct in treatment of generalized chronic periodontitis.

Clinical effects of 2% chlorhexidine gel on patients undergoing orthodontic treatment

Objectives The purpose of this study was to compare the short-term clinical effects of a single intrasulcular injection of 2% chlorhexidine gluconate gel (CG) and placebo gel (PG) in orthodontic patients with fixed appliances and established gingivitis aged from 12 to 20 years. Methods and materials 50 patients (31 females and 19 males) as subjects were divided into two groups (CG and PG). This study was single-blind randomized split mouth clinical trial. As randomly assigned by coin toss, the first permanent molars on the right or left side of the mouth received either CG or PG. Probing depth (PD) was measured with a Michigan 0 probe. The gingival index (GI) of Löe and Silness and papilla bleeding index (PBI) of Mühlemann were recorded on the first permanent molars. These indices were measured at baseline, and in treatment on 2nd, 4th, 8th, and the 12th weeks. t-Test and Chi-square test were used to analyze the data. Results t-Test showed that PD was reduced in experimental group in comparison with the control group in the 4th week and following intervals ( p < 0.001). Chi-square showed that PBI was improved in experimental group in comparison with the control group in the 2nd week and following intervals ( p < 0.001). The same test showed that GI was improved in experimental group in the 2nd week and following intervals ( p < 0.001). Conclusion The data indicate that the use of a single application of 2% CG was effective in reducing gingivitis related to banded first permanent premolars in adolescents undergoing orthodontic treatment in short time.

Short-term Clinical Effects of Tolvaptan, an Oral Vasopressin Antagonist, in Patients Hospitalized for Heart Failure: The EVEREST Clinical Status Trials

Short-term Clinical Effects of Tolvaptan, an Oral Vasopressin Antagonist, in Patients Hospitalized for Heart Failure: The EVEREST Clinical Status Trials

Influence of cardiac resynchronisation therapy on different types of sleep disordered breathing

This study investigates the influence of cardiac resynchronisation therapy (CRT) on sleep disordered breathing (SDB) in patients with severe heart failure (HF). Seventy-seven patients with HF (19 females; 62.6+/-10 years) eligible for CRT were screened for presence, type, and severity of SDB before and after CRT initiation (5.3+/-3 months) using cardiorespiratory polygraphy. NYHA class, frequency of nycturia, cardiopulmonary exercise, 6-minute walking test results, and echocardiography parameters were obtained at baseline and follow-up. Central sleep apnoea (CSA) was documented in 36 (47%), obstructive sleep apnoea (OSA) in 26 (34%), and no SDB in 15 (19%) patients. CRT improved clinical and haemodynamic parameters. SDB parameters improved in CSA patients only (apnoea hypopnoea index: 31.2+/-15.5 to 17.3+/-13.7/h, p<0.001; SaO2min: 81.8+/-6.6 to 84.8+/-3.3%, p=0.02, desaturation: 6.5+/-2.3 to 5.5+/-0.8%, p=0.004). Daytime capillary pCO2 was significantly lower in CSA patients compared to those without SDB with a trend towards increase with CRT (35.5+/-4.2 to 37.9+/-5.7 mm Hg, ns). After classifying short term clinical and haemodynamic CRT effects, improved SDB parameters in CSA occurred in responders only. In patients with severe HF eligible for CRT, CSA is common and can be influenced by CRT, this improvement depends on good clinical and haemodynamic response to CRT.

Selective endothelinA receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease

Introduction:Endothelin receptor antagonism has become an important component in the treatment of pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD). The purpose of this study was to analyse...

Short-Term Clinical and Microbiologic Effects of Pocket Debridement With an Er:YAG Laser During Periodontal Maintenance

Short-Term Clinical and Microbiologic Effects of Pocket Debridement With an Er:YAG Laser During Periodontal Maintenance

Short‐term effects of tetrabenazine on chorea associated with Huntington's disease

We sought to assess the short-term clinical effects of tetrabenazine (TBZ) on choreic movements in Huntington's disease patients. A total of 10 patients on stable doses of TBZ were enrolled in this observational study. Patients took their evening dose of TBZ and presented the next day to the Baylor College of Medicine Movement Disorders Clinic without taking the usual morning dose. They were assessed using the Unified Huntington's Disease Rating Scale (UHDRS) motor assessment and Beck Depression Inventory. The usual morning dose of TBZ was then administered and patients were followed with serial UHDRS motor examinations approximately every 2 hours until choreic movements subsided and then returned. TBZ decreased the UHDRS chorea score on average 42.4% +/- 17.8%. The duration of effect varied from a minimum of 3.2 hours to a maximum of 8.1 hours (mean = 5.4 +/- 1.3). No patient experienced an adverse event related to TBZ or its withdrawal. During short-term follow-up after a single dose, TBZ improves chorea for approximately 5 hours.

