Cardiorenal Interactions Nohria, Anju, MD; Hasselblad, Vic, PhD; Stebbins, Amanda, PhD ...
Journal of the American College of Cardiology,
04/2008, Volume:
51, Issue:
13
Journal Article
Peer reviewed
Open access
Cardiorenal Interactions: Insights From the ESCAPE Trial Anju Nohria, Vic Hasselblad, Amanda Stebbins, Daniel F. Pauly, Gregg C. Fonarow, Monica Shah, Clyde W. Yancy, Robert M. Califf, Lynne W. ...Stevenson, James A. Hill Examination of the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) database shows that baseline renal insufficiency impacts outcomes more than worsening renal function (WRF) in patients with advanced decompensated heart failure. Neither baseline renal function nor WRF were explained by measured cardiac hemodynamics. These results suggest that poor forward flow alone does not explain the renal perturbations seen in advanced heart failure. In-hospital hemodynamic optimization using a pulmonary artery catheter–guided treatment strategy does not prevent WRF or improve renal function and short- and long-term outcomes compared with a strategy based on clinical assessment alone.
Abstract Background Hodgkin lymphoma (HL) survivors treated with thoracic radiation therapy (RT) have impaired exercise tolerance and increased cardiovascular mortality. Objectives The purpose of ...this study was to evaluate the prevalence of autonomic dysfunction and its implications on exercise capacity and mortality in long-term survivors of HL. Methods Exercise parameters in 263 HL survivors referred for exercise treadmill testing at a median interval of 19 years after RT were compared with 526 age-, sex-, and cardiovascular risk score–matched control subjects. Within the RT cohort, the presence of autonomic dysfunction, defined by an elevated resting heart rate (HR) (≥80 beats/min) and abnormal heart rate recovery (HRR) at 1 min (≤12 beats/min if active cool-down, or ≤18 beats/min if passive recovery), was correlated with exercise capacity and all-cause mortality over a median follow-up of 3 years. Results RT was associated with elevated resting HR and abnormal HRR after adjusting for age, sex, cardiovascular risk factors, medications, and indication for exercise treadmill testing: odds ratio: 3.96 (95% confidence interval CI: 2.52 to 6.23) and odds ratio: 5.32 (95% CI: 2.94 to 9.65), respectively. Prevalence of autonomic dysfunction increased with radiation dose and time from RT. Both elevated resting HR and abnormal HRR were associated with reduced exercise capacity in RT patients. Abnormal HRR was also associated with increased all-cause mortality (age-adjusted hazard ratio: 4.60 95% CI: 1.62 to 13.02). Conclusions Thoracic RT is associated with autonomic dysfunction, as measured by elevated resting HR and abnormal HRR. These abnormalities are associated with impaired exercise tolerance, and abnormal HRR predicts increased all-cause mortality in RT patients.
Cardiac allograft vasculopathy (CAV), the major cause of late allograft loss after cardiac transplantation, results from donor-directed cellular and humoral alloimmune responses. Graft vascular ...endothelial cells (EC) are primary targets of these destructive responses, suggesting that factors associated with endothelial injury and repair could serve as biomarkers of CAV.
Using a protein profiler array platform, we measured the levels of 55 angiogenesis-related proteins in sera from 33 adult heart transplant recipients, including 17 with angiographically documented CAV and 16 age- and gender-matched controls without CAV. All patients were >2 years after heart transplant.
The study population was 75% male with a mean age of 62 ± 11 years. On average, patients were 12 ± 5 years after heart transplantation. We found that vascular endothelial growth factor (VEGF)-C, VEGF-A, angiopoietin-2, artemin, urokinase-type plasminogen activator and vasohibin were strongly associated with established CAV (all p < 0.01). Multivariable modeling identified VEGF-C, VEGF-A and platelet factor-4 (PF-4) as significant independent biomarkers of CAV. Furthermore, receiver-operating characteristic curve analysis demonstrated that the combination of all 3 molecules provided outstanding performance for the diagnosis of CAV (area under the curve AUC = 0.98; p < 0.001).
Serum levels of VEGF-C, VEGF-A and PF-4 demonstrate strong associations with established CAV and, together with related angiogenesis factors, may serve as a reliable, non-invasive diagnostic test for CAV in cardiac transplant recipients.
Abstract Background STARBRITE, a multicenter randomized pilot trial, tested whether outpatient diuretic management guided by B-type natriuretic peptide (BNP) and clinical assessment resulted in more ...days alive and not hospitalized over 90 days compared with clinical assessment alone. Methods and Results A total of 130 patients from 3 sites with left ventricular ejection fraction ≤35% were enrolled during hospitalization for heart failure (HF) and randomly assigned to therapy guided by BNP and clinical assessment (BNP strategy) or clinical assessment alone. The clinical goal was resolution of congestion without hypotension or renal dysfunction. In the BNP arm, therapy was adjusted to achieve optimal fluid status, defined as the BNP level and congestion score obtained at the time of discharge. In the clinical assessment arm, therapy was titrated to achieve optimal fluid status, represented by the patient’s signs and symptoms at the time of discharge. Exclusion criteria were serum creatinine >3.5 mg/dL and acute coronary syndrome. Follow-up was done in HF clinics. BNP was measured with the use of a rapid assay test. There was no significant difference in number of days alive and not hospitalized (hazard ratio 0.72, 95% confidence interval 0.41–1.27; P = .25), change in serum creatinine, or change in systolic blood pressure (SBP). BNP strategy was associated with a trend toward a lower blood urea nitrogen (24 mg/dL vs 29 mg/dL; P = .07); BNP strategy patients received significantly more angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and the combination of ACE inhibitor or angiotensin receptor blocker plus beta-blockers. Conclusions BNP strategy was not associated with more days alive and not hospitalized, but the strategy appeared to be safe and was associated with increased use of evidence-based medications.
