Limited Response to Cardiac Resynchronization Therapy in Patients with Concomitant Right Ventricular Dysfunction

Limited Response to CRT in Patients with RVD . Introduction: Patients with left ventricular dysfunction (LVD) and LV dyssynchrony may respond to cardiac resynchronization therapy (CRT). However, right ventricular dysfunction (RVD) is a predictor of decreased survival in patients with LVD, and its influence on clinical response to CRT is unknown. The purpose of this study was to examine the effect of RVD on the clinical response to CRT. Methods and Results: A retrospective cohort of consecutive patients who underwent implantation of a CRT implantable cardioverter‐defibrillator (ICD) were included and deemed to have RVD based on a RV ejection fraction <0.40. A lack of response to CRT was defined as: death, heart transplantation, implantation of an LV assist device, absent improvement in NYHA functional class at 6 months or hospice care. Among 130 patients included (mean age 58 ± 11 years, 68.5% male, 87.7% Caucasian, 51.5% nonischemic cardiomyopathy), 77 (59.2%) had no response to CRT as defined above. Of the nonresponders, 43 (56%) had RVD and 34 (44%) did not have RVD (P = 0.02). After adjustment for age, race, gender, cardiomyopathy type, atrial fibrillation, serum sodium, and severe mitral regurgitation, RVD (adjusted OR = 0.34, 95%CI 0.14–0.82), female gender (adjusted OR = 0.36, 95%CI 0.14–0.95), and serum creatinine (adjusted OR = 0.25, 95%CI 0.09–0.71) were independently associated with decreased odds of response to CRT. There was a significant difference in survival of patients with and without RVD after CRT (log rank P = 0.01). Conclusion: RVD represents a strong predictor of lack of clinical response to CRT in patients with CHF due to LVD and should be considered when prescribing CRT. (J Cardiovasc Electrophysiol, Vol. 21, pp. 431–435, April 2010)     

心脏再同步治疗的研究进展

充血性心力衰竭是具有较高住院率和死亡率的一种严重的心血管疾病。充血性心力衰竭的主要治疗模式是基于抗神经激素和肾素-血管紧张素轴途径,这些药物治疗可缓解症状,有时亦会改善心脏结构异常,是心力衰竭治疗的基石。近30%的晚期心力衰竭患者伴有心脏电传导异常,导致心室收缩不同步。这种非同步收缩会导致心脏病理生理学改变,加重心力衰竭。因此,心脏起搏技术可能被用于恢复心室同步收缩。近来,国际上进行了一系列多中心临床研究表明,心脏再同步治疗可以改善患者心功能,提高患者运动耐量及生活质量。心脏再同步治疗在改善患者心脏结构和功能的同时,也明显降低心力衰竭恶化的危险。     

有关心脏再同步化治疗适应证的若干关注问题研究现状

自心脏再同步化治疗问世近20年以来,其临床疗效已得到肯定,现已成为慢性充血性心力衰竭非药物治疗的主要手段。为了使更多患者从该治疗中获益;严格入选适应证及合理拓展心脏再同步化治疗适应证便成了该研究领域的关注热点。     

Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) is a recently developed approach to treat dilated heart failure with discoordinate contraction. Such dyssynchrony typically stems from electrical delay that then translates into mechanical delay between the septal and lateral walls. Over the past decade, many studies have examined the pathophysiology of cardiac dyssynchrony, tested the effects of cardiac resynchronization on heart function and energetics,tested the chronic efficacy of this therapy to enhance symptoms and reduce mortality, and better established which patients are most likely to benefit. This brief review discusses these topics.     

提高CRT患者疗效的机理和方法

心脏再同步化治疗(CRT)是治疗顽固性心力衰竭的有效手段。通过运用以组织多普勒为基础的超声技术,合理评价心脏机械不同步收缩,选择合适的患者,并指导选择左室电极理想的起搏位置、设置最佳房室间期及室间间期,是目前实现提高CRT疗效的主要方法。但还需要更多的以临床事件为终点的数据以证实这些观点。应用新的超声方法,以心脏电标测方法指导电极放置,以腔内电图的方法优化参数设置可能有助于进一步提高CRT的疗效。     

Preoperative Hemoglobin and Outcomes in Patients with CKD Undergoing Cardiac Surgery

Background and objectives

Preoperative anemia adversely affects outcomes of cardiothoracic surgery. However, in patients with CKD, treating anemia to a target of normal hemoglobin has been associated with increased risk of adverse cardiac and cerebrovascular events. We investigated the association between preoperative hemoglobin and outcomes of cardiac surgery in patients with CKD and assessed whether there was a level of preoperative hemoglobin below which the incidence of adverse surgical outcomes increases.

