Serum heart-type fatty acid binding protein predicts cardiac events in elderly patients with chronic heart failure

BACKGROUND AND OBJECTIVES: Heart-type fatty acid binding protein (H-FABP) is released into the circulation from the damaged myocardium of patients with severe chronic heart failure. Chronic heart failure is the most frequent cause of death and disability in the elderly. However, there are no data for the prognostic value of H-FABP in the elderly population. This study investigated whether H-FABP can effectively predict the prognosis in elderly patients (> or = 70 years) with chronic heart failure. METHODS: Serum H-FABP levels were measured in 90 chronic heart failure patients > or =70 years old (mean age 77 +/- 4 years, range 70-92 years), and patients were followed-up for 421 +/- 326 days. RESULTS: There were 35 cardiac events (38.9%) including cardiac deaths and readmissions for worsening chronic heart failure. Multivariate analysis with the Cox proportional hazard model showed that H-FABP was the only independent predictor of cardiac events (chi2 = 6.640, p = 0.0100). Kaplan-Meier analysis revealed that H-FABP effectively risk stratified elderly patients with chronic heart failure for cardiac events. CONCLUSIONS: These findings suggest that H-FABP is a reliable marker for prognosis in elderly patients with chronic heart failure.     

A health perception score predicts cardiac events in patients with heart failure: results from the IMPRESS trial.

BACKGROUND: New York Heart Association (NYHA) class and treadmill exercise test variables are widely used for estimating prognosis and measuring the outcomes of treatment in patients with heart failure, but they do not take patients' perceptions into account. METHODS AND RESULTS: Five hundred forty-five patients enrolled in a multicenter 24-week comparison of the effects of omapatrilat and lisinopril on functional capacity in patients with heart failure reported a visual analog scale (VAS) score of their overall health perception at week 12 of the study. A total of 27 first events, defined as death or worsening heart failure (hospitalization, emergency room visit, or study discontinuation), occurred in the subsequent 12 weeks. The mean (+/-SD) health perception scores were 0.43 +/- 0.31 and 0.68 +/- 0.20 in patients with and without events, respectively (P =.0006). The risk ratio (RR) for an event associated with a decile change in the health perception score was 0.74 (95% confidence interval [CI], 0.61-0.88; P =.001). The RR was unaltered by adjustment for demographic variables, treadmill time, and NYHA functional class. Although the week 12 NYHA functional class was predictive of events (RR = 2.1; 95% CI, 1.2-4.6; P =.04), treadmill time was not (RR = 0.87; 95% CI, 0.73-1.03; P = 0.11). CONCLUSIONS: A patient-reported measure of perceived health predicts events in patients with heart failure.     

Serum carboxy-terminal telopeptide of type I collagen (ICTP) predicts cardiac events in chronic heart failure patients with preserved left ventricular systolic function.

BACKGROUND: Clinical markers to predict adverse outcome have not yet been established for patients with preserved left ventricular (LV) systolic function. The present study was designed to examine whether carboxy-terminal telopeptide of type I collagen (ICTP), a marker of collagen degradation, is useful for determining the prognosis of such patients. METHODS AND RESULTS: Serum levels of ICTP were measured at admission in 156 consecutive patients hospitalized for chronic heart failure (CHF). Patients were divided into 2 groups based on the LV ejection fraction (LVEF): reduced LV systolic function group (LVEF <50%, n=92) and preserved LV systolic function group (LVEF > or =50%, n=64). In preserved LV systolic function group, cardiac event-free rates were significantly lower in high ICTP group than in low ICTP group (p<0.001). The area under the receiver operating characteristic curve of ICTP in the preserved LV systolic function group was markedly larger than that in the reduced LV systolic function group. Cox multivariate analysis also revealed that ICTP was an independent predictor of cardiac events in the preserved LV systolic function group. CONCLUSION: Serum ICTP level is highly reliable for risk stratifying CHF patients with preserved LV systolic function.     

