PubMed Health⌕ Search

Biomedical subjects

Marvin A Konstam

Publications and source records attributed to Marvin A Konstam.

At least 19 recordsLinked to original sources
PubMed2026

Subgroups and Special Populations in Heart Failure Clinical Trials: Insights From the HFC-ARC Expert Consensus Panel.

In the evolving landscape of heart failure (HF) management, the identification and analysis of subgroups and special populations within clinical trials are crucial for enhancing clinical decision-making, guiding further research, and understanding heterogeneity in study outcomes. This expert consensus document results from the collaborative efforts of the Heart Failure Collaboratory and the Heart Failure Collaboratory Academic Research Consortium, which brought together stakeholders from academia, industry, the U.S. Food and Drug Administration, and patient representatives. The purpose of this assembly was to propose standardized definitions and critical endpoint considerations essential for shaping the design and conduct of clinical trials for drugs and devices in the field of HF. In this context, we propose definitions and endpoints for specific subgroups and special populations in the spectrum of HF. We enhanced the precision, efficacy, and applicability of clinical research and promote more "personalized" approaches to interpretation of clinical trials. Furthermore, we explore the burgeoning field of gene therapy as a promising avenue for addressing the genetic basis of certain cardiomyopathies within these specialized patient groups. We focus especially on methodological considerations for subgroup analyses in large-scale trials, highlighting the importance of proper interpretation of subgroups and best practices for identifying heterogeneity suggestive of differential treatment effects, including when these analyses should be considered hypothesis-generating and requiring subsequent validation. We advocate for a methodical approach to clinical trial design, one that prioritizes the strategic identification of subgroups and employs appropriate statistical methodologies to ensure the reliability and clinical relevance of findings. Through this lens, we envision a pathway toward more personalized and effective treatments for HF, ultimately aiming to improve patient outcomes by leveraging the insights garnered from meticulously designed and comprehensively analyzed clinical trials.

Humans↗
PubMed2006

Vasopressin v(2) receptor blockade with tolvaptan versus fluid restriction in the treatment of hyponatremia.

Hyponatremia is common and is associated with a poor prognosis. Traditional management with fluid restriction is difficult to maintain, and it is often ineffective. The objective of this study was to determine the effect of tolvaptan versus fluid restriction on serum sodium concentration. The study was a prospective, multicenter, randomized, active-controlled, open-label trial. Twenty-eight hospitalized subjects with serum sodium <135 mmol/L were enrolled in the study. After a 2-day run-in period, subjects were randomized 2:1 to tolvaptan alone (n = 17) or fluid restriction (1,200 ml/day) plus placebo (n = 11). Oral tolvaptan was started at 10 mg/day and increased to 60 mg/day as needed. Treatment was continued for up to 27 days, and follow-up continued for up to 65 days. The primary end point was the normalization of serum sodium, defined as >135 mmol/L or a > or =10% increase from baseline. At the last inpatient visit, serum sodium had increased by 5.7 +/- 3.2 mmol/L in the tolvaptan group and 1.0 +/- 4.7 mmol/L in the fluid restriction group (p = 0.0065). No differences in adverse events were observed between the groups. In conclusion, tolvaptan appears to be more effective than fluid restriction at correcting hyponatremia in hospitalized subjects, without an increase in adverse events.

Aged↗
PubMed2006

Hospital cost effect of a heart failure disease management program: the Specialized Primary and Networked Care in Heart Failure (SPAN-CHF) trial.

