Right ventricular dysfunction in chronic dilated cardiomyopathy and heart failure

In patients with advanced heart failure, the main focus has traditionally been placed on the functional assessment of the left ventricle. Therefore, the current body of literature examining the right ventricle and its influence on the pathophysiological processes in heart failure has been limited. Methods currently employed to assess the size and function of the right ventricle include: high frequency thermodilution, contrast ventriculography, radionuclide ventriculography, echocardiography, and magnetic resonance imaging; however, none of these techniques has proven to be a 'gold standard' for the assessment of right ventricular function. Nevertheless, when these methods are employed, right ventricular dysfunction has been shown to be a powerful predictor of reduced exercise capacity and survival. This relationship holds true for patients with heart failure secondary to either ischemic or non-ischemic dilated cardiomyopathy.     

Circulating tenascin-C levels in patients with idiopathic dilated cardiomyopathy

Circulating serum tenascin-C (an extracellular matrix glycoprotein) levels in patients with idiopathic dilated cardiomyopathy (IDC) were measured. Serum tenascin-C levels were increased in proportion to the severity of left ventricular dysfunction in patients with IDC. The associations of serum tenascin-C levels with serum troponin T and procollagen type III aminoterminal peptide levels suggest that increased levels of serum tenascin-C indicate ongoing replacement fibrosis after myocardial damage in IDC.     

Sustained left ventricular diastolic dysfunction after exercise in patients with dilated cardiomyopathy

Objective—To investigate the recovery process of exercise induced diastolic dysfunction in heart failure, using Doppler echocardiographic techniques.
Design and patients—Transmitral flow velocity profiles and standard non-invasive haemodynamic indices were obtained serially over seven days after symptom limited bicycle exercise tests in 18 patients with dilated cardiomyopathy and eight normal subjects. In three patients with cardiomyopathy we also measured the pulmonary capillary wedge pressure for 24 hours after exercise.
Results—The intensity of exercise, as assessed by respiratory gas analysis, was lower in patients with dilated cardiomyopathy than in normal subjects. Despite the higher exercise level, all haemodynamic variables returned to baseline within one hour after exercise in normal subjects. In contrast, patients with dilated cardiomyopathy showed a sustained decrease in the peak early diastolic filling velocity and a sustained increase in the deceleration time of early filling for 24 hours or more after exercise. Because other haemodynamic variables recovered within one hour after exercise even in patients with dilated cardiomyopathy, the postexercise changes in ventricular filling were not explained by changes in loading conditions.
Conclusions—Exercise induced diastolic left ventricular dysfunction of the failing heart persists for 24 hours or more after exercise. The efficacy of exercise training on a daily basis in dilated cardiomyopathy requires further evaluation.

Keywords: exercise;  chronic heart failure;  mitral flow velocity;  diastolic stunning     

Coronary flow reserve correlates left ventricular diastolic dysfunction in patients with dilated cardiomyopathy.

The relationship between altered coronary circulation and left ventricular (LV) function in dilated cardiomyopathy (DCM) remains unclear. We used the Doppler guidewire and transthoracic echo Doppler in 24 DCM patients to investigate the relationship between coronary flow reserve (CFR) and LV systolic/diastolic function, trying to predict diastolic dysfunction and evaluate DCM severity with CFR. CFR correlated better with the deceleration time (DT) of the E-wave and the ratio of E-wave peak value to that of the A-wave (E/A) than with LV ejection fraction (EF). The optimal CFR cutoff value for predicting the restrictive pattern of transmitral flow velocity (DT = 120 msec) was 2.6 (sensitivity 91%, specificity 100%). Dividing patients into two groups around the CFR = 2.6 cutoff, differences in DT and E/A between groups were more prominent than those for EF. CFR correlates better with LV diastolic than systolic function and may be useful for predicting diastolic dysfunction in DCM patients.     