Serum YKL-40 predicts adverse clinical outcomes in patients with chronic heart failure

BackgroundHuman cartilage glycoprotein-39 (YKL-40), a novel inflammatory marker, is secreted into circulation by macrophages, neutrophils, chondrocytes, vascular smooth muscle cells and cancer cells. Circulating levels of YKL-40 are related to the degree of inflammation, tissue remodeling, fibrosis, and cancer progression.Methods and ResultsWe examined serum YKL-40 levels in 121 patients with chronic heart failure (CHF) and 39 control subjects. The patients were followed up to register cardiac events for a mean of 720 days. Serum YKL-40 levels were measured by sandwich enzyme-linked immunoassay. Serum YKL-40 was significantly higher in New York Heart Association (NYHA) Class III/IV patients than control subjects and NYHA Class I/II patients (P < .0001). Serum YKL-40 was also higher in patients with cardiac events than in event-free patients (P = .0023). Cutoff value of YKL-40 was determined by receiver operating characteristic curve analysis. Kaplan-Meier analysis demonstrated that high level of YKL-40 was associated with higher rates of cardiac events than low levels of YKL-40 (P = .003). The multivariate Cox hazard analysis demonstrated that serum YKL-40 level was an independent prognostic factor of cardiac events (hazard ratio 2.085, 95% confidence interval 1.233-3.499, P < .0048).ConclusionsSerum YKL-40, a new marker of inflammation, was increased in CHF, and YKL-40 detected high risk patients for adverse outcomes in CHF.     

心脏再同步治疗前后血清胱抑素C的变化及临床意义

目的 了解心脏再同步治疗(CRT)前后血清胱抑素C(CysC)水平的变化,探讨CysC变化水平是否能反映CRT植入后心力衰竭患者心脏结构和功能改善程度.方法 对本院16例植入CRT/心脏再同步治疗除颤器(CRT-D)患者的随访资料进行分析,随访时间均＞6个月,平均随访(20.08±12.78)个月.根据治疗效果将患者分为有效组和无效组,有效定义为术后左心室收缩末容积缩小≥15％.结果 16例中有效10例(62.5％).有效组术后CysC水平明显降低[(1.54±0.38)对(1.22±0.29) P＜0.05];与临床及超声心动图指标比较,CysC在CRT术后1个月即出现明显变化且差异有统计学意义(P＜0.05).无效组术后各个时间点随访参数与术前相比均差异无统计学意义.而有效组术后6个月相关参数均明显优于无效组,但只有CysC在术后1个月即与无效组存在明显差异,且随时间延长,其差异越明显.随访时间≥6个月时,CysC水平的降低幅度(△Cys C％)与左心室舒张末期容积(LVEDV)缩小幅度(△LVEDV％)呈线性相关(R2=0.792,P＜0.05);无效组术后CysC与术前相比差别无统计学意义;CysC水平的变化与△LYEDV％无线性回归关系(P＞0.05).结论 血清CysC是一个有效地、较临床及超声心动图指标能更早的、可以常规用来监测CRT对于心力衰竭治疗效果的指标,可以更好地用于指导心力衰竭的再同步治疗.     

Echocardiography predicts adverse cardiac remodelling in heart failure

Congestive heart failure remains a primary cause of cardiovascular-related events. Heart failure patients face two health care challenges. First, they are uncertain about their prognosis and second, they have an unpredictable clinical course with recurrent exacerbations of heart failure. The echocardiogram is an easily accessible bedside test without any associated procedural complications. Additionally, it provides a wealth of information about chamber size and function, valve integrity and the pericardial sac. In the present review, the most common echocardiographic predictors of impending cardiac events in congestive heart failure are described.     

Pacemaker stress echocardiography predicts cardiac events in patients with permanent pacemaker

Purpose

Noninvasive pacemaker stress echocardiography is a newly introduced method for the diagnosis of coronary artery disease in patients with a permanent pacemaker. The prognostic value of pacemaker stress echocardiography has not been studied.

Subjects and methods

We studied 136 patients (mean age 64 ± 12 years) with a permanent pacemaker who underwent pacemaker stress echocardiography for evaluation of coronary artery disease. All patients underwent pacemaker stress echocardiography by external programming (pacing heart rate up to ischemia or target heart rate).

Results

Thirty-one patients (23%) had normal study results. Ischemia was detected in 75 patients (55%). During a mean follow-up of 3.5 ± 2.4 years, 35 deaths (26%) (20 the result of cardiac causes) and 2 nonfatal myocardial infarctions (1%) occurred. The annual cardiac death rate was 1.3% in patients without ischemia and 4.6% in patients with ischemia (P = .01). The annual all-cause mortality rate was 3.1% in patients without ischemia and 7% in patients with ischemia (P = .004). The presence of ischemia during pacemaker stress echocardiography was the strongest independent predictor of cardiac death (hazard ratio 4.1, confidence interval 1.2-14.5) and all-cause mortality (hazard ratio 2.7, confidence interval 1.2-6.0) in a multivariable model.