Design, setting, participants, & measurements

This prospective observational study included adult patients with CKD stages 3–5 (eGFR<60 ml/min per 1.73 m²) undergoing cardiac surgery from February 2000 to January 2010. Patients were classified into four groups stratified by preoperative hemoglobin level: <10, 10–11.9, 12–13.9, and ≥14 g/dl. The outcomes were postoperative AKI requiring dialysis, sepsis, cerebrovascular accident, and mortality.

Results

In total, 788 patients with a mean eGFR of 43.5±13.7 ml/min per 1.73 m² were evaluated, of whom 22.5% had preoperative hemoglobin within the normal range (men: 14–18 g/dl; women: 12–16 g/dl). Univariate analysis revealed an inverse relationship between the incidence of all adverse postoperative outcomes and hemoglobin level. Using hemoglobin as a continuous variable, multivariate logistic regression analysis showed a proportionally greater frequency of all adverse postoperative outcomes per 1-g/dl decrement of preoperative hemoglobin (mortality: odds ratio, 1.38; 95% confidence interval, 1.23 to 1.57; P<0.001; sepsis: odds ratio, 1.31; 95% confidence interval, 1.14 to 1.49; P<0.001; cerebrovascular accident: odds ratio, 1.31; 95% confidence interval, 1.00 to 1.67; P=0.03; postoperative hemodialysis: odds ratio, 1.38; 95% confidence interval, 1.11 to 1.75; P<0.01). Moreover, preoperative hemoglobin<12 g/dl was an independent risk factor for postoperative mortality (odds ratio, 2.6; 95% confidence interval, 1.1 to 7.3; P=0.04).

Conclusions

Similar to the general population, preoperative anemia is associated with adverse postoperative outcomes in patients with CKD. Whether outcomes could be improved by therapeutically targeting higher preoperative hemoglobin levels before cardiac surgery in patients with underlying CKD remains to be determined.     

Management of Heart Failure Patient with CKD

CKD is common in patients with heart failure, associated with high mortality and morbidity, which is even higher in people undergoing long-term dialysis. Despite increasing use of evidence-based drug and device therapy in patients with heart failure in the general population, patients with CKD have not benefitted. This review discusses prevalence and evidence of kidney replacement, device, and drug therapies for heart failure in CKD. Evidence for treatment with β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and sodium-glucose cotransporter inhibitors in mild-to-moderate CKD has emerged from general population studies in patients with heart failure with reduced ejection fraction (HFrEF). β-Blockers have been shown to improve outcomes in patients with HFrEF in all stages of CKD, including patients on dialysis. However, studies of HFrEF selected patients with creatinine <2.5 mg/dl for ACE inhibitors, <3.0 mg/dl for angiotensin-receptor blockers, and <2.5 mg/dl for mineralocorticoid receptor antagonists, excluding patients with severe CKD. Angiotensin receptor neprilysin inhibitor therapy was successfully used in randomized trials in patients with eGFR as low as 20 ml/min per 1.73 m². Hence, the benefits of renin-angiotensin-aldosterone axis inhibitor therapy in patients with mild-to-moderate CKD have been demonstrated, yet such therapy is not used in all suitable patients because of fear of hyperkalemia and worsening kidney function. Sodium-glucose cotransporter inhibitor therapy improved mortality and hospitalization in patients with HFrEF and CKD stages 3 and 4 (eGFR>20 ml/min per 1.73 m²). High-dose and combination diuretic therapy, often necessary, may be complicated with worsening kidney function and electrolyte imbalances, but has been used successfully in patients with CKD stages 3 and 4. Intravenous iron improved symptoms in patients with heart failure and CKD stage 3; and high-dose iron reduced heart failure hospitalizations by 44% in patients on dialysis. Cardiac resynchronization therapy reduced death and hospitalizations in patients with heart failure and CKD stage 3. Peritoneal dialysis in patients with symptomatic fluid overload improved symptoms and prevented hospital admissions. Evidence suggests that combined cardiology-nephrology clinics may help improve management of patients with HFrEF and CKD. A multidisciplinary approach may be necessary for implementation of evidence-based therapy.     

心律失常与心脏再同步化治疗无反应性的相关性

虽然基于肾素-血管紧张素-醛固酮抑制剂、β受体阻滞剂的药物治疗使心力衰竭治疗取得了很大进展,但心力衰竭患者的发病率及病死率仍居高不下.心脏再同步化治疗是近年心力衰竭非药物治疗上的重大进展.但是研究表明心脏再同步化治疗后,仍有约30%的心力衰竭患者对心脏再同步化无反应.现综述了心脏再同步化治疗无反应与心律失常之间的关系,并简要讨论对心脏再同步化治疗无反应的可能机制及预防策略.     