扩张型心肌病心室重构伴充血性心力衰竭的危险因素分析

目的:探讨扩张型心肌病(DCM)后心室重构(VRM)伴充血性心力衰竭(CHF)的危险因素。方法:选择DCM患者NYHA分级Ⅱ～Ⅳ级,且左心室射血分数(LVEF)<40%的96例为观察组;心功能Ⅰ级,LVEF≥40%的35例患者为对照组,比较2组临床资料,在单因素分析基础上,采用Logistic多因素逐步分析方法确立DCM后VRM伴CHF的独立危险因素。结果:单因素分析结果显示,观察组中男性患病率、心房颤动(房颤)及脉压≥70mmHg(1mmHg=0.133kPa)者较对照组高,差异有统计学意义(P<0.01)。Logistic逐步回归分析脉压≥70mmHg、房颤为DCM后VRM伴CHF的独立危险因素。结论:脉压≥70mmHg、房颤是DCM后VRM伴CHF的独立危险因素。     

Effect of revascularization on left ventricular remodeling in patients with heart failure from severe chronic ischemic left ventricular dysfunction

Few data exist regarding the effect of revascularization on left ventricular (LV) geometry in patients with severe LV systolic dysfunction and viable myocardium. We hypothesized that patients with chronic ischemic LV dysfunction but viable myocardium will have improved LV geometry after revascularization, which in turn will improve long-term outcome. Accordingly, 70 patients with severe ischemic LV dysfunction (LV ejection fraction <0.35) were studied at rest. They then either underwent revascularization (n = 36) or were treated medically (n = 34). Fifty-four patients had viable myocardium, and 16 did not. They were evaluated for change in LV function and geometry (size and shape) a mean of 21 months later. Further follow-up was performed for a mean of 3.5 years to determine outcome. Patients with viable myocardium had improvement not only in regional and global function, but also in LV geometry (shape and size), which was independent of and incremental to the improvement in function. On long-term follow-up, change in LV end-systolic volume was the only multivariate discriminator between 15 patients who died and 55 who did not, irrespective of whether they had undergone revascularization. Thus, measurement of the effect of revascularization of viable myocardium in chronic ischemic heart disease should not only include improvement in resting regional and global LV function, but also LV geometry. Improvement in LV geometry contributes to better LV systolic function, which in turn is the best predictor of survival after revascularization.     

抗心肌纤维化治疗家兔慢性心力衰竭的实验研究

目的 探讨姜黄素的抗心肌纤维化作用对家兔慢性心力衰竭(心衰)的影响.方法 30只新西兰大耳白兔随机分为对照组、心衰组、姜黄素组,每组10只.心衰组和姜黄素组采用主动脉瓣反流及主动脉缩窄法制作心衰模型,对照组做假手术但不造成主动脉瓣反流和主动脉缩窄.姜黄素组口服姜黄素(100 nag·kg-1·d-1),对照组和心衰组口服安慰剂.主动脉瓣反流术及其假手术前,主动脉缩窄术及其假手术后8周,所有动物做2次心脏超声检查.第2次超声检查后,取出心脏行基质金属蛋白酶(MMP)-2和MMP-9的免疫组织化学染色和Masson染色,观察MMP表达的改变和心肌纤维化情况.结果 前后2次超声结果 比较,心衰组左室射血分数和左室内径缩短分数显著下降,左室内径、左室后壁和室间隔厚度显著增大;姜黄素组上述指标也有显著改变,但程度较心衰组轻;对照组上述指标无显著改变.Masson染色显示,心衰组胶原含量高于姜黄素组和对照组(P<0.05);免疫组织化学染色显示,心衰组MMP-2和MMP-9的表达低于姜黄素组和对照组(P<0.05).结论 姜黄素通过提高MMP的表达可减轻心衰时的心肌纤维化,该作用可能是其改善心衰时心肌重构和心脏收缩功能的重要机制之一.抗纤维化治疗有可能成为心衰治疗的新方法 .     

Recovery and recurrence of left ventricular systolic dysfunction in patients with idiopathic dilated cardiomyopathy

BACKGROUND:

Some patients with nonischemic left ventricular (LV) systolic failure recover to have normal LV systolic function. However, few studies on the rates of recovery and recurrence have been reported, and no definitive indicators that can predict the recurrence of LV dysfunction in recovered idiopathic dilated cardiomyopathy (IDCMP) patients have been determined. It was hypothesized that patients who recovered from nonischemic LV dysfunction have a substantial risk for recurrent heart failure.