Conclusion

Myocardial ischemia during pacemaker stress echocardiography is an independent predictor of cardiac death and all-cause mortality in patients with a permanent pacemaker.     

Exogenous midkine administration prevents cardiac remodeling in pacing-induced congestive heart failure of rabbits

Midkine (MK), a heparin-binding growth factor, has been shown to prevent cardiac remodeling after ischemic injury through its anti-apoptotic effect. Cell apoptosis is central to the pathophysiology of cardiac remodeling in congestive heart failure (CHF) of ischemic as well as non-ischemic origin. We hypothesized that MK exerts the anti-apoptotic cardioprotective effect in CHF of non-ischemic etiology. MK protein or vehicle (normal saline) was subcutaneously administered in tachycardia-induced CHF rabbits (right ventricular pacing, 350 beats/min, 4 weeks). The vehicle-treated rabbits (n = 19, control) demonstrated severe CHF and high mortality rate, whereas MK (n = 16) demonstrated a well-compensated state and a lower mortality rate. In echocardiography, left ventricular (LV) end-diastolic dimension decreased in MK versus control, whereas LV systolic function increased. In histological analysis (picrosirius red staining), MK decreased collagen deposition area compared with control. TUNEL staining showed that MK prevented cell apoptosis and minimized myocyte loss in the CHF rabbit ventricle, associated with activation of PI3-K/Akt signaling, producing a parallel decrease of Bax/Bcl-2 ratio. MK prevented progression of cardiac remodeling in the CHF rabbit, likely by activation of anti-apoptotic signaling. Exogenous MK application might be a novel therapeutic strategy for CHF due to non-ischemic origin.     

Ventricular asynchrony predicts a better outcome in patients with chronic heart failure receiving cardiac resynchronization therapy

OBJECTIVES: The aim of this study was to evaluate whether the clinical benefit of cardiac resynchronization therapy (CRT) can be prospectively predicted by means of the baseline evaluation of left ventricular asynchrony. BACKGROUND: The reverse remodeling associated with CRT is more evident in patients with severe heart failure (HF) and left bundle branch block (LBBB) who have left ventricular asynchrony. METHODS: Baseline left ventricular asynchrony was assessed in 60 patients with severe HF and LBBB by calculating the electrocardiographic duration of QRS and the echocardiographic septal-to-posterior wall motion delay (SPWMD). Left ventricular size and left ventricular ejection fraction (LVEF), mitral valve regurgitation, and functional capacity were also evaluated. The progression toward HF (defined as a worsening clinical condition leading to a sustained increase in conventional therapies, hospitalization, cardiac transplantation, and death) was assessed during follow-up, as were the changes in LVEF after six months. RESULTS: During the median follow-up of 14 months, 16 patients experienced HF progression. Univariate analysis showed that ischemic cardiomyopathy, changes in the QRS duration after implantation, and SPWMD significantly correlated with events. At multivariate analysis, a long SPWMD remained significantly associated with a reduced risk of HF progression (hazard ratio: 0.91; 95% confidence interval: 0.83 to 0.99; p <0.05). An improvement in LVEF was observed in 79% of the patients with a baseline SPWMD of > or =130 ms and in 9% of those with an SPWMD of <130 ms (p <0.0001). CONCLUSIONS: Baseline SPWMD is a strong predictor of long-term clinical improvement after CRT in patients with severe HF and LBBB.     

Noninvasive assessment of cardiac pumping capacity during exercise predicts prognosis in patients with congestive heart failure