Sclerosing polidocanol injections to treat chronic painful shoulder impingement syndrome-results of a two-centre collaborative pilot study

The histological changes found in the supraspinatus tendon have similarities with the findings in Achilles-, patellar- and extensor carpi radialis brevis (ECRB)-tendinopathy. In recent studies, we have found a vasculo-neural ingrowth in chronic painful Achilles and patellar tendinopathy, and demonstrated good short-term clinical effects with injections of the sclerosing substance polidocanol. In this collaborative two-centre pilot study, 15 patients (10 males and 5 females, mean age 46 years) with a long duration of shoulder pain (mean 28 months), and given the diagnosis chronic painful shoulder impingement syndrome, were included. They had tried rest, traditional rehabilitation exercises and multiple subacromial corticosteroid injections, without effect. We found vascularity (neovessels) in chronic painful, but not in pain-free, supraspinatus tendons, and prospectively studied the clinical effects of ultrasound (US) and colour Doppler (CD)-guided injections of polidocanol, targeting the area with neovessels. The patients evaluated the amount of shoulder pain during horizontal shoulder activity on a visual analogue scale (VAS), and satisfaction with treatment. Two (median) (range 1-5) polidocanol treatments (with 4-8 weeks in between) were given. In four patients (considered treatment failure), cortisone was injected into an inflamed subacromial bursa at one separate occasion weeks after the last polidocanol injection. At follow-up, 8 (median) (range 4-17) months after the treatment, 14 patients were satisfied with the result. Using the visual analogue scale evaluation (VAS), the pain dropped from 79 before treatment to 21 at follow-up (P < 0.05). In the short-term perspective, sclerosing polidocanol injections targeting the neovessels in the supraspinatus tendon and/or bursa wall seems to have a potential to reduce the pain during shoulder loading activity.

Head-to-head comparison of clinical, biochemical and functional effects of fosinopril and enalapril in patients with systolic heart failure

The aim of this study was to evaluate short-term clinical, biochemical and functional effects of fosinopril versus enalapril in patients with heart failure. 59 consecutive patients (mean age 57 +/- 8 years, EF 18.9 +/- 6.3%, NYHA III or IV class 19/59) were randomized to receive fosinopril or enalapril for three months. All patients underwent echocardiography, metabolic testing, and a 6-minute walk test and completed the Minnesota questionnaire on inclusion and three months later. Additionally, serum creatinine, BUN, total cholesterol and triglycerides were measured. Kaplan-Meier curve was created to assess event-free survival for cardiac death and hospitalization for heart failure. There was no statistically significant difference in event-free survival between patients on fosinopril and enalapril (86.7% vs. 82.8%, log rank 4.21 p=0.43). However, time to the event was longer in patients on fosinopril (77.0 +/- 25.35 vs. 40.2 +/- 6.8 days, p=0.04). At the end of the study, no difference between fosinopril and enalapril group existed with respect to maximal oxygen consumption (20.90 +/- 4.47 vs. 20.89 +/- 6.86 ml/kg/min), ejection fraction (20.5 +/- 7.4 vs. 21.4 +/- 7.8%), distance during the 6-minute test walk (313 +/- 74 vs. 352 +/- 129 meters) and quality of life (23.8 +/- 15.8 vs. 25.6 +/- 20.3 points), but patients on enalapril had higher creatinine (99 +/- 13 vs. 113 +/- 17 micromol/L, p=0.002) and BUN (7.28 +/- 1.7 vs. 8.89 +/- 2.39 mmol/L, p=0.01) levels. Increase in fosinopril dose during the study was higher than increase in enalapril dose (24.1% +/- 23.8% vs. 9.5 +/- 24.5%, p=0.04). Fosinopril and enalapril have similar short-term effects on event-free survival, ejection fraction, functional capacity and quality of life in patients with heart failure. Patients on fosinopril presented with longer survival without event and had lower creatinine and BUN at the end-of the follow-up. Additionally, fosinopril can be easily titrated to the maximum therapeutic dose.

