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Sidney Goldstein

Publications and source records attributed to Sidney Goldstein.

At least 19 recordsLinked to original sources
PubMed2004

Echocardiographic predictors of prognosis after first acute myocardial infarction.

We prospectively studied 490 patients who had a first myocardial infarction and performed a complete 2-dimensional echocardiographic study <or=48 hours of admission. In addition to left ventricular ejection fraction, multiple echocardiographic parameters of left ventricular systolic and diastolic performances were found to be independent predictors of 2-year mortality rate and congestive heart failure.

Echocardiography↗
PubMed2004

Long-term effects of non-excitatory cardiac contractility modulation electric signals on the progression of heart failure in dogs.

OBJECTIVE: We previously showed that acute delivery of non-excitatory cardiac contractility modulation (CCM) electric signal during the absolute refractory period improved LV function in dogs with chronic heart failure (HF). In the present study we examined the long-term effects of CCM signal delivery on the progression of LV dysfunction and remodeling in dogs with chronic HF. METHODS: Chronic HF was produced in 12 dogs by multiple sequential intracoronary microembolizations. The CCM signal was delivered using a lead implanted in the distal anterior coronary vein. A right ventricular and a right atrial lead were implanted and used for timing of CCM signal delivery. In six dogs, CCM signals were delivered continuously for 6 h daily with an average amplitude of 3.3 V for 3 months. Six HF dogs did not have leads implanted and served as controls. RESULTS: In control dogs, LV end-diastolic volume (EDV) and LV end-systolic volume (ESV) increased (64+/-5 ml vs. 75+/-6 ml, P=0.003; 46+/-4 ml vs. 57+/-4 ml, P=0.003; respectively), and ejection fraction (EF) decreased (28+/-1% vs. 23+/-1%, P=0.001) over the course of 3 months of follow-up. In contrast, CCM-treated dogs showed a smaller increase in EDV (66+/-4 vs. 73+/-5 ml, P=0.01), no change in ESV, and an increase in EF from 31+/-1 to 34+/-2% (P=0.04) after 3 months of therapy. CONCLUSIONS: In dogs with HF, long-term CCM therapy prevents progressive LV dysfunction and attenuates global LV remodeling. These findings provide compelling rationale for exploring the use of CCM for the treatment of patients with chronic HF.

Animals↗
PubMed2004

The changing epidemiology of sudden death in heart failure.

Worsening and progressive heart failure has been the most common mode of death in patients with heart failure. With the development of drugs that primarily have modulation of the renin-angiotensin and sympathetic nervous systems as their mechanism, relative importance of progressive heart failure has decreased. Sudden death has become a larger issue and the dominant mode of death in heart failure. This change requires the clinician to redirect therapy to the prevention and treatment of sudden death.

Adrenergic beta-Antagonists↗
PubMed2004

Consistency of the beneficial effect of metoprolol succinate extended release across a wide range dose of angiotensin-converting enzyme inhibitors and digitalis.

BACKGROUND: The effects of beta-blockade with different extent of angiotensin-converting enzyme inhibitors (ACEI) and digitalization are unknown. To assess the effect of metoprolol succinate controlled release/extended release (CR/XL) combined with high versus low doses of ACEI and digitalis, we analyzed data from The Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) in which patients with heart failure and left ventricular ejection fraction < or =40% were randomized to metoprolol CR/XL versus placebo. METHODS AND RESULTS: Outcome was analyzed separately for those on a low dose (< or =median) of the ACEI or digitalis versus high dose (> median). The mean dose of ACEI in the high-dose group (n = 1457) was 3 times higher than that in the low-dose group (n = 2094). Mortality was reduced to a similar extent in the high- and low-dose ACEI subgroups (RR = .69 versus .64, respectively). Corresponding figures for combined mortality/all hospitalization and for mortality/hospitalization for heart failure were .85 versus .83, and .70 versus .68, respectively. Likewise, reduction in total mortality with metoprolol CR/XL was similar in patients receiving no digitalis (n = 1447; RR = .56), low dose (n = 1122; RR = .71), or high dose (n = 1421; RR = .71). CONCLUSION: This analysis of MERIT-HF demonstrates consistent and similar improvement in outcome of patients receiving metoprolol CR/XL when combined with either a high or low dose of an ACEI or digitalis, or no digitalis at all. Thus regardless of ACEI and digitalis dose and whether patients are treated with digitalis or not, it is very important to add a beta-blocker to the existing heart failure therapy. beta-blockers should not be withheld until target doses of ACEI have been achieved.

