Heart failure (HF) is a syndrome characterized by high mortality, frequent hospitalization, reduced quality of life, and a complex therapeutic regimen. Knowledge about HF is accumulating so rapidly ...that individual clinicians may be unable to readily and adequately synthesize new information into effective strategies of care for patients with this syndrome. Trial data, though valuable, often do not give direction for individual patient management. These characteristics make HF an ideal candidate for practice guidelines. The 2006 Heart Failure Society of America comprehensive practice guideline addresses the full range of evaluation, care, and management of patients with HF.
Intravascular ultrasound (IVUS) is established as the optimal method for early detection of transplant vasculopathy. The association between cellular rejection and development of transplant ...vasculopathy remains controversial. This study attempts to determine the rate of progression of transplant vasculopathy lesions and its relationship with cellular rejection in a long-term (> 1 year) IVUS serial follow-up.
A study cohort of 47 patients undergoing heart transplantation from 1993 to 1995 was evaluated. Intravascular ultrasound was performed at baseline (within 8 weeks) and annually for a period of 3 years to determine maximum intimal thickness and maximum plaque area in each coronary segment. Significant allograft vasculopathy was defined as a site with intimal thickness > 0.5 mm not present at baseline. Biopsy results were scored by assigning a numerical weight to each ISHLT grade during the first year.
Donor lesions ranged from 0.86 to 1.1 mm, showing no evidence of progression at serial follow-up. De novo lesions were identified in 30 patients. These lesions appeared yearly but progressed slowly. The average biopsy score in the entire cohort was 1.1 ± 0.8. Average biopsy score was > 1.0 in 35 patients with significant linear correlation between the rate of intimal progression and biopsy score (
r = 0.42,
p = 0.01). Multivariate analysis demonstrated that only the biopsy score correlated with the rate of progression.
Lesions of donor atherosclerosis do not change significantly after transplantation. However, de novo lesions continue to develop every year. In patients with evidence of rejection, the rate of progression of transplant vasculopathy correlates with the severity of rejection.
Abstract Background There is increased interest in mechanical circulatory support devices (MCSDs), such as implantable left ventricular assist devices (LVADs), as “destination” therapy for patients ...with advanced heart failure. Because patient availability to evaluate these devices is limited and randomized trials have been slow in enrolling patients, a workshop was convened to consider designs for MCSD development including alternatives to randomized trials. Methods and Results A workshop was jointly planned by the Heart Failure Society of America and the US Food and Drug Administration and was convened in March 2006. One of the panels was asked to review different designs for evaluating new MCSDs. Randomized trials have many advantages over studies with no controls or with nonrandomized concurrent or historical controls. These advantages include the elimination of bias in the assignment of treatments and the balancing, on average, of known and unknown baseline covariates that influence response. These advantages of randomization are particularly important for studies in which the treatments may not differ from one another by a large amount (eg, a head-to-head study of an approved LVAD with a new LVAD). However, researchers have found it difficult to recruit patients to randomized studies because the number of clinical sites that can carry out the studies is not large. Also, there is a reluctance to randomize patients when the control device is considered technologically inferior. Thus ways of improving the design of randomized trials were discussed, and the advantages and disadvantages of alternative designs were considered. Conclusions The panel concluded that designs should include a randomized component. Randomized designs might be improved by allowing the control device to be chosen before randomization, by first conducting smaller vanguard studies, and by allowing crossovers in trials with optimal medical management controls. With use of data from completed trials, other databases, and registries, alternative designs that include both a randomized component (eg, 2:1 allocation for new device versus control) and a nonrandomized component (eg, concurrent nonrandomized control, historical control, or a comprehensive cohort design) should be evaluated. This will require partnerships among academic, government, and industry scientists.
Previous studies of the association between acute cellular rejection and cardiac allograft vasculopathy (CAV) have yielded conflicting conclusions. We explored a possible association between acute ...cellular rejection and the extent of CAV, and we found a potential confounding variable that may obscure such an association.
We investigated 140 patients (mean age, 51 ± 11 years) who underwent serial intravascular ultrasound examinations at baseline and at 1 year after heart transplantation to assess CAV as change in maximal intimal thickness (CMIT). Patients were classified according to the presence or absence of biopsy-proven myocardial fibrosis. We used a standard biopsy-scoring system and a novel biopsy-scoring system, developed in our institution, to assess acute cellular rejection. Using univariate analysis, we found that CMIT was not associated with acute cellular rejection in the overall patient population (
n = 140). However, we observed a correlation between CMIT and acute cellular rejection (standard method,
r = 0.30,
p = 0.01; novel method,
r = 0.51,
p < 0.0001) in patients who had no evidence of ischemic injury or fibrosis in their biopsy specimens (
n = 57). Step-wise multiple regression showed that the rejection score derived from our novel method was associated more closely with the CMIT than was that derived from the traditional method.
This data indicate that the presence of myocardial fibrosis masks an actuarial association between acute cellular rejection and the development of de novo allograft vasculopathy. As previously suspected, myocardial fibrosis is a marker for non–immune-mediated graft injury independently associated with an increased incidence of CAV.
The study was done to prospectively measure the echocardiographic, hemodynamic and clinical outcomes after partial left ventriculectomy (PLV).