Evaluation of Short Term Clinical Effects and Presumptive Mechanism of Botulinum Toxin Type A as a Treatment Modality of Benign Prostatic Hyperplasia

The purpose of this study was to evaluate the effect and investigate the putative mechanism of botulinum toxin type A (BTA) applied to the treatment of benign prostatic hyperplasia (BPH). A total of 52 patients with symptomatic BPH were evaluated. Transperineal intraprostatic injection under transrectal ultrasonography was carried out. BTA dissolved in 4 to 9 mL of saline was used from 100 U to 300 U, according to prostate volume. Twenty-six patients received only BTA (BT group), and 26 received both BTA and one month of an α-adrenergic antagonist (BTα group). The therapeutic outcomes were evaluated by comparing parameters such as international prostate symptom score (IPSS), quality of life, prostate specific antigen, prostate volume, post-void residual urine, and peak urinary flow rate. At the one month follow-up, 18 patients in the BT group and 21 in the BTα group had subjective symptomatic relief (p = 0.337). Only IPSS5 (weak stream) was significantly different between the BT group and BTα groups (p = 0.034). At the three month follow-up, 39 patients had subjective symptomatic relief. The storage symptoms were improved more than the voiding symptoms. Additionally, about 50 percent of the patients whose voiding symptom improved expressed improved erectile function. BTA injection seems to be an alternative treatment for BPH. The differences after the one month evaluation between the BT and the BTα groups might suggest that the adrenergic influence could be relatively reinforced by the anticholinergic effect of BTA. Nitric oxide would thus be involved in a BTA action mechanism in BPH.

Effects of Kinesthesia and Balance Exercises in Knee Osteoarthritis

In patients with knee osteoarthritis (OA), there is a prominent loss in proprioception and kinesthesia sensation compared with control subjects of the same age and gender. The aim of this study is the investigation of short-term clinical effects of kinesthesia and balance exercises in patients with knee OA. This 8-week study was conducted on 66 female patients with knee OA who were randomized into 2 groups. The first group received kinesthesia and balance exercises (such as retrowalking, walking on their toes, leaning to the sides, balance board exercises, minitrampoline exercises, plyometric exercises, and so on) in addition to strengthening exercises. The second group received only strengthening exercises. : Statistically significant improvements were observed postexercise for both groups with respect to baseline for WOMAC, SF-36 Form, times for performing activities of daily living, isokinetic quadriceps muscle strength, and proprioceptive sensation levels. In the first group with kinesthesia training, compared with the second group, significantly greater improvements were obtained in all the subparameters that measure functional status (WOMAC-physical function value, SF-36 Form [physical function, role limitations-physical and vitality-energy or fatigue variables], 10 stairs climbing, and 10-m walking times) and in isokinetic muscle strength at high angular velocities (P < 0.05). The absolute angular error percentage (to assess proprioceptive accuracy) was significantly improved postexercise in both groups. There were no differences between the groups. Additive positive effects of kinesthesia and balance exercises in knee OA have been demonstrated. Used in clinical applications, they should be able to increase the functional capacities of patients. Long-term studies about efficacy and cost-effectivity of these exercises are needed.

Experience in donor-recipient gender mismatching heart transplantation: analysis of seven female patients receiving male donor hearts

To summarize the experience in donor-recipient gender mismatching heart transplantation. Seven female patients with end-stage cardiopathy aged 13 approximately 44, underwent orthotopic transplantation of hearts from male donors. Fine-tuning immunosuppressive protocols were adopted: Stanford classic therapy was applied on 3 cases and immunosupression induction therapy was applied on 4 cases. The clinical outcomes were observed for an average of 20 months (5 approximately 54 months). No acute reject reaction was found in all 7 cases within 3 months postoperatively. The earliest 2 patients died of refractory rejection 38 and 34 months postoperatively due to immunosuppressive withdrawal because of financial difficulty. The other 5 cases resumed their normal work and daily life. No allograft dysfunction, severe opportunistic infection episodes, and injury of liver and kidney functions were found in all cases. Fine-tuning immunosuppressive protocols improve the short-term and long-term clinical effects of donor-recipient gender mismatching heart transplantation.