Adrenergic beta-Antagonists↗
PubMed2004

Beta blocker therapy in African American patients with heart failure.

Data from a number of clinical trials of beta blocker therapy in heart failure, although limited in the size of African American patients included, suggest that they achieve a similar benefit as Caucasians. African Americans were usually at higher risk when enrolled in all of these studies with a higher incidence of hypertension and diabetes mellitus. The only exception is the Beta Blocker Evaluation of Survival Trial (BEST) that studied the efficacy of Bucindolol in heart failure. In that study there appeared to be a unique differential effect in African Americans compared to Caucasians which may have been in part related to the severity of the disease.

Adrenergic beta-Antagonists↗
PubMed2003

Metoprolol CR/XL in black patients with heart failure (from the Metoprolol CR/XL randomized intervention trial in chronic heart failure).

A subgroup analysis was performed in black patients who participated in the Metoprolol CR/XL Randomized Intervention trial in Congestive Heart Failure trial. Results suggest a beneficial effect of beta blockade and support the use of beta blockers in black patients with clinically stable heart failure and left ventricular dysfunction.

Adrenergic beta-Antagonists↗
PubMed2003

Selective versus nonselective beta-blockade for heart failure therapy: are there lessons to be learned from the COMET trial?

The recently reported COMET trial found that the beta1/beta2/alpha1 receptor blocking agent carvedilol given in a relatively high beta1-receptor blocking dose regimen was superior in mortality reduction to immediate release metoprolol given in a relatively low beta1-receptor blocking dose schedule. We analyze the problems with the trial design of COMET from the standpoint of comparing 2 therapeutic agents at different positions on a common dose-response curve, and discuss the theoretical reasons why postjunctional adrenergic receptor blockade that is in addition to beta1-receptor antagonism will likely produce only minimal or no incremental benefit in chronic heart failure.

Adrenergic beta-Antagonists↗
PubMed2003

How should subgroup analyses affect clinical practice? Insights from the Metoprolol Succinate Controlled-Release/Extended-Release Randomized Intervention Trial in Heart Failure (MERIT-HF).