Although PLV can improve symptoms of advanced heart ...failure, immediate postoperative echocardiographic findings remain abnormal.
Fifty-nine patients with cardiomyopathy and advanced heart failure underwent PLV and concomitant mitral valve surgery between May 1996 and December 1997. Thirty-nine percent were on inotropic therapy. All were New York Heart Association (NYHA) functional class III or IV. Mechanical circulatory support (LVAD) and transplant were provided for rescue therapy when hemodynamic compromise occurred. Patients were followed for a mean of 405+/-168 days, and clinical, echocardiographic and hemodynamic measures were obtained preoperatively, immediately postoperatively, and at 3 and 12 months prospectively.
Comparing preoperative and 12-month postoperative values in event-free survivors, we found: NYHA functional class improved from 3.6 to 2.1, p < 0.0001; peak oxygen consumption increased from 10.8 to 16.0 ml/kg/min, p < 0.0001; LV ejection fraction increased from 13+/-6.0% to 24+/-6.9%, p < 0.0001; LV end diastolic diameter decreased from 8.2+/-1.03 to 6.2+/-0.64 cm, p < 0.0001, and volume was reduced from 167+/-60 to 105+/-38 ml/m2, p = 0.02. Central hemodynamics did not normalize after surgery.
Partial left ventriculectomy can provide structural remodeling of the heart that may result in temporary improvement in clinical compensation. However, perioperative failures and the return of heart failure limit the propriety of this procedure.
Objectives The aim of this study was to determine whether results with the HeartMate (HM) II left ventricular assist device (LVAD) (Thoratec Corporation, Pleasanton, California) in a commercial ...setting are comparable to other available devices for the same indication. Background After a multicenter pivotal clinical trial conducted from 2005 to 2008, the U.S. Food and Drug Administration approved the HM II LVAD for bridge to transplantation (BTT). A post-approval study was required by the U.S. Food and Drug Administration to determine whether results with the device in a commercial setting are comparable to other available devices for the same indication. Methods The study was a prospective evaluation of the first 169 consecutive HM II patients enrolled in the national INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) who were listed for transplant or likely to be listed. Patients were enrolled from April through August 2008 at 77 U.S. centers and followed for at least 1 year after implant. A comparison group (COMP) included all patients (n = 169 at 27 centers) enrolled in the INTERMACS registry with other types of LVADs (79% HeartMate XVE, 21% Implantable Ventricular Assist Device Thoratec Corporation) for the same BTT indication in the same time period. Survival rates, adverse events, and quality of life with the EuroQol EQ-5D visual analog scale were obtained in the INTERMACS registry. Results Baseline characteristics were similar, but creatinine and blood urea nitrogen were lower in the HM II versus COMP groups, and there were fewer patients in the highest-risk INTERMACS patient profile Number 1 (24% for HM II vs. 39% for COMP). Adverse event rates were similar or lower for HM II versus COMP for all events. Bleeding was the most frequent adverse event for both groups (1.44 vs. 1.79 events/patient-year). Operative 30-day mortality for HM II was 4% versus 11% for COMP. The percentage of patients reaching transplant, cardiac recovery, or ongoing LVAD support by 6 months was 91% for HM II and 80% for COMP, and the Kaplan-Meier survival for patients remaining on support at 1 year was 85% for HM II versus 70% for COMP. Quality of life was significantly improved at 3 months of support and sustained through 12 months in both groups compared with baseline. Conclusions The results in a post-market approval, actual patient care setting BTT population support the original findings from the pivotal clinical trial regarding the efficacy and risk profile of the HM II LVAD. These data suggest that dissemination of this technology after approval has been associated with continued excellent results.
Abstract Objectives This study sought to determine the relationship of KIM-1 levels with adverse clinical outcomes in acute decompensated heart failure (ADHF). Background Kidney injury molecule ...(KIM)-1 is a biomarker expressed by the nephron in acute tubular injury, and is a sensitive and specific marker for early acute kidney injury. Although commonly measured in urine, KIM-1 levels are also detectable in plasma, but its clinical and prognostic utility in ADHF is unknown. Methods Baseline, 48- to 72-h, and 30-day KIM-1 plasma levels were measured in 874 subjects in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial. Multivariable logistic and Cox models were used to assess the relationship between KIM-1 levels and outcomes during and after ADHF. Results The median circulating KIM-1 level at baseline was 375.4 pg/ml (interquartile range IQR: 237.0 to 633.1 pg/ml), at 48 to 72 h was 373.7 pg/ml (IQR: 220.3 to 640.5 pg/ml), and at 30 days was 382.6 pg/ml (IQR: 236.5 to 638.0 pg/ml). There were no associations between KIM-1 levels and any 30-day outcomes. In univariable analysis, both baseline and follow-up KIM-1 were associated with greater 180-day mortality risk. However, after adjusting for blood urea nitrogen or creatinine in addition to established risk predictors from ASCEND-HF, higher KIM-1 at all time points during hospitalization was not associated with in-hospital or post-discharge outcomes (all p > 0.05), but KIM-1 levels measured at 30 days were associated independently with 180-day mortality (hazard ratio: 1.49; p = 0.04). Conclusions In our study cohort, circulating KIM-1 at baseline and during hospitalization was not associated with adverse clinical outcomes in ADHF after adjusting for standard indices of kidney function.
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