Prospective comparison and 1-year follow-up of a single endoscopic subureteral polydimethylsiloxane versus dextranomer/hyaluronic acid copolymer injection for treatment of vesicoureteral reflux in children

Objectives To compare, in a prospective study, the efficacy of a single injection of polydimethylsiloxane (Macroplastique) or dextranomer/hyaluronic acid copolymer (Deflux), a new biodegradable substance, and to assess the short-term and 1-year clinical effects concerning reflux resolution and the safety of these two bulking agents. Subureteral injection of bulking agents has recently demonstrated good success rates for endoscopic treatment of vesicoureteral reflux. Macroplastique has been one of the most popular bulking agents during the past years. Nevertheless, considering the synthetic property, new biodegradable substances have become more relevant. Methods From January 2000 to June 2001, 16 boys and 56 girls (total of 114 ureters) with a mean age of 34.5 months were treated endoscopically for vesicoureteral reflux. A single subureteral Macroplastique or Deflux injection was performed in 34 children (58 ureters) and 38 children (56 ureters), respectively. Both groups were comparable in terms of baseline parameters. Vesicoureteral reflux was grade II in 52, grade III in 57, and grade IV in 5 ureterorenal units. The procedure was performed on an outpatient basis, with the children under general anesthesia. In addition to the routine parameters, the follow-up evaluation consisted of renal ultrasonography and voiding cystourethrography at 3 and 12 months postoperatively. Results Endoscopic treatment was performed without any complications in all cases. At the 3-month follow-up visit, reflux was corrected in 50 (86.2%) of 58 refluxing ureters in the Macroplastique group and in 40 (71.4%) of 56 refluxing ureters in the Deflux group. At 1 year of follow-up, reflux correction was maintained in 80.9% of ureters in the Macroplastique group and in 67.6% of ureters in the Deflux group. No postoperative complications were observed in either group. Conclusions A single subureteral injection of either polydimethylsiloxane (Macroplastique) or dextranomer/hyaluronic acid copolymer (Deflux) is an effective treatment modality for children with vesicoureteral reflux. The procedure was well tolerated, safe, and associated with low morbidity. Deflux, a new biocompatible, biodegradable substance, seems to be an alternative modality to other bulking agents for treating vesicoureteral reflux in children, with acceptable short-term and 1-year results.

Neoadjuvant therapy of endometrial cancer with the aromatase inhibitor letrozole: endocrine and clinical effects

Objective: To investigate the short-term hormonal and clinical effects of the aromatase inhibitor letrozole (Femara ®) in patients with endometrial cancer. Materials and methods: Ten previously untreated, post-menopausal patients (mean age 59 years) with endometrial cancer, predominantly stage I disease, received letrozole 2.5 mg per day for 14 days before surgery. Clinical, sonographic, morphologic, cytologic, and hormonal-metabolic parameters (blood estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), glucose, and cholesterol by radioimmunoassay, enzyme immune assay, or enzyme-colorimetric methods; tumor progesterone receptors by ligand-binding assay; and aromatase activity by 3 H -water release assay) were evaluated before and after treatment. Results: Treatment was well-tolerated in all patients. In two patients, pain relief in the lower part of the belly and/or decrease in intensity of uterine discharge was reported. In the three cases, substantial decreases in endometrial M-echo (ultrasound) signal were noted; the mean value of this parameter after treatment was 31.1% lower than before treatment. Blood estradiol concentration decreased by an average of 37.8% after letrozole therapy, and tumor progesterone receptor levels and aromatase activity decreased by 34.4 and 17.5%, respectively. Treatment with letrozole did not influence surgery. Conclusions: These data show that short-term treatment with letrozole in the neoadjuvant setting resulted in some positive clinical changes. Longer-term and larger-scale trials of neoadjuvant letrozole in endometrial cancer are warranted.