Abstract Background In patients with advanced heart failure (HF), elevated jugular venous pressure (JVP) is the most reliable sign of elevated left-sided filling pressures. However, discordance ...between right- and left-sided filling pressure s (R-L mismatch) could lead to inadequate or excessive therapy guided by JVP. We determined the prevalence of R-L mismatch in the current era and investigated whether mismatch might be identified from clinical information. Methods and Results Right-sided heart catheterization was performed in 537 consecutive patients hospitalized with advanced HF during complete transplantation evaluation. Patients with high filling pressures were categorized as matched (right atrial pressure (RAP) ≥10 mm Hg and pulmonary wedge pressure (PCWP) ≥22 mm Hg), high-R mismatch (RAP ≥10 but PCWP <22 mm Hg) or high-L mismatch (PCWP ≥22 but RAP <10 mm Hg). Among all of the patients, 195 (36%) were matched low and 194 (36%) were matched high, and 148 (28%) had R-L mismatch. Among patients with high filling pressures, 194 (57%) were matched high and 82 (24%) had high-L and 66 (19%) high-R mismatch. Mismatches were not associated with differences in demographic or clinical data, including pulmonary and hepatic function, or severity of valvular regurgitation and right ventricular function by echo. However, among all patients with RAP ≥10 mm Hg, pulmonary artery systolic pressure (PASP) was higher in those patients with matched high left- and right-sided pressures (59 ± 12 mm Hg) versus high-R mismatch (41 ± 13 mm Hg; P < .0001). Similarly among all patients with low RAP, PASP was lower in patients with matched low right- and left-side pressures (33 ± 11 mm Hg) versus high-L mismatch (53 ± 13 mm Hg; P < .0001). Conclusions R-L mismatch was present in >1 in 4 total patients, and >1 in 3 with elevated filling pressures. Regardless of clinical history, when empiric therapy to optimize volume status to JVP is not effective, additional measurement should be considered to establish the R-L relationship.
This study sought to assess the effects of neurohormonal therapies in preventing cardiotoxicity in patients receiving chemotherapy.
Various cardioprotective approaches have been evaluated to prevent ...chemotherapy-related cardiotoxicity; however, their overall utility remains uncertain.
This meta-analysis included randomized clinical trials of adult patients that underwent chemotherapy and neurohormonal therapies (β-blockers, mineralocorticoid receptor antagonists, or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers) versus placebo with follow-up ≥4 weeks. The primary outcome was change in left ventricular ejection fraction (LVEF) from baseline to the end of the trial. Other outcomes of interest were measures of LV size, strain, and diastolic function. Pooled estimates for each outcome were reported as standardized mean difference and weighted mean difference between the neurohormonal therapy and placebo groups using random effects models.
We included 17 trials, collectively enrolling 1,984 participants. In pooled analysis, neurohormonal therapy (vs. placebo) was associated with significantly higher LVEF on follow-up (standardized mean difference: +1.04 95% confidence interval (CI): 0.57 to 1.50) but with significant heterogeneity in the pooled estimate (I2 = 96%). Compared with placebo-treated patients, those randomized to neurohormonal therapies experienced a 3.96% (95% CI: 2.90 to 5.02) less decline in LVEF estimated by weighted mean difference, but with significant heterogeneity (I2 = 98%). There was a trend toward lower adverse clinical events with neurohormonal therapy (vs. placebo) that did not meet statistical significance (risk ratio: 0.80 95% CI: 0.53 to 1.20; I2 = 71%).
Neurohormonal therapies are associated with higher LVEF in follow-up among cancer patients receiving chemotherapy, although absolute changes in LVEF are small and may be within inter-test variability. Furthermore, significant heterogeneity is observed in the treatment effects across studies highlighting the need for larger trials of cardioprotective strategies.
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The relative contribution of heart failure (HF) compared with other medical and nonmedical factors on diminished quality of life (QOL) across subtypes with reduced, better, and preserved left ...ventricular ejection fraction (LVEF) in a large ambulatory HF population was evaluated.
Dominant factors influencing limited QOL in patients with HF have not been investigated.
Before routine HF clinic visits, 726 patients with ambulatory HF (mean age 56 ± 15 years, 37% women) completed a 1-page questionnaire that assessed QOL and relative contributions of HF compared with other medical and nonmedical factors to their QOL limitations. Visual analogue scales were used to assess overall QOL, breathing, and energy level. Results were compared across reduced (57%), preserved (16%) and better (improvement in LVEF ≥50%) (19%) subtypes.
Just under one-half of patients (48%) rated QOL as limited dominantly by HF, 19% rated HF and medical problems as equally limiting, 18% cited medical problems as dominant, and 15% cited nonmedical factors. Patients with HF with better LVEF had the highest overall QOL score and less dyspnea burden than those with HF with preserved EF. Independent correlates of HF-dominated diminished QOL were prior cardiac surgery, worse New York Heart Association functional class, renin-angiotensin-aldosterone antagonism, use of diuretic agents, lower body mass index, lower LVEF, and lack of arthritis or history of cancer.
Fewer than one-half of patients with ambulatory HF rated HF as the greatest limitation to their QOL, suggesting that this important outcome will be difficult to affect by HF-targeted therapies alone, particularly in those with higher LVEFs and comorbidities. Patients with HF with better LVEF represent a distinct subtype with better overall QOL.
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