Cardiac Resynchronization Therapy: Strategies for Device Programming,Troubleshooting and Follow-Up

Cardiac resynchronization therapy (CRT) improves symptoms, exercise performance, ventricular function, and survival in patients with left ventricular dysfunction, prolonged QRS, and drug-refractory moderate to severe CHF. The growing application of CRT has created a large number of patients with complicated devices that need follow-up care from general practitioners, cardiologists, heart failure specialists and electrophysiologists. Optimal care of the CRT patient includes recognition and management of peri-implantation complications, optimal programming of atrio-ventricular and sequential ventricular timing, and troubleshooting device-related problems during long-term follow-up. A basic awareness of fundamental device features, the techniques to maximize the response to CRT, and an understanding of stored device data to track the response to therapy provide clinicians the ability to maximize clinical outcomes in the CHF patient. As evolving technology continues to increase the complexity of device therapies, clinicians must understand these therapies in order to properly treat heart failure patients. This work summarizes many of the issues involving early complications of CRT device implant, the strategies to optimize device function, and suggests a scheme for follow-up care of patients with CRT devices.     

心脏再同步治疗心力衰竭最新研究进展

心脏再同步治疗是一种非药物治疗心力衰竭的新方法。多项临床研究已证实,心脏再同步治疗可以显著改善患者的心功能,提高生活质量,减少患者的病死率及再住院率。     

Importance of Heart Rate During Exercise for Response to Cardiac Resynchronization Therapy

Background: Cardiac resynchronization therapy (CRT) is an established therapy for patients with severe heart failure and mechanical dyssynchrony. Response is only achieved in 60–70% of patients.
Objectives: To study exercise-related factors predicting response to CRT.
Methods: We retrospectively examined consecutive patients in whom a CRT device was implanted. All underwent cardiopulmonary exercise testing prior to implantation and after 6 months. The occurrence of chronotropic incompetence and heart rates exceeding the upper rate of the device, thereby compromising biventricular stimulation, was studied. Response was defined as a decrease in LVESV of 10% or more after 6 months.
Results: We included 144 patients. After 6 months 86 (60%) patients were responders. Peak VO₂ significantly increased in responders. Chronotropic incompetence was more frequently seen in nonresponders (21 [36%] vs 9 [10%], P = 0.03), mostly in patients in SR. At moderate exercise, defined as 25% of the maximal exercise tolerance, that is, comparable to daily life exercise, nonresponders more frequently went above the upper rate of the device (13 [22%] vs 2 [3%], P < 0.0001), most of whom were patients in permanent AF. Multivariate analysis revealed heart rates not exceeding the upper rate of the device during moderate exercise (OR 15.8 [3.3–76.5], P = 0.001) and nonischemic cardiomyopathy (OR 2.4 [1.0–5.7], P = 0.04) as predictive for response.
Conclusions: Heart rate exceeding the upper rate during moderate exercise is an independent predictor for nonresponse to CRT in patients with AF, whereas chronotropic incompetence is a predictor for patients in SR.     

心脏再同步治疗晚期扩张型心肌病的临床研究

目的 探讨心脏再同步治疗（CRT）治疗扩张型心肌病（DCM）晚期慢性心力衰竭（HF）的疗效。方法DCM晚期发生慢性HF患者植入CRT。术后观察左室射血分数（LVEF）、左室舒张末内径（LVEDD）、心电图、NT—ProBNP,评估NYHA心功能分级,6min步行试验。结果所有患者均成功地植入右房-双心室三腔起搏器,并且无术后并发症。术后随访6～12个月心功能分级、LVEF、LVEDD、房室瓣反流速、NT—ProBNP水平、QRS波宽度较术前均明显改善,差异有统计学意义（P〈0．05）。结论CRT可以改善心功能,逆转左室重构,改善生活质量。     

超声心动图在慢性心力衰竭的再同步化治疗中的应用

慢性心力衰竭患者存在不同程度的心室不同步化运动,心脏再同步化治疗是治疗充血性心力衰竭的新方法,它有助于改善患者的血流动力学状态,并具有抗心律失常作用。超声心动图具有无创性和可重复性的特点,可用于筛选接受心脏再同步化治疗的患者,预测和评价心脏再同步化治疗的短期和长期效果。现就超声心动图在慢性心力衰竭的再同步化治疗中的应用进行综述。