Tolerance to the Organic Nitrates

Nitroglycerin (NTG) and other organic nitrates continue to be important drugs that are often used in cardiovascular medicine. All organic nitrates undergo denitrification, releasing nitric oxide (NO) through a biotransformation process that remains poorly understood to date. NO activates the enzyme soluble guanylyl cyclase in smooth muscle cells, causing increased levels of the second messenger cGMP. Finally, cGMP activates a cGMP-dependent protein kinase. This enzyme mediates vasorelaxation through inhibitory phosphorylation of different proteins involved in the regulation of intracellular Ca2+ levels. See p 2338 All of the organic nitrates have potent short-term vascular, hemodynamic, and clinical effects. A critical limitation in their clinical application is the development of tolerance, whereby their initial effects are rapidly lost during sustained administration. Although there seems to be little doubt that NO, or some NO adjunct, mediates the pharmacodynamic effect of nitrates, the mechanism(s) underlying the development of tolerance remain an important and vexing problem for cardiovascular pharmacology. The phenomenon of nitrate tolerance has been recognized for more than a century and has been intensely investigated for 3 decades. Despite these efforts, a unifying hypothesis concerning the mechanism of tolerance continues to be elusive. Initial investigations focused on abnormalities in biotransformation and denitrification of organic nitrates. Almost 30 years ago, Needleman and Johnson1 proposed that tolerance might result from impaired nitrate metabolism caused by the reduced bioavailability of sulfhydryl groups. Although sulfhydryl depletion is no longer thought to play a causal role in tolerance,2 abnormalities in nitrate biotransformation remain the subject of active investigation.3 Importantly, investigations in this area are severely limited by our poor understanding of the biotransformation pathway and by significant analytical problems in quantifying NO and/or NO adjunct production rates. Approximately 10 years ago, research in the field of nitrate tolerance shifted toward the description of systemic, …

The role of angiotensin receptor blockers in heart failure.

The effectiveness of ACE inhibitors in reducing morbidity and mortality in patients with heart failure is largely attributable to their suppression of angiotensin II production. Despite chronic therapy with ACE inhibitors, angiotensin II levels may be incompletely suppressed and contribute to the high mortality of patients with heart failure. Recently, angiotensin receptor blockers, which block the effects rather than the production of angiotensin II, have become available. Angiotensin receptor blockers have been evaluated as both monotherapy and in combination with ACE inhibitors. In short term studies, angiotensin receptor blocker monotherapy appears to share many of the hemodynamic and clinical features of ACE inhibitors. In a long-term study, the Losartan Heart Failure Survival Study, angiotensin receptor blockers failed to demonstrate any beneficial effect over that seen with ACE inhibitors. The addition of an angiotensin receptor blocker to an ACE inhibitor appears to exert favorable short term hemodynamic, clinical, and neurohormonal effects. Four ongoing trials, Valsartan Heart Failure Trial, Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity, Optimal Therapy in Myocardial Infarction with Angiotensin II Antagonist Losartan study, and Valsartan In Acute Myocardial Infarction study, are evaluating the role of angiotensin receptor blockers either alone or in combination with ACE inhibitors in the management of left ventricular dysfunction. (c)2000 by CHF, Inc.

Short-term and long-term hemodynamic and clinical effects of metoprolol alone and combined with amlodipine in patients with chronic heart failure

Background Initiation of β-blocker therapy is often limited by worsening congestive heart failure, which may manifest as worsening hemodynamics. Deleterious hemodynamic effects might be mitigated with the vasodilation of combined calcium channel/β-blocker therapy. Methods and Results This prospective, randomized study assessed the safety and efficacy of metoprolol alone or combined with amlodipine on hemodynamic parameters at baseline, 2 hours after the first dose of study medication, and after 12 weeks of therapy in patients receiving background triple therapy for mild to severe heart failure. Functional, exercise, and hormonal status were assessed at baseline and end of study. Twenty-nine patients (mean age 50 ± 12.1 years) were enrolled; 21 completed 12 weeks of treatment. Mean ejection fraction at baseline was 13.4% ± 5.7%; 79% of patients had heart failure classified as New York Heart Association class III, and 66% had heart failure of idiopathic origin. Heart rate and blood pressure did not change with short-term therapy in either group. The first dose of both regimens produced significant increases in systemic vascular resistance and significant decreases in cardiac output and index and stroke volume and stroke work indexes; combination therapy acutely yielded small but statistically significant increases in pulmonary artery, pulmonary capillary wedge, and right atrial pressures. Long-term therapy with both regimens produced significant decreases in heart rate, systemic vascular resistance, and pulmonary capillary wedge pressure and significant increases in cardiac output and index and stroke volume and stroke work indexes. Combination therapy produced significant long-term decreases in blood pressure. Conclusions There was no further measurable benefit with the addition of amlodipine to metoprolol compared with the effects of metoprolol alone. Therapy with metoprolol alone and the combination of metoprolol and amlodipine was well tolerated in patients with mild to severe heart failure, as evidenced by a lack of adverse effects on hemodynamic parameters over the short term and clinical and hemodynamic improvement with long-term treatment. (Am Heart J 1999;138:261-8.)