CONTEXT: The Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF), the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), and the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) have all demonstrated highly significant positive effects on total mortality as well as total mortality plus all-cause hospitalization in patients with heart failure. While none of these trials are large enough to provide definitive results in any particular subgroup, it is of interest for physicians to examine the consistency of results as regards efficacy and safety for various subgroups or risk groups. OBJECTIVE: To summarize results from both predefined as well as post-hoc subgroup analyses performed in the MERIT-HF trial, and to provide guidance as to whether any subgroup is at increased risk, despite an overall strongly positive effect, and to discuss the difficulties and limitations in conducting such subgroup analyses. For some subgroups we performed metaanalyses with data from the CIBIS II and COPERNICUS trials in order to obtain more robust data on mortality in subgroups with a small number of deaths (e.g. for women). SETTING: MERIT-HF was run in 14 countries, and randomized a total of 3,991 patients with symptomatic systolic heart failure (NYHA class II to IV with ejection fraction < or =0.40). Treatment was initiated with a very low dose with careful titration to a maximum target dose of 200 mg metoprolol succinate controlled release/extended release (CR/XL), or highest tolerated dose. MAIN OUTCOME MEASURES: Total mortality (first primary endpoint), total mortality plus all-cause hospitalization (second primary endpoint), and total mortality plus hospitalization for heart failure (first secondary endpoint) analyzed on a time to first event basis. RESULTS: Overall, MERIT-HF demonstrated a 34% reduction in total mortality ( p = 0.00009 nominal) and a 19% reduction for mortality plus all-cause hospitalization ( p = 0.00012). The first secondary endpoint of mortality plus hospitalization for heart failure was reduced by 31% ( p = 0.0000008). The results were remarkably consistent for both primary outcomes and the first secondary outcome across all predefined subgroups as well as nearly all post-hoc subgroups. Metoprolol CR/XL has been very well tolerated, overall as well as in all subgroups analyzed. Overall 87% of the patients reached a dose of 100 mg or more of metoprolol CR/XL once daily, and 64% reached the target dose of 200 mg once daily. CONCLUSION: Our results show that when carefully titrated, metoprolol CR/XL can safely be instituted for the overwhelming majority of outpatients with clinically stable systolic heart failure, with minimal side effects or deterioration. The time has come to overcome the barriers that physicians perceive to beta-blocker treatment, and to provide it to the large number of patients with heart failure in need of this therapy, including also high risk patients like elderly patients, patients with severe heart failure, and patients with diabetes. Because of the increased risk, these are the patients in whom treatment will have the greatest impact as shown by number of lives saved and number of hospitalizations avoided. The target dose should be strived for in all patients who tolerate this dose. We should expect some variation of the treatment effect around the overall estimate as we examine a large number of subgroups due to small sample size in subgroups and due to chance. However, we believe that the best estimate of treatment effect for any particular subgroup should be the overall effect observed in the trial.

Adrenergic beta-Antagonists↗
PubMed2003

Effects of the AT1-receptor antagonist eprosartan on the progression of left ventricular dysfunction in dogs with heart failure.

1. We examined the effects of eprosartan, an AT(1) receptor antagonist, on the progression of left ventricular (LV) dysfunction and remodelling in dogs with heart failure (HF) produced by intracoronary microembolizations (LV ejection fraction, EF 30 to 40%). 2. Dogs were randomized to 3 months of oral therapy with low-dose eprosartan (600 mg once daily, n=8), high-dose eprosartan (1200 mg once daily, n=8), or placebo (n=8). 3. In the placebo group, LV end-diastolic (EDV) and end-systolic (ESV) volumes increased after 3 months (68+/-7 vs 82+/-9 ml, P<0.004, 43+/-1 vs 58+/-7 ml, P<0.003, respectively), and EF decreased (37+/-1 vs 29+/-1%, P<0.001). In dogs treated with low-dose eprosartan, EF, EDV, and ESV remained unchanged over the course of therapy, whereas in dogs treated with high-dose eprosartan, EF increased (38+/-1 vs 42+/-1%, P<0.004) and ESV decreased (41+/-1 vs 37+/-1 ml, P<0.006), Eprosartan also decreased interstitial fibrosis and cardiomyocyte hypertrophy. 4. We conclude that eprosartan prevents progressive LV dysfunction and attenuates progressive LV remodelling in dogs with moderate HF and may be useful in treating patients with chronic HF.

Acrylates↗
PubMed2003

Cardiac contractility modulation with nonexcitatory electric signals improves left ventricular function in dogs with chronic heart failure.

BACKGROUND: Nonexcitatory electrical, signals termed cardiac contractility modulation (CCM) have been shown to improve contractile force of isolated papillary muscles. In this study, we examined the effects of CCM signal delivery on left ventricular function in dogs with chronic heart failure (HF). METHODS AND RESULTS: Chronic HF (ejection fraction </=35%) was produced in 7 dogs by intracoronary microembolizations. The CCM signal was delivered during the absolute refractory period using a lead implanted in the anterior coronary vein. A right ventricular and an atrial lead were implanted and used for timing of the CCM signal delivery. Hemodynamic measurements were made at baseline and at 1, 2, 3, 4, 5, and 6 hours after initiating CCM signal delivery. Ejection fraction increased from 31 +/- 1% at baseline to 41 +/- 1% at 1 hour (P <.05), 42 +/- 1% at 3 hours (P <.05), and 44 +/- 2% at 6 hours (P <.05). Similarly, stroke volume increased from 26 +/- 2 mL to 31 +/- 3 mL at 1 hour (P <.05), 33 +/- 3 mL at 3 hours (P <.05), and 34 +/- 3 mL at 6 hours (P <.05). There were no significant changes compared to baseline in ejection fraction or stroke volume in 5 HF control dogs studied for up to 4 hours. CONCLUSION: In dogs with HF, CCM signal delivery for 6 hours elicited marked improvement in LV function. This novel approach may represent a useful adjunctive therapy for the treatment of patients with HF.