BACKGROUND: Prognostic parameters in patients with congestive heart failure (CHF) are important for guiding therapeutic options. Maximal oxygen uptake (O(2)max) is a widely used parameter for prognostic assessment in patients with CHF and correlates with exercise cardiac output; however, afterload is not taken into account. METHODS: The concept of a noninvasive surrogate of cardiac power output combines exercise systolic BP (SBP), as an estimate of afterload, with O(2)max, as an estimate of exercise cardiac output neglecting preload. Thus, a variable termed exercise cardiac power (ECP) is defined as the product of O(2)max (expressed as a percent predicted value) and SBP (ECP, expressed as %mm Hg, is the product of O(2)max, expressed as percentage of predicted maximum, times systolic pressure. The prognostic value of ECP obtained during routine treadmill ergospirometry was assessed in patients referred to our heart failure clinic. Patients undergoing heart transplantation were censored at the time of transplantation. RESULTS: One hundred fifty-four patients were followed prospectively for a mean (+/- SE) duration of 625 +/- 32 days. Thirty-two patients (21%) died. ECP was the most powerful predictor of mortality, was the combined end point of mortality or hospitalization for worsening heart failure (all p < 0.001), and was an independent predictor in multivariate analysis. An ECP of < 5,000 %mm Hg indicated a poor prognosis with a 1-year mortality rate of 37%, whereas only 2% of the patients having an ECP of > 9,000 %mm Hg died during the first year. CONCLUSION: The integration of afterload and O(2)max improves the prognostic value of each indicator, and provides an easily available and independent predictor of mortality and morbidity in CHF patients. This integrative concept of cardiac hydraulic performance is superior to O(2)max and can be used in routine ergospirometry.     

The Seattle heart failure model predicts survival in patients with cardiac resynchronization therapy: a validation study

BackgroundThe Seattle Heart Failure Model (SHFM) predicts mortality in patients with heart failure, but no study has investigated model performance in subjects with cardiac resynchronization therapy (CRT).Methods and ResultsProspectively collected registry data of 427 patients with CRT were used for the evaluation of the discrimination and calibration performance of the SHFM. The primary end point was all-cause mortality. Calibration profile was assessed with the use of Hosmer-Lemeshow tests, and discrimination was assessed by calculating areas under receiver operating characteristic curves (AUCs) derived from the model. Mean (SD) age of the study population was 61.2 (11.1) years (72.6% male). During a median follow-up of 24.7 months, 16.9% (72/427) of the patients reached the primary end point, with observed outcomes of 34/303, 54/234, and 72/97 at years 1, 2, and 5, respectively. No evidence of insufficient fit was found in any calibration tests. AUC estimates in all subjects were 0.7377 (95% CI 0.6575–0.8179) at year 1, 0.7936 (95% CI 0.7317–0.8556) at year 2, and 0.7572 (95% CI 0.6455–0.8689) at year 5.ConclusionsSHFM offers an accurate prediction of survival in patients with CRT, with good observed calibration and AUC estimates indicating discrimination performance similar to those found by earlier validation studies.     

Periodic breathing during incremental exercise predicts mortality in patients with chronic heart failure evaluated for cardiac transplantation

OBJECTIVES: We hypothesized that exercise-related periodic breathing (EPB) would be associated with poor prognosis in advanced chronic heart failure (CHF). BACKGROUND: Patients with CHF might present instability of the ventilatory control system characterized by cyclic waxing and waning of tidal volume (periodic breathing [PB]). This condition is associated with several deleterious circulatory and neuro-endocrine responses; in fact, PB in awake and asleep patients has been identified as an independent risk factor for cardiac death. During exercise, however, the prognostic value of PB is still unknown in CHF patients awaiting heart transplantation. METHODS: Eighty-four patients with established CHF (65 male, 19 female) were submitted to clinical evaluation, echocardiogram, ventricular scintigraphy, determination of resting serum norepinephrine levels, and an incremental cardiopulmonary exercise test on cycle ergometer. Patients were followed for up to 49.7 months (median = 15.3), and 26 patients (30.9%) died during this period. RESULTS: Twenty-five of 84 patients presented EPB (29.7%). The following variables were related to mortality according to Kaplan-Meier and univariate Cox regression analysis: EPB (p = 0.004), New York Heart Association class (p = 0.04), serum norepinephrine (p = 0.06), peak oxygen uptake (ml.min(-1).kg(-1) and % predicted; p = 0.085 and p = 0.10, respectively), slope of the ratio of change in minute ventilation to change in carbon dioxide output during exercise (p = 0.10), and scintigraphic left ventricular ejection fraction (p = 0.10). Cox multivariate analysis identified EPB as the only independent variable for cardiac death prediction (p = 0.007). Therefore, EPB alone was associated with a 2.97-fold increase in risk of death in this population (95% confidence interval = 1.34 to 6.54). CONCLUSIONS: Exercise-related periodic breathing independently predicts cardiac mortality in CHF patients considered for heart transplantation.