METHODS:

Forty-two patients (32 men) with IDCMP (mean [± SD] age 56.9±8.7 years) who recovered from systolic heart failure (LV ejection fraction [LVEF] of 26.5±6.9% at initial presentation) to a near-normal state (LVEF of 40% or greater, and a 10% increase or greater in absolute value) were monitored for recurrence of LV systolic dysfunction. Patients with significant coronary artery disease were excluded. Patients were monitored for 41.0±26.3 months after recovery (LVEF 53.4±7.6%) from LV dysfunction.

RESULTS:

LV systolic dysfunction reappeared (LVEF 27.5±8.1%) during the follow-up period in eight of 42 patients (19.0%). No significant difference between the groups with or without recurrent heart failure was observed in the baseline clinical and echocardiographic characteristics. However, more patients in the recurred IDCMP group than those in the group that maintained the recovery state had discontinued antiheart failure medication (62.5% versus 5.9%, P<0.05).

CONCLUSIONS:

LV dysfunction recurs in some patients with reversible IDCMP. The recurrence was significantly correlated with the discontinuation of antiheart failure drugs. The results suggest that continuous medical therapy may be mandatory in patients who recover from LV systolic dysfunction.     

Relations among heart failure severity,left ventricular loading conditions,and repolarization length in advanced heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

In patients with heart failure (HF), low peak oxygen consumption (VO(2)) and prolonged QT interval or enhanced QT variability are associated with poor prognosis. Whether HF severity or left ventricular (LV) loading conditions can influence repolarization length is unknown. Survival, QTc interval, peak VO(2), clinical, laboratory, echocardiographic, and invasive hemodynamic data were analyzed in 154 transplant candidates; mortality was examined after a mean follow-up of 4.3 +/- 1.8 years. The relation between the QTc interval and other variables was examined using multivariate analysis and multiple correlation coefficients. Patients were stratified by peak VO(2) to study its relation with peak VO(2), mortality, loading conditions, and QTc intervals. Mean ejection fraction was 10 +/- 9%; mean cardiac index was 2.06 +/- 0.7 L/min/m(2). Seventy-one patients (47%) were dead at the end of study. Mortality and nonfatal ventricular arrythmias were higher (p <0.01) in patients with lower peak VO(2) and longer QTc intervals (p <0.001). An inverse correlation was found between QTc interval length and peak VO(2) (r = -0.790, p <0.0001). No correlation was found between QTc interval and LV loading conditions or the other analyzed variables. Thus, repolarization length measured by the QTc interval is inversely correlated with HF severity measured by peak VO(2) and is independent of LV loading conditions in patients with severe HF.     

神经内分泌因子在扩张型心肌病心室重构及心力衰竭中的表达

目的：观察神经内分泌因子对扩张型心肌病（DCM）心室重构及心力衰竭的影响。方法：DCM患者120例，按心功能分级分为3组，心功能Ⅱ级组34例，心功能Ⅲ级组45例，心功能Ⅳ级组41例。另选取80例心功能正常者作为对照组。所有患者人院第2天均检测去甲肾上腺素（NE）、血管紧张素Ⅱ（AngⅡ）、细胞肿瘤坏死因-α（TNT-α）、白介素-6（IL-6）、细胞可溶性凋亡因子（sFas）。结果：DCM心功能Ⅱ～Ⅳ级患者与正常组对照，NE，AngⅡ、TNF-α、IL-6、sFas水平明显升高，且随着心功能恶化逐渐增强（P〈0．01）。DCM组中不同功能级别者与对照组相比差异有统计学意义（P〈0．05或P〈0．01〉。结论：DCM患者其NE，AngⅡ、TNF-α、IL-6、sFas常过度表达，通过影响心肌收缩力，引起心肌肥大，诱导心肌凋亡、纤维化，加重心室重构和心力衰竭发生、发展。     

Reverse left ventricular remodeling by intermittent dobutamine infusions and amiodarone in end-stage heart failure due to idiopathic dilated cardiomyopathy