BACKGROUND: Determine the effect on hospitalization cost of a heart failure disease management (HFDM) program delivered within a diverse provider network as demonstrated in the SPAN-CHF randomized controlled trial. METHODS: The SPAN-CHF trial was a prospective randomized assessment of the effectiveness of HFDM delivered for 90 days across a diverse provider network in a heterogeneous population of 200 patients. Baseline clinical and demographic data were obtained on each patient, mortality was monitored, and hospitalizations were tracked for 90 days. Cost estimates for each hospitalization were based on a subsample of patients seen at Tufts-New England Medical Center for whom hospitalization costs were calculated. Heart failure disease management program costs were estimated using a programmatic budget model. Hospital utilization and cost data were combined to estimate medical costs for intervention and control groups. RESULTS: Heart failure disease management had a favorable effect on heart failure hospitalization, which was partially offset by noncardiac hospitalizations. The relative odds of at least one all-cause hospitalization during the intervention period trended less for the intervention group compared with the control group (0.76 [95% CI 0.38-1.51]). The point estimate of the differential hospitalization cost between control and intervention groups was a reduction in cost of $375 per patient. The net effect including the costs of the program was an increase of $488 per patient for the intervention group compared with the control group. The program would have been cost saving if HFDM costs had been 24% lower. CONCLUSION: The HFDM intervention, administered over 90 days to patients hospitalized for heart failure, succeeded in reducing the rate of heart failure hospitalizations, although this effect was partially offset by an increase in non-heart failure hospitalizations. The resulting modest reduction in all-cause hospitalization costs was exceeded by the cost of the intervention. Thus, although the reduction in heart failure may be interpreted as an improvement in health status, it could not be considered cost saving.

Cardiac Output, Low↗
PubMed2005

Continuous aortic flow augmentation: a pilot study of hemodynamic and renal responses to a novel percutaneous intervention in decompensated heart failure.

BACKGROUND: Diminished aortic flow may induce adverse downstream vascular and renal signals. Investigations in a heart failure animal model have shown that continuous aortic flow augmentation (CAFA) achieves hemodynamic improvement and ventricular unloading, which suggests a novel therapeutic approach to patients with heart failure exacerbation that is inadequately responsive to medical therapy. METHODS AND RESULTS: We studied 24 patients (12 in Europe and 12 in the United States) with heart failure exacerbation and persistent hemodynamic derangement despite intravenous diuretic and inotropic and/or vasodilator treatment. CAFA (mean+/-SD 1.34+/-0.12 L/min) was achieved through percutaneous (n=19) or surgical (n=5) insertion of the Cancion system, which consists of inflow and outflow cannulas and a magnetically levitated and driven centrifugal pump. Hemodynamic improvement was observed within 1 hour. Systemic vascular resistance decreased from 1413+/-453 to 1136+/-381 dyne.s.cm(-5) at 72 hours (P=0.0008). Pulmonary capillary wedge pressure decreased from 28.5+/-4.9 to 19.8+/-7.0 mm Hg (P<0.0001), and cardiac index (excluding augmented aortic flow) increased from 1.97+/-0.44 to 2.27+/-0.43 L.min(-1).m(-2) (P=0.0013). Serum creatinine trended downward during treatment (overall P=0.095). There were 8 complications during treatment, 7 of which were self-limited. Hemodynamics remained improved 24 hours after CAFA discontinuation. CONCLUSIONS: In patients with heart failure and persistent hemodynamic derangement despite intravenous inotropic and/or vasodilator therapy, CAFA improved hemodynamics, with a reduction in serum creatinine. CAFA represents a promising, novel mode of treatment for patients who are inadequately responsive to medical therapy. The clinical impact of the observed hemodynamic improvement is currently being explored in a prospective, randomized, controlled trial.

Adult↗
PubMed2005

Reliability of ventricular remodeling as a surrogate for use in conjunction with clinical outcomes in heart failure.

As the number of treatments for heart failure (HF) increases and mortality decreases in the setting of clinical trials, the size of the study population required to demonstrate an incremental difference in survival with each new agent may become prohibitive. There has been increasing interest in identifying and validating surrogate end points for assessing HF treatments. The strong association between ventricular remodeling and clinical outcomes supports the incorporation of measures of ventricular volumes into clinical trials of new therapies for HF. A finding of reduced left ventricular volumes renders a particular survival signal more credible. It is therefore appropriate to consider ventricular remodeling in conjunction with outcome events in the construct of clinical trials in HF.