Animals↗
PubMed2003

Use of beta-blockers in congestive heart failure.

While beta-adrenergic blockers have been used for decades in a variety of cardiovascular illnesses, they have traditionally been avoided in chronic heart failure. In spite of significant advances in management, mortality in patients suffering from heart failure remains unacceptably high and new therapies are urgently needed. Recently, several large clinical trials have shown a significant reduction in both morbidity and mortality in heart failure patients when beta-blockers are added to standard therapy. While further investigation is warranted in certain subgroups, the use of beta-adrenergic blockers in New York Heart Association (NYHA) class II to IV heart failure should now be considered routine. The purpose of this article is to outline and review the five major clinical trials of beta-blocker therapy in chronic heart failure; the US Carvedilol heart failure Program (USCP), the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), the Metoprolol CR/XL Randomized Intervention Trial in chronic Heart Failure (MERIT-HF), the Beta-blocker Evaluation of Survival Trial (BEST) and the Carvedilol Prospective Randomized Cumulative Survival trial (COPERNICUS), and to aid the reader in the selection of appropriate candidates for beta-blocker therapy.

Adrenergic beta-Antagonists↗
PubMed2003

A COMET lost.

Explore the source record for details and available documents.

Adrenergic beta-Antagonists↗
PubMed2002

Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure.

BACKGROUND: In heart failure (HF), aldosterone has been implicated in the formation of reactive interstitial fibrosis, a maladaptation that contributes to left ventricular (LV) remodeling. Eplerenone is a novel selective aldosterone blocker. The present study examined the effects of long-term monotherapy with eplerenone on the progression of LV dysfunction and remodeling in dogs with chronic HF. METHODS AND RESULTS: HF was produced in 14 dogs by intracoronary microembolizations that were discontinued when LV ejection fraction (EF) was between 30% and 40%. Two weeks after the last embolization, dogs were randomized to 3 months of oral therapy with eplerenone (10 mg/kg twice daily, n=7) or no therapy at all (control, n=7). Hemodynamic measurements were made just before randomization and were repeated at the end of 3 months of therapy. In control dogs, LV end-diastolic and end-systolic volume increased significantly (62+/-4 versus 68+/-4 mL, P<0.001, and 38+/-3 versus 47+/-3 mL, P<0.001, respectively), and EF decreased significantly (38+/-1% versus 31+/-2%, P<0.001). In contrast, end-diastolic volume, end-systolic volume, and EF remained unchanged during the 3 months of treatment in eplerenone-treated dogs. LV end-diastolic wall stress increased significantly in control dogs but decreased significantly in eplerenone-treated dogs. Compared with control, eplerenone was associated with a 28% reduction in cardiomyocyte cross-sectional area, a 37% reduction of volume fraction of reactive interstitial fibrosis, and a 34% reduction of volume fraction of replacement fibrosis. CONCLUSIONS: Our results indicate that long-term therapy with eplerenone prevents progressive LV dysfunction and attenuates LV remodeling in dogs with chronic HF.

Administration, Oral↗
PubMed2002

Dose of metoprolol CR/XL and clinical outcomes in patients with heart failure: analysis of the experience in metoprolol CR/XL randomized intervention trial in chronic heart failure (MERIT-HF).