BACKGROUND: The aim of this study was to evaluate the long-term effect of combined intermittent dobutamine infusions (IDI) and oral amiodarone on reverse left ventricular (LV) remodeling and hemodynamics of patients with idiopathic dilated cardiomyopathy (IDC) and end-stage congestive heart failure (CHF). METHODS: This non-randomized, prospective, clinical trial included sixteen consecutive patients suffering from dyspnea for a mean of 76+/-43 months, who presented with acute cardiac decompensation and were weaned from dobutamine therapy after an initial 72-h infusion. They were then placed on a regimen of oral amiodarone, 400 mg/day and weekly IDI, 10 microg/kg/min, for 8 h. The long-term clinical outcomes and the effects of treatment on reverse LV remodeling (echocardiographic parameters) and hemodynamics were evaluated at 3, 6, and 12 months of follow up. RESULTS: A significant degree of reverse LV remodeling, hemodynamic improvements, and survivals >1.5 years were observed in 9 of the 16 patients (56%). In addition, 5 patients (31% of entire cohort) were weaned from IDI after a mean of 61+/-41 weeks, and 4 remained clinically stable for 116+/-66 weeks thereafter. At 12 months of follow-up, LV end-diastolic and end-systolic volume indices had decreased from 231+/-91 to 206+/-80 ml/m2 (P=0.002) and from 137+/-65 to 110+/-50 ml/m2 (P=0.003), respectively, right atrial pressure from 16+/-6 to 5.6+/-4 mm Hg, (P=0.031), and pulmonary capillary wedge pressure from 29+/-4 to 16+/-5.4 mm Hg, P=0.000, while LV ejection fraction had increased from 22+/-6% to 27.3+/-8% (P=0.006). CONCLUSIONS: In end-stage CHF due to IDC, long-term treatment with IDI and oral amiodarone caused reverse LV remodeling, and allowed permanent and successful weaning from IDI in 1/4 of patients.     

扩张型心肌病患者血红蛋白水平、细胞因子与左室功能相关性分析

目的：探讨扩张型心肌病（DCM）患者血红蛋白（Hb）水平、炎症细胞因子与心功能变化的相关性。方法：入选69例DCM患者,按Hb水平分为DCM贫血组（30例）和非贫血组（39例）,同时选择21例正常人作为正常对照组,测定所有研究对象血红蛋白（Hb）、肿瘤坏死因子－α（TNF-α）、自细胞介索-6（IL-6）水平及左室射血分数（LVEF）,评价心功能,并对上述指标进行比较分析。结果：与正常对照纰比较,DCM组TNF-α（25．21±4．26）ng／L比（82．43±42．13）ng／L]、IL-6[（41．18±4．15）μg／L比（134．95±60．5）μg／]水平显著升高,而LVEF[（66．54±7．08）％比（47．69±16．79）％]显著降低（P〈0．01）;在DCM患者中,与非贫血组比较,贫血组TNF-α（55．63±10．16）ng／L比（92．33±6．39）ng／L]、IL-6[（106．5±20．36）μg／L比（145．22±13．53）μg／L]水平显著升高,而LVFF[（45．35±8．82）％比（33．94±5．23）％]显著降低（P〈0．01）;随着NYHA心功能等级的升高,TNF-α、IL-6水平明屁升高,Hb和LVEF明显降低（P均〈0．01）;DCM患者Hb水平与LVEF呈正相关（r=0．6919,P〈0．01）,与TNF-α、1L-6水平早负相关（r=0．8407,0．6634,P均〈0．01）。结论：扩张型心肌病患者炎症细胞因子影响并促进贫血与心力衰竭相互影响的病理生理过程。     

Time course of left ventricular reverse remodeling in response to pharmacotherapy: clinical implication for heart failure prognosis in patients with idiopathic dilated cardiomyopathy