Heart Failure↗
PubMed2005

ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society.

Explore the source record for details and available documents.

Adult↗
PubMed2005

The economic effect of a tertiary hospital-based heart failure program.

OBJECTIVES: This study was designed to determine the economic effect of a tertiary heart failure (HF) program at an academic medical center. BACKGROUND: Most hospitals use cross-sectional financial models to analyze the economic contribution of clinical programs for a budget period. We estimated the incremental value of a tertiary hospital HF program on the basis of the longitudinal utilization of a sample of HF patients. METHODS: The primary data source was a sample of 82 HF patients referred for cardiac transplant evaluation at an academic medical center during calendar years 2000 to 2001. Cumulative recurrent rates of utilization, cost, and reimbursement for hospital services were computed as functions of time using reliability models. The economic contribution of patients transplanted was contrasted with those not transplanted. RESULTS: Mean hospitalizations and outpatient encounters per patient at the end of the first year of follow-up for those transplanted were 2.1 (95% confidence interval [CI] 1.6 to 2.7) and 11.9 (95% CI 9.2 to 15.4), compared with 1.1 (95% CI 0.8 to 1.6) and 6.0 (95% CI 4.8 to 7.6), respectively, for those not transplanted. Mean revenue and direct cost per patient were 194,470 dollars (95% CI 136,683 dollars to 276,689 dollars) and 146,623 dollars (95% CI 96,377 dollars to 233,065 dollars), respectively, for transplanted patients and 43,587 dollars (95% CI 28,149 dollars to 67,503 dollars) and 33,424 dollars (95% CI 21,584 dollars to 51,760 dollars), respectively, for non-transplanted patients. The point estimates of first-year contribution margins per patient for transplanted and non-transplanted patients were 47,847 dollars and 10,163 dollars, respectively. CONCLUSIONS: Newly evaluated patients for cardiac transplantation at an academic medical center generated substantial incident demands for inpatient and outpatient services over a two-year follow-up period. The estimated contribution margin associated with these services was positive. Hospitals without cardiac transplantation that serve high-acuity HF patients may generate favorable long-term contribution margins, on the basis of the results for the non-transplant group.

Academic Medical Centers↗
PubMed2005

Ventricular assist device therapy normalizes inducible nitric oxide synthase expression and reduces cardiomyocyte apoptosis in the failing human heart.

OBJECTIVES: We examined the effect of mechanical unloading with ventricular assist device (VAD) therapy on myocardial inducible nitric oxide synthase (iNOS) expression and cardiomyocyte apoptosis in patients with end-stage heart failure (HF). BACKGROUND: Despite advances in medical therapy, HF continues to be a progressive and ultimately fatal disorder. High levels of iNOS expression are present in the myocardium of failing hearts, suggesting a potential role for iNOS in HF progression. METHODS: Inducible NOS protein expression was analyzed by Western blotting and cardiomyocyte apoptosis by terminal deoxynucleotidyltransferase dUTP nick end-labeling (TUNEL) in myocardial samples from failing hearts. Included in these analyses were tissues from 9 patients at the time of transplantation (HF-transplant group), 10 patients at the time of VAD insertion (pre-VAD group), and 11 patients undergoing transplant after VAD support (post-VAD group). Seven control samples were obtained at autopsy. RESULTS: Low or undetectable levels of iNOS were present in controls (0.005 +/- 0.002). The HF-transplant and pre-VAD myocardial specimens exhibited a marked increase in iNOS expression (1.48 +/- 0.34 and 1.29 +/- 0.26, respectively; p < 0.01 for both vs. controls). The increase in iNOS expression was reversed in the post-VAD group (0.36 +/- 0.16; p < 0.01 vs. HF-transplant and pre-VAD groups). The rate of TUNEL-positive cardiomyocytes was high in the pre-VAD group and significantly lower in the post-VAD group (0.64 +/- 0.15% in pre-VAD group and 0.16 +/- 0.07% in post-VAD group; p < 0.01). The iNOS levels correlated significantly with cardiomyocyte apoptosis (r = 0.66, p < 0.01). CONCLUSIONS: Therapy with VAD normalizes iNOS expression in association with diminished cardiomyocyte apoptosis in the failing heart. Further work is required to define whether a causal relationship exists between iNOS and cardiomyocyte apoptosis.