OBJECTIVES: We performed a post-hoc subgroup analysis in the Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) with the aim of reporting on the heart rate (HR) response during the titration phase and clinical outcomes from the three-month follow-up visit to end of study in two dosage subgroups: one that had reached more than 100 mg of metoprolol CR/XL once daily (high-dose group; n = 1,202; mean 192 mg) and one that had reached 100 mg or less (low-dose group; n = 412; mean 76 mg). BACKGROUND: Clinicians have questioned whether patients need to reach the target beta-blocker dose to receive benefit. METHODS; Outcome (Cox-adjusted) was compared with all placebo patients with dose available at the three-month visit (n = 1,845). RESULTS: Data indicated somewhat higher risk in the low-dose group compared with the high-dose group. Heart rate was reduced to a similar degree in the two dose groups, indicating higher sensitivity for beta-blockade in the low-dose group. The reduction in total mortality with metoprolol CR/XL compared with placebo was similar: 38% (95% confidence interval [CI], 16 to 55) in high-dose group (p = 0.0022) and also 38% (95% CI, 11 to 57) in the low-dose group (p = 0.010). CONCLUSIONS: Risk reduction was similar in the high- and low-dose subgroups, which, at least partly, may be the result of similar beta-blockade as judged from the HR response. The results support the idea of an individualized dose-titration regimen, which is guided by patient tolerability and the HR response. Further research is needed to shed light on why some patients respond with a marked HR reduction and reduced mortality risk on a relatively small dose of a beta-blocker.

Adrenergic beta-Antagonists↗
PubMed2002

Benefits of beta-blocker therapy for heart failure: weighing the evidence.

Our understanding of factors contributing to the progression of heart failure has advanced dramatically over the past 2 decades. We have also gained considerable insight into the pharmacology of beta-adrenergic receptor blockers (beta-blockers). Based on this knowledge, we can now appreciate the potential of these drugs for the treatment of heart failure. Several beta-blockers have been shown to be clinically effective in the treatment of heart failure. Critical evaluation of the evidence from basic research studies, as well as clinical trials in patients with heart failure, helps to delineate the theoretical and clinical benefits of beta-blockers.

Adrenergic beta-Antagonists↗
PubMed2002

Effects of pre-existing left ventricular hypertrophy on ventricular dysfunction and remodeling following myocardial infarction in rats.

BACKGROUND: Myocardial hypertrophy is a characteristic component of left ventricular (LV) remodeling that may, at least initially, have a beneficial effect on LV function following myocardial infarction (MI). In the present study, we examine the effects of pre-existing left ventricular hypertrophy (LVH) on LV function and chamber enlargement following MI in inbred Lewis rats. METHODS: The one-kidney, one-clip model (1K1C) of hypertension was used to produce LVH. Four weeks after 1K1C, rats were randomized to left anterior descending coronary artery ligation (LVH + MI group, n = 8) or sham ligation (LVH group, n = 11). Another group of rats underwent sham 1K1C. Four weeks later, they were randomized to coronary ligation (MI group, n = 12) or sham ligation (Sham group, n = 12). LV end-diastolic pressure (EDP, mm Hg), end-diastolic volume (EDV, ml), end-systolic volume (ESV, ml) and ejection fraction (EF) (determined by angiography) were measured in all groups 2 months after MI. RESULTS: LV EDP was 20 +/- 2 mm Hg in the LVH + MI group compared with 9 +/- 1 mm Hg in the MI group (p < 0.05). LV EDV and ESV were significantly greater with LVH + MI than with MI alone (EDV 0.90 +/- 0.03 vs 0.75 +/- 0.02 ml; ESV 0.68 +/- 0.02 vs 0.50 +/- 0.03 ml; p < 0.05). Pre-existing LVH resulted in a greater reduction in EF following MI (25 +/- 2% for LVH + MI vs 34 +/- 2% for MI alone; p < 0.05). CONCLUSIONS: Pre-existing LVH is an important determinant of progressive LV dysfunction and remodeling following MI in Lewis inbred rats.

Animals↗