The present study aimed to identify the clinical significance of differences in detection timings of left ventricular reverse remodeling (LVRR) on heart failure (HF) prognosis in patients with idiopathic dilated cardiomyopathy (IDCM). We investigated 207 patients with IDCM who underwent pharmacotherapeutic treatment. LVRR was defined as improvements in both LV ejection fraction ≥10 % and indexed LV end-diastolic dimension (LVEDDi) ≥10 %. Patients were stratified into 3 groups by LVRR timing: patients with LVRR <24 months (Early LVRR), those with LVRR ≥24 months (Delayed LVRR), and those without LVRR during the entire follow-up period (No LVRR). The major endpoint was first detection of composite event including readmission for decompensated HF, major ventricular arrhythmias, or all-cause mortality. LVRR was recognized in 108 patients (52 %): Early LVRR in 83 (40 %), Delayed LVRR in 25 (12 %), and No LVRR in 99 (48 %). The survival rate for the major endpoint was significantly higher for Delayed LVRR than for No LVRR (P = 0.001); there was no significant difference between Early and Delayed LVRR. Among patients without LVRR <24 months (Delayed + No LVRR), receiver operating characteristic curve analysis showed that the area under the curve for improvement in LVEDDi during the first 6 months for predicting subsequent LVRR (Delayed LVRR) [0.822 (95 % confidence interval, 0.740–0.916; P = 0.038)] was greater than that for improvement in LVEF. In conclusion, LVRR was a favorable prognostic indicator in patients with IDCM irrespective of its detection timing. Reduced LVEDDi during the first 6 months was predictive for subsequent LVRR in the later phase.     

Comparison of left ventricular systolic and diastolic function in patients with idiopathic dilated cardiomyopathy and mild heart failure versus those with severe heart failure

Achieving recommended cholesterol and triglyceride targets for the prevention of cardiovascular events is difficult and frequently requires the use of >1 lipid-lowering medication. This study evaluated the tolerability and effectiveness of combination regimens in high-risk dyslipidemic patients resistant to monotherapy. A retrospective chart review of all patients referred to a cardiovascular risk reduction clinic over a 7.5-year period identified 136 patients who received combination therapy with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) plus fibrate (n = 106) or a statin plus niacin (n = 30) regimen. During follow-up (mean 18.5 months), 28 patients (20.6%) discontinued combination therapy: 11 (8.1%) experienced myalgia with or without elevated creatine kinase, 3 had gastrointestinal upset, and 1 had asymptomatic creatine kinase elevation. No patient had combination therapy discontinued due to elevated liver enzymes. Medications were stopped in 8 patients for reasons other than reported adverse effects or biochemical abnormalities, and 5 patients were switched to alternate monotherapy. Mean percent change from baseline to treatment with combination therapy for total cholesterol (-35%), low-density lipoprotein cholesterol (-37%), high-density lipoprotein cholesterol (+23%), triglycerides (-62%), and total cholesterol/high-density lipoprotein cholesterol ratio (-41%) were all statistically significant (p <0.01). These results demonstrate that combination statin-fibrate and statin-niacin regimens are safe and effective in managing dyslipidemias in most patients at risk for cardiovascular events who are inadequately treated with one of these agents alone.     

Long-term prognosis in patients with echocardiographic left ventricular dysfunction masquerading as dilated cardiomyopathy]

The long-term prognosis and prognostic factors were assessed in patients with left ventricular dilatation with impaired function secondary to idiopathic dilated cardiomyopathy (DCM) or to heart diseases of various pathogeneses masquerading as DCM (DCM-like). The echocardiographic criteria for DCM-like disease were 1) left ventricular end-diastolic dimension exceeding 60 mm and 2) fractional shortening less than 15%. Those who showed improvement in either of these 2 parameters within 3 months were excluded from this study. One hundred and fifty-eight of 35,250 serially examined patients fulfilled the definitions. The pathogeneses of diseases were valvular heart disease (VHD) in 30 patients, ischemic heart disease (IHD) in 37, alcoholic cardiomyopathy (AC) in 12, hypertensive heart disease (HHD) in 31 and DCM in 48. All of the survivors were followed for more than 24 months; an average of 40 months. During this period, there were a total of 75 deaths, 18 (27%) of whom were judged as sudden death. Five-year survival rates calculated using the Kaplan-Meier method in AC and HHD were 86% and 77%, respectively, which were significantly higher than those in DCM (48%; p < 0.05); whereas, patients with VHD and IHD had lower values (60% and 46%, respectively) which were nearly equal to those in DCM. Factors that contributed to the increase in total cardiac mortality were advanced age, higher NYHA functional class, larger cardiac size on chest radiograph and history of heavy alcohol intake. Each of these factors were closely related to the specific pathogeneses as follows: age to IHD, cardiac size to VHD, and NYHA functional class to DCM. Long-term prognosis of DCM-like heart diseases, especially those of IHD and VHD, seemed to be as bad as those of DCM.     