Adult↗
PubMed2005

Gender-specific patterns of left ventricular and myocyte remodeling following myocardial infarction in mice deficient in the angiotensin II type 1a receptor.

Left ventricular (LV) remodeling after myocardial infarction (MI) results from hypertrophy of myocytes and activation of fibroblasts induced, in part, by ligand stimulation of the ANG II type 1 receptor (AT1R). The purpose of the present study was to explore the specific role for activation of the AT 1a R subtype in post-MI remodeling and whether gender differences exist in the patterns of remodeling in wild-type and AT 1a R knockout (KO) mice. AT 1a R-KO mice and wild-type littermates underwent coronary ligation to induce MI or sham procedures; echocardiography and hemodynamic evaluation were performed 6 wk later, and LV tissue was harvested for infarct size determination, morphometric measurements, and gene expression analysis. Survival and infarct size were similar among all male and female wild-type and AT 1a R-KO mice. Hemodynamic indexes were also similar except for lower systolic blood pressure in the AT 1a R-KO mice compared with wild-type mice. Male and female wild-type and male AT 1a R-KO mice developed similar increases in LV chamber size, LV mass corrected for body weight (LV/BW), and myocyte cross-sectional area (CSA). However, female AT 1a R-KO mice demonstrated no increase in LV/BW and myocyte CSA post-MI compared with shams. Both male and female wild-type mice demonstrated higher atrial natriuretic peptide (ANP) levels after MI, with female wild types being significantly greater than males. However, male and female AT 1a R-KO mice developed no increase in ANP gene expression with MI despite an increase in LV mass and myocyte size in males. These data support that gender-specific patterns of LV and myocyte hypertrophy exist after MI in mice with a disrupted AT 1a R gene, and suggest that myocyte hypertrophy post-MI in females relies, in part, on activation of the AT 1a R. Further work is necessary to explore the potential mechanisms underlying these gender-based differences.

Animals↗
PubMed2005

Highlights of the 2004 scientific sessions of the Heart Failure Society of America, Toronto, Canada, September 12 to 15, 2004.

The annual scientific meeting of the Heart Failure Society of American (HFSA) brings together cardiologists, surgeons, nurses, and allied health care workers who are interested in improving the diagnosis, treatment, quality of life, and survival of patients affected by heart failure. The meeting integrates the best of basic advances with clinical trials and outcomes observations in a single seamless forum. The meeting in Toronto, Canada, attracted close to 3,000 attendees.

Cell Transplantation↗
PubMed2005

Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial.