扩张型心肌病患者心外膜脂肪厚度与左心室重构的相关性

目的研究扩张型心肌病(DCM)患者心外膜脂肪厚度与左心室重构及左心室功能不全的关系。方法收集DCM患者120例(DCM组)和健康体检者76例(对照组),应用常规心脏超声测量左心室收缩末内径(LVESD)、左心室舒张末内径(LVEDD)、左心室收缩末容积(LVESV)、左心室舒张末容积(LVEDV)、左心室收缩末容积指数(LVESVI)、左心室舒张末容积指数(LVEDVI)、左心室收缩末球形指数(SIs)、左心室舒张末球形指数(SId)、LVEF、心外膜脂肪厚度等,比较2组各超声指标的关系。结果 DCM组LVESD[(53.0±9.6)mmvs(33.2±4.5)mm]、LVEDD[(68.5±9.3)mmvs(38.3±3.0)mm]、LVESV[(79.5±13.6)ml vs(42.0±10.5)ml]、LVEDV[(165.0±18.6)ml vs(98.2±14.0)ml]、LVESVI[(49.2±10.7)ml/m2 vs(30.6±9.6)ml/m2]、LVEDVI[(101.8±10.0)ml/m2 vs(61.4±9.0)ml/m2]较对照组明显增高,LVEF[(31.5±7.2)%vs(64.9±6.4)%]、SIs[(1.3±0.2)vs(2.0±0.3)]、SId[(1.3±0.2)vs(1.8±0.2)]和心外膜脂肪厚度[(4.9±1.1)mmvs(7.8±2.0)mm]较对照组明显降低(P<0.05)。DCM组心外膜脂肪厚度与LVESD、LVEDD、LVESV、LVEDV、LVEDVI、LVESVI、SIs、SId呈正相关(P<0.05)。结论 DCM患者的心外膜脂肪厚度与左心室重构明显相关,与左心室功能不全无相关性。     

Chronic monotherapy with rosuvastatin prevents progressive left ventricular dysfunction and remodeling in dogs with heart failure.

OBJECTIVES: This study examined the effects of long-term monotherapy with rosuvastatin (RSV) on the progression of left ventricular (LV) dysfunction and remodeling in dogs with heart failure (HF). BACKGROUND: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or "statins" possess other noncholesterol-lowering properties that include inhibiting proinflammatory cytokines, attenuating LV hypertrophy, and stimulating the release of bone marrow-derived stem cells (BMSCs). METHODS: Twenty-one dogs with microembolization-induced HF were randomized to 3 months oral monotherapy with low-dose (LD) RSV (0.5 mg/kg once daily, n = 7), high-dose (HD) RSV (3.0 mg/kg once daily, n = 7), or to no therapy (control group, n = 7). The change (Delta) from pre- to post-therapy (treatment effect) in LV end-diastolic volume (EDV) and end-systolic volume (ESV) and ejection fraction (EF) was measured. Protein level of tumor necrosis factor (TNF)-alpha in LV tissue and the number of circulating Sca-1-positive BMSCs was also determined. Blood and LV tissue from 6 normal dogs was obtained and used for comparison. RESULTS: There were no differences in DeltaEDV, DeltaESV, and DeltaEF between control group and LD RSV. In contrast, DeltaEDV and DeltaESV were significantly lower, and DeltaEF was significantly higher in HD RSV compared with control group. High-dose, but not LD, RSV also normalized protein levels of TNF-alpha and was associated with a significant increase in the number of circulating BMSCs. CONCLUSIONS: In dogs with HF, chronic therapy with HD RSV prevents progressive LV dysfunction and dilation. This benefit may be partly derived from normalization of TNF-alpha expression and partly from increased mobilization of BMSCs.