BACKGROUND: Selective inhibition of cyclooxygenase-2 (COX-2) may be associated with an increased risk of thrombotic events, but only limited long-term data have been available for analysis. We report on the cardiovascular outcomes associated with the use of the selective COX-2 inhibitor rofecoxib in a long-term, multicenter, randomized, placebo-controlled, double-blind trial designed to determine the effect of three years of treatment with rofecoxib on the risk of recurrent neoplastic polyps of the large bowel in patients with a history of colorectal adenomas. METHODS: A total of 2586 patients with a history of colorectal adenomas underwent randomization: 1287 were assigned to receive 25 mg of rofecoxib daily, and 1299 to receive placebo. All investigator-reported serious adverse events that represented potential thrombotic cardiovascular events were adjudicated in a blinded fashion by an external committee. RESULTS: A total of 46 patients in the rofecoxib group had a confirmed thrombotic event during 3059 patient-years of follow-up (1.50 events per 100 patient-years), as compared with 26 patients in the placebo group during 3327 patient-years of follow-up (0.78 event per 100 patient-years); the corresponding relative risk was 1.92 (95 percent confidence interval, 1.19 to 3.11; P=0.008). The increased relative risk became apparent after 18 months of treatment; during the first 18 months, the event rates were similar in the two groups. The results primarily reflect a greater number of myocardial infarctions and ischemic cerebrovascular events in the rofecoxib group. There was earlier separation (at approximately five months) between groups in the incidence of nonadjudicated investigator-reported congestive heart failure, pulmonary edema, or cardiac failure (hazard ratio for the comparison of the rofecoxib group with the placebo group, 4.61; 95 percent confidence interval, 1.50 to 18.83). Overall and cardiovascular mortality was similar in the two groups. CONCLUSIONS: Among patients with a history of colorectal adenomas, the use of rofecoxib was associated with an increased cardiovascular risk.

Adenomatous Polyps↗
PubMed2005

Comparison of losartan and captopril on heart failure-related outcomes and symptoms from the losartan heart failure survival study (ELITE II).

BACKGROUND: Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors improves outcomes and symptoms in patients with heart failure (HF). We compared effects of losartan to captopril on mortality, morbidity, and functional status for patients in the ELITE II study. METHODS AND RESULTS: A total of 3152 patients, aged 60 years or older, with New York Heart Association (NYHA) classes II to IV HF and ejection fraction < or = 40% were assigned to receive losartan 50 mg once daily or captopril 50 mg 3 times daily. Outcome measures included all-cause and HF-related mortality, hospitalizations, and discontinuations; change in NYHA class; and quality of life (QoL). HF-related outcomes were not significantly different between therapies. Similar improvements from baseline (P < .01) in NYHA class were observed within both treatment groups. Among 1856 QoL participants, 1343 patients survived at least 1 year; the QoL for 1-year survivors improved in both treatment groups (P < .001 vs baseline) and did not differ between groups. CONCLUSIONS: In ELITE II, the effects of losartan on HF-related outcomes, NYHA class, and QoL were not superior to those of captopril. Although angiotensin-converting enzyme inhibitors remain the treatment of choice for patients with HF, the similarity of the findings in the present analysis supports a role for angiotensin-receptor antagonists in this patient population.

Aged↗
PubMed2005

Rationale and design of the multicenter, randomized, double-blind, placebo-controlled study to evaluate the Efficacy of Vasopressin antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST).

BACKGROUND: Hospitalizations for worsening heart failure due to fluid overload (congestion) are common. Agents that treat congestion without causing electrolyte abnormalities or worsening renal function are needed. Tolvaptan is an oral vasopressin (V 2 ) antagonist that decreases body weight and increases urine volume without inducing renal dysfunction or hypokalemia. The Efficacy of Vasopressin antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial is evaluating mortality, morbidity, and patient-assessed global clinical status in patients treated with tolvaptan compared with standard care. METHODS AND RESULTS: Patients are eligible for inclusion if they have a reduced left ventricular ejection fraction and are hospitalized for worsening heart failure with evidence of systemic congestion. Patients are randomized 1:1 to tolvaptan 30 mg/day or matching placebo for a minimum of 60 days. Time to all-cause mortality and time to cardiovascular mortality or heart failure hospitalization are the coprimary end points. Patient-assessed global clinical status and quality of life are also evaluated. EVEREST will be continued until 1065 deaths occur. As of April 18, 2005, 2260 patients have been enrolled. CONCLUSION: Tolvaptan has been shown to reduce body weight in patients with worsening heart failure without inducing renal dysfunction or causing hypokalemia. The results of EVEREST will determine whether these effects translate into improved clinical outcomes.

Antidiuretic Hormone Receptor Antagonists↗